[Coagulation changes during aortofemoral bifurcation bypass: is volume and plasma substitution possible with hydroxyethyl starch alone?].
The study explored the possibility of eliminating the need for plasma replacement with expensive human albumin (HA) and fresh frozen plasma (FFP) and instead using hydroxyethyl starch (HES). Patients undergoing infrarenal aortofemoral bifurcation grafting were randomly assigned to one group, which received FFP and HA, or another group, which received HES as volume replacement. Blood specimens were collected at five time intervals: preoperatively, prior to cross-clamping of the aorta, prior to declamping, at the end of the operation, and 6 h postoperatively. Preoperative coagulation values were all within normal limits. The basic coagulation tests were generally affected by the standardized heparin dose of 5000 IU administered during the clamping phase. Euglobulin lysis demonstrated a perioperative climb that was particularly marked within the HES group at the time of clamping. Values returned to initial levels 6 h postoperatively. Plasminogen, fibrinogen, antithrombin III, and antiplasmin concentrations fell significantly in both groups; 10% to 20% lower values were determined within the HES group due to the lack of factor substitution. The reduction in the coagulation factors can be explained as a dilution effect, but there are also signs of a consumption reaction taking place at the onset of the operation involving activation of coagulation and fibrinolysis. Restricting the use of FFP and simultaneously increasing HES administration is justifiable in procedures involving the abdominal aorta with moderate blood loss.


Clinical outcomes and left ventricular function in diabetic patients with acute myocardial infarction treated by primary coronary angioplasty.
The objective of the present study was to compare left ventricular (LV) function and clinical outcomes in diabetics versus nondiabetics with acute myocardial infarction (AMI) treated by primary coronary angioplasty. A total of 327 consecutive AMI subjects were reperfused by primary coronary angioplasty within 12 hours from onset. Diabetes mellitus (DM) was present in 104 of the 327 patients. LV function was serially determined by left ventriculograms taken in the acute and chronic phases (6 months after onset). (I) The early ST-segment resolution rate was lower in DM patients compared with non-DM patients (59% versus 83%, P < 0.0001). (II) During a 6-month follow-up, the percentages of target vessel revascularization (TVR), coronary aorta bypass grafting (CABG), and cardiac death were higher in the DM patients compared with the non-DM patients (TVR: 29% versus 19%; P < 0.05, CABG: 10% versus 5% ; P < 0.05, cardiac death: 12% versus 4%; P = 0.01). (III) The differences in left ventricular ejection fraction (LVEF) between two stages (delta-LVEF) were significantly lower in the DM patients than the non-DM patients (1 +/- 9% versus 7 +/- 10%, P < 0.0001). (IV) Multivariate analysis identified DM as an independent predictor of cardiac death (Odds ratio 5.5, 95% CI, 1.3-23.7, P < 0.05) and as a sole independent predictor of LVEF deterioration (Odds ratio 5.8, 95% CI, 2.8-11.8, P < 0.001). In patients with AMI treated using primary coronary angioplasty, DM is closely related to left-ventricular systolic dysfunction and a poor patient outcome, including mortality.


Z protein in hepatic uptake and esterification of long-chain fatty acids.
Fatty acids radioactivity was bound to Z protein in liver after administration of['3H]oleate to rats or to a perfused rat liver preparation. Pretreatment withflavaspidic acid (340 mumol/kg), a potent inhibitor of fatty acid binding to hepatic Zprotein in vitri, effectively reduced oleate radioactivity bound to Z by 90.2 plusor minus 4.3% and 85.0 plus or minus 6.2% in the intact rat and perfused liver, respectively. In spite of this effect, pretreatment of rats with flavaspidic acid did notalter plasma clearance, hepatic uptake, and esterification of ['3H]oleate. In contrast, in the perfused liver preparation, infusion of flavaspidic acid (340 mumol/kg)or bromosulphalein (360 mumol/kg) increased uptake of ['3H]oleate at least twofold,and oleate esterification was decreased by 15-30%. These results suggest that the binding of long-chain fatty acids to Z protein is not an obligatory step in their uptakeby the liver and that Z protein may be involved in fatty acid esterification.


Autophagy is an important action mode for functionalized selenium nanoparticles to exhibit anti-colorectal cancer activity.
Selenium nanoparticles (SeNPs) have attracted much interest as potential anticancer nanodrugs. Our previous studies also demonstrated that SeNPs could be developed as carriers of clinically used anticancer drugs to achieve synergistic efficacy. Here, we describe the synthesis of Pleurotus tuber-regium (PTR)-conjugated SeNPs (PTR-SeNPs) and their application in the treatment of colorectal cancer (CRC), which is one of the principal causes of cancer morbidity and mortality in the world. PTR-SeNPs were absorbed by cancer cells via clathrin-mediated endocytosis into lysosomes and caveolae-mediated endocytosis into the Golgi apparatus. Internalized PTR-SeNPs trigger intracellular dose- and time-dependent G2/M phase arrest and apoptosis. Moreover, as shown by using a pEGFP-LC3 plasmid transfection model, PTR-SeNPs activate autophagy to promote the death of cancer cells via upregulation of beclin 1-related signaling pathways. In summary, this study demonstrates the high efficacy of functionalized SeNPs for therapy of colorectal cancer and reveals the important role of autophagy in promoting apoptosis and cell cycle arrest to induce cell death.


[The contribution of umbilical Doppler velocimetry in suspected echographic IUGR].
Doppler pulses or continuous flow in the umbilical artery is a technique recently used in practical obstetrics and of value particularly in screening at risk pregnancies. The authors wish to study its value as a diagnostic and prognostic tool in the special cases where ultrasound has given rise to a suggestion that there may be intra-uterine growth retardation (I.U.G.R.). In a preliminary publication they report their experience in 100 normal pregnancies so that they have obtained a control diagram. Then, working on a population of 117 pregnancies with ultrasonically diagnosed I.U.G.R. they studied the birth-weight, the early neonatal morbidity and the neonatal mortality as a function of the Pourcelot S - D/S index. They were able to separate out 63 cases of I.U.G.R. without any hypertension and 54 cases associated with hypertension. They analyse the same parameters. They then discuss first the value of the diagram they have made in comparison with other known curves, also the diagnostic and prognostic performance of the method. They conclude that there is a moderate diagnostic value in Doppler velocimetry. The prognostic value is much better because the Doppler can differentiate those case of slow growth that are going to do well against those that are going to do badly.


Single-molecule nanoprobes explore defects in spin-grown crystals.
Thin, platelike single crystals of p-terphenyl (PT) doped with terrylene impurity molecules can be prepared by spin-coating from solution. Strikingly, individual terrylene molecules can be observed traveling inside the crystal over distances of several micrometers by using single-molecule fluorescence imaging at room temperature. Analysis of the motion by single-particle tracking and correlation methods indicates that the molecules act as nanoprobes by exploring long, thin crack-like defects with correlated orientations, defects that can be difficult to observe by other means. Apparently, the regions accessible to the moving molecules are in the interior of the crystal and hence are partially protected from oxidation. In addition to the traveling molecules, which photobleach in times on the order of 32 s under continuous irradiation at 2 kW/cm2, two other spatially fixed populations are observed: one with transition dipole oriented along the c-axis of the crystal with a characteristic photobleaching time greater than 32 h, and one with a characteristic photobleaching time of 18 min.


Targeted association mapping demonstrating the complex molecular genetics of fatty acid formation in soybean.
The relative abundance of five dominant fatty acids (FAs) (palmitic, stearic, oleic, linoleic and linolenic acids) is a major factor determining seed quality in soybean. To clarify the currently poorly understood genetic architecture of FAs in soybean, targeted association analysis was conducted in 421 diverse accessions phenotyped in three environments and genotyped using 1536 pre-selected SNPs. The population of 421 soybean accessions displayed significant genetic variation for each FA. Analysis of the molecular data revealed three subpopulations, which reflected a trend depending on latitude of cultivation. A total of 37 significant (p < 0.01) associations with FAs were identified by association mapping analysis. These associations were represented by 33 SNPs (occurring in 32 annotated genes); another four SNPs had a significant association with two different FAs due to pleiotropic interactions. The most significant associations were cross-verified by known genes/QTL or consistency across cultivation year and subpopulations. The detected marker-trait associations represent a first important step towards the implementation of molecular-marker-based selection of FA composition with the potential to substantially improve the seed quality of soybean with benefits for human health and for food processing.


Switching Circuit Optimization for Matrix Gradient Coils.
Matrix gradient coils with up to 84 coil elements were recently introduced for magnetic resonance imaging. Ideally, each element is driven by a dedicated amplifier, which may be technically and financially infeasible. Instead, several elements can be connected in series (called a "cluster") and driven by a single amplifier. In previous works, a set of clusters, called a "configuration," was sought to approximate a target field shape. Because a magnetic resonance pulse sequence requires several distinct field shapes, a mechanism to switch between configurations is needed. This can be achieved by a hypothetical switching circuit connecting all terminals of all elements with each other and with the amplifiers. For a predefined set of configurations, a switching circuit can be designed to require only a limited amount of switches. Here we introduce an algorithm to minimize the number of switches without affecting the ability of the configurations to accurately create the desired fields. The problem is modeled using graph theory and split into 2 sequential combinatorial optimization problems that are solved using simulated annealing. For the investigated cases, the results show that compared to unoptimized switching circuits, the reduction of switches in optimized circuits ranges from 8% to up to 44% (average of 31%). This substantial reduction is achieved without impeding circuit functionality. This study shows how technical effort associated with implementation and operation of a matrix gradient coil is related to different hardware setups and how to reduce this effort.


Acute appendicitis, inflammatory appendiceal mass and the risk of a hidden malignant tumor: a systematic review of the literature.
Acute appendicitis is significantly common. Despite the increased use of computed tomography, the number of perforated cases has been stable in the past three decades. Between 2% and 6% of patients with acute appendicitis present appendiceal mass, often described as inflammatory phlegmon or abscess. Malignant tumors are confirmed by pathological analysis in 0.9-1.4% of all appendectomies performed to treat acute appendicitis. However, recent series demonstrate an elevated incidence of malignancies, ranging from 5.9 to 12%, in patients with inflammatory appendiceal mass. The analysis was based on a systematic review of the literature. The articles were searched in PubMed for the period from 1987 to 2016. Articles presenting the incidence of the hidden malignancy among patients with appendiceal inflammatory mass were selected. Variables as age, interval appendectomy rate, the incidence of neoplasm, time to surgery, minimally invasive assessment, histology, right colectomy rate and morbidity were analyzed. A total of 13.244 patients were described as presenting acute appendicitis. Appendiceal tumor is present in approximately 1% of the appendectomies, while the rate of neoplasm varies from 10 to 29% in patients presenting appendiceal inflammatory mass. Interval appendectomies, despite been the minority of the procedures, disregard the higher morbidity associated with right sided colectomies. The review of literature also describes oncologic, histologic and clinical aspects of patients presenting appendiceal neoplasm, describing the most frequent histologic subtypes of this illness. Hidden appendiceal neoplasm in acute appendicitis are rare, fortunately. However, its incidence is much higher in patients presenting appendiceal inflammatory mass. Hence, interval appendectomy should be considered in this subgroup of patients.


