Hierarchical amorphous vanadium oxide and carbon nanotubes microspheres with strong interface interaction for Superior performance aqueous Zinc-ion batteries.
Aqueous zinc-ion batteries have attracted more and more attention due to their safety, environmental benignity and high theoretical capacity. However, the lack of appropriate cathode materials with high capacity and long cycle life have become an obstacle to the development of aqueous zinc-ion batteries. Herein, the hierarchical amorphous vanadium oxide and carbon nanotubes (a-V2O5@CNTs) microspheres with strong interface interaction were successfully prepared by combing facile spray drying technique with annealing treatment. Benefiting from the a-V2O5 amorphous characters, CNTs framework high conductivity and hierarchical microspheres with strong interface interaction, the a-V2O5@CNTs exhibited abundant active sites, fast reaction kinetics as well as eminent structure stability. As a promising electrode material, the a-V2O5@CNTs displayed high specific capacity (480 mAh g-1 at 0.5 A g-1), good rate capability and long-term stability under high current density (158 mAh g-1 at 30 A g-1 over 1000 cycles). Meanwhile, the corresponding mechanism was further illustrated through different characterizations. Furthermore, the as-assembled flexible pouch battery based on the a-V2O5@CNTs delivered outstanding flexibility and feasibility. Hence, this work provides a new idea for developing high performance cathode materials of aqueous zinc-ion batteries.


Molecular detection of ochratoxin A producers: an updated review.
Ochratoxin A (OTA) can be detected worldwide from various food and feed sources. It is produced byPenicillium nordicum andP. verrucosum as well as by variousAspergillus species, withA. ochraceus andA. carbonarius as the predominant producers. Various pairs of PCR primers based on AFLP, RAPD as well as primers specific to ribosomal RNA and genes coding for calmodulin and OTA biosynthetic pathway components were recently developed to detect and identify OTA producers in conventional and real-time PCR assays. Application of such assays in contaminated samples was demonstrated only in few cases. The current review gives an updated overview over the methods at hand.


Craniosynostosis: an assessment of blood loss and transfusion practices.
Assessment and accurate replacement of blood loss during primary craniosynostosis repair is difficult due to patient size and surgical technique. Eighty-five charts of all patients undergoing primary craniosynostosis repair over a 15-year period were reviewed to determine blood loss and to assess blood transfusion practices both intraoperatively and postoperatively. Blood loss was calculated on the basis of estimated red cell mass (ERCM). Blood transfusion management was considered appropriate if the postoperative or posttransfusion ERCM was within 15 per cent of the preoperative value. Isolated sagittal craniectomy was the most common operation performed (60 per cent). Mean blood loss for sagittal craniectomies was 24 per cent of estimated blood volume (EBV) or approximately 20 ml.kg-1 and for metopic craniectomies 42 per cent of EBV (P less than 0.05). Intraoperatively, 70 per cent of all patients were appropriately managed with respect to blood transfusion. Postoperatively only 29 per cent of patients receiving transfusions were transfused appropriately. At our institution, intraoperative blood transfusion practices are appropriate, but postoperative transfusions are frequently unnecessary.


Effects of HOXC8 on the Proliferation and Differentiation of Porcine Preadipocytes.
Transcription factor Homeobox C8 (HOXC8) is identified as a white adipose gene as revealed by expression profile analysis in fat tissues. However, the specific role of HOXC8 in fat accumulation remains to be identified. This study was designed to reveal the effects of HOXC8 on preadipocyte proliferation and differentiation. We first make clear that the expression of HOXC8 is associated with fat contents in muscles, highlighting a role of HOXC8 in fat accumulation. Next, it is demonstrated that HOXC8 promotes the proliferation and differentiation of preadipocytes through gain- and loss-of-function assays in primary cultured porcine preadipocytes. Then, mechanisms underlying the regulation of HOXC8 on preadipocyte proliferation and differentiation are identified with RNA sequencing, and a number of differentially expressed genes (DEGs) in response to HOXC8 knockdown are identified. The top GO (Gene Ontology) terms enriched by DEGs involved in proliferation and differentiation, respectively, are identical. IL-17 signaling pathway is the common one significantly enriched by DEGs involved in preadipocyte proliferation and differentiation, respectively, indicating its importance in mediating fat accumulation regulated by HOXC8. Additionally, we find that the inhibition of proliferation is one of the main processes during preadipocyte differentiation. The results will contribue to further revealing the mechanisms underlying fat accumulation regulated by HOXC8.


Effect of inhaled carbon ultrafine particles on reactive hyperemia in healthy human subjects.
Ultrafine particles (UFP) may contribute to the cardiovascular effects of exposure to particulate air pollution, partly because of their relatively efficient alveolar deposition and potential to enter the pulmonary vascular space. This study tested the hypothesis that inhalation of elemental carbon UFP alters systemic vascular function. Sixteen healthy subjects (mean age, 26.9 +/- 6.5 years) inhaled air or 50 microg/m3 elemental carbon UFP by mouthpiece for 2 hr, while exercising intermittently. Measurements at preexposure baseline, 0 hr (immediately after exposure), 3.5 hr, 21 hr, and 45 hr included vital signs, venous occlusion plethysmography and reactive hyperemia of the forearm, and venous plasma nitrate and nitrite levels. Peak forearm blood flow after ischemia increased 3.5 hr after exposure to air but not UFP (change from preexposure baseline, air: 9.31 +/- 3.41; UFP: 1.09 +/- 2.55 mL/min/100 mL; t-test, p = 0.03). Blood pressure did not change, so minimal resistance after ischemia (mean blood pressure divided by forearm blood flow) decreased with air, but not UFP [change from preexposure baseline, air: -0.48 +/- 0.21; UFP: 0.07 +/- 0.19 mmHg/mL/min; analysis of variance (ANOVA), p = 0.024]. There was no UFP effect on pre-ischemia forearm blood flow or resistance, or on total forearm blood flow after ischemia. Venous nitrate levels were significantly lower after exposure to carbon UFP compared with air (ANOVA, p = 0.038). There were no differences in venous nitrite levels. Inhalation of 50 microg/m3 carbon UFP during intermittent exercise impairs peak forearm blood flow during reactive hyperemia in healthy human subjects.


Effects of mercuric chloride on the resting membrane potentials of blue crab (Callinectes sapidus) muscle fibers.
The effects of concentrations of mercuric chloride ranging from 3.68 to 368 microM (1--100 ppm) on the resting membrane potentials of muscle fibers in the extensor muscle of the carpopodite in walking legs of adults blue crabs were investigated in vitro. Glass micropipettes filled with saturated solutions of potassium chloride and conventional electronic equipment were used. Resting membrane potentials in uncontaminated artificial sea water averaged -78 mV +/- 4 mV (S.E.M.). Mercuric chloride added to the control bath at 3.68 or 9.2 microM did not affect the resting membrane potentials. At 18.4 microM threshold effects were obtained in 50% of the preparations. At concentrations ranging from 25.7 to 368 microM progressive deterioration of membrane polarization occurred as the mercury concentration was increased. This effect was irreversible despite multiple washes with normal sea water. We conclude that mercuric chloride has very powerful toxic effects at the peripheral motor effector elements in blue crabs. These results do not, of course, rule out more central effects on enzymatic systems or neuronal networks.


Intestinal Reg4 deficiency confers susceptibility to high-fat diet-induced liver steatosis by increasing intestinal fat absorption in mice.
Regenerating gene family member 4 (REG4) is a novel marker for enteroendocrine cells and is selectively expressed in specialised enteroendocrine cells of the small intestine. However, the exact roles of REG4 are largely unknown. In this study we investigate the effects of REG4 on the development of dietary fat-dependent liver steatosis and the mechanisms involved. Mice with intestinal-specific Reg4 deficiency (Reg4 ΔIEC ) and Reg4-floxed alleles (Reg4 fl/fl ) were generated to investigate the effects of Reg4 on diet-induced obesity and liver steatosis. Serum levels of REG4 were also measured in children with obesity using ELISA. Reg4 ΔIEC mice fed a high-fat diet demonstrated significantly increased intestinal fat absorption and were prone to obesity and hepatic steatosis. Importantly, Reg4 ΔIEC mice exhibit enhanced activation of adenosine monophosphate-activated protein kinase (AMPK) signalling and increased protein abundance of the intestinal fat transporters, as well as enzymes involved in triglyceride synthesis and packaging at the proximal small intestine. Moreover, REG4 administration reduced fat absorption, and decreased the expression of intestinal fat absorption-related proteins in cultured intestinal cells possibly via the CaMKK2-AMPK pathway. Serum REG4 levels were markedly lower in children with obesity with advanced liver steatosis (p <0.05). Serum REG4 levels were inversely correlated with levels of liver enzymes, homeostasis model assessment of insulin resistance, low-density lipoprotein cholesterol, and triglycerides. Our findings directly link Reg4 deficiency with increased fat absorption and obesity-related liver steatosis, and suggest that REG4 may provide a potential target for prevention and treatment of liver steatosis in children. Hepatic steatosis is a key histological feature of non-alcoholic fatty liver disease, which is the leading chronic liver disease in children leading to the development of metabolic diseases; however, little is known about mechanisms induced by dietary fat. Intestinal REG4 acts as a novel enteroendocrine hormone reducing high-fat-diet-induced liver steatosis with decreasing intestinal fat absorption. REG4 may be a novel target for treatment of paediatric liver steatosis from the perspective of crosstalk between intestine and liver.


The principle of double effect and external whistleblowing in nursing.
Nurses are generally expected to raise concerns when a harm or wrongdoing is committed against patients. Should their concerns not be adequately addressed, then nurses may take the decision to engage in external whistleblowing. Given that it could have a negative effect on the health care organization or service, nurses may question whether they should engage in external whistleblowing. Consequently, is there an ethical criterion to discern whether the negative effect on the health care organization or service is ethically permissible? This paper argues for the suitability of the Principle of Double Effect as an ethical criterion. The position of this paper is that external whistleblowing by a nurse when understood as an advocacy act with two effects (i.e. the effect of defending a patient and the further negative effect on the health care organization or service) can be ethically permissible through meeting the conditions of the Principle of Double Effect.


