Nurses' experiences working with families in an NICU during implementation of family-focused developmental care.
To explore and describe nurses' experiences while working with parents and infants receiving family-focused developmental care (FFDC), to gain insight into the process of changing from a traditional model of care to FFDC. The qualitative design was based on Spradley's method. Data were collected by interviewing ten nurses who worked in an NICU during a pilot study of FFDC. Transcripts were analyzed using Spradley's domain analysis. Four themes describe aspects of the transition from traditional care to FFDC: (1) negative experiences of FFDC, (2) transitions central to partnering with parents, (3) positive experiences of parental participation, and (4) organizational transitions necessary for the move to a family-centered model of care. Learning to share responsibility with families will require change in the NICU culture as well as in nurses' role identity.


Visualizing priming of virus-specific CD8+ T cells by infected dendritic cells in vivo.
The rational design of vaccines that elicit CD8+ T cell responses requires knowledge of the identity of the antigen-presenting cell (APC), the location and time of presentation and the nature of the antigen presented by the APC. Here we address these questions for an antigen encoded by a recombinant vaccinia virus. We found that, following local infection, vaccinia virus infected macrophages and dendritic cells in draining lymph nodes. However, only the dendritic cells presented antigen to naïve CD8+ T cells, as determined by direct visualization of sectioned nodes by confocal microscopy. Presentation occurred as rapidly as 6 h after inoculation and quickly declined in parallel with the number of infected cells present in the nodes. These data provide direct evidence that virus-infected APCs prime naïve CD8+ T cells in vivo.


Beyond skin testing: state of the art and new horizons in food allergy diagnostic testing.
Food allergy affects approximately 1% to 10.8% of the general population, and its prevalence seems to be increasing. An accurate diagnosis is particularly important because a misdiagnosis could lead to life-threatening reactions or to unnecessary restrictive diets. However, allergy tests currently used in clinical practice have limited accuracy, and an oral food challenge, considered as the gold standard, is often required to confirm or exclude a food allergy. This article reviews several promising novel approaches for the diagnosis of food allergy, such as new molecular diagnostic technologies and functional assays, along with their potential clinical applications.


Forensic dental training in Australia.
To facilitate in the identification of victims of a major disaster a trained dental manpower reserve is required. In the state of New South Wales, Australia, an annual three-day training course has been designed to familiarize dentists from both the public and private sectors with identification techniques. The course is aimed to preserve the flexibility of personnel so that they can be utilized in a variety of roles rather than rigidly structuring the make up of a team. It is envisaged though, that in a mass disaster situation teams would be specialized into dental autopsy, antemortem or comparison roles.


Rumen-bypassed tributyrin alleviates heat stress by reducing the inflammatory responses of immune cells.
Heat stress (HS) in summer will seriously affect the health and performance of dairy cows. To alleviate the injury to dairy cows caused by HS, we added the rumen-bypassed tributyrin to the feed. We determined whether cows were in a heat-stressed environment by testing the temperature humidity index in the morning, at noon, and in the evening. The detection of anal temperature and respiratory frequency further proved the HS state of the dairy cows. The quantificational real time PCR results showed that tributyrin could significantly reduce the relative expression of tumor necrosis factor α, interleukin 1β, and Interleukin 6. Western blot results showed that tributyrin could alleviate the lymphocyte inflammatory response by inhibiting the mitogen-activated protein kinase and nuclear factor-кB signaling pathways. To further detect the effect of tributyrin on HS in dairy cows, routine biochemical and blood tests were carried out. The results showed that the contents of aspartate aminotransferase, total bilirubin, creatinine, albumin, and globulin were significantly reduced by tributyrin. The results showed that tributyrin could significantly alleviate the liver and kidney injury induced by heat stress in dairy cows. Moreover, tributyrin could also significantly reduce the numbers of intermediate cells and increase the level of hemoglobin. Tributyrin could also improve the performance of dairy cows. These results suggested that tributylglycerol may have a positive effect on breast health of dairy cows. In conclusion, these results indicated that tributyrin could relieve HS and increase the production performance of dairy cows by reducing the inflammatory responses of lymphocytes.


Evaluating the Construct of Damage in Systemic Lupus Erythematosus.
The Systemic Lupus International Collaborating Clinics (SLICC), American College of Rheumatology (ACR), and the Lupus Foundation of America are developing a revised systemic lupus erythematosus (SLE) damage index (the SLICC/ACR Damage Index [SDI]). Shifts in the concept of damage in SLE have occurred with new insights into disease manifestations, diagnostics, and therapy. We evaluated contemporary constructs in SLE damage to inform development of the revised SDI. We conducted a 3-part qualitative study of international SLE experts. Facilitated small groups evaluated the construct underlying the concept of damage in SLE. A consensus meeting using nominal group technique was conducted to achieve agreement on aspects of the conceptual framework and scope of the revised damage index. The framework was finally reviewed and agreed upon by the entire group. Fifty participants from 13 countries were included. The 8 thematic clusters underlying the construct of SLE damage were purpose, items, weighting, reversibility, impact, time frame, attribution, and perspective. The revised SDI will be a discriminative index to measure morbidity in SLE, independent of activity or impact on the patient, and should be related to mortality. The SDI is primarily intended for research purposes and should take a life-course approach. Damage can occur before a diagnosis of SLE but should be attributable to SLE. Damage to an organ is irreversible, but the functional consequences on that organ may improve over time through physiological adaptation or treatment. We identified shifts in the paradigm of SLE damage and developed a unifying conceptual framework. These data form the groundwork for the next phases of SDI development.


Considerations in patients undergoing implantation of a biventricular pacemaker.
To compare hemodynamics and oxygenation in patients with congestive heart failure and broad QRS complexes before and with biventricular DDD pacing and to report experience with this new procedure. Prospective, observational study. Major university-affiliated community hospital. Ten patients with congestive heart failure (New York Heart Association III to IV) and broad QRS complexes (>160 msec). Patients underwent implantation of a biventricular pacemaker (n = 4) or implantation of a combined biventricular pacemaker and cardioverter-defibrillator (n = 6). Anesthesia was performed using remifentanil (0.2 to 0.3 microg/kg/min) and propofol. Propofol was used as target-controlled infusion (plasma target concentration, 1.5 to 2.5 microg/mL). Hemodynamics and oxygenation were measured before and with biventricular DDD pacing. Mean arterial pressure was significantly increased from 64.7 +/- 5.8 mmHg to 77.8 +/- 10.6 mmHg by biventricular pacing, whereas cardiac index (2.2 +/- 0.3 L/min/m(2) before and 2.3 +/- 0.3 L/min/m(2) with biventricular pacing) and pulmonary capillary wedge pressure (12.1 +/- 3.8 mmHg before and 14.2 +/- 3.6 mmHg with biventricular pacing) remained unchanged. Left ventricular stroke work index was increased >10% in 7 patients. Oxygen delivery, oxygen consumption, and difference in arteriovenous oxygen concentration were not affected. Anesthesia with remifentanil and propofol was safe and well-controllable and allowed immediate extubation at the end of the operation. There was no acute intraoperative improvement of hemodynamics except increased mean arterial pressure with biventricular pacing. Left ventricular performance seemed to improve with biventricular pacing in some patients. These results might be due to a nonoptimized atrioventricular delay. Postoperatively, atrioventricular delay was individually programmed for each patient by Doppler transmitral flow patterns.


Genetic aspects of heart failure.
Heart failure is a major health problem and is associated with a high mortality and morbidity. Recently, the role of the genetic background in the onset and the development of the disease has been evidenced in both heart failure with and without systolic dysfunction and in familial and non-familial forms of this condition. Preliminary studies suggest that the I/D polymorphism of the Angiotensin Converting Enzyme gene influence the development of left ventricular hypertrophy, a major determinant of heart failure. Familial hypertrophic cardiomyopathy (FHC) is a highly heterogenous autosomal dominant disease. Seven genes have been identified which all encode proteins of the sarcomere or proteins involved in the regulation of contraction. More than one hundred mutations have been evidenced. Modifier genes such as the I/D polymorphism seem to play a role in the expression of the disease. Susceptibility genes have been searched for in sporadic forms of dilated cardiomyopathy and conflicting results have been published with regard to the I/D polymorphism. Finally, familial forms of dilated cardiomyopathy (FDC) are frequent. Various modes of inheritance and phenotypes have been reported and this condition appears genetically highly heterogenous. It has been postulated that the molecular defect involved in FDC is an abnormality in the transmission of contractile force. The analysis of genetic factors that predispose to heart failure looks promising: it should allow better understanding of the underlying mechanisms that promote the progression of the disease, to identify subjects at risk of the disease who would benefit from early medical management and promote the development of pharmacogenetics.


Long-term effects of antibiotics, norfloxacin, and sulfamethoxazole, in a partial life-cycle study with zebrafish (Danio rerio): effects on growth, development, and reproduction.
A partial life-cycle study with zebrafish (Danio rerio) was conducted to evaluate the long-term effects of antibiotics, norfloxacin (NOR) and sulfamethoxazole (SMX). A series of bio-endpoints correlated to the growth, development, and reproduction was assessed. The results showed that the body weight and the condition factor were depressed by SMX at 200 μg/L during the growth period. Meanwhile, the activities of metabolic enzyme (ethoxyresorufin O-deethylase, EROD) and antioxidant enzymes (superoxide dismutase, SOD and catalase, CAT) were stimulated in all cases. The consequences of parental exposure to antibiotics for the next generation were also examined. The egg production of parents were depressed by the 200 μg/L NOR and SMX alone or in combination. Similarly, decreased hatching, survival, and enhanced development abnormality of the next generation also occurred after parental exposure to SMX at the highest concentration. The heartbeat however was not altered in all cases. Furthermore, there was no significant difference in the bio-endpoints between the combined and individual treatment in most cases, with the exception of lower EROD activity and egg production in the co-treatment. The results suggest that long-term exposure to NOR and SMX at environmentally relevant concentrations, individually and in a mixture, may not significantly pose a threat to the growth, development, and reproduction of zebrafish, and an adverse effect may be expected at high concentration.


Antihypertensive therapy with a single daily dose of acebutolol in essential hypertension, response and ophthalmological assessment in the Japanese.
Twenty patients with essential hypertension were given 400 mg acebutolol once daily for 24 weeks. In order to study if side effects resembling the "Practolol syndrome" developed, ocular effects were sought and antinuclear antibody (ANA) in blood was assessed before and after treatment. ANA was negative both before and after the study in 17 patients; in one patient ANA was positive, but the titre (1:10) was low and did not change during the study. Acebutolol produced no undesirable effects on cornea, conjunctiva or lens. During acebutolol treatment, tear secretion was reduced but tear lysozyme concentration was not significantly altered. Overall, acebutolol had no undesirable action similar to the practolol-induced syndrome, nor did it cause such common clinical ocular symptoms such as dry or gritty eyes.


