[Imaging analysis of temporomandibular joint anatomy changes after intraoral condylectomy combined with orthognathic surgery].
To quantitatively analyze the changes of facial symmetry and temporomandibular joint structure at different periods after intraoral condylectomy combined with orthognathic surgery, and to evaluate the long-term stability after the operation. Spiral CT data of 10 cases treated by intraoral condylectomy combined with orthognathic surgery were collected, and then reconstructed by ProPlan software. Mark points were drawn on the 3D-images reconstructed immediately after the operation, and 6 months and 12 months after the operation. The measurements parameters included condylar axis angle in three dimensions, condylar-glenoid relative position and condylar facial morphology related indicators. The results were statistically analyzed by the consistency test and the variance of repeated measurement data. The facial asymmetry of the patients was corrected after operation, the height of the affected mandibular ascending ramus(T1: [67.81±6.95]mm, T2: [64.49±6.24]mm, T3: [63.05±7.07]mm)as well as the degree of pogonion deviation decreased(T1: [2.79±4.93]mm, T2: [0.37±4.20]mm, T3: [0.33 ± 3.97]mm)(P<0.05). But the tilt angle of the occlusion plane and the degree of mandibular height asymmetry had no significant difference between all the post-operative periods(P>0.05). The post-operative 3D changes of the position and shape of the resected and its contralateral condylar showed that the bilateral condylar axis angle in the horizontal plane gradually grew after operation(affected condyle: 71.95° ± 7.47°, 74.73°±8.44°, 76.56°±5.22°; control condyle: 72.60°±5.56°, 76.00°±5.30°, 77.19°±6.20° and had significant difference between all the post-operative periods)(P<0.05), the condyle moved slowly upward on both sides(superior space on the affected side: [8.78±4.38]mm, [4.11±2.49]mm, [3.27±1.96]mm; on the control side: [3.63±1.49]mm, [2.52±1.19]mm, [2.38±1.11]mm)(P<0.05), and moved inward only on the affected side(P< 0.05). All the above changes slowed down over time, and the disc-condyle-fossa relative position tended to be stable over time as well. The condyle diameter on the inside-outside direction gradually decreased on the affected side(T1: [14.98±2.39]mm, T2: [14.04±2.68]mm, T3: [13.74±2.89]mm)(P<0.05), and the surface morphology of the resected condyle was similar to the normal side. There were also some condylar surface morphological changes on the control side, but no statistical significance was found between different periods after the peration(P>0.05). The intraoral condylectomy combined with orthognathic surgery can eliminate condylar lesions effectively and correct the facial asymmetry caused by condylar benign tumor and hyperplasia. The facial symmetry can be maintained well after the operation, and the post-operative condylar morphology changes tended to be stable six months after the operation.


Epidemiology of chemical burns: An 11-year retrospective study of 126 patients at a referral burn centre in the north of Iran.
The etiology and outcomes of chemical burns vary worldwide, influenced by the local population structure, industry distribution, and geographical and social environments. The aim of this study was to evaluate the epidemiology of chemical burns among patients referred to a burn centre in the north of Iran. A single-centre, retrospective study was conducted on patients with chemical burns between 2011 and 2021. Data collection was carried out using the hospital information system (HIS), and data collected from medical records included gender, age, marital status, occupations, burn season, place of residence, intention to burn, location of the accident, percent of total body surface area (%TBSA), the primary cause of burns, the body region of the burn, length of hospital stay (days), infection, and discharge status. The data were analysed using descriptive statistical methods and SPSS 24.0 software. Of the 10 133 burn patients treated in a burn centre in the north of Iran between 2011 and 2021, 1.2% had chemical burns. The average age of patients was 34.45 (SD = 22.16) years, and most chemical burns cases were male (70.6%, n = 89). Chemical burns occurred most frequently in patients aged 20 to 49 years (69.8%, n = 107), and most of the burns were accidental (84.9%, n = 107). The home was the most common place of chemical burn injury, accounting for 49.2% (62 cases), followed by the workplace (43.7%, n = 55), respectively. Most chemical burns occurred in the summer season (36.5%, n = 46), and acid (74.6%, n = 94) was the most common cause of chemical burns. The mean TBSA was 16.41 (SD = 15.10). The most common burn area was the lower limb (34.9%, n = 44), and the overall mortality rate was 4.8%. The average length of stay in the hospital was 6.53 (SD = 5.57) days. Community education on household safety, restricting non-specialists' access to chemical substances, and the promotion of early consultation could reduce chemical burn prevalence and improve outcomes.


CaMKII inhibition promotes neuronal apoptosis by transcriptionally upregulating Bim expression.
The effects of Ca/calmodulin-dependent protein kinase II (CaMKII) on neuronal apoptosis are complex and contradictory, and the underlying mechanisms remain unclear. Bcl-2-interacting mediator of cell death (Bim) is an important proapoptotic protein under many physiological and pathophysiological conditions. However, there is no evidence that CaMKII and Bim are mechanistically linked in neuronal apoptosis. In this study, we showed that CaMKII inhibition by the inhibitors KN-62 and myristoylated autocamtide-2-related inhibitory peptide promoted apoptosis in cerebellar granule neurons in a dose-dependent manner. CaMKII inhibition increased Bim protein and messenger RNA levels. The expression of early growth response factor-1, a transcription factor of Bim, was also induced by CaMKII inhibitors. These data suggested that CaMKII repressed the transcriptional expression of Bim. Moreover, knockdown of Bim using small interfering RNAs attenuated the proapoptotic effects of CaMKII inhibition. Taken together, this is the first report to show that CaMKII inhibition transcriptionally upregulates Bim expression to promote neuronal apoptosis, providing new insights into the proapoptotic mechanism of CaMKII inhibition.


Jarisch-Herxheimer reaction associated with ciprofloxacin administration for tick-borne relapsing fever.
A 14-year-old girl was seen at a community clinic with a chief complaint of abdominal pain and fevers and was treated with oral ciprofloxacin for presumed pyelonephritis. She became tachycardic and hypotensive after her first dose of antibiotic, and she developed disseminated intravascular coagulation. She was admitted to our hospital for presumed sepsis. Her outpatient peripheral blood smear was reviewed, revealing spirochetes consistent with Borrelia sp. To our knowledge this is the first reported case of the Jarisch-Herxheimer reaction to ciprofloxacin.


A Calcium- and Diacylglycerol-Stimulated Protein Kinase C (PKC), Caenorhabditis elegans PKC-2, Links Thermal Signals to Learned Behavior by Acting in Sensory Neurons and Intestinal Cells.
Ca2+- and diacylglycerol (DAG)-activated protein kinase C (cPKC) promotes learning and behavioral plasticity. However, knowledge of in vivo regulation and exact functions of cPKCs that affect behavior is limited. We show that PKC-2, a Caenorhabditis elegans cPKC, is essential for a complex behavior, thermotaxis. C. elegans memorizes a nutrient-associated cultivation temperature (Tc ) and migrates along the Tc within a 17 to 25°C gradient. pkc-2 gene disruption abrogated thermotaxis; a PKC-2 transgene, driven by endogenous pkc-2 promoters, restored thermotaxis behavior in pkc-2-/- animals. Cell-specific manipulation of PKC-2 activity revealed that thermotaxis is controlled by cooperative PKC-2-mediated signaling in both AFD sensory neurons and intestinal cells. Cold-directed migration (cryophilic drive) precedes Tc tracking during thermotaxis. Analysis of temperature-directed behaviors elicited by persistent PKC-2 activation or inhibition in AFD (or intestine) disclosed that PKC-2 regulates initiation and duration of cryophilic drive. In AFD neurons, PKC-2 is a Ca2+ sensor and signal amplifier that operates downstream from cyclic GMP-gated cation channels and distal guanylate cyclases. UNC-18, which regulates neurotransmitter and neuropeptide release from synaptic vesicles, is a critical PKC-2 effector in AFD. UNC-18 variants, created by mutating Ser311 or Ser322, disrupt thermotaxis and suppress PKC-2-dependent cryophilic migration.


A comparison of two recently developed health status instruments for patients with arthritis: Dutch-AIMS2 and IRGL. Arthritis Impact Measurement Scales. Impact of Rheumatic diseases on General health and Lifestyle.
Two multidimensional health status instruments of rheumatic diseases, the Dutch-AIMS2 and the IRGL (Impact of Rheumatic diseases on General health and Lifestyle), were compared in a sample of 284 rheumatoid arthritis patients with regard to their measurement properties and usefulness for research purposes. Both questionnaires showed an excellent reliability (Cronbach's alpha), and were highly comparable with regard to their construct and convergent validity. Second-order factor analysis confirmed the physical, psychological and social health dimensions for both questionnaires. The comparability between the instruments was established by high intercorrelations between the physical and psychological health dimensions. Sufficient convergent validity was indicated by the strong correlations between the physical functioning scales and clinical and laboratory measures. The main differences between both questionnaires relate to their length and emphasis on health aspects. The Dutch-AIMS2 is characterized by a more extensive assessment of the physical dimension and the additional measurement of general health aspects. The shorter IRGL exclusively assesses the main health dimensions with a more comprehensive measurement of the psychological and social dimensions. The instrument that reflects the subject in question most adequately should be chosen.


Identification of Unsaturated and 2H Polyfluorocarboxylate Homologous Series and Their Detection in Environmental Samples and as Polymer Degradation Products.
A pair of homologous series of polyfluorinated degradation products have been identified, both having structures similar to perfluorocarboxylic acids but (i) having a H substitution for F on the α carbon for 2H polyfluorocarboxylic acids (2HPFCAs) and (ii) bearing a double bond between the α-β carbons for the unsaturated PFCAs (2uPFCAs). Obtaining an authentic sample containing 2uPFOA and 2HPFOA, we optimized a mass-spectrometric multiple-reaction-monitoring (MS/MS) technique and then identified uPFCA and HPFCA homologous series in sludge-applied agricultural soils and fodder grasses for cattle grazing. Analysis of samples from a degradation experiment of commercial fluorotelomer-based polymers (FTPs), the dominant product of the fluorotelomer industry, confirmed that commercial FTPs are a potential source of uPFCAs and HPFCAs to the environment. We further confirmed the identity of the uPFCAs by imposing high-energy ionization to decarboxylate the uPFCAs then focused on the fluorinated chains in the first MS quadrupole. We also employed this high-energy ionization to decarboxylate and analyze PFCAs by MS/MS (for the first time, to our knowledge). In exploratory efforts, we report the possible detection of unsaturated perfluorooctanesulfonate in environmental samples, having a conceptual double-bond structure analogous to uPFOA. Using microcosms spiked with fluorotelomer compounds, we found 2uPFOA and 2HPFOA to be generated from unsaturated 8:2 fluorotelomer acid (8:2 FTUCA) and propose β- and α-oxidation mechanisms for generation of these compounds from 8:2 FTUCA. In light of these experimental results, we also reexamined the proposed biodegradation pathways of 8:2 fluorotelomer alcohol.


