Anti-Inflammatory, Anti-Diabetic, Anti-Oxidant and Cytotoxicity Assays of South African Herbal Teas and Bush Tea Blends.
South Africa is home to a variety of herbal teas, such as bush tea (Athrixia phylicoides DC.), honeybush tea (Cyclopia intermedia E. Mey and C. subternata Vogel), special tea (Monsonia burkeana Planch. ex Harv.), and rooibos tea (Aspalathus linearis (Burm.f.) R. Dahlgren) that are known to possess anti-oxidant, anti-inflammatory and anti-diabetic properties. The objective of this study was to determine the in vitro anti-oxidant activity of selected tea blends using 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays, as well as to assess their anti-inflammatory properties using the 15-lipoxygenase inhibitory assay. Furthermore, the study measured glucose utilisation in C2C12 myotubes. Lastly, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was used to test the safety of the tea extracts on Vero cells (African green monkey kidney cell line). Special tea and its blend with bush tea exhibited potent anti-oxidant and anti-inflammatory activity. The blending of bush tea with special tea at different ratios resulted in increased anti-oxidant activity. Although special tea had a level of cell toxicity, its toxicity was lowered during blending. All of the tea samples showed anti-diabetic effects, although with less potency as compared to insulin. The current investigation supports the use of blended herbal teas, and the positive anti-inflammatory effect of special tea warrants further research.


Long-term in vitro growth of a heterologous mixed Müllerian tumor of the ovary.
This paper describes the long-term culture and characterization of a human ovarian heterologous mixed Müllerian tumor, initially acquired from a nude mouse heterotransplant. Microscope examination of the heterotransplants revealed that epithelial and heterologous elements of the original tumor were serially transplanted. After an initial 2- to 4-day lag period, the cells entered a linear growth phase until confluence was reached and the cells passaged. The cells have been in culture for 15-18 months, and passaged approximately 8-10 times. DNA flow cytometry of the cultures revealed the presence of two hyperdiploid cell populations, presumably the epithelial and heterologous portions of the tumor. The cells remain tumorigenic in the nude mouse and form colonies on semisolid medium, attesting to the maintenance of their neoplastic identity following long-term culture. Immunofluorescent labeling for collagen revealed the presence of types I, III, V. The presence of types I, III and V collagen was also confirmed using gel electrophoresis of radiolabeled collagen from these cells. This is consistent with bony tissue, since fibroblasts make types I and III, chondrocytes, type II. In view of the poor prognosis of patients bearing these aggressive tumors, this in vitro tumor cell line could serve as a useful model for the study of this type of carcinoma.


[The use of diuretics in kidney disease].
Diuretics are an important part of the therapy for a number of medical conditions such as heart, liver and kidney failure and hypertension. This article presents updated knowledge on the use of diuretics in kidney disease. The article is based on a literature search in PubMed, information obtained from textbooks on neurophysiology and kidney disease and on the authors' clinical experience. Kidney disease affects the pharmacokinetics and pharmacodynamics of diuretics, and this must be taken into account when selecting a drug and determining the dosage. This applies particularly to nephrotic syndrome and severe chronic renal disease (GFR < 30 ml/min/1.73 m²). Knowledge of the pharmacology of diuretics is crucial to the rational use of diuretics in renal disease. Dose titration under close clinical monitoring and an optimal dosage interval make it possible to find the lowest possible effective dose and reduce the occurrence of side effects.


