Mutant strains of Saccharomyces cerevisiae lacking sphingolipids synthesize novel inositol glycerophospholipids that mimic sphingolipid structures.
Mutant strains of Saccharomyces cerevisiae, termed SLC, make no detectable sphingolipids when cultured without a sphingolipid long chain base such as phytosphingosine (Dickson, R.C., Wells, G.B., Schmidt, A., and Lester, R.L. (1990) Mol. Cell. Biol. 10, 2176-2181). When grown with phytosphingosine they make sphingolipids in normal amounts. SLC strains carry a secondary suppressor mutation that bypasses the need to synthesize a long chain base. Hypothetically, the suppressor mutation could function by mutating a gene whose protein product required a sphingolipid for function, by increasing the level of one or more endogenous lipids, or by making new lipid(s). Here we demonstrate that SLC strains make novel inositol glycerophospholipids when cultured without a long chain base. The novel lipids are phosphatidylinositol (PI), mannosyl-PI, and inositol-P-(mannosyl-PI), containing 1 mol of C26 fatty acid, ordinarily found in yeast sphingolipids but not usually found in glycerophospholipids; the C26 fatty acid appears to be located at the SN-2 position of the glycerol. In addition, mono-fattyacyl versions of these three compounds were also identified. The polar head groups and hydrophobic portions of these novel lipids are strikingly similar to S. cerevisiae sphingolipids found in wild-type cells. We speculate that the novel lipids structurally mimic sphingolipids and thereby compensate for some sphingolipid function(s) necessary for growth.


Aortic sclerosis and mitral annulus calcification: a window to vascular atherosclerosis?
Several similarities exist between atherosclerosis in the vasculature and chronic degenerative changes in valvular structures. It has been suggested that aortic valve sclerosis (AVS) and mitral annulus calcification (MAC) are manifestations of a generalized atherosclerosis, have similar pathogenesis, share common risk factors and are observed with higher prevalence in patients with different forms of atherosclerotic vascular disease. Moreover, recent studies have shown a close relation of MAC and AVS with adverse cardiovascular and cerebrovascular outcomes. However, many patients with AVS or MAC do not have coexisting peripheral vascular atherosclerosis and vice versa. Lipid-reducing therapy has been uniformly unsuccessful in slowing valvular calcification. Thus, whether valve calcifications are the result of a more generalized atherosclerosis, or reflect a primary degenerative process, progressing with advancing age, still remains. From a clinical point of view, it is of great importance to identify common links between valve calcification and vascular atherosclerosis with a view to assess whether the detection of AVS, MAC or both are indicative of subclinical atherosclerosis and predicts cardiovascular or cerebrovascular events. Thus, in this article, the authors review current evidence regarding the association between AVS and MAC with vascular atherosclerosis.


[The value of doppler velocimetry of umbilical and middle cerebral arteries in pregnancy complicated by diabetes mellitus].
Fifty-three diabetic pregnant treated in Dpt of Obstetrics and Perinatology in Lublin were investigated. The paper presents correlations between metabolic parameters in diabetic patients and Doppler welocimetry in umbilical and middle cerebral arteries and also analyses way of delivery and outcomes. Correlations between fetal Doppler parameters and metabolic status of mothers have been found. We estimate that Doppler velocimetry hasn't prognostic value in predicting of fetal distress.


BRAF inhibitor-associated ERK activation drives development of chronic lymphocytic leukemia.
Patients with BRAFV600E/K-driven melanoma respond to the BRAF inhibitor vemurafenib due to subsequent deactivation of the proliferative RAS/RAF/MEK/ERK pathway. In BRAF WT cells and those with mutations that activate or result in high levels of the BRAF activator RAS, BRAF inhibition can lead to ERK activation, resulting in tumorigenic transformation. We describe a patient with malignant melanoma who developed chronic lymphocytic leukemia (CLL) in the absence of RAS mutations during vemurafenib treatment. BRAF inhibition promoted patient CLL proliferation in culture and in murine xenografts and activated MEK/ERK in primary CLL cells from additional patients. BRAF inhibitor-driven ERK activity and CLL proliferation required B cell antigen receptor (BCR) activation, as inhibition of the BCR-proximal spleen tyrosine kinase (SYK) reversed ERK hyperactivation and proliferation of CLL cells from multiple patients, while inhibition of the BCR-distal Bruton tyrosine kinase had no effect. Additionally, the RAS-GTP/RAS ratio in primary CLL cells exposed to vemurafenib was reduced upon SYK inhibition. BRAF inhibition increased mortality and CLL expansion in mice harboring CLL xenografts; however, SYK or MEK inhibition prevented CLL proliferation and increased animal survival. Together, these results suggest that BRAF inhibitors promote B cell malignancies in the absence of obvious mutations in RAS or other receptor tyrosine kinases and provide a rationale for combined BRAF/MEK or BRAF/SYK inhibition.


Impact of conjunctivochalasis on visual quality of life: a community population survey.
Conjunctivochalasis (Cch) is a very common ocular disorder, which can cause an unstable tear film and ocular discomfort. The study of vision-related quality of life (VR-QoL) in a community population with Cch can provide a better understanding of the impact of Cch on common people than objective clinical examinations alone. This cross-sectional comparative study enrolled 360 participants ≥ 40 years old living in Sanle Community, Shanghai. In the study, 198 subjects were diagnosed with Cch and 86 with dry eye syndrome (DES) without Cch. The remaining 76 subjects were normal controls. Socio-demographical data were collected, and Cch and related ocular symptoms and signs were evaluated. In addition, all participants were required to complete the Chinese version of the 25-item National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) and Ocular Surface Disease Index Questionnaire (OSDI). Main outcome measures include the comparison on the OSDI score and VFQ-25 score among the subgroups, and the correlation of these scores with the socio-demographical and clinical data. The results revealed that subjects with Cch had significantly decreased tear film stability even compared with those with DES (P = 0.001). The participants with either Cch or DES reported significantly higher OSDI scores and lower VFQ-25 composite scores than the normal controls (P<0.001 and 0.007 respectively). Further comparisons among the subgroups of Cch revealed that the following factors were associated with higher OSDI scores and lower VFQ-25 composite scores: nasal-side Cch, chalasis folds higher than tear meniscus height, punctal occlusion, or increased extent of chalasis on digital pressure. In conclusion, Cch was associated with an adverse impact on VR-QoL in a community population, and the impairment in VR-QoL had a significant correlation with disease severity and tear film abnormalities.


Presentation and management of venous aneurysms.
Venous aneurysms have been reported to occur in most major veins. These aneurysms may be misdiagnosed as soft tissue masses or as inguinal or femoral hernias. Venous aneurysms of the deep system have been associated with deep venous thrombosis (DVT) and pulmonary embolism (PE). To more precisely characterize these lesions, we reviewed our experience with the disease. A retrospective analysis of our experience over 22 years was performed. The presentation and management of these lesions were reviewed and compared with the literature. Thirty-nine venous aneurysms were reported in 30 patients. There were 14 men and 16 women. The patients' ages ranged from 3 to 75 years. Thirty aneurysms were located in the lower extremities, four in the upper extremity, and five in the internal jugular vein. Fifty-seven percent of lower extremity aneurysms occurred in the deep system. Patients' symptoms were a mass (75%) associated with pain (67%) and swelling (42%). Thromboembolism occurred in six patients, DVT in three, and PE in three. Eight of nine patients (89%) who had aneurysms of the superficial venous system had their condition misdiagnosed. Diagnosis was made by phlebography (60%), color flow duplex scanning (27%), continuous-wave Doppler scanning (10%), or magnetic resonance imaging (10%). The aneurysm size ranged from 1.7 to 6.0 cm. Management consisted of tangential excision in five (17%), total excision in 23 (77%), and observation in seven (6%). Venous aneurysms are unusual vascular malformations that occur equally between the sexes and are seen at any age. Most patients have a painful mass of the extremity, and diagnosis is achieved by radiologic examination. Superficial venous aneurysms of the inguinal region are often misdiagnosed. Thromboembolism is more common in aneurysms involving the deep venous system. Because of their potential morbidity, management should be surgical in the majority of cases.


Nuclear receptors and AMPK: can exercise mimetics cure diabetes?
Endurance exercise can lead to systemic improvements in insulin sensitivity and metabolic homeostasis, and is an effective approach to combat metabolic diseases. Pharmacological compounds that recapitulate the beneficial effects of exercise, also known as 'exercise mimetics', have the potential to improve disease symptoms of metabolic syndrome. These drugs, which can increase energy expenditure, suppress hepatic gluconeogenesis, and induce insulin sensitization, have accordingly been highly scrutinized for their utility in treating metabolic diseases including diabetes. Nevertheless, the identity of an efficacious exercise mimetic still remains elusive. In this review, we highlight several nuclear receptors and cofactors that are putative molecular targets for exercise mimetics, and review recent studies that provide advancements in our mechanistic understanding of how exercise mimetics exert their beneficial effects. We also discuss evidence from clinical trials using these compounds in human subjects to evaluate their efficacy in treating diabetes.


Police officers' knowledge of, and attitudes towards, mental illness in southwest Scotland.
Questionnaires were sent to all operational officers in a regional police service regarding their level of knowledge about and attitudes towards, mental illness. It was widely accepted by police officers that mental illness occurred commonly, can be effectively treated in the community and that the main risk of harm is to patients themselves. There was a good knowledge of relevant legislation, but most officers felt they did not have sufficient training in mental illness, and were keen for more. Improved liaison between sector psychiatrists and local police may be of value in the earlier identification and treatment of the mentally ill.


How can the landscape ecological security pattern be quantitatively optimized and effectively evaluated? An integrated analysis with the granularity inverse method and landscape indicators.
The optimization of the landscape ecological security pattern aims to construct a suitable ecological environment and promote the harmonious development between humans and nature. The optimization model of the ecological security pattern for the main urban area of Chongqing was constructed with the granularity inverse method, minimum cumulative resistance model, and spatial network analysis method. We used ecological nodes to optimize the landscape ecological security pattern by organically combining the landscape quantity and spatial structure, and analyzed the effectiveness of the optimized pattern. The results were as follows: (1) The optimal granularity for selecting the ecological source in the study area was 500 m. There were 220 ecological sources with a total area of 188691.03 hm2 and a minimum area of 75.15 hm2. (2) The ecological buffer zone, protection and utilization zone, key development zone, coordinated control zone, and restricted development zone accounted for 57.78%, 20.87%, 12.36%, 6.48%, and 2.50%, respectively, of the total area. (3) The construction of the landscape ecological security pattern contained 70 ecological corridors with a total length of 415.89 km. The longest and shortest ecological corridors had lengths of 20.33 km and 1153.23 m, respectively. There were 17 ecological nodes of corridor-resistance and 27 ecological nodes of corridor-corridor. (4) 41 ecological node service areas were constructed, with a total area of approximately 236.0723 hm2, accounting for 0.04% of the total study area, and the largest and smallest ecological node areas were 6.0744 hm2 and 0.0057 hm2, respectively. (5) The optimized result of the landscape ecological security pattern converted 209.1384 hm2 of nonecological land into ecological land.


