[Diclofenac inhibits proliferation and matrix formation of osteoblast cells].
Cell culture studies have shown that NSAID may influence osteogenic activities of osteoblast cultures. However, these studies did not consider long-term effects on differentiating cells. The influence of Voltaren with the non-steroidal agent diclofenac on proliferation and gene expression of the osteoblast-like cell line SaOS-2 was investigated 2, 9, and 16 days after incubation. Two days after 24 h of incubation, 50 microg/ml diclofenac reduced the proliferation and collagen type I expression while 9 and 16 days later no effect was found on either of the parameters. In contrast, 50 microg/ml NSAID has no effect on alkaline phosphatase expression 2 days after incubation while 9 and 16 days later expression had been reduced. Lower concentrations (1.56 and 0.19 microg/ml) had no effects on the studied parameters. BrdU and MTT test showed that 50 microg/ml diclofenac reduced proliferative and metabolic activity. Lower concentrations (< or =25 microg/ml) had a lower or no influence. The findings indicate that the NSAID impairment depends on cellular differentiation stage and is not confined to the time during or immediately after NSAID incubation. According to these results in vitro testing of drugs should be performed over a longer time period to detect possible long-term impacts.


Characterization of changes in global gene expression in the brain of neuron-specific enolase/human Tau23 transgenic mice in response to overexpression of Tau protein.
Tau is a neuronal phosphoprotein responsible for the formation of the neurofibrillary tangles in Alzheimer's disease. To characterize the changes in global gene expression in the brain of transgenic mice that overexpress human Tau23 protein in response to the increase of Tau23 phosphorylation, total RNA extracted from the hippocampus of 12-month-old transgenic and wild-type mice was converted to cDNA, labeled with biotin and hybridized to oligonucleotide microarrays. The microarray results were confirmed by real-time RT-PCR and Western blotting method. It was determined that 43 genes were up-regulated and 8 genes were down-regulated by Tau23 in transgenic mice compared to controls, based on the arbitrary difference in the 2-fold change. Among the up-regulated transcripts, those encoding for transporter and oxidoreductase were dramatically over-represented, followed by those related to regulatory molecule, cytoskeletal protein, signaling molecule, and extracellular matrix protein. Genes encoding for transcription factor, regulatory molecule, miscellaneous function, and chaperone were significantly reduced in the down-regulated group. The major genes in the up-regulated categories included Ecrg4, Folr1, Defb11, Aqp1 and Soctdc1. The major genes in the down-regulated categories were Ncor1, Gpm6a, and Hspd1. These results indicate that the microarray analysis identifies several gene functional groups and individual genes that respond to a sustained increase in Tau23 phosphorylation levels in the brain of transgenic mice. In addition, the results suggest the microarray test is a useful tool for increased understanding of the role of Tau23 protein in regulating neurodegenerative disorders.


Resistance to thyroid hormone: report of 2 kindreds with 35 patients.
To report two kindreds with resistance to thyroid hormone (RTH), particularly the clinical and laboratory evolution after thyroidectomy and with antithyroid drug treatment. Clinical data and thyroid function were determined in 82 members from three different generations of both families. Unaffected relatives were used as a control group. Response of thyroid-stimulating hormone (TSH) to the hypothalamic thyrotropin-releasing hormone (TRH) was evaluated in five patients and compared with five nonaffected relatives. Thirty-five (22 male and 13 female) patients had high serum levels of thyroxine and triiodothyronine in conjunction with nonsuppressed TSH. Goiter was present in 66% of affected family members; prevalence was 10% in childhood and 88% in adulthood. The prevalence of goiter was 18% in nonaffected relatives. No patient showed evidence of thyroid hypofunction or hyperfunction, and the TSH response to TRH was similar to that of nonaffected relatives. The incidence of RTH in offspring was 60%, consistent with autosomal dominant transmission. Four patients had undergone thyroidectomy, and two required a second operation because of recurrence of goiter. Patients who had undergone thyroidectomy had normal or near-normal levels of thyroid hormone and very high values of TSH despite thyroid hormone therapy. Five patients were treated with antithyroid drugs for 2 to 10 years, but their thyroid function remained similar to that of nontreated patients. RTH is a relatively rare and benign condition that can be misdiagnosed as hyperthyroidism. The disease is responsible for a high prevalence of goiter in affected families. Thyroidectomy and treatment with antithyroid drugs are not indicated and may have lifelong implications.


The long-term consequences of living-related or unrelated kidney donation.
Since the frequency of living-related and unrelated kidney donation has increased in the past decade, the risk of uninephrectomy should not be neglected. Major complications after kidney donation are rare. No serious problems like infection or bleeding are common with an overall perioperative complication rate of 14%. Risk of long-term mortality is lower compared to the expected mortality. Little decrease of glomerular filtration rate immediately after transplantation occurs with no further decline. Risk of end-stage renal failure in living donors is approximately 0.2-0.5%. Only a few patients develop proteinuria. After age adjustment, no increase of blood pressure is noted. The benefit of living kidney transplantation is superceding the potential risks. After careful work-up of the donor short- and long-term risks are minimal.


A toolkit for studying cellular reorganization during early embryogenesis in Arabidopsis thaliana.
Considerable progress has been made in understanding the influence of physical and genetic factors on the patterns of cell division in various model systems. However, how each of these factors directs changes in subcellular structures has remained unclear. Generic machineries for the execution of cell expansion and division have been characterized, but how these are influenced by genetic regulators and physical cell properties remains an open question. To a large degree, the complexity of growing post-embryonic tissues and a lack of precise predictability have prevented the extraction of rigid correlations between subcellular structures and future orientation of cell division. The Arabidopsis embryo offers an exquisitely predictable and simple model for studying such correlations, but so far the tools and methodology for studying subcellular structures in the early embryo have been lacking. Here, we describe a set of markers to visualize a range of subcellular structures in the early Arabidopsis embryo. We have designed a series of fluorescent cellular reporters optimized for embryos, and demonstrate the effectiveness of using these 'ACE' reporters with simple three-dimensional imaging procedures that preserve delicate cellular structures. We describe the ontogeny of subcellular structures in the early embryo and find that central/peripheral cell polarity is established much earlier than suspected. In addition, we show that the actin and microtubule cytoskeleton has distinct topologies in the embryo. These tools and methods will allow detailed analysis of the events of cellular reorganization that underlie morphogenesis in the Arabidopsis embryo.


NICE, in Confidence: An Assessment of Redaction to Obscure Confidential Information in Single Technology Appraisals by the National Institute for Health and Care Excellence.
Health technology assessment (HTA) aims to provide a transparent framework within which normative judgements can be applied for decision making. Such transparency enables the public to understand the rationale for decision making, but conflicts with companies being able to offer commercially sensitive discounts. We investigated how to balance these conflicting ideals. National Institute for Health and Care Excellence (NICE) submissions were reviewed for products with an approved, simple Patient Access Scheme (PAS) discount. The approach to censoring was noted (e.g. total cost and clinical outcomes redacted). Submissions were then assessed for transparency (i.e. whether the decision appeared justifiable given the available information) and confidentiality (i.e. whether the PAS discount could be 'back calculated'). One hundred and eighteen products have an approved commercial arrangement, of which 110 have simple PAS discounts considered within the NICE Single Technology Appraisal programme. A definitive incremental cost-effectiveness ratio was presented within final NICE guidance in only 20 appraisals. Documentation for seven appraisals allowed for the straightforward 'back calculation' of PAS discounts. Furthermore, a large amount of information was censored as academic-in-confidence and remains so many years later. Appropriate redaction ensures discounts remain confidential, yet maintains the transparency of the HTA decisions made. Complete redaction does not allow for transparent, justifiable decision making. However, redacting 'enough' information to preclude direct estimation of discounts provides a means of maintaining both transparency and confidentiality. This study demonstrates a lack of consensus regarding presentation of results, and the importance of appropriate redaction.


Neurogenic arthropathy of the knee due to chronic alcoholism: two case reports.
The authors report two cases of neurogenic arthropathy of the knee in patients affected by chronic alcoholism. The aim of the authors is to discuss the etiopathogenic theory (neurotraumatic or/and neurovascular) as well as the mechanism by which alcohol damages joints.


Evaluation of Short-Term and Long-Term Migration Testing from Can Coatings into Food Simulants: Epoxy and Acrylic-Phenolic Coatings.
Traditionally, migration testing during 10 days at 40 °C has been considered sufficient and appropriate for simulating the potential migration of substances from food-contact materials into foods. However, some packages, such as food cans, may be stored holding food for extended time periods (years). This study attempts to verify whether common testing conditions accurately estimate long-term migration. Two types of can coatings, epoxy and acrylic-phenolic, were subjected to short-term and long-term migration testing (1 day-1.5 years) using food simulants (water, 3% acetic acid, 50% ethanol, and isooctane) at 40 °C. Using HPLC-DAD/CAD, HPLC-MS, UHPLC-HRMS (where HRMS is accurate mass, mass spectrometry), and DART-HRMS, we identified potential migrants before starting the experiment: BPA, BADGE, BADGE derivatives, benzoguanamine, and other relevant marker compounds. During the experiment using a water-based food simulant, migrants remained stable. Most of the cans in contact with 3% acetic acid did not survive the experimental conditions. Tracked migrants were not detected in isooctane. In the presence of 50% ethanol, the traditional migration test during 10 days at 40 °C did not predict migration during long-term storage. These results suggest that migration protocols should be modified to account for long-term storage.


Suppression of third ventricular NPY-elicited feeding following medullary reticular formation infusions of muscimol.
The appetitive component of feeding is controlled by forebrain substrates, but the consummatory behaviors of licking, mastication, and swallowing are organized in the brainstem. The target of forebrain appetitive signals is unclear but likely includes regions of the medullary reticular formation (RF). This study was undertaken to determine the necessity of different RF regions for mastication induced by a descending appetitive signal. We measured solid food intake in response to third ventricular (3V) infusions of the orexigenic peptide neuropeptide Y 3-36 in awake, freely moving rats and determined whether focal RF infusions of the GABAA agonist muscimol suppressed eating. RF infusions were centered in either the lateral tegmental field, comprising the intermediate (IRt) and parvocellular (PCRt) RF, or in the nucleus gigantocellularis (Gi). Infusions of NPY 3-36 (5 microg/5 microl) into 3V significantly increased feeding of solid food over a 90-min period compared with the noninfused condition (4.3 g +/- 0.56 vs. 0.57 g +/- 0.57, p < .001). NPY 3-36-induced food intake was suppressed (1.7 g +/- 0.48) by simultaneous infusions of muscimol (0.6 mM/100 nl) into the IRt/PCRt (p < .01). Coincident with the decrease in feeding was a decrease in the amplitude of anterior digastric muscle contractions in response to intraoral sucrose infusions. In contrast, infusions of muscimol into Gi had no discernible effect on food intake or EMG amplitude. These data suggest that the IRt/PCRt is essential for forebrain-initiated mastication, but that the Gi is not a necessary link in this pathway.


