Implementing federal food service guidelines in federal and private worksite cafeterias in the United States leads to improved health outcomes and is cost saving.
Poor diet increases cardiometabolic disease risk, yet the impact of food service guidelines on employee health and its cost effectiveness is poorly understood. Federal food service guidelines (FFSG) aim to provide United States (U.S.) government employees with healthier food options. Using microsimulation modeling, we estimated changes in the incidence of cardiometabolic disease, related mortality, and the cost effectiveness of implementing FFSG in nationally representative model populations of government and private company employees across 5 years and lifetime. We based estimates on changes in workplace intake of six FFSG dietary targets and showed lifetime reductions of heart attacks (- 107/million), strokes (- 30/million), diabetes (- 134/million), ischemic heart disease deaths (- 56/million), and stroke deaths (- 8/million). FFSG is cost saving overall, with total savings in discounted healthcare costs from $4,611,026 (5 years) to $539,809,707 (lifetime) $U.S. This study demonstrates that FFSG improves health outcomes and is cost saving.


Wounding coordinately induces cell wall protein, cell cycle and pectin methyl esterase genes involved in tuber closing layer and wound periderm development.
Little is known about the coordinate induction of genes that may be involved in agriculturally important wound-healing events. In this study, wound-healing events were determined together with wound-induced expression profiles of selected cell cycle, cell wall protein, and pectin methyl esterase genes using two diverse potato genotypes and two harvests (NDTX4271-5R and Russet Burbank tubers; 2008 and 2009 harvests). By 5 d after wounding, the closing layer and a nascent phellogen had formed. Phellogen cell divisions generated phellem layers until cessation of cell division at 28 d after wounding for both genotypes and harvests. Cell cycle genes encoding epidermal growth factor binding protein (StEBP), cyclin-dependent kinase B (StCDKB) and cyclin-dependent kinase regulatory subunit (StCKS1At) were induced by 1 d after wounding; these expressions coordinated with related phellogen formation and the induction and cessation of phellem cell formation. Genes encoding the structural cell wall proteins extensin (StExt1) and extensin-like (StExtlk) were dramatically up-regulated by 1-5 d after wounding, suggesting involvement with closing layer and later phellem cell layer formation. Wounding up-regulated pectin methyl esterase genes (StPME and StPrePME); StPME expression increased during closing layer and phellem cell formation, whereas maximum expression of StPrePME occurred at 5-14 d after wounding, implicating involvement in later modifications for closing layer and phellem cell formation. The coordinate induction and expression profile of StTLRP, a gene encoding a cell wall strengthening "tyrosine-and lysine-rich protein," suggested a role in the formation of the closing layer followed by phellem cell generation and maturation. Collectively, the genes monitored were wound-inducible and their expression profiles markedly coordinated with closing layer formation and the index for phellogen layer meristematic activity during wound periderm development; results were more influenced by harvest than genotype. Importantly, StTLRP was the only gene examined that may be involved in phellogen cell wall thickening after cessation of phellogen cell division.


Investigating driver injury severity patterns in rollover crashes using support vector machine models.
Rollover crash is one of the major types of traffic crashes that induce fatal injuries. It is important to investigate the factors that affect rollover crashes and their influence on driver injury severity outcomes. This study employs support vector machine (SVM) models to investigate driver injury severity patterns in rollover crashes based on two-year crash data gathered in New Mexico. The impacts of various explanatory variables are examined in terms of crash and environmental information, vehicle features, and driver demographics and behavior characteristics. A classification and regression tree (CART) model is utilized to identify significant variables and SVM models with polynomial and Gaussian radius basis function (RBF) kernels are used for model performance evaluation. It is shown that the SVM models produce reasonable prediction performance and the polynomial kernel outperforms the Gaussian RBF kernel. Variable impact analysis reveals that factors including comfortable driving environment conditions, driver alcohol or drug involvement, seatbelt use, number of travel lanes, driver demographic features, maximum vehicle damages in crashes, crash time, and crash location are significantly associated with driver incapacitating injuries and fatalities. These findings provide insights for better understanding rollover crash causes and the impacts of various explanatory factors on driver injury severity patterns.


Association between immunohistochemical expression of matrix metalloproteinases and metastasis in oral squamous cell carcinoma: Systematic review and meta-analysis.
The aim of this systematic review (SR) was to summarize and critically appraise available evidence on the association of the immunohistochemical expression of matrix metalloproteinases (MMPs) with the occurrence of lymph node/distant metastasis of oral squamous cell carcinoma (OSCC). Searches were conducted in five main electronic and three gray literature databases. From 2128 records identified, 50 were included for qualitative analysis. A total of 12 MMPs were identified (-1, -2, -3, -7, -8, -9, -10, -11, -13, -25, -26, and MT1-MMP). Most included studies reported a positive association of MMP-1, -2, -3, -7, -9, and MT1-MMP with lymph node metastasis. MMP-8, -25, and -26 were not associated with lymph node metastasis. According to this SR, MMP-1, -2, -3, -7, -9, and MT1-MMP seem to play an important role in lymph node metastasis of OSCC.


Enantioselective Rh(I)-catalyzed cyclization of arylboron compounds onto ketones.
Rhodium complexes based upon chiral sulfinamide-alkene, TADDOL-derived phosphoramidite, or diene ligands catalyze cyclizations of arylboron compounds onto ketones, generating a variety of products containing five-, six-, or seven-membered rings with good yields and high enantioselectivities.


Circular RNA circSLC7A11 contributes to progression and stemness of laryngeal squamous cell carcinoma via sponging miR-877-5p from LASP1.
Laryngeal squamous cell carcinoma (LSCC) belongs to tumors of head and neck. Circular RNA circSLC7A11 functions as oncogenes in various tumors. However, the role of circSLC7A11 in LSCC remains largely unknown. Here, we aimed to clarify the circSLC7A11 function in LSCC. Relevance between circSLC7A11 expressions and LSCC clinicopathological was checked using chi-square. Relevance between circSLC7A11 expressions and LSCC patients' survival time was validated using Kaplan-Meier analysis. CircSLC7A11 expressions in LSCC tissues and cells were determined using quantitative real-time PCR. CircSLC7A11 functions in LSCC were examined by Cell Counting Kit-8, EdU analysis, Western blot, flow cytometry, sphere formation assay, and Transwell analysis. Meanwhile, circSLC7A11 mechanism in LSCC was determined using dual-luciferase reporter analysis, RNA pull-down, RNA Immunoprecipitation. CircSLC7A11 was highly expressed in LSCC, and high circSLC7A11 expressions were interrelated to the TNM stage. Also, LSCC patients with high circSLC7A11 owned shorter overall survival. Functional studies revealed that circSLC7A11 knockdown reduced LSCC cell proliferation, migration, invasion, stemness characteristics, and enhanced cell apoptosis. Mechanistic study data corroborated that circSLC7A11 targeted miR-877-5p, miR-877-5p targeted LASP1. LASP1 was negatively interrelated to miR-877-5p and was positively interrelated to circSLC7A11 in LSCC tissues. Also, circSLC7A11 knockdown reduced the LASP1 levels, and miR-877-5p inhibitor co-transfection reversed this reduction. Rescue assays further demonstrated that circSLC7A11 accelerated LSCC through miR-877-5p/LASP1. CircSLC7A11 exerted oncogenic functions in LSCC by miR-877-5p/LASP1, hinting that circSLC7A11 was a novel biomarker for LSCC.


Cryotherapy in phthiriasis palpebrarum.
A 5-year-old white girl had phthiriasis palpebrarum of both upper eyelids. Excellent cooperation by the patient permitted the destruction of adult lice and the nits by cryoapplication under the slit lamp. Cryotherapy seems to be a promising method of treating phthiriasis palpebrarum in a single office visit.


New Drugs for Asthma--IBC's International Conference. 16-17 June 1998, National Heart & Lung Institute, London, UK.
The latest in this series of biennial meetings looking at new drugs for asthma was chaired by Professor Peter Barnes (National Heart and Lung Institute, Imperial College School of Medicine, London, UK). In contrast to earlier meetings in this series the emphasis was more on potential new therapeutic approaches, with many of the topics addressed describing therapeutic approaches which have yet to reach clinical evaluation.


Perceived levels of satisfaction with the preoperative assessment service experienced by patients undergoing general anaesthesia in a day surgery setting.
Primary aim--to explore patient satisfaction with preoperative assessment for day surgery and compare patient satisfaction between two specialties, General Surgery and Urology. Secondary aim--to compare numbers of patients being preoperatively assessed in General Surgery and Urology. Patient-centred care is increasingly gaining significance, and patient satisfaction is an outcome measure assuming greater importance [Department of Health (2005) Creating a Patient Led NHS. Crown Copyright, London]. There is a paucity of literature on patient satisfaction with preoperative assessment. This article reports the findings of a study investigating satisfaction levels in patients undergoing preoperative assessment for general anaesthesia in a day surgery setting. Cross-sectional survey using a questionnaire. A questionnaire was distributed to General Surgery and Urology patients on their day of admission in one general hospital. The questionnaire was designed to capture data on the type of preoperative assessment received and satisfaction levels of patients' experiences of the preoperative assessment service. The questionnaire was completed by 275 patients. There were no significant differences in expressed satisfaction between specialties with the preoperative assessment service or the type of preoperative assessment experienced. However, more General Surgery respondents felt preoperative assessment prepared them for hospital admission than Urology respondents, a chi-square test revealed a significant difference between the specialties (p = 0.046). Although patients expressed overall satisfaction with preoperative assessment, their responses reveal there are key issues. Several themes emerged indicating that exchange of preoperative information, a supportive attitude, anxiety and fearfulness, proceedings and aftercare are significant aspects of preoperative assessment for patients. Although there is some satisfaction, this study reveals that various aspects of this preoperative assessment service could be improved. This information will help inform future development of the preoperative assessment service. If preoperative assessment is to be patient centred, enjoying high levels of patient satisfaction, attention to patients' individual needs must be a priority.


Subcellular localization and membrane topology of serine palmitoyltransferase, 3-dehydrosphinganine reductase, and sphinganine N-acyltransferase in mouse liver.
Serine palmitoyltransferase, 3-dehydrosphinganine reductase and sphinganine N-acyltransferase are responsible for the first steps in sphingolipid biosynthesis forming 3-oxosphinganine, sphinganine, and dihydroceramide, respectively. We confirmed the localization of these enzymes in the endoplasmic reticulum (ER) using highly purified mouse liver ER and Golgi preparations. Mild digestion of sealed "right-side out" mouse liver ER derived vesicles with different proteolytic enzymes under conditions where latency of mannose-6-phosphatase was 90% produced approximately 60-80% inactivation of serine palmitoyltransferase, 3-dehydrosphinganine reductase, and sphinganine N-acyltransferase activities. These sphingolipid biosynthetic activities (serine palmitoyltransferase, 3-dehydrosphinganine reductase, and sphinganine N-acyltransferase) are not latent, indicating that they face the cytosolic side of the ER, so that substrates have free access to their active sites. Moreover, the membrane-impermeable compound, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, which binds to a large number of ER proteins, inhibits serine palmitoyltransferase and sphinganine N-acyltransferase activities by 30-70%.


