The tumor volume and clonogen number relationship: tumor control predictions based upon tumor volume estimates derived from computed tomography.
While tumor volume is an important parameter predicting clinical outcome, its relationship to clonogen number remains uncertain. This uncertainty is related to many factors, among them treatment response heterogeneity, which obscures the influence of patients and treatment-related parameters. In this study, we analyze the effect of tumor volume on local and regional recurrence in a setting tightly controlled for dose, treatment time, and patient selection. The hypothesis that changes in clonogen number scale directly with changes in tumor volume is tested. Using digital reconstruction of diagnostic computed tomography (CT) scans, primary and total tumor volumes were estimated in 51 cases of advanced squamous cell carcinoma of the head and neck. All patients were managed with a concomitant boost accelerated superfractionated schedule to a median dose of 70.2 Gy. Clinical data were fitted to a mixture model to relate tumor volume parameters to control probability where volume and clonogen number were related by the relationship m = a.Vb, where m is initial clonogen number, a is a proportionality constant, V is tumor volume, and b is the volume exponent. Tumor volume estimates for primary tumor ranged from 3-196 cm3 and for total tumor volume 5-196 cm3. Actuarial local-regional control is 63%. The estimated volume exponent b is 0.85 (95%, confidence interval (c.i.): 0.40-1.29) for primary tumor volume and 1.1 (95%, c.i.: 0.33-1.85) for total tumor volume. This study quantifies the adverse influence of tumor volume on local-regional disease control in advanced head and neck cancer. The derived volume exponent approximates to one, the theoretical expectation if the growth fraction is roughly constant and clonogen number increases linearly with volume. Finally, these results suggest that radiobiological parameters are more reliably estimated from clinical data with narrowly defined strata.


Pathologic complete response after palliative 3rd line chemotherapy with capecitabine alone in metastatic colorectal cancer.
We report the case of a 46-year-old female who showed excellent clinical outcomes after palliative 3rd line capecitabine monotherapy followed by 2nd liver metastasectomy. She had been diagnosed with colon cancer with liver metastasis and initially treated with synchronous colectomy and liver metastasectomy. But she experienced immediate relapse in liver and received palliative 1st line FOLFIRI and 2nd line FOLFOX, both of which failed to show responses. Capecitabine alone as palliative 3rd line treatment did show clinical response in this patient, indeed, and she received 2nd liver metastasectomy which revealed pathologic complete response. In this report, we intended to emphasize that response to chemotherapy could be an important factor in patients who are potential candidates for metastasectomy and that catching the very moment of repeated metastasectomy is in the state of the art.


Fluoroquinolones versus beta-lactam based regimens for the treatment of osteomyelitis: a meta-analysis of randomized controlled trials.
A meta-analysis of randomized control trials. To compare fluoroquinolones to beta-lactams for the treatment of osteomyelitis. Treatment of osteomyelitis remains a real challenge in medicine necessitating the use of broad-spectrum antibiotics, because of the variety of the pathogens causing the infection and the fact that the infected bone may become necrotic and avascular, preventing systemic antibiotics from adequately penetrating to the infection site. A literature search was performed by 2 reviewers independently (PubMed database and the Cochrane Central Register of Controlled Trials). We identified 7 studies eligible for inclusion in our meta-analysis; ciprofloxacin, ofloxacin, and pefloxacin were used in 3, 3, and 1 study, respectively, while various beta-lactams (mainly in the intravenous form) were used as comparators. There was no difference in treatment success for osteomyelitis between fluoroquinolones and beta-lactams [194 patients, fixed effect model (FEM), odds ratio (OR) = 0.99, 95% confidence interval (CI) 0.51-1.91], bacteriological success (201 isolates, FEM, OR = 0.88, 95% CI = 0.45-1.70), superinfections (173 patients, FEM, OR = 1.75, 95% CI = 0.63-4.90), relapses (153 patients, FEM, OR = 1.23, 95% CI = 0.46-3.31), or adverse events (170 patients, FEM, OR = 0.47, 95% CI = 0.21-1.06). Fluoroquinolones are as effective as beta-lactams for the treatment of osteomyelitis and can be considered as a useful alternative in the physician's armamentarium. The value of fluoroquinolones for the treatment of osteomyelitis lies in the fact that they can be administered in an outpatient setting. However, they should be used with caution, so as to preserve their activity against increasingly resistant bacteria.


Factors contributing to global cognitive impairment in heart failure: results from a population-based cohort.
Heart failure (HF) and cognitive impairment are both common in older adults. However, the association between the two has not been well studied. We explored the relationship between very probable HF, determined by self-reported symptoms, and cognitive impairment, defined as four or fewer correct on the Six-item Screener, in 14,089 participants of the Reasons for Geographic and Racial Differences in Stroke cohort. We determined the effect of adding demographic, socioeconomic status (SES), health behavior, and comorbidity covariates. In the univariate model, participants with very probable HF were 1.51 (95% confidence interval: 1.15-1.96) times more likely to have cognitive impairment than those without HF. As covariates were added to the model, the relationship between HF and cognitive impairment was attenuated and lost statistical significance after adjustment for depression. Demographic variables, Stroke Belt location (1.28 [1.11-1.48]), SES factors, prior stroke (1.43 [1.18-1.73]), and depression (1.66 [1.38-2.01]) remained significant in the multivariable model. Higher hemoglobin was associated (0.95 [0.9-1.00]) with modestly reduced odds of cognitive impairment. The relationship between cognitive impairment and HF can be accounted for by multiple demographic and SES factors, and by comorbidities, some of which are modifiable. Persons with HF and cognitive impairment should be screened for anemia and depression.


Late results with synthetic valved external conduits from venous ventricle to pulmonary arteries.
Eighty-five patients operated on before January 1976 have survived at least 30 days after insertion of a valved external conduit by the venous ventricle (usually the right) and the pulmonary arteries as a part of the repair of their congenital heart disease. Follow-up information is available on 83 patients, and mean follow-up time has been 27.7 months. Seven patients have required reoperation because of obstructive complications. Actuarial analysis indicates that the proportion of patients requiring reoperation is 4.0 +/- 2.8% at 2 years, 12.9 +/- 5.5% at 3 1/2 years, and 30.4 +/- 12.1% at 5 years. In five patients compression of the conduit between the sternum and heart was the primary cause of the obstruction. The proportion requiring reoperation for conduit compression is 2.0 +/- 2.0% at 2 years, 8.6 +/- 4.9% at 3 1/2 years, and 27 +/- 12.4% at 5 years. Age at operation is not related to the proportion of patients requiring reoperation, nor is the type of conduit. No patients have yet required reoperation for conduit compression whose operation has been done since we began systematically to position the conduit well away from the sternum. By actuarial analysis the proportion of patients surviving 5 years is 76.7%. Of those alive at follow-up examination, 78% were without limitation of activity.


Analytical determination of stress patterns in the periodontal ligament during orthodontic tooth movement.
A dedicated software package that allows simulation of tooth movement can lead to shortening of the treatment program in orthodontics. A first step in the development of this software is the modelling of the movement of a single tooth. Forces applied to the crown of the tooth are transmitted to the alveolar bone through the periodontal ligament, stretching, and compressing the ligament, eventually resulting in tooth movement. This paper presents an analytical model that predicts stresses and strains inside this ligament by approximating the shape of the root as an elliptic paraboloid. The model input consists of 2 material parameters and 4 geometrical parameters. To assess the accuracy of the model a finite element model (FEM) was constructed to compare the results and the influence of the eccentricity of the root was studied. The results show that the model is able to successfully describe the global behavior of the PDL and, except at a region near the alveolar crest, the differences between analytical and FEM results are small. In contrast to FEM, the analytical model does not require setting up a 3D-model and creating a mesh, allowing for significantly lower computational times and reducing cost when implementing in clinical practice.


Interfacial effects in the spreading kinetics of liquid droplets on solid substrates.
Several theories deal with the spreading kinetics of liquids on solid substrate, most of which relate the rate of spreading to the surface tension and the viscosity of the liquid. Measurements of the spreading of a number of liquids exhibiting a wide range of surface tension and viscosity on dry soda-lime glass have been carried out to validate the proposed models. The measurements used a small droplet of constant volume to minimize gravitational effects. The contact radius was acquired as a function of time by an image analysis system. It was noted that power law theories describe the spreading rate for silicone oil on glass. However, significant departures were noted in the case of other liquids. Mechanistic considerations of our data suggest that equal volume droplets of similar surface tension and of diverse viscosity spread to the same area but at different rates. On the other hand, the spreading rate of glycerine, which exhibits incomplete spreading on glass, and that of silicone oil, with comparable viscosity behave similarly. These observations seemingly support the view that surface tension acts to retain the spherical shape of the droplet, whereas the difference between the solid-liquid and solid-vapor interfacial energies acts to enlarge the contact area. In the meantime, viscous dissipation acts to retard the spreading rate, past a constant rate regime.


Male esthetic genital surgery: recommendations and gaps to be filled.
The reason behind the spread of penis enlargement practices over time is rooted in the virility that the appearance of the genitals can give a man, as well as an altered perception of his own body. The approach should be to modulate the interventions on the real needs of patients, carefully evaluating the history, the psychological picture, and possible surgical advantages. The aim of this study was to shed light on cosmetic surgery of male genitalia through minimally invasive and more radical techniques, with the purpose of laying the foundation for possible indications and recommendations for the future. A non-systematic literature review using the PubMed and Scopus databases was conducted to retrieve papers written in English on cosmetic surgery of the penis published over the past 15 years. Papers discussing cosmetic surgery in patients with concomitant pathologies associated with sexual dysfunction were excluded. The main outcomes recorded were change in penile dimensions in term of length and girth and surgical complications.


Attenuation of experimental atherosclerosis by interleukin-19.
Interleukin-19 (IL-19) is a putative Th2, anti-inflammatory interleukin. Its expression and potential role in atherogenesis are unknown. IL-19 is not detected in normal artery and is expressed to a greater degree in plaque from symptomatic versus asymptomatic patients, suggesting a compensatory counter-regulatory function. We tested whether IL-19 could reduce atherosclerosis in susceptible mice and identified plausible mechanisms. LDLR(-/-) mice fed an atherogenic diet and injected with either 1.0 or 10.0 ng/g per day recombinant mouse IL-19 had significantly less plaque area in the aortic arch compared with controls (P<0.0001). Weight gain, cholesterol, and triglyceride levels were not significantly different. Gene expression in splenocytes from IL-19-treated mice demonstrated immune cell Th2 polarization, with decreased expression of T-bet, interferon-γ, interleukin-1β, and interleukin-12β and increased expression of GATA3 and FoxP3 mRNA. A greater percentage of lymphocytes were Th2 polarized in IL-19-treated mice. Cellular characterization of plaque by immunohistochemistry demonstrated that IL-19-treated mice have significantly less macrophage infiltrate compared with controls (P<0.001). Intravital microscopy revealed significantly less leukocyte adhesion in wild-type mice injected with IL-19 and fed an atherogenic diet compared with controls. Treatment of cultured endothelial cells, vascular smooth muscle cells, and bone marrow-derived macrophages with IL-19 resulted in a significant decrease in chemokine mRNA and mRNA stability protein human antigen R. These data suggest that IL-19 is a potent inhibitor of experimental atherosclerosis, with diverse mechanisms including immune cell polarization, decrease in macrophage adhesion, and decrease in gene expression. This may identify IL-19 as a novel therapeutic to limit vascular inflammation.


