Low-Dose Total Skin Electron Beam Therapy as Part of a Multimodality Regimen for Treatment of Sézary Syndrome: Clinical, Immunologic, and Molecular Analysis.
Sézary syndrome (SS) is an advanced form of cutaneous T-cell lymphoma with few long-term remissions observed. To profile 3 patients with SS who have experienced long-term remission following the addition of low-dose total skin electron beam therapy (TSEBT) to systemic regimens of extracorporeal photopheresis, bexarotene, and interferon-γ. This is a retrospective case series with additional investigations of patient-donated samples to assess therapeutic response. The study was conducted at the University of Pennsylvania Cutaneous Lymphoma Clinic and follows 3 patients with stage IVA1 CD4+ SS who presented to the clinic between November 1, 2009, and November 1, 2017, and who had a history of SS that was refractory to multimodality systemic therapy prior to receiving low-dose TSEBT. Patients were treated in a multimodality fashion with combined extracorporeal photopheresis, bexarotene, interferon-γ, and low-dose TSEBT. To characterize treatment responses in these patients, the extent of skin disease was measured with the modified severity weighted assessment tool. Blood disease was measured with flow cytometric assessments of Sézary cell count, CD4:CD8 ratio, and high throughput sequencing of the T-cell receptors. To assess for restoration of immune function, we measured markers of immune exhaustion, including PD-1 (programmed cell death 1), TIGIT (T-cell immunoreceptor with immunoglobulin and ITIM domains), CTLA4 (cytotoxic T-lymphocyte-associated protein 4), TOX (thymocyte selection-associated high mobility group box protein), and Foxp3 (forkhead box P3) on circulating CD4 and CD8 T cells, along with production capacity of interferon-γ by lymphocytes following activation stimuli. Following administration of low-dose TSEBT and maintenance of the other therapies, remissions ranged from 24 to 30 months, with complete responses in 2 patients ongoing. Markers of immune exhaustion including PD-1, TIGIT, CTLA4, TOX, and Foxp3 were significantly reduced from baseline following TSEBT, along with enhanced production capacity of interferon-γ by lymphocytes following activation stimuli. High throughput sequencing demonstrated near-complete eradication of the circulating clone among 2 of 3 patients with stable levels in 1. We describe 3 patients who achieved long-term clinical and molecular remissions following low-dose TSEBT as part of a multimodality regimen for treatment of SS. As long-term remissions in SS are uncommon, this approach demonstrates promise, and clinical trials should be considered.


The brain development and behaviour of autistic children. Notes on the research situation.
The relationships between brain functions and behaviour characteristics during various phases of the development of autistic children were looked into. In doing so, the concept of stability on the one hand as well as change on the other hand is the main topic and is illustrated with examples. The state of neuroscientific ideas and methodical possibilities on the theme is not only broached but also discussed in connection with the treatment (in the sense of an optimal coordination between brain and environment). It thus results that the connections between genetical disposition, brain development, environmental influences and behaviour in autistic children become more and more clear. Utilizing this, though, better treatment possibilities can only be expected on the basis of integrating bio-psychosocial research which emphasizes the development aspect.


Total parenteral nutrition and home parenteral nutrition: an effective combination to sustain malnourished children with cancer.
A patient with Wilms' tumor and severe failure to thrive required total parenteral nutrition (TPN) for "catch-up" growth. This case underscores how TPN might be useful in the management of a child with cancer. Cancer cachexia, chemotherapy, radiation, and infections caused by immune suppression can lead to potentially serious macro- and micronutrient deficiencies.


Neuropsychiatric effects of cocaine use disorders.
Individuals who use cocaine report a variety of neuropsychiatric symptoms that are yet to be adequately targeted with treatment modalities. To address this problem requires an understanding of these symptoms and their neurobiological origins. Our paper reviewed the existing data on the neuropsychiatic implications of cocaine. We conducted a Medline search from 1984-2004 using terms, such as "cocaine", "cocaine addiction", "cocaine abuse", "cocaine neuropsychiatry" and "dual diagnosis". The search produced additional reference materials that were used in this review, although we focused on data that have likely clinical implications. The literature evidence suggested that, whereas acute cocaine overdose is potentially fatal, the ingestion of mild-to-moderate doses could result in fatal or nonfatal neuropsychiatric events. Also, chronic cocaine use may be associated with deficits in neurocognition, brain perfusion and brain activation patterns. Some of these deficits were unresolved with periods of abstinence ranging from 3-200 days. Taken together, these studies suggest the need for further investigations to fully characterize the neurobiological substrates of cocaine use disorders (CUDs) with the future possibility of more efficient treatment modalities.


A Review of the Gumbel-max Trick and its Extensions for Discrete Stochasticity in Machine Learning.
The Gumbel-max trick is a method to draw a sample from a categorical distribution, given by its unnormalized (log-)probabilities. Over the past years, the machine learning community has proposed several extensions of this trick to facilitate, e.g., drawing multiple samples, sampling from structured domains, or gradient estimation for error backpropagation in neural network optimization. The goal of this survey article is to present background about the Gumbel-max trick, and to provide a structured overview of its extensions to ease algorithm selection. Moreover, it presents a comprehensive outline of (machine learning) literature in which Gumbel-based algorithms have been leveraged, reviews commonly-made design choices, and sketches a future perspective.


Molecular Characteristics of Regional Chromoblastomycosis in Guangdong, China: Epidemiological, Clinical, Antifungal Susceptibility, and Serum Cytokine Profiles of 45 Cases.
Chromoblastomycosis (CBM) is a chronic disease caused by several species of dematiaceous fungi. In this study, a regional collection of 45 CBM cases was conducted in Guangdong, China, a hyper-endemic area of CBM. Epidemiology findings indicated that the mean age of cases was 61.38 ± 11.20 years, long duration ranged from 3 months to 30 years, and the gender ratio of male to female was 4.6:1. Thirteen cases (29%) declared underlying diseases. Verrucous form was the most common clinical manifestation (n = 19, 42%). Forty-five corresponding clinical strains were isolated, and 28 of them (62%) were identified as F. monophora; the remaining 17 (38%) were identified as F. nubica through ITS rDNA sequence analysis. Antifungal susceptibility tests in vitro showed low MICs in azoles (PCZ 0.015-0.25 μg/ml, VCZ 0.015-0.5 μg/ml, and ITZ 0.03-0.5 μg/ml) and TRB (0.015-1 μg/ml). Itraconazole combined with terbinafine was the main therapeutic strategy used for 31 of 45 cases, and 68% (n = 21) of them improved or were cured. Cytokine profile assays indicated upregulation of IL-4, IL-7, IL-15, IL-11, and IL-17, while downregulation of IL-1RA, MIP-1β, IL-8, and IL-16 compared to healthy donors (p < 0.05). The abnormal cytokine profiles indicated impaired immune response to eliminate fungus in CBM cases, which probably contributed to the chronic duration of this disease. In conclusion, we investigated the molecular epidemiological, clinical, and laboratory characteristics of CBM in Guangdong, China, which may assist further clinical therapy, as well as fundamental pathogenesis studies of CBM.


Pyridazine N-Oxides as Photoactivatable Surrogates for Reactive Oxygen Species.
A method for the photoinduced evolution of atomic oxygen from pyridazine N-oxides was developed. This underexplored oxygen allotrope mediates arene C-H oxidation within complex, polyfunctional molecules. A water-soluble pyridazine N-oxide was also developed and shown to promote photoinduced DNA cleavage in aqueous solution. Taken together, these studies highlight the utility of pyridazine N-oxides as photoactivatable O(3P) precursors for applications in organic synthesis and chemical biology.


Mitigating Silica Fouling and Improving PPCP Removal by Modified NF90 Using In Situ Radical Graft Polymerization.
This study in-situ modified a commercial nanofiltration membrane, NF90, through the concentration-polymerization-enhanced radical graft polarization method by applying two agents of 3-sulfopropyl methacrylate potassium salt (SPM) and 2-hydroxyethyl methacrylate (HEMA) with different dosages. Surface characterization revealed that the modified membranes became rougher and more hydrophilic compared with the pristine membrane. The modified membranes exhibited considerably enhanced separation performance with 5.8-19.6% higher NaCl rejection and 17.2-19.9% higher pharmaceuticals and personal care products (PPCPs) rejection than the pristine membrane. When treating the feedwater with high silica concentration, the modified membranes exhibited relatively less flux decline with high percentage of reversible fouling, especially the ones modified using a lower monomer concentration (0.01 M SPM and 0.01 M HEMA). Moreover, membrane modification enhanced the PPCP rejection (1.3-5.4%) after silica fouling by mitigating foulant deposition on the membrane surface. The fouling mechanism was confirmed to be intermediate blocking of membrane pores. Therefore, the in-situ modification technique with a low monomer concentration proved to be effective for mitigating silica fouling and improving PPCP rejection, which can be easily performed and cost-effective in practical application.


Perceptions of a tattooed college instructor.
128 undergraduates' perceptions of tattoos on a model described as a college instructor were assessed. They viewed one of four photographs of a tattooed or nontattooed female model. Students rated her on nine teaching-related characteristics. Analyses indicated that the presence of tattoos was associated with some positive changes in ratings: students' motivation, being imaginative about assignments, and how likely students were to recommend her as an instructor.


Respiratory syncytial virus. II. Isolation and morphology of the glycoproteins.
Treatment of respiratory syncytial (RS) virus with Triton X-100 in solutions of low ionic strength solubilized not only glycoproteins but also some non-glycosylated proteins. Rate zonal sedimentation of the solubilized materials resulted in separation of the glycoproteins from the other components, i.e. one fraction predominantly composed of two glycoproteins each with molecular weight (mol. wt.) of approximately 100,000 and 53,000 was obtained. Electron microscopic observation of this fraction revealed numerous club- or rod-shaped fine structures, suggesting that these were spikes of RS virus. After removal of Triton X-100 the structures aggregated and formed oligomers and polymers.