Noncovalent Substrate-Directed Enantioselective Heck Reactions: Synthesis of S- and P-Stereogenic Heterocycles.
S- and P-Stereogenic heterocycles were synthesized by a remarkably simple enantioselective Heck desymmetrization reaction based on the unprecedented noncovalent directing effect of S=O and P=O functionalities. Selected prochiral symmetric substrates were efficiently arylated using the recently disclosed chiral PyraBOx ligand under mild and open-flask reaction conditions. Several five-membered aryl- sulfones, sulfoxides, and phosphine oxides were synthesized in good to excellent yields, in good to high diastereoselectivity, and enantiomeric ratios up to 98:2. Theoretical calculations also support the noncovalent directing effect of the S=O and P=O functionalities during the arylation process.


Identification of single-nucleotide polymorphisms by the oligonucleotide ligation reaction: a DNA biosensor for simultaneous visual detection of both alleles.
Although single nucleotide polymorphisms (SNPs) can be identified by direct hybridization with allele-specific oligonucleotide probes, enzyme-based genotyping methods offer much higher specificity and robustness. Among enzymatic methods, the oligonucleotide ligation reaction (OLR) offers the highest specificity for allele discrimination because two hybridization events are required for ligation. We report the development of a DNA biosensor that offers significant advantages over currently available methods for detection of OLR products: It allows simultaneous visual discrimination of both alleles using a single ligation reaction. Detection is complete within minutes without the need for any specialized instruments. It does not involve multiple cycles of incubation and washing. The dry-reagent format minimizes the pipetting steps. The need for qualified personnel is much lower than current methods. The principle of the assay is as follows: Following PCR amplification, a single OLR is performed using a biotinylated common probe and two allele-specific probes labeled with the haptens digoxigenin and fluorescein. Ligation products corresponding to the normal and mutant allele are double-labeled with biotin and either digoxigenin or fluorescein, respectively. The products are captured by antidigoxigenin or antifluorescein antibodies, or both, that are immobilized at the two test zones of the biosensor and react with antibiotin-functionalized gold nanoparticle reporters. The excess nanoparticles bind to biotinylated albumin that is immobilized at the control zone of the biosensor. The genotype is assigned by the characteristic red lines that appear at the two test zones. The proposed DNA biosensor constitutes a significant step toward point-of-care SNP genotyping.


The communication path and improvement strategy of symbolic culture of sneaker consumption culture using the big data analysis.
With the emergence of Artificial Intelligence technology and the advancement of science and technology, the current mainstream path of social development is continuously updating and improving various industries using technology. Therefore, in order to promote the development of sneaker consumer culture, this study explores the use of technological means to improve the dissemination effect of symbolic culture in sneaker consumer culture. Firstly, the development concept and mainstream direction of sneaker consumer culture in the era of big data are discussed, and the application principle of big data technology is introduced. Then, a sneaker culture dissemination model based on big data technology is designed. Finally, the model is optimized using a Convolutional Neural Network (CNN), and its effectiveness is evaluated. The results show that the Convolutional Neural Network-Big Data (CNN-BD) model designed in this study has the highest fitting degree of 93% and a lowest fitting degree of 78% in the UT-Zap50K dataset. In the Ai2 dataset, the highest fitting degree of the big data classification model is 94%, and the lowest is 76%. In the Kaggle Women's Shoe dataset, the highest fitting degree of the big data classification model is 92%, and the lowest is 77%. In the Kaggle Men's Shoe dataset, the highest fitting degree of the big data classification model is 94%, and the lowest is 79%. The designed model has the highest accuracy rate of 93% in sneaker classification, while other models have the highest accuracy rate of around 82% in sneaker classification. Compared with traditional big data technology, the designed model has greatly improved and can adapt to more working environments. This study not only provides technical support for the application of big data technology but also contributes to improving the dissemination effect and promoting the comprehensive development of sneaker consumer culture.


Three-dimensional super-resolution range-gated imaging based on Gaussian-range-intensity model.
Current range-gated imaging methods based on triangular or trapezoidal models face significant limitations in terms of the accuracy and precision of three-dimensional (3D) reconstruction. Here, we establish a range-gated 3D super-resolution image reconstruction method based on a Gaussian-range-intensity model. A denoised optimization method for image preprocessing is established to improve the distance accuracy of the reconstruction. The experimental results show that the model can reduce the error of target distance by 64% and possess the reconstruction of multiple kinds of targets with a distance resolution of 1.5 cm and lower noise, realizing better reconstruction results compared with the existing range-gated 3D imaging techniques.


Recent advances in testing for latent TB.
After more than a century of relying on skin testing for the diagnosis of latent TB infection, clinicians now have access to blood-based diagnostics in the form of interferon γ release assays (IGRAs). These tests are generally associated with higher sensitivity and specificity for diagnosis of latent TB infection. This article reviews the indications for testing and treatment of latent TB infection in the overall context of a TB control program and describes how IGRAs might be used in specific clinical settings and populations, including people having close contact with an active case of TB, the foreign born, and health-care workers.


Identification of key genes involved in the recurrence of glioblastoma multiforme using weighted gene co-expression network analysis and differential expression analysis.
Glioblastoma multiforme (GBM) is the most fatal malignancy, and despite extensive treatment, tumors inevitably recur. This study aimed to identify recurrence-associated molecules in GBM. The gene expression profile GSE139533, containing 70 primary and 47 recurrent GBM tissues and their corresponding clinical traits, was downloaded from the Gene Expression Omnibus (GEO) database and used for weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) analysis. After identifying the hub genes which differentially expressed in recurrent GBM tissues and in the gene modules correlated with recurrence, data from the Chinese Glioma Genome Atlas (CCGA) and The Cancer Genome Atlas (TCGA) databases were analyzed with GSE43378 to determine the relationship between hub genes and patient prognosis. The diagnostic value of the identified hub genes was verified using 52 GBM tissues. Three gene modules were correlated with recurrence and 2623 genes were clustered in these clinically significant modules. Among these, 13 genes - EHF, TRPM1, FXYD4, CDH15, LHX5, TP73, FBN3, TLX1, C1QL4, COL2A, SEC61G, NEUROD4 and GPR139 - were differentially expressed in recurrent GBM samples; low LHX5 and TLX1 expression predicted poor outcomes. LHX5 and TLX1 expression showed weak positive relationships with Karnofsky performance scale scores. Additionally, LHX5 and TLX1 expression was found to be decreased in our recurrent GBM samples compared with that in primary samples; these genes exhibited high diagnostic value in distinguishing recurrent samples from primary samples. Our findings indicate that LHX5 and TLX1 might be involved in GBM recurrence and act as potential biomarkers for this condition.


Evidence for participation of transglutaminase in receptor-mediated endocytosis.
We report evidence that the enzyme transglutaminase (glutaminyl-peptide gamma-glutamyltransferase; R-glutaminyl-peptide:amine gamma-glutamyltransferase, EC220.127.116.11) participates in receptor-mediated endocytosis. Clustering and internalization of rhodamine-labeled alpha 2-macroglobulin (R alpha 2 M) in normal rat kidney (NRK) cells is inhibited by a wide spectrum of compounds that inhibit transglutaminases, including that from NRK cells. The pattern of clustering inhibition resembles the pattern of transglutaminase inhibition as follows: (i) The most potent transglutaminase inhibitors are dansylcadaverine and the transglutaminase-directed affinity label N-benzyloxy-carbonyl-5-diazo-4-oxonorvaline p-nitrophenyl ester; these were also the most potent inhibitors of clustering and internalization of R alpha 2M. (ii) The inhibition of clustering of R alpha 2M occurs in the same concentration range as that required for transglutaminase inhibition. (iii) Linear primary amines are more effective blockers than the iso-chain primary amines. (iv) The transglutaminase affinity label N-benzyloxycarbonyl-5-diazo-4-oxonorvaline p-nitrophenyl ester irreversibly inhibits a significant fraction of the NRK transglutaminase and the clustering and internalization of R alpha 2M. A closely related compound, N-trifluoroacetyl-6-diazo-5-oxonorleucine ethyl ester, does not significantly inhibit transglutaminase or clustering and internalization. (v) Clustering and internalization is inhibited 10-fold more effectively by the heptapeptide Ac-Gly2-LLeu-LLys-Gly3 than by the heptapeptides Ac-Gly2-LLeu-DLys-Gly3 or AcGly3-DLys-DLeu-Gly2. This is the pattern of stereospecificity for the inhibition of purified transglutaminases.


Trophoblast differentiation of human embryonic stem cells.
Molecular mechanisms regulating human trophoblast differentiation remain poorly understood due to difficulties in obtaining primary tissues from very early developmental stages in humans. Therefore, the use of human embryonic stem cells (hESCs) as a source for generating trophoblast tissues is of significant interest. Trophoblast-like cells have been obtained through treatment of hESCs with bone morphogenetic protein (BMP) or inhibitors of activin/nodal/transforming growth factor-β signaling, or through protocols involving formation of embryoid bodies (EBs); however, there is controversy over whether hESC-derived cells are indeed analogous to true trophoblasts found in vivo. In this review, we provide an overview of previously described efforts to obtain trophoblasts from hESCs. We also discuss the merits and limitations of hESCs as a source of trophoblast derivatives.