Characterization of intra- and extracellular transforming growth factors from normal and avian sarcoma virus-transformed rat cells.
Intra- and extracellular transforming growth factors (TGFs) have been characterized in an avian sarcoma virus-transformed rat cell line, 77N1, and the nontransformed parental cell line, NRK. Serum-free conditioned medium from 77N1 and cell extracts from NRK and 77N1 were subjected to ion exchange column chromatography. Intracellular TGFs in cell extracts of NRK and 77N1 cells showed a major peak of DNA synthesis-stimulating and colony-forming activities which eluted in the 0.10 to 0.15 M salt concentration region. Extracellular TGF in conditioned medium of 77N1 cells showed a major peak of activity which eluted at 0.05 to 0.06 M salt concentration. Furthermore partially purified extracellular TGF had a molecular weight of about 40,000 daltons, whereas that for intracellular TGF was about 12,000 daltons. These intra- and extracellular TGFs, as well as TGF gamma 2 which was purified from 77N1 cell extract, were heat- and acid-labile polypeptides sensitive to treatment with dithiothreitol. Radioimmunoprecipitation analyses with antiserum against TGF gamma 2 demonstrated that intra- and extracellular TGFs in 77N1 and NRK cells were immunologically identical or very closely related to each other and suggested the possibility that extracellular TGF from 77N1 cells was released into serum-free conditioned medium after formation of complex with other cellular components.


Mechanism of calcium-induced reptilase clot retraction.
Calcium ions induce retraction of reptilase clots. This could also be induced by thrombin. Heparin inhibited the reptilase clot retraction induced either by thrombin or calcium, but did not influence the clot retraction induced by ADP. This indicated that the clot retraction induced by Ca2+ was mediated by an activation of the coagulation system with the formation of thrombin.


Definitive experimental evidence for two-band superconductivity in MgB2.
The superconducting-gap of MgB2 has been studied by high-resolution angle-resolved photoemission spectroscopy. The results show that superconducting gaps with values of 5.5 and 2.2 meV open on the sigma band and the pi band, respectively, but both the gaps close at the bulk transition temperature, providing a definitive experimental evidence for the two-band superconductivity with strong interband pairing interaction in MgB2. The experiments validate the role of k-dependent electron-phonon coupling as the origin of multiple-gap superconductivity as well as the high transition temperature of MgB2.


Nonradiative relaxation dynamics in the [Au25-nAgn(SH)18]-1 (n = 1, 12, 25) thiolate-protected nanoclusters.
Evaluation of the electron-nuclear dynamics and relaxation mechanisms of gold and silver nanoclusters and their alloys is important for future photocatalytic, light harvesting, and photoluminescence applications of these systems. In this work, the effect of silver doping on the nonradiative excited state relaxation dynamics of the atomically precise thiolate-protected gold nanocluster [Au25-nAgn(SH)18]-1 (n = 1, 12, 25) is studied theoretically. Time-dependent density functional theory is used to study excited states lying in the energy range 0.0-2.5 eV. The fewest switches surface hopping method with decoherence correction was used to investigate the dynamics of these states. The HOMO-LUMO gap increases significantly upon doping of 12 silver atoms but decreases for the pure silver nanocluster. Doped clusters show a different response for ground state population increase lifetimes and excited state population decay times in comparison to the undoped system. The ground state recovery times of the S1-S6 states in the first excited peak were found to be longer for [Au13Ag12(SH)18]-1 than the corresponding recovery times of other studied nanoclusters, suggesting that this partially doped nanocluster is best for preserving electrons in an excited state. The decay time constants were in the range of 2.0-20 ps for the six lowest energy excited states. Among the higher excited states, S7 has the slowest decay time constant although it occurs more quickly than S1 decay. Overall, these clusters follow common decay time constant trends and relaxation mechanisms due to the similarities in their electronic structures.


Differentiating event-related potential components sensitive to emotion in middle childhood: evidence from temporal-spatial PCA.
Event-related potentials (ERPs) may be particularly useful for examining emotional processing across development. Though a number of ERP components are sensitive to emotional content in adults, previous studies have yet to systematically examine the components sensitive to emotion in children. The current study used temporal-spatial principal components analysis (PCA) to identify ERP components in response to complex emotional images in 9-year-old children. Three components were modulated by emotional content and were similar to those previously observed in adults, including: the early posterior negativity, the P300, and a sustained relative positivity similar to the late positive potential (LPP). Compared to those previously observed in adults, the components sensitive to emotion in children were maximal over more occipital regions and the LPP component appeared to be less protracted in time, perhaps indicative of less elaborative processing of emotional stimuli.


Intra-arterial versus intravenous administration of gastric secretory inhibitors in conscious dogs. Effects of somatostatin, serotonin and isoprenaline on acid and pepsin secretion.
The purpose of the present study was to evaluate the effects of both intra-arterial and intravenous infusions of somatostatin, serotonin (5-hydroxytryptamine) and isoprenaline beta 1- + beta 2-adrenoceptor agonist) on gastric acid and pepsin secretion in conscious dogs with a gastric fistula. The drugs mentioned have been examined earlier for effects on gastric secretion in vivo during intravenous infusions and these effects could be hampered by the possible indirect mechanism of action as well as the different kinetics of metabolism. A catheter (vascular access port) allowed repeatedly gastric intra-arterial infusions. Somatostatin and serotonin possessed inhibitory effects on gastric acid and pepsin secretion and were without significant differences between the analyzed ways of administration. Intra-arterial infusion, isoprenaline possessed less potent inhibitory effects on gastric secretion: the effects were significant for pepsin secretion but were nonsignificant for acid secretion. The results suggest the mechanism of action of isoprenaline, somatostatin and sertonin to diverge, and for somatostatin and serotonin it was independent of the route of administration.


Xanthones from a lignicolous freshwater fungus (BCC 28210).
Four xanthones (1‒4) and a known compound, mansonone D (5), were isolated from the lignicolous freshwater fungus BCC 28210 (family, Chaetosphaeriaceae). The structures of these compounds were elucidated by extensive spectroscopic analysis. Among the isolated metabolites, compound 2 and the known mansonone D (5) displayed antimalarial activity against Plasmodium falciparum K1 with IC50 values of 7.75 and 0.55 μg/mL, respectively. Compound 4 displayed antibacterial activity against Bacillus cereus with an MIC value of 6.25 μg/mL.


Increase Functional β-Cell Mass in Subcutaneous Alginate Capsules With Porcine Prenatal Islet Cells but Loss With Human Adult Islet Cells.
Alginate (Alg)-encapsulated porcine islet cell grafts are developed to overcome limitations of human islet transplantation. They can generate functional implants in animals when prepared from fetal, perinatal, and adult pancreases. Implants have not yet been examined for efficacy to establish sustained, metabolically adequate functional β-cell mass (FBM) in comparison with human islet cells. This study in immune-compromised mice demonstrates that subcutaneous implants of Alg-encapsulated porcine prenatal islet cells with 4 × 105 β-cells form, over 10 weeks, a FBM that results in glucose-induced plasma C-peptide >2 ng/mL and metabolic control over the following 10 weeks, with higher efficiency than nonencapsulated, while failing in peritoneum. This intracapsular FBM formation involves β-cell replication, increasing number fourfold, and maturation toward human adult β-cells. Subcutaneous Alg-encapsulated human islet cells with similar β-cell number establish implants with plasma C-peptide >2 ng/mL for the first 10 weeks, with nonencapsulated cells failing; their β-cells do not replicate but progressively die (>70%), explaining C-peptide decline and insufficient metabolic control. An Alg matrix thus helps establish β-cell functions in subcutis. It allows formation of sustained metabolically adequate FBM by immature porcine β-cells with proliferative activity but not by human adult islet cells. These findings define conditions for evaluating its immune-protecting properties.


On naming H2 haplotypes: functional significance of MHC class Ib alleles.
George D. Snell began defining and naming the H2 haplotypes many years ago by histogenetic typing. Since then, a few haplotypes have been given an additional letter, such as bc for strain 129, to show that they are minor variants from the prototype (b). But by and large, differences in nonclassical class I antigens have been known (only?) to those in the field without being acknowledged by a separate haplotype symbol. Thus, strains BALB/c and NZB/BlNJ are both considered H2d and strains C3H/HeJ and B10.BR are both called H2k, although each pair differs in the TL and Qa1 antigens. In parallel with the interest in nonclassical class I antigens, the need for an appropriate haplotype nomenclature is growing. The haplotypes that require splitting are b, d, k, q, and s; the symbol bc should be retained and used, and, for the other haplotypes, the suffix 2 denotes a Qa1a haplotype with highly TL-positive thymocytes.


The aromatic amino acid hydroxylase genes AAH1 and AAH2 in Toxoplasma gondii contribute to transmission in the cat.
The Toxoplasma gondii genome contains two aromatic amino acid hydroxylase genes, AAH1 and AAH2 encode proteins that produce L-DOPA, which can serve as a precursor of catecholamine neurotransmitters. It has been suggested that this pathway elevates host dopamine levels thus making infected rodents less fearful of their definitive Felidae hosts. However, L-DOPA is also a structural precursor of melanins, secondary quinones, and dityrosine protein crosslinks, which are produced by many species. For example, dityrosine crosslinks are abundant in the oocyst walls of Eimeria and T. gondii, although their structural role has not been demonstrated, Here, we investigated the biology of AAH knockout parasites in the sexual reproductive cycle within cats. We found that ablation of the AAH genes resulted in reduced infection in the cat, lower oocyst yields, and decreased rates of sporulation. Our findings suggest that the AAH genes play a predominant role during infection in the gut of the definitive feline host.