Trichinella britovi biomass in naturally infected pine martens (Martes martes) of Latvia.
Parasites of the genus Trichinella are cosmopolitan nematodes infecting primarily wild animals, which represent the main reservoirs of these zoonotic pathogens. To investigate the transmission patterns of Trichinella spp. from wild to domestic animals and to humans and for the risk assessment of these parasites in a geographical area, it is important to know the number of possible transmission events deriving from carcasses of infected hosts. For this purpose, the evaluation of the larval biomass in reservoir hosts is needed. No data is available on how to estimate the biomass of Trichinella spp. larvae in muscles of naturally infected animals. The aim of this study was to evaluate the larval biomass in naturally infected pine martens (Martes martes) of Latvia, in which the prevalence of Trichinella britovi infection was over 50%. Single muscles or group of muscles (abdomen, back, diaphragm, intercostal muscles, muscles from the head, left and right shoulders, lower and upper parts of the forelimbs and hind limbs, neck, rump with tail, and base and tip of the tongue) were collected from five skinned and eviscerated carcasses of T. britovi infected pine martens. Muscles were entirely removed from the bones and weighted. Each muscle or group of muscles was separately digested to detect the larvae per gram (LPG). Using linear regression, the larval burden in each muscle or group of muscles was evaluated to measure the possible prediction of the total animal larval burden (both as total number of larvae and as average LPG). All muscles were significantly predictive of the total burden with high "goodness of fit" (all adjusted R2>0.80; P≤0.01), and the left shoulder provided the highest adjusted R2 (0.999). Then, to estimate the Trichinella britovi biomass in the pine marten population of Latvia, recent literature data on prevalence (56.2%, 95% CI: 47.8-64.3) and geometric mean LPG (1.26, 95% CI: 0.89-1.79) in the limb muscles of a sample representative of the whole Latvian pine marten population, were used. Using the predictive estimated relationship between LPG in the limb and that in the entire animals and by the estimated animal population and their mean total muscle weight, the Trichinella britovi biomass in the pine marten population of Latvia was estimated to be of 6,647,092 (95% CI: 3,840,030-11,100,000) larvae. The assessment of the biomass in nature can help to understand the epidemiological pattern of these pathogens, to implement actions aimed at controlling the infection in target animal species, and to acquire basic information on the complex biology of this group of zoonotic nematodes.


Influence of prostacyclin and two metabolites on the contractility of cultured rat heart cells.
Heart cells were cultured from newborn rats, and the contractile activity (CA) and beating frequency (BF) were recorded using an electrooptical technique. Myocardial cells were found to be highly sensitive to Prostacyclin (PGI2) since a 10(-11) M concentration increased the BF and CA. Increasing the concentration (2.7 x 10(-10) to 2.7 x 10(-8) M) resulted in a dose-dependent decrease in CA and BF. The stable product of the non-enzymatic degradation of PGI2 (6 Keto PGF1 alpha) was found to be completely ineffective, and the stable product of the enzymatic PGI2 metabolism (6 Keto PGE1) exerted only a dose-dependent (10(-6) to 10(-5) M) positive inotropic effect. PGI2 was also effective in the presence of serum instead of culture medium but the decrease in CA was less marked than in culture medium, probably due to protein-binding of the drug. When the CA was decreased by PGI2, perfusion with the intracellular calcium-releasing and phosphodiesterase inhibiting agent, caffeine, reversed the PGI2-induced negative inotropic effect. These results suggest that PGI2 participates in the regulation of the heart cell contractility. Its metabolite 6 Keto PGEI could also influence heart cell contractility but higher concentrations are needed. Moreover myocardial intracellular calcium availability seems to be influenced by PGI2.


[Current Status for Anaplastic Lymphoma Kinase in Non-small Cell Lung Cancer].
The incidence of ALK gene rearrangement in non-small cell lung cancer (NSCLC) was about 3% to 5%. ALK gene inhibitors have made great breakthrough in recent years, significantly extending the survival period of patients with ALK(+) advanced NSCLC. But the majority of patients will be acquired drug resistance after treatment. This article has been explained separately from the ALK genetic background, the detection method, the treatment of the three generations of ALK inhibitors and the strategy after drug resistance. It is desire to have reference value and reference meaning for clinical work. .


Outcome of azacitidine treatment in patients with therapy-related myeloid neoplasms with assessment of prognostic risk stratification models.
Azacitidine's efficacy in therapy-related myeloid neoplasms (t-MN) has not been well-studied. In our retrospective review of 84 t-MN patients treated with azacitidine, median overall survival (OS) was 14.5 months and overall response rate was 43%, including 11% complete remission, 4% marrow complete remission, and 11% partial remission. In patients who underwent allogeneic transplant (25%), median OS was 19.2 versus 12.8 months (P=0.023) for those who did not. Response rates were comparable to those reported for de novo myelodysplastic syndrome. When we analyzed outcomes according to five scoring systems, only the Global MD Anderson Risk Model predicted survival with statistical significance.


Identification of the Drosophila melanogaster homolog of the human spastin gene.
The human SPG4 locus encodes the spastin gene, which is responsible for the most prevalent form of autosomal dominant hereditary spastic paraplegia (AD-HSP), a neurodegenerative disorder. Here we identify the predicted gene product CG5977 as the Drosophila homolog of the human spastin gene, with much higher sequence similarities than any other related AAA domain protein in the fly. Furthermore we report a new potential transmembrane domain in the N-terminus of the two homologous proteins. During embryogenesis, the expression pattern of Drosophila spastin becomes restricted primarily to the central nervous system, in contrast to the ubiquitous expression of the vertebrate spastin genes. Given this nervous system-specific expression, it will be important to determine if Drosophila spastin loss-of-function mutations also lead to neurodegeneration.


Non-autoimmune subclinical hypothyroidism due to a mutation in TSH receptor: report on two brothers.
Subclinical hypothyroidism (SH) is a condition characterized by a mild persistent thyroid failure. The main cause is represented by autoimmune thyroiditis, but mutations in genes encoding proteins involved in TSH pathway are thought to be responsible for SH, particularly in cases arising in familial settings. Patients with the syndrome of TSH unresponsiveness may have compensated or overt hypothyroidism with a wide spectrum of clinical and morphological alterations depending on the degree of impairment of TSH-receptor (TSH-R) function. We describe the case of two brothers with non autoimmune SH carrying the same heterozygous mutation in the extracellular domain of TSH-R and presenting with different clinical, biochemical and morphological features. The first one had only a slight persistent elevation of TSH, a normal thyroid ultrasound and did never require l- thyroxine (L-T4) replacement treatment. The second one had a neonatal persistent moderate TSH levels increase associated with a thyroid gland hypoplasia and was treated with L-T4 since the first months of life.These two cases support the recent association of TSH-R mutations inheritance as an autosomal dominant pattern with variable expressivity and suggest that the decision to start replacement therapy in patients with persistent SH due to TSH resistance should be individualized.


Oil content and fatty acid composition of promising Indian Brassica campestris L. (Toria) genotypes.
Seeds of sixty four genotypes of Brassica campestris L. (Toria) were analyzed for oil content and fatty acid composition. Oil content varied from 38.9% to 44.6%. Major fatty acids viz. oleic, linoleic, linolenic, eicosenoic and erucic acids exhibited ranges from 10.1% to 17.3%, 5.9% to 14.5%, 5.2% to 15.0%, 7.7% to 13.7% and 39.6% to 59.9%, respectively. Compared to the standard cultivar ITSA, four genotypes contained 5 to 8% lower content of erucic acid; and six genotypes contained significantly higher content of linoleic acid. Oil was positively correlated with erucic acid. The observed inverse relationship between linoleic and erucic acid contents might be utilized in breeding nutritionally better Toria cultivars with both high linoleic and low erucic acid contents.


Predictable PaCO2 with two different flow settings using the Mapleson D system.
Two different settings of fresh gas flow (VFG) and minute ventilation (VE) used with the coaxial Mapleson D system (Bain), were evaluated in 59 adults (ASA I-III) during controlled ventilation and different types of surgical procedures. The two flow settings (alternatives A and B) were VFG of 75 and 110 ml.min-1.kg-1 and VE of 150 and 175 ml.min-1.kg-1, aiming to generate normocapnea and mild hypocapnea, respectively. The PaCO2 obtained with alternative A was 5.5 +/- 0.5 kPa (mean +/- s.d.), with 92% of the patients within the range 4.7-6.1 kPa. With alternative B, the PaCO2 was 4.4 +/- 0.5 kPa, with 82% of the patients within the range 3.5-4.9 kPa. It is concluded that these two flow regimes are suitable for clinical use when either normocapnea or mild hypocapnea is desired.


Macrophage phenotypes during tissue repair.
Mp are crucial for tissue repair and regeneration but can also contribute to tissue damage and fibrosis. Mp can adopt a variety of functional phenotypes in response to different stimuli; two of the best-characterized in vitro phenotypes are a proinflammatory "M1" phenotype, produced by exposure to IFN-γ and TNF-α, and an anti-inflammatory "M2a" phenotype, produced by IL-4 or IL-13. M2a Mp are frequently termed "wound healing" Mp, as they express factors that are important for tissue repair. This review will summarize current knowledge of Mp phenotypes during tissue repair and will argue that these in vivo Mp populations are heterogeneous and temporally regulated and do not conform to existing, in vitro-defined M1 or M2 phenotypes. Mp during the early stages of tissue repair exhibit a more proinflammatory phenotype than their later counterparts, which in turn may exhibit some M2a-associated characteristics. However, phenotypic markers that appear to be coregulated in cultured Mp can be expressed independently of each other in vivo. Additionally, M1- and M2-associated markers may be expressed simultaneously by actual tissue-repair Mp. Improved understanding of Mp phenotypes and their regulation may assist in generation of novel therapies based on manipulating Mp function to improve healing.