Cloning of three 2,3-dihydroxybiphenyl-1,2-dioxygenase genes from Achromobacter sp. BP3 and the analysis of their roles in the biodegradation of biphenyl.
Three 2,3-dihydroxybiphenyl 1,2-dioxygenase genes (designated as bphC1, bphC2 and bphC3) were cloned from a biphenyl-degrading strain Achromobacter sp. BP3. The amino acid sequence of BphC1 and BphC3 had high similarity (>99%) with the reported BphCs, while BphC2 showed relatively low identity (29.51-50.17%) with the reported BphCs, which indicated that bphC2 might be a novel gene. The bphC1, bphC2 and bphC3 genes were expressed in Escherichia coli BL21 and the products were homogenously purified. BphC1, BphC2 and BphC3 displayed maximum activity at 30°C, 30°C and 40°C, respectively. Their optimal catalysis pH was 8.0, 9.0 and 9.0, respectively. BphC1 and BphC2 had higher substrate affinity and catalytic efficiency on 2,3-dihydroxybiphenyl, while BphC3 exhibited these features on aromatic monocyclic substrates. The bphC1 gene was only induced by biphenyl and bphC3 was induced by both biphenyl and toluene, while bphC2 was constitutively expressed in strain BP3. These results suggested that BphC1 and BphC3 played a role in the upstream and downstream metabolic pathways of biphenyl, respectively. However, BphC2 might play a supplementary role and contribute more to the upstream than to the downstream pathway.


Green Biorefinery systems for the production of climate-smart sustainable products from grasses, legumes and green crop residues.
Grasses, legumes and green plant wastes represent a ubiquitous feedstock for developing a bioeconomy in regions across Europe. These feedstocks are often an important source of ruminant feed, although much remains unused or underutilised. In addition to proteins, these materials are rich in fibres, sugars, minerals and other components that could also be used as inputs for bio-based product development. Green Biorefinery processes and initiatives are being developed to better capitalise on the potential of these feedstocks to produce sustainable food, feed, materials and energy in an integrated way. Such systems may support a more sustainable primary production sector, enable the valorisation of green waste streams, and provide new business models for farmers. This review presents the current developments in Green Biorefining, focusing on a broad feedstock and product base to include different models of Green Biorefinery. It demonstrates the potential and wide applicability of Green Biorefinery systems, the range of bio-based product opportunities and highlights the way forward for their broader implementation. While the potential for new products is extensive, quality control approval will be required prior to market entry.


Neck abscess: an unusual presentation of a thoracic malignancy.
In general, malignancies presenting as abscesses are uncommon. We report on a patient that presented with a neck abscess originating in a cluster of metastatic lymph nodes from a primary squamous cell carcinoma arising in the thoracic oesophagus.


The first fossil record of the Emesinae genus Emesopsis Uhler (Hemiptera: Heteroptera, Reduviidae) from Eocene Baltic amber.
Two new fossil representatives of the assassin bug family Reduviidae are described as new from Baltic amber (Upper Eocene), belonging to the genus Emesopsis of the tribe Ploiariolini (Emesinae): Emesopsis putshkovi sp. nov. and E. similis sp. nov. These representatives of the Emesinae are the oldest fossil bugs of the genus Emesopsis known so far, and reported for the first time. This genus is also briefly diagnosed.


Interaction of alpha 2-macroglobulin-bound thrombin with hirudin.
The human thrombin bound to alpha 2-macroglobulin (alpha 2 M) in a 1:1 stoichiometry is still able to interact with one of its specific inhibitors, hirudin. The dissociation constant of the complex hirudin--alpha 2M-bound thrombin is 1 X 10(-7) M, whatever the mode of thrombin binding, covalent or non-covalent.


Assessing interactions between common genetic variant on 2q35 and hormone receptor status with breast cancer risk: evidence based on 26 studies.
Genome-wide association studies have identified 2q35-rs13387042 as a new breast cancer (BC) susceptibility locus in populations of European descent. Since then, the relationship between 2q35-rs13387042 and breast cancer has been reported in various ethnic groups; however, these studies have yielded inconsistent results. To investigate this inconsistency, we performed a meta-analysis of 26 studies involving a total of 101,529 cases and 167,363 controls for 2q35-rs13387042 polymorphism to evaluate its effect on genetic susceptibility for breast cancer. An overall random effects odds ratio of 1.14 (95% CI: 1.11-1.16, P<10⁻⁵) was found for rs13387042-A variant. Significant results were also observed using dominant (OR = 1.14, 95% CI: 1.12-1.17, P<10⁻⁵), recessive (OR = 1.17, 95% CI: 1.13-1.21, P<10⁻⁵) and co-dominant genetic model (heterozygous: OR = 1.15, 95% CI: 1.12-1.19, P<10⁻⁵; homozygous: OR = 1.20, 95% CI: 1.15-1.24, P<10⁻⁵). There was strong evidence of heterogeneity, which largely disappeared after stratification by ethnicity. Significant associations were found in East Asians, and White populations when stratified by ethnicity; while no significant associations were observed in Africans and other ethnic populations. An association was observed for both ER-positive (OR = 1.17, 95% 1.15-1.19; P<10⁻⁵) and ER-negative disease (OR = 1.08, 95% CI: 1.04-1.13; P<10⁻⁴) and both progesterone receptor (PR)-positive (OR = 1.18, 95% CI: 1.15-1.21; P<10⁻⁵) and PR-negative disease (OR = 1.10, 95% CI: 1.05-1.15; P<10⁻⁴). In conclusion, this meta-analysis demonstrated that the A allele of 2q35-rs13387042 is a risk factor associated with increased breast cancer susceptibility.


Evaluation of the correlation between time corpses spent in in-ground graves and findings at exhumation.
To determine how long pathological findings persist after burial and which factors play a role in decomposition of a corpse, we evaluated all bodies exhumed under the auspices of the Institute of Legal Medicine at the Hannover Medical School between 1978 and 1997. A total of 87 exhumations (54 men, 33 women) were performed in this period. The time bodies remained buried varied between 5 days and 16.8 years (mean 1.5 years, median 2.3 months). Fifty-six percent of the bodies were exhumed after at most 3 months, 10% remained buried for greater than 3 years. Pathomorphological changes of the soft tissues and the internal organs remained evident after several months, in some cases after several years of burial. Overall, it was possible to evaluate internal organs after 5 years of burial. Bodies became mostly decomposed after approximately 8 years at the earliest, although it was still possible to evaluate some soft tissue remnants after 16.8 years. In stepwise logistic regression, both the length of time the body was buried (p < 0.00005) and the time of year (p < 0.0019) clearly affected the rate of physical change. The variables of sex (p = 0.33), age (p = 0.61) and changes in the integrity of the body before burial (trauma, autopsy before burial; p = 0.15) did not influence the physical state of the body after exhumation. Our data show that much information may be gained from an exhumation even after significant time has passed since burial.


Association of vascular risk factors with increasing glycemia even in normoglycemic subjects in an older Chinese population: the Guangzhou Biobank Cohort Study.
Hyperglycemia increases cardiovascular disease risk, but the association between increasing glycemia and cardiovascular risk factors, angina, and coronary heart disease in normoglycemic subjects is less clear, particularly in Chinese. We report on possible associations in a large group of Mainland Chinese subjects. A total of 10,400 older subjects (> or = 50 years) were recruited, and vascular risk factors were measured, including anthropometry, blood pressure, and fasting plasma biochemical factors including glucose, lipid profile, and C-reactive protein (CRP). Subjects were categorized by glycemic status, and the relationship between glycemia and cardiovascular risk factors was investigated using analysis of variance and multiple linear regression analyses. Tertiles of fasting glucose levels showed a clear positive relationship with cardiovascular risk factors including age, obesity, blood pressure, lipid levels, and CRP (P < .001 for all). The overall prevalence of self-reported vascular disease was low, but significantly associated with increasing glycemia. Multiple regression showed that waist circumference (standardized regression coefficient beta = .10, P < .001), triglycerides (beta = 0.16, P < .001), CRP (beta = 0.06, P < .001), female sex (beta = .03, P = .007), high-density lipoprotein cholesterol (beta = -.02, P = .016), and mean arterial pressure (beta = .06, P < .001) were independently associated with fasting glucose levels. Among the normoglycemic subjects (n = 5190), increasing glycemia was still associated with increasing obesity indices, systolic blood pressure, triglyceride, and CRP levels (all P < .05). Increasing glycemia, even in the reference range, is associated with increasing prevalence of vascular risk factors. Control of these risk factors, particularly obesity, the most important avoidable independent determinant of glycemia in normoglycemic subjects, is critical to reduce the risk of the associated vascular disease.


Immunoelectrophoretic study of the host antigens of Sendai virus cultivated in different substrates (embryonated hen eggs and KB cells). Note I. Analysis of chorioallantoic membrane host antigens.
The immunoelectrophhoretic analysis of two preparations of the same virus cultivated in different substrates (Sendai/egg and Sendai/KB) demonstrate that virus envelopes contain: a) identical virus-specific antigens (but also some virus antigens with only partial immunochemical identity, or even non-identity); b) antigens incorporated by the virus from the host cell, during assembly and release. The latter differ according to the host, and some of them are only partially identical with the corresponding antigens of the host cell, which suggests that host cell glycoproteins are incorporated into the virus envelope after certain virus-induced modifications.


Effect of 5-HT depletion on cardiovascular vagal reflex sensitivity in awake and anesthetized rats.
Antagonism of central 5-HT1A and 5-HT7 receptors inhibits reflex-evoked vagal bradycardias indicating that 5-HT is released during these reflexes. The present experiments examined the effect of 5-HT depletion with para-chlorophenylalanine (p-CPA) on the cardiac vagal baroreflex and cardiopulmonary reflex in awake and anesthetized rats. Immunocytochemistry and neurochemical detection showed that p-CPA depleted the brainstem of 5-HT, but not of norepinephrine or dopamine. Depletion of 5-HT was associated with an increase in mean arterial pressure (MAP) in awake rats. This difference was abolished by anesthesia, which reduced MAP in both groups of animals. The baroreflex gain, whether calculated from the rise in pressure induced by phenylephrine or the fall in pressure evoked by sodium nitroprusside, was significantly attenuated in depleted rats compared to controls. This attenuation of the baroreflex gain was unaffected by subsequent anesthesia. 5-HT depletion also attenuated the cardiopulmonary reflex vagal bradycardias but this only reached statistical significance when the rats were anesthetized. The data support the view that 5-HT is released in the reflex activation of the cardiac vagal pathway.


