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Recent controlled trials, epidemiological analyses and basic research studies offer a comprehensive view of the short and long-term clinical repercussion of de novo acute kidney injury or AKI. While most post-AKI patients recover their baseline renal function, a significant number, approximately ~20% of those affected, will go on to develop long term illness characterized by an increase in late stage CKD, cardiovascular complications, and increased death rates. When AKI occurs in hospitalized patients, selected demographic and laboratory results can be incorporated into risk calculators that identify those at higher risk for long-term complications. This review touches on some of the salient epidemiological studies of the AKI to CKD transition. It also focuses on certain recent advancements in our understanding of the biological and functional impact of AKI on the renal tubule repair mechanism, as well as the important role that genetic, epigenetic, biochemical and inflammatory events, seemingly beneficial to the re-establishment of normal renal function, can be offset by mediators of progressive fibrosis and irreversible structural changes. Characterization of basic processes that mediate the AKI to CKD transition reveals promising pharmacological and biological agents that hopefully will one day be used in the early stages of AKI to prevent its deadly consequences.

Sixty-two cases of oligohydramnios diagnosed by ultrasound between 13-28 weeks' gestation were reviewed. Three experienced ultrasonographers used a subjective scale to rate the oligohydramnios as mild, moderate, severe, or anhydramniotic. Interobserver reliability was excellent (intraclass correlation coefficient 0.81). The overall perinatal mortality rate was 43%, and the incidence of pulmonary hypoplasia was 33%. One-third had lethal congenital anomalies. The frequency of adverse outcome correlated strongly with the most severe degrees of oligohydramnios; 88% of the fetuses with severe oligohydramnios or anhydramnios had lethal outcomes, compared with 11% in the mild/moderate group. The presence of an anuric urinary tract anomaly was associated with the most severe grades of oligohydramnios and was uniformly fatal. Pulmonary hypoplasia was diagnosed in 60% of the severe group versus 6% in the moderate group. We conclude that subjective grading of oligohydramnios by experienced observers is both reliable and predictive of outcome. The finding of severe oligohydramnios in the second trimester is highly predictive of poor fetal outcome and should stimulate a thorough search for etiology and consideration of intervention. Moderate grades of reduced amniotic fluid may be managed with relative optimism.

Integrating conjugative elements (ICEs) of the SXT/R391 family are major contributors to the spread of antibiotic resistance genes. These elements also catalyze their own diversity by promoting inter-ICE recombination through the action of the RecA-independent homologous recombination system that they encode. Here, we report that expression of this recombination system, which consists of the single-stranded DNA annealing protein Bet and the exonuclease Exo, is induced by DNA-damaging agents via ICE-encoded transcriptional regulators. We show that the bet and exo genes are part of a large polycistronic transcript that contains many conserved ICE genes that are not involved in the main integration/excision and conjugative transfer processes. We show that although the recombination genes are highly transcribed, their translation is subject to additional strong regulatory mechanisms. We also show that an ICE-encoded putative single-stranded DNA binding protein (Ssb) limits hybrid ICE formation. Finally, a thorough in silico analysis reveals that orthologues of Bet and Exo are widely distributed in bacterial strains belonging to very distantly related bacterial species and are carried by various mobile genetic elements. Phylogenetic analyses suggest that the annealing proteins and exonucleases that compose these systems sometimes have different evolutionary origins, underscoring the strong selective pressure to maintain the functionality of these unrelated cooperating proteins.

This article details the diagnosis and imaging of primary and secondary neoplasms of the liver. Benign conditions that can mimic malignancy are also discussed, such as focal nodular hyperplasia and adenoma. Considerable attention is given to hepatoma, which is the most common primary hepatic tumor in the United States. The roles of magnetic resonance imaging, computed tomography, and ultrasound are evaluated, with recommendations for their effective use. Pitfalls in imaging related to posttreatment changes and unusual patterns of metastatic disease are illustrated.

Perovskite solar cells have attracted significant attention due to their high efficiency and low cost. In the research on methylammonium lead-iodide (CH₃NH₃PbI₃), a lot of work has been devoted to optimize the film morphology and crystallinity resulting in an enhancement of the power conversion efficiency (PCE). A good surface coverage and uniform perovskite films are highly desirable along with a smooth and pinhole-free contact between the hole and electron extraction layers. Overall, this affects the charge transport and collection, and reduces charge recombination. Herein, we demonstrate a facile route to control perovskite crystallization by inserting an optimal amount of insulating polystyrene in the perovskite precursor solutions. The incorporation of a small amount of polystyrene results in much better surface coverage, and a smoother and uniform perovskite thin film leading to improved crystallization and larger grain size. <i>Via</i> careful optimization, and easy and low temperature solution-based processing, below 100 &#176;C, we realize a device with PCE exceeding 13% along with significantly reduced leakage current.

The efficiency of hemodialysis can be more than doubled. This involves deviating from conventional blood and dialysate flows, employing dialyzers with greater surface area and permeability, bicarbonate dialysate, and an apparatus capable of rigid volumetric control of the dialysate. Coupled with the better treatment tolerance described elsewhere in this volume, this self-contained and automated technique providing high diffusive and convective transfer permits drastic reductions in treatment time over conventional dialysis: in our study, to under 6 hrs/wk.

Photoacoustic measurements made at various chopping frequencies on dense acqueous melanin suspensions have revealed a significant dependence upon pH and redox state. It is shown that such behaviour, differing from the simple predictions of the Rosencwaig-Gersho theory, can be explained in terms of finite carrier diffusion and recombination times. The implications of these findings with respect to the amorphous semiconductor model proposed to describe the dynamic role of epidermal melanin are discussed. From the experimental data, values of physical parameters were calculated which allow a qualitative correlation between chemical states and electronic behaviour and, consequently, some aspects of the molecular biology of the melanosome, founded on a rigorous base.

We recently built a magnetic separation system to extend the applications of split-flow thin (SPLITT) fractionation to magnetically susceptible particles. Here, we characterize the magnetic SPLITT system using magnetically susceptible particles and ion-labeled particles. The flow axis of separation channel was orientated parallel and perpendicular to gravitational forces to exclude and include, respectively, gravitational effects on separation. Both operating modes were used to test the theory experimentally, with emphasis on the parallel mode. The magnetic susceptibilities of carrier and ion-labeled particles were varied, and various ion-labeled and unlabeled particles were studied experimentally, resulting in successful separation of labeled particles, yeasts, and cells from unlabeled ones. The minimal difference in magnetic susceptibility (delta(chi)) required for complete particle separation was about 1.75 x 10(-5) [cgs], corresponding to about 10(9) labeling ions per particle in this study. The throughput was around 7.2 x 10(8) particles/h using the present setup. Magnetic SPLITT fractionation shows good potential for use in obtaining particles magnetic susceptibilities from a simple theoretical treatment.

Right-angle dual-headed tomography has increased cardiac SPECT utility by cutting acquisition time in half which enhances gating capabilities. When gating, however, a deceleration in heart rate, due to a return to baseline rate after stress or lessened anxiety at the end of a study, may significantly affect the last step(s) of a gated study with possible frame or information loss. The purpose of this study was to illustrate the artifacts produced in myocardial perfusion studies when a frame or frames are lost in single- and dual-detector SPECT imaging methodologies.

The right hips of 69 five-day-old rabbits were dislocated surgically and left to develop in the dislocated position to determine the nature and timing of changes in the hip. Using the left hips as controls, 15 survivors were killed and studied macroscopically and microscopically at two months of age and 14 at four months of age. It was found that articular cartilage of the acetabulum in the dislocated hips showed fibrous degeneration in about 50% of the two-month-old rabbits cases and in all of the four-month-old rabbits. In the dislocated femoral heads the articular cartilage was normal, and only 25% of the four-month-old animals showed fibrous degeneration.

Lactic acid is an attractive target platform chemical obtained from biorefinery processes based on renewable resources. This study focuses on the recovery of lactic acid from corn stover hemicellulose-derived liquor. Two processes were investigated comparatively. In process I, under the optimized conditions of 10 wt % trioctylamine/octanol, the extraction efficiency and distribution coefficient of lactic acid were 50.8% and 1.03, respectively. In process II, a salting-out extraction step was introduced, which had significant impacts on the following reactive extraction process. The extraction efficiency and distribution coefficient of lactic acid were about 32.2% and 3.85 times higher than that of process I, respectively. All residual sugars and most of the salts (82.8%) could be removed by the salting-out extraction system used. Additionally, five extraction cycles with back-extraction and solvent regeneration were performed, and the results showed that the extraction system still exhibited stable performance. Effective extraction of lactic acid from crude reaction liquor of corn stover was realized by first salting-out and consecutive reactive extraction, which provided a potential method for recovery of lactic acid from actual biomass-derived liquor.

Alveolar echinococcosis cases diagnosed histopathologically in 2002, 2006, 2007, and 2009 in Ulaanbaatar, Mongolia were reconfirmed by evaluating the cytochrome c oxidase subunit I gene of mitochondrial DNA. The most recent three cases using paraffin-embedded and ethanol-fixed specimens revealed that one was of the "Asian" haplotype, whereas two others were of the "Inner Mongolian" type. All patients were born in the western provinces of Mongolia, they never resided outside of Mongolia, and they were given a preliminary diagnosis of malignant hepatic tumor or abscess. The most recent two cases were also confirmed serologically to be active alveolar echinococcosis.

Graduate teaching assistants (GTAs) play important roles in engineering education at the undergraduate level. Since there are lots of technological content knowledge (TCK) in engineering curriculums, the improvements of GTAs' teaching skills on TCK will help the teaching effectiveness of the curriculums. As the instructor's knowledge about technology-infused instruction for TCK is the core of the teaching skill, Technological Pedagogical Content Knowledge (TPACK) is taken as a framework to measure the extent to which instructor can teach with technology. In this study, an online questionnaires survey covering GTAs' program coordinator, teacher, graduate student and undergraduate student has done to explore the factors of enhancing GTAs' TPACK performance. The quantitative analyses through a structural equation modeling approach indicates that the roles of the GTAs should be clearly recognized by the teacher, program coordinators and GTAs themselves. An evaluating procedure for GTAs should be established; The attitude and self-efficacy of GTAs should be improved through the training courses and the field trips while the promising expectation from the undergraduate student on the roles of GTAs can improve the performance of GTAs' program. Our results will be helpful not only for engineering curriculum, but also for other curriculums.

The classic mapping of distinct aspects of working memory (WM) to mutually exclusive brain areas is at odds with the distributed processing mechanisms proposed by contemporary network science theory. Here, we use machine-learning to determine how aspects of WM are dynamically coded in the human brain. Using cross-validation across independent fMRI studies, we demonstrate that stimulus domains (spatial, number and fractal) and WM processes (encode, maintain, probe) are classifiable with high accuracy from the patterns of network activity and connectivity that they evoke. This is the case even when focusing on 'multiple demands' brain regions, which are active across all WM conditions. Contrary to early neuropsychological perspectives, these aspects of WM do not map exclusively to brain areas or processing streams; however, the mappings from that literature form salient features within the corresponding multivariate connectivity patterns. Furthermore, connectivity patterns provide the most precise basis for classification and become fine-tuned as maintenance load increases. These results accord with a network-coding mechanism, where the same brain regions support diverse WM demands by adopting different connectivity states.