S phase mouse embryo fibroblasts secrete varying amounts of a 45,000 dalton protein.
Synchronized cultures of mouse embryo fibroblasts upon release from hydroxyurea (HOU) arrest, secreted several proteins of which a polypeptide of molecular weight 45,000 (45K) was barely visible in the conditioned medium of cells that synthesized DNA at peak levels. The quantity of the 45K protein was higher in the medium of HOU arrested cells and the level got progressively reduced as the cells entered into the DNA synthetic phase. Conditioned media containing the 45K protein inhibit DNA synthesis when added to synchronized cultures. These results suggest that the 45K secreted protein may be involved in the autocrine regulation of turning-off of DNA synthesis at the end of S phase.


Patients' and Caregivers' Experiences with the Multi-Payer Advanced Primary Care Practice Demonstration.
The patient-centered medical home (PCMH) model aims to improve primary health care using a patient-centered approach. Little qualitative research has investigated how the PCMH model affects patient experience with care. To understand Medicaid and Medicare patient and caregiver experiences with PCMHs participating in the Multi-Payer Advanced Primary Care Practice (MAPCP) Demonstration. Qualitative study. Medicare, Medicaid, and dually eligible patients who were patients in primary care practices participating in the MAPCP Demonstration and caregivers of such patients (N = 490). From July through November 2014, a trained facilitator conducted 81 focus groups in the eight states participating in the MAPCP Demonstration. Separate groups were held for Medicare high-risk, Medicare low-risk, Medicaid, and dually eligible beneficiaries, their caregivers, and caregivers of Medicaid children (or, in Vermont, with patients participating in the Support and Services at Home program), in two different geographical areas in each state. Focus group discussions were recorded, transcribed, and analyzed using NVivo qualitative data analysis software. Participants' experiences with care were generally consistent with the expectations of a PCMH, although some exceptions were noted. Medicaid only and dually eligible beneficiaries generally had less-positive experiences than Medicare beneficiaries. Most participants said their practices had not solicited feedback from them about their experiences with care. Few participants knew what the term "medical home" meant or were aware that their practices were working to become PCMHs, but many had noticed changes in recent years, primarily related to the conversion to electronic health records. Most participants had positive experiences with their care. Opportunities exist, however, to improve care for Medicaid and dually eligible beneficiaries, and enhance patient awareness of and involvement in PCMH practice transformation.


Safety and efficacy of transoral robotic and endoscopic thyroidectomy: The first 100 cases.
The aim of this study was to evaluate the safety and efficacy of transoral robotic and endoscopic thyroidectomy. We analyzed and compared the first 100 cases of transoral robotic (71 cases) and endoscopic (29 cases) thyroidectomy with 207 cases of conventional transcervical thyroidectomy. Transoral thyroidectomy was completed successfully in all patients, except for three who were converted to the robotic facelift or transcervical approach. The mean operative time of the transoral procedure was significantly longer than that of the conventional procedure. Perioperative complications such as hypoparathyroidism, vocal cord palsy, hematoma, and seroma did not differ between the two groups. However, there were some unusual complications such as CO2 embolism, surgical site infection, skin trauma, burn, and ecchymosis in transoral thyroidectomy. Postoperative cosmesis was significantly better in the transoral group. Transoral robotic and endoscopic thyroidectomy is feasible and comparable to conventional transcervical thyroidectomy in highly selected patients.


Estrogen and estrogen-progestogen replacement: therapy and cardiovascular diseases.
The use of postmenopausal estrogens primarily to prevent heart disease should be reserved for women at high risk by virtue of an unfavorable low-density lipoprotein: high-density lipoprotein (LDL:HDL) ratio or the presence of manifest disease. Unopposed oral estrogen should improve lipoproteins within a few weeks, and this change, if sustained, should reduce the risk of cardiovascular disease. There is no reason to give progestins to a woman without a uterus. The management of a woman with an intact uterus is less well defined, given the unknowns about progestin's long-term effects on lipids or the heart.


Combinations of amitraz with essential oils from Lippia sidoides and Thymus vulgaris, thymol and thymol acetate for Rhipicephalus microplus control: studies under laboratory and field conditions.
This study aimed to assess the effect of combining amitraz with essential oils (EOs) from Thymus vulgaris and Lippia sidoides, as well as the monoterpenes thymol and thymol acetate, on Rhipicephalus microplus in laboratory conditions, and to select the most effective combination for testing in field conditions. The chemical analysis showed that EOs were mainly composed of monoterpenes, with thymol and p-cymene as the major compounds. In larval (LIT) and adult (AIT) immersion tests using different concentrations of the oils and terpenes mixed with amitraz, the results showed that both EOs and thymol improved the efficacy of amitraz against larvae and engorged females of R. microplus, whereas thymol acetate only enhanced activity against larvae. The most favorable outcome was obtained with the EO of L. sidoides combined with amitraz, resulting in 99 % and 100 % efficacy against larvae and engorged females, respectively. Furthermore, the combination of amitraz with thymol showed presented an efficacy of 94 % and 91 % against larvae and engorged females, respectively. Thus, for the other tests, the combination of thymol + amitraz was chosen due to the ease of working with pure thymol in bioassays, and easier standardization. The immersion test (thymol + amitraz) with semi-engorged females showed 100 % efficacy for the combination of thymol + amitraz, while in tests with different solvents (thymol + amitraz), ethanol being the most effective solvent among those tested (ethanol, Triton, and Tween), resulting in 95 % efficacy on engorged females. In the field test, in treatments with amitraz and thymol + amitraz, efficacy of 54 % and 74 % was observed on day + 3 and 33 % and 43 % on day + 7, respectively. Assessing the reproductive biology of females recovered from animals treated with amitraz or amitraz + thymol, in day + 7, efficacies of 33 % and 52 %, respectively, were observed. EOs from T. vulgaris and L. sidoides and thymol improved the acaricidal activity of amitraz on larvae and engorged females of R. microplus under laboratory conditions, while thymol acetate only enhanced activity against larvae. Thymol increased the efficacy of amitraz under field conditions, however for the development of a commercially available acaricide to R. microplus control, additional studies are needed to increase the efficacy. Further research is needed (by changing concentrations, adding other compounds and/or developing formulations) to increase acaricidal efficacy and develop new effective products to combat R. microplus infestations in cattle.


YAP regulates the liver size during the fasting-refeeding transition in mice.
Liver is the central hub regulating energy metabolism during feeding-fasting transition. Evidence suggests that fasting and refeeding induce dynamic changes in liver size, but the underlying mechanisms remain unclear. Yes-associated protein (YAP) is a key regulator of organ size. This study aims to explore the role of YAP in fasting- and refeeding-induced changes in liver size. Here, fasting significantly reduced liver size, which was recovered to the normal level after refeeding. Moreover, hepatocyte size was decreased and hepatocyte proliferation was inhibited after fasting. Conversely, refeeding promoted hepatocyte enlargement and proliferation compared to fasted state. Mechanistically, fasting or refeeding regulated the expression of YAP and its downstream targets, as well as the proliferation-related protein cyclin D1 (CCND1). Furthermore, fasting significantly reduced the liver size in AAV-control mice, which was mitigated in AAV Yap (5SA) mice. Yap overexpression also prevented the effect of fasting on hepatocyte size and proliferation. Besides, the recovery of liver size after refeeding was delayed in AAV Yap shRNA mice. Yap knockdown attenuated refeeding-induced hepatocyte enlargement and proliferation. In summary, this study demonstrated that YAP plays an important role in dynamic changes of liver size during fasting-refeeding transition, which provides new evidence for YAP in regulating liver size under energy stress.


Corneal opacification occurring after phacoemulsification and phacofragmentation.
Four patients developed progressive corneal opacification five to eight months after ultrasonic cataract extraction. Transmission electron microscopy was performed in all patients. Scanning electron microscopy, performed in only one patient, showed radiating folds of Descemet's membrane with pits on its posterior surface as well as focal traumatic disruption probably caused by probe contact. Bullous keratopathy was present in one patient. Two other patients had folds of Descemet's membrane and a thin retrocorneal fibrous layer. All four tumor specimens showed secondary epithelial and stromal changes. The common denominator was the total or partial absence of endothelium or marked alterations of its remnants.


Trials of the bronchodilator activity of the xanthine analogue SDZ MKS 492 in healthy volunteers during a methacholine challenge test.
An approximately steady-state reduction of specific airway conductance was induced in healthy human subjects by means of an individualized inhaled methacholine loading dose followed by a maintenance dose regime. Tested against this background bronchoconstriction, the xanthine analogue SDZ MKS 492, when administered as a single oral dose of 40 mg, showed a significant bronchodilator action, which lasted for up to 5.5 h. Bronchodilatation was not seen after administration of 10 or 20 mg doses. SDZ MKS 492 inhaled as a dry powder had a bronchodilator action that was small, most evident with the 12 mg dose and transient. The peak relief of imposed bronchoconstriction was 29% and the apparent half-time of removal of SDZ MKS 492 from its site of action was 5-6 min. Inhaled SDZ 492 had a bitter taste that was not masked by inclusion of menthol and aspartame in the formulation. The bronchodilatation seen in laboratory animals can also be produced by SDZ MKS 492 in man when administered orally or by inhalation. Its magnitude correlates better with the plasma concentration of parent drug than with that of either of the identified metabolites. Dispositional processes in the lung abbreviate its action after administration by inhalation.


Inhibition of short-term memory formation in the chick by blockade of extracellular glutamate uptake.
Injection of monosodium glutamate (40nmol/hemisphere) into the intermediate hyperstriatum ventrale of the day-old chick inhibits the formation of short-term memory for a single trial learning that discriminates between colours of beads. These experiments showed that an excess of glutamate close to learning could be damaging to memory. In the present experiments we have blocked the normal reuptake of glutamate and suggest that glutamate release plays a role in normal learning. Removal of glutamate, released from presynaptic neurones during learning, is achieved by various neuronal and astrocytic glutamate transporters. By blocking the primarily astrocytic removal of glutamate by the injection of L-aspartic acid beta-hydroxamate, we effectively increased extrasynaptic levels of glutamate and inhibited short-term memory in a similar manner to central injection of 40nmol glutamate per hemisphere. These experiments suggest that glutamate release within 2.5min of the learning experience is an important feature of short-term memory formation.


