[Diabetic neuopathy].
In view of increasing number of elderly diabetic patients and their westernized lifestyle, diabetic foot and fractures due to fall attributable to diabetic neuropathy may be common diseases which disturb patients' QOL. Since any therapeutic drugs for patients with diabetic neuropathy have not been fully accepted, much attention should be paid to intensification of self-care for foot lesion and exercise and balance training through education. Some of them may show orthostatic hypotension, gastroparesis, etc. Others may complain of pain in limbs. Taken together, management for elderly diabetic patients may well be achieved through education and with symptomatic therapy.


Utilizing Lean Six Sigma Methodology to Improve the Authored Works Command Approval Process at Naval Medical Center San Diego.
Inefficiencies in the command approval process for publications and/or presentations negatively impact DoD Graduate Medical Education (GME) residency programs' ability to meet ACGME scholarly activity requirements. A preliminary review of the authored works approval process at Naval Medical Center San Diego (NMCSD) disclosed significant inefficiency, variation in process, and a low level of customer satisfaction. In order to facilitate and encourage scholarly activity at NMCSD, and meet ACGME requirements, the Executive Steering Council (ESC) chartered an interprofessional team to lead a Lean Six Sigma (LSS) Rapid Improvement Event (RIE) project. Two major outcome metrics were identified: (1) the number of authored works submissions containing all required signatures and (2) customer satisfaction with the authored works process. Primary metric baseline data were gathered utilizing a Clinical Investigations database tracking publications and presentations. Secondary metric baseline data were collected via a customer satisfaction survey to GME faculty and residents. The project team analyzed pre-survey data and utilized LSS tools and methodology including a "gemba" (environment) walk, cause and effect diagram, critical to quality tree, voice of the customer, "muda" (waste) chart, and a pre- and post-event value stream map. The team selected an electronic submission system as the intervention most likely to positively impact the RIE project outcome measures. The number of authored works compliant with all required signatures improved from 52% to 100%. Customer satisfaction rated as "completely or mostly satisfied" improved from 24% to 97%. For both outcomes, signature compliance and customer satisfaction, statistical significance was achieved with a p < 0.0001. This RIE project utilized LSS methodology and tools to improve signature compliance and increase customer satisfaction with the authored works approval process, leading to 100% signature compliance, a comprehensive longitudinal repository of all authored work requests, and a 97% "completely or mostly satisfied" customer rating of the process.


Recognition characteristics of an adaptive vesicular assembly of amphiphilic baskets for selective detection and mitigation of toxic nerve agents.
We used isothermal titration calorimetry to investigate the affinity of basket 1 (470 Å(3)) for trapping variously sized and shaped organophosphonates (OPs) 2-12 (137-244 Å(3)) in water at 298.0 K. The encapsulation is, in each case, driven by favorable entropy (TΔS° = 2.9 kcal/mol), while the enthalpic component stays small and in some cases endothermic (ΔH° ≥ -1 kcal/mol). Presumably, a desolvation of basket 1 and OP guests permits the inclusion complexation at room temperature via a "classical" hydrophobic effect. The amphiphilic basket 1 shows a greater affinity (ΔG° ≈ -5 to -6 kcal/mol), both experimentally and computationally, for encapsulating larger organophosphonates whose size and shape correspond to VX-type agents (289 A(3)). Importantly, baskets assemble into a vesicular nanomaterial (DH ≈ 350 nm) that in the presence of neutral OP compounds undergoes a phase transition to give nanoparticles (DH ≈ 250 nm). Upon the addition of an anionic guest to basket 1, however, there was no formation of nanoparticles and the vesicles grew into larger vesicles (DH ≈ 750 nm). The interconversion of the different nanostructures is reversible and, moreover, a function of the organophosphonate present in solution. On the basis of (1)H NMR spectroscopic data, we deduced that neutral guests insert deep into the basket's cavity to change its shape and thereby promote the conversion of vesicles into nanoparticles. On the contrary, the anionic guests reside at the northern portion of the host to slightly affect its shape and geometric properties, thereby resulting in the vesicles merely transforming into larger vesicles.


Intra-operatively measured spastic semimembranosus forces of children with cerebral palsy.
The knee kept forcibly in a flexed position is typical in cerebral palsy. Using a benchmark, we investigate intra-operatively if peak spastic hamstring force is measured in flexed knee positions. This tests the assumed shift of optimal length due to adaptation of spastic muscle and a decreasing force trend towards extension. Previously we measured spastic gracilis (GRA) and semitendinosus (ST) forces. Presently, we studied spastic semimembranosus (SM) and tested the following hypotheses: spastic SM forces are (1) high in flexed and (2) low in extended positions. We compared the data to those of GRA and ST to test (3) if percentages of peak force produced in flexed positions are different. During muscle lengthening surgery of 8 CP patients (9years, 4months; GMFCS levels=II-IV; limbs tested=13) isometric SM forces were measured from flexion (120°) to full extension (0°). Spastic SM forces were low in flexed knee positions (only 4.2% (3.4%) and 10.7% (9.7%) of peak force at KA=120° and KA=90° respectively, indicating less force production compared to the GRA or ST) and high in extended knee positions (even 100% of peak force at KA=0°). This indicates an absence of strong evidence for a shift of optimal muscle length of SM towards flexion.


Keratin Biomaterials Improve Functional Recovery in a Rat Spinal Cord Injury Model.
Laboratory study using a rat T9 contusion model of spinal cord injury (SCI). The purpose of this study was to evaluate which method of delivery of soluble keratin biomaterials would best support functional restoration through the macrophage polarization paradigm. SCI is a devastating neurologic event with complex pathophysiological mechanisms that currently has no cure. After injury, macrophages and resident microglia are key regulators of inflammation and tissue repair exhibiting phenotypic and functional plasticity. Keratin biomaterials have been demonstrated to influence macrophage polarization and promote the M2 anti-inflammatory phenotype that attenuates inflammatory responses. Anesthetized female Lewis rats were subjected to moderate T9 contusion SCI and randomly divided into: no therapy (control group), an intrathecally injected keratin group, and a keratin-soaked sponge group (n = 11 in all groups). Functional recovery assessments were obtained at 3- and 6-weeks post-injury (WPI) using gait analysis performed with the DigiGait Imaging System treadmill and at 1, 3, 7, 14, 21, 28, 35, and 42 days post-injury by the Basso, Beattie, Bresnahan (BBB) locomotor rating scale. Histology and immunohistochemistry of serial spinal cord sections were performed to assess injury severity and treatment efficacy. Compared to control rats, applying keratin materials after injury improved functional recovery in certain gait parameters and overall trended toward significance in BBB scores; however, no significant differences were observed with tissue analysis between groups at 6 WPI. Results suggest that keratin biomaterials support some locomotor functional recovery and may alter the acute inflammatory response by inducing macrophage polarization following SCI. This therapy warrants further investigation into treatment of SCI.Level of Evidence: N/A.


A review of EBV-positive mucocutaneous ulcers focusing on clinical and pathological aspects.
Epstein-Barr virus (EBV)-positive mucocutaneous ulcers (EBVMCUs) were first described as a lymphoproliferative disorder in 2010. Clinically, EBVMCUs are shallow, sharply circumscribed, unifocal mucosal or cutaneous ulcers that occur in immunosuppressed patients, including those with advanced age-associated immunosenescence, iatrogenic immunosuppression, primary immune disorders, and HIV/AIDS-associated immune deficiencies. In general, patients exhibit indolent disease progression and spontaneous regression. Histologically, EBVMCUs are characterized by the proliferation of EBV-positive, variable-sized, atypical B-cells. According to conventional histopathologic criteria, EBVMCUs may diagnosed as lymphomas. However, EBVMCUs are recognized as pseudomalignant lesions because they spontaneously regress without anti-cancer treatment. Therefore, overtreatment must be carefully avoided and multilateral differentiation is important. In this article, we reviewed previously reported EBVMCUs focusing on their clinical and pathological aspects in comparison with other EBV-positive B-cell neoplasms.


[A case of selective embolization in treatment of advanced tonsillar cancer hemorrhage].
This paper reports a case of recurrence of tonsillar cancer on the right 6 months after radiotherapy with pharyngeal hemorrhage for 4 days and aggravation in the next day. The pharyngeal hemorrhage was severe in the case and the maximum of single amount of bleeding was approximately 200 ml. The examination showed active bleeding on the ulcer with a diameter of 2 cm in the right tonsil and the depth of 1 cm. After repeated compression hemostasis proved to be invalid, selective embolization was applied on the patient and the symtoms of pharyngeal hemorrhage disappeared without complications. The patient was discharged after 2 weeks of observation without any recurrence of hemorrhage.


[Presuture: back-up technique in plastic surgery. Review of 18 cases].
The recent technique of "presuturing" has been used in 18 cases of skin lesions in which primary wound closure after resection would not have been possible without undermining. This method, which takes a few more minutes, on the day before the operation, allows an easier surgical closure after resection. Our case reports concern melanomas, giant nevi, Bowen's disease and tattoos measuring 6 to 84 cm2. Some sites respond better than others to presuturing. The cosmetic gain for the patient confirms the surgical gain of this method.


Total synthesis of the tiacumicin B (lipiarmycin A3/fidaxomicin) aglycone.
Tiacumicin B (lipiarmycin A3, fidaxomicin) is an atypical macrolide antibiotic which is used for the treatment of Clostridium difficile infections. Tiacumicin B is also a potent inhibitor of Mycobacterium tuberculosis, but due to its limited oral bioavailability is unsuitable for systemic therapy. To provide a basis for structure-activity studies that might eventually lead to improved variants of tiacumicin B, we have developed an efficient approach to the synthesis of the tiacumicin B aglycone. The synthesis features a high-yielding intramolecular Suzuki cross-coupling reaction to effect macrocyclic ring closure. Key steps in the synthesis of the macrocyclization precursor were a highly selective, one-pot Corey-Peterson olefination and an ene-diene cross-metathesis reaction. Depending on the reaction conditions, the final deprotection delivered either the fully deprotected tiacumicin B aglycone or partially protected versions thereof.


