A Vibration Device to Control Injection Discomfort.
Pain from local anesthesia injections can be reduced by distraction and counter-stimulation techniques. This study investigated the DentalVibe® Injection Comfort System (third-generation, DV3), developed to lessen anesthesia pain through pulsed vibration, a form of counter-stimulation. The aim of the study was to evaluate both the efficacy of DV3 in reducing pain and discomfort from intraoral long buccal (LB) and inferior alveolar nerve (IAN) injections and the time needed to achieve complete anesthesia during an IAN block. The study enrolled 60 subjects, 30 men and 30 women, aged 21 to 32 years, who rated both injection pain on a visual analog scale and discomfort, unpleasantness, and difficulty in enduring the injection on a modified symptom severity index. Each subject received bilateral LB injections and an IAN block. Using block design, the third-generation DV (DV3) was randomly assigned to either the first or second LB injection and to 30 subjects on their third injection, the IAN block. No topical anesthesia was applied. Subjects receiving DV3 reported significantly less pain, discomfort, unpleasantness, and difficulty in enduring LB and IAN injections (P < .05), regardless of whether DV3 was used on the first or second LB injection. Time to complete anesthesia was not significantly different (P > .05) when DV3 was used on IAN block injections. The DV3 significantly (P < .02) reduced pain/discomfort from anesthetic injections in this pilot study, in which many subjects were either dental or medical students familiar with performing and enduring injections. More studies are warranted on layperson populations.


Assessing chemical risk within an ecosystem services framework: Implementation and added value.
An ecosystem services (ES) approach to chemical risk assessment has many potential advantages, but there are also substantial challenges regarding its implementation. We report the findings of a multi-stakeholder workshop that evaluated the feasibility of adopting an ES approach to chemical risk assessment using currently available tools and data. Also evaluated is the added value such an approach would bring to environmental decision making. The aim was to build consensus across disparate stakeholders and to co-produce a common understanding of the regulatory benefits and feasibility of implementing an ES approach in European chemicals regulation. Workshop discussions were informed by proof of concept studies and resulted in the development of a novel tiered framework for assessing chemical risk to ES delivery. There was consensus on the substantial added value of adopting an ES-based approach for regulatory decision making. Ecosystem services provide a common currency and a 'unifying approach' across environmental compartments, stressors and regulatory frameworks. The ES approach informs prioritisation of risk and remedial action and aids risk communication and risk management. It facilitates a more holistic assessment, enables ES trade-offs to be compared across alternative interventions, and supports comparative risk assessments and a socio-economic analysis of management options and decisions. Key to realising this added value is a shift away from using a single threshold value to categorise risk, towards a consideration of the exposure-effect distribution for individual ES of interest. Also required is the development of an integrated systems-level approach across regulatory frameworks and agreement on specific protection goals and scenarios for framing environmental risk assessments. The need to further develop tools for extrapolating toxicity data to service providers and ES delivery, including logic chains and ecological production functions, was highlighted. Also agreed was the need for methods and metrics for ES valuation to be used in assessing trade-offs.


Evaluation of the rupture of silicone breast implants by mammography, ultrasonography and magnetic resonance imaging in asymptomatic patients: correlation with surgical findings.
Different imaging methods can identify the integrity of breast implants and also the extent of possible silicone leakage. Mammography, ultrasonography and magnetic resonance imaging are often used to evaluate the integrity of breast implants, usually in patients that are symptomatic for rupture. A group of clinically asymptomatic patients was taken as a sample. These patients wanted to remove or change their breast implants for psychological or cosmetic reasons. The purpose of this study was to compare the efficacy of mammography, sonography and magnetic resonance imaging in the detection of breast implant rupture in an asymptomatic population. Prospective study. Department of Diagnostic Imaging, Universidade de São Paulo, São Paulo, Brazil. The participants were 44 asymptomatic patients who subsequently had implants surgically removed. Eighty-three implants were evaluated by both film-screen mammography and high-resolution sonography and 77 implants were evaluated by magnetic resonance imaging. The sensitivity and specificity of mammography, ultrasonography and magnetic resonance imaging were assessed using predetermined diagnostic criteria for implant rupture. All radiological signs were discussed and false positives and false negatives were retrospectively evaluated to identify the pitfalls in the investigations. The respective sensitivity and specificity of mammography were 20% and 89%; sonography, 30% and 81%; and magnetic resonance imaging, 64% and 77%. The differences between patients with breast implants for cosmetic and oncological reasons were discussed. Our experience suggests that magnetic resonance imaging seems to be the best imaging method on its own for the evaluation of rupturing among asymptomatic patients.


One-week treatment of chlamydia-positive urethritis with doxycycline and tetracycline chloride in males.
65 patients with chlamydia-positive urethritis were treated with doxycycline and 59 with tetracycline chloride 1 g/day for one week. All steady sexual partners of these patients were treated with the same regimen during the same period. At control visits 2 and 3 weeks after the beginning of the treatment, all re-examined doxycycline-treated patients and all except 4 tetracycline-treated patients showed clinical cure and were free from signs of urethritis in the microscopical examination of Gram-stained smears from the urethra. Isolation of C. trachomatis was positive in 7 of the doxycycline-treated and 10 of the tetracycline-treated patients at the first control visit and in one more tetracycline-treated patient at the second control visit. The study stresses the importance of attempts to isolate C. trachomatis in cases without clinical or microscopical evidence of nongonococcal urethritis at control visits after short-term treatment with tetracyclines. The present investigation indicates that this is true also in cases in which all steady sexual partners are treated simultaneously.


A-Kinase Interacting Protein 1 Promotes Cell Invasion and Stemness via Activating HIF-1α and β-Catenin Signaling Pathways in Gastric Cancer Under Hypoxia Condition.
A-Kinase interacting protein 1 (AKIP1) relates to gastric cancer growth, metastasis, and prognosis, while its regulation on gastric cancer invasion and stemness under hypoxia microenvironment is not reported. Therefore, this study aimed to explore this topic to uncover AKIP1's role in gastric cancer under hypoxia. Gastric cancer cell lines AGS and MKN45 were cultured under hypoxia condition, then transfected with AKIP1 or negative control (NC) overexpression plasmid or AKIP1 or NC knockdown plasmid. Furthermore, rescue experiments were conducted by transfecting HIF-1α or β-catenin overexpression plasmid, combined with AKIP1 or NC knockdown plasmid. Afterward, cell invasion, CD133+ cell proportion, sphere number/1,000 cells, and HIF-1α and β-catenin pathways were measured. The invasive cell count, CD133+ cell proportion, and sphere number/1,000 cells were enhanced in both AGS cells and MKN45 cells under hypoxia, and AKIP1 expression was also elevated. AKIP1 knockdown inhibited cell invasion, CD133+ cell proportion, sphere number/1,000 cells, HIF-1α, vascular endothelial growth factor (VEGF), β-catenin, and calcium-binding protein (CBP) expressions in AGS cells and MKN45 cells under hypoxia, while AKIP1 overexpression presented with the opposite effect. Then, in rescue experiments, HIF-1α overexpression and β-catenin overexpression both promoted cell invasion, CD133+ cell proportion, and sphere number/1,000 cells, which also attenuated the effect of AKIP1 knockdown on these functions in AGS cells and MKN45 cells. AKIP1 promotes cell invasion and stemness via activating HIF-1α and β-catenin signaling pathways in gastric cancer under hypoxia condition.


Smoothened goes molecular: new pieces in the hedgehog signaling puzzle.
A general aim of studies of signal transduction is to identify mediators of specific signals, order them into pathways, and understand the nature of interactions between individual components and how these interactions alter pathway behavior. Despite years of intensive study and its central importance to animal development and human health, our understanding of the Hedgehog (Hh) signaling pathway remains riddled with gaps, question marks, assumptions, and poorly understood connections. In particular, understanding how interactions between Hh and Patched (Ptc), a 12-pass integral membrane protein, lead to modulation of the function of Smoothened (Smo), a 7-pass integral membrane protein, has defied standard biochemical characterization. Recent structural and biochemical characterizations of Smoothened domains have begun to unlock this riddle, however, and lay the groundwork for improved cancer therapies.


Influence of Ni Precursors on the Structure, Performance, and Carbon Deposition of Ni-Al2O3 Catalysts for CO Methanation.
Three Ni-Al2O3 catalysts were prepared, in planetary ball-milling machine, by the mechanochemical method with Al(NO3)3·9H2O as the aluminum precursor, (NH4)2CO3 as the precipitant, and Ni(NO3)2·6H2O, NiCl2·6H2O, and Ni(CH3COO)2·4H2O as nickel precursors (the corresponding catalysts were labeled as Ni-NO, Ni-Cl, and Ni-Ac). The prepared catalysts were characterized by X-ray diffraction (XRD), temperature-programmed reduction (H2-TPR), and N2 adsorption-desorption technologies, and CO methanation performance evaluation was carried out for the catalysts. Results showed that the catalyst with Ni(NO3)2·6H2O as the precursor presented good Ni dispersibility and a small Ni grain size of 6.80 nm. CO conversion, CH4 selectivity, and yield of the catalyst were as high as 78.8, 87.9, and 69.8%, respectively. Carbon deposition analysis from temperature-programmed hydrogenation (TPH) characterization showed that the H2 consumption peak area of the three samples followed the order: Ni-NO (2886.66 au) < Ni-Cl (4389.97 au) < Ni-Ac (5721.65 au), indicating that the Ni-NO catalyst showed higher resistance to carbon deposition, which might be due to its small Ni grain size.


Spectroscopy of a narrow-line optical pumping transition in atomic dysprosium.
We present measurements of the hyperfine coefficients and isotope shifts of the Dy I 683.731 nm transition, using saturated absorption spectroscopy on an atomic beam. A King Plot is drawn resulting in an updated value for the specific mass shift δν(684,sms)(164-162)=-534±17 MHz. Using fluorescence spectroscopy, we measure the excited state lifetime τ684=1.68(5) μs, yielding a linewidth of γ684=95±3 kHz. We give an upper limit to the branching ratio between the two decay channels from the excited state showing that this transition is usable for optical pumping into a dark state and demagnetization cooling.


