Schistosoma japonicum cathepsin B2 (SjCB2) facilitates parasite invasion through the skin.
Cercariae invasion of the human skin is the first step in schistosome infection. Proteases play key roles in this process. However, little is known about the related hydrolytic enzymes in Schistosoma japonicum. Here, we investigated the biochemical features, tissue distribution and biological roles of a cathepsin B cysteine protease, SjCB2, in the invasion process of S. japonicum cercariae. Enzyme activity analysis revealed that recombinant SjCB2 is a typical cysteine protease with optimum temperature and pH for activity at 37°C and 4.0, respectively, and can be totally inhibited by the cysteine protease inhibitor E-64. Immunoblotting showed that both the zymogen (50 kDa) and mature enzyme (30.5 kDa) forms of SjCB2 are expressed in the cercariae. It was observed that SjCB2 localized predominantly in the acetabular glands and their ducts of cercariae, suggesting that the protease could be released during the invasion process. The protease degraded collagen, elastin, keratin, fibronectin, immunoglobulin (A, G and M) and complement C3, protein components of the dermis and immune system. In addition, proteomic analysis demonstrated that SjCB2 can degrade the human epidermis. Furthermore, it was showed that anti-rSjCB2 IgG significantly reduced (22.94%) the ability of the cercariae to invade the skin. The cysteine protease, SjCB2, located in the acetabular glands and their ducts of S. japonicum cercariae. We propose that SjCB2 facilitates skin invasion by degrading the major proteins of the epidermis and dermis. However, this cysteine protease may play additional roles in host-parasite interaction by degrading immunoglobins and complement protein.


Cricoid pressure: a review of the literature.
Aspiration pneumonitis (Mendelson's syndrome) is universally accepted as a complication of general anaesthesia. According to Ellis et al (2007) death from aspiration was first described by Simpson in 1848, and it was not until 1946 that Mendelson identified acid aspiration in a significant number of obstetric patients undergoing facemask anaesthesia. The advent of techniques to secure the airway, through the use of airway adjuncts has gone some way to reduce the likely incidence of aspiration in today's perioperative arena. The positive outcome for patients is corroborated by Neilipovitz & Crosby (2007) who report aspiration as a rare complication with an overall incidence of 1:2,000-3,000. As Ewart (2007) highlights, Mendelson's syndrome is due to pharmacological effects at a molecular level which occur in the airway tissues and are caused by the use of induction and neuromuscular blocking agents. The resultant loss of consciousness and consequent diminished protective airway reflexes ultimately places the patient at risk until their airway is secured. Preventative measures to protect the lung from contamination with gastric contents, for example preoperative fasting, are therefore instigated prior to securing the airway.


[Progress on cellulosic ethanol produced from beet pulp].
Cellulosic ethanol, with the advantages of renewable resource, cleanliness and safety, is the mainstream of new energy development and has obtained extensive attention worldwide. In this review, the biological characteristics of beets were introduced, and then the superiority and application progress of beets and its by-product sugar beet pulp in the bioethanol production were stated. At last, cellulosic ethanol production coupled with the component separation and comprehensive utilization of beet pulp was proposed.


Effect of caregiver education on pulmonary rehabilitation, respiratory muscle strength and dyspnea in lung cancer patients.
[Purpose] This study evaluated the effects of caregiver education on pulmonary rehabilitation of patients who have undergone lung resection for cancer. [Subjects] Patients were divided into experimental (n = 22) and control (n = 19) groups. [Methods] The caregivers of the experimental group patients received education on pulmonary rehabilitation, while the control group patients received general management advice for 4 weeks. [Results] Pulmonary muscle strength (maximum inspiratory pressure and maximum expiratory pressure) was increased significantly in the experimental group compared to the control group. Modified Borg scale scores were decreased significantly in the experimental vs. [Conclusion] Providing caregivers with education pertaining to pulmonary rehabilitation was associated with improved pulmonary function in lung cancer patients following lung resection.


Note on the free energy of transfer of fullerene C60 simulated by using classical potentials.
Diverse atomistic parameters of C60 have been developed and utilized to simulate fullerene solutions in biological environments. However, no thermodynamic assessment and validation of these parameters have been so far realized. Here, we employ extensive molecular dynamics simulations with the thermodynamic integration method in the isothermal-isobaric ensemble to investigate the transfer of a single fullerene C60 between different solvent environments using different potential models. A detailed analysis is performed on the structure and standard Gibbs free energy of transfer of C60 from benzene to ethanol. All of the interactions concerned in the transfer process are included via atomistic models. We notice that having only structural and dynamical properties is not decisive to validate reliable atomic parameters capable of describing a more realistic thermodynamic process. Thus, we employ the calculated free energy of transfer to validate more accurate atomic parameters for the solvation thermodynamics of fullerenes by direct comparison with the solubility experimental data.


Recent Advances in the Construction of Fluorinated Organoboron Compounds.
Fluorinated organoboron compounds are important synthetic building blocks that combine the unique characteristics of a fluorinated motif with the versatile synthetic applications of organoboron moiety. This review article guides the research on fluorinated organoboron compounds mainly from four aspects in recent years: selective monodefluoroborylation of polyfluoroarenes and polyfluoroalkenes, selective borylation of fluorinated substrates, selective fluorination of organoboron compounds, and borofluorination of alkynes/olefins. In addition, this review will provide a necessary guidance and inspiration for the research on the valuable synthetic building block fluorinated organoboron compounds.


Hyperbaric oxygen. A therapy in search of diseases.
The application of HBO to the therapy of various human diseases developed over a 300 year period. Like most of medicine, the basis of these applications was and continues to be pragmatic in nature, and involves uncritical and untested judgments. The possibility of risks has been understated and possible benefits have been overstated. Individual physicians offering HBO and organized groups, such as the Undersea Medical Society, advocating its use may well be highly motivated, well meaning, and sincerely convinced that HBO is an important therapeutic approach. It may be that, buried among the host of indications, will be some disorders for which HBO is uniquely and highly effective. If so, the present nonsystem for evaluating responses to HBO will require modification, so that these potentially valuable additions to therapeutics are not lost. Because of its almost global application to a wide variety of diseases, HBO therapy lends itself easily to medical adventurism (therapy in search of a disease) and economic exploitation. If there is some patient benefit to come from the experience of the last 300 years, changes in approach, initiated by baromedical devotees or by medicine generally, or resulting from pressures outside of medicine, will be required.


Engineered cyanobacteria with additional overexpression of selected Calvin-Benson-Bassham enzymes show further increased ethanol production.
Cyanobacteria are one of the most promising microorganisms to produce biofuels and renewable chemicals due to their oxygenic autotrophic growth properties. However, to rely on photosynthesis, which is one of the main reasons for slow growth, low carbon assimlation rate and low production, is a bottleneck. To address this challenge, optimizing the Calvin-Benson-Bassham (CBB) cycle is one of the strategies since it is the main carbon fixation pathway. In a previous study, we showed that overexpression of either aldolase (FBA), transketolase (TK), or fructose-1,6/sedoheptulose-1,7-bisphosphatase (FBP/SBPase), enzymes responsible for RuBP regeneration and vital for controlling the CBB carbon flux, led to higher production rates and titers in ethanol producing strains of Synechocystis PCC 6803. In the present study, we investigated the combined effects of the above enzymes on ethanol production in Synechocystis PCC 6803. The ethanol production of the strains overexpressing two CBB enzymes (FBA + TK, FBP/SBPase + FBA or FBP/SBPase + TK) was higher than the respective control strains, overexpressing either FBA or TK. The co-overexpression of FBA and TK led to more than 9 times higher ethanol production compared to the overexpression of FBA. Compared to TK the respective increase is 4 times more ethanol production. Overexpression of FBP/SBPase in combination with FBA showed 2.5 times higher ethanol production compared to FBA. Finally, co-overexpression of FBP/SBPase and TK reached about twice the production of ethanol compared to overexpression of only TK. This study clearly demonstrates that overexpression of two selected CBB enzymes leads to significantly increased ethanol production compared to overexpression of a single CBB enzyme.


Treatment of pyogenic liver abscess by surgical incision and drainage combined with platelet-rich plasma: A case report.
Pyogenic liver abscesses are insidious in the early stage. Some cases progress rapidly, and the patient's condition can worsen and even become life-threatening if timely treatment is not provided. Surgery and prolonged antibiotic treatment are often required if the abscess is large and liquefied and becomes separated within the lumen. We report a case of bacterial liver abscess with a poor outcome following pharmacological treatment, review the literature related to the use of platelet-rich plasma (PRP) in the treatment of hepatic impairment and partial hepatectomy in animals, and discuss the prognostic features of surgical incision and drainage combined with PRP in the treatment of bacterial liver abscesses. This is the first case describing the use of PRP in the treatment of a bacterial liver abscess in humans, providing new ideas for the treatment of this condition. This case highlights the importance of surgical treatment for bacterial liver abscesses that are well liquefied and poorly managed medically. PRP may produce antimicrobial effects and promote the regeneration and repair of liver tissue.


Genetic causes of inherited cardiac hypertrophy: Robert L. Frye Lecture.
Cardiac hypertrophy is well recognized as a cardiac manifestation of systemic disorders such as hypertension or intrinsic myocardial disease, but it can also reflect an underlying genetic defect. Molecular studies of inherited forms of cardiac hypertrophy have defined 2 novel pathways that lead to cardiac remodeling in adults, discoveries that increasingly provide insights relevant for both diagnosis and management. This article reviews the genetic studies that led to the current molecular understanding of hypertrophic cardiomyopathy and discusses more recently discovered causes of inherited cardiac hypertrophy.


Added value for tandem mass spectrometry shotgun proteomics data validation through isoelectric focusing of peptides.
A very popular approach in proteomics is the so-called "shotgun LC-MS/MS" strategy. In its mostly used form, a total protein digest is separated by ion exchange fractionation in the first dimension followed by off- or on-line RP LC-MS/MS. We replaced the first dimension by isoelectric focusing in the liquid phase using the Off-Gel device producing 15 fractions. As peptides are separated by their isoelectric point in the first dimension and hydrophobicity in the second, those experimentally derived parameters (pI and R(T)) can be used for the validation of potentially identified peptides. We applied this strategy to a cellular extract of Drosophila Kc167 cells and identified peptides with two different database search engines, namely PHENYX and SEQUEST, with PeptideProphet validation of the SEQUEST results. PHENYX returned 7582 potential peptide identifications and SEQUEST 7629. The SEQUEST results were reduced to 2006 identifications by validation with PeptideProphet. Validation of the PeptideProphet, SEQUEST and PHENYX results by pI and R(T) parameters confirmed 1837 PeptideProphet identifications while in the remainder of the SEQUEST results another 1130 peptides were found to be likely hits. The validation on PHENYX resulted in the fixation of a solid p-value threshold of <1 x 10(-04) that sets by itself the correct identification confidence to >95%, and a final count of 2034 highly confident peptide identifications was achieved after pI and R(T) validation. Although the PeptideProphet and PHENYX datasets have a very high confidence the overlap of common identifications was only at 79.4%, to be explained by the fact that data interpretation was done searching different protein databases with two search engines of different algorithms. The approach used in this study allowed for an automated and improved data validation process for shotgun proteomics projects producing MS/MS peptide identification results of very high confidence.