An asynchronous high-speed synchrotron shutter.
A high-repetition-rate mechanical shutter with asynchronous control and sub-millisecond operation has been developed and tested for specialist X-ray systems in the field of medical diagnostics and radiation therapy. Capacitor-coupled linear voice coil actuators are utilized to achieve opening and closing speeds as fast as 700 micros for an aperture height of 4 mm. The design allows for asynchronous control, permitting slave operation of the shutter, a feature that is distinctly suitable for a number of applications including particle image velocimetry, where high-frame-rate operation must be accurately synchronized and triggered by the image acquisition sequence of the detector or timing device. The design and construction of the shutter also makes it ideal, with simple and limited modifications, for applications requiring larger apertures, in particular wide beams as found in many synchrotron beamlines.


Impact of an educational program based on evidence related to Fever management.
Quality care is dependent on best evidence. Children's nurses are no exception to this and their philosophy of "the child first and always" will ensure that their evidence base for practice is commensurate with stance. For this reason, this study was conducted to assess the impact of an educational program based on evidence related to fever management on nurses' evidence-based knowledge and reported practices. An Educational program based on evidence was designed according to nurses' needs and new evidence findings in fever management. Results of the study showed that at the pre program phase, nurses had lower level of evidence-based knowledge than at the first follow-up. Their means of knowledge scores related to fever, measuring temperature, nursing management, administration of antipyretics and documentation were 3.69 vs 8.00, 5.06 vs 7.49, 3.99 vs 6.94, 4.07 vs 7.33 and 6.81 vs 9.76 respectively. Also, there was no statistical significant difference between level of evidence-based knowledge for nurses at the first and second follow-ups. It was concluded that an educational program based on evidence promotes the quality of nursing care in fever management.


Previously Unreported Sciatic Nerve Variation: Case Report.
The sciatic nerve typically follows its course through the greater sciatic foramen, below the piriformis muscle, and down the posterior aspect of the thigh, but many anatomical variations exist. Herein, we report an unusual relationship between the sciatic nerve and piriformis muscle in which the split common fibular nerve went through the piriformis and had a variant communication with the tibial nerve. To our knowledge, this anatomical variation has not been previously reported. Such variants are important to fully understand pathologies involving the sciatic nerve.


Genome architectures revealed by tethered chromosome conformation capture and population-based modeling.
We describe tethered conformation capture (TCC), a method for genome-wide mapping of chromatin interactions. By performing ligations on solid substrates rather than in solution, TCC substantially enhances the signal-to-noise ratio, thereby facilitating a detailed analysis of interactions within and between chromosomes. We identified a group of regions in each chromosome in human cells that account for the majority of interchromosomal interactions. These regions are marked by high transcriptional activity, suggesting that their interactions are mediated by transcriptional machinery. Each of these regions interacts with numerous other such regions throughout the genome in an indiscriminate fashion, partly driven by the accessibility of the partners. As a different combination of interactions is likely present in different cells, we developed a computational method to translate the TCC data into physical chromatin contacts in a population of three-dimensional genome structures. Statistical analysis of the resulting population demonstrates that the indiscriminate properties of interchromosomal interactions are consistent with the well-known architectural features of the human genome.


[Implementation and evaluation of a proper dietary behavior program in diabetes support groups].
Active promotion in recent years of the Diabetes Share Care Program by the national Department of Health and the medical profession has gradually established a diabetes support system as well as patient support groups in Taiwan. The program concept holds that, by participating in a patient support group, diabetes patients and people in high risk categories will learn to adopt a healthier lifestyle in order to delay / avoid diabetes onset and complications. Within the diabetes support group framework, we implemented correct dietary behavior programs and evaluated their efficacy. A study using a quasi-experimental, single-group pretest and posttest design was carried out from December 2007 to May 2008. Participants included 48 registered patient members of a diabetes patient group located at a regional teaching hospital in Kaohsiung. Researchers used the Donabedian framework to evaluate program efficacy. Results indicated that the program could effectively promote proper dietary behavior in patients. Providing instant data during program execution and evaluation can enhance program efficacy. We hope that this experience can serve as a reference for medical staff when executing such programs.


ATP induces sustained facilitation of craniofacial nociception through P2X receptors on neck muscle nociceptors in mice.
Noxious input from neck muscles probably plays a key role in tension-type headache pathophysiology. ATP selectively excites group III and IV muscle afferents in vitro. Accordingly, ATP infusion into trapezius muscle induces strong pain and local tenderness in healthy man. The present study addresses the impact of ATP on neck muscle nociception in anaesthetized mice. Craniofacial nociceptive processing was tested by the jaw-opening reflex via noxious electrical tongue stimulation. Within 2 h after injection of 100 nmol/l or 1 micromol/l ATP into semispinal neck muscles, reflex integrals significantly increased by 114% or 328%, respectively. Preceding intramuscular administration of the P2X receptor antagonist PPADS (3-100 nmol/l) suppressed the ATP effect. Subsequent application of PPADS (100 nmol/l) caused a total recovery of facilitated reflex to baseline values. ATP induces sustained facilitation of craniofacial nociception by prolonged excitation of P2X receptors in neck muscles.


Harmony but Not Uniformity: Role of Strigolactone in Plants.
Strigolactones (SLs) represent an important new plant hormone class marked by their multifunctional roles in plants and rhizosphere interactions, which stimulate hyphal branching in arbuscular mycorrhizal fungi (AMF) and seed germination of root parasitic plants. SLs have been broadly implicated in regulating root growth, shoot architecture, leaf senescence, nodulation, and legume-symbionts interaction, as well as a response to various external stimuli, such as abiotic and biotic stresses. These functional properties of SLs enable the genetic engineering of crop plants to improve crop yield and productivity. In this review, the conservation and divergence of SL pathways and its biological processes in multiple plant species have been extensively discussed with a particular emphasis on its interactions with other different phytohormones. These interactions may shed further light on the regulatory networks underlying plant growth, development, and stress responses, ultimately providing certain strategies for promoting crop yield and productivity with the challenges of global climate and environmental changes.


Enhanced detection of DNA sequences using end-point PCR amplification and online gel electrophoresis (GE)-ICP-MS: determination of gene copy number variations.
The design and evaluation of analytical methods that permit quantitative analysis of specific DNA sequences is exponentially increasing. For this purpose, highly sensitive methodologies usually based on labeling protocols with fluorescent dyes or nanoparticles are often explored. Here, the possibility of label-free signal amplification using end-point polymerase chain reaction (PCR) are exploited using on-column agarose gel electrophoresis as separation and inductively coupled plasma-mass spectrometry (ICP-MS) for the detection of phosphorus in amplified DNA sequences. The calibration of the separation system with a DNA ladder permits direct estimation of the size of the amplified gene fragment after PCR. With this knowledge, and considering the compound-independent quantification capabilities exhibited by ICP-MS for phosphorus (it is only dependent on the number of P atoms per molecule), the correlation of the P-peak area of the amplified gene fragment, with respect to the gene copy numbers (in the starting DNA), is then established. Such a relationship would permit the determination of copy number variations (CNVs) in genomic DNA using ICP-MS measurements. The method detection limit, in terms of the required amount of starting DNA, is ∼6 ng (or 1000 cells if 100% extraction efficiency is expected). The suitability of the proposed label-free amplification strategy is applied to CNVs monitoring in cells exposed to a chemical agent capable of deletion induction, such as cisplatin.


Functional results after total or near total glossectomy with laryngeal preservation.
Locally advanced tongue cancer is a devastating disease for which there are limited therapeutic options that will result in a high rate of cure while preserving function. To determine the oncologic effectiveness of total or near total glossectomy with laryngeal preservation and the possibility of speech and swallowing rehabilitation following treatment, we reviewed our experience with 27 patients treated between 1982 and 1989. Twenty-four patients were eligible for 2-year follow-up and their disease-specific survival was 51%. Swallowing was achieved initially in 18 patients (67%), while 12 had successful long-term deglutition (44%). Oral communication was accomplished in 25 patients (92%). Significant aspiration occurred in three patients and was severe enough to require interval laryngectomy in two patients. The role of laryngeal suspension, palatal augmentation prosthesis, and videofluoroscopy as rehabilitation adjuncts for the total glossectomy patient are described.


Drinking Refusal Self-Efficacy and Intended Alcohol Consumption During a Mass-Attended Youth Event.
Mass-attended youth events represent a substantial public health challenge due to high levels of alcohol consumption and corresponding high rates of alcohol-related harm. Although previous research has documented the protective effect of high drinking refusal self-efficacy (DRSE) on alcohol consumption in general, there is a lack of research examining the role of DRSE in reducing consumption during mass-attended youth events and the factors associated with DRSE in these contexts. This study aimed to identify potentially modifiable factors that influence DRSE and drinking intentions to inform interventions designed to reduce alcohol-related harm during mass-attended events. Australian secondary school students (n = 586; 70% female) in their final two years of high school completed an online survey assessing their alcohol consumption intentions for Schoolies, their perceived degree of DRSE, and other individual and environmental factors. Path analysis was used to assess a mediational model examining factors associated with DRSE and alcohol consumption intentions. DRSE was found to be significantly associated with intended alcohol consumption during Schoolies. Specifically, leavers who believed they would not be able to refuse others' offers of alcoholic drinks reported significantly greater alcohol consumption intentions. Results also revealed that DRSE was enhanced in those respondents who believed there would be a variety of non-drinking activities and non-alcoholic beverages available to them during Schoolies. Results suggest the need to increase leavers' confidence in their ability to refuse unwanted alcoholic beverages and highlight the importance of providing celebration options that do not involve alcohol consumption.