Volunteering and health benefits in general adults: cumulative effects and forms.
Although the health benefits of volunteering have been well documented, no research has examined its cumulative effects according to other-oriented and self-oriented volunteering on multiple health outcomes in the general adult public. This study examined other-oriented and self-oriented volunteering in cumulative contribution to health outcomes (mental and physical health, life satisfaction, social well-being and depression). Data were drawn from the Survey of Texas Adults 2004, which contains a statewide population-based sample of adults (n = 1504). Multivariate linear regression and Wald test of parameters equivalence constraint were used to test the relationships. Both forms of volunteering were significantly related to better health outcomes (odds ratios = 3.66% to 11.11%), except the effect of self-oriented volunteering on depression. Other-oriented volunteering was found to have better health benefits than did self-volunteering. Volunteering should be promoted by public health, education and policy practitioners as a kind of healthy lifestyle, especially for the social subgroups of elders, ethnic minorities, those with little education, single people, and unemployed people, who generally have poorer health and less participation in volunteering.


Spinal manipulative therapy reduces peripheral neuropathic pain in the rat.
Spinal manipulative therapy, including low-velocity variable-amplitude spinal manipulation (LVVA-SM), relieves chronic low back pain, especially in patients with neuropathic radiating leg pain following peripheral nervous system insult. Understanding the underlying analgesic mechanisms requires animal models. The aim of the current study was to develop an animal model for the analgesic actions of LVVA-SM in the setting of peripheral neuropathic pain. Adult male Sprague-Dawley rat sciatic nerve tibial and common peroneal branches were transected, sparing the sural branch (spared nerve injury, SNI). After 15-18 days, rats were assigned randomly to one of three groups (n=9 each group): LVVA-SM at 0.15-or 0.16-Hz or Control. LVVA-SM (20° flexion at the L5 vertebra with an innovative motorized treatment table) was administered in anesthetized rats for 10 min. Control rats were administered anesthesia and positioned on the treatment table. After 10, 25, and 40 min, the plantar skin of the hindpaw ipsilateral to SNI was tested for mechanical sensitivity (paw withdrawal threshold to a logarithmic series of Semmes-Weinstein monofilaments) and cold sensitivity (duration of paw lifting, shaking, and/or licking to topical acetone application). SNI produced behavioral signs of mechanical and cold allodynia. LVVA-SM reduced mechanical, but not cold, hypersensitivity compared with Control (0.15-Hz: P=0.04 at 10 min; 0.16-Hz: P<0.001 at 10 min, P=0.04 at 25 min). The analgesic effect of LVVA-SM in chronic low back pain patients with neuropathic leg pain can be reverse-translated to a rat model Video abstract: http://links.lww.com/WNR/A453.


They Can Handle the Stress: MPK17 and PMD1 act in a salt-specific pathway.
Arabidopsis MAP KINASE17 (MPK17) was recently identified as a novel regulator of peroxisome division in response to salt stress. Further, the known peroxisome division factor PEROXISOME AND MITOCHONDRIAL DIVISION FACTOR1 (PMD1) genetically acts downstream of MPK17. We previously showed that mutants defective in either MPK17 or PMD1 fail to proliferate peroxisomes in response to NaCl stress. Here, we show that, unlike their abnormal NaCl responses, mpk17 and pmd1 mutants display wild type responses to other stresses known to alter peroxisome proliferation, suggesting that plants distinguish among peroxisome division-inducing stresses and alter the peroxisome division pathway based on the stress applied.


Nutrients differentially regulate nucleobindin-2/nesfatin-1 in vitro in cultured stomach ghrelinoma (MGN3-1) cells and in vivo in male mice.
Nesfatin-1 is secreted, meal-responsive anorexigenic peptide encoded in the precursor nucleobindin-2 [NUCB2]. Circulating nesfatin-1 increases post-prandially, but the dietary components that modulate NUCB2/nesfatin-1 remain unknown. We hypothesized that carbohydrate, fat and protein differentially regulate tissue specific expression of nesfatin-1. NUCB2, prohormone convertases and nesfatin-1 were detected in mouse stomach ghrelinoma [MGN3-1] cells. NUCB2 mRNA and protein were also detected in mouse liver, and small and large intestines. MGN3-1 cells were treated with glucose, fatty acids or amino acids. Male C57BL/6 mice were chronically fed high fat, high carbohydrate and high protein diets for 17 weeks. Quantitative PCR and nesfatin-1 assays were used to determine nesfatin-1 at mRNA and protein levels. Glucose stimulated NUCB2 mRNA expression in MGN3-1 cells. L-Tryptophan also increased NUCB2 mRNA expression and ghrelin mRNA expression, and nesfatin-1 secretion. Oleic acid inhibited NUCB2 mRNA expression, while ghrelin mRNA expression and secretion was enhanced. NUCB2 mRNA expression was significantly lower in the liver of mice fed a high protein diet compared to mice fed other diets. Chronic intake of high fat diet caused a significant reduction in NUCB2 mRNA in the stomach, while high protein and high fat diet caused similar suppression of NUCB2 mRNA in the large intestine. No differences in serum nesfatin-1 levels were found in mice at 7 a.m, at the commencement of the light phase. High carbohydrate diet fed mice showed significantly elevated nesfatin-1 levels at 1 p.m. Serum nesfatin-1 was significantly lower in mice fed high fat, protein or carbohydrate compared to the controls at 7 p.m, just prior to the dark phase. Mice that received a bolus of high fat had significantly elevated nesfatin-1/NUCB2 at all time points tested post-gavage, compared to control mice and mice fed other diets. Our results for the first time indicate that nesfatin-1 is modulated by nutrients.


Analysis of Fcgamma receptor IIa (cd32) gene polymorphism and anti-malarial IgG subclass antibodies to asexual blood-stage antigen of Plasmodium falciparum in an unstable malaria endemic area of Iran.
One of the main host genetic factors involved in inflammation, immune responses and pathogenesis of malaria is FcγRIIa (cd32) gene. A single point mutation at position 131 replace an arginine (R) with a histidine (H) that can affect the affinity of the receptor for human IgG subclasses. This investigation was designed to explore the polymorphisms at FcγRIIa gene in association with both anti-malarial total IgG antibody and IgG subclass profiles to C-terminal region of Plasmodium falciparum merozoite surface protein 1 (PfMSP-1(19)). In this study, 166 infected patients with P. falciparum who are living in a malaria endemic area of Iran were studied using PCR-RFLP and ELISA methods. The results showed that the frequency of FcγRIIa-R/R131, -R/H131 and -H/H131 genotypes was 9.6%, 42.8% and 47.6%, respectively. Level of total IgG to recombinant PfMSP-1(19) antigen showed that there was no difference among the FcγRIIa-R/R131, -R/H131 and -H/H131 groups. With regards to the IgG subclasses, the anti-malarial IgG1 antibodies predominated. Also, there was a significant difference between the frequency of positive responders for anti-PfMSP-1(19) IgG and IgG1 antibodies in P. falciparum-infected individuals with FcγRIIa-R/R131, -R/H131 or -H/H131 genotypes (P<0.05, X(2) test). Regarding to IgG2-PfMSP-1(19) antibody, 27.27% (FcγRIIa-R/R131), 25.71% (FcγRIIa-R/H131) and 22.2% (FcγRIIa-H/H131) of IgG responders showed positive antibody response. Taken together, this study is the first report that exhibits the high frequency of both FcγRIIa-H131H genotypes and H131 allele in the Baluchi ethnic group, which was similar to the Fulani ethnic group. The present results provide additional data to understand the role of FcγRIIa-131 genotypes in the pathogenesis of malaria.


Primary paraganglioma located between the thyroid gland and the left common carotid artery: A case report.
Head and neck paraganglioma is a rare and predominantly asymptomatic tumor. In the present study, an extremely rare case of asymptomatic paraganglioma located between the left common carotid artery and the left thyroid is described. The clinical presentation, cytomorphology and the immunohistochemical characteristics for the diagnosis of head and neck paraganglioma are described. To the best of our knowledge, only two cases of paraganglioma located between the left common carotid artery and the left thyroid have previously been reported.


Cleaning up a bullying culture.
This month's Nursing Management features a disturbing report into bullying at a leading London healthcare provider. An investigation by academics at Plymouth University reveals a frequency of bullying at Barts Health NHS Trust four times the national average and a prevailing culture of incivility and unpleasantness.


Absorption Spectra of Ethanol and Water Using a Photothermal Lens Spectrophotometer.
In this work we report on the absorption spectra of ethanol and water in the region 430-700 nm using a homemade halogen lamp-based photothermal lens spectrophotometer with a multipass probe-beam configuration. The spectra also include well resolved, higher absorption overtones. The instrument achieves high sensitivity due to multiple reflections within the optical cavity containing the sample. Finally, an Arduino board was used for collecting and digitizing the signal, thus enabling a more compact device.


Update in renal transplantation.
Renal transplantation is the treatment of choice for most patients with end-stage renal disease. The shortage of donor organs, however, remains a major obstacle to successful, early transplantation. This shortage has actually worsened despite an increase in living family-related and unrelated donors. On the other hand, over the last 10 years, allograft and recipient survival have significantly improved. This encouraging outcome reflects many factors, particularly a favorable shift in the balance between the efficacy and toxicity of immunosuppressive regimens. As acute rejection and early graft loss have become less common, the focus is increasingly directed toward the prevention and treatment of the long-term complications of renal transplantation. These include suboptimal allograft function, premature death, cardiovascular disease, and bone disease. Thus, a multidisciplinary approach--rather than management of immunological issues alone--is now required to optimize long-term outcomes of renal transplant recipients.


Sarcopenia among people living with HIV and the effect of antiretroviral therapy on body composition.
To investigate the prevalence of sarcopenia among people living with HIV (PLWH) in Japan and analyze the relationship between HIV infection and ART effects on the body composition of Japanese PLWH for more appropriate drug selection and lifestyle guidance. Cross-sectional observational study. We included male patients aged ≥ 60 years whose body composition was measured by InBody 570 body composition analyzer during outpatient visits. Patients were classified by body shape based on body mass index (BMI) and body fat percentage measurements and by tenofovir alafenamide administration. Hidden obesity is a condition wherein the BMI is within the standard range but the body fat percentage is higher than the reference. Patients with low muscle mass and strength were considered to have sarcopenia, whereas those with only low muscle strength were considered to have pre-sarcopenia. In total, 87 patients were included. Based on body shape determined by BMI and body fat percentage, most patients had hidden obesity (40 patients, 46.0%). Sarcopenia was detected in 9 patients (10.3%) and pre-sarcopenia in 14 patients (16.1%). The tenofovir alafenamide (TAF) use group had significantly higher BMI, higher skeletal muscle mass, body fat mass, and skeletal muscle mass index relative to the non-TAF use group. Hidden obesity is a risk for lifestyle diseases. It is important to recognize it based on body composition measurements because it can be missed by BMI measurement alone. Tenofovir alafenamide therapy increases skeletal muscle mass, which may result in the prevention of sarcopenia. To clarify how TAF affects the development of sarcopenia and lifestyle diseases, future studies on a larger cohort are warranted.