The impact of microbiota-derived short-chain fatty acids on macrophage activities in disease: Mechanisms and therapeutic potentials.
Short-chain fatty acids (SCFAs) derived from the fermentation of carbohydrates by gut microbiota play a crucial role in regulating host physiology. Among them, acetate, propionate, and butyrate are key players in various biological processes. Recent research has revealed their significant functions in immune and inflammatory responses. For instance, butyrate reduces the development of interferon-gamma (IFN-γ) generating cells while promoting the development of regulatory T (Treg) cells. Propionate inhibits the initiation of a Th2 immune response by dendritic cells (DCs). Notably, SCFAs have an inhibitory impact on the polarization of M2 macrophages, emphasizing their immunomodulatory properties and potential for therapeutics. In animal models of asthma, both butyrate and propionate suppress the M2 polarization pathway, thus reducing allergic airway inflammation. Moreover, dysbiosis of gut microbiota leading to altered SCFA production has been implicated in prostate cancer progression. SCFAs trigger autophagy in cancer cells and promote M2 polarization in macrophages, accelerating tumor advancement. Manipulating microbiota- producing SCFAs holds promise for cancer treatment. Additionally, SCFAs enhance the expression of hypoxia-inducible factor 1 (HIF-1) by blocking histone deacetylase, resulting in increased production of antibacterial effectors and improved macrophage-mediated elimination of microorganisms. This highlights the antimicrobial potential of SCFAs and their role in host defense mechanisms. This comprehensive review provides an in-depth analysis of the latest research on the functional aspects and underlying mechanisms of SCFAs in relation to macrophage activities in a wide range of diseases, including infectious diseases and cancers. By elucidating the intricate interplay between SCFAs and macrophage functions, this review aims to contribute to the understanding of their therapeutic potential and pave the way for future interventions targeting SCFAs in disease management.


Influence of the Fukushima Dai-ichi nuclear accident on Spanish environmental radioactivity levels.
This paper presents measurements of the effect of the atmospheric radioactive release from the Fukushima Dai-ichi nuclear power station at three sites belonging to the Spanish environmental monitoring system. Measured values varied depending on the locations of the sites in Spain and their respective climatic characteristics. (134)Cs, (136)Cs, (137)Cs, (131)I, and (132)Te activity concentrations in filter samples were studied and associated levels of (131)I fallout were estimated from wet and dry deposition. Particulate aerosol activity concentrations ranges, in μBq/m(3), were 1.63-3080 ((131)I), 2.8-690 ((137)Cs), 1.3-620 ((134)Cs) and 3.6-330 ((132)Te), while the associated (131)I fallout was roughly estimated to be less than 20 Bq/m(2), Gaseous (131)I was also detected and the (131)I-gaseous/(131)I-total ratio increased at the three stations from approximately 0.75 at the end of March to 0.85-0.9 during the first few days of April. Finally, the presence of (131)I in some crucial parts of the food chain was also studied. (131)I was detected in samples from goat's and cow's milk (maximum levels of 1.11 Bq/L) and in broadleaf plants (maximum level 1.42 Bq/kg).


When Is Cone-Beam Computed Tomography Imaging Appropriate for Diagnostic Inquiry in the Management of Inflammatory Periodontitis? An American Academy of Periodontology Best Evidence Review.
Clinical and radiographic examinations are essential in establishing correct periodontal diagnoses as well as providing appropriate treatment options. Current radiographic examinations, however, do not provide adequate information regarding the severity of periodontal disease, presenting a need to investigate alternative methods. The aim of this best evidence consensus is to determine when cone-beam computed tomography (CBCT) imaging is appropriate for diagnostic inquiry in the management of inflammatory periodontitis. Literature was systematically reviewed to answer three clinically relevant focused questions regarding the role of CBCT in the management of inflammatory periodontitis. 1) Clinical situation: In patients with periodontitis, what (if any) clinical situations/conditions exist where CBCT imaging improves diagnostic acumen and subsequent treatment recommendations compared with two-dimensional radiographic interpretation? 2) Intervention: Does CBCT imaging improve the accuracy of a diagnostic assessment and establishment of a prognosis in the analysis of furcation and/or intrabony defects? Is the execution of therapy improved and facilitated, or is it therapeutically challenged? 3) Outcomes: Does the use of CBCT imaging provide superior short-term or long-term clinical outcomes, more favorable patient-reported outcomes, or more consistent clinical treatment decisions affecting tooth prognosis (as measured by defect fill, improvements in bone anatomy, mobility patterns, and ultimate tooth survival)? An extensive literature search was performed using the MEDLINE database and the most respected journals in the field. An electronic database search identified 885 citations, and a manual search yielded an additional five citations. After screening of article titles and abstracts, studies were excluded if irrelevant to the topic of this systematic review. Of the remaining full-text articles, 74 were obtained and reviewed. Sixty-two articles not meeting inclusion criteria were further excluded. Twelve total references met the inclusion criteria to determine the role of CBCT in diagnosis and treatment of both intrabony and furcation defects. Intrabony and furcation defects were the two most commonly discussed bony defects when comparing efficacy of CBCT versus intraoral radiographs (IRs). After a review of the literature, while diagnostic aspects of intrabony and furcation defects can be improved via the use of CBCT, limited evidence supported the use of CBCT imaging improving the execution of therapy for both types of defects. There was also a lack of literature to support the use of CBCT imaging for superior short-term or long-term clinical outcomes. None of the literature reported patient-reported outcomes when CBCT imaging was used. Currently, limited evidence supports the utilization of CBCT for diagnosis of intrabony and furcation defects. Despite the fact that there is rapidly accruing literature on CBCT, there are still no current evidence-based guidelines on its necessity and use for periodontal treatment planning. In selective cases, however, limited field of view CBCT may be useful for periodontal disease diagnoses due to less radiation dosage to the patient, higher spatial resolution, and shorter volumes to be interpreted.


Deconvolution of 238,239,240Pu conversion electron spectra measured with a silicon drift detector.
Internal conversion electron (ICE) spectra of thin 238,239,240Pu sources, measured with a windowless Peltier-cooled silicon drift detector (SDD), were deconvoluted and relative ICE intensities were derived from the fitted peak areas. Corrections were made for energy dependence of the full-energy-peak counting efficiency, based on Monte Carlo simulations. A good agreement was found with the theoretically expected internal conversion coefficient (ICC) values calculated from the BrIcc database.


Blood pressure and glycaemic effects of dapagliflozin versus placebo in patients with type 2 diabetes on combination antihypertensive therapy: a randomised, double-blind, placebo-controlled, phase 3 study.
Hypertension is a common comorbidity in patients with type 2 diabetes mellitus and a major risk factor for microvascular and macrovascular disease. Although the blood pressure-lowering effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors are already established, guidance is needed on how to use these drugs in patients already receiving antihypertensive therapy. We aimed to compare blood pressure and glycaemic effects of the SGLT2 inhibitor dapagliflozin with placebo in patients with inadequately controlled type 2 diabetes mellitus and hypertension. In this double-blind, placebo-controlled, phase 3 study we enrolled patients from 311 centres in 16 countries across five continents. Patients had uncontrolled type 2 diabetes (HbA1c 7·0%-10·5%; 53-91 mmol/mol) and hypertension (systolic 140-165 mm Hg and diastolic 85-105 mm Hg at both enrolment and randomisation, and a mean 24 h blood pressure of ≥130/80 mm Hg by ambulatory monitoring within 1 week of randomisation) and were receiving oral antihyperglycaemic drugs, insulin, or both, plus a renin-angiotensin system blocker and an additional antihypertensive drug. Using an interactive voice-response system, we randomly assigned (1:1) patients to dapagliflozin 10 mg once a day or to placebo, with randomisation stratified by additional antihypertensive drug use and insulin use at baseline, in a block size of two. The co-primary endpoints were changes in seated systolic blood pressure and HbA1c measured in the full analysis set, which included all patients who received at least one dose of study drug and had both a baseline and at least one post-baseline measurement of efficacy. This trial is registered with ClinicalTrials.gov, number NCT01195662. Between Oct 29, 2010, and Oct 4, 2012, we randomly assigned 225 patients to dapagliflozin and 224 to placebo. Seated systolic blood pressure was significantly reduced in the group assigned to dapagliflozin (adjusted mean change from baseline -11·90 mm Hg [95% CI -13·97 to -9·82]) compared with those assigned to placebo (-7·62 mm Hg [-9·72 to -5·51]; placebo-adjusted difference for dapagliflozin -4·28 mm Hg [-6·54 to -2·02]; p=0·0002). Reductions in HbA1c concentrations were also significantly greater in patients assigned to dapagliflozin (adjusted mean change from baseline -0·63% [95% CI -0·76 to -0·50]) than in those assigned to placebo (-0·02% [-0·15 to 0·12]; placebo-adjusted difference -0·61% [-0·76 to -0·46,]; p<0·0001). In a post-hoc analysis, we found difference in blood pressure versus placebo was greater in patients receiving a β blocker (-5·76 mm Hg [95% CI -10·28 to -1·23]) or a calcium-channel blocker (-5·13 mm Hg, [-9·47 to -0·79]) as their additional antihypertensive drug than in those receiving a thiazide diuretic (-2·38 mm Hg [-6·16 to 1·40]). Adverse events were similar in the dapagliflozin and placebo groups (98 [44%] patients vs 93 [42%], respectively, had at least one adverse event), with few adverse events related to renal function (1% vs <1%) or volume depletion (<1% vs 0%). Dapagliflozin 10 mg significantly improved blood pressure and HbA1c and was tolerated similarly to placebo. Its blood pressure-lowering properties were particularly favourable in patients already receiving a β blocker or calcium-channel blocker. Dapagliflozin could benefit patients with type 2 diabetes who need a diuretic-like effect to optimise control of blood pressure, adding meaningful efficacy to antihypertensive drug regimens. Bristol-Myers Squibb, AstraZeneca.


Effects of dichloroacetate on glycogen metabolism in B6C3F1 mice.
Dichloroacetate (DCA) is a by-product of drinking water chlorination. Administration of DCA in drinking water results in accumulation of glycogen in the liver of B6C3F1 mice. To investigate the processes affecting liver glycogen accumulation, male B6C3F1 mice were administered DCA in drinking water at levels varying from 0.1 to 3 g/l for up to 8 weeks. Liver glycogen synthase (GS) and glycogen phosphorylase (GP) activities, liver glycogen content, serum glucose and insulin levels were analyzed. To determine whether effects were primary or attributable to increased glycogen synthesis, some mice were fasted and administered a glucose challenge (20 min before sacrifice). DCA treatments in drinking water caused glycogen accumulation in a dose-dependent manner. The DCA treatment in drinking water suppressed the activity ratio of GS measured in mice sacrificed at 9:00 AM, but not at 3:00 AM. However, net glycogen synthesis after glucose challenge was increased with DCA treatments for 1-2 weeks duration, but the effect was no longer observed at 8 weeks. Degradation of glycogen by fasting decreased progressively as the treatment period was increased, and no longer occurred at 8 weeks. A shift of the liver glycogen-iodine spectrum from DCA-treated mice was observed relative to that of control mice, suggesting a change in the physical form of glycogen. These data suggest that DCA-induced glycogen accumulation at high doses is related to decreases in the degradation rate. When DCA was administered by single intraperitoneal (i.p.) injection to naïve mice at doses of 2-200 mg/kg at the time of glucose challenge, a biphasic response was observed. Doses of 10-25 mg/kg increased both plasma glucose and insulin concentrations. In contrast, very high i.p. doses of DCA (> 75 mg/kg) produced progressive decreases in serum glucose and glycogen deposition in the liver. Since the blood levels of DCA produced by these higher i.p. doses were significantly higher than observed with drinking water treatment, we conclude that apparent differences with data of previous investigations is related to substantial differences in systemic dose and/or dose-time relations.


