Comparison of the Effect of Coaddition of Li Compounds and Addition of a Single Li Compound on Reactivity and Structure of Magnesium Hydroxide.
Mg(OH)2 is a chemical heat storage material that is studied for the utilization of 300-350 °C waste heat. In this study, LiCl and LiOH were coadded to Mg(OH)2, and the reactivity and structural evolution were investigated. In the hydration of samples at 200 °C subsequent to dehydration at 270 °C, Mg(OH)2 with coadded LiCl and LiOH showed excellent hydration reactivity, with a heat output density of 1053 kJ kg-1. The coaddition of LiCl and LiOH enhanced both the dehydration and the hydration reactivity of Mg(OH)2. X-ray diffraction analysis indicated that the addition of LiOH to Mg(OH)2 promoted the decomposition of Mg(OH)2 and the diffusion of water on the surface of Mg(OH)2, whereas the addition of LiCl to Mg(OH)2 promoted these processes in the bulk phase of Mg(OH)2.


The definition of an MB related specificity by a monoclonal antibody.
A number of monoclonal antibodies have been described that react with monomorphic and polymorphic Ia-like specificities on human B cells, but it is not clear whether these react with HLA-DR encoded molecules or with the products of other closely linked genes within the MHC, such as MB, MT, or DC 1 antigens. A monoclonal antibody is described herein (MC-26.1) which detects a new Ia-like specificity as shown by B-cell reactivity, chemistry, family studies, including recombinant family and coprecipitation studies. The latter studies showed that specificity detected by the MC-26.1 antibody coprecipitated with determinants detected by conventional anti-MB3 and MT3, but not with HLA-DR4 antisera. The determinant was polymorphic but not related to any of the known MB or MT specificities. However, cross-reactions were demonstrated by the variability of reaction on different individuals. Coprecipitation studies indicate that the antigen defined by MC-26.1 coprecipitates with MB and MT specificities suggesting that the antibody defines a new specificity on the MB3 and MT3 molecules.


Spatial analysis of two-species interactions.
In this paper, I present and discuss some methods for the analysis of univariate and bivariate spatial point pattern data. Examples of such data in ecology include x-y coordinates of organisms in mapped field plots. I illustrate the methods with analyses of data from mapped field plots on Mount St. Helens, Washington state, USA. The statistical methods I emphasize are graphical methods that rely on analysis of distances between organisms. Hypothesis testing for methods like these is easily done using Monte Carlo methods, which I also discuss. For both univariate and bivariate analyses, I find that second-order methods such as K-function plots are often preferable to first-order methods (i.e., QQ-plots). However, for multivariate analyses, these second-order methods are more sensitive to small sample sizes than first-order analyses.


[Clinical trial on treatment of acute cerebral infarction with TCM treatment according to syndrome differentiation combining Western medicine by staging].
To observe the curative effect of integrated Chinese and Western medicine on acute cerebral infarction (ACI). Two hundred and seventy-nine ACI patients were assigned to two groups. The control group (140 cases) was treated with Western medicine by staging and the treated group (139 cases) was given TCM therapy according to syndrome differentiation on the basis of Western medicine. The end point was set at the 90th day of the administration. The curative effect was assessed by Chinese stroke scale (CSS), National Institutes of health stroke scale score (NIHSS), Rankin scale and Barthel index (BI). At the end point of the trial, the total effective rate was 73.38% in the treated group and 61.43% in the control group, the former was superior to the latter (P<0.05). There were 66 cases (47.14%) in the control group and 80 cases (57.55%) in the treated group with improvement rate of NIHSS > or =40%, 65 cases (46.43%) with their Rankin scale within 0-2 grade in the control group and 78 cases (56.12%) in the treated group, 60 cases (42.86%) in the control group and 71 cases (51.08%) in the treated group with BI > or =85, 61 cases (43.57%) in the control group and 72 cases (51.80%) in the treated group with improvement rate of CSS > or = 46%, comparison between them showed significant differences (P < 0.05). TCM therapy accord-ing to syndrome differentiation combined with Western medicine by staging shows better curative efficacy on ACI.


Readjustment of Urban Veterans: A Mental Health and Substance Use Profile of Iraq and Afghanistan Veterans in Higher Education.
To identify the prevalence of substance use and mental health problems among veterans and student service members/veterans (SSM/V) returning from Iraq and Afghanistan to New York City's low-income neighborhoods. A sample of 122 veterans attending college and 116 veterans not enrolled recruited using respondent-driven sampling. Logistic regression analysis of variation in characteristics of those veterans attending college; linear regression examining effects of college attendance on life satisfaction. Having a traumatic brain injury or disability was positively associated with college attendance. Being married, employed, or in college was predictive of overall life satisfaction. SSM/V were significantly less likely to screen positive for depression or drug use disorder. African American veterans were significantly less likely to attend college than white or Hispanic veterans. Substance use and some mental health disorders do not preclude inner-city veterans from entering higher education. This study contributes to the sparse literature on African American veterans and SSM/V.


Endoscopic studies on the minute structures of colonic mucosa in the follow-up observation of ulcerative colitis.
Thirty cases of ulcerative colitis were examined endoscopically by means of magnifying colonoscope with dye spraying method (the combined method), and their minute mucosal structures were classified into four categories endoscopically, which correlated well with the histological findings. By this procedure, it was easy to detect the subsidence of inflammation of the mucosa in the quiescent phase or to reveal the active inflammatory involvement of the bowel. Moreover, inspecting the minute changes of the colonic mucosa detected by the combined method, remission was more correctly decided and rigid control is contributing to the decrease in the recent rate of recurrence of ulcerative colitis.


Correlates of self-report chronic insomnia disorders with 1-6 month and 6-month durations in home-dwelling urban older adults - the Shih-Pai Sleep Study in Taiwan: a cross-sectional community study.
To examine the correlates of insomnia disorder with different durations in home-dwelling older adults. A cross-sectional survey in the Shih-Pai area of Taipei City, Taiwan (The Shih-Pai Sleep Study). A total 4047 subjects over the age of 65 years completed the study (2259 men and 1788 women). The Pittsburgh Sleep Quality Index and the duration of insomnia symptoms were used to identify DSM-IV 1-6 month and 6-month insomnia disorders. The prevalence of DSM-IV defined insomnia disorder was 5.8 %; two-thirds of these case lasted for ≥6 months. The shared correlates for both 1-6 and 6-month insomnia disorders were gender (women), depression and moderate pain. Pulmonary diseases were exclusively associated with 1-6 month insomnia disorder (OR: 2.57, 95 % CI: 1.46-4.52). In contrast, heart disease (OR: 1.73, 95 % CI: 1.21-2.49) and severe pain (OR: 2.34, 95 % CI: 1.14-4.40) were associated with 6-month insomnia disorder. The prevalence of persistent insomnia disorder is higher than short-term insomnia disorder. Correlates for less persistent and more persistent insomnia disorder appears to be partially different. Duration quantifiers may be important in the identification of the etiology of insomnia and further studies with follow-ups are needed to examine the order of developing insomnia disorder and associated conditions.


Techno-economic analysis of electricity generation from household sewage sludge in different regions of Nigeria.
Waste management has been a chronic environmental challenge in Nigeria, coupled with declining economic performance due to energy crises. This study was designed to estimate electricity potential of sewage sludge to meet the 2030 Renewable Energy target. However, there was a need to fill the gap in data related to wastewater management in Nigeria. The wastewater and sludge generated from households were evaluated based on data on population, access to water, and coverage of sewer networks. Consequently, the technical and economic feasibility of electricity generation was assessed using Anaerobic Digestion (AD)1 and Incineration (INC)2 scenarios. The core results found that North Central had the highest potential for wastewater generation (142.8-403.6 billion litres/yr) and collection (8.3-37.5 billion litres/yr) over 20 years. However, the South East had the highest average sewer collection rate of 9.08 %. The AD technology was the most technically viable, with a maximum generation of 6.8 GWh/yr in the North Central. In comparison, the INC outperformed AD in most of the financial viability indicators considered viz-a-viz: Life Cycle Cost (LCC),3 Net Present Value (NPV),4 Pay Back Period (PBP),5 Internal Rate of Return (IRR),6 Levelized Cost of Energy (LCOE).7 The AD had a higher NPV of 16.3-69.58 million USD and a shorter PBP of about 4 years. The INC had a lower LCC of 0.1-0.34 million USD, LCOE of 0.046-0.094 USD/kWh, and a higher IRR of 19.3-25 %. Additionally, the sensitivity of NPV and INC to changes in economic factors would be noteworthy for investors and policymakers. Ultimately, the choice of technology should reflect the fiscal goal and priorities of a project.


Correction: Public communication by research institutes compared across countries and sciences: Building capacity for engagement or competing for visibility?
[This corrects the article DOI: 10.1371/journal.pone.0235191.].


The mechanism of GABAB-mediated slowing of the activation phase of high voltage-activated Ca2+ channels in rat sensory neurons.
The mechanism underlying the slowed activation of the high voltage-activated Ca2+ current (HVA-ICa) in the presence of (-)-baclofen was studied in cultured neurons of rat dorsal root ganglia. The decay phase of the baclofen-sensitive component of HVA-ICa was described by a sum of two exponential functions. Although the inhibited portion in the amplitude of the baclofen-sensitive component of HVA-ICa was increased in a concentration-dependent manner, the two decay time constants remained unaffected regardless of the concentration of baclofen. Furthermore, the baclofen-sensitive component of HVA-ICa was largely inactivated by a depolarizing prepulse (-30 mV for 0.5 s). These results support the notion that the slowed activation of the HVA-ICa in the presence of baclofen is due to a preferential inhibition of the inactivating component of HVA-ICa rather than due to voltage-dependent unblocking of a single population of HVA-ICa.


Evaluation of efficacy and safety of gefitinib as monotherapy in Chinese patients with advanced non-small cell lung cancer and very poor performance status.
This paper reports the outcome of gefitinib for Chinese advanced NSCLC patients with poor performance status (PS) at the Peking Union Medical College Hospital. From Oct 2002 to Apr. 2006, 42 advanced NSCLC patients with PS 3/4 received gefitinib 250 mg/day treatment. Median survival (MS) were calculated using the Kaplan-Meier method and a Cox regression model was used to find main factors affecting MS. Adverse events (AEs) were generally mild (grade 1 and 2) and reversible. The most frequent AEs were rash 72.2% (26/42) and diarrhea 44.4% (26/42). The objective tumor response rate and stable disease rate were 40.5% and 26.2% respectively, and median survival(MS) of all patients was 10.1 months (95% confidential interval CI, 3.4 ~ 16.8), and progression-free survival (PFS) was 5.7 months (95% CI, 4.5 ~ 6.9). The MS were significantly related with objective response of gefitinib. Objective responses was significantly related with rashes induced with gefitinib. Our study suggest that treatment with gefitinib may be well tolerated and beneficial for Chinese patients with poor PS, and the safety and efficacy were similar to patients with good PS.


