Evaluating osteogenic effects associated with the incorporation of ascorbic acid in mineralized collagen scaffolds.
Current treatments for craniomaxillofacial (CMF) defects motivate the design of instructive biomaterials that can promote osteogenic healing of complex bone defects. We report methods to promote in vitro osteogenesis of human mesenchymal stem cells (hMSCs) within a model mineralized collagen scaffold via the incorporation of ascorbic acid (vitamin C), a key factor in collagen biosynthesis and bone mineralization. An addition of 5 w/v% ascorbic acid into the base mineralized collagen scaffold significantly changes key morphology characteristics including porosity, macrostructure, and microstructure. This modification promotes hMSC metabolic activity, ALP activity, and hMSC-mediated deposition of calcium and phosphorous. Additionally, the incorporation of ascorbic acid influences osteogenic gene expression (BMP-2, RUNX2, COL1A2) and delays the expression of genes associated with osteoclast activity and bone resorption (OPN, CTSK), though it reduces the secretion of OPG. Together, these findings highlight ascorbic acid as a relevant component for mineralized collagen scaffold design to promote osteogenic differentiation and new bone formation for improved CMF outcomes.


Analysis of diagnostic criteria for ventilator-associated pneumonia: a cohort study.
to analyze the diagnostic criteria for ventilator-associated pneumonia recommended by the Brazilian Health Regulatory Agency and the National Healthcare Safety Network/Centers for Disease Control and Prevention, as well as its risk factors. retrospective cohort study carried out in an intensive care unit throughout 12 months, in 2017. Analyses included chi-square, simple linear regression, and Kappa statistical tests and were conducted using Stata 12 software. the sample was 543 patients who were in the intensive care unit and under mechanical ventilation, of whom 330 (60.9%) were men and 213 (39.1%) were women. Variables such as gender, age, time under mechanical ventilation, and oral hygiene proved to be significant risk factors for the development of ventilator-associated pneumonia. patients submitted to mechanical ventilation need to be constantly evaluated so the used diagnostic methods can be accurate and applied in an objective and standardized way in Brazilian hospitals.


Asymptomatic carotid artery stenosis: state of the art management.
In 2011, numerous guidelines were updated to advise on the optimal management of patients with asymptomatic carotid disease. Despite being based on interpretation of the same body of literature, there was actually little international consensus. Whilst we now know much more about what constitutes "state of the art" medical management, we still cannot identify the small proportion of "high risk for stroke" patients in whom to target carotid endarterectomy or carotid artery stenting. This is essential, as about 95% of patients undergoing either treatment strategy will ultimately undergo an unnecessary intervention. There is compelling evidence that the annual risk of stroke (on medical therapy) in patients with asymptomatic carotid disease has declined significantly. Guideline makers cannot continue to extrapolate rationales for justifying "mass interventions" in contemporary practice that are based on historical trial data. Accordingly, there is no consensus as to what should be considered "state of the art" management of asymptomatic carotid disease.


Serial lung and IVC ultrasound in the assessment of congestive heart failure.
Management of congestive heart failure (CHF) is dependent on clinical assessments of volume status, which are subjective and imprecise. Point-of-care ultrasound (POCUS) is useful in the diagnosis of CHF, but how POCUS findings correlate with therapy remains unknown. This study aimed to determine whether the changes in clinical evaluation of CHF with treatment are mirrored with changes in the number of B lines on lung ultrasound (LUS) and inferior vena cava (IVC) size. In this prospective observational study, investigators performed serial clinical and ultrasound assessments within 24 h of admission (T1), day 1 in hospital (T2) and within 24 h of discharge (T3). Clinical assessments included an evaluation of the jugular venous distension (JVD), hepatojugular reflux (HJR), pulmonary rales and a clinical congestion score was calculated. Ultrasound assessment included the IVC size and collapsibility, and the number of B lines in an 8-point scan. Fifty consecutive patients were recruited with a mean age of 71.2 years (SD 12.7). Mean clinical congestion score on admission was 5.6 (SD 1.4) and declined significantly over time to 1.3 (0.91), as did the JVP, HJR and pulmonary rales. No significant changes were found in the IVC size between T1 [1.9 (0.65)] and T3 [2.0 (0.50)] or in the IVC collapsibility index [T1 0.3 (0.19) versus T3 0.25 (0.16)]. The mean number of B lines decreased from 11 (6.1) at T1 to 8.3 (5.5) at T3, although this decrease did not reach statistical significance. Spearman correlation between JVP and HJR versus IVC collapsibility and total B lines did not yield significant results. Clinical exam findings correlate over time during the management of CHF, whereas LUS and IVC results did not. The number of B lines did decrease with therapy, but did not reach statistical significance likely because the sampled population was small and had only mild heart failure. Further studies are warranted to further explore the use of lung ultrasound in this patient population.


Thyrotropin receptor and CD40 mediate interleukin-8 expression in fibrocytes: implications for thyroid-associated ophthalmopathy (an American Ophthalmological Society thesis).
To better understand the pathogenesis of thyroid-associated orbitopathy (TAO) through elucidating the role of thyrotropin receptor (TSHR) and CD40 in the expression of interleukin-8 (IL-8) in peripheral blood fibrocytes. Fibrocytes infiltrate the orbit of patients with TAO, where they differentiate into fibroblasts. Fibrocyte precursors occur with increased frequency in the peripheral blood expressing TSHR and CD40 in TAO patients. We hypothesize that in vitro derived fibrocytes and peripheral blood fibrocyte precursors express proinflammatory chemoattractant molecules including IL-8 initiated by TSHR and CD40 signaling. Since nearly all TAO patients express activating antibodies to TSHR, this is particularly relevant for activation of peripheral blood fibrocytes. TSHR and CD40 expression on peripheral blood fibrocytes was determined by flow cytometry. IL-8 RNA was quantitated by real-time polymerase chain reaction. IL-8 protein production was measured by Luminex and flow cytometry. Thyroid-stimulating hormone and CD40 ligand-stimulated phosphorylation of Akt in peripheral blood fibrocytes was studied by flow cytometry. Both TSHR- and CD40-mediated signaling lead to IL-8 expression in mature fibrocytes. Fibrocyte precursors assayed directly from circulating peripheral blood demonstrate intracellular IL-8 expression with addition of thyroid-stimulating hormone or CD40 ligand. TSHR- and CD40-induced IL-8 production is mediated by Akt phosphorylation. Peripheral blood TSHR(+) and CD40(+) fibrocytes express IL-8 and may promote the recruitment of inflammatory cells, mitogenesis, and tissue remodeling in TAO. TSHR- and CD40-mediated IL-8 signaling is mediated by Akt. Delineating the molecular mechanisms of fibrocyte immune function may provide potential therapeutic targets for TAO.


Purification and properties of methyl formate synthase, a mitochondrial alcohol dehydrogenase, participating in formaldehyde oxidation in methylotrophic yeasts.
Methyl formate synthase, which catalyzes methyl formate formation during the growth of methylotrophic yeasts, was purified to homogeneity from methanol-grown Candida boidinii and Pichia methanolica cells. Both purified enzymes were tetrameric, with identical subunits with molecular masses of 42 to 45 kDa, containing two atoms of zinc per subunit. The enzymes catalyze NAD(+)-linked dehydrogenation of the hydroxyl group of the hemiacetal adduct [CH2(OH)OCH3] of methanol and formaldehyde, leading to the formation of a stoichiometric amount of methyl formate. Although neither methanol nor formaldehyde alone acted as a substrate for the enzymes, they showed simple NAD(+)-linked alcohol dehydrogenase activity toward aliphatic long-chain alcohols such as octanol, showing that they belong to the class III alcohol dehydrogenase family. The methyl formate synthase activity of C. boidinii was found in the mitochondrial fraction in subcellular fractionation experiments, suggesting that methyl formate synthase is a homolog of Saccharomyces cerevisiae Adh3p. These results indicate that formaldehyde could be oxidized in a glutathione-independent manner by methyl formate synthase in methylotrophic yeasts. The significance of methyl formate synthase in both formaldehyde resistance and energy metabolism is also discussed.


Mycophenolate mofetil prevents high-fat diet-induced hypertension and renal glomerular injury in Dahl SS rats.
We designed experiments to test the hypothesis that Dahl salt-sensitive (SS) rats are sensitive to high-fat diet (HFD)-induced hypertension and renal injury via an inflammatory mechanism. Twelve-week-old Dahl SS rats were maintained on a normal diet (ND; 14% fat), HFD (59% fat), or HFD supplemented with the lymphocyte immunosuppressive agent, mycophenolate mofetil (HFD + MMF; 30 mg/kg/day orally in diet), for a period of 4 weeks. Mean arterial pressure (MAP), metabolic parameters, T lymphocyte (CD3(+)) localization, and renal structural damage were assessed during the studies. Four weeks of HFD significantly elevated MAP and visceral adiposity without changing circulating levels of lipids or adipokines. Immunohistochemical analysis demonstrated that SS rats on HFD had significantly greater numbers of CD3(+) cells in renal glomerular and medullary areas compared to ND SS rats. Additionally, HFD led to increased glomerular injury, but did not alter renal medullary injury. Chronic MMF treatment in HFD-fed Dahl SS rats reduced MAP, visceral adiposity, infiltration of CD3(+) cells in the glomerulus, as well as glomerular injury. However, MMF treatment did not alter HFD-induced infiltration of CD3(+) cells in the renal medulla. In conclusion, Dahl SS rats are sensitized to HFD-induced hypertension and renal glomerular injury via infiltration of T lymphocytes.


The comparative susceptibility of five breeds of sheep to foot-rot.
Five breeds of sheep, Romney Marsh, Dorset Horn, Border Leicester, Peppin Merinos and Saxon Merinos were examined for their susceptibility to foot-rot by exposure to natural transmission of infection on irrigated pasture or by the application of pure cultures of Bacteroides nodosus to each foot in a pen experiment. On pasture, the sheep encountered a moderate challenge and the British breeds were more resistant than Merinos to the development of severe foot-rot. Resistance was manifested by a rapid resolution of relatively benign lesions in the interdigital skin, rather than a reduction in the number of feet affected. However, under more severe challenges with foot-rot in pens, all breeds were equally susceptible. There was little difference between resistant and susceptible sheep in the kinetics and magnitude of their antibacterial immune responses indicating that resistance did not depend on pre-existing antibody or a more rapid induction of antibody production. In each experiment, humoral immune responses against B. nodosus were not greatly elevated until under-running lesions of the hoof developed.


