Membrane barriers for guided bone regeneration: An overview of available biomaterials.
Dental implants revolutionized the treatment options for restoring form, function, and esthetics when one or more teeth are missing. At sites of insufficient bone, guided bone regeneration (GBR) is performed either prior to or in conjunction with implant placement to achieve a three-dimensional prosthetic-driven implant position. To date, GBR is well documented, widely used, and constitutes a predictable and successful approach for lateral and vertical bone augmentation of atrophic ridges. Evidence suggests that the use of barrier membranes maintains the major biological principles of GBR. Since the material used to construct barrier membranes ultimately dictates its characteristics and its ability to maintain the biological principles of GBR, several materials have been used over time. This review, summarizes the evolution of barrier membranes, focusing on the characteristics, advantages, and disadvantages of available occlusive barrier membranes and presents results of updated meta-analyses focusing on the effects of these membranes on the overall outcome.


Social and emotional loneliness: an examination of Weiss's typology of loneliness.
This study examined Weiss' conceptualization of social and emotional loneliness. Using data from an extensive survey of undergraduate and graduate students at the University of Iowa, we measured social and emotional loneliness, students' affective and behavioral reactions to loneliness, students' social relationships, and their judgments of the degree to which their relationships supply the six social provisions described by Weiss. As expected, we found differences in the subjective experiences of social and emotional loneliness, although both forms of loneliness were also characterized by a common core of experiences. The results generally supported Weiss's ideas concerning the determinants of social and emotional loneliness. Predictions concerning the affective and behavioral consequences associated with each type of loneliness, however, were only partly supported, although the two forms of loneliness were associated with different affective reactions and coping behaviors. The implications of these findings for Weiss's typology of loneliness are discussed.


Supplemental Oxygen Requirements of Critically Injured Adults: An Observational Trial.
The optimal amount of oxygen to deploy with pararescue personnel for combat casualty care is currently unknown. The purpose of this prospective observational trial was to determine the proportion of trauma patients requiring supplemental oxygen, whether high or low flow rates were needed, and to evaluate associations between injury characteristics and oxygen requirements. Over 6 months, dedicated study assistants observed oxygen requirements and delivery during the first 3 hours of emergency care for trauma patients meeting our institution's highest level trauma team activation criteria. The mean age of 204 enrolled subjects was 37 years, 79% were male, median injury severity score was 9 (interquartile range 1-21), 58% suffered penetrating injuries. Most (69%) were admitted; 17% went directly to the operating room, and 38% went directly to the intensive care unit from the emergency department. 136/160 nonintubated patients were managed with no or low-flow supplemental oxygen. Penetrating injuries were less likely to require supplemental oxygen (relative risk 0.65, 95% confidence interval 0.50-0.84). Subjects with Glasgow Coma Scale scores <15, abdominal or chest injury, or hypotension were more likely to require supplemental oxygen. There is significant opportunity to reduce the need for high-flow oxygen delivery to the battlespace.


Evaluation of anticholinergic burden in elderly outpatients and the risk factors.
The use of anticholinergic drugs in the elderly may lead to negative events such as falls, delirium, urinary retention and cognitive decline, and the higher the number of anticholinergic drugs use, the more such negative events occur. This study aims to analyze the risk factors associated with the prescription of total anticholinergic drugs in elderly outpatients and evaluate the rationality of anticholinergic drugs, and to provide a reference for reducing the adverse effects of anticholinergic drugs. A list of drugs with anticholinergic activity based on the Beers criteria was established. The basic information (such as age and gender), clinical diagnosis, and medications of elderly outpatient were extracted from hospital electronic medical records, and the Anticholinergic Cognitive Burden (ACB) Scale was used to calculate the anticholinergic burden for each patient. Logistic regression analysis was used to identify the potential risk factors for the occurrence of problems such as multiple medication and insomnia. A total of 1 840 prescriptions for elderly patients were reviewed. Of these patients, ACB score was more than or equal to 1 in 648 (35.22%) patients. Number of prescription medication (95% CI: 1.221 to 1.336) and insomnia (95% CI: 3.538 to 6.089) were independent factors affecting ACB scores (both P<0.01). Medications for patients of ACB scores were most commonly treated with the central nervous system drugs (such as alprazolam and eszopiclone) and for the cardiovascular system drugs (such as metoprolol and nifedipine). There is a high rate of ACB drugs use in geriatric patients, and the clinical focus should be on multiple medication prescriptions, especially on the central nervous system drugs (such as alprazolam and eszopiclone) and cardiovascular system drugs (such as metoprolol and nifedipine). The prescription review should be emphasized to reduce adverse reactions to anticholinergic drugs in elderly patients.


Benign giant cell tumor of bone with osteosarcomatous transformation ("dedifferentiated" primary malignant GCT): report of two cases.
It is not uncommon for sarcomatous transformation of giant cell tumor (GCT) of bone to occur after radiation, but rarely does malignant transformation occur spontaneously, with less than 15 cases reported up to 1995. Only four of these cases have been documented in detail. We report two additional cases of GCT of bone spontaneously transforming or "dedifferentiating" into osteosarcoma without radiation therapy. The first case is absolutely unique and most interesting in that the dedifferentiation process occurred in one of multiple GCT lung metastases 6 years after successful eradication of a primary tibial tumor. The right lung was resected due to development of a large tumor, and at pathologic examination, demonstrated several small nodules of conventional GCT and a much larger, 14-cm mass composed of a mixture of GCT and high-grade osteosarcoma. The second case involved a physician, who had a large tumor in the sacrum with vague symptoms for 8 years. Open biopsy revealed conventional, benign GCT of bone with a secondary aneurysmal bone cyst. Complete curettage 2 weeks later revealed, in addition to areas of conventional, benign GCT a second component of very high grade osteosarcoma. Both patients died less than 1.5 years from diagnosis. This report of osteosarcomatous transformation of a conventional GCT of bone strengthens the theory that there is a mesenchymal cell line in GCT that may spontaneously transform to sarcoma.


Regulation of cardiac contractility in a cold stenothermal fish, the burbot Lota lota L.
In the present study, burbot (Lota lota L.) was used as a model to study the effects of acute temperature changes on cardiac contractility in a cold stenothermal fish. The burbot were captured in the breeding season (February) and were maintained for 4 weeks at 1-2 degrees C in the laboratory before the contractile properties of the heart were measured. Both isometric force and the pumping capacity of in vitro perfused hearts were maximum at the acclimation temperature (1 degrees C) and declined markedly when the temperature increased. At 1 degrees C heart rate was 25 beats min(-1) and increased to a maximum of 72 beats min(-1) at 18 degrees C, above which atrio-ventricular block was observed. Ryanodine (10 micromol l(-1)), an inhibitor of sarcoplasmic reticulum (SR) Ca2+ release channels, reduced the maximum developed force of paced atrial and ventricular preparations at 1 degrees C by 32+/-8 % and 16+/-3 %, respectively. At 7 degrees C, ryanodine-induced inhibition of force increased to 52+/-3 % and 44+/-5 % in the atrium and ventricle, respectively. At 1 degrees C, ryanodine abolished rest-potentiation and turned it into rest-decay in both atrial and ventricular muscle. Ryanodine, however, had no effect on the mechanical refractory period or on the rate constants of mechanical and relaxation restitution in either preparation at 1 degrees C. The activity of myofibrillar Ca2+Mg2+-ATPase was higher in atrial than ventricular muscle and the temperature optimum of the ATPase in vitro was approximately 10 degrees C in both preparations. Our results indicate a significant dependence on SR Ca2+ stores for contractile activation in the burbot heart at temperatures that are known to inhibit SR function in mammalian heart. This suggests that the ryanodine receptors of the teleost heart, unlike those of the endotherms, are not leaky as temperatures approach 0 degrees C. Reliance on SR Ca2+ stores in both cold stenothermal burbot and cold-acclimated eurythermal teleosts suggests that enhanced SR Ca2+-release is a common characteristic of cold-living fish and may improve cardiac contractility in the cold.


Nairobi terrorist bombing: the personal experience of a mental health adviser.
This is a personal account of the author's involvement as an adviser in the wake of the Nairobi terrorist bombing in 1998. Much has been written in the literature about the problems for and reactions of first responders, emergency personnel and those who provide care for victims of trauma. Less is known about the role of the specialist adviser. The author describes the terrorist incident, how the Kenyans responded to it and his own role. He also highlights important learning points, dilemmas and challenges which an adviser might encounter.


Rationale for dipeptidyl peptidase 4 inhibitors: a new class of oral agents for the treatment of type 2 diabetes mellitus.
To review advances in understanding the pathophysiologic basis of type 2 diabetes mellitus and the pharmacology and mechanism of action of dipeptidyl peptidase 4 (DPP-4) inhibition in correcting the underlying defects in glycemic control. Articles were identified through MEDLINE for the period 1966 through November 2006. Abstracts and presentations from the American Diabetes Association Scientific Sessions and the European Association for the Study of Diabetes (2002-2006) were also searched for scientific reports on DPP-4 inhibitors. Abstracts, original clinical and preclinical research reports, and review articles published in the English language were identified for review. Literature discussing glucose regulation, incretin hormones, type 2 diabetes pathophysiology, and DPP-4 inhibition were evaluated and selected based on consideration of their support for the proof of concept, mechanistic and in vivo findings, and timeliness. The search for new and effective therapies for type 2 diabetes has led to the identification of a novel therapeutic target, the incretin hormones, which play a role in mediating glucose homeostasis via effects on glucagon and insulin secretion from pancreatic islet alpha- and beta-cells, respectively. The incretins' glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide are rapidly inactivated by the enzyme DPP-4. DPP-4 inhibitor agents act by blocking the active site of DPP-4, thereby preventing inactivation of and prolonging the duration of action of incretins, which in turn helps to correct the defective insulin and glucagon secretion that marks type 2 diabetes. Clinical studies to date indicate that DPP-4 inhibitors effectively stimulate insulin secretion, suppress glucagon release, and improve glucose control in patients with type 2 diabetes. These agents are well tolerated and have a low incidence of adverse effects. The DPP-4 inhibitors are novel agents for the treatment of type 2 diabetes. Compounds under development in this new class of oral antidiabetic drugs may be free of the limitations of current therapies.