The cellular inflammatory response in nicotinate skin reactions.
Sequential skin biopsies of nicotinate-treated skin from nine normal subjects, three aspirin-pretreated normal subjects and six atopic eczema patients were examined. An erythematous skin reaction was seen in the nine normal subjects and to a lesser degree in one atopic eczema patient, but not in the aspirin-pretreated subjects nor in five remaining atopics. Accumulation of a mononuclear cell perivascular infiltrate was seen from 15 min onwards in the normal subjects. Neutrophils became the predominant cell invading thickened vessel walls and in the perivascular space beginning at 2 h and persisting up to 48 h. Leucocytoclasis was observed at 24 h. Immunofluorescence studies showed only non-specific fibrinogen deposits in papillary capillaries in the three groups of subjects. The chloroacetate esterase reaction and immunohistochemical labelling with OKM I confirmed a marked neutrophilia at 2 h and 24 h. Neutrophils were seen in one atopic eczema patient, but were not observed in the remainder, nor in the skin of the aspirin-pretreated normal subjects. Topical application of nicotinate causes non-allergenic, leucocytoclastic vascular damage in normal skin which can be inhibited by aspirin and which is reduced or absent in atopic eczema.


Pupal diapause termination in Bactrocera minax: an insight on 20-hydroxyecdysone induced phenotypic and genotypic expressions.
The Chinese citrus fruit fly, Bactrocera minax, is an economically important pest of citrus. It exhibits pupal diapause from November to May to combat harsh environmental conditions. Such a long pupal diapause is a barrier for laboratory rearing and development of control strategies against this pest. In the present study, 20-hydroxyecdysone (20E) was used to break pupal diapause of B. minax by topical application. After diapause termination by 20E treated, the pupal ontogenetic processes were observed along the temporal trajectory. The pupal response time to 20E was estimated by detecting the relative expression of 20E responsive genes at different times after 20E-treatment. Results revealed that 20E could effectively terminate the pupal diapause in a dose-dependent manner and significantly shorten the time for 50% adult emergence (Et50). 20E response genes, including ecr, broad and foxo, were up-regulated within 72h, indicating these genes are involved in pupal metamorphosis and diapause termination processes. Morphological changes showed the pupal metamorphosis began ~7 days after 20E-treatment at 22 °C. This study does not only pave the way for artificial rearing in the laboratory through manipulating of pupal diapause termination, but also deepens our understanding of the underlying pupal diapause termination mechanism of B. minax.


A Machine-Based Approach to Preoperatively Identify Patients with the Most and Least Benefit Associated with Resection for Intrahepatic Cholangiocarcinoma: An International Multi-institutional Analysis of 1146 Patients.
Accurate risk stratification and patient selection is necessary to identify patients who will benefit the most from surgery or be better treated with other non-surgical treatment strategies. We sought to identify which patients in the preoperative setting would likely derive the most or least benefit from resection of intrahepatic cholangiocarcinoma (ICC). Patients who underwent curative-intent resection for ICC between 1990 and 2017 were identified from an international multi-institutional database. A machine-based classification and regression tree (CART) was used to generate homogeneous groups of patients relative to overall survival (OS) based on preoperative factors. Among 1146 patients, CART analysis revealed tumor number and size, albumin-bilirubin (ALBI) grade and preoperative lymph node (LN) status as the strongest prognostic factors associated with OS among patients undergoing resection for ICC. In turn, four groups of patients with distinct outcomes were generated through machine learning: Group 1 (n = 228): single ICC, size ≤ 5 cm, ALBI grade I, negative preoperative LN status; Group 2 (n = 708): (1) single tumor > 5 cm, (2) single tumor ≤ 5 cm, ALBI grade 2/3, and (3) single tumor ≤ 5 cm, ALBI grade 1, metastatic/suspicious LNs; Group 3 (n = 150): 2-3 tumors; Group 4 (n = 60): ≥ 4 tumors. 5-year OS among Group 1, 2, 3, and 4 patients was 60.5%, 35.8%, 27.5%, and 3.8%, respectively (p < 0.001). Similarly, 5-year disease-free survival (DFS) among Group 1, 2, 3, and 4 patients was 47%, 27.2%, 6.8%, and 0%, respectively (p < 0.001). The machine-based CART model identified distinct prognostic groups of patients with distinct outcomes based on preoperative factors. Survival decision trees may be useful as guides in preoperative patient selection and risk stratification.


The influence of negative emotion on brand extension as reflected by the change of N2: a preliminary study.
The aim of the present study is to find the neural features of the impact of induced negative emotion on brand extension. Facing three sequential stimuli in triples consisted of negative emotion pictures (stimulus 1), beverage brand names (stimulus 2), and product names (stimulus 3) in other categories, 20 participants were asked to indicate the suitability of extending the brand in stimulus 2 to the product category in stimulus 3. The stimulus triples were divided into six conditions depending on the emotion (neutral and negative) and the extension product category in stimulus 3: beverage, clothing, and the household appliance. A negative component reflecting conflict, N2, was recorded for each condition on the subjects' scalp. The induced negative emotion elicited significantly larger amplitude of N2 than did the induced neutral emotion in the moderate extension type (extending to the clothing product), whereas no significant difference was observed in any of the other two extension types. The findings indicate that the induced negative emotion has a specific negative impact on moderate brand extension, and the amplitude of N2 can be viewed as a reference measure reflecting such effect.


Noninvasive mechanical ventilation in a patient with respiratory failure after hematopoietic progenitor transplantation.
Respiratory failure requiring orotracheal intubation (OTI) and mechanical ventilation (MV) is almost always a fatal complication in patients who undergo hematopoietic progenitor transplantation (HPT). We present the case of a woman who suffered respiratory failure with bilateral infiltrates on a chest X-ray taken on day +14 following autologous bone marrow transplantation. We managed the patient satisfactorily with noninvasive ventilation, avoiding OTI. We believe that patients with non-progressive pulmonary lesions and without multiple system organ failure, may be correctly managed with noninvasive positive-pressure ventilation (NPPV).


Correction: A Novel Narrative E-Writing Intervention for Parents of Children With Chronic Life-Threatening Illnesses: Protocol for a Pilot, Open-Label Randomized Controlled Trial.
[This corrects the article DOI: 10.2196/17561.].


Definitive diagnosis of early enamel and dentin cracks based on microscopic evaluation.
The diagnoses of cracked teeth and incomplete coronal fracture have historically been symptom based. The dental operating microscope at 16x magnification can fundamentally change a clinician's ability to diagnose such conditions. Clinicians have been observing cracks under extreme magnification for nearly a decade. Patterns have become clear that can lead to appropriate treatment prior to symptoms or to devastation to tooth structure. Conversely, many cracks are not structural and can lead to misdiagnosis and overtreatment. Methodic microscopic examination, an understanding of crack progression, and an appreciation of the types of cracks will guide a doctor to make appropriate decisions. Teeth can have structural cracks in various stages. To date, diagnosis and treatment are very often at end stage of crack development. This article gives new guidelines for recognition, visualization, classification, and treatment of cracked teeth based on the routine use of 16x magnification. The significance of enamel cracks as they relate to dentinal cracks is detailed.


Disease Burden, Treatment Patterns, and Economic Impact of Rectovaginal Fistulas in Patients with Crohn's Disease: Findings from a Retrospective, Observational, Longitudinal Study Based on US Claims Databases.
Crohn's-related rectovaginal fistulas (RVF) greatly impact quality of life and are notoriously difficult to treat. The aim of this study was to assess the burden of recurrent episodes of care for RVF and its economic impact. A retrospective observational cohort study of administrative US claims databases was conducted. Eligible patients were female adults, with a diagnosis code for Crohn's disease with or without a diagnosis/procedural code for RVF. For the RVF cohort, rates of recurrence of RVF episodes of care were estimated using Kaplan-Meier analyses. Healthcare resource utilization (HCRU) and direct healthcare costs were compared between the RVF cohort and RVF-free cohort. Mean ages in the RVF cohort (n = 963) and RVF-free cohort (n = 56,564) were 47.2 and 50.8 years, with a mean follow-up period of 58.7 and 49.8 months, respectively. For the RVF cohort, the probability of having a second RVF episode of care within 2 years of the first one was estimated to be 35.9% and of having a third episode within 2 years of the second was 47.8%. During the first 2 years, the RVF cohort had 67% more inpatient admissions than the RVF-free cohort with each RVF episode of care being associated with 16% more admissions. The estimated incremental cost associated with having RVF was US$17,561, with an incremental cost of US$11,607 for each additional RVF episode of care. This real-world study highlights the significant impact of RVF in patients with Crohn's disease with regard to repeat interventions and associated HCRU and direct healthcare costs, suggesting novel therapeutics are needed in this patient population.


A speech-aid prosthesis for anterior maxillary implant-supported prostheses.
A procedure has been described that can improve speech deficiencies associated with anterior maxillary implant-supported prostheses. The speech-aid prosthesis has been found to be safe, effective, and cost-efficient.


Preparation of HCV NS3 and NS5B proteins to support small-molecule drug discovery.
Production of high-quality, well-characterized recombinant proteins facilitates screening of compound libraries. The protocols detailed in this unit are used to purify three recombinant enzymes that are widely used in HCV research: the HCV NS3 protease domain, the helicase domain as an NS3+NS4A complex, and the NS5B RNA-dependent RNA polymerase. The active enzymes are purified to homogeneity by two-column chromatography to support a screening program for HCV inhibitors.


Molecular analysis of the echovirus 18 prototype: evidence of interserotypic recombination with echovirus 9.
Echovirus 18 (EV18) is one of the echovirus serotypes associated with human diseases and in particular aseptic meningitis. To facilitate studies of the molecular epidemiology of EV18 and the evolution of enteroviruses in general, the complete nucleotide (nt) sequence was determined for the echovirus 18 prototype strain (Metcalf, EV18M). Excluding the poly A sequence, the genome consists of 7410 nt divided into a 740 nt 5' untranslated region (5' UTR), a 6567 nt long open reading frame coding for a 2189 amino acid (aa) polyprotein and a 103 nt 3' UTR. Molecular analysis of the EV18M genome showed a typical enterovirus-like organization. Phylogenetic analysis of the structural and non-structural genes revealed a pattern of different relationships to other echo- and coxsackieviruses. Similarity analysis demonstrated that the Hill strain of echovirus 9 is most likely the result of a previous recombination event between ancestors of the echovirus 9 strain Barty (5' half of the genome) and EV18M (3' half). Using a maximum likelihood approach, the recombination point was mapped to the 2C gene.


