Toxicity of polyvinyl chloride microplastics on Brassica rapa.
Microplastics (MPs) can pose high risk to living organisms due to their very small sizes. This study selected polyvinyl chloride MPs (PVC-MPs) which experienced up to 1000 h UV light radiation to investigate the influence of PVC-MPs on Brassica rapa growth. The outcomes showed the presence of PVC-MPs inhibited the plants' growth. The stem length, root length, fresh weight and dry weight of plants exposed to PVC-MPs after 30 days reduced by 45.9%, 35.2%, 26.1% and 5.2%, respectively. The chlorophyll, soluble sugar, malondialdehyde (MDA) and catalase (CAT) concentrations for plants exposed to PVC-MPs after 30 days increased by 25.9%, 135.7%, 88.7% and 47.1% respectively. It was also observed that PVC-MPs blocked the plants' leaf stomata and even entered plants' bodies. This might lead to PVC-MPs movement within the plants and influence plants' growth. The transcriptomic analysis results indicated that exposure to PVC-MPs up-regulated metabolic pathway of plant hormone signal transduction of the plants and down-regulated pathway network of ribosome. However, the research outcomes also showed that the PVC-MPs' locations in soil (located at the upper layers or at lower layers) and the UV light radiation time did not exert significantly different influences on inhibiting plants' growth. This can be attributed to PVC-MPs' small sizes and not much decomposition under light radiation. These imply that longer light radiation time and different particle sizes should be included into future research in order to further explore photodegraded MPs' toxicity effects on plants.


The non-synonymous C1858T substitution in the PTPN22 gene is associated with susceptibility to the severe forms of alopecia areata.
Alopecia areata is an acquired hair loss disorder resulting from an immunologically- mediated attack on hair follicles and autoimmunity may play a part in its pathogenesis. The non-synonymous C1858T substitution in the PTPN22 gene, which encodes lymphoid protein tyrosine phosphatase, has been shown to be associated with susceptibility to autoimmune disorders. In this study, the objective was to ascertain whether or not the disease-associated 1858T (W620) allele was associated with alopecia areata. For this, the allelic distribution of the PTPN22 C1858T alleles was determined in 196 English patients with alopecia areata and 507 healthy subjects in a case control study using a restriction fragment length polymorphism-polymerase chain reaction (PCR-RFLP) genotyping method. The results indicated that the frequency of the 1858T allele did not differ significantly between the alopecia areata patient group and the control cohort: of 392 alopecia areata alleles, 41 (10.5%) encoded the W620 variant compared to 86 of 1014 (8.5%) control alleles. However, in patients with severe disease, 25/168 (14.9%) alleles were 1858T and this frequency differed from that in the control group (P = 0.0127; OR, 95% CI = 1.89, 1.17 - 3.05). These results suggest that the non-synonymous C1858T substitution in the PTPN22 gene may have an influence on the severity of alopecia areata and provide further evidence for autoimmunity as an aetiological factor in this disorder.


The Heart Beats as It Breathes, or Is It the Other Way Around?
One third of human life is spent sleeping, thus the importance of sleep in the maintenance of correct homeostatic balance is well established [...].


The role of vasopressin in the impaired water excretion of myxedema.
The plasma vasopressin response to acute water ingestion was evaluated in 20 patients with myxedema prior to definitive treatment and in eight of these same patients following therapy of their hypothyroidism. Vasopressin levels were elevated and failed to completely suppress following water ingestion in 15 subjects (75 per cent). Two hypothyroid patients with elevated plasma vasopressin levels (10 per cent) had a normal renal response to the water challenge suggesting partial end organ hormonal unresponsiveness. In three (15 per cent) of the five patients with suppressible vasopressin, water excretion was impaired indicating a nonvasopressin-mediated renal defect. In eight patients restudied after achievement of a euthyroid state, vasopressin inhibition and urinary excretion were normal following the oral water load. Although intrinsic renal changes in the hypothyroid state may contribute to the observed defect in water diuresis, the present study suggests a role of endogenous vasopressin in this disorder.


Debate on the compositions of influenza B in northern hemisphere seasonal influenza vaccines.
Annual influenza vaccination is the most effective way to prevent influenza. Influenza vaccines have traditionally included the hemagglutinins (HA) and neuraminidases (NA) from the two A viruses (H1N1 and H3N2) and either B Yamagata or B Victoria. Mismatches between circulating isolates of influenza B and the vaccines are very common. Taking 2017/2018 winter in northern hemisphere as an example, this study was designed to find out the reasons for mismatch between the trivalent influenza vaccine (TIV) and most of the epidemic isolates at that time, and to discuss if there are some optimized programs for seasonal influenza vaccines. HA and NA sequences of the seasonal isolates circulating from December 1, 2017 to February 28, 2018, and in the previously other 7 winters in northern hemisphere from Global Initiative on Sharing All Influenza Data (GISAID) and the influenza database of National Center for Biotechnology Information (NCBI). Phylogenetic trees and genetic distances were constructed or calculated by using MAFFT and MEGA 6.0 software. Influenza B composition in the TIV recommendation mismatched most of circulating viruses in 2017/2018 winter; the vaccine strain was from the B/Victoria lineage, while most of epidemic isolates were from the B/Yamagata lineage. The epidemic lineage of influenza B reached its peak a little late in the previous winter might be responsible for this mismatch. During 2010-2018, the mean genetic distances between epidemic isolates of influenza A (H1N1 and H3N2) and the vaccines were no higher than 0.02375 ± 0.00341 in both HA and NA. However, concerning influenza B virus, when forecasting done well, the mean genetic distances between epidemic isolates and the vaccines were no higher than 0.02368 ± 0.00272; otherwise, the distances could reach 0.13695 ± 0.00238. When applying quadrivalent influenza vaccines (QIVs) for vaccination, the recommendations of compositions for influenza B could be altered and assessed once in 3 or 4 years; when economic burden was considered intensively and TIVs were utilized, the recommended compositions for influenza B could be announced in April or May, rather than in February or March as now.


Minimizing acquisition-related radiomics variability by image resampling and batch effect correction to allow for large-scale data analysis.
To identify CT-acquisition parameters accounting for radiomics variability and to develop a post-acquisition CT-image correction method to reduce variability and improve radiomics classification in both phantom and clinical applications. CT-acquisition protocols were prospectively tested in a phantom. The multi-centric retrospective clinical study included CT scans of patients with colorectal/renal cancer liver metastases. Ninety-three radiomics features of first order and texture were extracted. Intraclass correlation coefficients (ICCs) between CT-acquisition protocols were evaluated to define sources of variability. Voxel size, ComBat, and singular value decomposition (SVD) compensation methods were explored for reducing the radiomics variability. The number of robust features was compared before and after correction using two-proportion z test. The radiomics classification accuracy (K-means purity) was assessed before and after ComBat- and SVD-based correction. Fifty-three acquisition protocols in 13 tissue densities were analyzed. Ninety-seven liver metastases from 43 patients with CT from two vendors were included. Pixel size, reconstruction slice spacing, convolution kernel, and acquisition slice thickness are relevant sources of radiomics variability with a percentage of robust features lower than 80%. Resampling to isometric voxels increased the number of robust features when images were acquired with different pixel sizes (p < 0.05). SVD-based for thickness correction and ComBat correction for thickness and combined thickness-kernel increased the number of reproducible features (p < 0.05). ComBat showed the highest improvement of radiomics-based classification in both the phantom and clinical applications (K-means purity 65.98 vs 73.20). CT-image post-acquisition processing and radiomics normalization by means of batch effect correction allow for standardization of large-scale data analysis and improve the classification accuracy. • The voxel size (accounting for the pixel size and slice spacing), slice thickness, and convolution kernel are relevant sources of CT-radiomics variability. • Voxel size resampling increased the mean percentage of robust CT-radiomics features from 59.50 to 89.25% when comparing CT scans acquired with different pixel sizes and from 71.62 to 82.58% when the scans were acquired with different slice spacings. • ComBat batch effect correction reduced the CT-radiomics variability secondary to the slice thickness and convolution kernel, improving the capacity of CT-radiomics to differentiate tissues (in the phantom application) and the primary tumor type from liver metastases (in the clinical application).


Neutralization of transforming growth factor-beta attenuates hypertension and prevents renal injury in uremic rats.
We investigate the role of transforming growth factor-beta (TGF-beta) in hypertension and renal failure progression in uremic rats, and whether it modulates the endothelin (ET) system. Following renal mass reduction, uremic rats (Nx) received the pan-specific TGF-beta neutralizing antibody 1D11 (0.5 mg/kg, three times/week), the isotype control antibody 13C4 or the AT1 antagonist losartan (10 mg/kg per day) for 6 weeks. Before treatment, the blood pressure was higher in Nx rats and increased further over time in Nx+13C4 rats. At the end of the study, Nx+13C4 rats exhibited increased serum creatinine, proteinuria and renal expression and excretion of TGF-beta1 and ET-1. ET-1 concentrations were greater in vascular and renal tissues, whereas the ETB receptor expression was reduced. Renal injuries were comprised of blood vessel hypertrophy, glomerular sclerosis, tubular atrophy and interstitial fibrosis, which was associated with increased alpha-smooth muscle actin expression. Treatment of uremic rats with the 1D11 antibody attenuated the increase in blood pressure and the decline in renal function. Losartan normalized the blood pressure and significantly attenuated the increase in serum creatinine and proteinuria. However, both treatments prevented renal TGF-beta1 and ET-1 overexpression, and prevented all renal histological injuries. The 1D11 antibody only improved ETB receptor expression. Neutralization of TGF-beta attenuates hypertension and renal failure progression in uremic animals, in part, by preventing renal injury processes. These effects may be related to the modulation of the ET system, preventing renal ET-1 overproduction and the reduction of ETB receptor expression. Our data also suggest that TGF-beta1 is involved, at least in part, in the pathological effects related to angiotensin II in chronic renal failure.


In vivo activation of midbrain dopamine neurons via sensitized, high-affinity alpha 6 nicotinic acetylcholine receptors.
Alpha6-containing (alpha6*) nicotinic ACh receptors (nAChRs) are selectively expressed in dopamine (DA) neurons and participate in cholinergic transmission. We generated and studied mice with gain-of-function alpha6* nAChRs, which isolate and amplify cholinergic control of DA transmission. In contrast to gene knockouts or pharmacological blockers, which show necessity, we show that activating alpha6* nAChRs and DA neurons is sufficient to cause locomotor hyperactivity. alpha6(L9'S) mice are hyperactive in their home cage and fail to habituate to a novel environment. Selective activation of alpha6* nAChRs with low doses of nicotine, by stimulating DA but not GABA neurons, exaggerates these phenotypes and produces a hyperdopaminergic state in vivo. Experiments with additional nicotinic drugs show that altering agonist efficacy at alpha6* provides fine tuning of DA release and locomotor responses. alpha6*-specific agonists or antagonists may, by targeting endogenous cholinergic mechanisms in midbrain or striatum, provide a method for manipulating DA transmission in neural disorders.