[Seeing the sounds--chest and lung ultrasonography].
Chest ultrasonography was considered hampered and deficient but it is now taking a prominent role as a bedside tool for the diagnosis of lung ailments. Technological development has made it accurate, fast and reliable to the extent that it is gradually replacing the traditional chest X-ray and sometimes also the computed tomography scan. In this article we review and display in a few images the diagnostic possibilities of the thoracic ultrasound examination in a diverse range of maladies such as pneumonia, pulmonary congestion, pleural effusion and other conditions.


Maxillary Ameloblastoma in an Asiatic Black Bear (Ursus thibetanus).
An approximately 30-year-old intact female Asiatic black bear (Ursus thibetanus) was presented for annual examination and a history of ptyalism. A large 9.5 cm × 5 cm × 5 cm, firm, round mass was identified attached to the hard palate on physical examination. A computed tomography scan was performed, and the heterogeneous, mineral-attenuating mass was seen arising from the right aspect of the palatine bone and extending rostrally to the level of the last maxillary molars, caudally into the oropharynx, and dorsally into the nasal choana. Surgical debulking was performed to remove the portion of the mass within the oral cavity. Histopathologic analysis was consistent with a keratinizing ameloblastoma. Nine months postoperatively, the patient was asymptomatic for the tumor. The patient was euthanized 23-months postoperatively, and severe diffuse pustular dermatitis, growth of the ameloblastoma on the hard palate, and various degenerative and aging changes were noted on necropsy at that time. This is the first report of an ameloblastoma in a member of the Ursidae family.


The acetylcholine receptor as a cellular receptor for rabies virus.
Characterization of specific host cell receptors for enveloped viruses is a difficult problem because many enveloped viruses bind to a variety of substrates which are not obviously related to tissue tropisms in the intact host. Viruses with a limited cellular tropism in infected animals present useful models for studying the mechanisms by which virus attachment regulates the disease process. Rabies virus is a rhabdovirus which exhibits a marked neuronotropism in infected animals. Limited data suggest that spread occurs by transsynaptic transfer of virus. The results of recent experiments at Yale suggest that viral antigen is localized very soon after injection at neuromuscular junctions, the motor nerve endings on muscle tissue. On cultured muscle cells, similar co-localization with the acetylcholine receptor is seen both before and after virus multiplication. Pretreatment of these cells with some ligands of the acetylcholine receptor results in reduced viral infection. These findings suggest that a neurotransmitter receptor or a closely associated molecule may serve as a specific host cell receptor for rabies virus and thus may be responsible for the tissue tropism exhibited by this virus. In addition to clarifying aspects of rabies virus pathogenesis, these studies have broad implications regarding the mechanism by which other viruses or viral immunizations might mediate autoimmune diseases such as myasthenia gravis.


Structure and gelation mechanism of silk hydrogels.
Silk fibroin was regenerated from cocoons produced by the silkworm Bombyx Mori. Light scattering showed that an aqueous solution of the regenerated silk fibroin (RSF) was made of individual proteins with a weight average molar mass of about 4 x 10(5) g mol(-1) and a hydrodynamic radius of about 10 nm. Gel formation of RSF in acidic solutions was investigated as a function of the pH (2-4), concentration (0.5-10 g L(-1)) and temperature (5-70 degrees C). The structure of the gels was studied using light scattering and confocal laser scanning microscopy. The structure was found to be self-similar from length scales of less than 15 nm up to length scales of about 1 microm, and characterized by a correlation length of a few microns. Gel formation was tracked using turbidity, rheology, light scattering and circular dichroism. Gelation involves the formation of self-similar aggregates with a growth rate that increases exponentially. The protein aggregation is correlated to, and perhaps caused by, the formation of beta-sheets, the fraction of which also increases exponentially with time.


Induction chemotherapy with a new regimen alternating cisplatin, fluorouracil with mitomycin, hydroxyurea and bleomycin in carcinomas of nasopharynx or other sites of the head and neck region.
Sixty-six patients with locally advanced (Stages III and IV) carcinoma of the head and neck were treated with three cycles of induction chemotherapy, consisting of cisplatin, fluorouracil (FU) infusion, bleomycin, mitomycin, and hydroxyurea, followed by radiotherapy and/or surgery. There were 48 men and 18 women with a median age of 55 years (range, 18 to 75 years) and Karnofsky performance status of 80 (range, 40 to 90). Primary site was nasopharynx (28 patients), followed by larynx (12) and others (26). Forty-one (62%) patients were presented with Stage IV disease. The response rate to induction chemotherapy was 27% complete response, 50% partial response, 20% stable disease, and 3% progressive disease. There was no significant difference in response rate between patients with cancer of nasopharynx or other sites (P greater than 0.1). Survival was 61% at 24 months. Patients with cancer of nasopharynx had a better survival than those with other primaries (P = 0.033). Toxicities from chemotherapy included alopecia (73%), nausea/vomiting (66%), leukopenia (54%), stomatitis (36%), anemia (32%), thrombocytopenia (16%), and diarrhea (9%). Grade IV toxicity was not observed. Induction chemotherapy with this new regimen resulted in a high response rate but may not be superior to cisplatin and FU alone. It can be safely combined with radiotherapy as a potentially curative therapy in squamous cell carcinoma of the head and neck. Chemotherapy followed by radiation therapy may yield survival similar to radical surgery in laryngeal and other head and neck cancers.


Utilizing Secondary Agricultural Education Programs to Deliver Evidence-Based Grain Safety Training for Young and Beginning Workers.
Purdue University's Agricultural Safety and Health Program (PUASHP) has collaborated with secondary agricultural education programs, including FFA Chapters, for over 70 years to deliver and promote agricultural safety and health programming. With support from a U.S. Department of Labor Susan Harwood Program grant, PUASHP utilized a Developing a Curriculum (DACUM) process to develop, implement, and evaluate an evidence-based curriculum for use with young and beginning workers, ages 16-20, exposed to hazards associated with grain storage and handling. The primary audience was students enrolled in secondary agricultural education programs. A review of the literature identified a gap in educational resources that specifically addresses this target population. The curriculum developed was based on fatality and injury incident data mined from Purdue's Agricultural Confined Space Incident Database and input from a panel of experts. The process identified 27 learning outcomes and finalized a pool of test questions, supported by empirical evidence and confirmed by a panel of experts. An alignment process was then completed with the current national standards for secondary agricultural education programs. Seventy-two youth, ages 16-20, enrolled in secondary-school agricultural education programs, and a smaller group of post-secondary students under the age of 21 interested in working in the grain industry pilot tested the curriculum. Based on student and instructor feedback, the curriculum was refined and submitted to OSHA for approval as part of OSHA's online training resources. The curriculum was delivered to 3,665 students, ages 16-20. A total of 346 pre- and post-tests were analyzed, and the results used to confirm content validity and assess knowledge gain. Findings led to additional modifications to curriculum content, affirmed knowledge gain, and confirmed appropriateness for use with secondary agricultural education programs. The curriculum has been promoted nationally and made available for free download from www.agconfinedspaces.org . Findings further confirmed the value of delivering safety programming through established programs such as secondary agricultural education programs and FFA Chapters serving youth.


Folate-targeted star-shaped cationic copolymer co-delivering docetaxel and MMP-9 siRNA for nasopharyngeal carcinoma therapy.
The co-delivery of drug and gene has become the primary strategy in cancer therapy. Based on our previous work, to co-deliver docetaxel (DOC) and MMP-9 siRNA more efficiently for HNE-1 nasopharyngeal carcinoma therapy, a folate-modified star-shaped copolymer (FA-CD-PLLD) consisting of β-cyclodextrin (CD) and poly(L-lysine) dendron (PLLD) was synthesized, and then used for DOC and MMP-9 co-delivery. Different from commonly used amphiphilic copolymers micelles, the obtained CD derivative could be used directly for the combinatorial delivery of nucleic acid and hydrophobic DOC without a complicated micellization process. In vitro and in vivo assays are carried out to confirm the effectiveness of the target strategy and combined treatment. It was found that the conjugation of CD-PLLD with FA could enhance the DOC/MMP-9 delivery effect obviously, inducing a more significant apoptosis and decreasing invasive capacity of HEN-1 cells. In vivo assays showed that FA-CD-PLLD/DOC/MMP-9 could inhibit HNE-1 tumor growth and decrease PCNA expression effectively, indicating a promising strategy for nasopharyngeal carcinoma therapy. Moreover, the in vivo distribution of DOC and MMP-9, blood compatibility and toxicity are also explored.


Bone marrow origin of mucosal mast cells.
Infection with the intestinal parasite Nippostrongylus brasiliensis stimulates an accumulation of mucosal mast cells (MMC) in the villi of the small intestine of normal but not athymic or W/Wv anemic mice. W/Wv mice are congenitally deficient in both MMC and skin and connective tissue mast cells (CTMC). Athymic mice have normal or elevated numbers of CTMC but are severely deficient in MMC. CTMC derive from the bone marrow. To determine the origin of MMC, athymic and W/Wv mice were given various hematopoietic or lymphoid tissues from normal littermate or beige mice and the MMC response to N. brasiliensis infection was evaluated. The MMC defect in athymic mice was repaired by grafts of thymus cells, thymus gland, or spleen cells, but not by bone marrow cells or anti-Thy 1-treated bone marrow or spleen cells. The MMC and CTMC defects of W/Wv mice were repaired by grafts of bone marrow, spleen cells, or anti-Thy 1-treated bone marrow or spleen cells. Neither the MMC nor the CTMC defect in W/Wv mice was repaired by grafts of thymus cells or thymus glands. These results indicate the following, MMC, like CTMC, derive from the bone marrow and not from the thymus. MMC require a thymic influence for development. Athymic mice possess bone marrow precursors for both MMC and CTMC but lack a thymus-dependent component necessary for MMC development. W/Wv mice lack both MMC and CTMC mast cell precursors but possess the thymus-dependent component required for MMC development.