Quantitative T2 Mapping Shows Increased Degeneration in Adjacent Intervertebral Discs Following Kyphoplasty.
A minimally invasive treatment of osteoporotic and nonosteoporotic thoracic and lumbar spine fractures is cement augmentation (kyphoplasty). Little is known about the impact on adjacent intervertebral discs. A quantitative magnetic resonance imaging (MRI) approach in addition to morphological MRI is desirable to evaluate changes in the intervertebral disc. Our study aims to evaluate the feasibility of T2 mapping for the detection of subtle changes in the intervertebral discs in spines after kyphoplasty. Intervertebral discs were assessed by quantitative MRI (3.0 T) using T2 relaxation time mapping. Region of interest (ROI; 6 per disc) analyses were performed. The ROIs at the anterior and posterior edges were interpreted as annulus fibrosus (AF). The 2 very inner zones were regarded as nucleus pulposus (NP) and the regions in between as intermediate transition zone. We compared T2 relaxation time values of intervertebral discs adjacent to the vertebrae after kyphoplasty with those nonadjacent to vertebrae after kyphoplasty, especially in the NP. The analysis of the ROIs showed that the intervertebral discs of the adjacent vertebral segments are associated with reduced T2 values compared to those that are nonadjacent to the affected vertebrae. This study is to our knowledge the first investigation of intervertebral discs after kyphoplasty by quantitative MRI. Quantitative T2 mapping shows increased degeneration in adjacent intervertebral discs following kyphoplasty. Besides its contribution to a broader knowledge of postoperative changes after kyphoplasty, our findings may help to improve differentiation between healthy and degenerated intervertebral discs using these techniques.


Standardization of the NEO-PI-3 in the Greek general population.
The revised NEO Personality Inventory (NEO-PI-3) includes 240 items corresponding to the Big Five personality traits (Extraversion, Agreeableness, Conscientiousness, Neuroticism, and Openness to Experience) and subordinate dimensions (facets). It is suitable for use with adolescents and adults (12 years or older). The aim of the current study was to validate the Greek translation of the NEO-PI-3 in the general Greek population. The study sample included 734 subjects from the general Greek population of whom 59.4% were females and 40.6% males aged 40.80 ± 11.48. The NEO-PI-3 was translated into Greek and back-translated into English, and the accuracy of the translation was confirmed and established. The statistical analysis included descriptive statistics, confirmatory factorial analysis (CFA), the calculation of Cronbach's alpha, and the calculation of Pearson product-moment correlations. Sociodemographics groups were compared by ANOVA. Most facets had Cronbach's alpha above 0.60. Confirmatory factor analysis showed acceptable loading of the facets on their own hypothesized factors and very good estimations of Cronbach's alphas for the hypothesized factors, so it was partially supportive of the five-factor structure of the NEO-PI-3.The factors extracted with Procrustes rotation analysis can be considered reasonably homologous to the factors of the American normative sample. Correlations between dimensions were as expected and similar to those reported in the literature. The literature suggests that overall, the psychometric properties of NEO-PI-3 scales have been found to generalize across ages, cultures, and methods of measurement. In accord with this, the results of the current study confirm the reliability of the Greek translation and adaptation of the NEO-PI-3. The inventory has comparable psychometric properties in its Greek version in comparison to the original and other national translations, and it is suitable for clinical as well as research use.


A shifting focus on cancer.
This installment of our quarterly series on clinical management issues focuses on trends in oncology services. Even with the threat of overbuilding in certain markets, proposed cuts to Medicare reimbursements and competition from niche facilities, hospitals are placing renewed emphasis--and spending--on cancer.


Dietary effects on coagulation factor VII vary across genotypes of the R/Q353 polymorphism in elderly people.
The objective of this study was to evaluate the association of factor VII with dietary factors while also considering the R/Q353 polymorphism. Nutrition is an important determinant of coagulation factor VII, which is also genetically determined by the R/Q353 polymorphism. High levels of coagulation factor VII clotting activity (FVII:C) are associated with the risk of myocardial infarction; nutrition may have an effect on these levels if people are genetically susceptible to dietary changes. FVII:C was measured in 3005 elderly subjects, and the extreme quintiles of the FVII:C distribution were selected for measurement of the R/Q353 genotype and FVII:Chr (reflects total factor VII). In these 1158 subjects, habitual diet was assessed with a semiquantitative food-frequency questionnaire. The frequency of the Q353 allele was 0.24 in the lowest and 0.09 in the highest quintile. The quintiles were combined for linear regression analyses. FVII:C was inversely associated with fiber [beta = -0.64 %pooled plasma (PP)/g, confidence interval (CI): -1.07,-0.21] and protein intake (beta = -0.16 %PP/g, CI: -0.31,-0. 01) and positively with saturated fat intake (beta = 0.19 %PP/g, CI: -0.10,0.48). FVII:Chr was inversely associated with fiber (beta = -0. 38 %PP/g, CI: -0.71,-0.05). No other associations with diet were observed. The inverse association of FVII:C with fiber was stronger in subjects with the RR genotype (beta = -0.76 %PP/g, CI: -1.23,-0. 29), than in those with the RQ/QQ genotypes (beta = -0.19 %PP/g, CI: -0.97,0.59). The same was found for FVII:Chr. The association of FVII:C with saturated fat was positive in those with the RR allele and inverse in those carrying the Q allele. These findings suggest that the strength of the association between coagulation factor VII and diet varies across the genotypes of the R/Q353 polymorphism.


Age-Friendly Environments in ASEAN Plus Three: Case Studies from Japan, Malaysia, Myanmar, Vietnam, and Thailand.
Promoting age-friendly environment is one of the appropriate approaches to support quality of life toward ageing populations. However, the information regarding age-friendly environments in the Association of Southeast Asian Nations (ASEAN) Plus Three countries is still limited. This study aimed to survey the perceived age-friendly environments among ASEAN Plus Three older populations. This study employed cross-sectional quantitative research using multistage cluster sampling to select a sample of older adults in the capital cities of Japan, Malaysia, Myanmar, Vietnam and Thailand. The final sample was composed of 2171 older adults aged 55 years and over, including 140 Japanese, 510 Thai, 537 Malaysian, 487 Myanmarese, and 497 Vietnamese older adults. Data collection was conducted using a quantitative questionnaire with 20 items of perceived age-friendly environments with the rating scale based on the World Health Organization (WHO) standard. The score from the 20 items were analyzed and examined high-risk groups of "bad perception level" age-friendly environments using ordinal logistic regression. The research indicated the five highest inadequacies of age-friendly environments including: (1) participating in an emergency-response training session or drill which addressed the needs of older residents; (2) enrolling in any form of education or training, either formal or non-formal in any subject; (3) having opportunities for paid employment; (4) involvement in decision making about important political, economic and social issues in the community; and (5) having personal care or assistance needs met in the older adult's home setting by government/private care services. Information regarding the inadequacy of age-friendliness by region was evidenced to guide policy makers in providing the right interventions towards older adults' needs.


Targeted deletion of Atoh8 results in severe hearing loss in mice.
Atoh8, also named Math6, is a bHLH gene reported to have important functions in the developing nervous system, pancreas and kidney. However, the expression pattern and function of Atoh8 in the inner ear are still unclear. To study the function of Atoh8 in the developing mouse inner ear, we performed targeted deletion of Atoh8 by intercrossing Atoh8lacZ/+ mice. We studied the expression pattern of Atoh8 in the inner ear and found interesting results that Atoh8-null (Atoh8lacZ/lacZ ) mice were viable but smaller than their littermates and they were severely hearing impaired, which was confirmed by hearing tests (ABR, DPOAE). We collected 129 viable newborns from 18 litters by crossing Atoh8lacZ/+ mice and found that the distributions of Atoh8lacZ/+ , Atoh8lacZ/lacZ and wild type were very close to their expected Mendelian ratio by χ2 testing. However, no remarkable morphological changes in cochleae in mutant mice were detected under plastic sectioning and electron microscopy. No remarkable differences in the expression of Myosin6, Prestin, TrkC, GAD65, Tuj1, or Calretinin were detected between the mutant mice and the control mice. These findings indicate that Atoh8 plays an important role in the development of normal hearing, while further studies are required to elucidate its exact function in hearing.


Equity and efficiency preferences of health policy makers in China--a stated preference analysis.
Macroeconomic growth in China enables significant progress in health care and public health. It faces difficult choices regarding access, quality and affordability, while dealing with the increasing burden of chronic diseases. Policymakers are pressured to make complex decisions while implementing health strategies. This study shows how this process could be structured and reports the specific equity and efficiency preferences among Chinese policymakers. In total, 78 regional, provincial and national level policymakers with considerable experience participated in a discrete choice experiment, weighting the relative importance of six policy attributes describing equity and efficiency. Results from a conditional logistic model are presented for the six criteria, measuring the associated weights. Observed and unobserved heterogeneities were incorporated and tested in the model. Findings are used to give an example of ranking health interventions in relation to the present disease burden in China. In general, respondents showed strong preference for efficiency criteria i.e. total beneficiaries and cost-effectiveness as the most important attributes in decision making over equity criteria. Hence, priority interventions would be those conditions that are most prevalent in the country and cost least per health gain. Although efficiency criteria override equity ones, major health threats in China would be targeted. Multicriteria decision analysis makes explicit important trade-offs between efficiency and equity, leading to explicit, transparent and rational policy making.


Agreement analysis comparing iPad LCVA and Sloan testing in multiple sclerosis patients.
Visual symptoms are common in multiple sclerosis (MS). Low-contrast visual acuity (LCVA) testing using Sloan charts has demonstrated increased sensitivity for visual deficits compared to high-contrast acuity testing. Computerized testing of visual acuity may facilitate use in the clinic setting. To evaluate the agreement between an iPad-based and Sloan testing of LCVA in a cohort of MS patients. A total of 38 patients with relapsing-remitting MS were enrolled after providing informed written consent at Partners MS Center, Brigham and Women's hospital. Monocular LCVA was measured using retroilluminated Sloan chart and iPad-based LogMAR chart. Number of correct letters and agreement between two measurements were assessed for each eye using Bland-Altman analysis and paired t-test. For both eyes, there was no significant difference in number correct between the two measurements using a paired t-test, and there was high correlation between two measurements (oculus dextrus (OD) r = 0.89, p < 0.001; oculus sinister (OS) r = 0.78, p < 0.001). The limits of agreement were -7.9 to +8.5 letters for the right eye and -10.9 to +11.2 letters for the left eye. An iPad-based LCVA test shows good agreement with Sloan testing in MS patients.