Metabolism and excretion of a new anxiolytic drug candidate, CP-93, 393, in healthy male volunteers.
CP-93,393 [(7S,9aS)-1-(2-pyrimidin-2-yloctahydropyrido[1,2-a] pyrazin-7-ylmethyl)pyrrolidine-2,5-dione] is a new anxiolytic drug with highly selective serotonin 5-hydroxytryptamine 1A autoreceptor agonist, alpha2-adrenergic antagonist, and dopamine D2 agonist properties. The excretion, biotransformation, and pharmacokinetics of CP-93,393 were investigated in six healthy male volunteers after oral administration of a 5-mg dose of [14C]CP-93,393. The administered radioactivity was excreted predominantly in the urine. One week after administration of the dose, cumulative excretion amounted to 67.8 +/- 2.5% in the urine and 22.0 +/- 5.6% in the feces. In total, 89.8 +/- 5.7% of the radioactive dose was recovered in urine and feces. Mean maximum plasma concentration values for unchanged CP-93,393 were 10.92 and 1.02 ng/ml for poor metabolizers (PMs) and extensive metabolizers (EMs) of dextromethorphan, respectively. AUC0-infinity values for unchanged CP-93,393 were also greater for PMs than for EMs, whereas the mean maximum plasma concentration and AUC0-infinity values for total radioactivity were similar for the two phenotypes. Less than 0.5% of the dose was excreted in urine as unchanged drug for both EMs and PMs, suggesting extensive metabolism of CP-93,393 in both phenotypes. Hydroxylation at the 5-position of the pyrimidine ring was identified as the main metabolic pathway. 5-Hydroxy-CP-93,393 (M-15) and its glucuronide and sulfate conjugates (M-7 and M-13, respectively) accounted for approximately 51% of the administered dose in excreta of both PMs and EMs. Hydrolysis of the succinimide ring, in combination with 5-hydroxylation and/or conjugation or not, accounted for approximately 9% of the dose. A novel metabolite, apparently resulting from oxidative degradation of the pyrimidine ring, was characterized as the amidine analog M-18. M-15 (47-62%), its sulfate conjugate (M-13, approximately 9%), and the pyrimidine ring-cleaved product (M-18, 7-13%) were identified as the major circulating metabolites for both EMs and PMs. Therefore, CP-93,393 undergoes metabolism by three primary pathways, i.e. 1) aromatic hydroxylation followed by conjugation with glucuronic acid and sulfuric acid, 2) oxidative degradation of the pyrimidine ring, and 3) hydrolysis of the succinimide ring. The identified metabolites accounted for approximately 90, 91, and 92% of the total radioactivity present in urine, plasma, and feces, respectively. The major in vivo oxidative metabolites were also observed after in vitro incubations with human liver microsomes.


Anterior lumbar interbody fusion for discogram concordant pain.
Twenty-two patients undergoing anterior lumbar interbody fusion (ALIF) for discogram concordant low-back pain were retrospectively evaluated by objective criteria. Results were poor in all two-level fusions. Among single-level fusions, there were 35% good, 18% fair, and 47% poor results. Patients with previous surgery or workmen's compensation did poorly as a group despite positive discography. Subjective results were difficult to assess.


Tobacco industry youth smoking prevention programs: protecting the industry and hurting tobacco control.
This report describes the history, true goals, and effects of tobacco industry-sponsored youth smoking prevention programs. We analyzed previously-secret tobacco industry documents. The industry started these programs in the 1980s to forestall legislation that would restrict industry activities. Industry programs portray smoking as an adult choice and fail to discuss how tobacco advertising promotes smoking or the health dangers of smoking. The industry has used these programs to fight taxes, clean-indoor-air laws, and marketing restrictions worldwide. There is no evidence that these programs decrease smoking among youths. Tobacco industry youth programs do more harm than good for tobacco control. The tobacco industry should not be allowed to run or directly fund youth smoking prevention programs.


Toxicity of PCB 1232 on mitochondria of fish Arius caelatus (Valenciennes).
Mitochondrial proteins and phospholipids were estimated and SDH, Na(+)-K(+)-ATPase and Mg(2+)-ATPase activities were analysed in the gill, liver and heart tissues of PCB 1232 (sublethal doses) treated fish A. caelatus. Protein and phospholipids were found to be decreased significantly and SDH, Na(+)-K(+)-ATPase, Mg(2+)-ATPase and other enzyme systems displayed an inverse relationship with PCB dosage. Statistical analysis was carried out to indicate the relationship between sublethal doses of varying concentration and the activities of the enzyme systems involved in energy metabolism. The studies indicated impairment in mitochondrial functions.


Persistent Ulnar Nerve Palsy with Cubitus Valgus Deformity Following a Surgically Treated Flexion-type Supracondylar Humeral Fracture - A Case Report.
Supracondylar humeral fractures (SHFs) in children are mostly extension-type. SHFs have a high risk of cubitus varus deformity, while valgus deformity is rarely described. Nerve palsy can also occur during or after the injury, with most cases recovering spontaneously. Here, we present a rare case of cubitus valgus deformity after a flexion-type SHF with ulnar nerve (UN) palsy, which was successfully treated by corrective osteotomy and anterior transposition of the UN. A 10-year-old girl had left-sided cubitus valgus deformity with persistent UN palsy 4 months after open reduction and internal fixation (ORIF) at another hospital. Half a year after the initial operation, corrective osteotomy of the distal humerus with neurolysis and subcutaneous anterior transposition of the UN were performed. She showed excellent recovery 14-month postoperatively and reported restored motor and sensory function with symmetrical elbow appearance. Surgeons usually observe the elbow angle carefully to avoid cubitus varus deformity. However, when treating a case of flexion-type SHFs, ORIF should be conducted to avoid cubitus valgus deformity, which could potentially cause UN traction as well as cosmetic dissatisfaction.


Enrichment of estradiol receptor from calf uterus.
A three-step procedure to enrich estradiol receptor protein from calf uterus nearly 30,000-fold has been described. Over-all yield is 12%. Control of the single steps has been performed by sodium dodecyl sulfate-electrophoresis, sucrose density gradient centrifugation, gel filtration and determination of receptor quantity. Immunological properties of the preparation obtained have not been controlled.


Dose-dependent impact of oxytetracycline on the veal calf microbiome and resistome.
Antibiotic therapy is commonly used in animal agriculture. Antibiotics excreted by the animals can contaminate farming environments, resulting in long term exposure of animals to sub-inhibitory levels of antibiotics. Little is known on the effect of this exposure on antibiotic resistance. In this study, we aimed to investigate the long term effects of sub-inhibitory levels of antibiotics on the gut microbiota composition and resistome of veal calves in vivo. Forty-two veal calves were randomly assigned to three groups. The first group (OTC-high) received therapeutic oral dosages of 1 g oxytetracycline (OTC), twice per day, during 5 days. The second group (OTC-low) received an oral dose of OTC of 100-200 μg per day during 7 weeks, mimicking animal exposure to environmental contamination. The third group (CTR) did not receive OTC, serving as unexposed control. Antibiotic residue levels were determined over time. The temporal effects on the gut microbiota and antibiotic resistance gene abundance was analysed by metagenomic sequencing. In the therapeutic group, OTC levels exceeded MIC values. The low group remained at sub-inhibitory levels. The control group did not reach any significant OTC levels. 16S rRNA gene-based analysis revealed significant changes in the calf gut microbiota. Time-related changes accounted for most of the variation in the sequence data. Therapeutic application of OTC had transient effect, significantly impacting gut microbiota composition between day 0 and day 2. By metagenomic sequence analysis we identified six antibiotic resistance genes representing three gene classes (tetM, floR and mel) that differed in relative abundance between any of the intervention groups and the control. qPCR was used to validate observations made by metagenomic sequencing, revealing a peak of tetM abundance at day 28-35 in the OTC-high group. No increase in resistance genes abundance was seen in the OTC-low group. Under the conditions tested, sub-therapeutic administration of OTC did not result in increased tetM resistance levels as observed in the therapeutic group.


Comparison of Meconium Microbiome in Dizygotic and Monozygotic Twins Born by Caesarean Section (CS).
The early-life microbiota triggers life-long effects on physiological functions and health disorders. Previous studies in adult twins or animal models have revealed associations between host genetics and the harmonious microbiota. However, such associations may be obscured by the fact that each intra-pair of twins will continually encounter various environmental factors as they grow up. Here, we collected the meconium samples from nineteen dizygotic pairs (DZ, n = 38) and nine monozygotic pairs (MZ, n = 18) with cesarean delivery, and 16S rRNA gene sequencing was performed to profile the microbiome at birth. Diversity analysis showed that alpha diversity was not significantly different between two groups, whereas beta diversity of MZ twins was significantly lower than that of either DZ twins or unrelated individuals (i.e., randomly selected individual pairs of non-twinship) (p < 0.05). Two groups had very similar microbial classifications but different relative abundances of certain taxa including more Firmicutes (p = 0.05, Wilcoxon test) at the phylum level and lower abundances of five genera (p < 0.05) in DZ group compared to MZ group, including Rheinheimera, Proteus, SMB53, Sphingobium, and Megamonas. Co-occurrence analysis in each group showed slightly more complicated microbial interactions in DZ than MZ twins, although 22 shared bacterial genera co-existed in two groups, with both Rheinheimera and Megamonas having different centralities in their respective co-occurrence networks. Mean intra-class correlation coefficient (ICC) were also significantly higher for MZ (0.312) compared to DZ twins (0.138) (p < 0.05). The predicted microbial gene functions related to carbohydrate were higher in DZ group, whereas folding, sorting, degradation, cell motility pathways and energy metabolism were markedly over-represented in the microbiota of MZ group. In summary, our study uncovered that microbial diversity and components of the meconium microbiome between DZ and MZ twins were partially consistent with that in singleton neonates by cesarean delivery, but several distinctions related to the heritability supported genetic contributions to intestinal microbiome in early life.


Alcohol use patterns of graduate students in social work and in business.
This comparative study is among the first to survey the drinking behavior of graduate students in social service (N = 256) and in business (N = 147). A large majority (88%) drank. A significantly greater number of social service students abstained. Irrespective of school, age or religion, men and women drank at a similar level of frequency--several times weekly. Only business school women, controlling for age and religion, were significantly heavier drinkers than were women in social service. Older Hispanic social service men were significantly lighter drinkers than similar Caucasians. All women preferred wine, whereas men had no particular beverage preference. Although there was no significant difference in the location of drinking--in bars, restaurants or at home--most students drank in restaurants. Irrespective of previous course work or work experience with alcoholics, social service students wanted alcohol education. However, business students showed almost no interest in this area of study, despite the known deleterious role that alcohol misuse plays in the employment arena. Major conclusions are that both business and social service students lack alcohol education, although most drink. This is an important blind spot among business students, who will be making critical business decisions. It is also inadequate preparation for social service practice.