The pathogenesis of schizophrenia is rarely attributed to dysfunction of the cerebellum. However, coordination of mental processes might involve the cerebellum and a cortico-cerebellar-thalamic-cortical circuit (CCTCC) that can mediate that process has been proposed. We present the case of a 31-year-old male patient with a family history of psychosis who developed schizophrenia in association with a slow-growing glioblastoma at the left posterior cerebellar pontine angle. Of interest is that his psychosis became refractory after surgical removal of the tumor that had no motor deficit consequences, suggesting that the greater disruption of the CCTCC due to surgical excision might be related to the worsening psychosis. The case supports the hypothesis of cognitive dysmetria and psychosis.

Mild hyperthermia, local heating of the tumour up to temperatures <43 °C, has been clinically applied for almost four decades and has been proven to substantially enhance the effectiveness of both radiotherapy and chemotherapy in treatment of primary and recurrent tumours. Clinical results and mechanisms of action are discussed in this review, including the molecular and biological rationale of hyperthermia as radio- and chemosensitizer as established in in vitro and in vivo experiments. Proven mechanisms include inhibition of different DNA repair processes, (in)direct reduction of the hypoxic tumour cell fraction, enhanced drug uptake, increased perfusion and oxygen levels. All mechanisms show different dose effect relationships and different optimal scheduling with radiotherapy and chemotherapy. Therefore, obtaining the ideal multi-modality treatment still requires elucidation of more detailed data on dose, sequence, duration, and possible synergisms between modalities. A multidisciplinary approach with different modalities including hyperthermia might further increase anti-tumour effects and diminish normal tissue damage.

An intergenerational community study in Islington, north London, has considered psychiatric disorder in mothers and their adolescent and early adult daughters and the role of parenting in any link between the two. The results indicate that daughters are more likely to have disorders at a case level when their mothers have chronic or recurrent episodes of disorder at this level. Such conditions in the mother relate to the daughters' reports of adverse family experience involving maternal antipathy and neglect and physical and sexual abuse, most usually at the hands of a father or stepfather. These adverse experiences are associated with disorder in daughters independently of any disorder in the mother.

Atmospheric particles larger than 0.2 μm were collected at the top of Mt. Tai (36.25°N, 117.10°E, 1534 m a.s.l.) in eastern China in May 2008 during the passage of a strong cyclone. The particles were analyzed with electron microscopes and characterized by morphology, equivalent diameter and elemental composition. Soot particles with coating (coated soot particles) and those without apparent coating (naked soot particles) were predominant in the diameter range smaller than 0.6 μm in all samples. The number-size distribution of the relative abundance of naked soot particles in the prefrontal air was similar to that in the postfrontal air and their size modes were around 0.2-0.3 μm. However, the distribution of inclusions of coated soot particles showed a mode in the range of 0.1-0.3 μm. The coating degree of coated soot particles, which was defined by the ratio of the diameter of inclusion to the diameter of particle body, showed a mode around 0.5 with the range of 0.3-0.6. These results indicate that the status of soot particles in the prefrontal and postfrontal air was similar although air pollution levels were dramatically different. In addition, the relative abundance of accumulation mode particles increased with the decrease of soot particles after the front passage.

Infantile hepatic haemangioma (IHH) is a rare vascular tumour that is potentially lethal due to its associated complications, including heart failure, hepatic failure, hypothyroidism and abdominal compartment syndrome. The authors report a case of an asymptomatic diffuse IHH in a newborn male, which was presented as an incidental finding at the time that the patient was diagnosed with pyloric stenosis. The patient was treated with increasing doses of propranolol that were well tolerated. With the regression of the IHH by the time that the patient reached one year of age, there was a significant imagiologic improvement. Because there is no consensus on the optimal approach for the treatment of liver tumours in newborns, it is important to adopt a systematic approach. After the diagnosis of diffuse IHH has been established, the decision to initiate treatment and the therapeutic of choice is often controversial. Regular follow-up is recommended to monitor possible complications.

Non-contact real time microwave measurement and signal analysis techniques to extract high temperature material parameters from the mono-static reflections gathered by a compact air cooled corrugated horn are presented in this work. Non-contact in situ microwave measurements gathered over 20-24 GHz inside a closed furnace were processed to identify the thermodynamic phase change temperature of metal and glass melts. The melting point of aluminum alloy and glass transition of a borosilicate glass matrix extracted from the time gated and processed microwave measurements were in good agreement with differential scanning calorimetry measurements. Thus, the ability to measure high temperature material process parameters using non-contact microwave measurements is demonstrated.

1. We have compared the mRNA distribution of sodium channel alpha subunits known to be expressed during development with the known auxiliary subunits Nabeta1.1 and Nabeta2.1 and the novel, recently cloned subunit, beta3. 2. In situ hybridisation studies demonstrated high levels of Nav1.2, Nav1.3, Nav1.6 and beta3 mRNA at embryonic stages whilst Nabeta1.1 and Nabeta2.1 mRNA was absent throughout this period. 3. Nabeta1.1 and Nabeta2.1 expression occurred after postnatal day 3 (P3), increasing steadily in most brain regions until adulthood. beta3 expression differentially decreased after P3 in certain areas but remained high in the hippocampus and striatum. 4. Emulsion-dipped slides showed co-localisation of beta3 with Nav1.3 mRNA in areas of the CNS suggesting that these subunits may be capable of functional interaction. 5. Co-expression in Xenopus oocytes revealed that beta3 could modify the properties of Nav1.3; beta3 changed the equilibrium of Nav1.3 between the fast and slow gating modes and caused a negative shift in the voltage dependence of activation and inactivation. 6. In conclusion, beta3 is shown to be the predominant beta subunit expressed during development and is capable of modulating the kinetic properties of the embryonic Nav1.3 subunit. These findings provide new information regarding the nature and properties of voltage-gated sodium channels during development.

Enoxaparin (Clexane), Lovenox) is a low molecular weight heparin (LMWH) that has been widely used in the prevention of venous thromboembolism (VTE) in surgical patients. More recently, with the recognition of the high incidence of VTE in acutely ill medical (nonsurgical) patients, enoxaparin has been evaluated for thromboprophylaxis in this patient population. Subcutaneous enoxaparin 40 mg once daily has shown efficacy in the short-term thromboprophylaxis of VTE in nonsurgical patients with severely restricted mobility due to acute illness in well controlled clinical trials. The drug is at least similar in efficacy to unfractionated heparin (UFH) and its pharmacological profile allows once-daily administration, in contrast to the twice- or three-times-daily administration required with UFH. The tolerability profile of enoxaparin is also similar to that of UFH, except that the incidences of local haematomas and increased liver enzymes are lower with enoxaparin. The optimal duration of prophylaxis in nonsurgical patients is currently being evaluated and the results of extended prophylaxis with enoxaparin evaluated in the EXCLAIM (EXtended CLinical prophylaxis in Acutely Ill Medical patients) trial are awaited with interest. Currently, short-term enoxaparin appears to provide a cost-effective treatment alternative to UFH for VTE prophylaxis in nonsurgical patients.

This paper concerns the discourse features of verbal hallucinations and negative symptoms of schizophrenia. A total of 46 schizophrenics, varying in verbal hallucination and in negative symptoms status, and 22 controls were tested on the Reporter Test. The frequency with which they issued inadequate instructions, attempted to repair the inadequacies, and the success of repairs were compared. We observed that schizophrenics, on the whole, issued more wrong and incomplete instructions. This was in part related to their worse working memory, but it was not affected by verbal hallucinations or negative symptoms. We observed, further, that schizophrenics had no particular problems monitoring messages for inadequacies. We did find, however, that schizophrenics with verbal hallucinations had a specific problem with self-repairing wrong instructions. We interpret these results in the framework of Hoffman's (1986b) plan disruption-based model of verbal hallucinations; the Frith (1987) and Frith and Done (1988) internal monitoring model of positive and negative symptoms; and finally Frith and Frith's (1990) model of negative and positive schizophrenia and we use the results to specify the models.

Bioorthogonal reactions that are fast and reversible under physiological conditions are in high demand for biological applications. Herein, it is shown that an ortho boronic acid substituent makes aryl ketones rapidly conjugate with α-nucleophiles at neutral pH. Specifically, 2-acetylphenylboronic acid and derivatives were found to conjugate with phenylhydrazine with rate constants of 10(2) to 10(3) M(-1) s(-1) , comparable to the fastest bioorthogonal conjugations known to date. (11) B NMR analysis revealed the varied extent of iminoboronate formation of the conjugates, in which the imine nitrogen forms a dative bond with boron. The iminoboronate formation activates the imines for hydrolysis and exchange, rendering these oxime/hydrazone conjugations reversible and dynamic under physiological conditions. The fast and dynamic nature of the iminoboronate chemistry should find wide applications in biology.

Schwannomas of the gastrointestinal tract are rare. Herein, we report a case of schwannoma originating from the small intestine. A 78-year-old woman underwent medical follow-up after surgery for bladder cancer, and a mass in the upper part of the pelvis was revealed by abdominal CT. With the diagnosis of a submucosal tumor of the small intestine, she underwent partial intestinal resection. The submucosal tumor was pathologically composed of S100-positive spindle cells and diagnosed as schwannoma. We report this case of rare schwannoma of the small intestine and review the literature.

Evolutionary emergence of agents in the empirical world is a direct consequence of the indexicality of matter itself. It is grounded upon the act of quantum origin that is accessible indexically with use of our language. One unique aspect of our language rests upon its appraisal of different grammatical tenses, such as the present progressive tense and the perfect one. Both the tenses are indexical in pointing to some movements in progress or registered in stasis as such out there as admitting no anthropocentric interventions. In particular, the material movement mediated by the transfer of the quantum particles is punctuated by the event of the transfer completed so far that can be referred to in the present perfect tense. At the same time, the transfer of the quantum particles can constantly induce the similar transfer in sequence in the following present progressive tense. Constant update of the present perfect tense in the subsequent progressive tense is agential in keeping no inconsistency between the two left behind in the finished record. That is the inconsistency-mediating cohesion acting between the present perfect and the progressive tenses. A most conspicuous case demonstrating the competency of inconsistency-mediating cohesion may be the origins of life. Molecular recognition widely observed in the biological realm is a specific instance of demonstrating such a molecular cohesion.