Mitral valvuloplasty: when the art of repair meets the biological science.
The majority of approaches currently described and practiced in mitral repair surgery result in the vertical immobilization of the posterior leaflet, with the anterior leaflet striving to produce an adequate coaptation. Despite the satisfactory hemodynamic outcome and disappearance of mitral regurgitation, this non-physiological situation results in a redistribution of forces within the mitral apparatus with an increased stress on the leaflets. Biological evidences are pointing at the ability of the valvular interstitial cells to actively respond to biomechanical changes, switching their phenotype and producing different patterns of extracellular matrix proteins. This biological event translates to changes in the anatomical and mechanical properties of the leaflets, leading to an increased stiffening and a susceptibility to develop calcification. These concepts find a clinical reflex in reports on the long-term thickening and calcification of the leaflets after mitral repair, and in the leaflets remodeling phenomena described in chronically dilated ventricles. The importance of respecting the physiological movement and dynamics of the leaflets when performing a valvuloplasty is underlined, and a potential pharmacological modulation of the aforementioned biological processes to ameliorate long-term results of the repair is hypothesized.


Eales' Disease: When the Rare Sounds Frequent.
Eales' disease is a peripheral occlusive retinal phlebitis, with an unclear pathogenesis. The classic association with hypersensitivity to Mycobacterium tuberculosis protein infers that immunologic disturbance may be involved. Here, we described three cases of Eales' disease. All patients are Caucasian men aged 27-58 years and presented with vitreous hemorrhage and/or peripheral venous vasculitis. Tuberculin skin sensitive test (Mantoux screening test) and interferon-gamma release assay (IGRA) were positive in all patients. Therapeutic approach included antituberculosis therapy and systemic steroids, associated or not to immunosuppressive therapy, and retinal scatter photocoagulation in all cases. Antivascular endothelial grow factor (VEGF) intravitreal injections were also required in two cases. Since various retinal diseases can resemble this presentation, Eales' disease is considered a diagnosis of exclusion. Early diagnosis and appropriate therapeutic approach are both essential to accomplish disease control and reduce ophthalmologic complications.


The prognostic impact of variant allele frequency (VAF) in TP53 mutant patients with MDS: A systematic review and meta-analysis.
Tumor protein p53 (TP53) is frequently expressed in patients with myelodysplastic syndromes (MDS). Studies have already reported the poor prognostic impact of TP53 gene mutations in MDS patients. However, parts of this subgroup of patients with low-risk MDS still have relatively better survival and longer remission times. Therefore, we performed a meta-analysis to evaluate the prognostic difference intra-gene of variant allele frequency (VAF). The primary endpoint was overall survival (OS), and event-free survival (EFS) was selected as the secondary endpoint. We extracted the hazard ratio (HR) and 95% confidence interval (CI) for OS and EFS from univariate and multivariate Cox proportional hazard models. A total of 4003 MDS patients and 1278 TP53-mutated patients from 13 cohorts of 11 studies up to February 24, 2020, were included in our meta-analysis. Pooled HRs suggested that a high mutant VAF had an adverse impact on OS (HR = 2.11, 95% CI: 1.48-3.01, P < .0001) but no impact on EFS (HR = 15.57, 95% CI: 0.75-324.44, P = .003) in MDS patients. Twenty percent is a proper threshold to set (HR = 2.02, 95% CI: 1.31-3.13, P = .001) and is a rough line between high clone burden and low clone burden, while 40% is an exact cutoff point (HR = 2.11, 95% CI: 1.26-3.55, P < .0001) to guide diagnosis and treatment. Beyond the traditional binary classification of gene mutation, we aimed to find a way to divide mutant molecular markers more specifically by VAF to provide clinical therapeutic values. Our meta-analysis indicates that a high VAF is an independent, adverse prognostic factor for OS in TP53 mutant MDS patients. Patients with mediate/low-frequency parts who could be treated like wide-type patients have relatively better survival and may choose allogeneic hematopoietic stem cell transplantation as conditions permitting. Further prospective studies are needed in the future, and a large subgroup analysis of the same cutoff point subgroups is needed to obtain a more reliable basis for the impact of other mutant gene VAFs on the prognosis of MDS.


Forward scattering detection of a submerged moving target based on adaptive filtering technique.
Forward scattered waves are always overwhelmed by severely intense direct blasts when a submerged target crosses the source-receiver line. A processing scheme called direct blast suppression based on adaptive filtering (DBS-AF) is proposed to suppress such blasts. A verification experiment was conducted in a lake with a vertical hydrophone array and 10 kHz CW impulses. Processing results show that the direct blast is suppressed in a single channel, and an intruding target is identified by the lobes in the detection curve. The detection performance is improved by adopting a time-delay beam-former on the array as a pre-processing technique.


The epidemiology of hyperuricaemia and gout in Taiwan aborigines.
To determine the prevalence of hyperuricaemia, gout and gout-related factors in Central Taiwan Atayal aborigines, 342 subjects over 18 yr old were interviewed and examined. A questionnaire was designed to screen for signs and symptoms of gout and gout-related risk factors. Serum uric acid, triglyceride and creatinine were measured in all subjects. The prevalence of hyperuricaemia was 41.4% and that of gout 11.7% in aborigines. The uric acid level was 7.9+/-1.7 mg/dl in males and 5.7+/-1.5 in females, and differed significantly under age 70 yr (P < 0.001). Significantly increased triglyceride, creatinine and alcoholism was found in gouty patients compared with non-gouty patients. In 40 cases with gout, 54% had tophi and 35% of their first-degree relatives had gout. The high prevalence of hyperuricaemia and gout in Taiwan Atayal aborigines, a significant family predisposition, increased creatinine level and alcoholism suggest multiple factors affecting the hyperuricaemia.


Liquid Sulfur Impregnation of Microporous Carbon Accelerated by Nanoscale Interfacial Effects.
Impregnation of porous carbon matrices with liquid sulfur has been exploited to fabricate composite cathodes for lithium-sulfur batteries, aimed at confining soluble sulfur species near conducting carbon to prevent both loss of active material into the electrolyte and parasitic reactions at the lithium metal anode. Here, through extensive computer simulations, we uncover the strongly favorable interfacial free energy between liquid sulfur and graphitic surfaces that underlies this phenomenon. Previously unexplored curvature-dependent enhancements are shown to favor the filling of smaller pores first and effect a quasi-liquid sulfur phase in microporous domains (diameters <2 nm) that persists ∼30° below the expected freezing point. Evidence of interfacial sulfur on carbon is shown to be a 0.3 eV red shift in the simulated and measured interfacial X-ray absorption spectra. Our results elucidate the critical morphology and thermodynamic properties necessary for future cathode design and highlight the importance of molecular-scale details in defining emergent properties of functional nanoscale interfaces.


Calf circumferences in fetuses and neonates with and without talipes equinovares. A prospective cohort study.
Children and adults with talipes equinovarus (TEV) have smaller calves and shorter feet compared to non-affected controls. Do these changes have a prenatal onset? A prospective cohort study (January 2020-July 2021) was conducted with serial ultrasonographic measurements at 20 and 28 weeks gestation and measurements directly and 6 weeks after birth. Calf circumference and width, foot length and length of humerus, ulna, radius, femur, tibia and fibula were measured in TEV and were compared to a control population. Calculated sample size necessitated a minimal population of 10 cases with TEV and 50 controls. Twenty cases with TEV and 62 controls were included. Fetal calf circumference (p < 0.001) and width (p < 0.001) were smaller in the TEV group in comparison to the control group, which persisted after birth. Growth in foot length (p < 0.001) and calf width (p 0.003) declined prenatally over time. The bone lengths and upper leg circumference were not smaller or shorter in TEV compared to controls. This prospective cohort study demonstrated the prenatal onset of reduced calf and foot size in fetuses with TEV from 20 weeks and onwards, which persists directly after birth. To investigate whether reduction in circumference initiates TEV or is caused by TEV, further examination is needed.


[Phenotypic modulation of corpus cavernous smooth musle cells and its influencing factors].
Corpus cavernous smooth muscle cells are the main functional component of the corpus cavernosum penis, whose phenotypic modulation is the key initial step in the proliferation and migration of smooth muscle cells. Therefore, an insight into the mechanism of the phenotypic modulation of smooth muscle cells and its influencing factors is important for the prevention and management of penis erectile dysfunction. Smooth muscle cells are generally divided into contracting (differentiated) and composing (undifferentiated, proliferated or dedifferentiated) types. It is found that TGF-beta, transcription factor E2F1, BTEB2 and insulin may affect the phenotypic modulation of smooth muscle cells. This paper presents an overview of the progress in the researches on the phenotypic modulation of corpus cavernous smooth muscle cells and its influencing factors.


[Efficiency of a new standard chemotherapy regimen in the treatment of patients with recurrent pulmonary tuberculosis].
The efficiency of conventional chemotherapy regimens was comparatively studied in 75 patients with recurrent pulmonary tuberculosis. In the patients with recurrent pulmonary tuberculosis, conventional chemotherapy regimen "2b" including isoniazid, rifampicin, pyrazinamide, ethambutol, fluoroquinolone (ofloxacin, ciprofloxacin, and levofloxacin), and canamycin (amikacin) versus conventional chemotherapy regimen "2a" including isoniazid, rifampicin, pyrazinamide, ethambutol, and streptomycin could cease bacterial isolation after 3-month therapy, as evidenced by sputum microscopy (86.1 and 62.5%, respectively; p < 0.05). Cavity closure was more frequently observed after 6-month chemotherapy using regimen "2b" (76.7 and 48.0%, respectively; p < 0.05). In patients with recurrent pulmonary tuberculosis who isolated Mycobacterium tuberculosis (MBT) resistant to isoniazid and other antituberculous drugs (exclusive of rifampicin), 3-month use of conventional regimen "2b" led to cessation of bacterial isolation (as evidenced by the inoculation test) in 66.7% of cases; but this did not occur with conventional regimen "2a" in any case. Similarly, 3-month use of regimens "2b" and "2a" in patients isolating MBT resistant to rifampicin and other agents (exclusive of isoniazid) resulted in the cessation of bacterial isolation in 80 and 0% of cases, respectively. In multidrug resistance, these parameters were 11.1 and 0%, respectively.