[Construction and identification of a lentiviral vector for RNA interference of human GLUT3 gene].
To construct an effective lentiviral vector for RNA interference (RNAi) with human glucose transporter 3 (GLUT3)gene. Four pairs of shRNA sequences against different parts of GLUT3-mRNA were separately cloned into the RNAi plasmid vector pLV-shRNA by recombinant DNA technology to construct shRNA expression vectors pLV-shRNA-GLUT3-1, pLV-shRNA-GLUT3-2, pLV-shRNA-GLUT3-3, and pLV-shRNA-GLUT3-4. The vectors were transfected into HeLa cells to detect the effectiveness of GLUT3 gene silencing. One of effective vectors was selected and co-transfected into 293T cells with lentivirus packaging plasmids to obtain packaged lentivirus particles LV-GLUT3. After viral titer determination, U251 glioblastoma cells were infected with LV-GLUT3 at a multiplicity of infection (MOI) of 10. Finally, the expression of GLUT3 protein was detected by Western blot. DNA sequencing demonstrated that the shRNA sequences were successfully inserted into the pLV-shRNA vectors. In HeLa cells, the expression of GLUT3-mRNA was significantly down-regulated by the recombinant vectors compared with negative control. The recombinant lentivirus LV-GLUT3 harvested from 293T cells had a titer of 1.5×10(9) TU/mL. After infection with LV-GLUT3, the expression of GLUT3 protein in U251 glioblastoma cells was down-regulated. An effective lentiviral shRNA expression vector targeting the GLUT3 gene is successfully constructed and can be used for further study on the functions of GLUT3 gene.


Stimulation-specific contribution of p38 and JNK to IFN-beta gene expression in human macrophages.
Induction of interferon-beta (IFN-beta) gene expression is a tightly regulated process, and a plethora of studies identified the signal transduction pathway TANK-binding kinase-1 (TBK-1)/IFN regulatory factor-3 (IRF-3) as essential to the induction of IFN-beta gene expression. Data regarding the role of p38 and JNK are rare, however. We investigated the contribution of these kinases to IFN-beta expression in human macrophages treated with poly(I:C), lipopolysaccharide (LPS), Sendai virus, or vesicular stomatitis virus (VSV). We found that all the stimuli induced IFN-beta mRNA, albeit to a different extent. Whereas LPS and VSV induced the phosphorylation of p38 and JNK, neither poly(I:C) nor Sendai virus led to the detection of phosphospecific signals. When inhibiting p38, a VSV-triggered IFN-beta mRNA response was inhibited, whereas inhibiting JNK suppressed an LPS-triggered response, but only when macrophages were primed with IFN-gamma. Neither poly(I:C)-induced nor Sendai virus-induced IFN-beta mRNA expression was affected when p38 and JNK were inhibited. Collectively, the data show that the contribution of p38 and JNK to the expression of IFN-beta occurs in a stimulation-specific manner in human macrophages.


Role of Perceived Maternal Favoritism and Disfavoritism in Adult Children's Psychological Well-Being.
The detrimental consequences of parents' differential treatment on children's well-being have been documented in earlier stages of the life course; however, little is known about this pattern in midlife. Drawing from theories of equity and social comparison, we tested whether psychological well-being was affected only by adult children's perceptions that their mothers treated some offspring in the family differently or by their perceptions that they were favored or disfavored. Further, we explored the extent to which these patterns differed by race. Multilevel regression modeling was conducted using data collected from 725 adult children nested within 309 later-life families as part of the Within-Family Differences Study-II. Depressive symptoms were higher when offspring perceived that they had the most emotional closeness to mothers or the greatest conflict with mothers. Depressive symptoms were also higher when respondents identified themselves as being the children in whom the mothers were most disappointed. The findings shed new light on the role of intergenerational relations in adult children's well-being in midlife by taking into consideration the respondents' direct reports of their perceptions of their mothers' favoritism and disfavoritism. Further, the findings provide evidence that the association between maternal differentiation and psychological well-being in adulthood is stronger in Black than in White families. These patterns suggest that the association between psychological well-being and both favoritism and disfavoritism can be accounted for by processes involving social comparison rather than equity for both Black and White adult children in midlife.


Oncogenic HRAS mutations cause prolonged PI3K signaling in response to epidermal growth factor in fibroblasts of patients with Costello syndrome.
Costello syndrome (CS) is a rare congenital disorder characterized by failure to thrive, craniofacial dysmorphisms, cardiac and skin abnormalities, mental retardation, and predisposition to malignancies. CS is caused by heterozygous gain-of-function mutations in HRAS that also occur as somatic alterations in human tumors. HRAS is one of the three classical RAS proteins and cycles between an active, GTP- and an inactive, GDP-bound conformation. We used primary human skin fibroblasts from patients with CS as a model system to study the functional consequences of HRAS mutations on endogenous signaling pathways. The GTP-bound form of HRAS was significantly enriched in CS compared with normal fibroblasts. Active HRAS is known to stimulate both the RAF-MEK-ERK and the PI3K-AKT signaling cascade. Phosphorylation of MEK and ERK was normal in CS fibroblasts under basal conditions and slightly prolonged after epidermal growth factor (EGF) stimulation. Interestingly, basal phosphorylation of AKT was increased yet more in CS fibroblasts. Moreover, AKT phosphorylation was diminished in the early and enhanced in the late phase of EGF stimulation. Taken together, these results document that CS-associated HRAS mutations result in prolonged signal flux in a ligand-dependent manner. Our data suggest that altered cellular response to growth factors rather than constitutive activation of HRAS downstream signaling molecules may contribute to some of the clinical features in patients with CS.


Localization of interleukin-1 type I receptor and interleukin-1 beta in human endometrium throughout the menstrual cycle.
Previous studies in the human suggest that the interleukin-1 (IL-1) system, may be an important paracrine/autocrine mediator in local intercellular interaction in endometrial tissue. In this study we have determined that IL-1 receptor type I (IL-1R tI) is expressed at the messenger RNA (mRNA) and protein levels in glandular cells and its ligand, IL-1 beta has been localized by immunohistochemical methods in endothelial cells and isolated stromal cells in the human endometrium throughout the menstrual cycle. IL-1R tI mRNA was detected in glandular epithelium using both specific complementary DNA and complementary RNA 32P-labeled probes. Human glandular epithelium contains a 5.1-kilobase mRNA transcript throughout the complete menstrual cycle. Quantitative densitometric analysis of slot blot hybridization signals shows an increase of IL-1R tI mRNA in both early and mid-late secretory phases in comparison with the proliferative phase (P < 0.05). IL-1R tI protein was localized in endometrial glandular epithelial cells using both indirect immunofluorescence and avidin-biotin-peroxidase methods. However, more intense staining for IL-1R tI was observed in lumenal epithelial cells compared with the staining present deep in the endometrial glands. Using the same methods, IL-1 beta was detected in endothelial cells of spiral vessels and isolated stromal cells throughout the menstrual cycle, and an increased staining from proliferative to secretory phase was observed. The detection of IL-1R tI in the human endometrial epithelium and its ligand, IL-1 beta, in isolated stromal cells and endothelial cells, is another example of possible communication between the immune and reproductive systems with special relevance to human implantation.


Increased maternal genome dosage bypasses the requirement of the FIS polycomb repressive complex 2 in Arabidopsis seed development.
Seed development in flowering plants is initiated after a double fertilization event with two sperm cells fertilizing two female gametes, the egg cell and the central cell, leading to the formation of embryo and endosperm, respectively. In most species the endosperm is a polyploid tissue inheriting two maternal genomes and one paternal genome. As a consequence of this particular genomic configuration the endosperm is a dosage sensitive tissue, and changes in the ratio of maternal to paternal contributions strongly impact on endosperm development. The fertilization independent seed (FIS) Polycomb Repressive Complex 2 (PRC2) is essential for endosperm development; however, the underlying forces that led to the evolution of the FIS-PRC2 remained unknown. Here, we show that the functional requirement of the FIS-PRC2 can be bypassed by increasing the ratio of maternal to paternal genomes in the endosperm, suggesting that the main functional requirement of the FIS-PRC2 is to balance parental genome contributions and to reduce genetic conflict. We furthermore reveal that the AGAMOUS LIKE (AGL) gene AGL62 acts as a dosage-sensitive seed size regulator and that reduced expression of AGL62 might be responsible for reduced size of seeds with increased maternal genome dosage.


Effects of nitric oxide modulators on cardiovascular risk factors in mild hyperhomocysteinaemic rat model.
Hyperhomocysteinaemia is considered to be an independent risk factor in atherosclerosis. In the present article, we observed the effect of nitric oxide modulators on cardiovascular risk factors in mild hyperhomocysteinaemic rats. A rat model of mild hyperhomocysteinaemia was established by administering methionine (1 g/kg body weight, orally) for 4 weeks. The other groups were concomitantly treated with sodium nitroprusside (SNP) and N(omega)-nitro-l-arginine (LNNA) during the induction of hyperhomocysteinaemia. Lipid profile, total antioxidant capacity and the level of homocysteine and NO(x) (nitrates and nitrites) was examined in serum at 0 and 4 weeks. Activity of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the mRNA level of caveolin, P2 receptors and cardiovascular risk factors were also analysed. Stimulated lipid profile of rats by the treatment of methionine (1 g/kg body weight) reduced significantly by the treatment of SNP with methionine. LNNA increased the level of cholesterol in aorta (P < 0.05 versus group II). SNP significantly suppressed the activity of HMG-CoA reductase. The mRNA levels of caveolin (P < 0.05), P2X (P < 0.05) and P2Y (P < 0.05) showed a significant decrease in rats administered with SNP. LNNA showed significant induction in the expression of caveolin (P < 0.01) and P2Y (P < 0.01) expression. The level of P2X showed no remarkable change in animals treated with LNNA and methionine both. These data conclude that nitric oxide modulators modulate the effect of hyperhomocysteinaemia on the other cardiovascular risk factors and confirm the finding that nitric oxide plays an important role in homocysteine-induced cardiovascular diseases.


Dipyridodiazepinone analogs as human immunodeficiency virus type 1-specific non-nucleoside reverse transcriptase inhibitors: an overview.
According to World Health Organization (WHO)/Joint United Nations Programme on human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) (UNAIDS) Report in 2007, 33.2 million people are living with HIV, 2.5 million ones have been newly infected with HIV, and 2.1 million ones died from AIDS, including 330,000 children. Therefore, HIV/AIDS still remains a public health emergency and a leading cause of mortality worldwide. It is believed that reverse transcriptase (RT) is a crucial enzyme in the life cycle of HIV-1, and thereby RT has been the important drug target for antiretroviral (ARV) chemotherapy against AIDS. To our knowledge, dipyridodiazepinone analogs have been considered as one class of potential non-nucleoside reverse transcriptase inhibitors (NNRTIs), especially the structurally and chemically related nevirapine (Viramune(R)), which was the first NNRTI approved by the U. S. Food and Drug Administration (FDA) for the treatment of HIV-1 infection for adults in 1996 and for children in 1998. This review mainly highlights the progress of synthesis and structure-activity relationship (SAR) of dipyridodiazepinone analogs; in the meantime, the mechanism of action is also presented. It will pave the way for the design and development of novel dipyridodiazepinone analogs as NNRTIs in AIDS chemotherapy in the future.