[Résistance à l'aspirine : l'ennemi de mon ami est mon ennemi].
Low dose aspirin is an efficient antiplatelet agent to decrease the risk of occlusive arterial events, however it is not infallible. Aspirin resistance describe its inability to block the formation of thromboxane A2 in platelets and/or to produce an inhibitory effect on platelet aggregation. Detection of aspirin resistance relies on the results of various platelet function tests or on blood and urinary thromboxane metabolites concentrations, but these methods show very low correlation and reproducibility. Moreover, light-transmission aggregometry using arachidonic acid, known as the reference functional assay, requires technical expertise. The incidence rate of aspirin resistance amoung populations suffering from cardiovascular diseases is about 25%, however there is a wide variability depending on the specificity of the used test and the clinical features of the considered population. Aspirin resistance is associated with the recurrence of arterial occlusive events: the odds ratio is about 4 all tests combined, therefore it could be considered as a risk marker. Evidence is lacking regarding the relevance of these tests to resort an intensification of the antithrombotic treatment, and experts recommend to reserve their use for high-risk situations. Nevertheless several studies have explored the effect of dose increases or intake frequency increases, and revealed encouraging results regarding pharmacodynamic endpoints. The reasons for aspirin resistance are numerous, often remain debate, and can accumulate to result in poor response to aspirin.


Identification of benzhydrol as a urinary metabolite of diphenylmethane in the rat.
Liquid-liquid extraction and preparative thin-layer chromatography were used to isolate 30 micromoles of benzhydrol from the beta-glucuronidase treated 24 hour urine of rats administered 5.3 mmoles of diphenylmethane. The benzhydrol was identified by its melting point, elemental analysis, infrared, nuclear magnetic resonance, and mass spectra.


High-fat diet impairs cognitive function of zebrafish.
An unhealthy diet with excessive fat intake has often been claimed to induce not only obesity but also cognitive dysfunction in mammals; however, it is not known whether this is the case in zebrafish. Here, we investigated the effect of excessive fat in the diet on cognitive function and on gene expression in the telencephalon of zebrafish. Cognitive function, as measured by active avoidance test, was impaired by feeding of a high-fat diet compared with a control diet. In RNA sequencing analysis of the telencephalon, 97 genes were identified with a fold change in expression greater than 2 and a p-value less than 0.05 between the two diets. In quantitative real-time PCR analysis of the telencephalon, genes related to neuronal activity, anti-oxidative stress, blood-brain barrier function and amyloid-β degradation were found to be downregulated, whereas genes related to apoptosis and amyloid-β production were found to be upregulated, in the high-fat diet group, which are changes known to occur in mammals fed a high-fat diet. Collectively, these results are similar to those found in mammals, suggesting that zebrafish can serve as a suitable animal model in research into cognitive impairment induced by excessive fat in the diet.


Isolated Retrodental Epidural Hematoma Without Dens Fracture.
Traumatic spinal epidural hematomas (TSEDH) are rare, with the reported incidence being < 1% of all spinal injuries. Causes of TSEDHs include vertebral fractures, obstetrical birth trauma, lumbar punctures, postsurgical bleeding, epidural anesthesia, and missile injuries. The retrodental location has not been reported as a location for spontaneous epidural hematoma. A 4-year-old boy was admitted to our Emergency Department after falling down and experiencing head trauma. Glasgow Coma Scale score was 15/15 with no neurologic deficit. Brain computed tomography scan showed isolated hyperdense hematoma in the retrodental area without any fractures in the skull or cervical vertebrae. Brain and cervical magnetic resonance imaging showed a retrodental acute hematoma that was isointense in T1-weighted sequences and hypointense in T2-weighted sequences. The hematoma was in the epidural space with possible odontoid process intracapsular origin. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Isolated retrodental epidural hematoma without dens fracture is an extremely rare pathology and finding, and to the best of our knowledge, this is the first case to be reported in the literature. Emergency physicians should consider this pathology for any patients presenting for head trauma with head hematoma.


A novel gross deletion caused by non-homologous recombination of the PDHX gene in a patient with pyruvate dehydrogenase deficiency.
We report here the molecular analysis of a pyruvate dehydrogenase E3-binding protein (PDH-E3BP) deficiency in a new patient, born to first cousin parents. She has initially presented with a non-progressive and unspecific encephalopathy, followed by an acute neurological deterioration at 14 years of age. E3BP subunit was undetectable on Western blot. The sequence of exons 1-9 and exon 11 of the PDHX gene were normal, but exon 10 was impossible to amplify with standard PCR. Long-range PCR including exons 9-11 (11.5 kb) was performed. The patient's sample displayed a unique PCR product of 7.5 kb, whereas the parents' samples displayed two bands (11.5 and 7.5 kb). The deletion breakpoints were determined by restriction analysis followed by direct sequencing. The homozygous deletion covered the end of intron 9, exon 10 and the beginning of intron 10 and was found to be 3913 bp long. The cDNA sequencing confirmed the deletion of exon 10. The most probable mechanism for this gross deletion appears to be a slipped mispairing mediated by an exact direct repeat CCACTG. It is the first time that a non-homologous recombination is reported in the PDHX gene causing pyruvate dehydrogenase complex (PDHc) deficiency.


Coagulation and fibrinolytic systems during liver regeneration in the early period after adult living related partial liver transplantation.
In this study, we investigated the differences in the perioperative blood coagulation and fibrinolytic systems (BCF) between donor and recipient after adult living related partial liver transplantation (ALRPLT), with particular reference to serum plasminogen-activator inhibitor-1 (PAI-1) and soluble fibinogen level. The BCF were unstable in the recipient compared with the donor. The recipient fibrinolytic system was the same as the donor system except for PAI-1, which was remarkably increased on day 1 after transplantation in the recipient. The recipient is thought to have disseminated intravascular coagulation in the early period after ALRPLT. Soluble fibrinogen may be a useful marker for improvement in the BCF system. The elevation of PAI-1 in recipients on day 1 after transplantation may be a marker of injury from the shear stress from excessive portal hypertension after ALRPLT.


Gonadotropin receptors of human corpus luteum during menstrual cycle and pregnancy.
Specific high-affinity low-capacity binding of human chorionic gonadotropin (hCG) and lutropin (hLH) was demonstrated in the plasma membrane fractions of human corpora lutea. The number of binding sites for both hormones increased from early to late luteal phase, whereas regressing corpus luteum from proliferative phase did not bind either hormone. On the basis of apparent dissociation constants the affinity of the receptor for hLH is highest during early luteal phase and decreases toward the end of the cycle, which may reflect an increasing insensitivity of the corpus luteum to circulating hLH. By contrast, the affinity of the receptor for hCG is highest in the midluteal phase. There are gonadotropin binding sites in the human corpus luteum also during pregnancy, but they are saturated by endogenous hCG. Evidence for this was obtained by elution of hCG with 0.15M sodium chloride at pH 2.3 from washed plasma membrane fractions of luteal tissue from six to 16 week's gestation. After acid treatment and neutralization these preparations showed specific binding for 125I-labeled hCG, but not for 125I-labeled hLH. Our results demonstrate a shift in the balance of affinity of the gonadotropin receptor from hLH to hCG during the course of luteal phase, and during pregnancy the binding sites appear to be available for hCG only.


Association between prolonged breastfeeding and bone mineral density and osteoporosis in postmenopausal women: KNHANES 2010-2011.
This study showed that a negative correlation between duration of breastfeeding and bone mineral density (BMD) in the lumbar spine and prolonged breastfeeding is an independent risk for osteoporosis in postmenopausal women. The present study suggests that postmenopausal women with a history of prolonged breastfeeding require more careful screening for osteoporosis. Several studies suggest that breastfeeding and childbirth lead to maternal calcium loss and a decline in BMD. While the association between breastfeeding and BMD immediately after weaning is well-established, the effects of breastfeeding on postmenopausal women have been controversial. The aim of this study was to examine the effects of breastfeeding on bone mineral density (BMD) and the prevalence of osteoporosis in postmenopausal women. The present study was a cross-sectional survey based on the Korea National Health and Nutrition Examination Survey (KNHANES) 2010 and 2011 data. The association between breastfeeding and BMD and osteoporosis was examined in 1222 postmenopausal women. The duration of breastfeeding and BMD in the lumbar spine showed a negative correlation. The association between duration of breastfeeding and BMD remained significant after adjustment for reproductive factors and other confounding factors (P = 0.008). However, the number of deliveries and age at the time of delivery did not correlate with BMD at any site after adjustment. Moreover, the prevalence of osteoporosis in postmenopausal women with a history of prolonged breastfeeding was significantly higher than that in women with a short history of breastfeeding (≥37 months, OR = 3.292; 95 % CI 1.485-7.299). The prevalence of lumbar spine fracture showed a significant increasing trend with the increase in the duration of breastfeeding. Prolonged breastfeeding was significantly associated with low BMD in the lumbar spine and higher prevalence of osteoporosis. However, the number of deliveries or age at the time of childbirth did not influence BMD.


The effect of single weekly paclitaxel in heavily pretreated patients with recurrent or persistent advanced ovarian cancer.
We have reported that single weekly paclitaxel has moderate activity in heavily pretreated ovarian cancer patients and is associated with a favorable toxicity profile. The purpose of this study was to reconfirm the effect of weekly paclitaxel in more number of cases. Although 39 patients were enrolled, 37 patients with recurrent or persistent ovarian cancer previously treated with between one and three chemotherapeutic regimens containing platinum were eligible. Patients had measurable or assessable disease defined by clinical exam, radiographic studies, or serum CA 125. One cycle of treatment consisted of paclitaxel 80 mg/m2/week in 1-h infusion, 3 weeks on, 1 week off, and repeated at least twice. Two patients were withdrawn because of refusal of further treatment for neuropathy after the first cycle. Clinical responses were defined by established criteria. Thirty-seven patients were included in this intent-to-treat study. The overall clinical response rate was 45.9% (5 complete responses, 12 partial responses). The clinical response rate in patients with measurable tumor was 25.0% (2 complete responses, 1 partial response), while that in patients without measurable tumor and with assessable CA 125 levels was 56.0% (3 complete responses, 11 partial responses). Clinical response rate in patients with chemotherapy-free interval more than 6 months had about twice higher than that in patients with chemotherapy-free interval less than 6 months. The clinical response rate by number of prior regimens revealed that as number of prior regimens increases, the response rate decreases. Weekly paclitaxel has significant antitumor activity in heavily pretreated patients with recurrent or persistent ovarian carcinoma and warrants as second or third line chemotherapy in such setting.