Has the Pectoralis Major flap Really Become Obsolete?
To evaluate the current role of pectoralis major (PM) flap including the reasons for selecting it over free flaps. All patients who underwent PM flap at Apollo Hospitals Ahmedabad during the 3-year period from January 2020 to December 2022 were included. Patient demographics, tumour characteristics and complications were studied and reasons for selecting pectoralis major flap were analyzed. Data was entered in Microsoft excel spreadsheet and analyzed using online statistical calculators. The p value of < 0.05 was considered statistically significant. 57 patients underwent reconstruction with PM flap while 154 patients underwent free flap reconstruction. 54 were male and 3 were female. Median age was 51 years. PM flap was used for intraoral lining in 25 patients, and it was bilobed in 26 patients with full thickness cheek defect. Most common complication was wound infection seen in 10 patients. 5 patients developed marginal necrosis of the flap and 5 had donor site wound dehiscence. No complete flap loss was seen. During the same period, 15/154 (9.74%) patients with free flaps developed complete flap necrosis and this was statistically significant (p = 0.012). Reasons for choosing PM flap were also analyzed. 14 patients had major comorbidities, 18 had extensive disease, in 5 patients it was used for salvage post free flap failure, while 10 previously treated patients had unavailability of suitable vessels for anastomosis. 12 patients underwent PM flap due to financial constraints. Thus, PM flap is not obsolete and continues to maintain its place in head and neck reconstruction.


Quality of life in osteogenesis imperfecta.
The purpose of this study was to quantify the physical and mental health of a diverse adult cohort of patients with osteogenesis imperfecta (OI) utilizing a validated health self-assessment questionnaire (SF-36). In addition, a specific demographic questionnaire and a functional questionnaire were utilized to assess more specifically the physical limitations imposed by osteogenesis imperfecta in adulthood. The results of the SF-36 revealed significantly lower physical function scores compared to the U.S. adult norms. However, the SF-36 mental component scores were equal to the U.S. adult norms. The demographic questionnaire revealed high levels of educational achievement, as well as employment, despite significant physical impairments. The functional questionnaire clearly demonstrated limitations mostly related to ambulation.


Flowering time regulation produces much fruit.
Many of the molecular details regarding the promotion of flowering in response to prolonged exposure to cold temperatures (vernalization) and daylength have recently been elucidated in Arabidopsis. The daylength and vernalization pathway converge in the regulation of floral promoters referred to as floral integrators. In the meristem, vernalization promotes flowering through the epigenetic repression of the floral repressor FLOWERING LOCUS C. This allows for the induction of floral integrators by CONSTANS under inductive long days. In the vasculature of leaves, CONSTANS protein is produced only in long days where it acts to promote the expression of FLOWERING LOCUS T (FT). FT protein is then translocated to the meristem where it acts to promote floral induction. Thus a detailed molecular framework for the regulation of flowering time has now been established in Arabidopsis.


Contact angle patterns on low-energy surfaces.
It is well-known that on a given low-energy solid surface, the contact angles of different organic liquids follow a regular pattern. The experimental evidence for this, and semi-empirical equations describing the pattern, are reviewed. Theoretical and computational efforts to explain the pattern are discussed, and a simplified analytical approach is presented. The main pattern of contact angles is seen to arise from two factors: a common combining rule for liquid-solid molecular interactions, and the reduced density of liquid molecules adjacent to a lower-energy solid surface. Irregular departures from the main pattern are due to chemical effects originating in molecular structure.


Distinct lineages of influenza virus H4 hemagglutinin genes in different regions of the world.
To understand the determinants of influenza virus evolution, phylogenetic relationships were determined for nine hemagglutinin (HA) genes of the H4 subtype. These genes belong to a set of viruses isolated from several avian and mammalian species from various geographic locations around the world between 1956 and 1985. We found that the HA gene of the H4 subtype is 1738 nucleotides in length and is predicted to encode a polypeptide of 564 amino acids. The connecting peptide, which is removed from the precursor polypeptide by peptidases to yield the mature HA1 and HA2 polypeptides, contains only one basic amino acid. This type of connecting peptide is a feature of all avian avirulent HAs. On the basis of pairwise nucleotide sequence homology comparisons the genes can be segregated into two groups: influenza virus genes isolated in North America and those isolated from other parts of the world. A high degree of homology exists between pairs of genes from viruses of similar geographic origin. The nucleotide sequences within a group differ by 1.5 to 10.6%; in contrast, between groups the differences range from 15.8 to 19.4%. An evolutionary tree for the nine sequences suggests that North American isolates have diverged extensively from those circulating in other parts of the world. Geographic barriers which determine flyway outlay may prevent the gene pools from extensive mixing. The lack of correlation between date of isolation and evolutionary distance suggests that different H4 HA genes cocirculate in a fashion similar to avian H3 HA genes (H. Kida et al., 1987, Virology 159, 109-119) and influenza C genes (D. Buonagurio et al., 1985, Virology 146, 221-232) implying the absence of selective pressure by antibody that would give a significant advantage to antigenic variants. In contrast to avian influenza virus genes, human influenza virus genes evolve rapidly under the selective pressure of antibody.


Assembly and Rearrangement of Particles Confined at a Surface of a Droplet, and Intruder Motion in Electro-Shaken Particle Films.
Manipulation of particles at the surface of a droplet can lead to the formation of structures with heterogeneous surfaces, including patchy colloidal capsules or patchy particles. Here, we study the assembly and rearrangement of microparticles confined at the surface of oil droplets. These processes are driven by electric-field-induced hydrodynamic flows and by 'electro-shaking' the colloidal particles. We also investigate the motion of an intruder particle in the particle film and present the possibility of segregating the surface particles. The results are expected to be relevant for understanding the mechanism for particle segregation and, eventually, lead to the formation of new patchy structures.


Staphylococcus aureus-derived lipoteichoic acid induces temporary T-cell paralysis independent of Toll-like receptor 2.
The interplay between microbes and surface organs, such as the skin, shapes a complex immune system with several checks and balances. The first-line defense is mediated by innate immune pathways leading to inflammation. In the second phase specific T cells invade the infected organ, amplifying inflammation and defense. Consecutively, termination of inflammation is crucial to avoid chronic inflammation triggered by microbes, such as in patients with atopic dermatitis. We aimed to elucidate how the Staphylococcus aureus-derived cell-wall component lipoteichoic acid (LTA) governs the second phase of immune responses when high concentrations of LTA access T cells directly through disrupted skin. We analyzed the direct exposure of T cells to LTA in vitro. For in vivo analyses, we used fluorescein isothiocyanate contact hypersensitivity and ovalbumin-induced dermatitis as models for TH2-mediated cutaneous inflammation. We observed that LTA potently suppressed T-lymphocyte activation in a Toll-like receptor 2-independent manner. LTA-exposed T cells did not proliferate and did not produce cytokines. Importantly, these T cells remained completely viable and were responsive to consecutive activation signals on subsequent removal of LTA. Thus LTA exposure resulted in temporary functional T-cell paralysis. In vivo experiments revealed that T-cell cytokine production and cutaneous recall responses were significantly suppressed by LTA. We identified a new mechanism through which bacterial compounds directly but temporarily modulate adaptive immune responses.


Experts: time to prepare for next flu season.
While 98% of hospitals indicate they offer staff vaccinations, only 40% of health care workers receive them. Planning for each flu season should begin in February or March of the previous year. Cost and inconvenient scheduling are among the major barriers to staff vaccination.


Delayed Diagnosis of Dopa responsive Dystonia in Two Siblings.
Dopa responsive dystonia is characterized by progressive disabling dystonia, diurnal variation and a dramatic response to Levodopa. Two siblings presented with regression of motor milestones and hypertonia in lower limbs. History of diurnal variation was present in elder sibling. Both responded dramatically to Levodopa. The genomic DNA analysis of elder sibling revealed a novel mutation. A trial of Levodopa should be considered in a child with motor regression with diurnal variation, in the presence of extrapyramidal features.


Anther smuts of Caryophyllaceae: molecular analyses reveal further new species.
Recent collections of Microbotryum (Pucciniomycotina, Basidiomycota) specimens inhabiting anthers of different caryophyllaceous host plants were analysed using LM and electron microscopy, as well as molecular phylogenetic analyses using rDNA (ITS and LSU) sequences. The phylogenetic relationships of caryophyllaceous anther parasites are discussed. Three new species, Microbotryum adenopetalae, M. minuartiae, and M. silenes-acaulis, are described based on morphological, ecological, and molecular characteristics. New host plants are reported for Microbotryum dianthorum (Dianthus jacquemontii and Petrorhagia saxifraga) and M. lychnidis-dioicae (Cucubalus baccifer and Silene zawadskii). For Microbotryum violaceum, a neotype is selected.


Relevance of sample preparation for flow cytometry.
Flow cytometry is a useful tool for diagnosis and minimal residual disease (MRD) study of hematological diseases. Standard sample preparation protocols are characterized by stain-lyse-wash (SLW). To prevent nonspecific bindings and achieve high sensitivity in MRD studies, lyse-wash-stain-wash (LWSW) is required. To our knowledge, no comparison between the two methods has been performed. We compared mean fluorescence intensity (MFI), stain index, signal-to-noise ratio, and percentage of positive cells of 104 antibodies and of 13 selected antibodies tested in 10 samples simultaneously prepared with the two methods. MFI and percentages of positive cells obtained by the two methods did not show significant differences and showed a very high correlation. Stain index and signal-to-noise ratio presented higher values for kappa and lambda surface chains in LWSW samples and a trend of higher values for the other antibodies in SLW samples. We suggest to use LWSW method also at diagnosis to obtain more comparable antibody intensity expressions when samples from the same patient are processed for MRD evaluation after bulk lysis. Moreover, LWSW can prevent nonspecific bindings, shows no differences in the identification and quantitation of the populations of interest, and reduces acquisition of cell debris.


Impact of warmer constant and fluctuating temperatures in the male Jamaican field cricket, Gryllus assimilis (Fabricius, 1775) (Orthoptera: Gryllidae).
Ectotherms, such as insects, are susceptible to climate changes because their body temperature is not physiologically regulated. Forecasts indicate a worldwide temperature rise of 1.4-6 °C by 2100, and an increase in heatwave frequency is expected. This study investigated the effects of constant temperatures (CT; 27, 34, 39, 40 and 41 °C) and fluctuating temperature (FT; 27/34 °C: 12/12 h) on the survival, metabolic rate, locomotor activity, gas exchange pattern, heat loss and water content of the male Jamaican field cricket, Gryllus assimilis (Fabricius, 1775) (Orthoptera: Gryllidae). It was found that 39 °C was the estimated lethal temperature for 50% of the population and that 41 °C was considered the thermal limit, causing 100% mortality in 96 h. Furthermore, FT caused slightly higher mortality (8.9 ± 3.8%) than CT27 (0%) and CT34 (1.43 ± 1.43%). FT caused a greater increase in the metabolic rate and locomotor activity than CT27. It was found that G. assimilis males had a continuous gas exchange as a standard at CT27; however, CT34 changed the gas exchange pattern from continuous to cyclic in 27% of crickets. FT decreased heat loss in crickets more than CT34; however, no significant differences were found in locomotor activity and metabolic rate. In addition, no significant differences between CT27, CT34 and FT were observed in terms of water content, thus suggesting no difference in water loss. Thus, it is suggested that FT, despite involving a modest warming, increased the climate sensitivity of G. assimilis males and led to a change in their optimum temperature, pushing it beyond its usual thermal limits. However, higher mortality in FT compared to CT27 (control) and CT34 must be interpreted with caution. In addition, the risk of higher mortality of G. assimilis males is predicted, especially in South America, where this cricket is widely distributed.