PAI-1 promotes extracellular matrix deposition in the airways of a murine asthma model.
Dysregulation of matrix metalloproteinases (MMPs) and ineffective fibrinolysis are associated with the deposition of extracellular matrix (ECM). We hypothesized that elevated plasminogen activator inhibitor (PAI)-1 promotes ECM deposition in the asthmatic airway by inhibiting MMP-9 activity and fibrinolysis. Degree of airway inflammation was similar in PAI-1(-/-) and wild type (WT) mice after ovalbumin (OVA) challenge. PAI-1 production, deposition of collagen and fibrin, and MMP-9 activity in the lung tissue or airways were greater after OVA challenge compared with saline challenge. However, in PAI-1(-/-) mice, collagen deposition was 2-fold less, fibrin deposition was 4-fold less, and MMP-9 activity was 3-fold higher. This is the first direct evidence that the plasmin system regulates ECM deposition in the airways of a murine asthma model, independently of the effect of PAI-1 on inflammatory cells. The results suggest that the PAI-1-dependent inhibition of MMP-9 activity and fibrinolysis is a major mechanism by which ECM deposition occurs.


Qualitative interviewing: encountering ethical issues and challenges.
This article, in which Amanda Clarke recounts her own experiences as a novice researcher, explores the ways in which research can affect participants. The author argues that researchers must be mindful of the impact their questioning can have on subjects, especially those who are vulnerable, and suggests that a reflexive approach can help minimise the risk of harmful effects.


Recent Advances in Organic Thermoelectric Materials: Principle Mechanisms and Emerging Carbon-Based Green Energy Materials.
Thermoelectric devices have recently attracted considerable interest owing to their unique ability of converting heat to electrical energy in an environmentally efficient manner. These devices are promising as alternative power generators for harvesting electrical energy compared to conventional batteries. Inorganic crystalline semiconductors have dominated the thermoelectric material fields; however, their application has been restricted by their intrinsic high toxicity, fragility, and high cost. In contrast, organic thermoelectric materials with low cost, low thermal conductivity, easy processing, and good flexibility are more suitable for fabricating thermoelectric devices. In this review, we briefly introduce the parameters affecting the thermoelectric performance and summarize the most recently developed carbon-material-based organic thermoelectric composites along with their preparation technologies, thermoelectric performance, and future applications. In addition, the p- and n-type carbon nanotube conversion and existing challenges are discussed. This review can help researchers in elucidating the recent studies on carbon-based organic thermoelectric materials, thus inspiring them to develop more efficient thermoelectric devices.


Effect of Different Crosslinking Strategies on Physical Properties and Biocompatibility of Freestanding Multilayer Films Made of Alginate and Chitosan.
Freestanding multilayer films prepared by layer-by-layer technique have attracted interest as promising materials for wound dressings. The goal is to fabricate freestanding films using chitosan (CHI) and alginate (ALG) including subsequent crosslinking to improve the mechanical properties of films while maintaining their biocompatibility. Three crosslinking strategies are investigated, namely use of calcium ions for crosslinking ALG, 1-ethyl-3-(-3-dimethylaminopropyl) carbodiimide combined with N-hydroxysuccinimide for crosslinking ALG with CHI, and Genipin for crosslinking chitosan inside the films. Different characteristics, such as surface morphology, wettability, swelling, roughness, and mechanical properties are investigated showing that films became thinner, exhibited rougher surfaces, had lower water uptake, and increased mechanical strength after crosslinking. Changes of wettability are moderate and dependent on the crosslinking method. In vitro cytotoxicity and cell attachment studies with human dermal fibroblasts show that freestanding CHI-ALG films represent a poorly adhesive substratum for fibroblasts, while studies using incubation of plastic-adherent fibroblast beneath floating films show no signs of cytotoxicity in a time frame of 7 days. Results from cell experiments combined with film characteristics after crosslinking, indicate that crosslinked freestanding films made of ALG and CHI may be interesting candidates for wound dressings.


Renal responses to intra-arterial administration of nitric oxide donor in dogs.
Inhibition of nitric oxide synthesis by intra-arterial administration of nitro-L-arginine (NLA) leads to attenuation of the slope of the relation between renal arterial pressure (RAP) and sodium excretion without an alteration in renal autoregulatory efficiency. In the present study, we examined whether only the presence of nitric oxide or, alternatively, changes in nitric oxide production during changes in RAP are required for pressure natriuresis to occur. Anesthetized sodium-replete dogs (n = 8) were treated with NLA (50 micrograms.kg-1 x min-1) to inhibit endogenous nitric oxide formation, and S-nitroso-n-acetylpenicillamine (SNAP) was infused intra-arterially at a constant rate (2 micrograms.kg-1 x min-1) to replenish intrarenal nitric oxide levels. Renal responses to reductions in RAP within the autoregulatory range were assessed before and during NLA infusion followed by SNAP+NLA infusion. As reported previously, NLA infusion alone increased renal vascular resistance and decreased renal blood flow, urine flow, sodium excretion, and fractional excretion of sodium, with no change in glomerular filtration rate. Autoregulatory efficiency remained intact, whereas the pressure-induced natriuretic responses were attenuated. During SNAP+NLA infusion, renal blood flow increased from 2.8 +/- 0.3 to 3.5 +/- 0.3 mL.min-1 x g-1 (P < .001), without significant changes in glomerular filtration rate (0.75 +/- 0.07 to 0.81 +/- 0.05 mL.min-1 x g-1); the autoregulatory efficiency of renal blood flow and glomerular filtration rate remained intact. SNAP increased urine flow (4.8 +/- 1.8 to 10.0 +/- 2.5 microL.min-1 x g-1), sodium excretion (0.63 +/- 0.26 to 1.70 +/- 0.37 mumol.min-1 x g-1), and fractional excretion of sodium (0.55 +/- 0.20% to 1.38 +/- 0.27%).(ABSTRACT TRUNCATED AT 250 WORDS)


The Frequency of Subarachnoid Hemorrhage from Very Small Cerebral Aneurysms (< 5 mm): A Population-Based Study.
The prevailing view amongst neurosurgeons is that the larger the aneurysm, the higher the chance of rupture. This implies that very small aneurysms rarely rupture. To investigate this theory, we conducted a cross-sectional hospital-based study of aneurysmal subarachnoid hemorrhage, with an emphasis on aneurysm size at the time of rupture. We retrospectively reviewed hospital records and radiological tests of all patients admitted to Foothills Medical Center, Calgary, Alberta, with a ruptured saccular aneurysm from January 2008 to January 2012. The size of the dome and neck (in millimeters), the aspect ratio (aneurysm depth to aneurysm neck), and location of the aneurysms were determined using preoperative computed tomography angiography and digital subtraction angiography. One hundred and twenty-three patients with a ruptured saccular aneurysm were identified. The average size of the dome, neck, and the aspect ratio was 6.6±4.4 mm (range: 1.5-26 mm), 3.1 mm, and 2.6±0.9, respectively. Forty-six patients (37%) had a ruptured aneurysm with dome size < 5 mm (range: 1.5-4.9 mm). For these small aneurysms, the average size of the dome, neck, and the aspect ratio was 3.9+1.1 mm, 1.6 mm, and 2.1+0.6, respectively. The anterior communicating artery was the most common location regardless of size. Small aneurysms (< 5 mm) are a common cause of aneurysmal subarachnoid hemorrhage. When unruptured, looking for other risk factors for rupture is highly recommended before simply leaving them alone.


Role of mast cell activation in inducing microglial cells to release neurotrophin.
The brain-derived neurotrophic factor (BDNF) plays a critical role in pain hypersensitivity. BDNF is the ligand of P2X4 receptors (P2X4R) in the microglia. The causative factors involving the P2X4R over expression in the microglia remains unclear. Mast cell activation has a close relation with pain hypersensitivity. However, the underlying mechanism between mast cell activation and pain hypersensitivity is unknown. The present study aimed to elucidate the mechanism by which mast cell activation promoted the expression of P2X4R in the microglia. The results of present study showed that mast cell activation markedly promoted the expression of P2X4R and BDNF in microglial cells, which significantly enhanced the release of BDNF from microglial cells upon exposure to adenosine triphosphate. Mast cell-derived tryptase activated PAR2 that resulted in promoting the expression of P2X4R in microglial cells. Pretreatment with antibodies against tryptase or PAR2, or using tryptase-deficient HMC-1 cells or PAR2-deficient microglial cells abolished the increase in P2X4R expression and BDNF release. Increase in mitogen activated protein kinase phosphorylation was observed in the processes of mast cell-induced BDNF release and P2X4R expression. We conclude that mast cell activation has the capacity to promote the expression of P2X4R and BDNF in microglial cells.


Electrochemical bromocyclization enables 3,5-diversification of heterocyclic indolines.
Electrophilic bromocyclization reactions are widely used as key steps in the synthesis of diverse functionalized tetrahydrofuroindolines and hexahydropyrroloindolines. However, the direct dibromination variants of these reactions for the synthesis of 3,5-dibromoindolines remain undeveloped. Here, we report a protonic-acid-promoted electrooxidative protocol for the dearomative C3,C5-dibromocyclizations of tryptophol and tryptamine derivatives. This electrosynthetic approach, which enables direct selective construction of heterocyclic 3a,5a-dibromoindolines with inexpensive, non-hazardous NaBr as both the electrolyte and Br source, provides a convenient, practical method for the late-stage 3,5-diversification of heterocyclic indolines.


Production and characterization of mouse monoclonal antibodies to wild-type and oncogenic FLI-1 proteins.
Mouse monoclonal antibodies were raised against the C-terminal domain of human FLI-1, a member of the ETS family of transcription factors which is involved in various murine and human malignancies. This FLI-1 specific domain is included in the fusion product EWS-FLI-1, an oncogenic variant of FLI-1 expressed in Ewing tumors. Antibodies were screened first by enzyme-linked immunosorbent assay onto recombinant FLI-1-coated plates. Positive clones were then tested for their ability to immunoprecipitate over-expressed EWS-FLI-1 protein. Three monoclonal antibodies were selected and further characterized. One of them, termed 7.3 MoAb, was shown to react with FLI-1 and EWS-FLI-1 in immunoblotting, immunoprecipitation, and immunofluorescence experiments. With all three methods, this antibody not only enabled the detection of overexpressed proteins but also more interestingly, that of endogenously expressed proteins. Furthermore, the 7.3 MoAb can specifically inhibit the interaction of FLI-1 with its DNA-binding site as shown by electrophoretic mobility shift assay. The 7.3 MoAb appears to be specific for FLI-1 because it does not react with ERG, the ETS family member most closely related to FLI-1. This antibody should be a useful tool in the diagnostic evaluation of Ewing tumors and should permit biochemical analyses to study the function of the wild-type FLI-1 protein and of the EWS-FLI-1 fusion protein.