Calorimetrically measurable enthalpic isotope effect.
Calorimetric techniques have revealed that the enthalpy of reaction with water is more exothermic by about 2.2 kcal/mol, for the perdeuteriated naphthalene anion radical (K+C10D8*-(s) + H2O(liq) --> 1/2C10D8H2(s) + 1/2C10D8(s) + KOH(aq)) than it is for the perprotiated system. These results, when coupled with the known enthalpy of electron transfer between naphthalene and its perdeuteriated analogue imply that the heat of hydrogenation of naphthalene decreases by about 1.8 kcal/mol upon perdeuteriation of the naphthalene.


Resistance to CO2 diffusion in cuticular membranes of amphibious plants and the implication for CO2 acquisition.
Cuticular membranes (CMs) were isolated from leaves of amphibious and submerged plants and their CO2 resistances were determined as a contribution to establish quantitatively the series of resistances met by CO2 diffusing from bulk water to the chloroplasts of submerged leaves. The isolation was performed enzymatically; permeabilities were determined and converted to resistances. The range of permeance values was 3 to 43 x 10(-6) m s(-1) corresponding to resistance values of 23 to 295 x 10(3) s m(-1), i.e. of the same order of magnitude as boundary layer resistances. The sum of boundary layer, CM, leaf cell and carboxylation resistances could be contained within the total diffusion resistance as determined from the photosynthetic CO2 affinity of the leaf. From the same species, the aerial leaf CM resistance was always higher than the aquatic leaf CM resistance. In a terrestrial plant, the CM resistance to CO2 diffusion was found lower in leaves developed submerged.


A comparison of the effects of exercise and lifestyle modification on the resolution of overuse symptoms of the shoulder in polio survivors: a preliminary study.
To compare the effectiveness of exercise and lifestyle modification therapy in treating shoulder symptoms in polio survivors with lower-extremity weakness. A randomized parallel group study. Research laboratory. Twenty-three subjects recruited from a cohort of 194 polio survivors who had participated in a previous study had bilateral hip-extensor and knee-extensor weakness and reported experiencing shoulder pain on a regular basis with daily activity. Subjects were randomly assigned to 1 of 3 treatment groups. Members of group 1 were placed on a home exercise program that focused on strengthening their hip and knee extensors. Members of group 2 were instructed in lifestyle modification techniques designed to avoid shoulder overuse. Members of group 3 received both interventions. Shoulder symptoms were quantified in terms of number and severity. Isometric strength of bilateral hip and knee extensors was measured with a hand-held dynamometer. Symptoms improved in all 3 groups. However, members of the exercise-only group (group 1) were the only ones to show a significant difference in both number and severity of symptoms when pre- and posttreatment values were compared. Both exercise and lifestyle modification therapies that focus on reducing the stress related to lower-extremity weakness are effective in treating shoulder overuse symptoms in polio survivors. A trend toward greater improvement in shoulder symptoms in subjects who participated in the exercise program and who also showed a trend toward increased knee-extensor strength supports muscle strength and/or endurance as a key factor.


Desmoplastic melanoma presenting as primary alopecia neoplastica: a report of two cases.
Desmoplastic melanoma is an uncommon form of melanoma characterized by atypical spindled melanocytes and abundant collagen deposition. It typically presents in sun-damaged skin of the elderly as an amelanotic, indurated lesion. It has a higher tendency for local recurrence but lower risk of lymph node metastasis vs. conventional malignant melanoma. We report two cases in women aged 59 and 66 who presented with small scalp lesions clinically suggestive of alopecia. The differential diagnosis included alopecia areata, lupus erythematosus and lichen planopilaris. Biopsies performed according to alopecia protocol were reviewed at our institutions. Biopsies revealed atypical spindled and nested epithelioid melanocytes set in a sclerotic dermis with scattered lymphoid aggregates and immunohistochemical expression of S100 protein, features diagnostic of combined desmoplastic melanoma. Wide local excision with skin graft was performed on the older patient. Excision showed combined desmoplastic melanoma with a Breslow thickness of 8.5 mm with melanoma in situ identified in the adjacent epidermis. The other patient sought treatment elsewhere and was lost to follow up. These cases illustrate desmoplastic melanoma as an unusual etiology and dangerous clinical pitfall in patients with scar-like alopecia. To the authors' knowledge, these represent the second and third reported cases of desmoplastic melanoma presenting as primary alopecia neoplastica.


Prescribing error reporting in primary care: a narrative synthesis systematic review.
Prescribing errors can cause avoidable harm to patients. Most prescriptions originate in primary care, where medications tend to be self-administered and errors have the most potential to cause harm. Reporting prescribing errors can identify trends and reduce the risk of the reoccurrence of incidents; however, under-reporting is common. The organisation of care and the movement of prescriptions from general practice to community pharmacy may create difficulties for professionals to effectively report errors. This review aims specifically to identify primary research studies that examine barriers and facilitators to prescription error reporting across primary care. A systematic research of the literature was completed in July 2019. Four databases (PubMed/Medline, Cochrane, CINAHL and Web of Science) were searched for relevant studies. No date or language limits were applied. Eligible studies were critically appraised using the Mixed Methods Appraisal Tool, and data were descriptively and narratively synthesised. Ten articles were included in the final analysis. Seven studies considered prescription errors and error reporting within general practice and three within a community pharmacy setting. Findings from the included studies are presented across five themes, including definition of an error, prescribing error reporting culture, reporting processes, communication and capacity. Healthcare professionals appreciate the value of prescription error reporting, but there are key barriers to implementation, including time, fear of reprisal and organisation separation within primary care.


Intravenous Injection of Myelin Oligodendrocyte Glycoprotein-coated PLGA Microparticles Have Tolerogenic Effects in Experimental Autoimmune Encephalomyelitis.
The abnormal function of the T lymphocytes causes a range of autoimmune diseases, particularly multiple sclerosis; hence, several methods have been used to treat these disorders through the induction of antigen-specific tolerance in T cells. The present study aims to use a simple and low-cost method to produce poly (lactic-co-glycolic acid) (PLGA) nanoparticles for carrying antigens and inducing antigen-specific tolerance. In this study, PLGA nanoparticles were produced using the water/oil/water (W/O/W) method. The myelin oligodendrocyte glycoprotein (MOG) peptide and ovalbumin peptide(OVA) were covalently bound to the synthetic PLGA nanoparticles in the presence of 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDCI) and were injected to six groups of C57BL/6 mice one week before the induction of the experimental autoimmune encephalomyelitis (EAE) intravenously or subcutaneously; one group was considered as control; finally, immunologic responses including delayed-type hypersensitivity (DTH) response and lymphocyte proliferation were investigated. The results showed that the intravenous injection of microparticles containing MOG peptides before the development of the EAE model, not only could delay the incidence of syndrome, but also increase the antigen-specific tolerance. Moreover, a reduced delayed-type hypersensitivity response was observed in the mice primed with microparticles containing MOG peptides. In addition, a reduced spleen lymphocyte proliferation was found in the same mice when challenged with antigens. The present study proposes a simple, inexpensive, effective and safe method for preparing MOG-conjugated PLGA microparticles with immune tolerance properties that can be used in the treatment or reducing clinical syndromes of EAE model.


Differential ovarian and adrenal vein catheterization.
Twenty-two hirsute women underwent percutaneous adrenal and ovarian vein catheterization to differentiate and localize excessive hormonal output. All studies were done under fluoroscopic control; catheter placement was verified by venography, and blood samples were withdrawn for hormonal analysis. The right ovarian vein was successfully sampled in 42 per cent of attempts; the left ovarian vein, in 75 per cent; the right adrenal vein, in 56 per cent; and the left adrenal vein, in 100 per cent. Bilateral catheterization did not prove clinically useful. First, anatomic variations in venous size and drainage made catheterization and bilateral sampling difficult. Second, adrenal secretion is both episodic and parallel, necessitating both simultaneous catheterization and serial sampling for adequate diagnosis. The stress of the procedure may provoke increased adrenal output. Third, since ovarian secretion is not parallel, and since increased hormone output has been documented in that ovary containing developing follicles or a corpus luteum, distinguishing ovarian dysfunction proved difficult. Finally, for a time-consuming procedure, patient discomfort cannot be disregarded. This technique has not proved to be a reliable means of determining the site of androgen hypersecretion and thus cannot be recommended in the routine evaluation of female hirsutism.


Architectonics: Design of Molecular Architecture for Functional Applications.
The term architectonics has its roots in the architectural and philosophical (as early as 1600s) literature that refers to "the theory of structure" and "the structure of theory", respectively. The concept of architectonics has been adapted to advance the field of molecular self-assembly and termed as molecular architectonics. In essence, the methodology of organizing molecular units in the required and controlled configurations to develop advanced functional systems for materials and biological applications comprises the field of molecular architectonics. This concept of designing noncovalent systems enables to focus on different functional aspects of designer molecules for biological and nonbiological applications and also strengthens our efforts toward the mastery over the art of controlled molecular self-assemblies. Programming complex molecular interactions and assemblies for specific functions has been one of the most challenging tasks in the modern era. Meticulously ordered molecular assemblies can impart remarkable developments in several areas spanning energy, health, and environment. For example, the well-defined nano-, micro-, and macroarchitectures of functional molecules with specific molecular ordering possess potential applications in flexible electronics, photovoltaics, photonic crystals, microreactors, sensors, drug delivery, biomedicine, and superhydrophobic coatings, among others. The functional molecular architectures having unparalleled properties are widely evident in various designs of Nature. By drawing inspirations from Nature, intended molecular architectures can be designed and developed to harvest various functions, as there is an inexhaustible resource and scope. In this Account, we present exquisite designer molecules developed by our group and others with an objective to master the art of molecular recognition and self-assembly for functional applications. We demonstrate the tailor-ability of molecular self-assemblies by employing biomolecules like amino acids and nucleobases as auxiliaries. Naphthalenediimide (NDI), perylenediimide (PDI), and few other molecular systems serve as functional modules. The effects of stereochemistry and minute structural modifications in the molecular designs on the supramolecular interactions, and construction of self-assembled zero-dimensional (OD), one-dimensional (1D), and two-dimensional (2D) nano- and microarchitectures like particles, spheres, cups, bowls, fibers, belts, helical belts, supercoiled helices, sheets, fractals, and honeycomb-like arrays are discussed in extensive detail. Additionally, we present molecular systems that showcase the elegant designs of coassembly, templated assembly, hierarchical assembly, transient self-assembly, chiral denaturation, retentive helical memory, self-replication, supramolecular regulation, supramolecular speciation, supernon linearity, dynamic pathway complexity, supramolecular heterojunction, living supramolecular polymerization, and molecular machines. Finally, we describe the molecular engineering principles learnt over the years that have led to several applications, namely, organic electronics, self-cleaning, high-mechanical strength, and tissue engineering.