The changes in sulfhydryl compounds in plasma, liver and brain after acute and chronic ethanol administration in rats.
The content of sulfhydryl compounds in proteins and non-proteins of plasma, liver and brain after acute and chronic ethanol administration was investigated in rats. After ethanol ingestion for 4 weeks (6 g/kg, day 30% w/v) significant changes were observed in plasma proteins and in liver proteins and non-proteins. In brain proteins and non-proteins we did not find any changes in sulfhydryl compounds content after acute and chronic ethanol administration.


Combined resection of invaded organs in patients with T4 gastric carcinoma.
To understand the efficacy of gastrectomy combined with the resection of other organs and to refine the indications for this type of surgery, the records of 156 patients with carcinoma of the stomach directly invading adjacent organs or structures (T4 gastric carcinoma) were analyzed retrospectively. The patients were divided into three groups, as follows: in group A, curative resection was performed by the combined resection of invaded organs or structures; in group B, although combined resection was performed, curative resection could not be performed because of the extent of lymph node metastasis, liver metastasis, and/or peritoneal metastasis; in group C, combined resection was not performed. In patients with peritoneal or liver metastasis, there was no significant difference in prognosis among the three groups. In patients without peritoneal and liver metastasis, the prognosis of group A was significantly better than that of group B or group C, irrespective of the extent of lymph node metastasis or the number of invaded organs. In these group A patients, the 5-year survival rates of those with localized tumors and no lymph node metastasis, those with localized tumors and lymph node metastasis, those with infiltrating tumors and no lymph node metastasis, and those with infiltrating tumors and lymph node metastasis were 100%, 56.2%, 57.1%, and 13.6%, respectively. Combined resection of involved organs should be carried out with curative intent in patients with localized gastric cancer or infiltrating gastric cancer without lymph node metastasis.


Rapid prototyping of microfluidic chips enabling controlled biotechnology applications in microspace.
Rapid prototyping of microfluidic chips is a key enabler for controlled biotechnology applications in microspaces, as it allows for the efficient design and production of microfluidic systems. With rapid prototyping, researchers and engineers can quickly create and test new microfluidic chip designs, which can then be optimized for specific applications in biotechnology. One of the key advantages of microfluidic chips for biotechnology is the ability to manipulate and control biological samples in a microspace, which enables precise and controlled experiments under well-defined conditions. This is particularly useful for applications such as cell culture, drug discovery, and diagnostic assays, where precise control over the biological environment is crucial for obtaining accurate results. Established methods, for example, soft lithography, 3D printing, injection molding, as well as other recently highlighted innovative approaches, will be compared and challenges as well as limitations will be discussed. It will be shown that rapid prototyping of microfluidic chips enables the use of advanced materials and technologies, such as smart materials and digital sensors, which can further enhance the capabilities of microfluidic systems for biotechnology applications. Overall, rapid prototyping of microfluidic chips is an important enabling technology for controlled biotechnology applications in microspaces, as well as for upscaling it into macroscopic bioreactors, and its continued development and improvement will play a critical role in advancing the field. The review will highlight recent trends in terms of materials and competing approaches and shed light on current challenges on the way toward integrated microtechnologies. Also, the possibility to easy and direct implementation of novel functions (membranes, functionalization of interfaces, etc.) is discussed.


Morphological characteristics and intercellular connections of corneal keratocytes.
To investigate the morphological characteristics of keratocytes and the interconnection of keratocytes with adjacent keratocytes using the flat preparation method and scanning electron microscopy with a frontal section of the human corneal stroma. The thin, corneal collagen lamellae were carefully dissected from the cornea (n=7), which had been stained by the flat preparation method. The remaining tissue was fixed in 3% glutaraldehyde and observed by transmission electron microscopy following the frontal section. The flat preparation revealed the corneal fibroblasts between the lamellae of the collagen fibers and showed that the ramifying cellular processes of the keratocytes were in contact with the cytoplasmic processes or cell bodies of neighboring fibroblasts. Two types of discrete subpopulations of keratocytes were identified: a smaller, cellular type of keratocyte with spindle-shaped nucleus with heterochromatin, and a larger, cellular type with a large indented nucleus with relatively scanty cytoplasm. Collagen fibers ran parallel to each other toward the fenestration of the cytoplasmic wall of the keratocyte. These flat preparation method results showed that the keratocytes within the corneal stroma are interconnected with the adjacent keratocytes, which indicates the presence of a functional communicating network through the keratocyte circuits within the stroma. A smaller, cellular type of keratocyte with spindle-shaped nucleus was morphologically differentiated from a larger, cellular type with a large, indented nucleus by flat preparation and transmission electron microscopy.


Surgeon-Directed Arthroscopic Infiltration Between the Popliteal Artery and Capsule of the Knee (IPACK) Block: Technical Description.
Advances in regional anesthesia techniques for knee surgery have led to drastic improvements in postoperative pain control and have reduced reliance on perioperative opioid analgesics. The infiltration between the popliteal artery and capsule of the knee (IPACK) block has been a useful tool for providing posterior knee analgesia as an adjuvant to traditional femoral or adductor canal blocks in knee surgery. We present a simple and reproducible technique for the arthroscopic administration of this block.


Evaluating the role of desorption in bioavailability of sediment-associated contaminants using oligochaetes, semipermeable membrane devices and Tenax extraction.
The success of the rapidly desorbing fraction as an available fraction was challenged by using sediment ingesting and non-ingesting oligochaetes (Lumbriculus variegatus) together with passive samplers (semipermeable membrane devices, SPMDs) in accumulation and kinetic modelling exercises for carbon-14 labelled model compounds (pyrene, benzo[a]pyrene and 3,4,3',4'-tetrachlorobiphenyl). Passive samplers clearly produced lower uptake rate constants and steady state factors than either of the oligochaete treatments when residue concentrations were based on animal lipid or total SPMD weight. The rapidly desorbing chemical fractions in sediments did not show a significant relationship with the biota sediment accumulation factors or SPMD accumulation factors. A distinctly better relationship was observed between the accumulation factors and the desorption rate constants. The results support the assumption that desorption plays an important role in bioavailability, although animal behaviour and the diffusional limitations of hydrophobic contaminants in sediment together probably affect the actual available pool.


Calcium handling coupled to the endothelin ETA and ETB receptor-mediated vasoconstriction in resistance arteries: Differential regulation by PI3K, PKC and RhoK.
Abnormal endothelin-1 (ET-1) activity is involved in the pathogenesis of vascular diseases such as essential and pulmonary arterial hypertension, coronary artery disease, and cerebrovascular disease, blockade of ET receptors having shown efficacy in clinical assays and experimental models of hypertension. Augmented Ca2+ influx and changes in Ca2+ sensitization associated with arterial vasoconstriction underlie increased systemic vascular resistance in hypertension. Since peripheral resistance arteries play a key role in blood pressure regulation, we aimed to determine here the specific Ca2+ signaling mechanisms linked to the ET receptor-mediated vasoconstriction in resistance arteries and their selective regulation by protein kinase C (PKC), Rho kinase (RhoK), the phosphatidylinositol 3-kinase (PI3K) and the mitogen-activated protein kinase (MAPK). ET-1-induced contraction was mediated by the endothelin ETA receptor with a minor contribution of vascular smooth muscle (VSM) endothelin ETB receptors. ET receptor activation elicited Ca2+ mobilization from intracellular stores, extracellular Ca2+ influx and Ca2+ sensitization associated with contraction in resistance arteries. Vasoconstriction induced by ET-1 was largely dependent on activation of canonical transient receptor potential channel 3 (TRPC3) and extracellular Ca2+ influx through nifedipine-sensitive voltage-dependent Ca2+ channels. PI3K inhibition reduced intracellular Ca2+ mobilization and Ca2+ entry without altering vasoconstriction elicited by ET-1, while PKC has dual opposite actions by enhancing Ca2+ influx associated with contraction, and by inhibiting Ca2+ release from intracellular stores. RhoK was a major determinant of the enhanced sensitivity of the contractile filaments underlying ET-1 vasoconstriction, with also a modulatory positive action on Ca2+ influx and intracellular Ca2+ release. Augmented RhoK and PKC activities are involved in vascular dysfunction in hypertension and vascular complications of insulin-resistant states, and these kinases are thus potential pharmacological targets in vascular diseases in which the ET pathway is impaired.


Clinical significance of Staphylococcus aureus in cystic fibrosis.
Staphylococcus aureus is usually the first bacterial pathogen detected in the respiratory secretions of patients with cystic fibrosis. This review briefly examines the characteristics of this host-parasite relationship in terms of current knowledge about the toxicity of the organism, mechanisms of respiratory tract injury, therapy and prevention. Recent evidence indicates that viral infection plays a role in the initial damage of the respiratory epithelial cells and staphylococcal colonization ensues. Affinity of staphylococcus for cystic fibrosis mucus, mucociliary abnormalities and unknown factors contribute to persistent colonization with this organism causing progressive pulmonary damage and possibly influencing Pseudomonas infection. Most of the evidence today indicates that aggressive antibiotic management directed against S. aureus is warranted in all stages of bronchopulmonary infection in cystic fibrosis. Future efforts to prevent colonization and the toxic and immunopathic consequences of staphylococcal infection are also important. One study is in progress that examines antibiotic prevention in the early stages of cystic fibrosis. Future investigations need to address other strategies including vaccines, antitoxins, anti-inflammatory agents, immunomodulators, and antibiotic regimens.


Aluminum accumulation in children on chronic dialysis: predictive value of serum aluminum levels and desferrioxamine infusion test.
In 7 children on chronic dialysis the correlation between serum aluminum, aluminum after desferrioxamine (DFO) challenge and bone aluminum was studied. In children the DFO challenge test is not superior to the serum aluminum level for the estimation of aluminum body burden. A significant correlation between serum aluminum and bone aluminum content was found. In all children, except one, aluminum bone content was markedly elevated.