Women's experiences of health care utilization in cases of early pregnancy loss: A scoping review.
Approximately 25% of pregnancies end in miscarriage, most occurring within the first trimester (<13 weeks). For many women early pregnancy loss has implications for short- and long- term mental health, and women's well-being following early pregnancy loss is impacted by their experiences within the healthcare setting. To improve quality of care, it is crucial to understand women's' experiences within the healthcare system in cases of early pregnancy loss. What does the research literature tell us about the experiences of early pregnancy loss within healthcare settings? Are these experiences positive or negative? 'How can care improve for those experiencing early pregnancy loss?' A scoping review of the research literature was undertaken. Three research databases were searched for relevant articles published in English since 2009, with key words related to 'Experience', 'Healthcare' and 'Early Pregnancy Loss'. A thematic analysis was undertaken to identify and summarize key findings emerging from the research literature. Twenty-seven (27) articles met our inclusion criteria. Three main themes were identified: (1) issues related to communication, (2) challenges within care environments, and (3) inadequacies in aftercare. The literature suggests that women's experiences related to healthcare for early pregnancy loss are largely negative, particularly within emergency departments. Recommendations to improve women's experiences should extend beyond attempts to improve existing care structures, to include emerging environments and providers. Women's experiences identified within the literature provide further insights on what women are seeking from their care, and how care models can be improved.


Review of Calcaneal Osteotomies Fixed With a Calcaneal Slide Plate.
The calcaneal slide osteotomy is a common procedure used for the surgical correction of heel varus and valgus deformities. A variety of fixation methods exist including screws and plates. The literature shows a high rate of hardware prominence with screws leading to subsequent removal of hardware. Few studies have examined the use of plates for fixation of a calcaneal osteotomy. The purpose of this study was to assess outcomes following fixation of a calcaneal osteotomy with a calcaneal slide plate. This is a retrospective consecutive case series of all patients who underwent either a medial or lateral calcaneal slide osteotomy using the specialized calcaneal slide plate between September 2013 and December 2018 by a single surgeon. The primary outcome measures were the rate of hardware removal, healing of the calcaneal osteotomy, and any associated complications such as infection or incision healing delays. Patient baseline demographics and procedure-related data were recorded. The minimum follow-up was 4 months. A total of 81 procedures were performed using this calcaneal slide plate. All of the patients had one or more additional procedures at the same time as the calcaneal osteotomy. All of the calcaneal osteotomies healed without displacement. Only 1 patient (1.2%) returned to the operating room and had removal of the calcaneal slide plate, which was after osteotomy union for an infected wound. There were no cases of hardware failure or removal due to it being symptomatic. A specialized calcaneal slide plate was an effective fixation device for both medial and lateral calcaneal slide osteotomies for a variety of foot and ankle conditions. The union rate was 100% and none of the patients had hardware symptoms, which is an improvement on published reports of symptomatic hardware after calcaneal slide osteotomy. Level IV, retrospective case series.


Brain Networks Connectivity in Mild to Moderate Depression: Resting State fMRI Study with Implications to Nonpharmacological Treatment.
Network mechanisms of depression development and especially of improvement from nonpharmacological treatment remain understudied. The current study is aimed at examining brain networks functional connectivity in depressed patients and its dynamics in nonpharmacological treatment. Resting state fMRI data of 21 healthy adults and 51 patients with mild or moderate depression were analyzed with spatial independent component analysis; then, correlations between time series of the components were calculated and compared between-group (study 1). Baseline and repeated-measure data of 14 treated (psychotherapy or fMRI neurofeedback) and 15 untreated depressed participants were similarly analyzed and correlated with changes in depression scores (study 2). Aside from diverse findings, studies 1 and 2 both revealed changes in within-default mode network (DMN) and DMN to executive control network (ECN) connections. Connectivity in one pair, initially lower in depression, decreased in no treatment group and was inversely correlated with Montgomery-Asberg depression score change in treatment group. Weak baseline connectivity in this pair also predicted improvement on Montgomery-Asberg scale in both treatment and no treatment groups. Coupling of another pair, initially stronger in depression, increased in therapy though was unrelated to improvement. The results demonstrate possible role of within-DMN and DMN-ECN functional connectivity in depression treatment and suggest that neural mechanisms of nonpharmacological treatment action may be unrelated to normalization of initially disrupted connectivity.


Prevalence of germline variants in consensus moderate-to-high-risk predisposition genes to hereditary breast and ovarian cancer in BRCA1/2-negative Brazilian patients.
This study aimed to identify and classify genetic variants in consensus moderate-to-high-risk predisposition genes associated with Hereditary Breast and Ovarian Cancer Syndrome (HBOC), in BRCA1/2-negative patients from Brazil. The study comprised 126 index patients who met NCCN clinical criteria and tested negative for all coding exons and intronic flanking regions of BRCA1/2 genes. Multiplex PCR-based assays were designed to cover the complete coding regions and flanking splicing sites of six genes implicated in HBOC. Sequencing was performed on HiSeq2500 Genome Analyzer. Overall, we identified 488 unique variants. We identified five patients (3.97%) that harbored pathogenic or likely pathogenic variants in four genes: ATM (1), CHEK2 (2), PALB2 (1), and TP53 (1). One hundred and thirty variants were classified as variants of uncertain significance (VUS), 10 of which were predicted to disrupt mRNA splicing (seven non-coding variants and three coding variants), while other six missense VUS were classified as probably damaging by prediction algorithms. A detailed mutational profile of non-BRCA genes is still being described in Brazil. In this study, we contributed to filling this gap, by providing important data on the diversity of genetic variants in a Brazilian high-risk patient cohort. ATM, CHEK2, PALB2 and TP53 are well established as HBOC predisposition genes, and the identification of deleterious variants in such actionable genes contributes to clinical management of probands and relatives.


The role of mediodorsal thalamus in temporal differentiation of reward-guided actions.
The mediodorsal thalamus (MD) is a crucial component of the neural network involved in the learning and generation of goal-directed actions. A series of experiments reported here examined the contributions of MD to the temporal differentiation of reward-guided actions. In Experiment 1, we trained rats on a discrete-trial, fixed-criterion temporal differentiation task, in which only lever presses exceeding a threshold duration value were rewarded. Pre-training MD lesions impaired temporal differentiation of action duration, by increasing the dispersion of the duration distribution. Post-training MD lesions also impaired differentiation, but by reducing the average emitted press durations, thus shifting the distribution without increasing the dispersion. In Experiment 2, we trained rats to space their lever pressing above criterion inter-press-intervals in order to earn rewards. Both pre-training and post-training MD lesions impaired the differentiation of inter-press-intervals. These results show that MD plays an important role in the acquisition and expression of action differentiation.


Experimental Agents for the Treatment of Atherosclerosis: New Directions.
Cardiovascular and related metabolic disorders constitute a worldwide health challenge. Atherosclerosis is a chronic inflammatory condition based on both dyslipidemia and inflammation. Therefore, even when dyslipidemia is controlled, the risk of atherosclerosis remains. Among the most efficient inflammatory mediators used as therapeutic tools in cardiovascular disease are the interleukins, which are pro-inflammatory mediators like cytokines. Moreover, a protein kinase inhibitors, p38 mitogen-activated protein kinase (MAPK) inhibitor, and an inhibitor of a leukocyte adhesion molecule, P-Selectin, have also presented therapeutic potential for this disorder. Colchicine, being an inexpensive therapeutic option, has been proved to be suitable for the prevention of atherosclerosis. In this review, we summarize all the studies, from 2010 to 2020, in which treatment approaches based on the agents mentioned above are evaluated in the management of atherosclerosis.


[Influence of the ileum on the regulation of gastrointestinal motility].
Under normal conditions a "physiologic malabsorption" and thus nutrients in the lower small intestine in the late postprandial state can be observed in humans. To study the effects of "physiologic" quantities of nutrients in the distal small intestine on upper gastrointestinal motor functions, 9 healthy subjects were intubated with an oro-ileal multi-lumen tube. The continuous perfusion of the duodenum with essential amino acids induced a fed motility pattern. In 12 out of 14 cases additional ileal perfusion with carbohydrates (60 kcal), but not with saline, converted the fed motility pattern to a pattern characteristic of the interdigestive state. These findings suggest that the ileum takes part in the late postprandial regulation of proximal gastrointestinal motor functions in humans.


Unusual delayed hydrocephalus after bare platinum coil embolization of an unruptured aneurysm.
A 69-year-old woman developed hydrocephalus after the embolization of an incidentally detected unruptured large internal carotid artery aneurysm with bare platinum coils. Endovascular embolization resulted in near-total aneurysm occlusion. She complained of mild headache 18 hours after the procedure and magnetic resonance (MR) imaging performed on the 6(th) post-treatment day revealed wall enhancement and perianeurysmal brain edema. Follow-up MR imaging showed recanalization of the aneurysm and gradual ventricular enlargement. She presented with typical symptoms of hydrocephalus including disorientation, gait disturbance, and urine incontinence at 7 months post-embolization. We removed 30 ml of cerebrospinal fluid by lumbar tap, which improved her condition without symptom recurrence for 2 months. She did not require shunt placement. Post-interventional hydrocephalus is known in patients with unruptured aneurysms embolized with bioactive second-generation coils. This case shows that hydrocephalus can occur after aneurysm embolization with bare platinum coils without intracranial hemorrhage.


Recombinant expression of an l-amino acid oxidase from the fungus Hebeloma cylindrosporum in Pichia pastoris including fermentation.
l-amino acid oxidases (LAAOs) are flavoenzymes that catalyze the oxidative deamination of l-amino acids to the corresponding α-keto acids, ammonia, and hydrogen peroxide. Here, we show the overexpression, purification, and the characterization of LAAO4 from the fungus Hebeloma cylindrosporum in the yeast Pichia pastoris with a 9His-tag and compare this with the recently characterized 6His-hcLAAO4 expressed in E. coli. The expression of the enzyme with an ER-signal sequence in P. pastoris resulted in a glycosylated, secreted protein. The enzymatic activity without activation was higher after expression in P. pastoris compared to E. coli. Due to treatment with acidic pH, a striking increase of activity could be detected for both expression systems resulting in similar specific activities after acid activation. Regarding the substrate spectrum, temperature stability, Km, and vmax values, hcLAAO4 showed very few differences when produced in these two expression systems. A higher yield of hcLAAO4 could be obtained by fermentation.