Repeatability, reliability and reproducibility of posterior curvature and wavefront aberrations in keratoconic and cross-linked corneas.
The aim was to assess the intra-session, inter-session and inter-observer repeatability of curvature and aberrometric measurements of Pentacam-derived posterior corneal surface in normal control (CG), keratoconic (KCG) and after corneal collagen cross-linked (CXLG) groups. This was a prospective, clinic-based, observational study that was conducted at the Eye Institute of Thrace (EIT) in Alexandroupolis, Greece. Sixty-two normal eyes formed the control group, 33 were in the keratoconic group, while 34 eyes, which already had received corneal collagen cross-linking formed the CXLG. Curvature and aberrometric measurements were obtained using the Pentacam by two operators within each of the two sessions. Precision (Pre), repeatability (COR) and the intra-class correlation coefficient (ICC) were calculated for evaluating intra-session and inter-session repeatability. Bland-Altman analysis was used for assessing inter-observer repeatability. Simulated keratometric parameters K1 and K2, asphericity at the central 8 mm zone (Q8) and central steepest radius of best fit toric ellipsoid reference body (Rs), achieved an acceptable level of accuracy. Aberrometric parameters were repeatable, reliable and reproducible only in terms of the root mean square (RMS) errors (coma, coma-like and the RMS of higher order aberrations or HOA RMS). For both observers, best precision and lowest range of agreement (ROA) was found for HOA RMS parameters in all groups (less than 0.27 and less than 0.29 for the control group, less than 0.95 and less than 0.72 for the keratoconic group and less than 0.67 and 0.53 for the collagen cross-linked group). The Pentacam system provides precise measurements of corneal posterior keratometry, reference body radius and asphericity for large diameter analysis. Although Zernike coefficients for individuals presented poor repeatability, the coma, coma-like and HOA RMS seem to be accurate indices in characterisation of back corneal aberrations.


Access site complications of postcardiotomy extracorporeal life support.
To assess the influence of primary arterial access in patients receiving peripheral postcardiotomy extracorporeal life support on associated complications and outcome. Of 573 consecutive patients requiring PC-ECLS between 2000 and 2019 at a single center, 436 were included in a retrospective analysis and grouped according to primary arterial extracorporeal life support access site. Survival and rate of access-site-related complications with special emphasis on fatal/disabling stroke were compared. The axillary artery was cannulated in 250 patients (57.3%), whereas the femoral artery was used as primary arterial access in 186 patients (42.6%). There was no significant difference in 30-day (axillary: 62%; femoral: 64.7%; P = .561) and 1-year survival (axillary: 42.5%; femoral: 44.8%; P = .657). Cerebral computed tomography-confirmed stroke with a modified ranking scale ≥4 was significantly more frequent in the axillary group (axillary: n = 28, 11.2%; femoral: n = 4, 2.2%; P = .0003). Stroke localization was right hemispheric (n = 20; 62.5%); left hemispheric (n = 5; 15.6%), bilateral (n = 5; 15.6%), or infratentorial (n = 2; 6.25%). Although no difference in major cannulation site bleeding was observed, cannulation site change for bleeding was more frequent in the axillary group (axillary: n = 13; 5.2%; femoral: n = 2; 1.1%; P = .03). Clinically apparent limb ischemia was significantly more frequent in the femoral group (axillary: n = 12, 4.8%; femoral: n = 31, 16.7%; P < .0001). Although survival did not differ, surgeons should be aware of access-site-specific complications when choosing peripheral PC-ECLS access. Although lower rates of limb ischemia and the advantage of antegrade flow seem beneficial for axillary cannulation, the high incidence of right hemispheric strokes in axillary artery cannulation should be considered.


Epigenetic modifiers either individually or in specific combinations impair viability of patient-derived glioblastoma cell line while exhibit moderate effect on normal stem cells growth.
Glioblastomas (GBM), also known as glioblastoma multiforme, are the most aggressive type of brain cancer. Currently, there is no effective treatment for GBM, highlighting the pressing need for new therapeutic strategies. In a recent study, we demonstrated that specific combinations of epigenetic modifiers significantly affect the metabolism and proliferation rate of the two most aggressive GBM cell lines, D54 and U-87. Importantly, these combinations exhibited minimal effects on the growth of normal stem cells. In this study, we extended our investigation to include a patient-derived GBM stem cell line. Our results showed that the combinations of modulators of histone and DNA covalent modifying enzymes that synergistically suppress D54 and U87 cell line growth also impair the viability of the patient-derived GBM stem cell line. These findings suggest that epigenetic modifiers alone or in specific combinations exhibit a cytotoxic effect on established and low-passage patient-derived GBM cell lines, and thus could be a promising therapeutic approach for this type of brain cancer.


Angiographic manifestations of renal hamartoma.
Two types of renal hamartoma (angiomyolipoma) are presented with emphasis on angiographic findings. Careful analysis of the angiograms can suggest a specific diagnosis. Two important considerations other than angiographic findings are (1) multiplicity of tumors in patients with tuberous sclerosis, and (2) a solitary mass in 40-60-year-old women.


A High-Performance Liquid Chromatography with Electrochemical Detection Method Developed for the Sensitive Determination of Ascorbic Acid: Validation, Application, and Comparison with Titration, Spectrophotometric, and High-Performance Liquid Chromatography with Diode-Array Detection Methods.
L-ascorbic acid (vitamin C, VC), an essential nutrient obtained from the diet to maintain various vital signs for the human body, is a crucial indicator of food quality and nutritional value. Herein, high-performance liquid chromatography with electrochemical detection (HPLC-ECD) was developed and validated with the advantages of higher sensitivity, simpler operation processes, and more rapid detection in measuring VC levels in honey samples when compared with the common methods (titration, spectrophotometric, and HPLC-DAD methods). The results of the HPLC-ECD methodological validation showed that the limit of detection (LOD) was 0.0043 µg mL-1; the relative standard deviations (RSDs) of the intra- and inter-day values were between 2.51% and 5.15%, and the regression coefficient was >0.999 in the linear range of 0.1 to 20 µg mL-1. The validated HPLC-ECD method was also successfully utilized to evaluate the VC levels in different varieties of honey samples with various storage durations as well as in fruit and biological samples. This study provided a perspective for the further accurate determination of VC content in food and biological samples.


Adrenergic innervation of the vasa nervorum in the cranial nerves and spinal roots in the subarachnoid space.
Fluorescence microscopy revealed that the innervation of the vasa nervorum of both cranial and spinal nerve roots in the subarachnoid space in the monkey is adrenergic in nature. The endoneurium of the cranial nerve roots contained free adrenergic nerve fibers which were not related to the vessel wall.


Fate of metastatic foci after chemotherapy and usefulness of contrast-enhanced intraoperative ultrasonography to detect minute hepatic lesions.
Along with advances in the chemotherapy for colorectal cancer, the strategy for hepatic metastasis has been changed. One of the most striking issues is that initially unresectable hepatic metastases can be resectable after chemotherapy with considerably high frequency. In addition, advanced chemotherapy leads to the downsizing of the metastatic foci in the liver, which is sometimes difficult to detect with conventional intraoperative ultrasonography (IOUS). To discover the undetectable hepatic lesions with IOUS, we have introduced contrast-enhanced intraoperative ultrasonography (CEIOUS). In the present study, we present evidence that viable cancer cells exist in even the shrunken tumors with high frequency and that CEIOUS contributes to detecting the minute foci. This study was composed of eight patients; four of them had initially unresectable metastasis, and the remaining four had either H2 or H3 status of hepatic metastases. All of them underwent hepatic resection after chemotherapy. A total of 57 metastatic lesions were detected before chemotherapy. Thirty lesions were demonstrated by CEIOUS with perflubutane and resected. In the pathological examination, tumor cells were not found in 12 of the 30 resected lesions. The degree of pathological liver damage was grade 1 or less in all patients, and no serious complication occurred after surgery in any of the patients. The present study showed that viable cancer cells remained with high frequency, even in the minute hepatic metastasis which was reduced in size after chemotherapy, and CEIOUS was a useful examination for detecting the minute hepatic foci.


[A case of recurrent breast cancer causing malignant pericardial effusion successfully managed with instillations of cisplatin].
A 44-year-old female patient was admitted to our hospital because of dyspnea caused by malignant cardiac tamponade 2 years and 8 months after standard radical mastectomy for a stage III breast cancer. Malignant pericardial effusion was diagnosed by echocardiography and differentiated by cytology. Pericardiocentesis improved her hemodynamics and 9 consecutive pericardial instillations of cisplatin (10 mg) prevented reaccumulation of pericardial effusion, which had never reoccurred until she died of breast cancer one year and 6 months later. Therefore, it is suggested that instillation of cisplatin is one of the beneficial alternatives to surgical treatment.


[Resident and supervisor perception of learning climate in public health resident training in the Netherlands].
The purpose of this study was to evaluate the perceived quality of the learning climate by public health residents in the Netherlands and compare residents' and supervisors' perceptions. Residents of five public health subfields, who started their residency programs in 2019 and onwards, as well as supervisors involved in the residency program, were invited to complete a web-based survey based on an adapted version of the D‑RECT questionnaire. Answers of residents and supervisors of the same training site and public health subfield were matched to compare perceived quality of the learning climate. One hundred fourteen residents responded (response rate 50.9%). Residents' overall assessment of the learning climate showed a mean score of 4.19 on a 5-point-scale. Thirty-eighth supervisor-resident matches were formed. There were no notable differences in the perception of residents and supervisors. Residents' overall assessment of the learning climate was positive. Supervisors and residents' perception of learning climate is equal. Our adapted version of D‑RECT seems to be suitable to evaluate the learning climate for public health residency programs in the Netherlands. Further research is necessary to validate our questionnaire and to confirm our findings.


On the evolution of SARS-CoV-2 and the emergence of variants of concern.
The epidemiology of COVID-19 has dramatically changed since the beginning of the pandemic as we witnessed significant changes in transmissibility and pathogenicity with the emergence of SARS-CoV-2 variants of concern (VoCs). Here I present and comment on working hypotheses about the evolutionary dynamics of the emergence of VoCs.


Effects of random hydrolysis on biofilament length distributions in a shared subunit pool.
The sizes of filamentous structures in a cell are often regulated for many physiological processes. A key question in cell biology is how such size control is achieved. Here, we theoretically study the length distributions of multiple filaments, growing by stochastic assembly and disassembly of subunits from a limiting subunit pool. Importantly, we consider a chemical switching of subunits (hydrolysis) prevalent in many biofilaments like microtubules (MTs). We show by simulations of different models that hydrolysis leads to a skewed unimodal length distribution for a single MT. In contrast, hydrolysis can lead to bimodal distributions of individual lengths for two MTs, where individual filaments toggle stochastically between bigger and smaller sizes. For more than two MTs, length distributions are also bimodal, although the bimodality becomes less prominent. We further show that this collective phenomenon is connected with the nonequilibrium nature of hydrolysis, and the bimodality disappears for reversible dynamics. Consistent with earlier theoretical studies, a homogeneous subunit pool, without hydrolysis, cannot control filament lengths. We thus elucidate the role of hydrolysis as a control mechanism on MT length diversity.