Morphogenesis and morphology of the brain stem nuclei of Cetacea. I. The hypoglossal nucleus.
1. The hypoglossal nucleus of whalebone whales is composed of four major subdivisions, forming four parallel columns, here called the dorsomedial, the dorsolateral, the ventromedial and the ventrolateral XII columns. 2. The ventromedial XII column extends throughout the hypoglossal nucleus, forming in whalebone whales the rostral as well as the caudal end of the nucleus. 3. The ventrolateral XII column is lamelliformed and splits into a dorsomedial and a ventrolateral part, the former intimately related topographically to the dorsomedial column. 4. The dorsomedial XII column is torpedo-shaped, tapering in rostral direction and terminating a little short of the rostral end of the ventromedial XII column, while the blunt end terminates immediately caudal to the obex. 5. The dorsolateral XII column is the shortest subdivision, approximately one fourth of the length of the entire hypoglossal nucleus. The blunt rostral end of the torpedo-shaped column blends with the dorsomedial XII column, its tapering caudal end terminating rostral to the obex. 6. The cells of the hypoglossal nucleus vary in size from small to medium-sized and large, the small ones dominating in the dorsomedial, the large ones in the dorsolateral and ventromedial XII columns. The ventrolateral column is characterized by spindle-shaped cells. 7. In the toothed whale Phocaena communis the differentiation of the hypoglossal nucleus is less clearcut than in whalebone whales, but a similar structural priniciple is recognizable.


Analysis of Spatial Distribution of CVD and Multiple Environmental Factors in Urban Residents.
Cardiovascular disease (CVD) poses a serious threat to urban health with the development of urbanization. There are multifaceted and comprehensive influencing factors for CVD, so clarifying the spatial distribution characteristics of CVD and multiple environmental influencing factors is conducive to improving the active health intervention of urban environment and promoting the sustainable development of cities The spatial distribution characteristics of CVD deaths in a certain district, Bengbu City, Huaihe River Basin, China, in 2019 were explored, and the correlation between multiple environmental factors and CVD mortality was investigated in this study, to reveal the action mechanism of multiple environmental factors affecting the risk of mortality. Relevant studies have shown that (1) CVD deaths are characterized as follows: male deaths are more than females; the mortality is higher in those of higher age; most of them are unemployed; cardiocerebral infarction is the main cause of death; and the deaths are mainly distributed in the central city and near the old urban area. (2) The increased CVD mortality can be attributed to the increased density of restaurants and cigarette and wine shops around the residential area, the increased traffic volume, the dense residential and spatial forms, the low green space coverage, and the distance from rivers. Therefore, appropriate urban planning and policies can improve the active health interventions in cities and reduce CVD mortality.


Death Due to Fractal Wood Burning: An Emerging Public Health Problem.
The art of pyrography, burning designs in wood, dates back to prehistory. Risks of traditional techniques included cutaneous burns and airway injury. Fractal wood burning is a niche technique using a high-voltage electrical source to burn branched designs into wood. While this technique has grown in popularity, the associated risks are not well understood. We describe a patient who presented to our burn center after sustaining high-voltage electrical injuries while making fractal wood art using an improvised a high-voltage transformer. During the wood-burning process, he contacted the electrodes and suffered full-thickness electrical burns to the neck, chest, and bilateral upper extremities. Bilateral upper extremity fasciotomies were performed on admission. Multiple subsequent operations culminated with autografting to most of the wounds and complex reconstruction of the left thumb. In evaluating online news reports, we found 25 unique individuals with death or injury attributed to fractal wood burning from July 2016 to January 2020. Five sustained substantial injuries, while 20 reportedly died. Ages ranged from 17 years old to the 60s. One death and one injury occurred in females, with the remainder of reports involving males. Of the survivors, four sustained significant upper extremity electrical injuries and three suffered cardiac arrest at the time of injury. Fractal wood burning is associated with devastating high-voltage electrical injuries and death. Prevention efforts should be focused on education about the potential for death and permanently disabling injuries from this art form.


Orbital-dependent modifications of electronic structure across the magnetostructural transition in BaFe2As2.
Laser angle-resolved photoemission spectroscopy (ARPES) is employed to investigate the temperature (T) dependence of the electronic structure in BaFe2As2 across the magnetostructural transition at T{N} approximately 140 K. A drastic transformation in Fermi surface (FS) shape across T{N} is observed, as expected by first-principles band calculations. Polarization-dependent ARPES and band calculations consistently indicate that the observed FSs at k{z} approximately pi in the low-T antiferromagnetic state are dominated by the Fe3d{zx} orbital, leading to the twofold electronic structure. These results indicate that magnetostructural transition in BaFe2As2 accompanies orbital-dependent modifications in the electronic structure.


MRI features in dengue encephalitis: A case series in South Indian tertiary care hospital.
Dengue virus, a RNA virus of family Flaviviradae is considered non-neurotropic. Increasing studies and case reports reveal neurological manifestations of dengue virus. In our case series, we have evaluated magnetic resonance imaging (MRI) findings of 3 patients with dengue fever diagnosed by positive dengue NS1 antigen with neurological symptoms, which revealed nonspecific imaging features of dengue encephalitis in two cases and dengue meningoencephalitis in one case. Autopsy findings are also correlated in 2 patients who succumbed to their disease. This case series underlines the consideration of dengue encephalitis in patients of dengue fever with neurological symptoms and relevant imaging findings.


Systematic review of the effectiveness of urinary continence products.
Urinary incontinence is common, and considerable advances have been made in treatments and therapies for this distressing and socially unacceptable condition. Most people with incontinence use continence products to conceal their loss in the short term or long term. A huge range of products is available, including absorbent products, collection devices, catheters, and accessories. However, little guidance is available to aid consumers and health professionals in product selection. Therefore, a systematic review of research literature from 1982 to 2000 concerning the effectiveness of continence products was conducted. More than 350 articles were retrieved, of which 75 met the selection criteria for this review. It is apparent that there is a lack of high-quality research into the effectiveness of continence products. A recurrent theme in the literature is the importance of individual assessment to find products to suit the particular needs of each consumer. This review indicates that the absence of research information about the effectiveness of continence aids and appliances makes selection difficult.


The role of pulse oximetry in the accident and emergency department.
Prompt recognition and treatment of hypoxia is an important part of management in the accident and emergency (A & E) department. Until recently the only reliable method of detecting hypoxia was by estimation of the arterial blood gases (ABG). Continuous monitoring of the arterial oxygen saturation (Sao2) is possible using an infra-red pulse oximeter. This study assessed the usefulness of this instrument in the A&E setting. The Sao2 was measured in 50 patients using a pulse oximeter. In 15 patients simultaneous ABG estimations were obtained. The Sao2 correlated closely with calculated values for Sao2. The use of the oximeter identified 21 patients (42%) with clinically unsuspected hypoxia. The pulse oximeter proved simple to use, accurate and a useful addition to our resuscitation equipment.


Confidence and Prediction Intervals for Pharmacometric Models.
Supporting decision making in drug development is a key purpose of pharmacometric models. Pharmacokinetic models predict exposures under alternative posologies or in different populations. Pharmacodynamic models predict drug effects based on exposure to drug, disease, or other patient characteristics. Estimation uncertainty is commonly reported for model parameters; however, prediction uncertainty is the key quantity for clinical decision making. This tutorial reviews confidence and prediction intervals with associated calculation methods, encouraging pharmacometricians to report these routinely.


New dengue antibody assay with unique differential detection of IgG and IgM antibodies.
Most of the serological methods, traditional and recent, that have been developed to assess laboratory confirmation of dengue infection, suffer from the need to use separate tests for IgM and for IgG and the need for paired serum specimens in order to establish a clinical interpretation. Moreover, most of the IgG tests ignore early convalescence as well as past exposure. The objectives of this study is to demonstrate the advantages of the ImmunoComb Dengue BiSpot, a new dengue antibody assay, that detects simultaneously both dengue-specific IgM and IgG, in determining type and status of infection in a single test. Single and paired positive and negative specimens obtained from various dengue-high prevalent regions and from dengue-free areas were used. The specimens were comprised of admission samples of suspected patients and secondary dengue infection individuals, a group of hospital patients, asymptomatic to dengue who originated from dengue high prevalence areas and dengue-negative volunteers. All samples were tested by the ImmunoComb Dengue BiSpot kit along with the gold standard assays of Hemagglutination-inhibition (HAI) and MAC ELISA. Testing 365 gold standard positive specimens from different regions, the ImmunoComb Dengue BiSpot kit revealed sensitivity for IgM of 97.5% and 99.1% for IgG. The IgG was segregated into 2 groups: 86.6% for high titer and 12.5% for low titer of IgG. The overall sensitivity was 98.9%. The overall specificity of the kit, testing 657 samples, mostly from dengue-free area was 97.9%. The higher diagnostic resolution of the Dengue BiSpot test was demonstrated when the performance of the kit on the various groups was compared to the gold standard tests and the dengue status was determined in paired specimens by the new assay. The results of the present studies demonstrate the advantages of ImmunoComb Dengue BiSpot assay as an alternate strategy for the determination of dengue infection status. The combined use of IgM and IgG to discriminate between primary and secondary infections, on one hand, and providing high resolution in distinction of convalescence stage and past infection, on the other hand, endow the kit with improved capacity in assessing the clinical status of a tested individual in a single test.