Computational screening of potential glioma-related genes and drugs based on analysis of GEO dataset and text mining.
Considering the high invasiveness and mortality of glioma as well as the unclear key genes and signaling pathways involved in the development of gliomas, there is a strong need to find potential gene biomarkers and available drugs. Eight glioma samples and twelve control samples were analyzed on the GSE31095 datasets, and differentially expressed genes (DEGs) were obtained via the R software. The related glioma genes were further acquired from the text mining. Additionally, Venny program was used to screen out the common genes of the two gene sets and DAVID analysis was used to conduct the corresponding gene ontology analysis and cell signal pathway enrichment. We also constructed the protein interaction network of common genes through STRING, and selected the important modules for further drug-gene analysis. The existing antitumor drugs that targeted these module genes were screened to explore their efficacy in glioma treatment. The gene set obtained from text mining was intersected with the previously obtained DEGs, and 128 common genes were obtained. Through the functional enrichment analysis of the identified 128 DEGs, a hub gene module containing 25 genes was obtained. Combined with the functional terms in GSE109857 dataset, some overlap of the enriched function terms are both in GSE31095 and GSE109857. Finally, 4 antitumor drugs were identified through drug-gene interaction analysis. In this study, we identified that two potential genes and their corresponding four antitumor agents could be used as targets and drugs for glioma exploration.


Cytologic features of subependymal giant cell astrocytom: a review of 7 cases.
To describe the cytologic features of subependymal giant cell astrocytoma (SEGA) on smears and analyze cytomorphologic parameters that may help in reaching the diagnosis of SEGA. Cytologic smears of 7 cases of SEGA were reviewed and graded semi-quantitatively for 11 cytologic features: clustering, cytoplasmic fibrillary processes (fibrillarity), cellularity, small prominent nudcleoli, binucleation or multinucleation, "strap cells", spindle-shaped cells, mitoses, intranuclear inclusions, nuclear atypia and perivascular palisading/pseudorosettes. Corresponding histologic sections were also reviewed. The study included 5 male and 2 female patients with an average age of 8.3 years (range, 3-16) at surgery. Cytologic examination revealed loosely cohesive clusters of large cells possessing round to oval nuclei with no or minimal atypia; fine, evenly distributed chromatin; and abundant eosinophilic cytoplasm enmeshed in abundant thin, hairlike processes. Predominant features included hypercellularity, cell clustering, and fibrillarity. Binucleation or multinucleation; small, prominent nucleoli; and strap cells were often seen. Although common in histologic sections, perivascular palisading/pseudorosettes and spindled astrocytic cells were rarely noted on smears. The cytologic features of SEGA are highly characteristic and thus are of great use in supporting a diagnosis of SEGA and in excluding mimics, primarily gemistocytic astrocytoma and ependymoma.


Mixed venous and arterial blood in bovine coccygeal vessel samples for blood gas analysis.
Bovine coccygeal (median, caudal) vessel samples are not always venous in origin but may be arterial or a mixture of venous and arterial blood. Results of blood gas analysis of blood samples collected from 39 cows were consistent with typical venous, mixed venous-arterial, or typical arterial blood. This observation was made while establishing reference intervals for a new blood gas instrument. The pO2 and the oxygen saturation of hemoglobin (S02) were most reflective of the amount of arterial blood contamination in the sample, but pCO2 and pH also were altered. The pO2 values ranged from 21 to 127 mm Hg, and SO2 ranged from 35% to 100%. The mean pCO2 in venous type samples was 46.3 mm Hg compared to 36.7 mm Hg in arterial type samples. The mean pH in venous type samples was 7.42 compared to 7.47 in arterial type samples.


Sibling relationship quality and social functioning of children and adolescents with intellectual disability.
We examined sibling relationships for children and adolescents with intellectual disability and assessed implications for their social functioning. Targets (total N = 212) had either intellectual disability, a chronic illness/physical disability, or no disability. Nontarget siblings reported on relationship quality, sibling interactions were observed, and teachers reported on social adjustment. Group comparisons highlighted the asymmetrical hierarchy and low conflict unique to siblings and targets with intellectual disability. Sibling relationships characterized by high warmth/closeness, positive affect, and few negative behaviors were predictive of fewer behavior problems for the targets at school. Both high warmth/ closeness and high conflict predicted greater social competence for the targets with intellectual disability, though warmth, conflict, and sibling management had different implications depending on the sibling's gender.


Given the high prevalence of alcohol use disorder (AUD) amongst patients in Emergency Rooms (ER), it is recommended to carry out a systematized screening of at-risk drinkers, followed if necessary by a brief intervention (BI) to prevent AUD-related damages. This intervention has been the subject of numerous efficacy and feasibility studies. The purpose of this review of the literature is to identify optimal strategies for systematic screening and BI that can be deployed in the ER. We selected randomized controlled trials, meta-analysis and reviews of the literature published between July 2014 and March 2019 evaluating the effectiveness of BI in the ER on reducing alcohol consumption. Thirteen articles were included. There is a significant heterogeneity of the methodologies used and the interventions carried out. The majority of studies conclude in the effectiveness of BI on reducing alcohol consumption, with however differences between the studies in effect size, and an effectiveness that seems to decrease over time. The BI in the ER appears to be effective on reducing alcohol consumption but with a modest effect size and heterogeneity of the interventions tested, so that the optimal modalities of its implementation remain to be defined. Further studies to compare different interventions and identify at-risk subgroups would be needed to optimize the use of BI in the ER.


Clinical outcome and risk factors for recurrence in borderline ovarian tumours.
We investigated the long-term prognosis of borderline ovarian tumours and determined risk factors for recurrence. One hundred and twenty-one borderline ovarian tumours treated between 1994 and 2003 at the participating institutions in the Tohoku Gynecologic Cancer Unit were retrospectively investigated for clinical stage, histopathological subtype, surgical technique, postoperative chemotherapy, the presence or absence of recurrence, and prognosis. The median follow-up period was 57 months (1-126 months). One hundred and nine cases (90.6%) were at clinical stage I. The histopathological subtypes consisted of 91 cases of mucinous tumour (75.2%), 27 cases of serous tumour (22.3%), and three cases of endometrioid tumour. Conservative surgery was used in 53 cases (43.8%), radical surgery in 68 cases (56.2%), a staging laparotomy in 43 cases (35.5%), and postoperative adjuvant therapy in 30 cases (24.8%). Recurrence was found in eight cases, but no tumour-related deaths were reported. Although no significant difference in disease-free survival rate was seen between different clinical stages, the difference in disease-free survival rate between serous and non-serous (mucinous and endometrioid) types was significant (P<0.05). The 10-year disease-free survival rate was 89.1% for the radical surgery group and 57.4% for the conservative surgery group -- this difference was significant (P<0.05). In the conservative surgery group, cystectomy and serous tumour were independent risk factors for recurrence. Although recurrence was observed, the long-term prognosis of borderline ovarian tumour was favourable, without tumour-related deaths. Considering the favourable prognosis, conservative surgery can be chosen as far as the patient has a non-serous tumour and receive adnexectomy. However, in cases of serous type and/or receiving cystectomy special care should be given as relative risk rates of recurrence elevate by 2-4-folds.


Parental choice: what parents want in a son-in-law and a daughter-in-law across 67 pre-industrial societies.
Parents are influential over mate choice, and in most human societies they choose spouses for their offspring according to their own preferences. However, surprising little is known about the qualities which make a woman desirable as a daughter-in-law and a man desirable as a son-in-law. Using evidence from 67 societies such traits are identified and three hypotheses are tested: first, the hypothesis is tested that parents desire in an in-law qualities which are beneficial to them and their kin. Second, it is hypothesized that such preferences are contingent upon the sex of the in-law, as traits are weighted differently in a daughter-in-law and in a son-in-law. The third hypothesis tested is that parental preferences vary according to the subsistence type of a given society, as traits are valued differently in agropastoral societies and foraging societies. The evidence presented here provides support for all three hypotheses.


[Disclosure of Adolescents in Residential Care Institutions and Boarding Schools after Exposure to Sexual Violence].
Disclosure of Adolescents in Residential Care Institutions and Boarding Schools after Exposure to Sexual Violence In international research, many papers exist about the issue of disclosure after having experienced sexual violence. However, specific research regarding disclosure processes of children and adolescents in institutional care are missing, even though those are particularly often affected by sexual violence. In the Germany-wide study "Sprich mit!", adolescents from the age of 15 up (n = 322; average age 16,69 (SD = 1,3); 57,1 % males) who live in residential care or boarding schools were asked for experiences of sexual violence and their consequences by means of a self-report questionnaire. Results showed that the majority of the adolescents (82 %) entrusted themselves to someone, mostly towards peers (56 %) and less frequent towards adults (24 %). Boys and girls opened up equally often, regardless of the severity of the experienced violence. Adolescents who entrusted themselves towards their peers indicated retrospectively more satisfaction than those entrusting themselves towards adults, even if there were no consequences following the disclosure. Considering that the disclosure towards peers did not initiate a process of help, adolescents in institutional care should be better informed about relevant possibilities to entrust themselves and receive support.


Structure and variability in the developmental trajectory of children's externalizing problems: impact of infant attachment, maternal depressive symptomatology, and child sex.
This study explores the developmental trajectory of externalizing problems in a sample of 101 children of adolescent mothers from preschool through third grade using hierarchical linear models (HLM). First, a detailed assessment of the structure of the developmental trajectory of externalizing problems is provided. Second, the impact of three risk factors (infant attachment, maternal depressive symptomatology, and child sex) on the developmental course of externalizing problems is assessed. Both avoidant and disorganized attachment and higher levels of maternal depressive symptomatology were associated with higher levels of externalizing problems at 9 years of age. Girls also showed higher externalizing problems relative to their same-sex peers than did boys. In addition, maternal depressive symptomatology related to the rate of change in these problems over time: the greater the mother's depression, the faster externalizing problems tended to increase. Although the overall level of maternal depressive symptomatology was related to children's externalizing problems for secure, avoidant, and disorganized groups, changes in maternal depressive symptomatology over time predicted levels of externalizing problems only for children with avoidant insecure attachments.