Three case reports of inherited antithrombin deficiency in China: double novel missense mutations, a nonsense mutation and a frameshift mutation.
Antithrombin is a plasma protein critical to the regulation of coagulation. It plays a pivotal anticoagulant role by preventing the activation of procoagulant proteinases. Inherited and (or) acquired deficiency of AT is an established risk factor for venous thromboembolism. Sequencing analysis of SERPINC1 gene of three families revealed that Family I had double novel missense mutations (c.134G > A&c.342T > G), Family II had a nonsense mutation (c.770G > A) while Family III had a frameshift mutation (c.800-803del). In addition, all of them had a large number of carriers in their families what was very rare in China.


Pulmonary hypertensive response to foreign body microemboli.
Pulmonary hypertension and foreign body granulomas are recognized sequelae of chronic intravenous drug abuse. We have recently described the development of transient pulmonary hypertension and increased permeability pulmonary edema after the intravenous injection of crushed, suspended pentazocine tablets in both humans and dogs. To determine the role of vasoactive substances in the development of this transient pulmonary hypertension, we measured pulmonary hemodynamics and accumulation of arachidonic acid metabolites in dogs during the infusion of indomethacin, a cyclooxygenase inhibitor, diethylcarbamazine (DEC), a lipoxygenase inhibitor, and FPL 55712, a receptor antagonist for leukotriene C4/D4 (LTC4/D4). Following the intravenous administration of crushed, suspended pentazocine tablets (3-4 mg/kg of body weight), mean pulmonary artery pressure increased from 14 +/- 2 mmHg to 30 +/- 6 mmHg (p less than 0.05) at 60 secs with a concomitant increase in plasma concentrations of 6-keto-PGF1 alpha from 187 +/- 92 pg/ml to 732 +/- 104 pg/ml and thromboxane B2 from 206 +/- 83 pg/ml to 1362 +/- 117 pg/ml (both p less than 0.05). Indomethacin prevented the increase in both cyclooxygenase metabolites, but had no effect on the pulmonary hypertension. In contrast, DEC had no effect on the increase in cyclooxygenase products, but blocked the pulmonary hypertension. FPL 55712 did not effect either the increase in cyclooxygenase metabolites or the pulmonary hypertension. We conclude that the transient pulmonary hypertension, induced by the intravenous injection of crushed, suspended pentazocine tablets, is not mediated by cyclooxygenase products but may be mediated by lipoxygenase product(s) other than LTC4/D4.


The use of dynamic MR imaging in patients with clinical pelvic floor disorders.
To determine the differences and challenging aspects of dynamic magnetic resonance defecography (MRD) compared to conventional defecography (CD) in diagnostic of clinical symptomatic pelvic floor dysfunction. Fifty patients (44 females, 6 males; mean age: 57 years) with symptomatic pelvic floor dysfunction underwent both examinations, CD and MRD. Results were retrospectively intra-individual and interindividual evaluated in this multicentre study. Visibility and accuracy in diagnosis and classification of rectal prolapse, rectocele, enterocele, sigma diverticula and Cul-de-sac phenomenon/syndrome were observed. Differences were analysed using Mann-Whitney U test. P-values < 0.05 were considered as statistically significant. CD was significantly superior to MRD in diagnosis and grading of rectal prolapse (p < .001), diagnosis and metric measurements of rectoceles (p = .016), diagnosis of elongated sigmoid colon (p = .008) and Cul-de-sac phenomenon and syndrome, respectively (p = .015; p = .008). MRD revealed equal results to CD in detection, localization, tendency to retention and enlargement of rectoceles (p = .337) and findings of enteroceles (p = .604) as well as sigma diverticula (p = .149). The complementary use of both examination methods, CD and MRD, is important to achieve a comprehensive look on every aspect of pelvic floor disorders and gain optimal results in detection and evaluation of all major disorders of the pelvic floor.


Evaluation of a novel powered gait orthosis for walking by a spinal cord injury patient.
The aim of this case study was to analyze the effect on gait parameters of a new design of powered gait orthosis which applied synchronized motions to both the hip and knee joints when utilized for walking by a spinal cord injury (SCI) patient. Two orthoses were evaluated while worn by an incomplete SCI subject. Gait evaluation was performed when walking with an isocentric reciprocating gait orthosis (IRGO) and compared to that demonstrated by a newly developed powered version. This new orthosis was based on the IRGO superstructure but incorporated powered hip and knee joints using electrically motorized actuators. These gait parameters were improved when compared to standard IRGO and initial testing with the orthosis with only the hip or the knee joints activated in isolation. Maximum hip flexion and extension angles, as well as the maximum knee flexion and extension angles all increased when walking with the powered RGO compared to the IRGO. Gait evaluation of this newly developed orthosis showed improvement in measured parameters when compared to walking with an IRGO. Clinical relevance This case study gave the authors confidence to extend the research to a more extensive study with a group of SCI patients.


Biostraticola tofi gen. nov., spec. nov., a novel member of the family Enterobacteriaceae.
Bacterial strain BF36T, isolated from the biofilm of a tufa deposit in a hard water rivulet, was characterized by a polyphasic taxonomic approach. Cells of these organisms were Gram-negative, motile, nonpigmented, rod-shaped, non-endospore-forming, and facultatively anaerobic. Cells, organized in loose consortia, were coated by a massive slime layer. Phylogenetic analyses using 16S rRNA gene sequences showed that strain BF36T was a member of the family Enterobacteriaceae, class Gammaproteobacteria, displaying a moderate degree of relationship (96.5% sequence similarity) to Sodalis glossinidius and "Sodalis pallipedes," intracellular symbionts of the tsetse fly Glossinis morsitans morsitans. Dendrograms of relationship generated by different algorithms consistently grouped isolate BF36T with Sodalis glossinidius, Pragia fontium, Budvicia aquatica, Serratia rubideae, and Brenneria spp (94.7-95.8% similarity) which also share many common metabolic properties. Differences between strain BF36T and Sodalis glossinidius DSM 13495T are seen in motility and in the pattern of substrates utilized. Membership to the family was also confirmed by a fatty acid profile consisting of major amounts of C16:0)and C16:1omega7, by the presence of isoprenoids of the ubiquinone Q8 and menaquinone MK8 types and a DNA G + C content of 54.2 mol%. The decision to classify strain BF36T into a new genus Biostraticola gen. nov. is based on its distant phylogenetic position as compared to any other representative of the family and the significant phenotypic differences to its nearest phylogenetic neighbor, Sodalis glossinidius. BF36T represents the type species, for which the name Biostraticola tofi sp. nov. is proposed. The type strain is BF36T (DSM 19580T; CIP109699T).


Hormonal regulation of RNA synthesis and specific gene expression in Xenopus oviduct cells in primary culture.
The studies described in this report were carried out as a first step towards the elucidation of mechanisms underlying the tissue specificity of regulation of gene expression by estrogen. Using a procedure established earlier in our laboratory for primary culture of Xenopus hepatocytes, we have characterized how estradiol-17 beta and progesterone affect the rate of synthesis of total RNA and that of accumulation of two oviduct-specific mRNAs in Xenopus oviduct cells in primary culture. In cells that had recovered from 'culture shock' 3 days after they were plated out, both hormones had only a slight or no effect on the overall rate of labelling of newly synthesized RNA over 24 h. Cloned cDNA probes for two mRNAs, termed 7F and 6G and specifying as yet unknown proteins expressed in the oviduct and not in the liver, were used to quantify the two mRNAs. The levels of both mRNAs declined for the first 2 days in culture after which they were stabilized. When added to the oviduct cell cultures 3 days after they were plated out, estradiol increased the steady-state concentration (relative to total RNA) of 7F and 6G mRNAs by 3- to 7-fold after 60-80 h, but with different time-course and dose-response kinetics for the two messages. The antiestrogen tamoxifen also exerted different degrees of antagonist effect on the estrogen-induced accumulation of 7F and 6G mRNAs. Although the protein products of these two oviduct-specific mRNAs have not yet been characterized, these studies set the stage for comparing the regulation by estrogen of their genes with that of vitellogenin genes in primary cultures of Xenopus oviduct cells and hepatocytes.


Legionella pneumophila infection induces programmed cell death, caspase activation, and release of high-mobility group box 1 protein in A549 alveolar epithelial cells: inhibition by methyl prednisolone.
Legionella pneumophila pneumonia often exacerbates acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Apoptosis of alveolar epithelial cells is considered to play an important role in the pathogenesis of ALI and ARDS. In this study, we investigated the precise mechanism by which A549 alveolar epithelial cells induced by L. pneumophila undergo apoptosis. We also studied the effect of methyl prednisolone on apoptosis in these cells. Nuclear deoxyribonucleic acid (DNA) fragmentation and caspase activation in L. pneumophila-infected A549 alveolar epithelial cells were assessed using the terminal deoxyribonucleotidyl transferase-mediated triphosphate (dUTP)-biotin nick end labeling method (TUNEL method) and colorimetric caspase activity assays. The virulent L. pneumophila strain AA100jm and the avirulent dotO mutant were used and compared in this study. In addition, we investigated whether methyl prednisolone has any influence on nuclear DNA fragmentation and caspase activation in A549 alveolar epithelial cells infected with L. pneumophila. The virulent strain of L. pneumophila grew within A549 alveolar epithelial cells and induced subsequent cell death in a dose-dependent manner. The avirulent strain dotO mutant showed no such effect. The virulent strains of L. pneumophila induced DNA fragmentation (shown by TUNEL staining) and activation of caspases 3, 8, 9, and 1 in A549 cells, while the avirulent strain did not. High-mobility group box 1 (HMGB1) protein was released from A549 cells infected with virulent Legionella. Methyl prednisolone (53.4 muM) did not influence the intracellular growth of L. pneumophila within alveolar epithelial cells, but affected DNA fragmentation and caspase activation of infected A549 cells. Infection of A549 alveolar epithelial cells with L. pneumophila caused programmed cell death, activation of various caspases, and release of HMGB1. The dot/icm system, a major virulence factor of L. pneumophila, is involved in the effects we measured in alveolar epithelial cells. Methyl prednisolone may modulate the interaction of Legionella and these cells.