Using a Visible Light-Polymerized Resin to Fabricate an Interim Partial Removable Dental Prosthesis.
An interim partial removable dental prosthesis (RDP) is any dental prosthesis that replaces some teeth in a partially dentate arch designed to enhance esthetics, stabilization, and/or function for a limited period of time, after which it is to be replaced by a definitive dental prosthesis. This article describes a technique that uses a visible light-polymerized (VLP) resin as the base material for an interim partial RDP. This technique can be easily accomplished in a dental office or laboratory and results in a predictable dental prosthesis. This technique eliminates the need for laboratory processing.


Increased plasma malondialdehyde and protein carbonyl levels and lymphocyte DNA damage in patients with angiographically defined coronary artery disease.
We investigated the oxidative modifications of lipids, proteins and DNA, three potential molecular targets of oxidative stress, in 30 patients with angiographically defined coronary artery disease (CAD) and 30 healthy control subjects. In addition, we examined relationships between these oxidative modifications and the severity of vascular lesions in patients with CAD. Malondialdehyde (MDA) and protein carbonyl (PC) levels, as well as ferric reducing antioxidant power (FRAP), were measured in the plasma. DNA damage was evaluated as single strand breaks (SSBs), formamidopyrimidine glycosylase (Fpg) and endonuclease III (E-III)-sensitive sites by the comet assay in DNA isolated from lymphocytes. MDA and PC levels increased, but FRAP values decreased, in patients as compared to controls. However, these values did not vary with the number of affected coronary vessels and were not correlated with Duke score, a parameter of the severity of vascular lesions in patients with CAD. We also found that lymphocyte DNA damage (SSBs, Fpg and E-III sites) were increased in patients. Although there were no significant differences in SSBs values in patients grouped according to affected vessel number, Fpg and E-III sites increased. We also detected significant correlations between Duke scores and SSBs and Fpg sites. Serum cholesterol, triglyceride and LDL-cholesterol levels were found to increase, but HDL-cholesterol levels decreased in CAD patients, but these lipids were not correlated with Duke scores. The results of this study reinforce the presence of increased combined oxidative modifications in lipid, protein and DNA in patients with CAD. However, lymphocyte DNA damage seems to be a more reliable assay than MDA and PC determinations to detect the severity of vascular lesions in patients.


Regulation of chondrocyte differentiation level via co-culture with osteoblasts.
The close apposition of osteoblasts and chondrocytes in bone and their interaction during bone development and regeneration suggest that they may each regulate the other's growth and differentiation. In these studies, osteoblasts and chondrocytes were co-cultured in vitro, with both direct and indirect contact. Proliferation of the co-cultured chondrocytes was enhanced using soluble factors produced from the osteoblasts, and the differentiation level of the osteoblasts influenced the differentiation level of the chondrocytes. In addition, the chondrocytes regulated differentiation of the co-cultured osteoblasts using soluble factors and direct contact. These data support the possibility of direct, reciprocal instructive interactions between chondrocytes and osteoblasts in a variety of normal processes and further suggest that it may be necessary to account for this signaling in the regeneration of complex tissues comprising cartilage and mineralized tissue.


Detection of medial arterial calcification on CBCT images of a patient with undiagnosed type 2 diabetes mellitus: a case report.
The finding of medial arterial calcification (MAC) on cone beam computed tomographic scans is more common than many clinicians realize. Medial arterial calcification is a specific pattern of vascular calcification that has been associated with diabetes mellitus. When MAC is identified on a scan, the clinician must refer the patient for evaluation of cardiovascular accident risk and for serologic evaluation to detect undiagnosed type 2 diabetes mellitus. This case report describes a patient with undiagnosed type 2 diabetes mellitus that was later confirmed by hemoglobin A1c levels after incidental detection of MAC on cone beam computed tomography. The article also reviews the literature on MAC and its relationship with diabetes and discusses radiographic features of MAC that are often unrecognized by clinicians.


Mechanisms of Feature Selectivity and Invariance in Primary Visual Cortex.
Visual object identification requires both selectivity for specific visual features that are important to the object's identity and invariance to feature manipulations. For example, a hand can be shifted in position, rotated, or contracted but still be recognized as a hand. How are the competing requirements of selectivity and invariance built into the early stages of visual processing? Typically, cells in the primary visual cortex are classified as either simple or complex. They both show selectivity for edge-orientation but complex cells develop invariance to edge position within the receptive field (spatial phase). Using a data-driven model that extracts the spatial structures and nonlinearities associated with neuronal computation, we quantitatively describe the balance between selectivity and invariance in complex cells. Phase invariance is frequently partial, while invariance to orientation and spatial frequency are more extensive than expected. The invariance arises due to two independent factors: (1) the structure and number of filters and (2) the form of nonlinearities that act upon the filter outputs. Both vary more than previously considered, so primary visual cortex forms an elaborate set of generic feature sensitivities, providing the foundation for more sophisticated object processing.


[Neutrophil enhanced matrix metalloproteinase production and invasion of synoviocytes of RA via CD147].
To study the effects of CD147 on neutrophil on matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) production by fibroblast-like synoviocytes (FLS) and the invasive potential of FLS in rheumatoid arthritis(RA). FLS were isolated from the synovial tissues which were resected from the patients with rheumatoid arthritis (RA) and ostarthritis (OA) during synovectomy, and CD14, CD90 on RA FLS were detected by FCM. HL-60 cells were differentiated into mature neutrophil by alltransretinoic acid (ATRA) and the degree of cell differentiation was detected through NBT reduction reaction. CD147 expression on the differentiated and undifferentiated HL-60 cells and FLS were detected by FCM. The release and activity of MMP-2 and MMP-9 were detected in the supernantents of HL-60 cells cocultured with RA FLS by Gelatin zymography. The invasive potential of RA FLS was detected by invasion assay. To further investigate the effect of CD147 on neutrophil on MMP production by FLS and the invasive potential of FLS in RA, antagonist peptide against EMMPRIN/CD147 (AP-9) was added to the coculture. The experimental system of FLS separation and culture and HL-60 differentiation were established successfully. The isolated FLS of RA were characterized by negative CD14 and positive CD90. CD147 expression on the differentiated HL-60 cells was higher than that on the undifferentiated HL-60 cells, and CD147 expression on both of them were higher than that on RA FLS (P < 0.05). The expressions of Pro-MMP-2, MMP-2 produced by RA FLS were higher than that produced by OA FLS (P < 0.05). Pro-MMP-2, MMP-2, Pro-MMP-9 and MMP-9 were significantly increased when RA FLS were cocultured with the undifferentiated or differentiated HL-60 cells (P < 0.05), and Pro-MMP-2 and MMP-2 in differentiated HL-60 cells cocultured with RA FLS increased more than those in the undifferentiated HL-60 cells cocultured with RA FLS (P < 0.05). The increase was inhibited by AP-9 significantly (P < 0.05). Invasion assay showed that the invasive potential of RA FLS was higher than that of OA FLS (P < 0.05), and the undifferentiated or differentiated HL-60 cells increased the invasive potential of RA FLS (P < 0.05), which could be blocked by AP-9. Neutrophil might increase the production of MMP-2 and MMP-9 and enhanced the invasion of RA FLS via CD147, which can be inhibited by HAb18G/CD147 antagonistic peptide (AP9). Our research on RA pathogenesis and the mechanism of cartilage destruction may give us some good ideas for RA therapy in future.


Enhancement of radiotherapy efficacy by silver nanoparticles in hypoxic glioma cells.
Radiotherapy is one of the most widely used treatments for therapy of malignant tumors, but resistance to radiation of hypoxic cells in tumor tissues is still a serious concern. Previous studies have demonstrated that silver nanoparticles (AgNPs) enhance the radiosensitivity of human glioma cells in vitro, but the effect of AgNPs on hypoxic glioma cells has not been investigated in detail. The main purpose of this study is to evaluate the radiosensitizing efficacy of AgNPs on hypoxic glioma cells. The half maximal inhibitory concentration (IC50) values of AgNPs for the hypoxic U251 cells and C6 cells were 30.32 μg/mL and 27.53 μg/mL, respectively. The sensitization enhancement ratio (SER) demonstrated that AgNPs exhibit higher capacity in radiosensitization in hypoxic cells (U251: 1.78; C6: 1.84) than that in normoxic cells (U251: 1.34; C6: 1.45). The underlying mechanism of AgNPs' radiosensitization in hypoxic cells is through the promotion of apoptosis and enhanced destructive autophagy. There is evidence of crosstalk between apoptosis and autophagy in AgNPs-radiosensitized hypoxic cells where inhibition of autophagy results in decreased apoptosis. These findings suggest that AgNPs can be used as a highly effective nano-radiosensitizer for the treatment of hypoxic glioma.


Stomatal control in tomato with ABA-deficient roots: response of grafted plants to soil drying.
The hypothesis that ABA produced by roots in drying soil is responsible for stomatal closure was tested with grafted plants constructed from the ABA-deficient tomato mutants, sitiens and flacca and their near-isogenic wild-type parent. Three types of experiments were conducted. In the first type, reciprocal grafts were made between the wild type and sitiens or flacca. Stomatal conductance accorded with the genotype of the shoot, not the root. Stomates closed in all of the grafted plants in response to soil drying, regardless of the root genotype, i.e. regardless of the ability of the roots to produce ABA. In the second type of experiment, wild-type shoots were grafted onto a split-root system consisting of one wild-type root grafted to one mutant (flacca or sitiens) root. Water was withheld from one root system, while the other was watered well so that the shoots did not experience any decline in water potential or loss of turgor. Stomates closed to a similar extent when water was withheld from the mutant roots or the wild-type roots. In the third type of experiment, grafted plants with wild-type shoots and either wild-type or sitiens roots were established in pots that could be placed inside a pressure chamber, and the pressure increased as the soil dried so that the shoots remained fully turgid throughout. Stomates closed as the soil dried, regardless of whether the roots were wild type or sitiens. These experiments demonstrate that stomatal closure in response to soil drying can occur in the absence of leaf water deficit, and does not require ABA production by roots. A chemical signal from roots leading to a change in apoplastic ABA levels in leaves may be responsible for the stomatal closure.