Frugivore-Mediated Selection in A Habitat Transformation Scenario.
Plant-animal interactions are strong drivers of phenotypic evolution. However, the extent to which anthropogenic habitat transformation creates new selective scenarios for plant-animal interactions is a little explored subject. We examined the effects of native forest replacement by exotic Eucalyptus trees on the frugivore-mediated phenotypic selection coefficients imposed by the relict marsupial Dromiciops gliroides upon traits involved in frugivore attraction and germination success of the mistletoe Tristerix corymbosus (Loranthaceae). We found significant gradients for seed weight and sugar content along the native - transformed habitat gradient. While selection for larger seed weight was more relevant in native habitats, fruits with intermediate sugar content were promoted in transformed habitats. The spatial habitat structure and microclimate features such as the degree of sunlight received influenced the natural selection processes, as they correlated with the phenotypic traits analysed. The response of this plant-frugivore interaction to human disturbance seemed to be context-dependent, in which extremely transformed habitats would offer new opportunities for natural selection on dispersal-related traits. Even in recent transformation events like this, human disturbance acts as a strong contemporary evolution driver.


Identification of the template binding polypeptide in the pea chloroplast transcriptional complex.
We have identified the template-binding polypeptide in the pea chloroplast transcriptional complex by photoaffinity labelling. This polypeptide has an apparent molecular weight of about 150 kDa and binds to both, chloroplast ribosomal (16S rRNA) and messenger (psbA) promoters. The 16S rRNA and psbA promoters were amplified from chloroplast DNA by the polymerase chain reaction and labelled with a photoactive analogue of TTP, 5-bromodeoxy UTP, as well as with alpha-32P-dCTP. Using the filter-binding assay, the conditions for binding of the RNA polymerase complex to chloroplast promoters were optimized. The polypeptide directly interacting with the template was photo-crosslinked to it and resolved by denaturing gel electrophoresis. The photoaffinity labelling of the 150 kDa polypeptide was dependent on photoactivation by UV irradiation, and the presence of chloroplast promoters. Competition experiments showed that the protein formed a strong interaction with the plastid promoters which could not be displaced by lambda-phage DNA or synthetic polynucleotides. The photo-crosslinked and nuclease-treated promoter-polypeptide complex was resistant to further digestion with DNase and RNase, but could be hydrolyzed by Proteinase K. Binding of the promoters by the 150 kDa polypeptide could not be surpressed by transcription inhibitors like rifampicin and alpha-amanitin. However, heparin (0.001%) inhibited the formation of the enzyme-promoter complex, and interfered with the photoaffinity labelling of the 150 kDa polypeptide. The extent of photoaffinity labelling of 150 kDa polypeptide exhibits some degree of correlation to total transcriptional activity under various salt concentrations. The results demonstrate that the 150 kDa polypeptide is a functional template binding polypeptide of the pea chloroplast transcription complex.


Benefits of Genomic Insights and CRISPR-Cas Signatures to Monitor Potential Pathogens across Drinking Water Production and Distribution Systems.
The occurrence of pathogenic bacteria in drinking water distribution systems (DWDSs) is a major health concern, and our current understanding is mostly related to pathogenic species such as Legionella pneumophila and Mycobacterium avium but not to bacterial species closely related to them. In this study, genomic-based approaches were used to characterize pathogen-related species in relation to their abundance, diversity, potential pathogenicity, genetic exchange, and distribution across an urban drinking water system. Nine draft genomes recovered from 10 metagenomes were identified as Legionella (4 draft genomes), Mycobacterium (3 draft genomes), Parachlamydia (1 draft genome), and Leptospira (1 draft genome). The pathogenicity potential of these genomes was examined by the presence/absence of virulence machinery, including genes belonging to Type III, IV, and VII secretion systems and their effectors. Several virulence factors known to pathogenic species were detected with these retrieved draft genomes except the Leptospira-related genome. Identical clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins (CRISPR-Cas) genetic signatures were observed in two draft genomes recovered at different stages of the studied system, suggesting that the spacers in CRISPR-Cas could potentially be used as a biomarker in the monitoring of Legionella related strains at an evolutionary scale of several years across different drinking water production and distribution systems. Overall, metagenomics approach was an effective and complementary tool of culturing techniques to gain insights into the pathogenic characteristics and the CRISPR-Cas signatures of pathogen-related species in DWDSs.