Radical hysterectomy for stage IB1 cervical carcinoma: lymph node metastasis as a prognostic factor.
Lymph node metastasis is one of the most important factors influencing prognosis and further therapy in patients with cervical carcinoma. The aim of this study was to confirm the impact of nodal metastasis od disease-free interval in women with stage IB1 cancer of the uterine cervix. From June 1986 to December 1999 269 patients with stage IB1 cervical carcinoma were operated on. Two hundred thirty-six (87.84%) patients had class III and 33 (12.16%) class II radical hysterectomy, according to Piver's classification. The median number of the removed lymph nodes was 21. Positive lymph nodes were found in 71 (25.28%) patients. All patients with positive lymph nodes received postoperative adjuvant external beam radiotherapy. Patients with bulky nodal disease received also chemotherapy.Overall 5-year disease-free interval in 212 patients was 80%. Five-year disease-free interval for patients without lymph node metastasis was 91%, while it was 40% in those with lymph node metastasis (p < 0.0001). Surgical staging of cervical cancer, which includes pelvic and para-aortic lymphadenectomy,together with pathological data, can provide potentially useful information for the radiation oncologist and precise analysis of survival and prognostic risk factors.


Radiologic-pathologic correlation from the Armed Forces Institute of Pathology. Lymphangiomyomatosis.
The radiologic patterns caused by interstitial lung disease evoke a long list of differential diagnostic possibilities. Though the problem may at first seem insoluble, subdivision into conditions that spare the pulmonary architecture, as opposed to those that lead to an end-stage "honeycomb lung", and consideration of the clinical findings will frequently narrow down the list. Occasionally, key associated findings such as pleural effusion, pneumothorax, and systemic involvement of many organs will help rule out inappropriate diagnoses. Lymphangiomyomatosis is a rare cause of "honeycomb lung" that may result in a very specific combination of radiologic and clinical findings.


Development of a decision model for the techno-economic assessment of municipal solid waste utilization pathways.
Economic competitiveness is one of the key factors in making decisions towards the development of waste conversion facilities and devising a sustainable waste management strategy. The goal of this study is to develop a framework, as well as to develop and demonstrate a comprehensive techno-economic model to help county and municipal decision makers in establishing waste conversion facilities. The user-friendly data-intensive model, called the FUNdamental ENgineering PrinciplEs-based ModeL for Estimation of Cost of Energy and Fuels from MSW (FUNNEL-Cost-MSW), compares nine different waste management scenarios, including landfilling and composting, in terms of economic parameters such as gate fees and return on investment. In addition, a geographic information system (GIS) model was developed to determine suitable locations for waste conversion facilities and landfill sites based on integration of environmental, social, and economic factors. Finally, a case study on Parkland County and its surrounding counties in the province of Alberta, Canada, was conducted and a sensitivity analysis was performed to assess the influence of the key technical and economic parameters on the calculated results.


Ion aggregation in concentrated aqueous and methanol solutions of polyoxometallates Keggin anions: the effect of counterions investigated by molecular dynamics simulations.
Aqueous solutions of the polyoxometallate alpha-PW(12)O(40)(3-) Keggin anion "PW(3-)" have been simulated by molecular dynamics, comparing two anion concentrations (0.06 and ca. 0.15 mol l(-1)) and Cs(+), NBu(4)(+), UO(2)(2+), Eu(3+), H(3)O(+) and H(5)O(2)(+) as neutralizing M(n+) counterions. They reveal marked counterion effects of the degree of salt dilution, cation-anion and anion-anion relationships. The hydrophobic NBu(4)(+) cations tend to surround PW(3-)'s via loose contacts, leading to "phase separation" between water and a humid salty domain, overall neutral, where all ions are concentrated. The other studied cations are more hydrophilic and generally separated from the PW(3-) anions. The most important finding concerns the aggregation of PW's, mostly as dimers with short contacts (PP < 12 A), but also as higher (PW(3-))(n) oligomers (n = 3 to 5) in concentrated solutions where the proportion of the aggregates ranges from ca. 9 to 46%, depending on the counterion. While Eu(3+) and UO(2)(2+) are fully hydrated and interact at short distances with PWs as solvent-separated ion pairs, Cs(+) can form contact ion pairs, as well as solvent-separated ions. Among the mono-charged counterions, H(5)O(2)(+) gives highest aggregation (ca. 47%, involving 32% of dimers, 11% of trimers and 3% of tetramers), pointing to the influence of the proton state (H(5)O(2)(+)vs. H(3)O(+)) on PW's aggregation and condensation. The dynamic properties are also dependent on M(n+): the PW's diffusion coefficients are lowest with NBu(4)(+), and highest for Cs(+), thus reflecting the degree of ion condensation in water. The role of water on the solution state of the PW salts is further demonstrated by simulating the most concentrated systems in methanol solution. Because MeOH solvates less well the M(n+) cation than does H(2)O and cannot afford bridging relays between PW's, one finds a higher proportion of PW(3-)M(n+) contacts, and no (PW(3-))(n) oligomers with short contacts in methanol.


Preparation and evaluation of enteric coated tablets of hot-melt extruded lansoprazole.
The objective of this work was to use hot-melt extrusion (HME) technology to improve the physiochemical properties of lansoprazole (LNS) to prepare stable enteric coated LNS tablets. For the extrusion process, we chose Kollidon® 12 PF (K12) polymeric matrix. Lutrol® F 68 was selected as the plasticizer and magnesium oxide (MgO) as the alkalizer. With or without the alkalizer, LNS at 10% drug load was extruded with K12 and F68. LNS changed to the amorphous phase and showed better release compared to that of the pure crystalline drug. Inclusion of MgO improved LNS extrudability and release and resulted in over 80% drug release in the buffer stage. Hot-melt extruded LNS was physically and chemically stable after 12 months of storage. Both formulations were studied for compatibility with Eudragit® L100-55. The optimized formulation was compressed into a tablet followed by coating process utilizing a pan coater using L100-55 as an enteric coating polymer. In a two-step dissolution study, the release profile of the enteric coated LNS tablets in the acidic stage was less than 10% of the LNS, while that in the buffer stage was more than 80%. Drug content analysis revealed the LNS content to be 97%, indicating the chemical stability of the enteric coated tablet after storage for six months. HME, which has not been previously used for LNS, is a valuable technique to reduce processing time in the manufacture of enteric coated formulations of an acid-sensitive active pharmaceutical ingredient as compared to the existing methods.


Free oligosaccharides with Lewis x structure expressed in the segmentation period of zebrafish embryo.
We previously reported that zebrafishalpha1-3fucosyltrasferase 1 (zFT1) was expressed in embryos at the segmentation period, and was capable of synthesizing the Lewis x epitope [Gal beta1-4(Fuc alpha1-3)GlcNAc] [Kageyama et.al, J. Biochem., 125, 838-845 (1999)]. In the current study, we attempted to detect the enzyme products of zFT1 in zebrafish embryos. Oligosaccharides were prepared from the zebrafish embryos at 12, 18 and 48 h after fertilization and labelled with a fluorophore, 2-aminopyridine, for highly sensitive detections. Pyridylamino (PA)-oligosaccharides that were alpha1-3/4fucosidase sensitive and time-dependently expressed at 18 h after fertilization were identified as candidates for the in vivo products synthesized by zFT1. Structures of these oligosaccharides were determined by a combination of exoglycosidase digestions and two-dimensional HPLC sugar mapping to be the biantennary complex-type structures with two Lewis x epitopes: (Gal beta1-4)(0,1,2)-{Gal beta1-4(Fuc alpha1-3)GlcNAc beta1-2Man alpha1-6[Gal beta1-4(Fuc alpha1-3)GlcNAc beta1-2Man alpha1-3]}Man beta1-4GlcNAc, and (Gal beta1-4)(0,1)-{Gal beta1-4(Fuc alpha1-3)GlcNAc beta1-2Man alpha1-6[Gal beta1-4(Fuc alpha1-3)GlcNAc beta1-2Man alpha1-3]} Man beta1-4GlcNAc beta1-4GlcNAc. The presence of Lewis x structure of these oligosaccharides together with their expression time suggests that they are products of zFT1. Remarkably, most of these oligosaccharides were free form. Furthermore, we detected an endo-beta-N-acetylglucosaminidase activity in the 18 h embryo. These results suggest that the oligosaccharides synthesized by zFT1 are present in the embryo at the segmentation period in free form, owing to the liberation from glycoproteins with endo-beta-N-acetylglucosaminidase(s) and/or glycoamidase(s).


Inter- and Intraobserver Agreement of Canine and Feline Nervous System Tumors.
In routine diagnostic activity, pathologists may be confronted with nervous system tumors. The lack of clinical information, economic restrictions for additional testing, and the lack of expertise in neuropathology may render the diagnosis challenging. The goals of this study were to assess the agreement in diagnosing nervous system tumors in domestic carnivores among 4 board-certified surgical pathologists without particular expertise in neuropathology and a neuropathologist expert, and to investigate the utility of special stains frequently used in routine diagnostic laboratories. Forty-six tumors (7 cats, 38 dogs, and 1 unknown carnivore) were retrieved and 1 hematoxylin and eosin-stained slide per tumor was selected. Diagnoses (tumor type and subtype) were formulated based on histological features and available clinical information. Confidence in the diagnosis was also scored. Subsequently, a panel of histochemical and immunohistochemical stains (Gordon Sweet silver stain and immunohistochemistry for AE1/AE3, vimentin, glial fibrillary acid protein, S100, neuron-specific enolase and neurofilament) was evaluated by the pathologists, who either confirmed or changed their original diagnoses. Intraobserver and interobserver agreement and confidence in relation to diagnosis before and after analysis of special stains were assessed. The use of special stains increased the complete agreement among surgical pathologists, with regard to tumor type, from 63% to 74%. Cases with a high confidence score had a higher interobserver agreement than cases with a low confidence score. These results suggest that pathologists without expertise in neuropathology agree in the diagnosis of most nervous system tumors, and special stains available in most laboratories only slightly increase this agreement.


The pattern of failure and predictors of locoregional control in lateralized buccogingival cancer after postoperative radiation therapy.
To evaluate the failure pattern and identify predictors of locoregional control in lateralized buccogingival cancer after postoperative radiotherapy (RT) at a single institution. We retrospectively reviewed the clinical data of 150 patients with lateralized oral squamous cell carcinoma, including carcinoma of the buccal mucosa, gingiva and retromolar trigone. All patients underwent radical surgery followed by postoperative RT with or without concurrent chemotherapy. We registered planning computer tomography images with images obtained at recurrence and categorized the failure pattern as in-field, marginal, or out-field recurrence. The median follow-up duration was 47 months (range, 2-131 months). Twenty-eight patients (19%) experienced locoregional failure, including 20 local failure, 5 regional failure and 3 with both. Among the 24 patients who had image studies at recurrence, 15 patients had in-field recurrence, 5 were marginal recurrence and 4 were out-field recurrence. Seven patients (5%) had contralateral neck failure. Four of 5 patients with marginal failure had recurrent tumors in the infratemporal fossa. In multivariate analysis, extracapsular spread and positive or close surgical margin were associated with poor locoregional control. Local in-field recurrence is the most common failure pattern in lateralized buccogingival cancer after postoperative RT. The infratemporal fossa is a risk area for marginal failure and should be encompassed adequately in the postoperative RT field. Extracapsular spread and positive or close margin are predictors of locoregional control for lateralized oral cancer. Patients exhibiting such adverse features require more aggressive treatment.