Two approaches for the stabilization of Bacillus anthracis recombinant protective antigen.
Anthrax is a zoonotic disease caused by the gram-positive spore-forming bacteria Bacillus anthracis. There is a need for safe, highly effective, long-term storage vaccine formulations for mass vaccination. However, the development of new subunit vaccines based on recombinant protective antigen (rPA) faces the problem of vaccine antigen instability. Here, the potential of simultaneous application of two different approaches to stabilize rPA was demonstrated. Firstly, we employed spherical particles (SPs) obtained from the tobacco mosaic virus (TMV). Previously, we had reported that SPs can serve as an adjuvant and platform for antigen presentation. In the current work, SPs were shown to increase the stability of the full-size rPA without loss of its antigenic properties. The second direction was site-specific mutagenesis of asparagine residues to avoid deamidation that causes partial protein degradation. The modified recombinant protein comprising the PA immunogenic domains 3 and 4 (rPA3 + 4) was stable during storage at 4 and 25°C. rPA3 + 4 interacts with antibodies to rPA83 both individually and as a part of a complex with SPs. The results obtained can underpin the development of a recombinant vaccine with a full-size modified rPA (with similar amino acid substitutions that stabilize the protein) and SPs.


Intensity of Therapy for Malignancy and Risk for Recurrent and Complicated Clostridium difficile Infection in Children.
Clostridium difficile infection (CDI) is common in pediatric oncology patients and is often associated with recurrences and complications. We hypothesized that higher intensity of chemotherapy would be associated with these outcomes. We conducted a retrospective cohort study including all cases of primary CDI in children with malignancy in our institution for over 7 years. Intensity of chemotherapy was measured by the Intensity of Treatment Rating Scale, third edition, ranging from level 1 (minimal) to 4 (highest). Outcomes included recurrence within both 56 and 180 days, CDI-associated complications, and primary treatment failure (PTF). Risk of recurrence was compared using Cox proportional hazards regression. Among 192 patients with CDI and malignancy, 122 met inclusion criteria. CDI recurred in 27% (31/115) of patients followed for 56 days and 46% (48/104) of patients followed for 180 days. Fourteen patients (11.4%) had a CDI-associated complication, including 4 intensive care unit admissions and 3 surgical procedures, but no deaths. Ten patients (8.2%) had PTF. Although PTF and severe complications were infrequent, recurrence was common in our cohort. None of these outcomes were associated with level of treatment intensity. More research is required to assess oncologic and nononcologic risk factors for CDI recurrence, PTF, and severe CDI-associated complications.


[Paradigm of radiation-laser medical equipment and technology].
Based on quantum chemistry and chemical kinetics, the paper formulates basically new concepts of the possibility of controlling biochemical reactions in biological tissues by simultaneously making abnormal human visceral foci, in cancer diseases in particular, exposed to two rays via radiation and optic laser radiations. The paper also presents experimental findings of the channeling of X-ray and fluxes of charged particles along the fiber wave guides. It considers the circuit engineering of a medical endoscopic device that concurrently transmits optic laser radiation and fluxes of penetrating radiation into the viscera.


Comparison of surrogate indices for insulin sensitivity with parameters of the intravenous glucose tolerance test in early lactation dairy cattle.
The aim of this study was to investigate the correlation between different surrogate indices and parameters of the intravenous glucose tolerance test (IVGTT) in dairy cows at the start of their lactation. Ten dairy cows underwent IVGTT on Days 3 to 7 after calving. Areas under the curve during the 90 min after infusion, peak and nadir concentrations, elimination rates, and times to reach half-maximal and basal concentrations for glucose, insulin, nonesterified fatty acids, and β-hydroxybutyrate were calculated. Surrogate indices were computed using the average of the IVGTT basal samples, and their correlation with the IVGTT parameters studied through the Spearman's rank test. No statistically significant or strong correlation coefficients (P > 0.05; |ρ| < 0.50) were observed between the insulin sensitivity measures derived from the IVGTT and any of the surrogate indices. Therefore, these results support that the assessment of insulin sensitivity in early lactation cattle cannot rely on the calculation of surrogate indices in just a blood sample, and the more laborious tests (ie, hyperinsulinemic euglycemic clamp test or IVGTT) should be employed to predict the sensitivity of the peripheral tissues to insulin accurately.


Grating-tuned dual-wavelength Nile red dye laser.
Dual-wavelength operation of grating-tuned dye laser systems was demonstrated in this paper. We used the second harmonic generation of a Q-switched Nd:YAG laser to pump the Nile red solvent (dissolved in ethanol) in the Littrow configuration and the Littman-Metcalf configuration. By rotating the grating 3.6° in the Littrow configuration and the tuning mirror 3.9° in the Littman-Metcalf configuration, we obtained a 72 and 46 nm tuning-range dye laser output, respectively. Meanwhile by parallelly moving the grating in the Littrow configuration and the tuning mirror in the Littman-Metcalf configuration, we achieved the separation of dual wavelength from 0.7 to 5 nm in the former and 1.5 to 4 nm in the latter, which were in the terahertz range and could find applications in the terahertz source after using difference frequency technology. Finally, after considering the laser trajectories in the two configurations, we theoretically analyzed the reasons for overall tuning and separation tuning of dual wavelength.


The Prevalence of Individual Histopathologic Features Varies according to Autoantibody Status in Muscle Biopsies from Patients with Dermatomyositis.
Individual dermatomyositis (DM)-associated autoantibodies are associated with distinct clinical phenotypes. This study was undertaken to explore the association of these autoantibodies with specific muscle biopsy features. DM subjects with a muscle biopsy reviewed at Johns Hopkins had sera screened for autoantibodies recognizing Mi-2, transcriptional intermediary factor 1-γ (TIF1-γ), NXP2, MDA5, Ro52, PM-Scl, and Jo1. We also included anti-Jo1–positive patients with polymyositis (PM) who had a biopsy read at Johns Hopkins. Analyzed histological features included perifascicular atrophy, perivascular inflammation, mitochondrial dysfunction, primary inflammation, and myofiber necrosis. Duration of disease, biopsy location, and treatment at biopsy were also analyzed. We studied 91 DM and 7 anti-Jo1–positive patients with PM. In univariate analyses, TIF1-γ+ patients had more mitochondrial dysfunction (47% vs 18%; p = 0.05), NXP2+ patients had less primary inflammation (0% vs 28%; p = 0.01), Mi-2+ patients had more primary inflammation (50% vs 19%; p = 0.03), and PM-Scl+ patients had more primary inflammation (67% vs 18%; p = 0.004) than those who were negative for each autoantibody. Although reliability was limited because of small sample numbers, multivariate analysis confirmed that TIF1-γ+ patients had more mitochondrial dysfunction [prevalence ratio (PR) 2.6, 95% CI 1.0–6.5, p = 0.05] and PM-Scl+ patients had more primary inflammation (PR 5.2, 95% CI 2.0–13.4; p = 0.001) independent of disease duration at biopsy, biopsy site, and treatment at biopsy. No differences in muscle biopsy features were noted between anti-Jo1–positive patients diagnosed with DM and PM. The prevalence of different histological features varies according to autoantibody status in DM. Muscle biopsy features are similar in anti-Jo1 patients with and without a rash.


Severe medical illness complicating cesarean section.
The care of the perioperative cesarean birth patient who has serious medical illnesses has changed in the past decade. The increasing sophistication of monitoring has allowed the obstetrician and anesthesiologist better to modify certain physiologic parameters that are important in the care of the patient whose physiology has been altered by surgery or disease. As an increasing segment of the obstetric population becomes older, and with better survival of medical diseases, the profession as a whole will be challenged by these patients. It will become more important that a certain subset of physicians develop the skills necessary to undertake the care of these patients and that the special needs of these patients be recognized.


Effects of supplementation with spray-dried porcine plasma on blood variables on piglets feed with diet contaminated by mycotoxins.
The aim of this study was to evaluate the supplementation spray-dried porcine plasma (SDPP) effects on body weight, glucose levels and hematological and immunology variables for piglets fed with diet contaminated with low or high aflatoxin and fumonisin levels. Thus, 24 piglets were allotted in four groups, and the group A received a control diet; the group B received a diet with 6% of SDPP; the group C 300 μg/kg of aflatoxins and 8000 μg/kg of fumonisin; the group D 300 μg/kg of aflatoxins, 8000 μg/kg of fumonisin and 6% of SDPP, respectively. A significant increase on hemoglobin concentration and hematocrit levels was observed between C and A groups, result similar also in group D to hemoglobin concentration. A significant reduction on leukocytes and monocytes levels was observed in the group C compared to group A. Most important finding was that SDPP prevented reduction on leukocytes, but not in the monocytes levels in animals of group D. Moreover, the animals of group C presented lower weight, in the same way presented lower on glucose levels. In the other hand, animals in the group C had higher levels of nitrate/nitrite (NOx) and C-reactive protein (CRP) compared other groups. Based on these evidences, the present study showed ingestion of diet contaminated with elevated aflatoxins and fumonisins levels may negatively affected the white cell count and the weight, increasing the seric biomarkers related to inflammatory response, and consequently impairs the immune system. Additionally, SDPP supplementation for piglets prevents the reduction on leukocytes levels and the negative effects associated with weight gain, as well as minimizing the inflammatory response, demonstrating that SDPP can modulate the inflammatory processes and consequently may improve the immune system due active proteins presents in SDPP.


Effects of Host Sex, Plant Species, and Putative Host Species on the Prevalence of Wolbachia in Natural Populations of Bemisia tabaci (Hemiptera: Aleyrodidae): A Modified Nested PCR Study.
Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) is a globally distributed pest. One of the key endosymbionts in B. tabaci is Wolbachia, an α-proteobacterium implicated in many important biological processes. Previous studies indicated that the infection frequency of Wolbachia in Middle East-Asia Minor 1 (MEAM1) and Mediterranean (MED) varied greatly among populations in different areas. However, little is known about the factors that influence the prevalence of Wolbachia in B. tabaci. In this paper, 25 field populations were collected from different locations in China, and 1,161 individuals were screened for the presence of Wolbachia using a nested polymerase chain reaction (PCR)-based method, which targets the wsp gene, to confirm Wolbachia infection status. The prevalence of Wolbachia ranged from 1.54 to 66.67% within the 25 field populations, and the infection frequency of Wolbachia was affected significantly by the putative species of B. tabaci. The infection frequency (51.55%) of Wolbachia was significantly greater in native species than in the MED (25.65%) and MEAM1 (14.37%). With the exception of host plant, all factors, including putative species, geographic location, and the sex of the host, affected the Wolbachia infection frequency in whiteflies. Six Wolbachia strains were found and clustered into four distinct clades upon phylogenetic analyses. Furthermore, Wolbachia in B. tabaci have close relationships with those from other host species, including Liriomyza trifolii (Burgess), Sogatella furcifera (Horvath), Nilaparvata lugens (Stål), and Culex pipiens L. The results demonstrated the variation and diversity of Wolbachia in B. tabaci field populations, and that the application of nested PCR extended our knowledge of Wolbachia infection in B. tabaci, especially in invasive whiteflies.