[Neurophysiology of visual aura in migraine].
Visual processing in migraine has been targeted because the visual symptoms that are commonly associated with attack, either in the form of aura or other more subtle symptoms, indicate that the visual pathways are involved in migrainous pathophysiology. The visual aura of the migraine attack has been explained by the cortical spreading depression (CSD) of Leão, neuroelectric event beginning in the occipital cortex and propagating into contiguous brain region. Clinical observations suggest that hyperexcitability occurs not only during the attack, typically in the form of photophobia, but also between attacks. Numerous human neuroimaging, neurophysiological and psychophysical studies have identified differences in cortical visual processing in migraine. The possibility of imaging the typical visual aura with BOLD functional MRI has revealed multiple neurovascular events in the occipital cortex within a single attack that closely resemble CSD. As transient synchronized neuronal excitation precedes CSD, changes in cortical excitability underlie the migraine attack. Independent evidence for altered neuronal excitability in migraineurs between attacks emerges from visual evoked potentials (VEPs) and transcranial magnetic stimulation (TMS), recordings of cortical potentials and psychophysics. Recently, both TMS and psycho-physical studies measuring visual performance in migraineurs have used measures which presumably measure primary visual (V1) and visual association cortex. Our VEP and blink reflex study showed that migraine patients exhibiting allodynia might show central sensitization of braistem trigeminal neuron and had contrast modulation dysfunction during the cortical visual processing of V1 and visual association cortex in-between attacks. In pathophysiology of migraine, these neurophysiological and psychophysical studies indicate that abnormal visual and trigeminal hyperexcitability might persist between migraine attacks. The influence of migraine on cortical neural processing is likely to extend beyond V1 and abnormal cortical activity might lead to CSD when enhanced activation coincides with other factors.


Control of the koala (Phascolarctos cinereus) anterior pituitary-gonadal axis with analogues of GnRH.
The aim of the present study was to determine whether analogues of gonadotrophin-releasing hormone (GnRH) could be used to both induce an acute testosterone response and suppress anterior pituitary function in male koalas, and induce a luteal phase in female koalas. Experiment 1 characterised the steroidogenic response of male koalas to administration of 30 microg (4.3 microg kg(-1)) natural-sequence GnRH. Intra-muscular injection of natural-sequence GnRH induced the release of LH and testosterone with peak concentrations at 30 min (3.7 +/- 1.9 ng mL(-1)) and 2 h (5.4 +/- 0.5 ng mL(-1)), respectively. In Experiment 2, a single injection of the GnRH antagonist acyline (100 microg (14.3 microg kg(-1)) or 500 microg (71.4 microg kg(-1))) did not influence the testosterone response to subsequent injections of natural-sequence GnRH. In Experiment 3, 4 microg (~0.67 microg kg(-1)) of the GnRH agonist buserelin induced a luteal phase in five female koalas based on a LH surge, secretion of progestogen, and a normal-length oestrous cycle. The findings have shown that (1) natural-sequence GnRH can be used to test gonadotroph cell function and determine the testosterone-secreting capacity of male koalas, (2) the GnRH antagonist, acyline, at the dose rates used, does not suppress the pituitary-testis axis in male koalas, and (3) the GnRH agonist, buserelin, induces a normal luteal phase in female koalas.


Kinetics, equilibria, and modeling of the formation of oligosaccharides from D-glucose with Aspergillus niger glucoamylases I and II.
Near-homogeneous forms of glucoamylases I and II, previously purified from an industrial Aspergillus niger preparation, were incubated with D-glucose at a number of temperatures and pH values. Kinetics and equilibria of the formation of alpha,beta-trehalose, kojibiose, nigerose, maltose, isomaltose, panose, and isomaltotriose, which with isomaltotetraose were the only products formed, were determined. There was no difference in the abilities of GA I and GA II to form these products. Activation energies for the formation of maltose and panose were lower than those of the other Oligosaccharides. Relative rates of oligosaccharide production based on glucoamylase hydrolytic activity did not vary significantly between pH 3.5 and 4.5 but were lower at pH 5.5. Maltose was formed much faster than any other product. Equilibrium concentrations at higher dissolved solids concentrations decreased in the order isomaltose, isomaltotriose, kojibiose, nigerose, maltose, alpha, beta-Mrehalose, panose, and isomaltotetraose. They were not appreciably affected by changes in temperature or pH. A kinetic model based on adsorption of D-glucose and the seven di- and trisaccharides by the first three glucoamylase subsites was formulated. Oligosaccharide formation was simulated with the model, using equilibrium data gathered for this article and subsite binding energies and kinetic parameters for oligosaccharide hydrolysis measured earlier. Agreement of simulated and actual oligosaccharide formation data through the course of the reaction was excellent except at very high solid concentrations.


Tryptophan metabolism-related gene expression patterns: unveiling prognostic insights and immune landscapes in uveal melanoma.
Uveal melanoma (UVM) remains the leading intraocular malignancy in adults, with a poor prognosis for those with metastatic disease. Tryptophan metabolism plays a pivotal role in influencing cancerous properties and modifying the tumor's immune microenvironment. In this study, we explore the relationship between tryptophan metabolism-related gene (TRMG) expression and the various features of UVM, including prognosis and tumor microenvironment. Our analysis included 143 patient samples sourced from public databases. Using K-means clustering, we categorized UVM patients into two distinct clusters. Further, we developed a prognostic model based on five essential genes, effectively distinguishing between low-risk and high-risk patients. This distinction underscores the importance of TRMGs in UVM prognostication. Combining TRMG data with gender to create nomograms demonstrated exceptional accuracy in predicting UVM patient outcomes. Moreover, our analysis reveals correlations between risk assessments and immune cell infiltrations. Notably, the low-risk group displayed a heightened potential response to immune checkpoint inhibitors. In conclusion, our findings underscore the dynamic relationship between TRMG expression and various UVM characteristics, presenting a novel prognostic framework centered on TRMGs. The deep connection between TRMGs and UVM's tumor immune microenvironment emphasizes the crucial role of tryptophan metabolism in shaping the immune landscape. Such understanding paves the way for designing targeted immunotherapy strategies for UVM patients.


Morphological and compositional changes of rat plasma triglyceride-rich lipoproteins incubated with adipose tissue.
Triglyceride-rich rat lipoproteins (mainly VLDL), purified by ultracentrifugation and dialysis, were incubated for 120 min in the presence of epididymal fat-pad pieces from fed rats in media containing heparin. During this process, the lipoproteins were depleted of triglycerides and proportionally enriched with proteins, causing their increased density. After incubation, electron microscopic study of the triglyceride-rich lipoproteins revealed partially degraded structures, and some particles had atypical discoid flattened form and marked lamellar structure. These findings are in agreement with those of Blanchette-Mackie & Scow (1976) in triglyceride hydrolysed chylomicrons and confirm their observation of monolayers formed by accumulated lipolytic products that move by lateral diffusion, giving rise to a spiral fold between the core triglycerides and the aqueous space.


Rapid Detection of Cyprinid Herpesvirus 3 in Latently Infected Koi by Recombinase Polymerase Amplification.
Since the emergence of cyprinid herpesvirus 3 (CyHV-3), outbreaks have been devastating to Common Carp Cyprinus carpio and koi (a variant of Common Carp), leading to high economic losses. Current diagnostics for detecting CyHV-3 are limited in sensitivity and are further complicated by latency. Here we describe the detection of CyHV-3 by recombinase polymerase amplification (RPA). The RPA assay can detect as low as 10 copies of the CyHV-3 genome by an isothermal reaction and yields results in approximately 20 min. Using the RPA assay, the CyHV-3 genome can be detected in the total DNA of white blood cells isolated from koi latently infected with CyHV-3, while less than 10% of the latently infected koi can be detected by a real-time PCR assay in the total DNA of white blood cells. In addition, RPA products can be detected in a lateral flow device that is cheap and fast and can be used outside of the diagnostic lab. The RPA assay and lateral flow device provide for the rapid, sensitive, and specific amplification of CyHV-3 that with future modifications for field use and validation could lead to enhanced surveillance and early diagnosis of CyHV-3 in the laboratory and field. Received September 14, 2015; accepted April 9, 2016.


Post-transcriptional regulation of cancer/testis antigen MAGEC2 expression by TRIM28 in tumor cells.
Cancer/testis antigen MAGEC2 (also known as HCA587) is highly expressed in a wide variety of tumors and plays an active role in promoting growth and metastasis of tumor cells. However, little is known for the regulation of MAGEC2 expression in cancer cells. Western blotting and quantitative RT-PCR were performed to analyze MAGEC2 expression. Co-immunoprecipitation assay was applied for detecting the endogenous interaction of MAGEC2 and TRIM28 in tumor cells. Overexpression and knockdown assays were used to examine the effects of TRIM28 on the expression of MAGEC2 protein. Immunohistochemistry (IHC) staining was performed in hepatocellular carcinoma patients to evaluate the association between the expression of MAGEC2 and TRIM28. Proteasome inhibitors MG132 or PS-341 and lysosome inhibitor Chloroquine (CQ) were used to inhibit proteasomal or lysosomal-mediated protein degradation respectively. We demonstrate that MAGEC2 interacts with TRIM28 in melanoma cells and MAGEC2 expression in tumor cells depends on the expression of TRIM28. The expression level of MAGEC2 protein was significantly reduced when TRIM28 was depleted in tumor cells, and no changes were observed in MAGEC2 mRNA level. Furthermore, expression levels of MAGEC2 and TRIM28 are positively correlated in MAGEC2-positive human hepatocellular carcinoma tissues (p = 0.0011). Mechanistic studies indicate that the regulatory role of TRIM28 on MAGEC2 protein expression in tumor cells depends on proteasome-mediated pathway. Our findings show that TRIM28 is necessary for MAGEC2 expression in cancer cells, and TRIM28 may serve as a new potential target for immunotherapy of cancer.


Metabolic differences between Caucasian and African-American children and the relationship to type 2 diabetes mellitus.
Type 2 diabetes mellitus (DM) has historically been considered an adult disease. However, the incidence of type 2 DM has increased dramatically in pediatric populations in recent years. This increase parallels the recent rise in childhood obesity and has been greatest among minority adolescents. Differences between African-American and white American youths are discussed, including risk factor differences that may help to account for the overwhelming number of African-American children with type 2 DM as compared with white children. African-American youths have higher rates of insulinemia, obesity, family history, and acanthosis nigricans than their white counterparts. In addition, despite similar declines in insulin action during puberty, there is no compensatory increase in insulin secretion in African-American children, contrary to the observation in white children. These differences are likely to have a genetic basis modulated by environmental and lifestyle influences. Treatment of type 2 DM should focus on identifying individuals at risk and instituting lifestyle changes to reduce the risk and stem the development of DM.


Cementifying fibroma of the ethmoidal sinus.
An interesting case of cementifying fibroma of the ethmoidal sinus is presented. This benign tumour, in this unusual site, tends to behave in an aggressive manner and radical surgery is necessary. Recurrence is frequent.