Investigation and evaluation of a 3D-printed optical modified cultivation vessel for improved scattered light measurement of biotechnologically relevant organisms.
In the field of bioprocess development miniaturization, parallelization and flexibility play a key role reducing costs and time. To precisely meet these requirements, additive manufacturing (3D-printing) is an ideal technology. 3D-printing enables rapid prototyping and cost-effective fabrication of individually designed devices with complex geometries on demand. For successful bioprocess development, monitoring of process-relevant parameters, such as pH, dissolved oxygen (DO), and biomass, is crucial. Online monitoring is preferred as offline sampling is time-consuming and leads to loss of information. In this study, 3D-printed cultivation vessels with optical prisms are evaluated for the use in upstream processes of different industrially relevant microorganisms and cell lines. It was shown, that the 3D-printed optically modified well (OMW) is of benefit for a wide range of biotechnologically relevant microorganisms and even for mammalian suspension cells. Evaluation tests with Escherichia coli, Bacillus subtilis, Saccharomyces cerevisiae, and Chinese hamster ovary (CHO) cells were performed, providing highly reproducible results. Growth behavior of OMW cultures was comparable to behavior of shake flask (SF) cultivations and the signal to noise ratio in online biomass measurement was shown to be reduced up to 95.8% by using the OMW. Especially the cultivation phases with low turbidity respective optical densities below 1.0 rel.AU could be monitored accurately for the first time. Furthermore, it was demonstrated that the 3D-printed optics are transferable to different well geometries and sizes, enabling efficient biomass monitoring for individual requirements with tailor-made 3D-printed cultivation vessels in small scale.


Using the deformable mirror as a spatial filter: application to circular beams.
Adaptive optics correction of a wave front by a deformable mirror that acts as a lossless spatial filter is studied. The decomposition of the wave front into Zernike polynomials provides a means for deriving the rms error of a corrected wave front in analytic form. The spatial filter is given in a functional form related to deformable mirror characteristics. A step filter approximation is derived and the conditions where the approximation holds are examined. An example is provided to demonstrate the utility of the spatial filtering concept for adaptive optics systems analysis.


Emerging trends in silicosis research: a scientometric review.
Silicosis is a global disease whose prevention efforts cannot be ignored today. Although numerous silicosis-related data have been published recently, emphasizing the characteristics and nature of silicosis, a summary of the developmental laws of research is lacking, especially in the visual analysis of the literature. We aim to address this issue through a scientometric review. The Web of Science Core Collection and the All Databases were searched with "silicosis" as the topic, excluding unrelated publications, and obtained data from 9802 and 1613 publications, respectively. The data was then analyzed using the Web of Science's online scientometric analysis function and CiteSpace's visual analysis functionality, including publication volume analysis, co-occurrence analysis, co-citation analysis, cluster analysis, and explosive detection. The results identify the "respiratory system" as the most influential area over a century. Furthermore, the publication's number was correlated with the gross domestic product. We ranked countries and institutions based on the frequency of publications and discovered that Europe, the USA, and China are the leading regions for silicosis research, with the USA and Europe having a stronger influence. Many reports related to artificial stone and denim jean production have been studied through citation analysis, indicating new epidemic trends in silicosis. Besides, silicosis-related diseases and the pathogenesis of silicosis were the research hotspots of silicosis through co-occurrence keyword analysis and outbreak detection. Furthermore, related diseases include coal workers' pneumoconiosis and tuberculosis, while the mechanism of silicosis includes studies on inflammation and fibrosis, oxidative stress, alveolar macrophages, apoptosis, and pathways.


Fractures of the proximal third of femur.
Requests for '? fractured neck of femur' form a major part of the work in the accident and emergency X-ray department today. Good quality radiographs are essential for the correct diagnosis to be made. The type of fracture shown, together with age and health of the patient, will determine the repair undertaken. Regular radiography of the fracture site will demonstrate any subsequent local complications.


Lipoblastoma in head and neck--a rare childhood tumour.
Lipoblastoma is an uncommon benign mesenchymal tumour that occurs primarily in children younger than 3 yrs of age. Despite the lesions being benign, great difficulty can be encountered in its management because of its tendency to invade the different fascial planes. A rare case of huge lipoblastoma diagnosed in a 22 months old child, involving various spaces of face and skull base has been reported. This huge tumour was completely and successfully removed through cheek incision without any postoperative complications.


Electroencephalographic characterization of subgroups of children with learning disorders.
Electroencephalographic alterations have been reported in subjects with learning disorders, but there is no consensus on what characterizes their electroencephalogram findings. Our objective was to determine if there were subgroups within a group of scholars with not otherwise specified learning disorders and if they had specific electroencephalographic patterns. Eighty-five subjects (31 female, 8-11 years) who scored low in at least two subscales -reading, writing and arithmetic- of the Infant Neuropsychological Evaluation were included. Electroencephalograms were recorded in 19 leads during rest with eyes closed; absolute power was obtained every 0.39 Hz. Three subgroups were formed according to children's performance: Group 1 (G1, higher scores than Group 2 in reading speed and reading and writing accuracy), Group 2 (G2, better performance than G1 in composition) and Group 3 (G3, lower scores than Groups 1 and 2 in the three subscales). G3 had higher absolute power in frequencies in the delta and theta range at left frontotemporal sites than G1 and G2. G2 had higher absolute power within alpha frequencies than G3 and G1 at the left occipital site. G3 had higher absolute power in frequencies in the beta range than G1 in parietotemporal areas and than G2 in left frontopolar and temporal sites. G1 had higher absolute power within beta frequencies than G2 in the left frontopolar site. G3 had lower gamma absolute power values than the other groups in the left hemisphere, and gamma activity was higher in G1 than in G2 in frontopolar and temporal areas. This group of children with learning disorders is very heterogeneous. Three subgroups were found with different cognitive profiles, as well as a different electroencephalographic pattern. It is important to consider these differences when planning interventions for children with learning disorders.


Multifactorial mortality in bongos and other wild ungulates in the north of the Congo Republic.
Wildlife mortality involving bongos, Tragelaphus eurycerus, and other ungulates was investigated in the north of the Congo Republic in 1997. Four bongos, one forest buffalo, Syncerus caffer nanus, and one domestic sheep were examined and sampled. Although an outbreak of rinderpest had been suspected, it was found that the animals, which had been weakened by an Elaeophora sagitta infection and possibly also by adverse climatic conditions, had been exsanguinated and driven to exhaustion by an unusual plague of Stomoxys omega.


Evaluation of three immunoassays used for detection of anti-rubella virus immunoglobulin M antibodies.
Three automated assays (Abbott AxSYM, Bayer ADVIA Centaur, and bioMerieux VIDAS) used for the detection of rubella virus-specific immunoglobulin M were evaluated. A total of 57 samples from individuals with evidence of infection with rubella virus were used to estimate sensitivity, and 220 samples from blood donors and individuals attending an antenatal clinic who had no evidence of recent infection were used to estimate specificity. Seroconversion panels comprising an additional 31 samples from four individuals were used to determine clinical sensitivity. Samples containing potentially cross-reacting substances were also tested. The sensitivities of the three assays ranged from 84.2 to 96.5%, and the specificities ranged from 96.8 to 99.9%. The Abbott AxSYM assay detected more reactive samples than the other two assays when a panel of 57 positive samples was tested. Bayer ADVIA Centaur detected more reactive samples in the seroconversion panels than the other two assays. All three assays evaluated reported a reactive result in 1 or more of the 48 samples containing potentially cross-reacting analytes. The assays demonstrated comparable performance in testing of a well-characterized panel of samples.


Adapting low-adhesive thin films from mixed polymer brushes.
The concept of the responsive/adaptive mixed polymer brushes was applied to the development of the thin film coatings possessing low adhesive properties that were evaluated with AFM probes in different media. Mixed brushes composed of polydimethylsiloxane (PDMS) and polyethyleneoxide (PEO) revealed a selective layered segregation in air and water. Immersion of the sample into an aqueous environment drove PEO chains to the brush-water interface while upon drying the surface undergoing reconstruction and was occupied with PDMS. Low interfacial energies of PDMS in air and PEO in water provided low-adhesive properties of the PDMS-PEO brushes to the probes in both media due to the spontaneous and rapid reconstruction of the mixed brush.


Cognitive decline correlates with low plasma concentrations of copper in patients with mild to moderate Alzheimer's disease.
Alzheimer's disease (AD) is a devastating brain disorder clinically characterised by progressive loss of characteristic cognitive abilities. Increasing evidence suggests a disturbed copper (Cu) homeostasis to be associated with the pathological processes. In the present study we analysed the plasma Cu levels and cognitive abilities using the Alzheimer's disease Assessment Scale-cognitive subscale (ADAS-cog) in 32 patients with mild to moderate AD. Statistical analysis revealed a negative correlation between plasma Cu levels and cognitive decline (r=-0.49; P<0.01). Patients with low plasma Cu (mean 82 +/- SD 9) had significant higher ADAS-cog values (mean 23 +/- SD 7), than patients with medium plasma Cu (mean 110 +/- SD 7), who exhibited lower ADAS-cog scores (mean 16 +/- SD 4; ANOVA, P<0.0001). Despite the fact that all patients had plasma Cu levels within the physiological range between 65 microg and 165 microg/dL, 87.5% of the patients revealed a significant negative correlation between plasma Cu and ADAS-cog. This finding supports the hypothesis of a mild Cu deficiency in most AD patients.


The health status of newly arrived Syrian refugees at the Refugee Health Service, South Australia, 2016.
Prior to the armed conflict, Syria had undergone an epidemiologic transition in disease burden from communicable to non-communicable diseases. Therefore, it is likely that the health status of Syrian refugees would be different from other refugee cohorts. The aim of this study was to describe the health status of Syrian refugees seen at the Refugee Health Service in South Australia in 2016. A cross-sectional study was conducted, and data were collected from medical records. Variables included demographics, infectious diseases, nutritional deficiencies, non-communicable diseases, mental illness and distress, and physical disabilities. The results of the study identified a relatively young cohort with large families. The prevalence of infectious diseases was low (<10%), whereas there was a high prevalence of vitamin and micronutrient deficiencies. The rates of chronic disease in adults were high, as were the chronic disease risk factors (overweight/obesity and smoking). In the adult population, 26.9% reported symptoms such as anxiety, depressed mood and poor sleep. The findings are consistent with the transitioning burden of communicable to non-communicable disease and chronic diseases in the Syrian population. The study reinforces the importance of comprehensive health screening for new arrival refugees. A validated mental health screening tool was not used, and this requires further research.