Amylin receptor ligands reduce the pathological cascade of Alzheimer's disease.
Amylin is an important gut-brain axis hormone. Since amylin and amyloid-β peptide (Aβ) share similar β sheet secondary structure despite not having the same primary sequences, we hypothesized that the accumulation of Aβ in the brains of subjects with Alzheimer's disease (AD) might compete with amylin for binding to the amylin receptor (AmR). If true, adding exogenous amylin type peptides would compete with Aβ and reduce the AD pathological cascade, improving cognition. Here we report that a 10-week course of peripheral treatment with human amylin significantly reduced multiple different markers associated with AD pathology, including reducing levels of phospho-tau, insoluble tau, two inflammatory markers (Iba1 and CD68), as well as cerebral Aβ. Amylin treatment also led to improvements in learning and memory in two AD mouse models. Mechanistic studies showed that an amylin receptor antagonist successfully antagonized some protective effects of amylin in vivo, suggesting that the protective effects of amylin require interaction with its cognate receptor. Comparison of signaling cascades emanating from AmR suggest that amylin electively suppresses activation of the CDK5 pathway by Aβ. Treatment with amylin significantly reduced CDK5 signaling in a receptor dependent manner, dramatically decreasing the levels of p25, the active form of CDK5 with a corresponding reduction in tau phosphorylation. This is the first report documenting the ability of amylin treatment to reduce tauopathy and inflammation in animal models of AD. The data suggest that the clinical analog of amylin, pramlintide, might exhibit utility as a therapeutic agent for AD and other neurodegenerative diseases.


Characterization of Genetic and Allelic Diversity Amongst Cultivated and Wild Lentil Accessions for Germplasm Enhancement.
Intensive breeding of cultivated lentil has resulted in a relatively narrow genetic base, which limits the options to increase crop productivity through selection. Assessment of genetic diversity in the wild gene pool of lentil, as well as characterization of useful and novel alleles/genes that can be introgressed into elite germplasm, presents new opportunities and pathways for germplasm enhancement, followed by successful crop improvement. In the current study, a lentil collection consisting of 467 wild and cultivated accessions that originated from 10 diverse geographical regions was assessed, to understand genetic relationships among different lentil species/subspecies. A total of 422,101 high-confidence SNP markers were identified against the reference lentil genome (cv. CDC Redberry). Phylogenetic analysis clustered the germplasm collection into four groups, namely, Lens culinaris/Lens orientalis, Lens lamottei/Lens odemensis, Lens ervoides, and Lens nigricans. A weak correlation was observed between geographical origin and genetic relationship, except for some accessions of L. culinaris and L. ervoides. Genetic distance matrices revealed a comparable level of variation within the gene pools of L. culinaris (Nei's coefficient 0.01468-0.71163), L. ervoides (Nei's coefficient 0.01807-0.71877), and L. nigricans (Nei's coefficient 0.02188-1.2219). In order to understand any genic differences at species/subspecies level, allele frequencies were calculated from a subset of 263 lentil accessions. Among all cultivated and wild lentil species, L. nigricans exhibited the greatest allelic differentiation across the genome compared to all other species/subspecies. Major differences were observed on six genomic regions with the largest being on Chromosome 1 (c. 1 Mbp). These results indicate that L. nigricans is the most distantly related to L. culinaris and additional structural variations are likely to be identified from genome sequencing studies. This would provide further insights into evolutionary relationships between cultivated and wild lentil germplasm, for germplasm improvement and introgression.


Accurate calling of homeoallelic genotypes of iSelect markers using inbred structured populations.
Genetic map construction is a foundational step in the analysis of structured experimental populations. For markers that hybridize to several genetically similar locations, or where several alleles are present (such as in multiparental populations), current methods often discard the marker or incorrectly call the genotypes. These errors result in information loss, or incorrect genotypes that can corrupt map construction. We present a new approach for simultaneously performing genetic map construction and marker calling. Our new approach allows the calling of a larger number of markers, a larger number of unique alleles per marker and the correct use of markers which hybridize to multiple genetically similar locations. We demonstrate our new approach using simulations, a biparental wheat population and an eight-parent population of spring bread wheat. Applying our method to the eight-parent population increased the number of mapped markers by 71%. We show that the new genetic map allows the investigation of synteny in ways that were not previously possible in that dataset. The method described in this article has been incorporated into R package mpMap2. It is available from CRAN and also from https://github.com/rohan-shah/mpMap2. Supplementary data are available at Bioinformatics online.


Theoretical studies of the early stage coagulation kinetics for a charged colloidal dispersion.
We study the early stage coagulation kinetics for a charged colloidal dispersion which is here modeled by an effective two-body colloid-colloid potential. The colloidal system was physically prepared by choosing sets of colloidal parameters varying in particular the Hamaker constant and the particle's size. The kinetics of coagulation process was driven by the addition of an indifferent electrolyte and assumed to proceed in two quasi-steady steps. In the first step, colloidal particles are destabilized by the presence of a second potential minimum to diffuse from a bulk-stabilized liquid phase to a flocculated phase. In the second step, we assume that different entities are found in the second potential minimum. The entities comprise secondary dimers, secondary dimers undergoing redispersion, and monomers still in singlet states. If, under favorable condition, this kind of interaction-driven diffusive motion continues, a fraction of the secondary dimers will be induced to undergo primary dimers formation in the first deep minimum. Whether or not the latter process occurs is determined either energetically by the potential barrier falling below a prescribed value, say of 15k(B)T, or/and the second potential minimum becoming negligibly small (with a magnitude <k(B)T). A prototype example to exhibit this kind of the coagulation kinetics phenomenon is an aqueous dispersion of polystyrene latex particles. Our detailed analysis on this system showed the connection between the change of rate constants and the reversible flocculation<==>coagulation transition and would throw a fresh light on the use of both the energy and the kinetic criteria for understanding the colloidal stability such as those observed in the liquid-liquid coexistence.


Preparation of human serum albumin microspheres by a novel acetone-heat denaturation method.
Human serum albumin (HSA) microspheres have been produced in the size range of 200 nm to 10 microns by the controlled addition of acetone to an aqueous solution of HSA, followed by stabilization of the formed microspheres at an elevated temperature. Microspheres produced by this acetone-heat denaturation method could be stabilized at relatively low temperatures (75 degrees C) over a short time period (15-30 min). The acetone-heat denaturation method is different from the traditional oil/water technique for preparation of HSA microspheres, both in terms of production method and the avoidance of high temperatures (> 100 degrees C) and extended heating times (> 30 min) for stabilization. This paper describes the influence of process conditions, such as volumes of acetone and HSA concentration, on the formation of the microspheres and their morphological characteristics. A loading efficiency of 8 per cent was achieved for the HSA microspheres when using rose bengal as a model compound. The release of rose bengal from the microspheres in phosphate buffered saline at 37 degrees C was dependent on the presence of the surfactant Tween 80, and varied from a 5 per cent release in 14 days in the absence of surfactant to a 50 per cent release in 8 h in the presence of surfactant.


Wear and creep of highly crosslinked polyethylene against cobalt chrome and ceramic femoral heads.
The wear and creep characteristics of highly crosslinked ultrahigh-molecular-weight polyethylene (UHMWPE) articulating against large-diameter (36mm) ceramic and cobalt chrome femoral heads have been investigated in a physiological anatomical hip joint simulator for 10 million cycles. The crosslinked UHMWPE/ceramic combination showed higher volume deformation due to creep plus wear during the first 2 million cycles, and a steady-state wear rate 40 per cent lower than that of the crosslinked UHMWPE/cobalt chrome combination. Wear particles were isolated and characterized from the hip simulator lubricants. The wear particles were similar in size and morphology for both head materials. The particle isolation methodology used could not detect a statistically significant difference between the particles produced by the cobalt chrome and alumina ceramic femoral heads.


Growth stimulation of BHK cells in culture by free biotin in serum.
A dialysate of fetal bovine serum stimulated the growth of BHK cells in a medium containing 1% dialyzed serum. The growth-stimulating activity of the dialysate was separated in a single peak with Biogel P-2 chromatography, and a single active component was further fractionated with paper and thin-layer chromatography. The component was identified as biotin. Pure biotin behaved the same as the active component in the dialysate and had the same growth-stimulating activity. The dialysate contained only the free biotin that was present in serum. Free biotin was found in relatively large amounts in fetal (bovine and human) sera, and only a very small percentage of dialysates of adult (bovine, horse, swine, and human) sera had traces of growth-stimulating activity. The possible role of free biotin in the body is discussed.


Using fine-scale spatial genetics of Norway rats to improve control efforts and reduce leptospirosis risk in urban slum environments.
The Norway rat (Rattus norvegicus) is a key pest species globally and responsible for seasonal outbreaks of the zoonotic bacterial disease leptospirosis in the tropics. The city of Salvador, Brazil, has seen recent and dramatic increases in human population residing in slums, where conditions foster high rat density and increasing leptospirosis infection rates. Intervention campaigns have been used to drastically reduce rat numbers. In planning these interventions, it is important to define the eradication units - the spatial scale at which rats constitute continuous populations and from where rats are likely recolonizing, post-intervention. To provide this information, we applied spatial genetic analyses to 706 rats collected across Salvador and genotyped at 16 microsatellite loci. We performed spatially explicit analyses and estimated migration levels to identify distinct genetic units and landscape features associated with genetic divergence at different spatial scales, ranging from valleys within a slum community to city-wide analyses. Clear genetic breaks exist between rats not only across Salvador but also between valleys of slums separated by <100 m-well within the dispersal capacity of rats. The genetic data indicate that valleys may be considered separate units and identified high-traffic roads as strong impediments to rat movement. Migration data suggest that most (71-90%) movement is contained within valleys, with no clear source population contributing to migrant rats. We use these data to recommend eradication units and discuss the importance of carrying out individual-based analyses at different spatial scales in urban landscapes.


Unsuccessful consequence of optic canal decompression for a case of craniometaphyseal dysplasia.
We have described a case of craniometaphyseal dysplasia in which decompression of bilateral optic canals for treatment of threatened damage of the optic nerve resulted in bilateral visual loss. We speculate that a specific mechanism exists whereby decompression of the optic canal can cause blindness.