Synthesis of caged 2,3,3a,7a-tetrahydro-3,6-methanobenzofuran-7(6H)-ones: Evaluating the minimum structure for apoptosis induction by gambogic acid.
We have reported the discovery of gambogic acid (GA) as a potent apoptosis inducer and the identification of transferrin receptor as its molecular target. In order to understand the basic pharmacophore of GA for inducing apoptosis and to discover novel and simplified derivatives as potential anti-cancer agents, we explored the synthesis of caged 2,3,3a,7a-tetrahydro-3,6-methanobenzofuran-7(6H)-ones (4-oxatricyclo[188.8.131.52]decan-2-ones). Three types of 2,3,3a,7a-tetrahydro-3,6-methanobenzofuran-7(6H)-ones based on xanthone, 2-phenylchromene-4-one and benzophenone, were synthesized using a Claisen/Diels-Alder reaction cascade. All the reactions produced the targeted caged compound as well as its neo-isomer. The caged compounds based on xanthone and 2-phenylchromene-4-one were found to maintain the apoptosis inducing and cell growth inhibiting activity of GA, although with less potency. The caged compounds based on benzophenone were found to be inactive. Our study determined the minimum structure of GA for its apoptosis inducing activity, which could lead to the development of simple derivatives as potential anti-cancer drugs.


Granin proteins (chromogranin A and secretogranin II C23-3 and C26-3) in the intestine of amphibians.
The occurrence, distribution and possible cellular colocalizations of chromogranin A (CgA) and of two synthetic secretogranin II peptides (SgIIC23-3 and SgIIC26-3) with serotonin, somatostatin, neurotensin, pancreatic polypeptide and bombesin have been investigated immunohistochemically in the amphibian gut. CgA or SgIIC26-3-immunostained enterocytes were found throughout along the frog intestine, while no immunoreaction for any of the tested antisera against granins was seen in the same organ of newts. Variable amounts of serotonin-immunoreactive cells co-storing CgA or SgIIC26-3, but never both granins, were encountered in all intestinal segments of the frogs investigated. In addition, CgA was co-localized with somatostatin in a few endocrine cells of the frog (genus Rana) duodenum and small intestine. In the duodenum of another frog (genus Xenopus) several enterocytes co-stored SgIIC26-3 and neurotensin. Pancreatic polypeptide- and bombesin-immunoreactive cells, the latter detected only in the duodenum of Xenopus, did not contain and granin. The results suggest that, in spite of their relatively restricted occurrence in the intestine of frogs and even of their absence in that of newts, the granins are well conserved during phylogeny. On the other hand, the heterogeneous distributions of these anionic glycoproteins, related to the entero-endocrine cell types, make their previously assigned usefulness as markers of all neuro-endocrine cells unlikely.


Identification and localization of the CupB protein involved in constitutive CO2 uptake in the cyanobacterium, Synechocystis sp. strain PCC 6803.
Antibody against cMyc cross-reacted strongly with the CupB protein tagged with His6-cMyc (HM) in thylakoid membrane of Synechocystis sp. strain PCC 6803 but only faintly with the cytoplasmic membrane fraction. The protein was not detected in the membranes of the DeltandhD4 and DeltandhF4 mutants in which CupB was tagged with HM. We concluded that a CupB complex containing NdhD4 and NdhF4 is largely, if not exclusively, confined to the thylakoid membrane. Both CupB and NdhH were detected in a fraction containing protein complexes of > 450 kDa, obtained after nickel column and gel filtration chromatography of the membranes solubilized with n-dodecyl-beta-maltoside.


A novel immunodeficiency syndrome as a rare cause of secondary pulmonary alveolar proteinosis: a diagnosis after 5 decades.
Case report of a male patient with a five-decade follow-up history in a tertiary care hospital distinguished for malabsorption syndrome, failure-to-thrive, meningitis and recurrent bacterial, fungal and mycobacterial pulmonary infections. Additionally, he developed epidermodysplasia verruciformis, several in situ spinocellular carcinomas and an uncharacteristic parenchymal lung disease. Surgical lung biopsy suggested pulmonary alveolar proteinosis with fibrotic change. Retrospectively, severe monocytopenia had been overlooked in the past, as well as low B and NK cell blood counts. Flow cytometry confirmed the absence of the previous cell subsets along with an undetectable population of dendritic blood cells. Dendritic cell, monocyte, B and NK lymphoid Human Deficiency Syndrome (DCMLS) is a novel rare immunodeficiency described in 2010, linked to GATA-2 mutation. This syndrome should be highlighted as a rare cause of acquired PAP, with a radiological pattern encompassing potential fibrotic change. Failure to recognize monocytopenia may impede the chance to diagnose.


Acute problems of hemodialysis access: Thrombosis, aneurysms, symptomatic high-flow fistulas, and complications related to central lines.
Hemodynamic complications frequently affect vascular access and are important causes of morbidity and mortality. We present a review of acute complications affecting vascular accesses, focusing on classical and new treatments. Acute complications in hemodialysis vascular access are often underestimated and undertreated, and can present a challenge for both vascular surgeons and anesthesiologists. Accordingly, we considered different anesthesiologic approaches to both hemorrhagic and nonhemorrhagic patients. A strict collaboration among nephrologists, surgeons, and anesthesiologists can potentially improve prevention and management of acute complications and quality of life.


Qualitative study of chromosomal lesions induced by neutrons and neon ions in human lymphocytes at G0 phase.
Chromosomal lesions, mitotic index and cell cycle progression delay induced by neutron (protons 34 MeV on beryllium) and neon (250 MeV/i) particles are studied in human lymphocytes. The cell cycle progression is slightly decreased at a dose of 1 Gy. Mitotic indexes are significantly decreased after irradiation by the different particles, except neon in 52-h cultures. By comparison to chromosome damages caused by gamma-rays, previously published, it is found that the lesions observed here are frequently more complex: the number of breaks is higher per abnormal mitosis and higher per rearrangement on the average. This complexity is higher for neon ions than for neutron beams.


Tracing of sensory neurones and spinal motoneurones of the pigeon by injection of fluorescent dyes into peripheral nerves.
The projection of peripheral sensory and motor nerves was investigated in the pigeon (Columba livia) by means of retrogradely transported fluorescent dyes. Two combinations of fluorescent tracers were used that could be identified within the same cell when excited by light of 405 nm: 1) Propidium iodide and Bisbenzimide, which label the cytoplasm orange and the nucleus blue, respectively; 2) Fast Blue, which labels the cytoplasm blue, and Nuclear Yellow, which labels the nucleus (especially the nucleolar ring) yellow. The presence of the tracers in a given cell was confirmed microspectrophotometrically. Following injection of the tracers into peripheral nerves, labelled sensory neurones were seen in the dorsal root ganglia and motoneurones of the spinal cord. The peroneal and tibial nerves projected to L2-L5 and L2-L7, respectively, whereas the median and ulnar nerves projected to C12-Th2 and C13-Th1. Double-labelled sensory neurones were observed when both peroneal and tibial, or median and ulnar nerves were injected with different tracers. This indicates that some sensory neurones possess peripheral processes that dichotomize to pass down two different peripheral nerves. Double labelling was never seen in motoneurones, or in sensory neurones after tracer injection into the sciatic and femoral nerves.


Tropism Analysis of Two Coxsackie B5 Strains Reveals Virus Growth in Human Primary Pancreatic Islets but not in Exocrine Cell Clusters In Vitro.
Human Enteroviruses (HEVs) have been implicated in human pancreatic diseases such as pancreatitis and type 1 diabetes (T1D). Human studies are sparse or inconclusive and our aim was to investigate the tropism of two strains of Coxsackie B virus 5 (CBV-5) in vitro to primary human pancreatic cells. Virus replication was measured with TCID50 titrations of aliquots of the culture medium at different time points post inoculation. The presence of virus particles or virus proteins within the pancreatic cells was studied with immunohistochemistry (IHC) and electron microscopy (EM). None of the strains replicated in the human exocrine cell clusters, in contrast, both strains replicated in the endocrine islets of Langerhans. Virus particles were found exclusively in the endocrine cells, often in close association with insulin granules. In conclusion, CBV-5 can replicate in human endocrine cells but not in human exocrine cells, thus they might not be the cause of pancreatitis in humans. The association of virus with insulin granules might reflect the use of these as replication scaffolds.


[Correlation analysis of Filifactor alocis detection with periodontal status].
The study investigated the epidemiology of Filifactor alocis (F. alocis) in subgingival plaque samples from subjects with different periodontal statuses. The relationship between the prevalence of F. alocis and clinical periodontal parameters was also analyzed. Subgingival plaque samples and periodontal data were collected from 68 healthy sites (H groups) in 17 healthy subjects, 64 healthy (G-H group) and 76 diseased sites (G-D group) in 19 patients with chronic gingivitis, and 36 healthy (P-H group) and 56 diseased sites (P-D group) in 14 patients with chronic periodontitis. The plaque samples were analyzed by polymerase chain reaction, and possible correlations between the F. alocis detection rate and the bleeding index, probing depth, or clinical attachment level were determined. The detection levels of F. alocis increased in both healthy and diseased groups. The lowest level at 30.88% (21/68) was noted in the H group, whereas the highest level at 91.07% (51/56) was obtained from the P-D group. A significant correlation was found between the F. alocis detection levels and periodontal disease condition (P < 0.000 1). Further analyses showed that a significant correlation also existed between the detection level of F. alocis and the abnormal clinical periodontal parameters, namely, bleeding index, probing depth, and clinical attachment loss. The odds ratios were 5.26, 8.85, and 11.65, respectively. F. alocis was found at increased-levels in subjects with periodontal disease. The presence of F. alocis increases the risk of sites with abnormal clinical periodontal parameters.


Implications of RAS Mutations on Oncological Outcomes of Surgical Resection and Thermal Ablation Techniques in the Treatment of Colorectal Liver Metastases.
Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related death. More than 50% of patients with CRC will develop liver metastases (CRLM) during their disease. In the era of precision surgery for CRLM, several advances have been made in the multimodal management of this disease. Surgical treatment, combined with a modern chemotherapy regimen and targeted therapies, is the only potential curative treatment. Unfortunately, 70% of patients treated for CRLM experience recurrence. RAS mutations are associated with worse overall and recurrence-free survival. Other mutations such as BRAF, associated RAS /TP53 and APC/PIK3CA mutations are important genetic markers to evaluate tumor biology. Somatic mutations are of paramount interest for tailoring preoperative treatment, defining a surgical resection strategy and the indication for ablation techniques. Herein, the most relevant studies dealing with RAS mutations and the management of CRLM were reviewed. Controversies about the implication of this mutation in surgical and ablative treatments were also discussed.