Differential regulation of MMP-13 expression in two models of experimentally induced periodontal disease in rats.
Evaluate expression of MMP-13 during the course of two models experimentally induced periodontal disease in rats. Expression of MMP-13 at mRNA and protein levels was studied, respectively, by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Two experimental models were used: LPS injections and ligature placement. 30mug of LPS from Eschericia coli was injected twice a week into the palatal aspect of upper molars. Ligatures were placed at the gingival margin around lower first molars. Controls received injections of PBS vehicle and no ligatures on lower molars. Samples were collected 5, 15 and 30 days after initiation of periodontal disease and processed for extraction of total RNA, total protein, and routinely processed for histology. Both experimental models produced a significant increase on the inflammatory infiltrate that paralleled elevated levels of MMP-13 mRNA and protein at 5 and 15 days. The LPS model was associated with a sustained level of inflammation and increased MMP-13 mRNA throughout the 30 days, whereas the ligature model showed a decrease on the severity of inflammation and MMP-13 mRNA at the 30-day period. Interestingly, MMP-13 protein levels were diametrically contrary to the mRNA levels. MMP-13 expression during LPS- and ligature-induced experimental periodontal disease follows the increase on severity of inflammation at the earliest periods. At 30 days, there is a decrease on the severity of inflammation on the ligature model associated with decreased MMP-13 mRNA. There is a lack of transcription-translation coupling of MMP-13 gene in both experimental models.


Job satisfaction of maternity care providers in the Netherlands: Does working in or with a birth centre influence job satisfaction?
In the Netherlands birth centres have recently become an alternative option as places where women with uncomplicated pregnancies can give birth. This article focusses on the job satisfaction of three groups of maternity care providers (community midwives, clinical care providers and maternity care assistants) working in or with a birth centre compared to those working only in a hospital or at home. In 2015, an existing questionnaire was adapted and distributed to maternity care providers and 4073 responses were received. Using factor analyses, two composite measures were constructed, a Composite Job Satisfaction scale and an Assessment-of-Working-in-or-with-a-Birth-Centre scale. Differences between groups were tested with Student's t-test and MANOVA with post hoc test and linear regression analyses. The overall score on the Composite Job Satisfaction scale did not differ between community midwives or clinical care providers working in or with a birth centre and those working in a different setting. For maternity care assistants there was a small but significantly higher score for those not working in a birth centre. Maternity care assistants' overall job satisfaction score was higher than that of both other groups. In a linear regression analysis working or not working in or with a birth centre was related to the overall job satisfaction score, but repeated for the three professional groups separately, this relation was only found for maternity care assistants. Job satisfaction is generally high, but, except for maternity care assistants, not related to the setting (working or not working in or with a birth centre).


Effects of multiphase transitions and reactive extrusion on in situ thermoplasticization/succination of cassava starch.
In this work, the effects of the multiphase transitions of starch, the screw configuration, and the conditions of reactive extrusion (REX) on the in situ thermoplasticization/succination of cassava starch were studied. Spectroscopic analyses indicated successful esterification during the REX with the appearance of characteristic bands of carbonyl ester groups. After the REX, the starch developed B- and V-type structures, with the OSA starches showing an additional peak at 7.1°. As the degree of substitution increased, a greater number of partially gelatinized granules were embedded in the starch matrix; an additional degradation temperature of 364.5 °C and a lower weight loss at the degradation temperature of the starch were observed. The incorporation of OS groups via REX imparts better thermal stability. The processing conditions helped prepare a thermoplastic-succinate starch in a single step through an environmentally friendly process.


[Telangiectatic osteosarcoma--a case report].
Telangiectatic osteosarcoma, being a subtype of osteosarcoma, is rare. In this paper, one case is reported. The patient, a sixteen year old man, was admitted into our hospital in 1983 because of swelling and pain in the left knee for 3 months. On physical examination, a mass, 7 x 5 x 5 cm in size, was found in the distal end of the left thigh. A misdiagnosis of hemangioma of the bone was made by puncture biopsy before operation. After three months, the disease progressed and amputation had to be performed. The pathological diagnosis of telangiectatic osteosarcoma was established after operation. Finally, clinical and roentgenographic manifestations, histological and ultrastructural findings, biologic behavior, diagnosis and differential diagnosis are discussed. In particular, the differentiation from aneurysmal bony cyst and hemangioma of the bone is emphasized.


[The ocular manifestations of human immunodeficiency virus and syphilis coinfection].
Objective: To investigate the ocular manifestations of human immunodeficiency virus (HIV) and syphilis coinfection. Methods: A retrospective analysis of the ocular manifestations was carried out in 27 patients (54 eyes) diagnosed as syphilis and HIV coinfection by the Department of Infectious Medicine in Peking Union Medical College Hospital during the years of 2006-2017. The research included 26 males and 1 female, aging from 24 to 76 years old, with a mean age of 40.40±12.94 years old. Ocular anterior segments were examined with slit-lamp microscope. Fundus examinations were conducted with papillary dilation, fundus photography. Results: At the first visit, there were 2 eyes without light perception, 4 eyes with light perception, 1 eye with hand movement, 1 eye with finger counting, 2 eyes with 0.01-0.09 eyesight, 8 eyes with 0.1-0.2 eyesight, 12 eyes with 0.25-0.4 eyesight, 15 eyes with 0.5-0.9 eyesight, 9 eyes with 1.0-1.5 eyesight. Among the 27 patients (54 eyes) coinfected with HIV and syphilis, keratic precipitates were identified in 20 eyes, aqueous flare positive in 20 eyes, float positive in 15 eyes, and iris posterior synechias in 7 eyes. Nineteen eyes were diagnosed as syphilis uveitis, including 2 eyes with syphilis anterior uveitis and 17 eyes with syphilis panuveitis, among which, vitreous inflammatory opacity was observed in all 19 eyes, disk atrophy in 2 eyes, optic edema in 1 eye, vitreous hemorrhage in 1 eye, retinal detachment in 2 eyes, retinal hemorrhage and white vein in 1 eye. In addition, 8 eyes were diagnosed as HIV retinopathy, all manifested as cotton-wool spot. Among the 8 eyes, 4 were diagnosed as cytomegalovirus retinitis, 3 showed retinal yellow-white lesions, and 1 was in late phase which showed retinal pigmentation. The incidence of both HIV and syphilis coinfection patients and male homosexuality population increased. The most common ocular manifestation of HIV and syphilis coinfection was syphilis panuveitis. Six patients first visited the Department of Ophthalmology, and were then diagnosed as HIV and syphilis coinfection. Conclusions: The ocular manifestations of HIV and syphilis coinfection are diversified, which can be manifested as fundus necrotic lesions as well as anterior and posterior inflammatory. For HIV positive patients, syphilis serologic test should be routinely performed. The same, syphilis positive patients should be tested for HIV serum antibodies, in order to improve the diagnosis level of HIV/syphilis coinfection and give timely etiological treatment, which is of vital importance for saving visual acuity. (Chin J Ophthalmol, 2019, 55:267-272).


Voltage-gated potassium channels: regulation by accessory subunits.
Voltage-gated potassium channels regulate cell membrane potential and excitability in neurons and other cell types. A precise control of neuronal action potential patterns underlies the basic functioning of the central and peripheral nervous system. This control relies on the adaptability of potassium channel activities. The functional diversity of potassium currents, however, far exceeds the considerable molecular diversity of this class of genes. Potassium current diversity contributes to the specificity of neuronal firing patterns and may be achieved by regulated transcription, RNA splicing, and posttranslational modifications. Another mechanism for regulation of potassium channel activity is through association with interacting proteins and accessory subunits. Here the authors highlight recent work that addresses this growing area of exploration and discuss areas of future investigation.


The impact of non-alcoholic fatty liver disease on incident type 2 diabetes mellitus in non-overweight individuals.
The aim of this study was to evaluate the impact of non-alcoholic fatty liver disease (NAFLD) on incident type 2 diabetes mellitus (T2DM) in non-overweight individuals with NAFLD. A population-based retrospective cohort study of 4629 participants who were enrolled in a health check-up programme for more than 10 years. A standardized questionnaire and abdominal ultrasonography were used to diagnose NAFLD. A cut-off point of BMI 23 kg/m(2) was used to define overweight (≥23.0 kg/m(2)) or non-overweight (<23.0 kg/m(2)). The primary outcome was incident T2DM. Over a mean follow-up of 12.8 years, 351 participants (7.6%) developed T2DM. The incidence rate of T2DM was 3.2% in the non-overweight without NAFLD group, 14.4% in the non-overweight with NAFLD group, 8.0% in the overweight without NAFLD group and 26.4% in the overweight with NAFLD group. The adjusted hazard ratios for incident T2DM compared with the non-overweight without NAFLD group were as follows: 3.59 (95% CI: 2.14-5.76) in the non-overweight with NAFLD group, 1.99 (95% CI: 1.47-2.69) in the overweight without NAFLD group and 6.77 (95% CI: 5.17-8.91) in the overweight with NAFLD group. The adjusted hazard ratio in the non-overweight with NAFLD group was significantly higher than that in the overweight without NAFLD group or that in the non-overweight without NAFLD group. Non-overweight individuals with NAFLD had a high risk of incident T2DM. Diagnosis of NAFLD is important in non-overweight individuals, and therefore it might be necessary to follow their health conditions on a long-term basis after detection of NAFLD.


Deep Learning-Based Chest CT Image Features in Diagnosis of Lung Cancer.
This study was to evaluate the diagnostic value of deep learning-optimized chest CT in the patients with lung cancer. 90 patients who were diagnosed with lung cancer by surgery or puncture in hospital were selected as the research subjects. The Mask Region Convolutional Neural Network (Mask-RCNN) model was a typical end-to-end image segmentation model, and Dual Path Network (DPN) was used in nodule detection. The results showed that the accuracy of DPN algorithm model in detecting lung lesions in lung cancer patients was 88.74%, the accuracy of CT diagnosis of lung cancer was 88.37%, the sensitivity was 82.91%, and the specificity was 87.43%. Deep learning-based CT examination combined with serum tumor detection, factoring into Neurospecific enolase (N S E), cytokeratin 19 fragment (CYFRA21), Carcinoembryonic antigen (CEA), and squamous cell carcinoma (SCC) antigen, improved the accuracy to 97.94%, the sensitivity to 98.12%, and the specificity to 100%, all showing significant differences (P < 0.05). In conclusion, this study provides a scientific basis for improving the diagnostic efficiency of CT imaging in lung cancer and theoretical support for subsequent lung cancer diagnosis and treatment.


[Application of fuzzy mathematics on modifying taste of oral solution of traditional Chinese drug].
To apply Fuzzy mathematical methods to choose the best taste modifying prescription of oral solution of traditional Chinese drug. Jin-Fukang oral solution was used as a model drug. The oral solution was prepared in different taste modifying prescriptions, whose tastes were evaluated by the fuzzy quality synthetic evaluation system. Compound-sweeteners with Sucralose and Erythritol was the best choice. Fuzzy integrated evaluation can be used to evaluate the taste of traditional Chinese medicinal pharmaceuticals, which overcame the artificial factors and achieve more objective conclusion.