Markedly increased expression of interleukin-8 in the colorectal mucosa of inflammatory colorectal polyps in miniature dachshunds.
Inflammatory colorectal polyps (ICRPs) in miniature dachshunds were recently recognized as a major cause of large bowel diarrhea in this dog breed in Japan. ICRPs are characterized by the formation of multiple small polyps and/or space-occupying large polyps in the colorectal area and are thought to be a novel form of inflammatory bowel disease (IBD). To explore key mediators in the pathogenesis of ICRPs, we analyzed several pro-inflammatory cytokine (IL-1β, IL-6, TNF-α, IL-8, IL-12p35, IL-12/23p40, and IL-23p19) mRNA expressions in colorectal polyps in ICRP dogs by quantitative PCR. Among these cytokines, IL-8 mRNA expression was markedly up-regulated in large polyps. To examine IL-8 protein expression, we analyzed IL-8 protein level and its location in colorectal mucosal specimens of ICRP dogs by ELISA and immunofluorescence microscopy. IL-8 protein was significantly increased in large polyps and serum in dogs with ICRPs compared to controls. By immunofluorescence microscopy, IL-8 was only localized in macrophages, but not in mucosal epithelial cells or neutrophils. IL-8-positive macrophages were significantly increased in large polyps compared to controls. These results suggest that IL-8 is produced mainly by macrophages and may induce neutrophil infiltration in the colorectal area of ICRP dogs.


Characteristics of diesel truck emission in China based on portable emissions measurement systems.
Seventy-five diesel vehicles were measured in China using a portable emissions measurement system (PEMS). Particular matter (PM) emission factors and gaseous emission factors for Euro 0 (E0), Euro 1 (E1), Euro 2 (E2), and Euro 3 (E3) trucks were obtained under highway, urban, and rural driving conditions. Vehicle emission regulations in China have successfully reduced carbon monoxide (CO), hydrocarbons (HC) and PM by 62, 56, and 72% on average. Most of the emission reductions were achieved when the control technology went from E0 to E1 in Xi'an, and E2 to E3 in Beijing, which resulted in PM reductions of 79% associated with highway driving and 60% associated with urban or rural driving. Emission levels of oxides of nitrogen (NO(X)) were not improved from previous emission control steps. Compared with Xi'an, the emission rate is lower in Beijing, which is strong evidence of the effectiveness of the present comprehensive emission control strategy in Beijing. Emissions were grouped into driving bins that corresponded to the energy demand placed on the vehicles. By using this binning approach, it was found that E3 trucks were successfully controlling the high emission rates in aggressive driving bins, which led to the low average emission for E3 trucks.


Mucosal morphology, cell proliferation and faecal bacteriology in acute pouchitis.
A study was performed to investigate whether acute reservoir ileitis (pouchitis) is associated with specific changes in mucosal morphology, crypt cell kinetics and faecal bacteriology in the ileal pouch. Forty-six patients were studied (ileal reservoir, 36; end ileostomy, ten) using clinical grading, sigmoidoscopy and biopsy; 24 patients with a reservoir were restudied after therapy for 1 month with metronidazole 400 mg three times daily. An index of villus atrophy and crypt cell production rate (CCPR) were determined in all biopsy material. Faecal bacteriology was assessed in 12 patients with a pouch before and after metronidazole therapy. The mucosa of patients with pouchitis was associated with a lower villus atrophy index (P = 0.052), a higher CCPR (P = 0.03) and a higher grade of acute inflammation than that in those without pouchitis. There was no difference in faecal bacterial counts between patients with and without pouchitis. A low atrophy index correlated with a high CCPR (P < 0.001), worse functional score (P < 0.001) and more severe pouch mucosal acute inflammation (P < 0.001), but not with faecal bacteriology. Following metronidazole therapy there was resolution of acute pouch inflammation, increased villus atrophy index (P = 0.049), decreased CCPR (P = 0.049) but no differences in faecal bacterial counts apart from Bacteroides species. These data show that metronidazole therapy does not specifically alter the growth of common faecal bacteria in patients with pouchitis, apart from Bacteroides species. However, metronidazole causes resolution of the typical changes in pouch mucosal morphology and crypt cell kinetics associated with pouchitis.


Emerging Insights into the Distinctive Neuronal Methylome.
The genomes of mammalian neurons are enriched for unique forms of DNA methylation, including exceptionally high levels of non-CG methylation. Here, we review recent studies defining how non-CG methylation accumulates in neurons and is read out by the critical regulator of neuronal transcription, MeCP2. We discuss the role of gene expression and genome architecture in establishing non-CG methylation and highlight emerging mechanistic insights into how non-CG methylation and MeCP2 control transcription. Further, we describe the cell type-specific functions of this methylation and explore growing evidence that disruption of this regulatory pathway contributes to neurodevelopmental disorders. These findings uncover how the distinctive epigenome in neurons facilitates the development and function of the complex mammalian brain.


What Can be Done to Reduce the Public Stigma of Gambling Disorder? Lessons from Other Stigmatised Conditions.
Gambling is embedded in Australian cultural history, and perceived as a normal, legitimate leisure activity. Despite this normalisation, people who experience gambling problems are heavily stigmatised which can lead to a variety of harms that extend beyond the individual. The stigma from the general public appears to be based on a stereotype of a typical "problem gambler"-selfish, greedy, impulsive and irresponsible. However, research suggests that people experiencing gambling problems have widely varying characteristics and do not conform to this stereotype. Regardless of whether the stigma is justified, it is both present and problematic. Gamblers experiencing problems delay help-seeking due to feelings of shame and, not unwarranted, expectations of negative judgement because of the heavy stigma associated with the stereotype. As stigma is a primary barrier to treatment and a reason why gambling problems can take longer to acknowledge, it is important to understand and address how stigma can be reduced to minimise the negative consequences of gambling on individuals, their families and friends and the wider community. There is little research on reducing gambling-related stigma, so there is a need to examine strategies used in other stigmatised conditions, such as mental health, to understand the general principles of effective stigma reduction measures. Because gambling disorder is unique, well-hidden and consequently not well understood, there is a need to recognise that techniques used in other domains may differ in their effectiveness within the context of gambling stigma.


N-methyl-D-aspartate preconditioning improves short-term motor deficits outcome after mild traumatic brain injury in mice.
Traumatic brain injury (TBI) causes impairment of fine motor functions in humans and nonhuman mammals that often persists for months after the injury occurs. Neuroprotective strategies for prevention of the sequelae of TBI and understanding the molecular mechanisms and cellular pathways are related to the glutamatergic system. It has been suggested that cellular damage subsequent to TBI is mediated by the excitatory neurotransmitters, glutamate and aspartate, through the excessive activation of the N-methyl-D-aspartate (NMDA) receptors. Thus, preconditioning with a low dose of NMDA was used as a strategy for protection against locomotor deficits observed after TBI in mice. Male adult mice CF-1 were preconditioned with NMDA (75 mg/kg) 24 hr before the TBI induction. Under anesthesia with O(2)/N(2)O (33%: 66%) inhalation, the animals were subjected to the experimental model of trauma that occurs by the impact of a 25 g weight on the skull. Sensorimotor gating was evaluated at 1.5, 6, or 24 hr after TBI induction by using footprint and rotarod tests. Cellular damage also was assessed 24 hr after occurrence of cortical trauma. Mice preconditioned with NMDA were protected against all motor deficits revealed by footprint tests, but not those observed in rotarod tasks. Although mice showed motor deficits after TBI, no cellular damage was observed. These data corroborate the hypothesis that glutamatergic excitotoxicity, especially via NMDA receptors, contributes to severity of trauma. They also point to a putative neuroprotective mechanism induced by a sublethal dose of NMDA to improve motor behavioral deficits after TBI.


Characterization of the hardened single line of sight camera at the National Ignition Facility.
The hardened single line of sight camera has been recently characterized in preparation for its deployment on the National Ignition Facility. The latest creation based on the pulse-dilation technology leads to many new features and improvements over the previous-generation cameras to provide better quality measurements of inertial confinement fusion experiments, including during high neutron yield implosions. Here, we present the characterization data that illustrate the main performance features of this instrument, such as extended dynamic range and adjustable internal magnification, leading to improved spatial resolution.


Retroperitoneal haematoma in a postoperative ALIF patient taking rivaroxaban for atrial fibrillation.
Novel oral anticoagulants (NOACs) are being increasingly used in the secondary prevention of thromboembolic stroke in patients with atrial fibrillation. Patients taking NOACs are difficult to manage perioperatively, and several unexpected complications have been reported in these patients. We report a case of a rivaroxaban-induced retroperitoneal haematoma in a 72-year-old man who underwent an L5/S1 anterior lumbar interbody fusion (ALIF) for grade 1 spondylolytic spondylolisthesis. The patient suffered from atrial fibrillation and was taking rivaroxaban, a factor Xa inhibitor, for thromboembolic risk reduction. In accordance with perioperative Novel Oral Anticoagulant (NOAC) guidelines, rivaroxaban was stopped 2 days preoperatively and restarted on the third postoperative day. The patient presented on the ninth postoperative day, complaining of severe left iliac fossa pain, nausea, and vomiting, accompanied by swelling and bruising around the surgical site. A computed tomography (CT) scan showed a large expanding retroperitoneal haematoma. The patient was taken back to theatre for an evacuation of the haematoma and subsequently recovered without any further complications. This is the first case of a rivaroxaban-induced retroperitoneal haematoma reported in the literature, secondary to elective spinal surgery. This report adds to the body of evidence on the risk of postoperative bleeding in patients taking NOACs. If patients on NOACs present with abdominal symptoms following anterior approach to the lumbar spine, treating clinicians should have a high index of suspicion for retroperitoneal haematoma.