Association of NAFLD With Diabetes and the Impact of BMI Changes: A 5-Year Cohort Study Based on 18,507 Elderly.
Previous studies about the relationship between nonalcoholic fatty liver disease (NAFLD) and diabetes are limited by inconsistent conclusions, mainly being cross-sectional and having a small sample size, no elderly people, or a lack of prediabetes. This study sought to examine the relationship between NAFLD and diabetes and prediabetes in a large cohort based on Chinese male elderly. This was a retrospective cohort study that was followed up for ∼5 years. This study was conducted in Beijing, China. Chinese male elderly (n = 18,507). Participants with diabetes/prediabetes at baseline were excluded. Ultrasound was used for diagnosis of NAFLD. Mean age of the 18,507 participants was 71.38 ± 14.15 years. The prevalence of NAFLD was 18.77% (3474/18,503), and participants with NAFLD had higher body mass index (BMI), blood pressure levels, blood lipid levels, and also higher alanine aminotransferase levels (P < 0.001). The total 5-year incidence was 2.448% for diabetes and 10.628% for prediabetes. Participants with NAFLD at baseline had a higher incidence of both diabetes and prediabetes. The adjusted relative risks (RRs) were 1.672 [95% confidence interval (CI), 1.361 to 2.052] and 1.336 (95% CI, 1.205 to 1.481). The RRs were closely related to BMI changes. The adjusted RRs for diabetes according to three BMI change groups (<-1.00 kg/m2, -1.00 to 1.00 kg/m2, >1.00 kg/m2) were 1.599 (95% CI, 1.054 to 2.426), 1.640 (95% CI, 1.241 to 2.167), and 1.918 (95% CI, 1.239 to 2.969), respectively. Similar results were obtained when prediabetes was used as the dependent variable. There was a strong and independent association between NAFLD and both diabetes and prediabetes among Chinese male elderly, and this relationship was closely related to BMI changes.


Examination of minoxidil-induced acute cardiotoxicity in miniature swine.
Minoxidil, a vasodilating antihypertensive agent, was given orally in doses of 1, 3 or 10 mg/kg to miniature swine on 2 consecutive days. Mean arterial pressure decreased and heart rate increased most consistently after the 10 mg/kg dose. However, all 3 doses of minoxidil induced myocardial hemorrhages and/or left ventricular papillary muscle necrosis within 24 h after the second dose. Necrosis, characterized by hypercontraction of muscle cells and myofibrillar damage, occurred in 1 of 8 pigs given 1 mg/kg, 3 of 13 given 3 mg/kg and 7 of 14 given 10 mg/kg of minoxidil. The pharmacological effects of minoxidil, hypotension and reflex tachycardia, probably led to ischemia and necrosis in left ventricular papillary muscles. Gross hemorrhages involving the left atrium and to a lesser extent the left ventricle were found in 4 of 8 pigs given 1 mg/kg, 9 of 13 given 3 mg/kg and 11 of 14 given 10 mg/kg of minoxidil. The atrial lesions were manifested grossly by diffuse redness and microscopically by interstitial edema, extravasation of erythrocytes and infiltration of areas around small arteries and arterioles with acute and chronic inflammatory cells. The hemmorhagic areas were concentrated along the epicardial surfaces, and to a lesser extent along the endocardial surfaces. Atrial lesions induced by minoxidil preferentially involve the left atrium in pigs and the right atrium in dogs. These differences may be related to the anatomic patterns of coronary circulation in the 2 species.


[Mechanical failure of porous hydroxyapatite ceramics 7.5 years after implantation in the proximal tibial].
The treatment of osseous defects is widely established in the elderly. The number of positive reports on the successful application of bovine as well as coralline hydroxyapatite ceramics has continuously increased during the last few years. In trauma surgery hydroxyapatite ceramics are most commonly applied in metaphyseal defects evoked by traumatic fractures of the long bones. The bovine and coralline materials applied are biocompatible and exhibit an interconnecting porous system. Good osteoconductive properties of such materials have repeatedly been demonstrated. Due to possible harmful effects caused by abrasion of the material, intra-articular application should be strictly avoided. Biological degradation of the materials does not occur even during long-term follow-up. The application of hydroxyapatite ceramics was introduced at our institution in 1992. Since then, no adverse events have been observed and only a few relevant complications were described in the literature. We report on a patient revealing a mechanical failure of a bovine hydroxyapatite (Endobon) 7.5 years after implantation into a metaphyseal defect of the proximal tibia caused by a traumatic fracture.


Effects of the insecticide chlorpyrifos, on hatching, mortality and morphology of Duttaphrynus melanostictus embryos.
In an attempt to assess the effects of chlorpyrifos [O,O-diethyl O-(3,5,6-trichloropyridin-2-yl) phosphorothioate], the second largest selling insecticide in India, studies were made with reference to some non-target organisms. The present study was undertaken to evaluate the effects in the embryos of Duttaphrynus melanostictus caused by the commercial formulations of chlorpyrifos (Tricel, chlorpyrifos, 20% EC). The LC50 value for Duttaphrynus melanostictus embryos after 48 h (h) of treatment with chlorpyrifos was found to be 57.525 ppm. The mortality of the embryo was significantly affected by different concentrations of chlorpyrifos when compared with the control groups. An increase in concentration of chlorpyrifos resulted in the simultaneous decrease of the hatching percentage and an increase in the morphological abnormalities such as compression of the embryo, reduced body size and curling of tail.


Investigation of degradation mechanisms by portable Raman spectroscopy and thermodynamic speciation: the wall painting of Santa María de Lemoniz (Basque Country, North of Spain).
This article presents the "in situ" and totally non destructive investigation of a wall painting in Santa María de Lemoniz (Biscay, Basque Country, Spain) by Raman microprobe spectroscopy 14 years after its restoration. Although no sample was allowed to be taken, it has been possible to determine the original pigments in the artwork (vermilion, red iron oxide, yellow iron oxide, carbon black, lead white), as well as some degradation products (calcium oxalate dihydrate, anhydrite). For the first time, the mechanism for the transformation of malachite into copper basic sulphates has been ascertained by the integration of Raman data with thermodynamic speciation studies. Moreover, some remarks regarding the unsuitability of the past intervention procedure with regard to the chemical stability of the artwork are made.


Alteration of radiosensitivity of quiescent cell populations in solid tumors irradiated with X-rays twice at various intervals.
5-Bromo-2'-deoxyuridine (BUdR) was injected into SCC VII or EMT6/KU tumor-bearing mice intraperitoneally to label all the proliferating tumor cells. First, the mice were irradiated with X-rays at a dose of 10 Gy, followed by a dose of 0-20 Gy at 0, 12, 24 or 48 h later. During the interval, no BUdR was injected. Immediately after the second irradiation, the tumors were excised and trypsinized. The micronucleus (MN) frequency in cells without BUdR labeling was determined by means of incubation with cytochalasin-B (a cytokinesis-blocker) and immunofluorescence staining for BUdR. When the tumors were not pretreated with BUdR before the first irradiation, the MN frequency in all tumor cells was determined. To determine the labeling indices of SCC VII and EMT6/KU tumors at the time of the second irradiation, each group also included mice that were continuously administered BUdR until just before the second irradiation using mini-osmotic pumps which had been implanted subcutaneously 5 days before the first irradiation. The MN frequency of all tumor cell populations obtained immediately after the second irradiation decreased in proportion to the increase in interval time. However, in both tumor systems, the MN frequency of unlabeled cell populations, which could be regarded as quiescent cells in the tumors at the time of the first irradiation, was raised with increase in the interval time. In addition, the labeling index at the second irradiation was higher than that at the first irradiation. These findings support the occurrence of recruitment from quiescent to proliferating state during fractionated irradiation.


Resveratrol stimulates StAR expression and progesterone production by GPER-mediated downregulation of Snail expression in human granulosa cells.
Steroidogenic acute regulatory protein (StAR) plays a critical role in the regulation of progesterone (P4) production. Resveratrol (RSV), a natural polyphenol, has beneficial effects on reproductive function. However, its effects on StAR expression and P4 production in human granulosa cells remain undetermined. In this study, we showed that treatment of RSV upregulated StAR expression in human granulosa cells. G protein-coupled estrogen receptor (GPER) and ERK1/2 signaling were involved in RSV-stimulated StAR expression and P4 production. In addition, the expression of a transcriptional repressor, Snail, was downregulated by RSV, which contributed to the RSV-induced inductions of StAR expression and P4 production.


Using chirality to probe the conformational dynamics and assembly of intrinsically disordered amyloid proteins.
Intrinsically disordered protein (IDP) conformers occupy large regions of conformational space and display relatively flat energy surfaces. Amyloid-forming IDPs, unlike natively folded proteins, have folding trajectories that frequently involve movements up shallow energy gradients prior to the "downhill" folding leading to fibril formation. We suggest that structural perturbations caused by chiral inversions of amino acid side-chains may be especially valuable in elucidating these pathways of IDP folding. Chiral inversions are subtle in that they do not change side-chain size, flexibility, hydropathy, charge, or polarizability. They allow focus to be placed solely on the question of how changes in amino acid side-chain orientation, and the resultant alterations in peptide backbone structure, affect a peptide's conformational landscape (Ramachandran space). If specific inversions affect folding and assembly, then the sites involved likely are important in mediating these processes. We suggest here a "focused chiral mutant library" approach for the unbiased study of amyloid-forming IDPs.


Enzyme-Modified Particles for Selective Biocatalytic Hydrogenation by Hydrogen-Driven NADH Recycling.
We describe a new approach to selective H2-driven hydrogenation that exploits a sequence of enzymes immobilised on carbon particles. We used a catalyst system that comprised alcohol dehydrogenase, hydrogenase and an NAD+ reductase on carbon black to demonstrate a greater than 98 % conversion of acetophenone to phenylethanol. Oxidation of H2 by the hydrogenase provides electrons through the carbon for NAD+ reduction to recycle the NADH cofactor required by the alcohol dehydrogenase. This biocatalytic system operates over the pH range 6-8 or in un-buffered water, and can function at low concentrations of the cofactor (10 μm NAD+) and at H2 partial pressures below 1 bar. Total turnover numbers >130 000 during acetophenone reduction indicate high enzyme stability, and the immobilised enzymes can be recovered by a simple centrifugation step and re-used several times. This offers a route to convenient, atom-efficient operation of NADH-dependent oxidoreductases for selective hydrogenation catalysis.


Sedative load, carious teeth and infection in the periodontium among community-dwelling older people.
To study the relation of sedative load to carious teeth and periodontal pocketing - indication of infectious periodontal disease - among older people. This cross-sectional study was based on a subpopulation of 158 community-dwelling, dentate, non-smoking, 75-year-old or older people from the Oral Health Geriatric Multidisciplinary Strategy study. The data were collected by interviews and clinical oral examinations during 2004-2005. Sedative load was measured by means of the sedative load model, and Poisson multivariate regression models were used to estimate relative risk (RR) with 95% confidence intervals (CI). Participants with a sedative load of either 1-2 (n = 31) or ≥3 (n = 12) had an increased likelihood of having carious teeth (RR: 1.8, CI: 1.2-2.6 and RR: 2.4, CI: 1.4-4.1, respectively) compared to participants without a sedative load. There was an inverse association between sedative load and the number of teeth with periodontal pockets. Presence of dental caries was associated with the use of drugs with sedative properties. The use of drugs with sedative properties was not associated with the presence of periodontal pockets.