The malin-laforin complex suppresses the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system.
Lafora disease (LD), a progressive form of inherited epilepsy, is associated with widespread neurodegeneration and the formation of polyglucosan bodies in the neurons. Laforin, a protein phosphatase, and malin, an E3 ubiquitin ligase, are two of the proteins that are defective in LD. We have shown recently that laforin and malin (referred together as LD proteins) are recruited to aggresome upon proteasomal blockade, possibly to clear misfolded proteins through the ubiquitin-proteasome system (UPS). Here we test this possibility using a variety of cytotoxic misfolded proteins, including the expanded polyglutamine protein, as potential substrates. Laforin and malin, together with Hsp70 as a functional complex, suppress the cellular toxicity of misfolded proteins, and all the three members of this complex are required for this function. Laforin and malin interact with misfolded proteins and promote their degradation through the UPS. LD proteins are recruited to the polyglutamine aggregates and reduce the frequency of aggregate-positive cells. Taken together, our results suggest that the malin-laforin complex is a novel player in the neuronal response to misfolded proteins and could be potential therapeutic targets for neurodegenerative disorders associated with cytotoxic proteins.


Analysis of Virus-Derived siRNAs in Strawberry Plants Co-Infected with Multiple Viruses and Their Genotypes.
Plants can be infected with multiple viruses. High-throughput sequencing tools have enabled numerous discoveries of multi-strain infections, when more than one viral strain or divergent genomic variant infects a single plant. Here, we investigated small interfering RNAs (siRNAs) in a single strawberry plant co-infected with several strains of strawberry mottle virus (SMoV), strawberry crinkle virus (SCV) and strawberry virus 1 (StrV-1). A range of plants infected with subsets of the initial viral species and strains that were obtained by aphid-mediated transmission were also evaluated. Using high-throughput sequencing, we characterized the small RNA fractions associated with different genotypes of these three viruses and determined small RNA hotspot regions in viral genomes. A comparison of virus-specific siRNA (vsiRNA) abundance with relative viral concentrations did not reveal any consistent agreement. Strawberry mottle virus strains exhibiting considerable variations in concentrations were found to be associated with comparable quantities of vsiRNAs. Additionally, by estimating the specificity of siRNAs to different viral strains, we observed that a substantial pool of vsiRNAs could target all SMoV strains, while strain-specific vsiRNAs predominantly targeted rhabdoviruses, SCV and StrV-1. This highlights the intricate nature and potential interference of the antiviral response within a single infected plant when multiple viruses are present.


Non-gravimetric contributions to QCR sensor response.
Quartz crystal resonator (QCR) sensors are commonly known as mass sensitive devices, usually called QCM (Quartz Crystal Microbalance). This constricted view should not be applied to biosensor applications. In many cases the sensor response is strongly influenced or even governed by non-gravimetric effects; the QCR sensor does not act as a microbalance. For better understanding of the sensor response as well as for sensor optimization a more general description of the sensor principle is required. The Transmission Line Model (TLM) is a powerful tool to describe the transduction scheme of QCR and other acoustic-wave based sensors. It is therefore applied to the analysis of the sensor behavior under several conditions, which can be expected in biochemical experiments. The generalization of acoustic parameters provides a concept to overcome some of the limiting assumptions of the present TLM.


Nonadiabatic dynamics and simulation of time resolved photoelectron spectra within time-dependent density functional theory: Ultrafast photoswitching in benzylideneaniline.
We present a theoretical approach for the nonadiabatic dynamics "on the fly" based on the combination of the time-dependent density functional theory (TDDFT) with Tully's stochastic surface hopping method. Our formulation is based on localized Gaussian basis sets and is suitable for the simulation of ultrafast processes in complex molecular systems including all degrees of freedom. Our approach is used for the simulation of time resolved photoelectron spectra in the framework of the Wigner distribution approach. In order to illustrate the scope of the method, we study the ultrafast photoswitching dynamics of the prototype Schiff base benzylideneaniline (BAN). The nonradiative lifetime of the S(1) state of BAN is determined to be approximately 200 fs. The mechanism of the photoisomerization has been investigated and a connection between the time resolved photoelectron signal and the underlying nonadiabatic processes has been established.


Cellular attachment to implanted foreign bodies in relation to tumorigenesis.
Previous experiments demonstrating a reduction of tumorigenicity by roughening the surfaces of plastics implanted in rodents, or by increasing the pore size of cellulose filter implants, were repeated with observations on cellular attachment to these objects and to filters strengthened and made impermeable by bonding to plastic. Round 13-mm discs of methylmethacrylate implanted S.C. in A/BiF/F50 + mice produced sarcomas in 12 percent of mice at 64 weeks. Tumor incidence increased to 60 percent (p less than 0.001) in mice receiving discs to which cellulose filters with pore sizes of 0.025 to 0.1 micrometer were bonded. No tumors occurred with discs covered by 0.45-micrometer filters, followed up to 83 weeks. Vinyl coverslips 15 mm square also produced no sarcomas when covered by 0.45 micrometer filters; plain vinyl produced sarcomas in 40 percent of mice at 64 weeks (p less than 0.001). Sanding of vinyl surfaces reduced tumorigenicity (p less than 0.05). Permeability, fragility, and storage capacity of filters are apparently not related to tumorigenicity. Surface roughness probably is related. Cells, mostly macrophages, were densely and uniformly attached to nontumorigenic surfaces from 24 hr to 2 years after inplantation but were distinctly fewer and not uniformly distrubuted on tumorigenic surfaces. Topology favoring attachment was inherent in 0.45-mum filters and was produced in plastic by gouging irregular excavations 10 to 15 micrometer deep.


Demystifying the Capitella capitata complex (Annelida, Capitellidae) diversity by morphological and molecular data along the Brazilian coast.
The sibling species of Capitella capitata are globally known for their tolerance to disturbed habitats and the C. capitata complex is often used as an ecological indicator. A recent re-description proposed that C. capitata, originally described in Greenland is restricted to the Artic and Subarctic regions. Given their ecological relevance, we conducted a morphological and molecular analyses based on mtDNA sequences to investigate the diversity and distribution of the C. capitata complex along the Brazilian coast. Our morphological and molecular data were congruent and revealed the existence of four new species distinct from C. capitata, collected from the type locality. This study is the first characterization of the biodiversity and distribution of Capitella species made along the Brazilian coast and yielded a set of morphological characters corroborated by the mtDNA sequences for species identification. Our results increase the biodiversity of the genus along the Brazilian coast by describing four new species (Capitella aracaensis sp. n., Capitella biota sp. n., Capitella neoaciculata sp. n. and Capitella nonatoi sp. n.). One species was collected from only one sampling site, while the others are distributed along the coast.


Sheng-Xue-Xiao-Ban Capsule-induced ischemic colitis and pulmonary embolism in an idiopathic thrombocytopenic purpura patient: a rare case report.
Sheng-Xue-Xiao-Ban Capsule (SXXBC), as a classic Chinese traditional medicine comprised of natural indigo, cortex moutan, forsythia, herba agrimoniae, and licorice, exhibits a heat-clearing and detoxicating function, hemostasis, and stasis dissipation, which is widely applied to treat idiopathic thrombocytopenic purpura (ITP). However, report on ischemic colitis and pulmonary embolism induced by SXXBC therapy is never disclosed. We report the case of an ITP patient who received SXXBC for ascending platelets that then induced ischemic colitis and pulmonary embolism. A 74-year-old female patient was admitted in June 2021 due to "bleeding in stool for 1 day," she was then re-admitted in July 2021 due to "repeated bleeding in stool for 2 days". Abdominal computed tomography (CT), colonoscopy, and a pathological examination suggested ischemic colitis according to the American College of Gastroenterology (ACG) clinical guidelines. Pulmonary artery CT angiography suggested pulmonary embolism reflected by multiple filling defects, and the patient presented with shortness of breath. It was noted that the patient had started taken SXXBC for ascending platelets 2 months before the onset of hematochezia. After the diagnosis of hematochezia was made, the patient received phenethylamine and carbazochrome for hemostasis, mesalazine enteric-coated tablets for anti-inflammation, and SXXBC was stopped. The hematochezia then ceased, and the ischemic colitis was attenuated. Afterwards, low-molecular-weight heparin was administered, followed by a 3-week treatment of rivaroxaban anticoagulant, which was taken orally after discharge. The pulmonary embolism was then obviously ameliorated. After excluding other causes, the patient was diagnosed with SXXBC-induced ischemic colitis complicated by pulmonary embolism. After conducting research, we came to the view that natural indigo, which is the main component of SXXBC, contributed to the patient's illness. Ischemic colitis complicated with pulmonary embolism are rare; however, close attention such as regular abdominal CT test needs to be paid and preventive steps such as anti-coagulant treatment could to be taken (if symptoms occur) when treating patients with SXXBC.


[Toward therapeutic application of IL-10-producing regulatory T cells].
IL-10 is an anti-inflammatory cytokine with an important role in preventing inflammatory and autoimmune responses. IL-10 is also important for suppressive function of inducible regulatory T (iTreg) cells, several types of which were reported in succession. Type1 regulatory T (Tr1) cell is a representative of IL-10-prroducing regulatory T cells. Although specific surface markers or origin of Tr1 cells have not fully been clarified yet, IL-27 was recently reported to induce IL-10 production in T cells and be an inducer of Tr1 cells. We previously reported that CD4(+)CD25(-)lymphocyte activation gene (LAG-3)(+) Treg (LAG3(+) Treg) is one of the peripherally inducible Tregs and functions as an immune-regulator through IL-10 production. We found that the expression level of Egr-2, a transcription factor required for T cell anergy induction, is elevated in LAG3(+) Treg and that forced expression of Egr-2 induces LAG-3 expression and IL-10 production. Egr-2 has been suggested to be a key player of regulatory function in LAG3(+) Treg. In this study, we review Tr1 cells and the mechanism of IL-10 induction by IL-27 in T cells. Also, we introduce LAG3(+) Treg and discuss the therapeutic potential of these regulatory T cells.