Outcomes following repair of incarcerated and strangulated ventral hernias with or without synthetic mesh.
The use of synthetic mesh for ventral hernia repair under contaminated conditions is a controversial issue due to the considerable risk of surgical site infection (SSI). This study aimed to review the outcomes of repair of incarcerated and strangulated ventral hernias with or without synthetic mesh in compliance with established clinical guidelines regarding the incidence of SSI and hernia recurrence. The records of patients with complicated ventral hernias who were treated with or without synthetic mesh repair were reviewed. Variables collected included the characteristics of patients and of ventral hernias, type of repair, and incidence of SSI and recurrence. One hundred twenty-two patients (56 males) of a mean age of 56 years were included. Fifty-two (42.6%) and 70 (57.4%) patients presented with incarcerated and strangulated ventral hernias, respectively. Sixty-six (54%) patients were treated with on-lay mesh repair, and 56 (46%) were managed with suture repair. Twenty-one patients required bowel resection. SSI was detected in eight (6.5%) patients. There was no significant difference between both groups regarding the incidence of SSI (7.5% for mesh group vs 5.3% for suture group). Recurrence occurred in seven patients. Median follow-up period was 24 months. The suture repair group had a significantly higher incidence of recurrence than the mesh group. Diabetes mellitus, previous recurrence, and intestinal resection were significant predictors for SSI. Following established guidelines, synthetic mesh repair of incarcerated and strangulated ventral hernias attained lower recurrence rate, comparable incidence of SSI, and higher rate of seroma formation than suture repair. Research Registry, researchregistry1891.


[Abnormal movements caused by L-DOPA in patients with Parkinson's disease: correlation with the plasma concentrations of DOPA and O-methyl-DOPA].
This study involved twleve parkinsonian patients exposed to abnormal movements provoked by L-DOPA. Including six patients with "mid-dose" dyskinesias and six others with "onset and end of dose" dyskinesias, Correlation between the circumstances of onset of abnormal movements and plasma concentrations of DOPA and O-methyl-DOPA, after administration of a dose of L-DOPA + IDC, gave the following results: 1) mid-dose dyskinesias appeared with the highest plasma concentrations of DOPA, at the maximum therapeutic effect; 2) onset and end of dose occurred during rise and fall in plasma levels of DOPA, coinciding with the relief and the reappearance of parkinsonian symptoms respectively; 3) no correlation could be established between plasma concentrations of O-methyl-DOPA and the duration of the period of clinical remission or of abnormal movements. These biochemical data, completed by the neuropharmacological study of one patient with onset and end of dose abnormal movements suggest the predominant role of a disturbance in central dopaminergic mechanisms in the genesis of abnormal movements, whatever their nature.


Endogenous and Exogenous Antioxidants As a Tool to Ameliorate Male Infertility Induced by Reactive Oxygen Species.
Significance: Antioxidants are essential for the maintenance of cellular redox homeodynamics in the male reproductive tract, playing a key role in fertilizing potential. Reactive oxygen species (ROS), at physiological levels, are essential for sperm function and fertilization. Under pathological conditions, abnormal production of ROS may occur. Redox control is primarily regulated by the inner antioxidant system. However, these endogenous antioxidants may be present at abnormal amounts or may be insufficient. Exogenous antioxidants obtained through the diet may have an important role, particularly in specific pathological conditions. This review addresses the regulation of redox homeodynamics in the male reproductive tract by endogenous and exogenous antioxidants and the importance of their cooperation for the maintenance of fertility. Recent Advances: Many studies have shown the importance of antioxidants for the preservation of male fertility, mostly under pathological conditions. Excessive antioxidants can inhibit ROS-induced signaling pathways that are essential for the reproductive system. The challenge is to keep the balance between oxidants and antioxidants to maintain ROS-amount at physiological concentration. Critical Issues: Although antioxidant therapies are gaining popularity and showing promising results in the improvement of male fertility, there is a lack of knowledge regarding the type of exogenous antioxidant, the doses and time to be administered. Future Directions: It would be of great importance to find a way to restore redox homeostasis under stress conditions. Understanding the poorly studied mechanisms by which exogenous antioxidants cooperate with the inner cellular antioxidant system to counteract free radicals may help in the development of new fertility therapies.


Does national expenditure on research and development influence stroke outcomes?
Background Expenditure on research and development is a macroeconomic indicator representative of national investment. International organizations use this indicator to compare international research and development activities. Aim We investigated whether differences in expenditures on research and development at the country level may influence the incidence of stroke and stroke mortality. Methods We compared stroke metrics with absolute amount of gross domestic expenditure on R&D (GERD) per-capita adjusted for purchasing power parity (aGERD) and relative amount of GERD as percent of gross domestic product (rGERD). Sources included official data from the UNESCO, the World Health Organization, the World Bank, and population-based studies. We used correlation analysis and multivariable linear regression modeling. Results Overall, data on stroke mortality rate and GERD were available from 66 countries for two periods (2002 and 2008). Age-standardized stroke mortality rate was associated with aGERD (r = -0.708 in 2002 and r = -0.730 in 2008) or rGERD (r = -0.545 in 2002 and r = -0.657 in 2008) (all p < 0.001). Multivariable analysis showed a lower aGERD and rGERD were independently and inversely associated with higher stroke mortality (all p < 0.05). The estimated prevalence of hypertension, diabetes, or obesity was higher in countries with lower aGERD. The analysis of 27 population-based studies showed consistent inverse associations between aGERD or rGERD and incident risk of stroke and 30-day case fatality. Conclusions There is higher stroke mortality among countries with lower expenditures in research and development. While this study does not prove causality, it suggests a potential area to focus efforts to improve global stroke outcomes.


Evidence for effects of chronic lead exposure on blood pressure in experimental animals: an overview.
Information obtained in a number of experimental studies conducted over the last 40 years on the effects of lead on blood pressure is reviewed. Differences in animal species, age at beginning of exposure, level of lead exposure, indices of lead burden, and blood pressure effects of each study are reported. In several of the high-dose experiments, hypertension was observed, but nephrotoxicity of lead may have contributed to its development. Moreover, in other high-dose experiments, no hypertension was observed, and in at least one experiment, the evidence suggested that lead could reduce an elevated blood pressure. In contrast, the lower dose experiments consistently demonstrated a hypertensive effect. Overall, the data suggest a biphasic dose response. Establishment of an appropriate animal model to study blood pressure effects of lead will require careful assessment of dietary interactions with lead, unstressed blood pressure monitoring with standardized techniques, and documentation of biologically effective lead burden. Future research should examine lead exposure at more environmentally appropriate levels in order to determine the validity of associating this pollutant with blood pressure effects in the human population.


Evaluation of the QuantiFERON-Tuberculosis Gold Plus Assay in Children with Tuberculosis Disease or Following Household Exposure to Tuberculosis.
Interferon-gamma release assays are increasingly used in children to establish evidence of tuberculosis (TB) infection and to assist in the diagnosis of TB disease. The QuantiFERON-TB Gold In-Tube assay is being phased out in favor of a next-generation test, the QuantiFERON-TB Gold Plus (QFT-Plus) assay. The QFT-Plus assay is designed with two antigen tubes to differentially stimulate CD4+ and CD8+ T cells. The performance of this assay has been documented extensively in adults but has not yet been evaluated in children. Here, we compare the performance of the two assays in a cohort of 46 children exposed to TB and 12 children diagnosed with TB disease in Eswatini. The tests demonstrated excellent concordance in both TB disease (100% agreement, Cohen's kappa = 1) and TB infection (96% agreement, Cohen's kappa = 0.91). Most of the children with household exposure tested negative for TB infection by both tests, indicating the ongoing need for new tests for TB infection that can be easily implemented in TB high-burden settings at minimal cost.


Rous sarcoma virus Gag protein-oligonucleotide interaction suggests a critical role for protein dimer formation in assembly.
The structural protein Gag is the only viral product required for retrovirus assembly. Purified Gag proteins or fragments of Gag are able in vitro to spontaneously form particles resembling immature virions, but this process requires nucleic acid, as well as the nucleocapsid domain of Gag. To examine the role of nucleic acid in the assembly in vitro, we used a purified, slightly truncated version of the Rous sarcoma virus Gag protein, Delta MBD Delta PR, and DNA oligonucleotides composed of the simple repeating sequence GT. Apparent binding constants were determined for oligonucleotides of different lengths, and from these values the binding site size of the protein on the DNA was calculated. The ability of the oligonucleotides to promote assembly in vitro was assessed with a quantitative assay based on electron microscopy. We found that excess zinc or magnesium ion inhibited the formation of virus-like particles without interfering with protein-DNA binding, implying that interaction with nucleic acid is necessary but not sufficient for assembly in vitro. The binding site size of the Delta MBD Delta PR protein, purified in the presence of EDTA to remove zinc ions at the two cysteine-histidine motifs, was estimated to be 11 nucleotides (nt). This value decreased to 8 nt when the protein was purified in the presence of low concentrations of zinc ions. The minimum length of DNA oligonucleotide that promoted efficient assembly in vitro was 22 nt for the zinc-free form of the protein and 16 nt for the zinc-bound form. To account for this striking 1:2 ratio between binding site size and oligonucleotide length requirement, we propose a model in which the role of nucleic acid in assembly is to promote formation of a species of Gag dimer, which itself is a critical intermediate in the polymerizaton of Gag to form the protein shell of the immature virion.


Inoculating chlamydospores of Trichoderma asperellum SM-12F1 changes arsenic availability and enzyme activity in soils and improves water spinach growth.
Arsenic (As)-contaminated agricultural soils threaten crop yields and pose a human health risk. Augmentation of exogenous microorganisms exhibiting plant-growth promoting and As speciation changing shows potential to improve crop growth and change soil As availability. Trichoderma asperellum SM-12F1 exhibiting both traits was developed into chlamydospores to improve its persistence in contaminated soils. After inoculation, As availability and enzyme activity in two types of soils and the growth as well as As uptake of water spinach (Ipomoea aquatic Forsk.) were investigated. The results indicated that inoculation significantly improved water spinach growth in both soils. Inoculating chlamydospores at 5% significantly increased As concentration (139%), bioconcentration factor (150%), and translocation factor (150%) in water spinach grown in Chenzhou (CZ) soils, while no significant change for these in Shimen (SM) soils. Inoculating chlamydospores at 5% caused a significant increase (16%) of available As content in CZ soils, while a significant decrease (13%) in SM soils. Inoculation significantly caused As methylation in both soils, while significant As reduction merely observed in CZ soils. The differential changes in available As contents in both soils were attributed to the soil pH, As fractionations and speciation characteristics. Furthermore, Inoculating chlamydospores at 5% significantly improved the activities of β-glucosidase (155%), chitinase (211%), and phosphatase (108%) in SM soils, while significant decreases in β-glucosidase (81%), phosphatase (54%), aminopeptidase (60%), and catalase (67%) in CZ soils. Bioaugmentation and As availability change were responsible for this result. These observations will be helpful for the application of fungal chlamydospores in the future bioremediation.