The anatomy of death.
Medical science does not treat death as an independent physiological phenomenon. It believes that disease is the cause of death and treats both as preventable phenomena. Doctors and relatives nurture a guilt complex when death occurs. The moment of natural death is robbed of its poignancy. There is no cause of death. Death of the physical body is an intrinsic, time governed, built-in ontolytic program. It completes the biologic trajectory of the individual organism which begins at conception and ends with death. In this article, the actual built-in mechanism and operation of the physiological process of death is suggested vis-a-vis biology and medicine. The physical body of an individual is like a biological gadget which is constantly charged with life force received from cosmic energy through the subtle body which is an implement that cannot be objectified in the same way as the gross physical body but is experienced only subjectively by one and all, as mind (antahkaran in Sanskrit and Indian languages, meaning inner instrument, a subtler instrument in contrast to external organs of actions like limbs, tongue, etc. of the physical body). This life force keeps the subtle body and the entire physical body live and functioning. It maintains the body's integrity and internal homeostasis throughout life. The physical body like a gadget has a built-in program which decides how much total capacity, pace and quantum of life force it can use. It is often referred to as breath quota and heartbeat quota, however, they are manifestations and not the mechanism and operation of life and death in the physical body. When the quantum of life force of the physical body is exhausted, the subtle body, a connector for life forces departs, leaving behind the physical body. The vital functions stop and the person is declared dead. It is usually referred to as departure of soul (Pran or Jiva in India) from the physical body in common parlance. This phenomenon of predetermined capacity, pace and fixed quota of life force is operational in all the components of the body. Each cell, each organ, each system and the whole body is a packed unit of bioenergy. They are in structural and functional dynamic homeostasis under constant flux resulting in constant change in the body. The rate of expenditure contributes towards deciding the total life span of the cell, organ, systems and individual. It accounts for the phenomena of cell death, progressive diminution in vitality, change in organ and system functions during life and physical death of an individual at the end. Death is a bio-cosmic phenomenon governed by biological laws. There is variation in life span at the interspecies and intraspecies levels because we measure lifespan of an individual in terms of physical time and not in terms of biological time which is an independent entity, not measurable and predictable as physical time. Everyone lives one full unit of life in terms of biological time which begins at conception and ends with death. The normal distribution of each biological feature, including the biological unit of life, is independent of one another making each individual unique. The biological clock runs at its own dynamic unique pace in every individual. The biological timer starts ticking at conception and stops when the life force quantum is over. When the person dies, the physical body stops functioning and is left behind for others to dispose of. The timing of death is beyond the realm of objective perception and cannot be equated with chronological or physical time. It is a trans-science and trans-technique phenomenon beyond the ken of humankind to alter its mechanism and operation. The article explains the impact of extrinsic and intrinsic diseases, various treatments such as organ transplant, as well as the impact of lifestyle on the biological time scale of an individual. It spells out the difference between natural and unnatural death. With this understanding, death can be appreciated, accepted and respected as a built-in operational intrinsic physiological phenomenon for the end of one's life. It is a must for the survival and healthy continuity of all the species in the biological world including mankind.


Survival-apoptosis associated signaling in GNE myopathy-cultured myoblasts.
GNE Myopathy (GNEM) is a neuromuscular disorder caused by mutations in the GNE gene. It is a slowly progressive distal and proximal muscle weakness sparing the quadriceps. In this study, we applied our model of mutated M743T GNE enzyme skeletal muscle-cultured myoblasts and paired healthy controls to depict the pattern of signaling proteins controlling survival and/or apoptosis of the PI3K/AKT, BCL2, ARTS/XIAP pathways, examined the effects of metabolic changes/stimuli on their expression and activation, and their potential role in GNEM. Immunoblot analysis of the GNEM myoblasts indicated a notable increased level of activated PTEN and PDK1 and a trend of relative differences in the expression and activation of the examined signaling molecules with variability among the cultures. ANOVA analysis showed a highly significant interaction between the level of PTEN and the patients groups. In parallel, the interaction between the level of BCL2, BAX and PTEN with the specific PI3K/AKT inhibitor-LY294002 was highly significant for BCL2 and nearly significant for PTEN and BAX. The pattern of the ARTS/XIAP signaling proteins of GNEM and the paired controls was variable, with no significant differences between the two cell types. The response of the GNEM cells to the metabolic changes/stimuli: serum depletion and insulin challenge, as indicated by expression of selected signaling proteins, was variable and similar to the control cells. Taken together, our observations provide a clearer insight into specific signaling molecules influencing growth and survival of GNEM muscle cells.


Identification of Gene Signature Associated with Type 2 Diabetes Mellitus by Integrating Mutation and Expression Data.
Type 2 Diabetes Mellitus (T2DM) is a chronic disease. The molecular diagnosis should be helpful for the treatment of T2DM patients. With the development of sequencing technology, a large number of differentially expressed genes were identified from expression data. However, the method of machine learning can only identify the local optimal solution as the signature. The mutation information obtained by inheritance can better reflect the relationship between genes and diseases. Therefore, we need to integrate mutation information to more accurately identify the signature. To this end, we integrated Genome-Wide Association Study (GWAS) data and expression data, combined with expression Quantitative Trait Loci (eQTL) technology to get T2DM predictive signature (T2DMSig-10). Firstly, we used GWAS data to obtain a list of T2DM susceptible loci. Then, we used eQTL technology to obtain risk Single Nucleotide Polymorphisms (SNPs), and combined with the pancreatic β-cells gene expression data to obtain 10 protein-coding genes. Next, we combined these genes with equal weights. After Receiver Operating Characteristic (ROC), single-gene removal and increase method, gene ontology function enrichment and protein-protein interaction network were used to verify the results showed that T2DMSig-10 had an excellent predictive effect on T2DM (AUC=0.99), and was highly robust. In short, we obtained the predictive signature of T2DM, and further verified it.


An Enhancer's Length and Composition Are Shaped by Its Regulatory Task.
Enhancers drive the gene expression patterns required for virtually every process in metazoans. We propose that enhancer length and transcription factor (TF) binding site composition-the number and identity of TF binding sites-reflect the complexity of the enhancer's regulatory task. In development, we define regulatory task complexity as the number of fates specified in a set of cells at once. We hypothesize that enhancers with more complex regulatory tasks will be longer, with more, but less specific, TF binding sites. Larger numbers of binding sites can be arranged in more ways, allowing enhancers to drive many distinct expression patterns, and therefore cell fates, using a finite number of TF inputs. We compare ~100 enhancers patterning the more complex anterior-posterior (AP) axis and the simpler dorsal-ventral (DV) axis in Drosophila and find that the AP enhancers are longer with more, but less specific binding sites than the (DV) enhancers. Using a set of ~3,500 enhancers, we find enhancer length and TF binding site number again increase with increasing regulatory task complexity. Therefore, to be broadly applicable, computational tools to study enhancers must account for differences in regulatory task.


Clinical experience of raltegravir with abacavir/lamivudine or zidovudine/lamivudine in HIV-infected Korean adults.
The efficacy and safety of raltegravir (RAL) with tenofovir (TDF)/emtricitabine (FTC) have been well studied in human immunodeficiency virus (HIV)-infected patients. However, limited clinical data are available on the use of RAL with abacavir (ABC)/lamivudine (3TC) or zidovudine (ZDV)/3TC. We investigated HIV-1-infected Korean adults, including 13 antiretroviral-naïve patients and 15 antiretroviral-experienced patients, treated with RAL plus ABC/3TC or ZDV/3TC. Virological suppression was achieved in 12 of the 13 (92%) antiretroviral-naïve patients within 24 weeks and in all (100%) patients within 96 weeks. In 13 of the 15 treatment-experienced patients, ritonavir-boosted lopinavir (LPV/r) was replaced with RAL because of hyperlipidemia (n = 11) and diarrhea (n = 2). A significant decrease in median total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels was observed in these patients (P < 0.01, each). No adverse event related to RAL was observed in any of the 28 patients. The RAL plus ABC/3TC or ZDV/3TC regimens were effective and safe in antiretroviral-naïve Korean HIV-infected patients, and replacing LPV/r with RAL significantly improved lipid abnormalities in patients previously treated with regimens including LPV/r.


Effect of the thromboxane receptor antagonist, BM 13.505, on the sequelae of endotoxemia in the conscious rat.
The purpose of this study was to examine the effects of the thromboxane receptor antagonist, BM 13.505, on the responses to endotoxemia in the conscious rat. The pharmacodynamics of BM 13.505 (30 mg/kg, i.v.) were first determined by pretreating male Sprague-Dawley rats 5 min, 24 h or 48 h prior to an LD90 dose of the thromboxane mimetic U 46619. Administration of a single dose of BM 13.505 5 min or 24 h prior to the challenge with U 46619 protected completely against sudden death (100% survival, p less than 0.01), while injection of BM 13.505 48 h prior to the U 46619 challenge did not protect against death. In a separate group of conscious rats, endotoxemia (30 mg/kg i.v. Salmonella enteritidis endotoxin) produced a decrease in the number of circulating platelets to 45 +/- 4% and 20 +/- 4% of the initial value at 1 and 6 h, respectively. The number of circulating white blood cells was reduced to 21 +/- 4% of the initial value at 1 h and returned to 68 +/- 9% of the initial value at 6 h. Survival following endotoxin administration was 44% at 48 h. In endotoxemic animals pretreated with BM 13.505 (30 mg/kg, i.v.), the endotoxin-induced thrombocytopenia was significantly attenuated (p less than 0.05), but there was no effect on either the endotoxin-induced early leukopenia or late leukocytosis. Survival in the BM 13.505-treated endotoxemic group was 31% at 48 h (p greater than 0.05, compared to the endotoxin + vehicle group).(ABSTRACT TRUNCATED AT 250 WORDS)


Microsurgical resection of spinal cord hemangioblastomas.
Hemangioblastomas are not uncommon intramedullary spinal cord neoplasms. They are highly vascular, benign tumors that occur either sporadically or in the presence of von Hippel-Lindau disease. Despite their exceptionally vascular nature, these lesions can consistently be resected completely and safely with minimal blood loss. We describe a microsurgical method for removal of these tumors from the spinal cord.


FMRI Study of Neural Responses to Implicit Infant Emotion in Anorexia Nervosa.
Difficulties in social-emotional processing have been proposed to play an important role in the development and maintenance of anorexia nervosa (AN). Few studies, thus far, have investigated neural processes that underlie these difficulties, including processing emotional facial expressions. However, the majority of these studies have investigated neural responses to adult emotional display, which may be confounded by elevated sensitivity to social rank and threat in AN. Therefore, the aim of this study was to investigate the neural processes underlying implicit processing of positively and negatively valenced infant emotional display in AN. Twenty-one adult women with AN and twenty-six healthy comparison (HC) women were presented with images of positively valenced, negatively valenced, and neutral infant faces during a fMRI scan. Significant differences between the groups in positive > neutral and negative > neutral contrasts were investigated in a priori regions of interest, including the bilateral amygdala, insula, and lateral prefrontal cortex (PFC). The findings revealed that the AN participants showed relatively increased recruitment while the HC participants showed relatively reduced recruitment of the bilateral amygdala and the right dorsolateral PFC in the positive > neutral contrast. In the negative > neutral contrast, the AN group showed relatively increased recruitment of the left posterior insula while the HC groups showed relatively reduced recruitment of this region. These findings suggest that people with AN may engage in implicit prefrontal down-regulation of elevated limbic reactivity to positively social-emotional stimuli.