The role of affective evaluation in conflict adaptation: An LRP study.
Conflict between incompatible response tendencies is typically followed by control adjustments aimed at diminishing subsequent conflicts, a phenomenon often called conflict adaptation. Dreisbach and Fischer (2015, 2016) recently proposed that it is not the conflict per se but the aversive quality of a conflict that originally motivates this kind of sequential control adjustment. With the present study we tested the causal role of aversive signals in conflict adaptation in a more direct way. To this end, after each trial of a vertical Simon task participants rated whether they experienced the last trial as rather pleasant or unpleasant. Conflict adaptation was measured via lateralized readiness potentials as a measure of early motor-related activation that were computed on the basis of event-related brain potentials. Results showed the typical suppression of automatic response activation following trials rated as unpleasant, whereas suppression was relaxed following trials rated as pleasant. That is, sequential control adaptation was not based on previous conflict but on the subjective affective experience. This is taken as evidence that negative affect even in the absence of actual conflict triggers subsequent control adjustments.


Stereoselective synthesis using immobilized Diels-Alderase ribozymes.
Development of artificial ribozymes by in vitro selection has so far, mostly been addressed from the viewpoint of fundamental research. However, such ribozymes also have high potential as selective catalysts in practical syntheses. Immobilization of an active and selective ribozyme is an important step towards this end. A 49-nucleotide RNA molecule that was previously found to stereoselectively catalyze Diels-Alder reactions between various anthracene dienes and maleimide dienophiles was quantitatively immobilized on an agarose matrix by periodate oxidation of the 3'-terminal ribose and coupling to a hydrazide moiety. Typical loadings were 45 pmol microL(-1) gel. The specific activity was comparable to that of soluble ribozyme, and high enantioselectivities were obtained in catalyzed cycloadditions. The catalytic matrix was found to be stable and could be regenerated about 40 times with only minimal reduction of catalytic activity. Like the soluble ribozyme, the immobilized catalyst stereoselectively converts various diene and dienophile substrates. By using either natural D-RNA or enantiomeric L-RNA, both product enantiomers were made synthetically accessible with similar selectivities.


Social exclusion and psychopathology in an online cohort of Moroccan-Dutch migrants: Results of the MEDINA-study.
Migration is seen as a risk factor for developing psychiatric symptoms and experiencing social exclusion. In the Netherlands, the Moroccan-Dutch population is the second largest migrant group. 70% of all young Moroccan-Dutch people meet each other in the online community www.marokko.nl. Within this community, we investigated the association between experiences of social exclusion and self-reported depressive symptoms and psychotic experiences. Participants were recruited via the website www.marokko.nl. They completed an online survey, with screening instruments for depressive symptoms (K10) and psychotic experiences (PQ-16), measures of social exclusion (perceived discrimination, social defeat and social support), and questions about demographical information. With regression analysis the association between social exclusion and psychiatric symptoms was investigated. We included 267 participants; 87% were female. 27% of the sample has received mental healthcare in the past. Over 50% of these people screened positive for depressive symptoms and psychotic experiences. Perceived discrimination and social defeat were significantly associated with psychotic experiences and social defeat was associated with depressive symptoms. Social support and higher education were associated with less depressive symptoms and psychotic experiences. Our findings suggest that the online environment allows for epidemiological research and early symptom detection. Levels of psychopathology were high in our sample. This suggests that a part of this young ethnic minority population might not get adequate mental healthcare. Since this population can be reached through Internet, the online environment may therefore also offer an appropriate setting for intervention, to increase resilience towards social exclusion.


Rotation of both X- and Y-axes is a predictive confounder of ulnar nerve injury and open reduction in pediatric lateral flexion supracondylar humeral fractures: A retrospective cohort study.
Rotation of the distal fragment often occurs in flexion-type supracondylar humerus fractures (SCHFs), potentially leading to ulnar nerve injury (UNI) and open reduction. We analyzed the correlation between the rotations and UNI or open reduction and then assessed the risk factors associated with these rotations. Data of Wilkins type III lateral flexion SCHFs were collected over a 10-year time period (1 January 2012 to 31 December 2021) in Children's Hospital of Fudan University Anhui Hospital. We defined the rotation of the distal fragment on the coordinate axis as two types, IIIA (X-axis rotation) and IIIB (the rotation of both X- and Y-axes) on X-ray radiography. Demographic data, the incidence of the two-type rotation, odds ratios (ORs) of UNI and open reduction, and risk factors of the rotation of both X- and Y-axes were analyzed. Totally, 152 patients were found (50 with IIIA vs. 102 IIIB). The UNI rate was 13%, and the open reduction rate was 22%. The UNI rate of the IIIB was five-fold higher than that of the IIIA [OR, 5.143; 95% confidence interval (CI), 1.414-23.125; p = 0.019], and the open reduction rate of the IIIB was nearly five-fold higher than that of the IIIA (OR, 4.729, 95%CI, 1.584-14.495; p = 0.003). In these two types, patients with UNI had a higher risk of open reduction than those without UNI (OR, 9.816; 95%CI, 3.503-27.508; p = 0.001). In the multiple regression analysis, a high level of fracture was identified as a risk factor for the rotation of both X- and Y-axes. Type IIIB lateral flexion-type SCHFs have higher rates of UNI and open reduction, and a high level of fracture is a risk factor associated with this type.


Pulmonary tuberculosis in infants: radiographic and CT findings.
As complications of tuberculosis are frequent in infancy, correct diagnosis of tuberculosis in infants is important. The purposes of this study are to summarize radiographic and CT findings of pulmonary tuberculosis in infants and to determine the radiologic features frequently seen in infants with this disease. Frequent radiologic findings of pulmonary tuberculosis in infants are mediastinal or hilar lymphadenopathy with central necrosis and air-space consolidations, especially masslike consolidations with low-attenuation areas or cavities within the consolidation. Disseminated pulmonary nodules and airway complications are also frequently detected in this age group. CT is a useful diagnostic technique in infants with tuberculosis because it can show parenchymal lesions and tuberculous lymphadenopathy better than chest radiography. CT scans can also be helpful when chest radiographs are inconclusive or complications of tuberculosis are suspected.


Emery A. Rovenstine and regional anesthesia.
Emery Andrew Rovenstine was a dominant figure in anesthesiology in the United States between 1935 and 1960. Among his many contributions to the specialty, his regional anesthesia practice remains less well known. This paper explores Rovenstine's career and his contributions to regional anesthesia. Original documents studied and classified for this investigation included all of Rovenstine's published papers and the extant documents of the original American Society of Regional Anesthesia. Interviews with several physicians who knew Rovenstine were conducted. Secondary source materials, including biographies of Rovenstine, were perused. Rovenstine made a major contribution to regional anesthesia through patient care, teaching, and political action. Many of his students went on to become leaders in anesthesiology and emphasized regional anesthesia in the second half of the twentieth century. Emery A. Rovenstine did much to popularize regional anesthesia and ensure a rightful place for its techniques within the armamentarium of the anesthesiologist. Keeping alive the traditions of Gaston Labat at Bellevue, Rovenstine's contributions to regional anesthesia on all levels were considerable. Most importantly, he ensured an enduring role for regional anesthesia through the recurring contributions of his pupils.


Structure-Activity Relationship Exploration of NNIBP Tolerant Region I Leads to Potent HIV-1 NNRTIs.
Previous efforts in our lab have led to the development of human immunodeficiency virus type 1 (HIV-1) non-nucleoside reverse transcriptase inhibitor (NNRTI) thiophene[3,2-d]pyrimidine compound 1 (K-5a2) with promising activity against wild-type and mutant HIV-1 strains. In this work, a series of novel diarylpyrimidines derivatives carrying a structurally diverse motif at the right wing of the lead K-5a2 was designed and synthesized as potential anti-HIV-1 agents. The results demonstrated that 8a yielded exceptionally potent activity against HIV-1 wild-type (50% effective concentration (EC50) = 3.30 nM) and mutant strain RES056 (EC50 = 22.6 nM) in MT-4 cells; in the reverse transcriptase inhibitory assay, 8a (half maximal inhibitory concentration (IC50) = 0.028 μM) was remarkably superior to that of K-5a2 (IC50 = 0.300 μM) and comparable to that of etravirine (ETR; IC50 = 0.011 μM). Notably, 8a exhibited better druggability than that of K-5a2, including significantly reduced CYP enzymatic inhibitory activity (IC50 > 50 μM), lower human ether-à-go-go related gene (hERG) inhibition (IC50 > 30 μM), and improved metabolic stability (short half-life, T1/2 = 77.5 min) in vitro.


Amyloid precursor protein in pancreatic islets.
The amyloid precursor protein (APP) has been extensively investigated for its role in the production of amyloid beta (Aβ), a plaque-forming peptide in Alzheimer's disease (AD). Epidemiological evidence suggests type 2 diabetes is a risk factor for AD. The pancreas is an essential regulator of blood glucose levels through the secretion of the hormones insulin and glucagon. Pancreatic dysfunction is a well-characterized consequence of type 1 and type 2 diabetes. In this study, we have examined the expression and processing of pancreatic APP to test the hypothesis that APP may play a role in pancreatic function and the pathophysiology of diabetes. Our data demonstrate the presence of APP within the pancreas, including pancreatic islets in both mouse and human samples. Additionally, we report that the APP/PS1 mouse model of AD overexpresses APP within pancreatic islets, although this did not result in detectable levels of Aβ. We compared whole pancreas and islet culture lysates by Western blot from C57BL/6 (WT), APP-/- and APP/PS1 mice and observed APP-dependent differences in the total protein levels of GLUT4, IDE and BACE2. Immunohistochemistry for BACE2 detected high levels in pancreatic α cells. Additionally, both mouse and human islets processed APP to release sAPP into cell culture media. Moreover, sAPP stimulated insulin but not glucagon secretion from islet cultures. We conclude that APP and its metabolites are capable of influencing the basic physiology of the pancreas, possibly through the release of sAPP acting in an autocrine or paracrine manner.