To expose causes leading to the delayed arrival of phenylketonuria (PKU) patients at a governmental reference centre (RC), and to describe their clinical characteristics. Material and methods PKU files registered during the past 18 years at the National Institute of Pediatrics in Mexico City were evaluated. Patients were classified into two groups according to their age at arrival: Group I (early reference), patients arriving during the first month of life; and Group II (late reference), those who arrived after thirty days of age. Time and causes of delay were documented.

Vasculitis can be defined as vascular inflammation which is usually immune mediated, leading to structural and functional damage to the vessel wall. Our concept of vasculitis has been built around the events surrounding immune-complex-triggered leukocytoclastic vasculitis, while the role of lymphocyte mediated vasculitis remains largely undefined. This may be due to maintaining a stereotypic image of lymphocytic vasculitis as one associated with vascular necrosis, fibrin deposition and haemorrhage and merely substituting lymphocytes for neutrophils. Our understanding of lymphocytic vasculitis may be advanced by identifying the clinical settings in which such reactions may occur, such as autoimmune skin diseases sharing features with graft vs host disease, as well as recognizing that lymphocyte mediated inflammation may lead to a morphologically distinct group of vasculitides, apart from those associated with angiodestruction. Lymphocytic endovasculitis, lymphocytic lichenoid vasculitis and granulomatous vasculitis are potential examples of lymphocytic vasculitis that differ from the histological pattern seen in association with immune complex leukocytoclastic vasculitis. Ultimately, the proof that these vasculitides are examples of lymphocytic vasculitis will rest on new techniques emerging in molecular pathology that have the capacity of analysing the immunological events beyond the current limitations posed by routine histopathology.

DNA barcoding was proposed in 2003, the Consortium for the Barcode of Life was established in 2004, and the movement has since attracted more than $80 million funding. Here we investigate how many species of multicellular animals have been barcoded. We compare the numbers in a public database (GenBank as of January 2012) with those in the Barcode of Life Database (BOLD) and find that GenBank contains COI (cytochrome c oxidase subunit 1) sequences for ca. 60 000 species while BOLD reports barcodes for ca. 150 000 species. The discrepancy is likely due to a large amount of unpublished data in BOLD. Overall, the species coverage remains sparse, growth rates are low, and the barcode accumulation curve for Metazoa is linear with only 4788 species having been added in 2011. In addition, the vast majority of species in the public database (73%) were barcoded by projects that are unlikely to be related to the DNA barcoding movement. Particularly surprising was the large number of DNA barcodes in GenBank that were not identified to species (Jan 2012: 74%), with insect barcodes often being identified only to order. Of these several hundred thousand have since been suppressed by NCBI because they did not satisfy the iBOL/GenBank early release agreement. Species coverage is considerably better for target taxa of DNA barcoding campaigns (e.g. birds, fishes, Lepidoptera), although it also falls short of published campaign targets. © The Willi Hennig Society 2012.

The present study describes the psychological impact of human papillomavirus (HPV)-related conditions or preventive interventions on Taiwanese women. Women with an HPV-related diagnosis or intervention within the past 3 months were invited to participate in a cross-sectional survey before the receipt of HPV-related diagnostic results. Participants completed a 29-item HPV impact profile (HIP), which was a questionnaire designed to represent the full spectrum of potential HPV-related impacts. The HIP assesses worries and concerns; emotional impact; sexual impact; self-image; partner issues and transmission; interactions with doctors; and control/life impact. The final sample size was 249 women from three hospitals. The mean HIP score (0-100) was normal Pap: 28.2; abnormal Pap: 44.3; CIN: 47.5; genital warts: 62.5; abnormal Pap with high-risk HPV positive: 48.8. This study indicates that significant psychological impact is found in women diagnosed with abnormal Pap, CIN, high-risk HPV test positive and genital wart compared to women with a normal Pap. Women with genital warts had the highest psychological impact scores. This is the first quantitative data that can lay the ground work for future studies that enable the comparison of the effectiveness of different interventions in alleviating the psychological burden of HPV-associated infection and preventive interventions in Taiwan.

A new multipotential pulse technique called square wave voltcoulometry (SWVC), based on the analysis of the difference of converted charge signals obtained between two successive half-cycles when a square wave potential is applied, is developed to study charge-transfer processes taking place in electroactive monolayers. The use of SWVC presents the advantage of giving rise to a peak-shaped response, which evolves to a charge plateau at high square wave pulse amplitudes, from which the total surface excess and the formal potential can be immediately measured for quasi-reversible and reversible processes. This characteristic represents its main advantage versus other multipotential step techniques, which lead to a negligible current under reversible conditions. The formal potential of the electroactive systems can be measured from the peak potential of the SWVC curves, even for quasi-reversible behavior. Moreover, the non-faradic effects on the response can be easily evaluated and avoided as is demonstrated in this paper. Experimental verification of the theoretical predictions is given for reversible and quasi-reversible systems.

The separation of enantiomers of biologically important molecules, such as chiral pharmaceuticals and amino acids, is an important issue because a significant difference in the activity of the enantiomers is usually observed in biological systems. Chiral separations can be carried out by so-called direct methods or by indirect methods following derivatization with a chiral reagent. Many such chiral labeling reagents have been developed for various functional groups, such as amino groups, carboxyl groups, thiols, and hydroxyl groups. This chapter describes methodologies for the indirect HPLC determination of chiral molecules, based upon diastereomer formation. The derivatization, separation, and detection procedures with the chiral benzofurazan-bearing reagents, i.e., 4-(3-aminopyrrolidin-1-yl)-7-(N,N-dimethylaminosulfonyl)-2,1,3-benzoxadiazole (DBD-APy) and 4-(3-isothiocyanatopyrrolidin-1-yl)-7-(N,N-dimethylaminosulfonyl)-2,1,3-benzoxadiazole (DBD-PyNCS), are described as representative examples.

While knowledge of cardiovascular disease (CVD) has improved, it remains low among minority women, thereby contributing to disparities and posing health challenges. Moreover, substantial numbers of women do not recognize that excess weight imposes CVD risk and increases morbidity and decreases survival. In order to test the hypothesis that CVD knowledge is reduced among overweight and obese women, CVD knowledge and weight perception was compared among Hispanic and non-Hispanic white (NHW) women.

This article presents the results of spatial analysis of gastric cancer and its relation to environmental conditions in Shenqiu County, China. Retrospective data on gastric cancer mortality (GCM) were analysed at various spatial scales, with its relation to environmental factors explored at an appropriate scale. The results considered 2 × 2 km(2) grid as the optimal level for characterising GCM due to the highest Moran's I (I = 0.68, p < 0.01). Then, three clustering regions were clearly identified. Meanwhile, GCM was obviously associated with topography (r = -0.11, p < 0.10), farmland (r = 0.11, p < 0.10), population density (r = 0.10, p < 0.10) and river density (r = 0.11, p < 0.10) in the buffered zones. It indicates that spatial grid technique is suitable for characterising GCM in Shenqiu County, and that GCM was geographically associated with environmental conditions. We suggest that preventive measures for controlling the environment-related malignant neoplasm should not be limited in the regions suffering from this disease but be reasonably extended to surrounding areas.

The Nuclear Regulatory Commission has developed a proposed rulemaking for a comprehensive revision of its regulations governing the medical use of byproduct material in 10 CFR Part 35, "Medical Use of Byproduct Material," and a proposed revision of its 1979 Medical Use Policy Statement (MPS). Throughout the development of the proposed rule and MPS, the Commission solicited input from the various interests that may be affected by these proposed revisions. The Commission now plans to solicit comments on the proposed rule and MPS through two mechanisms--publishing the documents in the Federal Register for public comment (scheduled for August 1998); and convening three facilitated public meetings, during the public comment period, to discuss the Commission's proposed resolution of the major issues. The public meetings will be held in San Francisco, California, on August 19-20, 1998; in Kansas City, Missouri, on September 16-17, 1998; and in Rockville, Maryland, on October 21-22, 1998. All meetings will be open to the public. Francis X. Cameron, Special Counsel for Public Liaison, in the Commission's Office of the General Counsel, will be the convener and facilitator for the meetings.

The San Antonio Military Pediatric Center has developed an innovative humanitarian civic assistance (HCA) program. Many medical HCA programs focus on short-term medical interventions and provide transient benefit. To have a more lasting impact, this program focuses on public health surveillance. U.S. military medics conduct random household nutritional surveys and train in austere settings and on rounds in Honduran hospitals. Since 2001, >200 military medics have been trained in population assessment, primary medical care in developing nations, and other skills critical for medical civil-military operations. All activities are coordinated with the host nation. Public health data are collected and reported to Honduran public health leaders, the U.S. Agency for International Development, and nongovernmental organizations, to assist with program and policy development. This innovative project is a potential model to improve both military training and host nation benefit from HCA programs.

Supra-threshold disorders in the form of auditory neuropathy (AN)/auditory dys-synchrony (AD) or central auditory processing disorders (CAPD), a special type of retrocochlear hearing loss; and also children with mild permanent hearing loss (PHL), may be missed on current hearing protocols. Otoacoustic emissions (OAE) and Brain stem evoked response audiometry (BERA), are tests, when used in combination, can indirectly help diagnose the different types of hearing loss. To correlate the parental awareness and the pattern of hearing loss (HL) in children with/without auditory and/or speech problems, using both OAE and BERA as hearing tests for indirect identification of suprathreshold disorders and mild PHL. An Observational Prospective study carried out on 100 children in the age group of 0-5 years, for detection of type of HL by both OAE and BERA and correlating it with parental awareness of HL and speech defects. In 72.22% of children with speech problem only and without any complaints of HL, some form of HL (confirmed HL-OAE refer/BERA fail or auditory neuropathy/auditory dys-synchrony-OAE pass/BERA fail) was diagnosed, whereas 24.07% had no detectable HL on both OAE and BERA pass, and were considered as indirect evidence of CAPD. 3.7% with OAE refer and BERA pass were considered indicative of mild PHL. AN/AD/CAPD/Mild PHL are important cause of speech delay without parental awareness of HL. OAE and BERA together can be used as an indirect evidence of their presence.

We report on the design of an electric tube furnace that can be used for the fabrication of doped glass microsphere lasers. The tube furnace has a short hot zone of length 133 mm and is based on a quartz tube design. Doped laser glass particles, specifically Er:Yb phosphate glass (IOG-2), of approximately 1 microm diameter are blown into the furnace using a 60 ml syringe and microspheres ranging in size from 10 to 400 microm are collected at the output of the tube furnace in a Petri dish. The furnace operates at a wall temperature of approximately 900 degrees C and is capable of making microspheres from glasses with glass transition temperatures of at least 375 degrees C. High quality (Q approximately 10(5)) whispering gallery modes have been excited within the microspheres by optically pumping at 978 nm via a tapered optical fiber.