Comparative assessment of study groups of elderly female computer users from four European countries: questionnaires used in the NEW study.
There is a lack of consistent and comprehensive questionnaire forms for the studies of factors associated with work-related musculoskeletal disorders at the European level. One of the results of the EU-funded project, neuromuscular assessment in the elderly worker (NEW), is a set of questionnaires for the screening of musculoskeletal status and the studies of factors that are believed to affect musculoskeletal health. The questionnaires have been used among elderly women (45+) in different occupations and organisations in Denmark, The Netherlands, Sweden and Switzerland. The aim of this short communication is to present the questionnaires used in the NEW study and to evaluate the appropriateness of pooling data gathered in each participating country into a common database. It is concluded that although differences exist among the study samples, these are not of such a magnitude or pattern that data from the four groups cannot be pooled. The questionnaires are available in Danish, Dutch, English, German and Swedish.


Long-term results of iliac aneurysm repair with iliac branched endograft: a 5-year experience on 100 consecutive cases.
Iliac branch device (IBD) technique has been introduced as an appealing and effective solution to avoid complications occurring during repair of aorto-iliac aneurysm with extensive iliac involvement. Nevertheless, no large series with long-term follow-up of IBD are available. The aim of this study was to analyse safety and long-term efficacy of IBD in a consecutive series of patients. Between 2006 and 2011, 100 consecutive patients were enrolled in a prospective database on IBD. Indications included unilateral or bilateral common iliac artery aneurysms combined or not with abdominal aneurysms. Patients were routinely followed up with computed tomography. Data were reported according to the Kaplan-Meier method. There were 96 males, mean age 74.1 years. Preoperative median common iliac aneurysm diameter was 40 mm (interquartile range (IQR): 35-44 mm). Sixty-seven patients had abdominal aortic aneurysm >35 mm (IQR: 40-57 mm) associated with iliac aneurysm. Eleven patients presented hypogastric aneurysm. Twelve patients underwent isolated iliac repair with IBD and 88 patients received associated endovascular aortic repair. Periprocedural technical success rate was 95%, with no mortality. Two patients experienced external iliac occlusion in the first month. At a median follow-up of 21 months (range 1-60) aneurysm growth >3 mm was detected in four iliac (4%) arteries. Iliac endoleak (one type III and two distal type I) developed in three patients and buttock claudication in four patients. Estimated patency rate of internal iliac branch was 91.4% at 1 and 5 years. Freedom from any reintervention rate was 90% at 1 year and 81.4% at 5 years. No late ruptures occurred. Long-term results show that IBD use can ensure persistent iliac aneurysm exclusion at 5 years, with low risk of reintervention. This technique can be considered as a first endovascular option in patients with extensive iliac aneurysm disease and favourable anatomy.


Complete Second Branchial Fistula: A Rare Entity.
Second branchial anomalies like branchial cyst, sinus or fistula are common lateral neck masses in pediatric age group but it is rare to encounter complete branchial fistula with external as well as internal openings. We present a case of 16 yrs old female patient with complete Branchial fistula which was diagnosed with the help of CT fistulogram and thereafter taken up for surgical excision of fistula under general anaesthesia. Histopathology confirmed the diagnosis of branchial fistula. In case of lateral neck mass with external opening in pediatric age group strong possibility of diagnosis of branchial fistula should be kept, timely management of the case improves the quality of life.


Phosphoprotein extraction from the dentine/cementum complex of human tooth roots.
Root shards were placed in dialysis tubing and demineralized to completion in either 10% disodium EDTA, pH 7.4, 0.6 M HCl, 0.1 M HCl, 0.5 M acetic or 75 mM-25 mM lactic-acetic acids. The demineralized shards were then re-extracted with 0.05 M tris-HCl, 1.0 M NaCl. DEAE chromatography revealed that the major peak of the 0.6 M CHl and EDTA extracts contained organic phosphorus, whereas much less organic phosphorus was found in the major peak of the 0.1 M HCl extract. Analysis of the re-extracts gave a pattern opposite to that obtained from the initial extractions. Measurements of protein and organic phosphorus released during extraction and re-extraction confirmed these results. Staining of SDS-PAGE gels for phosphoprotein with Stains-All resulted in a blue smear in fractions containing organic phosphorus. Thus the extraction of phosphoproteins from human tooth roots differed depending upon the demineralizing conditions. This ability to remove phosphoprotein differentially will allow further investigation of the role of phosphoprotein in mineralization and remineralization.


Use of heart failure medications in older individuals and associations with cognitive impairment.
To achieve the best treatment of heart failure, it is important to use all recommended drugs at their target doses. Given that underuse of medications can occur in individuals with cognitive impairment, we investigated the filled prescriptions and target doses of heart failure medication for older individuals with and without cognitive impairment as well as associated factors. The study was based on two separate datasets. The first dataset, which was based on data from questionnaires sent to nursing homes in Sweden, included 405 individuals with heart failure. The data were linked with the Swedish Prescribed Drug Register and the National Patient Register to obtain information regarding filled prescriptions of heart failure medications and heart failure diagnoses among the population. In the second dataset, medical records of individuals aged 75 years or older admitted to a hospital in northern Sweden were reviewed and individuals with heart failure were identified. Target doses of heart failure medications were evaluated in 66 individuals who lived at home. Filled prescriptions of mineralocorticoid receptor antagonists and loop diuretics were significantly more common in individuals without cognitive impairment (OR 1.087; 95% CI 1.026-1.152, p < 0.05) and (OR 1.057; 95% CI 1.017-1.098, p < 0.05), respectively. There were no significant differences between individuals with and without cognitive impairment in terms of achieving target doses for any of the drug classes. A higher age was associated with fewer filled prescriptions and less ability to reach the target doses of beta blockers (OR 0.950; 95% CI 0.918-0.984, p < 0.05) and (OR 0.781; 95% CI 0.645-0.946, p < 0.05), respectively. Our results suggest that individuals with cognitive impairment are partly undertreated for heart failure in that they had fewer filled prescriptions of important heart medications. Separately, the relatively low proportion of older individuals reaching target doses is an important observation and indicates that treatment of heart failure could be further optimised among older individuals.


Genetic alterations in children and adolescents with acute myeloid leukaemia.
Acute Myeloid Leukemia is a clinically and genetically heterogeneous disease, in which cytogenetic aberrations are the most important factors to determine biological behavior and prognosis. More than 20 different chromosomal abnormalities have been identified in a high percentage of children (70-85%) with the novo AML. We reviewed the most frequently found and the impact of these aberrations on prognosis. Differences according to the age of patients and mainly in relation to adult population have been enhanced, although the low incidence of AML in children and the high number of abnormalities make difficult to accurately define the prognosis significance of these aberrations.


Medial collateral ligament injury in the overhand-throwing athlete.
Medial collateral ligament injuries are rare and occur almost exclusively in overhand-throwing athletes. The late cocking phase of the overhand throw places a marked valgus moment across the medial elbow. This repetitive force reaches the tensile limits of the medial collateral ligament, subjecting it to microtraumatic injury and attenuation. The anterior bundle of the medial collateral ligament has been identified as the primary restraint to valgus load and is the focus of reconstruction. Diagnosis of medial collateral ligament injuries should be suspected in any overhand-throwing athlete with a history of medial-sided elbow pain, decreased control, and reduced throwing velocity. Injury to the medial collateral ligament can be confirmed by physical examination (moving valgus stress test) and appropriate imaging studies (computed tomography arthrogram and magnetic resonance imaging). Reconstructive techniques of the medial collateral ligament have evolved over time and currently provide superior outcomes, with 80% to 90% of athletes returning to the same level of competitive play. As our understanding of the pathoanatomy of medial elbow injuries progresses and newer hybrid techniques evolve, our ability to care for the overhand-throwing athlete can be expected to improve.


[Long-term complication of laparoscopic uterine morcellation: iatrogenic parasitic myomas].
Identify parasitic myomas following uterine laparoscopic morcellation and describe the circumstances of diagnosis, management, potential consequences and possible preventive measures. Retrospective study of observed cases in a university hospital between 2000 and 2012 and review of the literature. Five cases were identified in our department. Pelvic pain was the main symptom in three patients while one was asymptomatic and one consulted for a cystocele. The average time to diagnosis was 88 months (3-192). Surgical removal was performed in four cases by laparoscopy and vaginally for one case. Histological examination showed typical leiomyomas, but in one case, an atypical leiomyoma with limited experience for a typical primary lesion. In the literature, there are about 50 cases. One required a bowel resection and for another one, after subtotal hysterectomy, histological examination showed complex atypical endometrial hyperplasia for normal endometrium initially. This study should draw the attention of laparoscopic surgeon. It emphasizes, beyond a potential reoperation, a risk of atypical histological secondary processing. Surgical resection should be discussed even in case of asymptomatic lesions.


Intake of grape procyanidins during gestation and lactation impairs reverse cholesterol transport and increases atherogenic risk indexes in adult offspring.
Cardiovascular disease (CVD) is one of the most prevalent noncommunicable diseases in humans. Different studies have identified dietary procyanidins as bioactive compounds with beneficial properties against CVD by improving lipid homeostasis, among other mechanisms. The aim of this work was to assess whether grape seed procyanidin consumption at a physiological dose during the perinatal period could influence the CVD risk of the offspring. Wistar rat dams were treated with a grape seed procyanidin extract (GSPE; 25mg/kg of body weight per day) or vehicle during gestation and lactation. The adult male offspring of GSPE-treated dams presented decreased high-density lipoprotein cholesterol (HDL-C) levels, increased total cholesterol-to-HDL-C ratios and an exacerbated fasting triglyceride-to-HDL-C ratios (atherogenic index of plasma) compared to the control group. Impaired reverse cholesterol transport (RCT) was evidenced by the accumulation of cholesterol in skeletal muscle and by decreased fecal excretion of cholesterol and bile acids, which was consistent with the observed mRNA down-regulation of the rate-limiting enzyme in the hepatic bile acid synthesis pathway Cyp7A1. Conversely, GSPE programming also resulted in up-regulated gene expression of different key components of the RCT process, such as hepatic Npc1, Abcg1, Abca1, Lxra, Srebp2, Lcat, Scarb1 and Pltp, and the repression of microRNA miR-33a expression, a key negative controller of hepatic RCT at the gene expression level. Our results show that maternal intake of grape procyanidins during the perinatal period impacts different components of the RCT process, resulting in increased CVD risk in the adult offspring.


[An infant with remarkable soles of his feet].
We describe a 4-month-old male infant with a ridge across the soles of both feet without clinical signs of illness. The abnormality was diagnosed as a precalcaneal congenital fibrolipomatous hamartoma.


