Exercise ameliorates chronic inflammatory response induced by high-fat diet via Sestrin2 in an Nrf2-dependent manner.
Chronic inflammation is a major contributor to the development of metabolic disorders and is commonly seen in studies of diet-induced obesity in humans and rodents. Exercise has been shown to have anti-inflammatory properties, though the exact mechanisms are still not fully understood. Sestrins and Nrf2 are of interest to researchers as they are known to protect against inflammation and oxidative stress. In this study, we aim to explore the interconnection between Sestrin2 (SESN2) and Nrf2 and their roles in exercise benefits on chronic inflammation. Our data showed that SESN2 knockout aggravated the abnormalities of body weight, fat mass, and serum lipid that were induced by a high-fat diet (HFD), and a concomitant increase of TNF-α, IL-1β and IL-6 in both serum and skeletal muscle. Notably, exercise was found to reverse these changes, and SESN2 was found to be necessary for exercise to reduce the inflammatory response in skeletal muscles, though not in serum. Immunoprecipitation and bioinformatics prediction experiments further revealed that SESN2 directly binds to Nrf2, indicating a protein-protein interaction between the two. Furthermore, our data demonstrated that SESN2 protein is necessary for exercise-induced effects on Nrf2 pathway in HFD-fed mice, and Nrf2 protein is necessary to enable SESN2 to reduce the inflammation caused by palmitic acid (PA)+ oleic acid (OA) treatment in vitro. Our findings indicate that exercise mitigates chronic inflammation induced by HFD through SESN2 in an Nrf2-dependent manner. Our study reveals a novel molecular mechanism whereby the SESN2/Nrf2 pathway mediates the positive impact of exercise on chronic inflammation.


MetExploreViz: web component for interactive metabolic network visualization.
MetExploreViz is an open source web component that can be easily embedded in any web site. It provides features dedicated to the visualization of metabolic networks and pathways and thus offers a flexible solution to analyse omics data in a biochemical context. Documentation and link to GIT code repository (GPL 3.0 license) are available at this URL: http://metexplore.toulouse.inra.fr/metexploreViz/doc/.


Can triclosan-coated sutures reduce the postoperative rate of wound infection? Data from a systematic review and meta-analysis.
Wound infections are typical postoperative complications with considerable therapeutic consequences and high personnel and financial costs. Previous meta-analyses have shown that triclosan-coated sutures can reduce the risk of postoperative wound infection. This work aimed to update previous meta-analyses with a special focus on different subgroups. A systematic review with meta-analysis was performed (registration: PROSPERO 2022 CRD42022344194). The search was independently performed in the Web of Science, PubMed, and Cochrane databases by 2 reviewers. A critical methods review of all included full texts took place. The trustworthiness of the evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation method. An analysis of the cost-effectiveness of the suture material was carried out. In this meta-analysis of 29 randomized controlled trials, the use of triclosan-coated suture material resulted in a significant reduction of postoperative wound infection rate (24%) (random-effects model; risk ratio: 0.76; 95% confidence interval: [0.67-0.87]). The effect was evident in the subgroups according to wound contamination class, underlying oncologic disease, and pure preoperative antibiotic prophylaxis. In the subgroup analysis by the operating department, the significant effect was visible only in the abdominal surgery group. Based on the randomized controlled clinical trials reviewed, triclosan-coated sutures reduced postoperative wound infection rates in the main study and most subgroups. Additional costs of up to 12 euros for the coated suture material appear to be justified to generate an economic benefit for the hospital by reducing postoperative wound infections. The additional socioeconomic benefit of reducing wound infection rates was not investigated here.


Psychometric properties of the Spanish version of the Thougth-Shape Fusion Questionnaire.
The objectives of the study were to analyze the psychometric properties, factor structure and internal consistency of the Spanish version of the Thought-Shape Fusion Questionnaire (TSF-Q), as well as to determine its validity by evaluating the relationship of the TSF-Q to different instruments. Two groups were studied: one comprising 146 patients with a diagnosis of anorexia (n = 82), bulimia (n = 33) or unspecified eating disorder (n = 31), and another group of 115 undergraduates with no history of psychological disorder. All participants completed the TSF-Q, TAF-Q, EDI-2, STAI, BDI and SCL-90-R. Differences in TSF-Q scores between the diagnostic subgroups were also analyzed. Two factors were obtained which coincided with the two sections indicated by the authors of the questionnaire: conceptual and interpretative. The internal consistency of the TSF-Q and its subscales was determined by means of Cronbach's alpha, with values ranging between .93 and .96. The correlations with other instruments reflected adequate validity. There were no significant differences between the diagnostic subgroups. The Spanish version of the TSF-Q meets the psychometric requirements for measuring thought-shape fusion and shows adequate internal consistency and validity.


Glutamine and glucose metabolism in human peripheral lymphocytes.
The metabolism of glutamine and glucose in resting and concanavalin A-stimulated human peripheral lymphocytes was investigated. Glutamine was metabolized at a high rate by resting and mitogen-stimulated human peripheral lymphocytes and the major end-products of glutamine metabolism were glutamate, aspartate, CO2, and ammonia: the carbon from glutamine may contribute about 21% to respiration. Concanavalin A enhanced the formation of all end-products except glutamate, indicating that more glutamine was metabolized beyond the stage of glutamate in the mitogen-stimulated cells. Mitogenic stimulation caused an increase in the rates of glucose utilization, lactate production and 14CO2 from variously labeled [14C] glucose. Concanavalin A caused an increase in the oxidation of pyruvate as indicated by the enhanced release of 14CO2 from [2-14C]-, [3,4-14C]-, and [6-14C]-glucose. When both glucose and glutamine were presented to the cells, the rates of utilization of both substrates increased and the increased rates of glucose and glutamine utilization could be accounted for mainly by increased rates of lactate and glutamate production, respectively.


Intracellular signaling and hepatocellular carcinoma.
Liver cancer is the fifth most common cancer and the third most common cause of cancer related death in the world. The recent development of new techniques for the investigations of global change in the gene expression, signaling pathways and wide genome binding has provided novel information for the mechanisms underlying liver cancer progression. Although these studies identified gene expression signatures in hepatocellular carcinoma, the early steps of the development of hepatocellular carcinomas (HCC) are not well understood. The development of HCC is a multistep process which includes the progressive alterations of gene expression leading to the increased proliferation and to liver cancer. This review summarizes recent progress in the identification of the key steps of the development of HCC with the focus on early events of carcinogenesis and on the role of translational and epigenetic alterations in the development of HCC. Quiescent stage of the liver is supported by several tumor suppressor proteins including p53, Rb and C/EBPα. Studies with chemical models of liver carcinogenesis and with human HCC have shown that the elevation of gankyrin is responsible for the elimination of these three proteins at early steps of carcinogenesis. Later stages of progression of the liver cancer are associated with alterations in many signaling pathways including translation which leads to epigenetic silencing/activation of many genes. Particularly, recent reports suggest a critical role of histone deacetylase 1, HDAC1, in the development of HCC through the interactions with transcription factors such as C/EBP family proteins.


Estimation of the beta+ dose to the embryo resulting from 18F-FDG administration during early pregnancy.
Although 18F-FDG examinations are widely used, data are lacking on the dose to human embryo tissues in cases of exposure in early pregnancy. Although the photon component can easily be estimated from available data on the pharmacokinetics of 18F-FDG in female organs and from phantom measurements (considering the uterus as the target organ), the intensity of embryo tissue uptake, which is essential for deriving the beta+ dose, is not known. We report the case of a patient who underwent 18F-FDG PET/CT for tumor surveillance and who was later found to have been pregnant at the time of the examination (embryo age, 8 wk). The patient received 320 MBq of (18)F-FDG. Imaging started with an unenhanced CT scan 1 h after the injection, followed by PET acquisition. PET images were used to compute the total number of beta+ emissions in embryo tissues per unit of injected activity, from standardized uptake value (SUV) measurements corrected for partial-volume effects. A Monte Carlo track structure code was then used to derive the beta+ self-dose and the beta+ cross-dose from amniotic fluid. The photon and CT doses were added to obtain the final dose received by the embryo. The mean SUV in embryo tissues was 2.7, after correction for the partial-volume effect. The mean corrected SUV of amniotic fluid was 1.1. Monte Carlo simulation showed that the beta+ dose to the embryo (self-dose plus cross-dose from amniotic fluid) was 1.8E-2 mGy per MBq of injected 18F-FDG. Based on MIRD data for the photon dose to the uterus, the estimated photon dose to the embryo was 1.5E-2 mGy/MBq. Thus, the specific 18F-FDG dose to the embryo was 3.3E-2 mGy/MBq (10.6 mGy in this patient). The CT scan added a further 8.3 mGy. The dose to the embryo is 3.3E-2 mGy/MBq of 18F-FDG. The beta+ dose contributes 55% of the total dose. This value is higher than previous estimates in late nonhuman-primate pregnancies.


Morphological and functional evaluation of the pancreatic duct with secretin-stimulated magnetic resonance cholangiopancreatography in alcoholic pancreatitis patients.
The aim of this investigation was to evaluate the pancreatographic findings and dynamics of pancreatic duct diameter, as determined by secretin-enhanced magnetic resonance cholangiopancreatography (S-MRCP), in patients with acute alcoholic pancreatitis or chronic alcoholic pancreatitis and in a control group. S-MRCP was performed in patients with acute alcoholic pancreatitis who did not manifest the functional and radiological (ultrasonography and computed tomography) criteria of chronic pancreatitis (n = 21), in patients with chronic alcoholic pancreatitis (n = 28) and in a control group (n = 16). The diameter of the main pancreatic duct (MPD) was monitored before secretin administration and at 3 and 10 min after secretin administration. Morphological features were also assessed before and after the administration of secretin. All ductal diameters were significantly larger in chronic alcoholic pancreatitis (P < 0.0001). There were no differences in MPD caliber between patients with acute alcoholic pancreatitis and the control group. The percentage of variation between basal MPD diameter and at 3 min post-secretin administration was lower in patients with chronic (35.5%) pancreatitis than in those with acute alcoholic pancreatitis (52.3%) and the control group (52.5%). There were no significant differences between patients with acute alcoholic pancreatitis and the control group in terms of the frequency of visualization of side branches, ductal narrowing, intraluminal filling defects, and ductal irregularity. One patient with acute alcoholic pancreatitis presented ductal criteria of chronic pancreatitis following the administration of secretin. The dynamics of MPD visualized on S-MRCP in patients with acute alcoholic pancreatitis is similar to that observed in the control group and different from that observed in patients with chronic alcoholic pancreatitis. There were no significant differences between patients with acute alcoholic pancreatitis and the control group in terms of morphological pancreatographic features.