Lactate dehydrogenase-B is silenced by promoter methylation in a high frequency of human breast cancers.
Under normoxia, non-malignant cells rely on oxidative phosphorylation for their ATP production, whereas cancer cells rely on Glycolysis; a phenomenon known as the Warburg effect. We aimed to elucidate the mechanisms contributing to the Warburg effect in human breast cancer. Lactate Dehydrogenase (LDH) isoenzymes were profiled using zymography. LDH-B subunit expression was assessed by reverse transcription PCR in cells, and by Immunohistochemistry in breast tissues. LDH-B promoter methylation was assessed by sequencing bisulfite modified DNA. Absent or decreased expression of LDH isoenzymes 1-4, were seen in T-47D and MCF7 cells. Absence of LDH-B mRNA was seen in T-47D cells, and its expression was restored following treatment with the demethylating agent 5'Azacytadine. LDH-B promoter methylation was identified in T-47D and MCF7 cells, and in 25/25 cases of breast cancer tissues, but not in 5/5 cases of normal breast tissues. Absent immuno-expression of LDH-B protein (<10% cells stained), was seen in 23/26 (88%) breast cancer cases, and in 4/8 cases of adjacent ductal carcinoma in situ lesions. Exposure of breast cancer cells to hypoxia (1% O(2)), for 48 hours resulted in significant increases in lactate levels in both MCF7 (14.0 fold, p = 0.002), and T-47D cells (2.9 fold, p = 0.009), but not in MDA-MB-436 (-0.9 fold, p = 0.229), or MCF10AT (1.2 fold, p = 0.09) cells. Loss of LDH-B expression is an early and frequent event in human breast cancer occurring due to promoter methylation, and is likely to contribute to an enhanced glycolysis of cancer cells under hypoxia.


Comparison of topical dorzolamide and ketorolac treatment for cystoid macular edema in retinitis pigmentosa and Usher's syndrome.
To investigate the topical effect of dorzolamide versus ketorolac on retinitis pigmentosa (RP) and Usher's syndrome (US) macular edema. Prospective, randomized and interventional study. A total of 28 eyes of 18 patients were included. Five eyes had US, 23 had RP. Fifteen eyes were allocated to ketorolac tromethamine 0.5% (4 drops daily regimen) and 13 eyes to dorzolamide hydrochloride 2% (3 drops daily regimen) treatment groups. Snellen's best-corrected visual acuity (BCVA), foveal thickness (FT) and foveal zone thickness (FZT) measured by Stratus® optical coherence tomography (OCT) were evaluated at baseline, 1, 3, 6 and 12 months after treatment. Patients assigned to ketorolac had a baseline BCVA of 0.37 ± 0.17 logMAR which improved at the end of 1 year to 0.28 ± 0.16 (p = 0.02). Three eyes (20%) of 2 patients improved by 7 letters or more. Mean FT and FZT did not change significantly during the study follow-up. After 1 year of treatment, 4 eyes (27%) of 3 patients showed an improvement of at least 16% of FT and 11% of FZT. Patients assigned to dorzolamide had a baseline BCVA of 0.48 ± 0.34 logMAR which improved in the first 6 months (0.40 ± 0.30; p = 0.01), with a decrease at 1 year (0.42 ± 0.27; p = 0.20). Seven eyes (54%) of 5 patients had an improvement of 7 letters or more. Mean FT and FZT did not change significantly either. After 1 year of treatment, 3 eyes (23%) of 2 patients showed an improvement of at least 16% on FT and 11% on FZT. RESULTS suggest that dorzolamide and ketorolac might improve visual acuity and therefore be of interest in selected cases. No relationship between retinal thickness fluctuation and visual acuity was found. Sample size was a limitation to the study.


Direct excess entropy calculation for a Lennard-Jones fluid by the integral equation method.
The present work is devoted to the calculation of excess entropy by means of correlation functions, in the framework of integral equation theory. The tangent linear method is set up to get exact thermodynamic derivatives of the pair-correlation function, essential for the calculation of the physical quantities, as well as to carry out an optimization process for the achievement of thermodynamic consistency. The two-body entropy of the Lennard-Jones fluid is in very good agreement with the available molecular dynamics results, attesting the high degree of accuracy of the integral equation scheme. It is shown that an accurate prediction of the excess entropy and the resulting residual multiparticle entropy relies on the correct evaluation of the excess chemical potential, especially at high density. Two independent routes to calculate the latter are compared, and the consequences are discussed.


The prenatal, postnatal, neonatal, and family environmental risk factors for Developmental Coordination Disorder: A study with a national representative sample.
Knowledge of obstetric and environmental influences on Developmental Coordination Disorder (DCD) helps provide increased understanding of the mechanisms underlying the disorder. However, the literature to date has not adequately examined the obstetric and environmental risk factors for DCD in a population-based sample. The current study was therefore conducted to explore the prenatal, perinatal, neonatal, and family environmental risk factors for DCD. A total of 2185 children aged 3-10 years from a national representative sample in China were included; the Movement Assessment Battery for Children-2 was used to assess motor function, and a questionnaire was completed by parents. DCD was identified in 156 children according to the DSM-5 criteria. Multilevel logistic regression was used, and comparisons were made between the DCD and non-DCD group. The results confirmed that male sex, BMI score, preterm birth, and some prenatal conditions are significant risk factors for DCD. Parents' education level and one-child status as two significant environmental risk factors for DCD appear largely independent of other risk factors in the Chinese population. This study provides an opportunity to explore the etiology of DCD and suggest potential assessment, monitoring and intervention programs for DCD that could be examined in the future.


Food energy values of dietary fibre components and decreased deposition of body fat.
The effects of guar gum (GG) and solka floc cellulose (SF) on food intake, stomach emptying and body fat deposition in rats were assessed together with their food energy values. Voluntary food intake in meal-fed rats (ca 100 g, male Wistar kept at 21C) was depressed initially by 40 per cent on adding 10 g GG to 100 g fibre free (FF) semisynthetic diet. This effect was not sustained, intake doubling within 15 d. Similar effects were not observed with SF. In pair-fed animals neither GG nor SF affected the rate of stomach emptying after 28 days. Digestible energy (DE) intake per rat over the 28 days was GG diet = 4616, SF diet = 4410, FF diet = 4373 kJ but body fat was lower in GG (25%) and SF (16%) fed rats than in FF fed rats. The calculated DE values of the fibre components were 10.1 kJ/g GG and 1.5 kJ/g SF (sem 1 kJ/g). After including body fat into the equations for metabolizable energy, the energy values were -7.1 kJ/g GG and -4.8 kJ/g SF (sem 2 kJ/g). This is equivalent to an increased energy expenditure of 17.2 kJ/g GG and 6.3 kJ/g SF. For GG an increased intestinal mucosal mass and cell turnover explains part of the apparent increase in energy demand. Our overall conclusion is that under certain circumstances and with regard to fat deposition some fibre components can be attributed negative energy values.


Targeted disruption of the PME-1 gene causes loss of demethylated PP2A and perinatal lethality in mice.
Phosphoprotein phosphatase 2A (PP2A), a major serine-threonine protein phosphatase in eukaryotes, is an oligomeric protein comprised of structural (A) and catalytic (C) subunits to which a variable regulatory subunit (B) can associate. The C subunit contains a methyl ester post-translational modification on its C-terminal leucine residue, which is removed by a specific methylesterase (PME-1). Methylesterification is thought to control the binding of different B subunits to AC dimers, but little is known about its physiological significance in vivo. Here, we show that targeted disruption of the PME-1 gene causes perinatal lethality in mice, a phenotype that correlates with a virtually complete loss of the demethylated form of PP2A in the nervous system and peripheral tissues. Interestingly, PP2A catalytic activity over a peptide substrate was dramatically reduced in PME-1(-/-) tissues, which also displayed alterations in phosphoproteome content. These findings suggest a role for the demethylated form of PP2A in maintenance of enzyme function and phosphorylation networks in vivo.


Regulation of antibody formation in chickens escaping from tolerance to human serum albumin.
The immune capacity of chickens made tolerant to human serum albumin just after hatching was studied after a primary and secondary challenge at 7--14 weeks of age, of either 1 mg/kg or 100 mg/kg. The class and avidity of antibody produced by birds "escaping" from tolerance was similar to normal controls. The escaping chickens made a normal peak antibody response to a high dose but not to a low dose (except that the response to a low secondary dose after priming with a high dose was normal); but the decline of the antibody titer was abrupt, indicating inability to maintain the response. It is concluded that the antibody-forming capacity of B cells is normal, but regulation of antibody formation is impaired in previously tolerant chickens.


Dry Eye in Vernal Keratoconjunctivitis: A Cross-Sectional Comparative Study.
The purpose of this comparative cross-sectional study was to investigate the use of standardized clinical tests for dry eye in pediatric patients with active and quiet vernal keratoconjunctivitis (VKC) and to compare them with healthy children.We recruited 35 active VKC, 35 inactive VKC, and 70 age-matched control healthy subjects. Each child underwent a complete eye examination, including visual analog scale symptoms assessment, biomicroscopy, fluorescein break-up time (BUT), corneal fluorescein and conjunctival lissamine green staining, corneal esthesiometry, Schirmer test with anesthetic, and meibomian glands inspection and expression.Active VKC patients showed significantly increased symptoms and signs of ocular surface disease, compared with the other 2 groups. Inactive VKC patients, compared with control subjects, showed increased photophobia (P < 0.05; Mann-Whitney U test), conjunctival lissamine green staining and Schirmer test values, and reduced BUT and corneal sensitivity [P < 0.05 by analysis of variance (ANOVA) least significant difference posthoc test for BUT and Schirmer; P < 0.001 by Mann-Whitney U test for lissamine green staining and corneal sensitivity].Our results confirm the association between VKC and short-BUT dry eye. This syndrome seems to affect the ocular surface in quiescent phases too, determining abnormalities in tear film stability, epithelial cells integrity, and corneal nerves function. The very long-term consequences of this perennial mechanism of ocular surface damage have not been fully understood yet.