Elasticity estimates from images of crawling waves generated by miniature surface sources.
We describe a surface-based approach to the generation of shear wave interference patterns, called crawling waves (CrW), within a medium and derive local estimates of biomechanical properties of tissue. In previous experiments, elongated bars operating as vibration sources were used to generate CrW propagation in samples. In the present study, however, a pair of miniature circular vibration sources was applied to the overlying skin to generate the CrW within the medium. The shape and position of the miniature sources make this configuration more applicable for in vivo implementation. A modified ultrasound imaging system is used to display the CrW propagation. A shear speed mapping algorithm is developed using a detailed analysis of the CrW. The proposed setup is applied to several biomaterials including a homogeneous phantom, an inhomogeneous phantom and an ex vivo human liver. The data are analyzed using the mapping algorithm to reveal the biomechanical properties of the biomaterials.


Effects of endotoxin on proliferation of human hematopoietic cell precursors.
In examining the effects of corticosteroids on hematopoiesis in vitro, we observed that results were highly dependent on the lot of commercial fetal calf serum (FCS) utilized. We hypothesized that this variability correlated with the picogram (pg) level of endotoxin contaminating the FCS. Randomly obtained commercial lots of FCS contained 0.39 to 187 pg/ml of lipopolysaccharide (LPS). Standard FCS concentrations in hematopoietic precursor proliferation assays (granulocyte-marcrophage colony forming units [CFU-GM]) resulted in final LPS levels as high as 40 pg/ml. LPS (2-5 pg/ml) added to essentially endotoxin-free cultures, induced human mononuclear cell release of interleukin (IL)-1, IL-6 and granulocyte colony stimulating factor (G-CSF). Lots of FCS induced the release of IL-1, IL-6, and G-CSF from human mononuclear cells and the release of these factors correlated with the level of contaminating LPS. Human bone marrow CFU-GM proliferation, in response to granulocyte-macrophage colony stimulating factor (GM-CSF), positively correlated with the level of LPS contaminating the FCS and the FCS-induced release of IL-6 from mononuclear cells. CFU-GM proliferation of human bone marrow cluster of differentiation (CD) 34+CD14-cells were not affected by the presence of endotoxin. These data suggest that LPS at 2-5 pg/ml may induce bone marrow accessory cell release of hematopoietic growth factors, thus altering proliferative response of hematopoietic precursors and confounding the study of exogenously added cytokines to culture systems.


[Radiotelemetric study of heart rate and electroencephalogram during parachute jumping (author's transl)].
Twelve subjects, experienced parachutists, have been recorded by telemetry before, during and after free-fall parachute jumps. The heart rate showed a statistically significant tachycardia during the different events of the jump (exit, free-fall, opening, open parachute and landing) compared to the baseline before boarding the aircraft. This tachycardia indicates a stress reaction confirmed by a significant increase of adrenalin and noradrenalin in urine. The electroencephalographic invesitgation does not show any adnormalities. Alpha rhythms have been recorded from alpha reactive subjects during free-fall stabilization.


An active domain SA-2 derived from cystatin-SA, and its antifungal activity.
Infections induced by fungi, especially the drug-resistant fungi, are difficult clinical problems. Conventional antifungal treatment is effective but due to resistance, treatment failure, and treatment-related toxicity, there is a need for new antifungal drugs. In this study, SA-2 (YYRRLLRVLRRRW) was derived from Cystatin-SA, a saliva protein with a molecular weight of 14 kDa. Meanwhile, the structure-activity of SA-2 and its mutants was also studied. We detected the antimicrobial activity and cytotoxicity of SA-2 and found that SA-2 had a low cytotoxicity toward mammalian cells but a good inhibitory effect on Candida albicans (C. albicans) and Cryptococcus neoformans (C. neoformans), with MIC values of 16-64 μg/mL and 8-32 μg/mL, respectively. Interestingly, SA-2 effectively killed fluconazole-resistant C. neoformans and C. albicans within 12 h. This antifungal activity against fluconazole-resistant fungi was comparable to that of amphotericin B. In addition, the C. neoformans-infected mice model was established to evaluate the anti-infective activity of SA-2 in vivo. Results showed that SA-2 significantly reduced the counts of fungi in lung and brain tissues to protect fluconazole-resistant C. neoformans-infected mice from death without changing mice body weights. Moreover, the dramatically increased pro-inflammatory cytokines TNF-α, IL-6 and IL-1β induced by intranasal infection of C. neoformans could be obviously declined due to the treatment of SA-2, which may be attributed to the elimination of C. neoformans in time in the infected tissue. For the mode of actions underlying SA-2 against C. neoformans, we found that the cationic peptide SA-2 could adhere to the negatively charged fungal cell membrane to increase the surface potential of C. neoformans in a dose-dependent manner, and finally disrupted the integrity of fungal cell membrane, reflecting as a 60% positive rate of propidium iodide uptake of C. neoformans cells after SA-2 (4 × MIC) treatment. Our study indicated that SA-2 has the potential to develop as a new therapeutic agent against infection induced by drug-resistant fungi.


Isolation of mannose-binding C-type lectin from sea lamprey (Petromyzon marinus) plasma and binding to Aeromonas salmonicida.
The sea lamprey (Petromyzon marinus) is a parasitic cartilaginous fish of the North American Great Lakes and a predator of many bony fish species of commercial importance to the fishing industry. Mannose-binding C-type lectin (MBL) was isolated by mannan-agarose affinity chromatography from sea lamprey plasma. Mannose-binding lectin has not before been identified and quantitated in the plasma of this sea lamprey species. The affinity-purified and 2-ME reduced lamprey MBL showed two bands of 35kDa and 65kDa by SDS-PAGE and Western blotting using guinea pig anti-MBL IgG as the primary antibody. Amino acid composition analysis (mol%) of the purified lamprey MBL found high amounts of histidine, threonine, tyrosine and phenylalanine present when compared with three other vertebrate MBLs. N-terminal amino acid sequencing by Edman degradation for the first 10 residues gave XXXTKGCPDA. Lamprey plasma contained 261mug of MBL/ml of plasma. Plasma protein concentration was 40.1mg/ml. Lamprey MBL was present then in plasma at 6.5mug MBL/mg total protein. The sea lamprey MBL also specifically binds to mannose on the surface of the pathogen Aeromonas salmonicida. The presence of MBL in high concentration in lamprey plasma could be important in their innate immunity and resistance to infection. This study describes the presence of MBL in sea lamprey plasma and evidence for a C-type lectin complement pathway of innate immunity.


On the molecular conformation of human haemopexin. II. Analysis of circular dichroic spectra.
The circular dichroic (CD) spectra of haemopexin in the far ultraviolet region exhibit an atypical positive maximum at 231 nm, which prevents determination of the secondary structure by the usual methods. We have developed a modified analytical method by which it was possible to calculate the secondary structure of the protein (8% of alpha-helix, 10% of beta-conformation) and the actual wavelength (229 nm) and intensity of the above-mentioned positive band. Measurements and analysis of the CD spectra of haemopexin in an alkaline medium gave information ascribing a major part of intensity of the band at 229 nm to the B1u transition of Tyr; we believe that some other electronic transitions contribute to this band, too. An assignation of the individual extremes of the CD spectrum in the near ultraviolet region to the individual electronic transitions is propounded. The dichroic bands of Trp in this region and the temperature dependence of the CD spectra in the far ultraviolet region corroborate our idea that the haemopexin molecule contains a very compact hydrophobic peptide core. Similarities of the CD spectra of haemopexin to those of the haem. haemopexin complex throughout the ultraviolet region suggest a conformational likeness of these two molecules.


Thermal biology of the common garter snake Thamnophis sirtalis (L.) : II. The effects of melanism.
The thermoregulatory significance of a striped-melanic colour polymorphism in the common garter snake, Thamnophis sirtalis, was assessed through a combination of labortory experimentation and field study. In experiments with living snakes the melanic morph maintained a higher body temperature than the striped morph, when exposed to natural insolation. Experiments with excised skin showed that this thermal advantage is attributable to some integumental difference between the two morphs. Body temperatures of snakes in the field revealed that, during the colder part of the active season, melanics were able to stay warmer than striped snakes by an amount (1.24 C°) approximating the difference observed in the laboratory. Some evidence and argument is presented to suggest that melanism also may confer protection against overheating in warm periods.


A series of pyrido[2,3-b]pyrazin-3(4H)-one derivatives as aldose reductase inhibitors with antioxidant activity.
A series of pyrido[2,3-b]pyrazin-3(4H)-one based derivatives were designed as inhibitors of aldose reductase (ALR2), the enzyme which plays a key role in the development of diabetes complications as well as in the oxidative stress processes associated with diabetes and other pathologies. Most of the derivatives, having a substituted C2 aromatic group and a N4 acetic acid group on the core structure, were found to be potent and selective aldose reductase inhibitors with submicromolar IC50 values, and 9c was the most active with IC50 value 0.009 μM. Particularly, a number of the designed compounds bearing phenolic hydroxyl substituted C2-styryl side chain showed excellent not only in ALR2 inhibition but also in antioxidant, and among these 11i was proved to be the top one with an antioxidant ability even comparable to that of the well-known antioxidant Trolox. Structure-activity relationship and molecular docking studies highlighted the importance of phenolic hydroxyl substituents and vinyl spacer in C2 side chain of the scaffold for the construction of efficient and multifunctional ALR2 inhibitors.