Anticarcinogenic effect of common carotenoids.
Of the common carotenoids present in food, beta carotene, alpha carotene, lycopene, lutein, zeaxanthin as well as canthaxanthin can be considered potential prophylactic agents against carcinogenesis. They are absorbed by the human organism in reasonable amounts, and they have antioxidant properties, immunomodulating effects and may possibly influence gene expression enhancing gap junction communication. Recent suggestions that beta carotene may be metabolized directly to retinoic acid in retinoic acid target tissue and the discovery of retinoic acid nuclear receptors open up new perspectives for research. The best established chain of evidence for a protective effect of carotenoids against cancer development is available for beta carotene. Positive effects were observed in cell culture and experimental animal studies as well as in dietary and blood level studies in humans. More conclusive evidence will be provided by double-blind intervention trials in humans that are in progress. Beta carotene appears to be active in the promotion phase of carcinogenesis stabilizing initiated cells. Canthaxanthin, which has often been included in animal experiments for comparative purposes having little or no provitamin A activity, also exhibits strong protective effects. Of the other carotenoids only limited data are available. Depending on the experimental model used, lycopene, lutein or alpha carotene was particularly active. In preliminary human blood level studies, lycopene was inversely associated with cancers of the pancreas and cervix. Much work remains to be done. Of particular interest is the question of organ specificity of individual carotenoids.


Sodium fluoride or sodium monofluorophosphate? A critical view of a meta-analysis on their relative effectiveness in dentifrices.
A detailed examination of nine publications used in a meta-analysis to compare the relative effectiveness of sodium fluoride and sodium monofluorophosphate in dentifrices showed important flaws in the process. Some studies were inappropriately chosen. Other selected comparisons between the two compounds favored sodium fluoride when more appropriate comparisons in the same studies, showing either an advantage for sodium monofluorophosphate or a lesser advantage to sodium fluoride, were ignored. Some simple errors also appear to have been made when taking data from the publications. When all these factors are taken into account it seems that three studies favor sodium monofluorophosphate, two favor sodium fluoride and the remaining five either could not or should not be included in a meta-analysis. The only two scientifically conceived and conducted studies failed to demonstrate an advantage of one compound over the other.


Functional clonal deletion in immunological tolerance to major histocompatibility complex antigens.
CBA (H-2k) mice were rendered tolerant to H-2d antigens by injection of (CBA X BALB/c)F1 spleen cells at birth. At intervals of 2 days to 12 weeks, the frequencies of anti-H-2d cytotoxic T lymphocyte precursor cells (CTL-P) in thymus and spleen were determined by using a limiting-dilution microculture assay system for CTL-P. This assay, utilizing irradiated H-2d stimulator cells and concanavalin A-induced spleen cell conditioned medium, was shown to be linear over the range 30 to 100,000 responder cells and uninfluenced by IJ-positive cells. A profound and long-lasting deficit in activatable CTL-P, first demonstrable by day 5 of life in the thymus and day 8-10 in the spleen, developed in mice rendered tolerant, reaching a greater than 95% reduction by 6 weeks. Functional clonal deletion thus seems to be at least as important in the tolerant state as suppressor T cells. Repeated in vivo administration of anti-IJk serum partially inhibited clonal deletion, suggesting either that suppressor T cells are actively involved in producing clonal deletion or that IJk-bearing cells in the donor inoculum or the host represent an important factor.


Regulation of Proliferation, Differentiation and Functions of Osteoblasts by Runx2.
Runx2 is essential for osteoblast differentiation and chondrocyte maturation. During osteoblast differentiation, Runx2 is weakly expressed in uncommitted mesenchymal cells, and its expression is upregulated in preosteoblasts, reaches the maximal level in immature osteoblasts, and is down-regulated in mature osteoblasts. Runx2 enhances the proliferation of osteoblast progenitors by directly regulating Fgfr2 and Fgfr3. Runx2 enhances the proliferation of suture mesenchymal cells and induces their commitment into osteoblast lineage cells through the direct regulation of hedgehog (Ihh, Gli1, and Ptch1), Fgf (Fgfr2 and Fgfr3), Wnt (Tcf7, Wnt10b, and Wnt1), and Pthlh (Pthr1) signaling pathway genes, and Dlx5. Runx2 heterozygous mutation causes open fontanelle and sutures because more than half of the Runx2 gene dosage is required for the induction of these genes in suture mesenchymal cells. Runx2 regulates the proliferation of osteoblast progenitors and their differentiation into osteoblasts via reciprocal regulation with hedgehog, Fgf, Wnt, and Pthlh signaling molecules, and transcription factors, including Dlx5 and Sp7. Runx2 induces the expression of major bone matrix protein genes, including Col1a1, Spp1, Ibsp, Bglap2, and Fn1, in vitro. However, the functions of Runx2 in differentiated osteoblasts in the expression of these genes in vivo require further investigation.


Complex behavior in solution of homodimeric SecA.
SecA, a homodimeric protein involved in protein export in Escherichia coli, exists in the cell both associated with the membrane translocation apparatus and free in the cytosol. SecA is a multifunctional protein involved in protein localization and regulation of its own expression. To carry out these functions, SecA interacts with a variety of proteins, phospholipids, nucleotides, and nucleic acid and shows two enzymic activities. It is an ATPase and a helicase. Its role during protein localization involves interaction with the precursor polypeptides to be exported, the cytosolic chaperone SecB, and the SecY subunit of the membrane-associated translocase, as well as with acidic phospholipids. At the membrane, SecA undergoes a cycle of binding and hydrolysis of ATP coupled to conformational changes that result in translocation of precursors through the cytoplasmic membrane. The helicase activity of SecA and its affinity for its mRNA are involved in regulation of its own expression. SecA has been reported to exist in at least two conformational states during its functional cycle. Here we have used analytical centrifugation, as well as column chromatography coupled with multi-angle light scatter, to show that in solution SecA undergoes at least two monomer-dimer equilibrium reactions that are sensitive to temperature and to concentration of salt.


Cell-free wheys from bifidobacteria fermented milks exert a regulatory effect on the intestinal microflora of mice and humans.
Bacteroides fragilis and clostridia are normally present in the human colon but they may exert pathogenic effects when the homeostasis is upset following various forms of stress. One approach to preventing gastrointestinal disorders is to use bifidobacteria fermented milk. It has been suggested that the efficacy of such a product is related to abiotic compounds produced during milk fermentation. Experiments reported in this paper attempt to check this theory. Six whey retentates were prepared by fermenting cow's milk with six human strains of Bifidobacterium breve and acetic and lactic acids were eliminated by ultrafiltration. Their ability to reduce intestinal clostridial carriage was assessed in C3H mice. Only one whey retentate led to a decrease in clostridia, bacilli, B. fragilis and fecal pH and to an increase in bifidobacteria. Assays in ten human volunteers resulted in similar changes in fecal flora and fecal pH within 7 days of whey retentate intake (30 mL/day). No antibiotic-like effect was demonstrated in vitro. Compounds involved in microflora regulation were located in two ultrafiltrated fractions (30-100 and 100-300 kDa). Both fractions contained mainly low molecular weight glycoproteins (20-40 kDa) and two high molecular weight glycoproteins (121, 211 kDa) that were almost undetectable in the inactive 10-30 kDa fraction.


[Screening of atherosclerosis related polypeptide from phage display peptide library].
To screen atherosclerosis (AS) related polypeptide from phage display 12-peptide library, and verify the binding activity of selected positive phages and synthetic protein fragment. We collected plasma from AS patients as target for biopanning against phage-displayed 12-peptide library. After 3 rounds of screening, 10 positive phages were picked up and the binding activity was proved by ELISA. Single-stranded DNA of the phages were purified and sequenced, and a similar polypeptide was synthesized to test the binding activity to AS patients plasma. Selected phages significantly bound to AS patients' plasma. Five of ten phages had GPRPPSAPNMPL sequence. Corresponding synthetic polypeptide also showed a high binding activity to AS patient plasma. AS-related polypeptide can be obtained by phage display, which facilitates the research into the immune mechanism of AS.


Comparisons of bone mineral density and bone quality in adult rock climbers, resistance-trained men, and untrained men.
The nature of muscular contractions and episodes of impact loading during technical rock climbing are often varied and complex, and the resulting effects on bone health are unclear. The purpose of this study was to compare total body, lumbar spine, proximal femur, and forearm areal bone mineral density (aBMD) and tibia and forearm bone quality in male rock climbers (RC) (n = 15), resistance trained men (RT) (n = 16), and untrained male controls (CTR) (n = 16). Total body, anteroposterior (AP) lumbar spine, proximal femur, and forearm aBMD and body composition were measured using dual-energy X-ray absorptiometry (DXA) (Lunar Prodigy, v. 10.50.086; GE Healthcare, Waukesha, Wisconsin, U.S.A.). Volumetric BMD (vBMD), bone content, bone area, and muscle cross-sectional area (MCSA) of the tibia and forearm were measured using pQCT (peripheral quantitative computed tomography; Stratec XCT 3000, Pforzheim, Germany). No significant group differences were seen in bone-free lean body mass. CTR had significantly (p < 0.05) greater body fat % than RC and RT and significantly (p < 0.05) greater fat mass than RC. Lumbar spine and femoral neck aBMD were significantly (p < 0.05) greater in RT compared to both RC and CTR. RC had significantly (p < 0.05) lower aBMD at the 33% radius site than CTR. Forearm MCSA was significantly (p < 0.05) lower in CTR than in the other groups. No significant differences were seen between groups for vBMD or bone area of the tibia and forearm. In conclusion, resistance-trained men had higher bone density at the central skeletal sites than rock climbers; however, bone quality variables of the peripheral limbs were similar in rock climber and resistance-trained groups.