Traditional Chinese Medicine Bionic Tiger Bone Powder for the Treatment of AI-Associated Musculoskeletal Symptoms.
Background. Aromatase inhibitors (AIs) are used for adjuvant therapy of breast cancer; however AIMSS (AI-Associated Musculoskeletal Symptoms) can negatively affect quality of life and compliance. Most patients in China moved to TCM (traditional Chinese medicine) for help. TB (tiger bone) is used to treat bone disease, whose main ingredients are calcium and collagen. The objective of this study was to evaluate whether the TB prevented AIMSS in postmenopausal women with ER/PR+ breast cancer. Methods. We conducted a randomized, blind, controlled study of comparing TB versus placebo for 12 weeks in postmenopausal women with breast cancer who have taken AI for less than a month. Patients completed the M-BPI, VAS, and FACT-B at baseline, 6 weeks, and 12 weeks. M-BPI and VAS were used as the primary outcomes. FACT-B was used as the secondary outcome. Serum E2 and FSH were tested every 6 weeks. Results. Of 70 evaluable cases, 8 of 35 patients (22.9%) developed new or worsening point symptoms in TB group, compared to 21 of 35 (60%) in placebo group (P < 0.001). We also found differences between 2 groups in average pain (2 to 5.6), worst pain (3.9 to 8), pain interference severity (1.9 to 5.3), stiffness (2.4 to 6.9), and joint symptom interference (1.8 to 5.7), all P < 0.001; similar findings were seen in VAS value (3 to 6.6) at the end of intervention. HRQoL measured by FACT-B (P < 0.05) was improved. No change of serum estradiol and FSH between two groups. Conclusions. TB appeared to be effective and safe in the prevention of AIMSS. This trial is registered with ChiCTR-IPR-15007081.


Collagen metabolism in infected colonic anastomoses.
Infection of the peritoneum has an adverse effect on the healing of colonic anastomoses. It has been suggested that infection results in a disturbance of colonic collagen metabolism, but the precise nature of the biochemical disorder is uncertain. Colonic collagen metabolism was studied in infected anastomoses in the left colon of rats. The rats were labeled with radioactive proline from an early stage of growth, and infected anastomoses were compared with anastomoses of the control group of uninfected rats. Infection resulted in significant changes in collagen metabolism during the early phase of colonic healing. There was a significant reduction in the amount of salt soluble collagen in infected anastomoses on the third postoperative day compared with anastomoses of the control group, and reduced amounts of acid soluble collagen and insoluble collagen were found in infected anastomoses on the seventh postoperative day. These observations suggest that the defective healing of infected colonic anastomoses results either from an increased lysis of newly formed--salt soluble--collagen or from a reduction in the intracellular formation of collagen.


Development and Performance Evaluation of Wearable Respiratory Self-Training System Using Patch Type Magnetic Sensor.
Respiratory training system that can be used by patients themselves was developed with a micro-electro-mechanical-system (MEMS)-based patch-type magnetic sensor. We conducted a basic function test and clinical usability evaluation to determine the system's clinical applicability. The system is designed with a sensor attached to the patient's chest and a magnet on the back to monitor the patient's respiration by measuring changes in magnetic intensity related to respiratory movements of the thoracic surface. The system comprises a MEMS-based patch-type magnetic sensor capable of wireless communication and being applied to measurement magnets and mobile applications. System performance was evaluated by the level of systemic noise, the precision of the sensor in various breathing patterns, how measurement signals change for varying distances, or the presence or absence of material between the sensor and the magnet. Various breathing patterns were created using the QUASAR respiratory motion phantom; the data obtained were analyzed using the fitting and peak value analysis methods. The sensor had a noise ratio of <0.54% of the signal; the average errors in signal amplitude and period for breathing patterns were 78.87 um and 72 ms, respectively. The signal could be measured consistently when the sensor-magnet distance was 10-25 cm. The signal difference was 1.89% for the presence or absence of a material, indicating that its influence on the measurement signal is relatively small. The potential of our MEMS-based patch-type wearable respiratory self-training system was confirmed via basic function tests and clinical usability evaluations. We believe that the training system could provide thorough respiratory training for patients after a clinical trial with actual patients confirming its clinical efficacy and usability.


Second-Degree Burns and Aloe Vera: A Meta-analysis and Systematic Review.
Aloe vera is a cost-effective, accessible wound care adjunct with a minimal risk profile. Despite its centuries-long history being used to treat varying wound types, published reports remain inconclusive on its efficacy. In this article, the authors report the results of a systematic review assessing the efficacy of topical aloe vera products in wound care applications, as well as a meta-analysis of its utility in burn healing where data are most robust. In accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, the authors searched PubMed, EMBASE, and Cochrane CENTRAL for randomized controlled trials assessing the use of aloe vera in healing various wound types. The database search identified 91 articles. After duplicates were removed, 74 articles were screened, and of those, 47 were assessed for eligibility. Ultimately, 28 articles were included in the qualitative synthesis, and 4 studies assessing second-degree burns were included in the meta-analysis. The following data points were collected from each study: number of participants/wounds, treatment type, adjunctive therapy (if any), and primary outcomes. Risk-of-bias analysis was conducted on included articles, and results were compiled. A meta-analysis was undertaken for studies focusing on the treatment of burns. Cumulatively, these studies had a total of 133 patients with 163 wounds being assessed. Analysis revealed a statistically significant mean difference in time to healing of 4.44 days in favor of aloe vera treatment (P = .004). Topical aloe vera usage for second-degree burn wound healing demonstrated significantly faster time to healing compared with other treatments.


Antiviral effects of Retro-2cycl and Retro-2.1 against Enterovirus 71 in vitro and in vivo.
Enterovirus 71 (EV71) is one of the causative pathogens of hand, foot and mouth disease (HFMD), especially the form associated with fatal neurological disorders. Sustained outbreaks of EV71 infections remain a serious health threat worldwide. However, no antiviral agent against EV71 for clinical therapy has been approved. Retro-2cycl and Retro-2.1 are inhibitors of several pathogens specifically targeting the intracellular vesicle transport, which also participates in the EV71 lifecycle processes including progeny virus release. Here, we reported that Retro-2cycl and Retro-2.1, respectively, could inhibit EV71 infection with 50% effective concentrations of 12.56 μM and 0.05 μM in a cytopathic effect inhibition assay and showed relatively low cytotoxicity with 50% cytotoxicity concentrations of more than 500 μM and 267.80 μM. Preliminary mechanism studies revealed that Retro-2cycl and Retro-2.1 did not inhibit EV71 protein synthesis or RNA replication but could block progeny EV71 release specifically. Furthermore, administration of Retro-2cycl at the dose of 10 mg/kg significantly protected 90% of newborn mice from lethal EV71 challenge. Consequently, our results for the first time identified Retro-2cycl and Retro-2.1 as effective inhibitors of EV71 as well as lead compounds, which would contribute to anti-EV71 drug development. We also identified progeny virus release and the intracellular vesicle transport as antiviral targets for EV71.


[Defining characteristics of the dysfunctional ventilatory weaning response as indicators of accuracy of ventilatory weaning].
The study aimed to analyze the defining characteristics of the Dysfunctional Ventilatory Weaning Response as an indicator of the accuracy of ventilatory weaning. Observational study of 38 events of ventilatory weaning in adult patients admitted to intensive care. For the defining characteristics, it was calculated: sensitivity, specificity, positive and negative predictive values, accuracy or efficiency, likelihood ratio positive and negative, and diagnostic odds ratio. It was also considered the median number of defining characteristics in the event of success and failure. It was considered accurate: agitation, deterioration in arterial blood gases from baseline parameters, moderate use of accessory muscles of respiration, increased respiratory rate from baseline parameters and respiratory rate increases significantly with respect to baseline parameters. There was statistical difference in the median number of defining characteristics observed. It was concluded that the defining characteristic and the number of them would influence the success of the weaning decision.


Effects of simvastatin on plasma antioxidant status and vitamins in hypercholesterolemic patients.
Statins are known to possess antioxidant properties in addition to their cholesterol-lowering effects. However, recent studies have suggested that statins reduce the levels of antioxidant vitamins such as vitamin E and coenzyme Q(10), possibly resulting in impaired left ventricular function. We investigated the effects of simvastatin on the blood lipids, LDL oxidation and plasma antioxidant status, and whether these effects were associated with changes in plasma antioxidant vitamin levels. Simvastatin (20-40 mg/day) was administered for 8 weeks in seventy-six hypercholesterolemic patients. We measured plasma lipids, oxidized LDL, total radical trapping antioxidant potential (TRAP) and plasma antioxidant vitamin levels at baseline and after 8 weeks of simvastatin administration. Simvastatin significantly lowered serum levels of total cholesterol and LDL-cholesterol by 30.1% and 41.9%, respectively. A significant reduction in oxidized LDL levels (p<0.0001) and improvement in plasma antioxidant status as measured by TRAP (p<0.05) after the 8-week simvastatin treatment were observed. Regarding the effects of simvastatin on plasma antioxidant vitamin levels, there were significant increases in the levels of lipid-corrected retinol (p<0.001), alpha-tocopherol (p<0.001) and gamma-tocopherol (p<0.005) after the 8-week simvastatin treatment. Lipid-corrected levels of coenzyme Q10 and carotenoids remained unchanged after simvastatin treatment. Our results show that simvastatin reduced blood lipids and circulating oxidized LDL, and improved plasma antioxidant status without altering the antioxidant vitamin system. These data indicate that simvastatin not only decreases blood lipids and circulating oxidized LDL but also increases lipid corrected levels of antioxidant vitamins and may improve plasma antioxidant status synergizing with the biological effects of antioxidants.


Whole-Genome Resequencing Reveals the Diversity of Patchouli Germplasm.
As an important medicinal and aromatic plant, patchouli is distributed throughout most of Asia. However, current research on patchouli's genetic diversity is limited and lacks genome-wide studies. Here, we have collected seven representative patchouli accessions from different localities and performed whole-genome resequencing on them. In total, 402,650 single nucleotide polymorphisms (SNPs) and 153,233 insertions/deletions (INDELs) were detected. Based on these abundant genetic variants, patchouli accessions were primarily classified into the Chinese group and the Southeast Asian group. However, the accession SP (Shipai) collected from China formed a distinct subgroup within the Southeast Asian group. As SP has been used as a genuine herb in traditional Chinese medicine, its unique molecular markers have been subsequently screened and verified. For 26,144 specific SNPs and 16,289 specific INDELs in SP, 10 of them were validated using Polymerase Chain Reaction (PCR) following three different approaches. Further, we analyzed the effects of total genetic variants on genes involved in the sesquiterpene synthesis pathway, which produce the primary phytochemical compounds found in patchouli. Eight genes were ultimately investigated and a gene encoding nerolidol synthetase (PatNES) was chosen and confirmed through biochemical assay. In accession YN, genetic variants in PatNES led to a loss of synthetase activity. Our results provide valuable information for understanding the diversity of patchouli germplasm resources.