Hematopoietic growth factor glycosylation. Multiple forms of chicken myelomonocytic growth factor.
The production of chicken myelomonocytic growth factor (cMGF) can be rapidly induced by bacterial lipopolysaccharide from the macrophage cell line HD11. Immunoprecipitation analysis of lipopolysaccharide-induced HD11 cells labeled with various radioactive precursors showed the secretion of a variety of cMGF forms. The precursor-product relationships of the different cMGF forms were studied by pulse-chase experiments, by long-term metabolic labeling in the presence or absence of glycosylation- and oligosaccharide-processing inhibitors, as well as by glycosidase treatment of immunoprecipitates. Our results show that the half-time for intracellular processing/secretion is less than 10 min, making cMGF one of the most rapidly processed proteins. The different forms of the factor are generated from a 24-kDa polypeptide precursor by co- and post-translational acquisition of one or two N-linked oligosaccharides and by O-linked glycosylation. In addition, a fraction of cMGF is modified by long chain, chondroitinase-sensitive, sulfated glycans. This modification is tunicamycin-sensitive, suggesting that the sulfated glycans are attached to N-linked rather than to O-linked oligosaccharides.


The importance and status of the micronutrient selenium in South Africa: a review.
Selenium (Se) is a vital micronutrient with widespread biological action but leads to toxicity when taken in excessive amounts. The biological benefits of Se are mainly derived from its presence in active sites of selenoproteins such as glutathione peroxidase (GPx). An enzyme whose role is to protect tissues against oxidative stress by catalysing the reduction of peroxidase responsible for various forms of cellular damage. The benefits of Se can be harvested when proper regulations of its intake are used. In South Africa, Se distribution in people's diets and animals are low with socio-economic factors and heterogeneous spread of Se in soil throughout the country playing a significant role. The possible causes of low Se in soils may be influenced by underlying geological material, climatic conditions, and anthropogenic activities. Sedimentary rock formations show higher Se concentrations compared to igneous and metamorphic rock formations. Higher Se concentrations in soils dominates in humid and sub-humid areas of South Africa. Furthermore, atmospheric acid deposition dramatically influences the availability of Se to plants. The studies reviewed in this article have shown that atomic absorption spectroscopy (AAS) is the most utilised analytical technique for total Se concentration determination in environmental samples and there is a lack of speciation data for Se concentrations. Shortcomings in Se studies have been identified, and the future research directions of Se in South Africa have been discussed.


Assessing strain mapping by electron backscatter diffraction and confocal Raman microscopy using wedge-indented Si.
The accuracy of electron backscatter diffraction (EBSD) and confocal Raman microscopy (CRM) for small-scale strain mapping are assessed using the multi-axial strain field surrounding a wedge indentation in Si as a test vehicle. The strain field is modeled using finite element analysis (FEA) that is adapted to the near-indentation surface profile measured by atomic force microscopy (AFM). The assessment consists of (1) direct experimental comparisons of strain and deformation and (2) comparisons in which the modeled strain field is used as an intermediate step. Direct experimental methods (1) consist of comparisons of surface elevation and gradient measured by AFM and EBSD and of Raman shifts measured and predicted by CRM and EBSD, respectively. Comparisons that utilize the combined FEA-AFM model (2) consist of predictions of distortion, strain, and rotation for comparison with EBSD measurements and predictions of Raman shift for comparison with CRM measurements. For both EBSD and CRM, convolution of measurements in depth-varying strain fields is considered. The interconnected comparisons suggest that EBSD was able to provide an accurate assessment of the wedge indentation deformation field to within the precision of the measurements, approximately 2×10(-4) in strain. CRM was similarly precise, but was limited in accuracy to several times this value.


Design of screen-printed potentiometric platform for sensitive determination of mirabegron in spiked human plasma; molecular docking and transducer optimization.
The integration of molecular modelling simulation and electrochemical sensors is of high interest. Herein, for the first time, a portable solid-contact potentiometric electrode was designed for the sensitive determination of mirabegron (MIR) in human plasma and pharmaceutical formulation. A two-step optimization protocol was investigated for the fabrication of an ion on sensing polymeric membrane. First, molecular docking was used for optimum ionophore selection. Calix[6]arene showed the highest affinity towards MIR with a better docking score (-4.35) and potential energy (-65.23) compared to other calixarene derivatives. Second, carbon nanotubes and gold nanoparticles were investigated as ion-electron transducers using a drop-casting procedure. Gold nanoparticle-based sensors showed better slope, potential stability, and rapid response compared to carbon nanotubes. The proposed solid contact sensors (V-VII) showed comparable sensitivity and ease of handling compared to liquid contact sensors (I-IV). The optimized gold nanoparticles sensor VII produced a Nernstian response over the range of 9.77 × 10-7 to 1 × 10-3 M with LOD of 2.4 × 10-7 M. It has also been used to determine MIR in its pharmaceutical formulation in the presence of a co-formulated antioxidant butylated hydroxytoluene and spiked human plasma. This would offer a feasible and economic platform for monitoring MIR in pharmaceutical preparation and biological fluids.


Management of anteriorly located C1-C2 neurofibromata.
The authors discuss their recent experience with anteriorly located C1-C2 neurofibromata in five patients with cervical myelopathy and magnetic resonance scans consistent with intradural extramedullary masses in this region. Surgery was performed using a posterolateral approach with microscopic intradural exploration. Gross total intradural tumor removal was achieved in all cases. Improvement in cervical myelopathy occurred in all patients. This report concludes that C1-C2 neurofibromata located anterior to the spinal cord can be totally and safely removed using a posterolateral approach. Improvement in neurologic dysfunction accompanies posterior decompression and gross total intradural tumor removal.


What's new in steroid receptor immunocytochemistry in clinical oncology?
In this review we outline the many practical advantages of immunocytochemistry for estrogen receptors (ER) and the staining intensity index for its interpretation. We discuss the heterogenous distribution of ER in malignant and non-malignant breast tissue and the correlation of ER staining with pathologic features. In predicting the response of breast cancer to endocrine therapy, we conclude that both fine needle aspirates and tissue sections are adequate for the assessment of ER.


Plasmonic Pd Nanoparticle- and Plasmonic Pd Nanorod-Decorated BiVO4 Electrodes with Enhanced Photoelectrochemical Water Splitting Efficiency Across Visible-NIR Region.
The photoelectrochemical (PEC) water splitting performance of BiVO4 is partially hindered by insufficient photoresponse in the spectral region with energy below the band gap. Here, we demonstrate that the PEC water splitting efficiency of BiVO4 electrodes can be effectively enhanced by decorating Pd nanoparticles (NPs) and nanorods (NRs). The results indicate that the Pd NPs and NRs with different surface plasmon resonance (SPR) features delivered an enhanced PEC water splitting performance in the visible and near-infrared (NIR) regions, respectively. Considering that there is barely no absorption overlap between Pd nanostructures and BiVO4 and the finite-difference time domain (FDTD) simulation indicating there are substantial energetic hot electrons in the vicinity of Pd nanostructures, the enhanced PEC performance of Pd NP-decorated BiVO4 and Pd NR-decorated BiVO4 could both benefit from the hot electron injection mechanism instead of the plasmon resonance energy transfer process. Moreover, a combination of Pd NPs and NRs decorated on the BiVO4 electrodes leads to a broad-band enhancement across visible-NIR region.


Transforming Growth Factor-α Acts in Hypothalamic Paraventricular Nucleus to Upregulate ERK1/2 Signaling and Expression of Sympathoexcitatory Mediators in Heart Failure Rats.
Activation of epidermal growth factor receptor (EGFR) tyrosine kinase is associated with increased extracellular signal-regulated kinase (ERK) 1/2 signaling in the hypothalamic paraventricular nucleus (PVN), which contributes to the sympathetic excitation in heart failure (HF). Transforming growth factor (TGF)-α is a major endogenous ligand for EGFR. The present study sought to determine whether TGF-α increases in the PVN in HF and promotes the activation of EGFR to increase ERK1/2 activity. Male rats received bilateral PVN microinjections of an EGFR siRNA or a scrambled siRNA followed by an intracerebroventricular (ICV) injection of TGF-α or vehicle one week later. In rats pretreated with the scrambled siRNA, ICV TGF-α increased phosphorylated (p-) EGFR and upregulated the expression of p-ERK1/2 and mRNA levels of proinflammatory cytokines (PICs) and renin-angiotensin system (RAS) components in the PVN, when compared with the untreated age-matched control rats. These responses to ICV TGF-α were significantly attenuated in rats pretreated with the EGFR siRNA. Furthermore, bilateral PVN microinjection of a TGF-α siRNA in HF rats significantly decreased the elevated levels of TGF-α, p-EGFR, p-ERK1/2 and the mRNA expression of PICs and RAS components in the PVN, compared with the HF rats treated with a scrambled siRNA. The TGF-α siRNA-treated HF rats also exhibited lower plasma norepinephrine levels and improved peripheral manifestations of HF. These data suggest that TGF-α expression is upregulated in the PVN in HF and induces the activation of EGFR-mediated ERK1/2 signaling to augment the inflammation and RAS activity that drives sympathetic excitation in HF.


Control of osteoclast activity and bone loss by IKK subunits: new targets for therapy.
Transcription factor NF-kappaB has been well recognized as a pivotal player in osteclastogenesis and inflammation-induced bone loss. Here, we discuss our recent results obtained using a genetic approach in mice that indicate the importance of IKKbeta, and not IKKalpha, as a transducer of signals from receptor activator of NF-kappaB (RANK) to NF-kappaB. Ablation of IKKbeta results in lack of osteoclastogenesis and unresponsiveness of IKKbeta-deficient mice to inflammation-induced bone loss. In the need of a more effective therapy for the treatment of inflammatory diseases causing bone resorption, specific inhibition of IKKbeta represents a logical alternative strategy to the current therapies.