Coupled electrorotation: two proximate microspheres spin in registry with an AC electric field.
We report a novel approach to micro- and nanoparticle rotation, uniting the fine translational control afforded by optical trapping with the flexibility and simplicity of dipole-field-induced coupled electrorotation (CER). Fluorescence imaging using a microparticle photopatterning technique was combined with optical trapping to quantify both the senses and speeds of rotation for individual pairs of particles. Laser tweezers allowed controlled positioning of a pair of particles within a dipole field while simultaneously providing an axis about which the particles rotated. The particle-particle interactions inherent in CER offer several distinct advantages compared with electrorotation in multipole fields. Results from several investigations highlight the utility of this approach, including quantification of rotation in spheres as small as 750 nm in diameter, observation of rotation rates as high as 1800 rpm, fabrication of coupled electrorotational "antigears", trapping and rotation of sphere dimers, and exploitation of the registry of sphere rotation to probe the dielectric properties of immobile objects.


Enzyme Method-Based Microfluidic Chip for the Rapid Detection of Copper Ions.
Metal ions in high concentrations can pollute the marine environment. Human activities and industrial pollution are the causes of Cu2+ contamination. Here, we report our discovery of an enzyme method-based microfluidic that can be used to rapidly detect Cu2+ in seawater. In this method, Cu2+ is reduced to Cu+ to inhibit horseradish peroxidase (HRP) activity, which then results in the color distortion of the reaction solution. The chip provides both naked eye and spectrophotometer modalities. Cu2+ concentrations have an ideal linear relationship, with absorbance values ranging from 3.91 nM to 256 μM. The proposed enzyme method-based microfluidic chip detects Cu2+ with a limit of detection (LOD) of 0.87 nM. Other common metal ions do not affect the operation of the chip. The successful detection of Cu2+ was achieved using three real seawater samples, verifying the ability of the chip in practical applications. Furthermore, the chip realizes the functions of two AND gates in series and has potential practical implementations in biochemical detection and biological computing.


Retinitis pigmentosa locus on 17q (RP17): fine localization to 17q22 and exclusion of the PDEG and TIMP2 genes.
This group has previously reported the mapping of a novel locus for autosomal dominant retinitis pigmentosa (adRP) in a South African kindred to 17q. Using a new series of microsatellite markers in this study, twopoint and multipoint analysis provide evidence for the localization of the disease gene to the 17q22 region. In addition, a second South African adRP family is shown to be linked to this 17q22 locus. Disease-associated haplotypes constructed for both families and multipoint linkage analysis place the gene in the 10-cM interval between D17S1607 and D17S1874. Three candidate genes on 17q were investigated: PDEG, the gamma subunit of rod phosphodiesterase; TIMP2, tissue inhibitor of metalloproteinases-2; and PRKCA, protein kinase C alpha. Recombination events between the adRP locus and: (1) a single-stranded conformation polymorphism in PDEG; and (2) a restriction fragment length polymorphism in TIMP2 provided evidence for the exclusion of these candidate genes as being responsible for adRP in the South African kindred.


Lepirudin-induced thrombocytopenia following subcutaneous administration.
A case of lepirudin-induced thrombocytopenia is reported. A 61-year-old white man arrived at the emergency department with complaints of pain in his left thigh that worsened with walking. His medical history was significant for extensive thromboses over a period of six months. He had recently been discharged from the hospital for suspected heparin-induced thrombocytopenia (HIT) while on enoxaparin. A venous duplex scan revealed two new deep venous thromboses in the left common, superficial, and popliteal veins. The patient was admitted and initiated on aspirin 325 mg and warfarin sodium 2 mg daily. Intravenous lepirudin with an activated partial thromboplastin time (aPTT) goal of 60-80 seconds was also started. Because of his recurrent thrombotic event, a new International Normalized Ratio (INR) goal of 3.0-3.5 was established for warfarin therapy. Eighteen days after admission, the patient's INR and aPTT were high; therefore, his warfarin dose was reduced and i.v. lepirudin was changed to subcutaneous administration. The patient was transferred to the intensive care unit (ICU) and, 5 days later, he developed melena. During the 7 days of treatment with subcutaneous lepirudin, a drop in platelet counts was observed. Subcutaneous lepirudin was discontinued after resolution of melena, and i.v. lepirudin was restarted. After 15 days, his platelet counts increased and he was switched back to subcutaneous lepirudin, which again led to a drop in platelets. After 27 days in the ICU, the patient's INR and aPTT remained high. Lepirudin was discontinued and i.v. bivalirudin was initiated. His platelet count increased and he was discharged. Eleven days later, the patient was found unresponsive with left-sided fasciculations. The patient died secondary to respiratory arrest as a consequence of intracranial hemorrhage. A 61-year-old white man with a history of thromboses and suspected HIT developed thrombocytopenia possibly associated with receiving two courses of subcutaneous lepirudin. Careful monitoring of platelet counts are warranted in patients who have a history of HIT and are receiving subcutaneous lepirudin.


Expression and developmental regulation of the Hydra-RFamide and Hydra-LWamide preprohormone genes in Hydra: evidence for transient phases of head formation.
Hydra magnipapillata has three distinct genes coding for preprohormones A, B, and C, each yielding a characteristic set of Hydra-RFamide (Arg-Phe-NH2) neuropeptides, and a fourth gene coding for a preprohormone that yields various Hydra-LWamide (Leu-Trp-NH2) neuropeptides. Using a whole-mount double-labeling in situ hybridization technique, we found that each of the four genes is specifically expressed in a different subset of neurons in the ectoderm of adult Hydra. The preprohormone A gene is expressed in neurons of the tentacles, hypostome (a region between tentacles and mouth opening), upper gastric region, and peduncle (an area just above the foot). The preprohormone B gene is exclusively expressed in neurons of the hypostome, whereas the preprohormone C gene is exclusively expressed in neurons of the tentacles. The Hydra-LWamide preprohormone gene is expressed in neurons located in all parts of Hydra with maxima in tentacles, hypostome, and basal disk (foot). Studies on animals regenerating a head showed that the prepro-Hydra-LWamide gene is expressed first, followed by the preprohormone A and subsequently the preprohormone C and the preprohormone B genes. This sequence of events could be explained by a model based on positional values in a morphogen gradient. Our head-regeneration experiments also give support for transient phases of head formation: first tentacle-specific preprohormone C neurons (frequently associated with a small tentacle bud) appear at the center of the regenerating tip, which they are then replaced by hypostome-specific preprohormone B neurons. Thus, the regenerating tip first attains a tentacle-like appearance and only later this tip develops into a hypostome. In a developing bud of Hydra, tentacle-specific preprohormone C neurons and hypostome-specific preprohormone B neurons appear about simultaneously in their correct positions, but during a later phase of head development, additional tentacle-specific preprohormone C neurons appear as a ring at the center of the hypostome and then disappear again. Nerve-free Hydra consisting of only epithelial cells do not express the preprohormone A, B, or C or the LWamide preprohormone genes. These animals, however, have a normal phenotype, showing that the preprohormone A, B, and C and the LWamide genes are not essential for the basic pattern formation of Hydra.


The involvement of mRNA secondary structure in protein synthesis.
Translation initiation in eukaryotes is a complex process involving many factors. A key step in this process is the binding of mRNA to the 43S preinitiation complex. This is generally the rate-limiting step in translation initiation and consequently a major determinant of mRNA translational efficiency. The primary and secondary structure of the mRNA 5' noncoding region have been implicated in modulating translational efficiency. Translational efficiency was shown to be inversely proportional to the degree of secondary structure at the mRNA 5' noncoding region. Furthermore, it was shown that cap-binding proteins that interact with the 5' cap structure (m7GpppN) of eukaryotic mRNAs are involved in the "unwinding" of the mRNA secondary structure, in an ATP hydrolysis mediated event, to facilitate ribosome binding. Thus, cap-binding proteins can potentially regulate mRNA translation. Here, we discuss the available data supporting the notion that eukaryotic 5' mRNA secondary structure plays an important role in translation initiation and the possible regulation of this process.


Computing "anomalous" contaminant transport in porous media: the CTRW MATLAB toolbox.
We describe the continuous time random walk (CTRW) MATLAB toolbox, a collection of MATLAB scripts and functions that compute breakthrough curves (BTCs) and one-dimensional/two-dimensional (1D/2D) resident concentration profiles for passive tracer dispersion. The transport model is based on the CTRW theory. CTRW includes as special cases the classical Fickian dispersion based advection-dispersion equation, multirate and mobile-immobile models, and the fractional-in-time derivative transport equation. Several models for treating the memory effects responsible for the anomalous character of dispersion have been implemented in the CTRW toolbox. In the current version of the toolbox, it is possible to solve explicitly for the forward problem (concentration prediction) in 1D and 2D and for the inverse problem (parameter identification from experimental BTC data) in 1D. Future extensions will include explicit treatment of sorbing tracers, simple subroutines for treating radial flow from wells, introduction of arbitrary initial conditions, treatment of heterogeneous domains by use of the Fokker-Planck with Memory equation, and treatment of transport in multidimensional systems.


Lesion of dentatothalamic pathways in severe post-traumatic tremor.
The present study investigates evidence of dentatothalamic pathway lesions in nineteen patients with severe kinetic post-traumatic tremor respectively by magnetic resonance imaging (MRI). Kinetic tremor is thought to be characteristic of lesions of the cerebellar outflow. While this hypothesis is supported by experimental data, neuropathological and neuroradiological findings have been limited. The appendicular tremors were unilateral in 13 patients and bilateral in 6, accounting for 25 instances of tremor. The tremor developed after severe head trauma in 18 patients. These patients had evidence of diffuse axonal injury on MRI. Postural and kinetic tremor was present in all patients, and was accompanied by tremor also present at rest in 14 instances. Multiplanar MRI studies were performed on a high-field MRI system operating at 2.0 T in 13 patients and on intermediate-field strength MRI systems in 6 patients according to a standardized protocol. To detect small deposits of hemosiderin after post-traumatic lesions, the protocol included a heavily T2-weighted spin-echo pulse sequence. Lesions of the dentatothalamic pathways were found in 22 instances. The lesions were classified into different types of according to their distribution. A lesion of the dentate nucleus ipsilateral to the tremor (type 1) was found in one instance (4%), lesions involving the ipsilateral predecussational dentatothalamic pathway (type II and III) were found in 14 instances (56%), and lesions involving the contralateral post-decussational course (type IV) in 7 instances (28%). One patient with a mild head trauma had a lesion of the contralateral thalamus. The lesions appeared as hypointense, hyperintense or mixed. Two of three patients with a parkinsonian-like rest tremor had type IV lesions involving the substantia nigra. The nosological concepts of tremors are discussed. 'Midbrain' tremor may have distinct pathoanatomical lesion sites.