Precursor to the onset of the bulk oxidation of Cu(100).
Using density-functional theory within the generalized gradient approximation, we investigate the energetics of oxygen subsurface adsorption governing the onset of bulk oxidation of Cu(100) surface. It shows that the presence of boundaries formed from merged missing-row nanodomains mismatched by a half unit-cell leads to preferred oxygen adsorption at the subsurface tetrahedral sites. The resulting Cu-O tetrahedrons along the domain boundary strikingly resemble that of the bulk oxide phase of Cu(2)O. These results provide direct atomic-scale insight into the microscopic origin of the crystallographic orientation relationships for oxide overlayer growth. Our results also suggest that the oxidation of an atomically flat terrace can still be a heterogeneous nucleation process controlled by defects in the oxygen-chemisorbed adlayer.


Biomechanical properties of intermediate filaments: from tissues to single filaments and back.
The animal cell cytoskeleton consists of three interconnected filament systems: actin-containing microfilaments (MFs), microtubules (MTs), and the lesser known intermediate filaments (IFs). All IF proteins share a common tripartite domain structure and the ability to assemble into 8-12 nm wide filaments. Electron microscopy data suggest that IFs are built according to a completely different plan from that of MFs and MTs. IFs are known to impart mechanical stability to cells and tissues but, until recently, the biomechanical properties of single IFs were unknown. However, with the discovery of naturally occurring micrometer-wide IF bundles and the development of new methodologies to mechanically probe single filaments, it is now possible to propose a more unified view of IF biomechanics. Unlike MFs and MTs, single IFs can now be described as flexible, extensible and tough, which has important implications for our understanding of cell and tissue mechanics. Furthermore, the molecular mechanisms at play when IFs are deformed point toward a pivotal role for them in mechanotransduction.


The Staudinger Ligation.
While the Staudinger reaction has first been described a hundred years ago in 1919, the ligation reaction became one of the most important and efficient bioconjugation techniques in the 1990s and this century. It holds the crucial characteristics for bioorthogonal chemistry: biocompatibility, selectivity, and a rapid and high-yielding turnover for a wide variety of applications. In the past years, it has been used especially in chemical biology for peptide/protein synthesis, posttranslational modifications, and DNA labeling. Furthermore, it can be used for cell-surface engineering, development of microarrays, and drug delivery systems. However, it is also possible to use the reaction in synthetic chemistry for general formation of amide bonds. In this review, the three major types, traceless and nontraceless Staudinger Ligation as well as the Staudinger phosphite reaction, are described in detail. We will further illustrate each reaction mechanism and describe characteristic substrates, intermediates, and products. In addition, not only its advantages but also stereochemical aspects, scope, and limitations, in particular side reactions, are discussed. Finally, the method is compared to other bioorthogonal labeling methods.


Two-Level factorial screening of new plasmid/strain combinations for prodution of recombinant-DNA products.
This article treats the basic problem of selection of experimental conditions for microbiological experiments for evaluation of newly isolated bacterial strains, mutants, or plasmid/strain combinations. For this purpose shake flask experiments in a 2(10-4)confounded factorial design at resolution IV with four blocks of 16 flasks were used. The design was used for testing of two new strain/plasmid combinations (E. coli MT 102/403-SD2 and W 3110/403-SD2) i.e., both strains with the same plasmid 403-SD2. Both strains were integrated in the design, so both strains were tested with nine factors (temperature, aeration, glucose, initial pH, pH regulation, reduced aeration, chloramphenicol, acetate, and glycerol). With both strains the interaction between initial pH and reduced aeration had a significant influence on the yield of the recombinant-DNA product nuclease. There was more than a factor of 10 between lowest and highest yield of product. In this interactive system the strains reacted differently. MT 102/403-SD2 had highest yields at high initial pH (8.4) and no reduction in aeration, whereas W 3110/403-SD2 had highest yields of nuclease at low initial pH (7.4) and reduced aeration (rubber stopper inserted after cultivation for 12 h). These data (and previous work) clearly demonstrate that it is impossible to suggest a simple set of experimental conditions for testing of new plasmid/strain combinations. It is clear that the exclusive application of a standardized growth technique e.g., LB-medium at 37 degrees C at an unspecified and uncontrolled aeration level, may lead to wrong conclusions on properties and potentials of now plasmid/strain combinations and may lead to rejection of useful strains or plasmids.


Polynuclear lanthanide hydroxo complexes: new chemical precursors for coordination polymers.
The synthesis of hexanuclear lanthanide hydroxo complexes by controlled hydrolysis led to polymorphic compounds. The hexanuclear entities crystallize in four different ways that depend on the extent of their hydration. The four structures can be described as hexanuclear lanthanide entities with formula [Ln(6)(mu(6)-O)(mu(3)-OH)(8)(NO(3))(6)(H(2)O)(12)](2+). Two additional NO(3)(-) ions intercalate between the hexanuclear entities in order to ensure the electroneutrality of the crystal structure. Some crystallization water molecules fill the intermolecular space. The three first families of compounds (1-3) exhibit crystal structures that have previously been reported. The fourth family of compounds (4) is described here for the first time. Its chemical formula is [Ln(6)(mu(6)-O)(mu(3)-OH)(8)(NO(3))(6)(H(2)O)(12)](NO(3))(2).2H(2)O (Ln = Gd, Er, and Y). In this paper, the chemical and thermal stabilities of the hexanuclear lanthanide compounds are reported together with the magnetic properties of the Gd(III)-containing species. To use these entities as precursors for new materials, the substitution of the nitrato groups by chloride ions has been studied. Two byproduct compounds have so been obtained: The first (compound 5) is a nitrato/chloride hexanuclear compound of chemical formula [Er(6)(mu(6)-O)(mu(3)-OH)(8)(NO(3))(6)(H(2)O)(12)](NO(3))Cl.2H(2)O. The second one (compound 6) is a polymeric compound in which the hexanuclear entities are linked by an unexpected and original N(2)O(4) bridge. Its chemical formula is [Er(6)(mu(6)-O)(mu(3)-OH)(8)(NO(3))(4)(H(2)O)(11)(OH)(ONONO(2))]Cl(3).2H(2)O. Its crystal structure can be described as the juxtaposition of chainlike molecular motifs. To the best of our knowledge, this is the first example of a coordination polymer synthesized from an isolated polylanthanide hydroxo complex.


A decision analytic approach to a futility analysis of a phase II pharmaceutical study.
In this paper we describe a decision analytic approach to doing a futility analysis of a phase II study on a drug under development. For this analysis we build a model that estimates the expected monetary value of the drug and the expected costs of development. These statistics are used to help decide whether to continue the study.


Efficacy and Tolerability Evaluation of a Nutraceutical Composition Containing Vitex agnus-castus Extract (EVX40™), Pyridoxine, and Magnesium in Premenstrual Syndrome: A Real-World, Interventional, Comparative Study.
Background Pre-menstrual syndrome (PMS) is a condition associated with altered hormone levels during the menstrual phase of females and is characterised by physical, emotional, and behavioural symptoms that have a negative impact on the quality of life of females. The symptoms of PMS may vary between individuals, but the major complication is pain, especially during menstrual days. The current treatment strategy involves the use of hormonal therapies and analgesics for symptomatic relief, but these therapies have a risk of potential side effects. The use of herbal and nutraceutical supplements in PMS conditions is increasing due to their long-term safety and proven efficacy. The current real-world study aimed to evaluate the efficacy and tolerability of Ezedayz® tablets containing Vitex agnus-castus extract (EVX40™), vitamin B6, and magnesium in PMS subjects. Methodology A real-world, open-label study was conducted involving 64 participants with varied severity of PMS symptoms. Participants were categorised into Group A (N=23) receiving standard therapies, Group B (N=20) receiving Ezedayz® tablets, or Group C (N=21) receiving standard and Ezedayz® therapy. Standard therapies were provided as per physician supervision, and Ezedayz® tablets were given for 90 days. All subjects were evaluated on core symptoms of PMS like menstrual backache, menstrual cramps, joint or muscle pain, and headache using the numerical rating scale (NRS), and quality-of-life (QoL) was evaluated using a QoL questionnaire. A spontaneous reporting methodology was used to evaluate the tolerability of the therapies provided. Statistical analysis was performed as per the statistical plan. A p-value of <0.05 was considered statistically significant. Results Out of 64 participants, five were lost to follow-up, and the data of 59 participants were included in the final analysis. All groups showed improvement in all evaluated parameters, but Group B and Group C showed greater improvement at the end of the study in all evaluated parameters. The quality-of-life assessment revealed greater improvement in Group B and Group C participants compared to Group C in all evaluated QoL parameters. No serious side effects were observed in any subjects. Conclusion The results of the current study conclude that the nutraceutical composition of Vitex agnus-castus extract, vitamin B6, and magnesium is effective in reducing the severity of PMS symptoms and improving the quality of life of PMS subjects. The nutraceutical therapy provided greater relief from PMS symptoms compared to standard therapy alone, and this effect was augmented when the nutraceutical therapy was provided in combination with standard therapies. Similarly, the improvement in quality-of-life parameters was greater in subjects treated with nutraceuticals alone or in combination therapy. Despite the limitations of the study, the results of the current study are promising, and the nutraceutical composition (Ezedayz®) can be effectively used in clinical settings to control symptoms and improve the quality of life of PMS patients.


Thyroglobulin synthesis of oxyphilic cells in various types of neoplastic and autoimmune thyroid diseases.
To determine the content of thyroglobulin in oxyphilic cells of the thyroid, which have been considered as non-thyroglobulin producing cells, the degree of stainability of the various oxyphilic cells for thyroglobulin was compared with that of non-oxyphilic follicular cells in either same or different lesion. A total of 13 oxyphilic lesions, including three follicular adenomas containing oxyphilic cell nodules, four pure oxyphilic cell adenomas, and six Hashimoto's thyroiditis were compared with 16 of non-oxyphilic lesions such as, seven follicular adenomas, four chronic lymphocytic thyroiditis, and five Graves' disease. Many oxyphilic cells stained positively for thyroglobulin regardless of their morphologic variation, but less intensely than the usual follicular cells in follicular adenomas, chronic lymphocytic thyroiditis, and Graves' disease. The stainability of oxyphilic cells for thyroglogulin did not show any significant correlation with morphologic features, whereas in follicular adenomas, the non-oxyphilic follicular cells forming microfollicles stained less strongly for thyroglobulin than the same cells lining large mature follicles in a reproducible way. With above findings, we concluded that oxyphilic cells maintain the functional activity in terms of thyroglobulin synthesis, although the content of the thyroglobulin is less than that of non-oxyphilic colloid forming follicular cells.