A case of extrafoveal focal choroidal excavation.
To describe an extrafoveal presentation of focal choroidal excavation and corresponding imaging findings. Retrospective case report. Single patient with diagnosis of extrafoveal focal choroidal excavation. A 28-year-old man was referred for evaluation of a suspicious lesion in his right posterior fundus. Functional examination demonstrated best-corrected visual acuity of 20/40 in the right eye and 20/20 in the left eye. Ophthalmoscopy exam and fundus photography revealed a yellowish lesion superior to the fovea of the right eye. The lesion was hyperfluorescent on fundus autofluorescence imaging and late phase fluorescein angiography demonstrated staining of the lesion without leakage. Optical coherence tomography (OCT) of the lesion was consistent with focal choroidal excavation. Five months after presentation, the patient's vision, exam, and imaging remained stable. Focal choroidal excavation is a recently recognized clinical entity that is often incidentally found, and presents asymptomatic or with mildly decreased visual acuity in the affected eye. It has characteristic findings on optical coherence tomography (OCT) that can be used to distinguish it from other retinal lesions that may appear similar on ophthalmoscopy. We present the case of an uncommon extrafoveal presentation of FCE at a relatively young age, which may represent either a congenital abnormality or the sequelae of an unidentified chronic process. While most FCE remain stable, patients are often followed for lesion progression and the possibility of choroidal vascular pathology which might necessitate intervention.


Impact of myopenia and myosteatosis on postoperative outcome and recurrence in Crohn's disease.
Myopenia and myosteatosis have been proposed to be prognostic factors of surgical outcomes for various diseases, but their exact role in Crohn's disease (CD) is unknown. The aim of this study is to evaluate their impact on anastomotic leakage, CD recurrence, and postoperative complications after ileocecal resection in patients with CD. A retrospective analysis of CD patients undergoing ileocecal resection at our tertiary referral center was performed. To assess myopenia, skeletal muscle index (skeletal muscle area normalized for body height) was measured using an established image analysis method at third lumbar vertebra level on MRI cross-sectional images. Muscle signal intensity was measured to assess myosteatosis index. A total of 347 patients were retrospectively analyzed. An adequate abdominal MRI scan within 12 months prior to surgery was available for 223 patients with median follow-up time of 48.8 months (IQR: 20.0-82.9). Anastomotic leakage rate was not associated with myopenia (SMI: p = 0.363) or myosteatosis index (p = 0.821). Patients with Crohn's recurrence had a significantly lower SMI (p = 0.047) in univariable analysis, but SMI was not an independent factor for recurrent anastomotic stenosis in multivariable analysis (OR 0.951, 95% CI 0.840-1.078; p = 0.434). Postoperative complications were not associated with myopenia or myosteatosis. Based on the largest cohort of its kind with a long follow-up time, we could provide some data that MRI parameters for myopenia and myosteatosis may not be reliable predictors of postoperative outcome or recurrence in patients with Crohn's disease undergoing ileocecal resection.


Contralateral and ipsilateral control of fingers following callosotomy.
The extent of ipsilateral control of the distal limbs is not documented. In this experiment visuo-motor control of fingers was investigated in two callosotomy patients. A substantial amount of ipsilateral control was evident, especially for the left hand fingers. Ipsilateral control of the right hand was evident for the thumb and index fingers, but not for the other fingers. Left hand fingers did not vary significantly in degree of ipsilateral control.


Water relations and growth of shrubs before and after fire in a semi-arid woodland.
Plant water relations and shoot growth rate of shrubs resprouting after fire or unburnt were measured in a semi-arid poplar box (Eucalyptus populnea) shrub woodland of eastern Australia. In vegetation unburnt for about 60 years, the dawn xylem water potential (ψx) of the dominant shrub species was about-1.0 MPa when the soil was wet and-8.0 MPa when the soil was very dry. At any one time, the dominant shrub species,Eremophila mitchellii, E. sturtii, Geijera parviflora andCassia nemophila, were similar in ψx butAcacia aneura andDodonaea viscosa were consistently higher in ψx than this group when the soil was moist and lower when the soil was dry. The dominant tree species,Eucalyptus populnea andE. intertexta, appeared to have access to additional water beneath the hardpan which is located 60-80 cm below the surface. When shrubs were under extreme water stress (ψx of-8 MPa), the trees had a ψx of-3 to-3.6 MPa. Following a fire, both ψx and leaf stomatal conductance (g s) of resprouting shrubs were higher for about 5 years than comparable-aged unburnt vegetation, with relative differences in ψx increasing with drought stress. Elongation rate of resprouts was positively linked to prefire shrub height in 3 of 4 species. However, shrubs resprouting after high intensity fires had substantially higher rates of shoot elongation than after low intensity fires which were in turn higher than for foliar expansion of unburnt shrubs. It is concluded that the growth rate of resprouting shrubs is primarily determined by physiological/ morphological factors associated with plant size but is also assisted by greater availability of water and possibly nutrients for a period after fire.


Myocardial dysfunction in the periinfarct and remote regions following anterior infarction in rats quantified by 2D radial strain echocardiography: an observational cohort study.
Heart failure from adverse ventricular remodeling follows myocardial infarction, but the contribution of periinfarct and remote myocardium to the development of cardiomyopathy remains poorly defined. 2D strain echocardiography (2DSE) is a novel and sensitive tool to measure regional myocardial mechanics. The aim is to quantify radial strain in infarcted (I), periinfarct (PI) and remote (R) myocardial regions acutely and chronically following anterior infarction in rats. The left anterior coronary artery of male Sprague-Dawley rats (270-370 g) were occluded for 20-30 minutes and 2DSE was performed in the acute setting (n = 10; baseline and 60 minutes post-reperfusion) and in the chronic setting (n = 14; baseline, 1, 3 and 6 weeks). Using software, radial strain was measured in the mid-ventricle in short axis view. The ventricle was divided into 3 regions: I (anteroseptum, anterior and anterolateral), PI - (inferoseptum and inferolateral) and R - (inferior). Infarct size was measured using triphenyl tetrazolium chloride in the acute group. Following infarct, adverse remodeling occurred with progressive increase in left ventricular size, mass and reduced fractional shortening within 6 weeks. Radial strain decreased not only in the infarct but also in the periinfarct and remote regions acutely and chronically (I, PI, R, change vs. baseline, 60 minutes -32.7 +/- 8.7, -17.4 +/- 9.4, -13.5 +/- 11.6%; 6 weeks -24.4 +/- 8.2, -17.7 +/- 8.3, -15.2 +/- 8.4% respectively, all p < 0.05). Reduced radial strain in periinfarct and remote regions occurred despite minimal or absent necrosis (area of necrosis I, PI, R: 48.8 +/- 23, 5.1 +/- 6.6, 0 +/- 0%, p < 0.001 vs. I). Following left anterior coronary occlusion, radial strain decreased at 60 minutes and up to 6 weeks in the periinfarct and remote regions, similar to the reduction in the infarct region. This demonstrates early and chronic myopathic process in periinfarct and remote regions following myocardial infarction that may be an under recognized but important contributor to adverse left ventricular remodeling and progression to ischemic cardiomyopathy.


First detection of human infection by Cache Valley and Kairi viruses (Orthobunyavirus) in Argentina.
Human sera samples from Córdoba Province, Argentina were analyzed by reduction neutralization test for Cache Valley (CVV) and Kairi (KRIV) viruses. A 5.72% (27/472) prevalence of neutralizing antibodies for CVV and 5.92% (31/524) for KRIV was detected in Córdoba City, whereas the prevalences in Jesús María and Colonia Caroya suburban cities was 7.83% (13/166) and 5.42% (9/166) for CVV and KRIV, respectively. The neutralizing antibody titers ranged between 1/20 and >or=1/160. Our results report the first known infection by CVV and KRIV in human inhabitants from temperate areas of Argentina.


Effects of cadmium on integration and resource allocation in the clonal fern Salvinia molesta.
In clonal plants exposed to pollution, ramets which are physiologically integrated may be less fit than ramets which are independent, if (a) translocation of toxins from contaminated ramets produced toxicity, or (b) toxicity in parent ramets reduced the degree of nutritional support to otherwise non-exposed daughters. These hypotheses were tested in the aquatic fern Salvinia molesta exposed to cadmium. Pre-treatment of parent ramets with cadmium decreased the number and biomass of daughters subsequently produced in a cadmiumfree medium, because of reduced parental support of the first daughter generation. Second generation and later daughters were unaffected. Pre-treatment did not affect the pattern of integration (which, in terms of apical daughters' biomass, was bimodal with increasing colony size), or concentrations of essential elements in new growth. However, a diversion of resources from lateral to apical daughters occurred as a result of pre-treatment, especially in colonies with ≤3 attached parents. Loss/gain analysis showed that the diversion was almost reciprocal in terms of biomass, ramet numbers and phosphorus content. Integration between contaminated and uncontaminated ramets was not disadvantageous to the clone as a whole. However, integration was disadvantageous for Ca, Mg and Zn concentrations in daughters, which declined 15-22%. Because of enhanced apical growth, an indirect benefit of integration may be a more rapid fragmentation and dispersal of daughters from the site of contamination than if the parents were independent.


Euclidean and fractal geometry of microvascular networks in normal and neoplastic pituitary tissue.
In geometrical terms, tumour vascularity is an exemplary anatomical system that irregularly fills a three-dimensional Euclidean space. This physical characteristic and the highly variable shapes of the vessels lead to considerable spatial and temporal heterogeneity in the delivery of oxygen, nutrients and drugs, and the removal of metabolites. Although these biological characteristics are well known, quantitative analyses of newly formed vessels in two-dimensional histological sections still fail to view their architecture as a non-Euclidean geometrical entity, thus leading to errors in visual interpretation and discordant results from different laboratories concerning the same tumour. We here review the literature concerning microvessel density estimates (a Euclidean-based approach quantifying vascularity in normal and neoplastic pituitary tissues) and compare the results. We also discuss the limitations of Euclidean quantitative analyses of vascularity and the helpfulness of a fractal geometry-based approach as a better means of quantifying normal and neoplastic pituitary microvasculature.


A diverse family of thermostable cytochrome P450s created by recombination of stabilizing fragments.
Thermostable enzymes combine catalytic specificity with the toughness required to withstand industrial reaction conditions. Stabilized enzymes also provide robust starting points for evolutionary improvement of other protein properties. We recently created a library of at least 2,300 new active chimeras of the biotechnologically important cytochrome P450 enzymes. Here we show that a chimera's thermostability can be predicted from the additive contributions of its sequence fragments. Based on these predictions, we constructed a family of 44 novel thermostable P450s with half-lives of inactivation at 57 degrees C up to 108 times that of the most stable parent. Although they differ by as many as 99 amino acids from any known P450, the stable sequences are catalytically active. Among the novel functions they exhibit is the ability to produce drug metabolites. This chimeric P450 family provides a unique ensemble for biotechnological applications and for studying sequence-stability-function relationships.