Meningiomas: causes and risk factors.
Meningiomas are among the most common primary intracranial tumors. Although the vast majority of these tumors are considered histologically benign, the incidence of complications can be high. Few studies have investigated the causes and risk factors for meningioma; this review highlights the current state of knowledge. Gaining a better understanding of the origin of this disease is essential so that treatments and outcomes can be improved and prevention strategies can be developed.


Whole-genome sequencing analysis and CRISPR genotyping of rare antibiotic-resistant Salmonella enterica serovars isolated from food and related sources.
For decades, Salmonella Typhimurium and Salmonella Enteritidis have prevailed in several countries as agents of salmonellosis outbreaks. In Brazil, the largest exporter of poultry meat, relatively little attention has been paid to infrequent serovars. Here, we report the emergence and characterization of rare serovars isolated from food and related sources collected between 2014 and 2016 in Brazil. Twenty-two Salmonella enterica isolates were analyzed through the use of whole-genome sequencing (WGS) and clustered regularly interspaced short palindromic repeats (CRISPR) genotyping. These isolates were classified into 10 infrequent serovars, including S. Abony, S. Isangi, S. Rochdale, S. Saphra, S. Orion, S. Ouakam, S. Grumpensis, S. Carrau, S. Abaetetuba, and S. Idikan. The presence of six antimicrobial resistance (AMR) genes, qnrB19, blaCMY-2, tetA, aac(6')-Iaa, sul2 and fosA7, which encode resistance to quinolones, third-generation cephalosporin, tetracycline, aminoglycoside, sulfonamide and fosfomycin, respectively, were confirmed by WGS. All S. Isangi harbored qnrB19 with conserved genomic context across strains, while S. Abony harbored blaCMY-2. Twelve (54.5%) strains displayed chromosomal mutations in parC (Thr57→Ser). Most serovars were classified as independent lineages, except S. Abony and S. Abaetetuba, which phylogenetically nested with Salmonella strains from different countries. CRISPR analysis revealed that the spacer content was strongly correlated with serovar and multi-locus sequence type for all strains, independently confirming the observed phylogenetic patterns, and highlighting the value of CRISPR-based genotyping for Salmonella. These findings add valuable information to the epidemiology of S. enterica in Brazil, where the emergency of antibiotic-resistant Salmonella continues to evolve.


ZEA and DON inhibited inflammation after L. monocytogenes infection and induced ribosomal hyperfunction.
The complex microbial community in food environment is a major problem of human or animal health and safety. Mycotoxins and food-borne bacteria can both induce inflammation in the body and cause a series of changes in biological functions. In this study, mice were gavaged with low doses of ZEA, DON, or ZEA + DON, and then infected with L. monocytogenes. A cytokine microarray, including 40 inflammation-related serum cytokines, and proteomics were used to verify the effects of ZEA, DON, and ZEA + DON on the host inflammation and biological function after L. monocytogenes infection. The results showed that mononucleosis after bacterial infection was inhibited by ZEA, DON, and ZEA + DON, while the balance of macrophage differentiation was shifted toward M2-type. ZEA, DON, and ZEA + DON decreased the levels of serum proinflammatory cytokines IL-1β and IL-12 after infection. In addition, the signal of the NF-κB pathway was inhibited. Proteomic results showed that ZEA, DON, and ZEA + DON led to biological dysfunction in ribosomal and metabolic cells, primarily leading to abnormal ribosomal hyperfunction. This study showed that ZEA, DON, and ZEA + DON can aggravate disease progression by inhibiting the inflammatory response following foodborne bacterial infection. These metabolites may also disrupt normal biological functions, which may lead to ribosomal hyperfunction, making bacterial clearance more difficult.


Long Noncoding RNAs and Their Regulatory Network: Potential Therapeutic Targets for Adult Moyamoya Disease.
To investigate long noncoding ribonucleic acid (lncRNA) expression patterns in adult moyamoya disease (MMD) patients and explore their possible roles in the pathophysiology of MMD. A healthy control group (n = 10) and an MMD group (n = 15) were evaluated. RNA was extracted from peripheral blood samples and hybridized to microarray to get lncRNA expression profiles. Then predicted lncRNA target genes were identified, and bioinformatics analysis was performed to investigate their molecular functions. In the MMD group, 3649 lncRNAs exhibited more than 2-fold expression than their counterparts in the healthy control group; of these, 1494 were upregulated, while 2155 were downregulated. Principal component analysis and Hclust analysis produced completely different clusters between the 2 groups. Gene ontology and KEGG pathway enrichment analysis suggested that the differentially expressed lncRNAs regulate multiple signaling pathways that were related with inflammation and vascular disease, and mitogen-activated protein kinase (MAPK) signaling pathway was the core regulatory pathway. Long noncoding RNA expression profiles were quite different between MMD and control groups. Multiple signaling pathways that were closely associated with immune response, vasculogenesis, and smooth muscle contraction were indicated to participate in lncRNAs regulatory mechanism; of these, MAPK signaling pathway, which has been well studied for the treatment of many other cardiovascular diseases, was the core of this regulatory network. Our findings could help further understand the pathophysiology of MMD and provide new potential therapeutic targets.


Assessing jugular venous compliance with optical hemodynamic imaging by modulating intrathoracic pressure.
The internal jugular veins (IJV) are critical cerebral venous drainage pathways that are affected by right heart function. Cardiovascular disease and microgravity can alter central venous pressure (CVP) and venous return, which may contribute to increased intracranial pressure and decreased cardiac output. Assessing jugular venous compliance may provide insight into cerebral drainage and right heart function, but monitoring changes in vessel volume is challenging. We investigated the feasibility of quantifying jugular venous compliance from jugular venous attenuation (JVA), a noncontact optical measurement of blood volume, along with CVP from antecubital vein cannulation. CVP was progressively increased through a guided graded Valsalva maneuver, increasing mouth pressure by 2 mmHg every 2 s until a maximum expiratory pressure of 20 mmHg. JVA was extracted from a 1-cm segment between the clavicle and midneck. The contralateral IJV cross-sectional area (CSA) was measured with ultrasound to validate changes in the vessel size. Compliance was calculated using both JVA and CSA between four-beat averages over the duration of the maneuver. JVA and CSA were strongly correlated (median and interquartile range) over the Valsalva maneuver across participants (r = 0.986, [0.983, 0.987]). CVP more than doubled on average between baseline and peak strain (10.7 ± 4.4 vs. 25.8 ± 5.4 cmH2O; p < 0.01). JVA and CSA increased nonlinearly with CVP, and both JVA- and CSA-derived compliance decreased progressively from baseline to peak strain (49% and 56% median reduction, respectively), with no significant difference in compliance reduction between the two measures (Z = - 1.24, p = 0.21). Pressure-volume curves showed a logarithmic relationship in both CSA and JVA. Optical jugular vein assessment may provide new ways to assess jugular distention and cardiac function.


Low maternal serum concentrations of human chorionic gonadotropin as part of the triple test screening: a follow-up study.
To determine whether low maternal serum concentrations of human chorionic gonadotropin (hCG) were associated with poor pregnancy outcome. Between 1999 and 2000, 20,880 women underwent triple test screening in our hospital. The levels of hCG were detected by fluorescent immunoassay. Low hCG levels (< or = 0.20 MoM in our center) were considered to be a marker for increased risk for trisomy 18 or adverse pregnancy outcome. Each patient completed a questionnaire regarding fetal karyotype, complications of pregnancy and pregnancy outcome. Low maternal serum concentrations of hCG were detected in 119 pregnancies (0.57%). Of these, 19 (16%) were found to be missed abortions. The distribution of the remaining 100 cases was as follows: 72% had an isolated low hCG level, 24% had a low hCG level and a combination of hCG + alpha-fetoprotein < 0.80 MoM, and 4% had a low hCG level and a combination of hCG + unconjugated estriol < 0.80 MoM. No trisomy 18 or other chromosomal abnormalities were detected in our patient population. However, there were perinatal complications. Based on our screened population, a combination of multiple analytes seemed to be a better marker than an isolated finding of low maternal serum concentrations of hCG with regards to abnormal fetal karyotype, specifically trisomy 18, although it did determine a high-risk group in terms of complications of pregnancy.


A comparison of the effects of epidural and meperidine analgesia during labor on fetal heart rate.
To estimate the effects of initiation of epidural analgesia on fetal heart rate (FHR) patterns compared with intravenous meperidine analgesia. Fetal heart rate patterns in 200 nulliparous women with term pregnancies randomized to epidural analgesia with 0.25% bupivacaine were compared with those of 156 similar women given intravenous meperidine. Fetal heart rate patterns occurring within 40 minutes of initiation of labor analgesia were retrospectively read by three maternal-fetal medicine specialists who were blind to clinical events, including type of labor analgesia. Meperidine, compared with epidural analgesia, was associated with statistically significantly less beat-to-beat variability (absent or less than 5 beats per minute) of the FHR (30% versus 7% of fetuses, P <.001) in the first 40 minutes after initiation of analgesia, as well as with fewer FHR accelerations (88% versus 62% of fetuses, P <.001). Neither the incidence of FHR decelerations nor the type of deceleration were significantly different between methods of labor analgesia. Specifically, 41% of women given meperidine exhibited FHR decelerations within 40 minutes, compared with 34% given epidural analgesia (P =.353). Epidural analgesia does not have deleterious effects on FHR.


From Mouse to Man: N-Methyl-d-Aspartic Acid Receptor Activation as a Promising Pharmacotherapeutic Strategy for Autism Spectrum Disorders.
The BALB/c mouse displays hypersensitivity to behavioral effects of MK-801 (dizocilpine), a noncompetitive N-methyl-d-aspartic acid (NMDA) receptor "open-channel" blocker, and shows both no preference for an enclosed stimulus mouse over an inanimate object and reduced social interaction with a freely behaving stimulus mouse. NMDA receptor agonist interventions improved measures of social preference and social interaction of the BALB/c mouse model of autism spectrum disorder (ASD). A "proof of principle/proof of concept" translational 10-week clinical trial with 8-week of active medication administration was conducted comparing 20 DSM-IV-TR-diagnosed older adolescent/young adult patients with ASD randomized to once-weekly pulsed administration (50 mg/d) versus daily administration of d-cycloserine (50 mg/d). The results showed that d-cycloserine, a partial glycine agonist, was well tolerated, the 2 dosing strategies did not differ, and improvement was noted on the "lethargy/social withdrawal" and "stereotypic behavior" subscales of the Aberrant Behavior Checklist. NMDA receptor activation contributes to the regulation of mTOR signaling, a pathologic point of convergence in several monogenic syndromic forms of ASD. Furthermore, both NMDA receptor hypofunction and imbalance between NMDA receptor activation mediated by GluN2B and GluN2A-containing NMDA receptors occur as "downstream" consequences of several genetically unrelated abnormalities associated with ASD. NMDA receptor-subtype selective "positive allosteric modulators (PAMs)" are particularly appealing medication candidates for future translational trials.