Extent of hypoattenuation on CT angiography source images in basilar artery occlusion: prognostic value in the Basilar Artery International Cooperation Study.
The posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) quantifies the extent of early ischemic changes in the posterior circulation with a 10-point grading system. We hypothesized that pc-ASPECTS applied to CT angiography source images predicts functional outcome of patients in the Basilar Artery International Cooperation Study (BASICS). BASICS was a prospective, observational registry of consecutive patients with acute symptomatic basilar artery occlusion. Functional outcome was assessed at 1 month. We applied pc-ASPECTS to CT angiography source images of patients with CT angiography for confirmation of basilar artery occlusion. We calculated unadjusted and adjusted risk ratios (RRs) of pc-ASPECTS dichotomized at ≥8 versus <8. Primary outcome measure was favorable outcome (modified Rankin Scale scores 0-3). Secondary outcome measures were mortality and functional independence (modified Rankin Scale scores 0-2). Of 158 patients included, 78 patients had a CT angiography source images pc-ASPECTS≥8. Patients with a pc-ASPECTS≥8 more often had a favorable outcome than patients with a pc-ASPECTS<8 (crude RR, 1.7; 95% CI, 0.98-3.0). After adjustment for age, baseline National Institutes of Health Stroke Scale score, and thrombolysis, pc-ASPECTS≥8 was not related to favorable outcome (RR, 1.3; 95% CI, 0.8-2.2), but it was related to reduced mortality (RR, 0.7; 95% CI, 0.5-0.98) and functional independence (RR, 2.0; 95% CI, 1.1-3.8). In post hoc analysis, pc-ASPECTS dichotomized at ≥6 versus <6 predicted a favorable outcome (adjusted RR, 3.1; 95% CI, 1.2-7.5). pc-ASPECTS on CT angiography source images independently predicted death and functional independence at 1 month in the CT angiography subgroup of patients in the BASICS registry.


EGFR Mutations in Cell-free Plasma DNA from Patients with Advanced Lung Adenocarcinoma: Improved Detection by Droplet Digital PCR.
Analysis of cell-free DNA from blood could provide an alternative method for identifying genomic changes in the tumors of patients with advanced lung adenocarcinoma. We compared the performance of droplet digital PCR (ddPCR) and Cobas® EGFR Mutation Test v2 (Cobas) for detecting EGFR mutations in cell-free plasma DNA. Plasma samples from patients with advanced EGFR-mutated lung adenocarcinoma were analyzed for EGFR T790M, exon 19 deletions, and L858R mutations by both ddPCR and Cobas. T790M testing was performed in 354 plasma samples collected from 129 patients. The concordance rate between ddPCR and Cobas for T790M, sensitivity, and specificity were 86, 100, and 85%, respectively. Exon 19 deletions were analyzed in 196 plasma samples obtained from 71 of the 129 patients using both platforms. The concordance rate between ddPCR and Cobas for exon 19 deletions, sensitivity, and specificity were 90, 92, and 89%, respectively. L858R mutations were studied in 124 plasma samples obtained from 44 of the 129 patients using both assays. The concordance rate between ddPCR and Cobas for L858R, sensitivity, and specificity were 90, 91, and 89%, respectively. In patients who progressed under treatment with an EGFR TKI (n = 50), the T790M positivity rate was 66% using ddPCR, but only 24% using Cobas. We observed a high concordance between ddPCR and Cobas in detecting EGFR mutations in plasma samples of patients with advanced EGFR-mutated lung adenocarcinoma, but ddPCR was more sensitive than Cobas.


The self-association of cytoplasmic malate dehydrogenase 1 promotes malate biosynthesis and confers disease resistance in cassava.
Malate dehydrogenase (MDH) as an essential metabolic enzyme is widely involved in plant developmental processes. However, the direct relationship between its structural basis and in vivo roles especially in plant immunity remains elusive. In this study, we found that cytoplasmic cassava (Manihot esculenta, Me) MDH1 was essential for plant disease resistance against cassava bacterial blight (CBB). Further investigation revealed that MeMDH1 positively modulated cassava disease resistance, accompanying the regulation of salicylic acid (SA) accumulation and pathogensis-related protein 1 (MePR1) expression. Notably, the metabolic product of MeMDH1 (malate) also improved disease resistance in cassava, and its application rescued the disease susceptibility and decreased immune responses of MeMDH1-silenced plants, indicating that malate was responsible for MeMDH1-mediated disease resistance. Interestingly, MeMDH1 relied on Cys330 residues to form homodimer, which was directly related with MeMDH1 enzyme activity and the corresponding malate biosynthesis. The crucial role of Cys330 residue in MeMDH1 was further confirmed by in vivo functional comparison between overexpression of MeMDH1 and MeMDH1C330A in cassava disease resistance. Taken together, this study highlights that MeMDH1 confers improved plant disease resistance through protein self-association to promote malate biosynthesis, extending the knowledge of the relationship between its structure and cassava disease resistance.


Hepatotoxicity and renal toxicity in rats of corn samples associated with field cases of equine leukoencephalomalacia.
Currently there is no convenient bioassay to determine the potential toxicity of corn naturally contaminated with Fusarium moniliforme. A short-term bioassay would be useful for future investigations aimed at isolating as yet unidentified toxins produced by this fungus. Two groups of five male Sprague-Dawley rats were each fed one of two F. moniliforme contaminated corn samples, designated CS-1 and CS-2, that were associated with separate field cases of equine leukoencephalomalacia (ELEM). A control group, also consisting of five male rats, was fed uncontaminated seed corn. All animals survived to the end of the study and there were no apparent differences in appearance or behaviour among groups. Weight loss and irregular food consumption occurred in all groups and probably resulted from nutritional deficiencies inherent in the corn diets. Hepatocellular degeneration, necrosis and hyperplasia as well as biliary hyperplasia were found in the test groups only and were attributed to F. moniliforme. Serum transaminase and alkaline phosphatase activities in animals fed CS-1 and CS-2 for 4 wk were significantly increased compared with the controls, while serum bilirubin concentration was increased only in the CS-1 group. Tubular nephrosis was also present in the renal cortex of all animals fed CS-1 and CS-2. These effects may have been related to fumonisins B1 and B2, recently discovered metabolites of F. moniliforme, that were found in both CS-1 and CS-2. Short-term studies of this type may be useful in screening naturally-contaminated grains and other materials for hepatotoxic metabolites produced by F. moniliforme.


Functional outcomes and complications of open elbow dislocations.
The current study investigated the clinical outcome of open elbow dislocations, focusing on the influence of associated soft tissue and bone injury. From October 2008 to August 2015, 230 patients with elbow dislocations were treated at the study center. Our retrospective study comprised 21 cases of open elbow dislocations. The mean age of patients was 49 years (20-83 years); there were six (29%) female and 15 (71%) male patients. The range of motion (ROM) of the injured and uninjured elbow was measured, and the Mayo Elbow Performance Score (MEPS), Mayo Wrist Score (MWS), and Disability of Arm, Shoulder and Hand (DASH) score were assessed. Complications and revision surgeries were recorded. The influence of the severity of soft tissue injury (I°/II° open vs. III° open) and type of dislocation (simple vs. complex) was evaluated. After a 57-month follow-up (range, 24-98 months), the mean DASH score was 20 ± 15, the MEPS was 82 ± 11, and the MWS was 74 ± 22. The ROM of the injured elbow was significantly decreased compared with the uninjured one (arc of ulnohumeral motion: 104° vs. 137°; p = 0.001). Patients with I°/II° open elbow dislocations had a better clinical outcome according to the MEPS (86 ± 11 vs. 76 ± 9; p = 0.045) and a comparable outcome according to the DASH score (19 ± 18 vs. 21 ± 9; p = 0.238). In all, 11 patients (52%) had postoperative complications and 11 patients underwent at least one revision surgery. Complex elbow dislocations had significantly more complications and revision surgeries than simple dislocations (77% vs. 13%; p = 0.008). Favorable clinical outcomes can be achieved after treatment of open elbow dislocations. These injuries are prone to neurovascular damage and complex dislocations are linked to high rates of complications and revision surgeries.


Diagnostic classification of the instantaneous wave-free ratio is equivalent to fractional flow reserve and is not improved with adenosine administration. Results of CLARIFY (Classification Accuracy of Pressure-Only Ratios Against Indices Using Flow Study).
This study sought to determine if adenosine administration is required for the pressure-only assessment of coronary stenoses. The instantaneous wave-free ratio (iFR) is a vasodilator-free pressure-only measure of the hemodynamic severity of a coronary stenosis comparable to fractional flow reserve (FFR) in diagnostic categorization. In this study, we used hyperemic stenosis resistance (HSR), a combined pressure-and-flow index, as an arbiter to determine when iFR and FFR disagree which index is most representative of the hemodynamic significance of the stenosis. We then test whether administering adenosine significantly improves diagnostic performance of iFR. In 51 vessels, intracoronary pressure and flow velocity was measured distal to the stenosis at rest and during adenosine-mediated hyperemia. The iFR (at rest and during adenosine administration [iFRa]), FFR, HSR, baseline, and hyperemic microvascular resistance were calculated using automated algorithms. When iFR and FFR disagreed (4 cases, or 7.7% of the study population), HSR agreed with iFR in 50% of cases and with FFR in 50% of cases. Differences in magnitude of microvascular resistance did not influence diagnostic categorization; iFR, iFRa, and FFR had equally good diagnostic agreement with HSR (receiver-operating characteristic area under the curve 0.93 iFR vs. 0.94 iFRa and 0.96 FFR, p = 0.48). iFR and FFR had equivalent agreement with classification of coronary stenosis severity by HSR. Further reduction in resistance by the administration of adenosine did not improve diagnostic categorization, indicating that iFR can be used as an adenosine-free alternative to FFR.


137Caesium, 40K and total K in Boletus edulis at different maturity stages: Effect of braising and estimated radiation dose intake.
We studied activity concentrations of artificial 137Cs and natural 40K and concentration of total potassium (K) in Boletus edulis at different maturity stages (button, young - white, large - white and large - yellow), and the effect of braising and human dietary intake. Mushrooms were collected from the northern region of Poland in 2019. The 137Cs activity concentration was significantly higher in raw and braised button stage samples and decreased as the fruitbody matured, but conversely, 40K was lower in the raw button stage than in older fruitbodies. 137Cs activity concentrations in raw, button stage B. edulis were 36 ± 1 Bq kg-1 ww (360 ± 1 Bq kg-1 dw), increasing to 70 ± 2 Bq kg-1 ww (290 ± 7 Bq kg-1 dw) when braised. This activity was around fourteen-fold higher (p < 0.0001) than at higher maturity stages which showed 2.5 ± 0.7 Bq kg-1 ww (25 ± 7 Bq kg-1 dw) in raw and 4.9 ± 0.7 Bq kg-1 ww (19 ± 4 Bq kg-1 dw) in braised fruitbodies. In comparison to raw B. edulis, braising enriched the activity concentrations of 137Cs at 110 ± 69% and 40K at 80 ± 56% on a whole (wet) weight basis.