Mannose-binding lectin gene polymorphisms in the East Siberia and Russian Arctic populations.
Mannose-binding lectin (MBL) encoded by MBL2 gene is a protein with the ability to form carbohydrate complexes with microbial wall promoting their subsequent elimination. Genetically determined levels of MBL can modify the risk and clinical characteristics of many infectious diseases. The frequency of MBL2 genotypes exhibits significant population differences. The data on the distribution of MBL2 genotypes among the aborigines of the Russian Arctic territories have not yet been published. A total of 880 specimens of dried blood spots of the newborns were genotyped. The newborns represented four populations: Nenets, Dolgan-Nganasans, Mixed aboriginal population, and Russians (Caucasians, Krasnoyarsk). Six polymorphisms of the MBL2 gene were studied: rs11003125, rs7096206, rs7095891, rs5030737, rs1800450, and rs1800451. The frequency of the combined rare O allele (composed of the coding region variants rs5030737, rs1800450, and rs1800451) in the homozygous state was significantly higher in Russians: 10% vs 2% in Nenets and 1% in Dolgan-Nganosans (p < 0.001 for Russians vs other populations). The frequency of the high-producing haplotype (HYPA) was 35.4% in the Russian newborns, in keeping with European populations (27-33%); 64% for Nenets and 56% for Dolgan-Nganasans, similar to the estimates obtained for Eskimos and North Amerinds (64-81%). Our study results are in line with the hypothesis that human evolution has been moving in the direction of accumulation of the genotypes associated with low activity of the lectin complement activation pathway because of the prevalence of some intracellular infections such as tuberculosis, whereby low MBL activity may have a protective effect.


Trending 7 years of in vitro activity of tigecycline and comparators against Gram-positive and Gram-negative pathogens from the Asia-Pacific region: Tigecycline Evaluation Surveillance Trial (TEST) 2004-2010.
A total of 10948 clinical isolates was collected throughout the Asia-Pacific region as part of the Tigecycline Evaluation Surveillance Trial (TEST) during 2004-2010, consisting of 7549 Gram-negative and 3399 Gram-positive pathogens. Susceptibility trends for all species demonstrated several significant species-dependent susceptibility changes to multiple antibiotics. The most notable was minocycline, for which significant decreases in susceptibility (P<0.001) were observed for six of the ten species studied. In contrast, statistically significant susceptibility changes for tigecycline were observed in only two of the ten species, namely Klebsiella pneumoniae and Serratia marcescens. Seven years following the introduction of tigecycline into clinical use, this agent remains highly active against a wide range of pathogens from the Asia-Pacific region.


Suture type and ultrasound-indicated cerclage efficacy.
To assess whether type of suture material affects cerclage efficacy for preterm birth (PTB) prevention. Secondary analysis of a multicenter trial of ultrasound-indicated cerclage for short cervical length (CL), in which women with prior spontaneous PTB at 16-33 6/7 weeks, a singleton gestation and CL < 25 mm between 16-22 6/7 weeks, were randomized to McDonald cerclage or no cerclage. Outcomes of women who underwent cerclage were analyzed by type of suture material, comparing polyester braided thread (Mersilene™ or Ethibond™) to Mersilene tape™. Primary outcome was PTB < 35 weeks. 138 women underwent McDonald cerclage: 84 (61%) received polyester braided thread and 46 (33%) Mersilene tape™. Eight (6%) received monofilament suture and were excluded from analysis. Rates of PTB < 35 weeks were similar, 35% for polyester braided thread vs 24% for Mersilene tape™ (p = .24). Birth gestational age was also similar among the 2 groups (p = .18). Type of suture material may not affect ultrasound-indicated cerclage efficacy in high-risk women with short CL, but further study is needed. Polyester braided thread (Mersilene™ or Ethibond™) and polyester braided Mersilene tape™ seem to have similar efficacy.


Resting-state functional connectivity predicts individual language impairment of patients with left hemispheric gliomas involving language network.
Language deficits following brain tumors should consider the dynamic interactions between different tumor growth kinetics and functional network reorganization. We measured the resting-state functional connectivity of 126 patients with left cerebral gliomas involving language network areas, including 77 patients with low-grade gliomas (LGG) and 49 patients with high-grade gliomas (HGG). Functional network mapping for language was performed by construction of a multivariate machine learning-based prediction model of individual aphasia quotient (AQ), a summary score that indicates overall severity of language impairment. We found that the AQ scores for HGG patients were significantly lower than those of LGG patients. The prediction accuracy of HGG patients (R2 = 0.27, permutation P = 0.007) was much higher than that of LGG patients (R2 = 0.09, permutation P = 0.032). The rsFC regions predictive of LGG's AQ involved the bilateral frontal, temporal, and parietal lobes, subcortical regions, and bilateral cerebro-cerebellar connections, mainly in regions belonging to the canonical language network. The functional network of language processing for HGG patients showed strong dependence on connections of the left cerebro-cerebellar connections, limbic system, and the temporal, occipital, and prefrontal lobes. Together, our findings suggested that individual language processing of glioma patients links large-scale, bilateral, cortico-subcortical, and cerebro-cerebellar functional networks with different network reorganizational mechanisms underlying the different levels of language impairments in LGG and HGG patients.


Common null variant, Arg192Stop, in a G-protein coupled receptor, olfactory receptor 1B1, associated with decreased serum cholinesterase activity.
Non-functioning single nucleotide polymorphisms (nSNPs) that result in premature termination codons, that is null-alleles of the respective genes, may have phenotypic effects on clinical parameters. We conducted association studies involving several G-protein coupled receptors (GPCRs) that harbor nSNPs, using clinical parameters of liver function in a general population consisting of 2969 Japanese adults. SNP typings were performed with TaqMan and Invader assays. Quantitative associations between genotypes and clinical parameters were analyzed by analysis of variance. Linkage disequilibrium (LD) was tested by Haploview Version 3.3. Haplotype-based association was performed using the haplo.stats program. A significant correlation (P = 0.0057) was identified between serum cholinesterase activity (CHE) and an nSNP (Arg192Stop) in the olfactory receptor (OR) 1B1 gene, a member of the GPCR gene family. This nSNP was associated with decreased serum CHE (P = 0.0013). LD analysis based on eight selected SNPs at the locus revealed three LD blocks. The Arg192Stop nSNP was located on the second LD block, which covered one-third of the 3'-portion of the gene. These results suggested that the null-allele of OR1B1 might affect metabolism of serum cholinesterase in carriers of this nSNP.


The Uni-Gold™ Streptococcus pneumoniae urinary antigen test: an interassay comparison with the BinaxNOW® Streptococcus pneumoniae test on consecutive urine samples and evaluation on patients with bacteremia.
The performance of the recently commercialized Uni-Gold™ Streptococcus pneumoniae test for the detection of pneumococcal antigen in urine was studied in a multicenter study. First, we studied the interassay agreement between Uni-Gold™ and the BinaxNOW® S. pneumoniae urinary antigen test on 337 consecutive urine samples sent to the laboratory for the detection of pneumococcal antigen. The two tests performed similarly (κ = 0.82): both tests positive in 27 cases, both tests negative in 299 cases, and with divergent test results in 11 cases. Secondly, the tests were run on urine samples from 203 patients with bacteremia, including 51 patients with pneumococcal bacteremia. The sensitivities and specificities were 67 and 86 % for Uni-Gold™, and 57 % and 94 % for BinaxNOW®, respectively. The false-positivity rate was significantly higher for Uni-Gold™ compared with BinaxNOW® in patients with Escherichia coli bacteremia (15 vs. 2.1 %, p = 0.04), and tended to be higher in patients with bacteremia with alpha-hemolytic streptococci (32 vs. 11 %, p = 0.13). When cases with E. coli and alpha-hemolytic streptococci were excluded from the analysis, the overall false-positivity rate was 9/85 (11 %) for Uni-Gold™ and 6/85 (7.1 %) for BinaxNOW®. In conclusion, the study showed that Uni-Gold™ was not inferior to BinaxNOW® for the detection of pneumococcal urinary antigen in patients with pneumococcal bacteremia. The specificity of Uni-Gold™ was suboptimal due to false-positive results in cases with E. coli and alpha-hemolytic streptococci bacteremia. However, in patient populations usually subjected to testing for pneumococcal urinary antigen, such as pneumonia and meningitis patients, bacteremia with these pathogens is uncommon. The diagnostic usefulness of the Uni-Gold™ test should be further evaluated.


Lack of correlation of verapamil plasma level with cumulative protective effects against halothane--epinephrine ventricular arrhythmias.
The effect of verapamil, 0.2 mg/kg i.v. over 30 s, on the amount of epinephrine required to elicit a reproducible ventricular arrhythmia during 0.9% halothane in oxygen anesthesia was investigated in two groups of dogs after three consecutive doses of verapamil given at 90 (group I) and 120 min (group II) intervals, respectively. Verapamil caused a stepwise cumulative increase in the arrhythmogenic dose of epinephrine in both groups despite plasma verapamil levels that declined to low levels (28 and 22 ng/ml, respectively) between doses. Control epinephrine arrhythmogenic doses were 2.89 +/- 0.54 and 2.74 +/- 0.19 microgram/kg/min (mean +/- SEM), respectively, for groups I and II, and rose to 4.58 +/- 0.72 and 4.55 +/- 0.30 microgram/kg/min after the first verapamil dose, to 6.20 +/- 0.74 and 6.13 +/- 0.40 microgram/kg/min after the second verapamil dose, and 8.16 +/- 0.85 and 8.09 +/- 0.95 microgram/kg/min after the third verapamil dose, respectively. All postverapamil epinephrine arrhythmogenic dose values were significantly elevated above control and above the preceding values, although there was no significant difference between the two groups. Changes in heart rate or blood pressure were similar among the three doses of verapamil in each group. These results can be interpreted to indicate that, unlike hemodynamic effects that appear to parallel plasma verapamil concentrations, the protective effects of verapamil against halothane--epinephrine ventricular arrhythmias may not be accurately reflected by plasma verapamil levels and may be significantly present when plasma levels are too low to cause measurable hemodynamic effects.


Current Management of Congenital Choanal Atresia: Litteratur Review.
Congenital Choanal Artesia (CCA) is a rare cause of upper airway obstruction, yet it is the most common congenital anomaly of the nose. While the unilateral condition could be undiagnosed, bilateral CCA may be life-threatening, especially for newborns. Some CCA may be associated with other congenital abnormalities, which leads to a systematic screening during the diagnostic assessment. The diagnosis is easy. However, surgical management is still controversial. We conducted a retrospective study gathering data on management of CCA over 42 months. We reported epidemiological aspects and results of our series, and discussed management issues. We operated 22 choanae using the endoscopic technique. The age of bilateral CCA patients on the day of surgery ranged from 8 to 21 days (mean 11.7+/_ 2.6 days). Their birth weight ranged from 2.9 to 4.5 kg (mean 3.4 +/_ 0.5 kg), and their gestational age ranged from 30 to 41 weeks. Surgery duration for neonatal bilateral CCA repair ranged from 75 to 110 min (mean 90 min +/_ 11.5 min). We performed an exclusive endonasal endoscopic approach for all patients with no stenting or mitomycin C application. We deplore one post operative complication related to minor palatal perforation resolved spontaneously. Since newborns solely depend on nasal breathing during the first month of life, bilateral CCA is an emergency. Endonasal endoscopic management is the primary procedure. Currently, surgery steps are standardized. However, how to prevent post-operative synechiae and restenosis is still controversial. The mainstream is meticulous post-operative nursing with frequent endonasal saline irrigation, regular removal of crust, and prevention of inflammation due to reflux or infection.