Prospective cohort study of body mass index in adolescence and death from stomach cancer in Japan.
We investigated the association between body mass index (BMI) values and the risk of death from stomach cancer later in life. From 1992 to 2000, 28 443 participants (13 211 men and 15 232 women) were followed, and 129 deaths from stomach cancer (86 men and 43 women) occurred. BMI (BMI at the baseline) and BMI(20y) (BMI at age 20 years) were obtained by questionnaire at the beginning of the study. Men in the middle and highest tertiles of BMI(20y) had a higher risk of death from stomach cancer than those in the lowest tertile (after controlling for covariates, hazard ratio [HR] = 2.73 with 95% confidence interval [CI] 1.26-5.89 for the middle tertile; HR = 2.15 with 95% CI 0.97-4.73 for the highest tertile), although there was no significant trend (P = 0.30). Likewise, women in the middle and highest tertiles of BMI(20y) had an increased risk of death from stomach cancer (HR = 5.17 with 95% CI 1.50-17.87 for the middle tertile; HR = 4.22 with 95% CI 1.18-15.05 for the highest tertile; P for trend = 0.05). The analysis of BMI at the baseline did not show a significant relationship with the risk of death from stomach cancer. These results suggest that a high BMI(20y) is associated with an increased risk of death from stomach cancer.


A comparison between analysis time and inter-analyst reliability using spectral analysis of kinematic data and posture classification.
This study compares the time needed to analyze data and the inter-analyst variability using observational posture classification vs. spectral analysis of upper limb kinematic measurements made using an electrogoniometer for selected industrial jobs. Eight trained analysts studied four jobs using both methods. An incomplete fixed block experimental design was used, whereby each analyst used one method for each job. The four jobs included (1) punch press operation, (2) packaging, (3) parts hanging, and (4) construction vehicle operation. The posture classification analysis method involved visually classifying tipper extremity joint angles into specific zones relative to the range of motion for every one-third second (10 frames) of videotape. Spectral analysis required the analysts to identify cycle break points. The electrogoniometer signals were synchronized with each cycle, and power spectra for each joint were computed. The average difference in RMS joint deviation among analysts was 0.9 (SD = 0.61 degrees) for spectral analysis and 7.1 (SD = 2.53 degrees) for posture classification. The average difference in mean joint angle was 0.8 (SD = 0.59 degrees) for spectral analysis and 11.4 (SD = 1.58 degrees) for posture classification. Repetition frequency differed an average of 0.05 Hz (SD = 0.054 Hz) for spectral analysis and 0.07 Hz (SD = 0.058 Hz) for posture classification. Posture classification took a factor of 6.3 more time than cycle break point assignment for spectral analysis. Even considering the additional time needed for sensor attachment for direct measurement, posture classification took an average factor of 1.29 more time than spectral analysis using electrogoniometer data.


Gender differences in patients with atrial fibrillation.
We aimed to compare gender differences with respect to presentation of consecutive ambulatory patients with atrial fibrillation (AF), management of their disease, and outcomes. Post-hoc analysis of an observational (non-interventional) study performed by 616 office- and hospital-based cardiologists in Germany. Consecutive (mainly ambulatory) patients with Electrocardiography (ECG) -confirmed AF and available data from baseline (BL) and two follow-up visits at 6 and 12 months were assessed. A total of 2,742 patients (62.8% males, mean age 67.5 years; 37.2% women, mean age 71.2 years) were analysed. Women had more frequently paroxysmal and less frequently permanent AF. Quality of life scores were slightly worse in women compared to men, for all types of AF. For class III anti-arrhythmic drugs at baseline (more frequent in men), and for digitalis (less frequent in men at BL and 1 year) statistically significant differences were noted. Oral anti-coagulation (OAC) without anti-platelet drugs was given in 67.9% at BL and in 62.7% at 1 year (no differences between genders). During follow-up, drug conversions in men/women were reported in 12.3%/14.9% (p=0.054), and electrical conversions in 14.6%/11.7% (p=0.03). Hospitalisations occurred in 25.9% and strokes in 3.5%. Patients with higher CHA2DS2-VASc scores had increased stroke rates (0, 1 and ≥2 points: 0.0, 1.5 and 3.9%, respectively; with no significant gender differences). In everyday management of patients with AF, there were no differences in treatment and major outcomes, in particular stroke, between women and men. This finding is opposed to earlier studies reporting OAC undertreatment of women and higher stroke rates.


Early morphometric and anisotropic change in periarticular cancellous bone in a model of experimental knee osteoarthritis quantified using microcomputed tomography.
To quantify early stage microstructural changes of periarticular cancellous bone in a canine anterior cruciate ligament transection model for experimental osteoarthritis. Unilateral transection of the anterior cruciate ligament was performed in 10 animals. Bone structure changes were quantified in five animals at 3-week post-transection and five animals at 12-week post-transection. An additional two non-operated animals were used as controls. Changes in trabecular architecture of the periarticular cancellous bone in early stage post-traumatic osteoarthritis is not well understood. Previous studies have found alterations in bone mineral density in experimental osteoarthritis suggesting adaptation of the trabecular structure. Early change of the periarticular bone following a ligament injury may contribute to the long-term development of osteoarthritis. ++. Bone cores from the medial condyles of the femoral and tibial pairs were scanned with a three-dimensional microtomographic system. Structural indices were quantified including bone volume ratio, bone surface ratio, trabecular thickness, trabecular separation, trabecular number, as well as structural anisotropy determined by the mean-intercept-length method.Results. Significant structural changes were observed at 3-week post-transection, and were more prominent at 12-week post-transection. These changes were accompanied by decreasing anisotropy. Periarticular cancellous bone microstructure is significantly altered in experimental osteoarthritis. These changes occurred as early as 3-week post-transection, and were large at 12-week post-transection. The pathogenesis of post-traumatic osteoarthritis is poorly understood, but it is clear that this disease involves the entire organ system of the joint, including the cartilages, synovium, ligaments, and bones. This study focuses on the changes that occur in the bones during the early stages following a joint injury, and contributes to a better overall understanding of the disease aetiology.


Weight stigma, policy initiatives, and harnessing social media to elevate activism.
Efforts to promote positive body image and body acceptance confront considerable challenges in the face of pervasive societal stigma against people who have a high body weight or large body size. Despite decades of evidence documenting the prevalence and harmful consequences of weight stigma and discrimination, policies to address this social injustice are lacking and primarily absent. This article summarizes the current status of policies to address societal weight-based mistreatment and highlights evidence documenting public support for different types of policies and laws that could be implemented to reduce weight-based bullying and discrimination. While considerable public policy support is present, efforts to scale up activism are needed to help curtail societal weight stigma. Social media has been an underutilized approach that could provide a powerful platform to elevate public awareness and promote policy change to help eliminate weight stigma.


[Hemodynamics of the liver. II. Hemodynamics of the dog liver after resection of 70% of the liver and ligation of the left branch of the portal vein].
Blood supply to the liver was determined by help of the direct method after 70 per cent hepatic resection and after ligation of the left branch of portal vein in dogs. The total blood supply remains unchanged after both surgical procedures, while the circulation in the remaining lobes, resp. in those patent for portal blood stream, considerably increases. After the resection portal hypertension develops. This elevated portal pressure was not observed after ligation of the left portal branch.


Cloning and high-level SUMO-mediated fusion expression of a serine protease inhibitor from Hyphantria cunea Drury that exhibits activity against papain.
Insect-derived serine protease inhibitors (serpins) exhibit multiple inhibitory activities. Todate some functional roles for serpins in Hyphantria cunea Drury have been identified. Here, new functional features of the H. cunea serine protease inhibitor (dHC-serpin) were characterized. In this study, the cDNA encoding serpin was amplified from H. cunea (dHC) pupa fat body total RNA using RT-PCR. The full-length dHC-serpin cDNA encoded a protein of 440 amino acids with a predicted 19-amino acid signal peptide and a 421-amino acid functional domain. The functional domain was cloned into a pSUMO vector and transformed into Escherichia coli, resulting in the production of a pSUMO-dHC-serpin fusion protein. The soluble form of this protein was then purified by Ni-IDA chromatography. The SUMO-dHC-serpin fusion protein was then cleaved using a SUMO protease and purified again by Ni-IDA chromatography. dHC-serpin did not inhibit trypsin, elastase, proteinase K or cathepsin B, but strongly inhibited papain. The inhibitor retained its inhibitory activity over a broad range of pH (pH 2-12), temperature (20-50 °C), and DTT concentration (up to 100 mM). A complete loss of inhibitory activity was observed at pH 13 and 70 °C. Serpins generally serve as inhibitors that use a mobile reactive center loop (RCL) as bait to trap protease targets. dHC-serpin, like others serpins, binds papain using the RCL structure.


Age-related changes in Folliculogenesis and potential modifiers to improve fertility outcomes - A narrative review.
Reproductive aging is characterized by a decline in oocyte quantity and quality, which is directly associated with a decline in reproductive potential, as well as poorer reproductive success and obstetrical outcomes. As women delay childbearing, understanding the mechanisms of ovarian aging and follicular depletion have become increasingly more relevant. Age-related meiotic errors in oocytes are well established. In addition, it is also important to understand how intraovarian regulators change with aging and how certain treatments can mitigate the impact of aging. Individual studies have demonstrated that reproductive pathways involving antimullerian hormone (AMH), vascular endothelial growth factor (VEGF), neurotropins, insulin-like growth factor 1 (IGF1), and mitochondrial function are pivotal for healthy oocyte and cumulus cell development and are altered with increasing age. We provide a comprehensive review of these individual studies and explain how these factors change in oocytes, cumulus cells, and follicular fluid. We also summarize how modifiers of folliculogenesis, such as vitamin D, coenzyme Q, and dehydroepiandrosterone (DHEA) may be used to potentially overcome age-related changes and enhance fertility outcomes of aged follicles, as evidenced by human and rodent studies.