Intriguing and Beautiful: Adamacrocera adami gen. et sp. nov. from the Upper Cretaceous Amber of Myanmar Represents a New Subfamily of Keroplatidae (Diptera: Bibionomorpha).
A new fossil genus and species of Keroplatidae (Diptera, Bibionomorpha, Sciaroidea), Adamacrocera adami gen. et sp. nov., from the Upper Cretaceous Burmese amber is described and illustrated. Based on morphological evidence, it is placed in a new subfamily Adamacrocerinae subfam. nov. The new genus, as well as the subfamily, possesses the wing venation characteristic of the genera of some Sciaroidea incertae sedis, as well as that of the fossil families Archizelmiridae, Antefungivoridae and Mesosciophilidae, in combination with macrocerine-like habitus and male terminalia.


Shortening velocity is different in longitudinal and circular muscle layers of the rabbit urethra.
The aim of the study was to investigate whether the functional difference between circular and longitudinal muscles in the female rabbit urethra is reflected in their shortening properties and lactate dehydrogenase (LDH) activity. For mechanical experiments the preparations were chemically skinned to avoid influence of membrane-related mechanisms and to enable maximal activation. Force velocity relations and the maximal shortening velocity (v(max)) were determined using the isotonic quick-release method. The v(max) was three times higher in longitudinal muscle. LDH isoform pattern was determined on agarose gels. The M-subunit, favourable for lactate formation, constituted 70% of the total in both types of muscle. There was no difference in the LDH isoform pattern despite the marked difference in v(max). We conclude that the difference in v(max) reflects differences in the contractile machinery itself. These mechanical characteristics are advantageous for the role of the circular as a tonic muscle contracting during bladder filling, and the longitudinal as a phasic muscle active in opening up the urethra during micturition.


Potential effects of reward and loss avoidance in overweight adolescents.
Reward system and inhibitory control are brain functions that exert an influence on eating behavior regulation. We studied the differences in inhibitory control and sensitivity to reward and loss avoidance between overweight/obese and normal-weight adolescents. We assessed 51 overweight/obese and 52 normal-weight 15-y-old Chilean adolescents. The groups were similar regarding sex and intelligence quotient. Using Antisaccade and Incentive tasks, we evaluated inhibitory control and the effect of incentive trials (neutral, loss avoidance, and reward) on generating correct and incorrect responses (latency and error rate). Compared to normal-weight group participants, overweight/obese adolescents showed shorter latency for incorrect antisaccade responses (186.0 (95% CI: 176.8-195.2) vs. 201.3 ms (95% CI: 191.2-211.5), P < 0.05) and better performance reflected by lower error rate in incentive trials (43.6 (95% CI: 37.8-49.4) vs. 53.4% (95% CI: 46.8-60.0), P < 0.05). Overweight/obese adolescents were more accurate on loss avoidance (40.9 (95% CI: 33.5-47.7) vs. 49.8% (95% CI: 43.0-55.1), P < 0.05) and reward (41.0 (95% CI: 34.5-47.5) vs. 49.8% (95% CI: 43.0-55.1), P < 0.05) compared to neutral trials. Overweight/obese adolescents showed shorter latency for incorrect responses and greater accuracy in reward and loss avoidance trials. These findings could suggest that an imbalance of inhibition and reward systems influence their eating behavior.


The impact of custom semirigid foot orthotics on pain and disability for individuals with plantar fasciitis.
Single-group, pre-, and postintervention repeated measures design. To determine the impact of custom semirigid foot orthotics on pain and disability for individuals with plantar fasciitis. Few studies have examined the efficacy of foot orthotics for plantar fasciitis, and no single study has yet examined the effects of semirigid foot orthotics on an established quality-of-life instrument. Eight men and 7 women (mean ages 44.7 +/- 9.0 years) who reported having plantar fasciitis symptoms for an average of 21.3 +/- 23.7 months participated in the study. Subjects were timed for a 100-m walk at a self-selected speed, then they rated the pain they experienced during the walk using a 10-cm visual analog scale. Subjects also completed the pain and disability subsections of the Foot Function Index questionnaire. All measures were acquired before the fabrication of custom semirigid foot orthotics and 12 to 17 days following onset of foot orthotic use. Postorthotic 100-m walk times were not significantly different (t = 0.39, P = 0.70) than preorthotic values. Postorthotic pain ratings (mean = 0.7 +/- 0.7) for the 100-m walk were significantly less than (Wilcoxon t = 1, P < 0.005) preorthotic pain ratings (mean = 3.0 +/- 1.7). Postorthotic Foot Function Index pain subsection ratings (Wilcoxon t = 0, P < 0.005) were significantly less than preorthotic ratings, demonstrating a 66% reduction in pain ratings. Postorthotic Foot Function Index disability subsection ratings (Wilcoxon t = 0, P < 0.005) were significantly less than preorthotic ratings, demonstrating a 75% reduction in disability ratings. Custom semirigid foot orthotics may significantly reduce pain experienced during walking and may reduce more global measures of pain and disability for patients with chronic plantar fasciitis.


Isolation and characterisation of disodium (4-amino-4-deoxy-beta-L- arabinopyranosyl)-(1-->8)-(D-glycero-alpha-D-talo-oct-2-ulopyranosylona te)- (2-->4)-(methyl 3-deoxy-D-manno-oct-2-ulopyranosid)onate from the lipopolysaccharide of Burkholderia cepacia.
A trisaccharide was isolated from the core oligosaccharide in the lipopolysaccharide (LPS) of Burkholderia cepacia GIFU 645 (ATCC 25416, type strain) by methanolysis followed by HPLC and saponification. It was identified by MS, methylation analysis and 1H and 13C NMR spectroscopy as disodium (4-amino-4-deoxy-beta-L-arabinopyranosyl)-(1-->8)-(D-glycero- alpha-D-talo-oct-2-ulopyranosylonate)-(2-->4)-(methyl 3-deoxy-D-manno-oct-2-ulopyranosid)onate. In addition to the trisaccharide derivative, methanolysis gave dimethyl (D-glycero-alpha-D- talo-oct-2-ulopyranosylonate)-(2-->4)-(methyl 3-deoxy-D-manno-oct-2- ulopyranosid)onate in a relative proportion to the trisaccharide of 3:1, indicating a non-stoichiometric (approximately 25%) substitution of the octulosonic acid by 4-amino-4-deoxyarabinose in the LPS.


Modulation of the rat hippocampal-cortex network and episodic-like memory performance following entorhinal cortex stimulation.
Entorhinal cortex (EC) deep brain stimulation (DBS) has shown a memory enhancement effect. However, its brain network modulation mechanisms remain unclear. The present study aimed to investigate the functional connectivity in the rat hippocampal-cortex network and episodic-like memory performance following EC-DBS. 7.0 T functional MRI (fMRI) scans and episodic-like memory tests were performed 3 days and 28 days after EC-DBS in healthy rats. The fMRI data processing was focused on the power spectra, functional connectivity, and causality relationships in the hippocampal-cortex network. In addition, the exploration ratio for each object and the discrimination ratio of the "when" and "where" factors were calculated in the behavioral tests. EC-DBS increased the power spectra and the functional connectivity in the prefrontal- and hippocampal-related networks 3 days after stimulation and recovered 4 weeks later. Both networks exhibited a strengthened connection with the EC after EC-DBS. Further seed-based functional connectivity comparisons showed increased connectivity among the prefrontal cortex, hippocampus and EC, especially on the ipsilateral side of DBS. The dentate gyrus is a hub region closely related to both the EC and the prefrontal cortex and receives information flow from both. Moreover, acute EC-DBS also enhanced the discrimination ratio of the "where" factor in the episodic-like memory test on Day 3. EC-DBS caused a reversible modulation effect on functional connectivity in the hippocampal-cortex network and episodic-like memory performance.


Cutting edge: DGYW/WRCH is a better predictor of mutability at G:C bases in Ig hypermutation than the widely accepted RGYW/WRCY motif and probably reflects a two-step activation-induced cytidine deaminase-triggered process.
A feature of Ig hypermutation is the presence of hypermutable DNA sequences that are preferentially found in the V regions of Ig genes. Among these, RGYW/WRCY is the most pronounced motif (G:C is a mutable position; R=A/G, Y=C/T, and W=A/T). However, a molecular basis for the high mutability of RGYW was not known until recently. The discovery that activation-induced cytidine deaminase targets the DNA encoding V regions, has enabled the analysis of its targeting properties when expressed outside of the context of hypermutation. We analyzed these data and found evidence that activation-induced cytidine deaminase is the major source of the RGYW mutable motif, but with a new twist: DGYW/WRCH (G:C is the mutable position; D=A/G/T, H=T/C/A) is a better descriptor of the Ig mutation hotspot than RGYW/WRCY. We also found evidence that a DNA repair enzyme may play a role in modifying the sequence of hypermutation hotspots.


Influences of electrical lesions of the dopaminergic system on morphine- and U-50,488H-induced analgesia in rats.
The effects of electrical lesions of brain areas containing dopamine cell bodies and terminals on morphine analgesia were investigated and compared with those of a selective kappa-opioid agonist, U-50,488H. The analgesic effect of morphine 10 mg/kg IP was potentiated significantly in substantia nigra (SN)- or caudate-putamen-lesioned rats, but not by ventral tegmental area (VTA) or nucleus accumbens lesions. However, electrical lesions of neither SN nor VTA affected the analgesic activity of U-50,488H 32 mg/kg IP. Although the tolerance to morphine analgesia developed in all four of the lesioned groups as well as in sham-lesioned rats, a significant analgesic effect in the SN-lesioned group prevailed during chronic treatment for 14 days as compared with that of sham-lesioned rats. From these results, it is suggested that morphine analgesia is potentiated by dysfunction of the nigro-striatal dopaminergic system, but not by that of the mesolimbic dopaminergic system, the central dopaminergic system is not involved in the appearance of U-50,488H analgesia and is not basically related to the development of tolerance to morphine analgesia.


Red Light-Triggered CO Release from Mn2(CO)10 Using Triplet Sensitization in Polymer Nonwoven Fabrics.
Applicability of phototherapeutic CO-releasing molecules (photoCORMs) is limited because they are activated by harmful and poorly tissue-penetrating near-ultraviolet light. Here, a strategy is demonstrated to activate classical photoCORM Mn2(CO)10 using red light (635 nm). By mixing in solution a triplet photosensitizer (PS) with the photoCORM and shining red light, energy transfer occurs from triplet excited-state 3PS* to a photolabile triplet state of Mn2(CO)10, which, like under near-UV irradiation, led to complete release of carbonyls. Crucially, such "triplet-sensitized CO-release" occurred in solid-state materials: when PS and Mn2(CO)10 were embedded in electrospun nonwoven fabrics, CO was liberated upon irradiation with low-intensity red light (≤36 mW 635 nm).