The East Asian-specific LPL p.Ala288Thr (c.862G > A) missense variant exerts a mild effect on protein function.
Lipoprotein lipase (LPL) is the key enzyme responsible for the hydrolysis of triglycerides. Loss-of-function variants in the LPL gene are associated with hypertriglyceridemia (HTG) and HTG-related diseases. Unlike nonsense, frameshift and canonical GT-AG splice site variants, a pathogenic role for clinically identified LPL missense variants should generally be confirmed by functional analysis. Herein, we describe the clinical and functional analysis of a rare LPL missense variant. Chinese patients with HTG-associated acute pancreatitis (HTG-AP) were screened for rare nonsense, frameshift, missense or canonical GT-AG splice site variants in LPL and four other lipid metabolism-related genes (APOC2, APOA5, GPIHBP1 and LMF1) by Sanger sequencing. The functional consequences of the LPL missense variant of interest were characterized by in vitro expression in HEK-293T and COS-7 cells followed by Western blot and LPL activity assays. Five unrelated HTG-AP patients were found to be heterozygous for a rare East Asian-specific LPL missense variant, c.862G > A (p.Ala288Thr). All five patients were adult males, and all were overweight and had a long history of alcohol consumption. Transfection of LPL wild-type and c.862G > A expression vectors into two cell lines followed by Western blot analysis served to exclude the possibility that the p.Ala288Thr missense variant either impaired protein synthesis or increased protein degradation. Contrary to a previous functional study that claimed that p.Ala288Thr had a severe impact on LPL function (reportedly having 36% normal activity), our experiments consistently demonstrated that the variant had a comparatively mild effect on LPL functional activity, which was mediated through its impact upon LPL protein secretion (~ 20% reduced secretion compared to wild-type). In this study, we identified the East Asian-specific LPL c.862G > A (p.Ala288Thr) missense variant in five unrelated HTG-AP patients. We demonstrated that this variant exerted only a relatively mild effect on LPL function in two cell lines. Heterozygosity for this LPL variant may have combined with alcohol consumption to trigger HTG-AP in these patients.


Pseudothrombosis with T2-weighted fast spin-echo MR images caused by static portal venous flow in severe cirrhosis.
Unenhanced T2-weighted fast spin-echo images obtained in a 65-year-old woman with severe cirrhosis showed an area of high signal intensity occupying the left second-order portal vein branch, suggesting portal vein thrombosis in cirrhosis. Doppler sonography, which revealed virtually no blood flow in the vessel, also supported the diagnosis. Gadolinium-enhanced MRI subsequently revealed the patency of the vessel. The extremely slow portal venous flow was considered to be the cause of false-positive findings with unenhanced MRI and sonography.


Application of a non-invasive tool and identification of genetic markers in swine to enhance ham quality: a preliminary study.
A genome-wide association study (GWAS) was performed as a preliminary step to identify regions potentially related to ham quality traits. In this research, genomic information was obtained from 238 commercial hybrid pigs utilising the GeneSeek® Genomic Profiler genome-wide porcine genotyping array. Carcasses were tested for hot weight, the thickness of backfat and loin, and lean meat percentage. The corresponding fresh hams were assayed for weight and ultimate pH; the activities of Cathepsin B and Ferrochelatase of Semimembranosus muscle were determined through fluorimetric methods. The lean meat percentage of fresh ham (LMPH), salt absorbed after first (SALT1) and overall salting stages (SALT) were estimated online by the Ham Inspector™ apparatus. Hams were processed in compliance with the procedures established for Protected Designation of Origin Parma ham, and ham weight losses were measured at the main processing stages. Hot carcass weights showed a significant negative correlation with their lean meat percentage and LMPH, while LMPH was correlated positively with carcass lean meat, SALT1, SALT, and weight losses. The GWAS detected genome-wide association for 12 single nucleotide polymorphisms with Ferrochelatase activity. The results obtained in this preliminary study were achieved by combining innovative and non-destructive technologies for screening hams under processing, measures of enzymatic muscle properties relevant to dry-cured ham quality, and genomic information obtained through a GWAS. Additional studies carried out in a larger number of pigs have been planned to investigate the effect of gene variants of Ferrochelatase activity in the dry-cured ham's quality with main reference to colour development and to confirm the GWAS results obtained in this study.


Factors Associated With Revascularization in Women With Spontaneous Coronary Artery Dissection and Acute Myocardial Infarction.
In contrast to atherosclerotic acute myocardial infarction (AMI), conservative therapy is considered preferable in the acute management of spontaneous coronary artery dissection (SCAD) if clinically possible. The present study aimed to investigate factors associated with treatment strategy for SCAD. Women aged ≤60 years with AMI and SCAD were retrospectively identified in the Nationwide Readmissions Database 2010 to 2015 and were divided into revascularization and conservative therapy groups. The revascularization group (n = 1,273, 68.0%), compared with the conservative therapy group (n = 600, 32.0%), had ST-elevation AMI (STEMI) (anterior STEMI, 20.3% vs 10.5%; inferior STEMI, 25.1% vs 14.5%; p <0.001) and cardiogenic shock (10.8% vs 1.8%; p <0.001) more frequently. Multivariable logistic regression analysis demonstrated that anterior STEMI (vs non-STEMI, odds ratio 2.89 [95% confidence interval 2.08 to 4.00]), inferior STEMI (2.44 [1.85 to 3.21]), and cardiogenic shock (5.13 [2.68 to 9.80]) were strongly associated with revascularization. Other factors associated with revascularization were diabetes mellitus, dyslipidemia, smoking, renal failure, and pregnancy/delivery-related conditions; whereas known fibromuscular dysplasia and admission to teaching hospitals were associated with conservative therapy. Propensity-score matched analyses (546 pairs) found no significant difference in in-hospital death, 30-day readmission, and recurrent AMI between the groups. In conclusion, STEMI presentation, hemodynamic instability, co-morbidities, and setting of treating hospital may affect treatment strategy in women with AMI and SCAD. Further efforts are required to understand which patients benefit most from revascularization over conservative therapy in the setting of SCAD causing AMI.


Plasmacytoma of the parotid gland. Report of a case and review of the world literature.
Extramedullary plasmacytoma (EP) is a relatively rare neoplasm; about 90% of cases are localized in the head and neck area. EP has been considered a precursor of multiple myeloma but cases showing long disease free intervals or cure by surgery alone have been reported. A research of the world literature pointed out the extremely rare localization of solitary plasmacytoma in the salivary glands. Only 9 cases have been reported until now, 6 in the parotid gland, 2 in the submandibular glands and 1 in both the parotid and submandibular gland.


Scientists as spies?: Assessing U.S. claims about the security threat posed by China's Thousand Talents Program for the U.S. life sciences.
In 2008, the Chinese government created the Thousand Talents Program (TTP) to recruit overseas expertise to build up China's science and technology knowledge and innovation base. Ten years later, in 2018, the Federal Bureau of Investigation (FBI) announced a new "China Initiative" that aimed to counter the transfer by U.S.-based scientists involved in the TTP of knowledge and intellectual property that could support China's military and economic might and pose threats to U.S. national security. This initiative launched a number of investigations into major U.S. federal funding agencies and universities and charged several scientists, many of them life scientists, with failing to accurately report their work and affiliations with Chinese entities and illegally transferring scientific information to China. Although the FBI cases demonstrate a clear problem with disclosure of foreign contracts and research integrity among some TTP recipients, they have failed to demonstrate any harm to U.S. national security interests. At the heart of this controversy are core questions that remain unresolved and need more attention: What is required to transfer and develop knowledge to further a country's science and technology ambitions? And can the knowledge acquired by a visiting scientist be easily used to further a country's ambitions? Drawing on literature from the field of science and technology studies, this article discusses the key issues that should be considered in evaluating this question in the Chinese context and the potential scientific, intelligence, and policy implications of knowledge transfer as it relates to the TTP.


[The increased reactivity of isolated pulmonary artery rings from rats with hypoxia-induced pulmonary hypertension to activator of protein kinase C].
To observe the reactivity of isolated pulmonary artery rings from rats with chronic hypoxic pulmonary hypertension (HPH) to protein kinase.C (PKC) activator. Pulmonary artery rings from adult rats exposed to normobaric hypoxia for two weeks and normal rats were isolated for measurement of isometric contractions to PMA, the specific activator of PKC. Responses were examined as follows: (1) The maximal response (P(1)) to 0.5 micromol/L PMA and the time required to achieve a half-maximal response to 0.5 micromol/L PMA (t(1/2)); (2) Dose-response curve in response to PMA (0.01 - 10.0 micromol/L) and the dose of PMA that produced a contractile response as 50% of the maximal response (P(0)) to 80 mmol/L KCl (EC(50) KCl). P(1) of hypoxic group (34.3 +/- 2.4) P(0)% was greater than that of normal group [(26.2 +/- 2.9) P(0)%, n = 6, P < 0.05)], t(1/2) and EC(50) KCl of hypoxic group [(27 +/- 7) min, and (0.7 +/- 0.1) micromol/L] were smaller than those of normal group [(32 +/- 5) min, n = 6, P < 0.05, and (6.0 +/- 0.2) micromol/L, n = 12, P < 0.05]. The reactivity of pulmonary artery rings from hypoxic rats to PMA was enhanced, which indicates that protein kinase C may have an important role in the development of HPH.


[Bone mineral density in a population with severe infantile cerebral palsy].
To determine the bone mineral density (BMD) values in children and adolescents with moderate and severe infantile cerebral palsy (ICP) in our catchment area, and compare these values with a healthy population. A prognostic study of cases and controls for the assessment of BMD in patients from 2 to 18 years old with infantile cerebral palsy belonging to the Gross Motor Function Classification System (GMFCS) Groups IV and V. The BMD measurements were performed at distal femur level, dividing this region into 3 areas following the forearm protocol. The BMD for each of the three areas studied results in the final sample of 69 patients were much lower than the reference levels. There was a statistically significant difference (P<.05) between the BMD values in the two sub-groups studied. The greater the involvement, from a neurological point of view, in patients classified as Group V shows a very low BMD compared to patients of similar sex and age. The acquisition of bone capital in patients with ICP does not follow the normal pattern of the healthy population.