Red fox (Vulpes vulpes) cannibalistic behaviour and the prevalence of Trichinella britovi in NW Italian Alps.
Food habits of the red fox (Vulpes vulpes) were studied in the Aosta Valley region (NW Italian Alps) and were related to the prevalence of Trichinella infection in the red fox itself and in two Mustelid species (the stone marten (Martes foina) and the badger (Meles meles)). The search of Trichinella by the automatic digestion of muscles samples led us to determine a prevalence of 3.5+/-1.2% in red foxes, 7.9+/-4.3% in stone martens and 1.9+/-1.8% in badgers, with no significant differences among the species. All larvae were identified as Trichinella britovi. The fox diet was assessed through the analysis of both faeces (n=180) and the stomach contents of road-killed animals (n=109). Our results confirmed the opportunistic feeding behaviour of the red fox, which is able to use various trophic resources, both of animal and vegetal origin: e.g. wild and cultivated fruits (F%=47.1; V%=67.3), rodents (F%=22.8; V%=64.8) and carrion (F%=15.6; V%=78.6) formed the bulk of the fox's diet. The frequency of occurrence of potential events of cannibalism was 1.0%, even if the complete absence of undigested remains, other than hairs, suggested the possibility of confusing cannibalism with coat-cleaning. We suggest that intra-specific necrophagy could not represent the unique way of transmission of the nematode in natural conditions.


Synthesis and biological activity of new iodoacetamide derivatives on mutants of squalene-hopene cyclase.
New iodoacetamide derivatives, containing a dodecyl or a squalenyl moiety, were synthesized. The effect of these new thiol-reacting molecules was studied on two mutants of Alicyclobacillus acidocaldarius squalene-hopene cyclase constructed especially for this purpose. In the quintuple mutant, all five cysteine residues of the enzyme are substituted with serine; in the sextuple mutant, this quintuple substitution is accompanied by the substitution of aspartate D376, located at the enzyme's active site, with a cysteine. N-Dodecyliodoacetamide had little activity toward either mutant, whereas N-squalenyliodoacetamide showed a stronger effect on the sextuple than on the quintuple mutant, as expected.


Early and late components in cat Renshaw cell responses to random stimulation of motor axons: their differential sensitivity to preceding activation.
Lumbosacral Renshaw cells were activated by random stimulation of motor axons in muscle nerves or ventral roots. The stimulus patterns had mean rates of 9.5-13 or 20-23 pulses per second. The Renshaw cell responses were evaluated by two kinds of peristimulus-time histograms. "Conventional" peristimulus-time histograms were calculated by averaging the cell discharge with respect to all the stimuli in a train. "Conditional" peristimulus-time histograms were determined by averaging the cell discharge with respect to the second ("test") stimulus in pairs of stimuli which were separated by varied intervals. The effects of the conditioning stimuli were evaluated after correcting for the effect of linear superposition of the conditioning and test stimuli. The conventional peristimulus-time histograms showed an excitatory response which often consisted of two distinct components: a narrow and high "early" peak and a broad and low "late" elevation of firing probability. The early and late excitatory components were conditioned in different ways. Whereas the late component was virtually always depressed, the early component showed three patterns: (1) uniform depression; (2) uniform facilitation; (3) a mixture of depression and facilitation. Frequency responses (coherence and gain estimates) were also calculated separately for the cell discharges underlying either the early or the late components. The estimates for the "late spikes" showed a stronger decline with increasing frequency than those for the "early spikes". The origin of the different conditioning effects probably lies in a combination of pre and postsynaptic factors. They may play a role in tremor mechanisms.


Bone metabolism in young women taking a monophasic pill containing 20 mcg ethinylestradiol: a prospective study.
The present one-year prospective study was performed to evaluate the effects of an oral contraceptive containing 20 mcg ethinylestradiol plus 0.150 mg desogestrel on bone metabolism in young women. Nineteen women aged 20 to 30 years completed the trial. Bone density was measured in the distal radius by dual photon absorptiometry before starting pill use and at the 3rd, 6th and 12th cycle. At the same time intervals, urinary hydroxyproline-to-creatinine ratio and serum alkaline phosphatase were evaluated. Bone density showed a slight, but not significant, increase at the end of the trial. Both urinary hydroxyproline-to-creatinine ratio and serum alkaline phosphatase showed a significant decrease. The results suggest that bone resorption is reduced, although bone density in the distal radius is not significantly increased in young women using an oral contraceptive containing only 20 mcg ethinylestradiol for one year.


Double-entrapment radial tunnel syndrome.
A symptomatic double-level entrapment of the posterior interosseous branch of the radial nerve is described. In addition to the more common level of compression at its entrance into the supinator, the posterior interosseous nerve may be entrapped at its exit from the supinator or at multiple levels.


Long-term memory for DRL: a comparison between weanling, adult and senescent rats.
Weanling (24-day-old), adult (3- and 7-month-old) and senescent rats (24-month-old) were submitted for 10 days to a DRL 20 seconds schedule, at a pace of 4 sessions a day. After a 3 month interval, the subjects were tested for retention in an identical experimental setting. In training, the median Interresponse-Time (IRT) is directly related to the age of the subjects, whereas response rates are inversely related to it. Age-related differences subside at the end of training. In testing, adult rats improve their efficiency, whereas senescent and particularly former weanling rats do not catch up with training scores. These data are discussed in relationship with developmental variables in the temporal regulation of behavior, collateral activity, contextual and methodological variables in the study of memory.


Atrioventricular block following prolonged focal cryoablation for parahisian premature ventricular complexes.
A 54-year-old woman with symptomatic premature ventricular contractions (PVC) was referred for electrophysiological study. The earliest activation was located at the parahisian area, so it was decided to ablate using cryoenergy. No AV conduction impairment was observed during cryomapping. PVCs were abolished after the first 15 seconds of cryoablation, without recurrence. However, after 354 seconds of cryoablation, a mild PR prolongation was followed by first degree and 2-to-1 AV block. Termination of cryoablation led to complete recovery without definitive damage and with elimination of the PVC. This case illustrates how lesion formation using cryoenergy can continue to evolve even after several minutes, highlighting the need of monitoring throughout the whole target duration.


Oral condyloma lesions in patients with extensive genital human papillomavirus infection.
The incidence, location, and morphologic appearances of human papillomavirus oral lesions in patients with genital condylomatosis were investigated with clinical, colposcopic, and histologic examination as diagnostic procedures. The human papillomavirus types were also evaluated with filter in situ hybridization. One hundred one patients, 66 female and 35 male, with genital condyloma underwent an oral cavity examination. Ninety-nine (99%) practiced orogenital sex, and all were asymptomatic for oral lesions. Ninety-one underwent biopsy; histologic studies gave a diagnosis of condyloma in 48% of 101 specimens collected. In 8 of 91 (9%) oral lesions were suspected by naked-eye examination; they were confirmed histologically in all eight. Of 83 patients suspected of having oral condyloma on colposcopic examination, 38 (46%) were confirmed histologically. Thus 38 of 46 patients (83%) had oral condyloma not visible to the naked eye. Colposcopically, oral lesions appeared filiform (50%), moruloid (26%), and mixed (24%). Twenty cytologic oral samples were also collected for deoxyribonucleic filter in situ hybridization analysis. Human papillomavirus deoxyribonucleic genital types were observed in 45% (9/20) of all oral scrapings collected, and all were histologically confirmed. Our data indicate that genital human papillomavirus types are capable of establishing a local infection in the oral cavity and demonstrate a high incidence of human papillomavirus oral lesions in patients with genital condyloma.


Transtrochanteric rotational osteotomy for osteonecrosis of the femoral head: relation between radiographic features and secondary collapse.
Secondary collapse of the femoral head after transtrochanteric rotational osteotomy (TRO) for osteonecrosis of the femoral head is a major complication leading to failure. We investigated the relation between the extent and shape of a newly established healthy weight-bearing area and the incidence of secondary collapse. Altogether, 38 hips in 32 patients with a mean age of 33 years at the time of surgery were followed for a mean of 4 years. The outcome was satisfactory in 22 hips (58%) and unsatisfactory in 16 hips (42%), with 9 requiring total hip arthroplasty. The extent of the newly established healthy weight-bearing area as depicted on the immediate postoperative radiograph was significantly greater in the satisfactory group than in the unsatisfactory group. The rate of secondary collapse was significantly higher when the newly established weight-bearing area was thin, like a beak ("beak-shaped" healthy area). The incidence of a beak-shaped healthy area was significantly higher in the steroid group than in nonsteroid group. We concluded that we should be cautious when the newly established healthy weight-bearing area exhibits this beak shape, even if its extent in the weight-bearing area is large, because of the higher risk of postoperative secondary collapse. In such cases, alteration of the after-treatment program (e.g., prolonging the non-weight-bearing period) should be considered.


Proliferating giant pigmented nevus: a report of an unusual tumor occurring in association with a congenital giant pigmented nevus.
A 32-year-old Japanese woman with a giant pigmented congenital nevus of the torso presented with a massive pigmented tumor mass of the vulva which grew over an 8-year period. Histologically, the tumor was composed of benign appearing nevus-like cells with focal areas of extensive fibrous response. The tumor cells were positive for S-100 protein and with an antihuman melanoma antibody (MoAb 225, 28S) stain. Electron microscopy confirmed the nevomelanocytic nature of the tumor cells and demonstrated peculiar cytoplasmic crystalline tubular structures similar to those seen in cells infected with herpes virus type II. We propose the term "proliferating giant pigmented nevus" for this previous undescribed tumor.


Discovery of color compounds: Integrated multispectral omics on exploring critical colorant compounds of black tea infusion.
The present study provided a highly efficient and systematic workflow for identifying colorants of food and beverage. Generally, the objective colorimeter and subjective human eye had different systems to identify colors, which makes the color description very challenging. Here, the Lab/LCH color system was applied to clearly illustrate color changes. Our workflow was applied to determine and verify the differential colorant substances between two groups of black tea infusions. Regarding color parameters, the infusions of black tea from Camellia sinensis and Camellia assamica differed significantly. The differential substances between black tea infusions were correlated to color parameters by mass spectrometry and nuclear magnetic resonance based multivariate statistical analysis and verified by machine learning tool. Pyroglutamic acid-glucose Amadori product, quercetin-3-O-glucoside, quinic acid and theabrownins were identified as main color contributors to black teas' color difference, which were also verified by addition test with standard black tea infusion.