Evolution of normal and neoplastic tissue stem cells: progress after Robert Hooke.
The appearance of stem cells coincides with the transition from single-celled organisms to metazoans. Stem cells are capable of self-renewal as well as differentiation. Each tissue is maintained by self-renewing tissue-specific stem cells. The accumulation of mutations that lead to preleukaemia are in the blood-forming stem cell, while the transition to leukaemia stem cells occurs in the clone at a progenitor stage. All leukaemia and cancer cells escape being removed by scavenger macrophages by expressing the 'don't eat me' signal CD47. Blocking antibodies to CD47 are therapeutics for all cancers, and are currently being tested in clinical trials in the US and UK.


Mediastinal osteosarcoma with extension to lungs in a patient treated for Hodgkin's disease.
This article reports a patient with Hodgkin's disease in remission after combined modality therapy who developed metastatic pulmonary osteosarcoma, subsequently found to originate in soft tissue of the mediastinum, within a field irradiated 11 years previously. This patient developed a series of radiotherapy-induced complications in addition to osteosarcoma. Only 16 cases of extraskeletal osteosarcoma after radiation treatment have been reported, none originating in the mediastinum. To the authors' knowledge, this is the first reported case of extraskeletal osteosarcoma occurring in a patient previously treated for Hodgkin's disease and with the sarcoma originating within the irradiated field.


Maternal diet before and during pregnancy modulates microglial activation and neurogenesis in the postpartum rat brain.
The implications of poor maternal diet on offspring metabolic and neuroimmune development are well established. Increasing evidence now suggests that maternal obesity and poor diet can also increase the risk of postpartum mood disorders, but the mechanisms are unknown. Here we investigated the effects of a poor, high-fat-high-sugar diet (HFSD) on peripheral and central inflammation, neurogenesis and postpartum anxiety-like behaviours. We hypothesised that long-term consumption of a HFSD pre- and post-conception would increase the levels of circulating cytokines and induce microglial activation, particularly in the arcuate nucleus of the hypothalamus (ARC), as the primary brain region involved in the integration of satiety signalling; and this would lead to increased anxiety, stress responsivity and disrupted neurogenesis. We further hypothesised that these effects would be ameliorated by consumption of a healthier diet during pregnancy - specifically a diet high in omega-3 polyunsaturated fatty acids (PUFAs). As expected, the HFSD significantly increased pre-conception body weight, elevated circulating cytokines and activated microglia in the ARC, as well as in the basolateral amygdala. The HFSD also significantly increased the numbers of immature (doublecortin (DCX)-positive) neurons in the subgranular/granular region of the hippocampus, a neurogenic response that was, surprisingly, mimicked by consumption of a diet high in omega-3 PUFAs. Despite these effects of peri-pregnancy dietary imbalance, we detected no differences in anxiety-like behaviours or hypothalamic-pituitary-adrenal (HPA) axis reactivity between the groups. A shift to a healthier diet post-conception reversed the peripheral inflammation and alleviated the microglial activation. These novel data indicate the importance of a balanced peri-pregnancy diet and highlight the need for future research into key triggers that alter the neuroimmune balance in the maternal brain.


Serious complication of cement augmentation for damaged pilot hole.
Polymethl methacrylate (PMMA) screw reinforcement is frequently used in osteoporotic bone as well as in damaged pilot holes. However, PMMA use can be dangerous, since the amount of applied cement is uncontrolled. A 47-year-old male with traumatic cervical spondylolisthesis at C6-7 underwent anterior cervical plate fixation. During repeated drilling and tapping for false trajectory correction, a pilot hole was damaged. Although it was an unconventional method, PMMA augmentation was tried. However, PMMA was accidentally injected to the cervical spinal cord owing to lack of fluoroscopic guidance. The PMMA was surgically removed after corpectomy and durotomy. The patient had left side hemiparesis (Grade 2/5) immediately post operation. The patient improved spontaneously (Grade 4/5) except for 4th and 5th digit extension. Here, we report a rare complication of PMMA extrusion in the spinal cord during a damaged pilot hole injection, which has not previously been described.


Evaluation of Reactivity of Monoclonal Antibodies Against Omp25 of Brucella spp.
Brucellosis is a serious zoonosis occurring mainly in developing countries, and its diagnosis is largely dependent on serologic detection and bacterial culture. In this study, we developed the murine monoclonal antibodies (mAbs) against a conserved and major outer membrane protein 25 (Omp25) of Brucella species (B. spp.) for use in clinical diagnosis. The mAbs to Omp25 were produced by hybridoma technique, which were utilized for developing various immunoassays for detection of Brucellae, including Western blot (WB), enzyme-linked immunosorbent assay (ELISA), immunochemical staining (ICS), immunofluorescence staining (IFS), and flow cytometry assay (FCM). A number of five mAbs (2B10, 4A12, 4F10, 6C12, and 8F3) specific to Omp25 were selected, including 2 IgG1, 2 IgG2a, and 1 IgG2b. Among them, mAbs 6C12, 8F3, and 4A12 reacted highly with B. melitensis (M5-90), B. abortus (S19, 104M, and 2308), and B. suis strain (S2). No cross-reactivity with Yersinia enterocolitica O:9, Salmonella spp., and Escherichia coli was found. By mapping Omp25 epitopes, mAb 6C12 was found as reacting with a semi-conformational epitope, and mAbs 4A12 and 8F3 as recognizing a different linear epitope, respectively. The paired mAbs were tested for detecting Brucella species, suggesting that 8F3 was suitable for solid phase capture and 6C12 or 4A12 was suitable for conjugation with HRP for detection of Brucella Omp25 in ELISA. The FCM was established by mAb 6C12 for detecting intracellular Brucellae-infected peripheral blood mononuclear cells (PBMCs) from brucellosis patients. In conclusion, mAbs against Omp25 are precious reagents for detection of Brucellae in clinical samples with various immunoassays. mAb 6C12-based FCM could be potentially used for the monitoring of therapeutic efficacy for brucellosis in clinical practice.


The transcriptional response of the Pacific oyster Crassostrea gigas against acute heat stress.
The Pacific oyster, Crassostrea gigas, has evolved sophisticated mechanisms to adapt the changing ambient conditions, and protect themselves from stress-induced injuries. In the present study, the expression profiles of mRNA transcripts in the haemocytes of oysters under heat stress were examined to reveal the possible mechanism of heat stress response. There were 23,315, 23,904, 23,123 and 23,672 transcripts identified in the haemocytes of oysters cultured at 25 °C for 0, 6, 12, and 24 h (designed as B, H6, H12, H24), respectively. And 22,330 differentially expressed transcripts (DTs) were yielded in the pairwise comparisons between the above four samples, which corresponded to 8074 genes. There were 9, 12 and 22 Gene Ontology (GO) terms identified in the DT pairwise comparison groups of H6_B, H12_H6 and H24_H12, respectively, and the richest GO terms in biological process category were cellular catabolic process, translational initiation and apoptotic process, respectively. There were 108, 102 and 102 KEGG pathways successfully retrieved from DTs comparison groups DTH6_B, DTH12_H6 and DTH24_H12, respectively, among which 93 pathways were shared by all three comparison groups, and most of them were related to metabolism of protein, carbohydrate and fat. The expression patterns of 12 representative heat stress response-relevant genes detected by quantitative real-time PCR (qRT-PCR) were similar to those obtained from transcriptome analysis. By flow cytometric analysis, the apoptosis rate of haemocytes increased significantly after oysters were treated at 25 °C for 24 h and recovered at 4 °C for 12 h (p < 0.05) and 36 h (p < 0.01), and it also increased significantly when the heat treatment lasted to 60 h (p < 0.01). The present results indicated that, when oysters encountered short term heat stress, the expression of genes related to energy metabolism, as well as unfolded protein response (UPR) and anti-apoptotic system, were firstly regulated to maintain basic life activities, and then a large number of genes involved in stabilizing protein conformation and facilitating further protein refolding were activated to repair the stress injury. However, the stress injury gradually became irreparable with the stress persisting, and apoptosis was activated when the heat treatment prolonged to 24 h. The information was useful to better understand the molecular mechanism of heat stress response and develop strategies for the improvement of oyster survival rate during summer high-temperature period.


Injuries and musculoskeletal complaints in referees and assistant referees selected for the 2006 FIFA World Cup: retrospective and prospective survey.
There is a considerable amount of scientific literature on football, but few studies have focused on referees, despite their key role in this sport. Existing studies focus on the physiological demands and training of referees. To analyse injuries and musculoskeletal complaints in referees and assistant referees selected for the 2006 FIFA World Cup. Retrospective survey and prospective study. During the preparation camps for the 2006 FIFA World Cup in Germany, all 123 referees pre-selected for the tournament completed a questionnaire on injuries and musculoskeletal complaints. During the tournament, the characteristics and consequences of all injuries and complaints incurred by the 63 officiating referees were documented. More than 40% of the referees reported having incurred an injury and more than 60% having had musculoskeletal complaints during their career. About 20% of the group reported having suffered from musculoskeletal complaints in the last match. During the World Cup, 14 referees (22%) incurred an injury and more than 30% had musculoskeletal complaints. This prospectively collected data showed an incidence of 20.8 injuries per 1000 match hours (95% CI: 4.17 to 37.4). The most common acute injuries were hamstring strains, calf strains, and ankle sprains, while the most frequent locations of complaints were the low back, hamstring and knee. Considering the injury profile, the prevalence of associated musculoskeletal complaints, and the high physiological demands of refereeing, it appears that injury prevention programmes should be developed and integrated into the fitness training routine of the referee.


Partial proteolysis of simian virus 40 T antigen reveals intramolecular contacts between domains and conformation changes upon hexamer assembly.
Simian virus 40 large tumor antigen (Tag) is a multi-functional viral protein that binds specifically to SV40 origin DNA, serves as the replicative DNA helicase, and orchestrates the assembly and operation of the viral replisome. Tag associated with Mg-ATP forms hexamers and, in the presence of SV40 origin DNA, double hexamers. Limited tryptic digestion of monomeric Tag revealed three major stable structural domains. The N-terminal domain spans amino acids 1-130, the central domain comprises amino acids 131-476, and the C-terminal domain extends from amino acid 513 to amino acid 698. Co-immunoprecipitation of digestion products of monomeric Tag suggests that the N-terminal domain associates stably with sequences located in the central region of the same Tag molecule. Hexamer formation protected the tryptic cleavage sites in the exposed region between the central and C-terminal domains. Upon hexamerization, this exposed region also became less accessible to a monoclonal antibody whose epitope maps in that region. The tryptic digestion products of the soluble hexamer and the DNA-bound double hexamer were indistinguishable. A low-resolution model of the intramolecular and intermolecular interactions among Tag domains in the double hexamer is proposed.