Day-of-Free Tissue Transfer Qualitative Cultures Do Not Predict Limb Salvage Outcomes.
Successful free tissue transfer is critical for lower extremity salvage in the chronic wound population. The rates of lower extremity free tissue transfer success lag behind those for other anatomical sites. The aim of this study was to evaluate whether positive qualitative day-of-free tissue transfer cultures or pathogen virulence negatively impacts short- and long-term outcomes of lower extremity free tissue transfer. Between April of 2011 and January of 2018, 105 lower extremity free tissue transfer procedures were performed. Growth level and speciation were identified from qualitative cultures taken during free tissue transfer. The relationship between demographics, comorbidities, culture data, postoperative infection, free tissue transfer survival, and long-term limb salvage was examined using logistic regression. The median Charlson Comorbidity Index was 3. Intraoperative free tissue transfer cultures were positive in 39.1 percent. Flap survival was 93.3 percent. Postoperative infection developed in 12.4 percent. The limb salvage rate was 81.0 percent. Positive culture was not significant for flap survival, postoperative infection, or amputation. Cultures positive for Enterococcus species had a significant relationship with flap success (OR, 0.08; p = 0.01) and amputation (OR, 7.32; p = 0.04). Insufficient antimicrobial coverage had a significant relationship with postoperative infection (OR, 6.56; p = 0.01) despite the lack of pathogen concordance. On multivariate analysis, postoperative infection (OR, 12.85; p < 0.01) and Charlson Comorbidity Index were predictive of eventual amputation (OR, 1.44; p = 0.01). Positive day-of-free tissue transfer cultures, regardless of pathogen, had limited predictive value for short- and long-term outcomes of free tissue transfer in the authors' cohort. These findings call for a broader multicenter prospective analysis and consideration of health care-associated infections and their impact on limb salvage outcomes. Risk, III.


Roles of the monoaminergic system in the antidepressant effects of ketamine and its metabolites.
While the molecular target of (R,S)-ketamine (ketamine) is thought to be the NMDA receptor, subanesthetic doses of ketamine have been known to modulate monoaminergic neurotransmission in the central nervous system. Although the involvement of the serotonergic system in the antidepressant effects of ketamine has been reported in most studies of this topic, some recent studies have reported that the dopaminergic system plays a key role in the effects of ketamine. Additionally, several lines of evidence suggest that the antidepressant-like effects of (R)-ketamine might be independent of the monoaminergic system. Ketamine metabolites also differ considerably in their ability to regulate monoamine neurotransmitters relative to (S)-ketamine and (R)-ketamine, while (2R,6R)-hydroxynorketamine might share common serotonergic signaling mechanisms with ketamine. In the current review, we summarize the effects of ketamine and its metabolites on monoamine neurotransmission in the brain and discuss the potential roles of the monoaminergic system in the mechanism of action of ketamine.


[Relations of HLA A2, A3, B12 antigens, and A2-B12 supposed haplotype association, with latent herpes virus infection in patients with chronic renal disease (author's transl)].
Comparison of 105 patients suffering of chronical renal failure with 108 normal persons showed that, in the former group, a relation could be established between HLA A2, A3, and B12 histocompatibility antigens as well as haplotype association A2-B12, and chronic infection by herpes virus. The high number of herpes virus observed in patient group bearing the BW 35 antigen was discussed.


Exploring the feasibility and acceptability of a school-based self-referral intervention for emotional difficulties in older adolescents: qualitative perspectives from students and school staff.
Adolescents with emotional difficulties need accessible, acceptable and evidence-based mental health interventions. Self-referral workshops (DISCOVER workshops) were offered to stressed 16- to 19-year olds in 10 Inner London schools. Semistructured interviews were conducted with three groups of participants: students who attended a 1-day workshop (n = 15); students who initially showed interest in the DISCOVER workshop programme, but decided not to take part (n = 9); and school staff who helped organise the programme in their schools (n = 10). Students were purposively sampled to ensure that those from Black and minority ethnic (BME) backgrounds were represented. Data were analysed using thematic analysis. The accounts generally indicate that the delivery and evaluation of this intervention is perceived as feasible and acceptable. Students, including those from BME backgrounds, described the setting as suitable and reported that the workshop helped them develop new understandings of stress and how to handle it. They expressed a preference for engaging and interactive activities, and valued a personalised approach to workshop provision. School staff felt that the workshop was in line with school values. They described some logistical barriers to providing the workshops in school settings, and expressed a desire for more information about the workshop in order to provide follow-up support. The main reason students gave for nonparticipation was limited time. Findings are discussed in relation to increasing the feasibility of implementing school-based psychological interventions and the value of providing access to mental health support in schools.


Chymotryptic activation of glutamate dehydrogenase.
Treatment of bovine liver glutamate dehydrogenase (L-glutamate:NAD(P)+ oxidoreductase (deaminating), EC 126.96.36.199) with chymotrypsin generates a proteolytic derivative that is activated 3-4-fold over the native enzyme. Stable preparations of activated enzyme show altered kinetic parameters (5-fold increase in Km for glutamate, 3-fold increase in Vmax) and altered response to allosteric modulation by GTP and ADP. The proteolysed enzyme was less responsive to GTP and was no longer activated by ADP, although ADP binding sites remained intact on the enzyme. The effect of ADP upon substrate inhibition was altered and negative homotropic interactions in coenzyme binding were abolished.


A Step-by-Step Protocol for COMPASS, a Synthetic Biology Tool for Combinatorial Gene Assembly.
For industry-scale production of high-value chemicals in microbial cell factories, the elimination of metabolic flux imbalances is a critical aspect. However, a priori knowledge about the genetic design of optimal production pathways is typically not available. COMPASS, COMbinatorial Pathway ASSembly, is a rapid cloning method for the balanced expression of multiple genes in biochemical pathways. The method generates thousands of individual DNA constructs in modular, parallel, and high-throughput manner. COMPASS employs inducible artificial transcription factors derived from plant (Arabidopsis thaliana) regulators to control the expression of pathway genes in yeast (Saccharomyces cerevisiae). It utilizes homologous recombination for parts assembly and employs a positive selection scheme to identify correctly assembled pathway variants after both in vivo and in vitro recombination. Finally, COMPASS is equipped with a CRISPR/Cas9 genome modification system allowing for the one-step multilocus integration of genes. Although COMPASS was initially developed for pathway engineering, it can equally be employed for balancing gene expression in other synthetic biology projects.


Predictors of expressed breast milk volume in mothers expressing milk for their preterm infant.
An understanding of predictors of breast milk production may enable the provision of better advice and support to mothers with preterm infants who may need to express milk for long periods. To investigate factors predicting the amount of milk expressed by mothers for their preterm infant (1) during the first 10 days and (2) during the infant's whole hospital stay. 62 mothers with preterm infants <34 weeks who participated in a randomised trial comparing two breast pumps completed 10-day diaries including weight of milk expressed and questionnaires giving their opinion of the breast pump; 47 mothers provided data on milk expression up to the infant's hospital discharge. Significant predictors of 10-day milk weight in multivariate models were the number of episodes of 'breast feeding' (17 g (95% CI 8 to 26, p=0.001) increase per episode), the use of double versus single pumping (109 (31-186, p=0.007) g/day more) and the number of complete daily records (17 (1-33, p=0.04) g increase/day). Significant multivariate predictors of total milk production were double versus single pumping (491 (55) mL/day vs 266 (44) mL/day), expressing 500 mL/day by day 10 (525 (53) mL/day vs 232 (43) mL/day) and a higher score for breast pump 'comfort' (best=489 (39) mL/day, middle=335 (57) mL/day, worst=311 (78) mL/day). These results suggest that relatively simple, modifiable factors can favourably impact milk production in the neonatal intensive care unit setting and emphasise the importance of double pumping, early establishment of milk production and design features of the breast pump that promote comfort. NCT00887991.


Effect of cell growth rate and dose fractionation on chemically-induced ouabain-resistant mutations in Chinese hamster V79 cells.
Chinese hamster V79 cells were grown in medium containing either 10% or 2% FCS during the expression time following exposure to MNNG. The lower serum concentration was used to reduce the rate of cell replication, thereby allowing more time for DNA repair prior to "fixation" of the mutagenic lesion. In addition, fractionated and continuous exposures to MNNG and MAM, respectively, were carried out to determine their effect on the number of induced ouabain-resistant mutants. The results indicated that lowering the rate of cell growth effectively reduces the mutation frequency at low, but not at high doses of MNNG. Fractionated doses of MNNG result in a potentiation of their mutagenic effects compared to single doses. Also, continuous exposures to MAM result in an exponential increase in the mutation frequency. Collectively, these results suggest the importance of a repair process in Chinese hamster V79 cells which is dependent upon cell growth rate and the dose of the mutagen for its effectiveness.


Comprehensive Two-Dimensional Gas Chromatography in Petroleum Derived Samples: A Review on Advances in Source and Weathering Studies of Spilled Oil.
Since its introduction comprehensive two-dimensional gas chromatography (GC × GC) has been widely applied to analyze complex samples due to its enhanced peak capacity and selectivity, thereby increasing the number of identifiable peaks and improving coelution issues. Even though it is still undergoing development, GC × GC provides many advantages in the analysis of petroleum-derived samples, whether in reservoir geochemistry applications or in environmental studies associated with spilled oils. In general, it facilitates more thorough fingerprinting and compositional evaluation. In environmental studies, it helps enhance understanding of weathering processes and the environmental behavior of hydrocarbons, as its chromatographic retention indices can robustly estimate liquid vapor pressures, aqueous solubility and other physical chemical properties. This review presents a brief history of GC × GC instrumentation, discussing recent and significant advances in petroleum applications, from data handling techniques to reservoir geochemistry and environmental forensics, as well as some specific advantages achieved and certain limitations that continue to be encountered.