Non-Hodgkin's lymphomas presenting through oral symptoms.
Non-Hodgkin's lymphomas (NHL) presenting through oral symptoms are rare. Between 1976 and 1987, a total of 17 cases (7 male, 10 female) were diagnosed in our departments. The first symptom was an intraoral tumour mass in 9 cases, loosening of teeth in 2 cases and paraesthesia in another 2. Most tumours (13/17) were located in the lower jaw. In only 5 cases had the referring physician or dentist suspected malignancy. In 3 cases, the histological diagnosis was Burkitt's lymphoma. The grade of malignancy was classified as low in 4 cases, intermediate in 3 and high in 8. None of the patients was HIV-positive. Nine patients died of their disease within 1-132 months (mean 18.3 months).


Mechanisms responsible for the inhibitory effects of benfluorex on hepatic intermediary metabolism.
The effects of benfluorex on hepatic intermediary metabolism have been studied using the isolated hepatocyte system. The drug inhibits the synthesis of both glucose and fatty acids by hepatocytes. Evidence is obtained that hepatocytes rapidly split benfluorex into benzoic acid and 1-(3-trifluoromethylphenyl)-2-[N-(2-hydroxyethyl)amino]propane (THEP). Comparison of the effects of the parent compound with the effects of THEP and benzoic acid on gluconeogenesis and on fatty acid synthesis indicates that different metabolites of the drug are responsible for its various actions: THEP inhibits gluconeogenesis, whereas benzoic acid inhibits fatty acid synthesis. The latter pathway appears to be inhibited at two sites: mitochondrial pyruvate uptake is inhibited by benfluorex itself, whereas fatty acid synthase is inhibited by benfluorex-derived benzoic acid.


[Primary thrombophilia in México. VI: lack of statistical association among the inherited thrombophilic conditions].
Over a 70-month period, 100 consecutive Mexican mestizo individuals with a clinical marker associated with a primary hypercoagulable state were studied. We prospectively assessed: the sticky platelet syndrome (SPS), the activated protein C resistance (aPCR) phenotype, coagulation protein C activity and antigen, coagulation protein S, antithrombin III, plasminogen, IgG and IgM isotypes of antiphospholipid antibodies, homocysteine levels, the factor V gene Leiden, Cambridge, Hong Kong, and Liverpool mutations, the 677 C-->T mutation in the 5,10-methylenetetrahydrofolatereductase (MTHFR), and the G20210A polymorphism in the 3'-untranslated region of the prothrombin gene. Of the 100 consecutive patients prospectively accrued in the study, only 29% were males. In only 6 individuals could we not record any abnormality, whereas in most individuals (81%), two to five co-existing abnormalities were identified. In a multivariate analysis of the association of all these assesments, the only significant association was found between the factor V Leiden mutation and the aPCR phenotype (r = .495; p < 0.001). These results confirm previous observations on thrombophilia in Mexico underlining that it is a multifactorial disease. They also suggest that the abnormalities detected are not associated to each other.


COX inhibitors modulate bFGF-induced cell survival in MCF-7 breast cancer cells.
Basic fibroblast growth factor (bFGF) serves as a modulator of survival in breast cancer cells. The mechanisms by which bFGF transduces the anti-apoptotic signal and interacts with COX inhibitors were investigated. bFGF reduced apoptosis in MCF-7 breast cancer cells and up-regulated the expression of mitocondrial Bcl-2, whereas COX inhibitors meloxicam (selective COX-2) and aspirin (non-selective), induced apoptosis. bFGF up-regulated survivin protein expression and induced cdc-2 phosphorylation moderately at early (2-6 h), and substantially at late (24 h), time-points. Survivin mRNA expression was up-regulated only at the later time-point. COX inhibitors prevented up-regulation of survivin protein expression at both 2 and 24 h and prevented early modest increases in cdc-2 phosphorylation. Up-regulation of survivin mRNA was not found to be modulated by the COX-2 inhibitor meloxicam. bFGF regulation of survivin expression was found to be ERK1/2 kinase dependent and bFGF-induced phosphorylation of c-raf was prevented by the COX-2 inhibitor. bFGF was, however, unable to induce COX-2 protein expression or modulate COX-2 activity in MCF-7 cells as evidenced by unaltered PGE(2) production. These results indicate that bFGF regulates survivin expression in MCF-7 breast cancer cells by signaling through an ERK1/2 dependent pathway. COX-2 inhibitors can modulate bFGF-induced survivin expression in a COX-2 independent manner.


The in vitro anti-herpes simplex virus type-1 and type-2 activity of Long Dan Xie Gan Tan, a prescription of traditional Chinese medicine.
Long Dan Xie Gan Tan (LDXGT), a decoction of radix gentianae for purging the pathogenic inflammation of the liver, is a widely used prescription among many in traditional Chinese medicine. The prescription is primarily used to treat the disorders induced by damp-heat in the liver and the gall bladder. In this study, the in vitro anti-herpes simplex virus type-1 (HSV-1) and type-2 (HSV-2) activity of the water extract of LDXGT was investigated. LDXGT water extract was shown to exhibit anti-HSV activity. The IC(50) values of LDXGT against HSV-1 and HSV-2 infections were 257.5 +/- 12.2 and 494.6 +/- 1.8 microg/ml, respectively. It had a CC(50) value of 4,077.2 +/- 2.4 microg/ml towards Vero cells and showed no cytotoxic effect at a concentration of 2,000 microg/ml or below. The prescription was also found to inactivate HSV-2 infectivity in a dose-, time- and temperature-dependent manner. In summary, the water extract of LDXGT was concluded to inhibit HSV-1 and HSV-2 infection at different magnitudes of potency, and our observations also suggested that the effect was likely mediated by directly inactivating the virus infectivity.


Microengineered 3D pulmonary interstitial mimetics highlight a critical role for matrix degradation in myofibroblast differentiation.
Fibrosis, characterized by aberrant tissue scarring from activated myofibroblasts, is often untreatable. Although the extracellular matrix becomes increasingly stiff and fibrous during disease progression, how these physical cues affect myofibroblast differentiation in 3D is poorly understood. Here, we describe a multicomponent hydrogel that recapitulates the 3D fibrous structure of interstitial tissue regions where idiopathic pulmonary fibrosis (IPF) initiates. In contrast to findings on 2D hydrogels, myofibroblast differentiation in 3D was inversely correlated with hydrogel stiffness but positively correlated with matrix fibers. Using a multistep bioinformatics analysis of IPF patient transcriptomes and in vitro pharmacologic screening, we identify matrix metalloproteinase activity to be essential for 3D but not 2D myofibroblast differentiation. Given our observation that compliant degradable 3D matrices amply support fibrogenesis, these studies demonstrate a departure from the established relationship between stiffness and myofibroblast differentiation in 2D, and provide a new 3D model for studying fibrosis and identifying antifibrotic therapeutics.


Identification of myosin heavy chain in Saccharomyces cerevisiae.
Motility in biological systems is expressed in a variety of ways, such as cytoplasmic streaming, cell shaping, nuclear migration and muscle contraction. These functions are thought to be mediated by structural proteins, for example, myosin, actin and tubulin. The involvement of myosin in muscle contraction is well documented and this protein is implicated in generating the cleavage forces during cytokinesis in some non-muscle cells. Here, we report the isolation of a protein similar to myosin as judged by its biochemical and immunological properties, from the yeast Saccharomyces cerevisiae. Parts of the protein have been conserved through evolution at the protein and DNA sequence levels. The presence of this protein in the region bordering mother cell and bud, as revealed by immunofluorescence, suggests that it is involved in cell division.


Dopamine as a potential rescue therapy for refractory protein-losing enteropathy in Fontan-palliated patients.
PLE is an important cause of morbidity and mortality in patients who have undergone Fontan palliation. While multiple PLE therapies have been reported, none has proved consistently effective. Patients who do not respond to "standard" PLE therapies face poor long-term outcomes. We report here a significant response to dopamine infusion in three patients with chronic, refractory PLE. We hypothesize that this response may be at least partially due to a dopamine effect on lymphatic receptors rather than to an augmentation of cardiac output.


Can wood-feeding termites solve the environmental bottleneck caused by plastics? A critical state-of-the-art review.
The abundance of synthetic polymers has become an ever-increasing environmental threat in the world. The excessive utilization of plastics leads to the accumulation of such recalcitrant pollutants in the environment. For example, during the COVID-19 pandemic, unprecedented demand for personal protective equipment (PPE) kits, face masks, and gloves made up of single-use items has resulted in the massive generation of plastic biomedical waste. As secondary pollutants, microplastic particles (<5 mm) are derived from pellet loss and degradation of macroplastics. Therefore, urgent intervention is required for the management of these hazardous materials. Physicochemical approaches have been employed to degrade synthetic polymers, but these approaches have limited efficiency and cause the release of hazardous metabolites or by-products into the environment. Therefore, bioremediation is a proper option as it is both cost-efficient and environmentally friendly. On the other hand, plants evolved lignocellulose to be resistant to destruction, whereas insects, such as wood-feeding termites, possess diverse microorganisms in their guts, which confer physiological and ecological benefits to their host. Plastic and lignocellulose polymers share a number of physical and chemical properties, despite their structural and recalcitrance differences. Among these similarities are a hydrophobic nature, a carbon skeleton, and amorphous/crystalline regions. Compared with herbivorous mammals, lignocellulose digestion in termites is accomplished at ordinary temperatures. This unique characteristic has been of great interest for the development of a plastic biodegradation approach by termites and their gut symbionts. Therefore, transferring knowledge from research on lignocellulosic degradation by termites and their gut symbionts to that on synthetic polymers has become a new research hotspot and technological development direction to solve the environmental bottleneck caused by synthetic plastic polymers.