[Health inequalities in immigrant populations in Spain: a scoping review].
Health differences between immigrants and natives should be analyzed from an equity perspective due to socioeconomic inequality between them. The aim of this study is to Know the influence of social determinants of health in the immigrant population in Spain and/or inequalities compared with the Spanish population. SA scoping review of the literature published in the period 1998-2012 was performed. The literature search was conducted on Medline and MEDES-MEDicina databases. All studies that include the participation of immigrant population from areas such as Latin America, Africa, Asia and Eastern Europe and performed in Spain were selected. A 27 articles were included. Most of the studies were published in the year 2009 (n=11). Twelve used population health surveys at national (n=6) and autonomous (n = 6) level. A total of 23 studies focused on adult population over 15 years. The most frequently studied indicators were self-rated health (n=9) and mental health (n=7). The immigrant population is exposed to lower socioeconomic status than natives and, despite a lower prevalence of chronic diseases, it appears to experience more mental health problems and worse self-rated health, especially in women and with longer stay.


Proteomic analysis of koala (phascolarctos cinereus) spermatozoa and prostatic bodies.
The aims of this study were to investigate the proteome of koala spermatozoa and that of the prostatic bodies with which they interact during ejaculation. For this purpose, spermatozoa and prostatic bodies were fractionated from the semen of four male koalas and analysed by HPLC MS/MS. This strategy identified 744 sperm and 1297 prostatic body proteins, which were subsequently attributed to 482 and 776 unique gene products, respectively. Gene ontology curation of the sperm proteome revealed an abundance of proteins mapping to the canonical sirtuin and 14-3-3 signalling pathways. By contrast, protein ubiquitination and unfolded protein response pathways dominated the equivalent analysis of proteins uniquely identified in prostatic bodies. Koala sperm proteins featured an enrichment of those mapping to the functional categories of cellular compromise/inflammatory response, whilst those of the prostatic body revealed an over-representation of molecular chaperone and stress-related proteins. Cross-species comparisons demonstrated that the koala sperm proteome displays greater conservation with that of eutherians (human; 93%) as opposed to reptile (crocodile; 39%) and avian (rooster; 27%) spermatozoa. Together, this work contributes to our overall understanding of the core sperm proteome and has identified biomarkers that may contribute to the exceptional longevity of koala spermatozoa during ex vivo storage.


[Preparation of monoclonal antibody against enterovirus 71 capsid protein VP1].
Objective To prepare murine monoclonal antibody (mAb) against enterovirus 71 (EV71) capsid protein VP1. Methods VP1 protein was expressed and purified. BALB/c mice were immunized with inactivated and purified EV71 virus, and mAb specific to EV71 VP1 was generated by hybridoma technique. Indirect ELISA was used to test antibody titer and antibody subclass identification. The expression of VP1 protein was detected by Western blot in EV71-infected RD cells. The expression and distribution of VP1 protein was detected by immunofluorescence cytochemistry in EV71-infected RD cells. Results Six antibody strains were obtained, among which three were IgG2a and three were IgG2b, all of which could be used for ELISA, Western blot and immunofluorescence cytochemical staining. 2D7 exhibited neutralization capacity with 50% inhibitory concentrations(IC50) of 9.892 μg/mL. Conclusion Six strains of monoclonal antibodies with excellent reactivity were obtained, which laid a foundation for the further studies on the identification and diagnosis of EV71 as well as the functional of VP1 protein.


Radiologic placement of Hickman catheters using intravenous sedation in pediatric patients under 20 kg.
Surgeons generally perform Hickman catheter insertion in children under general anesthesia. At times, it is difficult to perform procedures with an anesthesiologist for an interventional radiologist. Several diagnostic and therapeutic procedures are efficiently and safely conducted using intravenous (IV) sedation in children with a pediatrician. This study aims to evaluate the efficacy and safety of radiologically placed Hickman catheters using IV sedation in children under 20 kg.Fifty-nine catheters were inserted in 45 children under IV sedation. With continuous monitoring of vital signs, IV midazolam and ketamine were slowly infused by a pediatrician. Mean age and body weights were 3.2 years and 15.2 kg, respectively. Acute leukemia was the most common disease for the procedure (72.9%). The location of the catheter tip was evaluated by measuring the height of the thoracic vertebra.Technical success rate was 100%, and IV sedation-related complications did not occur. The right internal jugular vein was accessed for 51 catheters (86.4%), and the mean procedure time was 21.5 minutes. The 2 vertebral body units below the carina were the cavoatrial junction on a fluoroscopy image. Mean catheter life was 285 days, and catheters were removed post-treatment (35.6%). During follow-up, complications occurred in 29 cases (1.72 per 1000 catheter-days). Catheter-related infections were suspected in 4 patients (6.8%), with 1 positive result.Radiological Hickman catheter placement in children under 20 kg using IV sedation by pediatricians is effective and safe, with minimal complications. The carina is a landmark to estimate the cavoatrial junction in pediatric patients.


[Impact of different admission ways on treatment efficiency in patients with acute ST-segment elevation myocardial infarction].
Objective: To analyze the impact of different admission ways on the timeliness of percutaneous coronary intervention and in-hospital mortality in patients with acute ST-segment elevation myocardial infarction (STEMI). Methods: A total of 1 044 patients with STEMI, who received primary percutaneous coronary intervention (PPCI) in 9 hospitals in Chengdu from January 2017 to June 2019, were retrospectively enrolled. According to the admission ways, patients were divided into ambulance group (n=100), self-transport group (n=584) and transferred group (n=360). Timeliness and in-hospital mortality were compared among the groups. Indicators of timeliness included the time from symptoms onset to arrive at the hospital, the time from arrive at the hospital to balloon and the total myocardial ischemia time (the time from symptoms to balloon). Multivariate logistic regression analysis was used to verify whether the admission ways was the determinant for in-hospital death in STEMI patients receiving PPCI. Results: The median total myocardial ischemic time in the ambulance group was significantly shorter than that in the self-transport group (180.0 (135.0, 282.0) minutes vs. 278.0 (177.8, 478.5) minutes, P<0.05) and the transferred group (180.0 (135.0, 282.0) minutes vs. 301.0 (204.3, 520.8) minutes, P<0.05). The median time from symptoms to door was as follows: ambulance group<self-transport group<transferred group (100.0 (56.3, 198.0) minutes vs. 149.0 (72.0, 313.5) minutes vs. 238.0 (135.0, 545.0) minutes, all P<0.05). The median door-to-balloon time was significantly shorter in the ambulance group and transferred group than in the self-transport group (75.0 (44.3, 101.8) minutes vs. 97.0 (71.0, 140.5) minutes, 67.0 (40.0, 91.8) minutes vs. 97.0 (71.0, 140.5) minutes, both P<0.05). There was no significant difference in all-cause mortality among the three groups (P>0.05). Multivariate logistic regression analysis showed that admission way was not significantly associated with in-hospital death (P>0.05). Conclusions: STEMI patients, who are admitted through the medical emergency system, are more likely to receive timely interventional therapy.Different admission ways have no impact on in-hospital mortality.


Development of three ecological spectroscopic methods for analysis of betrixaban either alone or in mixture with lercanidipine: greenness assessment.
Three eco-friendly spectrophotometric methods were developed for determination of the novel anticoagulant drug, betrixaban (BTX). The first method (method A) was based on direct analysis of BTX at 229.4 nm on the zero-order spectrum using methanol as the optimum solvent. While the second method (method B) was based on measuring difference absorption value (ΔA) of BTX at 335 nm, which was obtained from pH-induced spectral difference (difference spectra of BTX in 0.1 M NaOH versus 0.1 M HCl). The third method (method C) was based on measurement of the first-derivative amplitudes of BTX and its co-administered Ca channel blocker lercanidipine (LER) at 304 and 229 nm for simultaneous assay of BTX and LER, respectively. All methods were linear over concentration ranges of 1.0-20.0 and 8.0-80.0 µg ml-1 for BTX in methods A and B, respectively, and of 1.0-20.0 and 1.0-25.0 µg ml-1 for BTX and LER, respectively, in method C. The three methods were fully validated and assessed for greenness by three metrics: analytical eco-scale, green analytical procedure index and Analytical GREEnness metrics. The results indicated the validity and greenness of the proposed methods. Moreover, the methods were applied to assay the studied analytes in their dosage forms with high percentage of recovery and low percentage of relative s.d. values.


A Digital Feedback System to Support Implementation of Measurement-Based Care by School-Based Mental Health Clinicians.
Evidence supports the utility of measurement-based care (MBC) to improve youth mental health outcomes, but clinicians rarely engage in MBC practices. Digital measurement feedback systems (MFS) may reflect a feasible strategy to support MBC adoption and sustainment. This pilot study was initiated to evaluate the impact of a MFS and brief consultation supports to facilitate MBC uptake and sustainment among mental health clinicians in the education sector, the most common mental health service delivery setting for youth. Following an initial training in MBC, 14 clinicians were randomized to either a digital MFS and brief consultation supports or control. Baseline ratings of MBC attitudes, skill, and use were collected. In addition, daily assessment ratings tracked 2 core MBC practices (i.e., assessment tool administration, provision of feedback) over a 6-month follow-up period. Clinicians in the MFS condition demonstrated rapid increases in both MBC practices, whereas the control group did not significantly change. For clinicians in the MFS group, consultation effects were significant for feedback and approached significance for administration. Over the follow-up period, average decreases in the current study were moderate with only 1 of the 2 outcome variables (administration) decreasing significantly. Inspection of individual clinician trajectories revealed substantial within-group trend variation. MFS may represent an effective MBC implementation strategy beyond initial training, although individual clinician response is variable. Identifying feasible and impactful implementation strategies is critical given the ability of MBC to support precision health care.


Distraction of the temporomandibular joint condyle in patients with unilateral non-reducing disc displacement: Fact or fiction?
This study investigated the distractive effect of a unilateral pivot splint on patients with unilateral disc displacement without reduction. The study group was comprised of 18 patients who had no history of treatment with removable prosthetic restorations of molars, premolars, or canine teeth, and no previous treatment for temporomandibular disorder. Joint spaces measurements made on magnetic resonance images indicated the affected side to be narrower than the healthy side. Unilateral distraction splints were made for all patients. An ultrasonic motion analyzer was used to measure the vertical shift occurring on the affected side as patients closed their mouths with maximal force with the splint in their mouths. Closing with maximal force on the unilateral distraction splint led to a noticeable downward movement of the affected condyle. The findings of this study indicate that the TMJ condyle of patients with unilateral disc displacement without reduction may be unilaterally distracted if the articular space is narrowed.