The gene polymorphisms of IL-8(-251T/A) and IP-10(-1596C/T) are associated with susceptibility and progression of type 2 diabetic retinopathy in northern Chinese population.
PurposeThe aim of the present study is to investigate the association of the polymorphism of two genes in CXC chemokine family, interleukin-8 (IL-8) and interferon-inducible protein 10 (IP-10), with both susceptibility and progression of DR in T2D population of northern China.Patients and methodsA total of 1043 eligible type 2 diabetic patients from Heilongjiang of northern China were recruited for this study. They were grouped into: with diabetic retinopathy (DR, 528 cases) and without diabetic retinopathy (DNR, 515 cases). Single nucleotide polymorphism (SNP) genotyping of IL-8(-251T/A) and IP-10(-1596C/T) was performed by polymerase chain reaction. Multivariate analysis and stepwise multiple logistic progression analysis were conducted to evaluate the association between gene SNP and DR susceptibility and progression. Pooled odds ratio (OR) with 95% confidence interval (CI) was applied to assess the strength of the association among study groups.ResultsThe occurring of IL-8(-251) AA genotype was correlated with susceptibility (OR: 2.286, 95% CI: 1.382-3.782, P=0.001) and progression of high-risk proliferative diabetic retinopathy (PDR) (OR: 0.354, 95% CI: 0.162-0.770, P=0.009). Reversely, T allele of IP-10 (-1596) C/T was correlated with a reduced risk of DR (OR: 0.341, 95% CI: 0.249-0.466, P<0.001). However, gene polymorphisms of IL-8-251T/A and IP-10-1596C/T were not associated with diabetic macular edema (DME)(P>0.05).ConclusionsAA genotype of IL-8-251T/A was closely correlated to DR and high-risk proliferative diabetic retinopathy (PDR). -1596T allele of the IP-10 is a beneficial genotype for DR.


Association of XRCC3 and XPD751 SNP with efficacy of platinum-based chemotherapy in advanced NSCLC patients.
The aim of this study was to investigate whe- ther X-ray repair cross-complementing group 3 (XRCC3) and xeroderma pigmentosum group D (XPD) single nucleotide polymorphism (SNP) affects the outcome of platinum- based chemotherapy in advanced non-small-cell lung cancer (NSCLC) patients. From September 2005 to June 2009, 355 advanced-stage NSCLC patients were accrued to compare the SNP variants with the outcome of platinum-based chemotherapy. TaqMan RT-PCR was used to evaluate the SNPs of the XRCC3 codon241 (Thr/Met) and XPD codon751 (Lys/Gln) DNA repair genes. There was a lack of association between the studied SNPs and the response rate, progression-free survival or overall survival (OS) in the whole population. However, subgroup analysis revealed that XRCC3 241 Thr/Met or Met/Met allele was associated with marginally significantly longer OS than XRCC3 Thr/Thr allele (19.0 m vs. 12.5 m, p=0.081) in the patients treated with gemcitabine/ cisplatin or carboplatin (GP/GC) while it was correlated with a significantly shorter OS in the patients treated with non GP/GC (9.3 m vs. 16 m, p=0.003). XPD751 Lys/Lys had an association with statistical significantly longer OS than XPD751 Lys/Gln or Gln/Gln in the subgroup of elderly patients (14.10 m vs. 10 m, p=0.019) and patients with non-adenocarcinoma (12.6 m vs. 9 m, p=0.042). XRCC3 Thr241Met played an opposite role in predicting prognosis of chemotherapy in NSCLC patients according to the first-line regimens. XPD 751 Lys/ Lys might be a better prognostic marker of elderly or noncarcinoma NSCLC subgroup treated with platinum-based chemotherapy.


Interplant variation in creosotebush foliage characteristics and canopy arthropods.
We conducted a field study to test the hypothesis that creosotebush (Larrea tridentata) shrubs growing in naturally nutrient-rich sites had better quality foliage and supported greater populations of foliage arthropods than shrubs growing in nutrient-poor sites. Nutrient-rich sites had significantly higher concentrations of soil nitrogen than nutrient-poor sites. Multivariate analysis of variance revealed significant differences between high nutrient and low nutrient shrubs based on a number of structural and chemical characteristics measured. High nutrient shrubs were larger, had denser foliage, greater foliage production, higher concentrations of foliar nitrogen and water, and lower concentrations of foliar resin than low nutrient shurbs. Numbers of foliage arthropods, particularly herbivores and predators, were significantly higher on high nutrient shrubs. Shrub characteristics and foliage arthropod abundances varied considerably from shrub to shrub. Shrub characteristics representing shrub size, foliage density, foliage growth, and foliar nitrogen and water concentrations were positively correlated with arthropod abundances. Foliar resin concentrations were negatively correlated with foliage arthropod abundances. The positive relationship between creosotebush productivity and foliage arthropods is contradictory to the tenet that physiologically stressed plants provide better quality foliage to insect herbivores.


Cystoid macular edema as the primary sign of neurosyphilis.
A 34-year-old man had a six-month history of bilateral visual loss that was secondary to cystoid macular edema, which was assumed to be secondary to neurosyphilis on the basis of cerebrospinal fluid serology, cell count, and protein. Good visual acuity was recovered with systemic corticosteroids only after they were used in combination with antitreponemal therapy. This is the first report, to the best of our knowledge, of cystoid macular edema as the primary sign of neurosyphilis documented by fluorescein angiography.


Microbial lipid produced by Yarrowia lipolytica QU21 using industrial waste: a potential feedstock for biodiesel production.
This study aimed to evaluate the effect of medium composition and culture conditions on lipid content, fatty acid profile and biomass production by the yeast Yarrowia lipolytica QU21. Lipid production by the yeast growing on glycerol/(NH4)2SO4 (10%/0.1%) reached 1.48g/L (30.1% according to total cell dry weight). When glycerol was replaced by crude glycerol (industrial waste), the lipid yield was 1.27g/L, with no significant difference. Some particular fatty acids were found when crude glycerol was combined with fresh yeast extract (FYE, brewery waste), as linolenic acid (C18:3n3), eicosadienoic acid (C20:2), eicosatrienoic acid (C20:3n3) and eicosapentaenoic acid (C20:5n3). In addition, the FYE promoted an increase of more than 300% on polyunsaturated fatty acid content (PUFA), which is an undesirable feature for biodiesel production. The fatty acid composition of the oil produced by Y. lipolytica QU21 growing on crude glycerol/(NH4)2SO4 presented a potential use as biodiesel feedstock, with low PUFA content.


Audiovisual documentation of oral consent: a new method of informed consent for illiterate populations.
Informed consent is a legal and ethical requirement of most research in human beings, but obtaining proof of consent in illiterate populations can prove problematic. We used audiovisual documentation of oral consent (video and audiotape recording and photography), a new method of informed consent designed for illiterate populations, in the Guarani Indians Project, a genetic study in the Paraguayan Guarani Indians. We obtained consent from 42 of about 100 potential participants. We believe that our procedure allowed more than half the potential participants to exercise their freedom of refusal. We propose to include this new method as a standard procedure for clinical research in illiterate populations as an alternative to written and signed consent.


Principles of the morbidity and mortality conference.
The goals of the morbidity and mortality conference are learning from mistakes, recognising problems, and being aware of the risks of one's own procedures. Data are continuously collected, complications are classified, and the results of surgery are analyzed. By analysing and discussing the results every three months, total case mortality, mortality of specific procedures, incidence of haematomas, infection rate and incidence of thromboses and emboli are known and a continuous quality control is possible.


Mineral Quantification.
Optimal intakes of elements, such as sodium, potassium, magnesium, calcium, manganese, copper, zinc and iodine, can reduce individual risk factors including those related to cardiovascular diseases among humans and animals. In order to meet the need for vitamins, major minerals, trace minerals, fatty acids and amino acids, it is necessary to include a full spectrum programme that can deliver all of the nutrients in the right ratio. Minerals are required for normal growth, activities of muscles, skeletal development (such as calcium), cellular activity, oxygen transport (copper and iron), chemical reactions in the body, intestinal absorption (magnesium), fluid balance and nerve transmission (sodium and potassium), as well as the regulation of the acid base balance (phosphorus). The chapter discusses the chemical and instrumentation techniques used for estimation of minerals such as N, P, Ca, Mg, K, Na, Fe, Cu, Zn, B and Mb.


Pharmacokinetics in man of acebutolol and hydrochlorothiazide as single agents and in combination.
The pharmacokinetics of acebutolol and hydrochlorothiazide (HCT) alone or in combination were studied in 12 healthy subjects in a cross over study. Acebutolol and diacetolol (the main metabolite) in plasma and urine were determined by HPLC and hydrochlorothiazide by GLC. The main pharmacokinetic parameters of acebutolol did not differ significantly: AUC 4492 +/- 272 micrograms l-1h given alone versus 4118 +/- 354 micrograms l-1h with HCT, half-life (7,69 +/- 0,32 h vs 8,10 +/- 0,72 h) and renal clearance (13,1 +/- 0,5 lh-1 vs 13,8 +/- 0,9 lh-1), respectively. There was no difference in diacetolol pharmacokinetics. HCT values were not significantly different: AUC 784 +/- 48 micrograms l-1h given alone and 720 +/- 42 micrograms l-1h with acebutolol, t 1/2 (4,79 +/- 0,37 h vs 4,73 +/- 0,43 h). The renal clearance was slightly higher when HCT was given with acebutolol (26,2 +/- 2,6 vs 20,3 +/- 2,1 lh-1, p less than 0,05). This increase, observed during the first four hours, was probably due to competition between the drugs for binding to red blood cells.


Evaluation of applied public health emergency system at Prince Mohammed International Airport in Almedinah during Hajj season 2014: a qualitative case study.
During the Hajj season 2014, several public health measures were applied by the Ministry of Health at Prince Mohammed International Airport in Almedinah. However, several operational defects affected the provision of preventive health services for passengers and airport workers. This study aims to evaluate the applied public health emergency system at the airport, detect any potential gaps and to provide appropriate operational solutions. This is a qualitative case study conducted at Prince Mohammed International Airport in Almedinah during the 2014 Hajj season, September 2014. Data were collected via semi-structured interviews, focus groups and policy document reviews. Interviews were conducted with the 14 individuals of the airport's decision makers and relevant health practitioners. Data were recorded via taking notes during interviews and data coding was performed to produce the main themes and subthemes of the study. The main findings of the study revealed three main defects affecting the applied public health emergency system at the airport. The main themes were mainly related to shortage in logistics related to public health emergency systems, shortage in proper documentation of policies and lack of documented protocols of communications among airport stakeholders. The study highlighted the main factors hindering the application of public health emergency measures at the airport. A Public Health Emergency Contingency Plan was proposed as a method to regulate the process of providing logistics for public health preventive services, the method of producing documented policies and methods of producing Memoranda of Understandings as communication regulators.


The respiratory effects of the volatile oil of the black seed (Nigella sativa) in guinea-pigs: elucidation of the mechanism(s) of action.
1. The effect of the volatile oil (VO) of the black seed (Nigella sativa) on the respiratory system of the urethane-anaesthetized guinea-pig was investigated and compared with those of its constituent thymoquinone (TQ). 2. Intravenous administration of VO in the dose range (4-32 microliters kg-1) induced dose-dependent increases in the respiratory rate and the intratracheal pressure. 3. The effects of VO were significantly antagonized by treatment of the animals with mepyramine, atropine and reserpine. They were not antagonized by indomethacin, diethyl carbamazine or hydrocortisone. 4. Intravenous administration of TQ in the dose range (1.6-6.4 mg kg-1) induced significant increases in the intratracheal pressure without any effect in the respiratory rate. 5. The results suggested that VO-induced respiratory effects were mediated via release of histamine with direct involvement of histaminergic mechanisms and indirect activation of muscarinic cholinergic mechanisms. 6. Removal of TQ from VO may provide a potential centrally acting respiratory stimulant.