Game theory applications in host-microbe interactions toward disease manifestation: Mycobacterium tuberculosis infection as an example.
Game theory describes the interactions between two players and the pay-off from winning, losing, or compromising. In the present study, Mycobacterium tuberculosis (Mtb)-host interactions were used as an example for the application of game theory to describe and predict the different outcomes of Mtb-infection and introducing target molecules for use in protection or therapy. The gene expression for eight main markers (CCR1, CCR2, IDO, Tbet, TGFβ, iNOS, MMP3, MMP9) of host response and three Mtb virulence factors (Ag85B, CFP-10, ESAT-6) were assessed in broncho-alveolar lavage of TB+ and TB- patients. The players' strategies in the "Nash equilibrium", showed that Ag85B is the main virulence factor for Mtb in active phase, and also the most immunogenic factor, if the host can respond by high expression of T-bet and iNOS toward a Th1 response. In this situation, Mtb can express high levels of ESAT-6 and CFP10 and change the game to the latency, in which host responses by medium expression of T-bet and iNOS and medium level of TGF-β and IDO. Consistently, the IDO expression was 134-times higher in TB+s than the TB-s,and the T-bet expression,~200-times higher in the TB-s than the TB+s. Furthermore, Mtb-Ag85B had a strong positive association with CCR2, T-bet and iNOS, but had a negative correlation with IDO. Ag85B and maybe ESAT6 (without its suppressive C-terminal) should be considered for making subunit vaccines. And, preventing IDO formation in dendritic cells might be a novel target for immunotherapy of tuberculosis, to reduce the pressure of immune-suppression on Th1 responses.


The Children's Depression Inventory: error in cutoff scores for screening purposes.
The Children's Depression Inventory (CDI) is used to screen for depression in school-age children. Such screening uses the manual's reported information on suggested cutoff scores. These cutoff scores are based on an erroneous base-rate calculation and an inadequate methodology. Data are provided showing that for the suggested cutoff scores of 13 or 20, the CDI has poor receiver-operating characteristics. Indeed, for the cutoff score of 20, suggested as being suitable for screening in the general population (e.g., schools), clinicians will miss 86% of depressed children. In conclusion, it is recommended that the CDI is better suited as a continuous measure of mood and that cutoff scores should not be used to screen for the likely presence or absence of depression.


Apparatus for direct counting of beta-rays from two-dimensional protein gels: measurement of changes in protein synthesis due to changes in density of Chinese hamster ovary cells.
A method is described for scanning two-dimensional protein gels that utilizes direct counting of beta-rays instead of autoradiography. The methodology is compared with autoradiographic results and data are presented demonstrating changed patterns of protein synthesis accompanying changes in cell density. The method is rapid and permits identification of differences in protein abundance of approximately 10% for a substantial fraction of the more prominent proteins. A modulation effect of greater than 5 standard deviations is shown to occur for an appreciable number of the proteins that accompany the inhibition of cell growth due to contact inhibition. The method promises application to a variety of biochemical and genetic problems designed to delineate changes in protein synthesis accompanying changes in genome, molecular environment, history, and state of differentiation of the cell populations studied.


The role of population projections in environmental management.
California and other regions in the United States are becoming more populated and ethnically diverse, and thus, ecological impacts on the wildland-urban interface are a significant policy concern. In a socioeconomic assessment focused on the geographic regions surrounding four national forests in southern California, population projections are being formulated to assist in the update of forest plans. In southern California, the projected trend of explosive population growth combined with increased ethnic and racial diversity indicates four challenges for environmental management. First, patterns of recreation use on wildlands are likely to change, and management of these areas will have to address new needs. Second, as land-management agencies face changing constituencies, new methods of soliciting public involvement from ethnic and racial groups will be necessary. Third, growth in the region is likely to encroach upon wildland areas, affecting water, air, open space, and endangered species. Fourth, in order to address all these concerns in a climate of declining budgets, resource management agencies need to strengthen collaborative relationships with other agencies in the region. How environmental managers approach these changes has widespread implications for the ecological sustainability of forests in southern California.


Ultrastructural autoradiographic localization of somatostatin-28 in the rat pituitary gland.
To identify the anterior pituitary cell type(s) containing somatostatin-28 (SS-28)-binding sites and to study the internalization processes of this peptide by the target cells, autoradiography was performed on rat anterior pituitaries removed at specific intervals (2-60 min) after iv injection of the [125I]iodo-SS-28 agonist [Leu8,D-Trp22,Tyr25]SS-28 into intact, adrenalectomized, or castrated male rats. At the light microscopic level, the silver grains were found in 75% of cells. Concomitant injection of an excess of unlabeled peptide prevented the binding of label, verifying the specificity of binding. No specific labeling could be detected in the adrenocorticotrophs of adrenalectomized rats or gonadotrophs (castration cells) of castrated rats. At the electron microscopic level, three cell types (somatotrophs, thyrotrophs, and mammotrophs) appear to contain radiolabeled SS-28. The time-course study in somatotrophs of intact animals showed that 2 min after injection, most silver grains were associated with the plasma membrane. Five to 15 min after injection, label was found over both the plasma membrane and cytoplasmic organelles, especially the Golgi apparatus, lysosomes, and secretory granules. At the longest time interval (60 min), labeling was mostly associated with the cytoplasmic organelles. These results indicate that SS-28-binding sites are present only in those cell types in which somatostatin is known to regulate secretory functions. The present data also show that a rapid internalization of the radiolabeled peptide occurs.


Akathisia induced by mirtazapine after 20 years of continuous treatment.
Mirtazapine is an antidepressant blocking presynaptic alpha2-adrenergic receptors and an antagonist of 5-hydroxytryptamine 2A/2C, 5-hydroxytryptamine 3, and histaminergic (H) postsynaptic receptor. Acute dystonia restless legs syndrome (RLS) and manic syndromes are adverse effects of mirtazapine, whereas only few cases of acute akathisia, after the first doses of mirtazapine, are referred. Instead, mirtazapine is used to treat akathisia probably because of its antagonistic property at H1 postsynaptic receptors and dopaminergic action in the frontal cortex. A 72-year-old woman with depression, on mirtazapine treatment for almost 20 years, was admitted to an outpatient neurology clinic, with 1-week history of 3-kg weight loss and progressive intense "inner restlessness," constant movements of the legs and feet, remarkable distress, insomnia, and pacing up and down. Neurological examination had normal results, no deterioration of the depression was present, a magnetic resonance scan of the brain was unremarkable, and biochemical tests were within reference ranges. The disorder eventually resolved after the permanent withdrawal of the offending medication. After excluding other possible disorders, the diagnosis of severe akathisia, possibly induced by mirtazapine, was made. The reappearance of the symptoms after the patient had been rechallenged with mirtazapine ascertained the diagnosis of akathisia induced by mirtazapine. This report relates akathisia with mirtazapine intake after such a long period of treatment. It illustrates the importance of being alert to any movement disorder emerging in patients treated with mirtazapine, even after many years of treatment.


Juxtamembrane mutant V560GKit is more sensitive to Imatinib (STI571) compared with wild-type c-kit whereas the kinase domain mutant D816VKit is resistant.
Imatinib (Glivec; STI571) is an ATP-competitive kinase inhibitor of c-Abl, BCR/ABL, c-Kit, and platelet-derived growth factor receptor. Overexpression or constitutive activation of Kit by mutations have been associated with various malignancies. Mutations in the intracellular juxtamembrane region of Kit (e.g., V560G) are common in gastrointestinal stromal tumors and have been linked to poor prognosis. Mutations in the kinase domain of Kit (e.g., D816V) have been detected in mastocytosis, acute myeloid leukemia, and germ-cell tumors. To determine the sensitivity of Kit mutants to Imatinib in the same cellular background, wild-type Kit (WTKit), V560GKit and D816VKit were expressed in FDC-P1 cells. Growth of FDC(WTKit) was inhibited by Imatinib with GI50 (a concentration of drug at which 50% inhibition of growth occurs) of 0.1-0.2 microM but FDC(V560GKit) were more sensitive to Imatinib with a GI50 of 0.01-0.025 microM and FDC(D816VKit) were resistant to Imatinib with a GI50 greater than 5 microM. The naturally occurring isoforms of c-Kit did not differ in their sensitivity to Imatinib. Immunoprecipitation and Western blot analysis indicated that 1 microM Imatinib reduced phosphorylation of WTKit and completely blocked phosphorylation of V560GKit but did not affect D816VKit phosphorylation. In signaling studies, addition of stem cell factor (SCF) induced phosphorylation of ERK and Akt by WTKit, and ERK, Akt and STAT3 by V560GKit, which were all blocked by Imatinib. Imatinib also blocked the constitutive activation of Akt and STAT3 by V560GKit but had no affect on the constitutive activation of ERK, Akt, and STAT3 by D816VKit. Overall, these findings demonstrate the increased susceptibility of the Kit juxtamembrane mutant, V560G, and the resistance of the kinase domain mutant, D816V, to Imatinib compared with WTKit.


Uropharmacology: current and future strategies in the treatment of erectile dysfunction and benign prostate hyperplasia.
Because of the increasing percentage of the world male population suffering from erectile dysfunction (ED) and benign prostate syndrome (BPS), there is a need for new and innovative therapeutic approaches. Pharmacotherapy is an avenue presently being followed in the treatment of both these syndromes. A profound change in the therapy of ED has been obtained through use of the selective phosphodiesterase inhibitor sildenafil. The incidence of surgical intervention in BPS has been reduced by the introduction of uroselective alpha1-receptor antagonists and the new 5alpha-reductase inhibitors (such as finasteride, dutasteride). The investigation of mechanisms in CXC chemokine expression also offers new therapeutic possibilities in these diseases.


[Present situation of antibiotic resistances in tonsillar infections].
To obtain the main responsible organisms, its sensitivity and resistances to antibiotics in tonsillitis. We have studied the post-surgical tonsils, carrying out a microbiologic study, its culture and sensitivity. The most frequent isolated organisms were Staphylococcus aureus (29.3%), followed by Streptococcus pyogenes (23.4%), and Haemophilus influenzae (12.1%). The highest resistances were for the S. aureus (penicillin 91%, erythromycin 18% and 5% to the rest of the beta-lactams), followed by H. influenzae (50% clarithromycin, 30% amoxyciIlin and 2% cephalosporins) and S. pyogenes (28% erytromycin, 10% clindamycin and 3% penicillin). We noticed the minimal resistance found to cephalosporins, and for this reason they appear to be the safest option, except in children under five years old, in which amoxicillin is still the first line treatment, because the causative agent is S. pyogenes, sensitive to that antibiotic.