Epidemiology of Acute and Overuse Injuries in Underwater Rugby.
Underwater rugby (UWR) is a team sport. Athletes require a high degree of strength, endurance, speed, and coordination involving intense physical contact. Currently, a paucity of literature exists regarding injury occurrence in UWR. To examine the nature and prevalence of acute and overuse injuries in UWR. Descriptive epidemiology study. Between November 2020 and March 2021, a total of 720 German UWR athletes were invited to take an online survey developed by orthopaedic specialists with UWR athletes. Data were recorded regarding general and health-related information, training habits, acute injuries that necessitated an interruption in training and/or doctor consultation, as well as overuse injuries. Overuse injuries were evaluated using the Oslo Sports Trauma Research Centre Overuse Injury Questionnaire. Statistical analyses included t tests or rank sum tests depending on normality of distribution. A nonparametric Kruskal-Wallis 1-way analysis of variance on ranks was used for nonnormally distributed data among several groups. This study included 161 active athletes (mean ± SD, 36.1 ± 11.9 years old; 75.3% male) for analysis, of whom 90.1% were competing regularly. The performance-level distribution was as follows: first German national league (n = 73), second German national league (n = 46), state league (n = 17), district league (n = 1), and no league (n = 24). The mean ± SD sport-specific training workload was 5.6 ± 3.0 h/wk, including UWR training, additional swimming (n = 71; 44.1%), strength (n = 70; 43.5%), and/or endurance training (n = 102; 63.4%). Acute injuries were recorded in 78.9% of all athletes. The most typical locations for acute injuries were hand/finger (42.4%), head/face (concussion, ruptured eardrum; 18.1%), wrist (5.5%), or spine (5.0%). Overuse injuries were reported by 42.9% of the participants. The predominant locations for overuse injuries were hand/finger (18.8%), shoulder/clavicle (14.1%), spine and wrist (10.7% each), head/face (8.7%), and ankle joint and knee (6.7% each). In the current study, 3 of 4 athletes reported at least 1 acute injury, and 2 of 5 athletes reported at least 1 overuse injury. Leading injury regions were the hand/finger, head/ear, wrist, and spine.


Some properties of mumps virus neuraminidase.
Mumps virus strains were characterized by the neuraminidase activity of infected allantoic and amniotic fluids of chick embryos. Ovomucoid was used as substrate for determination of neuraminidase activity. Storage of virus samples at 4 degrees C led to great losses of enzyme activity. Alkali chlorides, divalent cations, EDTA and N-ethylmaleimide exerted a low to medium inhibitory activity. Surfactants, depending on their type, caused inhibition, activation or no effect on the enzyme--substrate reactions. The pH optimum was 5.6 and 5.3 with mumps virus strains Enders and Jeryl Lynn, respectively. The Michaelis constants of 9.43 X 10(-3) and 7.57 X 10(-3) mol/1 allowed a differentiation of the two mumps virus strains based on their neuraminidase.


Roles of lncRNAs in the transcription regulation of HIV-1.
Long noncoding RNAs (LncRNAs) is a class of RNA molecules that are more than 200bp but cannot be translated into proteins. More and more studies have proved that lncRNA plays a crucial role in various biological functions and disease processes, including virus infection. It's worth noting that studies have also shown that lncRNAs play an essential role in the pathogenesis of human immunodeficiency virus 1 (HIV-1), one of the lethal virus that can destroy immune system. Although lncRNA-mediated gene regulation involves a variety of mechanisms, such as transcription regulation, translation regulation, protein modification, and the formation of RNA-protein complexes, in this review, we primarily focus on the role of lncRNAs in HIV-1 transcription regulation, which is one of the most important mechanisms that control the activation and development of HIV-1. This review also briefly summarizes the latest research progress of lncRNAs related to HIV-1 infection and its potential application in HIV-1 therapy. Although there are antiretroviral drugs that interfere with the function of HIV-1 virus-encoded proteins, this treatment for the HIV-1 virus is limited by its ability to produce drug resistance. Hence, a further understanding of HIV-1 transcription regulation by lncRNAs might help develop non-traditional antiviral therapy strategies.


Differential-expression and tyrosine-phosphorylation profiles of caveolin isoforms in human T cell leukemia cell lines.
Caveolin, the essential structural component of caveolae, serves as a scaffolding protein onto which signaling molecules are assembled, and functions as a negative regulator for signal transduction. Caveolin-1 and -2 are expressed in most cell types, but are not expressed in normal blood cells and cell lines. We previously demonstrated that caveolin-1 is expressed in a panel of human leukemia cell lines that show an activated T cell phenotype. In that study, we detected two caveolin bands by Western blotting using a polyclonal antibody (pAb) reacting with caveolin-1, -2, and -3. We identified caveolin-1alpha by its large molecular weight, but did not discriminatively detect other caveolin families. Since anti-caveolin-1 monoclonal antibody (mAb) was reported not to detect caveolin-1 in some cases, here we developed a sensitive method for the discriminative detection of caveolin-1, -2, and -3 by modified Western blotting. Caveolins were solubilized using a two-step procedure and detected by immunoprecipitation with a pAb to caveolins followed by Western blotting with mAbs specific to each caveolin. Using this method we detected caveolin-1beta, -2alpha and -2beta, but not caveolin-3 in the leukemia cell lines. Caveolin-1alpha, which was identified by pAb, was not detected by this method. We show here that caveolin-1alpha and -2alpha, but not caveolin-1beta and -2beta, are tyrosine phosphorylated. This modification is likely to cause the lack of reactivity of caveolin-1alpha to the mAb, and suggests a possible close relationship to cell activation.


Weight Status, Physical Fitness, and Health-Related Quality of Life among Chinese Adolescents: A Cross-Sectional Study.
The impact of physical fitness (PF) on adolescents' health-related quality of life (HRQOL) is an important health issue in China. The purpose of this study was to identify whether body mass index (BMI), cardiorespiratory fitness (CRF), and musculoskeletal fitness (MSF) influences HRQOL among Chinese adolescents. The participants were 10,007 students (boys = 5276, 14.14 years ± 1.79; girls = 4829, 14.22 years ± 1.81) who were randomly selected from 30 secondary schools in Shandong, China. BMI, CRF, MSF, and HRQOL were measured and analyzed using ANCOVA and multiple regression. BMI and physical fitness variables were partially associated with HRQOL in Chinese adolescents. ANCOVA showed a significant difference among BMI categories in terms of physical sense (PS), living convenience, and self-satisfaction (SS) for boys, but this difference was only seen with social activity opportunity (SAO) for girls. Multiple regression found that BMI was significantly associated with SAO. For boys, CRF was associated with the teacher and student relationship and SS, whereas MSF was only associated with PS. For girls, CRF was significantly linked with the parent and children relationship, learning capacity, and attitudes and self-perception (S-P), while MSF was associated with S-P. Enforcing physical activity and enhancing PF will be a crucial pathway in improving adolescents' HRQOL in China.


Optical phased-array ladar.
We demonstrate a ladar with 0.5 m class range resolution obtained by integrating a continuous-wave optical phased-array transmitter with a Geiger-mode avalanche photodiode receiver array. In contrast with conventional ladar systems, an array of continuous-wave sources is used to effectively pulse illuminate a target by electro-optically steering far-field fringes. From the reference frame of a point in the far field, a steered fringe appears as a pulse. Range information is thus obtained by measuring the arrival time of a pulse return from a target to a receiver pixel. This ladar system offers a number of benefits, including broad spectral coverage, high efficiency, small size, power scalability, and versatility.


Social support, oxytocin, and PTSD.
A lack of social support and recognition by the environment is one of the most consistent risk factors for posttraumatic stress disorder (PTSD), and PTSD patients will recover faster with proper social support. The oxytocin system has been proposed to underlie beneficial effects of social support as it is implicated in both social bonding behavior and reducing stress responsivity, notably amygdala reactivity (Koch et al., 2014; Olff et al., 2010; Olff, 2012). The amygdala is found to be hypersensitive in people with PTSD. In order to investigate neurobiological mechanisms underlying potential preventive and therapeutic effects of intranasal oxytocin, we performed a series of fMRI studies (funded with a prestigious NWO TOP grant): BONDS standing for "Boosting Oxytocin after trauma: Neurobiology and the Development of Stress-related psychopathology" in acutely traumatized persons admitted to the emergency department (Frijling et al., 2014); BOOSTER "Boosting oxytocin after trauma: the effects of intranasal oxytocin administration on emotional and motivational processing and neural activity in PTSD" in police officers with and without PTSD. In this presentation, we present the BOOSTER results on the effects of a single oxytocin administration on amygdala reactivity in response to emotional faces in PTSD patients versus traumatized controls. We found significantly decreased bilateral amygdala reactivity towards emotional faces in PTSD patients compared to traumatized controls. These promising results call for intervention studies such as studying the effects of medication (oxytocin) enhanced psychotherapy in PTSD patients.


Comprehensive evaluation of the association between prostate cancer and genotypes/haplotypes in CYP17A1, CYP3A4, and SRD5A2.
Genes involved in the testosterone biosynthetic pathway - such as CYP17A1, CYP3A4, and SRD5A2 - represent strong candidates for affecting prostate cancer. Previous work has detected associations between individual variants in these three genes and prostate cancer risk and aggressiveness. To more comprehensively evaluate CYP17A1, CYP3A4, and SRD5A2, we undertook a two-phase study of the relationship between their genotypes/haplotypes and prostate cancer. Phase I of the study first searched for single-nucleotide polymorphisms (SNPs) in these genes by resequencing 24 individuals from the Coriell Polymorphism Discovery Resource, 92-110 men from prostate cancer case-control sibships, and by leveraging public databases. In all, 87 SNPs were discovered and genotyped in 276 men from case-control sibships. Those SNPs exhibiting preliminary case-control allele frequency differences, or distinguishing (ie, 'tagging') common haplotypes across the genes, were identified for further study (24 SNPs in total). In Phase II of the study, the 24 SNPs were genotyped in an additional 841 men from case-control sibships. Finally, associations between genotypes/haplotypes in CYP17A1, CYP3A4, and SRD5A2 and prostate cancer were evaluated in the total case-control sample of 1117 brothers from 506 sibships. Family-based analyses detected associations between prostate cancer risk or aggressiveness and a number of CYP3A4 SNPs (P-values between 0.006 and 0.05), a CYP3A4 haplotype (P-values 0.05 and 0.009 in nonstratified and stratified analysis, respectively), and two SRD5A2 SNPs in strong linkage disequilibrium (P=0.02). Undertaking a two-phase study comprising SNP discovery, haplotype tagging, and association analyses allowed us to more fully decipher the relation between CYP17A1, CYP3A4, and SRD5A2 and prostate cancer.