Vitamin D, a Secosteroid Hormone and Its Multifunctional Receptor, Vitamin D Receptor, in Alzheimer's Type Neurodegeneration.
Vitamin D is a secosteroid hormone exerting neurosteroid-like properties. Its well-known nuclear hormone receptor, and recently proposed as a mitochondrial transcription factor, vitamin D receptor, acts for its primary functions. The second receptor is an endoplasmic reticulum protein, protein disulfide isomerase A3 (PDIA3), suggested to act as a rapid response. Vitamin D has effects on various systems, particularly through calcium metabolism. Among them, the nervous system has an important place in the context of our subject. Recent studies have shown that vitamin D and its receptors have numerous effects on the nervous system. Neurodegeneration is a long-term process. Throughout a human life span, so is vitamin D deficiency. Our previous studies and others have suggested that the out-come of long-term vitamin D deficiency (hypovitaminosis D or inefficient utilization of vitamin D), may lead neurons to be vulnerable to aging and neurodegeneration. We suggest that keeping vitamin D levels at adequate levels at all stages of life, considering new approaches such as agonists that can activate vitamin D receptors, and utilizing other derivatives produced in the synthesis process with UVB are crucial when considering vitamin D-based intervention studies. Given most aspects of vitamin D, this review outlines how vitamin D and its receptors work and are involved in neurodegeneration, emphasizing Alzheimer's disease.


Evidence-based dentistry resources for dental practitioners.
The American Dental Association has taken an active role in support of an evidence-based approach to the practice of dentistry. This concept integrates clinically relevant scientific evidence into a clinician's decision-making process, along with the patient's oral and medical history, the dentist's own expertise and the patient's treatment needs and preferences. The purpose of this article is to assist dentists in locating and retrieving quality research reports and research evidence which can be integrated into the clinical decision making process. The research methodologies which constitute the foundation of evidence-based dentistry are described. The advantages and disadvantages associated with literature that summarizes research, such as the literature review, the systematic review and meta-analysis are described. Evidence-based resources for dentists are described, such as journals specializing in an evidence-based approach, online resources such as PubMed and the Cochrane Collaboration.


Atopy Does Not Influence the Clinical Outcome of Acute Urticaria: A Retrospective Study.
Acute urticaria (AU) may be associated with atopy, but the relationship between atopic status and the clinical features of the disease has not been fully described. The aim of the study was to determine the proportion of atopy in AU patients and to see whether atopy is related to the clinical characteristics of AU and whether it has an impact on the outcome of the disease. A retrospective analysis of patients with AU was performed. Demographic data, clinical features, and laboratory results were compared and analyzed between the atopic and non-atopic AU (napAU). In total, 139 participants were included. 54 (38.8%) patients were atopic AU (apAU) and 85 (61.2%) were napAU. Compared with napAU patients, apAU patients were more likely to have anaphylaxis, higher levels of C4, and lower levels of antistreptolysin. There were no significant differences between the two groups in terms of other clinical features, laboratory tests, the natural course of the disease, or disease outcomes. Atopy does exist in some patients with AU, and AU patients with an atopic background are at higher risk for anaphylaxis. Atopy does not influence the clinical outcome of AU and is not correlated with other clinical features and laboratory results of AU.


Examining influencing factors of express delivery stations' spatial distribution using the gradient boosting decision trees: A case study of Nanjing, China.
Online shopping has promoted the development of logistics and express delivery businesses. Express delivery stations are closely related to residents' daily lives, and it is an important topic for the study of urban consumption space and commercial service space. This paper analyzed the factors influencing the spatial distribution of terminal logistics space (express delivery stations) in the process of online shopping. The gradient boosting decision trees (GBDT) was selected for analyzing the factors influencing the distribution of express delivery stations. The results demonstrated that express delivery stations' distribution is mainly influenced by commercial retail and residential neighborhoods, showing a clustering toward consumer spaces and residential areas. This paper studied the association between express delivery stations and other functional spaces in the city, and established an analytical framework for the factors influencing the spatial distribution of express delivery stations. The research results help to improve the rationality and effectiveness of the setting and management of the terminal logistics space in the online shopping process.


Laparoscopic Splenectomy in Patients With Spleen Injuries.
Spleen injury appears in 10% to 30% of abdominal trauma patients. Mortality among the patients in the last 20 years remains high (6% to 7%) and shows no tendency to decline. Nowadays nonoperative management is widely accepted management of patients with low-grade spleen injury, whereas management of patients with high-grade spleen injury (III and higher) is not so obvious. There are 3 methods exist in treatment of such patients: conservative (with or without angioembolization), spleen-preserving operations, and splenectomy. Today laparoscopic splenectomy is not a widely used operation and only few studies reported about successful use of laparoscopic splenectomy in patients with spleen injury.The aim of the study was to determine indications and contraindications for laparoscopic splenectomy in abdominal trauma patients and to analyze results of the operations. The study involved 42 patients with spleen injury grade III who were admitted in our institute in the years of 2010 to 2014. The patients were divided in 2 groups. Laparoscopic splenectomy was performed in 23 patients (group I) and "traditional" splenectomy was carried out in 19 patients (group II). There was no difference in the demographic data and trauma severity between the 2 groups. Noninvasive investigations, such as laboratory investigations, serial abdominal ultrasound examinations, x-ray in multiple views, and computed tomography had been performed before the decision about necessity of an operation was made. Patients after laparoscopic operations had better recovering conditions compared with patients with the same injury after "traditional" splenectomy. Neither surgery-related complications nor mortalities were registered in both groups. Laparoscopic splenectomy was more time-consuming operation than "traditional" splenectomy. We suggest that as experience of laparoscopic splenectomy is gained the operation time will be reduced. Laparoscopic splenectomy is a safe feasible operation in patients with spleen injury. The operation is indicated in patients with spleen laceration >3 cm of parenchymal depth with moderate continuing bleeding or expanding hematoma and contraindicated in patients with hemodynamic instability and high bleeding rate (>500 mL/h on serial ultrasound examinations).


Comparison of Optic Nerve Head Blood Flow Autoregulation among Quadrants Induced by Decreased Ocular Perfusion Pressure during Vitrectomy.
The present study aimed to examine changes in optic nerve head (ONH) blood flow autoregulation in 4 quadrants (superior, nasal, inferior, and temporal) with decreased ocular perfusion pressure (OPP) during vitrectomy in order to determine whether there is a significant difference of autoregulatory capacity in response to OPP decrease at each ONH quadrant. This study included 24 eyes with an epiretinal membrane or macular hole that underwent vitrectomy at Toho University Sakura Medical Center. Following vitrectomy, the tissue mean blur rate (MBR), which reflects ONH blood flow, was measured. Mean tissue MBRs in the four quadrants were generated automatically in the software analysis report. Measurements were conducted before and 5 and 10 min after intraocular pressure (IOP) elevation of approximately 15 mmHg in the subjects without systemic disorders. The baseline tissue MBR of the temporal quadrant was significantly lower than that of the other 3 quadrants (all P < 0.05). However, the time courses of tissue MBR in response to OPP decrease were not significantly different among the four quadrants during vitrectomy (P = 0.23). There is no significant difference in the autoregulatory capacity of the four ONH quadrants in patients without systemic disorders during vitrectomy.


Anomalies of the lumbosacral nerve roots. An anatomical investigation and myelographic study.
Lumbosacral nerve root anomalies have been documented in the literature for over 30 years; however, no significant quantitative studies have been undertaken so far. We describe parallel studies of 100 cadaveric specimens and an equal number of metrizamide myelograms. The anatomical specimens were prepared by wide deroofing of the lumbar canal to permit precise examination of individual nerve roots and their intradural and extradural connections. The incidence of nerve root anomalies was 14%, the L5-S1 level being most commonly involved. In sharp contrast the incidence of nerve root anomalies determined by myelography was only 4%. The anomalies were classified into four groups and the diagnostic and practical implications of our findings are discussed.


High-Throughput Assay for Enantiomeric Excess Determination in 1,2- and 1,3-Diols and Direct Asymmetric Reaction Screening.
A simple and efficient method for determination of the yield, enantiomeric/diasteriomeric excess (ee/de), and absolute configuration of crude chiral diols without the need of work-up and product isolation in a high throughput setting is described. This approach utilizes a self-assembled iminoboronate ester formed as a product by dynamic covalent self-assembly of a chiral diol with an enantiopure fluorescent amine such as tryptophan methyl ester or tryptophanol and 2-formylphenylboronic acid. The resulting diastereomeric boronates display different photophysical properties and allow for fluorescence-based ee determination of molecules containing a 1,2- or 1,3-diol moiety. This method has been utilized for the screening of ee in a number of chiral diols including atorvastatin, a statin used for the treatment of hypercholesterolemia. Noyori asymmetric hydrogenation of benzil was performed in a highly parallel fashion with errors <1 % ee confirming the feasibility of the systematic examination of crude products from the parallel asymmetric synthesis in real time and in a high-throughput screening (HTS) fashion.


Age-related changes in murine myometrial transcript profile are mediated by exposure to the female sex hormones.
In humans, the risk of operative first delivery increases linearly with maternal age. We previously hypothesized that prolonged, cyclical, prepregnancy exposure to estrogen and progesterone contributes to uterine aging. Here, we test this hypothesis. Myometrium was obtained from four groups of virgin mice: (i) 10- to 12-week- and 28- to 30-week-old mice; (ii) 10- to 12-week- and 38- to 40-week-old mice; (iii) 38-week-old mice that had an ovariectomy or sham operation early in life; (iv) 38-week-old mice that had been treated with progesterone or vehicle containing implants from 8 to 36 weeks. Transcript profiling was carried out using Affymetrix Gene ST 1.1 arrays, and data were normalized. We identified 60 differentially regulated transcripts associated with advancing age (group 1). We validated these changes in group 2 (P for overlap = 5.8 × 10(-46) ). Early ovariectomy prevented the age-related changes in myometrial transcript profile. Similarly, progesterone-mediated long-term ovarian suppression prevented the age-related changes in myometrial transcript profile. Interferon regulatory factor 7 (Irf7) mRNA was regulated by age and hormonal exposure, and was identified as a predicted regulator of the other differentially expressed transcripts by both promoter sequence and canonical pathway activation analysis (P = 8.47 × 10(-5) and P < 10(-10) , respectively). Immunohistochemistry demonstrated IRF7 in both mouse and human myometrium. We conclude the following: (i) Myometrial aging in mice is associated with reproducible changes in transcript profile; (ii) these changes can be prevented by interventions which inhibit cyclical changes in the female sex hormones; and (iii) IRF7 may be an important regulator of myometrial function and aging.