Modifiable Pancreatic Ductal Adenocarcinoma (PDAC) Risk Factors.
This study aims to summarize the modifiable risk factors for pancreatic ductal adenocarcinoma (PDAC) that have been known for a long time, as well as information from the most recent reports. As a cancer with a late diagnosis and poor prognosis, accurate analysis of PDAC risk factors is warranted. The incidence of this cancer continues to rise, and the five-year survival rate is the lowest with respect to other tumors. The influence of cigarette smoking, alcohol consumption, and chronic pancreatitis in increasing the risk of pancreatic ductal adenocarcinoma is continually being confirmed. There are also newly emerging reports relating to the impact of lifestyle, including physical activity, the gut and oral microbiome, and hepatotropic viruses. A precise understanding of PDAC risk factors can help to identify groups of high-risk patients, and this may contribute to population awareness and education as well as earlier diagnoses with possible better treatment outcomes.


Non-aqueous capillary electrophoresis of p-quinone anion radicals.
The electrophoretic detection of two kinds of p-quinone anion radicals arising from the electrolysis of benzoquinone and chloranil was achieved by employing an acetonitrile medium. Sufficient dehydration of a running solution was necessary for the detection of the benzoquinone anion radical. Oxygen in the running solution also caused a serious decrease in the amount of the benzoquinone anion radical during electrophoresis. The addition of methanol as a hydrogen-donor decreased the electrophoretic mobility of the benzoquinone anion radical significantly, while that of the chloranil anion radical was little changed. This result is interpreted in terms of hydrogen-bonding interaction between the p-quinone anion radicals and methanol, reflecting the magnitude of their proton-accepting ability (benzoquinone anion radical > chloranil anion radical).


Effect of catgut implantation at acupoints on GABA(B) and mGluR1 expressions in brain stem of rats with spasticity after stroke. .
To investigate the effect of catgut implantation at acupoints on the expressions of γ-amino butyric acid B receptor (GABA(B)) and metabotropic glutamate receptor 1 (mGluR1) in the brain stem of rats with spasticity after stroke. In total, 60 male Sprague-Dawley rats were randomly divided into three groups: a sham group (n = 10), a model group (n = 25) and a treatment group (n = 25). The rats in both the model group and the treatment group were subjected to middle cerebral artery occlusion to establish a model of focal cerebral ischemia. Rats with limb-spasm met the inclusion criteria. Only the left carotid artery was isolated in sham group rats. Three days after modeling, the treatment group was subjected to catgut implantation at Dazhui (GV 14), Guanyuan (CV 4), and Zhongwan (CV 12). Neurological deficit symptoms were assessed with the Zea-Longa neurological deficit score. The Modified Ashworth Scale (MAS), and isolated muscle tone were used to evaluate spasticity before and after treatment. Immunohistochemistry was applied to determine the expression of GABA(B) and mGluR1 in the rat brain stem after treatment. After treatment, neural impairment symptoms had significantly improved in the treatment group when compared to the model group (P < 0.05). Both MAS and isolated muscle tone in the treatment group were significantly decreased when compared with the model group (P < 0.05), and were also lower than before treatment. GABA(B) expression was significantly higher and mGluR1 was lower in the treatment group when compared with the model group (P < 0.01 and P < 0.05, respectively). Catgut implantation at Dazhui (GV14), Guanyuan (CV 4), and Zhongwan (CV 12), can relieve limb spasticity by increasing the expression of GABA(B) and reducing the expression of mGluR1 in the brain stem of rats after stroke.


Factors affecting willingness to participate in vaccine clinical trials in an underdeveloped country: perspective from Nepal.
Due to the inherent complex nature of clinical trials, individual's willingness to participate and hence, enrollment in a clinical trial maybe challenging. When it comes to vaccine clinical trial in children, informed consent needs to be secured from the parents or legally acceptable representatives (LARs). Some of the factors which contribute to hesitancy in taking part in clinical trials are based on the level of education, living standards, part of the world they live, associated burden of disease, fear of different procedures in clinical trial, side effects, limited understanding, limited time, and mistrust with Investigational product. This study included 201 parents/LARs, who approached Kanti Children Hospital site in Kathmandu with the interest to get their children enrolled in a vaccine clinical trial with objectives of describing the reasons for agreeing or disagreeing to participate in the vaccine clinical trial, factors affecting decision making, and finding the major concerns of parents/LARs. The acceptance for the study vaccine was 136 (67.7%) whereas denial was 65 (32.3%). This study showed that age, education level, family structure, advice from family and friends, and medical guidance play important roles in willingness of parents to get their child enrolled in the trial. If a proper counseling is done, fear of blood sampling is not a big factor which is contrary to the belief among clinical researchers. Safety of vaccine, frequency of injections, and cost of vaccine were the main concerns of the parents, which need to be addressed extensively while planning for any clinical trial in children.


Carbon ion fragmentation effects on the nanometric level behind the Bragg peak depth.
In this study, fragmentation yields of carbon therapy beams are estimated using the Geant4 simulation toolkit version 9.5. Simulations are carried out in a step-by-step mode using the Geant4-DNA processes for each of the major contributing fragments. The energy of the initial beam is taken 400 MeV amu(-1) as this is the highest energy, which is used for medical accelerators and this would show the integral role of secondary contributions in radiotherapy irradiations. The obtained results showed that 64% of the global dose deposition is initiated by carbon ions, while up to 36% is initiated by the produced fragments including all their isotopes. The energy deposition clustering yields of each of the simulated fragments are then estimated using the DBSCAN clustering algorithm and they are compared to the yields of the incident primary beam.


Enhanced antinociception by intracerebroventricularly and intrathecally-administered orexin A and B (hypocretin-1 and -2) in mice.
Orexins are neuropeptides located exclusively in neurons of the lateral hypothalamic area, which send projections to most monoaminergic nuclei, such as noradrenergic locus coeruleus, dopaminergic ventral tegmental areas, and histaminergic tuberomammillary nuclei. The present work was carried out to examine the role of orexins in nociception in mice. C57BL/6 mice were administered with orexin A and B intracerebroventricularly (i.c.v.), intrathecally (i.t.) and subcutaneously (s.c.) to reveal the sites of action of these peptides and to examine the pain thresholds using four kinds of nociceptive tasks. Orexins showed antinociceptive effects in all four types of assays for thermal (hot-plate, tail-flick, paw-withdrawal), mechanical (tail-pressure), chemical (formalin, capsaicin and abdominal stretch) nociceptions and nociceptin-induced behavioral responses, when administered i.c.v. or i.t., whereas the s.c. administration was ineffective. The antinociceptive effects of orexin A were more remarkable than those of orexin B. The i.c.v. administration of orexin A was as effective as, or more potent than the i.t. administration. The effects of orexin A were completely blocked by adenosine type 1 receptor antagonists, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) and theophylline, but not by naloxone, suggesting a possible involvement of the adenosine-containing neurons and/or the adenosine pathway in these orexin actions. The i.c.v. administration of nociceptin had no significant effects on orexin expression in the brain and spinal cord. The present findings suggest that orexins have an antinociceptive role in at least four different types of pains, probably acting on both the brain and spinal cord.


Occurrence of Cryptosporidium oocysts in US wastewaters.
Wastewater samples collected from ten wastewater facilities across the US were analyzed to determine the occurrence of indigenous Cryptosporidium oocysts using methods based on modifications of USEPA Method 1622. Wastewater facilities participating in this study ranged in size from 0.6 to 193 mgd average daily flow. A total of 289 wastewater samples were analyzed over a 15-month period. ColorSeed is a commercial product containing gamma-irradiated Cryptosporidium oocysts that have been permanently stained with a Texas Red dye. ColorSeed was used as an internal control with each sample to assess method performance. In 500ml sample volumes, mean ColorSeed recoveries in raw influents and primary effluents were 26.1 17.7% and 33.0 +/- 17.9%, respectively. In 10 liter volumes of secondary effluent, mean ColorSeed recovery was 25.0 +/- 16.6%. Volumes analyzed for tertiary effluent samples ranged from 14.81 to 131.31 resulting in a mean ColorSeed recovery of 48.8 +/- 14.5%. Indigenous oocysts were detected in 30% of raw influents, 46% of primary effluents, 58% of secondary effluents and 19% of tertiary effluents analyzed. Indigenous oocyst concentrations ranged from <2 to 86 /liter across all wastewater matrices tested.


Chip/Ldb1 interacts with Tailup/islet1 to regulate cardiac gene expression in Drosophila.
The LIM-homeodomain transcription factor Tailup (Tup) is a component of the complex cardiac transcriptional network governing specification and differentiation of cardiac cells in Drosophila. LIM-domain containing factors are known to interact with the adaptor molecule Chip/Ldb1 to form higher order protein complexes to regulate gene expression thereby determining a cell's developmental fate. However, with respect to Drosophila heart development, it has not been investigated yet, whether Chip and tup interact to regulate the generation of different cardiac cell types. Here we show that Chip is required for normal heart development and that it interacts with tup in this context. Particularly the number of Odd skipped-expressing pericardial cells depends on balanced amounts of Chip and Tup. Data from luciferase assays using Hand- and even-skipped reporter constructs in Drosophila S2 cells indicate that Chip and Tup act as a tetrameric complex on the regulatory regions of Hand and even-skipped (eve). Finally we have identified and verified five Tup binding sites in the eve mesodermal enhancer, which adds Tup as novel factor to directly regulate eve expression. Taken together this study provides novel findings regarding cardiac gene expression regulation in Drosophila.


Evidence for human antibodies that recognize an aflatoxin epitope in groups with high and low exposure to aflatoxins.
Antibody activity against an aflatoxin epitope has been detected in serum from individuals who live in Kenya and who experience high exposure to aflatoxin B1. The activity was higher than in Danish people. The highest antibody activity was found in individuals who were recently exposed to aflatoxin B1. The ratio between IgG and IgM activities was higher in individuals with a high antibody titer. The specificity of the antibody activity differed in the serums obtained from Danish and Kenyan persons ("Danish" and "Kenyan" serum, respectively). The activity in Danish serum was inhibited by an aflatoxin-like substance isolated from human urine, whereas aflatoxin B1 did not inhibit the activity. In contrast, the activity in Kenyan serum was not inhibited by the aflatoxin-like substances. Therefore, the presence of antibodies against aflatoxin in humans indicates exposure to aflatoxin or aflatoxin-antigenic material. However, the biological consequences of these antibodies remain unknown.