A targeted enzyme approach to sensitization of tyrosine kinase inhibitor-resistant breast cancer cells.
Gefitinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) of potential use in patients with breast cancer. Unfortunately, in clinical studies, gefitinib is often ineffective indicating that resistance to EGFR inhibitors may be a common occurrence in cancer of the breast. EGFR has been shown to be overexpressed in breast cancer, and in particular remains hyperphosphorylated in cell lines such as MDA-MB-468 that are resistant to EGFR inhibitors. Here, we investigate the cause of this sustained phosphorylation and the molecular basis for the ineffectiveness of gefitinib. We show that reactive oxygen species (ROS), known to damage cellular macromolecules and to modulate signaling cascades in a variety of human diseases including cancers, appear to play a critical role in mediating EGFR TKI-resistance. Furthermore, elimination of these ROS through use of a cell-penetrating catalase derivative sensitizes the cells to gefitinib. These results suggest a new approach for the treatment of TKI-resistant breast cancer patients specifically, the targeting of ROS and attendant downstream oxidative stress and their effects on signaling cascades.


Parliamentarians' strategies for policy evaluations.
This article considers the question of which strategies parliamentarians pursue when they use parliamentary requests demanding an evaluation. In order to be re-elected or to achieve desirable policies, parliamentarians can either appeal to their constituency or to their party by adopting legislative roles. The study is based on twelve case studies of parliamentary requests from the Swiss parliament between 2010 and 2014. The analysis shows that parliamentarians of legislative committees submit parliamentary requests to oppose a policy, while parliamentarians of oversight committees submit parliamentary requests to obtain information on specific policies. On the contrary, the party membership of the responsible Federal Councillor does not influence the strategy. These findings suggest that parliamentarians use evaluations as an instrument rather than using the actual findings. This conclusion might be very relevant to understand how evaluations are used in the political process.


Novel Strategies Using Total Gastrodin and Gastrodigenin, or Total Gastrodigenin for Quality Control of Gastrodia elata.
Gastrodia elata Blume (G. elata), a traditional Chinese medicine, is widely used for treatment of various neuro dysfunctions. However, its quality control is still limited to the determination of gastrodin. In the present study, two novel strategies based on quantitative evaluation of total gastrodin and gastrodigenin with base hydrolysis and total gastrodigenin with base-enzymatic hydrolysis followed by HPLC-FLD were put forward and successfully applied to evaluate the quality of 47 batches of G. elata from eight localities. Meanwhile, a systematic comparison of the novel strategy with the multiple markers and the Pharmacopeia method was performed. The results showed that the parishins category could be completely hydrolyzed to gastrodin by sodium hydroxide solution, and gastrodin could further utterly hydrolyze to gastrodigenin with β-d-glucosidase buffer solution. The contents of total gastrodin and gastrodigenin ranged from 1.311% to 2.034%, and total gastrodigenin from 0.748% to 1.120% at the eight localities. From the comparison, we can conclude that the two novel strategies can comprehensively reveal the characteristics of overall active ingredients in G. elata for quality control. The present study provides a feasible and credible strategy for the quality control of G. elata, suggesting a revision of the latest Chinese Pharmacopoeia or European Pharmacopoeia methods for the modernization of G. elata use.


Habitat Effects on the Breeding Performance of Three Forest-Dwelling Hawks.
Habitat loss causes population declines, but the mechanisms are rarely known. In the European Boreal Zone, loss of old forest due to intensive forestry is suspected to cause declines in forest-dwelling raptors by reducing their breeding performance. We studied the boreal breeding habitat and habitat-associated breeding performance of the northern goshawk (Accipiter gentilis), common buzzard (Buteo buteo) and European honey buzzard (Pernis apivorus). We combined long-term Finnish bird-of-prey data with multi-source national forest inventory data at various distances (100-4000 m) around the hawk nests. We found that breeding success of the goshawk was best explained by the habitat within a 2000-m radius around the nests; breeding was more successful with increasing proportions of old spruce forest and water, and decreasing proportions of young thinning forest. None of the habitat variables affected significantly the breeding success of the common buzzard or the honey buzzard, or the brood size of any of the species. The amount of old spruce forest decreased both around goshawk and common buzzard nests and throughout southern Finland in 1992-2010. In contrast, the area of young forest increased in southern Finland but not around hawk nests. We emphasize the importance of studying habitats at several spatial and temporal scales to determine the relevant species-specific scale and to detect environmental changes. Further effort is needed to reconcile the socioeconomic and ecological functions of forests and habitat requirements of old forest specialists.


Metabolic Interaction between Ammonia and Baicalein.
Ammonia is treated as a primary waste product of cellular metabolism in vivo and can contribute to the alteration of neurotransmission, oxidative stress, and cerebral edema and astrocyte swelling when its concentration in the brain is high. The objective of this study was to determine whether bioactive polyphenol baicalein had the capacity to trap ammonia in vitro and in vivo. Under in vitro conditions, baicalein rapidly reacted with ammonia to generate two monoaminated products and one diaminated product under different reaction times. These three major aminated products were purified from the reaction mixture, and their structures were characterized as 5-NH2-baicalein, 6-NH2-baicalein, and 5,6-di-NH2-baicalein based on the analysis of their HR-MS and 1D- and 2D-NMR data. In mice, both 5-NH2-baicalein and 6-NH2-baicalein were detected in 24 h fecal and urine samples collected from mice treated with baicalein (200 mg/kg) through oral gavage, and 6-NH2-baicalein was also detected in mouse plasma and brain samples collected at 0.5 h after baicalein treatment. Significant amounts of 6-NH2-baicalein were detected in all mouse samples including feces, urine, plasma, and brain. The levels of 6-NH2-baicalein in feces and urine were significantly higher than those of 5-NH2-baicalein. Furthermore, the average level of 6-NH2-baicalein was very close to that of baicalein (3.62 vs 3.77 ng/g) in mouse brain, suggesting it is possible that baicalein has the capacity to be absorbed rapidly into the circulation system and then cross the blood-brain barrier into the brain to detoxify ammonia in the blood and brain. In conclusion, this study confirmed that baicalein, a flavonoid with a vic-trihydroxyl structure on the A-ring, has the potential to detoxify ammonia and treat ammonia-associated chronic diseases.


Transforming breast reconstruction: the pioneering role of artificial intelligence in preoperative planning.
Autologous breast reconstruction surgery is a vital part of the recovery process for patients with breast cancer. While various reconstructive options exist, the deep inferior epigastric artery perforator (DIEP) flap is often favoured for its ability to closely mimic natural breast tissue. However, the complex vascular anatomy associated with the deep inferior epigastric artery (DIEA) presents challenges for surgeons during DIEP flap execution. Preoperative imaging, such as computed tomography angiography (CTA), is commonly used to understand vascular architecture and aid in selecting appropriate perforators. Conventional reporting of CTA scans is a labour-intensive process that can be challenging and requires specific expertise. The integration of artificial intelligence (AI) and machine learning (ML) algorithms in medical imaging has the potential to address these challenges. AI can enhance CTA through improved data acquisition, image post-processing, and potentially interpretation. By automating the perforator selection process, AI applications can significantly reduce the time spent on preoperative imaging analysis and potentially improve accuracy and reliability. While AI shows promise in optimizing efficiency, accuracy, and reliability in breast reconstruction planning, challenges and ethical considerations need to be addressed. This article explores the challenges, opportunities, and future directions of using AI in the preoperative planning of autologous breast reconstruction.


Hemifacial Microsomia in a Cat.
A 7-month-old domestic medium hair cat presented with facial asymmetry affecting the bony and soft tissue structures of the right side of the head including the maxilla, nose, eye and pinna of the ear. Additionally, neurological dysfunction of the facial and vestibulocochlear nerves on the affected side was present. A congenital malformation affecting the first and second embryologic pharyngeal arches was suspected. This is the first case of hemifacial microsomia of likely congenital origin reported in a cat.


APG-1252-12A induces mitochondria-dependent apoptosis through inhibiting the antiapoptotic proteins Bcl-2/Bcl-xl in HL-60 cells.
Acute myeloid leukemia (AML) is the most common acute leukemia in adults. Despite improved remission rates, current treatment regimens for AML are often associated with a very poor prognosis and adverse effects, necessitating more effective and safer agents. B-cell leukemia/lymphoma 2 (Bcl-2) family proteins regulate apoptotic pathway that can be targeted with small molecule inhibitors. APG-1252-12A is a Bcl-2 homology (BH)-3 mimetic that specifically binds to Bcl-2 and Bcl-xl, which has shown efficacy in some Bcl-2 dependent hematological cancers. In this study, we investigated whether APG-1252-12A inhibits the growth of five leukemia cell lines in a concentration- or time-dependent manner by MTS assay. Following treatment of AML cell line HL-60 with this compound, cell apoptosis was detected using flow cytometry and nuclear condensation was observed after Hoechst 33258 dye. Immunoblotting for cytochrome c, cleaved caspase-3 and PARP-1 cleavage was used to demonstrate the mechanism of inducing mitochondria-dependent apoptosis by APG-1252-12A. Our findings showed that this new compound inhibited cell proliferation in five leukemia cell lines and induced apoptotic death. There was a link between the level of Bcl-2 protein and IC50. APG-1252-12A targeted mitochondria and induced caspase-dependent apoptosis by inducing the HL-60 cell cytochrome c released, PARP cleavage and caspase activation. These data suggested that APG-1252-12A is a candidate drug for the in vivo analysis and clinical evaluation in AML.