Demographics and Clinical Presentations of Patients Visiting the Emergency Department During the Holy Month of Ramadan: A Three-Year Retrospective Study in a Muslim-Majority Country.
Background and objective Ramadan is the Muslim's holiest month; it is a time when believers engage in special practices that include fasting from dawn till dusk and making cultural and dietary modifications in their everyday lives. The impact of Ramadan on human activity, sleeping patterns, and circadian rhythms of hormones have been addressed in the literature. Fasting, which constitutes the main pillar of practices during Ramadan and lasts from sunrise to sunset, can significantly affect common health conditions, leading many to seek medical care in the Emergency Department (ED). Hence, it is important to understand the pattern of ED visits and understand the impact caused by fasting during this holy month in a Muslim-majority country. In light of this, this study aimed to gather new insights into the pattern of ED visits during Ramadan at a busy tertiary care center in the period from 2019 to 2021. Methods This study was conducted by reviewing the hospital health information system to gather relevant information in May 2022. Data of patients who visited the ED during Ramadan were collected, as well as during a month prior to and after Ramadan for the purpose of comparison. Sociodemographic characteristics and clinical profiles were collected for analysis. Results The total number of ED visits in the three months of Ramadan during the study period (three years) was 33,142, all of which were included in our analysis. Sociodemographic data were analyzed for patients who visited the ED during the month of Ramadan and the two lunar months that precede and succeed Ramadan (Shaban and Shawal). Fever was the most common complaint (16.5%), followed by abdominal pain (14%). When analyzing the findings based on patient age groups, fever was found to be the most prevalent complaint in both adults (15.6%) and pediatric patients (34.4%). Of the total ED patient visits, 7,527 patients were admitted for further care, and 197 patients deceased. Conclusion Our study findings illustrate the change in ED visit patterns during the month of Ramadan in a Muslim-majority country. Also, the type of complaints was affected significantly due to the ongoing coronavirus disease 2019 (COVID-19) pandemic during the study period. The outcomes in patients reflected substantial progress and outcomes in the ED. These findings highlight that analyzing ED data can help provide accurate information that can be used to help modify/adjust the quality of services provided in the ED. However, these modifications may affect all hospital facilities, not just the ED.


Undifferentiated carcinoma of the nasopharynx: a light and electron microscopical study.
Light microscopical study of 29 cases of undifferentiated carcinoma of the nasopharynx showed evidence or origin of the tumour cells from overlying epithelium in 10 cases. In all cases the tumour cells had a distinctive cellular appearance of 'empty' chromatin deficient nuclei, prominent nucleoli and indefinite cytoplasmic margins. Electron microscopy indicated desmosomes and poorly defined tonofilaments in addition to the above cytoplasmic features. Undifferentiated carcinoma of the nasopharynx shows characteristic light and electron microscopic features which indicate that the tumour cells take origin from squamous epithelium, but are of an extreme degree of dedifferentiation.


[Bourneville's tuberous sclerosis].
Among the group of hereditary histodysplasia, Bourneville's tuberous sclerosis demonstrate original and important place. Its clinical and histopathological polymorphism make more difficult the diagnosis because many symptoms are non specific and/or appeared at different age of life. The variability of the expression and of the penetrance are a very serious unpeachement for the genetic counselling. A recent reevaluation of several series of case reports seems to demonstrate that the frequency of new mutations has been probably surestimated. The gene location in 9q3-4 is quite certain and will induce soon the possibility of a more efficient prenatal diagnosis. The gene action mechanism at the embryonic development is probably correlated with the "oncogene character" of the specific mutation.


Development of a Patient-Specific Finite Element Model for Predicting Implant Failure in Pelvic Ring Fracture Fixation.
Introduction. The main purpose of this study is to develop an efficient technique for generating FE models of pelvic ring fractures that is capable of predicting possible failure regions of osteosynthesis with acceptable accuracy. Methods. Patient-specific FE models of two patients with osteoporotic pelvic fractures were generated. A validated FE model of an uninjured pelvis from our previous study was used as a master model. Then, fracture morphologies and implant positions defined by a trauma surgeon in the preoperative CT were manually introduced as 3D splines to the master model. Four loading cases were used as boundary conditions. Regions of high stresses in the models were compared with actual locations of implant breakages and loosening identified from follow-up X-rays. Results. Model predictions and the actual clinical outcomes matched well. For Patient A, zones of increased tension and maximum stress coincided well with the actual locations of implant loosening. For Patient B, the model predicted accurately the loosening of the implant in the anterior region. Conclusion. Since a significant reduction in time and labour was achieved in our mesh generation technique, it can be considered as a viable option to be implemented as a part of the clinical routine to aid presurgical planning and postsurgical management of pelvic ring fracture patients.


Balloon crush: treatment of bifurcation lesions using the crush stenting technique as adapted for transradial approach of percutaneous coronary intervention.
The recent advent of drug-eluting stents has allowed the crush stenting technique to be adopted, thus simplifying the treatment of bifurcation coronary artery lesions. However, this can only be achieved in 7 Fr or greater guiding catheters, hence precluding most transradial percutaneous coronary interventions that are usually undertaken using 6 Fr or less guiding catheters. We assessed the feasibility of balloon stent crush as a stepwise procedure in achieving bifurcation crush stenting in 6 Fr transradial percutaneous coronary interventions. Since it is not possible to place two stents through a 6 Fr guiding catheter, we have adapted the crush stenting technique by initially placing a stent in the side branch and a balloon in the main vessel. The side branch stent is then deployed against the main vessel balloon that is later inflated, crushing the side branch stent within the main vessel. The main vessel is then stented and the side branch recrossed for kissing inflations. Seven patients (five males; age range, 47-78 years) with bifurcation lesions were treated using the above-described technique without major complications. Balloon crush of the side branch stent were successfully achieved in all cases without balloon trapping. In six cases where side branch recrossing was attempted, all were successful and kissing balloon inflations were undertaken in five cases. We have demonstrated that the modified crush stenting technique is feasible and can be safely adapted for use in a 6 Fr transradial percutaneous coronary intervention approach.


Microbiological parameters as indicators of compost maturity.
The objectives of this study were to determine the changes of microbial properties of pig manure collected from pens with different management strategies and composted using different turning and moisture regimes; relate their association with humification parameters and compost temperature; and identify the most suitable microbial indicators of compost maturity. Six different microbial parameters, including total bacterial count, oxygen consumption rate, ATP content, dehydrogenase activity, and microbial biomass C and N, along with humification parameters [humic acid (HA), fulvic acid (FA) and HA : FA ratio] and compost temperature were monitored during composting. Significant positive correlations were found between temperature and microbial properties, including O2 consumption rate, ATP content, dehydrogenase activity, and microbial biomass N. The humification parameters also showed significant correlations with microbial properties of the manure compost. For instance, HA contents of pig manures was positively correlated with total aerobic heterotrophs, and microbial biomass N and C; and negatively correlated with O2 consumption rate, ATP content, and dehydrogenase activity. Among the six microbial parameters examined, dehydrogenase activity was the most important factor affecting compost temperature and humification parameters. Composting strategies employed in this study affected the speed of composting and time of maturation. If the moisture content is maintained weekly at 60% with a 4-day turning frequency, the pig manure will reach maturity in 56 days. The composting process went through predictable changes in temperature, microbial properties and chemical components despite differences in the initial pig manure and composting strategies used. Among the six microbial parameters used, dehydrogenase activity is the most suitable indicator of compost maturity. Compared with respiration rate, ATP content and microbial biomass procedures, dehydrogenase activity is the simplest, quickest, and cheapest method that can be used to monitor the stability and maturity of composts. The results presented here show that microbial parameters can be used in revealing differences between composts and compost maturity. The statistical relationship established between humification parameters and microbial parameters, particularly dehydrogenase activity, demonstrates that it is possible to monitor the composting process more easily and rapidly by avoiding longer and more expensive analytical procedures.


Malignant melanoma within an intradermal nevus.
We describe a case of malignant "dermal" melanoma that arose within a preexisting intradermal nevus. Clinically, the lesion had recently enlarged. Histologically, two patterns were noted. One was an intradermal nevus in the upper portion of the dermis; the other was a deeper nodule composed of malignant neoplastic cells that extended into the reticular dermis. No melanocytic epidermal junctional activity was noted. Despite careful clinical investigation, no alternative primary source was found. Neoplastic transformation of the intradermal nevus without junctional activity is our proposed interpretation of the lesion's histology. Immunohistochemical stains demonstrated that the deeper dermal neoplastic cells were positive for both HMB-45 and PCNA, whereas the superficial nevoid-appearing cells were negative; these findings support our postulate that this melanoma arose within an intradermal nevus. It is important to distinguish this neoplasm from other diagnostic possibilities, including a metastatic lesion originating from another site.


Electrochemical deposition of ZnO nanostructures. mechanism of growth.
The growth kinetics of ZnO nanorods were studied by means of an electrochemical deposition process on ITO electrodes submerged in an aqueous solution of 5 mM ZCl+0.1 M KCl at 80 degrees C. The stages of the growth kinetics showed a mechanism of formation of nano-spheres which with time were transformed into hexagonal crystals of ZnO. Cathodic current densities of 0.1 to 1 mAcm2 formed hexagonal columns of 800 nm thickness while stronger currents formed a high-density layer of cylindrical nanorods 80 nm in diameter. An amorphous barrier layer was found between the surface of the electrode and the base of the nano-columns. The conditions assayed showed the possibility of adjusting the morphological characteristics of the layer in order to obtain different properties in different applications.