Imaging mitochondrial redox environment and oxidative stress using a redox-sensitive fluorescent protein.
Redox-sensitive green fluorescent protein (roGFP) is a fluorescent protein in which two cysteines are placed adjacently in the barrel structure. Disulfide formation (oxidation) increases the absorption at short wavelengths (410 nm) at the expense of absorption at longer wavelengths (490 nm). The fluorescence ratio indicates reduction/oxidation, i.e., the redox potential at specific cellular locations.


Effects of individualized music on confused and agitated elderly patients.
The Progressively Lowered Stress Threshold Model in conjunction with an identified theoretical basis provides a framework for the use of individualized music in individuals with Dementia of the Alzheimer's Type (DAT). The effects of individualized music is explored in five elderly patients who are confused and agitated and residing in a long-term care facility. The Modified Cohen-Mansfield Agitation Inventory is used to measure the outcome. The immediate and 1-hour residual effects suggest the potential of individualized music as an alternative approach to the management of agitation in confused elderly patients.


Toxicity and Antiviral Activity of the Extracts of Submerged Mycelium of Nematophagous Duddingtonia flagrans Fungus in Vero Cell Culture.
We studied toxicity and antiviral activity of aqueous and ethanol extracts of bioactive substances from the biomass of nematophagous fungus Duddingtonia flagrans prepared by submerged culturing of the mycelium. It is found that both extracts were characterized by low toxicity for cultured Vero cells and inhibited reproduction of DNA-viruses in this cell line. Ethanol extract of the fungus exhibited higher in vitro antiviral activity against Herpes simplex virus type 2, ectromelia virus, and vaccinia virus than water extract, which can be due to higher content of proteins, polysaccharides, flavonols, catechins, or carotenes or more effective their combination. The extracts of cultured mycelium of Duddingtonia flagrans fungus containing a complex of bioactive substances can be used for creation of broad-spectrum antiviral drugs against DNA-viruses.


R.A. Fisher's gene-centred view of evolution and the Fundamental Theorem of Natural Selection.
The background to R.A. Fisher's enunciation of his Fundamental Theorem of Natural Selection in 1930 is traced and the Theorem in its original form explained. It can now be seen as the centrepiece of Fisher's introduction of the gene-centred approach to evolutionary biology. Although this paper is a sequel to Edwards (1994) it is not a review of the recent literature on the Theorem, to which, however, reference is made at the end.


A form of synaptically induced metabotropic glutamate receptor-dependent long-term depression that does not require postsynaptic calcium.
The calcium control hypothesis posits that postsynaptic calcium increases are required to trigger synaptic plasticity, with large increases inducing LTP and small increases inducing LTD. In CA1 of the hippocampus, however, LTD induced by chemical activation of metabotropic glutamate receptors (agonist-LTD) is independent of increases in postsynaptic calcium. Here we tested whether LTD induced by pairing of presynaptic stimulation with postsynaptic depolarization (synaptic-LTD) is similarly calcium-independent. This protocol induced an NMDA-dependent LTP when paired at 0mV, which was converted to mGluR-dependent LTD when paired at -20mV. The LTD was not blocked by calcium chelation, blockers of L- or T-type voltage-dependent calcium channels, or hyperpolarization to -70mV. We conclude that synaptically induced mGluR-dependent LTD, like agonist induced mGluR LTD, does not require calcium influx for its induction.


Maternal diabetes and risk of childhood malignancies in the offspring: a systematic review and meta-analysis of observational studies.
Diabetes mellitus (DM) is widely recognized as a risk factor for diverse cancers in adults. However, the association between maternal diabetes and risk of childhood cancer in the offspring has so far not been well studied. We thus conducted a meta-analysis to evaluate the role of maternal diabetes on the risk of childhood cancer. We performed a comprehensive literature search to identify eligible studies published up to June 20, 2020, including the PubMed, Web of science and Embase databases. Summary odds ratios (OR) and 95% confidence intervals (CI) were computed using a random-effects model (I2 ≥ 25%) or a fixed-effect model (I2 < 25%). Totally, sixteen case-control and six cohort studies on the risk of childhood cancer associated with maternal diabetes were included. Overall, children of diabetic women had a significantly increased risk in childhood malignancy (OR, 1.30; 95% CI, 1.10-1.53). Notably, a significantly elevated risk of childhood cancer in the offspring was found for women with pre-existing diabetes (OR, 1.41; 95% CI, 1.17-1.70), but not for women with gestational diabetes mellitus (GDM) (OR, 1.10; 95% CI, 0.94-1.28). For site-specific cancers, maternal diabetes was associated with a higher risk of leukemia in offspring (OR, 1.30; 95% CI, 1.15-1.48), especially for acute lymphoblastic leukemia (OR, 1.44; 95% CI, 1.27-1.64). However, no significant associations were observed between maternal diabetes and the risk of lymphomas and retinoblastoma. Our meta-analysis indicates that maternal diabetes is associated with an increased risk of childhood cancer in the offspring, particularly for acute lymphoblastic leukemia. Future study should investigate the underlying biological mechanisms behind the association.


Protein structure to function: insights from computation.
Computation plays an important role in functional genomics. THEMATICS is a computational method that predicts chemical and electrostatic properties of residues in enzymes and utilizes information contained in those predictions to identify active sites. The only input required is the three-dimensional structure of the query protein. The identification of residues involved in catalysis and in recognition is discussed. The two serine proteases Kex2 from Saccharomyces cerevisiae and subtilisin from Bacillus subtilis are used as examples to illustrate how the method finds the catalytic residues for both enzymes. In addition, Kex2 is specific for dibasic sites and THEMATICS finds the recognition residues for both the S1 and S2 sites of Kex2. In contrast, no such recognition sites are found for the non-specific enzyme subtilisin. The ability to identify sites that govern recognition opens the door to better understanding of specificity and to the design of highly specific inhibitors.


Transmission and recombination of chloroplast genes in asexual crosses of Chlamydomonas reinhardtii. II. Comparisons with observations of sexual diploids.
Patterns of biparental chloroplast gene transmission in Chlamydomonas reinhardtii diploids produced by polyethylene glycol (PEG) fusion were found to be similar to those seen in sexual diploids (VanWinkle-Swift and Birky 1978). Examination of the phenotypes of diploid clones showed that the PEG diploids produced a heterogeneous set of allelic frequencies. Neither the frequencies of parental nor recombinant phenotypes were normally distributed. In addition, frequencies of reciprocal recombinant phenotypes showed no significant correlation in the clones from individual PEG diploids. The frequencies of parental phenotypes, on the other hand, were significantly negatively correlated. Like the data from sexual diploids, this is evidence that recombinant frequencies from clones of PEG diploids are not directly related to frequencies of reciprocal recombination. The similarity of results obtained in sexual and PEG diploids supports the hypothesis that the mechanisms operating during biparental chloroplast gene inheritance in PEG diploids are identical to those in sexual diploids.


Nutraceuticals in Migraine: A Summary of Existing Guidelines for Use.
The use of nutraceuticals or food/herbal products for health benefits is expanding in adults with migraine as they seek relief from pain in an effective and tolerable manner not always afforded by current conventional pharmacologic therapies. Guidelines from the American Academy of Neurology/American Headache Society, Canadian Headache Society, and European Federation of Neurological Societies have discussed nutraceuticals in varying degrees of detail with at times conflicting recommendations. This review serves to provide a summary of existing guidelines for the use of certain nutraceuticals including riboflavin, coenzyme Q10, magnesium, butterbur, feverfew, and omega-3 polyunsaturated fatty acids. The review will also discuss the regulation of nutraceuticals in North America and the current controversy regarding butterbur and its safety.


An electrophysiological and spectroscopic study of the properties and structure of biological calcium channels. Investigations of a model ion channel.
The N- and C-terminally protected peptide N-acetyl-Asp-Phe-Ala-Asn-Arg-Val-Leu-Leu-Ser-Leu-Phe-Thr-Ile-Glu-Met-Leu -Leu-Lys-Met-Leu-NH2, closely based on the sequence of the putative S2 membrane spanning helix of domain II of the dihydropyridine receptor calcium channel of the T-system of skeletal muscle, residues 465-486 (Tanabe et al. (1987) Nature 328, 313-318) has been synthesised. Conductance measurements in planar lipid bilayers show that the peptide is capable of inducing the transmembrane passage of calcium and barium ions, in preference to monovalent cations. No anion conductance is observed. 1H-NMR spectroscopy demonstrates that in an amphilic solvent, methanol, the peptide forms highly stable structures characterised by very slow exchange with solvent of peptide N-H protons. Double-quantum filtered phase-sensitive COSY shows that, on the basis of NH-CH alpha scalar coupling constants, most peptide torsion angles are appropriate to an overall alpha-helical conformation; the presence of some alpha-helix is also supported by CD measurements. Most side-chain connectivities have been identified in a DIPSI-TOCSY experiment. This evidence has been used to construct a low-resolution model of the ion-conducting channel of the muscle T-system dihydropyridine receptor from the sequences of the four homologous putative channel-lining stretches. It is characterised by an association of acidic residues at the putative extra-membranous face of the channel, followed by a predominantly hydrophobic band. The next prominent feature of the model is an ordered array of four acidic residues (glutamates 100, 478, 846 and 1164), followed by four lysines (104, 482, 850 and 1168) which may play a gating role.


Constitutive plasma membrane targeting and microdomain localization of Dok5 studied by single-molecule microscopy.
In the present study, single-molecule fluorescence microscopy was used to examine the characteristics of plasma membrane targeting and microdomain localization of enhanced yellow fluorescent protein (eYFP)-tagged wild-type Dok5 and its variants in living Chinese hamster ovary (CHO) cells. We found that Dok5 can target constitutively to the plasma membrane, and the PH domain is essential for this process. Furthermore, single-molecule trajectories analysis revealed that Dok5 can constitutively partition into microdomain on the plasma membrane. Finally, the potential mechanism of microdomain localization of Dok5 was discussed. This study provided insights into the characteristics of plasma membrane targeting and microdomain localization of Dok5 in living CHO cells.