Size- and Morphology-Dependent Auger Recombination in CsPbBr3 Perovskite Two-Dimensional Nanoplatelets and One-Dimensional Nanorods.
CsPbX3 (X = Cl, Br, I) perovskite nanocrystals (NCs), including zero-dimensional (0D) quantum dots (QDs), one-dimensional (1D) nanorods (NRs), and two-dimensional (2D) nanoplatelets (NPLs), have shown promising performances in light-emitting diode (LED) and lasing applications. However, Auger recombination, one of the key processes that limit their performance, remains poorly understood in CsPbX3 2D NPLs and 1D NRs. We show that the biexciton Auger lifetimes of CsPbBr3 NPLs (NRs) scale linearly with the NPL lateral area (NR length) and deviates from the "universal volume scale law" that has been observed for QDs. These results are consistent with a model in which the Auger recombination rate for 1D NRs and 2D NPLs is a product of binary collision frequency in the nonquantum confined dimension and Auger probability per collision. Comparisons of Auger recombination in CsPbBr3 NCs of different dimensionalities and similar band gaps suggest that Auger probability increases in NCs with a higher number of confined dimensions. Compared to CdSe and PbSe NCs with the same dimensionalities and similar sizes, Auger recombination rates in 0D-2D CsPbBr3 NCs are over 10-fold faster. Fast Auger recombination in CsPbBr3 NCs shows their potentials for Auger-assisted up-conversion and single photon source, while suppressing Auger recombination may further enhance their performances in LED and lasing applications.


Lights and shades on an historical vaccine canine distemper virus, the Rockborn strain.
Both egg- and cell-adapted canine distemper virus (CDV) vaccines are suspected to retain residual virulence, especially if administered to immuno-suppressed animals, very young pups or to highly susceptible animal species. In the early 1980s, post-vaccine encephalitis was reported in dogs from various parts of Britain after administration of a particular batch of combined CDV Rockborn strain/canine adenovirus type-1 vaccine, although incrimination of the Rockborn strain was subsequently retracted. Notwithstanding, this, and other reports, led to the view that the Rockborn strain is less attenuated and less safe than other CDV vaccines, and the Rockborn strain was officially withdrawn from the markets in the mid 1990s. By sequencing the H gene of the strain Rockborn from the 46th laboratory passage, and a commercial vaccine (Candur(®) SH+P, Hoechst Rousell Vet GmbH), the virus was found to differ from the commonly used vaccine strain, Onderstepoort (93.0% nt and 91.7% aa), and to resemble more closely (99.6% nt and 99.3% aa) a CDV strain detected in China from a Lesser Panda (Ailurus fulgens). An additional four CDV strains matching (>99% nt identity) the Rockborn virus were identified in the sequence databases. Also, Rockborn-like strains were identified in two vaccines currently in the market. These findings indicate that Rockborn-like viruses may be recovered from dogs or other carnivores with distemper, suggesting cases of residual virulence of vaccines, or circulation of vaccine-derived Rockborn-like viruses in the field.


Two approaches reveal a new paradigm of 'switchable or genetics-influenced allele-specific DNA methylation' with potential in human disease.
Imprinted genes are vulnerable to environmental influences during early embryonic development, thereby contributing to the onset of disease in adulthood. Monoallelic methylation at several germline imprints has been reported as DNMT1-dependent. However, which of these two epigenetic attributes, DNMT1-dependence or allelic methylation, renders imprinted genes susceptible to environmental stressors has not been determined. Herein, we developed a new approach, referred to as NORED, to identify 2468 DNMT1-dependent DNA methylation patterns in the mouse genome. We further developed an algorithm based on a genetic variation-independent approach (referred to as MethylMosaic) to detect 2487 regions with bimodal methylation patterns. Two approaches identified 207 regions, including known imprinted germline allele-specific methylation patterns (ASMs), that were both NORED and MethylMosaic regions. Examination of methylation in four independent mouse embryonic stem cell lines shows that two regions identified by both NORED and MethylMosaic (Hcn2 and Park7) did not display parent-of-origin-dependent allelic methylation. In these four F1 hybrid cell lines, genetic variation in Cast allele at Hcn2 locus introduces a transcription factor binding site for MTF-1 that may predispose Cast allelic hypomethylation in a reciprocal cross with either C57 or 129 strains. In contrast, each allele of Hcn2 ASM in J1 inbred cell line and Park7 ASM in four F1 hybrid cell lines seems to exhibit similar propensity to be either hypo- or hypermethylated, suggesting a 'random, switchable' ASM. Together with published results, our data on ASMs prompted us to propose a hypothesis of regional 'autosomal chromosome inactivation (ACI)' that may control a subset of autosomal genes. Therefore, our results open a new avenue to understand monoallelic methylation and provide a rich resource of candidate genes to examine in environmental and nutritional exposure models.


Chemical process-based reconstruction of exposures for an epidemiological study. Part II. Estimated exposures to chloroprene and vinyl chloride.
In a four-facility occupational epidemiology study of chloroprene monomer and polymer production workers, the chloroprene (CD) and vinyl chloride monomer (VCM) exposures were modeled for plant specific job title classes. In two facilities an acetylene-based process was used and in the other two plants only a butadiene-based process was used in the monomer synthesis. In the Acetylene process VCM was an undesirable by-product to be removed. In the newer butadiene-based process, VCM was not involved and the exposures to CD were considerably lower than they were in the earlier years. One of the limiting factors was the operator rotation within a number of job titles. This rotation and inability to differentiate between job titles subsumed in job classifications recorded in the work histories required an exposure classification scheme based on an order of magnitude separation of exposure classes. In the four facilities with considerable variation in the mix of the production methods, the CD exposures were remarkably similar in both calculated and measured values. The reductions in exposures were much more dependent upon the improvement of the production methods, rather than deliberate exposure control for occupational hygiene considerations. This is reasonable since the exposures were generally lower than the coeval exposure limits and/or guidelines. The estimated exposures were less than 100 ppm in the pre-1960 era and less than 10 ppm in the 1960-1980 era, less than 1 ppm 1980-1990 era and less than 0.5 ppm thereafter. The exposures were categorized in four classes for VCM and six classes for CD. The characteristic class exposure values were used to cumulate individual exposures over time with a quantification of the potential range for exposures that are reasonably certain to ascribe correct ranking to job classes.


Fat quantification of the rotator cuff muscles using CT histogram analysis in comparison with Dixon MRI sequence.
To quantify the proportion of fat within the rotator cuff muscles using CT histogram analysis (HA) and to compare fat fraction (FF) values obtained from CT and T2*-corrected 6-echo three-dimensional gradient-echo Dixon sequences. Twenty-six patients who underwent both shoulder CT and MRI were enrolled. The FF of rotator cuff muscles was measured on FF maps of the Dixon technique. Using CT, the FF values were obtained in two ways: 1) CT mean Hounsfield Unit (HU) measurement-based fat quantification using subcutaneous fat and the teres major muscle as internal standards; and 2) CT HA-based fat quantification in which pixels from -190 to -30 HU were arbitrarily classified as fat, and those from -30 to 150 HU as muscle. Afterward, the relationship between FF values from MRI (FF-MR), CT mean HU-based analysis (FF-HU), and CT HA (FF-HA) was assessed. There were strong positive correlations (p < 0.001) between FF-MR and FF-HA, which were higher when compared with FF-HU (r = 0.90 vs. 0.77 for total). For a total of 104 rotator cuff muscles, the intraclass correlation between FF-MR and FF-HA was excellent (ICC, 0.90), which was higher than that between FF-MR and FF-HU (ICC, 0.76). The ICCs showed excellent interobserver agreement between FF-MR, FF-HU, and FF-HA (ICCs, 0.93-0.96). Fat quantification within the rotator cuff muscles using CT HA is both feasible and reliable. CT HA provides reliable quantification of intramuscular fat and has strengths regarding its retrospective applicability to conventional CT studies without additional radiation dose to subjecting patients.


Oxidative Stress, GTPCH1, and Endothelial Nitric Oxide Synthase Uncoupling in Hypertension.
Significance: Hypertension has major health consequences, which is associated with endothelial dysfunction. Endothelial nitric oxide synthase (eNOS)-produced nitric oxide (NO) signaling in the vasculature plays an important role in maintaining vascular homeostasis. Considering the importance of NO system, this review aims to provide a brief overview of the biochemistry of members of NO signaling, including GTPCH1 [guanosine 5'-triphosphate (GTP) cyclohydrolase 1], tetrahydrobiopterin (BH4), and eNOS. Recent Advances: Being NO signaling activators and regulators of eNOS signaling, BH4 treatment is getting widespread attention either as potential therapeutic agents or as preventive agents. Recent clinical trials also support that BH4 treatment could be considered a promising therapeutic in hypertension. Critical Issues: Under conditions of BH4 depletion, eNOS-generated superoxides trigger pathological events. Abnormalities in NO availability and BH4 deficiency lead to disturbed redox regulation causing pathological events. This disturbed signaling influences the development of systemic hypertension as well as pulmonary hypertension. Future Directions: Considering the importance of BH4 and NO to improve the translational significance, it is essential to continue research on this field to manipulate BH4 to increase the efficacy for treating hypertension. Thus, this review also examines the current state of knowledge on the effects of eNOS activators on preclinical models and humans to utilize this information for potential therapy.


Daily home gardening improved survival for older people with mobility limitations: an 11-year follow-up study in Taiwan.
To test the hypothesis that gardening is beneficial for survival after taking time-dependent comorbidities, mobility, and depression into account in a longitudinal middle-aged (50-64 years) and older (≥65 years) cohort in Taiwan. The cohort contained 5,058 nationally sampled adults ≥50 years old from the Taiwan Longitudinal Study on Aging (1996-2007). Gardening was defined as growing flowers, gardening, or cultivating potted plants for pleasure with five different frequencies. We calculated hazard ratios for the mortality risks of gardening and adjusted the analysis for socioeconomic status, health behaviors and conditions, depression, mobility limitations, and comorbidities. Survival models also examined time-dependent effects and risks in each stratum contingent upon baseline mobility and depression. Sensitivity analyses used imputation methods for missing values. Daily home gardening was associated with a high survival rate (hazard ratio: 0.82; 95% confidence interval: 0.71-0.94). The benefits were robust for those with mobility limitations, but without depression at baseline (hazard ratio: 0.64, 95% confidence interval: 0.48-0.87) when adjusted for time-dependent comorbidities, mobility limitations, and depression. Chronic or relapsed depression weakened the protection of gardening. For those without mobility limitations and not depressed at baseline, gardening had no effect. Sensitivity analyses using different imputation methods yielded similar results and corroborated the hypothesis. Daily gardening for pleasure was associated with reduced mortality for Taiwanese >50 years old with mobility limitations but without depression.