10-year frailty trajectory is associated with Alzheimer's dementia after considering neuropathological burden.
Frailty is an established risk factor for cognitive decline and Alzheimer's disease. Few studies have examined the longitudinal relationship between frailty and cognition. Participants of Rush Memory and Aging project (n = 625, 67.5% female, 83.2 ± 5.9 years at baseline) underwent annual clinical evaluations (average follow-up 5.6 ± 3.7 years) followed by neuropathologic assessment after death. A frailty index was calculated from 41 health variables at each evaluation. Clinical diagnosis of MCI and/or dementia was ascertained by clinical data review (blinded to neuropathological data) after death. Age, sex, education, and neuropathological burden (10-item index) were evaluated as covariates. Frailty trajectories were calculated using a mixed effects model. At baseline the mean frailty index = 0.24 ± 0.12 and increased at rate of 0.026 or ~1 deficit per year. At death, 27.7% of the sample had MCI, and 38.6% had dementia. Frailty trajectories were significantly steeper among those individuals who were ultimately diagnosed as clinically impaired prior to death, even after controlling for age, sex, education, and neuropathological index. Findings suggest a strong link between health status (frailty index) and dementia, even after considering neuropathology. Frailty trajectories were associated with risk for MCI and dementia, underscoring the importance of addressing frailty to manage dementia risk.


Generation and Selection of Orf Virus (ORFV) Recombinants.
Orf virus (ORFV) is an epitheliotropic poxvirus, which belongs to the genus Parapoxvirus. Among them the highly attenuated, apathogenic strain D1701-V is regarded as a promising candidate for novel virus vector vaccines. Our recent work demonstrated that those ORFV-based recombinants were able to induce protective, long-lasting immunity in various hosts that are non-permissive for ORFV. In this chapter we describe procedures for the generation, selection, propagation, and titration of ORFV recombinants as well as transgene detection by PCR or immunohistochemical staining.


HMGA proteins in malignant peripheral nerve sheath tumor and synovial sarcoma: preferential expression of HMGA2 in malignant peripheral nerve sheath tumor.
Histological separation of synovial sarcomas from malignant peripheral nerve sheath tumors can be difficult and available immunohistochemical markers sometimes give rise to overlapping staining patterns. Additional markers are needed to better define the two entities in the routine surgical pathology practice. To this end, we explored diagnostic applications of HMGA (HMGA1 and HMGA2) protein immunohistochemistry in comparable groups of synovial sarcoma and malignant peripheral nerve sheath tumors. The histological diagnosis of these cases was confirmed by the presence or absence of synovial sarcoma specific SYT-SSX fusion transcript analyzed by real-time reverse transcription polymerase chain reaction. In all, 13 malignant peripheral nerve sheath tumors and 15 synovial sarcomas were included in this study. Immunohistochemically, most malignant peripheral nerve sheath tumors expressed both HMGA1 and HMGA2 protein (12/13 and 12/13 cases, respectively) with moderate to strong nuclear staining patterns. Most cases of synovial sarcomas demonstrated variable expression of HMGA1. However, significant immunoreactivity for HMGA2 was present in the glandular component of a biphasic tumor (1/1) and rarely detected in monophasic synovial sarcomas (1/14). In summary, expression of HMGA2 is a feature of MPNST but not of synovial sarcoma and immunohistochemical staining of HMGA2 may be a useful marker to separate malignant peripheral nerve sheath tumor from synovial sarcoma.


The use of the latissimus dorsi musculocutaneous flap following recurrence of cancer in irradiated breasts.
The latissimus dorsi musculocutaneous flap was used to provide chest wall coverage in 40 patients following mastectomy to treat recurrent cancer in irradiated breasts. Although the axillary region had received 50 to 55 grays, the neurovascular pedicle was never jeopardized, thus assuring vascularisation of the flap. In two cases, a small area of skin necrosis in the upper inner border of the flap was observed. Complete healing occurred within weeks. The authors advocate this fast and simple surgical procedure when the quality of the skin and/or the extent of resection prevents primary closure.


A pilot investigation of mild hypothermia in neonates receiving extracorporeal membrane oxygenation (ECMO).
To investigate the safety and feasibility of using mild hypothermia in neonates receiving extracorporeal membrane oxygenation (ECMO). Study design A prospective, nonrandomized pilot study of 25 neonates referred for ECMO. Whole body cooling was achieved by adjustment of the temperature of the extracorporeal circuit water bath. Five groups (N=5 per group) were each studied for the first 5 days of ECMO. The first group was maintained at 37 degrees C throughout the study period. Subsequent groups were cooled to 36 degrees C, to 35 degrees C, and, finally, to 34 degrees C, respectively, for 24 hours and the final group to 34 degrees C for 48 hours before being rewarmed to 37 degrees C. Patients were carefully assessed clinically and biologically. In addition to routine laboratory tests, cytokines (IL-6 and IL-8), complement (C3a), and molecular markers of coagulation (thrombin/antithrombin III [TAT], antithrombin III, and plasmin-alpha2plasminogen) were measured. No major clinical or circuit problems were noted during cooling or rewarming. In particular, there were no problems of bleeding or cardiac arrhythmia. No significant difference was found between groups in terms of molecular markers of coagulation, complement, cytokines, and platelet transfusions. Applying mild hypothermia (34 degrees C) for 24 or 48 hours to neonates receiving ECMO is both feasible and safe.


Prothrombinase complex assembly. Kinetic mechanism of enzyme assembly on phospholipid vesicles.
The kinetics of the assembly of the prothrombinase complex was studied using factor Xa modified with the active site-directed fluorophore dansylglutamylglycylarginyl chloromethyl ester (DEGR.Xa) as a reporter for the process. Stopped-flow kinetic studies of prothrombinase assembly were undertaken at saturating concentrations of calcium ion, using vesicles composed of phosphatidylcholine and phosphatidylserine (PCPS), factor Va, and DEGR.Xa. The rate of complex formation, studied under pseudo first-order conditions, depended on the premixing protocol used to initiate complex assembly and was most rapid when prothrombinase assembly was initiated by reacting Va with the preformed DEGR.Xa.PCPS complex. Under these conditions, reaction rate was linearly dependent on the concentration of PCPS with no evidence for saturation and was independent of the concentration of VA. Essentially identical reaction rates were observed when the association of Va with PCPS was independently assessed by stopped-flow light scattering. The data indicate that prothrombinase assembly initiated by mixing Va with the DEGR.Xa.PCPS complex is rate limited by the initial reaction between Va and available combining sites on the vesicle surface (k = 5.7 x 10(7) M-1.s-1) followed by extremely rapid reactions (k greater than 1 x 10(9) M-1.s-1) between PCPS-bound DEGR.Xa and PCPS-bound Va. The formation of a separate Va.PCPS complex is therefore required for prothrombinase assembly to proceed. Reaction rates obtained when prothrombinase assembly was initiated by reacting DEGR.Xa with the preformed Va.PCPS complex or by reacting PCPS with a mixture of DEGR.Xa and Va were lower. Under these initiation conditions, reaction rates were inhibited by increasing concentrations of factor Va. These data indicate that the formation of the DEGR.Xa.PCPS binary complex is also a prerequisite for prothrombinase assembly. The second-order rate constant for the reaction between factor Xa and PCPS (k = 2.9 x 10(7) M-1.s-1) and the first-order rates of dissociation of the Va.PCPS complex (koff = 0.17 s-1) and the Xa.PCPS complex (koff = 3.3 s-1) were independently determined by stopped-flow light scattering. Collectively, the data are consistent with the interpretation that prothrombinase assembly proceeds via the initial formation of separate Xa.PCPS and Va. PCPS binary complexes at near diffusion-limited rates on the same vesicle. The lipid-bound constituents then react rapidly via rearrangements on the vesicle surface to form prothrombinase.


Synthesis of bile acid analogs: 7-alkylated chenodeoxycholic acids.
This paper describes a method for the preparation of 7-alkylated chenodeoxycholic acids from 3 alpha-hydroxy-7-oxo-5 beta-cholanoic acid. The synthetic procedure is based upon a Grignard reaction between the keto bile acid and an alkyl magnesium halide. Under the conditions employed, the introduction of alkyl groups is highly stereoselective. Only 7 beta-alkylated epimers are obtained. The overall yield is several-fold higher than that obtained by the previous method, which involved the preparation of an oxazoline intermediate.


Musical pleasure beneficially alters stride and arm swing amplitude during rhythmically-cued walking in people with Parkinson's disease.
Entrainment of walking to rhythmic auditory cues (e.g., metronome and/or music) improves gait in people with Parkinson's disease (PD). Studies on healthy individuals indicate that entrainment to pleasant musical rhythm can be more beneficial for gait facilitation than entrainment to isochronous rhythm, potentially as a function of emotional/motivational responses to music and their associated influence on motor function. Here, we sought to investigate how emotional attributes of music and isochronous cues influence stride and arm swing amplitude in people with PD. A within-subjects experimental trial was completed with persons with PD serving as their own controls. Twenty-three individuals with PD walked to the cue of self-chosen pleasant music cue, pitch-distorted unpleasant music, and an emotionally neutral isochronous drumbeat. All music cues were tempo-matched to individual walking pace at baseline. Greater gait velocity, stride length, arm swing peak velocity and arm swing range of motion (RoM) were found when patients walked to pleasant music cues compared to baseline, walking to unpleasant music, and walking to isochronous cues. Cued walking in general marginally increased variability of stride-to-stride time and length compared with uncued walking. Enhanced stride and arm swing amplitude were most strongly associated with increases in perceived enjoyment and pleasant musical emotions such as power, tenderness, and joyful activation. Musical pleasure contributes to improvement of stride and arm swing amplitude in people with PD, independent of perceived familiarity with music, cognitive demands of music listening, and beat salience. Our findings aid in understanding the role of musical pleasure in invigorating gait in PD, and inform novel approaches for restoring or compensating impaired motor circuits.


The effect of supervised prenatal exercise on fetal growth: a meta-analysis.
To estimate the influence of structured prenatal exercise on newborn birth weight, macrosomia, and growth restriction. A structured search of MEDLINE, EMBASE, CINAHL, Sport Discus, Ovid's All EBM Reviews, and ClinicalTrials.gov databases up to January 13, 2015. The search combined keywords and MeSH-like terms including, but not limited, to "physical activity," "exercise," "pregnancy," "gestation," "neonatal," and "randomized controlled trial." Articles reporting randomized controlled trials comparing standard care with standard care plus supervised prenatal exercise for which birth size was available were included. Supervision was defined as at least one exercise session performed with study personnel every 2 weeks throughout the program. Interventions consisting solely of pelvic floor exercises, stretching, or relaxation were excluded. Our search yielded 1,036 publications of which 79 were assessed for eligibility. Twenty-eight studies reporting on 5,322 pregnancies were subsequently included in the analysis. Our meta-analysis demonstrated that prenatal exercise reduced the odds of having a large newborn (birth weight greater than 4,000 g or greater than the 90th percentile for gestational age and sex) by 31% (odds ratio [OR] 0.69, 95% confidence interval [CI] 0.55-0.86; I 25%) without altering the risk of having a small newborn (birth weight less than 2,500 g or less than the 10th percentile for gestational age and sex) (OR 1.02, 95% CI 0.72-1.46; I 0%) or gestational age at delivery (weighted mean difference -0.00 weeks, 95% CI -0.09 to 0.09; I 0%). Newborns of mothers assigned to exercise were lighter than those of nonexercising controls (weighted mean difference -31 g, 95% CI -57 to -4; I 0%). Maternal gestational weight gain (weighted mean difference -1.1 kg, 95% CI -1.5 to -0.6; I 53%) and odds of cesarean delivery (OR 0.80, 95% CI 0.69-0.94; I 0%) were also reduced. These data demonstrate that structured prenatal exercise reduces the risk of having a large newborn without a change in the risk of having a small newborn.