Variation of the Mycobacterium tuberculosis PE_PGRS 33 gene among clinical isolates.
PE_PGRS 33, one of about 60 PE_PGRS genes in the Mycobacterium tuberculosis genome, encodes a surface-expressed protein that may be involved in the antigenic variation of M. tuberculosis strains and evasion of the host immune system. While genetic differences between the PE_PGRS 33 genes of H37Rv and CDC 1551 have been noted, genetic variation in this gene among clinical isolates has not been evaluated. In order to gain a better understanding of the genetic basis for the role of PE_PGRS in antigenic variation and evasion of the host immune system, we investigated the genetic diversity of the PE_PGRS 33 gene among 123 clinical M. tuberculosis isolates from a population-based study, using PCR and DNA sequencing. The 123 isolates belonged to principal genetic groups 1, 2, and 3 and had IS 6110 copy numbers ranging from 1 to 22. Eighty-four (68.3%) of the 123 isolates were found to have at least one sequence variation in the PE_PGRS 33 gene, relative to that of H37Rv. Twenty-five different sequence variations were observed and included three insertions (ranging from 9 to 87 bp), nine deletions (ranging from 1 to 273 bp), one insertion-and-deletion event, and 12 single-nucleotide polymorphisms (six synonymous and six nonsynonymous). Analysis of the relationships among the different PE_PGRS 33 gene sequence variations suggests that polymorphisms in the gene are shifting along evolutionary lineages. The observed genetic diversity of the PE_PGRS 33 gene supports its role in antigenic variation and can serve as a basis for future investigations of the function of the PE_PGRS 33 gene among clinical isolates.


Prevalence of UDP-glucuronosyltransferase polymorphisms (UGT1A6∗2, 1A7∗12, 1A8∗3, 1A9∗3, 2B7∗2, and 2B15∗2) in a Saudi population.
Glucuronidation is an important phase II pathway responsible for many endogenous substances and drug metabolism. The present work evaluated allele frequencies of certain UDP-glucuronosyl-transferases (UGT 1A6∗2, A7∗12, A8∗3, A9∗3, 2B7∗2, and 2B15∗2) in Saudi Arabians that could provide essential ethnic information. Blood samples from 192 healthy unrelated Saudi males of various geographic regions were collected. Genomic DNA was isolated and genotyping of various UGTs was carried out using polymerase chain reaction (PCR) followed by direct sequencing. For UGT1A6∗2 A/G genotype, the most common variant was the homozygous repeat (AA) and the most common allele was (A) with a frequency of 46.5% and 67.3%, respectively. Similarly, the most common variant for UGT1A7∗12 T/C genotype was the heterozygous repeat (TC) with a frequency of 78.7% while the mutant allele (C) was present in 60.6% of the study population. Both UGT1A8∗3 (G/A) and UGT1A9∗3 (T/C) showed only a wild homozygous pattern in all screened subjects. For UGT2B7∗2, the heterozygous repeat (TC) was found with a frequency of 57.3% and the alleles (A) showed a frequency of 50.8%. In contrast, for UGT2B15∗2 (G253T), the heterozygous repeat (TG) presented 62.3% of the subjects where the most common allele (G) was with a frequency of 66.2%. In conclusion, our data indicate that Saudis harbor some important UGT mutations known to affect enzyme activity. Additional studies are therefore, warranted to assess the clinical implications of these gene polymorphisms in this ethnic group.


Cleavage site recognition by the tRNA splicing endoribonuclease.
A single tRNA-splicing endoribonuclease can cleave several precursors. In addition to the conserved nucleotides (nt), there are positions in the mature domain that, though not always occupied by the same nt, nevertheless play a fundamental role in intron excision reaction. The elements of the recognition set (invariant nt, nt at the cardinal positions) can contribute to the overall recognition process by providing either a direct contact for the enzyme or by dictating the spatial orientation of nt that are directly contacted.


Cytochrome P450 CYP6DB3 was involved in thiamethoxam and imidacloprid resistance in Bemisia tabaci Q (Hemiptera: Aleyrodidae).
High level resistance for a variety of insecticides has emerged in Bemisia tabaci, a globally notorious insect. Neonicotinoid insecticides have been applied widely to control B. tabaci. Whether a differentially expressed gene CYP6DB3 discovered from transcriptome data of B. tabaci is involved in the resistance to neonicotinoid insecticides remains unclear. In the study, CYP6DB3 expression was significantly up-regulated in both thiamethoxam- and imidacloprid-resistant strains relative to the susceptive strains. We also found that CYP6DB3 expression was up-regulated after B. tabaci adults were exposed to thiamethoxam and imidacloprid. Moreover, knocking down CYP6DB3 expression via feeding corresponding dsRNA significantly reduced CYP6DB3 mRNA levels by 34.1%. Silencing CYP6DB3 expression increased the sensitivity of B. tabaci Q adults against both thiamethoxam and imidacloprid. Overexpression of CYP6DB3 gene reduced the toxicity of imidacloprid and thiamethoxam to transgenic D. melanogaster. In addition, metabolic studies showed that CYP6DB3 can metabolize 24.41% imidacloprid in vitro. Collectively, these results strongly support that CYP6DB3 plays an important role in the resistance of B. tabaci Q to imidacloprid and thiamethoxam. This work will facilitate a deeper insight into the part of cytochrome P450s in the evolution of insecticide resistance and provide a theoretical basis for the development of new integrated pest resistance management.


Purification and characterization of alpha-amylases from the intestine and muscle of ascaris suum (Nematoda).
Alpha-Amylase (EC 188.8.131.52) was purified from the muscle and intestine of the parasitic helminth of pigs Ascaris suum. The enzymes from the two sources differed in their properties. Isoelectric focusing revealed one form of a-amylase from muscles with pl of 5.0, and two forms of amylase from intestine with pI of 4.7 and 4.5. SDS/PAGE suggested a molecular mass of 83 kDa and 73 kDa for isoenzymes of a-amylases from intestine and 59 kDa for the muscle enzyme. Alpha-Amylase from intestine showed maximum activity at pH 7.4, and the enzyme from muscle at pH 8.2. The muscle enzyme was more thermostabile than the intestinal alpha-amylase. Both the muscle and intestine amylase lost half of its activity after 15 min at 70 degrees C and 50 degrees C, respectively. The Km values were: for muscle amylase 0.22 microg/ml glycogen and 3.33 microg/ml starch, and for intestine amylase 1.77 microg/ml glycogen and 0.48 microg/ml starch. Both amylases were activated by Ca2+ and inhibited by EDTA, iodoacetic acid, p-chloromercuribenzoate and the inhibitor of a-amylase from wheat. No significant differences were found between the properties of a-amylases from parasites and from their hosts.


Aldehyde concentrations in wet deposition and river waters.
The process of pollutants removal from the atmosphere can be responsible for the appearance of aldehydes in surface waters. We observed that formaldehyde, acetaldehyde, propanal, glyoxal, methylglyoxal and acetone were commonly present in precipitations as well as in surface water samples, while semi-volatile and poorly soluble aldehydes as nonanal and decanal were observed seasonally. Particularly high level of carbonyls concentration was noted after periods of drought and at the beginning of rainy periods. We estimated that ca. 40% of aldehydes from wet precipitations were delivered into river waters. The level of carbonyl concentration in river was positively correlated with specific local meteorological conditions such as solar radiation and ozone concentration, in contrast, there was negative correlation between aldehyde concentration in the river samples and the precipitation intensity.


Local diagnostic reference levels for intraoral dental radiography in the public hospitals of Cyprus.
The purpose of this study was to determine local DRLs for children and adults undergoing intraoral dental examinations at the intraoral radiology units of the public hospitals in Cyprus. Measurements were made on all the twenty intraoral X-ray units of the public hospitals in Cyprus with the intention to establish the local DRLs for all the possible intraoral X-ray examinations for children and adults. All units are film based. The measurements were made by a Dose Area Product (DAP) meter (GAMMEX RMI 841-RD) placed at the surface of the dental unit's X-ray shaping cone (FSD 20cm). A diagnostic radiology dosimeter (Dosimax Plus A) was also placed at an FSD of 100cm to compare the dose reading between the two dosimeters. DRLs were established at the 3rd quartile for 7 exposure settings corresponding to 12 types of teeth (Adult and children mandibular and maxillary incisor, premolar and molar) with values of 197, 163, 128, 102, 81, 65 and 49mGycm-2 and 7.23, 5.94, 4.75, 3.68, 3.10, 2.41 and 1.88mGy for benchmark nominal exposure times of 1000, 800, 640, 500, 400, 320 and 250ms respectively, at a nominal exposure voltage of 70kVp. The local DRLs of the present study compare well with other similar published DRLs.


Molecular characterization of trichomonads isolated from animal hosts in the Philippines.
Trichomonads are amitochondrial anaerobic flagellated protists that are either parasites or commensals, generally living in the digestive or genitourinary tract of humans and animals. It has been reported that these protozoa can migrate to other sites in their target host, can adapt to new hosts, and are capable of zoonotic transmission. In this study, 59 trichomonad isolates from different animal hosts in the Philippines were identified and characterized. Primer sets were designed and were successful in amplifying the 18S rRNA gene sequences of the isolates. Phylogenetic trees were constructed using neighbor-joining (NJ), maximum parsimony (MP), maximum-likelihood (ML) and Bayesian inference (BI) analyses. Results showed that BLAST analysis of the isolates corresponded to the clustering of the isolates together with reference sequences in the constructed ML tree. Cattle and pig isolates were most likely Tetratrichomonas buttreyi, which were observed to be commensal in both animals. All duck and rooster isolates were similar with Tetratrichomonas gallinarum. All dog isolates together with single isolates from boa, goat, and owl were identical to Pentatrichomonas hominis. Occurrence of P. hominis in Boa constrictor imperator (boa) and Otus megalotis (Philippine scops owl) suggested the adaptation of the trichomonad to new hosts. Reptile hosts were observed to harbor Trichomitus batrachorum or Hypotrichomonas acosta. Three reptile isolates (Igu2, Igu4, and Liz7) suggest novel species belonging to Class Hypotrichomonadea. Furthermore, iguanas were infected with T. batrachorum or H. acosta. Trichomonads in animal hosts are commensal and the mode of transmission is via fecal-oral route. They are capable of adaptation to new hosts and therefore, zoonotic transmission is possible as well as pathogenesis in host. Thus, trichomonads can pose threats to the health of humans and animals.