Peutz-Jeghers polyps, dysplasia, and K-ras codon 12 mutations.
Peutz-Jeghers syndrome (PJS) is a rare, autosomal dominant, polyposis syndrome, associated with an increased risk of gastrointestinal and extragastrointestinal malignancy. Occasionally dysplasia occurs in PJS polyps. In colorectal carcinomas, mutations in codon 12 of the K-ras oncogene are common and are found at similar frequency in precursor adenomas. Therefore, K-ras codon 12 point mutations in PJS polyps, were evaluated. Fifty two PJS polyps, including four with dysplasia, collected from 19 patients with PJS, were analysed for mutations in the K-ras codon 12 by a mutant enriched polymerase chain reaction procedure, followed by allele specific oligodeoxynucleotide hybridisation. A K-ras codon 12 mutation was identified, in one colonic polyp with dysplasia. The mutation was found in the non-neoplasmic epithelial cells and not in the dysplastic component of the polyp. K-ras codon 12 point mutations are very rare in PJS polyps, by contrast with colorectal adenomas. The findings support previous evidence that there seems to be no intrinsic relation between K-ras codon 12 mutation and dysplasia.


Effect of aging on the sensitivity of pancreatic beta-cells to insulin secretagogues in rats.
Glucose-stimulated insulin release from rat pancreas is known to be blunted by aging. In the present study, we examined the effect of aging on insulin release induced by various secretagogues using the isolated perfused pancreas of female rats. Insulin release from the perfused pancreas in response to 16.7 mM glucose in 8-month-old rats (older rats) was much less than that in 2-month-old rats (young rats). The first phase of insulin release after glucose stimulation was attenuated in older rats. The addition of 0.1 mM 3-isobutyl-1-methylxanthine (IBMX) potentiated glucose-induced insulin secretion in both groups of rats. However, the second phase of insulin secretion in older rats was lower than that in younger rats. The phorbol ester 12-O-tetradecanoyl phorbol ester (TPA, 200 nM) enhanced both the first and the second phases of insulin release induced by glucose in both groups of rats. The amount of first phase insulin release induced by TPA with glucose in young rats was greater than that in older rats, whereas the second phase of insulin release was similar in both groups of rats. On the other hand, tolbutamide (200 uM) similarly stimulated the first phase of insulin release in both age groups of rat. In addition, the amount of cumulative insulin secretion induced by tolbutamide during the second phase was slightly but significantly greater in older rats than in young controls. Insulin content in the pancreas was significantly greater in older rats than in young rats and increased after the stimulation with TPA and tolbutamide.(ABSTRACT TRUNCATED AT 250 WORDS)


The Unengaged Mind: Defining Boredom in Terms of Attention.
Our central goal is to provide a definition of boredom in terms of the underlying mental processes that occur during an instance of boredom. Through the synthesis of psychodynamic, existential, arousal, and cognitive theories of boredom, we argue that boredom is universally conceptualized as "the aversive experience of wanting, but being unable, to engage in satisfying activity." We propose to map this conceptualization onto underlying mental processes. Specifically, we propose that boredom be defined in terms of attention. That is, boredom is the aversive state that occurs when we (a) are not able to successfully engage attention with internal (e.g., thoughts or feelings) or external (e.g., environmental stimuli) information required for participating in satisfying activity, (b) are focused on the fact that we are not able to engage attention and participate in satisfying activity, and (c) attribute the cause of our aversive state to the environment. We believe that our definition of boredom fully accounts for the phenomenal experience of boredom, brings existing theories of boredom into dialogue with one another, and suggests specific directions for future research on boredom and attention.


Self-reported voice problems among three groups of professional singers.
A vocal health questionnaire was administered to three groups of professional singers and a "friendship-matched" group of nonsingers in Melbourne, Australia. The responses of 79 opera, 57 musical theatre and 31 contemporary (excluding rock) singers and 86 nonsingers were analysed. The questionnaire solicited information regarding biographical data speaking and singing voice-use behaviours, and vocal health over the previous 12 months in terms of experiences of vocal impairment, vocal disability, and handicap. Significant differences between singers and nonsingers in the prevalence and nature of voice problems were reported. Of the singers, 44% reported one or more occurrences of a diagnosed vocal condition compared to 21% of nonsingers and 69% of singers experienced vocal disability compared to only 41% of nonsingers, over the previous 12 months. In contrast, no significant differences were found between the three different styles of singers in their experience of vocal impairment, disability or handicap.


[Clinical research on movement of intraocular contact lens during accommodation].
To study the movement of intraocular contact lens (ICL) during accommodation. Forty one eyes of 41 consecutive patients implanted ICL to correct high myopia were collected. The visual acuity and accommodation power were checked before and after the surgery. The movement of both the ICL and the lens was measured separately at nonaccommodated state and pilocarpine induced accommodation. The uncorrected visual acuity (UCVA) and best corrected visual acuity (BCVA) improved 3 months after surgery. The mean accommodation power before surgery was (2.12 + or - 1.06) D, and was (4.46 + or - 2.11) D 3 months after surgery. Accommodation power was improved significantly (t = 2.312, P = 0.022). The distance from the posterior surface of ICL to the anterior surface of the lens was (0.48 + or - 0.27) mm at nonaccommodated state, and (0.34 + or - 0.19) mm at drug induced accommodation, the difference was significant (t = 2.104, P = 0.038). The position from corneal endothelium to the anterior surface of ICL had no significant difference at nonaccommodated state and drug induced accommodation (t = 1.165, P = 0.149). Depth of the anterior chamber (from the posterior surface of the cornea to the anterior surface of the lens) between nonaccommodated and drug-induced accommodation had no statistically significant difference (t = 1.821, P = 0.071), but the anterior pole of the lens actually moved forward at drug induced accommodation checked with slit lamp. With ultrasound biomicroscopy we could see that in several surgical eyes, ICL loop contacted with periphery lens both in nonaccommodated state and drug induced accommodation condition. Although the constriction of pupil induced by pilocarpine decreases the distance from the posterior surface of ICL to the anterior lens surface significantly, there still has enough space to avoid the occurrence of subcapsular cataract. The contact between ICL loop and periphery lens might be one of the causes for periphery lens opacification, but the influence of this contact to the occurrence of central subcapsular opacification still requires further investigation.


What makes Hephaestus lame?
Hephaestus (or Hephaistos) is an Olympian Greek god, the divine smith, famed for inventions, who taught men glorious crafts. The fixed epithet for Hephaestus, used from the eighth century B.C. by Homer, Hesiod, and other ancient authors until the fifth century A.D., is "Amphiguéeis," i.e., with both feet crooked. He is also called "Kullopodíou," i.e., clubfooted. His body and his gait were described by Homer: "He spake, and from the anvil rose, a huge, panting bulk, halting the while, but beneath him his slender legs moved nimbly ... and with a sponge wiped his face and his two hands withal, and his mighty neck and shaggy breast, ... and grasped a stout staff, and went forth halting; but there moved swiftly to support their lord handmaidens wrought of gold in the semblance of living maids." His anomaly was congenital, as we learn from Hephaestus himself ("I was born misshapen") and from his mother Hera ("But my son Hephaestus whom I bare was weakly among all the blessed gods and shrivelled of foot."). Vase paintings of the sixth century B.C. depict Hephaestus' lameness, but his lameness is not emphasized in the fifth century and thereafter. It is most likely that bilateral congenital clubfeet made Hephaestus lame. Two sons of Hephaestus, Palaemonius and Periphetes, were also reported as having deformed feet.


Differential Impact of Unilateral and Bilateral Classifications of Diabetic Retinopathy and Diabetic Macular Edema on Vision-Related Quality of Life.
To evaluate and compare the impact of unilateral better-eye and bilateral categorizations of diabetic retinopathy (DR) and diabetic macular edema (DME) on vision-related quality of life (VRQoL) in individuals with type 2 diabetes (T2DM). We recruited 390 subjects (116 females; age range, 22-78 years) of Malay, Indian, and Chinese ethnicities from the Singapore Diabetes Management Project (S-DMP), a cross-sectional clinic-based study conducted from 2010 to 2013. Diabetic retinopathy and DME were graded using the Modified Airlie House and American Academy of Ophthalmology classification systems, respectively. Subjects were categorized, using unilateral better-eye classifications, into no DR (n = 189), any DR only (n = 164), and any DME (n = 37); and with bilateral classifications into no DR (n = 144), DR/DME in one eye only (n = 45), DR in one eye and DR/DME in the other (n = 164), and DME in both eyes (n = 37). Vision-related quality of life was assessed using the composite Rasch-transformed score of the Impact of Visual Impairment (IVI) questionnaire. For unilateral better-eye classifications, multivariable linear models revealed a 9% reduction in VRQoL for any DR (β [95% confidence interval (CI)], -0.44 [-0.86, -0.03]) and a 17% reduction for any DME (-0.81 [-1.53, -0.08]) compared to individuals with no DR/DME. Bilateral categorizations revealed significant decrements in VRQoL that occurred only when both eyes had either DR or DME (11%), which worsened when both eyes were affected by DME (22%). Our results suggest that interventions to prevent the onset of DR and/or DME in the second eye are strongly recommended to significantly reduce the bilateral impact of these conditions on VRQoL.


The effect of mefloquine-sulfadoxine-pyrimethamine vs quinine on patients with complicated falciparum malaria.
Sixty-six patients with complicated falciparum malaria (defined as anaemia, hyperpyrexia, jaundice, or more than 2% of RBC parasitised) were studied. Patients with cerebral signs and symptoms were not included in the study. Patients were randomised in pairs to receive either mefloquine 750 mg, sulfadoxine 1500 mg and pyrimethamine 75 mg (MSP) single oral dose or quinine (10 mg/kg tds X 7 days oral therapy). All the patients were admitted in hospital for 7 days and were followed on days 14, 21 and 28. All patients survived. The parasite clearance times in MSP treated patients were significantly shorter then those treated with quinine. There was no difference in fever clearance time in the two groups of patients. One patient was resistant to MSP at RII level and 5 patients were resistant at RI level. Among patients treated with quinine 3 patients were resistant at RI level.