Astrocytic gliomas WHO grades II and III.
World Health Organization grades II and III lower-grade astrocytomas are a challenging area in neuro-oncology. One the one hand, for proper diagnosis, the analysis of molecular factors, especially mutation status of isocitrate dehydrogenase and 1p/19q status in the tumor status needs to be done in addition to classical neuropathology. Further, the high clinical and prognostic value of a maximal safe resection requires a profound knowledge of presurgical diagnosis and surgical as well as imaging techniques to ensure optimal outcome for patients. Also medical treatment may be more intensive than previously believed, with randomized trials providing evidence for a benefit in overall survival by combined chemoradiation versus radiation alone. A critical problem concerns the considerable undesirable effects of therapeutic interventions on long-term health-related quality of life, cognitive and functional outcome as well as future developments in this still difficult disease that will need to be addressed in future trials.


Balloon dilatation of urethral strictures.
Balloon dilatation of the urethra in 9 male patients with either post-inflammatory or post-traumatic strictures was successfully performed. This procedure is primarily indicated in those patients with unsatisfactory results using conventional dilatation with metal sounds. A flexible endoscope was used for guide wire passage and fluoroscopic guidance for positioning the balloon and assuring complete dilatation of the urethral strictures or vesical neck contracture. In this manner, dilatation to 36 F can be performed in a relatively atraumatic manner with minimal discomfort.


Downregulation of Circ-CEP128 Enhances the Paclitaxel Sensitivity of Cervical Cancer Through Regulating miR-432-5p/MCL1.
Chemoresistance is a common problem in cancer treatment, and circular RNA (circRNA) has been found to be associated with the progression of chemoresistance in cancer. However, the role and mechanism of circRNA centrosomal protein 128 (circ-CEP128) in the chemoresistance of cervical cancer (CC) are still unclear. The expression of circ-CEP128, microRNA (miR)-432-5p, and myeloid cell leukemia-1 (MCL1) was measured by quantitative real-time PCR. The paclitaxel resistance of cells was assessed using MTT assay. Cell proliferation, apoptosis, migration, and invasion were determined using MTT assay, colony formation assay, flow cytometry, and transwell assay. The protein levels of metastasis markers and MCL1 were examined using western blot analysis. Mice xenograft models were constructed to assess the effect of circ-CEP128 silencing on CC tumor growth and paclitaxel sensitivity. The interaction between miR-432-5p and circ-CEP128 or MCL1 was confirmed by dual-luciferase reporter assay and RIP assay. Circ-CEP128 had highly expression in CC tumor tissues and cells. Silencing of circ-CEP128 could enhance the paclitaxel sensitivity of CC cells by decreasing cell growth, migration, and invasion. Also, knockdown of circ-CEP123 reduced CC tumor growth and promoted the paclitaxel sensitivity of CC tumors. MiR-432-5p was found to be sponged by circ-CEP128, and its inhibitor could reverse the promoting function of circ-CEP128 silencing on the paclitaxel sensitivity of CC cells. Additionally, MCL1 was a target of miR-432-5p, and circ-CEP128 could sponge miR-432-5p to regulate MCL1. Besides, overexpressed MCL1 also could reverse the enhancing effect of miR-432-5p on the paclitaxel sensitivity of CC cells. In conclusion, the present study showed that circ-CEP128 silencing could increase the paclitaxel sensitivity of CC by regulating the miR-432-5p/MCL1 axis.


Influence of genotype, growth regulators, sucrose level and preconditioning of donor plants on flax (Linum usitatissimum L.) anther culture.
The effect of genotype, growth regulators and preconditioning of donor plants on callus induction in anther culture of flax was investigated. Anthers were cultured on modified MS medium supplemented with five different combinations of plant growth regulators. The results suggested that specific combinations of growth regulators must be designed for each genotype. Major differences between the present results and previous reports are discussed. The influence of sucrose concentration was also investigated. For flax cultivar, 'Mikael', callus induction was higher in medium supplemented with 1 mg l(-1) BAP and 2 mg l(-1) 2,4D containing 6% sucrose, while this combination of growth regulators significantly increased callogenesis in cultivars 'Lirina', 'Barbara' and 'Szaphir' when supplemented with 9% or 12% sucrose. The preconditioning of donor plants influenced callogenesis in subsequently isolated anthers. Anthers from donor plants grown at a lower temperature (18/14 degrees C) significantly increased callus induction over those from plants grown at a higher temperature (22/18 degrees C), although each genotype still required optimization of growth regulator combinations in the induction medium. Only 'Mikael' regenerated shoots when the callus was from induction medium supplemented with 2 mg I(-1) BAP and 1 mg l(-1) NAA.


PTRAMP; a conserved Plasmodium thrombospondin-related apical merozoite protein.
A gene encoding a 352 amino acid protein with a putative signal sequence, transmembrane domain and thrombospondin structural homology repeat was identified in the genome of the human malaria parasite, Plasmodium falciparum and the rodent malaria parasite, Plasmodium berghei. The protein localises in the apical organelles of P. falciparum and P. berghei merozoites within intraerythrocytic schizonts and has, therefore, been termed the Plasmodium thrombospondin-related apical merozoite protein (PTRAMP). PTRAMP co-localises with the Apical Merozoite Antigen-1 (AMA-1) in developing micronemes and subsequently relocates onto the merozoite surface. Although the gene appears to be specific to the Plasmodium genus, orthologues are present in the genomes of all malaria parasite species examined suggesting a conserved function in host-cell invasion. PTRAMP, therefore, has all the features to merit further evaluation as a malaria vaccine candidate.


A multi-center diagnostic system for intrahepatic mass-forming cholangiocarcinoma based on preoperative MRI and clinical features.
To establish a non-invasive diagnostic system for intrahepatic mass-forming cholangiocarcinoma (IMCC) via decision tree analysis. Totally 1008 patients with 504 pathologically confirmed IMCCs and proportional hepatocellular carcinomas (HCC) and combined hepatocellular cholangiocarcinomas (cHCC-CC) from multi-centers were retrospectively included (internal cohort n = 700, external cohort n = 308). Univariate and multivariate logistic regression analyses were applied to evaluate the independent clinical and MRI predictors for IMCC, and the selected features were used to develop a decision tree-based diagnostic system. Diagnostic efficacy of the established system was calculated by the receiver operating characteristic curve analysis in the internal training-testing and external validation cohorts, and also in small lesions ≤ 3 cm. Multivariate analysis revealed that female, no chronic liver disease or cirrhosis, elevated carbohydrate antigen 19-9 (CA19-9) level, normal alpha-fetoprotein (AFP) level, lobulated tumor shape, progressive or persistent enhancement pattern, no enhancing tumor capsule, targetoid appearance, and liver surface retraction were independent characteristics favoring the diagnosis of IMCC over HCC or cHCC-CC (odds ratio = 3.273-25.00, p < 0.001 to p = 0.021). Among which enhancement pattern had the highest weight of 0.816. The diagnostic system incorporating significant characteristics above showed excellent performance in the internal training (area under the curve (AUC) 0.971), internal testing (AUC 0.956), and external validation (AUC 0.945) cohorts, as well as in small lesions ≤ 3 cm (AUC 0.956). In consideration of the great generalizability and clinical efficacy in multi-centers, the proposed diagnostic system may serve as a non-invasive, reliable, and easy-to-operate tool in IMCC diagnosis, providing an efficient approach to discriminate IMCC from other HCC-containing primary liver cancers. This study established a non-invasive, easy-to-operate, and explainable decision tree-based diagnostic system for intrahepatic mass-forming cholangiocarcinoma, which may provide essential information for clinical decision-making. • Distinguishing intrahepatic mass-forming cholangiocarcinoma (IMCC) from other primary liver cancers is important for both treatment planning and outcome prediction. • The MRI-based diagnostic system showed great performance with satisfying generalization ability in the diagnosis and discrimination of IMCC. • The diagnostic system may serve as a non-invasive, easy-to-operate, and explainable tool in the diagnosis and risk stratification for IMCC.


Proof of impact and pipeline planning: directions and challenges for social audit in the health sector.
Social audits are typically observational studies, combining qualitative and quantitative uptake of evidence with consultative interpretation of results. This often falters on issues of causality because their cross-sectional design limits interpretation of time relations and separation out of other indirect associations.Social audits drawing on methods of randomised controlled cluster trials (RCCT) allow more certainty about causality. Randomisation means that exposure occurs independently of all events that precede it--it converts potential confounders and other covariates into random differences. In 2008, CIET social audits introduced randomisation of the knowledge translation component with subsequent measurement of impact in the changes introduced. This "proof of impact" generates an additional layer of evidence in a cost-effective way, providing implementation-ready solutions for planners.Pipeline planning is a social audit that incorporates stepped wedge RCCTs. From a listing of districts/communities as a sampling frame, individual entities (communities, towns, districts) are randomly assigned to waves of intervention. Measurement of the impact takes advantage of the delay occasioned by the reality that there are insufficient resources to implement everywhere at the same time. The impact in the first wave contrasts with the second wave, which in turn contrasts with a third wave, and so on until all have received the intervention. Provided care is taken to achieve reasonable balance in the random allocation of communities, towns or districts to the waves, the resulting analysis can be straightforward.Where there is sufficient management interest in and commitment to evidence, pipeline planning can be integrated in the roll-out of programmes where real time information can improve the pipeline. Not all interventions can be randomly allocated, however, and random differences can still distort measurement. Other issues include contamination of the subsequent waves, ambiguity of indicators, "participant effects" that result from lack of blinding and lack of placebos, ethics and, not least important, the skills to do pipeline planning correctly.