Fibrocytes Differ from Macrophages but Can Be Infected with HIV-1.
Fibrocytes (fibroblastic leukocytes) are recently identified as unique hematopoietic cells with features of both macrophages and fibroblasts. Fibrocytes are known to contribute to the remodeling or fibrosis of various injured tissues. However, their role in viral infection is not fully understood. In this study, we show that differentiated fibrocytes are phenotypically distinguishable from macrophages but can be infected with HIV-1. Importantly, fibrocytes exhibited persistently infected cell-like phenotypes, the degree of which was more apparent than macrophages. The infected fibrocytes produced replication-competent HIV-1, but expressed HIV-1 mRNA at low levels and strongly resisted HIV-1-induced cell death, which enabled them to support an extremely long-term HIV-1 production at low but steady levels. More importantly, our results suggested that fibrocytes were susceptible to HIV-1 regardless of their differentiation state, in contrast to the fact that monocytes become susceptible to HIV-1 after the differentiation into macrophages. Our findings indicate that fibrocytes are the previously unreported HIV-1 host cells, and they suggest the importance of considering fibrocytes as one of the long-lived persistently infected cells for curing HIV-1.


Observation of a ZZW female in a natural population: implications for avian sex determination.
Avian sex determination is chromosomal; however, the underlying mechanisms are not yet understood. There is no conclusive evidence for either of two proposed mechanisms: a dominant genetic switch or a dosage mechanism. No dominant sex-determining gene on the female-specific W chromosome has been found. Birds lack inactivation of one of the Z chromosomes in males, but seem to compensate for a double dose of Z-linked genes by other mechanisms. Recent studies showing female-specific expression of two genes may support an active role of the W chromosome. To resolve the question of avian sex determination the investigation of birds with a 2A: ZZW or 2A: ZO genotype would be decisive. Here, we report the case of an apparent 2A: ZZW great reed warbler (Acrocephalus arundinaceus) female breeding in a natural population, which was detected using Z-linked microsatellites. Our data strongly suggest a role of W-linked genes in avian sex determination.


Colonization of Durum Wheat (Triticum turgidum L. var. durum) Culms Exhibiting Premature Senescence (Dead Heads) Associated with Fusarium pseudograminearum Crown Rot.
Fusarium crown rot is a significant disease of durum wheat (Triticum turgidum L. var. durum), which exhibits high levels of disease susceptibility. The most extreme symptom of crown rot is a prematurely senescing culm that typically fails to set grain. Individual crown rot-affected durum wheat plants displaying both nonsenescent and prematurely senescent culms were harvested to compare visual discoloration, Fusarium pseudograminearum biomass, and vascular colonization in culm sections sampled at three different heights above the crown. Field samples of EGA Bellaroi were collected at Wellcamp, QLD, in 2011, 2012, 2013, and 2014, and of Hyperno at Narrabri, NSW, in 2014. Prematurely senescent culms exhibited greater visual discoloration, F. pseudograminearum biomass, and vascular colonization than nonsenescent culms in each year they were examined. The extent of these differences varied between environments and timing of collection in each year. Vascular colonization initially occurred in xylem vessels and spread into phloem tissues as disease severity increased. The increased presence of hyphae in vascular bundles of prematurely senescing culms provides strong evidence for the hypothesis that restriction of water and nutrient movement in a diseased culm is a key factor in crown rot severity.


Simplified detection of a mutation causing familial hypercholesterolaemia throughout Britain: evidence for an origin in a common distant ancestor.
Familial hypercholesterolaemia (FH) is an inherited autosomal codominant disorder caused by many different mutations in the low-density lipoprotein receptor (LDLR) gene. The one described most frequently in patients with FH from England, arises from a G-->A transition at the first nucleotide of codon 80, resulting in the substitution of lysine for glutamic acid at residue 80 of the mature protein, FH E80K. We describe a simple method to detect this mutation in genomic DNA using the polymerase chain reaction (PCR). A 69 base pair (bp) fragment of exon 3 of the LDLR gene is amplified using a mutagenic upstream PCR primer. This substitutes a T for an A residue in the amplified product, 2 bp upstream from the mutant site, generating a restriction site for the endonuclease Taq I, in normal, but not in mutant DNA. Following digestion of amplified DNA with Taq I, normal but not mutant DNA is cut into two fragments of 29 and 40 bp, which are readily identified by polyacrylamide gel electrophoresis. Using this method, 410 patients with clinically diagnosed FH, attending lipid clinics in Edinburgh (72), Newport (158), Walsall (30) and Southampton (150), were screened for the mutation. Five individuals tested positive as heterozygotes, one from Edinburgh, three from Newport and one from Southampton. This finding was confirmed by DNA sequence analysis. We conclude that FH due to this mutation occurs in individuals throughout Great Britain and that it can be detected accurately using this simple technique. DNA from these and other individuals previously identified to be heterozygous for FH E80K, was then studied using PCR of highly informative microsatellite markers flanking the LDLR gene. Sixteen of 17 apparently unrelated individuals heterozygous for FH E80K also were heterozygous for an identical size (239 nucleotide) allele, of polymorphic microsatellite D19S394, located approximately 250 kb away from the LDLR gene. This supports the hypothesis that FH E80K in these 16 individuals arose from a single ancestor less than 1000 years ago.


Study of barium sulfate dissolution by scale dissolver based on solutions of DTPA.
In offshore oil wells it is very common to perform seawater injection through injection wells for hydrocarbon recovery. When seawater, rich in sulfate ion, mixes with formation water, whose composition can contain divalent cations such as barium and calcium, it often leads to sulfate salts formation due to their chemical incompatibility. These salts can cause serious damage in production wells. The barium sulfate (BaSO4) is the most problematic scale and may cause many complications. In order to solve this issue, polycarboxylic acids, such as diethylene triamine pentaacetic acid, are used. Thus, the primary focus of this work was to develop an experimental procedure to study the BaSO4 dissolution. Initially, through static tests to understand the relationship between dissolver concentration, temperature and dissolution time, and then through dynamic tests in sandstone reservoirs. Based on the results obtained, in the static tests the best condition for barite to dissolve was at high temperatures (80 ºC) and contact time of 48 hours, since from 50 °C there is an increase in dissolution rate, associated with a long contact time between dissolver and barite. In the dynamic tests, after scale formation, barite could be removed, but the high DTPA concentration should be avoided.


Disordered Eating Behaviors Are Not Increased by an Intervention to Improve Diet Quality but Are Associated With Poorer Glycemic Control Among Youth With Type 1 Diabetes.
This study examines whether participation in an 18-month behavioral intervention shown previously to improve overall diet quality inadvertently increases disordered eating behaviors (DEBs) in youth with type 1 diabetes and investigates the association of DEB with multiple measures of glycemic control and variability. Participants reported DEB and diabetes management at baseline and 6, 12, and 18 months; masked continuous glucose monitoring, HbA1c, and 1,5-anhydroglucitol (1,5-AG) were obtained concurrently. Linear mixed models estimated the intervention effect on DEB, the association of DEB with diabetes adherence and measures of glycemic control and variability, and whether DEB modified glycemic trajectories. There was no intervention effect on DEB (P = 0.84). DEB was associated with higher HbA1c (P = 0.001), mean sensor glucose (P = 0.001), and percent sensor glucose values >180 mg/dL (P = <0.001); with lower 1,5-AG (P = 0.01); and with worse diabetes adherence (P = 0.03). DEB was not associated with percent sensor glucose values <70 mg/dL or any measures of glycemic variability. There was a significant DEB × time interaction effect for mean sensor glucose (P = 0.05) and percent sensor glucose values >180 mg/dL (P = 0.04). Participants reporting less DEB had a developmentally expected deterioration in glycemic control throughout the study. Participants reporting more DEB had poor glycemic control at baseline that remained poor throughout the study. Findings show a potential to improve diet quality without increasing DEB and indicate an association of DEB with persistent hyperglycemia but not hypoglycemia or glycemic variability.


Accuracy of drawing coagulation samples from heparinized arterial lines.
To determine the accuracy of activated partial thromboplastin time and prothrombin time studies when samples are drawn through heparinized arterial lines. A total sample of 90 grouped blood samples (from 30 subjects) was used. Patients were all male, with a mean age of 65 and were studied within 24 hours of percutaneous transluminal coronary angioplasty. Each patient had three venous control and arterial line sample sets (a total of 90 blood samples) drawn when routinely ordered for monitoring therapy. For the arterial line sample, a discard volume of the deadspace, deadspace + 2 mL, or deadspace + 4 mL was randomly assigned for each sample. The venous control volumes were the same for all three sample sets. A 2 x 3 repeated measures analysis of variance was used to analyze the results. The independent variables were the source of the sample (venous vs arterial) and the discard volume of arterial blood (deadspace, deadspace + 2 mL, deadspace + 4 mL). The dependent variables were the activated partial thromboplastin time and prothrombin time values. Mean arterial activated partial thromboplastin time values were significantly higher than the corresponding venous values. Mean activated partial thromboplastin time values were not significantly different among the discard volumes of blood drawn. However, there was a significant source by volume interaction. Tukey post-hoc comparisons of venous-arterial activated partial thromboplastin time differences among the three volumes showed significant differences between deadspace volume and deadspace + 2 mL, and deadspace volume and deadspace + 4 mL. There was no significant difference between deadspace + 2 mL and deadspace + 4 mL volumes. Results indicated that the minimal amount of discard volume for accurate activated partial thromboplastin time values in this population of percutaneous transluminal coronary angioplasty patients was the catheter deadspace volume plus 2 mL (total 3.6 mL).


[Synthesis of signaling N-acyl-homoserine-lactones participating in quorum sensing in rhizosphere and soil bacteria Pseudomonas and Xanthomonas].
Signaling molecules assigned to N-acyl-homoserine-lactones (AHL) serve as autoinducers for the genes controlling the quorum sensing regulatory system. In many gram-negative bacteria, AHL are the key factors responsible for density-dependent regulation of exoenzyme and secondary metabolite production; they also participate in interaction between bacteria and higher organisms. The soil and rhisosphere bacteria Pseudomonas and Xanthomonas from different geographical zones of Russia and the former USSR were analyzed for the presence of the AHL producers. Screening was conducted by using a test system based on the mutant strain Chromobacterium violaceum, which was unable to synthesize AHL but produced a pigment violacein in the presence of exogenous AHL. The AHL-like compounds proved to be formed by 9.7% of the studied bacteria. Various Pseudomonas species differed in the capacity to synthesize this compounds. In at least a half of the isolated P. aureofaciens and P. aeruginosa, an intense AHL production was observed, whereas the AHL-producers were far less frequent among the P. fluorescens, P. chlororaphis, P. lemonnieri, P. geniculata, and P. putida. None of the 41 Xanthomonas maltophilia strains examined synthesized AHL.