Reasons for high retention in pediatric clinical trials: comparison of participant and staff responses in the Correction of Myopia Evaluation Trial.
The Correction of Myopia Evaluation Trial (COMET), a randomized, multicenter clinical trial of myopia progression in children, had an exceptionally high retention rate of 98.5% (462/469) at three years of follow-up. The present investigation was designed to evaluate and compare the reasons for COMET's high retention rate according to participating families and clinical center staff. Families (n = 411) and staff (n = 35) completed a confidential 19-item questionnaire by indicating families' levels of preference for each item, and rating its importance in keeping families in the study. The questionnaire evaluated study features in four categories: staff characteristics, operational aspects, specific study elements, and incentives. Results showed that most families viewed the study very favorably. Features that appealed to 90% or more families and promoted continued study participation included staff attributes such as friendliness, responsiveness and encouragement, and aspects pertaining to standard of care such as completeness of eye exam, quality of eye care and free eyeglasses. Compared to families, staff tended to underestimate the importance of the following features for retention: seeing the same staff at each visit, appointment reminders, center location, newsletters, commitment to the study, being part of a nationwide study, length of the study, association with a college of optometry, completeness of eye exam, and eye drops (p < 0.05 by chi-square analyses). However, staff responses also revealed less preferred components of the study protocol (e.g., eye drops), to which families might have been reluctant to respond unfavorably. Our findings highlight the importance of intangible factors such as staff attributes and participants' study commitment in maintaining high retention rates, and the usefulness of surveying both families and staff.


Identification of Escherichia coli O157:H7-strains from pigs with postweaning diarrhoea and amplification of their virulence marker genes by PCR.
Escherichia coli isolated from pigs with postweaning diarrhoea were examined by PCR for the presence of the O157 rfb gene responsible for the biosynthesis of E coli O157 lipopolysaccharide. Among the 372 isolates tested, 38 (10.2 per cent) were of the O157 serogroup, but none of these possessed the H7 determinant. Further analysis of the E coli O157 isolates revealed that seven of them had the genes responsible for the production of Shiga toxin 1 and eaeA intimin, four other strains had genes responsible for the production of Shiga toxin 2, and four other strains were positive for the enterohaemolysin gene.


Magnetic bead detection using nano-transformers.
A novel scheme to detect magnetic beads using a nano-scale transformer with a femtoweber resolution is reported. We have performed a Faraday's induction experiment with the nano-transformer at room temperature. The transformer shows the linear output voltage responses to the sinusoidal input current. When magnetic beads are placed on the transformer, the output responses are increased by an amount corresponding to the added magnetic flux from the beads when compared with the case of no beads on the transformer. In this way, we could determine whether magnetic beads are on top of the transformer in a single particle level.


Density of states and dynamical crossover in a dense fluid revealed by exponential mode analysis of the velocity autocorrelation function.
Extending a preceding study of the velocity autocorrelation function (VAF) in a simulated Lennard-Jones fluid [Phys. Rev. E 92, 042166 (2015)PLEEE81539-375510.1103/PhysRevE.92.042166] to cover higher-density and lower-temperature states, we show that the recently demonstrated multiexponential expansion method allows for a full account and understanding of the basic dynamical processes encompassed by a fundamental quantity as the VAF. In particular, besides obtaining evidence of a persisting long-time tail, we assign specific and unambiguous physical meanings to groups of exponential modes related to the longitudinal and transverse collective dynamics, respectively. We have made this possible by consistently introducing the interpretation of the VAF frequency spectrum as a global density of states in fluids, generalizing a solid-state concept, and by giving to specific spectral components, obtained through the VAF exponential expansion, the corresponding meaning of partial densities of states relative to specific dynamical processes. The clear identification of a high-frequency oscillation of the VAF with the near-top excitation frequency in the dispersion curve of acoustic waves is a neat example of the power of the method. As for the transverse mode contribution, its analysis turns out to be particularly important, because the multiexponential expansion reveals a transition marking the onset of propagating excitations when the density is increased beyond a threshold value. While this finding agrees with the recent literature debating the issue of dynamical crossover boundaries, such as the one identified with the Frenkel line, we can add detailed information on the modes involved in this specific process in the domains of both time and frequency. This will help obtain a still missing full account of transverse dynamics, in both its nonpropagating and propagating aspects which are linked through dynamical transitions depending on both the thermodynamic states and the excitation wave vectors.


Human papilloma virus type 16 E6 gene expression in oral exophytic epithelial lesions as detected by in situ rtPCR.
We adopted an in situ reverse transcriptase polymerase chain reaction method of detecting and determining the frequency of early (E6) gene expression of human papilloma virus type 16 at the individual cell level in a sample of oral exophytic lesions with various degrees of epithelial hyperplasia and dysplasia in immunosuppressed and immunocompetent patients. The significance of differences between the study groups was determined by Mantel-Haenszel chi-square analysis and calculation of odds ratios, accounting for immunosuppression and degree of dysplasia, respectively. Grouped together, the lesions of dysplasia (mild to severe) and squamous cell carcinoma were found to be 16 times more likely to express human papilloma virus E6 mRNA than the benign lesions (P = .0013); in the lesions of immunosuppressed patients, human papilloma virus 16 E6 was roughly 10 times more likely to be expressed than in those of the immunocompetent patients (P = .0008, accounting for dysplasia). Our data indicate that human papilloma virus 16 E6 gene expression, and perhaps integration of the virus in the host genome, might play a role in the development of oral neoplasia in association with immunosuppression.


Semi-rigid ureteroscope as a dilator in renal stone ureteroscopic treatment.
To determine the efficacy and safety of using the semi-rigid ureteroscope as the only ureteral dilator for primary ureteroscopy (URS) in the treatment of renal stones. A retrospective review of primary URS for renal stone disease was performed on consecutive patients treated by a single provider from 2013 to 2017. Utilizing wire placement under fluoroscopic guidance and direct visual ureteroscopic dilation with a semi-rigid ureteroscope, primary outcome was successful completion of stone treatment. In addition, perioperative safety was evaluated. A total of 126 consecutive cases of primary URS using the semi-rigid ureteroscope as the only ureteral dilator were attempted for renal stone treatment. The renal stones were treated in 124 (98.4%) patients without other forms of active ureteral dilation. Two (1.6%) patients required ureteral stent placement for passive dilation despite attempted other dilating techniques. No intraoperative ureteral perforations were identified. Postoperative radiographic follow up was available for 67% patients with a 91% stone free rate and no hydronephrosis or ureteral strictures were detected. Utilizing direct visual semi-rigid ureteroscopic dilation with a semi-ridged ureteroscope prior to flexible ureteroscopy leads to successful primary ureteroscopy for renal stone treatment in most patients. This technique is an effective, safe and possibly cost-effective method of obtaining ureteral access to facilitate primary URS for renal stone treatment.


Emergency Response for a Laboratory Biosafety Incident.
On December 14, 2017, a faculty member of a university in Hunan Province reported that an anthrax vaccine strain might have recovered virulence during an undergraduate experiment and potential exposure could not be ruled out for the students involved. Upon receiving the case report, the CDC, health bureaus, and local governments at the county, prefectural, and provincial levels promptly organized experts in different fields (including epidemiologists, biosafety experts, and laboratory testing experts) for case investigation, evaluation, and response. As the investigation results showed, no virulence recovery was identified in the involved anthrax vaccine strain; and no contamination of Bacillus anthracis was detected at the involved areas. Thus, the university returned to normal functioning.


Anatomic classification of the right aortic arch.
The term right aortic arch is used for an aorta that arches over the right bronchus. Right aortic arch was classified into two types by Felson et al, based on branching patterns, with a proposed embryological explanation, and into three types by Shuford et al. Other anatomical variants of right aortic arch were described later, including isolated left brachiocephalic artery and aberrant left brachiocephalic artery. We have classified right aortic arch anatomy into 10 variants, supported by radiological evidence, and with reference to possible embryology. This classification will help in understanding the morphological basis for the formation of different types of right aortic arch and the course of the recurrent laryngeal nerve in such cases.


Overexpression of the AtmybL2 gene represses trichome development in Arabidopsis.
Leaf trichome formation is known to be regulated by the TTG, GL1, GL2, and GL3 genes in Arabidopsis. GL1 and GL3 encode proteins with Myb and bHLH domains, respectively. Overexpression of the AtmybL2 gene, which encodes a single Myb-like DNA-binding domain, repressed trichome development in transgenic Arabidopsis plants. The amount of GL2 transcription was clearly reduced in the transgenic plants. Consistent with this, overexpression of AtmybL2 decreased beta-glucuronidase (GUS) activity in transgenic plants carrying a GUS-reporter gene regulated by the GL2 promoter. These findings, together with the results from our yeast two-hybrid analysis, suggest that GL3 gene function and overexpression of AtmybL2 act synergistically to inhibit trichome formation by negatively regulating GL2 expression.


Chronic paroxysmal hemicrania in a patient with a macroprolactinoma.
We report a patient with headaches meeting the criteria of chronic paroxysmal hemicrania, as defined by the International Headache Society classification. Headaches were fully responsive to indomethacin during the first 3 months of treatment but recurred when daily doses were lowered. Investigations revealed a macroprolactinoma. Headaches stopped after cabergoline treatment. This report further suggests that patients with paroxysmal hemicrania should be investigated for pituitary abnormalities.


[Study on occupational exposure limit of dimethoxymethane in workplace air].
To study the occupational exposure limit of dimethoxymethane (DMM) in workplace air. Literature research was conducted on DMM; information on its physicochemical properties, toxicology, and occupational epidemiology was collected. Upon analyzing these data, an occupational exposure limit of DMM in workplace air was proposed according to the guidelines and principles of developing occupational exposure limits for harmful factors in workplaces. A total of 165 air samples were collected from DMM manufacturers, 14 of which had a DMM concentration over 3000 mg/m(3), accounting for 8.48% of all samples. Compared with the control group, the exposed employees had a significantly increased incidence of discomfort symptoms when exposed to more than 6000 mg/m(3) DMN (P < 0.01).No significant differences in the constituent ratios of abnormal results in physical examinations were found between the exposure groups and control group (P > 0.05). We recommend to set the permissible concentration-time weighed average to 3100 mg/m(3) as the occupational exposure limit of DMM in workplace air in China. This occupational exposure limit standard meets the relevant requirements of toxicology and occupational epidemiology, as well as fits well with our country's current economical and technological levels. This standard has high applicability in China's domestic settings.