An attachment insecurity model of negative affect among women seeking treatment for an eating disorder.
The purpose of this study was to propose and test a model of attachment insecurity in a clinical sample of 268 eating disordered women. Structural relationships among attachment insecurity, BMI, perceived pressure to diet, body dissatisfaction, restrained eating, and negative affect were assessed. A heterogeneous sample of treatment seeking women with a diagnosed eating disorder completed psychometric tests prior to receiving treatment. The data were analysed using structural equation modeling. Fit indices indicated that the hypothesized model fit adequately to the data. Although cross-sectional in nature, the data suggested that attachment insecurity may lead to negative affect. As well, attachment insecurity may lead to body dissatisfaction, which in turn may lead to restrained eating among women with eating disorders. Attachment insecurity could be a possible vulnerability factor for the development of eating disorder symptoms among women.


Nuclear import of BCL11B is mediated by a classical nuclear localization signal and not the Krüppel-like zinc fingers.
The Krüppel-like transcription factor (KLF) BCL11B is characterized by a wide tissue distribution and crucial functions in key developmental and cellular processes, as well as in various pathologies including cancer and HIV infection. Although the basics of BCL11B activity and relevant interactions with other proteins have been uncovered, how this exclusively nuclear protein localizes to its compartment remained unclear. Here, we demonstrate that unlike other KLFs, BCL11B does not require the C-terminal DNA-binding domain to pass through the nuclear envelope but has an independent, previously unidentified, nuclear localization signal (NLS), which is located distantly from the zinc finger domains and fulfills the essential criteria of being an autonomous NLS. First, it can redirect a heterologous cytoplasmic protein to the nucleus. Second, its mutation causes aberrant localization of the protein of origin. Finally, we provide experimental and in silico evidences of the direct interaction with importin-α. The relative conservation of this motif allows formulating a consensus sequence (K/R)K-X13-14-KR+K++ ('+' indicates amino acids with similar chemical properties), which can be found in all BCL11B orthologs among vertebrates and in the closely related protein BCL11A.


Wall shear stresses in small and large two-way bypass grafts.
Wall shear stress, as one of the most important hemodynamic parameters of the cardiovascular system, has been studied extensively in the numerical and experimental approaches to blood flow in various arteries. In order to clarify the influence of graft diameter on the wall shear stress in a femoral two-way bypass graft, the pulsatile blood flows in two models were simulated with the finite element method. Both models were constructed with different diameters of grafts. The main geometric structure and the boundary conditions were identical for both models. The emphasis was on the comparison analysis of wall shear stresses in the vicinity of the distal anastomosis. The temporal-spatial distributions of wall shear stresses, wall shear stress gradients, and oscillating shear index were analyzed and compared. The present study indicated that femoral artery bypassed with a large graft demonstrated relatively uniform wall shear stresses and small wall shear stress gradients, whereas it does not have advantages in the oscillating shear index. The large model exhibits better and more regular hemodynamic phenomena and may be effective in decreasing the probability of the initiation and development of postoperative intimal hyperplasia and restenosis. Thus, appropriately large grafts are applicable in the clinical practice of femoral two-way bypass operation. More detailed studies are necessary on this problem for the purpose of increasing the success rates of the femoral bypass grafts.


Nuclear Vav3 is required for polycomb repression complex-1 activity in B-cell lymphoblastic leukemogenesis.
Acute B-cell lymphoblastic leukemia (B-ALL) results from oligo-clonal evolution of B-cell progenitors endowed with initiating and propagating leukemia properties. The activation of both the Rac guanine nucleotide exchange factor (Rac GEF) Vav3 and Rac GTPases is required for leukemogenesis mediated by the oncogenic fusion protein BCR-ABL. Vav3 expression becomes predominantly nuclear upon expression of BCR-ABL signature. In the nucleus, Vav3 interacts with BCR-ABL, Rac, and the polycomb repression complex (PRC) proteins Bmi1, Ring1b and Ezh2. The GEF activity of Vav3 is required for the proliferation, Bmi1-dependent B-cell progenitor self-renewal, nuclear Rac activation, protein interaction with Bmi1, mono-ubiquitination of H2A(K119) (H2AK119Ub) and repression of PRC-1 (PRC1) downstream target loci, of leukemic B-cell progenitors. Vav3 deficiency results in de-repression of negative regulators of cell proliferation and repression of oncogenic transcriptional factors. Mechanistically, we show that Vav3 prevents the Phlpp2-sensitive and Akt (S473)-dependent phosphorylation of Bmi1 on the regulatory residue S314 that, in turn, promotes the transcriptional factor reprogramming of leukemic B-cell progenitors. These results highlight the importance of non-canonical nuclear Rho GTPase signaling in leukemogenesis.


Weight-loss behaviors before pregnancy associate with increased risk of postpartum depression from the Japan Environment and Children's Study.
No studies showed the association between weight-loss behaviors before pregnancy and postpartum depression (PPD). We analyzed data from the nation-wide birth cohort study, the Japan Environment and Children's Study. Self-administrated questionnaires answered by 62,446 women was analyzed using logistic regression analysis. PPD was assessed using the Edinburgh Postnatal Depression Scale at 1 month after delivery. Women using at least one weight-loss method had higher risk of PPD than women using no weight-loss methods [women without antenatal psychological distress according to Kessler 6-Item Psychological Distress score: adjusted odds ratio (aOR) 1.318, 95% confidence interval (CI) 1.246-1.394; women with antenatal psychological distress: aOR 1.250, 95% CI 0.999-1.565]. Using extremely unhealthy weight-loss methods was associated with PPD compared with no use of each weight-loss method (vomiting after eating: aOR 1.743, 95% CI 1.465-2.065; smoking: aOR 1.432, 95% CI 1.287-1.591; taking diet pills: aOR 1.308, 95% CI 1.122-1.520). The association between weight-loss behaviors and PPD varied according to pre-pregnancy BMI. In normal-weight women, the weight-loss method score, which indicates the degree of weight-loss method use, was associated with PPD. These results indicate using weight-loss methods before pregnancy is associated with an increased risk of PPD in Japanese women.


An outbreak of influenza in a residential drug-rehabilitation community.
Influenza outbreaks can be difficult to control in confined settings where high-risk individuals are concentrated. Following the occurrence of a large number of cases of influenza-like illness in a rehabilitation community for drug users, between February and March 2004, surveillance activities were implemented. Attack rates of influenza-like illness were calculated, and risk factors for the development of disease and complications were evaluated through the use of relative risks (RR) with 95% confidence intervals (CI). Nasal-pharyngeal samples were collected for virological studies. Of 1,310 persons who were living in the community, 209 were diagnosed with influenza-like illness: the attack rate (15.9% overall) was higher for HIV-infected persons (RR: 1.77, 95% CI: 1.32-2.37), older individuals, and dormitory residents. HIV-infected participants were also more likely to develop complications compared with HIV-uninfected persons diagnosed with influenza-like illness (RR: 5.13, 95% CI: 2.52-10.20). The outbreak was attributable to Christchurch-like influenza A strains. Vaccination was ineffective because of the mismatch between wild and vaccine strains.


Disordered eating and weight control behaviors among male and female university students.
The purposes of this study were to develop an instrument capable of assessing factors potentially related to disordered eating and weight control behaviors among university students and then to compare male and female students on these factors. A 90 item instrument was developed. Sixty-four items were written by these authors, such that eight items would assess each of eight identified factors related to disordered eating. Additionally, all 26 items from the Eating Attitudes Test (EAT-26) were included and interspersed within the instrument. The instrument was administered to 502 female university students and their responses were factor analyzed. Ten factors were identified. The instrument was then administered to 94 female and 76 male university students. Results indicate that compared to males, females report a greater desire to be thin, less tolerance for cold, more frequent use of laxatives, and a greater occurrence of eating in response to internal and external cues. There were no other sex differences. The students in this study appeared to be engaging in appropriate health practices.


Label-free detection of kanamycin based on the aptamer-functionalized conducting polymer/gold nanocomposite.
Highly sensitive label-free detection of kanamycin is achieved with an aptamer sensor based on a conducting polymer/gold self-assembled nanocomposite. The sensor probe is fabricated by covalently immobilizing an in vitro selected DNA aptamer for kanamycin onto gold nanoparticle (AuNP)-comprised conducting polymer, poly-[2, 5-di-(2-thienyl)-1H-pyrrole-1-(p-benzoic acid)] (poly-DPB). The self-assembling of DPB on AuNP is investigated by TEM and UV-vis spectroscopy and the modification of the aptamer sensor is characterized using XPS and electrochemical impedance spectroscopy. The probe is applied to detect kanamycin by using voltammetric techniques. The sensor shows a pair of redox peaks around 0.26/ 0.08 V (vs. Ag/AgCl) for kanamycin captured by the aptamer-immobilized probe. The parameters that can affect the response, such as aptamer concentration, incubation time, temperature, and pH are optimized. The calibration plot shows a linear range from 0.05 μM to 9.0 μM kanamycin with a detection limit of 9.4±0.4 nM. The proposed aptamer sensor is examined with a real sample.


Nanostructured mucoadhesive microparticles for enhanced preocular retention.
We describe nanostructured microparticles (NMs) containing a mucoadhesive polymer for enhanced preocular retention and consider them as potential carriers of drugs to the eye. These NMs are each composed of entangled nanofibers to give an enlarged specific surface area, and thus can better adhere to the preocular mucus surface. This physical design allows the microparticles still to be composed mainly of a wall material, poly(lactic-co-glycolic acid), as required for controlled drug delivery, while the effects of an additive, mucoadhesive material, polyethylene glycol, can be synergistically improved via the nanostructured morphology. Thus, when formulated in a dry tablet dosage form, the NMs in this work show more than a 10-fold increase in preocular retention in vivo compared to conventional spherical microparticles. Therefore, we conclude that these mucoadhesive NMs can reside on the preocular surface for a prolonged period, and thus appear to be a promising system for topical drug delivery to the eye.


Inactivation of the prelimbic rather than infralimbic cortex impairs acquisition and expression of formalin-induced conditioned place avoidance.
Conditioned place avoidance (CPA) paradigm has been used to investigate the affective component of pain. Although the anterior cingulate cortex (ACC) has been demonstrated to play an important role in the affective aspect of pain, whether the other prefrontal subdivisions are involved in pain-related aversion is unknown. The present study investigated the role of the prelimbic cortex (PL) and infralimbic cortex (IL) in the acquisition and expression of formalin-induced CPA (F-CPA) in rats. GABAA receptor agonist muscimol was bilaterally microinjected into PL/IL before or after the formalin-paired training, to explore the effect of temporary inactivation of PL/IL on the acquisition and expression of F-CPA, respectively. The results showed that inactivation of PL rather than IL impaired the acquisition and expression of F-CPA. Moreover, the PL inactivation did not block the acquisition of LiCl-induced CPA, suggesting that PL may be specifically implicated in the pain-emotion related encoding. These results indicate that PL but not IL is involved in the aversive dimension of pain.