In this study, we examined the effect of genistein on the severity of dermatitis and level of serum IgE in NC/Nga (NC) mice. NC mice housed in conventional conditions develop spontaneous atopic-like dermatitis; however, oral administration of 20 mg/kg genistein suppresses the development of dermatitis. We also investigated the levels of serum IgE in genistein-treated NC mice and found that the levels were the same as those in control NC mice. We further investigated in vitro IFN-gamma and IL-4 production from spleen cells upon stimulation with anti-CD3 and anti-CD28 mAbs. IFN-gamma production level in NC mice that received 20 mg/kg genistein was significantly lower than that in control NC mice. In contrast, the production level of IL-4 in genistein-treated mice was not significantly different from that in control mice but tended to increase in a dose-dependent manner.

The most common causes of granulomatous inflammation are persistent pathogens and poorly-degradable irritating materials. A characteristic pathological reaction to intratracheal instillation, pharyngeal aspiration, or inhalation of carbon nanotubes is formation of epithelioid granulomas accompanied by interstitial fibrosis in the lungs. In the mesothelium, a similar response is induced by high aspect ratio nanomaterials, including asbestos fibers, following intraperitoneal injection. This asbestos-like behaviour of some engineered nanomaterials is a concern for their potential adverse health effects in the lungs and mesothelium. We hypothesize that high aspect ratio nanomaterials will induce epithelioid granulomas in nonadherent macrophages in 3D cultures.

Patient-administrative systems are becoming increasingly accepted in general practice. The market is now more mature than before. Many physicians are now purchasing computer systems for general practice the second time. Due to national characteristics of the health services the market for these systems is not truly international. In Norway this market is dominated by two makes: Infodoc and Profdoc. In future more physicians will use systems for general practice, and more functions will be added, although the usefulness of these may be a matter for discussion. Furthermore, the importance of telecommunications is expected to increase, and similarly, integration with other services. This development would be furthered by central government action for the purpose of harmonizing and standardizing data, systems and possibly user-interface.

Using the monoclonal antibody Ks8.12 directed against keratins 13 and 16, we have studied psoriatic and trauma-induced hyperproliferation. In normal skin 40 and 64 h after sellotape stripping and in psoriatic lesions, a pronounced suprabasal staining by Ks8.12 was observed. In unstripped normal skin and in the clinically uninvolved skin of psoriatic patients some patchy staining limited to the basal layer was seen. The clear distinction between normal and hyperproliferative skin in keratin expression as detected by Ks8.12 indicates that this antibody may serve as a marker for epidermal proliferation in psoriasis.

Translational control of gene expression is an important component of the regulation of cellular differentiation and development. To elucidate the function of the 3'untranslated region (UTR) of the nanos2 gene in mice, we compared the phenotypes of lacZ knock-in mice with or without a native nanos2 3'UTR and found that this region of the nanos2 gene has a potential role during translational regulation in germ cells. The nanos2-3'UTR functions to repress the translation of mRNA in oocytes, but enhances the production of protein in the male gonads. To further understand the significance of the nanos2 3'UTR in vivo, we generated the mouse line nanos2pA/pA, which lacks this region endogenously. In nanos2(-/pA) mice, the number of germ cell-depleted seminiferous tubules was increased when compared with that of nanos2pA/pA mice, indicating a dose-dependent defect in spermatogenesis. These results suggest that the level of nanos2 protein is critical for normal spermatogenesis, and that this pathway may be regulated through the nanos2-3'UTR. We found that the defects in nanos2pA/pA and nanos2(-/pA) mice were caused by apoptosis of gonocytes in the embryonic gonads and gonocyte/spermatogonia in neonatal testes. In addition, it was noted that the nanos2 expression was restricted to a particular subset of spermatogonia after birth, which indicates that nanos2 plays a role in the maintenance and differentiation of gonocytes/spermatogonia in neonatal testes.

Part 4 of the Ethical and Religious Directives for Catholic Health Care Services--which discusses such controversial issues as abortion, contraception, and assisted reproduction--is informed by a profound respect for human life and the institution of marriage. The controversies are familiar. But many in Catholic healthcare may be less familiar with the principles underlying Church teaching on these issues. Appropriate interpretation and application of these directives require that all concerned be educated in both the theological-ethical and the clinical dimensions of care giving. Directives 38 through 43 deal with reproductive technologies such as in vitro fertilization and surrogacy. Directives 52 and 53 express the Church's consistent teaching on contraceptive interventions. Directives 45 to 48, 50 to 51, and 54 reiterate the Church's firm stance on the inviolability of human life, including nascent human life. However, the directives also say that not all medical interventions resulting in fetal death are prohibited abortions. However, appropriate regard for human life, marriage, and the family require more than mere adherence to the directives' prescriptions and proscriptions. Ethics committees in Catholic healthcare should study clinical data as well as theological materials.

The relationship between the amount of silver-stained nucleolar organizer regions (AgNORs) and the DNA content of interphase neoplastic cells in 63 cases of human endometrial adenocarcinoma was studied. Interphase AgNOR content was determined as the mean AgNOR area per nucleus by image cytometry in silver-stained samples from paraffin-embedded sections. DNA content was evaluated by cytofluorometry on single cells from the same specimen and expressed in c units as DNA ploidy. The mean AgNOR area ranged from 1.26 to 4.48 microns2 and the modal DNA ploidy from 1.90 to 4.00c. No significant associations were found between mean AgNOR area and modal DNA ploidy when analyzed either by linear regression (beta = 0.18; P = 0.15) or as dichotomized variables by chi 2 analysis (chi 2 = 0.82; P = 0.37). On a homogeneous subset of 45 cases of stage I adenocarcinomas we also evaluated the prognostic relevance of AgNOR content and DNA ploidy. In monovariate analysis both parameters were significantly related to patient survival. When the mean AgNOR area and the modal DNA ploidy were entered into regression analysis together with the depth of myometrial invasion and histological grading, they showed an independent, high prognostic value.

The hydroperoxide of linoleic acid (13-HPODE) degrades to 9,12-dioxo-10(E)-dodecenoic acid (DODE), which readily modifies proteins. This study identified the major proteins in MCF7 cells modified by DODE. To reduce false positives, three methods were used to identify DODE-modified proteins. First, cells were treated with a synthetically biotinylated 13-HPODE (13-HPODE-biotin). Modified proteins were enriched by neutravidin affinity and identified by two-dimensional liquid chromatography--tandem mass spectrometry (2D LC-MS/MS). Second, cells were treated with native 13-HPODE. Protein carbonyls were biotinylated with an aldehyde reactive probe, and modified proteins were enriched by neutravidin affinity and identified by 2D LC-MS/MS. Third, using a newly developed DODE antibody, DODE-modified proteins were located by 2D sodium dodecyl sulfate--polyacrylamide gel electrophoresis and Western blot and identified by in-gel digestion and LC-MS/MS. Analysis of the proteins characterized by all three methods revealed a significant overlap and identified 32 primary proteins modified by DODE in MCF7 cells. These results demonstrated the feasibility for the cellular formation of DODE protein-carbonyl adducts that may be future indicators of oxidative stress.

Methods for atomic force microscopy (AFM) imaging of human metaphase chromosomes were -introduced in the present study. Chromosomes from the lymphocytes were fixed and prepared onto glass slides as the chromosome spread, and observed in phosphate-buffered saline by dynamic mode AFM. On the contrary, chromosomes from the human cell line BALL-1 were isolated using the hexylene glycol method, absorbed onto a silane-coated glass slide, and observed in a hexylene glycol buffer solution by dynamic mode AFM. AFM provides three-dimensional topographic images of both fixed and unfixed human chromosomes with height information. The ultrastructural image of a pair of chromatids was also obtained by AFM in a liquid condition. The combined use of the AFM and light microscopy of cytochemically and/or immunocytochemically stained chromosomes is also expected to be useful for studies on the localization of chemical components in relation to the higher-order structure of the chromosomes.

Epidemiological principles and biostatistical techniques are essential when performing research in human populations. This article describes the methods used for designing valid and reliable research and the statistical concepts necessary to analyze data from such studies. Specifically, the overview includes the different epidemiological study designs, sampling techniques, sources of bias encountered in research studies, and statistical tests to assess significance. It is hoped that clinical orthodontists will benefit from this review.

Osteoporosis frequently coexists with other chronic diseases and syndromes of aging, and therefore multimorbidity interactions can potentially complicate its evaluation and treatment. This article reviews osteoporosis comorbidity interactions with select common diseases of aging including cardiovascular, neurologic, and geriatric syndromes, and select commonly used medications by older adults. Using depression as a case example, we describe the complex relationship between osteoporosis, mood, and antidepressant medications, and the implications of these interactions for patients and clinicians.

<b>Aim:</b> Stage I small-cell lung cancer (SCLC) is a potentially curable disease that needs timely and multidisciplinary management. The aim of this study was to evaluate the probability of cause-specific mortality for patients with stage I SCLC. <b>Material &amp; methods:</b> We identified patients in the SEER database and constructed a proportional subdistribution hazard model to evaluate cancer-specific mortality. A nomogram was built based on Fine and Gray competing risk regression model. <b>Results:</b>&#160;A total of&#160;864 stage I SCLC patients were identified. The 5-year cumulative incidence of SCLC-specific mortality was 56.2%, while that for other causes of death was 17.3%. The c-index for the prognostic prediction model was 0.66. Besides, the nomogram was well calibrated. <b>Conclusion:</b> Our nomogram might serve as a reference for clinicians when evaluating the prognosis of stage I SCLC.

Leishmania infantum is endemic in the Maltese archipelago, a group of islands in the Mediterranean which are visited frequently by tourists from Northern European countries. The burden of leishmaniasis is highest in children who may present with cutaneous or visceral manifestations. We describe systematically the manifestations, diagnosis and management of leishmaniasis in children <14 years of age, who had a histopathological diagnosis of leishmaniasis in Malta, from 2004 to 2008. Eleven children were diagnosed with leishmaniasis; 8 children (15-44 months of age) had visceral disease and three (aged 9-13 years) suffered cutaneous infections. Prolonged high grade fever, pallor, hepatosplenomegaly, and pancytopenia were common presenting features of visceralisation. Diagnosis was based on the visualisation of amastigotes from bone marrow aspirates. Pentavalent antimonials were associated with treatment failure in two children, whilst liposomal amphotericin B was curative in all. Children with cutaneous leishmaniasis had dry crusted ulcero-nodular lesions on exposed areas which responded to intra-lesional instillation of sodium stibogluconate or to cryotherapy. Leishmaniasis should be included in the differential diagnosis of fever and hepatosplenomegaly or chronic cutaneous lesions in children who travel to Malta.