Vitamin D3 Produced by Skin Exposure to UVR Inhibits Murine Basal Cell Carcinoma Carcinogenesis.
The effect of UVR on human basal cell carcinoma (BCC) epidemiology is complex-the incidence rises until approximately 30,000 hours of lifetime sunlight exposure and then plateaus. We hypothesize that UVR has opposing effects on BCC carcinogenesis-stimulatory via mutagenesis and inhibitory via production of hedgehog-inhibiting vitamin D3 (D3). We find that UVR exposure of ionizing radiation-treated Ptch1+/- mice accelerates BCC carcinogenesis in male mice, in which UVR does not produce D3. By contrast, in female mice, in which UVR does produce D3, UVR fails to accelerate BCC carcinogenesis, thus mirroring the plateauing in humans. However, if D3 production is attenuated in female mice by deletion of keratinocyte lathosterol 5-desaturase, then UVR accelerates ionizing radiation-induced BCC carcinogenesis. Congruently, chronic topical application of D3 inhibits ionizing radiation-induced BCC tumorigenesis. These findings confirm that UVR-induced production of D3 in keratinocytes significantly restrains murine BCC tumorigenesis and demonstrate the counterintuitive conclusion that UVR has anti-BCC carcinogenic effects that can explain, at least in part, the complex relationship between exposure to UVR and BCC incidence.


Oral hydration rotavirus diarrhoea: a double blind comparison of sucrose with glucose electrolyte solution.
Of 57 male children, aged 5 months to 2 1/2 years with rotavirus diarrhoea, 28 were given oral therapy with sucrose electrolyte solution and 29 were given glucose electrolyte solution in a randomised double-blind trial. All were rehydrated and remained so on oral therapy alone. These patients were compared with 44 children, also with rotavirus, who were treated only with intravenous hydration. The oral therapy and intravenous therapy groups did not differ clinically in the rate of rehydration or the rate of purging. Vomiting did not prevent the giving of oral therapy during hospital admission. Bangladeshi children with rotavirus diarrhoea have a defect of carbohydrate digestion but this defect does not prevent the use of a sugar electrolyte solution for oral hydration.


Acute pulmonary oedema following percutaneous balloon pulmonary valvoplasty in children.
Pulmonary oedema complicating balloon dilation of the pulmonary valve is extremely rare. We describe two children who developed acute pulmonary oedema soon after successful dilation of the pulmonary valve. They were treated with diuretics, ionotropes, and ventilatory support. Despite the supportive therapy, the complication proved fatal in one.


Surgical management of otitis media (recurrent and nonsuppurative).
In 1977 Paradise outlined the role of tympanostomy tubes in nonsuppurative otitis media. Over the intervening 10 years the role has changed little. Exceptions would be the demonstrated advantage of tube placement over myringotomy alone in those patients with effusion for longer than 2 or 3 months, or over prophylactic sulfonamide or placebo in recurrent otitis media.


Regulation of the cd38 promoter in human airway smooth muscle cells by TNF-alpha and dexamethasone.
CD38 is expressed in human airway smooth muscle (HASM) cells, regulates intracellular calcium, and its expression is augmented by tumor necrosis factor alpha (TNF-alpha). CD38 has a role in airway hyperresponsiveness, a hallmark of asthma, since deficient mice develop attenuated airway hyperresponsiveness compared to wild-type mice following intranasal challenges with cytokines such as IL-13 and TNF-alpha. Regulation of CD38 expression in HASM cells involves the transcription factor NF-kappaB, and glucocorticoids inhibit this expression through NF-kappaB-dependent and -independent mechanisms. In this study, we determined whether the transcriptional regulation of CD38 expression in HASM cells involves response elements within the promoter region of this gene. We cloned a putative 3 kb promoter fragment of the human cd38 gene into pGL3 basic vector in front of a luciferase reporter gene. Sequence analysis of the putative cd38 promoter region revealed one NF-kappaB and several AP-1 and glucocorticoid response element (GRE) motifs. HASM cells were transfected with the 3 kb promoter, a 1.8 kb truncated promoter that lacks the NF-kappaB and some of the AP-1 sites, or the promoter with mutations of the NF-kappaB and/or AP-1 sites. Using the electrophoretic mobility shift assays, we determined the binding of nuclear proteins to oligonucleotides encoding the putative cd38 NF-kappaB, AP-1, and GRE sites, and the specificity of this binding was confirmed by gel supershift analysis with appropriate antibodies. TNF-alpha induced a two-fold activation of the 3 kb promoter following its transfection into HASM cells. In cells transfected with the 1.8 kb promoter or promoter constructs lacking NF-kappaB and/or AP-1 sites or in the presence of dexamethasone, there was no induction in the presence of TNF-alpha. The binding of nuclear proteins to oligonucleotides encoding the putative cd38 NF-kappaB site and some of the six AP-1 sites was increased by TNF-alpha, and to some of the putative cd38 GREs by dexamethasone. The EMSA results and the cd38 promoter-reporter assays confirm the functional role of NF-kappaB, AP-1 and GREs in the cd38 promoter in the transcriptional regulation of CD38.


Neuromuscular blocking properties of suxamethonium and decamethonium in normal and myasthenic rat muscle.
Patients with myasthenia gravis (MG) have increased tolerance to the neuromuscular blocking properties of suxamethonium (SCh) and decamethonium (C10) and exhibit a reversal of the C10-induced block by neostigmine. The effects of these drugs were compared in forelimb flexor digitorum longus muscle from normal rats and from rats with experimental autoimmune myasthenia gravis (EAMG) to investigate the similarity of EAMG to MG. The depolarization induced by 1, 5, 10 and 25 microM SCh or C10 at the motor end-plates was significantly higher in normal than in EAMG muscle. However, both normal and EAMG end-plates responded in a similar qualitative manner to each drug. The depolarization produced by SCh was typically maintained until the drug was washed from the bath. The depolarization produced by C10 tended to decrease after reaching its peak despite continued application of the drug. With both drugs, miniature end-plate potential (MEPP) amplitude reduction is maintained until a saline wash. Neostigmine interaction with SCh and C10 in normal and EAMG muscle was compared by measuring isometric twitch tension in vitro. Neostigmine potentiated the neuromuscular block produced by either SCh or C10 in both normal and EAMG muscle. Thus muscle from rats with EAMG shares with MG an increased tolerance to SCh and C10 when compared to normal muscle but does not exhibit the qualitatively different interaction of C10 affected muscle with neostigmine that is found in MG patients. This and other studies comparing EAMG and MG indicate that EAMG is an appropriate model of MG but differences such as we have noted should be considered when extrapolating data from EAMG to the human disease.


The large N limit of orbifold vertex operator algebras.
We investigate the large N limit of permutation orbifolds of vertex operator algebras. To this end, we introduce the notion of nested oligomorphic permutation orbifolds and discuss under which conditions their fixed point VOAs converge. We show that if this limit exists, then it has the structure of a vertex algebra. Finally, we give an example based on GL ( N , q ) for which the fixed point VOA limit is also the limit of the full permutation orbifold VOA.


Critical three-dimensional factors affecting outcome in osteochondral lesion of the talus.
This study aimed to investigate the relationship between clinical outcomes, patient demographics and the 3D-geometric profiles of the osteochondral lesion of the talus (OLT) following arthroscopic debridement and bone marrow stimulation. Between 2005 and 2011, arthroscopic debridement and bone marrow stimulation were performed on 50 ankles with OLT mean age of 36.0 (19.1) years and mean follow-up time of 35.5 (20.2) months. Clinical data were assessed using validated Japanese Society of Surgery of the Foot scoring. An outcome was deemed unsatisfactory if the JSSF score was less than 80. Magnetic resonance imaging and X-rays were used to assess the 3D-geometric profiles of the OLT. The mean preoperative and postoperative scores were 73.4 (13.6) and 89.6 (11.5), respectively (p < 0.001). Unsatisfactory outcomes were identified in 12 % of patients. Linear regression analyses showed that lesion depth and patient age were significantly negatively correlated with postoperative scores (p < 0.001). High prognostic significances were attributed to defect depth and age of patient, and cut-off values of 7.8 mm and 80 years, respectively, were recommended to avoid a postoperative score less than 80. No significant correlations between poor clinical outcome and the other lesion profiles or demographic factors were identified. Using 3D-geometric and demographic profiles, defect depth and age of patient are essential prognostic factors in OLT and may act as a basis for preoperative surgical decisions. A lesion depth ≥ 7.8 mm and age ≥ 80 years predict an unsatisfactory outcome following arthroscopic debridement and bone marrow stimulation.


Regulation effects of total flavonoids in Morus alba L. on hepatic cholesterol disorders in orotic acid induced NAFLD rats.
Mulberry leaves are the dried leaves of Morus alba L., flavonoids from mulberry leaves (MLF) has showed regulatory effect on abnormal lipid metabolism, but the regulatory mechanism of MLF on cholesterol metabolism is still missing. This study was designed to investigate the effect of MLF and its active metabolite quercetin on regulating cholesterol disorders. The mechanism of MLF on alleviating liver injury and regulating cholesterol was examined in dyslipidemic SD rats. The regulatory mechanism of quercetin for cholesterol disorders have also been detected through lipid laden HepG2 cell model. Our results showed that MLF significantly inhibited lipid accumulation and alleviate hepatic injury in NAFLD rat model. The hepatic expression level of SREBP2, HMGCR and miR-33a were significantly down-regulated, while CYP7A1 was induced by MLF treatment. In vitro, Quercetin significantly decreased lipid accumulation in HepG2 cells. Mechanistically, quercetin could inhibit the mRNA and protein expression level of SREBP2 and HMGCR with or without LDL treatment. In addition, quercetin could also reduce the LXRβ while induced SR-BI mRNA expression. Our findings indicate that MLF and quercetin could reduce the excessive cholesterol accumulation in vivo and in vitro. These cholesterol-regulating phenomenon might attribute to its effect on down-regulating the expression of lipid-related markers such as SREBP2 and HMGCR, which may exert a protective role in the NAFLD treatment.


Metabolic activation of chlorinated ethylenes: dependence of mutagenic effect on electrophilic reactivity of the metabolically formed epoxides.
In chlorinated ethylenes, the chlorine substitution exerts, by its electron withdrawal effect, a stabilization of the molecule which increases with the number auf chlorine residues. All chlorinated ethylenes are metabolically transformed, in a first step reaction, to epoxides which may rearrange to aldehydes or acyl chlorides, respectively, undergo hydrolysis to diols, conjugate with glutathione, or react, by alkylation, with cellular macromolecules. The electrophilicity of the epoxides is high with those having an unsymmetric chlorine substitution, and comparatively low with the others bearing symmetric chlorine residues. According to in vitro mutagenicity testing in a modified Ames system, the following rule on structure/activity-relationship has been worked out: mutagenic potential is bound to unsymmetric substitution and high chemical reactivity (as with vinyl chloride, vinylidene chloride, and trichloroethylene), symmetric substitution results in lower chemical reactivity and non-mutagenicity. So far, the rule is substantiated by positive carcinogenic effects in animal experiments with vinyl chloride, vinylidene chloride and trichloroethylene.