Chromosomal diversification and karyotype evolution of diploids in the cytologically diverse genus Prospero (Hyacinthaceae).
Prospero (Hyacinthaceae) provides a unique system to assess the impact of genome rearrangements on plant diversification and evolution. The genus exhibits remarkable chromosomal variation but very little morphological differentiation. Basic numbers of x = 4, 5, 6 and 7, extensive polyploidy, and numerous polymorphic chromosome variants were described, but only three species are commonly recognized: P. obtusifolium, P. hanburyi, and P. autumnale s.l., the latter comprising four diploid cytotypes. The relationship between evolutionary patterns and chromosomal variation in diploids, the basic modules of the extensive cytological diversity, is presented. Evolutionary inferences were derived from fluorescence in situ hybridization (FISH) with 5S and 35S rDNA, genome size estimations, and phylogenetic analyses of internal transcribed spacer (ITS) of 35S rDNA of 49 diploids in the three species and all cytotypes of P. autumnale s.l. All species and cytotypes possess a single 35S rDNA locus, interstitial except in P. hanburyi where it is sub-terminal, and one or two 5S rDNA loci (occasionally a third in P. obtusifolium) at fixed locations. The localization of the two rDNA types is unique for each species and cytotype. Phylogenetic data in the P. autumnale complex enable tracing of the evolution of rDNA loci, genome size, and direction of chromosomal fusions: mixed descending dysploidy of x = 7 to x = 6 and independently to x = 5, rather than successive descending dysploidy, is proposed. All diploid cytotypes are recovered as well-defined evolutionary lineages. The cytogenetic and phylogenetic approaches have provided excellent phylogenetic markers to infer the direction of chromosomal change in Prospero. Evolution in Prospero, especially in the P. autumnale complex, has been driven by differentiation of an ancestral karyotype largely unaccompanied by morphological change. These new results provide a framework for detailed analyses of various types of chromosomal rearrangements and karyotypic variation in polyploids.


Assessment of follow-up for low-grade cytological abnormalities in the National Breast and Cervical Cancer Early Detection Program, 2000-2005.
To assess the management of women in the National Breast and Cervical Cancer Early Detection Program with low-grade squamous intraepithelial lesions (LSIL) before and after the American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines for management of abnormal cytology were published in 2002. We examined the follow-up for 22,342 women with LSIL during 2 periods: 2000-2002 and 2003-2005. The percentage of providers who followed the recommended guidelines with colposcopy for an LSIL Pap test result increased by 9% from the pre-ASCCP to the post-ASCCP period. An increase was seen in every age and racial/ethnic group. Younger women (<30 years) and white women were more likely than comparison groups to be followed by colposcopy rather than a repeat Pap test. The increase in percentage of women having colposcopy in 2003, 1 year after the new guidelines were published, suggests a change in provider practices consistent with those guidelines.


Buried bumper syndrome: cut and leave it alone!
Buried bumper syndrome (BBS) occurs due to the overgrowth of gastric mucosa over the inner bumper of a gastrostomy tube. Various therapeutic approaches have been described for the management of BBS. However, no standardized clinical protocol deals with this complication. The authors describe their experience of dealing with BBS. Case notes of the patients undergoing percutaneous endoscopic gastrostomy (PEG) between February 2002 and December 2007 at their institute were reviewed retrospectively, and cases of BBS were analyzed. During this 71-month period, 356 PEG procedures were preformed. Seven patients with BBS were identified from the case note review (incidence of 1.97%). Attempts at endoscopic removal of the buried bumper were made but unfortunately failed. In view of the patients' associated comorbidity, the buried bumpers in these patients were left in situ, and a new PEG was inserted adjacent to the first site in 6 individuals. In 1 patient, a jejunal extension tube was inserted through the original PEG tube for feeding. No complications from the buried bumper arose in these patients during a median follow-up of 18 months (range, 1-46 months). Some patients being fed by a PEG tube are in poor general health and have significant comorbidities. They are therefore poor candidates for surgical or endoscopic removal of a buried bumper. In such patients, leaving the internal bumper in situ should be considered as a relatively safe treatment option.