The accumulation of advanced glycation end products (AGEs) causes metabolic dysfunction and neuronal cell damage. Methylglyoxal (MG) is a major glycating agent that reacts with basic residues present in proteins and promotes the formation of AGEs. Sciadopitysin, a type of biflavonoid, exerts protective effects against neuronal cell damage; however, the underlying mechanisms have not been studied. This study aimed to investigate the mechanisms underlying the protective effects of sciadopitysin against MG-mediated cytotoxicity in SK-N-MC neuroblastoma cells. Our results demonstrated that pretreatment of SK-N-MC cells with sciadopitysin improved the cell viability that was inhibited by MG and inhibited the apoptosis induced by MG. Sciadopitysin attenuated intracellular Ca²⁺ , NOX4 levels, oxidative stress, and MG-protein adduct levels, and increased nuclear Nrf2 and glyoxalase 1 levels in the presence of MG. These results suggest that sciadopitysin exerts neuroprotective effects against MG-induced death of human SK-N-MC cells via its antioxidative action. This study highlights sciadopitysin as a promising candidate for antioxidant therapy and designing natural drugs against AGE-induced neurodegenerative disorders.

Human factor XII was activated by limited proteolysis with trypsin, and the resulting beta-factor XIIa (Mr = 30,000) was isolated by DEAE-Sephacel column chromatography. The complete amino acid sequence of beta-factor XIIa was then determined on peptides produced by enzymatic digestion with either trypsin, chymotrypsin, or Staphylococcus aureus V8 protease and by chemical cleavage at methionyl and tryptophyl bonds. beta-Factor XIIa is a glycoprotein composed of a heavy chain (243 amino acid residues) and a light chain (9 amino acid residues), and these two chains are held together by a disulfide bond. The carbohydrate is attached to asparagine residue 61 in the heavy chain. The amino acid sequence of the heavy chain shows a high degree of homology to the corresponding regions of other plasma serine proteases, such as plasmin, thrombin, factor IXa and factor Xa, as well as the pancreatic digestive enzymes. These results demonstrate that factor XII is the precursor of a typical serine protease that participates in the coagulation cascade.

The aim of this study was to determine of the effect of casticin, as an anti-inflammatory agent, on an acute lung inflammation in vivo model established through exposure to cigarette smoke (CS). Casticin is a phytochemical from Vitex species such as Vitex rotundifolia and Vitex agnus-castus that was recently shown to exert an anti-inflammatory effect in vivo. To demonstrate the effects of casticin, C57BL/6 mice were whole-body exposed to mainstream CS or fresh air for two weeks and treated with 1, 2, and 10mg/kg casticin via an i.p. injection. Immune cell infiltrations and cytokine productions were assessed from bronchoalveolar lavage Fluid (BALF), and lung histological analysis was performed. Treatment with casticin was observed to significantly inhibit the numbers of total cells, neutrophils, macrophages, and lymphocytes and reduce the levels of proinflammatory cytokines and chemokines in the BALF. In addition, casticin significantly decreased the infiltration of peribronchial and perivascular inflammatory cells and the epithelium thickness. The results of this study indicate that casticin has significant effects on the lung inflammation induced by CS in a mouse model. According to these outcomes, casticin may have therapeutic potential in inflammatory lung diseases, such as chronic obstructive pulmonary disease (COPD).

The detection rate of intracranial aneurysms has increased with the improved availability of non-invasive imaging methods. Moreover, persons who have relatives with intracranial aneurysms increasingly demand imaging to rule out aneurysms. To deal with these problems, radiologists require basic knowledge regarding the detection and treatment of unruptured intracranial aneurysms. The prevalence of aneurysms in the normal population is 2 - 3 %. It increases to 4 - 10 % in persons with one relative with an aneurysm and to about 20 % in persons with two relatives with an aneurysm. The average natural rupture risk is estimated to be 5 % within 5 years of detection. In the individual case it depends on several variables that are discussed here. According to the literature, the risk of endovascular aneurysm treatment is about 5 %. On the basis of these data, the benefit of MRA screening needs to be discussed individually with the patient.

<b>Purpose.</b> This study contrasts views of university students with very low or high food security scores with respect to: obstacles to healthy eating, food pantry use, and managing dietary and educational needs. <b>Method.</b> Comments on open-ended survey questions (<i>n</i>&#8201;=&#8201;1374) were counted, compared, and thematically analyzed to discern differences between the two student groups. <b>Results.</b> Cost concerns were paramount among students with very low food security scores. Students with very low food security experienced significant challenges in reconciling dietary needs and long-term educational goals; this was not problematic among students with high food security. Students from both very low and high food security groups mostly expressed an openness to the campus food pantry, though stigma associated with its use remained a deterrent. <b>Conclusion.</b> While all students face similar challenges to healthy eating, food security status substantially shapes dietary health and the management of dietary and educational needs.

The objective of this paper is to evaluate the efficacy of modern antiemetic therapy for chemotherapy-induced nausea and vomiting for patients receiving multiple-day or high-dose chemotherapy. Published phase II and phase III studies as well as their personal experiences were evaluated by the authors to develop this consensus statement. The largest published experience with multiple-day chemotherapy is with 5-day cisplatin combination chemotherapy. The introduction of 5-HT3 antagonists greatly improved emetic control. However, day 4-5 nausea as well as delayed nausea and vomiting remains a clinical problem despite the inclusion of dexamethasone. A 5-HT3 antagonist plus dexamethasone is the preferred current option for patients receiving high-dose chemotherapy with stem cell transplant. However, the results do not appear as successful as for highly emetic standard-dose chemotherapy.

High-dose chemotherapy (HDCT) has curative potential in relapsed/refractory germ cell tumors (GCT). Due to the complexity of this population and the toxicity of HDCT, we evaluated the association between blood-based systemic inflammatory indexes and the outcome of GCT patients undergoing salvage treatment with HDCT in order to define additional prognostic factors able to orient clinical decision. Baseline characteristics, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and the systemic immune-inflammation index (SII) of 62 patients undergoing HDCT for GCT were retrospectively collected. The aim is to evaluate the correlation between each inflammatory marker (NLR, PLR, and SII) and response to HDCT, overall survival (OS), and progression-free survival (PFS). Using the receiver operating curve to identify the best cutoff values, it was found that patients with GCT with NLR ≥3.3 and SII ≥844,000 had shorter PFS and inferior OS. In the multivariable analysis including inflammatory markers, the International Prognostic Factor Study Group (IPFSG) risk group, age, and previous line of treatment, NLR ≥3.3 and SII ≥844,000 were identified to be independently associated with shorter PFS and OS. Moreover, NLR, PLR, and SII significantly correlate with overall response to HDCT. Associating IPFSG prognostic score to inflammatory markers at baseline of HDCT may improve prognostic information and could help physicians to make more personalized treatment decisions.

We have studied the role of protein synthesis in reconsolidation of memory, activated by reminder at different time period after initial acquisition. Mice were trained in a single-trial fear conditioning task and then subjected to reminder, preceded by injection of protein synthesis inhibitor cycloheximide. It was found that this procedure impaired later memory retrieval if applied at 3, 6 and 24 h as well as 14 and 30 days after initial training. This data suggests that reactivated memory is followed by protein synthesis-dependent reconsolidation both at short (3-6 h) and long (14-30 days) intervals after initial acquisition.

Loosely packed sand that is saturated with water can liquefy during an earthquake, potentially causing significant damage. Once the shaking is over, the excess pore water pressures that developed during the earthquake gradually dissipate, while the surface of the soil settles, in a process called post-liquefaction reconsolidation. When examining reconsolidation, the soil is typically divided in liquefied and solidified parts, which are modelled separately. The aim of this paper is to show that this fragmentation is not necessary. By assuming that the hydraulic conductivity and the one-dimensional stiffness of liquefied sand have real, positive values, the equation of consolidation can be numerically solved throughout a reconsolidating layer. Predictions made in this manner show good agreement with geotechnical centrifuge experiments. It is shown that the variation of one-dimensional stiffness with effective stress and void ratio is the most crucial parameter in accurately capturing reconsolidation.

A high degree of specialization between host and parasite is a well-known outcome of a long history of coevolution, and it is strikingly illustrated in a coordination of their life cycles. In some cases, the arms race ensued at the establishment of a symbiotic relationship results in the adoption of manipulative strategies by the parasite. We have already learned that Steinina ctenocephali, a gregarine living in the alimentary canal of cat flea, Ctenocephalides felis follows its phenology and metamorphosis. Despite these findings the outcome of their symbiotic partnership (mutualist, parasitic or commensal) remains unclear. To address this important question, we measured life history parameters of the flea in the presence of varying infection intensities of gregarine oocysts in laboratory conditions. We found that neither the emergence nor survival rate of fleas was affected by harbouring the gregarines. More surprisingly, our results show that flea larvae infected with gregarines developed faster and emerged earlier than the control group. This gregarine therefore joins the selected group of protists that can modify physiological host traits and provides not only new model taxa to be explored in an evolutionary scenario, but also potential development of control strategies of cat flea.

1. Fertility and hatchability of 3 White Leghorn strains and their 2-way crosses were examined in the 1st laying cycle to evaluate the effects of ageing on mean heterosis, reciprocal effects, additive (A), Z-chromosomne (Z) and heterotic effects (H), as well as on their variances. 2. Fertility and hatchability were evaluated at 37, 47 and 70 weeks of age for hens housed 1 per cage in a randomised block design. The mean heterosis was significant over time and increased with advancing age for both traits. Reciprocal effects were not significant across periods and did not show a consistent trend with age. 3. The pattern of age changes in A, Z and H effects varied among strains, indicating genotypic differences in response to ageing. The additive, heterotic, environmental and phenotypic variances increased at the end of the cycle for both traits, except for the additive variance of hatchability, which increased until 47 weeks of age but declined thereafter. 4. Heritability increased with age for fertility but did not show a consistent pattern across the cycle for hatchability. Genetic variance for fertility and hatchability increased at the end of the cycle, stggesting that improvement in performance during the 1st production cycle of layers could be achieved by selecting animals at older ages.

The K(+)-Cl(-) cotransporters (KCC1-KCC4) encompass a branch of the SLC12 family of electroneutral cation-coupled chloride cotransporters that translocate ions out of the cell to regulate various factors, including cell volume and intracellular chloride concentration, among others. L-WNK1 is an ubiquitously expressed kinase that is activated in response to osmotic stress and intracellular chloride depletion, and it is implicated in two distinct hereditary syndromes: the renal disease pseudohypoaldosteronism type II (PHAII) and the neurological disease hereditary sensory neuropathy 2 (HSN2). The effect of L-WNK1 on KCC activity is unknown. Using Xenopus laevis oocytes and HEK-293 cells, we show that the activation of KCCs by cell swelling was prevented by L-WNK1 coexpression. In contrast, the activity of the Na(+)-K(+)-2Cl(-) cotransporter NKCC1 was remarkably increased with L-WNK1 coexpression. The negative effect of L-WNK1 on the KCCs is kinase dependent. Elimination of the STE20 proline-alanine rich kinase (SPAK)/oxidative stress-responsive kinase (OSR1) binding site or the HQ motif required for the WNK-WNK interaction prevented the effect of L-WNK1 on KCCs, suggesting a required interaction between L-WNK1 molecules and SPAK. Together, our data support that NKCC1 and KCCs are coordinately regulated by L-WNK1 isoforms.