Chryseobacterium spp-associated bacteraemia in a haemodialysis patient: a diagnostic challenge.
Chryseobacterium species are Gram-negative bacillus widely distributed in nature. It is a rare human pathogen that has been isolated from water systems and humid surfaces of the hospital environment. We report a rare case of Chryseobacterium bacteremia in an end-stage renal disease nursing home resident, that was diagnosed using multiplex PCR and was successfully treated with intravenous piperacillin-tazobactam combination.


[Determination of fructosamine on the Cobas-Bio centrifuge system. Importance of white reagent].
An automated assay for fructosamine on Cobas-Bio centrifugal analyzer with subtracting the contribution of the albumin matrix present in standards is described. This rapid and simple test has suitable analytical performances. Fructosamine concentrations were measured in 100 healthy subjects and in 95 diabetic patients. For the diabetic patients, results were compared with those obtained from a commercialized test kit.


Berberine inhibits lipopolysaccharide- and polyethylene particle-induced mouse calvarial osteolysis in vivo.
Wear particle-induced osteolysis could lead to the aseptic loosening of implants. Studies have suggested that endotoxins, such as lipopolysaccharides (LPS), may be the primary causes of wear particle-mediated osteolysis, and that osteolysis may originate from subclinical levels of bacterial infection. However, effective therapies against wear particles and gram-negative bacterial or LPS-induced bone resorption are limited. In the current study, the effect of berberine on LPS- and polyethylene (PE) particle-induced osteolysis in vivo was investigated using a mouse calvarial model. Osteoclast number per bone perimeter and eroded surface per bone surface were measured. Berberine (10 mg/kg), injected either simultaneously with LPS or 3 d after LPS (25 mg/kg) treatment, blocked LPS-induced osteoclast recruitment and bone resorption in the mouse calvarial model. A daily single-dose of berberine (10 mg/kg), injected either simultaneously with PE particles or 4 d after treatment with PE particles, blocked PE particle-induced osteoclast recruitment and bone resorption. Berberine treatment markedly decreased LPS and PE particle-induced osteoclast recruitment and bone resorption in the murine calvarial model. These results suggest that berberine may have therapeutic effect for osteolysis induced by wear particles and LPS in gram-negative bacteria.


The dynamics of articular leukocyte trafficking and the immune response to self heat-shock protein 65 influence arthritis susceptibility.
Adjuvant arthritis (AA) shares several features with human rheumatoid arthritis, and it can be induced in the Lewis (LEW) rat but not the Wistar Kyoto (WKY) rat (both RT.1(l)) by immunization with heat-killed Mycobacterium tuberculosis (Mtb). We set out to unravel the mechanisms underlying the differential susceptibility to AA of these MHC-compatible rat strains. We compared the levels of T-cell proliferative and cytokine response to the immunoregulatory self (rat) hsp65 (Rhsp65) after an arthritogenic (Mtb) challenge and the kinetics of migration of adoptively transferred, (111)Indium-labeled, Mtb-primed leukocytes into the hind paw joints of recipient rats. The WKY rats raised a significantly higher level of T-cell proliferative response coupled with a temporally opposite cytokine profile against the disease-regulating Rhsp65 compared to that of LEW rats. Moreover, the arthritogenic leukocytes accumulated into the joints of WKY rats at significantly lower numbers than that in LEW rats. These results offer novel insights into the immune events influencing the pathogenesis of autoimmune arthritis.


The effect of nutrient-based standards on competitive foods in 3 schools: potential savings in kilocalories and grams of fat.
The study investigated how nutrient standards affected the number of kilocalories and grams of fat and saturated fat in competitive foods offered and sold in 3 high schools. The study is a quasi-experimental design with 3 schools serving as the units of assignment and analysis. The effect of the nutrient standards was measured by the change in kilocalories and grams of fat and saturated fat in offerings and purchases of competitive foods pre- and postimplementation of the standards. A paired sample t-test was used to compare kilocalories and grams of fat and saturated fat pre- and postimplementation of nutrition standards. After the implementation of the nutrition standards, students in 3 high schools purchased significantly smaller numbers of kilocalories and grams of fat and saturated fat, during the postpolicy school year of 2007-2008 than during the prepolicy school year of 2004-2005. Using nutrient standards to guide the selection of competitive foods offered in school cafeterias may positively affect intake of kilocalories, total grams of fat, and total saturated fat of those foods. The quantitative assessment is novel and demonstrates the reduction in kilocalories and fat in both the competitive food offerings and purchases as a result of nutrient standards.


A complication of the use of the laser in ENT surgery.
A case is reported of severe epistaxis resulting from the use of an aluminium foil-wrapped nasotracheal tube during laser surgery to the uvula.


Activation of Double-Stranded RNA-Activated Protein Kinase in the Dorsal Root Ganglia and Spinal Dorsal Horn Regulates Neuropathic Pain Following Peripheral Nerve Injury in Rats.
Double-stranded RNA (dsRNA)-activated kinase (PKR) is an important component in inflammation and immune dysfunction. However, the role of PKR in neuropathic pain remains unclear. Here, we showed that lumbar 5 spinal nerve ligation (SNL) led to a significant increase in the level of phosphorylated PKR (p-PKR) in both the dorsal root ganglia (DRG) and spinal dorsal horn. Images of double immunofluorescence staining revealed that p-PKR was expressed in myelinated A-fibers, unmyelinated C-fibers, and satellite glial cells in the DRG. In the dorsal horn, p-PKR was located in neuronal cells, astrocytes, and microglia. Data from behavioral tests showed that intrathecal (i.t.) injection of 2-aminopurine (2-AP), a specific inhibitor of PKR activation, and PKR siRNA prevented the reductions in PWT and PWL following SNL. Established neuropathic pain was also attenuated by i.t. injection of 2-AP and PKR siRNA, which started on day 7 after SNL. Prior repeated i.t. injections of PKR siRNA prevented the SNL-induced degradation of IκBα and IκBβ in the cytosol and the nuclear translocation of nuclear factor κB (NF-κB) p65 in both the DRG and dorsal horn. Moreover, the SNL-induced increase in interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) production was diminished by this treatment. Collectively, these results suggest that peripheral nerve injury-induced PKR activation via NF-κB signaling-regulated expression of proinflammatory cytokines in the DRG and dorsal horn contributes to the pathogenesis of neuropathic pain. Our findings suggest that pharmacologically targeting PKR might be an effective therapeutic strategy for the treatment of neuropathic pain.


[Chronic disease in ethnic minorities: tools for patient-centred care in diabetes, hypertension and COPD].
In the Netherlands, chronic diseases, such as diabetes mellitus and cardiovascular disease, are more common and have a poorer prognosis in patients of Surinamese, Turkish and Moroccan origin. Surinamese develop cardiovascular diseases more often and at an earlier age; it is recommended that their cardiovascular risk profile be checked at an earlier stage. Standard treatment of diabetes mellitus is less effective among ethnic minorities. Patient information that is in line with the educational level and cultural values of the patient leads to better glucose levels. Focus group research among ethnic minorities shows that lifestyle changes which conflict with their own cultural beliefs or lack support in their social environment are often not adopted. Ethnic differences in the efficacy and toxicity of drugs are mainly caused by genetically determined variations in the activity of drug metabolizing enzymes.


Insulin antibodies in patients with type 2 diabetic receiving recombinant human insulin injection: A report of 12 cases.
We report 12 cases of patients with type 2 diabetic receiving recombinant human insulin injection, who had uncontrolled hyperglycemia or frequent episodes of hypoglycemia, high levels of serum insulin and positive insulin antibodies. The clinical characteristics and insulin antibodies pharmacokinetics parameters were analyzed. After administration of glucocorticoids, changing insulin formulations or discontinuing the insulin and switching to oral antidiabetic agents, the level of insulin antibodies decreased and the plasma glucose restored. Thus, we recommend to identify the presence of high insulin antibodies in patients with type 2 diabetes who experience unexplained high plasma glucose or frequent reoccurrence of hypoglycemia.


Ultrastructure and architecture of the sarcoplasmic reticulum in frog sino-atrial fibres: a comparative study with various preparatory procedures.
Various preparatory procedures were tested to preserve the ultrastructure of the sarcoplasmic reticulum (SR) by the best possible method within frog sino-atrial muscle fibres. These procedures were: conventional aldehyde fixation with or without tannic acid, cryofracture, metallic impregnation and quick-freezing followed by freeze-substitution. Our results illustrated that, when optimally preserved, the SR architecture and ultrastructure of frog sino-atrial fibres were not fundamentally different from those described in many other vertebrate muscle fibres, particularly cardiac fibres. The three-dimensional arrangement of the SR and the structure of its main compartments were situated in a precise fashion: the peripheral SR, located close to the plasma membrane, was made of a tight network of tubules and showed typical couplings; the juxtafibrillar SR was made of a loose network of tubules, small cisternae and some tubules near Z-lines; the intermediary SR, associated with the mitochondria, was made of tubules and fenestrated cisternae. Contacts between SR and mitochondrial membranes were also studied; cryofractures revealed no special intramembrane particles at this level. Collapsed portions of the SR were found after quick-freezing. Because of its relative importance and its three-dimensional arrangement, the SR of frog sino-atrial fibres may have comparable functional significance to the SR of other cardiac muscle fibres.


Dual effect of glucose on cytoplasmic free Ca2+ concentration and insulin release reflects the beta-cell being deprived of fuel.
Influence of basal glucose concentration on the response evoked by subsequent stimulation with the sugar, was evaluated by investigating changes in free cytoplasmic Ca2+ concentration, [Ca2+]i, and insulin release, using beta-cells isolated from obese hyperglycemic mice. When increasing the glucose concentration from 0 to either 11 or 20 mM, there was a transient decrease in both [Ca2+]i and insulin release. The decrease was followed by a pronounced increase in both of the parameters. When increasing the basal glucose concentration, the initial decrease gradually disappeared, being abolished already at 5 mM of the sugar and the subsequent increase appeared more rapidly. It is suggested that the observed decrease in [Ca2+]i and thereby insulin release reflects a phenomenon associated with fuel deprived beta-cells.