[Therapeutic effect from the combined action of pyrogenal and irradiation on sarcoma 45 in rats].
The use of pyrogenal associated with radiotherapy in the experiment (rat sarcoma-45) contributes to a successful realization of radiotherapeutic effect, longer life-terms and non-recurrence period, the increased number of completely cured and survived animals. Pyrogenal would produce no adverse side-effects.


Aliovalent anion substitution as a design concept for heteroanionic Ruddlesden-Popper hydrides.
Substituting 2 O2- ⇒ N3- + H- in LiLa2HO3 yields dark-brown heteroanionic hydrides, which were synthesized by solid-state reactions from Li3N, LaH3 (and La2O3). They crystallize in the K2NiF4 type structure with mixed H/N sites in LiLa2N1.5H2.5 and with mixed N/O sites in LiLa2N0.84(6)H1.56(3)O1.16(6). The latter is a semiconductor with small band gap and partly covalent Li-H interaction.


Leukemic transformation in patients with the 5q- alteration: analysis of the behavior of the 5q- clones in preleukemic to leukemic phases.
Serial cytogenetic studies have been performed in four patients with myelodysplastic syndromes. In all four a 5q- alteration was present, but with a different pattern of presentation. One patient presented 5q- as the only alteration since diagnosis; two patients acquired this alteration during the course of the disease; and the fourth showed a 5q- plus other alterations since the first cytogenetic study. Likewise, three of the four patients showed a clone with trisomy 8 and without 5q-. According to these observations and others from the literature with similar cytogenetic behavior, we have analyzed the following points: 5q- as a primary event and as the only alteration, 5q- as a secondary event, 5q- plus other alterations, and presence of cytogenetically different clones. Analysis of these points suggests that the 5q- alteration can represent an early mutation conferring a slow capacity of expansion to the affected clones, with the possibility of cytogenetic evolution during the progression of the disease (about 30% of the patients). Likewise, the association of trisomy 8 clones with 5q- clones can be a nonrandom event.


In slow pace towards the proteome of equine body fluids.
Equine medicine represents a relevant field of veterinary science and the horse industry generates a significant economic impact. Horses can be involved in different sport disciplines, meat production, work and recreational purposes. Horses are also important for human health as they can be used as animal models for studying human diseases and in equine-assisted therapy. This review summarizes the data related to body fluids such as plasma/serum, urine, cerebrospinal fluid, synovial fluid, saliva, bronchoalveolar lavage fluid and peritoneal fluid obtained using proteomic analysis. Horse body fluid proteome analysis under various physiological and pathological conditions is a useful method for identifying new biomarkers for horse diseases which are still difficult to diagnose, but with serious consequences on equine health and welfare. The findings reported here reveal that further proteomic studies on equine body fluids collected from diseased animals are required. SIGNIFICANCE: Body fluids are sources of potential protein biomarkers for diagnosis and therapeutic target identification. Indeed, they contain proteins that play a crucial role in cell functions and whose presence or relative abundance are indicative of the health status of tissues/organs. The review reports the data on the equine body fluids obtained using proteomic analysis, including those which are commonly used to obtain a correct diagnosis and prognosis of horse diseases which still pose a significant challenge. For equine medicine, new biomarkers are needed to formulate early diagnosis and to distinguish among diseases with similar clinical signs.


A new method for rapid detection of the mutant allele for Chediak-Higashi syndrome in Japanese black cattle.
Chediak-Higashi syndrome (CHS) is an autosomal recessive hereditary disorder in Japanese Black cattle, caused by a mutation of the Lyst gene. So far, the mutation has been detected by PCR-restriction fragment length polymorphism (PCR-RFLP) analysis. However, this method is disadvantaged by its low-throughput performance. Here, we report an alternative method involving real-time PCR with TaqMan minor groove binder probes, which shortens the total assay time by more than 120 min, analyzing 10 samples in a duplicated manner. Using this method, we examined 102 Japanese Black cattle and found that 8.8% of the cattle were CHS-carriers. These data indicate that our technique is useful for routine diagnostic testing for CHS in Japanese Black cattle.


Is universal coverage a solution for disparities in health care? Findings from three low-income provinces of Thailand.
The policy on universal coverage (UC) of health care has been adopted and implemented incrementally by the government of Thailand since April 2001 with the aim of providing the access to care for the uninsured population. The success of UC, however, depends on how effective its design and implementation arrangements are in reaching population and affecting households' health seeking behavior and abilities to take up benefits of UC. The results from the household survey of 1834 respondents conducted in three low-income provinces (Tak, Sakol Nakorn, Narathiwat) show that the Gold card with exemption scheme was pro-poor while other insurance schemes tended to favor the rich with 2.6% of respondents reported having more than one type of health insurance coverage and 8.9% without health insurance. The insurance status had statistically significant association with health care use, and knowledge on family planning method and sexually transmitted diseases. Additionally, consumer preferences and socioeconomics factors are a key to disparities in health care utilization.


First report of Cryptosporidium canis in farmed Arctic foxes (Vulpes lagopus) in China.
Cryptosporidium is an important genus of enteric zoonotic parasites, which can infect a wide range of animals including foxes. Little information is available concerning the prevalence and molecular characterisation of Cryptosporidium spp. in farmed Arctic foxes (Vulpes lagopus) in China. Thus, the objective of the present study was to investigate the prevalence of Cryptosporidium spp. in Arctic foxes in China using nested PCR amplification of the small subunit ribosomal RNA (SSU rRNA) gene. The overall prevalence of Cryptosporidium spp. in Arctic foxes was 15.9 % (48/302), with 12.9 % in male (18/139) and 18.4 % in female (30/163) foxes, respectively. The prevalence in different farms varied from 0 to 31.43 %. The prevalence of infection in different age groups varied from 14.1 % to 19.0 %. Foxes from Hebei Province (7.8 %, 11/141) had a significantly lower Cryptosporidium spp. prevalence than those from Heilongjiang Province (22.9 %, 16/70) and Jilin Province (23.1 %, 21/91) (P= 0.0015). Sequence analysis of the SSU rRNA gene indicated that all the 48 isolates represented C. canis. This is the first report of C. canis infection in farmed Arctic foxes in China, which also provides foundation data for preventing and controlling Cryptosporidium infection in foxes, other animals and humans.


Synthesis and biological evaluation of novel (L)-alpha-amino acid methyl ester, heteroalkyl, and aryl substituted 1,4-naphthoquinone derivatives as antifungal and antibacterial agents.
A series of (S)-N-(1,4-naphthoquinon-2-yl)-alpha-amino acid methyl esters 3-9, 2-N,N-dialkylamino-1,4-naphthoquinones 10-11 and 2-hydroxy-3-(2'-mercaptoimidazolyl)-1,4-naphthoquinones and their cyclic analogs 12-15 were synthesized and evaluated for antifungal and antibacterial activities. The structure-activity relationships of these compounds were studied and the results show that the compounds 9b and 13c exhibited in vitro antifungal activity against Candida albicans, Cryptococcus neoformans, and Sporothrix schenckii, whereas compound 6a showed in vitro antibacterial activity against Streptococcus faecalis, K. pneumoniae, Escherichia coli, and Staphylococcus aureus.


Medical decisions in organ donors and heart transplant candidates with history of COVID-19 infection: An international practice survey.
A growing proportion of transplant donors and recipients have a history of COVID-19 infection. This study sought to characterize clinical practice after recipient or donor COVID-19 infection. An online survey was distributed to heart transplant clinicians through a professional society message board and social media. Responses were collected between September 29 and November 5, 2021. There were 222 health care professionals (68% transplant cardiologists, 22% transplant surgeons, 10% other) across diverse geographic regions who completed the survey. While there was significant variation in donor acceptance, as it relates to past and current COVID-19 infection, the respondents were fairly cautious: 28% would not typically accept a donor with a history of COVID-19 regardless of the infection course and > 80% would not accept donors who had evidence of myocardial dysfunction during past COVID-19 infection, or who died of COVID-19 or its complications. The timing of candidate reactivation on the waiting list after COVID-19 infection also varied and often diverged from scenarios addressed by social guidelines. Eighty-one percent of the respondents felt COVID-19 vaccine should be mandatory before transplant, but this rate varied by geographic region. Our results reflect evolving experience of the heart transplant field at a time of lack of high-quality evidence. In the absence of longer-term outcome data for donors and transplant candidates with history of COVID-19 infection, clinicians remain cautious; however, this approach will likely need to be refined as an increasing proportion of the population will continue to be infected with COVID-19.


Treatment with a gonadotrophin releasing hormone agonist before hysterectomy for leiomyomas: results of a multicentre, randomised controlled trial.
To ascertain whether uterine shrinkage induced by a gonadotrophin releasing hormone agonist before hysterectomy for fibroids increases the possibility of a vaginal procedure. A multicentre, prospective, randomised, controlled study. One hundred and twenty-seven premenopausal women with a uterine volume of 12 to 16 gestational weeks. Twelve weeks of triptorelin depot treatment before hysterectomy or immediate surgery. Number of vaginal and abdominal hysterectomies, operating time, blood loss, degree of difficulty of the procedure, perioperative serum haemoglobin and haematocrit levels, hospital stay, and patients' overall satisfaction with treatment. After randomisation, four women withdrew from the study, leaving 60 women in the triptorelin arm and 63 in the immediate surgery arm. At baseline evaluation a vaginal hysterectomy was indicated in seven women allocated to pre-operative medical therapy (12%), and in 10 of those allocated to immediate surgery (16%). Clinical assessment after the 12-week GnRH agonist course showed that abdominal hysterectomy was no longer indicated in 25/53 women (47%) as a vaginal procedure appeared appropriate. Thus the overall rate of indication for a vaginal procedure in the pre-operative medical treatment arm was 32/60 cases (53%), with a between-group difference of 37% (95% CI, 26% to 51%; chi2(1) = 19.18, P < 0.0001; OR 6.06; 95% CI, 2.60 to 14.10). Pre- and post-operative serum haemoglobin and haematocrit levels were significantly higher in the GnRH agonist than in the immediate surgery arm. No appreciable difference was observed between the groups in the other intra- and post-operative variables, including patients' satisfaction. Pre-operative GnRH agonist therapy increased the rate of vaginal hysterectomy in selected women with fibroids and uterine volume of 12 to 16 gestational weeks.