Verbal Short-Term Memory Deficits in Chinese Children with Dyslexia may not be a Problem with the Activation of Phonological Representations.
This study explored the underlying mechanism of the verbal short-term memory deficit in Chinese children with developmental dyslexia. Twenty-four children with dyslexia and 28 age-matched normal readers participated in the study. They were required to memorize a visually presented series of six Chinese characters and identify them from a list also including code-specific distracters and non-code-specific distracters. Error rates were recorded and were higher for code-specific distracters in all three conditions, revealing phonological, visual, and semantic similarity effects respectively. Group comparisons showed a stronger phonological similarity effect in dyslexic group, suggesting intact activation of phonological representations of target characters. Children with dyslexia also exhibited a greater semantic similarity effect, revealing stronger activation of semantic representations, while visual similarity effects were equivalent to controls. These results suggest that the verbal short-term memory deficit in Chinese dyslexics might not stem from insufficient activation of phonological information. Based the semantic activation of target characters in dyslexics is greater than in controls, it is possible that the memory deficit of dyslexia is related with deficient inhibition of target semantic representations in short-term memory.


[Geomagnetic field effects on circadian variability of cardiac rhythm].
To study the effect of geomagnetic field (GMF) on circadian rhythm of the heart the author has examined 23 healthy children aged 5-16 years (mean age 12 +/- 4.8). All the examinees have undergone 24-h Holter monitoring with assessment of circadian fluctuations n cardiac rhythm variability (CRV). The data obtained on the parameters Mean, SDNN, SDNN = i, SDANN = i, rMSSD and pNN50 were compared to circadian fluctuations of 3-h indices GMF Ap-index in the test day with estimation of paired correlation index (r). Positive and negative relations between CRV and GMF changes were found in 6 and 8 children, respectively. Groups of GMF-sensitive and GMF-negative children were formed. At 10-year follow-up 3 of 7 GMF-sensitive and 6 of 9 GMF-resistant children developed nonspecific diseases. It is suggested that GMF may have a synchronizing effect on cardiac circadian rhythm. The response of cardiac rhythm to fluctuations of GMF is thought an individual chronotype of the body. GMF-resistant group is characterized by self-regulation of cardiac rhythm which determines reduced availability of exogenic synchronizing effects of GMF.


An experimental approach to quantitative thermal coronary angiography.
Thermal coronary angiography is a noninvasive but not yet quantitative method to intraoperatively assess graft patency in CABG surgery. Aim of this study was to quantify graft flow by measuring perfusion-induced myocardial temperature changes over time. Saphenous vein grafts to the left anterior descending artery were perfused at flow rates of 16-105 ml/min with warm saline. A thermal scanner with a 256 x 256 focal-plane array detector providing a spatial resolution of 1.2 mrad was used. The resulting temperature curves were averaged and a non-linear fit procedure was performed to calculate the time constant (tau) at each flow rate. An increase of myocardial temperature along the LAD with different flow rates could be demonstrated. There was an excellent correlation between the calculated time constant and actual flow (r = 0.96, p < 0.0002). By determining the time constant for different flow rates an estimate of actual graft flow is possible using thermal coronary angiography. Clinical studies have to show if the time constant can be used as a predictor of graft flow in patients.


Reoperations after surgery for acute subdural hematoma: reasons, risk factors, and effects.
To analyze the reasons and patient-related and injury-related risk factors for reoperation after surgery for acute subdural hematoma (SDH) and the effects of reoperation on treatment outcome. Among adult patients operated on for acute SDH between 2013 and 2017, patients reoperated within 14 days after the primary surgery were identified. In all patients, parameters were identified that related to the patient (age, anticoagulation, antiplatelet, and antiepileptic treatment, and alcohol intoxication), trauma (Glasgow Coma Score, SDH thickness, midline shift, midline shift /hematoma thickness rate, other surgical lesion, primary surgery-trephination, craniotomy, or decompressive craniotomy), and Glasgow Outcome Score (GOS). The reasons for reoperation and intervals between primary surgery and reoperation were studied. Of 86 investigated patients, 24 patients were reoperated (27.9%), with a median interval of 2 days between primary surgery and reoperation. No significant differences in patients and injury-related factors were found between reoperated and non-reoperated patients. The rate of primary craniectomies was higher in non-reoperated patients (P = 0.066). The main indications for reoperation were recurrent /significant residual SDH (10 patients), contralateral SDH (5 patients), and expansive intracerebral hematoma or contusion (5 patients). The final median GOS was 3 in non-reoperated and 1.5 in reoperated patients, with good outcomes in 41.2% of non-reoperated and 16.7% of reoperated patients. Reoperation after acute SDH surgery is associated with a significantly worse prognosis. Recurrent /significant residual SDH and contralateral SDH are the most frequently found reasons for reoperation. None of the analyzed parameters were significant reoperation predictors.


Novel Presenting Phenotype in a Child With Autosomal Dominant Best's Vitelliform Macular Dystrophy.
Best's macular dystrophy (BMD) usually manifests with visual failure in the first or second decade of life; however, there is a large variability in expressivity of the disease, and some patients have no manifestation other than a pathological electro-oculogram (EOG). Autosomal dominant Best's vitelliform macular dystrophy (AD-BVMD) has a very specific phenotype that varies with the stage of the disease. In recent years, the authors have seen description of another clinical entity known as autosomal recessive BMD. Herein, the authors describe a 5-year-old girl referred from a peripheral hospital for investigation with a positive family history of BMD. Clinical findings included best-corrected visual acuity of 0.325 and 0.300 in the right and left eyes, respectively, by Sonksen logMar test, full color vision, normal orthoptic examination, and a small degree of hyperopia consistent with age. Macular optical coherence tomography (OCT) showed intraretinal fluid cysts and EOG showed reduced Arden ratio. Genetic testing was done for the proband and her father, who were found to be heterozygous for c.37C>T p. (Arg13Cys). The proband's younger sister will be reviewed and followed up once of age. The authors identified a new phenotype of AD-BVMD; although this is a single patient, more young children with BMD can now be scanned with the availability of hand-held OCT with better knowledge of the phenotype. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:580-585.].


[Rosiglitazone: a clinical development focused on cardio-vascular prevention].
Type 2 diabetes is a recognized independent cardio-vascular risk factor, which adds to other known risk factors. In in vitro or animal models, rosiglitazone and/or other thiazolidinediones induced favourable effects on the various mechanisms involved in atherosclerosis. In type 2 diabetic patients, rosiglitazone and/or other thiazolidinediones have shown beneficial effects on blood pressure, arterial wall, vasomotricity, PAI-1 levels and urinary albumin excretion. These data are briefly reviewed. They justify carrying out a large program of prospective studies aimed to assess the effects of rosiglitazone on cardiovascular morbidity and mortality in type 2 diabetic patients.


[ESTABLISHMENT OF A NEW RADIUS DEFECT MODEL BASED ON ULNA ANATOMICAL MEASUREMENT IN RABBITS].
To introduce a new bone defect model based on the anatomical measurement of radius and ulna in rabbits for offering a standard model for further tissue engineering research. Fifteen healthy 4-month-old New Zealand rabbits were selected for anatomic measurement and radiological measurement of the radius and ulna. Another 30 healthy 4-month-old New Zealand rabbits were randomly divided into groups A, B, and C (n=10). The radius bone defect was created bilaterally in 3 groups. In group A, the periosteum and interosseous membranes were fully removed with jig-saw by approach between extensor carpi radialis muscle and musculus extensor digitorum. The periosteum and interosseous membranes were fully removed in group B, and only periosteum was removed in group C with electric-saw by approach between extensor carpi radialis muscle and flexor digitorum profundus based on anatomical analysis results of ulnar and radial measurement. The gross observation, X-ray, micro-CT three-dimensional reconstruction, bone mineral density (BMD), and bone mineral content (BMC) were observed and recorded at immediate and 15 weeks after operation. HE staining and Masson staining were performed to observe bone formation in the defect areas. Blood vessel injury (1 rabbit), tendon injury (2 rabbits), postoperative hematoma (1 rabbit), and infection (1 rabbit) occurred in group A, postoperative infection (1 rabbit) in group C, and no postoperative complications in group B; the complication rate of group A (50%) was significantly higher than that of groups B (0%) and C (10%) (P<0.05). The radiological examination showed bone defects were fully repaired in groups A and B at 15 weeks, but bridging callus formation was observed in group C. There was no significant difference in BMC and BMD among 3 groups (P>0.05). HE staining and Masson staining results showed bone formation in group A, with structure disturbance and sclerosis. New bone formed in groups B and C, cartilage cells were observed in the center of bone cells. The radius bone defect model established by approach between extensor carpi radialis muscle and flexor digitorum profundus is an ideal model because of better exposures, less intra-operative blood loss, less complications. Interosseous membranes play a role in bone tissue repair process, and the mechanism needs further study.


[Spectacular neurologic manifestations after mild head trauma: retrospective study on 51 children].
Mild head traumas, as a rule, remain a- or paucisymptomatic. In a few cases however, spectacular manifestations develop despite absence of intracerebral lesion. POPULATION, METHODS: We have studied retrospectively 51 such children and contacted their family in order to clarify the follow-up. The dominant symptoms allowed to categorize the following situations: syncope-like loss of consciousness (11 cases), seizures (6), severe headaches with neurologic signs (15), confusion (8), visual disorders (6), amnesic ictus (5). Recurrences were possible but benign: in 8/11 children in the group "syncopes", in 1/6 in the group "seizures", in 5/21 in the 4 other groups. In the latter 4 groups, 11/21 children developed common migraine. Except for the only case who developed epilepsy later on, scholarship was normal in the 25 cases with sufficient follow-up. Beside syncopes and seizures, the long-lasting episodes suggested a migrainous pathogeny, perhaps at a maturative stage where the trigger of migrainous mechanism is at a low level in the brain. The mildness of the knock, the normality of CT scan including when the symptoms are present and the normality of both consciousness and examination once the symptoms have disappeared allow to avoid further investigations.