Recruiting adults with osteoarthritis into an aquatic exercise class: strategies for a statewide intervention.
Although research suggests that regular exercise can be helpful in reducing the dysfunction and discomfort of osteoarthritis, promoting exercise among older adults within this population is neither straightforward nor easily accomplished. This article describes the various methods, and their relative success rates, that were employed to recruit older adults throughout the state of Washington into an aquatic exercise program. Strategies included a recruitment letter distributed to Arthritis Foundation (AF) members in Washington state, local media news coverage, physician referrals, and advertisements in local papers and newsletters. The most successful methods for enrolling participants were through the AF recruitment letters and local television coverage. The AF recruitment letter was the most expensive method of generating responses, while the television coverage was the least expensive. Collaborating with a well-reputed community-based organization and capitalizing on available publicity resources are important strategies researchers can use to gain access to a difficult and geographically dispersed population.


Isokinetic maximal torque power of greek elite soccer players.
Eighteen elite Greek soccer players (age, 27.8 +/- 3.4 years; height, 176.6 +/- 5.2 cm; weight, 75.5 +/- 5.2 kg) were tested on the Cybex(R) II apparatus in order to determine 1) the maximal muscle power for the lower extremity dominant side at angular velocities of 30 degrees /sec, 90 degrees /sec, and 180 degrees /sec; 2) the total muscular output and the relative power at 30 degrees /sec; 3) the relationship between the muscle power of the agonist and antagonist musculature. The absolute maximal muscle power (Nm) at 30 degrees /sec for the different joint movements was as follows: Hip Ext = 269 +/- 39; Hip Flex = 179 +/- 29; Hip Add = 160 +/- 17; Hip Abd = 119 +/- 24; Knee Ext = 247 +/- 29; Knee Flex = 146 +/- 12; PI. Flex = 120 +/- 22; and Do. Flex = 32 +/- 6. The muscle agonist-antagonist percent relationship at 30 degrees /sec was found to be: (hip flex)/(hip ext) = 66%(hip abd)/(hip add) = 74%(knee flex)/(knee ext) = 60%(dor. fle)/(pl. fle) = 28%These findings have significant implications for preseason conditioning programs as well as for minimizing the rate of muscle injuries by restoring the correct relationship between agonist-antagonist musculature.J Orthop Sports Phys Ther 1985;6(5):293-295.


Ancestral haplotype reconstruction in endogamous populations using identity-by-descent.
In this work we develop a novel algorithm for reconstructing the genomes of ancestral individuals, given genotype or sequence data from contemporary individuals and an extended pedigree of family relationships. A pedigree with complete genomes for every individual enables the study of allele frequency dynamics and haplotype diversity across generations, including deviations from neutrality such as transmission distortion. When studying heritable diseases, ancestral haplotypes can be used to augment genome-wide association studies and track disease inheritance patterns. The building blocks of our reconstruction algorithm are segments of Identity-By-Descent (IBD) shared between two or more genotyped individuals. The method alternates between identifying a source for each IBD segment and assembling IBD segments placed within each ancestral individual. Unlike previous approaches, our method is able to accommodate complex pedigree structures with hundreds of individuals genotyped at millions of SNPs. We apply our method to an Old Order Amish pedigree from Lancaster, Pennsylvania, whose founders came to North America from Europe during the early 18th century. The pedigree includes 1338 individuals from the past 12 generations, 394 with genotype data. The motivation for reconstruction is to understand the genetic basis of diseases segregating in the family through tracking haplotype transmission over time. Using our algorithm thread, we are able to reconstruct an average of 224 ancestral individuals per chromosome. For these ancestral individuals, on average we reconstruct 79% of their haplotypes. We also identify a region on chromosome 16 that is difficult to reconstruct-we find that this region harbors a short Amish-specific copy number variation and the gene HYDIN. thread was developed for endogamous populations, but can be applied to any extensive pedigree with the recent generations genotyped. We anticipate that this type of practical ancestral reconstruction will become more common and necessary to understand rare and complex heritable diseases in extended families.


[An autopsy case of rheumatoid arthritis associated with proliferative endarteritis died of sudden severe melaena].
A 68-year-old male with a 2-year history of rheumatoid arthritis was hospitalized due to severe polyarthritis. Since level of rheumatoid factor was high, and subcutaneous nodules and cutaneous ulcers were present, the case was diagnosed as malignant rheumatoid arthritis (rheumatoid vasculitis). On 10th day after admission, severe dyspnea developed due to acute heart failure, followed by severe melaena. The patient did not respond to various treatments including steroid pulse therapy, and died 3 days later. Autopsy revealed widespread hemorrhagic infarction that was extended from the colon to the rectum. Proliferative endarteritis was recognized in mesenteric vessels, however neither necrosis nor inflammatory changes were observed. The melaena was caused by the interstinal infarction. The intestinal infarction was thought to be responsible for the circulatory disturbances due to heart failure in obstructive vessel lesion of mesenteric vessels.


Crystal structure of 2,9-diphenyl-17λ(6)-thia-tetra-cyclo-[220.127.116.11(3,8).0(11,16)]hepta-deca-1(10),2,4,6,8,11(16),12,14-octa-ene-17,17-dione.
The title compound, C28H18O2S, is composed of a naphthalene ring system fused with a benzo-thio-phene ring and attached to two phenyl rings. The phenyl rings make dihedral angles of 70.92 (8) and 79.23 (8)° with the essentially planar naphthalene ring system (r.m.s. deviation = 0.031 Å). There is an intra-molecular C-H⋯π inter-action present. In the crystal, mol-ecules are linked by C-H⋯O hydrogen bonds which generate C(7) zigzag chains running parallel to [10-1]. The chains are linked via further C-H⋯π inter-actions, forming a three-dimensional structure.


Cholesterol and bile acid synthesis in two families with homozygous and heterozygous hypercholesterolemia.
Measurements of cholesterol and bile acid synthesis and of cholesterol precursors were performed in two hypercholesterolemic families with two homozygous girls under basal conditions and during treatment with cholestyramine. The concentrations of serum methyl sterols, squalene, cholesterol, and triglycerides, and the responses to cholestyramine were not consistently different in the two families. However, in both families stimulation of cholesterol synthesis by cholestyramine markedly increased the methyl sterol content of serum lipoproteins both in heterozygotes (with a lowering of serum cholesterol) and in homozygotes (with virtually no lowering of serum cholesterol concentration). The bile acid and cholesterol synthesis rates were modestly low in one family and markedly high in the other both with and without cholestyramine treatment, the baseline production rates being significantly correlated with the increments in the synthesis caused by cholestyramine. The two families apparently represent low and high producing types of familial hypercholesterolemia. Cholesterol synthesis in the two homozygous girls was about twice that of their respective heterozygous parents with and without cholestyramine treatment, suggesting that the double dose of the mutant gene doubled cholesterol production. Furthermore, close child-to-parent correlations for the bile acid and cholesterol synthesis rates point to a genetic control of cholesterol metabolism.


Lesions of the pedunculopontine tegmental nucleus reduce paradoxical sleep (PS) propensity: evidence from a short-term PS deprivation study in rats.
Cholinergic neurons in the mesopontine tegmentum are thought to play a critical role in the generation of paradoxical sleep (PS). However, no study has yet examined whether lesions of these neurons cause deficits of PS in the rat. We describe here the effects of lesions of the pedunculopontine tegmental nucleus (PPT) on spontaneous PS and on PS propensity, expressed during and after a short period of PS deprivation. Lesions were induced by bilateral injections of ibotenate. PS deprivation was performed manually by gently waking rats each time they showed polygraphic signs of PS. Two weeks after lesions, an 8-h baseline recording was performed; the following day, rats were PS deprived for 6 h and polygraphic recordings were then continued for 2 h, to examine recovery sleep. The same protocol was repeated 1 week later. Compared with controls and with rats with limited PPT lesions, rats bearing > 60% NADPH-diaphorase-positive cell loss within the PPT showed unaffected PS under baseline conditions. However, they made fewer attempts to enter PS during deprivation and they exhibited an attenuated rebound increase in PS time after deprivation. The number of PS attempts and the magnitude of PS rebound were negatively correlated with the percent loss of diaphorase-positive neurons within the PPT. Thus, PS propensity that accumulated as a result of PS deprivation was reduced after extensive PPT lesions. In summary, although spontaneous PS was found to be unaltered, the PS deprivation procedure used in this study demonstrated the dysfunctioning of PS caused by PPT lesions.


Child and adolescent depression.
For much of the 20th century, major depression was viewed as a malady to which children were not susceptible. In recent years, this view has given way to an understanding that child and adolescent depression not only exist, but constitute an insidious and major public health problem. Depressive symptoms in children can be subtle and varied. The diagnosis in adolescents often is complicated by behavioral manifestations associated with hormonal changes. Both the etiology and the treatment of child and adolescent depression remain controversial. However, recent developments in pharmacotherapy appear promising. Primary prevention may not always be efficacious, but evidence suggests secondary prevention can reduce significantly future psychosocial problems.


Effect of the COVID-19 pandemic on dental interns in Saudi Arabia.
The coronavirus disease (COVID-19) has emerged as a global pandemic recognized by the World Health Organization. It has a significant impact on Saudi Arabia's educational process, resulting in several universities suspending on-campus teaching, exams, and training. The study aimed to evaluate the effect of COVID-19 on dental students' examination, internship placement, and subsequent impact on preparedness and confidence. A cross-sectional study was conducted to gather data from dental interns in Saudi Arabia using a pre-tested online questionnaire. Convenient sampling was applied to collect data from 5th September to 15th September 2020. Data were analyzed using SPSS version 23. Descriptive data were presented as frequency and percentages. The Chi-square test was used to evaluate the relationship between variables. Data of 409 dental interns from 8 dental schools reported that 209 (51%) participants' exams were affected as the format was changed to online examination. 130 (31.8%) dental interns strongly agreed that assistance in hospitals during the outbreak of COVID-19 would complement their learning opportunities. Whereas 115(28.1%) respondents strongly agreed that dental schools' measures to modify their curriculum were necessary.The impact of COVID-19 on dental intern preparedness discovered that the affected exams had a significant effect on final year students' readiness to begin the internship (p = 0.042). Considering students' confidence in starting the training earlier than expected, the student course had a statistically significant impact on their confidence (p = 0.002). The current study demonstrates that COVID-19 had disrupted dental interns' preparedness towards clinical rotation and decreased their confidence performing in the clinical setup. Due to being unprepared and having low confidence, most dental interns were not ready to start working in the hospital on time.