A semiautomatic image analyzer for cell counts in monolayers. I. Construction, experimental procedure, and precision obtained.
A simple, flexible, low-cost image analyzer system is presented for determination of the total number of cells and the number of viable cells in monolayers of nonconfluent cells. Viable cells were identified and counted using an immunofluorescence method using fluorescein diacetate. Alveolar macrophages from rabbits were used. The different possible counting procedures that could be performed are analyzed. The precision of the method of estimating the cell numbers is indicated by a coefficient of variation of 5%. The experimental procedure is given for a short-term toxicological in vitro test in which the semiautomatic counting procedures can be performed within 1.5 h.


Automatic motor cortex activation for natural as compared to awkward grips of a manipulable object.
It has been suggested that, relative to natural objects, man-made object representations in the brain are more specifically defined by functional properties that reflect how an object is used and/or what it is used for (Warrington and Shallice 1984). We recorded 123-channel event-related potentials (ERP) in healthy participants during a mental rotation task involving a manipulable (hammer) and a non-manipulable (church) object. Both stimuli had standard and mirror-image versions rotated in four different orientations, resulting for the manipulable object in some natural and some awkward grips. Using spatial cluster analysis, time periods were determined during which the ERP maps differed between stimulus conditions. Specific maps appeared for natural versus awkward grips with the manipulable object at a very early stage (60-116 ms) as well as during a later stage (180-280 ms). Source estimations derived from the topographic data indicated that during the second time window the left motor cortex was significantly activated in the case of natural grips. We argue that the motor programs that are semantically associated with the object are automatically activated when it is presented in graspable orientations.


Occurrence of anti-Neospora caninum antibodies in water buffaloes (Bubalus bubalis) from the Northern region of Brazil.
Anti-Neospora caninum antibodies were determined in sera of 196 water buffaloes (Bubalus bubalis) from three farms of the northern region of Brazil, using an indirect fluorescent antibody test. Antibody titers were found in 139 (70.9%) buffaloes with dilution values ranging from > or =25 to <200 in 41 animals, > or =200 to <800 in 35 animals, and > or =800 in 63 animals. The number of animals presenting titers > or =800 was statistically higher (p<0.05). All farms presented positive animals, however, the occurrence was higher (p<0.05) in farm 1 (87.2%) when compared with farm 2 (65.7%) and farm 3 (65.8%). The occurrence by age groups presented no differences (p>0.05). Results indicate a high exposure of water buffaloes to N. caninum in the Northern region of Brazil.


Are predefined decoy sets of ligand poses able to quantify scoring function accuracy?
Due to the large number of different docking programs and scoring functions available, researchers are faced with the problem of selecting the most suitable one when starting a structure-based drug discovery project. To guide the decision process, several studies comparing different docking and scoring approaches have been published. In the context of comparing scoring function performance, it is common practice to use a predefined, computer-generated set of ligand poses (decoys) and to reevaluate their score using the set of scoring functions to be compared. But are predefined decoy sets able to unambiguously evaluate and rank different scoring functions with respect to pose prediction performance? This question arose when the pose prediction performance of our piecewise linear potential derived scoring functions (Korb et al. in J Chem Inf Model 49:84-96, 2009) was assessed on a standard decoy set (Cheng et al. in J Chem Inf Model 49:1079-1093, 2009). While they showed excellent pose identification performance when they were used for rescoring of the predefined decoy conformations, a pronounced degradation in performance could be observed when they were directly applied in docking calculations using the same test set. This implies that on a discrete set of ligand poses only the rescoring performance can be evaluated. For comparing the pose prediction performance in a more rigorous manner, the search space of each scoring function has to be sampled extensively as done in the docking calculations performed here. We were able to identify relative strengths and weaknesses of three scoring functions (ChemPLP, GoldScore, and Astex Statistical Potential) by analyzing the performance for subsets of the complexes grouped by different properties of the active site. However, reasons for the overall poor performance of all three functions on this test set compared to other test sets of similar size could not be identified.


Toll-like receptor 2 as a major gene for asthma in children of European farmers.
The finding that the prevalence of asthma and allergies is less frequent in children raised on animal farms has led to the conjecture that exposure to microbial products modifies immune responses. The toll-like receptors (TLRs) represent an evolutionarily conserved family of innate immunity receptors with microbial molecules as ligands. We reasoned that polymorphisms in genes encoding TLRs might modulate the protective effects observed in farming populations. Farmers' and nonfarmers' children living in rural areas in Austria and Germany and who were enrolled in the cross-sectional ALEX study were genotyped for single nucleotide polymorphisms in the TLR2 and TLR4 genes. The frequencies of asthma, allergic rhinitis, and atopic sensitization were compared between the genotypes in relation to exposure to farming and endotoxin. Among farmers' children, those carrying a T allele in TLR2/-16934 compared with children with genotype AA were significantly less likely to have a diagnosis of asthma (3% vs 13%, P = .012), current asthma symptoms (3% vs 16%, P = .004), atopic sensitization (14% vs 27%, P = .023), and current hay fever symptoms (3% vs 14%, P = .01). The association between TLR2/-16934 and asthma among children of farmers was independent of atopy. No such association was found among children from the same rural communities but not living on farms. Our results suggest that genetic variation in TLR2 is a major determinant of the susceptibility to asthma and allergies in children of farmers.


Postmortem changes in endothelium-dependent and independent responses of porcine coronary arteries.
1. Studies were performed in porcine left circumflex coronary arteries to determine the time course of changes in their responses to smooth muscle and endothelial cell agonists following death. 2. The pigs were kept at room temperature for 3, 6, 12 and 24 hr after death before removing the arteries, and the responses compared with fresh arteries. Rings of the arteries were mounted in organ chambers filled with modified Krebs-Ringer solution for isometric tension recording. 3. Fresh rings with endothelium relaxed with stretching, whereas 3- and 6-hr rings developed an increase in tension and often rhythmic activity. In 3-hr rings, there were diminished contractile responses to KCl and serotonin. The contractile responses to prostaglandin F2 alpha were depressed at 3 and 6 hr. 4. At 6 hr, rings from six of 14 pigs failed to contract and the responses of the other eight to histamine and serotonin but not to KCl or acetylcholine, were depressed compared to fresh rings. 5. 6 hr after death endothelium-mediated relaxations to bradykinin and calcium ionophore A-23187 were depressed while endothelium-mediated as well as direct smooth muscle relaxation by adenosine diphosphate did not change. 6. These studies indicate that caution must be observed in interpreting the findings in autopsy specimens examined as early as 3 hr after death.


Comparison of two alternative methods for CD4+ T-cell determination (Coulter manual CD4 count and CyFlow) against standard dual platform flow cytometry in Uganda.
In this study we evaluated alternative CD4(+) T-cell counting methods in clients of a PMTCT Programme in rural Uganda. The Coulter Manual CD4 Count method for CD4(+) T-cell enumeration (Cyto-Spheres) and an automated method (volumetric, single-platform flow cytometry; CyFlow) were compared with a standard, dual-platform flow cytometry protocol (DPFC, FACScan). Correlation and precision of agreement were higher for the CyFlow method (r = 0.929 and eta = 0.08) when compared to DPFC than for the Cyto-Spheres method (r = 0.725 and eta = 0.3). Multiple linear regression analysis showed that CD4(+) cell counts by the CyFlow method were a stronger predictor for results of DPFC than those of the Cyto-Spheres method (r(2) = 0.864 and r(2) = 0.552, respectively). When compared to DPFC the CyFlow method generated higher CD4(+) cell counts than the Cyto-Spheres method, as expressed by a higher median and mean difference (+70 and +90 cells for CyFlow, +28 and -1.4 cells for Cyto-Spheres). Both, the manual Cyto-Spheres method and the CyFlow method can be used for the enumeration of CD4(+) cells in resource-limited settings. Under supervised conditions, the CyFlow method produced results more consistent with the reference method than the Cyto-Spheres method.


Magnetic resonance imaging of the wrist: bone and cartilage injury.
Magnetic resonance imaging (MRI) is particularly useful for imaging the wrist due to its superior soft tissue contrast and ability to detect subtle bone marrow changes and occult fractures. A high field (1.5T or greater) strength, dedicated wrist coil, and high in-plane and through-plane resolution must be utilized to successfully visualize the relatively thin cartilage of the wrist. MRI can be used to detect occult carpal bone fractures, identify complications following scaphoid fractures, and assess for avascular necrosis in the setting in Kienböck's and Preiser's disease. MRI is useful to identify secondary soft tissue and chondral pathology in impaction/impingement syndromes. The use of an intermediate-echo time fast spin echo sequence allows for accurate assessment of articular cartilage, allowing evaluation of chondral wear in the setting of primary osteoarthritis and posttraumatic degenerative arthrosis. MRI is the most sensitive imaging modality for the detection of early inflammatory arthropathies and can detect synovitis, bone marrow edema, and early erosions in the setting of negative radiographs.


Promotion of tumor invasion by cooperation of granulocytes and macrophages activated by anti-tumor antibodies.
We investigated the potential role of anti-tumor antibodies and tumor antigens in the formation of immune complexes which promote matrix degradation and angiogenesis. B-cell deficient or B-cell depleted mice showed a reduction in tumor invasion and metastasis. In vitro invasion assays and in vivo models of metastasis showed that anti-sTn antibodies and sTn tumor antigens form complexes which induce granulocytes and macrophages together to mediate tumor invasion and metastasis by processes including extracellular matrix degradation and angiogenesis. These results suggest the existence of a tumor promoting role of a B-cell immune response induced by shed tumor associated antigens of solid, nonlymphoid tumors.


Structural elucidation of full-length nidogen and the laminin-nidogen complex in solution.
Nidogen-1 is a key basement membrane protein that is required for many biological activities. It is one of the central elements in organizing basal laminae including those in the skin, muscle, and the nervous system. The self-assembling extracellular matrix that also incorporates fibulins, fibronectin and integrins is clamped together by networks formed between nidogen, perlecan, laminin and collagen IV. To date, the full-length version of nidogen-1 has not been studied in detail in terms of its solution conformation and shape because of its susceptibility to proteolysis. In the current study, we have expressed and purified full-length nidogen-1 and have investigated its solution behavior using size-exclusion chromatography (SEC), dynamic light scattering (DLS) and small angle X-ray scattering (SAXS). The ab initio shape reconstruction of the complex between nidogen-1 and the laminin γ-1 short arm confirms that the interaction is mediated solely by the C-terminal domains: the rest of the domains of both proteins do not participate in complex formation.