[The advertising message of drugs advertisements in Spanish medical journals].
To describe the characteristics of advertising in Spanish medical journals and to analyze the advertising message in drug advertisements. Six issues of 4 Spanish medical journals published in 2001 were reviewed to identify the number of advertisements and their characteristics. The journals selected were Atención Primaria, Anales Españoles de Pediatría, Medicina Clínica and Gaceta Sanitaria. The advertising message was analyzed by evaluating 5 factors: communication aim, sales argument, communication treatment, and use of text and image. 609 advertisements were found. Drug advertisements were the most numerous (69.9%). Advertising pressure was highest in Atención Primaria (36%), followed by Anales Españoles de Pediatría (22%), Medicina Clínica (12%) and Gaceta Sanitaria (4%). Of the 195 drug advertisements analyzed, the aim of the advertising message was mostly to present or remind readers of an existing product (70.8%). The sales argument was rational in 86.5%. The communication treatment was advertising in 72.6%. The text of the advertisement contained a headline in 82.4% or a slogan in 50.8%. The advertisement image was a photograph in 74.7% and the aim of the image was to present the product (48.7%), to promise a benefit (45.1%), or to argue its qualities (31.1%). In the journals aimed at prescribing physicians advertising pressure was higher and advertisements were intercalated in article text. Advertising concerned already existing products, used rational arguments, and the communication treatment was advertising.


An Unbalanced Inflammatory Cytokine Response Is Not Associated With Mortality Following Sepsis: A Prospective Cohort Study.
The prevailing theory of host response during sepsis states that an excessive production of pro-inflammatory mediators causes early deaths, whereas a predominantly anti-inflammatory response may lead to immunosuppression, secondary infection, and late deaths. We assessed inflammatory (im)balance by measuring pro-inflammatory interleukin-6 and anti-inflammatory interleukin-10 during three distinct time periods after sepsis, and assessed its association with mortality. Prospective observational cohort. Two tertiary mixed ICUs in The Netherlands. Consecutive patients presenting with severe sepsis or septic shock from 2011 to 2013. None. We repeatedly measured plasma interleukin-6 and interleukin-10 concentrations using cytometric bead array. Poisson regression was used to analyze the relation between inflammatory markers measured on 1) ICU admission and day 4 mortality, 2) day 4 and day 28 mortality, and 3) ICU discharge and 1-year mortality. Secondary outcome was development of ICU-acquired infections. Among 708 patients, 86 (12%) died within 4 days, 140 (20%) died between days 4 and 28, and an additional 155 (22%) died before 1 year. Interleukin-6 and interleukin-10 levels were both independently associated with mortality, but the balance of this response as modelled by an interleukin-6 and interleukin-10 interaction term was not (relative risk, 0.99; 95% CI, 0.95-1.04 on admission; relative risk, 1.02; 95% CI, 0.98-1.06 on day 4; and relative risk, 1.12; 95% CI, 0.98-1.29 at ICU discharge). However, inflammatory imbalance on day 4 was associated with development of ICU-acquired infections (subdistribution hazard ratio, 0.87; 95% CI, 0.77-0.98). Although both interleukin-6 and interleukin-10 productions are associated with death, the balance of these inflammatory mediators does not seem to impact either early, intermediate, or late mortality in patients presenting to the ICU with sepsis.


Ependymomas in children.
Ependymomas originate throughout the central nervous system (CNS), representing 10-12% of CNS tumors in children. The majority occur in children less than 5 years of age. Tumors occur most often in the 4th ventricular region. Current controversies regarding ependymomas include histologic categorization or 'differentiation'. It is estimated that approximately 25% of childhood tumors are appropriately categorized as anaplastic or 'high-grade' lesions. Surgical resection is curative for tumors originating in the cauda equina; recent data suggest that surgery alone has achieved disease control in 75% of intramedullary tumors. For intracranial ependymomas, postoperative irradiation has been shown to improve survival in series dating from the 1960-1980 era. Debate regarding the necessary volume for radiation therapy (i.e. local treatment or craniospinal irradiation) centers on the reported rate of neuraxis seeding. An overall incidence of 12% has been documented in the literature, with clinico-histologic correlation suggesting that anaplastic or high-grade infratentorial ependymomas are associated with the highest frequency of subarachnoid spread. Recent reports of chemotherapy show response to several single agents, with no clear documentation that adjuvant chemotherapy has improved survival to date. Current studies utilizing preirradiation chemotherapy address tumor response and ultimate control in a sequence of surgery, chemotherapy, and irradiation primarily in very young children or those with anaplastic or high-grade tumors.


Constructing a Multiple Sclerosis Diagnosis Model Based on Microarray.
Multiple sclerosis is an immune-mediated demyelinating disorder of the central nervous system. Because of the complexity of etiology, pathology, clinical manifestations, and the diversity of classification, the diagnosis of MS is very difficult. We found that McDonald Criteria is very strict and relies heavily on the evidence for DIS and DIT. Therefore, we hope to find a new method to supplement the evidence and improve the accuracy of MS diagnosis. We finally selected GSE61240, GSE18781, and GSE185047 based on the GPL570 platform to build a diagnosis model. We initially selected 54 MS susceptibility locus genes identified by IMSGC and WTCCC2 as predictors for the model. After Random Forests and other series of screening, the logistic regression model was established with 4 genes as the final predictors. In external validation, the model showed high accuracy with an AUC of 0.96 and an accuracy of 86.30%. Finally, we established a nomogram and an online prediction tool to better display the diagnosis model. The diagnosis model based on microarray data in this study has a high degree of discrimination and calibration in the validation set, which is helpful for diagnosis in the absence of evidence for DIS and DIT. Only one SLE case was misdiagnosed as MS, indicating that the model has a high specificity (93.93%), which is useful for differential diagnosis. The significance of the study lies in proving that it is feasible to identify MS by peripheral blood RNA, and the further application of the model and be used as a supplement to McDonald Criteria still need to be trained with larger sample size.


Current indications for pegging in the anophthalmic socket: are there any?
To highlight the development, problems, and current status of coupling porous orbital implants to the overlying prosthetic eye. Although increasing the risk of complications, pegging significantly contributes to prosthesis motility and satisfies the cosmetic expectations of some patients. Patients should be counseled regarding the increased risks in approximately one-third of individuals and that complications can occur even 10 years following implantation. Although implant peg placement has declined dramatically over the past decade, a precise and meticulous technique under intravenous anesthesia in the appropriately selected patient can be a successful outpatient procedure. Fortunately, most problems are of a minor nature, and over 85% of patients are able to retain their pegs following proper management and timely intervention. Additional visits to the ophthalmic plastic surgeon or ocularist are required that may not be necessary if a peg had not been placed.


Common variants of T-cells contribute differently to phenotypic variation in sarcoidosis.
The involvement of the immune system, particularly the role of T-cells, in sarcoidosis is unclear. The existence of higher CD4+ T-cells and increased CD4/CD8 ratio may indicate a pathogenic role of T-cells in the disease. In this study, we quantified the contribution of T-cells associated variants and of CD4/CD8 ratio in sarcoidosis phenotypes, Löfgren's syndrome (LS) and non- Löfgren's syndrome (non-LS). We employed a polygenic-based approach using genome-wide association studies results on relative levels of T-cells in healthy individuals to measure the genetic contribution of T-cells in sarcoidosis entities. Results revealed that the genetic architecture of LS is highly influenced by genetic variants associated with CD8+ T-cells and CD4/CD8 ratio, explaining up to 7.94% and 6.49% of LS variation, respectively; whereas, the genetic architecture of non-LS is minimally influenced by T-cells, explaining a phenotypic variation of <1%. Moreover, pleiotropy assessment between T-cells and LS/non-LS associated-variants led to the discovery of highly scored pathway maps that shared common factors related to antigen presentation and T-cell regulatory mechanisms. Differences in significant polygenic scores, presence of pleiotropy, and distinct genetic factors provide further insights on how genetic variants and genes associated with relative levels of T-cell subtypes contribute differently to sarcoidosis phenotypes.


Solid-phase library synthesis, screening, and selection of tight-binding reduced peptide bond inhibitors of a recombinant Leishmania mexicana cysteine protease B.
A one-bead-two-compound inhibitor library was synthesized by the split-mix method for the identification of inhibitors of a recombinant cysteine protease from Leishmania mexicana, CPB2.8DeltaCTE. The inhibitor library was composed of octapeptides with a centrally located reduced bond introduced by reductive amination of the resin-bound amines with Fmoc amino aldehydes. The library was screened on solid phase, and less than 1% of the library contained active compounds. The inhibitors displayed great specificity in the subsites flanking the enzyme catalytic triad with Cha and Ile/Leu preferred in P(2), Phe in P(1), Cha and Ile/Leu in P(1)', and Ile/Leu in P(2)'. Some of the inhibitors were resynthesized, and the kinetics of inhibition were determined in solution-phase assays. Most of the inhibitors had micromolar K(i) values, and a few inhibited the enzyme at nanomolar concentrations. One inhibitor, DKHF(CH(2)NH)LLVK (K(i) = 1 microm), was tested for antiparasite efficacy and shown to affect parasite survival with an IC(50) of approximately 50 microm.


Molecular population genetic studies of the island peoples of the South Pacific.
The introduction of molecular genetic techniques to survey DNA variation directly has greatly advanced the study of inter- and intra-population variability. One of the first DNA polymorphisms to be surveyed for population variation was the α-globin copy number variants in Melanesia, and this study indicated a new role for malarial selection. Subsequently, DNA sequence polymorphism was investigated by the definition of haplotypes, which result from linkage disequilibrium among site polymorphisms. Distributions of α-globin haplotypes clearly demonstrate the effects of migration on population affinities in Melanesia and Polynesia. Analysis of neutral diversity in the nuclear genome has been enriched by the discovery of variable numbers of tandem repeats (VNTRs), particularly the hypervariable mini-satellites. Highly allelic VNTRs are sensitive to the effects of genetic drift caused by bottlenecks or population subdivision, and in Oceania they reflect the demography of colonization. Because VNTRs are subject to high and variable rates of mutation, they are informative within a range of recent evolutionary time scales and, together with other DNA polymorphisms, contribute to a more complete interpretation of a population's history. © 1996 Wiley-Liss, Inc.


Effects of azelastine on neutrophil chemotaxis, phagocytosis and oxygen radical generation.
The effects of azelastine, an orally active anti-allergic drug, on several inflammatory parameters of human neutrophils, including human neutrophil chemotaxis, phagocytosis and generation of reactive oxygen species (ROS), was examined. ROS generated in a cell-free, xanthine-xanthine oxidase system was also assessed. The species investigated were superoxide radical anion (O2-), hydrogen peroxide (H2O2) and hydroxyl radical (OH.). Azelastine significantly inhibited human neutrophil phagocytosis and the generation of O2-, H2O2, OH. by human neutrophils. However, the drug did not markedly affect human neutrophil chemotaxis or the ROS levels generated in the xanthine-xanthine oxidase system. The present study indicates that azelastine may exert an anti-inflammatory action by inhibiting human neutrophil phagocytosis as well as oxygen radical generation at the sites of inflammation.