Spt6 directly interacts with Cdc73 and is required for Paf1 complex occupancy at active genes in Saccharomyces cerevisiae.
The Paf1 complex (Paf1C) is a conserved transcription elongation factor that regulates transcription elongation efficiency, facilitates co-transcriptional histone modifications, and impacts molecular processes linked to RNA synthesis, such as polyA site selection. Coupling of the activities of Paf1C to transcription elongation requires its association with RNA polymerase II (Pol II). Mutational studies in yeast identified Paf1C subunits Cdc73 and Rtf1 as important mediators of Paf1C association with Pol II on active genes. While the interaction between Rtf1 and the general elongation factor Spt5 is relatively well-understood, the interactions involving Cdc73 have not been fully elucidated. Using a site-specific protein cross-linking strategy in yeast cells, we identified direct interactions between Cdc73 and two components of the Pol II elongation complex, the elongation factor Spt6 and the largest subunit of Pol II. Both of these interactions require the tandem SH2 domain of Spt6. We also show that Cdc73 and Spt6 can interact in vitro and that rapid depletion of Spt6 dissociates Paf1 from chromatin, altering patterns of Paf1C-dependent histone modifications genome-wide. These results reveal interactions between Cdc73 and the Pol II elongation complex and identify Spt6 as a key factor contributing to the occupancy of Paf1C at active genes in Saccharomyces cerevisiae.


Scleroembolization for treatment of hypertension caused by intrarenal arterial fibrodysplasia.
This paper reports a 13-year-old girl with severe hypertension due to fibrodysplasia of intrarenal arterial branches in the upper pole of the left kidney. Scleroembolization of the abnormal vascular region was carried out by injecting, via a transcutaneous catheter, an 80% solution of sodium iothalamate in ethanol, followed by a suspension of Gore-Tex particles in the same solution, which resulted in complete and persistent normalization of blood pressure.


[Spinal surgery on patients with myelomeningocele. Results 1971-1990].
Between 1971 and 1990 33 kyphectomies were performed at the Orthopaedic Hospital, University of Heidelberg. The average age at time of surgery was 5 years/5 months; the follow-up period was 5 years. The best results were obtained in the group with congenital rigid kyphosis. A marked postoperative deterioration was considered in patients with a flexible paralytic kyphosis, probably due to a too short area of fusion. In 19 patients the correction of the kyphotic deformity was the prerequisite for being provided with orthotic devices. The most serious complication was the intraoperative death of 3 patients. It can be presumed, that after transection of the spinal cord a non-functioning CSF-shunt lead to an acute elevation of the intracranial pressure. Therefore an adequately functioning shunt must be secured preoperatively.


Comparative study of video-assisted thoracoscopic surgery versus open thymectomy for thymoma and myasthenia gravis.
Thymectomy is the preferred standard treatment in younger non-thymoma patients with myasthenia gravis as well as in patients with early stage thymoma. Total thymectomy by median sternotomy has been the surgical approach since resection of the thymus with video-assisted thoracoscopic surgery (VATS). To compare the clinical outcomes of VATS thymectomy with conventional open thymectomy for neoplastic and non-neoplastic thymic diseases. Forty patients underwent thymectomy between October 2012 and January 2016. Fifteen patients were male and 25 patients were female. The mean age was 40.3 ±17.7 years. Seventeen (55%) patients underwent VATS thymectomy and 23 (45%) patients underwent an open procedure. We retrospectively reviewed the data of the patients and compared these two techniques. The mean tumor size was 5.17 ±3.2 cm in the thymoma group (VATS 2.5 ±2.4 cm vs. open access 4.7 ±3.7 cm). None of the patients experienced a myasthenic crisis. Conversion to thoracotomy was required in 1 patient in the VATS group due to bleeding from the right internal mammary artery; therefore, the conversion rate was 2.5% among all the patients. No mortality occurred in either group. No significant difference was found in the perioperative blood loss, operative time or pain visual analogue scale scores. On the other hand, regarding postoperative drainage, duration of chest tube drainage and length of hospital stay, VATS thymectomy yielded better results and the differences were significant. Video-assisted thoracoscopic surgery thymectomy can be performed for both neoplastic and non-neoplastic thymic diseases with minimal morbidity and mortality.


Gene Expression Profiling associated with Hepatoxicity in Pregnant Rats treated with Ubi Gadong (Dioscorea hispida) Extract.
Dioscorea hispida (D.hispida) is the most well-known starchy tuber in Malaysia and called 'ubi gadong'. Despite concerns over toxicity effects, the tuber is known to possess therapeutic values due to the presence of bioactive compounds such as saponins. This study was performed to identify the changes in gene expression profiles associated with hepatoxicity in pregnant rat treated with D.hispida using RT² Profiler PCR Array. The identification of steroidal saponins from D.hispida was carried out by UHPLC/MS method. Treatment of D.hispida caused mortality when dosage above 2000 mg/kg b.w. was given to pregnant rats. The PCR array showed that several genes were significantly up and down-regulated upon treatment with D.hispida. Treatment of D.hispida at 2000 mg/kg b.w leads to significant upregulation of several genes such as Btg2, Gsr, L2hgdn, S100a8, Slc17a3, Bhmt, Cd68, Cyp1a2 whereas several genes were downregulated such as Abcb1a, Aldoa, Cdc14b, Icam1, Krt18, Hpn and Maob. The consumption of D.hispida extract when taken at lower dosage of 2000 mg/kg may not be harmful to rats. D.hispida extract given at the highest dosage to pregnant rats caused alterations of several genes categorized in different hepatotoxic group functions such as necrosis, cholestasis and phospholipodisis.


Phosphorylated 4E binding protein 1: a hallmark of cell signaling that correlates with survival in ovarian cancer.
Growth factor receptors and cell signaling factors play a crucial role in human carcinomas and have been studied in ovarian tumors with varying results. Cell signaling involves multiple pathways and a myriad of factors that can be mutated or amplified. Cell signaling is driven through the mammalian target of rapamycin (mTOR) and extracellular regulated kinase (ERK) pathways and by some downstream molecules, such as 4E binding protein 1 (4EBP1), eukaryotic initiation factor 4E, and p70 ribosomal protein S6 kinase (p70S6K). The objectives of this study were to analyze the real role that these pathways play in ovarian cancer, to correlate them with clinicopathologic characteristics, and to identify the factors that transmit individual proliferation signals and are associated with pathologic grade and prognosis, regardless specific oncogenic alterations upstream. One hundred twenty-nine ovarian epithelial tumors were studied, including 20 serous cystadenomas, 7 mucinous cystadenomas, 11 serous borderline tumors, 16 mucinous borderline tumors, 29 serous carcinomas, 16 endometrioid carcinomas, 15 clear cell carcinomas, and 15 mucinous carcinomas. Tissue microarrays were constructed, and immunohistochemistry for the receptors epidermal growth factor receptor (EGFR) and c-erb-B2 was performed and with phosphorylated antibodies for protein kinase B (AKT), 4EBP1, p70S6K, S6, and ERK. Among 129 ovarian neoplasms, 17.8% were positive for c-erb-B2, 9.3% were positive for EGFR, 47.3% were positive for phosphorylated AKT (p-AKT), 58.9% were positive for p-ERK, 41.1% were positive for p-4EBP1, 26.4% were positive for p70S6K, and 15.5% were positive for p-S6. Although EGFR, p-AKT, and p-ERK expression did not differ between benign, borderline, or malignant tumors, c-erb-B2, p-4EBP1, p-p70S6K, and p-S6 were expressed significantly more often in malignant tumors. Only p-4EBP1 expression demonstrated prognostic significance (P = .005), and only surgical stage and p-4EBP1 expression had statistical significance in the multivariate analysis. In patients with ovarian carcinoma, significant expression of p-4EBP1 was associated with high-grade tumors and a poor prognosis, regardless other oncogenic alterations upstream. This finding supports the study of this factor as a hallmark or pivotal factor in cell signaling in ovarian carcinoma that may crucial in the transmission of the proliferation cell signal and may reflect the real oncogenic role of this pathway in ovarian tumors.


In vitro activity of a new 8-methoxyquinolone, BAY 12-8039, against Chlamydia pneumoniae.
The in vitro susceptibilities of 10 strains of Chlamydia pneumoniae to a new 8-methoxyquinolone, BAY 12-8039, and to ofloxacin, doxycycline, and erythromycin were determined. The activity of BAY 12-8039 was similar to that of ofloxacin, with a MIC at which 90% of the isolates had no inclusions and a minimal chlamydicidal concentration at which 90% of the isolates had no inclusions after passage of 1.0 microg/ml, but this activity was less than those of doxycycline and erythromycin.


In vivo murine hepatic microRNA and mRNA expression signatures predicting the (non-)genotoxic carcinogenic potential of chemicals.
There is a high need to improve the assessment of, especially non-genotoxic, carcinogenic features of chemicals. We therefore explored a toxicogenomics-based approach using genome-wide microRNA and mRNA expression profiles upon short-term exposure in mice. For this, wild-type mice were exposed for seven days to three different classes of chemicals, i.e., four genotoxic carcinogens (GTXC), seven non-genotoxic carcinogens (NGTXC), and five toxic non-carcinogens. Hepatic expression patterns of mRNA and microRNA transcripts were determined after exposure and used to assess the discriminative power of the in vivo transcriptome for GTXC and NGTXC. A final classifier set, discriminative for GTXC and NGTXC, was generated from the transcriptomic data using a tiered approach. This appeared to be a valid approach, since the predictive power of the final classifier set in three different classifier algorithms was very high for the original training set of chemicals. Subsequent validation in an additional set of chemicals revealed that the predictive power for GTXC remained high, in contrast to NGTXC, which appeared to be more troublesome. Our study demonstrated that the in vivo microRNA-ome has less discriminative power to correctly identify (non-)genotoxic carcinogen classes. The results generally indicate that single mRNA transcripts do have the potential to be applied in risk assessment, but that additional (genomic) strategies are necessary to correctly predict the non-genotoxic carcinogenic potential of a chemical.


Impact of inflammatory bowel disease on educational achievements and work prospects.
Young people with inflammatory bowel disease can hope to achieve educational qualifications comparable with those of their peers and to find a supportive educational environment to encourage them. In contrast, at work they can expect discrimination and lack of support, although such treatment may not be overt.


Particle size effect on diffusion in tubes with dead ends: Nonmonotonic size dependence of effective diffusion constant.
Diffusion of a spherical particle of radius r in a tube with identical periodic dead ends is analyzed. It is shown that the effective diffusion constant follows the Stokes-Einstein relation, D(eff)(r) proportional to 1r, only when r is larger or much smaller than the radius of the dead end entrance. In between, D(eff)(r) not only deviates from the 1r behavior but may also even become a nonmonotonic function, which increases with the particle radius for a certain range of r.