Socioeconomic Equity in the Receipt of In-Hospital Care and Outcomes in Australian Acute Coronary Syndrome Patients: The CONCORDANCE Registry.
Socioeconomic status (SES) is a social determinant of both health and receipt of health care services, but its impact is under-studied in acute coronary syndrome (ACS). The aim of this study was to examine the influence of SES on in-hospital care, and clinical events for patients presenting with an ACS to public hospitals in Australia. Data from 9064 ACS patient records were collected from 41 public hospitals nationwide from 2009 as part of the Cooperative National Registry of Acute Coronary Syndrome Care (CONCORDANCE) registry. For this analysis, we divided the cohort into four socioeconomic groups (based on postcode of usual residence) and compared the in-hospital care provided and clinical outcomes before and after adjustment for both patient clinical characteristics and hospital clustering. Patients were divided into four SES groups (from the most to the least disadvantaged: 2042 (23%) vs. 2104 (23%) vs. 1994 (22%) vs. 2968 (32%)). Following adjustments for patient characteristics, there were no differences in the odds of receiving coronary angiogram, revascularisation, prescription of recommended medication, or referral to cardiac rehabilitation across the SES groups (p=0.06, 0.69, 0.89 and 0.79, respectively). After adjustment for clinical characteristics, no associations were observed for in-hospital and cumulative death (p=0.62 and p=0.71, respectively). However, the most disadvantaged group were 37% more likely to have a major adverse cardiovascular event (MACE) than the least disadvantaged group (OR (95% CI): 1.37 (1.1, 1.71), p=0.02) driven by incidence of in-hospital heart failure. Although there may be gaps in the delivery of care, this delivery of care does not differ by patient's SES. It is an encouraging affirmation that all patients in Australian public hospitals receive equal in-hospital care, and the likelihood of death is comparable between the SES groups.


Mild copper-catalyzed vinylation reactions of azoles and phenols with vinyl bromides.
An efficient and straightforward copper-catalyzed method allowing vinylation of N- or O-nucleophiles with di- or trisubstituted vinyl bromides is reported. The procedure is applicable to a broad range of substrates since N-vinylation of mono-, di-, and triazoles as well as O-vinylation of phenol derivatives can be performed with catalytic amounts of copper iodide and inexpensive nitrogen ligands 3 or 8. In the case of more hindered vinyl bromides, the use of the original bidentate chelator 8 was shown to be more efficient to promote the coupling reactions than our key tetradentate ligand 3. The corresponding N-(1-alkenyl)azoles and alkenyl aryl ethers are obtained in high yields and selectivities under very mild temperature conditions (35-110 degrees C for N-vinylation reactions and 50-80 degrees C for O-vinylation reactions). Moreover, to our knowledge, this method is the first example of a copper-catalyzed vinylation of various azoles. Finally, this protocol, practical on a laboratory scale and easily adaptable to an industrial scale, is very competitive compared to the existing methods that allow the synthesis of such compounds.


Adequacy of management and severity of asthma in children attending a summer camp.
To assess the adequacy of therapy in asthma, 46 children with asthma attending a summer camp were asked to complete a questionnaire about their symptoms and the treatment that they had received. Each child's height, weight, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were measured. According to defined criteria of symptom severity the children were categorized as suffering from severe (48%) or mild (52%) asthma. The mean FEV1/FVC ratio (P less than 0.05) and the mean FEV1 were lower (P less than 0.02) in the children with severe asthma compared with those with mild asthma. In the group with severe asthma, 68% of the children were considered to be receiving suboptimal therapy; 45% had never had their FEV1 or FVC measured. Among those who were receiving suboptimal therapy, 40% had measurable airflow obstruction compared with 17% of children with mild asthma. Because poor management of asthma remains common in children, the need to make doctors and parents aware of the fact that suboptimal therapy may contribute significantly to the morbidity of the condition is emphasized.


Elemental Mass Spectrometry for Absolute Intact Protein Quantification without Protein-Specific Standards: Application to Snake Venomics.
Absolute protein quantification methods based on molecular mass spectrometry usually require stable isotope-labeled analogous standards for each target protein or peptide under study, which in turn must be certified using natural standards. In this work, we report a direct and accurate methodology based on capLC-ICP-QQQ and online isotope dilution analysis for the absolute and sensitive quantification of intact proteins. The combination of the postcolumn addition of 34S and a generic S-containing internal standard spiked to the sample provides full compound independent detector response and thus protein quantification without the need for specific standards. Quantitative recoveries, using a chromatographic core-shell C4 column for the various protein species assayed were obtained (96-100%). Thus, the proposed strategy enables the accurate quantification of proteins even if no specific standards are available for them. In addition, to the best of our knowledge, we obtained the lowest detection limits reported in the quantitative analysis of intact proteins by direct measurement of sulfur with ICPMS (358 fmol) and protein (ranging from 7 to 15 fmol depending on the assayed protein). The quantitative results for individual and simple mixtures of model proteins were statistically indistinguishable from the manufacturer's values. Finally, the suitability of the strategy for real sample analysis (including quantitative protein recovery from the column) was illustrated for the individual absolute quantification of the proteins and whole protein content in a venom sample. Parallel capLC-ESI-QTOF analysis was employed to identify the proteins, a prerequisite to translate the mass of quantified S for each chromatographic peak into individual protein mass.


Therapeutic Management of Ocular Ischemia in Takayasu's Arteritis: A Case-Based Systematic Review.
Takayasu's arteritis (TA) is a rare, chronic granulomatous large-vessel vasculitis that can lead to ocular ischemia. Ocular outcomes after therapeutic management in TA remain largely unknown. We herein conduct a case-based systematic review to address the current treatment options in this particular cohort. PubMed, Medline, and EMBASE databases were searched pertaining to ocular outcomes after systemic treatment in TA. Studies reporting ocular examinations before and after treatment in TA patients with ocular ischemia were included. Clinical characteristics, therapies, ocular outcomes, and complications were recorded. A 29-year-old woman with newly diagnosed TA showed dramatic regression of Takayasu's retinopathy (TR) following balloon angioplasty. Optical coherence tomography angiography (OCTA) was used as a novel strategy for subsequent follow-up. A total of 117 eyes of 66 patients with a median age of 27 years were included for systematic review. TR was the most common ocular manifestation. Oral steroids were prescribed in nearly all patients (n = 65), followed by the use of methotrexate and antiplatelet therapy. Of the patients, 65.8% and 34.2% underwent open surgery and endovascular procedure, respectively. The median follow-up period was 12 weeks (interquartile range 8-33.5). Surgical therapy showed better ocular improvement (including visual and imaging responses) in both acute and chronic vision loss, along with fewer complications than medical therapy alone. In the surgical group, the visual prognosis was significantly better in patients with initial visual acuity better than 20/200 (p = 0.03) and those who underwent surgery before stage III TR (p = 0.01). Ocular outcomes were equivalent in the two surgical approaches. Clinicians should be familiar with ophthalmic manifestations of this potentially treatable complication in TA. Compared with medical therapy alone, surgical intervention might be a better choice for both acute and chronic vision loss. Surgery is best recommended before the onset of irreversible ischemia to the globe. A combined regimen (oral steroids, immunosuppressants, and antiplatelet drugs) might be effective for those with surgical contradictions or reluctance to an invasive procedure. Physicians should be aware of the importance of ocular examinations, including OCTA, during the diagnosis and follow-up in TA.


Application of 3D Printing in Implantable Medical Devices.
3D printing technology is widely used in the field of implantable medical device in recent decades because of its advantages in high precision, complex structure, and high material utilization. Based on the characteristics of 3D printing technology, this paper reviews the manufacturing process, materials, and some typical products of 3D printing implantable medical devices and analyzes and summarizes the development trend of 3D printed implantable medical devices.


Clinical significance of the muscle-retracting sign during colorectal endoscopic submucosal dissection.
During colorectal endoscopic submucosal dissection (ESD), the feature of a muscle layer being pulled toward a neoplastic tumor is sometimes detected. We call this feature the muscle-retracting sign (MR sign). The aim of this study was to evaluate whether the MR sign is associated with particular types of neoplastic lesions and whether it has any clinical significance for ESD sessions. A total of 329 patients underwent ESD for 357 colorectal neoplasms. The frequency of positivity for the MR sign was evaluated in different morphologic and histopathologic types of neoplasm. The success rate of complete resection and the incidence of complications were also evaluated according to whether lesions were positive or negative for the MR sign. The rates of positivity for the MR sign in the various lesion types were as follows: laterally spreading tumor - granular nodular mixed type (LST-G-M), 9.6 %; laterally spreading tumor - granular homogeneous type (LST-G-H) and laterally spreading tumor - nongranular type (LST-NG), 0 %; sessile type, 41.2 %. The resection rate was 100 % (329 /329) in lesions negative for the MR sign; however, it was 64.3 % (18 /28) in lesions positive for the MR sign, which was significantly lower (P < 0.001). The MR sign was present only in some protruding lesions, and more importantly, it was associated with a high risk of incomplete tumor removal by ESD. Our data indicate that lesions positive for the MR sign lesions should be dissected with great caution; alternatively, based on the features of the individual case, a switch to surgery should be considered for the benefit of the patient.


Antioxidant protection against PCB-mediated endothelial cell activation.
Certain environmental contaminants such as polyhalogenated aromatic hydrocarbons may be implicated in diseases of the vasculature by compromising normal functions of vascular endothelial cells. We have shown previously that 3,3',4,4'-tetrachlorobiphenyl (PCB 77), an aryl hydrocarbon (Ah) receptor agonist, can cause disruption of endothelial barrier function. This was supported by an increase in oxidative stress as measured by enhanced 2',7'-dichlorofluorescein (DCF) fluorescence and activation of the oxidative stress-sensitive transcription factor NF-kappaB. We have now tested the protective effects of antioxidants vitamin E (alpha-tocopherol) and pyrrolidine dithiocarbamate (PDTC) on endothelial cell activation induced by PCB 77. Only vitamin E completely blocked PCB 77-mediated endothelial barrier dysfunction. This protective effect by vitamin E was associated with a decrease in both oxidative stress, as measured by DCF fluorescence, as well as in NF-kappaB activation. Furthermore, vitamin E decreased PCB 77-mediated production of the inflammatory cytokine IL-6. Although pretreatment of endothelial cells with PDTC prevented the induction of NF-kappaB by PCB 77, this inhibition was not associated with a decrease in DCF levels or protection against endothelial barrier dysfunction. Pretreatment with alpha-naphthoflavone (alpha-NF), an Ah receptor partial antagonist and specific inhibitor of cytochrome P450 1A, partially protected against PCB 77-induced endothelial barrier dysfunction. This observation was paralleled by the fact that alpha-NF did not fully antagonize the PCB-induced increase in DCF in endothelial cells. Furthermore, PCB-mediated induction of NF-kappaB and production of IL-6 were only partially blocked by alpha-NF. Of all the tested compounds (vitamin E, PDTC and alpha-NF), vitamin E was most potent in blocking PCB 77-mediated endothelial cell activation. These data give an insight into the potential use of vitamin E and related antioxidants to limit PCB-mediated cell injury and into the use of alpha-NF to explore mechanisms underlying the injurious potential of Ah receptor agonists.