A purpose-built simulator for percutaneous ultrasound-guided renal biopsy.
To construct a simple and affordable simulator for ultrasoundguided percutaneous renal biopsy. The kidney biopsy phantom was constructed by embedding a porcine kidney in gelatine. Silicon carbide and aluminium oxide were used as scattering particles in order to mimic the ultrasound appearance of human tissues. Two porcine ribs were also embedded. A latex sheet was placed over the top of the gel layer to resemble skin. The simulator was used and feedback from participants obtained during a renal ultrasound course with an international audience of middle-grade trainees from adult and pediatric nephrology, many of whom had never done a renal biopsy. Biopsy was carried out a single-use biopsy gun. All participants were able to perform a biopsy and obtain a satisfactory sample. All trainees felt that our simulator was very realistic. 94% of participants agreed that the simulator would help to allay their fears in relation to renal biopsy The total cost of the simulator was around £ 50,- for consumables per simulator. We describe a purpose-built and affordable simulator for percutaneous ultrasound-guided renal biopsy. We suggest that others evaluate our simulator used as part of a structured approach to teach this important procedure.


The tryptophan requirement of male and female broilers during the 4-7 week period.
Studies with broiler type chickens were conducted to determine the minimum tryptophan requirement for maximum growth, optimum feed efficiency and molted body feather count for the 4-7 week period of growth for both male and females. Basal diets analyzed to contain 0.158, 0.157, and 0.147% tryptophan using analyzed tryptophan values of 0.09, 0.01, 0.31, 0.70, 0.40, and 0.46% for corn, gelatin, corn gluten meal, soybean meal, peanut meal-45, and peanut meal-50, respectively. Based on the regression equations for males, the calculated tryptophan requirement for maximum growth, optimum feed efficiency, and molted body feather count for the 4-7 week period is 0.179, 0.170, and 0.172%, respectively for 3300 Kcal. of M.E. per kg. of diet. When expressed as a function of energy, these requirements would be 0.054, 0.052, and 0.052% tryptophan per megacalorie of M.E. per kg. of diet, respectively. Based on the equations for females, the calculated tryptophan requirement for maximum growth, optimum feed efficiency, and molted body feather count is 0.173, 0.163, and 0.172%, respectively for 3300 Kcal. of M.E. per kg. of diet, respectively.


Psychological distress among homeless adults.
Recent studies have reported a high prevalence of mental illness among the homeless. As part of a community-based survey of 529 homeless adults, we developed and tested a model to increase our understanding of the factors related to their psychological distress. Using a previously validated and reliable scale of perceived psychological distress, we found that homeless adults were more likely to report psychological distress than the general population (80% vs. 49%). Distress levels were not associated with most demographic or homeless characteristics or general appearance. However, distress was related to unemployment, greater cigarette and alcohol use, worse physical health, fewer social supports, and perceived barriers to obtaining needed medical care. Since mental, physical, and social health are strongly related among homeless adults, alleviating distress among them may be most effectively done by implementing a broad-based health services package coupled with employment programs provided in an accessible service delivery setting.


Chromatographic and spectral studies of jetsam and archived ambergris.
We describe determination of the dichloromethane-soluble components of 12 samples of the natural product, ambergris, using capillary gas chromatography-mass spectrometry (GC-MS). Ambergris is produced in vivo in about 1% of Sperm whales and is used in perfumery and for odour fixation. Whilst descriptions of ambergris chemistry appeared until about 40 years ago, few accounts of analyses of whole extracts of multiple samples of ambergris by GC-MS have been published before. As expected, our analyses revealed that the major component (up to 97% of the dichloromethane-soluble material) was ambrein, with co-occurring, variable proportions of steroids. Moreover, we report apparently for the first time, mass spectra and retention indices of derivatised ambrein. These data should now allow reliable, rapid confirmation of even small amounts of jetsam, archived museum and customs samples of ambergris and an assessment of ambergris 'quality'.


Use of resources and cost implications of stroke prophylaxis with warfarin for patients with nonvalvular atrial fibrillation.
Patients with nonvalvular atrial fibrillation (NVAF) have often been excluded from long-term anticoagulant trials, and therefore patients in clinical practice may have different risk, compliance, and safety considerations from those usually included in such trials. The aim of this study was to investigate the use of resources and cost implications of stroke prophylaxis with warfarin in NVAF patients in clinical practice. New patients with NVAF referred to an anticoagulation clinic in the United Kingdom were interviewed in person at their first visit and then by telephone every 4 to 6 weeks by an investigator. They were asked about bleeding events and extra physician visits, procedures, or hospital admissions related to bleeding. They were also asked about the method and the cost of transportation to the anticoagulation clinic and the costs involved in days of work missed by the patient and caregiver. Costs of warfarin treatment consisted of the following: (1) cost of the drug, (2) cost of monitoring lie, international normalized ratio, traveling, nurse visits, work missed. postage), and (3) costs associated with complications (ie, bleeding-related physician visits, hospital admissions, related procedures). admissions, related procedures). A total of 402 patients were included. Mean (SD) age was 72.3 (10.3) years, and 224 patients (55.7%) were men. Mean (SD) follow-up was 19 (8.1) months (range, 1-31 months). Annual event rates were 1.7% (95% CI, 0.4-3.0) for major bleeding and 16.6% (95% CI, 13.0-20.2) for minor bleeding. The mean cost of warfarin treatment per patient per month was 11.0 pounds (95% CI, 10.2-11.6) in patients with no bleeding and 11.9 pounds (95% CI, 10.3-12.5) in patients with minor bleeding (P=NS). The cost was significantly higher in patients with major bleeding ( 299.0 pounds; 95% CI, 74.6-538.9; P<0.001). The total cost of warfarin treatment per patient per year was 159.4 pounds, and the cost to prevent 1 stroke per year was 5260.20 pounds. In clinical practice in the United Kingdom, anticoagulation with warfarin for prevention of ischemic stroke appeared to be cost-saving relative to the costs of stroke.


Isolation of retinal progenitor cells from post-mortem human tissue and comparison with autologous brain progenitors.
The goal of the present study was threefold: to determine whether viable human retinal progenitor cells (hRPCs) could be obtained from cadaveric retinal tissue, to evaluate marker expression by these cells, and to compare hRPCs to human brain progenitor cells (hBPCs). Retinas were dissected from post-mortem premature infants, enzymatically dissociated, and grown in the presence of epidermal growth factor and basic fibroblast growth factor. The cells grew as suspended spheres or adherent monolayers, depending on culture conditions. Expanded populations were banked or harvested for analysis by RT-PCR, immunocytochemistry, and flow cytometry. hBPCs derived from forebrain specimens from the same donors were grown and used for RT-PCR. Post-mortem human retinal specimens yielded viable cultures that grew to confluence repeatedly, although not beyond 3 months. Cultured hRPCs expressed a range of markers consistent with CNS progenitor cells, including nestin, vimentin, Sox2, Ki-67, GD2 ganglioside, and CD15 (Lewis X), as well as the tetraspanins CD9 and CD81, CD95 (Fas), and MHC class I antigens. No MHC class II expression was detected. hRPCs, but not hBPCs, expressed Dach1, Pax6, Six3, Six6, and recoverin. Minority subpopulations of hRPCs and hBPCs expressed doublecortin, beta-III tubulin, and glial fibrillary acidic protein, which is consistent with increased lineage restriction in subsets of cultured cells. Viable progenitor cells can be cultured from the post-mortem retina of premature infants and exhibit a gene expression profile consistent with immature neuroepithelial cells. hRPCs can be distinguished from hBPC cultures by the expression of retinal specification genes and recoverin.


A novel tyrosine hyperoxidation enables selective peptide cleavage.
A novel tyrosine hyperoxidation enabling selective peptide cleavage is reported. The scission of the N-terminal amide bond of tyrosine was achieved with Dess-Martin periodinane under mild conditions, generating a C-terminal peptide fragment bearing the unprecedented hyperoxidized tyrosine motif, 4,5,6,7-tetraoxo-1H-indole-2-carboxamide, along with an intact N-terminal peptide fragment. This reaction proceeds with high site-selectivity for tyrosine and exhibits broad substrate scope for various peptides, including those containing post-translational modifications. More importantly, this oxidative cleavage was successfully applied to enable sequencing of three naturally occurring cyclic peptides, including one depsipeptide and one lipopeptide. The linearized peptides generated from the cleavage reaction significantly simplify cyclic peptide sequencing by MS/MS, thus providing a robust tool to facilitate rapid sequence determination of diverse cyclic peptides containing tyrosine. Furthermore, the highly electrophilic nature of the hyperoxidized tyrosine unit disclosed in this work renders it an important electrophilic target for the selective bioconjugation or synthetic manipulation of peptides containing this unit.


Dietary intake of advanced glycation endproducts is associated with higher levels of advanced glycation endproducts in plasma and urine: The CODAM study.
Advanced glycation endproducts (AGEs) are formed by the reaction between reducing sugars and proteins. AGEs in the body have been associated with several age-related diseases. High-heat treated and most processed foods are rich in AGEs. The aim of our study was to investigate whether dietary AGEs, are associated with plasma and urinary AGE levels. In 450 participants of the Cohort on Diabetes and Atherosclerosis Maastricht study (CODAM study) we measured plasma and urine concentrations of the AGEs Nε-(carboxymethyl)lysine (CML), Nε-(1-carboxyethyl)lysine (CEL) and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) using UPLC-MS/MS. We also estimated dietary intake of CML, CEL and MG-H1 with the use of a dietary AGE database and a food frequency questionnaire (FFQ). We used linear regression to investigate the association between standardized dietary AGE intake and standardized plasma or urinary AGE levels, after adjustment for age, sex, glucose metabolism status, waist circumference, kidney function, energy- and macro-nutrient intake, smoking status, physical activity, alcohol intake, LDL-cholesterol and markers of oxidative stress. We found that higher intake of dietary CML, CEL and MG-H1 was associated with significantly higher levels of free plasma and urinary CML, CEL and MG-H1 (βCML = 0.253 (95% CI 0.086; 0.415), βCEL = 0.194 (95% CI 0.040; 0.339), βMG-H1 = 0.223 (95% CI 0.069; 0.373) for plasma and βCML = 0.223 (95% CI 0.049; 0.393), βCEL = 0.180 (95% CI 0.019; 0.332), βMG-H1 = 0.196 (95% CI 0.037; 0.349) for urine, respectively). In addition, we observed non-significant associations of dietary AGEs with their corresponding protein bound plasma AGEs. We demonstrate that higher intake of dietary AGEs is associated with higher levels of AGEs in plasma and urine. Our findings may have important implications for those who ingest a diet rich in AGEs.