The devil is in the details: The chemical basis and mechanistic versatility of flavoprotein monooxygenases.
The ubiquitous flavoenzymes commonly catalyze redox chemistry such as the monooxygenation of organic substrates and are both widely utilized in nature (e.g., in primary and secondary metabolism) and of significant industrial interest. In this work, we highlight the structural and mechanistic characteristics of the distinct types of flavoprotein monooxygenases (FPMOs). We thereby illustrate the chemical basis of FPMO catalysis, which enables reactions such as (aromatic) hydroxylation, epoxidation, (de)halogenation, heteroatom oxygenation, Baeyer-Villiger oxidation, α-hydroxylation of ketones, or non-oxidative carbon-hetero bond cleavage. This seemingly unmatched versatility in oxygenation chemistry results from extensive fine-tuning and regiospecific functionalization of the flavin cofactor that is tightly controlled by the surrounding protein matrix. Accordingly, FPMOs steer the formation of covalent flavin-oxygen adducts for oxygen transfer in the form of the classical flavin-C4a-(hydro)peroxide or the recently discovered N5-functionalized flavins (i.e. the flavin-N5-oxide and the flavin-N5-peroxide), while in rare cases covalent oxygen adduct formation may be foregone entirely. Finally, we speculate about hitherto undiscovered flavin-mediated oxygenation reactions and compare FPMOs to cytochrome P450 monooxygenases, before addressing open questions and challenges for the future investigation of FPMOs.


SYNTHESIS AND REACTIVITY OF ENAMINONE OF NAPHTHO[B] 1,4-OXAZINE: ONE POT SYNTHESIS OF NOVEL ISOLATED AND HETEROCYCLE-FUSED DERIVATIVES WITH ANTIMICROBIAL AND ANTIFUNGAL ACTIVITIES.
The synthesis of the multifunctional, hitherto unreported 3-(3-(dimethylamino)acryloyl)-2H-naphtho[1,2- b] [1,4]oxazin-2-one was described and its utility as a versatile building block was demonstrated for the synthesis of some new pyrimidines, pyrazoles, isoxazoles, pyrazolo[a]pyrimidines, triazolo[a]pyrimidines, pyrido[d]pyrimidines, pyrido[d]pyrimidines, piperidines, pyrido[a]benzimidazoles, 2H-pyran-3-carboxamides, benzofurans, naphtho[b]furans and pyrazolo[c] [1,2,4]triazines of potential biological activities. The synthesized compounds were characterized by IR, 1H NMR, 13C NHR and mass spectral data. Some of the compounds were evaluated for antimicrobial activities.


Efficient preparation of human monoclonal antibody-secreting heterohybridomas using peripheral B lymphocytes cultured in the CD40 system.
The use of peripheral B lymphocytes in the successful preparation of human monoclonal antibodies by hybridoma technology is highly dependent on lymphocyte activation procedures. We studied the ability of peripheral human B lymphocytes cultured in vitro and activated through their CD40 antigen (CD40 system) (Banchereau et al., 1991) to form antibody-secreting heterohybridomas after fusion with murine X63Ag8.653 myeloma cells. The frequency of antibody-secreting heterohybridomas formation was greatly increased (15 times) by culture of B cells in the CD40 system. The CD40 system offers many advantages over other procedures of B lymphocyte activation representing a significant technological advance in the preparation of human monoclonal antibodies by standard hybridoma technology.


Genome analysis of Thermosulfuriphilus ammonigenes ST65T, an anaerobic thermophilic chemolithoautotrophic bacterium isolated from a deep-sea hydrothermal vent.
Thermosulfuriphilus ammonigenes ST65T is an anaerobic thermophilic bacterium isolated from a deep-sea hydrothermal vent chimney. T. ammonigenes is an obligate chemolithoautotroph utilizing elemental sulfur as an electron donor and nitrate as an electron acceptor with sulfate and ammonium formation. It also is able to grow by disproportionation of elemental sulfur, thiosulfate and sulfite. Here, we present the complete genome sequence of strain ST65T. The genome consists of a single chromosome of 2,287,345 base pairs in size and has a G + C content of 51.9 mol%. The genome encodes 2172 proteins, 48 tRNA genes, and 3 rRNA genes. Genome analysis revealed a complete set of genes essential to CO2 fixation and gluconeogenesis. Homologs of genes encoding known enzyme systems for nitrate ammonification are absent in the genome of T. ammonigenes assuming unique mechanism for this pathway. The genome of strain ST65T encodes a complete set of genes necessary for dissimilatory sulfate reduction, which are probably involved in sulfur disproportionation and anaerobic oxidation. This is the first reported genome of a bacterium from the genus Thermosulfuriphilus, providing insights into the microbial contribution into carbon, sulfur and nitrogen cycles in the deep-sea hydrothermal vent environment.


Toxicity and mutual interactions of cadmium and zinc ions in normal and carcinogen-transformed mouse cells.
The toxicity of chloride salts of physiological (zinc, manganese, nickel) and non-physiological (cadmium) bivalent metal ions was studied in normal or carcinogen-transformed mouse embryo fibroblast cells. The dose response curves for toxicity to both types of cells exhibited similar shapes. The transformed cells, however, were about twice as sensitive to zinc toxicity as normal cells. When normal and transformed cells were grown together and incubated for several hours with an appropriate concentration of zinc, the malignant cells were selectively killed. Cadmium was much more toxic than the three other metal ions in both types of cells. Its toxic effect was reversed by simultaneous addition of zinc at nontoxic concentrations.


Impact of body mass index on survival outcome in patients with differentiated thyroid cancer.
Increased body mass index is known to be associated with the high prevalence of differentiated thyroid cancers; however data on its impact on survival outcome after thyroidectomy and adjuvant therapy is scanty. We aimed to evaluate the impact of body mass index on overall survival and disease free survival rates in patients with differentiated thyroid cancers. Between 2000 and 2011, 209 patients with differentiated thyroid cancers (papillary, follicular, hurthle cell) were treated with thyroidectomy followed by adjuvant radioactive iodine-131 therapy and thyroid-stimulating hormone suppression. Based on body mass index, patients were divided into five groups; (a) <18.5kg/m2 (underweight); (b) 18.5-25kg/m2 (normal weight); (c) 26-30kg/m2 (overweight); (d) 31-40kg/m2 (obese) and (e) >40kg/m2 (morbid obese). Various demographic, clinical and treatment characteristics and related toxicity and outcomes (overall survival, and disease free survival) were analyzed and compared. Median follow up period was 5.2years (0.6-10). Mean body mass index was 31.3kg/m2 (17-72); body mass index 31-40kg/m2 was predominant (89 patients, 42.6%) followed by 26-30kg/m2 seen in 58 patients (27.8%). A total of 18 locoregional recurrences (8.6%) and 12 distant metastasis (5.7%) were seen. The 10 year disease free survival and overall survival rates were 83.1% and 58.0% respectively. No significant impact of body mass index on overall survival or disease free survival rates was found (p=0.081). Similarly, multivariate analysis showed that body mass index was not an independent prognostic factor for overall survival and disease free survival. Although body mass index can increase the risk of thyroid cancer, it has no impact on treatment outcome; however, further trials are warranted.


Construction of single-chain antibodies that bind an overlapping epitope of HIV-1 Nef.
The light and heavy chain variable regions of three mouse hybridoma cell lines (AG11, AE6 and EH1) that produce monoclonal antibodies against an overlapping epitope at the C-terminus of Nef were cloned. Sequence analysis of the light and heavy chain variable regions indicated that clones AG11 and AE6, but not EH1, were highly related. Single-chain antibodies were constructed from the cDNA clones of AG11 and EH1, and subcloned into an eukaryotic expressing vector with the green fluorescent protein as marker for expression. Such intracellular antibodies may provide a way in which to inhibit the function of Nef during HIV-1 infection of cells.


Type I interferon-inducible gene expression in blood is present and reflects disease activity in dermatomyositis and polymyositis.
To apply gene expression profiling to the study of peripheral blood mononuclear cells from patients with inflammatory myopathies, in order to provide insight into disease pathogenesis and identify potential biomarkers associated with disease activity. We used Affymetrix whole-genome microarrays to measure the expression of approximately 38,500 genes in 65 blood and 15 muscle samples from 44 patients with dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM), myasthenia gravis, or genetically determined myopathies and from 12 healthy volunteers. In 9 patients, 2 samples were obtained at different time points, when disease was either active or improving, and these paired blood samples were also compared. Bioinformatics techniques were used to identify genes with significant differential expression among diagnostic categories and in relation to disease activity. We corroborated the microarray data with quantitative real-time reverse transcriptase-polymerase chain reaction. Most patients with active DM or PM, but not patients with IBM, had significant and high up-regulation of the type I interferon-alpha/beta (IFNalpha/beta)-inducible genes in blood. Furthermore, the up-regulation of these genes correlated with disease activity in DM and PM, with down-regulation occurring when disease was controlled with treatment. DM and PM are diseases characterized by the systemic overexpression of IFNalpha/beta-inducible genes. The magnitude of the overexpression of these genes is higher in DM and correlates with disease activity in both disorders. Although PM and IBM have been modeled as having similar immunologic processes occurring within muscle, there are substantial differences in the expression of IFNalpha/beta-inducible genes in blood in these diseases.


Structural characterization and antidiabetic activity of a glucopyranose-rich heteropolysaccharide from Catathelasma ventricosum.
Polysaccharides, which are the main bioactive constituents of edible mushrooms, have been shown to have a variety of useful biological activities. In this study, a polysaccharide fraction from the edible mushroom Catathelasma ventricosum was purified using anion exchange and size exclusion chromatographies. The structure of the resulting polysaccharide, named CVP-1S, was characterized on the basis of partial acid hydrolysis, periodic acid oxidation, methylation analysis, gas chromatography-mass spectrometry, Fourier-transform infrared spectroscopy, 1D/2D NMR spectroscopy, scanning electron microscopy, and atomic force spectroscopy. The results showed that CVP-1S is a heteropolysaccharide consisting of glucose (94.2%), galactose (3.51%) and fucose (1.3%) with a molecular weight of 1.5×10(4)Da. Its backbone is mainly linked by (1→6)-β-d-Glcp glycosidic bonds, and branches are attached to the backbone through 1,3-linked glycosidic bonds. CVP-1S was also found to have antioxidant, hypoglycemic, and hypolipidemic activities in the streptozoicin-induced diabetic mouse model. From these results, we conclude that CVP-1S should receive further attention as a potential agent for the treatment and prevention of diabetes.


[Clinical study of the effect of methylene blue combined with aprotinin on intraperitoneal adhesion].
To study the effect of methylene blue combined with aprotinin on intraperitoneal adhesion. From May 2000 to February 2004, there were 83 patients receiving total or partial colectomy and temporary ileostomy or colostomy, and second anastomosis was performed within 8-12 weeks after the first operation. These patients were divided into four groups and followed by intraperitoneal administration of saline,methylene blue,aprotinin,combined methylene blue and aprotinin respectively during the second operation, then adhesion formation was quantitatively graded. The adhesion rate was 15% in combination group, 83% in saline group, 40% in methylene blue group, and 45% in aprotinin group, respectively. The adhesion rate was significantly lower in combination group(P< 0.05). Methylene blue and aprotinin can decrease the incidence of intraperitoneal adhesion significantly. The combination of these two drugs has significant effectiveness in the treatment of intraperitoneal adhesion.