China's population figures: can the contradictions be resolved?
In recent years, the government of the People's Republic of China has been reporting the country's population as "nearly 800 million." A variety of evidence suggests that this approximation is the best currently available in China, and that it may be some time before further, more accurate, demographic data are produced. The paper presents and discusses alternate population estimates and projections by UN, US, and USSR specialists.


High-throughput screening in the C. elegans nervous system.
The nematode Caenorhabditis elegans is widely used as a model organism in the field of neurobiology. The wiring of the C. elegans nervous system has been entirely mapped, and the animal's optical transparency allows for in vivo observation of neuronal activity. The nematode is also small in size, self-fertilizing, and inexpensive to cultivate and maintain, greatly lending to its utility as a whole-animal model for high-throughput screening (HTS) in the nervous system. However, the use of this organism in large-scale screens presents unique technical challenges, including reversible immobilization of the animal, parallel single-animal culture and containment, automation of laser surgery, and high-throughput image acquisition and phenotyping. These obstacles require significant modification of existing techniques and the creation of new C. elegans-based HTS platforms. In this review, we outline these challenges in detail and survey the novel technologies and methods that have been developed to address them.


The vascular biology of S-nitrosothiols, nitrosated derivatives of thiols.
Nitric oxide (NO) is a simple heterodiatomic molecule with a broad range of biologic actions. In the cardiovascular system NO serves as an endothelium-dependent vasodilator, an antithrombotic agent, an antiproliferative molecule, and a regulator of cardiac contractility. Owing to its reactivity under physiologic conditions, accumulating data suggest that NO forms derivatives with several classes of biologic compounds. One group of biochemical functionalities that serves this role is that of thiols, which can form thionitrites or S-nitrosothiols with NO. In this paper we will examine the effects of the biologically known and the chemically produced S-nitrosothiols on the cardiovascular system in order to understand better what role these compounds may play in physiologic and pathologic states.


[Design of cell line stable expressing proteasomal subunit PSMD14 fused to the fluorescent protein EGFP and HTBH tag based on HEK293 cells].
A stable cell line based on HEK293 cells that expresses proteasome subunit PSMD14 fused to the fluorescent protein EGFP and HTBH tag has been selected. This chimera was shown to be incorporated completely into proteolitic active proteasomes. The created cell line can be used for further fluorescent studies of proteasomes localization in the cell.


Gut microbiota from patients with COVID-19 cause alterations in mice that resemble post-COVID symptoms.
Long-term sequelae of coronavirus disease (COVID)-19 are frequent and of major concern. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection affects the host gut microbiota, which is linked to disease severity in patients with COVID-19. Here, we report that the gut microbiota of post-COVID subjects had a remarkable predominance of Enterobacteriaceae strains with an antibiotic-resistant phenotype compared to healthy controls. Additionally, short-chain fatty acid (SCFA) levels were reduced in feces. Fecal transplantation from post-COVID subjects to germ-free mice led to lung inflammation and worse outcomes during pulmonary infection by multidrug-resistant Klebsiella pneumoniae. transplanted mice also exhibited poor cognitive performance. Overall, we show prolonged impacts of SARS-CoV-2 infection on the gut microbiota that persist after subjects have cleared the virus. Together, these data demonstrate that the gut microbiota can directly contribute to post-COVID sequelae, suggesting that it may be a potential therapeutic target.


Production of lymphotoxin by isolated human tonsillar B lymphocytes and B lymphocyte cell lines.
The expression of lymphotoxin (LT) mRNA and cytokine in human tonsillar B cells and B cell lines was examined by Northern blots and cytotoxicity assays, respectively. In tonsillar B cells, phorbol myristate acetate (PMA) or Staphylococcus aureus Cowan l (SAC) alone induced low levels of LT mRNA accumulation. However, SAC and anti-mu were strongly synergistic with PMA in this induction. Peak LT mRNA expression in tonsillar B cells stimulated by PMA plus SAC occurred between 48 and 72 h and was approximately half as much as that in PMA plus anti-CD3-stimulated T cells. Cyclosporine A was not effective in inhibiting LT mRNA accumulation by stimulated tonsillar B cells. A number of B cell lines could also be stimulated by PMA to express LT mRNA. Peak accumulation of LT mRNA in the cell line RPMI 1788 stimulated with PMA peaked about 8 h. A23187 in combination with PMA caused this accumulation to increase slightly and to peak earlier. The cytotoxic effects in the supernatants of stimulated B cells were contributed mostly by LT. The results indicate that tonsillar B cells are important in LT production and that there are important differences in the stimulation requirements for LT production and in LT mRNA expression kinetics between tonsillar B cells and B cell lines.


Globally coupled chaotic maps and demographic stochasticity.
The effect of noise on a system of globally coupled chaotic maps is considered. Demographic stochasticity is studied since it provides both noise and a natural definition for extinction. A two-step model is presented, where the intrapatch chaotic dynamics is followed by a migration step with global dispersal. The addition of noise to the already chaotic system is shown to dramatically change its behavior. The level of migration in which the system attains maximal sustainability is identified. This determines the optimal way to manipulate a fragmented habitat in order to conserve endangered species. The quasideterministic dynamics that appears in the large N limit of the stochastic system is analyzed. In the clustering phase, the infinite degeneracy of deterministic solutions emerges from the single steady state of the stochastic system via a mechanism that involves an almost defective Markov matrix.


Identification of metallic-smelling 1-octen-3-one and 1-nonen-3-one from solutions of ferrous sulfate.
Taste threshold tests of ferrous sulfate (FeSO4) solutions have been confounded by the presence of putative odorants. To detect the presence of odorants released from these solutions solid-phase microextraction (SPME) was used to collect volatiles in the headspace above FeSO4 solutions. Gas chromatography-olfactometry of samples collected over three time periods (1, 5, and 16 h) and at two temperatures (22 and 37 degrees C) revealed the presence of several metallic-smelling odorants in the headspace. Using authentic standards, two of the odorants were conclusively identified as 1-octen-3-one and 1-nonen-3-one. Trace levels of other odorants were also detected, but dilution experiments indicated that 1-nonen-3-one was at least 10 times more potent than anything else released from the solutions. 1-Octen-3-one and 1-nonen-3-one are excellent candidates for the metallic odor responses often observed in threshold testing of solutions of FeSO4.


Identification and characterization of a suppressor element in the 5'-flanking region of the mouse androgen receptor gene.
Androgens play an important role in the development and maintenance of male reproductive organs through the androgen receptor (AR). In order to study the mechanism of regulation of AR at the molecular level, a 1571 bp fragment in the 5'-flanking region of the mouse androgen receptor (mAR) gene was isolated and sequenced. Transfection of 5'-deletion constructs cloned into vectors containing the chloramphenicol acetyl transferase (CAT) gene indicated the presence of a promoter in the sequence -146 to +131. These experiments also suggested the presence of a suppressor element. Further characterization indicated that the suppressor is present between -486 to -351. It is functional in the context of the natural AR promoter and the heterologous thymidine kinase promoter. Transfection of a -546/ + 131 construct in which the putative suppressor element (-421 to -448) had been deleted caused increased basal CAT activity suggesting that the suppressor is limited to this 28 bp element in the 5'-flanking region of the mouse AR gene.


Inward- and outward-facing homology modeling of human concentrative nucleoside transporter 3 (hCNT3) predicts an elevator-type transport mechanism.
The human SLC28 family of concentrative (Na+-dependent) nucleoside transporters has three members, hCNT1, hCNT2 and hCNT3. Previously, we have used heterologous expression in Xenopus laevis oocytes in combination with an engineered cysteine-less hCNT3 protein hCNT3(C-) to undertake systematic substituted cysteine accessibility method (SCAM) analysis of the transporter using the membrane-impermeant thiol reactive reagent p-chloromercuribenzene sulfonate (PCMBS). A continuous sequence of more than 300 individual amino acid residue positions were investigated, including the entire transport domain of the protein, as well as important elements of the corresponding hCNT3 structural domain. We have now constructed 3D structural homology models of hCNT3 based upon inward-facing, intermediates and outward-facing crystal structures of the bacterial CNT Neisseria wadsworthii CNTNW to show that all previously identified PCMBS-sensitive residues in hCNT3 are located above (ie on the extracellular side of) the key diagonal barrier scaffold domain TM9 in the transporter's outward-facing conformation. In addition, both the Na+ and permeant binding sites of the mobile transport domain of hCNT3 are elevated from below the scaffold domain TM9 in the inward-facing conformation to above TM9 in the outward-facing conformation. The hCNT3 homology models generated in the present study validate our previously published PCMBS SCAM data, and confirm an elevator-type mechanism of membrane transport.


Exportin 1 modulates life span by regulating nucleolar dynamics via the autophagy protein LGG-1/GABARAP.
Altered nucleolar and ribosomal dynamics are key hallmarks of aging, but their regulation remains unclear. Building on the knowledge that the conserved nuclear export receptor Exportin 1 (XPO-1/XPO1) modulates proteostasis and life span, we systematically analyzed the impact of nuclear export on protein metabolism. Using transcriptomic and subcellular proteomic analyses in nematodes, we demonstrate that XPO-1 modulates the nucleocytoplasmic distribution of key proteins involved in nucleolar dynamics and ribosome function, including fibrillarin (FIB-1/FBL) and RPL-11 (RPL11). Silencing xpo-1 led to marked reduction in global translation, which was accompanied by decreased nucleolar size and lower fibrillarin levels. A targeted screen of known proteostatic mediators revealed that the autophagy protein LGG-1/GABARAP modulates nucleolar size by regulating RPL-11 levels, linking specific protein degradation to ribosome metabolism. Together, our study reveals that nucleolar size and life span are regulated by LGG-1/GABARAP via ribosome protein surveillance.