Charge transport in DNA molecules: Cooperative interplay between the disordered base-pair channel and the ordered backbone.
Charge transport in DNA molecules has raised considerable interest because of its importance in biological processes and potential applications in nanoscale devices. A DNA molecule can be viewed as a quasi-one-dimensional system composed of stacked base pairs (AT , CG) together with backbones of sugar phosphates. Motivated by recent experimental observations on the importance of the backbone integrity, we investigate the interplay between charge transport through the ordered backbone and disordered base stacks with random sequences. By analytical and numerical calculations, we find that the coupling between the backbone and base-pair channels plays an important role in charge transport. The backbone can generate effective hopping constants well beyond the adjacent base pairs, enhancing charge transport through the base-pair channel. The corresponding enhancement of the localization length is nearly independent of the length of the DNA and increases with increasing coupling between backbone and base pair. Our model can explain qualitatively several experimental observations.


Attachment of Chlamydia trachomatis L2 to host cells requires sulfation.
Chlamydia trachomatis is a pathogen responsible for a prevalent sexually transmitted disease. It is also the most common cause of infectious blindness in the developing world. We performed a loss-of-function genetic screen in human haploid cells to identify host factors important in C. trachomatis L2 infection. We identified and confirmed B3GAT3, B4GALT7, and SLC35B2, which encode glucuronosyltransferase I, galactosyltransferase I, and the 3'-phosphoadenosine 5'-phosphosulfate transporter 1, respectively, as important in facilitating Chlamydia infection. Knockout of any of these three genes inhibits Chlamydia attachment. In complementation studies, we found that the introduction of functional copies of these three genes into the null clones restored full susceptibility to Chlamydia infection. The degree of attachment of Chlamydia strongly correlates with the level of sulfation of the host cell, not simply with the amount of heparan sulfate. Thus, other, as-yet unidentified sulfated macromolecules must contribute to infection. These results demonstrate the utility of screens in haploid cells to study interactions of human cells with bacteria. Furthermore, the human null clones generated can be used to investigate the role of heparan sulfate and sulfation in other settings not limited to infectious disease.


Subtypes of sleep disturbance: associations among symptoms, comorbidities, treatment, and medical costs.
Medical claims and survey data were used to evaluate patients with sleep disturbance lasting 1 year or more, and to identify subtypes of sleep disturbance using latent class analysis. Four subtypes were identified from the 1,374 patients. Subtypes differed on the number of sleep disturbance symptoms, presence of non-restorative sleep and comorbidities, degree of daytime impairment, and insomnia severity. The results from this study suggest that patient-reported symptoms of sleep disturbance, the frequency of symptoms, functional impairment, and comorbid conditions are important elements in distinguishing among groups of patients with varying degrees of sleep problems. These data provide evidence that the Insomnia Severity Index (ISI) varies accordingly with the frequency and resulting impairment of symptoms captured in the 4 clusters.


The analysis and identification of charred suspected tea remains unearthed from Warring State Period Tomb.
Recently, a bowl containing charred suspected tea remains unearthed from the early stage of Warring States period tomb in Zoucheng City, Shandong Province, China. To identify the remains is significant for understanding the origin of tea and tea drinking culture. Scientific investigations of the remains were carried out by using calcium phytoliths analysis, Fourier transform infrared spectroscopy (FTIR), Gas Chromatograph Mass Spectrometer (GC/MS) and Thermally assisted hydrolysis-methylation Pyrolysis Gas Chromatography Mass Spectrometry (THM-Py-GC/MS) techniques. Modern tea and modern tea residue were used as reference samples. Through phytoliths analyses, calcium phytoliths identifiable from tea were determined in the archeological remains. The infrared spectra of the archaeological remains was found similar as modern tea residue reference sample. In addition, the biomarker compound of tea-caffeine was determined in the archaeological remains by THM-Py-GC/MS analysis. Furthermore, through GC/MS analysis, some compounds were found both in the archeological remains and the modern tea residue reference samples. Putting the information together, it can be concluded that the archaeological remains in the bowl are tea residue after boiling or brewing by the ancient.


The dose-response relationship between smoking and the risk factor for invasive pulmonary aspergillosis in patients with severe fever with thrombocytopenia syndrome.
Invasive pulmonary aspergillosis (IPA) is common in immuno-compromised people, and a high incidence of IPA has been found in patients with severe fever with thrombocytopenia syndrome (SFTS). Our study aimed to determine the independent risk factors for IPA and the relationship between smoking status and the risk of IPA in SFTS patients. A retrospective analysis of SFTS patients in the First Affiliated Hospital of Nanjing Medical University from May 2011 to December 2021 was reviewed. The patients were divided into two groups: IPA and non-IPA groups. We compared demographic characteristics, clinical manifestation, laboratory parameters, treatment, and prognosis, and explored the risk factors of IPA using logistic regression and ROC curve. The dose-dependent effect of smoking on the risk of IPA was further estimated, including the age of smoking initiation, daily smoking amount, smoking duration, and pack-years of smoking. In total, 189 individuals were included. Compared with the non-IPA group, the IPA group had higher levels of smoking, drinking, cough, dyspnea, aCCI scores, Dabie bandavirus (DBV) RNA load, ferritin, PCT, IL-6, APTT, LDH, BUN, creatinine, and lower levels of FT4 and TSH. The incidences of MODS, admission to ICU, ventilation, and broad-spectrum antibiotic treatment were significantly higher in the IPA group than in the non-IPA group. Multivariable logistic analysis showed that smoking history, cough, creatinine, admission to ICU, broad-spectrum, and corticosteroid therapies were the independent risk factors for IPA in SFTS patients. We further confirmed that the age of smoking initiation <30 years, smoking at least one pack per day, smoking for at least 40 years, and having at least 40 pack-years of smoking exposure were the independent risk factors for IPA among smokers. The prognosis of SFTS patients in the IPA group is worse than that of the non-IPA group. Attention should be paid to SFTS patients with a smoking history, cough, creatinine, admission to ICU, and broad-spectrum and corticosteroid therapies. There is a strong dose-dependent association between smoking and IPA development in SFTS patients. Prophylactic antifungal therapy should be considered for SFTS patients with these risk factors, but further studies are necessary to determine if it is beneficial for the prognosis of these patients.


Effect of dexamethasone on experimental brain edema in cats.
The authors studied the effects of dexamethasone, 0.3 mg/kg/hr administered intravenously beginning 1 hour before injury, in adult cats with brain edema secondary to cold-induced cortical lesions. Edema was quantitatively measured in cortex, gyral white matter, and central (deep) white matter at 3, 24, 48, and 72 hours, with and without dexamethasone, by determining specific gravity (density) of samples in a continuous gradient column. Cold-induced lesions resulted in edema, which was greatest in the white matter of the injured hemisphere but also present in the contralateral hemisphere. Except for a slight but significant increase in density (decreased edema) of cortex at 24 hours, dexamethasone therapy resulted in no reduction of cold-induced edema, and in some cases increased the edema.


Shared and differentiated motor skill impairments in children with dyslexia and/or attention deficit disorder: From simple to complex sequential coordination.
Dyslexia and Attention deficit disorder (AD) are prevalent neurodevelopmental conditions in children and adolescents. They have high comorbidity rates and have both been associated with motor difficulties. Little is known, however, about what is shared or differentiated in dyslexia and AD in terms of motor abilities. Even when motor skill problems are identified, few studies have used the same measurement tools, resulting in inconstant findings. The present study assessed increasingly complex gross motor skills in children and adolescents with dyslexia, AD, and with both Dyslexia and AD. Our results suggest normal performance on simple motor-speed tests, whereas all three groups share a common impairment on unimanual and bimanual sequential motor tasks. Children in these groups generally improve with practice to the same level as normal subjects, though they make more errors. In addition, children with AD are the most impaired on complex bimanual out-of-phase movements and with manual dexterity. These latter findings are examined in light of the Multiple Deficit Model.


The artificial pancreas.
Advances in diabetes technologies have enabled the development of artificial pancreas (closed-loop) systems for people with diabetes. We review the key studies which have led to the adoption of the artificial pancreas in clinical practice and consider ongoing challenges and areas for future enhancements. Studies have demonstrated safety and efficacy of closed-loop insulin delivery systems in free-living settings over periods of up to 6 months for children and adults with type 1 diabetes. Since 2017, four hybrid closed-loop systems have been approved by regulatory bodies worldwide, but these systems are not entirely automated, requiring user interaction to deliver mealtime insulin boluses. Improving usability of these devices in the real-world setting is an important challenge. The artificial pancreas has become the gold standard for the treatment of type 1 diabetes. First-generation systems are increasingly being adopted in clinical practice, however further work is required, developing advanced systems and faster acting insulin analogues to allow complete automation and further reduce the burden of type 1 diabetes.


Effect of industrial dehydration on the soluble carbohydrates and dietary fiber fractions in legumes.
The effects of soaking, cooking, and industrial dehydration treatments on soluble carbohydrates, including raffinose family oligosaccharides (RFOs), and also on total dietary fiber (TDF), insoluble dietary fiber (IDF), and soluble (SDF) dietary fiber fractions were studied in legumes (lentil and chickpea). Ciceritol and stachyose were the main alpha-galactosides for chickpea and lentil, respectively. The processing involved a drastic reduction of soluble carbohydrates of these legumes, 85% in the case of lentil and 57% in the case of chickpea. The processed legume flours presented low residual levels of alpha-galactosides, which are advisable for people with digestive problems. Processing of legumes involved changes in dietary fiber fractions. A general increase of IDF (27-36%) due to the increase of glucose and Klason lignin was observed. However, a different behavior of SDF was exhibited during thermal dehydration, this fraction increasing in the case of chickpea (32%) and decreasing in the case of lentil (27%). This is probably caused by the different structures and compositions of the cell wall networks of the legumes.


Postprandial hyperglycemia in urban South African blacks with and without coronary artery disease.
Coronary artery disease (CAD) is increasing in urban black South Africans during their transition from a rural to a western lifestyle. This study assessed postprandial hyperglycemia, which a risk factor for CAD, in blacks with and without CAD. Fasting lipid levels and postprandial glucometabolic profiles were measured in 40 patients and 20 controls. Normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetes mellitus (DM) were categorized according to American Diabetes Association criteria. Postprandial hyperglycemia was assessed by the oral glucose tolerance test (OGTT) and area under curve (AUC) analysis. Insulin resistance was evaluated by hyperinsulinemic euglycemic clamp (insulin-mediated glucose disposal, M-value). Glucose AUC was higher in patients than controls (p < 0.0001). Highest correlations were between AUC and 0-minute glucose (r = 0.7847; p < 0.0001), and 120-minute glucose (r = 0.9187; p < 0.0001). Patients had higher fasting and postprandial glucose responses (p < 0.05). Glucose concentrations increased among NGT, IGT, and DM categories in patients (p < 0.001) and controls (p < 0.01). Abnormal glucose tolerance was more prevalent in patients (50%) than controls (40%). M-values were lower in patients (p < 0.0001) and decreased between categories, significantly in DM patients (p < 0.02). More patients (70%) than controls (13%) had low M-values (p < 0.001). Postprandial hyperglycemia was common in black CAD patients and glucose concentrations at 0 minute and 120 minutes were the strongest determinants. As glucose tolerance declined, glycemic control deteriorated and insulin resistance worsened. Abnormal glucose tolerance and insulin resistance were more prevalent in patients with CAD.