The Effect of the acetone extract of Arctotis arctotoides (Asteraceae) on the growth and ultrastructure of some opportunistic fungi associated with HIV/AIDS.
In this study, the effect of the acetone extract of Arctotis arctotoides (L.f.) O. Hoffm. (Asteraceae) on the growth and ultrastructure of some opportunistic fungi associated with HIV/AIDS was analyzed by means of scanning electron microscope (SEM). Remarkable morphological alterations in the fungal mycelia which were attributed to the loss of cell wall strength ranged from loss of turgidity and uniformity, collapse of entire hyphae to evident destruction of the hyphae. The elements responsible for giving the fungi their characteristic virulence were detected and quantified by energy dispersive X-ray microanalysis techniques. X-ray microanalysis showed the specific spectra of sodium, potassium and sulfur as the principal intersection of the four pathogenic fungi studied. Since these ions have the potential of fostering fungal invasion by altering the permeability of hosts' membranes, their presence was considered inherent to the pathogenicity of the opportunistic fungi. Hence, these findings indicate the potential of the crude extract of A. arctotoides in preventing fungal invasion and subsequent infection of host's membranes.


Panel of genes transcriptionally up-regulated in squamous cell carcinoma of the cervix identified by representational difference analysis, confirmed by macroarray, and validated by real-time quantitative reverse transcription-PCR.
The Pap smear is currently the most widely used method of screening for squamous cell carcinoma of the cervix (SCCC). Because it is based on cell morphology, it is subject to variability in interpretation. Sensitive molecular markers capable of differentiating cancerous samples from noncancerous ones would be beneficial in this regard. We performed representational difference analysis (RDA) using paired, noncancerous (normal) and cancerous (disease) tissues taken from the same specimen obtained from a single patient with a confirmed diagnosis of SCCC. Linearly amplified cDNA from normal and diseased tissues of the original patient and seven others were hybridized to DNA macroarrays containing the candidate gene transcript fragments. Real-time quantitative reverse transcription-PCR was used to validate the macroarray results. RDA identified a candidate pool of 65 transcript fragments up-regulated in diseased tissue compared with normal tissue. Forty-one transcripts were found to be up-regulated in diseased compared with normal tissue in at least one half the patients by macroarray hybridization. Eleven of those genes were selected for real-time quantitative reverse transcription-PCR analysis, and all were confirmed as transcriptionally up-regulated in cancer compared with normal tissue in at least one half the patients. RDA using tissues from a single patient identified gene fragments confirmed to be transcriptionally up-regulated in SCCC both in the original patient and in seven others. The confirmed genes have a variety of functions and also have the potential to serve as diagnostic or prognostic markers.


Blood Transfusion Management for Patients Treated With Anti-CD38 Monoclonal Antibodies.
Daratumumab has proven to be highly efficacious for relapsed and refractory multiple myeloma (MM) and has recently been approved in the frontline setting for MM patients ineligible for transplantation. In the future, expanded indications are possible for daratumumab and other anti-CD38 monoclonal antibodies in development. For several years, it has been recognized that these therapies interfere with blood bank testing by binding to CD38 on red blood cells and causing panagglutination on the Indirect Antiglobulin Test. This can lead to redundant testing and significant delays in patient care. Given the anticipated increase in utilization of anti-CD38 monoclonal antibodies, as well as the transfusion needs of MM patients, it is critical to understand the nature of this interference with blood bank testing and to optimize clinical and laboratory procedures. In this review, we summarize the pathophysiology of this phenomenon, examine the clinical data reported to date, describe currently available methods to resolve this issue, and lastly provide a guide to clinical management of blood transfusions for patients receiving anti-CD38 monoclonal antibodies.


Expression Profiles of Long Noncoding RNA in UVA-Induced Human Skin Fibroblasts.
Long noncoding RNA (lncRNA) are differentially expressed across stages of differentiation and development, but the role of lncRNA in human skin photoaging mechanisms remains poorly understood. This study aimed to determine lncRNA expression changes in human dermal fibroblasts (HDF) induced by repeated UVA irradiation and to explore correlations between lncRNA and skin photoaging prognosis. In the UVA-HDF group, HDF were subjected to repeated UVA irradiation (10 J/cm2 UVA twice daily for 7 days); in the control group, HDF received no irradiation. High-throughput sequencing was used to detect lncRNA expression profiles. Functional annotation analysis and pathway enrichment were preformed via Gene Ontology and KEGG. Predicted lncRNA target genes were identified by bioinformatic analysis. In the UVA-HDF group, 1,730 lncRNA exhibited over 2-fold expression changes compared with the control group: 1,494 were upregulated, and 236 downregulated. Predicted lncRNA targets were associated with matrix metalloproteinases, cathepsin D, mitogen-activated protein kinase and TGF-β signaling pathways, and collagen fiber metabolism following repeated UVA damaging mechanisms. lncRNA profiles were aberrantly expressed in UVA-HDF and might play a key role in skin photoaging. This study provides novel insights into the repeated UVA-damaging pathology and potential targets for treatment of human skin photoaging.


A comparison of prediction models for fractures in older women: is more better?
A Web-based risk assessment tool (FRAX) using clinical risk factors with and without femoral neck bone mineral density (BMD) has been incorporated into clinical guidelines regarding treatment to prevent fractures. However, it is uncertain whether prediction with FRAX models is superior to that based on parsimonious models. We conducted a prospective cohort study in 6252 women 65 years or older to compare the value of FRAX models that include BMD with that of parsimonious models based on age and BMD alone for prediction of fractures. We also compared FRAX models without BMD with simple models based on age and fracture history alone. Fractures (hip, major osteoporotic [hip, clinical vertebral, wrist, or humerus], and any clinical fracture) were ascertained during 10 years of follow-up. Area under the curve (AUC) statistics from receiver operating characteristic curve analysis were compared between FRAX models and simple models. The AUC comparisons showed no differences between FRAX models with BMD and simple models with age and BMD alone in discriminating hip (AUC, 0.75 for the FRAX model and 0.76 for the simple model; P = .26), major osteoporotic (AUC, 0.68 for the FRAX model and 0.69 for the simple model; P = .51), and clinical fracture (AUC, 0.64 for the FRAX model and 0.63 for the simple model; P = .16). Similarly, performance of parsimonious models containing age and fracture history alone was nearly identical to that of FRAX models without BMD. The proportion of women in each quartile of predicted risk who actually experienced a fracture outcome did not differ between FRAX and simple models (P > or = .16). Simple models based on age and BMD alone or age and fracture history alone predicted 10-year risk of hip, major osteoporotic, and clinical fracture as well as more complex FRAX models.


The relationship between ethical climate at work and job satisfaction among nurses in Tehran.
This study aimed to provide an understanding of the relationship between the ethical climate at the workplace and job satisfaction among nurses. 210 nurses working in selected wards in the Tehran University of Medical Sciences were asked to fill out questionnaires on their work environment and level of job satisfaction. The data collection tools included a questionnaire to obtain demographic data, the Olson moral climate questionnaire and Minnesota job satisfaction questionnaire. The data were analysed using SPSS software version 14. We found a significant positive relationship between the ethical climate and the level of job satisfaction among the nurses. Among the demographic variables, the working shift, income level and type of duties allocated had a significant relationship with job satisfaction. Hospital managements should pay attention to the factors influencing job motivation among nurses, including the ethical climate of the work environment.


Single-Vehicular Delivery of Antagomir and Small Molecules to Inhibit miR-122 Function in Hepatocellular Carcinoma Cells by using "Smart" Mesoporous Silica Nanoparticles.
MicroRNAs (miRNAs) regulate a variety of biological processes. The liver-specific, highly abundant miR-122 is implicated in many human diseases including cancer. Its inhibition has been found to result in a dramatic loss in the ability of Hepatitis C virus (HCV) to infect host cells. Both antisense technology and small molecules have been used to independently inhibit endogenous miR-122 function, but not in combination. Intracellular stability, efficient delivery, hydrophobicity, and controlled release are some of the current challenges associated with these novel therapeutic methods. Reported herein is the first single-vehicular system, based on mesoporous silica nanoparticles (MSNs), for simultaneous cellular delivery of miR-122 antagomir and small molecule inhibitors. The controlled release of both types of inhibitors depends on the expression levels of endogenous miR-122, thus enabling these drug-loaded MSNs to achieve combination inhibition of its targeted mRNAs in Huh7 cells.


Parents about parenting dual career athletes: A systematic literature review.
To establish the scientific literature on the parents' view as supporters of dual career (DC) athletes, and to highlight practical implications for the development of education programmes to empower parents in this role. ology: The systematic literature review included four electronic databases, from which 438 articles published in English between 1999 and 2019 were retrieved. A total of 14 studies achieved the eligibility criteria (i.e., focus on DC, involving parents as participants) for inclusion. Results show that the 14 studies included in the review were characterised by sample sizes <15 to >50 parents of individual and/or team sports athletes, involving data collection based on interviews, semi-structured interviews focus groups, questionnaires and a survey. A thematic synthesis highlighted a two primary constructs: the individual level and the inter-individual level, respectively. The individual level comprised two main themes: Approach to both Sport and Education, and Stressors and Coping, which included five aspects of parenting. The inter-individual level presented three themes: Relationship with the Athlete; Relationship with the Sport Environment and Relationship with the Academic Environment. Findings highlighted a relevant parental role in supporting DC athletes and partial information on parental support strategies. In conclusions, the limited sample size and typology of sports, and the partial representativeness of countries have impacted the global application of the main findings. Furthermore, the need of an educational programme for parents and the need of regular parents-athlete-teacher/coach engagement were considered crucial to facilitate successful parental interventions at academic and/or sports levels and to limit the potential negative effects of DC parenting.