[Analysis of risk factors and prognosis for bleeding in very old male patients with stage 5 chronic kidney disease].
Objective: To analyze the risk factors and prognosis of bleeding in very old male patients with stage 5 chronic kidney disease (CKD). Methods: The clinical data of 143 very old male patients with stage 5 CKD was retrospectively analyzed. According to the occurrence of bleeding, the patients were divided into two groups including the hemorrhage group and the non-hemorrhage group. The history of diseases, renal function, blood cell parameters and coagulation index were compared and analyzed between the two groups. The prognosis of patients with a period of 12 months was studied. Results: Among 143 patients, 67 cases (46.85%) suffered bleeding, and the other 76 patients (53.15%) were without bleeding. The age[(89±4) vs (87±5) years, P=0.02], pulmonary infection (32.84% vs 9.21%, P<0.001), activated partial thromboplastin time[(40.86±8.02) vs (38.41±5.72) s, P=0.036], fibrinogen[(4.09±0.75) vs (3.62±0.67) g/L, P<0.001], blood urea nitrogen (BUN)[(37.19±10.66) vs (32.86±8.97)mmol/L, P=0.009]were significantly increased in the hemorrhage group compared with the non-hemorrhage group. Multivariate logistic regression analysis showed that the incidence of pulmonary infection (OR=0.286, P=0.014), lower levels of mean platelet volume (OR=1.290, P=0.048), higher levels of fibrinogen (OR=0.444, P=0.004), BUN (OR=0.959, P=0.034) and systolic blood pressure (OR=0.970, P=0.013) were the independent risk factors of bleeding in the very old male patients with stage 5 CKD (P<0.05). All patients were followed up for 12 months. The proportion of all causes of death at the 3rd month, and bleeding events at the 3rd or 12th month, and recurrent major bleeding events at the 12th month were significantly higher in the hemorrhage group than those in the non-hemorrhage group. Conclusions: Very old male patients with stage 5 CKD are prone to bleeding complications, and have more possibilities to bleed again. Pulmonary infection, average volume of blood platelet, fibrinogen, BUN, and systolic blood pressure were the independent risk factors of bleeding in these patients.


The oral gram-negative anaerobic microflora in young children: longitudinal changes from edentulous to dentate mouth.
Eruption of primary teeth has a great influence on the oral environment by providing suitable niches for bacterial colonization. The composition of oral gram-negative anaerobic microflora was investigated in 21 young children (mean age 32 months) with primary dentition. The bacterial findings of samples were compared with those of the same children collected at their edentulous infant period (mean age 3 months). During the primary period, 2 samples were collected from each child: a sample with dental floss from gingival margin of 2 teeth and stimulated saliva pooled with a mucosal swab sample. Both samples were cultured aerobically and anaerobically using nonselective and selective media. Prevotella melaninogenica, nonpigmented Prevotella spp., Fusobacterium nucleatum group and Capnocytophaga spp. were found in all children at the older age, whereas they occurred in edentulous mouth in 76%, 62%, 67% and 19%, respectively. The occurrence of Prevotella loescheii increased from 14% to 90%, Prevotella intermedia from 10% to 67%, Leptotrichia spp. from 24 to 71%, Campylobacter (Wolinella) spp. from 5 to 43% and Eikenella corrodens from 5 to 57%. Only the occurrence of Bacteroides gracilis and Veillonella spp. remained at about the same level. Species not isolated from the edentulous mouth, such as Prevotella denticola, Fusobacterium spp. other than the F. nucleatum group and Selenomonas spp. were now detected in 71%, 71% and 43% of the children. The stability of the colonizing P. melaninogenica strain(s) in the oral cavity was determined by using ribotyping; 1-2 isolates per child from the edentulous infant period of 9 children and 3-15 isolates per child from their primary dentition period were analyzed.(ABSTRACT TRUNCATED AT 250 WORDS)


Stepwise Evolution of Coral Biomineralization Revealed with Genome-Wide Proteomics and Transcriptomics.
Despite the importance of stony corals in many research fields related to global issues, such as marine ecology, climate change, paleoclimatogy, and metazoan evolution, very little is known about the evolutionary origin of coral skeleton formation. In order to investigate the evolution of coral biomineralization, we have identified skeletal organic matrix proteins (SOMPs) in the skeletal proteome of the scleractinian coral, Acropora digitifera, for which large genomic and transcriptomic datasets are available. Scrupulous gene annotation was conducted based on comparisons of functional domain structures among metazoans. We found that SOMPs include not only coral-specific proteins, but also protein families that are widely conserved among cnidarians and other metazoans. We also identified several conserved transmembrane proteins in the skeletal proteome. Gene expression analysis revealed that expression of these conserved genes continues throughout development. Therefore, these genes are involved not only skeleton formation, but also in basic cellular functions, such as cell-cell interaction and signaling. On the other hand, genes encoding coral-specific proteins, including extracellular matrix domain-containing proteins, galaxins, and acidic proteins, were prominently expressed in post-settlement stages, indicating their role in skeleton formation. Taken together, the process of coral skeleton formation is hypothesized as: 1) formation of initial extracellular matrix between epithelial cells and substrate, employing pre-existing transmembrane proteins; 2) additional extracellular matrix formation using novel proteins that have emerged by domain shuffling and rapid molecular evolution and; 3) calcification controlled by coral-specific SOMPs.


Homovanillic acid and 5-hydroxyindoleacetic acid levels in cerebrospinal fluid of patients with progressive myoclonus epilepsy.
The possibility of disturbed dopamine and serotonin metabolism in the progressive myoclonus epilepsy (PME) occurring in Finland (a type of PME without Lafora bodies) was examined. Both basal concentrations of HVA and 5-HIAA in the CSF and their increase after oral probenecid administration were studied in 19 PME patients and in 19 age- and sex-matched control patients. The control patients had grand mal epilepsy but not myoclonus or ataxia. The basal value of HVA was significantly reduced and that of 5-HIAA was also slightly reduced in the PME patients as compared to the values of the epileptic controls or to those of 26 nonepileptic controls. The concentrations of HVA and 5-HIAA also seemed to correlate with the severity of the PME. The most severely affected patients had generally the lowest values. After oral probenecid this trend was also seen when the increases of HVA and 5-HIAA were expressed per microgram CSF probenecid, i.e. the mildly affected PME group showed higher increases in response to probenecid than the most severely affected PME group. The PME patients had higher probenecid levels in the CSF than the epileptic controls.


NF-κB signaling is activated and confers resistance to apoptosis in three-dimensionally cultured EGFR-mutant lung adenocarcinoma cells.
Epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells in suspension undergo apoptosis to a greater extent than adherent cells in a monolayer when EGFR autophosphorylation is inhibited by EGFR tyrosine kinase inhibitors (TKIs). This suggests that cell adhesion to a culture dish may activate an anti-apoptotic signaling pathway other than the EGFR pathway. Since the microenvironment of cells cultured in a monolayer are substantially different to that of cells existing in three-dimension (3D) in vivo, we assessed whether two EGFR-mutant lung adenocarcinoma cell lines, HCC827 and H1975, were more resistant to EGFR TKI-induced apoptosis when cultured in a 3D extracellular matrix (ECM) as compared with in suspension. The ECM-adherent EGFR-mutant cells in 3D were significantly less sensitive to treatment with WZ4002, an EGFR TKI, than the suspended cells. Further, a marked degradation of IκBα, the inhibitor of nuclear factor (NF)-κB, was observed only in the 3D-cultured cells, leading to an increase in the activation of NF-κB. Moreover, the inhibition of NF-κB with pharmacological inhibitors enhanced EGFR TKI-induced apoptosis in 3D-cultured EGFR-mutant cells. These results suggest that inhibition of NF-κB signaling would render ECM-adherent EGFR-mutant lung adenocarcinoma cells in vivo more susceptible to EGFR TKI-induced cell death.


TEL/AML1-positive patients lacking TEL exon 5 resemble canonical TEL/AML1 cases.
The TEL/AML1 fusion gene which represents the most frequent genetic abnormality in childhood ALL, usually results from genomic breakpoints in TEL intron 5 and AML1 intron 1 or 2. At the protein level, the helix-loop-helix domain and exon 5-coded central region of TEL are typically fused to almost entire AML1 including DNA-binding domain. We identified two ALL patients with genomic breakpoints within TEL intron 4 resulting in variant TEL/AML1 fusion lacking the TEL exon 5-coded central region. This region was supposed to play an important role in TEL/AML1 function, particularly in TEL/AML1-mediated transcriptional repression of AML1 targets. We aimed at investigating the impact of the loss of this region on disease behavior and TEL/AML1 function. We compared clinical and biological characteristics, treatment response, and outcome of the variant versus classical TEL/AML1 cases, analyzed genome wide gene expression profiles and performed reporter gene assay. No distinct differences between variant and classical TEL/AML1 cases were observed including gene expression profiling and detailed immunophenotyping. By using reporter gene assay, we showed that the loss of the central region does not influence the TEL/AML1-mediated transcriptional repression. The deletion of the central region did not affect the TEL/AML1-specific phenotype; we did not find any relevant differences in clinical and biological features when variant versus classical TEL/AML1-positive cases were compared. Thus, our data does not support hypothesis that the central region of TEL is indispensable for TEL/AML1 driven leukemogenesis.


Fast and Simple Determination of 3-Aminopiperidine without Derivatization Using High Performance Liquid Chromatography-Charged Aerosol Detector with an Ion-Exchange/Reversed-Phase Mixed-mode Column.
A sensitive non-derivatization method for the determination of the highly polar compound 3-aminopiperidine was developed using a mixed-mode column combined with a charged aerosol detector (CAD). Chromatographic conditions, including the type of detector, separation mode, and mobile phase composition, were optimized to achieve high sensitivity towards and sufficient retention of 3-aminopiperidine. Compared to the precolumn derivatization UV method, the current method showed higher recovery and greater simplicify. High sensitivity (LOQ <2.73 μg mL-1) and good precision (RSD of peak area <2%) were also observed in the current method. Furthermore, the parameters such as buffer solution and column bleed that affected the sensitivity of the CAD were investigated. Finally, the current method was applied for the determination of 3-aminopiperidine in linagliptin samples. This is a new non-derivative for the determination of 3-aminopiperidine, and constitutes a novel application of the CAD for the quantitative analysis of highly polar basic compounds.


Vasculitic neuropathy.
Patients with vasculitic neuropathy may present with either mononeuritis multiplex, or a symmetrical or asymmetrical sensorimotor neuropathy. In those patients whose neuropathy is part of a systemic vasculitis the neuropathy can be expected to improve leaving only mild or moderate functional disability. Nevertheless, the long-term outlook for such patients is poor with a 5-year survival of around 50% with most excess deaths being due to vascular disease. The prognosis in non-systemic vasculitic neuropathy is almost certainly substantially better than this. Treatment of vasculitic neuropathy should be based on diagnosis by tissue biopsy, usually of nerve, and early use of aggressive immunosuppression.