Characterization of a monoclonal antibody recognizing a DAG-containing epitope conserved in aphid transmissible potyviruses: evidence that the DAG motif is in a defined conformation.
Two viral proteins, the helper component-protease and the coat protein, are required for the non-persistent aphid transmission of potyviruses. In the potyvirus coat protein, the tripeptide aspartate-alanine-glycine (DAG) has often been shown to be involved. A monoclonal antibody, raised against a synthetic decapeptide containing the DAG tripeptide, reacted with the peptide as well as with isolates of soybean mosaic, tobacco etch and tobacco vein mottling potyviruses. Experiments indicate that the monoclonal antibody recognizes a conformational rather than a sequential epitope. The data support the suggestion that the DAG region plays a structural role to determine a coat protein-helper component-protease conformation that influences aphid transmission.


Dependence on temperature and pressure of second cumulant and correlation effects during EXAFS in intermetallic alloys.
The present article is aimed to investigate the second cumulants, and the thermodynamic quantities are dependent on temperature and pressure in the X-ray absorption fine structure spectrum. The expressions have been build by using the model of the non-harmonic correlation of Einstein and Debye. A simple calculation was used to instead complex problems caused by the interaction of many particles in the system. The significant results of this work are the Morse potential parameters have been theoretically calculated method, determined the temperature dependence of the second cumulant, mean square displacement and correlation function for copper, tungsten, and copper-tungsten alloy of ratio 93-07 percent (W93Cu07) under pressure up to 14GPa. Calculated the second cumulant dependence on the pressure in a range from 0GPa to 14GPa and clearly analysed the difference between the second cumulant at different pressure for atoms of tungsten, copper and tungsten-copper alloy. Numerical results according to the present theory agree well with experimental data and previous views.


Crystal structure and aqueous solubility of ammonium D-glucarate.
Ammonium D-glucarate, NH(4)(C(6)H(9)O(8)) [ammonium D-saccharate, NH(4)-SAC], has been synthesized, and its crystal structure solved by single-crystal X-ray diffraction methods. NH(4)-SAC crystallizes in the monoclinic space group P2(1) (#4) with cell parameters a = 4.8350(4) Angstroms, b = 11.0477(8) Angstroms, c = 16.7268(12) Angstroms, beta = 90.973(1) degrees, V = 894.34(12) Angstroms(3), Z = 3. The structure was refined by full-matrix least-squares on F(2) yielding final R-values (all data) R1 = 0.0353 and R(w)2 = 0.0870. The structure consists of alternating (NH(4))(+) and (C(6)H(11)O(6))(-) layers parallel to the bc plane. An extended network of N-H...O(SAC) and O(SAC)-H...O(SAC) hydrogen bonds provide the 3-D connectivity. The aqueous solubility (S(w)) has been shown to be pH independent at ambient conditions within the range 4.5 < pH < 10 with S(w) = 2.19 M/L, whose value is about a factor of two lower than that of the ammonium isosaccharate analogue.


Decreased opioid-induced antinociception but unaltered G-protein activation in the genetic-diabetic NOD mouse.
Previous evaluation of antinociceptive action in experimental diabetes has been conducted almost exclusively in chemically induced diabetes mellitus. The purpose of the present study was to evaluate antinociceptive response and G-protein activation by mu-opioid receptor and delta-opioid receptor agonists in the genetic non-obese diabetic (NOD) mouse, a model of type I insulin-dependent diabetes mellitus (IDDM). Tail-flick latency before and after hyperglycemia was unaltered. Hyperglycemic NOD mice were hyporesponsive to intracerebroventricular (i.c.v.) injections of [D-Ala(2)]deltorphin II but not to [D-Ala(2), N-MePhe(4), Gly-ol(5)]enkephalin (DAMGO); however, G-protein activation in pons/medulla assessed by [35S]GTPgammaS binding was not diminished. This suggests that a G-protein defect in signaling cannot account for the hyporesponsiveness of antinociception in this genetic model of IDDM.


Isolation and identification of a novel cis-epoxysuccinate hydrolase-producing Bordetella sp. BK-52 and optimization of enzyme production.
To isolate and identify a novel strain with cis-epoxysuccinate hydrolase (CESH) activity and to optimize its enzyme production. The isolated strain was identified by electron microscopy, Biolog gram negative (GN) test, G+C (guanine plus cytosine) content measurement and 16S rDNA sequence. The purified enzymatic biotransformed product was identified by IR, 1H-NMR, 13C-NMR, MS and optical rotation analysis. Then the fermentation conditions for CESH production were optimized. A novel CESH-producing strain was isolated for biotransforming cis-epoxysuccinate to D(-)-tartaric acid. It was assigned to genus Bordetella and named Bordetella sp. BK-52. The optimal conditions were found to be 30 degrees C, pH 7.0, fermentation time 36 h, carbon source of saccharose, inorganic nitrogen source of ammonium sulfate and enzyme inducer of disodium cis-epoxysuccinate. Under these conditions, the maximum CESH activity reached 764 U/g biomass. The isolated Bordetella sp. BK-52 provided a new alternative for biosynthesis of D(-)-tartaric acid from cis-epoxysuccinate.


Does Sclerostin Depletion Stimulate Fracture Healing in a Mouse Model?
Sclerostin is a secreted glycoprotein that inhibits the intracellular Wnt signaling pathway, which, when inactivated, stimulates bone formation. This has been seen in fracture studies, which have shown larger and stronger calluses with accelerated fracture healing in sclerostin knockout and sclerostin antibody injection models. However, the effects of these two mechanisms have not been compared in the context of fracture healing. We sought to determine the degree to which sclerostin inhibition (Scl-Ab injection) and complete sclerostin depletion inhibit fracture healing in a mouse model as evaluated by (1) morphometric trabecular bone measures at the fracture site, and (2) fracture site structural strength. Ten-week-old male sclerostin knockout (n = 20) and wild type (n = 40) mice underwent insertion of a tibial intramedullary pin after which a midshaft tibial osteotomy was performed. The mice were divided in three groups: sclerostin knockout (n = 20), wild type with sclerostin antibody injection (intravenous dose of 100 mg/kg weekly) (n = 20), and wild type with saline injection (n = 20). The mice for each group where subdivided and euthanized at 14, 21, 28, and 35 days after surgery, at which time the fractured tibias were assessed with microCT (to assess morphometric trabecular bone measures: bone volume to total volume (BV/TV), trabecular thickness, trabecular number, and structural model index at the fracture site. Biomechanical testing in the form of three-point bending also was done to assess fracture site structural strength. A difference greater than 3.7% in our primary outcome (BV/TV) would be required to detect a difference between groups with a power of 80%, as per our power analysis. The wild type with sclerostin antibody and the sclerostin knockout groups showed increased trabecular BV/TV at the fracture site compared with the wild type group with saline at all times, however no difference was seen between the treatment groups with the numbers available, except at 28 days postoperatively when the sclerostin knockout group showed greater BV/TV than the wild type sclerostin antibody group (47.0 ± 3.5 vs 40.1 ± 2.1; p < 0.05). On biomechanical testing the wild type sclerostin antibody showed increased stiffness at Days 14 and 28 compared with the wild type with saline group (70.9 ± 6.4 vs 14.8 ± 8.1; p = 0.001), (106.8 ± 24.3 vs 74.9 ± 16.0; p = 0.004); respectively. However, with the numbers available, no differences were detected between the wild type with sclerostin antibody and the sclerostin knockout groups in terms of whole-bone structural strength. Sclerostin antibody injections showed promising results, which were not different with the numbers available, from results achieved with complete depletion of sclerostin, especially at earlier stages of the healing process, and therefore completed the healing process at an earlier time. Sclerostin antibody injections appear to enhance fracture healing to a degree that is not different than complete sclerostin depletion, but larger animal studies are required to assess the accurate dosage and timing of administration in the fracture healing process to further evaluate its potential clinical utility to enhance fracture healing.


Targeted ablation of epicardial ganglionated plexi during cardiac surgery with pulsed field electroporation (NEURAL AF).
Modulation of the cardiac autonomic nervous system (ANS) is a promising adjuvant therapy in the treatment of atrial fibrillation (AF). In pre-clinical models, pulsed field (PF) energy has the advantage of selectively ablating the epicardial ganglionated plexi (GP) that govern the ANS. This study aims to demonstrate the feasibility and safety of epicardial ablation of the GPs with PF during cardiac surgery with a primary efficacy outcome of prolongation of the atrial effective refractory period (AERP). In a single-arm, prospective analysis, patients with or without a history of AF underwent epicardial GP ablation with PF during coronary artery bypass grafting (CABG). AERP was determined immediately pre- and post- GP ablation to assess cardiac ANS function. Holter monitors were performed to determine rhythm status and heart rate variability (HRV) at baseline and at 1-month post-procedure. Of 24 patients, 23 (96%) received the full ablation protocol. No device-related adverse effects were noted. GP ablation resulted in a 20.7 ± 19.9% extension in AERP (P < 0.001). Post-operative AF was observed in 7 (29%) patients. Holter monitoring demonstrated an increase in mean heart rate (74.0 ± 8.7 vs. 80.6 ± 12.3, P = 0.01). There were no significant changes in HRV. There were no study-related complications. This study demonstrates the safety and feasibility of epicardial ablation of the GP using PF to modulate the ANS during cardiac surgery. Large, randomized analyses are necessary to determine whether epicardial PF ablation can offer a meaningful impact on the cardiac ANS and reduce AF. Clinical trial registration: NCT04775264.


Electrospun polyvinyl alcohol-chitosan dressing stimulates infected diabetic wound healing with combined reactive oxygen species scavenging and antibacterial abilities.
Diabetic wounds (DW) are constantly challenged by excessive reactive oxygen species (ROS) accumulation and susceptibility to bacterial contamination. Therefore, the elimination of ROS in the immediate vicinity and the eradication of local bacteria are critical to stimulating the efficient healing of diabetic wounds. In the current study, we encapsulated mupirocin (MP) and cerium oxide nanoparticles (CeNPs) into a polyvinyl alcohol/chitosan (PVA/CS) polymer, and then a PVA/chitosan nanofiber membrane wound dressing was fabricated using electrostatic spinning, which is a simple and efficient method for fabricating membrane materials. The PVA/chitosan nanofiber dressing provided a controlled release of MP, which produced rapid and long-lasting bactericidal activity against both methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) strains. Simultaneously, the CeNPs embedded in the membrane exhibited the desired ROS scavenging capacity to maintain the local ROS at a normal physiological level. Moreover, the biocompatibility of the multifunctional dressing was evaluated both in vitro and in vivo. Taken together, PVA-CS-CeNPs-MP integrated the desirable features of a wound dressing, including rapid and broad-spectrum antimicrobial and ROS scavenging activities, easy application, and good biocompatibility. The results validated the effectiveness of our PVA/chitosan nanofiber dressing, highlighting its promising translational potential in the treatment of diabetic wounds.