Metastasectomy and BRAF mutation; an analysis of survival outcome in metastatic colorectal cancer.
Resection of oligometastases improves survival in metastatic colorectal cancer (mCRC). It is unclear whether the benefit is consistent for BRAF V600E mutant (MT) and wild type (WT) mCRC. This retrospective analysis explores the influence of BRAF MT on survival after metastasectomy. Overall survival (OS) and recurrence-free survival (RFS) for BRAF MT and WT mCRC were evaluated. Survival was also analyzed in the cohort of BRAF MT with or without metastasectomy. Five hundred and thirteen patients who had undergone metastasectomy were identified, 6% were BRAF-MT. Median age 63. Median OS in BRAF MT vs WT: 25.7 vs 48.5 months (hazard ratio [HR] 1.95; 1.18-3.22). However, difference was not significant in a multivariate model. Right primary tumor, intact primary, >1 metastatic site, non-R0 resection, peritoneal metastasis, and synchronous metastasis were independent predictors of worse OS. Among 364 patients with RFS data there was no difference between BRAF MT and WT (16 vs 19 months, p=0.09). In another cohort of 158 BRAF-MT patients, OS was significantly better after metastasectomy compared to "no metastasectomy" (HR 0.34; 0.18-0.65, P= 0.001). Proficient mismatch repair status showed a trend toward worse survival after metastasectomy in BRAF MT (HR 1.71, P = 0.08). OS did not differ after metastasectomy between BRAF MT and WT in a multivariate model. Median OS was >2 years in this study after metastasectomy among BRAFV600E MT patients suggesting a survival benefit of metastasectomy in this group where systemic therapeutic options are limited. Metastasectomy may be considered in carefully selected BRAF-MT patients.


Satellite-based estimates of ambient air pollution and global variations in childhood asthma prevalence.
The effect of ambient air pollution on global variations and trends in asthma prevalence is unclear. Our goal was to investigate community-level associations between asthma prevalence data from the International Study of Asthma and Allergies in Childhood (ISAAC) and satellite-based estimates of particulate matter with aerodynamic diameter < 2.5 µm (PM₂.₅) and nitrogen dioxide (NO₂), and modelled estimates of ozone. We assigned satellite-based estimates of PM₂.₅ and NO₂ at a spatial resolution of 0.1° × 0.1° and modeled estimates of ozone at a resolution of 1° × 1° to 183 ISAAC centers. We used center-level prevalence of severe asthma as the outcome and multilevel models to adjust for gross national income (GNI) and center- and country-level sex, climate, and population density. We examined associations (adjusting for GNI) between air pollution and asthma prevalence over time in centers with data from ISAAC Phase One (mid-1900s) and Phase Three (2001-2003). For the 13- to 14-year age group (128 centers in 28 countries), the estimated average within-country change in center-level asthma prevalence per 100 children per 10% increase in center-level PM₂.₅ and NO₂ was -0.043 [95% confidence interval (CI): -0.139, 0.053] and 0.017 (95% CI: -0.030, 0.064) respectively. For ozone the estimated change in prevalence per parts per billion by volume was -0.116 (95% CI: -0.234, 0.001). Equivalent results for the 6- to 7-year age group (83 centers in 20 countries), though slightly different, were not significantly positive. For the 13- to 14-year age group, change in center-level asthma prevalence over time per 100 children per 10% increase in PM₂.₅ from Phase One to Phase Three was -0.139 (95% CI: -0.347, 0.068). The corresponding association with ozone (per ppbV) was -0.171 (95% CI: -0.275, -0.067). In contrast to reports from within-community studies of individuals exposed to traffic pollution, we did not find evidence of a positive association between ambient air pollution and asthma prevalence as measured at the community level.


Morphea in adults and children cohort II: patients with morphea experience delay in diagnosis and large variation in treatment.
Little is known about the diagnosis, evaluation, and therapy of morphea (localized scleroderma) in the United States. Delays in diagnosis and initiation of appropriate therapy, if present, may negatively affect patient care. Further, this gap in knowledge hinders planning for clinical trials and therapeutic guidelines. The morphea in adults and children (MAC) cohort is designed to address this gap. We sought to determine the duration between morphea onset and diagnosis, specialty of the diagnosing provider, and initial evaluation and therapy in the MAC cohort. This was a cross-sectional survey of the inception cohort of the MAC study. In all, 63% (n = 141 of 224) of patients were given the diagnosis more than 6 months after onset. Dermatologists diagnosed and treated the majority of patients (83.5%, n = 187). Rheumatologists diagnosed and treated the more severe forms of morphea (linear and generalized). The most commonly prescribed therapy was topical corticosteroids (63%). Dermatologists predominantly prescribed topical treatments or phototherapy (P < .0001, P = .0018, respectively), even to patients with linear and generalized morphea. In contrast, rheumatologists predominantly prescribed systemic immunosuppressives and physical therapy (P < .0001, P = .0021, respectively). Referral bias and recall bias may affect patterns of evaluation/therapy and ascertainment of disease duration before diagnosis. Patients with morphea experience delay in diagnosis, which likely impacts outcome. Therapeutic decision making is largely determined by the specialty of the provider rather than disease characteristics and many treatments with little or no proven efficacy are used, whereas others with proven efficacy are underused. This underscores the need for a collaborative, multispecialty approach in designing therapeutic trials and guidelines.


Effect of phosphate on removal of humic substances by aluminum sulfate coagulant.
The presence of humic acid may change the way phosphate is absorbed or stabilized by soil and how it influences the growth of plants. The binding of phosphate with the humic substance requires bridging between phosphate ions and humic acid by metal ions, such as aluminum or iron ions. The bridging reaction can take place in peat and allophane soil under acidic conditions, altering the effectiveness of the phosphate in soil. Whether ternary phosphate-metal-HA complexes are actually formed has not yet been verified. This study considers variation in fluorescence intensity (FI) under various coagulation conditions to assess the mechanism by which humic acids and phosphate react with aluminum ions. A bond between the functional group of the humic acid and the electron-releasing group of the phosphate will enhance the florescent intensity of humic acids. Consequently the removal efficiency of humic acid, measured by florescence, declines as the phosphate concentration increases at low pH. This observation suggests that at low coagulation pH, the positively charged aluminum species can be used to bridge between the phosphate ion and the humic acid molecules.


Identifying appropriate recipients for CDC infectious risk donor kidneys.
Over 10% of deceased donors in 2011 met PHS/CDC criteria for infectious risk donor (IRD), and discard rates are significantly higher for kidneys from these donors. We hypothesized that patient phenotypes exist for whom the survival benefit outweighs the infectious risk associated with IRDs. A patient-oriented Markov decision process model was developed and validated, based on SRTR data and meta-analyses of window period risks among persons with IRD behaviors. The Markov model allows patients to see, for their phenotype, their estimated survival after accepting versus declining an IRD offer, graphed over a 5-year horizon. Estimated 5-year survival differences associated with accepting IRDs ranged from -6.4% to +67.3% for a variety of patient phenotypes. Factors most predictive of the survival difference with IRD transplantation were age, PRA, previous transplant, and the expected time until the next non-IRD deceased donor offer. This study suggests that survival benefit derived from IRD kidneys varies widely by patient phenotype. Furthermore, within the inherent limitations of model-based prediction, this study demonstrates that it is possible to identify those predicted to benefit from IRD kidneys, and illustrates how estimated survival curves based on a clinical decision can be presented to better inform patient and provider decision-making.


Electron tomography of viruses.
Understanding the molecular architectures of enveloped and complex viruses is a challenging frontier in structural biology. In these viruses, the structural and compositional variation from one viral particle to another generally precludes the use of either crystallization or image averaging procedures that have been successfully implemented in the past for highly symmetric viruses. While advances in cryo electron tomography of unstained specimens provide new opportunities for identification and molecular averaging of individual subcomponents such as the surface glycoprotein spikes on purified viruses, electron tomography of stained and plunge-frozen cells is being used to visualize the cellular context of viral entry and replication. Here, we review recent developments in both areas as they relate to our understanding of the biology of heterogeneous and pleiomorphic viruses.


Low dose of insulin for assessment of growth hormone and cortisol release in short children.
In 55 prepubertal children with growth failure, aged 8.62 +/- 2.89 years, we evaluated the efficacy of a test using only half the usual dose of insulin by comparing the results with those obtained during a classical arginine tolerance test, performed separately. The patients were randomly divided into two groups: group A consisting of 37 children received 0.05 U/kg insulin, while group B consisting of 18 patients received 0.1 U/kg insulin. Each child received the same dose of arginine per kg during the second test. Serum growth hormone (GH) peak levels were significantly (p < 0.01) lower in children of group A (6.59 +/- 4.10 ng/ml) than in those of group B (10.12 +/- 5.80 ng/ml). No differences of GH peak levels were found in patients of the two groups after arginine infusion. The injection of 0.05 U/kg insulin induced a significantly (p < 0.0001) lower percent decrease of serum glucose than 0.1 U/kg. No difference of the percent increase of serum cortisol induced by insulin at 0.05 U/kg and 0.1 U/kg was observed. The diagnosis of GH deficiency in children can be supported by a blunted GH response after two or more pharmacological stimuli including hypoglycaemia induced by only half the usual dose of insulin.


Assembly of root-associated bacterial community in cadmium contaminated soil following five-year consecutive application of soil amendments: Evidences for improved soil health.
Soil amendments have been extensively used to remediate heavy metal contaminated soils by immobilizing or altering edaphic properties to reduce the bioavailability of heavy metals. However, the potential influences of long-term soil amendments applications on microbial communities and polluted soil health are still in its infancy despite that have been applied for decades. We used amplicon sequencing and q-PCR array to characterize the root-associated microbial community compositions and rhizosphere functional genes in a five-year field experiment with consecutive application of four amendments (lime, biochar, pig manure, and a commercial Mg-Ca-Si conditioner). Compared with the control, soil amendments reduced the available Cd (CaCl2 extractable Cd) in soils and strongly affected bacterial community compositions in four root-associated niches. Five rare keystone bacterial species were found belonging to the family Gallionellaceae (1), Haliangiaceae (1), Anaerolineaceae (2), and Xanthobacteraceae (1), which significantly correlated with soil pH and the functional genes nifH and phoD. Random forest analysis showed that rhizosphere soil pH and microbial functions, and root-associated keystone bacterial community compositions mainly influenced the Cd concentrations in rice grains. Altogether, our field data revealed five-year consecutive application of soil amendments regulated root-associated microbial community assembly and enhanced microbial functions, thereby improved rhizosphere health of Cd-contaminated soils.