In summary, paraplegia following procedures on the thoracic and thoraco-abdominal aorta is an unpredictable and dreadful complication of multifactorial origin. However, it appears that the major causes of immediate post-operative paraplegia are the depth and duration of ischemia during the period of aortic cross-clamping and failure to identify and reimplant critical vessels that supply blood to the spinal cord. Delayed paraplegia, which has been reported to occur from 1 to 21 days after surgery, is most commonly caused by postoperative hypotension. We believe that the final approach to the prevention of paraplegia following procedures on the thoracic aorta will be one that involves the use of a technique to assure oxygenation of the spinal cord during aortic cross-clamping, through an alternate vascular tree, along with a method that can uniformly depict critical vessels that must be reimplanted at the time of surgery.

Caged neurotransmitters, in combination with focused light beams, enable precise interrogation of neuronal function, even at the level of single synapses. However, most caged transmitters are, surprisingly, severe antagonists of ionotropic gamma-aminobutyric acid (GABA) receptors. By conjugation of a large, neutral dendrimer to a caged GABA probe we introduce a "cloaking" technology that effectively reduces such antagonism to very low levels. Such cloaked caged compounds will enable the study of the signaling of the inhibitory neurotransmitter GABA in its natural state using two-photon uncaging microscopy for the first time.

Temporal fluctuations in plant species coexistence are key to understanding ecosystem state transitions and long-term maintenance of species diversity. Although plant microbiomes can alter plant competition in short-term experiments, their relevance to natural temporal patterns in plant communities is unresolved. In a semiarid grassland, the frequency and magnitude of change in plant species composition through time varied from relatively static to highly dynamic among patches across the landscape. We field tested whether these alternative successional trajectories correlated with alternative plant-soil interactions. In temporally stable patches, we found negative plant-soil feedbacks, where plants grew worse with conspecific than heterospecific soil biota-a mechanism that maintains stability in mathematical models. In contrast, feedbacks in temporally dynamic patches were neutral to positive. Importantly, the magnitude of feedbacks depended on plant frequency, enabling plant species to increase in cover when rare, which theory predicts will promote long-term, stable coexistence. Although our study does not determine the direction of causality, our results reveal a novel link between plant-microbe interactions and temporal stability of plant species coexistence and help to explain 20+ yr of plant abundance dynamics at the patch-to-landscape scales.

Although glycogen synthase kinase 3beta (GSK3beta) is emerging as a prominent drug target in the treatment of neurodegenerative diseases such as Alzheimer's disease (AD) and stroke, very little is known about age-related changes in GSK3beta expression and GSK3beta phosphorylation. Therefore, we examined age-related changes in immunoreactivities for GSK3beta and phosphorylated GSK3beta (pGSK3beta) in the central nervous system. In aged rats, there were significant increases in GSK3beta immunoreactivity in the cell bodies and processes of pyramidal cells in most cortical regions. GSK3beta immunoreactivity was also significantly increased in the pyramidal layer of CA1-3 regions, and the granule cell layer of dentate gyrus. Age-related increases were prominent in lateral septal nuclei, compared to the medial septal nuclei. Interestingly, both GSK3beta and pGSK3beta was increased in the prefrontal cortex, while GSK3beta and pGSK3beta was differentially localized in the cerebellar cortex. The first demonstration of age-related alterations in immunoreactivities for GSK3beta and pGSK3beta in the basal forebrain area and cholinergic projection targets may provide useful data for investigating the pathogenesis of age-related neurodegenerative diseases including AD.

The literature on the oestrous cycle in the bitch is briefly reviewed. 283 bitches were studied in order to develop a procedure by which to determine the time of ovulation, i.e., the optimum time for mating or insemination. Examination of vaginal smears, clinical observations of the bitch and sugar tests of the vaginal discharge showed that the sugar test is the most satisfactory method in dog-breeding and, particularly, that it is simple to use. The mean conception rate of the bitches which were inseminated was 71 per cent.

Drug therapy can lower the blood pressure levels of most hypertensive patients. The agents now in use are usually better tolerated and more effective than many of those available a few years ago. It seems probable that there is a close relationship between the elevated blood pressure and the increased mortality rate of hypertensive persons and that a significant lowering of this pressure would result in a decrease in mortality. In a pertinent study, the average pre-treatment blood pressure of a group of 76 patients with moderate to severe hypertension was 198/119 mm. of mercury in the prone position and 192/118 in the standing position. The patients were treated for a two-year period and with treatment their average pressure over a nine-month period was 164/99 mm. prone and 142/94 mm. standing. Many drugs used for the treatment of high blood pressure have more effect on the lowering of this pressure when the patient is in the standing position. For this reason, the blood pressure, while the patient is standing, should be used as the guide for dosage of these drugs.

We present details of two separate nodular lesions of atypical adenomatous hyperplasia, within one of which a small area of overt hepatocellular carcinoma was detected. The patient was positive for serum hepatitis B surface antigen, and Southern blot analysis revealed that deoxyribonucleic acid from the lesions of hepatocellular carcinoma and surrounding atypical adenomatous hyperplasia showed the same restriction pattern of integrated hepatitis B virus deoxyribonucleic acid, indicating that the two lesions were derived from an identical clone. It was also indicated that the two separate lesions of atypical adenomatous hyperplasia were independently derived through clonal expansion of different cells.

DNA topoisomerase IV removes undesirable topological features from DNA molecules in order to help maintain chromosome stability. Two constructs of 56 and 59 kDa spanning the DNA-cleavage domain of the A subunit of topoisomerase IV from Staphylococcus aureus (termed GrlA56 and GrlA59) have been crystallized. Crystals were grown at 291 K using the sitting-drop vapour-diffusion technique with PEG 3350 as a precipitant. Preliminary X-ray analysis revealed that GrlA56 crystals belong to space group P2(1), diffract to a resolution of 2.9 A and possess unit-cell parameters a = 83.6, b = 171.5, c = 87.8 A, beta = 90.1 degrees, while crystals of GrlA59 belong to space group P2(1)2(1)2, with unit-cell parameters a = 41.5, b = 171.89, c = 87.9 A. These crystals diffract to a resolution of 2.8 A. This is the first report of the crystallization and preliminary X-ray analysis of the DNA-cleavage domain of a topoisomerase IV from a Gram-positive organism.

1. Aldosterone-producing adenomas (APA) of the adrenal gland may be responsive or un-responsive to the renin-angiotensin system. 2. We have described increased expression of renin mRNA in angiotensin-responsive aldosterone-producing adenomas (AII-R-APA) compared with angiotensin-un-responsive aldosterone-producing adenomas (AII-U-APA) and significantly different allelic frequencies of the BglI, TaqI and HinfI restriction fragment length polymorphisms of the renin gene between the two groups. 3. An area including the 5' flanking region -500 bp from exon 1, exon 1 and intron A contained no gross insertions or deletions when studied by a long polymerase chain reaction technique. 4. In the present study, polymerase chain reaction-single strand conformation polymorphism analysis (PCR-SSCP) revealed no single base pair alteration in the proximal promoter region (-600 bp to transcription start) of the renin gene in patients with APA (either AII-U-APA or AII-R-APA) when compared with normal subjects. 5. Therefore, mutations in this regulatory region do not appear to explain the different levels of renin gene expression observed in these two subtypes of APA.

Coronavirus disease 19 (COVID-19) is currently a global pandemic that affects patients with other pathologies. Here, we investigated the influence of treatments for osteoporosis and other non-inflammatory rheumatic conditions, such as osteoarthritis and fibromyalgia, on COVID-19 incidence. To this end, we conducted a cross-sectional study of 2,102 patients being treated at the Rheumatology Service of Hospital del Mar (Barcelona, Spain). In our cohort, COVID-19 cumulative incidence from March 1 to May 3, 2020 was compared to population estimates for the same city. We used Poisson regression models to determine the adjusted relative risk ratios for COVID-19 associated with different treatments and comorbidities. Denosumab, zoledronate and calcium were negatively associated with COVID-19 incidence. Some analgesics, particularly pregabalin and most of the studied antidepressants, were positively associated with COVID-19 incidence, whereas duloxetine presented a negative association. Oral bisphosphonates, vitamin D, thiazide diuretics, anti-hypertensive drugs and chronic non-steroidal anti-inflammatory drugs had no effect on COVID-19 incidence in the studied population. Our results provide novel evidence to support the maintenance of the main anti-osteoporosis treatments in COVID-19 patients, which may be of particular relevance to elderly patients affected by the SARS-CoV-2 pandemic.

Autoimmune hemolytic anemia (AIHA) is an uncommon but clinically significant disorder in primary Sjögren's syndrome (pSS). Among 565 pSS patients hospitalized in Peking University People's Hospital from January 2000 to March 2013, 16 patients were diagnosed with AIHA (2.8% prevalence). AIHA presented at the onset of pSS without overt sicca symptoms in 3 of the 16 patients. Primary biliary cirrhosis (PBC) was more prevalent in the patients with SS-AIHA than in those without (p = 0.007). Edema, fever, and liver involvement occurred significantly more frequently in pSS patients with AIHA than those without AIHA (p = 0.035, p = 0.029, p = 0.024, respectively). The pSS patients with AIHA were more vulnerable to leukopenia and thrombocytopenia than those without AIHA (p = 0.004 and p = 0.001, respectively). Additionally, the levels of complement component 3 (C3) and complement component 4 (C4) were significantly lower in the SS-AIHA group (p = 0.008 and p = 0.037, respectively). Taken together, our results indicate that pSS should be considered in the differential diagnosis of AIHA, even in the absence of sicca symptoms. Among pSS patients, the existence of PBC, cytopenia, or hypocomplementemia suggests a higher risk of suffering from AIHA.

Blood group studies were conducted in 330 patients suffering from gastro intestinal disorders and 180 patients with congenital malformations and compared with normal subjects. Statistical analysis has shown that (a) there is significant correlation between B group and thalassaemia, (b) congenital malformations show higher incidence in B and O groups. It would be pertinent to draw attention to the fact that B group was found to be significantly correlated to duodenal ulcer from the present study contrary to the early reports. In addition, these observations show that blood groups are linked with diseases.

Effector-triggered immunity (ETI) is a common defense strategy used by mammalian host cells that is engaged upon detection of the enzymatic activities of pathogen-encoded proteins or the effects of their expression on cellular homeostasis. However, in contrast to the effector-triggered responses engaged upon bacterial infection, much less is understood about the activation and consequences of these responses following viral infection. Several recent studies have identified novel mechanisms by which viruses engage ETI, highlighting the importance of these immune responses in antiviral defense. We summarize recent advances in understanding how mammalian cells sense virus-encoded effector proteins, the downstream signaling pathways that are triggered by these sensing events, and how viruses manipulate these pathways to become more successful pathogens.