Nuclear receptor coactivator 3 transactivates proinflammatory cytokines in collagen-induced arthritis.
Rheumatoid arthritis (RA) is an autoimmune disorder in which the immune system mistakenly attacks joints. The molecular mechanisms underlying RA pathology are still under investigation. In this study, we discovered overexpression of nuclear receptor coactivator 3 (NCOA3) in the joint tissues of type II collagen-induced arthritis (CIA) mice, an important autoimmune model of human RA. Administration of two NCOA3 inhibitors, gossypol (GSP) and SI-2 hydrochloride (SHC), significantly alleviated inflammation and improved the outcomes of CIA mice. In vivo and in vitro experiments revealed that NCOA3 assembled a transcriptional complex with a histone acetyltransferase p300 and two subunits of nuclear factor kappa B (NF-κB). This complex specifically controlled the expression of proinflammatory cytokine genes by binding to their promoters. Knockdown of NCOA3 or in vitro treatments with GSP and SHC impaired the assembly of NCOA3-p300-NF-κB complex and decreased the expression of proinflammatory cytokine genes. Taken together, our results demonstrated that NCOA3 acts as a mediator of proinflammatory cytokine genes in CIA mice and that inhibition of the NCOA3-p300-NF-κB complex may represent a new avenue for improving RA outcomes.


Dietary flavonols: chemistry, food content, and metabolism.
The flavonols belong to a large group of compounds called flavonoids, which are diverse in their chemical structure and characteristics. Fruits, vegetables, and beverages such as tea and red wine are major sources of flavonols in the human diet. The daily consumption of flavonols is difficult to estimate because values depend on accurate assessment of feeding habits and flavonol content in foods. Food sources, dietary intakes, and bioavailability of flavonols are strongly influenced by variations in plant type and growth, season, light, degree of ripeness, food preparation, and processing, all of which are discussed. In the past few years, a number of studies on the absorption and metabolism of flavonols in humans have been published and the findings from these studies are reviewed. We do not discuss the health effects of flavonols.


Density and composition of trabecular and cortical bone in perinatally irradiated beagles with chronic renal failure.
Bone density and composition were studied in trabecular and cortical bone from control 2 and 4 year old beagles and those which had various degrees of renal failure as a result of perinatal irradiation. Changes in the two types of bone were qualitatively similar but consistently greater in trabecular bone. In a group identified as markedly uremic, the decrease (P less than 0.025) from control levels in specific gravity was about 4 times greater in trabecular than in cortical samples. The decrease (P less than 0.025) in grams of ash/ml was 9% in trabecular bone and 2% in cortical bone. These changes were associated with an increase (P less than 0.001) in water content and, on a percent by volume basis, approximately equal decreases in ash (P less than 0.025) and combustible matter (P less than 0.025). In a mildly uremic group there were similar trends in mean values but the only significant difference was an increase (P less than 0.001) in trabecular bone water.


Effect of environmental factors and cell physiological state on Pulsed Electric Fields resistance and repair capacity of various strains of Escherichia coli.
The aim was to determine the resistance variation of four strains of Escherichia coli to Pulsed Electric Fields (PEF), the role of the sigma factor RpoS in PEF resistance, as well as the influence of several environmental factors and the cell physiological state on the PEF resistance and repair capacity. The rpoS null mutant, E. coli BJ4L1, exhibited decreased PEF resistance as compared with its wild-type parent, BJ4. W3110 and O157:H7 were the most PEF-resistant strains: whereas 2 and more than 3 Log10 cycles of BJ4 and BJ4L1 cells, respectively, were inactivated after 50 pulses at 35 kV/cm, only 0.5 Log10 cycle of inactivation of W3110 and O157:H7 was attained. A different pattern was observed and the resistance variation among strains was largely reduced, when selective recovery media were used. At exponential growth phase, the resistance of the four strains was lower, and more than 4 Log10 cycles of inactivation of all strains tested were attained at 30 kV/cm. Previous heat and cold shock treatments scarcely influenced cell PEF resistance. PEF survival increased with the reduction in water activity of the treatment medium to 0.94: the occurrence of sublethally injured cells was negligible, and less than 1 Log10 cycle of inactivation was attained at 35 kV/cm. PEF-treated cells were sensitive to a subsequent storage at pH 4.0 or in the presence of sorbic acid, attaining a final inactivation of 4-5 Log10 cycles after 24 hour-incubation. In conclusion, the work confirms the role of rpoS in PEF resistance. E. coli strains exhibit large differences in PEF resistance. These differences were less important when cells were recovered under selective conditions. Both resistance variation among strains and occurrence of sublethal damage were noticeably influenced by the environmental factors tested.


Multiplicity reactivation of vaccinia virus particles treated with nitrogen mustard.
The nitrogen mustard bis(beta-chloroethyl)methylamine, a radiomimetic alkylating agent, is known for its ability to inactivate viruses in general and poxvirus in particular. These experiments show that vaccinia virus is rapidly inactivated by it. They show, in addition, that the treated virus exhibits multiplicity reactivation in L cells, closely resembling that experienced with the same virus after exposure to ultraviolet rays. These findings have come from observations of plaque titer, on the one hand, and virus particle aggregation (measured in the electron microscope), on the other. The titer of the treated virus is very sensitive to particle aggregation, increasing and decreasing in a reversible manner as the degree of clumping among the particles is changed. The magnitude of these changes is such that they must be considered in any situation involving plaque assay of the fraction of virus surviving treatment with nitrogen mustard.


Hepatic glutaminase expression: relationship to kidney-type glutaminase and to the urea cycle.
Glutamine functions as a major transport form of nitrogen and carbon within the body. In the liver, glutamine is hydrolyzed by a unique liver-type, phosphate-activated glutaminase, and the end products of hepatic glutamine catabolism are glucose and urea. Other tissues possess a different, kidney-type, glutaminase isozyme. The predicted amino acid sequences for the two glutaminases show a high degree of identity, indicating that they are products of different but related genes. Hepatic glutaminase activity is increased during diabetes, starvation, and on feeding high-protein diets, and decreased on feeding low-protein diets, whereas renal glutaminase appears to be regulated only by changes in acid-base status. Changes in the rate of gene transcription are the principal mechanism responsible for the long-term regulation of hepatic glutaminase, but the renal enzyme is regulated at the level of mRNA turnover. The pattern of regulation of hepatic glutaminase parallels that seen for genes encoding key enzymes of gluconeogenesis and urea synthesis, and indicates coordinate regulation of expression in keeping with the role of hepatic glutamine catabolism in these pathways.


A randomized trial of the effect of vitamin E on plasma prostacyclin (6-keto-PGF1 alpha) levels in healthy adults.
We conducted a randomized, placebo-controlled double blind trial of the effect of vitamin E (800 IU/day) on plasma prostacyclin levels. After drawing baseline blood samples, 30 healthy adults were randomly assigned to vitamin E or placebo. After eight weeks, we again collected blood and assayed the plasma for 6-keto-PGF1 alpha, the principal stable degradation product of prostacyclin. Mean levels of 6-keto-PGF1 alpha in those patients who received placebo was essentially unchanged, 27 pg/ml at baseline and 29 pg/ml at 8 weeks. The mean level of those patients on vitamin E declined dramatically, from 29 to 13 pg/ml. The mean net difference due to vitamin E, -18 pg/ml (95% confidence limits from -32 to -3), was statistically significant, p = .02. It is not clear whether this effect is restricted to prostacyclin or if vitamin E exerts a similar tendency on other arachidonic acid derived products.


Changes of extracellular volumes measured by whole and segmental bioimpedance analysis during hemodialysis in end-stage renal disease (ESRD) patients.
The bioimpedance technique is postulated as not expensive and non-invasive method for measurement of body water compartments in humans. However, the accuracy of the whole body bioimpedance technique has been questioned by several authors because of nonhomogenic nature of the human body. In the present study we used the whole body bioimpedance technique in comparison to segmental measurement from the arm and leg for assessment of extracellular water compartment. The extracellular water compartment value as measured by the whole body technique significantly correlated with extracellular water compartment value measured from segmental measurement in the leg. We postulate practical use of segmental measurement from the leg as an indicator of body hydration.


Non-coding RNAs in Ischemic Stroke: Roles in the Neuroinflammation and Cell Death.
Ischemic stroke is one of the leading causes of death and long-term disability worldwide. As an important class of pervasive genes involved in many pathophysiological processes of ischemic stroke, non-coding RNAs (ncRNAs) have received attention in the past decades. ncRNAs are a class of functional RNAs that regulate gene expression in a post-transcriptional manner, and including microRNAs, long non-coding RNAs, and circular RNAs. Several studies have deciphered that ncRNAs have a key role in the ischemic stroke-induced neuroinflammation and cell death via different molecules and pathways. Thus, ncRNAs show great promise as novel molecular targets in ischemic stroke. In this article, we provide an updated review of the current state of our knowledge about the roles of different types of ncRNAs in neuroinflammation and cell death following ischemic stroke, which may facilitate the translation of ncRNAs research into clinical practice to improve the clinical outcome of stroke therapy.


Cytotoxicity mechanism of α-MMC in normal liver cells through LRP1 mediated endocytosis and JNK activation.
Alpha-momorcharin (α-MMC), a type I ribosome-inactivating protein isolated from Momordica charantia, is a potential drug candidate with strong anti-tumor activity. However, α-MMC has a severe hepatotoxicity when applied in vivo, which may greatly hinders its use in clinic in the future. The biological mechanism of hepatotoxicity induced by α-MMC is largely unknown, especially the mechanism by which α-MMC enters the hepatocytes. In this study, we investigated α-MMC-induced cytotoxicity in normal liver L02 cell line as well as the mechanism underlying it. As expected, α-MMC is more toxic in L02 cells than in various normal cells from other organs. The cytotoxic effect of α-MMC on L02 cells is found to be mediated through cell apoptosis as detected by flow cytometry and fluorescence microscopy. Importantly, α-MMC was shown to bind to a specific receptor on cell membrane, as the density of the cell membrane receptor is closely related to both the amount of α-MMC endocytosed and the cytotoxicity in different cell lines. By using LRP1 competitive inhibitor α2-M or siRNA targeting LRP1, we further identified that LRP1 protein served as the membrane receptor for α-MMC. Both α2-M and siRNA targeting LRP1 can significantly inhibit α-MMC's endocytosis as well as its cytotoxicity in L02 cells. In addition, it was found that α-MMC can activate the JNK signalling pathways via LRP1 in L02 cells. As JNK activation often leads to cell apoptosis, the activation of JNK may play an important role in α-MMC-induced cytotoxicity. To our knowledge, this is the first report showing that LRP1 mediates the cytotoxicity of α-MMC through (1) endocytosis and induced apoptosis and (2) the activation of the JNK pathway. Our findings shed light on the fundamental mechanism of hepatotoxicity of α-MMC and offer reference to understand its mechanism of lymphocytotoxicity and neurotoxicity.