Study of the dynamic performance of a thrust stand for small-thrust liquid-pulsed thrusters.
Small-thrust liquid-pulsed thrusters can achieve higher efficiency and more accurate control when operating in pulsed mode. However, the pulsed characteristic makes it challenging to measure the thrust. This paper describes a thrust stand for directly measuring the pulsed thrust from small-thrust liquid-pulsed thrusters. The proposed stand is based on a unique piezoelectric dynamometer on which the thruster is mounted through a connecting frame. A thrust experiment is conducted by applying a trapezoidal pulsed force, similar to the thrust generated by small-thrust liquid-pulsed thrusters, to the thrust stand. The experimental results show that the thrust stand can quickly trace the input trapezoidal force signal, although its output waveform exhibits obvious oscillations. Based on the experimental frequency response data, a thrust stand transfer function model is constructed, and this model is used to analyze the dynamic response performance of the thrust stand. The step response and trapezoidal pulse response of the thrust stand are obtained, and the influence of the damping ratio on the dynamic performance of the thrust stand is analyzed. A damping compensation transfer function is established to improve the dynamic measurement performance of the thrust stand. Compensated results are obtained by using the raw output from the thrust stand as the input to the damping compensation transfer function. The damping compensation method does not change the natural frequencies of the thrust stand, does not need any additional filtering process, effectively eliminates the waveform oscillations of the thrust stand output, and ensures good consistency between the input and output signals.


A possible link between hepatic mitochondrial dysfunction and diet-induced insulin resistance.
Mitochondria are the main cellular sites devoted to ATP production and lipid oxidation. Therefore, the mitochondrial dysfunction could be an important determinant of cellular fate of circulating lipids, that accumulate in the cytoplasm, if they are not oxidized. The ectopic fat accumulation is associated with the development of insulin resistance, and a link between mitochondrial dysfunction and insulin resistance has been proposed. Recent data on the possible link existing between mitochondrial dysfunction in the liver and diet induced obesity will be summarized, focusing on the three factors that affect the mitochondrial oxidation of metabolic fuels, i.e. organelle number, organelle activity, and energetic efficiency of the mitochondrial machinery in synthesizing ATP. Search in PubMed relevant articles from 2003 to 2014 was conducted, by using query "liver mitochondria and obesity" "hepatic mitochondria and obesity" "liver mitochondria and high fat diet" and "hepatic mitochondria and high fat diet" and including related articles by the same groups. Several works, by using different physiological approaches, have dealt with alteration in mitochondrial function in obesity and diabetes. Most results show that hepatic mitochondrial function is impaired in models of obesity and insulin resistance induced by high-fat or highfructose feeding. Since mitochondria are the main producers of both cellular energy and free radicals, dysfunctional mitochondria could play an important role in the development of insulin resistance and ectopic fat storage in the liver, thus supporting the emerging idea that mitochondrial dysfunction is closely related to the development of obesity, type 2 diabetes mellitus and non-alcoholic steatohepatitis.


Tackling organ donation among minority ethnic communities in the UK-a whole systems approach.
There are inequalities experienced by minority ethnic groups in the UK in organ donation and transplant services, with significant variation in relation to demand for, access to and waiting times for these services. A narrative review of research obtained via several databases, including PubMed and Medline, was conducted. A vision of equity and inclusion, which meets the need of the heterogeneous UK population, can only be realized by adopting a culturally competent approach to systems-wide working in organ donation in four core areas-transplant services; workforce and staff training; diversity and inclusion research; and public engagement. Most of the data on the background of organ donors and recipients use general categories such as Asian or Black. We need to progress to a position of more granular data by more specific ethnicity so that we can better understand the trends and target action accordingly. By positively embracing the heterogeneity of the UK population, demand for transplantation can be reduced through a sustained commitment to public health interventions and culturally competent approaches in the management of long-term conditions. Improved access to transplantation and reduced waiting times can be achieved to increase the number of organ donors from minority ethnic groups if there are concerted and adequately resourced culturally competent interventions with concomitant evaluation programmes.


Unraveling the Allosteric Mechanism of Four Cancer-related Mutations in the Disruption of p53-DNA Interaction.
The p53 protein plays active roles in the physiological regulation of cell cycle as well as in cancer developments. In more than half of human cancers, the protein is inactivated by mutations located primarily in its DNA-binding domain (DBD), and some mutations located in the β-sandwich region of DBD are reported to decrease p53-DNA binding affinities. To understand the long-range correlation between p53 β-sandwich and DNA, and the allosteric mechanism of β-sandwich mutations in the disruption of p53-DNA interactions, we first identify three regions with a strong correlation with DNA based on microsecond molecular dynamics (MD) simulations of wild-type p53-DNA complex and then perform multiple MD simulations on four cancer-related mutants L145Q, P151S, Y220C, and G266R, which are located in these three regions. Our simulations show that these mutations allosterically destabilize the structural stability of the DNA-binding groove in p53 and disrupt the p53-DNA interactions. Network analyses reveal optimal correlation paths through which the mutation-induced allosteric signal passes to DNA, and the disturbance effect of these mutations on the global connectivity and dynamical correlation of the p53-DNA complex. This work paves the way for the in-depth understanding of the mutation-induced loss in p53's DNA-recognition ability and the pathological mechanism of cancer development.


CDON contributes to Hedgehog-dependent patterning and growth of the developing limb.
Hedgehog (HH) signaling is a major driver of tissue patterning during embryonic development through the regulation of a multitude of cell behaviors including cell fate specification, proliferation, migration, and survival. HH ligands signal through the canonical receptor PTCH1 and three co-receptors, GAS1, CDON and BOC. While previous studies demonstrated an overlapping and collective requirement for these co-receptors in early HH-dependent processes, the early embryonic lethality of Gas1;Cdon;Boc mutants precluded an assessment of their collective contribution to later HH-dependent signaling events. Specifically, a collective role for these co-receptors during limb development has yet to be explored. Here, we investigate the combined contribution of these co-receptors to digit specification, limb patterning and long bone growth through limb-specific conditional deletion of Cdon in a Gas1;Boc null background. Combined deletion of Gas1, Cdon and Boc in the limb results in digit loss as well as defects in limb outgrowth and long bone patterning. Taken together, these data demonstrate that GAS1, CDON and BOC are collectively required for HH-dependent patterning and growth of the developing limb.


Sexually Transmitted Infections and HIV in Ophthalmology.
The ocular and periocular manifestations of sexually transmitted infections (STIs) are heterogeneous in etiology, manifestations, and complications. Etiologic agents include bacteria, viruses, parasites, and protozoa, which are most frequently transmitted via direct ocular contact with an active lesion or infected bodily fluid, autoinoculation, or dissemination from a distant site. Vertical transmission most commonly occurs perinatally during vaginal delivery. The complications of ophthalmia neonatorum can be severe with the potential for permanent blindness or life-threatening systemic involvement if untreated. Clinical features, diagnostic modalities, and therapeutic regimens vary based on etiology and are summarized in this review. Prompt diagnosis is imperative, given the severe sequelae that may result from ocular involvement in these infections, including permanent vision loss. A multidisciplinary approach, involving both ophthalmology and dermatology, to diagnosis and management is essential to mitigate the risk of morbidity associated with STIs resulting in eye disease.


FcR interactions do not play a major role in inhibition of experimental autoimmune encephalomyelitis by anti-CD154 monoclonal antibodies.
It has been demonstrated that anti-CD154 mAb treatment effectively inhibits the development of experimental autoimmune encephalomyelitis (EAE). However, although it appears to prevent the induction of Th1 cells and reactivation of encephalitogenic T cells within the CNS, little information is available regarding the involvement of alternative mechanisms, nor has the contribution of Fc effector mechanisms in this context been addressed. By contrast, efficacy of anti-CD154 mAbs in models of allotransplantation has been reported to involve long-term unresponsiveness, potentially via activation of T regulatory cells, and recently was reported to depend on Fc-dependent functions, such as activated T cell depletion through FcgammaR or complement. In this study we demonstrate that anti-CD154 mAb treatment inhibits EAE development in SJL mice without apparent long-term unresponsiveness or active suppression of disease. To address whether the mechanism of inhibition of EAE by anti-CD154 mAb depends on its Fc effector interactions, we compared an anti-CD154 mAb with its aglycosyl counterpart with severely impaired FcgammaR binding and reduced complement binding activity with regard to their ability to inhibit clinical signs of EAE and report that both forms of the Ab are similarly protective. This observation was largely confirmed by the extent of leukocyte infiltration of the CNS; however, mice treated with the aglycosyl form may display slightly more proteolipid protein 139-151-specific immune reactivity. It is concluded that FcR interactions do not play a major role in the protective effect of anti-CD154 mAb in the context of EAE, though they may contribute to the full abrogation of peripheral peptide-specific lymphocyte responses.


18β-Glycyrrhetinic acid from licorice root impairs dendritic cells maturation and Th1 immune responses.
18β-Glycyrrhetinic acid (β-GA) is a natural triterpenoid compound derived from licorice root. β-GA has been demonstrated to exert antiviral and antitumor effects. However, the effects of the maturation and immunostimulatory functions of dendritic cells (DCs) remain to be clearly elucidated. In this study, we attempted to determine whether β-GA could influence DCs surface molecule expression, antigen uptake capacity, cytokine production and capacity to induce T-cell differentiation. The DCs used in this study were derived from murine bone marrow cells, and were used as immature or lipopolysaccharide (LPS)-stimulated mature DCs. The DCs were then assessed with regard to surface molecules expression, cytokine production, capacity to induce T-cell differentiation and proliferation. β-GA was shown to significantly suppress the expression of surface molecules CD80, CD86, major histocompatibility complex (MHC) class I and MHC class II as well as the levels of interleukin-12 production in LPS-stimulated DCs. Moreover, β-GA-treated DCs showed an impaired induction of the T helper type 1 immune response. These findings provide important understanding of the immunopharmacological functions of β-GA and have ramifications for the development of therapeutic adjuvants for the treatment of DCs-related acute and chronic diseases.