Therapeutic Outcome of Stereotactic Body Radiotherapy for Small Hepatocellular Carcinoma Lesions - A Systematic Review and Network Meta-analysis.
Surgical resection, stereotactic body radiotherapy (SBRT) and radiofrequency ablation (RFA) have seldom been compared for small hepatocellular carcinoma (HCC). We explored the treatment outcomes of SBRT for small HCC by conducting a network meta-analysis (NMA). We compared the efficacy and safety of surgical resection, RFA and SBRT for liver-confined small HCC (three or fewer lesions with a diameter ≤5 cm). The study endpoint included the odds ratios of the 1-, 3- and 5-year progression/recurrence/disease-free survival (disease progression-free survival; DPFS) and overall survival rates, as well as severe complications. Forty-five studies included 21 468 patients. In the NMA with comparable data, SBRT had comparable 1-, 3- and 5-year DPFS but significantly worse pooled long-term overall survival (3- and 5-year overall survival) than surgical resection (odds ratio 1.39, 95% confidential interval 1.3-1.89; odds ratio 1.33, 95% confidence interval 1.06-1.69, respectively). SBRT was associated with significantly better pooled 1-year DPFS compared with RFA (odds ratio 0.39, 95% confidence interval 0.15-0.97), with the remaining outcomes being comparable. SBRT had significantly less incidence of severe complications compared with surgical resection (odds ratio 0.62, 95% confidence interval 0.42-0.88) and RFA (odds ratio 0.2, 95% confidence interval 0.03-0.94). In conclusion, for small HCCs (≤5 cm) with one to three nodules, SBRT may be favourable to reduce the risks of severe complications. In terms of DPFS, SBRT may be recommended as an alternative first-line therapy for RFA and surgical resection. The results regarding overall survival should be interpreted with caution, considering the potentially uneliminated bias. There is a clear need for well-designed randomised trials to conclusively identify real differences in efficacy between these treatments, especially SBRT and surgical resection.


Huperzine A injection ameliorates motor and cognitive abnormalities via regulating multiple pathways in a murine model of Parkinson's disease.
As a common progressive neurodegenerative disorder, the satisfied therapies for Parkinson's disease (PD) are still unavailable. As a natural acetylcholinesterase inhibitor, the neuroprotective characteristic of Huperzine A (HupA) was supported by previous studies. However, questions remain on whether HupA injection (HAI, a main preparation of HupA) intervention conduces to PD treatment and if so, the potential molecular mechanisms. In this study, the efficacies of HAI treatment on PD-like pathological phenotypes were evaluated in a MPTP-induced PD murine model. The network pharmacology, transcriptome sequencing and experimental verification were integrated to comprehensively reveal the primary molecular mechanisms. Therapeutically, HAI intervention significantly improved the impaired locomotor behaviors as well as learning and memory abilities, and prevented the degeneration of dopaminergic neurons of PD mice. The network pharmacology analysis combined with experimental results showed that HAI treatment could effectively restore the disordered transcriptional levels of inflammatory factors and apoptosis related genes in the SNpc and striatum tissues of PD mice. Transcriptome sequencing results found that inflammation and oxidative phosphorylation served as significant functional mechanisms involved in HAI administration. The experimental verification indicated that HAI treatment effectively regulated the abnormal transcription levels of inflammation and oxidative phosphorylation related hub genes in the hippocampal samples of PD mice. In addition, molecular docking suggested strong affinity between HupA and the above core targets. Overall, this work displayed the reliable therapeutic effects of HAI on ameliorating the pathological symptoms of PD mice via modulating multiple pathways. The current findings were expected to provide a potential anti-PD agent.


What is coronary blood flow reserve? Insights using myocardial contrast echocardiography.
This review will briefly describe the principles of myocardial contrast echocardiography, and then discuss the clinical and experimental observations that led to the use of this approach to investigate the pathophysiological basis of coronary blood flow reserve. The insights offered by myocardial contrast echocardiography are unique and novel, and highlight the importance of the myocardial capillaries in determining coronary blood flow reserve in health and disease.


Predictive Value of the HEART Score Combined with Hypersensitive C-Reactive Protein for 30 d Adverse Cardiovascular Events in Patients with Acute Chest Pain.
This study aimed to explore the predictive value of the HEART score combined with hypersensitive C-reactive protein (hs-CRP) for 30 d major adverse cardiovascular events (MACEs) in patients with acute chest pain. 103 patients with acute chest pain admitted to the emergency department of our hospital from May 2020 to May 2022 were selected as the study subjects. The patients' HEART score and plasma hs-CRP level were recorded. The patients were followed up for 30 d to observe whether MACE occurred. Among 103 patients with acute chest pain, MACE occurred in 8 cases within 30 d of follow-up, and the probability of MACE was 7.76%. There was a statistically significant difference in 30 d MACE risk among patients with different HEART score stratification (P < 0.05). The age, HEART score, and hs-CRP levels of patients in the MACE group were higher than those in the non-MACE group (P < 0.05). The HEART score and the hs-CRP level were independent risk factors for 30 d MACE in patients with acute chest pain (P < 0.05). The AUC of the HEART score combined with hs-CRP in the occurrence of 30 d MACE in patients with acute chest pain was 0.901, which was significantly higher than 0.720 and 0.758 of single detection. The HEART score combined with hs-CRP can better predict the occurrence of 30 d MACE in patients with acute chest pain.


Greenhouse gas production: a comparison between aerobic and anaerobic wastewater treatment technology.
Anaerobic wastewater treatment offers improved energy conservation with potential reduction in greenhouse gas emissions. Pitfalls exist in that the methane produced in anaerobic treatment can offset any reductions in carbon dioxide emissions, if it is released to the environment. This paper analyzes greenhouse gas emissions from both aerobic and anaerobic treatment systems, including sludge digestion and the losses of dissolved methane in digested biosolids and process effluents. There exists cross over points, ranging from 300 to 700 mg/L influent wastewater BODu, which are functions of the efficiency of the aerobic treatment system. Anaerobic treatment becomes favorable when treating influents higher in concentrations than the cross over values. A technology to recover dissolved methane would make anaerobic treatment favorable at nearly all influent strengths.


Analysis of alopecia areata surveys suggests a threshold for improved patient-reported outcomes.
Although alopecia areata (AA) greatly impacts patients' quality of life (QoL), there is no adequate validation of AA-targeted QoL surveys in clinical trials, hindering sufficient representation of patient-reported outcomes. Better understanding of patient-reported outcomes may guide treatment goals and future clinical trials. In a recent randomized controlled trial testing dupilumab in AA, patients were administered the Alopecia Areata Quality of Life Index (AA-QLI) and the Alopecia Areata Symptom Impact Scale (AASIS) surveys, specifically evaluating QoL in patients with AA. An in-depth analysis was performed to assess the utility of these questionnaires in this patient population, both at baseline and after treatment, and to determine a threshold for improved patient-reported outcomes. While AASIS correlated with baseline Severity of Alopecia Tool (SALT) scores and with therapeutic response, AA-QLI showed no correlation with AA severity before or after treatment. Itch strongly correlated with serum IgE levels across both surveys. Using various approaches to estimate a discriminative threshold for decreased impact of AA on QoL (by AASIS) following treatment, a SALT score of 20 points or less post-treatment was associated with improved patient-reported outcomes, including both AA-related symptoms and items within the daily activities/feelings domain such as 'feeling sad' and 'feeling anxious or worry'. AASIS is better than AA-QLI to assess patient-reported outcomes. SALT ≤ 20 following treatment should be considered as a threshold for meaningful therapeutic outcome and as a clinical endpoint in future clinical trials for AA. What is already known about this topic? Alopecia areata greatly compromises quality of life, and affected patients have increased prevalences of depression, anxiety and social phobia. Despite the significant negative impact of the disease on patients' wellbeing, validation of targeted questionnaires in alopecia areata is lacking, and a therapeutic response threshold for improved patient-reported outcomes is unknown. What does this study add? This study investigated the utility of two different alopecia areata-targeted questionnaires - Alopecia Areata Quality of Life Index and Alopecia Areata Symptom Impact Scale (AASIS) - in a clinical trial setting. AASIS was found to correlate strongly with alopecia areata severity and clinical response. What are the clinical implications of this work? Patients with ≤ 20% scalp hair loss after treatment reported improvement in multiple quality-of-life items, suggesting this as a meaningful therapeutic outcome that may guide clinicians and improve the development of future clinical trials.


Antifungal Resistance, Susceptibility Testing and Treatment of Recalcitrant Dermatophytosis Caused by Trichophyton indotineae: A North American Perspective on Management.
There is an ongoing epidemic of chronic, relapsing dermatophytoses caused by Trichophyton indotineae that are unresponsive to one or multiple antifungal agents. Although this new species may have originated from the Indian subcontinent, there has been a notable increase of its reporting in other countries. Based on current literature, antifungal susceptibility testing (AFST) showed a large variation of terbinafine minimum inhibitory concentrations (MICs) (0.04 to ≥ 32 µg/ml). Elevated terbinafine MICs can be attributed to mutations in the squalene epoxidase gene (single mutations: Leu393Phe, Leu393Ser, Phe397Leu, and double mutations: Leu393Phe/Ala448Thr, Phe397Leu/Ala448Thr). Itraconazole MICs had a lower range when compared with that of terbinafine (0.008-16 µg/ml, with most MICs falling between 0.008 µg/ml and < 1 µg/ml). The interpretation of AFST results remains challenging due to protocol variations and a lack of established breakpoints. Adoption of molecular methods for resistance detection, coupled with AFST, may provide a better evaluation of the in vitro resistance status of T. indotineae. There is limited information on treatment options for patients with confirmed T. indotineae infections by molecular diagnosis; preliminary evidence generated from case reports and case series points to itraconazole as an effective treatment modality, while terbinafine and griseofulvin are generally not effective. For physicians working outside of endemic regions, there is currently an unmet need for standardized clinical trials to establish treatment guidelines; in particular, combination therapy of oral and topical agents (e.g., itraconazole and ciclopirox), as well as with other azoles (i.e., fluconazole, voriconazole, ketoconazole), warrants further investigation as multidrug resistance is a possibility for T. indotineae.


Local dose-effect relations for lung perfusion post stereotactic body radiotherapy.
To model the local dose-effect relation for lung perfusion reduction in lung cancer patients treated with stereotactic body radiotherapy (SBRT). Forty-two patients having upper-lobe peripheral tumours <5 cm treated with SBRT (3×18 Gy) underwent single-photon emission computed-tomography (SPECT) scans to measure the lung perfusion 2 weeks pre-SBRT, 4-months post-SBRT, and for 8 patients 15-months post-SBRT. The relation between the calculated relative local perfusion reduction and the normalised total dose (α/β=3 Gy) at 4-months post-SBRT was modeled by 3-parameter logistic model and 2-parameter linear-maximum model. The relation between local dose and perfusion reduction at 4-months post-SBRT showed a maximum effect of 42.6% at doses >100 Gy and was best described by the logistic model with parameters (95% CI): M=42.6% (40.7-44.6), D50=28.7 Gy (26.3-31.1) and k=2.2 (1.8-2.5). A significant increase of this maximum effect to 65.2% was found at 15-months post-SBRT. The relation between local dose and perfusion reduction in patients treated with SBRT can be modeled by a 3-parameter logistic model. This demonstrated relationship 4-months post-SBRT approaches a plateau for doses >100 Gy, where 90% of the maximum lung-perfusion reduction is observed at NTD=78 Gy. A further perfusion reduction compared to 4-months post-SBRT was observed fifteen months post-SBRT.