Nasal reconstruction.
Congenital malformations, trauma, benign or malignant tumors may call for reconstructive surgical procedures to cover the defect. In order to establish a proper diagnosis a careful examination including X-rays and biopsies is mandatory. A close contact with with the radiotherapist is most desirable in order to combine the therapy if necessary. After the excision of scars or growth, we differentiate between three phases of treatment: 1. The immediate reconstruction either by local flaps or by free grafts. 2. The delayed excision of the tumor after the establishment of the proper diagnosis. This waiting period (two to three weeks) is used to preform the missing nasal parts in the vicinity of the lesion either on the cheek or forehead. Rib cartilage with split skin grafts or composite grafts is used for this purpose. After the excision of the tumor the nasal reconstruction is carried out during the same operation. 3. Tumor excision and coverage of the raw surface with split grafts in order to inspect the area for several months for any recurrence and the delayed reconstruction with adjacent or distant flaps. The operative techniques are described.


Stimulation and Sequestration Mechanism of CO2 Waterless Fracturing for Continental Tight Oil Reservoirs.
CO2 fracturing is a promising technology for oil field development in tight, continental deposits, with potential advantages of enhanced oil recovery (EOR), CO2 sequestration, and water conservation. Compared with CO2-EOR techniques, such as CO2 huff and puff and CO2 flooding, CO2 can interact with reservoir rock and fluid under higher pressure conditions during fracturing, resulting in CO2 stimulation and sequestration effects that differ from those that occur during conventional CO2-EOR. In this paper, the CO2 interactions between CO2 and reservoirs in continental tight oil reservoirs under fracturing conditions are systematically studied through laboratory experiments. The results show that under high pressure, CO2 effectively changes the pore structure through the extraction of hydrocarbons, dissolution of the rock matrix, and migration of minerals. CO2 dissolution of the rock matrix can significantly increase the number and complexity of fractures. Furthermore, CO2 has a higher solubility in formation fluid under high-pressure conditions. Given the higher pressures, CO2 forms a miscible phase with crude oil, diffuses more deeply into the formation, and reacts fully with the reservoir minerals and fluid during CO2 fracturing. Accordingly, CO2 can improve the permeability of the reservoir and flowability of crude oil significantly. Hence, CO2 fracturing can enhance oil recovery and CO2 sequestration more effectively. Core displacement experiments indicate that oil recovery of CO2 soaking process after CO2 fracturing is 36%, which is 12% and 9% higher than those of CO2 huff and puff and CO2 flooding with 5 pore volume, respectively. Field tests show that average oil production after CO2 fracturing is 1.42 times higher than that after CO2 flooding, which further validates the advantage of CO2 fracturing and demonstrates its huge application potential.


[Methods and current therapy of varicosis].
Improvements in the surgical approach to varicose veins have resulted in more elaborate and less traumatic surgery. Removing varicosities through mini-stab incisions just a few millimeters long, and individual shortening or even omitting of the stripping manoeuvre, reduce lesions to surrounding tissues and improve the cosmetic result. The condition sine qua non for tailored treatment is careful examination and classification of the varicose veins based on pathofunctional properties and less on the visible appearance. In addition to clinical examination, Doppler investigation is recommended to assess the origin of the varicosities. Evidence of a reflux from the deep into the superficial venous system is the criterion for stem varices and incompetent perforators. No leaking points of importance can be demonstrated in the other two groups of varicosities, namely in reticular varices and in spider webs. Treatment of these minor forms and of small perforators is sclerotherapy, whereas surgery is recommended for saphenous incompetence and big perforators.


MRI of cervical carcinoma.
MRI is useful for demonstrating enlarged retroperitoneal lymph nodes and for demonstrating the carcinoma mass in patients with carcinoma of the cervix. MRI evaluation of the parametria appears promising, but further studies are necessary to elucidate the optimal imaging parameters and to better define the overall accuracy of MRI compared to the clinical evaluation of the parametria.


[Atherosclerosis imaging to assess plaque progression].
Cardiovascular disease is the first cause of morbidity and mortality for both men and women in developed countries. Tracking the progression of the atherosclerotic plaque appears to be an effective way to predict modification of risk in individual patients. Quantitative coronary angiography was initially proposed as a method of choice to assess coronary disease progression. With this methodology it was possible to demonstrate a strong association of plaque regression with reduction in adverse cardiovascular outcomes. More recently, the focus of research has turned to the development of noninvasive modalities to image the atherosclerotic plaque in its preclinical stages and to evaluate the effectiveness of preventive therapies with sequential imaging. The ease of performance of these tests enabled their use as intermediate endpoints in clinical trials to test new strategies to treat atherosclerosis. If proven successful, these imaging tools may allow a reduction in size and duration of clinical trials with a substantial cost benefit for society.


Management of gastrointestinal food allergy in childhood.
Gastrointestinal food allergy in childhood is characterised by onset of gastrointestinal symptoms following food ingestion where the underlying mechanism is an immunologically mediated reaction within gastrointestinal tract. Presentation may be quick, slow or quick and slow after food ingestion. Diagnosis depends on response to food elimination, response to food challenge and analysis of response to food elimination. Management centres upon an elimination diet, the need for this is temporary. Cow's milk protein hydrolysates or amino acid formulae are preferred to soy formulae.


Age matters: differential impact of service quality on contraceptive uptake among post-abortion clients in Kenya.
This paper analyses the impact of high quality, user-friendly, comprehensive sliding-scale post-abortion services on clients' uptake of contraception in a Kenyan town. Data were drawn from detailed physician records in a private clinic that served 1080 post-abortion clients in 2006. All clients received confidential family planning counselling and were offered a complete range of contraceptives at no additional cost. One quarter of clients were below age 19. Prior to the abortion, no client aged 10-18 years reported having used contraception, as compared to 60% of clients aged 27-46 years. After the abortion and family planning counselling session, only 6% of clients aged 10-18 chose a method, as compared to 96% of clients aged 27-46, even though contraception was free, the provider strongly promoted family planning to everyone and all clients had just experienced an unwanted pregnancy. Significant predictors of contraceptive uptake post-abortion were: having a child, a previous termination, prior contraceptive use and being older than 21. These findings suggest that availability, affordability and youth-friendliness are not sufficient to overcome psycho-social barriers to contraceptive use for sexually-active young people in Kenya. To reduce unwanted pregnancies, more attention may be needed to developing youth-friendly communities that support responsible sexuality among adolescents.


Roux-en-Y gastric bypass decreases pro-inflammatory and thrombotic biomarkers in individuals with extreme obesity.
The low-grade inflammatory state in obesity leads to insulin resistance and endothelial dysfunction, which promote cardiovascular diseases in individuals with obesity. The purpose of this study was to evaluate the early effects of weight loss achieved through bariatric surgery on the inflammatory and prothrombotic states. This study also aimed to identify the role of hyperleptinemia on the prothrombotic state. The sample was composed of 41 extremely obese who underwent Roux-en-Y gastric bypass (RYGB). Anthropometric and clinical data, and biochemical markers of inflammation were collected prior to surgery and 6 months post-RYGB. It was found that plasminogen activator inhibitor-1 (PAI-1) concentrations were higher among extremely obese individuals with hyperleptinemia than in those without hyperleptinemia (p < 0.01).In relation to the baseline, post-surgery body mass index (BMI) was reduced by 12.9 kg/m(2), corresponding to 63.50 % of excess weight loss. Additionally, waist circumference was found to decrease significantly from 126.2 to 101.4 cm. Plasma total cholesterol (p < 0.01), LDL cholesterol (p = 0.02), triglycerides (p < 0.01), and glucose (p = 0.01) were also found to decrease. Pro-inflammatory biomarkers were observed to decrease: PAI-1 by 55.9 ± 6.0 % (p < 0.01), C-reactive protein (CRP) by 18.8 ± 3.4 % (p < 0.01), intercellular adhesion molecule-1 (ICAM-1) by 89.9 ± 5.7 % (p < 0.01), leptin by 27.9 ± 3.2 % (p < 0.01), and resistin by 69.3 ± 5.8 % (p < 0.01). Additionally, significant decreases of tumor necrosis factor alpha (TNF-α) and leptin/adiponectin ratio were observed. Anti-inflammatory cytokines adiponectin and interleukin-10 (IL-10) were significantly increased (170.7 ± 82.5 %, p < 0.01; 122.7 ± 55.1 %, p = 0.02). CRP levels were predictive of ICAM-1 (p = 0.04), and changes in leptin concentrations were associated with decreased PAI-1 levels (p = 0.03). We observed that individuals with obesity that have hyperleptinemia have higher circulating PAI-1 levels, which could indicate increased risk for cardiovascular disease. The biomarkers of inflammation and thrombosis measured in this study decreased after RYGB, suggesting that the surgery may be effective in reducing pro-inflammatory and thrombotic risk in individuals with extreme obesity.


Long-term Results of Adjuvant Imatinib Treatment for Localized Gastrointestinal Stromal Tumors after Surgery
Objective: Despite the development of two significant classifications for recurrence risk evaluation among patients engaged with gastrointestinal stromal tumor and corresponding treatment criteria, recurrence happens in a number of the patients who were once classified as ineligible for treatment and hence removed from treatment program. As such, the aim of the present study is to increase the number of patients recognized as eligible for treatment, so as to further reduce recurrence rate of this disease. Materials and Methods: A total of 26 patients from Ilam, Kermanshah, Lorestan, Kurdistan, and some parts of Hamedan, entered this study from 2006 until 2016. The western provinces included have similar socioeconomical conditions. Inclusion criteria were operable tumors confirmed radiologically with a gross size larger than 3 centimeters regardless of the mitosis rate in microscopic power fields, tumor location, or presence of peritoneal involvement during the surgery. Imatinib capsules were administered daily at 400 mg for 3 years. The patients were followed up every 3 months by radiology, ultrasonography, biochemical assessment, and clinical examination. Results and Conclusions: The overall survival after 10-years follow up was 100%, while 5-year survival without relapse was 95%. Mean overall survival was 106 months, and only one patient who had limited peritoneal involvement experienced relapse and he is still alive after 2 years. The drug was well tolerated and no significant side effects were observed.