Reproductive responses to varying food supply in a population of Darwin's finches: Clutch size, growth rates and hatching synchrony.
I show how food shortage affects reproduction in a population of Darwin's Medium Ground Finches, Geospiza fortis. Despite the common occurrence of starvation and absence of nest predation, hatching is typically nighly synchronous and adaptive brood reductionappears to be absent. Variation in both growth rates and clutch size in association with the varying conditions is documented. This variation is interpreted as being a direct response to environmental conditions rather than adaptive phenotypic plasticity. I conclude that selection pressures to raise one or two chicks during times of food shortage, or to delay growth rates, are weak or absent.


Cone dysfunctions in retinitis pigmentosa with retinal nerve fiber layer thickening.
To investigate whether or not thicker retinal nerve fiber layer (RNFL) in retinitis pigmentosa (RP) patients relates to functional abnormalities of the photoreceptors. Optical coherence tomography-based RNFL thickness was measured by Stratus-3™ (Zeiss, Basel, Switzerland) optical coherence tomography and electroretinogram (ERG) recordings made using the RETI-port(®) system (Roland, Wiesbaden, Germany) in 27 patients with retinitis pigmentosa and in 30 healthy subjects. Photopic ERG b-wave amplitude, cone ERG b-wave latency, 30 Hz flicker amplitude, and 30 Hz flicker latency had significant correlations to the RNFL-temporal (r = -0.55, P = 0.004, r = 0.68, P = 0.001, r = -0.65, P = 0.001, and r = -0.52, P = 0.007, respectively). Eyes with thicker RNFL (ten eyes) differed significantly from those with thinner RNFL (eight eyes) regarding cone ERG b-wave latency values only (P = 0.001). Thicker RNFL in patients with retinitis pigmentosa may be associated with functional abnormality of the cone system.


Operative outcomes of adult-to-adult right lobe live donor liver transplantation: a comparative study with cadaveric whole-graft liver transplantation in a single center.
To evaluate and compare the operative and survival outcomes of patients who underwent right lobe live donor liver transplantation (RLDLT) and cadaveric whole-graft liver transplant (CWLT) recipients in a single institution. Current data suggest that RLDLT has an inferior graft survival outcome when compared with CWLT. A prospective study was performed on 180 consecutive adult patients who underwent primary liver transplantation from January 2000 to February 2004. The operative and survival outcomes of RLDLT (n = 124) were compared with those of CWLT (n = 56). Fifty-five (44%) and 16 (29%) patients were on high-urgency list in the RLDLT group and the CWLT group, respectively (P = 0.045). The preoperative Model for End-Stage Liver Disease scores were comparable in both groups. The waiting time for liver transplantation was significantly shorter in the RLDLT group. The graft weight to estimated standard liver weight ratio was significantly lower in the RLDLT group. The postoperative hospital stay and hospital mortality were comparable in the RLDLT group (1.6%) and the CWLT group (5.4%). Thirty-one (25%) patients in the RLDLT group and 3 (5%) patients in the CWLT group developed biliary stricture on follow-up (P = 0.002). At a median follow-up of 27 months, the actuarial graft and patient survival rates were 88% and 90%, respectively, in the RLDLT group, and both were 84% in the CWLT group. RLDLT results in favorable operative outcomes comparable with those of CWLT. However, there is a significantly higher incidence of biliary stricture associated with RLDLT.


[Delayed healings of the epithelium of the cornea due to soft lenssolutions].
Six different soft lens solution have been tested to investigate their effect on the healing process of a corneal erosion, experimentally scratched in rabbit-cornea. Healing delays have been observed in every cases; also by three medicaments which are used for "dry" eyes. The latter ones should never have a conjunctival application. Theexplanation of those healing delays is given by the concentration properties of HEMA-lenses for disinfectants. The admixtures of soft lens solutions like buffers and liquid polymerscause and additive effect on retardment of coeneal regeneration.


The relationship between ocular melatonin and dopamine rhythms in the pigeon: effects of melatonin inhibition on dopamine release.
Our previous study has shown that the phases of circadian rhythms of ocular melatonin and dopamine are always opposite and intraocular melatonin injection suppresses dopamine release. Therefore, it is possible that dopamine rhythms result from inhibitory action of melatonin. We have examined this possibility in the following experiments. In the first experiment effects of continuous light on melatonin and dopamine release were examined. The data indicated that continuous light exposure resulted in loss of circadian rhythmicity of melatonin and dopamine by suppressing melatonin and enhancing dopamine levels throughout the day. To further examine the effects of light in the second experiment, 2 h light pulse was applied during the night, then temporal changes of melatonin and dopamine release were studied. The light pulse rapidly suppressed melatonin release, whereas it rapidly increased dopamine release. These changes occurred within 30 min in both melatonin and dopamine. However, the recovery after the cessation of the light stimulus was slower in melatonin than dopamine. In the third experiment it was tested if dopamine release was increased by lowering melatonin release with an intraocular injection of the D2 agonist, quinpirol. Although quinpirol strongly inhibited melatonin release independently of the time of injection, dopamine did not always increase by the inhibition of melatonin. These results indicate that ocular dopamine rhythms are not simply produced by melatonin inhibitory action.


Post-mortem toxicological analysis of cocaine: main biological samples and analytical methods.
This scoping review intends to identify the most used analytical methods and biological samples in the post-mortem forensic toxicological analysis of cocaine and its metabolites. A scoping review was performed based on the question "What are the analytical methods and types of biological samples most frequently used to identify and quantify cocaine in post-mortem forensic toxicology?" The studies were selected from five databases and, after exclusions, the data were tabulated, analyzed, and reported. Twenty-one articles published between 2012 and 2022 were filtered from five different databases to be studied. The collected data indicate that the most used biological samples were blood and hair. The most used sample preparation technique was solid phase extraction, while the most mentioned chromatography method was liquid chromatography with mass spectrometry. This review presents and discusses the state of the art regarding methods for the detection sensitivity spectrum, why limits of quantification are so important for these methods, and what are the most suitable biological samples to be utilized in each case. Cocaine and metabolites are important in forensic toxicologic post-mortem analysis. However, there is little concern in the development of miniaturized and automated sample preparation in this field. Besides, there is not enough understanding of post-mortem redistribution, tolerance, drug-drug interactions, and pre-existing medical conditions.


Validation of a Modified Version of Actero™ Salmonella Enrichment Media for Rapid Detection of Salmonella spp. in Environmental and Food Samples.
Actero™ Salmonella Enrichment Media1 (Actero™ Salmonella) is a culture broth developed to recover Salmonella spp. from foods and environmental surfaces. Performance of Actero™ Salmonella broth has already been assessed and validated (AOAC Performance Tested MethodSM 041403) for the detection of Salmonella spp. in various foods, feeds and environmental samples. This study aimed to validate the performance of a modified version of Actero™ Salmonella broth by incorporating one of the two liquid supplements into the powdered formula. Inclusivity, exclusivity, stability, and lot-to-lot studies were carried out. Raw ground beef, chicken carcass rinse, dry pet food and stainless steel samples were enriched for 14-20 h at 35-39°C and analyzed using real-time PCR assay as well as by direct plating. The Probability of Detection assay confirmed the equivalent performance of the alternative methods as compared to the reference methods. All Salmonella strains, except Salmonella II : 57: z29:-, were able to grow in Actero™ Salmonella broth. One-half of the non-target strains did not grow in Actero™ Salmonella broth, whereas the atypical for Salmonella growth was observed for other non-target microorganisms subsequently plated onto selective and differential agars. Lot-to-lot consistency was demonstrated for three consecutively manufactured lots of the broth. The liquid broth was proven to be stable at 4°C for up to 9 weeks of storage. The incorporation of one of the two specific supplements into a powdered formula of Actero™ Salmonella broth made it more convenient to use without compromising the performance and accuracy.


Multiple regulatory mechanisms of the biological function of NRF3 (NFE2L3) control cancer cell proliferation.
Accumulated evidence suggests a physiological relationship between the transcription factor NRF3 (NFE2L3) and cancers. Under physiological conditions, NRF3 is repressed by its endoplasmic reticulum (ER) sequestration. In response to unidentified signals, NRF3 enters the nucleus and modulates gene expression. However, molecular mechanisms underlying the nuclear translocation of NRF3 and its target gene in cancer cells remain poorly understood. We herein report that multiple regulation of NRF3 activities controls cell proliferation. Our analyses reveal that under physiological conditions, NRF3 is rapidly degraded by the ER-associated degradation (ERAD) ubiquitin ligase HRD1 and valosin-containing protein (VCP) in the cytoplasm. Furthermore, NRF3 is also degraded by β-TRCP, an adaptor for the Skp1-Cul1-F-box protein (SCF) ubiquitin ligase in the nucleus. The nuclear translocation of NRF3 from the ER requires the aspartic protease DNA-damage inducible 1 homolog 2 (DDI2) but does not require inhibition of its HRD1-VCP-mediated degradation. Finally, NRF3 mediates gene expression of the cell cycle regulator U2AF homology motif kinase 1 (UHMK1) for cell proliferation. Collectively, our study provides us many insights into the molecular regulation and biological function of NRF3 in cancer cells.


Association between perioperative NSAID use and post-cardiothoracic surgery atrial fibrillation, blood transfusions, and cardiovascular outcomes: a nested cohort study from the AF Suppression Trials (AFIST) I, II and III.
Nonsteroidal anti-inflammatory drug (NSAID) use may reduce the incidence of post-cardiothoracic surgery (CTS) atrial fibrillation (AF). The cerebrovascular and cardiovascular safety of using NSAIDs for post-CTS AF has not been determined. To evaluate whether NSAIDs could reduce the incidence of post-CTS atrial fibrillation without increasing patients' risk of stroke or myocardial infarction (MI). Patients (n = 555) undergoing CTS from the Atrial Fibrillation Suppression Trials I, II and III were evaluated in this nested cohort study. Demographic, surgical and medication use characteristics were prospectively collected as part of the AFIST trials. Endpoints included post-CTS atrial fibrillation, stroke, MI and the need for red blood cell transfusion. Multivariable logistic regression was used to control for potential confounders and calculate adjusted odds ratios with 95% confidence intervals. The population was 67.8 +/- 8.6 years old and 77.1% male with 127 (22.9%) patients receiving an NSAID postoperatively. Overall, 14.6% underwent valve surgery, 6.1% had prior AF, 12.6% had heart failure and 84.0% and 44.1% received postoperative beta-blockade and prophylactic amiodarone. NSAID use was associated with reductions in the adjusted odds of post-CTS atrial fibrillation (0.54 (0.32-0.90)) and the need for RBC transfusions (0.63 (0.41-0.97)). No elevation in the odds of developing stroke (1.10 (0.21-5.66)) or MI (1.70 (0.40-7.10)) was observed. Patients were not randomized to receive NSAIDs versus a control. We may not have had adequate power to evaluate stoke or MI in this analysis. NSAIDs decreased the odds of developing post-CTS atrial fibrillation, further supporting the hypothesis of inflammation as a trigger for post-CTS atrial fibrillation. The need for RBC transfusions was also reduced with NSAID use. We may have been underpowered to evaluate stroke or MI incidence, but the qualitative elevations in these variables suggest more safety data is needed before NSAIDs can be routinely recommended.