[Clinical evaluation of the severity of hidradenitis suppurativa].
Treatment and long-term management of patients with chronic diseases require the use of instruments to measure severity and outcome. In the case of hidradenitis suppurativa, such instruments are currently poorly understood and utilised. Herein, we describe the main instruments, their scope of application, their qualities and their shortcomings. The Hurley classification, which was devised for surgical assessment and is limited to description of impairment at a given site, is too often used to assess overall severity in individual patients. The Sartorius score (and variants thereof) combines global and local measurements; it is widely used, but because of its hybrid nature, the global score, or PGA-HS, is currently used; the latter, focusing on inflammatory signs, is perfectly suitable for daily assessment of pharmaceutical treatment. The HiSCR score, derived from the foregoing grading system, is used as a global criterion in clinical trials. Patient-based instruments, such as pain or suppuration score, and, to a lesser extent, quality-of-life score constitute very useful supplements. Since the disease is extremely heterogeneous, no instruments cover the entire array of situations and the requirements of medical and surgical practitioners involved in the management of this patient population.


Reliability of peer and self-assessment scores compared with trainers' scores following third molar surgery.
It is sometimes claimed that self-assessment is inaccurate and that clinicians over-rate their performance. There is a need to find out why this should be. Is poor self-assessment caused by some clinicians' inability to accurately judge performance? Or does over-scoring result from a desire to convey a more favourable impression? Peer assessment is widely advocated and is said to be of benefit to both assessor and assessee. In this study, we wanted to see if postgraduates were able to peer-assess and if this form of assessment was more reliable than self-assessment when compared with assessment by a trainer. We used checklist and global rating scales to evaluate surgical skills in removing a mandibular third molar tooth. There was no statistically significant difference between peer-assessed and trainer-assessed scores. We found that, on average, peer assessment (especially global rating scales) reflected trainer scores more accurately than self-assessment of surgical skills. Self-assessment scores were significantly higher on average than those given in peer assessment. Although peers and trainee surgeons came from the same group, the surgeons were more likely to over-score when measuring their own performances. The greatest variability (and over-scoring) between assessor and trainee surgeon appeared to occur in those with lower mean scores. Formative peer assessment may be a useful and less stressful mechanism for encouraging reflection.


Purification and aqueous phase atomic force microscopic observation of recombinant P2X2 receptor.
Recombinant P2X2 receptor was observed by atomic force microscope in the aqueous phase. The P2X2 receptor was expressed in an insect cell line, and recombinant proteins were prepared under native conditions. The membrane fractions were extracted, and histidine-tagged receptor protein was purified from the fractions by column chromatography. When the purified protein fraction was diluted with water and served for atomic force microscopy, dispersed particles of about 3 nm in height were observed. In the presence of 1 mM ATP, the assembly-like images of the particles were obtained. More densely assembled images of the particles were achieved when the protein was dissolved in a Tris buffer containing 1 mM ATP. Under this condition, imaging of the surface of the particles exhibited a circular structure with a diameter of about 10 nm having a pore-like structure. These results suggest that atomic force microscopy provides structural information about P2X2 receptor in aqueous phase.


Outcome and Refractory Factor of Intensive Treatment for Geriatric Traumatic Brain Injury: Analysis of 1165 Cases Registered in the Japan Neurotrauma Data Bank.
With the increase in the aged population, geriatric traumatic brain injury (gTBI) is also rapidly increasing in Japan. There is thus a need to review the effect of intensive treatments for gTBIs. The aim of this study was 1) to assess how intensive treatments influenced patient outcome and 2) to identify the refractory factor against these intensive treatments in gTBI, from the Japan Neurotrauma Data Bank (JNTDB). Of all 3194 patients in the JNTDB, 1165 (≥ 65 years old) with severe gTBIs were enrolled in this study. The clinical features and their outcomes based on the Glasgow Outcome Scale on discharge and 6 months after injury were compared. Intensive treatments were administered to 71.4% of all patients with severe gTBI showing a significant increase over 15 years. Accordingly, mortality decreased significantly (from 62.7% to 51.1%, P = 0.001). On the other hand, severely disabled dependent survivors, who need daily help from others for living, increased accordingly (from 63.2% to 68.4%). The existence of intraventricular hemorrhage (IVH) rather than the patient's age was identified as the strongest refractory factor (odds ratio, 5.762; 95% confidence interval, 1.317-25.216) against intensive treatment. This study clarified that 1) intensive treatments are associated with higher survival rates (however, they also increase the incidence of severely disabled survivors) and 2) the strongest refractory factor for intensive treatment in cases of severe gTBI was not age but the existence of IVH. These results warrant further establishment of a seamless strategy for both the acute and the chronic phase of gTBI.


Narrow electrodes on YZ-LiNbOO3 as an alternative to etched grooves for dispersive delay lines.
Narrow, open-circuited aluminum electrodes can provide controllable, weak reflectivity necessary for many applications such as surface acoustic wave (SAW) tags and dispersive delay lines (DDLs). We show, using finiteand boundary element method (FEM-BEM) based simulations and experiments, that a reflectivity of 0.3% per wavelength can be achieved easily and controlled by varying the electrode width.


Safety of fluoroscopy guided percutaneous access to the thoracic spine.
Fluoroscopy-guided percutaneous access to thoracic vertebrae is technically demanding due to the complex radiological anatomy and close proximity of the spinal cord, major vessels and pleural cavity. There is a trend towards computed tomography (CT) guidance due to a perceived reduction in the risk of spinal canal intrusion by instrumentation causing neurological injury. Due to limited access to CT guidance, there is a need for safe fluoroscopy-guided percutaneous access to the thoracic spine. To evaluate the safety of a strict radio-anatomical protocol in avoiding access-related neurological complications due to tool misplacement in fluoroscopy-guided percutaneous procedures on the thoracic spine. A combined two-surgeon prospective case series of 444 procedures (biopsy, vertebroplasty or kyphoplasty) covering all thoracic vertebral levels T1-T12. Clinical examination and routine observations were used to identify access-related complications including neurological, vascular and visceral injury using physiological parameters. No patient in our series was identified to have sustained a neurological deficit or deterioration of preoperative neurological status. Percutaneous access to the thoracic spine using fluoroscopic guidance is safe. The crucial step of the protocol is not to advance the tool beyond the medial pedicle wall on the anterior-posterior projection until the tip of the instrument has reached the posterior vertebral cortex on the lateral projection.


Gestational weight gain and foetal acidosis in vaginal and caesarean deliveries: The Japan Environment and Children's Study.
Inappropriate gestational weight gain (GWG), either above or below the recommended values, has been associated with an increased risk of adverse obstetric outcomes. To evaluate the risks of GWG for foetal acidosis according to pre-pregnancy body mass index (BMI) and mode of delivery, we analysed women with singleton pregnancies between 2011 and 2014 in the Japan Environment and Children's Study. Participants (n = 71,799) were categorised according to pre-pregnancy BMI. GWG was categorised into insufficient, appropriate, or excessive. Foetal acidosis was defined as umbilical artery pH (UmA-pH) < 7.20 or < 7.10. Multiple logistic regressions were performed for each BMI category to identify the risks of GWG for foetal acidosis, accounting for the mode of delivery. Excessive GWG was significantly associated with increased foetal acidosis in overweight women and in women whose pre-pregnancy BMI was 23.0-25.0 kg/m2 especially in those with vaginal deliveries. Conversely, excessive GWG was not significantly associated with increased foetal acidosis in obese women and in women whose pre-pregnancy BMI was ≥ 25.0 kg/m2.


Trapping of oxidized LDL in lysosomes of Kupffer cells is a trigger for hepatic inflammation.
Non-alcoholic steatohepatitis (NASH) is characterized by steatosis and inflammation. The transition from steatosis towards NASH represents a key step in pathogenesis, as it will set the stage for further severe liver damage. Under normal conditions, lipoproteins that are endocytosed by Kupffer cells (KCs) are easily transferred from the lysosomes into the cytoplasm. Oxidized LDL (oxLDL) that is taken up by the macrophages in vitro is trapped within the lysosomes, while acetylated LDL (acLDL) is leading to normal lysosomal hydrolysis, resulting in cytoplasmic storage. We have recently demonstrated that hepatic inflammation is correlated with lysosomal trapping of lipids. So far, a link between lysosomal trapping of oxLDL and inflammation was not established. We hypothesized that lysosomal trapping of oxLDL in KCs will lead to hepatic inflammation. Ldlr(-/-) mice were injected with LDL, acLDL and oxLDL and sacrificed after 2, 6 and 24 h. Electron microscopy of KCs demonstrated that after oxLDL injection, small lipid inclusions were present inside the lysosomes after all time points and were mostly pronounced after 6 and 24 h. In contrast, no lipid inclusions were present inside KCs after LDL or acLDL injection. Hepatic expression of several inflammatory genes and scavenger receptors was higher after oxLDL injections compared with LDL or acLDL. These data suggest that trapping of oxLDL inside lysosomes of KCs in vivo is causally linked to increased hepatic inflammatory gene expression. Our novel observations provide new bases for prevention and treatment of NASH.


Detection and quantification of Mycobacterium leprae in tissue samples by real-time PCR.
Real-time PCR technology has improved molecular diagnostics of many pathogens, but no such test is available for Mycobacterium leprae. In this report we describe the establishment and the pre-clinical evaluation of such an assay. The test achieved a theoretical analytical sensitivity limit of 194 M. leprae cells per skin biopsy specimen and facilitated quantification of mycobacteria in tissue over a range of 54-54,000,000 cells per sample. In punch skin biopsies from 39 untreated Ugandan patients with newly diagnosed leprosy, the clinical diagnosis could be confirmed in 88.9% of multibacillary and 33.3% of paucibacillary (microscopically negative) patients. Real-time detection thus did not increase the clinical sensitivity of PCR as compared to conventional protocols, in spite of its evidently high analytical sensitivity. On the other hand, as still no culture system exists for M. leprae, the assay appears to be a robust tool for detection of the bacterium in selected clinical situations, as well as for quantitation in experimental settings.


Employer-sponsored health insurance and the gender wage gap.
During prime working years, women have higher expected healthcare expenses than men. However, employees' insurance rates are not gender-rated in the employer-sponsored health insurance (ESI) market. Thus, women may experience lower wages in equilibrium from employers who offer health insurance to their employees. We show that female employees suffer a larger wage gap relative to men when they hold ESI: our results suggest this accounts for roughly 10% of the overall gender wage gap. For a full-time worker, this pay gap due to ESI is on the order of the expected difference in healthcare expenses between women and men.