Prenatal diagnosis study using array comparative genomic hybridization for genotype-phenotype correlation in 772 fetuses.
The aim was to evaluate the main indications for prenatal diagnosis, the prevalence of abnormal copy number variations (CNVs), correlate them with clinical findings, analyze the prevalence of VUS, report the rare variants found and additionally highlight the clinical importance of microarray-based comparative genomic hybridization (aCGH) in prenatal diagnosis. We retrospectively analyzed a cohort of 772 fetuses with indication for genetic study in two tertiary hospitals, in a 9-years-period, using aCGH. Our results demonstrated 8.3 % (6.4-10.5 %, 95 % CI) detection rate of pathogenic CNVs. Within this group, the main indication was structural malformations (57 %) mainly involving central nervous system, skeletal and cardiac systems. Pathogenic results in cases with multiple malformations were higher than in cases with isolated anatomical system malformations showing statistical significant differences (p < 0.001). The second indication where we found more pathogenic CNVs was increased nuchal translucency (5-6.4 mm). In fact, the rate of pathogenic CNVs did not show significant differences between structural and non-structural malformations (p > 0.001), highlighting the relevance of genetic study by aCGH also in cases with no structural malformations. A total of 217 fetuses with CNVs classified as VUS were identified, mainly involving chromosomes X, 1 and 16. Our findings demonstrate 4.9 % (4.2-5.6 %, 95 % CI) increased in the diagnostic yield using aCGH compared to the use of conventional karyotype alone, confirming that the aCGH can improve the accuracy of prenatal diagnosis. Our survey provides a full genotype-phenotype analysis that can be clinically useful for the classification of variants in the context of prenatal setting, helping to provide a better reproductive genetic counselling.


Using novel biomarkers to triage young adult women with minor cervical lesions: a cost-effectiveness analysis.
To evaluate the short-term consequences and cost-effectiveness associated with the use of novel biomarkers to triage young adult women with minor cervical cytological lesions. Model-based economic evaluation using primary epidemiological data from Norway, supplemented with data from European and American clinical trials. Organised cervical cancer screening in Norway. Women aged 25-33 years with minor cervical cytological lesions detected at their primary screening test. We expanded an existing simulation model to compare 12 triage strategies involving alternative biomarkers (i.e. reflex human papillomavirus (HPV) DNA/mRNA testing, genotyping, and dual staining) with the current Norwegian triage guidelines. The number of high-grade precancers detected and resource use (e.g. monetary costs and colposcopy referrals) for a single screening round (3 years) for each triage strategy. Cost-efficiency, defined as the additional cost per additional precancer detected of each strategy compared with the next most costly strategy. Five strategies were identified as cost-efficient, and are projected to increase the precancer detection rate between 18 and 57%, compared with current guidelines; however, the strategies did not uniformly require additional resources. Strategies involving HPV mRNA testing required fewer resources, whereas HPV DNA-based strategies detected >50% more precancers, but were more costly and required twice as many colposcopy referrals compared with the current guidelines. Strategies involving biomarkers to triage younger women with minor cervical cytological lesions have the potential to detect additional precancers, yet the optimal strategy depends on the resources available as well as decision-makers' and women's acceptance of additional screening procedures. Women with minor cervical lesions may be triaged more accurately and effectively using novel biomarkers.


[Outpatient rehabilitation after myocardial infarction or for heart failure].
Reducing cardiac mortality and improving quality of life are the main objectives of cardiac rehabilitation. In recent years, outpatient rehabilitation within easy patient reach has achieved the same status as inpatient rehabilitation. Outpatient rehabilitation permits close involvement of the patient's family and social environment, thus easing reintegration into everyday life. However, the health care system is not yet utilizing outpatient rehabilitation to its full potential. This contribution illustrates the principles of rehabilitation following myocardial infarction or for heart failure in an outpatient setting, as well as its potential and future development.


Detection of a plant enzyme exhibiting chlorogenate-dependant caffeoyltransferase activity in methanolic extracts of arbuscular mycorrhizal tomato roots.
When Glomus intraradices-colonised tomato roots were extracted in methanol at 6 °C, chlorogenic acid (5-caffeoylquinic acid), naturally present in the extract, was slowly converted by transesterification into methyl caffeate. The progress of the reaction could be monitored by HPLC. The reaction only occurred when the ground roots were left in contact with the hydro-alcoholic extract and required the presence of 15-35% water in the mixture. When the roots were extracted in ethanol, chlorogenic acid was transformed to ethyl caffeate in the same conditions. The reaction was also detected in Glomus mosseae-colonised tomato root extracts. It was also detectable in non-mycorrhizal root extracts but was 10-25 times slower. By contrast it was undetectable in extracts of the aerial parts of tomato plants, which also contain high amounts of chlorogenic acid, whether or not these plants were inoculated by the arbuscular mycorrhizal fungus. We found that this transesterification reaction is catalysed by a tomato enzyme, which remains active in hydro-alcoholic mixtures and exhibits chlorogenate-dependant caffeoyltransferase activity in the presence of methanol or ethanol. This transferase activity is inhibited by phenylmethanesulfonyl fluoride. The 4- and 3-caffeoylquinic acid isomers were also used as substrates but were less active than chlorogenic acid. Highest activity was detected in mycorrhizal roots of nutrient-deprived tomato plants. Surprisingly this caffeoyltransferase activity could also be detected in hydro-alcoholic extracts of G. intraradices-colonised roots of leek, sorghum or barrel medic.


Nitazoxanide: a review of its use in the treatment of gastrointestinal infections.
Nitazoxanide (Alinia, Daxon, Dexidex, Paramix, Kidonax, Colufase, Annita) has in vitro activity against a variety of microorganisms, including a broad range of protozoa and helminths. Nitazoxanide is effective in the treatment of protozoal and helminthic infections, including Cryptosporidium parvum or Giardia lamblia, in immunocompetent adults and children, and is generally well tolerated. Nitazoxanide is a first-line choice for the treatment of illness caused by C. parvum or G. lamblia infection in immunocompetent adults and children, and is an option to be considered in the treatment of illnesses caused by other protozoa and/or helminths.


Pelvic lymph node visualization with MR imaging using local administration of ultra-small superparamagnetic iron oxide contrast.
To determine if interstitial injection of iron oxide particles improves visualization of pelvic lymph nodes at magnetic resonance imaging (MRI) and to determine the effect of injection site on location of visualized nodes. In nine healthy volunteers, ferumoxtran-10 iron oxide (0.28 mg iron per kg) was injected into the anterior thigh (three subjects) or perianal (three subjects) or periprostatic tissues (three subjects). MRI at 1.5 T was performed before injection and one, three, and seven days after injection. The mean of 30 nodes seen post-injection was greater than the mean of 5.8 seen pre-injection (P < 0.001). After thigh injection, a mean of three internal vs. 36 external nodes were seen. Compared with thigh injection, there was a higher fraction of internal nodes with perianal (mean of nine internal vs. 14 external, P < 0.001) and periprostatic injection (mean of 11 internal vs. five external, P < 0.001). More nodes were seen with gradient-echo sequences than with other sequences (P < 0.001). Interstitial injection of iron oxide particles increases visualization of pelvic lymph nodes. Perianal and periprostatic injection increases the number of internal pelvic lymph nodes seen compared with thigh injection.


[Explanations to the patients: a proposed method (author's transl)].
A stepwise explanatory process is proposed: through a brochure in which the type, significance, and, for the cautious patient, the major as well as minor risks are described (1st step), through a conference in which the individual circumstances are considered and the patient has the opportunity to ask more detailed questions (2nd step). The patient should guarantee in writing that he received the brochure, that he does or does not wish further explanation of the risks, that he consents to the operation and to necessary changes or elaborations.


Possible role of oxidized glutathione for the regulation of the myocardial hexose monophosphate shunt.
Infusion of the isolated perfused Langendorff rat heart with tert-butyl hydroperoxide (3 X 10(-4) M) resulted in a marked enhancement of the concentration of oxidized glutathione, in an increase of the NADP+/NADPH ratio, and in an elevation of the available pool of 5-phosphoribosyl-1-pyrophosphate, which is one of the end products of the hexose monophosphate shunt. Since it has been shown that oxidized glutathione overcomes the inhibition of glucose-6-phosphate dehydrogenase exerted by NADPH, these results suggest that the myocardial hexose monophosphate shunt can be stimulated rapidly and markedly through this control mechanism.


Chromosome-damaging effect of betel leaf.
The chewing of betel leaf with other ingredients is a widespread addiction in India. The chromosome damaging effect was studied in human leukocyte cultures. There was an increase in the frequency of chromatid aberrations when the leaf extract was added to cultures.


Design, synthesis, and evaluation of original carriers for targeting vascular endothelial growth factor receptor interactions.
Angiogenesis is a key event in tumor growth and metastasis, chronic inflammatory disease, and cardiovascular disease. It is controlled by positive and negative regulators, which include vascular endothelial growth factor (VEGF) as the most active of these. VEGF/VEGF receptors are important targets not only for therapy but also for imaging. Based on the structural study of VEGF, we developed a novel cyclopeptide (cyclo-VEGI) that exhibits powerful antitumor properties. We herein report the design of novel molecules derived from cyclo-VEGI as potential targeting agents in cancer and other angiogenesis-related diseases. We performed selective chemical modification of the most active VEGF-derived cyclopeptide (cyclo-VEGI). Original hydrophilic linkers were synthesized and coupled to cyclo-VEGI. These reactions provide nanocarriers for delivery. The inhibitory effect of the different compounds on VEGF binding was evaluated in competition assays with 125I-VEGF. A fluorescent cyclo-VEGI peptide was synthezised to assess direct binding and internalization of cyclo-VEGI. Chemical modifications of cyclo-VEGI do not diminish the biological activity of cyclo-VEGI as measured in competition assays; in fact, it is even increased. Moreover there is a strong cellular accumulation of the fluorescent-labeled cyclo-VEGI. Conjugates synthesized in this study may be useful leads to design delivery systems for targeting approaches in cancer and other angiogenesis-related diseases. The modified cyclo-VEGIs may have a wide range of applications and represent a useful tool to develop delivery/carrier systems for therapeutic targeting or imaging.


Primary neuroendocrine tumor in the liver treated by hepatectomy: report of a case.
A 49-year-old woman was admitted to our hospital under suspicion of an enlarging hepatic tumor, which had been previously diagnosed to be a cavernous hemangioma. Computed tomography revealed three enhanced tumors, one measuring 15 cm in diameter within the right lobe of the liver and two intrahepatic metastases in Couinaud's hepatic segments 3 and 5. We diagnosed the patient to have primary liver cancer, and suspected a combined liver tumor preoperatively. We performed a right trisectionectomy with radiofrequency ablation of the intrahepatic metastasis in S3. According to the immunohistochemical findings of the resected specimen and the findings of postoperative imaging studies, the tumor was diagnosed to be a primary neuroendocrine tumor in the liver. The patient is presently alive without recurrence at 33 months after the operation.