[Methods of definition staphylococcal enterotoxin in foodstuff].
In the review the literary data on methods of definition staphylococcal enterotoxin (SE) generalized. Are cited the data on kinds staphylococcal, producing SE and about existence various types SE and types SE, having practical value. The special attention is given to the internationals recognized methods of definition SE: reactions of passive latex-agglutination, to a microslide method, enzyme-linked immunosorbent assay to the analysis, enzyme-immuno to the analysis. In work process of preparation of tests for the analysis is submitted, to an opportunity and partial clearing SE. Commercial diagnostic preparations existing now for definition SE are submitted in work with the instruction (indication) of their sensitivity and specificity, and also an opportunity of reception with use of some of them of false-positive results at definition SE in the certain foodstuff and the instruction (indication) of elimination of the reasons which potentially can yield false-positive results.


Cyclosporine therapy for steroid-resistant nephrotic syndrome. A controlled study.
We have conducted a controlled trial on the efficacy of cyclosporine in eight patients with steroid-resistant nephrotic syndrome (four with idiopathic minimal lesion nephrotic syndrome and four with focal segmental glomerulosclerosis). Patients were randomly allocated to a cyclosporine (5 mg/kg/d) or a control group. After eight weeks of therapy and one month without cyclosporine therapy, patients in the control group were given cyclosporine for eight weeks and those in the cyclosporine group became controls. Before the initiation of treatment, there was no difference between the groups with regard to proteinuria and serum albumin levels. Proteinuria remained unchanged in the cyclosporine group, while there was a significant increase in proteinuria in the control group. There were no significant changes in serum albumin levels in either group during the trial. This study does not support the use of cyclosporine at the dose of 5 mg/kg/d in patients with steroid-resistant minimal lesion nephrotic syndrome or focal segmental glomerulosclerosis.


C5a enhances Vδ1 T cells recruitment via the CCL2-CCR2 axis in IgA nephropathy.
Mucosal immune-associated γδ T cells have been implicated in IgA nephropathy (IgAN). However, the involvement of Vδ1 T cells, the major γδ T cells subtype, in renal damage and the mechanism underlying their migration from peripheral blood to kidney in IgAN remain unclear. Clinical data from IgAN patients and healthy controls (HC) were analyzed. Phenotypes and chemokine receptors of γδ T cell were compared between IgAN patients and HC. Immunohistochemistry and immunofluorescence were performed to assess the infiltration of γδ T cell subsets and the expression of chemokine in renal tissues. In vitro, C5a was used to stimulate the human glomerular mesangial cells (HMCs) and chemotaxis experiment was used to examine Vδ1 T cells migration. Correlation between Vδ1 T cells and related clinical indicators were analyzed. IgAN patients exhibited decreased Vδ1 T cell in blood but increased levels in kidneys compared to HC. Increased CCR2-expressing Vδ1 T cells and serum level of CCL2 were observed in IgAN patients. CCL2 co-localized with CCR2 in HMCs of IgAN. In vitro, C5a enhanced Vδ1 T cells recruitment by HMCs through CCL2-CCR2 axis. Importantly, circulating Vδ1 T cell levels showed a negatively correlated with both the urinary protein creatinine ratio (UACR) and 24-hour urine protein (UP). Moreover, kidney infiltration of Vδ1 cells positively correlated with UACR, UP, mesangial hyperplasia and renal tubule atrophy/interstitial fibrosis in IgAN. C5a-induced production of CCL2 by HMCs facilitates Vδ1 T cells recruitment via the CCL2-CCR2 axis, contributing to renal damage in IgAN.


Inhibitory Mechanism of Epigallocatechin Gallate on Fibrillation and Aggregation of Amidated Human Islet Amyloid Polypeptide.
The abnormal fibrillation of human islet amyloid polypeptide (hIAPP) is associated with development of type II diabetes mellitus (T2DM). (-)-Epigallocatechin gallate (EGCG) can bind amyloid proteins to inhibit the fibrillation of these proteins. However, the mechanic detail of EGCG inhibiting amyloid formation is still unclear at the molecular level. In the present work, we sought to investigate the effect of EGCG on amidated hIAPP (hIAPP-NH2 ) fibrillation and aggregation by using spectroscopic and microscopic techniques, and also sought to gain insights into the interaction of EGCG and hIAPP22-27 by using spectroscopic experiments and quantum chemical calculations. ThT fluorescence, real-time NMR, and TEM studies demonstrated that EGCG inhibits the formation of hIAPP-NH2 fibrils, while promoting the formation of hIAPP-NH2 amorphous aggregates. Phenylalanine intrinsic fluorescence and NMR studies of the EGCG/hIAPP22-27 complex revealed three important binding sites including the A ring of EGCG, residue Phe23, and residue Ile26. DFT calculations identified the dominant binding structures of EGCG/Phe23 and EGCG/Ile26 complexes, named structure I and structure II, respectively. Our study demonstrates the inhibitory mechanism of EGCG on fibrillation and aggregation of hIAPP-NH2 in which EGCG interacts with hIAPP-NH2 through hydrogen bonding and π-π interactions between the A ring and residue Phe23 as well as hydrophobic interactions between the A ring and residue Ile26, which can thus inhibit the interpeptide interaction between hIAPP-NH2 monomers and finally inhibit fibrillation of hIAPP-NH2 . This study agrees with and reinforces previous studies and offers an intuitive explanation at both the atomic and molecular levels. Our findings may provide an invaluable reference for the future development of new drugs in the management of diabetes.


Polymorphism of the complement components in human pathology.
The complement system is an important part of non clonal or innate immunity that collaborates with acquired immunity to kill pathogens and to facilitate the clearance of immune complexes. The complement is made up of 20 distinct plasma proteins and 9 different membrane proteins. Three components, factor B, C2 and C4 (with 2 isotypes), are coded by polymorphic HLA-linked genes and are sometimes referred to as class III antigens, inherited as compact units called complotypes. The C4 genes are the most polymorphic, including a common null allele (Q0) at both the C4A and C4B loci. Other polymorphic complement factors (not linked to HLA) are C3 (2 common alleles), C6 and C7 (closely linked, with 3 and 2 alleles, respectively). A certain degree of polymorphism has also been described for complement receptors and membrane control proteins. No differences in functional activity are usually detected among different alleles. Immune-mediated diseases are associated with C4Q0, in particular: systemic lupus erythematosus and discoid-systemic lupus erythematosus, insulin-dependent diabetes mellitus, liver cirrhosis, celiac disease and IgA/IgG4 deficiency. Even if optimal HLA markers do become available, genetic counselling is usually not the ultimate goal for dealing with most of the HLA-associated common diseases, although their study could help to better delineate disease pathogenesis.


Preventing Future Harm: Identifying the Drivers of an Unsafe Discharge to Improve Safety on an Inpatient Oncology Service.
Cancer Morbidity, Mortality, and Improvement Rounds is a series of articles intended to explore the unique safety risks experienced by oncology patients through the lens of quality improvement, systems and human factors engineering, and cognitive psychology. For purposes of clarity, each case focuses on a single theme, although, as is true for all medical incidents, there are almost always multiple, overlapping, contributing factors. The quality improvement paradigm used here, which focuses on root cause analyses and opportunities to improve care delivery systems, was previously outlined in this journal.This article describes the care of a young patient with aggressive breast cancer, declining performance status, and multiple hospital admissions who died shortly after being discharged home without essential medications or an adequate plan for follow-up. The patient's death due to her malignancy was unavoidable, but she had inadequate resources before her death, leading to avoidable suffering. This outcome resulted from a series of minor errors attributable to inadequate handoffs, challenges establishing realistic goals of care, and hierarchy within and between medical teams that resulted in major lapses at the time of discharge. We explore these issues and discuss how this case led to the establishment of programs designed to empower health care providers and increase engagement of outpatient oncologists at critical points of patients' disease courses.


Preparation and characterization of a degradable magnesium phosphate bone cement.
A kind of degradable magnesium phosphate bone cement (MPBC) was fabricated by using the mixed powders of magnesium oxide (MgO), potassium dihydrogen phosphate (KH2PO4) and calcium dihydrogen phosphate (Ca(H2PO4)2.H2O). As MgKPO4, the main product of MgO and KH2PO4 was alkaline, the Ca(H2PO4)2.H2O was added to neutralize the alkali of the system. And the effects of Ca(H2PO4)2.H2O on the performance of MPBC were discussed. The results showed that the adding of Ca(H2PO4)2.H2O extended the setting time, which was about 6 min to 18 min. The compressive strength increased first and then decreased, and maximum value reached 31.2 MPa after setting for 24 h without any additional pressure. The MPBC was degradable in Tris-HCl solution, and the extracts of the cytotoxicity assay showed that the MPBC had good biocompatibility, indicating that the MPBC had good biodegradable and biocompatible properties.


[Injuries to the knee extensors. Rupture of the patellar tendon and the quadriceps].
Authors discuss, based on the experiences of their 18 cases, the injuries of the knee extensors. 5 ruptures of the quadriceps and 9 of the lig. patellae propr. were observed in the 14 cases controlled. Based on their own experiences and the standpoints of the literature they suggest the operative therapy within 6 hours in the open injury and within 1-5 days following the accident in closed cases. The experiences, the operative technique, the viewponts of the aftercare and the end results are described.


Algae biogas production focusing on operating conditions and conversion mechanisms - A review.
Global warming is the result of traditional fuel use and manufacturing, which release significant volumes of CO2 and other greenhouse gases from factories. Moreover, rising energy consumption, anticipated limitations of fossil fuels in the near future, and increased interest in renewable energies among scientists, currently increase research in biofuels. In contrast to biomass from urban waste materials or the land, algae have the potential to be a commercially successful aquatic energy crop, offering a greater energy potential. Here we discuss the importance of Anaerobic Digestion (AD) for enhanced biogas yield, characterization, and comparisons between algae pretreatment methods namely, mechanical, thermal, microwave irradiation, and enzymatic and catalytic methods. The importance of anaerobic digestion enhances biogas yield, characterization, and comparisons between mechanical, thermal, microwave irradiation, and enzymatic and catalytic treatment. Additionally, operational aspects such as algal species, temperature, C/N ratio, retention period, and particle size impact biofuel yield. The highest algal biogas yield reported was 740 mL/gVS, subtracted from Taihu de-oiled algae applying thermos-chemical pretreatment under conditions of temperature, time, and catalyst concentration of 70 °C, 3 h, and 6%, respectively. Another high yield of algal-based biogas was obtained from Laminaria sp. with mechanical pretreatment under temperature, time, and VS concentration of 38 ± 1 °C, 15 min, and 2.5% respectively, with a maximum yield of 615 ± 7 mL/g VS. Although biofuels derived from algae species are only partially commercialized, the feedstock for biogas might soon be commercially grown. Algae and other plant species that could be cultivated on marginal lands as affordable energy crops with the potential to contribute to the production of biogas are promising and are already being worked on.