Prevalence of methicillin-resistant (mecA gene) and heat-resistant Staphylococcus aureus strains in pasteurized camel milk.
Staphylococcus aureus is a significant opportunistic pathogen in humans, dairy cattle, and camels. The presence of antibiotic-resistant and heat-resistant bacteria in camel milk has become a potential public health issue. The phenotypic and molecular characterization of methicillin-resistant staphylococcal strains recovered from pasteurized camel milk distributed in retail markets of Saudi Arabia was assessed. A total of 100 samples were collected between March and May 2017. Out of the 20 S. aureus isolates that were recovered from the pasteurized camel milk, 10 were found to be resistant to cefoxitin (30 µg) and, thus, were designated as methicillin-resistant strains. The resistance ratio of methicillin-resistant S. aureus isolates for a different class of antibiotics was determined by performing the antimicrobial susceptibility test and was estimated to be approximately 60%. Polymerase chain reaction assay was performed to amplify the methicillin-resistant gene mecA, and furthermore, nucleotide sequencing was performed to detect and verify the presence of methicillin-resistant strains. Upon sequencing the putative S. aureus methicillin-resistant strains, we obtained 96 to 100% similarity to the penicillin-binding protein 2a gene (mecA) of the S. aureus strain CS100. Moreover, the 10 methicillin-resistant S. aureus isolates were also identified to be heat resistant and were stable at temperatures up to 85°C for 60 s, with 3 isolates being heat resistant even at 90°C for 60 or 90 s. The mean decimal reduction time (D85 value) was 111 s for all the 10 isolates. No difference was observed in the profile of total protein between the 10 methicillin- and heat-resistant S. aureus isolates and the S. aureus strain ATCC 29737, which was determined by sodium dodecyl sulfate-PAGE analyses. Therefore, we could conclude that a relatively high percentage of the tested pasteurized camel milk samples were contaminated with S. aureus (20%) and methicillin- and heat-resistant S. aureus (10%).


Implementing the NICE OCD/BDD guidelines.
The National Institute of Clinical Excellence (NICE) has produced a nationally coordinated programme of clinical guidelines which provide rigorous and systematically derived statements of best evidence to improve patient care. Successful implementation of the NICE guidelines into clinical practice is complex and challenging and this paper focuses on the specific barriers and facilitators of implementing the obsessive compulsive disorder (OCD) and body dysmorphic disorder (BDD) guidelines. Particular challenges for this guideline are the very nature of OCD/BDD, the adoption of the stepped care model and specific treatment and training issues.


[Blood xylose as a screening test for malabsorption in jejunal mucosa abnormalities; importance of diet in interpretation].
Blood xylose level 60 min. after an oral dose of 10 g/m2 xylose was compared with the histology of the jejunal mucosa in 56 children. Ninety-two percent of children with blood xylose below 20 mg/100 ml had an abnormal jejunal mucosa; 98% of children with a normal mucosa had a blood xylose above 20 mg/100 ml. In children with coeliac disease the following observations were made: 1) blood xylose was above 20 mg/100 ml in 50% of children with flat mucosa; all were given a diet excluding gluten; 2) blood xylose levels which were initially below 20 mg/100 ml were found above this level 3 to 12 days after the onset of the diet; 3) all the histological relapses following re-introduction of gluten in the diet were not associated with a decrease of blood xylose level below 20 mg/100 ml.


[The way for carrying medicine and its containers (XI): "dosage form of patent medicine in the Edo Period"].
In the Edo period, there was a prescribed medicine and a patent one. The former was liquid preparation to be decocted and the latter was solid one. It took a lot of time to prepare a decoction medicine and it was troublesome work. A scene where a person was preparing a decoction medicine in a tumble-down house for a patient was often described in literature of the Edo period to express that they have a serious patent by a novelist. On the other hand, a solid preparation was handy to carry it and convenient for taking so that it was accepted by customers.


[Oxatomide: review of pharmacodynamic effects and clinical effects in dermatology].
Oxatomide is a new anti-allergy drug, derived from benzamidazole, which has shown original pharmacological properties at different stages of the degranulation of mastocytes and basophils, inhibition of the increase of intracellular calcium, inhibition of histamine release and of the synthesis of leukotrienes and prostaglandins. In addition, it has an antagonistic action on the histamine H1 receptors and inhibits the effects of serotonin and SRSA leukotrienes. Clinical trials have shown the clinical efficacy of oxatomide on chronic urticaria and atopic dermatitis, double blind against placebo. Also its action is quicker than certain reference molecules with which it was compared. The product seems to have excellent tolerance. Oxatomide is a molecule of which the pharmacological properties are coupled with clinical efficacy on allergic dermatoses.


Genome analyses of three strains of Rhodobacter sphaeroides: evidence of rapid evolution of chromosome II.
Three strains of Rhodobacter sphaeroides of diverse origin have been under investigation in our laboratory for their genome complexities, including the presence of multiple chromosomes and the distribution of essential genes within their genomes. The genome of R. sphaeroides 2.4.1 has been completely sequenced and fully annotated, and now two additional strains (ATCC 17019 and ATCC 17025) of R. sphaeroides have been sequenced. Thus, genome comparisons have become a useful approach in determining the evolutionary relationships among different strains of R. sphaeroides. In this study, the concatenated chromosomal sequences from the three strains of R. sphaeroides were aligned, using Mauve, to examine the extent of shared DNA regions and the degree of relatedness among their chromosome-specific DNA sequences. In addition, the exact intra- and interchromosomal DNA duplications were analyzed using Mummer. Genome analyses employing these two independent approaches revealed that strain ATCC 17025 diverged considerably from the other two strains, 2.4.1 and ATCC 17029, and that the two latter strains are more closely related to one another. Results further demonstrated that chromosome II (CII)-specific DNA sequences of R. sphaeroides have rapidly evolved, while CI-specific DNA sequences have remained highly conserved. Aside from the size variation of CII of R. sphaeroides, variation in sequence lengths of the CII-shared DNA regions and their high sequence divergence among strains of R. sphaeroides suggest the involvement of CII in the evolution of strain-specific genomic rearrangements, perhaps requiring strains to adapt in specialized niches.


Abnormally expressed miR-23b in Chinese Mongolian at high cardiovascular risk may contribute to monocyte/macrophage inflammatory reaction in atherosclerosis.
Background: The prevalence of coronary heart disease (CHD) appears to be high among Chinese Mongolians. MiR-23b has been proven to play a key role in atherosclerosis. The expression and role of miR-23b in the Mongolians at high cardiovascular risk were explored in the present study.Methods: Forty cases of blood samples from the Mongolians at high cardiovascular risk were enrolled in the present study. The expression of miR-23b was quantified by quantitative real-time PCR. To induce monocytes differentiation into macrophages, HP-1 cells were cultured with phorbol 12-myristate 13-acetate. The level of inflammatory markers was determined by the enzyme-linked immunosorbent assay. The interaction between miR-23b and A20 was explored by the dual luciferase reporter assay.Results: The expression of miR-23b in the Mongolian at high cardiovascular risk was higher than that in healthy Mongolian volunteers. Decrease in ATP-binding cassette transporter A1 caused by miR-23b is responsible for TC accumulation in the Mongolian at high cardiovascular risk. MiR-23b enhanced the oxidized low-density lipoprotein (oxLDL)-induced inflammatory response of THP-1 derived macrophage. MiR-23b regulated nuclear factor-κB (NF-κB) pathway through targeting A20. MiR-23b mediated oxLDL-induced inflammatory response of peripheral blood mononuclear cell in the Mongolian at high cardiovascular risk.Conclusion MiR-23b enhanced oxLDL-induced inflammatory response of macrophages in the Mongolian at high cardiovascular risk through the A20/NF-κB signaling pathway, and thus contributing to atherosclerosis.


Tunable Artificial Relaxor Behavior in [BaTiO_{3}]_{m}/[BaZrO_{3}]_{n} Superlattices.
[BaTiO_{3}]_{m}/[BaZrO_{3}]_{n} (m, n=4-12) superlattices are used to demonstrate the fabrication and deterministic control of an artificial relaxor. X-ray diffraction and atomic-resolution imaging studies confirm the production of high-quality heterostructures. With decreasing BaTiO_{3} layer thickness, dielectric measurements reveal systematically lower dielectric-maximum temperatures, while hysteresis loops and third-harmonic nonlinearity studies suggest a transition from ferroelectriclike to relaxorlike behavior driven by tuning the random-field strength. This system provides a novel platform for studying the size effect and interaction length scale of the nanoscale-polar structures in relaxors.


Lack of relationship between 17-hydroxyprogesterone response to buserelin testing and hyperinsulinemia in polycystic ovary syndrome.
To determine whether hyperinsulinism affects cytochrome P450c17 alpha activity by investigating the correlation between 17-hydroxyprogesterone (17-OHP) hyper-responsiveness to the gonadotropin-releasing hormone (GnRH) agonist, buserelin, and the insulin response to oral glucose in polycystic ovary syndrome (PCOS). Ultrasound, clinical and hormonal parameters were used to define PCOS in this prospective clinical study. We investigated the correlation between the 17-OHP response to buserelin testing and the insulin response to oral glucose in PCOS. Twenty-eight women with PCOS and eighteen normal women were included in the study. 17-OHP response to buserelin, and insulin and C-peptide responses to oral glucose were measured. Twenty-five women with PCOS had an increased 17-OHP response. The PCOS patients showed significantly higher mean post-glucose load insulin and C-peptide levels than controls (P < 0.05). No significant correlations were found between basal 17-OHP and fasting insulin or fasting C-peptide, between peak 17-OHP and fasting insulin, peak insulin or peak C-peptide, between 17-OHP area under the curve (AUC) and insulin AUC or C-peptide AUC, and between percent increment in 17-OHP and insulin AUC or C-peptide AUC (P > 0.05). Lack of a relationship between the 17-OHP response to the GnRH agonist buserelin and hyperinsulinism suggests that hyperinsulinism may not play a role in the dysregulation of the cytochrome P450c17 alpha enzyme seen in PCOS.