Molecular diversity of the base-promoted reaction of phenacylmalononitriles with dialkyl but-2-ynedioates.
In the presence of tetrabutylammonium bromide (TBAB), the cycloaddition reaction of phenacylmalononitriles with dialkyl but-2-ynedioates in acetonitrile at room temperature resulted in 3,3-dicyano-5-hydroxy-5-arylcyclopent-1-ene-1,2-dicarboxylates in high yields. More importantly, the DABCO-promoted domino reaction of two molecules of each phenacylmalononitrile and dialkyl but-2-ynedioate in acetonitrile at room temperature afforded unique multifunctionalized carboxamide-bridged dicyclopentenes in moderate to good yields and with high diastereoselectivity.


Assessing the perceived benefits of a new condom wrapper/integrated applicator: an exploratory study.
Errors and problems associated with male condom use are very prevalent and increase the likelihood of inconsistent and incomplete use, thereby compromising condom effectiveness. The aim of this study was to assess the perceived benefits of a new condom wrapper/integrated applicator designed to reduce barriers to condom use and lessen the likelihood of user errors and problems. After viewing videos depicting features of the wrapper/applicator, participants (N = 547; 62.9% male, M age = 29.2) completed online questionnaires. Most participants reported that the product would make condom application easier and quicker, make them more confident that condoms had been applied correctly and make sex more pleasurable and playful. The majority of participants who had recent experience of condom use errors/problems reported that the use of the product would likely prevent these issues from occurring. Reduced chance of condom damage, the design features of the wrapper and not having to touch the condom itself during application were perceived as particular benefits of the product. The findings suggest that the product might reduce the likelihood of a range of condom user errors and problems and enhance pleasure during condom-protected sex. Future larger-scale studies that involve participants physically testing the condom wrapper/applicator are warranted.


Facile Synthesis of 2-Methylenebenzothiazoles from Benzothiazole Salts and 4-Hydroxycoumarins by Ball Milling.
A simple and practical method for the synthesis of 2-methylenebenzothiazoles via the coupling of a benzothiazole salts and 4-hydroxycoumarins have been described herein. The reaction showed a good substrate range and functional compatibility under mechanochemical conditions, and proceeded without catalysts or solvents. The 2-methylenebenzothiazoles products were achieved via the formation of a C=C double bond and exhibited strong luminescence and typical aggregation-induced emission (AIE) properties, indicating their potential for use as fluorescent materials.


Eysenck's theory of criminality applied to women awaiting trial.
American women awaiting trial were administered the Eysenck Personality Questionnaire. Compared to a heterogeneous control group, these women scored significantly higher on the neuroticism and psychoticism scales and on Burgess's 'hedonism' variable, though they did not differ with respect to extraversion or lie scale scores. Women awaiting trial were more likely to fall in the neurotic-extravert quadrant (a trend more marked for non-white women). In general, the results support Eysenck's theory of criminality and the usefulness of Burgess's 'hedonism' variable.


The evolutionary psychology of left and right: costs and benefits of lateralization.
Why do the left and right sides of the vertebrate brain play different functions? Having a lateralized brain, in which each hemisphere carries out different functions, is ubiquitous among vertebrates. The different specialization of the left and right side of the brain may increase brain efficiency--and some evidence for that is reported here. However, lateral biases due to brain lateralization (such as preferences in the use of a limb or, in animals with laterally placed eyes, of a visual hemifield) usually occur at the population level, with most individuals showing similar direction of bias. Individual brain efficiency does not require the alignment of lateralization in the population. Why then are not left--and right-type individuals equally common? Not only humans, but most vertebrates show a similar pattern. For instance, in the paper I report evidence that most toads, chickens, and fish react faster when a predator approaches from the left. I argue that invoking individual brain efficiency (lateralization may increase fitness), evolutionary chance or direct genetic mechanisms cannot explain this widespread pattern. Instead, using concepts from mathematical theory of games, I show that alignment of lateralization at the population level may arise as an "evolutionarily stable strategy" when individually asymmetrical organisms must coordinate their behavior with that of other asymmetrical organisms. Thus, the population structure of lateralization may result from genes specifying the direction of asymmetries which have been selected under "social" pressures.


Use of micro-positron emission tomography with (18)F-fallypride to measure the levels of dopamine receptor-D2 and (18)F-FDG as molecular imaging tracer in the pituitary glands and prolactinomas of Fischer-344 rats.
Dopamine receptor-D2 (DRD2) is the most important drug target in prolactinoma. The aim of this current study was to investigate the role of using micro-positron emission tomography (micro-PET) with (18)F-fallypride and (18)F-fluorodeoxyglucose ((18)F-FDG) as molecular imaging tracer in the pituitary glands and prolactinomas of Fischer-344 (F344) rats and detect the difference of the levels of DRD2 in the pituitary glands and prolactinomas of F344 rat prolactinoma models. Female F344 rat prolactinoma models were established by subcutaneous administration of 15 mg 17β-estradiol for 8 weeks. The growth of tumors was monitored by the small-animal magnetic resonance imaging and micro-PET. A series of molecular biological experiments were also performed 4 and 6 weeks after pump implantation. The micro-PET molecular imaging with (18)F-fallypride revealed a decreased expression of DRD2 in F344 rat prolactinoma models, but the micro-PET molecular imaging with (18)F-FDG presented an increased uptake in the prolactinoma compared with the pituitary gland. A decreasing trend of levels of DRD2 in F344 rat prolactinoma models was also detected by molecular biological experiments. From this, we can conclude that micro-PET with (18)F-fallypride and (18)F-FDG can be used to assess tumorigenesis of the prolactinomas in vivo and molecular imaging detection of DRD2 level in prolactinoma may be an indication of treatment effect in the animal experiment.


Cell biological aspects of HIV-1 infection: effect of the anti-HIV-1 agent Avarol.
HTLV-I, II, HIV-1, 2 and other retroviruses possess genes for the transcriptional activators, tax and tat, the expression of which is closely related with the pathogenesis of leukemia and human immunodeficiency syndrome (AIDS) and induced by the virus infection. The effects of these activators on the expression of host cell genes, however, are still largely unknown. Recently the authors have discovered that infection with HIV or Mo-MuLV causes a specific acceleration of the synthesis of an UAG suppressor glutamine tRNA in the host cell; they could demonstrate that this phenomenon is based on transcriptional promotion of tRNA genes which is due to a new transcriptional activator synthesized as a function of viral infection and/or increased virus levels. The present paper discusses the significance of the suppressor tRNA and explains the role of the virus in the regulation of its expression.


[Prophylaxis of acute pancreatitis during resection of the stomach for "difficult" complicated of duodenal ulcers].
The authors have performed 407 resections of the stomach for duodenal ulcers. In 9 cases the major duodenal papilla was found to be involved into the zone of ulcer destruction. It was noted that operations for "difficult" complicated ulcers of the duodenum with the involvement into the zone of destruction of the major duodenal papilla required a delicate surgical strategy directed to minimization of trauma and blockade of the main factors of the development of acute postoperative pancreatitis, the proximal duodenojejunoanastomosis being the operation of choice for "difficult" complicated ulcers of the duodenum.


Influence of Hydrocarbon Moiety of DMMP on Flame Propagation in Lean Mixtures.
Phosphorus-containing compounds (PCCs) have been found to be significantly more effective than CF3Br for reducing burning velocity when added to stoichiometric hydrocarbon-air flames. However, when added to lean flames, DMMP (dimethylmethylphosphonate) is predicted to increase the burning velocity. The addition of DMMP to lean mixtures apparently increases the equivalence ratio (fuel/oxidizer) and the combustion temperature, as a result of hydrocarbon content of DMMP molecule. Premixed flames studies with added DMMP, OP(OH)3, and CF3Br are used to understand the different behavior with varying equivalence ratio and agent loading. Decrease of the equivalence ratio leads to the decrease of inhibition effectiveness of PCCs relative to bromine-containing compounds. For very lean mixtures CF3Br becomes more effective inhibitor than PCCs. Calculations of laminar burning velocities for pure DMMP/air mixtures predict the maximum burning velocity of 10.5 cm/s at 4.04 % of DMMP in air and at an initial temperature of 400 K. Adiabatic combustion temperature is 2155 K at these conditions.


Substrate stereo-specificity in tryptophan dioxygenase and indoleamine 2,3-dioxygenase.
The first and rate-limiting step of the kynurenine pathway, in which tryptophan (Trp) is converted to N-formylkynurenine is catalyzed by two heme-containing proteins, Indoleamine 2,3-dioxygenase (IDO), and Tryptophan 2,3-dioxygenase (TDO). In mammals, TDO is found exclusively in liver tissue, IDO is found ubiquitously in all tissues. IDO has become increasingly popular in pharmaceutical research as it was found to be involved in many physiological situations, including immune escape of cancer. More importantly, small-molecule inhibitors of IDO are currently utilized in cancer therapy. One of the main concerns for the design of human IDO (hIDO) inhibitors is that they should be selective enough to avoid inhibition of TDO. In this work, we have used a combination of classical molecular dynamics (MD) and hybrid quantum-classical (QM/MM) methodologies to establish the structural basis that determine the differences in (a) the interactions of TDO and IDO with small ligands (CO/O(2)) and (b) the substrate stereo-specificity in hIDO and TDO. Our results indicate that the differences in small ligand bound structures of IDO and TDO arise from slight differences in the structure of the bound substrate complex. The results also show that substrate stereo-specificity of TDO is achieved by the perfect fit of L-Trp, but not D-Trp, which exhibits weaker interactions with the protein matrix. For hIDO, the presence of multiple stable binding conformations for L/D-Trp reveal the existence of a large and dynamic active site. Taken together, our data allow determination of key interactions useful for the future design of more potent hIDO-selective inhibitors.