Myelodysplastic syndrome.
The last decade has witnessed a multistep evolution in the understanding of the natural history, clinical manifestations, and some of the molecular mechanisms that underlie the ineffective hematopoiesis and leukemic transformation in the myelodysplastic syndrome (MDS). The international prognostic scoring system, FAB, and WHO classifications have helped define specific subgroups with their characteristic cytogenetic, molecular and immunological abnormalities. Until recently the mainstay of the treatment has been entirely supportive with blood and platelet transfusions. What is increasingly manifest now is the considerable excitement generated by the emergence of novel therapeutic strategies based on painstaking research findings from the laboratories. In Section I, Dr. Alan List reviews the therapeutic strategies with the specific emphasis on the relevance of molecular mechanism of apoptosis and targeted therapies using small molecules. Of particular interest is the excitement surrounding the clinical benefit obtained from potent immunomodulatory derivative (IMiD) of thalidomide CC5013. The review provides an update of the role of small molecule inhibitors of VEGF receptor tyrosine kinase, arsenic trioxide, oral matrix metalloprotease inhibitors, farnesyl transferase inhibitors, and imatinib mesylate in the treatment of MDS subgroups. In Section II, Dr. Steven Gore describes the results of clinical trials of inhibitors of DNA methylation such as 5 azacytidine (5 AC) and 5-aza 2-deoxycytidine (Decitabine). The review also provides an update on the rationale and results obtained from the combination therapy using histone deacetylases (HDAC) and DNA methyltransferase inhibitors in the treatment of MDS. In Section III, Professor Ghulam Mufti and Dr. Aloysius Ho describe the role of bone marrow transplantation with particular emphasis on recent results from reduced-intensity conditioned transplants, exploiting the graft versus leukemia effect without significant early treatment-related mortality. The section provides an update on the results obtained from the manipulation of the host's immune system with immunosuppressive agents such as ALG and/or cyclosporine A.


Systematic review of descriptive studies that investigated associated factors with the management of incontinence in older people in care homes.
Incontinence is prevalent among older populations and residents in care homes. This paper is a review of descriptive studies that investigated associated factors related to managing urinary incontinence in older people in care homes. A systematic literature review was undertaken. MEDLINE and CINHAL were searched from 1996-2010 using the Cochrane Incontinence Review Group search strings for urinary and faecal incontinence including all research designs. Sixteen studies were identified that reported on associated factors related to comorbidities, management preferences, policies, staff views and knowledge or methodological studies. Non-invasive methods involving toileting and use of pads were common management approaches. No studies aimed at maintaining continence were identified. Factors associated with incontinence need to also be considered when planning and managing care for individuals, and developing and designing systems of care within care homes. Further study in care home populations to change or inform practice and provide effective care is warranted. Preventive studies that maintain continence are required. Older people and their families should be involved with decisions regarding their preferred care, goals, management and outcomes for managing incontinence, promoting or maintaining continence.


Formation mechanism and spectroscopy of C6H radicals in extreme environments: a theoretical study.
This study examined the reaction mechanisms of singlet (rhombic) and triplet (linear) C4 with acetylene by using accurate ab initio CCSD(T)/CBS//B3LYP/6-311G(d,p) calculations followed by a kinetic analysis of various reaction pathways and computations of relative product yields in combustion and planetary atmospheres. These calculations were combined with the Rice-Ramsperger-Kassel-Marcus (RRKM) calculations of reaction rate constants for predicting product-branching ratios, which depend on the collision energy under single-collision conditions. The results demonstrate that the initial reaction begins with the formation of an intermediate 3i2 with an entrance barrier of 3.0 kcal mol-1 and an intermediate 1i1 without entrance barriers. The product-branching ratios obtained by solving kinetic equations with individual rate constants calculated using the RRKM and variational transition-state theories for determining the collision energies between 5 kcal mol-1 and 25 kcal mol-1 demonstrate that l-C6H + H is the dominant reaction product, whereas HC3C3 + H, l-C6 + H2, c-C6H + H, and c-C6 + H2 are minor products. The electronic absorption spectra of solid neon matrices in the range of 17 140-22 200 cm-1 were obtained by Maier et al., and the optimized ground and excited state structures of C6H were used to simulate the absorption spectra by one-photon excitation equations. The displaced harmonic oscillator approximation and the Franck-Condon approximation were used to simulate the absorption spectrum of the B2Π ← X2Π transition of C6H. This indicates that the vibronic structures were dominated by one of the six active completely symmetric modes, with v3 being the most crucial.