Controlled trial of D-cycloserine adjuvant therapy for treatment-resistant major depressive disorder.
Compounds that reduce N-methyl-d-aspartate receptor (NMDAR) function, including NMDAR antagonists and partial agonists at the NMDAR-associated glycine (GLY) site, may act as antidepressants. The antibiotic drug d-cycloserine (DCS) acts as a partial agonist at the NMDAR-GLY site. Preclinical and clinical data suggest that at dosages >or=100 mg/day DCS acts as a functional NMDAR antagonist and may have antidepressant effects. Twenty-two treatment resistant major depression patients participated in a double-blind, placebo-controlled 6-week crossover trial with 250 mg/day DCS added to their ongoing antidepressant medications. DCS treatment was well tolerated and resulted in symptom reductions. However, biweekly-performed clinical assessments, including the Hamilton Depression Rating Scale, Hamilton Rating Scale for Anxiety and Zung Self-Rating Depression Scale did not reveal statistically significant therapeutic advantages of DCS vs. placebo adjuvant treatment. Small sample, uneven treatment resistance criteria across subjects. The exposure to DCS (dose/length of treatment) may not have been sufficient. This exploratory study represents the first attempt to assess the effects of a NMDAR-GLY site partial agonist in depression treatment. The findings and limitations of this study should be taken into account in the planning of future clinical trials with NMDAR modulators in depression.


EVAR may reduce the risk of aneurysm rupture despite persisting type Ia endoleaks.
To determine the risk of aneurysm rupture in patients with persisting proximal type Ia endoleaks following endovascular aneurysm repair (EVAR) in comparison to the risk of rupture of untreated abdominal aortic aneurysms (AAA) of similar size. Among 400 patients who where treated with EVAR from 1996 to 2003 at a single center, 21 (5.3%) patients (13 men; mean age 78.0±5.0 years, range 67-86) with large (≥5.5 cm) aneurysms had imaging evidence of type Ia endoleaks that persisted >10 months (type Ia group) despite secondary endovascular treatment. These patients were compared to 24 untreated AAA patients (17 men; mean age 73.8±5.2 years, range 64-88) with large aneurysms from a separate geographic region with a well-established aneurysm treatment program before EVAR became available (1990-1998). There were no significant differences between the type Ia and the untreated AAA patients with regard to age (79±8 vs. 74±5 years), gender (38% vs. 29% women), baseline aneurysm diameter (6.1±0.7 vs. 6.4±0.9 cm), or length of follow-up (32±23 vs. 29±40 months). During the follow-up period, the rate of aneurysm enlargement was significantly lower in type Ia patients (0.19 cm/y) than in untreated AAA patients (0.54 cm/y, p = 0.03). One (4.8%) patient with a persisting type Ia endoleak and 2-cm aneurysm enlargement (0.8 cm/y) had aneurysm rupture after 2.5 years, while 12 (50%) of the 24 untreated aneurysms ruptured (p = 0.001), which was the primary cause of death in this group. The rupture rate was 1.8 per 100 patient-years in the type Ia group and 20.7 per 100 patient-years in the untreated AAA group. Aneurysm-related mortality was significantly reduced in the type Ia group compared to the untreated AAA group at 36 months (11% vs. 52%, p = 0.004). In the multivariate analysis, factors associated with death were an untreated AAA (odds ratio 97, p = 0.004), female gender (odds ratio 9.7, p = 0.02), and baseline aneurysm size (odds ratio 4.7/cm, p = 0.03). This study suggests that EVAR may reduce the risk of rupture and aneurysm-related death despite the presence of a persisting type Ia endoleak. This finding is limited to patients with aortic endografts that are in good position. The mechanism of protection from rupture is unclear but may be related to reducing the rate of aneurysm enlargement.


Sustained multilineage engraftment of allogeneic hematopoietic stem cells in NOD/SCID mice after in utero transplantation.
Substantial barriers exist to the engraftment of hematopoietic cells in mice after in utero transplantation. Although high levels of donor-derived hematopoiesis have been reported in SCID mice, the majority of chimeric recipients exhibit decreasing levels of donor cells over time. To directly test whether the natural killer cell and macrophage activity of the recipients represents a barrier to sustained engraftment, fetal NOD/SCID mice were injected on day 13.5 of gestation with an enriched congenic hematopoietic progenitor cell population. Forty-four percent of pups showed the presence of Ly5.1+ donor cells 4 weeks after transplantation. The mean number of donor-derived nucleated cells in the peripheral blood (PB) was 30%. Although the majority of circulating donor cells were lymphocytes, up to 15% expressed myelomonocytic markers. Serial PB samples from individual mice indicated that the percentage of circulating donor cells increased from 17% to 55% between 4 and 24 weeks. At 6 months posttransplantation, an increased frequency of multilineage, donor-derived cells was also observed in the bone marrow (BM) and the spleen of chimeric recipients. The engraftment of pluripotent hematopoietic stem cells was evaluated by transplanting BM from chimeric mice into irradiated congenic recipients. Irradiated secondary recipients also exhibited multilineage donor-derived hematopoiesis in the PB, BM, and spleen for up to 6 months. These results show that the in utero transplantation of lineage-depleted BM cells into NOD/SCID recipients produces a high frequency of sustained engraftment of allogeneic hematopoietic stem cells.


[Current issues of disability and rehabilitation of elderly and senile patients with lower limb loss due to vascular pathology.]
The majority of patients with amputation defect of the lower extremities are elderly citizens with high co- and polymorbidity, the presence of several geriatric syndromes, which adversely affects the prognosis, reduces the rehabilitation potential, in some cases leads to the development of cardiovascular complications, amputation of the second limb, severe disability and high postoperative mortality. The key link in the rehabilitation process of disabled people with a lower limb stump is to provide them with a functional prosthesis. The article provides an analysis of morbidity, primary disability in the period from 2015 to 2019, gender, age and clinical characteristics of patients living in St. Petersburg who underwent amputation of the lower limb due to obliterating artery diseases is presented. It was found that there is no information on the survival rate of patients after amputation at various times of the post-hospital period in St. Petersburg. We have identified a pronounced imbalance between the number of lower limb amputations performed and the number of applications of disabled people to the bureau of medical and social expertise for providing technical means of rehabilitation and referral to primary prosthetics.


Diets high in resistant starch and arabinoxylan modulate digestion processes and SCFA pool size in the large intestine and faecal microbial composition in pigs.
The effects of a high level of dietary fibre (DF) either as arabinoxylan (AX) or resistant starch (RS) on digestion processes, SCFA concentration and pool size in various intestinal segments and on the microbial composition in the faeces were studied in a model experiment with pigs. A total of thirty female pigs (body weight 63.1 (sem 4.4) kg) were fed a low-DF, high-fat Western-style control diet (WSD), an AX-rich diet (AXD) or a RS-rich diet (RSD) for 3 weeks. Diet significantly affected the digestibility of DM, protein, fat, NSP and NSP components, and the arabinose:xylose ratio, as well as the disappearance of NSP and AX in the large intestine. RS was mainly digested in the caecum. AX was digested at a slower rate than RS. The digesta from AXD-fed pigs passed from the ileum to the distal colon more than twice as fast as those from WSD-fed pigs, with those from RSD-fed pigs being intermediate (P< 0.001). AXD feeding resulted in a higher number of Faecalibacterium prausnitzii, Roseburia intestinalis, Blautia coccoides-Eubacterium rectale, Bifidobacterium spp. and Lactobacillus spp. in the faeces sampled at week 3 of the experimental period (P< 0.05). In the caecum, proximal and mid colon, AXD feeding resulted in a 3- to 5-fold higher pool size of butyrate compared with WSD feeding, with the RSD being intermediate (P <0.001). In conclusion, the RSD and AXD differently affected digestion processes compared with the WSD, and the AXD most efficiently shifted the microbial composition towards butyrogenic species in the faeces and increased the large-intestinal butyrate pool size.


[Child orthopedics].
Children's fractures are a challenge to the treatment system, in that 17,000 children are treated in Denmark each year. The true burden on patients and society is unknown. It is estimated that 1000 new-born infants are treated for hip instability in Denmark per year, and 30 are diagnosed late. Ultrasound scanning is recommended for secondary screening and selective screening of children at risk. Identification of acetabular dysplasia followed by surgical correction could be an important prophylactic measure, with a potential reduction in expenses to society. To some extent, congenital clubfoot is hereditary. Environmental factors are important, maternal smoking being one. Early operative treatment yields good results. There is a need for prospective registration. Perthes' disease is an idiopathic necrosis of the capital femoral epiphysis. Passive smoking is a significant factor. A young age (< 7 years) and limited necrosis carry a good prognosis, and active treatment can improve the prognosis for the other patients.


An accurate semi-empirical potential model for the a 3Σu + state of the alkali dimers Na2, K2, Rb2, and Cs2 which reproduces the scattering length.
A new four parameter Tang-Toennies type potential model is described for the a 3Σu + triplet state of the alkali dimers Na2, K2, Rb2, and Cs2. Compared to an earlier three parameter semi-empirical model based on the experimental well depth, De, well location, Re, and the harmonic vibrational frequency, ωe [Lau et al., J. Chem. Phys. 145, 194308 (2016)], the new model is also adjusted to be consistent with the scattering length. The results are shown to have a similar good agreement with the spectroscopic term values as the earlier model with the advantage that the scattering length is properly described. The deviations from recent potentials for Cs2 are discussed.


[Symptomatic therapy in a possible animal model for Huntington's chorea].
This is a report on first symptomatic therapy trials of a possible animal model with beta,beta-iminodipropiontrile (IDPN) for Huntington's disease. 1. Experiments to quantitatively measure the choreiform head movements of the rat after IDPN-application were not successful. 2. Of all substances tested, thyroxine was the only one that prevented the choreiform movement disturbances in the rat induced by IDPN. 3. Glucosamine, isonicotinic acid, -hydrazide (isoniazid) and bromocriptine caused a slight retardation of the occurrence of the IDPN-symptoms in the rat for about 1-2 days. 4. Thyroxine does not improve the IDPN-symptoms in the rat. 5. All the other substances tested (mephenytoin, glucosamine, isonicotinic acid-hydrazide, bromocriptine and isonicotinic acid-hydrazide in combination with glucosamine) do temporarily improve the choreiform movement disturbances induced by IDPN. Furthermore during the treatment, these rats were calmer and their landing showed better results. 6. After these first results, the IDPN-model would appear to be a suitable animal model for Huntington's disease in man. With this animal model, new drugs for the symptomatic treatment of this disease can be tested.