Health effects of adopting low greenhouse gas emission diets in the UK.
Dietary changes which improve health are also likely to be beneficial for the environment by reducing emissions of greenhouse gases (GHG). However, previous analyses have not accounted for the potential acceptability of low GHG diets to the general public. This study attempted to quantify the health effects associated with adopting low GHG emission diets in the UK. Epidemiological modelling study. UK. UK population. Adoption of diets optimised to achieve the WHO nutritional recommendations and reduce GHG emissions while remaining as close as possible to existing dietary patterns. Changes in years of life lost due to coronary heart disease, stroke, several cancers and type II diabetes, quantified using life tables. If the average UK dietary intake were optimised to comply with the WHO recommendations, we estimate an incidental reduction of 17% in GHG emissions. Such a dietary pattern would be broadly similar to the current UK average. Our model suggests that it would save almost 7 million years of life lost prematurely in the UK over the next 30 years and increase average life expectancy by over 8 months. Diets that result in additional GHG emission reductions could achieve further net health benefits. For emission reductions greater than 40%, improvements in some health outcomes may decrease and acceptability will diminish. There are large potential benefits to health from adopting diets with lower associated GHG emissions in the UK. Most of these benefits can be achieved without drastic changes to existing dietary patterns. However, to reduce emissions by more than 40%, major dietary changes that limit both acceptability and the benefits to health are required.


Excavating the functionally crucial active-site residues of the DXS protein of Bacillus subtilis by exploring its closest homologues.
To achieve a high yield of terpenoid-based therapeutics, 1-deoxy-d-xylulose-5-phosphate (DXP) pathway has been significantly exploited for the production of downstream enzymes. The DXP synthase (DXS) enzyme, the initiator of this pathway, is pivotal for the convergence of carbon flux, and is computationally studied well for the industrially utilized generally regarded as safe (GRAS) bacterium Bacillus subtilis to decode its vital regions for aiding the construction of a functionally improved mutant library. For the 546 sequence dataset of DXS sequences, a representative set of 108 sequences is created, and it shows a significant evolutionary divergence across different species clubbed into 37 clades, whereas three clades are observed for the 76 sequence dataset of Bacillus subtilis. The DXS enzyme, sharing a statistically significant homology to transketolase, is shown to be evolutionarily too distant. By the mutual information-based co-evolutionary network and hotspot analysis, the most crucial loci within the active site are deciphered. The 650-residue representative structure displays a complete conservation of 114 loci, and only two co-evolving residues ASP154 and ILE371 are found to be the conserved ones. Lastly, P318D is predicted to be the top-ranked mutation causing the increase in the thermodynamic stability of 6OUW. The study excavates the vital functional, phylogenetic, and conserved residues across the active site of the DXS protein, the key rate-limiting controller of the entire pathway. It would aid to computationally understand the evolutionary landscape of this industrially useful enzyme and would allow us to widen its substrate repertoire to increase the enzymatic yield of unnatural molecules for in vivo and in vitro applications.


Nurses' Moral Experiences of Ethically Meaningful End-of-Life Care: Distress, Resilience, Responsibility, and Care.
Moral distress, the phenomenon in which an agent is constrained in acting on their ethical choice, is a reoccurring theme in the literature on nurses' experiences of end-of-life care (EOLC). Understanding moral engagement solely through a lens of moral distress can be limiting-as such, we sought to explore the diverse experiences nurses consider ethically meaningful in their palliative and EOLC practice. This article presents an exploration and analysis of stories told to us, within an interpretive description study, by five nurses practicing in EOLC in diverse settings across Canada. Although these stories were told to us in a research context, the purpose of this theory article is to explore what these stories demonstrate about the moral engagement of nurses caring for dying patients. Our analysis suggests that while moral distress is a feature of nursing stories, so too are many other dimensions of moral experience, including resilience, responsibility, and care. Expanding how we understand nurses' moral engagement in the care of dying patients has implications for how we account for the many responsibilities that nurses shoulder in striving to provide "good" care to people at the end of life.


A new technique for creation of a sigmoid neobladder for urinary reconstruction: clinical outcome in 42 men.
To present the results of a new technique for construction of a sigmoid neobladder after radical cystectomy. Forty-two men, 43 to 74 years of age (mean age 62 +/- 8), underwent radical cystectomy for invasive bladder cancer and had a sigmoid neobladder created using a modification of the standard ureterointestinal anastomosis with rotation of the reservoir. The mean follow-up of this retrospective study was 35 +/- 20 months (range 6 to 90). The blood chemistry was analyzed routinely during follow-up, and complications, continence, and voiding pattern were assessed at regular intervals. There were 21 early complications in 14 patients: persistent urinary leakage in 2; wound infection in 9; prolonged ileus in 4; leakage from the colonic anastomosis in 2; and pulmonary embolus in 2. One patient each had venous thrombus of the lower extremities and methicillin-resistant Staphylococcus aureus colitis. One patient died in the perioperative period of massive pulmonary embolus, yielding a mortality rate of 2.4%. Eleven late complications occurred in 9 patients. Stenosis of the ureterointestinal anastomosis developed in 2 of 82 anastomoses, stenosis of urethral anastomosis in 4, and neobladder-ureteral reflux in 1. A reservoir stone was found in 1 patient, and adenoma and adenocarcinoma of the reservoir occurred in 1 patient each. One patient developed symptomatic hyperchloremic metabolic acidosis, and routine electrolyte evaluation revealed a slight metabolic acidosis in 6 patients. Hypovitaminosis B(12) did not occur in any patients. Of the 42 patients, 40 could void volitionally without catheterization. Patient satisfaction on continence, by day and night, was 77.3% and 72.7%, respectively. The mean neobladder capacity and the mean residual urine volume was 375 +/- 116 mL (range 234 to 624) and 68 +/- 86 mL (range 4 to 365), respectively. The modified sigmoid neobladder provides satisfactory results after radical cystectomy.


"The eye sees only what the mind is prepared to comprehend": Unrecognized incidental findings on intraoperative computed tomography during spine instrumentation surgery.
Intraoperative computed tomography (CT) is becoming more widely utilized in spine fusion surgeries. The use of CT-based image guidance has been shown to increase the accuracy in instrumentation placement and to reduce the rate of reoperation. However, incidental findings that are obvious in retrospect are still missed in spinal fusion surgeries due to the concept of inattentional blindness and surgeons' preoccupation with the main objective of intraoperative CT (i.e. instrumentation accuracy). The first case describes a 60-year-old male who underwent posterior spinal laminectomy and interbody fusions from L2-L5. Intraoperative CT confirmed appropriate placement of hardware. However, when he was transferred out to the care unit and extubated, he developed a severe headache for which the source was confirmed to be a pneumocephalus from durotomy and cerebrospinal fluid leakage on repeat CT. A retrospective review of his intraoperative CT demonstrated the intrathecal air at L5-S1 interlaminar space that was missed on evaluation during surgery. The second case describes a 68-year-old female who was treated with a successful T4 to pelvis instrumentation and fusion with vertebral column resection at T10 confirmed with imaging. Postoperatively, she developed rapidly progressive oxygen desaturation and was found to have a pneumothorax which had been present on the intraoperative imaging. This case report of two patients with missed intraoperative findings demonstrates the importance of looking beyond instrumentation placement and evaluating the entire intraoperative CT imaging to find abnormalities that could complicate the patients' postoperative recovery and overall hospital stay.


Electrophoretic pattern of NADPH-dependent oxidoreductive activities in K 562 and HL 60 leukemic cell lines.
Morphological and functional differentiation of hemopoietic cells is accompanied by the expression of lineage-specific protein markers. NADPH-oxidoreductive enzymatic activities in HL 60 and K 562 leukemic cell lines, compared with granulocytes and erythrocytes, show a NADPH-oxidizing and a NADPH-diaphorase activity. The oxidizing activity, absent in erythrocytes, has the same electrophoretic migration in HL 60 cells and granulocytes while it is different in K 562 cells. The diaphorase, absent in HL 60 cells and granulocytes, has the same migration in erythrocytes and K 562 cells, although with a slightly different quantitative expression. K 562 cells induced to differentiation with arabinofuranosylcytosine show the appearance of a band of NADPH-oxidizing activity of granulocytic type, together with the major band found in these cells.


A toddler with an unusually severe polyarticular arthritis and a lung involvement: a case report.
COPA syndrome is a rare hereditary inflammatory disease caused by mutations in the gene encoding the coatomer protein subunit alpha, causing excessive production of type I interferon. This case is a reminder for the general paediatrician, highlighting the relevance of the association between arthritis and lung involvement in toddlers. We report the case of a 2-year-old girl with intermittent limping and joint pain. Her family history was relevant for a Still disease with lung involvement in the mother. Physical examination showed moderate wrist swelling. Laboratory findings on admission showed an increase in inflammatory markers, positive rheumatoid factor, antibodies antinuclear antibody (ANA) and cyclic citrullinated peptide (anti-CCP). Wrists' ultrasound documented synovial thickening, and chest X-rays showed an unexpected severe interstitial pneumopathy. Genetic testing confirmed the diagnosis of a heterozygous mutation of the COPA gene in c.841C > T (p.R281W). Janus kinase treatment was started (baricitinib, 4 mg daily per os) with a remarkable improvement in limping and joint pain after two weeks. In cases of recurrent arthritis with family history and multiple involvement organs, a genetic disorder should be suspected and genetic testing should be performed. Furthermore, this case suggests that therapy with jak inhibitors may be effective and safe in interferonopathies.