Microbial mats are layered communities of bacteria that form cohesive structures, some of which are preserved in sedimentary rocks as stromatolites. Certain rocks, approximately three and a half thousand million years old and representing the oldest known fossils, are interpreted to derive from microbial mats and to contain fossils of microorganisms. Modern microbial mats (such as the one described here from Matanzas, Cuba) and their fossil counterparts are of great interest in the interpretation of early life on Earth. Since examination of microbial mats and stromatolites increases our understanding of long-term stability and change, within the global environment, such structures should be protected wherever possible as natural science preserves. Furthermore, since they have existed virtually from the time of life's origin, microbial mats have developed exemplary mechanisms of local community persistence and may even play roles in the larger global environment that we do not understand.

We previously reported an assay method for serum glycated aplipoprotein B (G-apo B) using protease. The present study demonstrated correlations between serum G-apo B levels and some other serum parameters, from which a clinical significance of the G-apo B in diabetics was deduced. Serum G-apo B determined by the present method was significantly correlated with glyco-albumin and glycohemoglobin. However, no significant difference was observed between G-apo B levels and total cholesterol and the other lipid items. The mean levels of serum G-apo B in type 2 diabetics with or without hyperlipidemia were significantly higher than in normal subjects (p<0.001). In a comparison of type 2 diabetics with and without hyperlipidemia, the G-apo B levels were not significant between the former and the latter. However, those levels were significantly higher in the nodular and disrupted type of LDL than in the symmetry type of LDL. Even more, the G-apo B levels in the nodular type of LDL were significantly higher than in the disrupted type of LDL. Therefore, the G-apo B levels might be considered an independent risk marker of diabetes hyperlipidemia and atherogenesis.

Postnatal serum concentrations of IgG2a of paternal allotype, measured in congenitally thymusless nude mice, increase with kinetics and titers comparable to their normal congeneic counterparts. Lipid A, the mitogenic part of LPS, stimulates IgG synthesis in nude mice when it is given 7 days after birth. IgG concentrations at 15 days of age are 6- to 8-fold higher than in untreated control nudes; this is considerably lower, however, than in normal mice, which show up to 45-fold higher IgG2ab levels after lipid A treatment. A thymus graft from nearly congeneic donors of the same age, transplanted at 4 days after birth, also stimulates long-lasting IgG synthesis in the nude recipients. If the grafted nudes are injected with lipid A 3 days later, IgG synthesis is further stimulated 8- to 16-fold. The data are discussed in relation to the thymus dependency of IgG production and the conditions for lipid A stimulation.

Rapid advances in our understanding of the molecular basis of cancer development and progression over the past three decades have led to the design of new potential cancer therapies. High throughput target validation and expression studies are expected to yield a powerful arsenal of new cancer treatments, but untangling the complex pathways underlying the major cancer phenotypes remains a significant challenge. A considerable body of evidence in recent years implicates deregulated expression of a single multi-component enzyme, telomerase, as a causative factor at the heart of immortalization in the vast majority of human tumors. This review highlights the potential of telomerase as a target for novel cancer therapies. The potential of exploiting the selectivity of the telomerase family of genes within cancer cells to develop gene therapy strategies is discussed, and the progress towards translating these novel therapeutics from the laboratory to the clinic is reviewed.

The supramammillary region (SuM) is a posterior hypothalamic structure, known to regulate hippocampal theta oscillations and arousal. However, recent studies reported that the stimulation of SuM neurons with neuroactive chemicals, including substances of abuse, is reinforcing. We conducted experiments to elucidate how SuM neurons mediate such effects. Using optogenetics, we found that the excitation of SuM glutamatergic (GLU) neurons was reinforcing in mice; this effect was relayed by their projections to septal GLU neurons. SuM neurons were active during exploration and approach behavior and diminished activity during sucrose consumption. Consistently, inhibition of SuM neurons disrupted approach responses, but not sucrose consumption. Such functions are similar to those of mesolimbic dopamine neurons. Indeed, the stimulation of SuM-to-septum GLU neurons and septum-to-ventral tegmental area (VTA) GLU neurons activated mesolimbic dopamine neurons. We propose that the supramammillo-septo-VTA pathway regulates arousal that reinforces and energizes behavioral interaction with the environment.

525 patients with acute lymphoblastic leukemia (ALL) between the ages of 15 and 44 were treated according to the German study protocol. 41 patients received HLA-identical sibling bone marrow transplants in first remission. Disease-free survival was compared in patients with transplants and patients who were intended for further chemotherapy. After adjusting for potential biases, prognostic profiles of the two groups could be determined, the impact of time-to-transplant bias estimated and similar patients compared after appropriate adjustments. The initial patient characteristics of both groups were quite comparable as was the treatment outcome. The three year probability of disease-free survival was 34% (95% confidence interval: 16% to 52%) in both groups after statistical adjustment.

The free osteocutaneous fibula flap is an established method of reconstruction of maxillary and mandibular defects. The vascularity of the skeletal and the cutaneous components is provided by the peroneal artery via the nutrient artery and the septo- and musculocutaneous perforators. In rare situations, these perforators may arise from other major leg arteries. In such circumstances, the procedure has to be either abandoned or modified so that neither the vascularity of the flap nor the donor limb is compromised. We present a case of an anomalous musculocutaneous perforator, which originated from the proximal part of the posterior tibial artery, passed through the soleus muscle and supplied the skin paddle. The flap was elevated as a single composite unit and was managed by two separate vascular anastomosis at the recipient site, one for the peroneal vessels and the other for the anomalous perforator.

The natriuretic peptides (NPs), atrial natriuretic peptide, and brain natriuretic peptide (BNP) have been shown to have important roles in fluid volume homeostasis and blood pressure regulation. In addition, plasma NP levels are elevated in a number of cardiac pathologies and have been used as biochemical markers of left-ventricular dysfunction (LVD) in small- and large-scale clinical studies. In this review, the authors describe NP physiology and summarize the findings of selected studies that have examined the reliability and feasibility of NP measurement in LVD. In particular, BNP is proposed to be a biochemical marker that may provide a useful and inexpensive screening test of LVD. In addition, the authors discuss possible roles of the NPs in the etiology and progression of LVD. The findings of these studies suggest that the NPs may directly contribute to cardiac pathophysiology and LVD progression.

Escherichia coli diacylglycerol kinase (DAGK) represents a family of integral membrane enzymes that is unrelated to all other phosphotransferases. We have determined the three-dimensional structure of the DAGK homotrimer with the use of solution nuclear magnetic resonance. The third transmembrane helix from each subunit is domain-swapped with the first and second transmembrane segments from an adjacent subunit. Each of DAGK's three active sites resembles a portico. The cornice of the portico appears to be the determinant of DAGK's lipid substrate specificity and overhangs the site of phosphoryl transfer near the water-membrane interface. Mutations to cysteine that caused severe misfolding were located in or near the active site, indicating a high degree of overlap between sites responsible for folding and for catalysis.

miR-138 modulates cardiac morphogenesis in zebrafish. We explored whether a genetic polymorphism in miR-138 might contribute to the occurrence of sporadic congenital heart disease (CHD) and the potential mechanism. We performed a case-control study consisting of 857 CHD cases and 938 non-CHD controls by genotyping miR-138 in a Chinese population. Two SNPs, including rare rs139365823 located in the pre-miR-138 sequence and rs76987351 located in the pri-miR-138 sequence, were identified by sequencing miR-138. The results demonstrated that the genotypes and allele frequencies of the rs139365823 minor allele A were significantly associated with the increased risk of CHD cases overall or in the Tetralogy of Fallot (TOF) subtype, but not with the rs76987351 A/G allele. Real-time PCR data showed that the rs139365823 minor allele A significantly increased the expression of mature miR-138, whereas the rs76987351 minor allele A had the opposite effect. As TOF is caused by severe outflow tract (OFT) development and an alignment defect, we identified Dvl2, involved in OFT development, as a direct target of miR-138. Further, the rs139365823 minor allele A enhanced the miR-138-mediated inhibitory regulation of Dvl2. Taken together, our results demonstrated for the first time that the functional variant rs139365823 in pre-miR-138 altered the expression of mature miR-138 and its inhibitory effect on target genes and conferred the risk for CHD in the population studied here.

The objective of this case-control study was to determine the association between herbal medicine use during pregnancy and perinatal mortality in Tumpat District, Kelantan, Malaysia. Cases were mothers who gave birth from June 2002 to June 2005 with a history of perinatal mortality, while controls were those without a history of perinatal infant mortality. A total of 316 mothers (106 cases and 210 controls) were interviewed. The use of unidentified herbs prepared by traditional midwives and other types of herbal medicines during the first trimester of pregnancy were positively associated with perinatal mortality (OR = 5.24, 95% CI = 1.13; 24.23 and OR = 8.90, 95%, CI = 1.35; 58.53, respectively). The use of unidentified "Orang Asli" herbs and coconut oil during the third trimester of pregnancy were negatively associated with perinatal mortality in Tumpat (OR = 0.10, 95% CI = 0.02; 0.59 and OR = 0.48, 95% CI = 0.25; 0.92, respectively). These findings suggest the use of unidentified "Orang Asli" herbs and coconut oil in late pregnancy are protective against perinatal mortality, while the use of unidentified herbs prepared by traditional midwives and other types of herbal medicines in early pregnancy has an increased risk of perinatal infant mortality. Pharmacological studies to confirm and identify the compounds in these herbs and their effects on the fetus should be conducted in the future.

Pyrethroids are insecticides with low acute toxicity in mammals but their world-wide use for domestic and occupational purposes has caused concern about the risks of long-term exposure. The mammalian toxicity of pyrethroids is related to disturbances of membrane function in neuronal tissues whereas their influence on nonneuronal tissues is poorly understood. Recently, selected pyrethroids were shown to affect the function of rat synaptosomal and leukocyte membranes similarly. The present investigation explores to what extent their influence on the function of intact cells, i. e. isolated rat mast cells, correlates with these membrane interactions.

The use of navigation during joint arthroplasty is believed to allow better placement of components. Gross fracture or stress fracture through navigation tracker pin placement is a complication reported in the literature. This case series presents details of stress fracture of tibial shaft through navigation pin track in 3 patients of 220 cases who underwent total knee arthroplasty at our institution. All the fractures eventually healed after a course of protected weight bearing. As a result, we use smaller-diameter self-tapping and self-drilling pins routinely and avoid placement of pins in the diaphysis and ensure that pins are inserted in different plains during insertion into metaphysis.

As microRNA silencing processes are mediated by the protein Argonaute 2 and for target RNA binding only a short sequence at the microRNA's 5' end (seed region) is crucial, we report a novel inhibitor class: the microRNA-specific Argonaute 2 protein inhibitors that not only block this short recognition sequence but also bind to the protein's active site. We developed a model for rational drug design, enabling the identification of Argonaute 2 active site binders and their linkage with a peptide nucleic acid sequence (PNA), which addresses the microRNA of interest. The designed inhibitors targeting microRNA-122, a hepatitis C virus drug target, had an IC50 of 100 nM, 10-fold more active than the simple PNA sequence (IC50 of 1 μM), giving evidence that the strategy has potential. Due to their lower molecular weight, these inhibitors may show better pharmacokinetic properties than reported oligonucleotide inhibitors, enabling them for potential therapeutic use.