[The Budapest agglomeration, 1980-1990].
"The study analyses the development of Budapest and [the] 6 towns and 37 communes forming its conurbation between 1980 and 1990." Consideration is given to the city's population dynamics; housing conditions, including availability of utilities, transportation, telecommunications, and retail stores; health conditions of the population; and educational opportunities for residents. (SUMMARY IN ENG AND RUS)


Interfacial Charge Transfer Complexes in TiO2-Enediol Hybrids Synthesized by Sol-Gel.
Metal oxide-organic hybrid semiconductors exhibit specific properties depending not only on their composition but also on the synthesis procedure, and particularly on the functionalization method, determining the interaction between the two components. Surface adsorption is the most common way to prepare organic-modified metal oxides. Here a simple sol-gel route is described as an alternative, finely controlled strategy to synthesize titanium oxide-based materials containing organic molecules coordinated to the metal. The effect of the molecular structure of the ligands on the surface properties of the hybrids is studied using three enediols able to form charge transfer complexes: catechol, dopamine, and ascorbic acid. For each system, the process conditions driving the transition from the sol to chemical, physical, or particulate gels are explored. The structural, optical, and photoelectrochemical characterization of the amorphous hybrid materials shows analogies and differences related to the organic component. In particular, electron paramagnetic resonance (EPR) spectroscopy at room temperature reveals the presence of organic radical species with different evolution and stability, and photocurrent measurements prove the effective photosensitization of TiO2 in the visible range induced by interfacial ligand-to-metal charge transfer.


[Microendoscopy of the Eustachian tube and the middle ear. Indications and clinical application].
Progressive miniaturization of flexible fibreoptic systems has made it possible for the first time to perform atraumatic endoscopy of the Eustachian tube and tympanic cavity with the ear drum intact. With the aid of special actively steerable microcatheters, flexible fibrescopes having outer diameters of 350 to 650 microns are inserted into the opening of the naso-pharyngeal tube and advanced into the tympanic cavity under direct visual control. This new technique is indicated for any disturbance of sound conduction and in those sensorineural hearing disorders in which direct inspection of the middle ear cavity can provide information on the pathogenesis of the disturbance. In the future it may thus replace purely diagnostic tympanoscopy. In combination with fibre-delivery laser systems, this new method forms the basis of "microendoscopically controlled laser surgery" of pathological changes within this anatomical region.


Follicular lesion of undetermined significance in thyroid FNA revisited.
Controversy exists regarding the validity of follicular lesion of undetermined significance (FLUS), an indeterminate diagnostic category of The Bethesda System for Reporting Thyroid Cytopathology (BSRTC). According to BSRTC, FLUS carries a 5-15% risk of cancer. This study was designed to determine if cytomorphology could stratify FLUS into subgroups with different risks of malignancy. Reports of 127 consecutive FNAs reported as FLUS with subsequent tissue diagnoses were evaluated for the presence of various cytologic features and the results were correlated with histological diagnoses. FLUS cases with focal nuclear atypia (nuclear overlap/crowding, nuclear grooves/membrane irregularities, nuclear enlargement, and/or nuclear pseudoinclusions) were more frequently malignant on excision whereas those with architectural atypia (microfollicles) were more often benign on excision (P < 0.05). The presence of any one or more of these nuclear features increased the risk of carcinoma in subsequent thyroid resection. Papillary carcinomas predominated in excised FLUS cases with focal nuclear atypia whereas most FLUS with architectural atypia were adenomas or hyperplastic nodules on histological evaluation. BSRTC recommends that thyroid aspirates containing follicular cell nuclear and/or architectural atypia insufficient for a diagnosis of suspicious for follicular neoplasm, suspicious for malignancy or malignant be classified as FLUS. Our findings indicate that FLUS cases with focal nuclear atypia carry a risk for malignancy that is substantially higher than that assigned to FLUS and are best classified as suspicious. FLUS cases lacking these atypical nuclear features have a risk for malignancy that approximates the risk BSRTC has assigned to FLUS.


Technical potential of electricity production from municipal solid waste disposed in the biggest cities in Brazil: landfill gas, biogas and thermal treatment.
This article presents an analysis of possibilities for electrical energy production by using municipal solid waste disposed in the biggest Brazilian cities. Currently, the municipal solid waste in Brazil is collected and disposed of at landfills, but there are also other technologies, which in addition to dealing with the garbage can also provide benefits in terms of energy provision. The following scenarios were studied in this work: electricity production from landfill gas (reference scenario); incineration of all municipal solid waste; anaerobic digestion of organic waste and incineration of refuse-derived fuel fractions after being separated in separation plants. According to this study, the biggest cities in Brazil generate about 18.9 million tonnes of municipal solid waste per year (2011), of which 51.5% is biogenic matter. The overall domestic consumption of electricity is 480,120 GWh y(-1) in Brazil and the municipal solid waste incineration in the 16 largest cities in the country could replace 1.8% of it using incinerators. The city of São Paulo could produce 637 GWh y(-1) with landfill gas, 2368 GWh y(-1) with incineration of municipal solid waste and 1177 GWh y(-1) with incineration of refuse-derived fuel. The latter two scenarios could replace 27% and 13.5% of the residential electrical energy consumption in the city. This shows that thermal treatment might be a viable option of waste-to-energy in Brazil.


Molecular mechanistic associations of human diseases.
The study of relationships between human diseases provides new possibilities for biomedical research. Recent achievements on human genetic diseases have stimulated interest to derive methods to identify disease associations in order to gain further insight into the network of human diseases and to predict disease genes. Using about 10000 manually collected causal disease/gene associations, we developed a statistical approach to infer meaningful associations between human morbidities. The derived method clustered cardiometabolic and endocrine disorders, immune system-related diseases, solid tissue neoplasms and neurodegenerative pathologies into prominent disease groups. Analysis of biological functions confirmed characteristic features of corresponding disease clusters. Inference of disease associations was further employed as a starting point for prediction of disease genes. Efforts were made to underpin the validity of results by relevant literature evidence. Interestingly, many inferred disease relationships correspond to known clinical associations and comorbidities, and several predicted disease genes were subjects of therapeutic target research. Causal molecular mechanisms present a unifying principle to derive methods for disease classification, analysis of clinical disorder associations, and prediction of disease genes. According to the definition of causal disease genes applied in this study, these results are not restricted to genetic disease/gene relationships. This may be particularly useful for the study of long-term or chronic illnesses, where pathological derangement due to environmental or as part of sequel conditions is of importance and may not be fully explained by genetic background.


Simultaneous hyper- and hypomethylation at imprinted loci in a subset of patients with GNAS epimutations underlies a complex and different mechanism of multilocus methylation defect in pseudohypoparathyroidism type 1b.
Most patients with pseudohypoparathyroidism type 1b (PHP-1b) display a loss of imprinting (LOI) encompassing the GNAS locus resulting in PTH resistance. In other imprinting disorders, such as Russell-Silver or Beckwith-Wiedemann syndrome, we and others have shown that the LOI is not restricted to one imprinted locus but may affect other imprinted loci for some patients. Therefore, we hypothesized that patients with PHP-1b might present multilocus imprinting defects. We investigated, in 63 patients with PHP-1b, the methylation pattern of eight imprinted loci: GNAS, ZAC1, PEG1/MEST, ICR1, and ICR2 on chromosome 11p15, SNRPN, DLK1/GTL2 IG-DMR, and L3MBTL1. We found multilocus imprinting defects in four PHP-1b patients carrying broad LOI at the GNAS locus (1) simultaneous hypermethylation at L3MBTL1 differentially methylated region 3 (DMR3), and hypomethylation at PEG1/MEST DMR (n = 1), (2) hypermethylation at the L3MBTL1 (DMR3) (n = 1) and at the DLK1/GTL2 IG-DMR (n = 1), and (3) hypomethylation at the L3MBTL1 DMR3 (n = 1). We suggest that mechanisms underlying multilocus imprinting defects in PHP-1b differ from those of other imprinting disorders having only multilocus loss of methylation. Furthermore, our results favor the hypothesis of "epidominance", that is, the phenotype is controlled by the most severely affected imprinted locus.


Mmu-miR-1894-3p Inhibits Cell Proliferation and Migration of Breast Cancer Cells by Targeting Trim46.
Breast cancer is the second leading cause of cancer death in women and the presence of metastasis significantly decreases survival. MicroRNAs are involved in tumor progression and the metastatic spreading of breast cancer. Here, we reported that a microRNA, mmu-miR-1894, significantly decreased the lung metastasis of 4TO7 mouse breast cancer cells by 86.7% in mouse models. Mmu-miR-1894-3p was the functional mature form of miR-1894 and significantly decreased the lung metastasis of 4TO7 cells by 90.8% in mouse models. A dual-luciferase reporter assay indicated that mmu-miR-1894-3p directly targeted the tripartite motif containing 46 (Trim46) 3'-untranslated region (UTR) and downregulated the expression of Trim46 in 4TO7 cells. Consistent with the effect of mmu-miR-1894-3p, knockdown of Trim46 inhibited the experimental lung metastasis of 4TO7 cells. Moreover, knockdown of human Trim46 also prohibited the cell proliferation, migration and wound healing of MBA-MD-231 human breast cancer cells. These results suggested that the effect of knockdown of Trim46 alone was sufficient to recapitulate the effect of mmu-miR-1894 on the metastasis of the breast cancer cells in mouse and that Trim46 was involved in the proliferation and migration of mouse and human breast cancer cells.


Hydrophobic Cu2O Quantum Dots Enabled by Surfactant Modification as Top Hole-Transport Materials for Efficient Perovskite Solar Cells.
The utilization of an inorganic hole-transport layer (HTL) is one of the most effective methods to improve the stability and reduce the cost of perovskite solar cells (PSCs). However, achieving high-quality inorganic HTL films, especially HTL films in n-i-p structures, via solution processes remains a big challenge. Here, a simple surface modification strategy for low-cost and stable cuprous oxide (Cu2O) quantum dots is proposed, which utilizes a silane coupling agent. The modified Cu2O can be directly deposited on the perovskite film as the top HTL without decomposing the perovskite to maintain an n-i-p structure. The efficiency (18.9%) of PSCs with surface-modified Cu2O as the HTL is significantly higher than that (11.9%) of PSCs with unmodified Cu2O, which is also the record efficiency for a Cu2O-based perovskite solar cell in n-i-p structure. The enhanced performance of PSCs is attributed to the remarkably enhanced film properties achieved through surface modification. Moreover, because of the dopant-free technology and hydrophobic surface, the Cu2O-based PSCs have distinctly better stability than 2,2',7,7'-tetrakis[N,N-di(4-methoxyphenyl)amino]-9,9'-spiro-bifluorene-based PSCs.