Digital micromirror device-based common-path quantitative phase imaging.
We propose a novel common-path quantitative phase imaging (QPI) method based on a digital micromirror device (DMD). The DMD is placed in a plane conjugate to the objective back-aperture plane for the purpose of generating two plane waves that illuminate the sample. A pinhole is used in the detection arm to filter one of the beams after sample to create a reference beam. Additionally, a transmission-type liquid crystal device, placed at the objective back-aperture plane, eliminates the specular reflection noise arising from all the "off" state DMD micromirrors, which is common in all DMD-based illuminations. We have demonstrated high sensitivity QPI, which has a measured spatial and temporal noise of 4.92 nm and 2.16 nm, respectively. Experiments with calibrated polystyrene beads illustrate the desired phase measurement accuracy. In addition, we have measured the dynamic height maps of red blood cell membrane fluctuations, showing the efficacy of the proposed system for live cell imaging. Most importantly, the DMD grants the system convenience in varying the interference fringe period on the camera to easily satisfy the pixel sampling conditions. This feature also alleviates the pinhole alignment complexity. We envision that the proposed DMD-based common-path QPI system will allow for system miniaturization and automation for a broader adaption.


First Draft Genome for a Burkholderia mallei Isolate Originating from a Glanderous Mule from Brazil.
Burkholderia mallei is the etiological agent of glanders. Here, we present the draft genome sequence of Burkholderia mallei strain 16-2438_BM#8 that was isolated from a mule found dead in Pernambuco, northeast Brazil. It is the first available genomic sequence from a strain isolated on the American continent.


Sensitivity and specificity of pulsed Doppler echocardiography in detection of aortic and mitral regurgitation.
In order to assess the value of pulsed Doppler echocardiography in detection of valvular regurgitation, 63 patients were evaluated for aortic and/or mitral regurgitation using pulsed Doppler echocardiography and selective cineangiography. The Doppler study was considered as positive when a turbulent flow was detected below the aortic valve for aortic insufficiency and behind the mitral valve for mitral insufficiency on a graphic display (time interval histogram) when technically adequate and/or on an audiosignal. These results were compared with standard angiographic evaluation of the regurgitation: pulsed Doppler echocardiography had 94% sensitivity and the specificity rate was very high (87.5%) even for mild regurgitation. Thus, Doppler technique is highly specific and sensitive in detection of aortic and mitral regurgitation when both audiosignal and time-interval histogram are simultaneously performed.


Assessment of Cardiac Function--Basic Principles and Approaches.
Increased access and ability to visualize the heart has provided a means to measure a myriad of cardiovascular parameters in real or near real time. However, without fundamental knowledge regarding the basis for cardiac contraction and how to evaluate cardiac function in terms of loading conditions and inotropic state, appropriate interpretation of these cardiovascular parameters can be difficult and can lead to misleading conclusions regarding the functional state of the cardiac muscle. Thus, in this series of Comprehensive Physiology, the basic properties of cardiac muscle function, the cardiac cycle, and determinants of pump function will be reviewed. These basic concepts will then be integrated by presenting approaches in which the effects of preload, afterload, and myocardial contractility can be examined. Moreover, the utility of the pressure-volume relation in terms of assessing both myocardial contractility as well as critical aspects of diastolic performance will be presented. Finally, a generalized approach for the assessment and interpretation of cardiac function within the intact cardiovascular system will be presented.


Genetic determination of phagocytic activity of polymorphonuclear leucocytes.
Sixty-three persons with the known HLA-A, -B, -C, -DR and -Dw antigens were investigated for phagocytic ability, candidacidal activity, respiratory burst values, and the levels of circulating immune complexes, C2, C4, IgG, IgM, and IgA. The investigated persons were divided into the HLA-DR2/Dw2, the HLA-DR3/Dw3 and a control group, members of which possessed neither antigen in question. The phagocytic activity of polymorphonuclear leucocytes ingesting dead cells of C. albicans and the candidacidal activity were found to be significantly lower (P less than 0.02) in the HLA-DR3/Dw3 compared to the control group. The respiratory burst values did not considerably differ in all three groups under study. The levels of circulating immune complexes were higher in both the HLA-DR2/Dw2 and HLA-DR3/Dw3 in comparison with the control group.


Simultaneous Determination of Genotoxic Impurities in Fudosteine Drugs by GC-MS.
A simple, sensitive and reliable gas chromatography mass spectrometry (GC-MS) method has been developed, optimized and validated for the simultaneous determination of 3-chloro-1-propanol (CHP), 1,3-dichloropropane (DCP), 3-chloropropylacetate (CPA) and chloropropyl hydroxypropyl ether (CHE) contents in fudosteine, using chlorobenzene as internal standard. Efficient chromatographic separations were achieved on an Agilent J&W DB-WAXetr, 30 m long with 0.32 mm i.d., 1.0 µm particle diameter column that consists of bonded and cross-linked polyethylene glycol as a stationary phase by passing helium as the carrier gas. The analytes were extracted in dichloromethane and monitored by gas chromatography electron ionization mass spectrometry (GC-EI-MS) with selective ion monitoring (SIM) mode. The performance of the method was assessed by evaluating specificity, precision (repeatability and reproducibility), sensitivity, linearity and accuracy. The limit of detection and limit of quantification established for CHP, DCP, CPA and CHE were in the range of 0.05-0.08 µg mL(-1) and 0.10-0.17 µg mL(-1), respectively. The recoveries for CHP, DCP, CPA and CHE were in the range of 92.0-101.5%. The results proved that the method is suitable for the simultaneous determination of contents of CHP, DCP, CPA and CHE in fudosteine.


Assessment of ventilatory thresholds from heart rate variability in well-trained subjects during cycling.
The purpose of this study was to implement a new method for assessing the ventilatory thresholds from heart rate variability (HRV) analysis. ECG, VO2, VCO2, and VE were collected from eleven well-trained subjects during an incremental exhaustive test performed on a cycle ergometer. The "Short-Term Fourier Transform" analysis was applied to RR time series to compute the high frequency HRV energy (HF, frequency range: 0.15 - 2 Hz) and HF frequency peak (fHF) vs. power stages. For all subjects, visual examination of ventilatory equivalents, fHF, and instantaneous HF energy multiplied by fHF (HF.fHF) showed two nonlinear increases. The first nonlinear increase corresponded to the first ventilatory threshold (VT1) and was associated with the first HF threshold (T(RSA1) from fHF and HFT1 from HF.fHF detection). The second nonlinear increase represented the second ventilatory threshold (VT2) and was associated with the second HF threshold (T(RSA2) from fHF and HFT2 from HF.fHF detection). HFT1 , T(RSA1), HFT2, and T(RSA2) were, respectively, not significantly different from VT1 (VT1 = 219 +/- 45 vs. HFT1 = 220 +/- 48 W, p = 0.975; VT1 vs. T(RSA1) = 213 +/- 56 W, p = 0.662) and VT2 (VT2 = 293 +/- 45 vs. HFT2 = 294 +/- - 48 W, p = 0.956; vs. T(RSA2) = 300 +/- 58 W, p = 0.445). In addition, when expressed as a function of power, HFT1, T(RSA1), HFT2, and T(RSA2) were respectively correlated with VT1 (with HFT1 r2 = 0.94, p < 0.001; with T(RSA1) r2 = 0.48, p < 0.05) and VT2 (with HFT2 r2 = 0.97, p < 0.001; with T(RSA2 )r2 = 0.79, p < 0.001). This study confirms that ventilatory thresholds can be determined from RR time series using HRV time-frequency analysis in healthy well-trained subjects. In addition it shows that HF.fHF provides a more reliable and accurate index than fHF alone for this assessment.


Extension of dental abscess to the orbit.
A week after dental treatment, a dentoalveolar abscess developed in a 14-year-old boy. Surgical intervention was needed to evacuate pus and remove the cause of infection. It is suggested that initially establishing drainage after dental treatment would have prevented the sequela that ensued.


Liposome-mediated augmentation of catalase in alveolar type II cells protects against H2O2 injury.
Oxidant injury to the alveolar epithelium can be mediated by exposure to oxidant gases such as O2 at high concentrations and O3, inflammatory cell-derived reactive O2 species, and the intracellular metabolism of xenobiotics such as paraquat. An in vitro model of alveolar epithelial oxidant injury was developed based on exposure of cultured rat type II pneumocytes to superoxide and hydrogen peroxide (H2O2) enzymatically generated in the culture medium. Cytotoxicity was assessed by the release of lactate dehydrogenase (LDH) into the culture medium, which was a more reliable indicator of damage than release of 51Cr by prelabeled cells. Incubation of cells for 6-8 h with xanthine plus xanthine oxidase and glucose plus glucose oxidase induced the release of greater than 50% of total intracellular LDH. Oxidant exposure also resulted in significant detachment of cells from culture dishes. Modulation of oxidant damage was accomplished using liposomes as vectors for the delivery of catalase. Treatment of cells with catalase liposomes for 2 h resulted in augmentation of cellular catalase specific activities up to 631% of controls. Catalase was partitioned into intracellular and surface-associated compartments in catalase liposome-treated cells. Partial and complete protection against oxidant injury, induced by xanthine plus xanthine oxidase and glucose plus glucose oxidase, respectively, was achieved by pretreatment of cells with catalase liposomes. LDH release during oxidant exposure was inversely related to augmentation of cellular catalase activities. Catalase liposome-treated cells also exhibited an enhanced ability to scavenge enzymatically generated H2O2 from the culture medium. These observations suggest a useful approach to modulation of alveolar injury induced by reactive O2 species.


Footfall patterns, stride length and speed of vertical climbing in spider monkeys (Ateles fusciceps robustus) and woolly monkeys (Lagothrix lagotricha).
Vertical climbing is central to theories surrounding the locomotor specialisations of large primates. In this paper, we present spatiotemporal gait parameters obtained from video recordings of captive spider monkeys (Ateles fusciceps robustus) and woolly monkeys (Lagothrix lagotricha) in semi-natural enclosures, with the aim of discovering the influence of body weight and differences in general locomotor behaviour on vertical climbing kinematics on various substrates. Results show that there are only few differences between gait parameters of climbing on thin trees, vertical and oblique ropes, while climbing on large-diameter trees differs considerably, reflecting the higher costs of locomotion on the latter. At the same speed, Ateles takes longer strides and the support phase takes a smaller percentage of cycle duration than in Lagothrix. Footfall patterns are more diverse in Ateles and include a higher proportion of ipsilateral limb coupling. Compared to other primates, the gait characteristics of vertical climbing of atelines most closely resemble those of African apes.