Gut microbiota and irritable bowel syndrome.
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that poses a significant health concern. Although its etiology remains unknown, there is growing evidence that gut dysbiosis is involved in the development and exacerbation of IBS. Previous studies have reported altered microbial diversity, abundance, and composition in IBS patients when compared to controls. However, whether dysbiosis or aberrant changes in the intestinal microbiota can be used as a hallmark of IBS remains inconclusive. We reviewed the literatures on changes in and roles of intestinal microbiota in relation to IBS and discussed various gut microbiota manipulation strategies. Gut microbiota may affect IBS development by regulating the mucosal immune system, brain-gut-microbiome interaction, and intestinal barrier function. The advent of high-throughput multi-omics provides important insights into the pathogenesis of IBS and promotes the development of individualized treatment for IBS. Despite advances in currently available microbiota-directed therapies, large-scale, well-organized, and long-term randomized controlled trials are highly warranted to assess their clinical effects. Overall, gut microbiota alterations play a critical role in the pathophysiology of IBS, and modulation of microbiota has a significant therapeutic potential that requires to be further verified.


N-Terminal deletions modify the Cu2+ binding site in amyloid-beta.
Copper is implicated in the in vitro formation and toxicity of Alzheimer's disease amyloid plaques containing the beta-amyloid (Abeta) peptide (Bush, A. I., et al. (2003) Proc. Natl. Acad. Sci. U.S.A. 100, 11934). By low temperature electron paramagnetic resonance (EPR) spectroscopy, the importance of the N-terminus in creating the Cu(2+) binding site in native Abeta has been examined. Peptides that contain the proposed binding site for Cu(2+)-three histidines (H6, H13, and H14) and a tyrosine (Y10)-but lack one to three N-terminal amino acids, do not bind Cu(2+) in the same coordination environment as the native peptide. EPR spectra of soluble Abeta with stoichiometric amounts of Cu(2+) show type 2 Cu(2+) EPR spectra for all peptides. The ligand donor atoms to Cu(2+) are 3N1O when Cu(2+) is bound to any of the Abetapeptides (Abeta16, Abeta28, Abeta40, and Abeta42) that contain the first 16 amino acids of full-length Abeta. When a Y10F mutant of Abeta is used, the coordination environment for Cu(2+) remains 3N1O and Cu(2+) EPR spectra of this mutant are identical to the wild-type spectra. Isotopic labeling experiments show that water is not the O-atom donor to Cu(2+) in Abeta fibrils or in the Y10F mutant. Further, we find that Cu(2+) cannot be removed from Cu(2+)-containing fibrils by washing with buffer, but that Cu(2+) binds to fibrils initially assembled without Cu(2+) in the same coordination environment as in fibrils assembled with Cu(2+). Together, these results indicate (1) that the O-atom donor ligand to Cu(2+) in Abeta is not tyrosine, (2) that the native Cu(2+) binding site in Abeta is sensitive to small changes at the N-terminus, and (3) that Cu(2+) binds to Abetafibrils in a manner that permits exchange of Cu(2+) into and out of the fibrillar architecture.


Lipofibromatous hamartoma of the median nerve: case report with magnetic resonance imaging correlation.
The authors report a case of lipofibromatous hamartoma of the median nerve in a patient who presented with symptoms of carpal tunnel syndrome. The diagnosis was made by magnetic resonance imaging and confirmed by intraoperative findings and histological diagnosis; distinctive magnetic resonance imaging features of this entity are described. In this patient, surgery was limited to biopsy to confirm the diagnosis and external neural decompression, which helped to stop the progression of the symptoms. In their review of the literature, the authors found four types of lipomatous masses in the extremities affecting the function of peripheral nerves, commonly the median nerve. Treatment and the extent of surgery differ for each patient, based on the anatomical findings and extent of neurological deficit. The etiology, pathogenesis, differential diagnosis, and surgical management of lipofibromatous hamartoma are described.


Collagen-coated Ba(2+)-alginate microcarriers for the culture of anchorage-dependent mammalian cells.
Several types of microcarriers suitable for large-scale cultivation of mammalian cells are commercially available. However, many of these carriers have disadvantages, e.g., the need for enzymatic digestion for cell harvesting, size limitations and insufficient biocompatibility. These limitations have been overcome by the development of collagen-coated Ba(2+)-alginate microcarriers. Ba(2+)-alginate microspheres, made with the air-jet droplet generator technique, were collagen-coated by incubation in a 0.5% collagen solution, with subsequent gelling of the collagen layer around the alginate microspheres. Human chang liver (CCL-13) and mouse fibroblast (L929) cell lines were cultivated in stationary, unstirred cultures as model systems. After a lag phase of nearly 24 h, the cells grew rapidly on these microcarriers and reached confluence after 3 days. The microcarrier cultures were stable for an additional 4-9 days and longer. Cells were harvested either by trypsinization or by dissolution of the alginate matrix using 5 mM EDTA. The main advantages of this new microcarrier system are that the preparation procedure is easy and can be accomplished on demand with standard laboratory equipment.


Suppression of genes related to hypertrophy and osteogenesis in committed human mesenchymal stem cells cultured on novel nitrogen-rich plasma polymer coatings.
Mesenchymal stem cells (MSCs) are pluripotent progenitor cells with the ability to generate cartilage, bone, muscle, tendon, ligament, and fat. However, recent evidence indicates that a major drawback of current cartilage- and intervertebral disc-tissue engineering is that human MSCs isolated from some arthritic patients (a clinically relevant source of stem cells) express type X collagen (a marker of chondrocyte hypertrophy associated with endochondral ossification) and osteogenic markers. Some studies have attempted to use growth factors to inhibit type X collagen expression, but none has addressed the possible effect of the chemical composition of the substratum on chondrocyte hypertrophy and osteogenesis. Here, we examine the growth and differentiation potential of human MSCs cultured on nitrogen (N)-rich plasma polymer layers (N-doped plasma-polymerized ethylene, containing up to 36% nitrogen; PPE:N). We show that PPE:N almost completely suppresses the expression not only of type X collagen, but also of osteogenic marker genes such as alkaline phosphatase, bone sialoprotein, and osteocalcin. In contrast, neither aggrecan nor type I collagen expression were significantly affected. These results indicate that PPE:N coatings may be suitable surfaces for inducing MSCs to a chondrocyte or disc-like phenotype for tissue engineering of cartilage or intervertebral discs, in which hypertrophy and osteogenesis are suppressed.


Intrapleural Epinephrine Irrigation for Massive Malignant Hemothorax.
Massive malignant hemothorax (MMH) is a rare and serious complication encountered in the field of oncology and can be life threatening. It is often difficult and complex to manage. Herein, we present cases of four patients who had MMH and in whom a hemothorax was successfully stopped via continuous intrapleural irrigation with epinephrine (5-mg epinephrine/1,000-mL normal saline, infused at 100 mL/h) instead of a conventional surgical approach. Although no patient deaths were attributed to intractable bleeding, two deaths were related to multiple organ failure. Despite the limited number of cases, this method was a convenient, effective, and inexpensive alternative to open surgical or thoracoscopic drainage for MMH.


Novel strains of Bacteroides fragilis and Bacteroides ovatus alleviate the LPS-induced inflammation in mice.
Lipopolysaccharide (LPS) can promote the expression of pro-inflammatory cytokines, damage the tight junction of epithelial walls, and thereby lead to chronic low-grade intestinal inflammatory disorders. Evidences of many beneficial functions from Bacteroides strains suggest their intervention capabilities in LPS-induced inflammation. In the present study, both healthy and LPS-treated mice were consistently treated with Bacteroides strains for 5 days. The intestinal microbiota alteration, epithelial permeability, cytokine expression, and autoimmune and innate immune responses were analyzed. B. fragilis HCK-B3 and B. ovatus ELH-B2 from our laboratory collection were demonstrated to assist intestinal equilibrium by maintaining the diversity of gut microbiota and relieve LPS-induced inflammation by either modulating cytokine production or restoring the Treg/Th-17 balance. Our research indicated that the Bacteroides strains with capabilities of alleviating inflammation have the potential as therapeutics to prevent intestinal inflammatory disorders and provided scientific supports for discovering next-generation probiotics.


Genistein affects ER beta- but not ER alpha-dependent gene expression in the hypothalamus.
Isoflavone phytoestrogens are growing increasingly popular because of their reported cardiovascular and anticarcinogenic properties, but the effects of these compounds in the brain are largely unknown. In a previous study, we found that an isoflavone supplement, containing a mixture of soy phytoestrogens, inhibited estrogen-dependent female sexual behavior and was antiestrogenic for both ER alpha- and ER beta-dependent gene expression in the hypothalamus. Here we examined the impact of the soy isoflavone genistein, a major component of the supplement, on estrogen-dependent female sexual behavior and ER alpha- and ER beta-dependent gene expression in the rat brain. Genistein, at a dietary concentration of 100 or 500 ppm had no effect on lordosis behavior in rats. However, at 500 ppm genistein had differential activity through ER alpha and ER beta in the hypothalamus. Genistein had no effect, in either the presence or absence of 17 beta-E2, on oxytocin receptor density in the ventromedial nucleus of the hypothalamus, an estrogen-dependent action thought to be regulated via ER alpha. However, genistein increased ER beta mRNA expression in the paraventricular nucleus of the hypothalamus by 24%, whereas 17 beta-E2 decreased ER beta mRNA expression by 26%, a process likely mediated by ER beta itself. These results suggest that at this dose, genistein has antiestrogenic action through ER beta in the paraventricular nucleus but negligible activity through ER alpha in the brain.


[Pay attention to the standardization of uveitis nomenclature].
Uveitis is multiple disease entities with complicated causes and various manifestations. To better understand and compare the severity and improve multi centers clinical research, standardized nomenclature and grade is needed. Based on the result of Standardization of Uveitis Nomenclature working group, this paper briefly introduce the classification, onset and course, inflammation grading, diagnosis standard for complications.