Management of an inadvertent late filtering bleb and hypotony in a scleral fixated intraocular lens implantation.
To report a case of inadvertent cystic filtering bleb in a patient with scleral fixated intraocular lens (SFIOL) implantation 7 years after initial procedure. A 14-year-old boy underwent lensectomy, vitrectomy and a sutured rigid SFIOL for microspherophakia in the right eye. Seven years later, the patient presented with hypotony related ocular changes. Examination revealed an inadvertent cystic filtering bleb at the scleral section. Anterior segment optical coherence tomography (ASOCT) revealed gap in inner lips of the scleral wound, bridged by a thin strip of scleral tissue. A conservative management with bandage contact lens (BCL) failed after an initial improvement. Injection of trypan blue dye in the anterior chamber confirmed the presence and site of wound filtration. Surgical closure of the fistula was done and patient showed both structural and visual improvement. Meticulous wound construction and water tight closure at the end of the surgery can avoid such complications. ASOCT can be helpful in diagnosing the area of fistula. A conservative management with BCL can help by tamponading the filtering bleb. However, in unresponsive cases, surgical closure of the fistula is recommended to improve the hypotony-related changes.


Demonstration and evaluation of commercial and municipal equipment for urban biological decontamination.
Large-scale biological contamination incidents pose unique yet significant challenges to remediation operations. Previous incidents have demonstrated the utility of readily available commercial and municipal equipment for conducting remediation tasks. Preidentification and evaluation of such equipment could reduce lag time for response initiation and enhance overall response effectiveness and efficiency. The current study aimed to identify commercial and municipal equipment that could be beneficial in wide-area biological remediation operations. Equipment were identified by market research, their utility was assessed by a group of subject matter experts, and a subset of those equipment was observed under operational conditions in a realistic urban environment. Observations and feedback from demonstration participants are presented within the article. This information is intended to support rapid decision-making following large-scale biological incidents, broaden the universe of potentially useful equipment to support the response, enhance response operations, and reduce the impact on the public.


Ultrasonic margin preparation for fixed prosthodontics: a pilot study.
Atraumatic, oscillating ultrasonic instruments have recently been developed for prosthodontic margin finishing. This in vitro observational pilot study aimed to compare the condition of crown preparation margins finished using new ultrasonic instruments with margins finished with conventional rotary instruments. Two extracted human canine teeth were prepared for crowns. A split-tooth model was used to refine the margins: half of the margin was finished with conventional rotary instruments, the other with ultrasonic instruments. The profiles of the margins were observed using scanning electron microscopy, and a quantitative comparison of surface roughness was obtained using surface roughness analysis software. The margins finished with the ultrasonic instruments exhibited a better-defined axial wall/margin angle and a smoother marginal surface. Rotary instruments produced a sharper and more continuous external line angle. Two-dimensional surface roughness analysis showed that the margins produced with the ultrasonic instruments were approximately half as rough as the margins prepared with the conventional rotary instruments. The ultrasonic instruments produce margins in better condition than the current standard and appear to have some practical advantages. Preparations for fixed prosthodontics finished with these ultrasonic instruments created better-defined margins, which could result in more successful prostheses.


Enfuvirtide (T-20): a novel human immunodeficiency virus type 1 fusion inhibitor.
The development of highly active antiretroviral therapy has improved life expectancy and reduced progression to acquired immunodeficiency syndrome in human immunodeficiency virus (HIV)-infected patients. However, resistance to currently available classes of antiretroviral drugs has become a problem, limiting the options for patients with advanced disease who have been heavily treated. Enfuvirtide (T-20; ENF), a synthetic peptide, is the first of a new class of antiretrovirals that block entry of virus into host cells. ENF interferes with conformational changes required for membrane fusion and injection of virus into the host cell. Optimal treatment of HIV infection will likely require combinations of drugs that target novel stages of HIV type 1 entry and replication.


Comparison of RNase T1 fingerprints of U1, U2, and U3 small nuclear RNA's of HeLa cells, human normal fibroblasts, and Novikoff hepatoma cells.
To determine whether there are differences between the U1, U2, and U3 small nuclear RNA's of human cancer cells (HeLa cells) and human normal fibroblasts (IMR-90 cells), and between these uridine-rich small nuclear RNA's of human and Novikoff hepatoma cells, the cells were first incubated in Eagle's medium with [32P]Pi to label these RNA's uniformly. No differences were found between the RNase T1 fingerprints of the purified U1, U2, and U3 RNA's of HeLa cells and IMR-90 cells. The RNase T1 fingerprints of U1 RNA's from human tissues were very similar to that of the U1 RNA of Novikoff hepatoma cells. The RNase T1 fingerprints of U2 and U3 RNA's from human tissues had many similarities to those of Novikoff hepatoma cells, but a few differences were found, such as a point mutation of the U-U-Gp in the rat U2 RNA to A-U-Gp (U leads to A) in human U2 RNA. Unlike the three U3 RNA's of Novikoff hepatoma cells, U3 RNA from human tissues appears to be only one species. These results indicate that U1, U2, and U3 RNA's of human cancer cells are essentially the same as those of human normal cells. In addition, the uridine-rich small nuclear RNA's appear to be conserved through evolution.


Two phases of rod photoreceptor differentiation during rat retinal development.
We have conducted a comprehensive analysis of the relative timing of the terminal mitosis and the onset of rhodopsin expression in rod precursors in the rat retina in vivo. This analysis demonstrated that there are two distinct phases of rod development during retinal histogenesis. For the majority of rod precursors, those born on or after embryonic day 19 (E19), the onset of rhodopsin expression was strongly correlated temporally with cell cycle withdrawal. For these precursors, the lag between the terminal mitosis and rhodopsin expression was measured to be 5.5-6.5 d on average. By contrast, for rod precursors born before E19, the lag was measured to be significantly longer, averaging from 8.5 to 12.5 d. In addition, these early-born rod precursors seemed to initiate rhodopsin expression in a manner that was not correlated temporally with the terminal mitosis. In these cells, onset of rhodopsin expression appeared approximately synchronous with later-born cells, suggesting a synchronous recruitment to the rod cell fate induced by environmental signals. To examine this possibility, experiments in which the early-born precursors were exposed to a late environment were conducted, using a reaggregate culture system. In these experiments, the early-born precursors appeared remarkably uninfluenced by the late environment with respect to both rod determination and the kinetics of rhodopsin expression. These results support the idea that intrinsically distinct populations of rod precursors constitute the two phases of rod development and that the behavior exhibited by the early-born precursors is intrinsically programmed.


Gynecologic operative laparoscopy: new training programs are needed.
The revolution in laparoscopic surgery demands implementation of adequate training programs preferably in an academic setting. The most dramatic progress over the last decade in the field of gynecology was undoubtedly the development of advanced operative laparoscopy. This has been initiated by an unprecedented technological revolution.


A randomized, controlled trial comparing arteriovenous to venovenous rewarming of severe hypothermia in a porcine model.
The purpose of this study was to evaluate active rewarming using continuous arteriovenous rewarming (CAVR) and continuous venovenous rewarming (CVVR) methods during severe hypothermia using an electromagnetic fluid warmer. Rapid rewarming using these techniques is superior to passive rewarming and is possible with commercially available equipment. Eighteen swine (55-65 kg) were assigned to CAVR, CVVR, or control. Vascular access was obtained via central lines (8.5-French) in all subjects. Subjects were cooled to 27 degrees C (80.6 degrees F) in an ice bath, and then dried, covered, and connected to the rewarming device. The carotid artery (CAVR) or internal jugular vein (CVVR) was used for circuit inflow. Warmed 39 degrees C (102.2 degrees F) blood was returned via the femoral vein. Hemodynamic parameters and temperatures (pulmonary artery and rectal) were recorded until reaching an endpoint of a pulmonary artery temperature of 37 degrees C (98.6 degrees F). Mean rewarming time in the CAVR group was 2 hours 14 minutes, with a mean rewarming rate of 4.5 degrees C/h (8.1 degrees F/h, 0.034 degrees C/kg/h). Total circulating volume averaged 65 L. CVVR averaged 3 hours 8 minutes, with a mean rewarming rate of 3.2 degrees C/h (5.8 degrees F/h, 0.024 degrees C/kg/h). Total circulating volume averaged 67 L. Controls averaged 10 hours 42 minutes, with a mean rate of 0.9 degrees C/h (1.7 degrees F/h, 0.007 degrees C/kg/h). The CAVR group was faster than the CVVR group in both the rewarming rate and total time to rewarming (p = 0.034 and p = 0.040, respectively). Both experimental groups were significantly different from controls in rewarming rate and total time to rewarming (p < 0.001). CAVR offers the most rapid rate of rewarming. CVVR offers a rapid rate using less invasive procedures. Both techniques are markedly superior to passive rewarming methods typically used during early resuscitation.


Overexpression of GαS in Murine Osteoblasts In Vivo Leads to Increased Bone Mass and Decreased Bone Quality.
GαS is a heterotrimeric G protein that transduces signals from activated G protein-coupled receptors on the cell surface to stimulate adenylyl cyclase/cyclic adenosine monophosphate (AMP) signaling. GαS plays a central role in mediating numerous growth and maintenance processes including osteogenesis and bone turnover. Decreased GαS expression or activating mutations in GαS both affect bone, suggesting that modulating GαS protein levels may be important for bone health and development. To examine the effects of increased osteoblastic GαS expression on bone development in vivo, we generated transgenic mice with GαS overexpression in osteoblasts (HOM-Gs mice) driven by the 3.6-kilobase (kb) Col1A1 promoter. Both male and female HOM-Gs mice exhibit increased bone turnover with overactive osteoblasts and osteoclasts, resulting in a high bone mass phenotype with significantly reduced bone quality. At 9 weeks of age, HOM-Gs mice have increased trabecular number, volumetric BMD (vBMD), and bone volume; however, the bone was woven and disorganized. There was also increased cortical bone volume despite an overall reduction in size in HOM-Gs mice along with increased cortical porosity and brittleness. The skeletal phenotype of HOM-Gs mice progressed into maturity at 26 weeks of age with further accrual of trabecular bone, whereas WT mice lost trabecular bone at this age. Although cortical bone volume and geometry were similar between mature HOM-Gs and WT mice, increased porosity persisted and the bone was weaker. At the cellular level, these alterations were mediated by an increase in bone resorption by osteoclasts and an overwhelmingly higher increase in bone formation by osteoblasts. In summary, our findings demonstrate that high osteoblastic GαS expression results in aberrant skeletal development in which bone production is favored at the cost of bone quality. © 2017 American Society for Bone and Mineral Research.