Pericyte detachment and renal congestion involve interstitial injury and fibrosis in Dahl salt-sensitive rats and humans with heart failure.
Congestive heart failure produces fluid volume overload, central and renal venous pressure elevation, and consequently renal congestion, which results in worsening renal function. Pericyte detachment and pericyte-myofibroblast transition (PMT) were linked to renal interstitial fibrosis. Dahl salt-sensitive hypertensive (DahlS) rats are a non-surgical renal congestion model. The relation, however, between renal interstitial damage, pericyte morphology, and PMT in the renal congestion of DahlS rats has not been reported. DahlS rats (8-week-old) were fed normal salt (NS, 0.4% NaCl) or high salt (HS, 4% NaCl), and the left kidney was decapsulated to reduce renal interstitial hydrostatic pressure (RIHP) at 9 weeks old. One week after capsulotomy, both kidneys were analyzed by molecular and histological techniques. Renal pericyte structure was assessed in the body donors with/without venous stasis. Markers of tubulointerstitial damage, interstitial fibrosis, and PMT were upregulated in the right non-decapsulated kidney of DahlS rats fed HS. Renal tubular injury and fibrosis were detected in the HS diet groups in histological analysis. Pericyte detachment was observed in the right non-decapsulated kidney of DahlS rats fed HS by low vacuum-scanning electron microscopy. Decapsulation in DahlS rats fed HS attenuated these findings. Also, renal pericytes detached from the vascular wall in patients with heart failure. These results suggest that pericyte detachment and PMT induced by increased RIHP are responsible for tubulointerstitial injury and fibrosis in DahlS rats and humans with renal congestion. Renal venous congestion and subsequent physiological changes could be therapeutic targets for renal damage in cardiorenal syndrome.


Prevalence and clinical characteristics of acute myeloid leukemia associated with disseminated intravascular coagulation.
Disseminated intravascular coagulation (DIC) is one of the important complications to develop in patients with acute myeloid leukemia (AML). While acute promyelocytic leukemia (APL) is a strong risk factor for DIC, other clinical features have not been fully defined. We retrospectively analyzed 161 consecutive adult patients with de novo non-APL AML. DIC was diagnosed in 52 patients (32%); 28 patients at diagnosis and 24 soon after the initiation of induction chemotherapy. Leukocyte counts, C-reactive protein, and lactate dehydrogenase were significantly higher in the DIC+ group. Negative expressions of CD13, CD19, CD34, and HLA-DR were more prevalent in the DIC+ group. On multivariate logistic-regression analysis, variables that were independently associated with the development of DIC were high C-reactive protein, high leukocyte count, negative expressions of CD13 and HLA-DR, and cytogenetics with a normal karyotype or 11q23 abnormality. Although DIC is considered to be associated with serious morbidity and occasional mortality, we did not find any significant differences in the complete remission rate, overall or disease-free survival between DIC+ and DIC- groups. This study is the first to define the clinical characteristics associated with DIC in patients with non-APL AML, but exactly how and when DIC should be treated remains to be determined.


[Amoebic liver abscess--case report].
The authors present a case of a young male, who suffered with extraintestinal form of amoebiasis-amoebic liver abscesses. The patient traveled to India two month before symptoms onset. The diagnosis based on ultrasonography and computed tomography was definetely confirmed by serological examination. Metronidazol treatment was given initially, followed by percutaneous drainage. Open surgical tretment was indicated due to failure of percutaneous treatment. Patient was discharged home in a good condition one month after surgery. At this time patient is doing well eight months after surgery.


A rare case of Bouveret's syndrome presenting with upper gastrointestinal bleeding.
We report a case of duodenal obstruction caused by a large gallstone wedged in the duodenal bulb (Bouveret's syndrome), presenting with acute upper gastrointestinal bleeding and successfully treated by surgery following a failed attempt at endoscopic retrieval of the stone. Haemorrhage is a very rare form of presentation. After an extensive review of the literature, the therapeutic options and surgical strategies (one-stage and two-stage procedure) are critically discussed.


Allylic Oxidation of Ester-Substituted 1,4-Dienes.
The cobalt-catalyzed hydrovinylation reaction and the Alder-ene reaction generate acyclic 1,4-dienes, which were investigated in the selenium dioxide oxidation to afford further functionalized dienes prone for follow-up reactions. The chemoselective allylic oxidation of ester-functionalized 1,4-dienes occurs at the most electron-rich double bond. The steric demand of the electron-rich, alkyl-substituted double bond determines the reaction pathway, whether the double bond transposition toward the conjugated 1,3-diene or the allylic oxidation is faster. As reaction products, 2,4-diene-6-ols or divinyl ketones were obtained.


Bioimaging in the mid-infrared using an organometallic carbonyl tag.
Two stable and water-soluble organometallic carbonyl cluster derivatives have been prepared and shown to enter the cell with ease. The CO stretching vibrations afford strong mid-infrared signals which have been demonstrated, for the first time, to be of utility in cell imaging via an IR microscope.


Expression and disruption of the Arabidopsis TOR (target of rapamycin) gene.
TOR (target of rapamycin) protein kinases were identified in yeasts, mammals, and Drosophila as central controllers of cell growth in response to nutrient and growth factors. Here we show that Arabidopsis thaliana possesses a single TOR gene encoding a protein able to complex with yeast 12-kDa FK506-binding protein and rapamycin despite the insensitivity of Arabidopsis vegetative growth to rapamycin. Analysis of two T-DNA insertion mutants shows that disruption of AtTOR leads to the premature arrest of endosperm and embryo development. A T-DNA-mediated translational fusion of AtTOR with the GUS reporter gene allows us to show that AtTOR is expressed in primary meristem, embryo, and endosperm, but not in differentiated cells. The implications of these features for the plant TOR pathway are discussed.


Deep Eutectic Solvents and Multicomponent Reactions: Two Convergent Items to Green Chemistry Strategies.
One of the highlights of green chemistry is the development of techniques and procedures with low environmental impact. In the last years, deep eutectic solvents (DES) have become an important alternative to conventional organic solvents. For a period ionic liquids have provoked remarkable interest, but they have been displaced by DES because they show easier preparation methods, lower prices, many of them are biodegradable and compatible with biological systems. In addition, they show adjustable physicochemical properties, high thermal stability, low volatility and are compatible with water. In this paper is reviewed the state of the art of the use of DES paying special attention to the role of reaction media in organic synthesis.


Progress and challenges in aminoacyl-tRNA synthetase-based therapeutics.
Aminoacyl-tRNA synthetases (ARSs) are universal enzymes that catalyze the attachment of amino acids to the 3' ends of their cognate tRNAs. The resulting aminoacylated tRNAs are escorted to the ribosome where they enter protein synthesis. By specifically matching amino acids to defined anticodon sequences in tRNAs, ARSs are essential to the physical interpretation of the genetic code. In addition to their canonical role in protein synthesis, ARSs are also involved in RNA splicing, transcriptional regulation, translation, and other aspects of cellular homeostasis. Likewise, aminoacylated tRNAs serve as amino acid donors for biosynthetic processes distinct from protein synthesis, including lipid modification and antibiotic biosynthesis. Thanks to the wealth of details on ARS structures and functions and the growing appreciation of their additional roles regulating cellular homeostasis, opportunities for the development of clinically useful ARS inhibitors are emerging to manage microbial and parasite infections. Exploitation of these opportunities has been stimulated by the discovery of new inhibitor frameworks, the use of semi-synthetic approaches combining chemistry and genome engineering, and more powerful techniques for identifying leads from the screening of large chemical libraries. Here, we review the inhibition of ARSs by small molecules, including the various families of natural products, as well as inhibitors developed by either rational design or high-throughput screening as antibiotics and anti-parasitic therapeutics.


Methionine enkephalin (MENK) improves lymphocyte subpopulations in human peripheral blood of 50 cancer patients by inhibiting regulatory T cells (Tregs).
MENK, a penta-peptide is considered as being involved in the regulatory feedback loop between the immune and neuroendocrine systems, with marked modulation of various functions of human immune cells. The aim of the present work was to investigate change of lymphocyte subpopulations in peripheral blood of 50 cancer patients before and after treatment with MENK. Peripheral blood mononuclear cells (PBMCs) of peripheral blood from 50 cancer patients were isolated by density gradient centrifugation using Ficoll-Paque solution and cultured with MENK. We measured proliferation of total nucleated cells, subpopulations of individual CD4+T cells, CD8+T cells, CD4+CD25+ regulatory T cells (Treg), natural killer cells (NK) before and after treatment with 10(-12)M MENK in cell culture by flow cytometry (FCM). Our results indicated that MENK showed a strong inhibiting effect on Treg cells while it stimulated marked proliferation of other lymphocyte subpopulations. All data obtained were of significance statistically. It was therefore concluded that MENK could work as a strong immune booster with great potential in restoring damaged human immune system and we could consider MENK as a drug to treat cancer patients, whose immune systems are damaged by chemotherapy or radiotherapy. Furthermore we could consider MENK as a chemotherapy additive, which would sustain immune system of cancer patients during the process of chemotherapy to get maximized efficacy with minimized side effect.


Biochemical changes during the aerobic-anaerobic transition in Ascaris suum larvae.
Ascaris suum L3 larvae isolated from rabbit lungs undergo the third ecdysis to L4 larvae after 3 days in culture under a gas phase of 85% N2/10% CO2/5% O2. The L3 larvae contain substantial malic enzyme activity and are capable of producing small amounts of the reduced organic acids characteristic of the fermentative pathways which operate in the adult. However, only a small portion of the total carbon utilized is accounted for by these reduced acids and their motility is cyanide-sensitive, suggesting that their energy-generating pathways are predominantly aerobic. In contrast, after ecdysis, the L4 larvae begin to utilize glucose at a greater rate and the proportion of total carbon utilized which is accounted for as propionate, 2-methylbutyrate and 2-methylvalerate also increases. In addition, motility becomes increasingly cyanide-insensitive, suggesting that these L4 larvae are able to utilize the anaerobic energy-generating pathways of the adult. Surprisingly, on day 10 in culture, these L4 larvae, although capable of producing reduced volatile acids, still retain substantial cyanide-sensitive cytochrome oxidase activity.