Demonstration of direct binding of cIAP1 degradation-promoting bestatin analogs to BIR3 domain: Synthesis and application of fluorescent bestatin ester analogs.
Overexpression of cIAP1 correlates with resistance to radiotherapy and chemotherapy in various cancers. Recently, we reported that a class of bestatin ester analogs represented by MeBS (2) destabilized and promoted the degradation of cIAP1 through auto-ubiquitination, and thereby sensitized cancer cells to apoptosis. Herein, we present chemical evidence that bestatin ester analogs directly interact with the cIAP1-BIR3 domain by means of fluorescence polarization assay and photoaffinity labeling assay using fluorescent probes.


The effect of a new antidepressant drug, C-45, and imipramine on some hemodynamic parameters in the dog.
C-45, given to dogs in doses corresponding to 1/30 and 1/10 of LD50 iv, slowed down the cardiac rhythm and depressed systolic, diastolic, and end-diastolic pressures in the left ventricle. A dose of 1/30 of LD50 slightly increased, and a dose of 1/10 of LD50 depressed the indices of contractility of the cardiac muscle. Imipramine produced similar effect but accelerated the cardiac rhythm, and when used in a dose of 1/10 of LD50, it impaired atrioventricular and intraventricular conduction.


Colour and brightness components of foveal visual evoked potentials in man.
The different effects of colour and brightness on the transient visual evoked potentials to a foveal stimulus have been investigated in a psycho-physically controlled stimulus set-up, in which equally bright red, orange and green stimuli were substituted for a standard yellow stimulus. These colour-evoked responses were compared with the responses to additional brightness increments and decrements of each of the colour stimuli. An initial component of small amplitude, P55, was followed by a colour-dominated component, N87, and a luminance-dominated component, P120, with a maximum at the occipital electrode. Both N87 and P120 showed a decline in amplitude at the parietal electrode and P120 had a reversed polarity at FZ. These results indicate that the responses to equally bright green and red stimuli have closely similar wave forms, but that this changes rapidly with additional brightness differences. Comparison with the reports of subdural recording of colour-evoked potentials in the macaque striate cortex suggests that P55 corresponds with the primary excitation via geniculo-cortical fibres and that N87 and P120 represent later stages of cortical processing.


NAD kinase sustains lipogenesis and mitochondrial metabolismthrough fatty acid synthesis.
Lipid storage in fat tissue is important for energy homeostasis and cellular functions. Through RNAi screening in Drosophila fat body, we found that knockdown of a Drosophila NAD kinase (NADK), which phosphorylates NAD to synthesize NADP de novo, causes lipid storage defects. NADK sustains lipogenesis by maintaining the pool of NADPH. Promoting NADPH production rescues the lipid storage defect in the fat body of NADK RNAi animals. Furthermore, NADK and fatty acid synthase 1 (FASN1) regulate mitochondrial mass and function by altering the levels of acetyl-CoA and fatty acids. Reducing the level of acetyl-CoA or increasing the synthesis of cardiolipin (CL), a mitochondrion-specific phospholipid, partially rescues the mitochondrial defects of NADK RNAi. Therefore, NADK- and FASN1-mediated fatty acid synthesis coordinates lipid storage and mitochondrial function.


Restraint or immobilization: A comparison of methodologies for restricting free movement in rodents and their potential impact on physiology and behavior.
Restriction of free movement has historically been used as a model for inducing acute and chronic stress in laboratory animals. This paradigm is one of the most widely employed experimental procedures for basic research studies of stress-related disorders. It is easy to implement, and it rarely involves any physical harm to the animal. Many different methods have been developed with variations in the apparatuses used and the degree of limitation of movement. Unfortunately, very few studies directly compare the differential impact of the distinct protocols. Additionally, restraint and immobilization terms are not differentiated and are sometimes used interchangeably in the literature. This review offers evidence of great physiological differences in the impact of distinct restraint and immobilization procedures in rats and mice and emphasizes the need for a standardized language on this topic. Moreover, it illustrates the necessity of additional systematic studies that compare the effects of the distinct methodologies, which would help to decide better which procedure should be used depending on the objectives of each particular study.


Etiopathogenesis of osteolytic cysts associated with total ankle arthroplasty, a histological study.
Osteolytic cyst formation after total ankle arthroplasty has been identified in recent years and is probably an important problem with longer follow-up. The aim of this study is to describe the outcome of a histological analysis of samples from periprosthetic intra-osseous cysts and joint capsules, retrieved during revision surgery after primary total ankle arthroplasty. All samples (n=22) were analyzed and scored using a semi-quantitative grading system. The main items of interest were polyethylene (PE) particles, metal particles, histiocytes, and giant cells. All cyst samples contained PE particles. A similar number of PE particles were found in talar and tibial cysts. No significant correlation between the number of PE particles and time to reoperation was found. Metal particles were found in 16 cysts. We suggest that PE particles are not the primary cause of osteolytic cyst formation but a secondary contributing factor probably accelerating the process of osteolysis. It is likely that implant design, biomechanical factors and local anatomic-physiological factors play an important role.


Characterization of a Lactobacillus gasseri JCM 1131T lipoteichoic acid with a novel glycolipid anchor structure.
We determined the chemical structure of lipoteichoic acid (LTA) from Lactobacillus gasseri JCM 1131(T). The repeating unit was comprised of glycerolphosphate and 2-alanylglycerolphosphate. The glycolipid anchor was tetrahexosylglycerol with two or three acyl groups. To our knowledge, this is the first demonstration of a tetrahexose structure in an LTA glycolipid anchor.


Comparing Cost-Effectiveness of HIV Testing Strategies: Targeted and Routine Testing in Washington, DC.
Routine HIV testing is an essential approach to identifying undiagnosed infections, linking people to care and treatment, and preventing new infections. In Washington, DC, where HIV prevalence is 2.4%, a combination of routine and targeted testing approaches has been implemented since 2006. We sought to evaluate the cost effectiveness of the District of Columbia (DC) Department of Health's routine and targeted HIV testing implementation strategies. We collected HIV testing data from 3 types of DC Department of Health-funded testing sites (clinics, hospitals, and community-based organizations); collected testing and labor costs; and calculated effectiveness measures including cost per new diagnosis and cost per averted transmission. Compared to routine testing, targeted testing resulted in higher positivity rates (1.33% vs. 0.44%). Routine testing averted 34.30 transmissions per year compared to targeted testing at 17.78. The cost per new diagnosis was lower for targeted testing ($2,467 vs. $7,753 per new diagnosis) as was the cost per transmission averted ($33,160 vs. $104,205). When stratified by testing site, both testing approaches were most cost effective in averting new transmissions when conducted by community based organizations ($25,037 routine; $33,123 targeted) compared to hospitals or clinics. While routine testing identified more newly diagnosed infections and averted more infections than targeted testing, targeted testing is more cost effective per diagnosis and per transmission averted overall. Given the high HIV prevalence in DC, the DC Department of Health's implementation strategy should continue to encourage routine testing implementation with emphasis on a combined testing strategy among community-based organizations.


Studies on the mechanism of thrombin. Interaction with fibrin.
Fibrin monomer Sepharose was used to investigate the interactions of thrombin with fibrin. Thrombin binding was found to be reversible and saturable and to depend on the thrombin: fibrin ratio. Scatchard analysis indicated a single class of binding sites with K alpha = 4.9 X 10(5) M-1. Ca2+ ions caused rapid desorption and elution of thrombin from fibrin monomer, and the Ca2+ concentration needed for maximal desorption depended on the fibrin:thrombin ratio. Mg2+, Mn2+, and Sr2+ also released thrombin from fibrin monomer but not as efficiently as Ca2+. These results indicate that divalent metal ions induce a physical change in fibrin monomer which results in desorption of thrombin. Thrombin binding to fibrin in a gel was compared to binding to fibrin monomer. These studies showed that as fibrin monomers polymerize to form the gel network, thrombin is released. Under static conditions the released thrombin remains associated with the gel because diffusion is limited by the gel. However, the thrombin can be readily removed when buffer is allowed to flow through the gel. These results lead to the possibility that thrombin binding to fibrin monomer and its subsequent release, either by Ca2+ or by polymerization, may have important consequences for regulating the effective thrombin concentration in vivo.


SERPINA3K induces apoptosis in human colorectal cancer cells via activating the Fas/FasL/caspase-8 signaling pathway.
SERPINA3K, also known as kallikrein-binding protein (KBP), is a serine proteinase inhibitor with anti-inflammatory and anti-angiogenic activities. Our previous studies showed that SERPINA3K inhibited proliferation in a dose-dependent manner and induced apoptosis of endothelial cells but had no influence on SGC-7901 gastric carcinoma cells or HepG2 hepatocarcinoma cells. However, it is unknown whether SERPINA3K has a direct impact on other carcinoma cells and which mechanisms are involved. In this study, we report for the first time that SERPINA3K not only decreased cell viability but also induced apoptosis in the colorectal carcinoma cell lines SW480 and HT-29. SERPINA3K-induced apoptosis of SW480 and HT-29 was rescued by interference with Fas ligand (FasL) small hairpin RNA. Moreover, SERPINA3K increased the expression of FasL and activated caspase-8. Peroxisome proliferator-activated receptor γ (PPARγ), a transcription factor of FasL, was also upregulated by SERPINA3K in a dose-dependent manner. The upregulation effect of FasL induced by SERPINA3K was reversed after interference with PPARγ small interfering RNA. These results demonstrated that SERPINA3K-induced SW480 and HT-29 cell apoptosis was mediated by the PPARγ/Fas/FasL signaling pathway. Therefore, our study provides additional insight into the direct anti-tumor function by inducing tumor cell apoptosis of SERPINA3K in colorectal tumors.