Tantalum coating on porous Ti6Al4V scaffold using chemical vapor deposition and preliminary biological evaluation.
Porous tantalum (Ta), produced via chemical vapor deposition (CVD) of commercially pure Ta onto a vitreous carbon, is currently available for use in orthopedic applications. However, the relatively high manufacturing cost and the incapability to produce customized implant using medical image data have limited its application to gain widespread acceptance. In this study, Ta film was deposited on porous Ti6Al4V scaffolds using CVD technique. Digital microscopy and scanning electron microscopy indicated that the Ta coating evenly covered the entire scaffold structure. X-ray diffraction analysis showed that the coating consisted of α and β phases of Ta. Goat mesenchymal stem cells were seeded and cultured on the Ti6Al4V scaffolds with and without coating. The tetrazolium-based colorimetric assay exhibited better cell adhesion and proliferation on Ta-coated scaffolds compared with uncoated scaffolds. The porous scaffolds were subsequently implanted in goats for 12weeks. Histological analysis revealed similar bone formation around the periphery of the coated and uncoated implants, but bone ingrowth is better within the Ta-coated scaffolds. To demonstrate the ability of producing custom implant for clinical applications via this technology, we designed and fabricated a porous Ti6Al4V scaffold with segmental mandibular shape derived from patient computerized tomography data.


Antimycobacterial activity of Juglans regia, Juglans mollis, Carya illinoensis and Bocconia frutescens.
Mycobacterium tuberculosis is a serious worldwide health threat, killing almost 2 million people per year. Alternative antimycobacterial drugs are urgently needed; studies have shown that medicinal plants traditionally used to treat respiratory diseases are a potential source of compounds to treat tuberculosis. This paper studied the antimycobacterial activity of 28 extracts from four different plant species that have been used in traditional Mexican medicine to treat tuberculosis. Bark and leaf crude extracts of Juglans regia L., Juglans mollis Engelm., Carya illinoensis (Wangenh) K. Koch and Bocconia frutescens showed in vitro anti-M. tuberculosis activity. Hexane bark extracts from C. illinoensis, J. mollis and J. regia were the most active with a minimal inhibitory concentration (MIC) of 31, 50 and 100 microg/mL, respectively. Ethanol bark extracts from C. illinoensis and J. mollis showed activity at 100 and 125 microg/mL, respectively. Leaf extracts had the lowest activity. Methanol and hexane leaves extracts from B. frutescens had a MIC of 125 microg/mL. None of the aqueous extracts showed antimycobacterial activity.


Discovery of novel non-competitive inhibitors of mammalian neutral M1 aminopeptidase (APN).
Neutral metallo-aminopeptidase (APN) catalyzes the cleavage of neutral and basic amino acids from the N-terminus of protein or peptide substrates. APN expression is dysregulated in inflammatory diseases as well as in several types of cancer. Therefore, inhibitors of APN may be effective against cancer and inflammation. By virtual screening and enzymatic assays, we identified three non-competitive inhibitors (α > 1) of the porcine and human APN with Ki values in the μM range. These non-peptidic compounds lack the classical zinc-binding groups (ZBG) present in most of the APN inhibitors. Molecular docking simulations suggested the novel inhibitors suppress APN activity by an alternative mechanism to Zn coordination: they interacted with residues comprising the S1 and S5' subsites of APN. Of note, these compounds also inhibited the porcine aminopeptidase A (pAPA) using a competitive inhibition mode. This indicated differences in the binding mode of these compounds with APN and APA. Based on sequence and structural analyses, we predicted the significance of targeting human APN residues: Ala-351, Arg-442, Ala-474, Phe-896 and Asn-900 for improving the selectivity of the identified compounds. Remarkably, the intraperitoneal injection of compounds BTB07018 and JFD00064 inhibited APN activity in rat brain, liver and kidney indicating good bio-distribution of these inhibitors in vivo. These data reinforce the idea of designing novel APN inhibitors based on lead compounds without ZBG.


Resveratrol prevents TNF-α-induced VCAM-1 and ICAM-1 upregulation in endothelial progenitor cells via reduction of NF-κB activation.
To assess the effects of resveratrol (RSV) on expression of adhesion molecules in endothelial progenitor cells (EPCs) following tumor necrosis factor-α (TNF-α) stimulation. EPCs were treated with RSV and stimulated with TNF-α. A mononuclear cell (MNC) adhesion assay was used to assess the effects of RSV on TNF-α-induced MNC adhesion. Vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin expression levels and nuclear factor κB (NF-κB) activation were assessed by immunoblotting. MNC adhesion to TNF-α-treated EPCs and VCAM-1/ICAM-1/E-selectin levels in EPCs were increased following TNF-α stimulation and decreased following RSV treatment. TNF-α enhanced NF-κB inhibitor α (IκB-α) phosphorylation in the cytosol as well as nuclear NF-κB p65 levels, both of which were decreased by RSV. These findings provide new insights into RSV's anti-inflammatory and anti-atherosclerotic effects. RSV's mechanism of action might involve downregulation of VCAM-1, ICAM-1 and E-selectin by partial blockade of TNF-α-induced NF-κB activation and IκB-α phosphorylation in EPCs.


What's new with the amnesic patient H.M.?
H.M. became amnesic in 1953. Since that time, nearly 100 investigators, first at the Montreal Neurological Institute and since 1966 at the Massachusetts Institute of Technology, have participated in studying him. We all understand the rare opportunity we have had to work with him, and we are grateful for his dedication to research. He has taught us a great deal about the cognitive and neural organization of memory. We are in his debt.


Distinguishing ankle and knee articular cartilage.
Degenerative changes in the tall and femoral distal cartilages of more than 2,000 tissue donors were graded based on the appearance of articular cartilage and osteophytes. In the ankle and the knee the degenerative changes increased with age; however, the rate of degeneration in the ankle was slower than in the knee. The degenerative changes in the ankle were more severe in men than in women, were predominantly bilateral, and seemed to be correlated with weight. The slower rate of change in the ankle may be caused, in part, by the biochemical and biomechanical tissue properties that distinguish ankle cartilage from that of the knee.


Tolerability and clinical safety of Implanon.
To evaluate the tolerability and clinical safety of the subdermal, long-acting hormonal contraceptive Implanon. This integrated safety analysis included 11 international studies concerning Implanon (68 mg etonogestrel) of which 10 had a duration of at least two years. Assessments included reports of adverse events (AEs), reasons and rates of discontinuation, insertion/removal complications, and the condition of the implant site. Metabolic and coagulation parameters are briefly discussed to fully describe the clinical safety profile. In total 942 women were exposed to Implanon for 24,679 cycles over the course of one to five years. The overall discontinuation rate was 32.7%; the most frequently reported reasons for discontinuation were adverse events (13.9%), bleeding irregularities (10.4%), and planning pregnancy (4.1%). The most commonly reported drug-related AE was headache (15.3%); however, headache was reported in only 1.6% of women as a reason for discontinuation. Insertion and removal times for Implanon were short with few complications, none of which were major. From earlier studies it is known that treatment with Implanon has little effect on metabolic and coagulation parameters. Implanon is a well-tolerated and safe method of long-acting hormonal contraception for women.


First-Trimester Echocardiographic Features and Perinatal Outcomes in Fetuses With Congenital Absence of the Aortic Valve.
The purpose of this study was to describe the echocardiographic features and perinatal outcomes of congenital absence of the aortic valve diagnosed by first-trimester echocardiography. This retrospective study assessed the feasibility of first-trimester echocardiography in detecting absence of the aortic valve. All cases of absence of the aortic valve diagnosed by first-trimester fetal echocardiography from January 2010 to December 2014 were identified at a single referral center using an established perinatal database. Demographic information, echocardiograms, perinatal outcomes, and autopsy reports were reviewed. Echocardiographic features were described. A total of 50,822 fetuses underwent first-trimester echocardiography during the study period. Ten cases of congenital absence of the aortic valve were diagnosed, for an overall incidence rate of 0.019%. The earliest gestational age at diagnosis was 11 weeks 6 days. The mean crown-lump length was 61.9 mm; mean gestational age was 12 weeks; and mean maternal body mass index ± SD was 21.2 ± 3.9 kg/m(2). Nine fetuses had increased nuchal translucency ranging from 2.4 to 12.4 mm (mean ± SD, 6.4 ± 3.6 mm). Color Doppler flow imaging revealed biphasic bidirectional flow in the ascending aorta and aortic arch and reversed flow in the ductus venosus during atrial systole in all cases. Reversed diastolic flow was present in the umbilical arteries and thoracic aorta. All cases had complex cardiac malformations as well as extracardiac abnormalities. Our study confirms that absence of the aortic valve is a rare cardiac defect that can be diagnosed by first-trimester fetal echocardiography. A "to-and-fro" flow pattern or biphasic bidirectional flow in the great arteries is a key echocardiographic feature in fetuses with absence of the aortic valve.


Tracking of green fluorescent protein labeled Escherichia coli confirms bacterial translocation in blind loop rat.
Previous investigators have documented small intestinal mucosal injury in blind loop rats. However, the definitive evidence of intestinal bacterial translocation in blind loop animals has been lacking. The purpose of this study was to confirm bacterial translocation in blind loop rats and to evaluate the preventive effect of glutamine on bacterial translocation caused by blind loops. Escherichia coli TG1 labeled with green fluorescent protein was used to track bacterial translocation by gavage to rats. Six groups (n = 10) of rats were studied: unoperated control rats; rats with self-emptying blind loop; rats with self-filling blind loop; unoperated control rats treated with glutamine, 400 mg/d; rats with self-emptying blind loop treated with glutamine, 400 mg/d; rats with self-filling blind loop treated with glutamine, 400 mg/d. Representative tissue specimens of the mesenteric lymph nodes, liver, spleen, and kidney were aseptically harvested for bacteria culture. Bacteria were detected in extraintestinal organs of rats with self-emptying blind loop, self-filling blind loop, and self-filling blind loop treated with glutamine. By fluorescence microscope and XbaI restriction digestion analysis, we elucidated that the bacteria isolated from extraintestinal organs were the same bacteria we gavaged to the rats. We confirmed bacterial translocation in self-filling blind loop and self-emptying blind loop rats. In addition, we also showed that glutamine prevents bacterial translocation in self-emptying blind loop rats.


[Coagulation system in patients with blood malignancies treated with estrogens in the course of cytostatic therapy].
To evaluate the effect of estrogen gestagenic drugs (EGD) on blood coagulation in patients with blood malignancies treated by polychemotherapy. 32 females of reproductive age treated with ovarioprotector marvelon during cytostatic therapy. The following indices were determined: activated partial thrombin time, prothrombin index of the ethanol test, fibrinogen and antithrombin III levels, factor XIIa dependent time of fibrinolysis, thrombin time. Dopplerography of the lower limb vessels was carried out. No significant alterations in coagulograms of the patients treated with cytostatics in combination with EGD were recorded. It is safe to use EGD as ovarioprotectors in females with hematological malignancies in hypercoagulation.