Kelp gulls Larus dominicanus as predators in kelp Macrocystis pyrifera beds.
Minimum daily consumption of bivalves Gaimardia sp by kelp gulls in a Macrocystis kelp bed at Porvenir, Tierra del Fuego, was calculated to be ca. 525 000 individuals, corresponding to an energy removal of ca. 21 kJ·m-2·d-1. This is far in excess of energy removal by any other higher-trophic-level predator in southern Chilean Macrocystis beds, but previous work has ignored kelp gulls as a component of the kelp bed community.


Using sensitivity analysis to validate the predictions of a biomechanical model of bite forces.
Biomechanical modelling has become a very popular technique for investigating functional anatomy. Modern computer simulation packages make producing such models straightforward and it is tempting to take the results produced at face value. However the predictions of a simulation are only valid when both the model and the input parameters are accurate and little work has been done to verify this. In this paper a model of the human jaw is produced and a sensitivity analysis is performed to validate the results. The model is built using the ADAMS multibody dynamic simulation package incorporating the major occlusive muscles of mastication (temporalis, masseter, medial and lateral pterygoids) as well as a highly mobile temporomandibular joint. This model is used to predict the peak three-dimensional bite forces at each teeth location, joint reaction forces, and the contributions made by each individual muscle. The results for occlusive bite-force (1080N at M1) match those previously published suggesting the model is valid. The sensitivity analysis was performed by sampling the input parameters from likely ranges and running the simulation many times rather than using single, best estimate values. This analysis shows that the magnitudes of the peak retractive forces on the lower teeth were highly sensitive to the chosen origin (and hence fibre direction) of the temporalis and masseter muscles as well as the laxity of the TMJ. Peak protrusive force was also sensitive to the masseter origin. These result shows that the model is insufficiently complex to estimate these values reliably although the much lower sensitivity values obtained for the bite forces in the other directions and also for the joint reaction forces suggest that these predictions are sound. Without the sensitivity analysis it would not have been possible to identify these weaknesses which strongly supports the use of sensitivity analysis as a validation technique for biomechanical modelling.


Predictive value of preoperative magnetic resonance imaging structural and diffusion indices for the results of trigeminal neuralgia microvascular decompression surgery.
To explore the predictive value of preoperative magnetic resonance imaging structural and diffusion indices of the spinal trigeminal tract (SpTV) on the results of microvascular decompression (MVD) in patients with trigeminal neuralgia (TN). This retrospective study included patients diagnosed with TN and treated with MVD in the Jining First People's Hospital between January 2020 and January 2021. The patients were divided into good and poor results groups according to postoperative pain relief. Logistic regression analysis was performed to explore independent risk factors for poor results of MVD, and their predictive value was examined using receiver operating characteristic (ROC) curves. A total of 97 TN cases were included, 24 cases with a poor result and 73 with a good result. They were comparable in demographic characteristics. Fractional anisotropy (FA) was lower (P < 0.001), and radial diffusivity (RD) was higher (P < 0.001) in the poor result group compared to the good result group. Patients in the good result group showed a higher proportion of grade 3 neurovascular contact (NVC) (39.7% vs. 16.7%, P = 0.001) and a lower RD (P < 0.001). The multivariate analysis showed that the RD of SpTV (OR = 0.000016, 95% CI: 0.000-0.004, P < 0.001) and NVC (OR = 8.07, 95% CI: 1.67-38.93, P = 0.009) were independently associated with poor results. The area under the curve (AUC) of RD and NVC were 0.848 and 0.710, and their combination achieved an AUC of 0.880. NVC and RD of SpTV are independent risk factors for poor results after MVD surgery, and combining the NVC and RD might achieve relatively high predictive value for poor results.


New kaempferol 3,7-diglycosides from Asplenium ruta-muraria and Asplenium altajense.
A flavonoid was isolated from the fronds of Asplenium ruta-muraria and A. altajense (Aspleniaceae) collected in the Altai Mountains and adjacent area. The compound was identified as kaempferol 3-O-β-[(6'''-E-caffeoylglucopyranosyl)-(1-->3)-glucopyranoside]-7-O-β-glucopyranoside (1) by UV, 1H and 13C NMR spectroscopy, LC-MS, and acid and alkaline hydrolyses. Another flavonoid (2) was isolated from A. altajense, as a minor compound, together with 1 and identified as deacylated compound 1, i.e. kaempferol 3-O-laminaribioside-7-O-glucoside. They were found in nature for the first time.


[Comparative crossover study of tiapride and meprobamate used in agitated states].
A comparative cross over study of the action of tiapride and meprobamate in behaviour problems with motor and verbal agitation was conducted on 42 hospitalized patients. Tiapride was shown to be statistically superior as far as its efficacy on agitation and its tolerance as it did not modified the patient's vigilance.


Orthorexia nervosa symptoms prospectively predict symptoms of eating disorders and depression.
The possible mental health impacts of orthorexia nervosa (ON) symptoms are poorly understood, as existing research in this field has mostly employed cross-sectional designs. This study investigated whether ON symptoms prospectively predict changes in eating disorder psychopathology and general mental health. A convenience, non-clinical sample of adults (n = 313; 83 % women) completed study measures at baseline (T1) and three-month follow-up (T2). Negative binomial regressions were computed to test whether T1 ON symptoms predict changes in binge eating and driven exercise episodes. Linear regressions were computed to test whether T1 ON symptoms predict changes in eating concerns, depressive symptoms, and life satisfaction. Higher ON symptoms prospectively predicted greater number of binge eating and driven exercise episodes at T2. Higher ON symptoms predicted increased eating concerns and depressive symptoms at T2. ON symptoms did not predict changes in life satisfaction. Findings highlight possible risks associated with ON symptomatology. Efforts to better inform the public about the risks of these pathological eating patterns are needed.


Lessons learned to aid the successful outcome of pediatric recurrent laryngeal nerve reinnervation.
While Ansa to recurrent laryngeal nerve reinnervation is gaining popularity in the treatment of unilateral vocal fold immobility, little has been reported on commonly encountered surgical challenges with this procedure. Here, we present a cohort of 21 pediatric patients who underwent this procedure with a full description of techniques used to overcome common challenges with this procedure. We report vocal and swallowing outcomes for these patients, with an overall success rate of 19/21 (90.5%) patients, with success defined as improvement of a half-consistency or resolution of vocal issues.


Effect of different muscle contraction mode on the expression of Myostatin, IGF-1, and PGC-1 alpha family members in human Vastus Lateralis muscle.
Muscle contraction stimulates a transient change of myogenic factors, partly related to the mode of contractions. Here, we assessed the response of IGF-1Ea, IGF-1Eb, IGF-1Ec, PGC1α-1, PGC1α-4, and myostatin to the eccentric Vs. the concentric contraction in human skeletal muscle. Ten healthy males were performed an acute eccentric and concentric exercise bout (n = 5 per group). For each contraction type, participants performed 12 sets of 10 repetitions knee extension by the dominant leg. Baseline and post-exercise muscle biopsy were taken 4 weeks before and immediately after experimental sessions from Vastus Lateralis muscle. Genes expression was measured by real-time PCR technique. There was a significant increase in PGC1α-1, PGC1α-4, IGF-1Ea and, IGF-1Eb mRNA after concentric contraction (p ≤ 0.05), while the PGC1α-4 and IGF-1Ec significantly increased after eccentric contraction (p ≤ 0.05). It is intriguing to highlight that; no significant differences between groups were evident for changes in any variables following exercise bouts (p ≥ 0.05). Our results found that concentric and eccentric contractions presented different responses in PGC1α-1, IGF-1Ea, IGF-1Eb, and IGF-1Ec mRNA. However, a similar significant increase in mRNA content was observed in PGC1α-4. Further, no apparent differences could be found between the response of genes to eccentric and concentric contraction.


WEB resources for pesticide toxicology, environmental chemistry, and policy: a utilitarian perspective.
Information about pesticides has grown exponentially over the last four decades and is marked by a diversity of sources including government, universities, environmental advocates, and industry. The internet has made access to this unprecedented amount of information faster than ever, but judging the validity and usefulness of the information is problematic. To avoid turning this discussion of web resources for pesticide information into a narrative about a personal 'top ten' list, a utilitarian perspective of resources useful to a research, educator, and risk communicator is elucidated. Useful web sites are fit into the context of information needed for risk assessment, which includes hazard identification, dose-response relationships, exposure assessment, and risk characterization. In addition resources for pesticide policy and regulations are considered. Specific ways in which the sites are useful are discussed along with information about site updating and validation of information.


Induced responses in three alkaloid-containing plant species.
In this paper we test three plant species for the inducibility of their alkaloid production. The plants were heavily damaged by cutting off 50% of their leaf surface using a pair of scissors. The cut-off leaf tips were used as controls for possible diurnal fluctuations. After 3, 6, 12, 24 and 48 h, respectively, the leaf bases of the damaged plants were harvested and the alkaloid concentration was measured. In Senecio jacobaea the pyrrolizidine alkaloid (Pa) concentration in damaged plants decreased within 6-12 h after damage. Within 24 h after damage the Pa concentration of Cynoglossum officinale doubled compared to control values. Indole alkaloid production in Catharanthus roseus was found not to be induced in this experiment. The responses are discussed in a functional context. We hypothesize that the nature of the response is not a feature of the type of secondary metabolite, but is related to whether the plants are damaged mainly by generalist or by specialist herbivores.


Delayed inflammatory reaction to hyaluronic acid lip filler after the Pfizer-BioNTech COVID-19 vaccine: A case report.
Hypersensitivity reactions can be a side effect to any vaccine, but they are usually rare. The COVID-19 vaccination may cause hypersensitivity, and several cases of delayed hypersensitivity (DH) to hyaluronic acid (HA) dermal filler have been documented. The current report presents a case of a 36-year-old female patient with DH to HA dermal filler after receiving the Pfizer-BioNTech COVID-19 vaccine. Symptoms, including dryness, swelling, and a painless nodule, appeared after the first and second doses of the vaccine. The patient was treated with intralesional hyaluronidase and triamcinolone in the outpatient clinic. Although HA is relatively safe and routinely used in aesthetic medicine, DH reactions must be considered. Therefore, an appropriate patient history should be obtained, and physicians should provide counselling on the potential reactions to avoid these adverse effects.