Comparison of the characteristics of bottom and fly ashes generated from various incineration processes.
This study analyzed and compared the characteristics of bottom and fly ashes from three municipal solid waste incinerators (MSWIs) in Taiwan. Different incineration furnaces were investigated, including: (1) fluidized bed, (2) mass-burning, and (3) mass-burning linked rotary kiln. The particle size distribution, morphology, mineralogical and chemical composition, and leaching behavior of heavy metals of ash samples were evaluated. The results revealed that three types of incineration processes have different characteristic for ashes due to transportation and mixing system inside furnace. Particle size distribution indicated that 28.5% of MSWI-B bottom ash has lower than 180 microm and 61.2% of MSWI-A fly ash has larger than the 250 microm. The leaching concentration of Pb exceeded the regulatory level set by the Taiwan EPA in fly ashes from MSWI-B and MSWI-C, and thus must be considered hazardous wastes. Specifically, the leaching concentration of heavy metals of fly ashes from MSWI-A (fluidized bed incinerator) was lower than that of the others, and was corresponded to the regulatory levels. Therefore, a fluidized bed incineration process appears a potential of handling heavy metals for ashes. The result was also provided the valuable information for incinerator design and operation.


The relation between disgust-sensitivity, blood-injection-injury fears and vasovagal symptoms in blood donors: disgust sensitivity cannot explain fainting or blood donation-related symptoms.
Page's (1994) prominent theory for the explanation of fainting in blood-injection-injury situations holds that disgust sensitivity contributes to syncopal reactions. We investigated if blood donation-related vasovagal symptoms (1) or fainting related to blood donations (2) are associated with disgust sensitivity. In an online sample of 361 blood donors, we assessed blood-injection-injury fears, disgust sensitivity, history of blood donation related fainting and retrospective self-ratings of vasovagal symptoms. For the assessment of blood-injection-injury fears we used the BII-Q which has excellent psychometric properties and does not confound disgust and anxiety sensitivity. Vasovagal symptoms were measured by the Blood Donation Reactions Inventory (BDRI) which captures mild and strong vasovagal symptoms and has been used in previous studies with blood donors. Disgust sensitivity did not significantly contribute to the explanation of self-reported vasovagal symptoms in a regression model with gender, blood-injection-injury fear and disgust sensitivity as predictors. We did not find any significant group differences in disgust sensitivity for blood donors with or without a fainting history (statistical power = 0.95) and a Bayesian model selection procedure showed that it is more likely that both groups are equally disgust sensitive than it is that the fainters are more disgust sensitive. Further research is required to confirm the findings in prospective studies. Our results indicate that disgust sensitivity is not relevant for the development of vasovagal syncopes.


Association of Interleukin-1 Receptor Antagonist ( IL-1RA ) Gene Polymorphism with Community-Acquired Pneumonia in North Indian Children: A Case-Control Study.
Background Community-acquired pneumonia (CAP) is the leading cause of death in children < 5 years of age. The primary objective of the study was to assess the association of IL-1RA gene polymorphism in children aged 2 to 59 months with CAP and the secondary objective was to assess the association of gene polymorphism with mortality among hospitalized CAP cases. Study Design This case-control study was conducted in a tertiary teaching institute in Northern India. Hospitalized children aged 2 to 59 months with World Health Organization-defined CAP were included as cases after parental consent. Age-matched healthy controls were recruited from the immunization clinic of the hospital. Genotyping was done using polymerase chain reaction to analyze the variable number of tandem repeats of IL-1RA gene polymorphism. Result From October 2019 to October 2021, 330 cases (123, 37.27% female), and 330 controls (151, 45.75% female) were recruited. Genotype A2/A2 of the IL-1RA gene was found to be associated with the increased risk for CAP children with adjusted odds ratio (AOR) of 12.24 (95% confidence interval [CI] 5.21-28.7, p < 0.001). A2 and A4 alleles were also found to be at risk for CAP. A1/A2 genotype was found to be protective for CAP with an AOR of 0.29 (95% CI 0.19-19.0.45). The genotype A2/A2 and A2 allele of IL-1RA gene was associated with child mortality with CAP cases. Conclusion In IL1RA gene, A2/A2 genotype and A2 allele were associated with increased risk of CAP and A1/A2 were found to be protective for CAP. The genotype A2/A2 and A2 was associated with CAP mortality.


Outcome measures in psoriatic arthritis clinical trials.
Outcome measures in psoriatic arthritis (PsA) have been primarily borrowed from the assessment of rheumatoid arthritis and ankylosing spondylitis, although several specific measures for PsA have been established. The advent of new therapeutic agents for the treatment of PsA has made the need for specific outcome measures for PsA more critical to evaluate the heterogeneous manifestations of this disease and features that are unique to its assessment. Several outcome measures have been validated for use in PsA clinical trials while others are being evaluated by groups such as The Group for Assessment of Psoriasis and Psoriatic Arthritis for future use in clinical trials.


Prediction equations for balance measured as sway speed by head tracking with eyes open and closed.
To provide prediction equations for balance measured as sway speed, a population of randomly selected subjects was used as a model. 265 subjects were selected from voter registration rolls in Arizona and Louisiana, USA. For validation these predicted values were compared with observed values obtained from a second population in California, USA. Sway speed with eyes open as a natural logarithm was: 1n (open) = -0.248333 -0.009634 x age +0.000164 x age2 and sway speed with eyes closed was: 1n (closed) = -0.585707 -0.023074 x age +0.000315 x age2 + 0.038496 x height (cm) The natural logarithm of balance with the eyes open was related to age by both linear and quadratic functions. Additionally with the eyes closed balance was dependent on height. These equations can be used to predict performance of groups being studied for effects of noise and chemicals. To define abnormality of individual subjects the predicted value plus 1.5 SDs could be used.


Antimony distribution and environmental mobility at an historic antimony smelter site, New Zealand.
A historic antimony smelter site at Endeavour Inlet, New Zealand has smelter residues with up to 17 wt.% antimony. Residues include coarse tailings (cm scale particles, poorly sorted), sand tailings (well sorted) and smelter slag (blocks up to 30 cm across). All of this material has oxidised to some degree over the ca. 100 years since the site was abandoned. Oxidation has resulted in acidification of the residues down to pH 2-5. Smelter slag contains pyrrhotite (FeS) and metallic antimony, and oxidation is restricted to surfaces only. The coarse tailings are the most oxidised, and few sulfide grains persist. Unoxidised sand tailings contain 10-20 vol.% stibnite (Sb2S3) containing up to 5% As, with subordinate arsenopyrite (FeAsS), and minor pyrite (FeS2). The sand tailings are variably oxidised on a scale of 2-10 cm, but original depositional layering is preserved during oxidation and formation of senarmontite (Sb2O3). Oxidation of sand tailings has resulted in localised mobility of both Sb and As on the cm scale, resulting in redistribution of these metalloids with iron oxyhydroxide around sand grain boundaries. Experiments demonstrate that Sb mobility decreases with time on a scale of days. Attenuation of both As and Sb occurs due to adsorption on to iron oxyhydroxides which are formed during oxidation of the smelter residues. There is no detectable loss of Sb or As from the smelter site into the adjacent river, <50 m away, which has elevated Sb (ca. 20 microg/l) and As (ca. 7 microg/l) from mineralised rocks upstream. Despite the high concentrations of Sb and As in the smelter residues, these metalloids are not being released into the environment.


Wheelchair seating: A study on the healthy elderly.
Many frail elderly and disabled persons have to use a manual wheelchair to remain mobile and active. Apart from a well-fitted wheelchair, an appropriate wheelchair cushion is considered crucial for postural support and to prevent complications. To examined the effect of two types of seat cushions in two types of wheelchairs with regard to pelvic rotation, respiratory function, and interface pressure. Forty healthy elderly between 67 and 85 years of age participated. Two types of commonly used manual wheelchairs and two types of seat cushions were tested. Interface pressure, pelvic position, and respiratory function were measured using a sensor array mat, a study-specific inclinometer, and a spirometer. Differences in interface pressure and pelvic rotation between cushions were found in both wheelchairs. Compared with sitting on a standard cushion, sitting on the positioning cushion increased peak pressure. The posterior pelvic tilt increased with the positioning cushion in the Etac Cross wheelchair and for both cushions in the Etac Cross wheelchair compared with the HD Balance wheelchair. No difference was observed in respiratory function. This study highlights the importance of a thorough evaluation of the effects of wheelchair interventions, especially for the elderly and disabled.


Xestospongin C, a novel blocker of IP3 receptor, attenuates the increase in cytosolic calcium level and degranulation that is induced by antigen in RBL-2H3 mast cells.
1. We evaluated the role of the cross-linking of Fc epsilon RI-mediated inositol 1,4,5-triphosphate (IP(3)) in the increase in cytosolic Ca(2+) level ([Ca(2+)](i)) using xestospongin C, a selective membrane permeable blocker of IP(3) receptor, in RBL-2H3 mast cells. 2. In the cells sensitized with anti-dinitrophenol (DNP) IgE, DNP-human serum albumin (DNP-HSA) and thapsigargin induced degranulation of beta-hexosaminidase and a sustained increase in [Ca(2+)](i). Xestospongin C (3 - 10 microM) inhibited both of these changes that were induced by DNP-HSA without changing those induced by thapsigargin. 3. In the absence of external Ca(2+), DNP-HSA induced a transient increase in [Ca(2+)](i). Xestospongin C (3 - 10 microM) inhibited this increase in [Ca(2+)](i). 4. In the cells permeabilized with beta-escin, the application of IP(3) decreased Ca(2+) in the endoplasmic reticulum (ER) as evaluated by mag-fura-2. Xestospongin C (3 - 10 microM) inhibited the effect of IP(3). 5. After the depletion of Ca(2+) stores due to stimulation with DNP-HSA or thapsigargin, the addition of Ca(2+) induced capacitative calcium entry (CCE). Xestospongin C (3 - 10 microM) inhibited the DNP-HSA-induced CCE, whereas it did not affect the thapsigargin-induced CCE. 6. These results suggest that Fc epsilon RI-mediated generation of IP(3) contributes to Ca(2+) release not only in the initial phase but also in the sustained phase of the increase in [Ca(2+)](i), resulting in prolonged Ca(2+) depletion in the ER. The ER Ca(2+) depletion may subsequently activate CCE to achieve a continuous [Ca(2+)](i) increase, which is necessary for degranulation in the RBL-2H3 mast cells. Xestospongin C may inhibit Ca(2+) release and consequently may attenuate degranulation.