Reliability and validity of the Hungarian version of the Pittsburgh Sleep Quality Index (PSQI-HUN): comparing psychiatric patients with control subjects.
The Pittsburgh Sleep Quality Index is used to evaluate subjective sleep quality, and it is commonly used in clinical research. Subjective sleep quality is also an important clinical measure in patients with psychiatric disorders. The aim of the present study was to evaluate the reliability and validity of the Hungarian version of the Pittsburgh Sleep Quality Index (PSQI-HUN) in both clinical and non-clinical samples. The original version of PSQI was translated into Hungarian according to standard guidelines. The PSQI-HUN and the Athens Insomnia Scale (AIS) were subsequently administered to 53 psychiatric patients (schizophrenia, recurrent depressive disorder, mixed anxiety, and depressive disorder) and 178 healthy controls. Internal consistency as measured by Cronbach's alpha in the whole sample was 0.79. Pearson's product-moment correlations between component scores and the global scores were high (0.59-0.88) in the PSQI-HUN indicating the homogeneity of the scale. PSQI-HUN global and component scores differed significantly between psychiatric patients and control subjects. In the psychiatric patient subsample, schizophrenics had lower global scores compared to the other two patient groups. The analysis of convergent validity showed significant correlations between the AIS and the global as well as the component scores of the PSQI-HUN (except the component of sleep latency). The present study concludes that the PSQI-HUN is a reliable, valid, and standardized measure for assessment of the subjective sleep quality in clinical and research settings.


Compact steady-state tokamak performance dependence on magnet and core physics limits.
Compact tokamak fusion reactors using advanced high-temperature superconducting magnets for the toroidal field coils have received considerable recent attention due to the promise of more compact devices and more economical fusion energy development. Facilities with combined fusion nuclear science and Pilot Plant missions to provide both the nuclear environment needed to develop fusion materials and components while also potentially achieving sufficient fusion performance to generate modest net electrical power are considered. The performance of the tokamak fusion system is assessed using a range of core physics and toroidal field magnet performance constraints to better understand which parameters most strongly influence the achievable fusion performance. This article is part of a discussion meeting issue 'Fusion energy using tokamaks: can development be accelerated?'.


Infrared Spectroscopy Based Study of Biochemical Changes in Saliva during Maximal Progressive Test in Athletes.
This study aims to explore biochemical changes in saliva during cardiorespiratory exercise using attenuated-total-reflectance-Fourier-transform-infrared-spectroscopy (ATR-FTIR). Saliva and blood samples were obtained from six athletes at rest, and after running at speeds of 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, and 20 kilometers-per-hour (km/h) on a treadmill (maximal stress test). Saliva ATR-FTIR spectra were analyzed using deconvolution and multivariate analysis. Area-under-the-curve calculations suggest differential changes in glucose, lactate, protein, lipids, carbohydrate and phosphate content in saliva during the test. Increases in glucose and lactate levels with increasing speeds were verified by simultaneous measurement of blood glucose and lactate levels using standard equipment (Roche®). Multivariate principal-component-analysis (PCA) showed discrete clusters for low (rest-14 km/h) and high (15 - 20 km/h) speeds, and PCA-linear-discriminant-analysis showed 100% classification of 18 - 20 km/h as high speed. Overall, results suggest the possibility of using this non-invasive saliva-based ATR-FTIR method for biochemical assessment during sports exercise and stress tests.


Rural long-term care: what do we need to know to improve policy and programs?
This article examines what is known and what we need to know about rural long-term care populations and the formal and informal service systems that support their long-term care needs. The article provides a framework for identifying some of the critical policy and research questions concerning the financing and delivery of rural long-term care that merit the attention of health services researchers and policymakers. It documents differences in the demographic and health characteristics of the rural and urban elderly and in the availability, organization, and use of health and long-term care services in rural areas that have significant implications for long-term care policy and programs. With this background in mind, the author discusses specific topics and questions relevant to long-term care policy and program improvements for rural communities and people: (a) the changing role of the rural nursing home; (b) residential care alternatives in rural areas; (c) health personnel and rural long-term care; (d) the quality of rural long-term care; (e) innovations in long-term care financing and service delivery; (f) use of technology in rural long-term care; and (g) the effects of Medicaid and Medicare policy changes on the rural long-term care system.


[Dilated cardiomyopathy (DCM) in dogs--pathological, clinical, diagnosis and genetic aspects].
Dilated cardiomyopathy (DCM) is a heart disease which is often found in humans and animals. The age of onset of this progressive disease varies between 3 and 7 years of age. A juvenile form of DCM has been found in Portuguese Water Dogs and Doberman Pinscher Dogs. Some breeds such as Doberman pinscher, Newfoundland, Portuguese Water dog, Boxer, Great Dane, Cocker Spaniel and Irish Wolfhound exhibit a higher prevalence to DCM. There also seems to be a sex predisposition as male dogs are affected more often than female dogs and in Great Danes an X-linked recessive inheritance is likely. In Newfoundland and Boxer an autosomal dominant inheritance was found whereas an autosomal recessive inheritance was described in Portuguese Water Dogs. Atrial fibrillation as a cause or consequence of DCM is assumed for certain breeds. The causes of DCM are widely unknown in dogs. A genetic basis for this heart disease seems to exist. Apart from a few exceptions the mode of inheritance and the possible underlying gene mutations are not known for DCM in dogs. In humans mutations in several genes responsible for DCM have been identified. Comparative genetic analyses in dogs using genes causing DCM in men and a genome-wide scan with anonymus markers were not able to detect causative mutations or genomic regions harboring gene loci linked to DCM. The investigation of the genetic basis of canine DCM may lead to new insights into the pathogenesis of DCM and may result in new therapeutic approaches and breeding strategies.


Chikungunya emergency in China: microevolution and genetic analysis for a local outbreak.
A small-scale local chikungunya outbreak occurred in a Guangdong village of southern China in October 2010. The five chikungunya viruses (CHIKV) isolated from the epidemic and three other imported cases obtained from the same period were sequenced and analyzed for phylogenesis. The results demonstrated that all of the eight sequences were clustered in the Eastern, Central, Southern, and African group. However, the local strains and imported isolates showed different sequence variations. A226V in E1 gene and V264A in E2 gene were detected in all three imported isolates, the unique substitutions S250P in E1 gene and H313Y in E2 genes could be observed in four of the five local strains. These significant variations might be some of the causes for the outbreak. It would be an important event for CHIKV to have mutated adaption to the local mosquitoes in China, Aedes albopictus and Aedes aegypti.


Effects of age on rapid ankle torque development.
When balance is disturbed, often only fractions of a second are available in which to make the initial responses needed for its restoration. Abilities to develop joint torques rapidly may be critical to such responses. We undertook this study to quantify age effects among healthy adults in abilities to develop ankle joint torques rapidly. Ankle dorsiflexion (DF) and plantarflexion (PF) torque development during rapid isometric and during isokinetic (30, 60, 120, 180, and 240 deg/sec) exertions was assessed in 24 healthy young (mean age 23 years) and 24 healthy old adults (mean age 72 years). The effects of age, gender, and torque direction on the times needed to reach given torque magnitudes, maximum rates of isometric torque development (MRTD), and maximum isokinetic torques were examined. The old adults required substantially more time to reach given torque magnitudes than the young adults. For example, the young and old females needed approximately 236 and 337 msec to develop 15 Nm of DF torque, of which 141 and 164 msec were reaction times. Isometric MRTD were 25 to 36% lower in the old than in the young adults. The age declines in isometric torque development time were associated with losses in maximum isometric strength. Maximum isokinetic torques developed by the old were 20 to 40% lower than those of young adults. The percent losses in isokinetic torques with age were independent of joint angular velocity for PF, but increased with velocity for DF. We found substantial age declines in abilities of healthy old adults to rapidly develop ankle joint torques. The capacities of even healthy old adults to recover balance or to carry out other time-critical actions that require moderate-to-substantial strengths may be considerably degraded by these declines.


The relation between the phenomena of disease, illness, and suffering.
Persons experiencing disease and illness experience suffering as well. How nurses assess patients' problems holistically has been debated a lot. This article suggests one possible way of assessing patients' situation as a whole by seeing patients' diseases in relation to suffering.


Hydrogen bonding-enhanced micelle assemblies for drug delivery.
Ring-opening polymerization (ROP) of functionalized cyclic carbonates derived from 2,2-bis(methylol)propionic acid (bis-MPA) allows for incorporation of H-bonding urea-functional groups into block copolymers with a potential application of supramolecular drug-delivery systems. The strong H-bonding functionalities of poly(ethylene glycol)-block-poly(ethyl-random-urea carbonate) (PEG-P(E(1-x)-U(x))C) block copolymers not only lowered critical micelles concentration (cmc) of the block copolymer (to 1/4x) in aqueous environment compared to conventional PEG-poly(trimethylene carbonate) (PEG-PTMC) block copolymer without the non-covalent stabilization, but also improved kinetic stability of micelles and Dox-loaded micelles in the presence of a destabilizing agent. It was observed that the incorporation of anticancer drug doxorubicin affected the micellization process of block copolymers in water and caused a sudden increase in sizes of drug-loaded micelles above 200 nm. This phenomenon that can be a significant drawback in drug delivery applications was considerably mitigated in urea-bearing block copolymer/Dox micelles with simultaneously accompanying a significant improvement in drug loading. In vitro drug release profile showed that the increase in urea content led to a slight decrease in Dox release rate. Block copolymer did not have any significant cytotoxicity against HEK293 and HepG2 cells up to 400 mg/L. Importantly, Dox-loaded micelles exerted cytotoxic effect against HepG2 cells.


Endoscopic management of foreign bodies in the upper gastrointestinal tract: A review.
Foreign body ingestion is a common condition, especially among children who represent 80% of these emergencies. The most frequently ingested foreign bodies in children are coins, toys, magnets and batteries. Most foreign body ingestions in adults occur while eating, leading to either bone or meat bolus impaction. Flexible endoscopy is the therapeutic method of choice for relieving food impaction and removing true foreign bodies with a success rate of over 95% and with minimal complications. This review describes a comprehensive approach towards patients presenting with foreign body ingestion. Recommendations are based on a review of the literature and extensive personal experience.


Retroperitoneal Necrotizing Soft Tissue Infection in a Healthy Adult Masquerading as Acute Pancreatitis.
Necrotizing soft tissue infections (NSTIs) are polymicrobial infections with high morbidity and mortality. We report a case of retroperitoneal NSTI in an immunocompetent young male, with clinical symptoms and signs mimicking acute pancreatitis (pseudo-Cullen's and pseudo-Grey-Turner's signs. The initiating lesion was a pustule which progressed and mimics acute pancreatitis. CT scan showed features of retroperitoneal NSTI. After extensive debridement and antibiotics, the patient improved. NSTI of the retroperitoneum is rare. The absence of external clinical signs and anatomical barriers make the disease difficult to manage.