Value of synthetic MRI quantitative parameters in preprocedural evaluation for TRUS/MRI fusion-guided biopsy of the prostate.
Transrectal ultrasonography (TRUS)/magnetic resonance imaging (MRI) fusion-guided biopsy has a high clinical application value. However, this technique has some limitations, which limit its use in routine clinical practice. Therefore, the selection of suitable proatate lesions for this technique is worthy of our attention. Synthetic MRI (SyMRI) is capable of quantifying multiple relaxation parameters, which might have potential value in preprocedural evaluation for TRUS/MRI fusion-guided biopsy of the prostate. The aim of our study is to examine the value of SyMRI quantitative parameters in preprocedural evaluation for TRUS/MRI fusion-guided biopsy of the prostate. We prospectively selected 148 lesions in 137 patients who underwent prostate biopsy in our hospital. Next, 2-4 needles of TRUS/MRI fusion-guided biopsy combined with 10 needles of system biopsy (SB) were used as the protocol for prostate biopsy. Before biopsy, the MAGiC sequences of the MRI images of the enrolled patients underwent post-processing, and the longitudinal relaxation time (T1), transverse relaxation time (T2), and proton density (PD) were extracted. The biopsy pathology results were used as a gold standard to compare the differences in SyMRI quantitative parameters between benign and malignant prostate lesions in the peripheral and transitional zones. The receiver operating characteristic (ROC) curves were plotted to confirm the optimal SyMRI quantitative parameter for prostate lesion benignancy/malignancy performance, and the cutoff values of these parameters were used for grouping the lesions. The single-needle biopsy prostate cancer (PCa)-positivity rates (number of positive biopsy needles/total biopsy needles) and PCa overall detection rates by TRUS/MRI fusion-guided biopsy and SB were compared in different subgroups. The T1 and T2 values can determine the benignancy/malignancy of prostate transition lesions(p < 0.01), and the T2 value has a greater diagnostic performance (p = 0.0376). The T2 value can determine the benignancy/malignancy of prostate peripheral lesions. The optimal diagnostic cutoff values for T2 were 77 and 81 ms, respectively. The single-needle PCa positivity rate of TRUS/MRI fusion-guided biopsy was higher than SB for any prostate lesions in different subgroups (p < 0.01). However, only in the subgroup of transition zone lesions with T2 ≤ 77 ms, the PCa overall detection rate of TRUS/MRI fusion-guided biopsy was significantly higher than that of SB (p = 0.031). SyMRI-T2 value can provide a theoretical basis for the selection of suitable lesions for TRUS/MRI fusion-guided biopsy.


The difference in spatiotemporal dynamics between modus ponens and modus tollens in the Wason selection task: an event-related potential study.
High-density, event-related brain potentials (ERPs) were recorded to explore differences in spatiotemporal dynamics between modus ponens (MP) and modus tollens (MT) in the Wason selection task. Results showed that MP elicits a more positive P3b-like component than MT from 400 to 800 ms. MP appeared to occur earlier than MT in various stages of proposition testing, such as stimulus processing and response selection. ERP results showed that MT has a longer duration and more negative later negative component (LNC) than MP at 2,000 ms. This result suggests that MT occupies more cognitive resources than MP in the final stages of proposition testing. The short and small left frontal LNC obtained by MP implies examination of the expectable conclusion, whereas the long and large left frontal LNC elicited by MT may be involved in the retention operation of the card in working memory from the monitoring and inspecting putative conclusion in the later stages of proposition testing.


The therapeutic potential of the neuroactive peptides of soluble amyloid precursor protein-alpha in Alzheimer's disease and related neurological disorders.
Soluble amyloid precursor protein-alpha (sAPPα) is a multi-functional brain-derived protein that has neuroprotective, neurogenic and neurotropic properties. Moreover, it is known to facilitate synaptic function and promote neural repair. These properties suggest sAPPα may be useful as a therapeutic agent for the treatment of neurological diseases characterized by synaptic failure and neuronal loss, such as occurs in Alzheimer's disease, and for neural repair following traumatic brain injury and stroke. However, sAPPα's relatively large size and the difficulty of ongoing delivery of therapeutics to the brain mean this is not currently practicable. Importantly, however, sAPPα is composed of several neuroactive domains that each possess properties that collectively are remarkably similar to those of sAPPα itself. Here, we review the molecular structure of sAPPα and identify the domains that contribute to its overall functionality. Four peptide motifs present as possible targets for therapeutic development. We review their physiochemical and neuroactive properties, both within sAPPα and as isolated peptides, and discuss their potential for future development as multipurpose therapeutic agents for the treatment of Alzheimer's disease and other disorders of neuronal function. Further, we discuss the role of heparin binding sites, found within sAPPα's structure and overlapping with the neuroactive domains, as sites for interactions with effector proteins and synaptic receptors. The potential role of the neuroactive peptides known as Cationic Arginine-Rich Peptides (CARPs) as neuroprotective motifs is also reviewed. Mechanisms of peptide delivery to the brain are briefly discussed. Finally, we summarise the potential benefits and pitfalls of using the isolated peptides, either individually or in combination, for the treatment of neurological diseases.


Intermittency as a consequence of turbulent transport in nonlinear systems.
Intermittent high-amplitude structures emerge in a damped and driven discrete nonlinear Schrödinger equation whose solutions transport both energy and particles from sources to sinks. These coherent structures are necessary for any solution that has statistically stationary transport properties.


Isocratic high-performance liquid chromatographic separation and multiple-wavelength ultraviolet detection of aldicarb and its soil degradation products. Optimization of stationary phase selectivity.
The unique selectivities which can be generated through optimization of stationary/mobile phase combinations have been applied to the development of an isocratic, reversed-phase high-performance liquid chromatographic method for the separation of aldicarb and its primary soil degradation products. The method utilizes a cyanopropyl bonded stationary phase and water-acetonitrile mobile phase and is capable of separating aldicarb and its various sulfoxide, sulfone and oxime derivatives in less than 10 min. When combined with multiple-wavelength UV detection and an appropriate preconcentration step, this method can in principle be applied to the routine monitoring of aldicarb and its soil derivatives in water at concentrations less than 1 microgram/l.


Novel processing of iron-manganese alloy-based biomaterials by inkjet 3-D printing.
The present work provides an assessment of 3-D printed iron-manganese biodegradable scaffolds as a bone scaffold material. Iron-based alloys have been investigated due to their high strength and ability to slowly corrode. Current fabrications of Fe-based materials generate raw material which must be machined into their desired form. By using inkjet 3-D printing, a technique which generates complex, customizable parts from powders mechanically milled Fe-30Mn (wt.%) powder was directly processed into scaffolds. The 3-D printed parts maintained an open porosity of 36.3% and formed a mixed phase alloy of martensitic ε and austenitic γ phases. Electrochemical corrosion tests showed the 3-D printed Fe-Mn to desirably corrode significantly more rapidly than pure iron. The scaffolds exhibited similar tensile mechanical properties to natural bone, which may reduce the risk of stress shielding. Cell viability testing of MC3T3-E1 pre-osteoblast cells seeded directly onto the Fe-Mn scaffolds using the live/dead assay and with cells cultured in the presence of the scaffolds' degradation products demonstrated good in vitro cytocompatibility compared to tissue culture plastic. Cell infiltration into the open pores of the 3-D printed scaffolds was also observed. Based on this preliminary study, we believe that 3-D printed Fe-Mn alloy is a promising material for craniofacial biomaterial applications, and represents an opportunity for other biodegradable metals to be fabricated using this unique method.


[Is anxiety your master or are you the master of your anxiety?].
By means of four cases the author demonstrates how he manages with varying success dental anxiety. There is a call for dentists willing to invest time and teach patients how to deal successfully with such anxiety. This activity is part of the dentist's competence, with back support of a supervising psychologist or therapist.


Long-term potentiation-like cortical plasticity is disrupted in Alzheimer's disease patients independently from age of onset.
Alzheimer's disease (AD) is considered an age-related disorder. However, it is unclear whether AD induces the same pathological and neurophysiological modifications in synaptic functions independently from age of disease onset. We used transcranial magnetic stimulation tools to investigate the mechanisms of cortical plasticity and sensory-motor integration in AD patients with a wide range of disease onset. We evaluated newly diagnosed sporadic AD (n = 54) in comparison with healthy age-matched controls (HS; n = 24). Cortical plasticity mechanisms of long-term potentiation (LTP) or of long-term depression (LTD) were assessed using respectively intermittent (iTBS) or continuous theta burst stimulation (cTBS) protocols. Sensory-motor integration was evaluated by means of short afferent inhibition (SAI) protocol. AD patients show after iTBS an impairment of LTP-like cortical plasticity forming a paradoxical LTD in comparison to HS. LTD-like cortical plasticity is similar between AD and HS. LTP-like cortical plasticity is not associated with age, but AD patients presenting with more altered LTP-like cortical plasticity have more-severe cognitive decline at 18 months. SAI is impaired in AD and shows a strong association with the individual age of subjects rather than with disease age of onset. Cortical LTP disruption is a central mechanism of AD that is independent from age of onset. AD can be described primarily as a disorder of LTP-like cortical plasticity not influenced by physiological aging and associated with a more-severe cognitive decline. Ann Neurol 2016;80:202-210.


Plasma Membrane Localization of CD36 Requires Vimentin Phosphorylation; A Mechanism by Which Macrophage Vimentin Promotes Atherosclerosis.
Vimentin is a type III intermediate filament protein expressed in cells of mesenchymal origin. Vimentin has been thought to function mainly as a structural protein and roles of vimentin in other cellular processes have not been extensively studied. Our current study aims to reveal functions of vimentin in macrophage foam cell formation, the critical stage of atherosclerosis. We demonstrated that vimentin null (Vim -/ - ) mouse peritoneal macrophages take up less oxidized LDL (oxLDL) than vimentin wild type (Vim +/+) macrophages. Despite less uptake of oxLDL in Vim -/ - macrophages, Vim +/+ and Vim -/ - macrophages did not show difference in expression of CD36 known to mediate oxLDL uptake. However, CD36 localized in plasma membrane was 50% less in Vim -/ - macrophages than in Vim +/+ macrophages. OxLDL/CD36 interaction induced protein kinase A (PKA)-mediated vimentin (Ser72) phosphorylation. Cd36 -/ - macrophages did not exhibit vimentin phosphorylation (Ser72) in response to oxLDL. Experiments using phospho-mimetic mutation of vimentin revealed that macrophages with aspartate-substituted vimentin (V72D) showed more oxLDL uptake and membrane CD36. LDL receptor null (Ldlr -/ - ) mice reconstituted with Vim -/ - bone marrow fed a western diet for 15 weeks showed 43% less atherosclerotic lesion formation than Ldlr -/ - mice with Vim +/+ bone marrow. In addition, Apoe -/ -Vim- / - (double null) mice fed a western diet for 15 weeks also showed 57% less atherosclerotic lesion formation than Apoe -/ - and Vim +/+mice. We concluded that oxLDL via CD36 induces PKA-mediated phosphorylation of vimentin (Ser72) and phosphorylated vimentin (Ser72) directs CD36 trafficking to plasma membrane in macrophages. This study reveals a function of vimentin in CD36 trafficking and macrophage foam cell formation and may guide to establish a new strategy for the treatment of atherosclerosis.