Roles of the ovarian surface epithelium in ovulation and carcinogenesis.
Although ovarian mechanisms of ovulation have been a subject of investigation for more than a century, essential regulatory pathways remain uncertain. A role for the ovarian surface epithelium in ovulation has recently been demonstrated. Ovarian surface epithelial cells in close contact with the apical wall of preovulatory ovine follicles secrete a urokinase-type plasminogen activator in response to surge concentrations of (locally delivered) gonadotrophins. Urokinase activates latent collagenases and stimulates release of tumour necrosis factor alpha from thecal endothelium. Tumour necrosis factor alpha progressively induces matrix metalloproteinase gene expression, apoptosis and inflammatory necrosis. Collagenolysis and cellular death are a prelude to stigma formation and ovarian rupture. Epithelium exfoliated from the dome of ovulatory follicles is replenished by generative stem cell replication and migration from the wound edges. Common epithelial ovarian cancer has been related to successive bouts of ovulation and mitosis. The integrity of the DNA of surface cells circumjacent to the ovarian rupture site is compromised during the ovulatory process. Clonal expansion of an epithelial cell with damaged (unrepaired) DNA is a putative factor in carcinogenesis. Ovarian cancer is a deadly insidious disease because typically it is asymptomatic until the malignancy has reached beyond the ovaries.


Reference values and standards for paired organs.
When estimating reference values for measurements on paired organs, the standard deviation for a single measurement can be obtained to a good approximation simply by ignoring the pairing. In practice, however, there are advantages in the use of conventional standards for pair means and differences.


Determinants of lifejacket use among boaters on Lake Albert, Uganda: a qualitative study.
Drowning is a major cause of unintentional injury death worldwide. The toll is greatest in low and middle-income countries. Over 95% of people who drowned while boating in Uganda were not wearing a lifejacket. We explored the determinants of lifejacket use among boaters on Lake Albert, Uganda. We conducted a qualitative enquiry with a hermeneutic phenomenological undertone leaning on relativism ontology and emic subjectivism epistemology. Focus group discussions (FGDs) and in-depth interviews (IDIs) were held with boaters in 10 landing sites. We explored experiences and perspectives on lifejacket use. We used thematic analysis technique to analyse data and report results according to the Consolidated Criteria for Reporting Qualitative Research. We recruited 88 boaters in 10 FGDs and 11 to take part in the IDIs. We identified three themes: motivators and opportunities for lifejacket use, barriers and threats to lifejacket use, and strategies to improve lifejacket use. Many boaters attributed their lifejacket use to prior experience or witness of a drowning. Perceived high costs of lifejackets, limited knowledge, reluctance to use lifejackets because of distrust in their effectiveness, and the belief that it is women who should wear lifejackets were among the barriers and threats. Participants mentioned the need for mandatory enforcement together with community sensitisations as strategies to improve lifejacket use. Determinants of lifejacket use among boaters include experience or witness of drowning, limited knowledge about lifejackets and distrust in the effectiveness of the available lifejackets. Mandatory lifejacket wearing alongside educational interventions might improve lifejacket use.


Plasma chemistry references values in psittaciformes.
Reference values for 17 plasma chemical variables in African greys. Amazons, cockatoos and macaws were established for use in avian clinical practice. The inner limits are given for the percentiles P(2.5) and P(97.5) with a probability of 90%. The following variables were studied: urea, creatinine, uric acid, urea/uric acid ratio, osmolality, sodium, potassium, calcium, glucose, aspartate aminotransferase, alanine aminotransferase, gamma glutamyltransferase, lactate dehydrogenase, creatine kinase, bile acids, total protein, albumin/globulin ratio. Differences between methods used and values found in this study and those reported previously are discussed.


Proverb preferences across cultures: dialecticality or poeticality?
Peng and Nisbett (1999) claimed that members of Asian cultures show a greater preference than Euro-Americans for proverbs expressing paradox (so-called dialectical proverbs; e.g., Too humble is half proud). The present research sought to replicate this claim with the same set of stimuli used in Peng and Nisbett's Experiment 2 and a new set of dialectical and nondialectical proverbs that were screened to be comparably pleasing in phrasing. Whereas the proverbs were rated as more familiar and (in Set 1) more poetic by Chinese than by American participants, no group differences were found in relation to proverb dialecticality. Both the Chinese and Americans in our study rated the dialectical proverbs from Peng and Nisbett's study as more likable, higher in wisdom, and higher in poeticality than the nondialectical proverbs. For Set 2, both groups found the dialectical proverbs to be as likable, wise, and poetic as the nondialectical proverbs. When poeticality was covaried out, dialectical proverbs were liked better than nondialectical proverbs across both stimulus sets by the Chinese and the Americans alike, and when wisdom was covaried out, the effect of dialecticality was reduced in both sets and groups. Our findings indicate that caution should be taken in ascribing differences in proverb preferences solely to cultural differences in reasoning.


Suicide and employment status during Ireland's Celtic Tiger economy.
Studies have identified employment as a protective factor against suicide. We examined employment status and risk of suicide in Ireland during the 11-year period 1996-2006, a period of economic boom commonly known as the Celtic Tiger. Data relating to the 5270 suicides and 789 deaths of undetermined intent registered as occurring in Ireland in 1996-2006 and relevant population data were obtained from the Irish Central Statistics Office and analysed using Poisson regression. Unemployment fell from 12% in 1996 to 4% in 2000, a level at which it remained until 2006. Male and female rates of suicide and undetermined death were stable during 1996-2006 though suicide among unemployed men increased. Relative to employment, unemployment was associated with a 2-3-fold increased risk of male suicide and undetermined death but generally a 4-6-fold increased risk in women. Unemployment was associated with greater increased risk of suicide and undetermined death when its level was low (2001-06) than in the period of decreasing unemployment (1996-2000). Unemployment was a stronger risk factor in men aged 35-54 years and with increasing age in women. Retired persons aged >55 years had a similar risk to their employed counterparts. Being a homemaker was associated with increased risk in women aged >35 years. The current Irish context of rapidly increasing unemployment suggests that rates may rise again as in previous recessions. Appropriate social policy responses are required to mitigate the potential impact of unemployment on suicides.


Inhibition of inducible nitric oxide synthase ameliorates rat lung allograft rejection.
Recently, the inducible isoform of nitric oxide synthase has been shown to be an important immunomodulation molecule in allograft rejection. We have observed the production of nitric oxide during rejection and the effect of nitric oxide synthase inhibition on allograft rejection in a rat lung transplant model. Rat left lung allotransplants were performed in two strain combinations: brown Norway-to-F344 (major histocompatibility complex incompatible); and Lewis-to-F344 (minor loci incompatible) as severe and mild rejection models respectively. Syngeneic F344-to-F344 transplants were performed as a negative control. Nitric oxide production during rejection was determined by measuring the recipient's serum nitrite/nitrate levels as a stable end product of nitric oxide. The progression of rejection was evaluated radiographically and the grade of rejection was determined histologically. After operation, recipients of allotransplantation were randomly divided into two groups and received either aminoguanidine (200 mg/kg, intraperitoneal every 6 hours), a potent inducible nitric oxide synthase inhibitor, or normal saline treatment. The levels of serum nitrite and nitrate in recipients increased in the early phase of rejection in both allotransplant combinations. However, in the terminal phase of rejection, the serum nitrite/nitrate level decreased significantly compared with the peak level in the brown Norway-to-F344 recipients. The serum nitrite/nitrate levels in the syngeneic transplant recipients were normal during the entire observation period. In aminoguanidine-treated animals, serum nitrite/nitrate levels remained normal in both allograft combinations. Significant suppression of rejection in aminoguanidine-treated recipients was observed histologically and radiographically in comparison with untreated recipients in the brown Norway-to-F344 combinations. In the Lewis-to-F344 combination, aminoguanidine treatment significantly ameliorated histologic rejection but did not affect radiologic appearance. We therefore conclude nitric oxide is produced during early allograft rejection and may prove to be a marker and mediator of early rejection. The inhibition of inducible nitric oxide synthase results in significant reduction in rat lung allograft rejection.


A generalized mean field theory of coarse-graining.
A general mean field theory is presented for the construction of equilibrium coarse-grained models. Inverse methods that reconstruct microscopic models from low resolution experimental data can be derived as particular implementations of this theory. The theory also applies to the opposite problem of reduction, where relevant information is extracted from available equilibrium ensemble data. Additionally, a complementary approach is presented and problems of representability in coarse-grained modeling analyzed using information theoretic arguments. These problems are central to the construction of coarse-grained representations of complex systems, and commonly used coarse-graining methods and variational principles for coarse-graining are derived as particular cases of the general theory.


Novel targets for the future development of antibacterial agents.
Recent advances in DNA sequencing technology have made it possible to elucidate the entire genomes of pathogenic bacteria, and advancements in bioinformatic tools have driven comparative studies of these genome sequences. These evaluations are dramatically increasing our ability to make valid considerations of the limitations and advantages of particular targets based on their predicted spectrum and selectivity. In addition, developments in gene knockout technologies amenable to pathogenic organisms have enabled new genes and gene products critical to bacterial growth and pathogenicity to be uncovered at an unprecedented rate. Specific target examples in the areas of cell wall biosynthesis, aromatic amino acid biosynthesis, cell division, two component signal transduction, fatty acid biosynthesis, isopreniod biosynthesis and tRNA synthetases illustrate how aspects of the above capabilities are impacting on the discovery and characterization of novel antibacterial targets. An example of a novel inhibitor of bacterial fatty acid biosynthesis discovered from high throughput screening processes is described, along with its subsequent chemical optimization. Furthermore, the application and importance of technologies for tracking the mode of antibacterial action of these novel inhibitors is discussed.


The phosphorylation site for Ste20p-like protein kinases is essential for the function of myosin-I in yeast.
The budding yeast Saccharomyces cerevisiae has two functionally redundant myosin-I isoforms encoded by the MYO3 and MYO5 genes. The function shared by these myosin proteins is required for proper yeast budding. Serine residue 357 in the head domain of Myo3p, conserved among myosin-I proteins including yeast Myo5p, was identified as a unique phosphorylation site for the serine/threonine protein kinase Ste20p and its closely related isoform Cla4p. These protein kinases share a function that is also essential for budding. Replacement of serine 357 with alanine disrupted the in vivo function of Myo3p, whereas this function was maintained by changing the serine residue to aspartate. This mutant version failed to compensate the growth defect of cells which lack both Ste20p and Cla4p, suggesting that myosin-I is not the only essential target of these protein kinases. Our results suggest that phosphorylation of the head domain by Ste20p-like protein kinases plays an essential role in the function of myosin-I in yeast cells.