We report here the quantitative expression of a set of immunity-related genes, including TNF family members, chemokine receptors, and transcription factors, in a CD4+ CD3- accessory cell. By correlating gene expression between cell-sorted populations of defined phenotype, we show that the genetic fingerprint of these CD4+ CD3- cells is distinct from dendritic cells, plasmacytoid dendritic cells, T cells, B cells, and NK cells. In contrast, it is highly similar to CD4+ CD3- cells isolated from embryonic and neonatal tissues, with the exception that only adult populations express OX40L and CD30L. We have previously reported that IL-7 signals regulate CD30L expression. In the present study, we show that both neonatal and adult CD4+ CD3- cells express the TNF family member, death receptor 3 (TNFRSF25), and that addition of TL1A (TNFSF15), the ligand for death receptor 3, up-regulates OX40L on neonatal CD4+ CD3- cells. Finally, we demonstrate that this differentiation occurs in vivo: neonatal CD4+ CD3- cells up-regulate both CD30L and OX40L after adoptive transfer into an adult recipient.

A 5-day method for determining the soluble silicon (Si) concentrations in nonliquid fertilizer products was developed using a sodium carbonate (Na2CO3)-ammonium nitrate (NH4NO3) extractant followed by visible spectroscopy with heteropoly blue analysis at 660 nm. The 5-Day Na2CO3-NH4NO3 Soluble Si Extraction Method can be applied to quantify the plant-available Si in solid fertilizer products at levels ranging from 0.2 to 8.4% Si with an LOD of 0.06%, and LOQ of 0.20%. This Si extraction method for fertilizers correlates well with plant uptake of Si (r2 = 0.96 for a range of solid fertilizers) and is applicable to solid Si fertilizer products including blended products and beneficial substances. Fertilizer materials can be processed as received using commercially available laboratory chemicals and materials at ambient laboratory temperatures. The single-laboratory validation of the 5-Day Na2CO3-NH4NO3 Soluble Si Extraction Method has been approved by The Association of American Plant Food Control Officials for testing nonliquid Si fertilizer products.

The aim of this study was to assess the impact of the different subtypes of patient comorbidities on the outcomes of head and neck microvascular reconstruction. A total of 423 patients who underwent head and neck free flap reconstruction in our institution between 2000 and 2010 were included in this retrospective study. The impact of the different subtypes of patient comorbidities (as defined by the Kaplan-Feinstein Index) and other global health status-related factors on free flap success, local and general complications, postoperative mortality and length of stay was assessed in univariate and multivariate analysis. We found no correlation between patient comorbidities and free flap failure. In multivariate analysis, we demonstrated a significant correlation between tobacco consumption (p = 0.04) and local complications. Gastro-intestinal comorbidity (p = 0.005) and malnutrition (p = 0.02) were associated with a higher risk of fistula formation. Diabetes mellitus (p = 0.003), gastro-intestinal (p = 0.02), systemic (p = 0.02) and cardiac comorbidities (p = 0.03) were significant predictors of medical complications. We concluded that the different subtypes of patient comorbidities were relevant predictors of complications in head and neck microvascular reconstruction.

Peroxisome proliferator-activated receptor (PPAR) δ is implicated in the carcinogenesis of several types of cancer. However, the therapeutic efficacy of PPARδ ligands against cancer progression is unclear. Here, we showed that PPARδ modulates the migration and invasion of melanoma cells by up-regulating Snail expression. Activation of PPARδ by GW501516, a specific ligand for PPARδ, significantly increased the migration and invasion of highly metastatic A375SM cells, but not that of low metastatic A375P cells. The migration- and invasion-promoting effects of PPARδ on A375SM cells was associated with increased Snail expression, which was accompanied by a decrease in E-cadherin expression. Furthermore, a significant concentration- and time-dependent increase in the levels of Snail mRNA and protein was observed in A375SM cells (but not A375P cells) treated with GW501516. The effects of GW501516 were almost completely abrogated by a small interfering RNA against PPARδ, suggesting that PPARδ mediates the effects of GW501516. Activation of PPARδ in SK-MEL-2 and SK-MEL-5 (but not SK-MEL-3) melanoma cell lines also led to significant increases in the expression of Snail mRNA and protein, which mirrored the invasive and migratory potential of these cell lines. These results suggest that PPARδ promotes the aggressive phenotype observed in highly metastatic melanoma cells by up-regulating Snail.

The inadvertent transfer and dispersal of non-indigenous marine species via shipping ballast water is of increasing environmental concern. Despite a major global effort to develop new ballast water treatment technologies, their acceptance has been hampered by the lack of suitable indicator species for assessing treatment effectiveness. Resistant dinoflagellate cysts are one proposed test organism, however their use has been limited due to difficulties in assessing their viability after treatment. The paper describes the development of a rapid method to determine the viability of cysts of the dinoflagellate Alexandrium catenella using staining with SYTOX Green and flow-cytometric analysis. The viability of A. catenella cysts was inversely proportional to their ability to take up the stain. There was excellent agreement between cysts measured as viable/non-viable using flow cytometry and cyst viability determined in standard long-term germination tests. Advantages of the flow-cytometric method include high test precision and rapid testing times of < 2 days, compared to > 4 weeks using existing germination methods.

Optical sensors based on fluorescence methods are used in numerous areas of society, ranging from healthcare to environmental monitoring. But the race to elaborate portable and highly sensitive detection systems leads to the huge development of nanomaterial-based sensors. Here, we have fabricated a silicon nanonet, or silicon nanowire (SiNW) network, -based biosensor for DNA hybridization detection by fluorescence microscopy. We demonstrate that by leveraging the properties of the SiNWs such as their large specific surface and the high aspect ratio, these nanonet sensors have significantly enhanced sensitivity and better selectivity compared to plane substrates. The fluorescence signal shows an intensity increasing with the SiNW density on the nanonet and for the denser nanonets, the detection limit for DNA hybridization is 1 nM. The elaborated Si nanonet-based DNA sensors present more than 50% change in fluorescence intensity between complementary DNA and 1 base mismatch DNA which shows their high selectivity. Finally, we have integrated the Si nanonet-based sensor into a DNA chip and we have shown that this selective sensor can be reproduced on a large scale area.

Alpha-tocopherol supplementation is reported to protect against cardiovascular disease and to influence cells involved in atherogenesis, such as monocytes. Interactions between monocytes and vascular endothelial cells occur early in atherogenesis, and adhesion is mediated by integrins. We evaluated the effects of alpha-tocopherol on expression of Mac-1 (CD11b/CD18) by monocytes after stimulation with oxidized low-density lipoprotein (LDL), which is implicated as a potent chemotactic agent in atherogenesis. Incubation of whole blood with oxidized LDL (100 microg/ml) increased Mac-1 expression on monocytes, and preincubation with alpha-tocopherol reduced this upregulation in a concentration dependent manner. In another experiment, whole blood was obtained from healthy adult volunteers after 10 days of alpha-tocopherol administration (600 mg/day) and was incubated with oxidized LDL (100 microg/ml). There was a decrease in the upregulation of Mac-1 compared with that measured before administration. Adherence of oxidized LDL-stimulated monocytes to human umbilical vein endothelial cells was reduced by pretreatment with alpha-tocopherol, and was also inhibited by an anti-CD18 monoclonal antibody. Experiments with protein kinase C inhibitors suggested that reduction of Mac-1 upregulation by alpha-tocopherol was secondary to a decrease of protein kinase C activity. In conclusion, alpha-tocopherol suppressed the upregulation of Mac-1 expression on monocytes by oxidized LDL.

Most forebrain GABAergic interneurons in rodents are born during embryonic development in the ganglionic eminences (GE) and migrate tangentially into the cortical plate. A subset, however, continues to be generated postnatally in the subventricular zone (SVZ). These interneurons populate the olfactory bulb (OB) reached via migration in the rostral migratory stream (RMS). Employing transgenic mice expressing EGFP in 5-HT(3)-positive neurons, we identified additional migratory pathways in the early postnatal brain. Time-lapse imaging experiments revealed massive migration of EGFP-positive cells from the SVZ into numerous forebrain regions, including cortex, striatum, and nucleus accumbens. The neuronal fate of the migratory EGFP-labeled cells was indicated by their doublecortin (DCX) expression. Birthdating experiments, by using 5-bromo-2'-deoxyuridine (BrdU) and retrovirus-based experiments, provided evidence that migrating neuroblasts were born in the SVZ postnatally and developed a distinct GABAergic phenotype. Our results demonstrate that the SVZ is a reservoir of GABAergic interneurons not only for the OB, but also for other cortical and subcortical areas.

In a series of 17 cases of Leigh's disease it has been observed that there is a close correlation between damage to the inferior olivary nuclei by vasculo-necrotic change and loss of Purkinje cells in the cerebellar cortex. It is suggested that this association may be explained on the basis of the selective loss of climbing fibres causing increased firing activity of Purkinje cells with consequent excessive entry of calcium ions. In these circumstances control of calcium ion regulation in the presence of reduced energy production, which is the basis of this metabolic disease, would be expected to put these cells' survival seriously at risk.

Serotonin synthesis critically depends on plasma levels of tryptophan (TRP). Earlier studies have shown that for mood and cognitive benefits to occur, the ratio between TRP and other large neutral amino acids (LNAA) has to be increased by approximately 40 %. The present study investigated the dose-dependent effects of a TRP-rich hydrolysed protein (egg-protein hydrolysate, EPH) on the plasma TRP:LNAA. Moreover, it was investigated whether EPH could increase TRP:LNAA in the presence of 2 g of milk protein (MP). In a randomised double-blind crossover design, plasma amino acids were measured every 30 min for 3·5 h after ingestion of a drink containing either three different doses of 4, 8 and 12 g EPH containing 270, 560 or 800 mg of TRP, respectively, the combination of 4 g EPH and 2 g MP (74 mg TRP), or 4 g MP (148 mg TRP) in twenty healthy subjects with a mean age of 52 years. All three EPH doses caused significant increases of TRP:LNAA above 40 % at 30, 60 and 90 min after consumption in a dose-dependent manner. Compared with the 4 g EPH, the increase in TRP:LNAA in the 4 g EPH with 2 g MP condition was significantly lower at 60 min (63 v. 44 %, P < 0·001) and did not differ significantly at 90 min (58 v. 53 %, P>0·05). The present study showed that a low dose of 4 g EPH with even the addition of 2 g MP was sufficient to increase the ratio of TRP:LNAA above 40 %. Thus, EPH offers a viable ingredient to increase TRP availability.