[Relationship between serum uric acid levels and patient conditions and prognosis in idiopathic pulmonary arterial hypertension].
To explore the relationship between serum uric acid levels and patient conditions and prognosis in idiopathic pulmonary arterial hypertension (IPAH). A total of 76 IPAH patients confirmed by right heart catheterization were enrolled consecutively and followed up until the endpoint of all-cause death. Their baseline data were recorded and analyzed by Spearman's rank test and independent t-test. And the follow-up outcomes were analyzed with Kaplan-Meier plots. There were 27 males and 49 females with a mean age of 29.7 ± 9.7 years. They were classified into World Health Organization functional class (WHO-FC)II (n = 28), class III (n = 45) and class IV (n = 3). Their baseline mean pulmonary artery pressure was (65 ± 16) mm Hg, pulmonary vascular resistance (1677 ± 669) dyn×s(-1)×cm(-5), pulmonary capillary wedge pressure (9.6 ± 5.0) mm Hg, mean right atrial pressure (9.8 ± 6.1) mm Hg, cardiac index (2.07 ± 0.57) L ×min(-1)× m(-2) and serum uric acid (391 ± 103) µmol/L. The correlation analysis indicated that the serum level of uric acid correlated positively with right ventricular diameter (r = 0.28, P = 0.018) and negatively with CI (r = -0.34, P = 0.003). Independent t-test results indicated that the patients with a higher level of uric acid were apt to have a worse WHO-FC, and the higher level uric acid group (serum uric acid > 416.5 µmol/L) had a relative higher level of WHO-FC, NT-proBNP and endothelin-1. A lower level of CI denoted more severe conditions and prognosis. Survival analysis indicated that the serum level of uric acid could strongly predict survival in IPAH patients with over time and those with a high level of uric acid had a worse prognosis. The serum level of uric acid correlates significantly with patient conditions and prognosis in IPAH. And a higher serum level of uric acid predicts worse conditions and prognosis.


Female gender and cardiovascular disease.
Despite a generalized belief that women are protected from cardiovascular disease, this remains the leading cause of death in women. This review focuses on differences in symptomatology, diagnostic modalities and therapeutic strategies in women with regard to cardiovascular disease.


Dental student attitudes towards communication skills instruction and clinical application.
This study investigated dental students' attitudes towards communication skills instruction and clinical application and explored the impact of a one-semester course and year in school on students' attitudes, measured by the Communication Skills Attitude Scale. Demographic characteristics and self-assessment of communication skills were also analyzed. The study employed a pretest-posttest survey design combined with cross-sectional data. Participants were first- and fourth-year students at a U.S. dental school. Out of a possible 120 students, 106 (fifty-seven D1 and forty-nine D4) participated in the pretest, an 88 percent response rate; out of a possible 121 students, 115 (fifty-seven D1 and fifty-eight D4) participated in the posttest, a 95 percent response rate. In the results, D4 students consistently demonstrated less positive attitudes towards communication skills instruction and more negative attitudes regarding the importance of interpersonal skills in clinical encounters than did their D1 counterparts. A single communications course had no discernible effect on attitudes or self-assessments for either cohort. Females reported more positive attitudes towards clinical application of interpersonal skills than did males. Gender significantly interacted with two demographic variables: primary language and parent as health care professional. Female children of health care professionals reported poorer attitudes towards clinical communication skills training and application than did their male counterparts. Generally, parental occupation in health care moderated the decrease in positive attitudes over time towards clinical usefulness of communication skills. The D4 students rated their communication skills higher than did the D1 students. Students who demonstrated more positive attitudes towards communication skills training and application were more likely to say their own skills needed improvement.


High cytoplasmic FOXO1 and pFOXO1 expression in astrocytomas are associated with worse surgical outcome.
FOXO1 is at a convergence point of receptor tyrosine kinase (RTK) signaling, which is one of the three core pathways implicated in glioblastoma. It was recently shown that FOXO1 can effectively induce glioma cell death and inhibit tumor growth through cell cycle arrest and apoptosis. We therefore evaluated FOXO1 and pFOXO1 protein expression in 181 primary astrocytoma samples and 16 normal brain samples. Astrocytoma samples expressed higher cytoplasmic FOXO1 and pFOXO1 than normal brain samples. Nuclear pFOXO1 level was significantly higher than nuclear FOXO1 in astrocytomas. High cytoplasmic FOXO1 expression was associated with older onset age (P = 0.001) and higher WHO grade (P = 0.001). The trend was also observed between cytoplasmic pFOXO1 expression and WHO grade although not significant. Univariate survival analysis showed that both high cytoplasmic FOXO1 and pFOXO1 expression indicated a significantly shorter median overall survival and progression-free survival. Multivariate survival analysis revealed cytoplasmic FOXO1 expression, cytoplasmic pFOXO1 expression, WHO grade, gender, extent of resection and radiotherapy to be independent prognostic factors for overall survival and progression-free survival. Thus, our data suggested that cytoplasmic FOXO1 and pFOXO1 expression may serve as valuable prognostic variables in astrocytomas and may have significant implications for the development and application of targeted therapy.


Women Convicted of Intimate Partner Homicide in Oromiya Regional State of Ethiopia: Profile and Associated Factors.
This study explored the factors associated with the engagement of women in intimate partner homicide (IPH) through 10 in-depth interviews with women incarcerated in three correction facilities in Oromiya Regional State of Ethiopia. In addition, key informant interviews and six focus groups involving traditional leaders, Kebele administrators, and community members help triangulate the findings. The study revealed insight into women's social, psychological, and economic status prior to their crime. Low levels of education and economic opportunity, forced marriage, marital dispute due to polygamy, spousal violence, and low levels of community support were associated with IPH. Implications for research, policy, and practice are discussed.


Differential diagnosis of nontraumatic intracranial hemorrhage.
Intracranial hemorrhage is a common initial symptom of intracranial vascular malformations. Although CT remains important in the acute setting, MR imaging has proved invaluable for diagnosis and characterization of intracranial hemorrhage. MR imaging of hemorrhage and the differential diagnosis of nontraumatic intracranial hemorrhage is presented in this article.


Mefenamic acid shows neuroprotective effects and improves cognitive impairment in in vitro and in vivo Alzheimer's disease models.
Nonsteroidal anti-inflammatory drugs (NSAIDs) exert anti-inflammatory, analgesic, and antipyretic activities and suppress prostaglandin synthesis by inhibiting cyclooxygenase, an enzyme that catalyzes the formation of prostaglandin precursors from arachidonic acid. Epidemiological observations indicate that the long-term treatment of patients suffering from rheumatoid arthritis with NSAIDs results in reduced risk and delayed onset of Alzheimer's disease. In this study, we investigated the therapeutic potential for Alzheimer's disease of mefenamic acid, a commonly used NSAID that is a cyclooxygenase-1 and 2 inhibitor with only moderate anti-inflammatory properties. We found that mefenamic acid attenuates the neurotoxicities induced by amyloid beta peptide (Abeta)(1-42) treatment and the expression of a Swedish double mutation (KM595/596NL) of amyloid precursor protein (Swe-APP) or the C-terminal fragments of APP (APP-CTs) in neuronal cells. We also show that mefenamic acid decreases the production of the free radical nitric oxide and reduces cytochrome c release from mitochondria induced by Abeta(1-42), Swe-APP, or APP-CTs in neuronal cells. In addition, mefenamic acid up-regulates expression of the antiapoptotic protein Bcl-X(L). Moreover, our study demonstrates for the first time that mefenamic acid improves learning and memory impairment in an Abeta(1-42)-infused Alzheimer's disease rat model. Taking these in vitro and in vivo results together, our study suggests that mefenamic acid could be used as a therapeutic agent in Alzheimer's disease.


Deposition of eosinophil granule major basic protein onto microfilariae of Onchocerca volvulus in the skin of patients treated with diethylcarbamazine.
We investigated the association between eosinophil degranulation, as evidenced by the deposition of granule major basic protein (MBP), and the killing of microfilariae of Onchocerca volvulus in vivo following treatment with diethylcarbamazine (DEC). Utilizing an immunofluorescence procedure for the cellular and extracellular localization of eosinophil MBP in formalin-fixed, paraffin-embedded tissues, we studied skin biopsies from onchocerciasis patients before and during treatment with topically or orally administered DEC. Before DEC, there was little or no inflammatory response in either dermis or epidermis and microfilariae were essentially intact. Immunofluorescent staining for MBP revealed some filamentous fluorescence associated with dermal collagen fibers, very few eosinophils, and no fluorescence in association with intact microfilariae. In contrast, during treatment with DEC, immunofluorescent staining for MBP revealed extensive eosinophil infiltrates in both dermis and epidermis with numerous intraepidermal eosinophil abscesses containing degenerating microfilariae. An intense extracellular immunofluorescence for MBP surrounded degenerating microfilariae in the dermis and epidermis in both the presence and absence of eosinophil infiltrates as early as 4.5 hours after starting therapy. Many intact nondegenerating microfilariae were also present, but they did not show immunofluorescent staining for MBP nor a surrounding inflammatory infiltrate. The results show that immediately following administration of DEC, eosinophils localize and degranulate around microfilariae in the skin and release granule MBP onto or in close proximity to the parasite's surface. Because of the striking association between eosinophil localization, degranulation, and deposition of MBP onto microfilarial surfaces, and the degeneration of microfilariae in the skin, these observations support the hypothesis that the eosinophil, through helminthotoxic granule proteins such as MBP, damages the microfilariae of O. volvulus.


[Comparative studies on the value of oscillography and venous occlusion plethysmography in the diagnosis of arterial occlusive diseases].
Oscillography and plethysmography in phlebembraxis also occupy an important place in the screening of arterial obstructive diseases. The two methods give reliable results. In patients who have--as was established by oscillography and clinical examination--healthy vessels, as well as in patients with arterial obstructive disease in stage II a good correspondence with the findings of plethysmography in phlebembraxis could be proved, if all the three measuring sizes (first flow, peak flow and peak flow time) were taken into consideration. Hereby the normal values given partly deviate from those ones given in literature. They are guide values which in the individual case may fall below or transgressed also in patients with healthy vessels, whereby the peak flow time is to be regarded as the most reliable measuring size. On account of the slight expenditure of time the plethysmography in phlebembraxis is suitable as screening method, however it is not sufficient as the only method for the angiological prediagnostics. It is a valuable supplementation to the hitherto known unbloody examination methods.


The relationship between psychosomatic factors and orthostatic dysregulation in young men.
We carried out a questionnaire survey regarding symptoms of orthostatic dysregulation and administered the Japanese Edition of the Cornell Medical Index-Health Questionnaire (JCMI) and the Yatabe-Guilford Personality Test (Y-G test) to 151 male medical students (mean age, 24.6 yr). Orthostatic dysregulation was identified in 19 (12.5%) of the subjects based on the questionnaire results. The percentage classed as types III (possible neurotic) and IV (probable neurotic) according to the health questionnaire was 47.3% in the 19 with orthostatic dysregulation and 8.9% in the controls (n = 78). The percentage classed as types B and E, suggestive of emotional or psychological disturbance according to the personality test, was 42.1% in those with orthostatic dysregulation and 8.9% in the controls. These differences were significant (P < 0.01). These results suggest that psychosomatic factors influence the occurrence of orthostatic dysregulation in young men.