Who's My Doctor? First-Year Residents and Patient Care: Hospitalized Patients' Perception of Their "Main Physician".
Studies have shown that a large portion of patient satisfaction is related to physician care, especially when the patient can identify the role of the physician on the team. Because patients encounter multiple physicians in teaching hospitals, it is often difficult to determine who the patient feels is his or her main caregiver. Surveys evaluating resident physicians would help to improve patient satisfaction but are not currently implemented at most medical institutions. We created a survey to judge patient satisfaction and to determine who patients believe is their "main physician" on the teaching service. Patients on a medical teaching service at The Miriam Hospital during 20 days in March 2008 were asked to complete the survey. A physician involved in the research project administered the surveys. Surveys included 3 questions that judged patient's perception and identification of their primary physician and 7 questions regarding patient satisfaction. Completed surveys were analyzed using averages. Of the 126 patients identified for participation, 102 (81%) completed the survey. Most patients identified the intern (first-year resident) as their main physician. Overall, more than 90% of patients expressed satisfaction with their main physician. Most patients on the teaching service perceived the intern as their main physician and were satisfied with their physician's care. One likely reason is that interns spend the greatest amount of time with patients on the teaching service.


Glucocorticoids inhibit the maturation of committed osteoblasts via SOX2.
During bone formation, mesenchymal progenitor cells mature into bone-forming osteoblasts after undergoing several stages of differentiation. Impaired bone formation is a predominant finding in glucocorticoid (GC)-induced osteoporosis (GIO). Osteoblasts at different stages of maturation can be affected by excessive endogenous or therapeutic GCs. Sex-determining region Y-box 2 (SOX2) is normally expressed in immature osteoblasts, but its overexpression can suppress osteoblast differentiation. This study aimed to evaluate whether GC affects SOX2 expression in osteoblasts, and whether SOX2 contributes to GC-induced inhibition of osteoblast differentiation. Treatment with GCs such as dexamethasone (Dex) or hydrocortisone enhanced SOX2 expression. Silencing SOX2 improved inhibition of GC-induced osteoblast differentiation, whereas SOX2 overexpression decreased mineralized nodule formation and RUNX2 and Osterix expression in MC3T3-E1 cells. On the contrary, when C3H10T1/2 uncommitted mesenchymal stem cells were subjected to SOX2 overexpression, RUNX2 expression increased. As a mechanism of Dex-induced SOX2 upregulation in preosteoblasts, we found that the STAT3 pathway or GC receptor (GR) is involved, using a GR antagonist, STAT3 regulators, and chromatin immunoprecipitation assays. Moreover, mice treated with Dex for 4 weeks showed a notable increase in SOX2 expression in the bones and an increased ratio of procollagen type 1 N-terminal propeptide to osteocalcin in the plasma than in control mice. This study demonstrated that GC enhances SOX2 expression in vitro in osteoblast and in vivo in the mice bone, which affects bone-forming activity differently depending on the differentiation stage of osteoblast-lineage cells. Our results provide new insights into prevention and treatment against impaired bone formation in GIO.


A hybrid approach to protein folding problem integrating constraint programming with local search.
The protein folding problem remains one of the most challenging open problems in computational biology. Simplified models in terms of lattice structure and energy function have been proposed to ease the computational hardness of this optimization problem. Heuristic search algorithms and constraint programming are two common techniques to approach this problem. The present study introduces a novel hybrid approach to simulate the protein folding problem using constraint programming technique integrated within local search. Using the face-centered-cubic lattice model and 20 amino acid pairwise interactions energy function for the protein folding problem, a constraint programming technique has been applied to generate the neighbourhood conformations that are to be used in generic local search procedure. Experiments have been conducted for a few small and medium sized proteins. Results have been compared with both pure constraint programming approach and local search using well-established local move set. Substantial improvements have been observed in terms of final energy values within acceptable runtime using the hybrid approach. Constraint programming approaches usually provide optimal results but become slow as the problem size grows. Local search approaches are usually faster but do not guarantee optimal solutions and tend to stuck in local minima. The encouraging results obtained on the small proteins show that these two approaches can be combined efficiently to obtain better quality solutions within acceptable time. It also encourages future researchers on adopting hybrid techniques to solve other hard optimization problems.


Complex community-wide consequences of consumer sexual dimorphism.
Sexual dimorphism is a ubiquitous source of within-species variation, yet the community-level consequences of sex differences remain poorly understood. Here, we analyse a bitrophic model of two competing resource species and a sexually reproducing consumer species. We show that consumer sex differences in resource acquisition can have striking consequences for consumer-resource coexistence, abundance and dynamics. Under both direct interspecific competition and apparent competition between two resource species, sexual dimorphism in consumers' attack rates can mediate coexistence of the resource species, while in other cases can lead to exclusion when stable coexistence is typically expected. Slight sex differences in total resource acquisition also can reverse competitive outcomes and lead to density cycles. These effects are expected whenever both consumer sexes require different amounts or types of resources to reproduce. Our results suggest that consumer sexual dimorphism, which is common, has wide-reaching implications for the assembly and dynamics of natural communities.


Repeated resection for malignant liver tumours.
Fifteen repeat hepatic resections were performed on 12 patients with either recurrent or residual malignant tumours of the liver. Of these, one patient underwent three repeat resections and another underwent two. Five had primary liver liver tumours and seven had liver metastases. Planned, 'staged', repeat resections were performed on three patients because of multiple deposits of tumour, cirrhosis or extensive disease at initial presentation. There was no operative mortality. The period of follow-up from the time of repeat sections ranged between 4 months and 36 months during which two patients died from recurrent disease. The mean survival after the repeat resection was 16.8 months (range 4-36 months). Although technically demanding, repeat hepatectomy is feasible and provide similar benefits.


Ancient hybridization fuels rapid cichlid fish adaptive radiations.
Understanding why some evolutionary lineages generate exceptionally high species diversity is an important goal in evolutionary biology. Haplochromine cichlid fishes of Africa's Lake Victoria region encompass >700 diverse species that all evolved in the last 150,000 years. How this 'Lake Victoria Region Superflock' could evolve on such rapid timescales is an enduring question. Here, we demonstrate that hybridization between two divergent lineages facilitated this process by providing genetic variation that subsequently became recombined and sorted into many new species. Notably, the hybridization event generated exceptional allelic variation at an opsin gene known to be involved in adaptation and speciation. More generally, differentiation between new species is accentuated around variants that were fixed differences between the parental lineages, and that now appear in many new combinations in the radiation species. We conclude that hybridization between divergent lineages, when coincident with ecological opportunity, may facilitate rapid and extensive adaptive radiation.


Effect of intrinsic organic carbon on the optical properties of fresh diesel soot.
This study focuses on the retrieval of the normalized mass absorption cross section (MAC) of soot using theoretical calculations that incorporate new measurements of the optical properties of organic carbon (OC) intrinsic to fresh diesel soot. Intrinsic OC was extracted by water and an organic solvent, and the complex refractive index of the extracted OC was derived at 532 and 355-nm wavelengths using cavity ring-down aerosol spectrometry. The extracted OC was found to absorb weakly in the visible wavelengths and moderately at blue wavelengths. The mass ratio of OC and elemental carbon (EC) in the collected particles was evaluated using a thermo-optical method. The measured EC/OC ratio in the soot exhibited substantial variability from measurement to measurement, ranging between 2 and 5. To test the sensitivity of the MAC to this variability, three different EC/OC ratios (21, 11, and 12) were chosen as representative. Particle size and spherule morphology were estimated using scanning electron microscopy, and the soot was found to be primarily in the form of aggregates with a dominant aggregate diameter mode in the range 200-250 nm. The measured refractive index of the extracted OC was used with a variety of theoretical models to calculate the MAC of internally mixed diesel soot at 532 and 355 nm. We conclude that Rayleigh-Debye-Gans theory on clusters of coated spherules and T-matrix of a solid EC spheroid coated by intrinsic OC are both consistent with previous measurements; however, Rayleigh-Debye-Gans theory provides a more realistic physical model for the calculation.


Determination of immunoglobulin class of alloantibodies in sera from hypersensitized renal patients.
26 sera from hypersensitized renal patients were analysed for immunoglobulin class of alloantibodies. To assess the participation of IgM and IgG in alloreactivity, sera were treated with dithiothreitol (DTT) or Staphylococcus aureus protein A (SpA), respectively. Treatment with both DTT and SpA was also performed to test the possible contribution of other immunoglobulin classes. Immunological complexes which may mimic alloreactivity were excluded by polyethylene glycol (PEG) treatment. Immunochemically modified sera were tested against a panel of allogeneic B and T lymphocytes. IgG class alloantibodies reactive with B lymphocytes were found two times more frequently than those reactive with T lymphocytes. In 22% of sera only IgM alloantibodies were detected. No contribution of other immunoglobulin classes of immune complexes was seen. Our results show that DTT and SpA treatment are technically simple and reproducible methods of discriminating between IgG and IgM alloantibodies and can be recommended for routine use in clinical analysis of sera from hypersensitized renal patients awaiting kidney graft.


Ultrastructure and innervation of the swimbladder of Tetractenos glaber (Tetraodontidae).
The general structure, ultrastructure and innervation of the swimbladder of the smooth toadfish, Tetractenos glaber, were examined with light-microscopic, fluorescence-histochemical, and transmission electron-microscopic techniques. The structure of the swimbladder is similar to that of other euphysoclists. Fluorescence histochemistry showed adrenergic fibres in both the secretory and resorptive areas of the swimbladder. Transmission electron microscopy revealed two morphologically distinct axon profiles: type-I profiles containing many small, flattened vesicles; type-II profiles containing both large, granular vesicles and rounded, small clear vesicles in varying proportions. The gas-gland cells and surrounding muscularis mucosae are innervated by both type-I and type-II fibres. Type-I fibres also innervate pre-rete arteries. The rete- and gas-gland capillaries do not appear to be innervated. Arteries running to the resorptive area are innervated by type-I fibres. Both type-I and type-II profiles make contact with the muscularis mucosae in the resorptive area. Only type-I fibres innervate the radial dilator muscle in the oval sphincter region, whereas only type II fibres innervate the circular muscle of the oval sphincter. Type-I fibres took up alpha-methyl-noradrenaline, and could not be found after pre-treatment with 6-hydroxydopamine. They are, therefore, assumed to be adrenergic. Type-II fibres were tentatively identified, by exclusion, as cholinergic.