[Purpose of the practical training courses].
Laparoscopy surgery started in the 90's decade and it is rapidly developing in the first years of this century; it is therefore a very recent surgical alternative. This has made that each teams formation has gone along very different ways, today that we have already expert services it is essential to systematize the training and to shorten the learning curve. For that purpose we have the practical training courses that combine surgery in patients with surgery in experimental operating theatres, which are absolutely indispensable.


Roles of subunit NuoL in the proton pumping coupling mechanism of NADH:ubiquinone oxidoreductase (complex I) from Escherichia coli.
Respiratory complex I has an L-shaped structure formed by the hydrophilic arm responsible for electron transfer and the membrane arm that contains protons pumping machinery. Here, to gain mechanistic insights into the role of subunit NuoL, we investigated the effects of Mg2+, Zn2+ and the Na+/H+ antiporter inhibitor 5-(N-ethyl-N-isopropyl)-amiloride (EIPA) on proton pumping activities of various isolated NuoL mutant complex I after reconstitution into Escherichia coli double knockout (DKO) membrane vesicles lacking complex I and the NADH dehydrogenase type 2. We found that Mg2+ was critical for proton pumping activity of complex I. At 2 µM Zn2+, proton pumping of the wild-type was selectively inhibited without affecting electron transfer; no inhibition in proton pumping of D178N and D400A was observed, suggesting the involvement of these residues in Zn2+ binding. Fifteen micromolar of EIPA caused up to ∼40% decrease in the proton pumping activity of the wild-type, D303A and D400A/E, whereas no significant change was detected in D178N, indicating its possible involvement in the EIPA binding. Furthermore, when menaquinone-rich DKO membranes were used, the proton pumping efficiency in the wild-type was decreased significantly (∼50%) compared with NuoL mutants strongly suggesting that NuoL is involved in the high efficiency pumping mechanism in complex I.


Effect of low-density lipoproteins on apolipoprotein AI kinetics in heterozygous familial hypercholesterolemia.
In patients with heterozygous familial hypercholesterolemia (FH), both synthetic and clearance rates of high-density lipoproteins (HDL) are increased compared with control subjects. According to in vitro data on hepatocytes, the expanded pool size of low-density lipoproteins (LDL) in FH could partly explain the enhanced HDL production. Therefore, we have tested the hypothesis that a reduction of LDL pool size, achieved by LDL-apheresis, is associated with a downregulation of HDL synthesis. We studied the kinetics of HDL by infusing [5,5,5-(2)H(3)]-leucine in 7 heterozygous FH patients before and after 3 biweekly LDL-apheresis using dextran sulfate columns. Both plasma and LDL-cholesterol levels were decreased after LDL-apheresis (169 +/- 35 v 422 +/- 27 mg/dL, P <.05, and 85 +/- 19 v 327 +/- 52 mg/dL, P <.05, respectively). Plasma triglyceride level was unaffected (162 +/- 43 v 176 +/- 35 mg/dL, not significant [NS]) and HDL composition remained stable (HDL-cholesterol 29 +/- 6 v 37 +/- 7 mg/dL, NS, and HDL-triglyceride 20 +/- 6 v 19 +/- 8 mg/dL, NS). Plasma apolipoprotein AI (apo AI) was also similar (122 +/- 20 v 115 +/- 18 mg/dL, NS). Mean HDL-apo AI fractional catabolic rate (FCR) was slightly higher (0.41 +/- 0.07 v 0.36 +/- 0.14 pool/d, NS), and absolute production rate (APR) was increased (22.1 +/- 5.7 v 18.0 +/- 5.7 mg/kg/d, P <.05) after LDL-apheresis. These human kinetic data suggest that LDL do not play a major role on HDL production in heterozygous FH patients.


[The use of magnesium sulfate during surgery of pheochromocytoma: apropos of 2 cases].
Maintenance of haemodynamic stability during anaesthesia for phaeochromocytoma resection is still a challenge. If magnesium sulfate is widely used for the control of arterial pressure during preeclampsia, its use during phaeochromocytoma resection has only been published by one author. We describe two cases where magnesium sulfate is the main agent used to control arterial pressure during resection of a phaeochromocytoma. Magnesium sulfate's hypotensive, antiarrhythmic and antiadrenergic properties are reviewed. The total doses administered were 11 g and 12 g, given as an infusion and boluses. Magnesium sulfate could be part of the anaesthetist's pharmacopoeia during phaeochromocytoma resection.


Epitope mapping using gram-positive surface display.
Antibodies have proven to be invaluable tools for a vast number of applications during the last decades, including protein purification and characterization, medical diagnosis and imaging, and treatment using therapeutic antibiotics. No matter what the aims of the application are, the antibody's binding characteristics will still be the main features determining the assay's reliability. Here, we describe a protocol for determination of antibody-binding epitopes using an antigen-focused, library-based approach where library members are generated by fragmentation of antigen DNA and presented as cloned peptides on the cell surface of the Gram-positive bacterium Staphylococcus carnosus. The rigid cell structure of this organism allows for multivalent expression and permits rapid library analysis and sorting of antibody-binding cells using flow-sorting devices. Epitopes are determined by DNA sequencing of the sorted cells and alignment back to the antigen sequence. The protocol described here has been shown useful for mapping of both monoclonal and polyclonal binders with varying epitope lengths.


Danish Urogynaecological Database.
The Danish Urogynaecological Database is established in order to ensure high quality of treatment for patients undergoing urogynecological surgery. The database contains details of all women in Denmark undergoing incontinence surgery or pelvic organ prolapse surgery amounting to ~5,200 procedures per year. The variables are collected along the course of treatment of the patient from the referral to a postoperative control. Main variables are prior obstetrical and gynecological history, symptoms, symptom-related quality of life, objective urogynecological findings, type of operation, complications if relevant, implants used if relevant, 3-6-month postoperative recording of symptoms, if any. A set of clinical quality indicators is being maintained by the steering committee for the database and is published in an annual report which also contains extensive descriptive statistics. The database has a completeness of over 90% of all urogynecological surgeries performed in Denmark. Some of the main variables have been validated using medical records as gold standard. The positive predictive value was above 90%. The data are used as a quality monitoring tool by the hospitals and in a number of scientific studies of specific urogynecological topics, broader epidemiological topics, and the use of patient reported outcome measures.


Yeast protein kinase C.
The mammalian protein kinase C (PKC) superfamily plays regulatory roles in many different cellular processes. However, due to the many members that exist in cells, it is very complicated to present experimental evidence of the particular function of each member. In contrast, yeasts have only one or two PKC members and genetic tools have unveiled their role as main regulators of cell integrity. In this review, we will discuss the function of yeast protein kinase C homologues, their mechanism of activation and the signalling pathways that they regulate in two model yeasts, Saccharomyces cerevisiae and Schizosaccharomyces pombe.


Effect of the myb gene product on expression of the PCNA gene in fibroblasts.
Tk-ts13 cells are BHK-derived fibroblasts that have a G1-specific temperature sensitive (ts) mutation so that the cells arrest in the G1 phase of the cell cycle at the restrictive temperature of 39.6 degrees. We have introduced into these cells a plasmid carrying the human c-myb cDNA under the control of the early SV40 promoter. The resulting cell line, ts13 myb cells, express the c-myb RNA and protein and, when serum-stimulated, they undergo one round of DNA replication even at the restrictive temperature. Under the same conditions, the parent cell line (tk-ts13 cells) are blocked in G1 and fail to replicate DNA. We have investigated the expression of two late growth-regulated genes, PCNA and histone H3, in tk-ts13 and in ts 13 myb cells, both at permissive and restrictive temperature. At the permissive temperature of 34 degrees, the mRNA levels for PCNA and histone H3 increase markedly after serum stimulation in both cell lines, reaching a peak at the time of DNA synthesis. At the restrictive temperature of 39.6 degrees, the mRNA's for PCNA, and histone H3 are detectable in serum-stimulated ts13 myb cells while they are not detectable in the parent tk-ts13 cell line. Run-on transcription assays indicate that these 2 genes are transcribed in tk-ts13 cells equally well at permissive and nonpermissive temperatures, and that the presence of the myb product does not significantly increase their rates of transcription. The stability of the respective mRNA's is roughly the same at either temperature and in both types of cells. These results indicate: (1) a constitutively expressed c-myb gene product confers to fibroblasts the ability of temporarily by-passing a ts block in the G1 phase of the cell cycle and (2) the myb product, under these conditions, regulates the mRNA levels of PCNA and histone H3 either directly or indirectly by a post-transcriptional mechanism.


Polarity-reversible conjugate addition tuned by remote electronic effects.
A new concept, polarity-reversible conjugate addition, has been described, based on the findings that the polarity of a classical Michael acceptor can be reversed through remote electronic effects. In addition, the remote electronic effects are tunable, and both five- and six-membered nitrogen rings can be constructed starting from acyclic precursors having the same enone structure unit simply by varying a remote substituent in the molecules.


[Effect of fermented morel liquid on immunity function in mice].
The experiments studied the effect of fermented morel liquid on immunity function in mice [correction of rats]. The results showed that fermented morel liquid could greatly enhance the non-specific immunity (macrophage's phagocytosis), specific immunity (delayed-type hypersensitivity), humoral immunity (the amount of hemolysin) and the weights of thymus. The author concluded that the fermented morel liquid could effectively regulate the immunity function in mice [correction of rats].


Analysis and design of a genetic circuit for dynamic metabolic engineering.
Recent advances in synthetic biology have equipped us with new tools for bioprocess optimization at the genetic level. Previously, we have presented an integrated in silico design for the dynamic control of gene expression based on a density-sensing unit and a genetic toggle switch. In the present paper, analysis of a serine-producing Escherichia coli mutant shows that an instantaneous ON-OFF switch leads to a maximum theoretical productivity improvement of 29.6% compared to the mutant. To further the design, global sensitivity analysis is applied here to a mathematical model of serine production in E. coli coupled with a genetic circuit. The model of the quorum sensing and the toggle switch involves 13 parameters of which 3 are identified as having a significant effect on serine concentration. Simulations conducted in this reduced parameter space further identified the optimal ranges for these 3 key parameters to achieve productivity values close to the maximum theoretical values. This analysis can now be used to guide the experimental implementation of a dynamic metabolic engineering strategy and reduce the time required to design the genetic circuit components.