Seismic target classification using a wavelet packet manifold in unattended ground sensors systems.
One of the most challenging problems in target classification is the extraction of a robust feature, which can effectively represent a specific type of targets. The use of seismic signals in unattended ground sensor (UGS) systems makes this problem more complicated, because the seismic target signal is non-stationary, geology-dependent and with high-dimensional feature space. This paper proposes a new feature extraction algorithm, called wavelet packet manifold (WPM), by addressing the neighborhood preserving embedding (NPE) algorithm of manifold learning on the wavelet packet node energy (WPNE) of seismic signals. By combining non-stationary information and low-dimensional manifold information, WPM provides a more robust representation for seismic target classification. By using a K nearest neighbors classifier on the WPM signature, the algorithm of wavelet packet manifold classification (WPMC) is proposed. Experimental results show that the proposed WPMC can not only reduce feature dimensionality, but also improve the classification accuracy up to 95.03%. Moreover, compared with state-of-the-art methods, WPMC is more suitable for UGS in terms of recognition ratio and computational complexity.


A Comparison of Cost and Reward Procedures With Interdependent Group Contingencies.
The present study evaluated the effectiveness of two variations of a token economy for reducing disruptive behavior within a general education classroom. One variation involved a group contingency in which tokens were removed contingent on disruptive behavior (response cost), and the other variation involved a group contingency in which tokens were gained according to a differential reinforcement of other behavior schedule. Two elementary school teachers and their students participated. Results indicated that both procedures were effective in reducing the overall number of students disrupting; however, both teachers and students indicated a greater preference for the response cost condition. Implications for the use of these behavior management strategies in the classroom are discussed in terms of effectiveness and ease of implementation.


Differentiation between Weissella cibaria and Weissella confusa Using Machine-Learning-Combined MALDI-TOF MS.
Although Weissella cibaria and W. confusa are essential food-fermenting bacteria, they are also opportunistic pathogens. Despite these species being commercially crucial, their taxonomy is still based on inaccurate identification methods. In this study, we present a novel approach for identifying two important Weissella species, W. cibaria and W. confusa, by combining matrix-assisted laser desorption/ionization and time-of-flight mass spectrometer (MALDI-TOF MS) data using machine-learning techniques. After on- and off-plate protein extraction, we observed that the BioTyper database misidentified or could not differentiate Weissella species. Although Weissella species exhibited very similar protein profiles, these species can be differentiated on the basis of the results of a statistical analysis. To classify W. cibaria, W. confusa, and non-target Weissella species, machine learning was used for 167 spectra, which led to the listing of potential species-specific mass-to-charge (m/z) loci. Machine-learning techniques including artificial neural networks, principal component analysis combined with the K-nearest neighbor, support vector machine (SVM), and random forest were used. The model that applied the Radial Basis Function kernel algorithm in SVM achieved classification accuracy of 1.0 for training and test sets. The combination of MALDI-TOF MS and machine learning can efficiently classify closely-related species, enabling accurate microbial identification.


PARAMETERS OF TEXTURE CHANGE IN PROCESSED FISH: CROSS-LINKAGE OF PROTEINS.
Soluble myosin and insoluble protein (i. e., soluble only in 5 % sodium dodecyl sulfate) were obtained from fresh and processed Sacramento blackfish and analyzed for the existence of possible cross-links. Free sulfhydryl groups decreased somewhat in freezing and more in frozen storage. None were present after dehydration or cooking nor in any insoluble fractions, so that presumably these were oxidized in the formation of cross-links. Ester bonds were much more numerous in insoluble protein than in soluble myosin, but their relative content was not clearly related to processing. Aldehyde groups decreased in myosin after cooking and dehydration, and were absent from insoluble protein. The presumptive Schiff base content was somewhat greater in soluble protein than in myosin and appeared to increase upon freezing and dehydration.


(EVICEL) for Augmentation of Dural Closure: Results of a Preliminary Clinical Study.
The authors prospectively evaluated the safety and efficacy of a new fibrin sealant in patients undergoing emergency and elective cranial/spinal surgery with documented cerebrospinal fluid (CSF) leakage after sutured dural repair. This study was designed as a prospective, nonrandomized clinical trial. EVICEL® Fibrin Sealant (Johnson & Johnson, Somerville, NJ) was used in 72 patients with documented intraoperative CSF leakage after neurosurgical dural repair for a variety of pathologies. Intraoperative CSF leakage was either spontaneous or induced by a Valsalva maneuver. Patients were monitored for 1 month postoperatively with physical examinations, clinical laboratory analyses, and diagnostic imaging (CT or MRI). The sealant was effective in closing intraoperative CSF leakage in all patients but one. There were no sealant-related adverse events, and all clinical outcomes were consistent with expectations for seriously ill patients undergoing prolonged neurosurgical procedures. EVICEL® Fibrin Sealant provides a safe and effective watertight closure when used as an adjunct to sutured dural repair during cranial surgery.


Mutational effects on the cooperativity of Ca2+ binding in calmodulin.
The importance of the aspartate ligand in the +Y Ca2+ coordinating position of two EF-hands of calmodulin has been investigated. Synthetic calmodulin genes were used to produce engineered proteins with the wild-type bovine sequence as well as with aspartate 58 in Ca(2+)-binding site II and/or aspartate 95 in site III changed to asparagine. The macroscopic Ca(2+)-binding constants of the intact calmodulins and of tryptic fragments comprising the N- and C-terminal domains were determined from titrations with Ca2+ in the presence of 5,5'-Br2BAPTA. Substitution of aspartate by asparagine in Ca(2+)-binding site II led to a slight increase in the total free energy change on Ca2+ binding, and the cooperativity of Ca2+ binding to the N-terminal sites was substantially increased. The change from aspartate to asparagine in site III decreased the Ca2+ affinity and also appeared to decrease the positive cooperativity between the sites in the C-terminal domain. Thus, identical mutations in sites II and III were found to result in opposite effects. The data imply that involvement of liganding side chains in interactions other than direct calcium attraction and calcium coordination is of considerable importance for the Ca(2+)-binding process, particularly for the cooperativity.


Intensive gestational glycemic management and childhood obesity: a systematic review and meta-analysis.
Hyperglycemia in pregnancy is associated with increased risk of offspring childhood obesity. Treatment reduces macrosomia; however, it is unclear if this effect translates into a reduced risk of childhood obesity. We performed a systematic review and meta-analysis of randomized controlled trials to evaluate the efficacy and safety of intensive glycemic management in pregnancy in preventing childhood obesity. We searched MEDLINE, EMBASE, CENTRAL and ClinicalTrials.gov up to February 2016 and conference abstracts from 2010 to 2015. Two reviewers independently identified randomized controlled trials evaluating intensive glycemic management interventions for hyperglycemia in pregnancy and included four of the 383 citations initially identified. Two reviewers independently extracted study data and evaluated internal validity of the studies using the Cochrane Collaboration's Risk of Bias tool. Data were pooled using random-effects models. Statistical heterogeneity was quantified using the I2 test. The primary outcome was age- and sex-adjusted childhood obesity. Secondary outcomes included childhood weight and waist circumference and maternal hypoglycemia during the trial (safety outcome). The four eligible trials (n=767 children) similarly used lifestyle and insulin to manage gestational hyperglycemia, but only two measured offspring obesity and waist circumference and could be pooled for these outcomes. We found no association between intensive gestational glucose management and childhood obesity at 7-10 years of age (relative risk 0.89, 95% confidence interval (CI) 0.65 to 1.22; two trials; n=568 children). Waist circumference also did not differ between treatment and control arms (mean difference, -2.68 cm; 95% CI, -8.17 to 2.81 cm; two trials; n=568 children). Intensive gestational glycemic management is not associated with reduced childhood obesity in offspring, but randomized data is scarce. Long-term follow-up of trials should be prioritized and comprehensive measures of childhood metabolic risk should be considered as outcomes in future trials.


Desmoid tumors: a clinical review of 30 patients with more than 20 years' follow-up.
We retrospectively studied the outcome in a consecutive series of 30 patients with desmoid tumors who were followed for more than 20 years after treatment (surgery in 29 patients). A local recurrence occurred in 12 patients and more than 1 recurrence occurred in 8. 3 patients had spontaneous complete regression of the tumor. At follow-up after mean 28 (20-54) years, all patients were tumor-free except 1 who had had a stable tumor for at least 11 years. Symptoms were related more to treatment than to the tumor. We conclude that desmoid tumors may have a high capacity for self-limitation and that conservative therapy should be considered in symptom-free patients.


Mobility in the context of exposure-based assessment of chemicals for drinking water resource protection.
In order to protect European Union (EU) drinking water resources from chemical contamination, criteria for identifying persistent, mobile, and toxic (PMT) chemicals and very persistent and very mobile (vPvM) chemicals under the EU REACH Regulation were proposed by the German Environment Agency (Umweltbundesamt-UBA). Additionally, new hazard classes for PMT and vPvM substances in the revised EU classification, labeling, and packaging (CLP Regulation) are intended. Therefore, a reliable approach in the identification of potential drinking water resource contaminants is needed. The scientific basis of the property-based PMT/vPvM criteria, focusing on mobility, which dictates the migration of chemical drinking water sources, was evaluated, and a critical analysis of the deviation of sorption metrics from simple behavior was carried out. Based on our evaluation, a Koc may be used for nonionic substances on a screening level only, requiring a higher tier assessment. It is considered inappropriate for hydrophilic and ionizable chemicals, particularly for soils with low organic carbon contents. The nonextractable residue formation is complex and not well understood but remains significant in limiting the mobility of chemicals through soils and sediments. In order to inform the EU commission's work on the introduction of new hazard classes for PMT and vPvM substances into the European legislation, the derivation of a tiered approach is proposed, which utilizes the weight of evidence available, with adoption of appropriate higher tier models commensurate with the nature of the substance and the data available. Integr Environ Assess Manag 2023;19:775-791. © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).


Successful treatment of massive air embolism.
Closure of a persistent ductus arteriosus through a median sternotomy on cardiopulmonary bypass in a 24-year-old man resulted in a tear of the descending aorta below the ductus. The repair of the aortic injury was attempted with deep hypothermia and low arterial flow, which resulted in massive air embolism of the aorta, the central arteries, and the arterial line. Air was expelled by reverse and perfusion by connecting the arterial line to the venous cannula in the superior vena cava. The patient was discharged from the hospital without neurological consequences.