Human CD40 ligand-expressing type 3 innate lymphoid cells induce IL-10-producing immature transitional regulatory B cells.
Type 3 innate lymphoid cells (ILC3s) are involved in maintenance of mucosal homeostasis; however, their role in immunoregulation has been unknown. Immature transitional regulatory B (itBreg) cells are innate-like B cells with immunosuppressive properties, and the in vivo mechanisms by which they are induced have not been fully clarified. We aimed to investigate the ILC3-B-cell interaction that probably takes place in human tonsils. ILC3s were isolated from peripheral blood and palatine tonsils, expanded, and cocultured with naive B cells. Tonsillar ILC3s and regulatory B cells were visualized with immunofluorescence histology. ILC3 frequencies were measured in tonsil tissue of allergic and nonallergic patients and in peripheral blood of allergic asthmatic patients and healthy control subjects. A mutually beneficial relationship was revealed between ILC3s and B cells: ILC3s induced IL-15 production in B cells through B cell-activating factor receptor, whereas IL-15, a potent growth factor for ILC3s, induced CD40 ligand (CD40L) expression on circulating and tonsillar ILC3s. IL-15-activated CD40L+ ILC3s helped B-cell survival, proliferation, and differentiation of IL-10-secreting, PD-L1-expressing functional itBreg cells in a CD40L- and B cell-activating factor receptor-dependent manner. ILC3s and regulatory B cells were in close connection with each other in palatine tonsils. ILC3 frequency was reduced in tonsil tissue of allergic patients and in peripheral blood of allergic asthmatic patients. Human CD40L+ ILC3s provide innate B-cell help and are involved in an innate immunoregulatory mechanism through induction of itBreg cell differentiation, which takes place in palatine tonsils in vivo. This mechanism, which can contribute to maintenance of immune tolerance, becomes insufficient in allergic diseases.


Comparison of 3 ankle braces in reducing ankle inversion in a basketball rebounding task.
Lateral ankle injury incidence rates are very high in the sport of basketball, with a significant proportion occurring during rebounding. Ankle braces are often used as preventative and rehabilitative techniques in the hope of minimizing the likelihood of experiencing excessive ankle inversion. This study aims to evaluate the effect of different ankle braces in preventing ankle inversion during a basketball rebounding task. Sixteen subjects participated in the study (11 males, 5 females; mean age = 26.94 years, SD = 5.32; mean height 1.72 m, SD = 0.08; mean weight 73.95 kg, SD = 13.68). Participants performed a simulated rebounding task in multiple braced conditions: unbraced (UB), Ossur Formfit (OF), Talarmade Ankleguard Air/Gel Stirrup (TAG) and Bauerfeind Malleoloc (BF). Ankle and foot inversion angles, ankle inversion moments and peroneus longus EMG activity were recorded and analysed to determine the effectiveness of each condition to resist inversion. All braced conditions reduced ankle and foot inversion angles compared to UB. In the non-dominant limb, OF showed reduced maximum ankle inversion compared to BF (non-dominant mean difference = 0.630°, p < 0.001) and reduced foot inversion compared to TAG (non-dominant mean difference = 0.966°, p = 0.035). Compared to UB, OF and TAG increased ankle inversion moments in the dominant ankle and showed decreases in the non-dominant ankle. BF reduced mean peak peroneus longus EMG activity compared to all other trials. Whilst statistically significant differences that were demonstrated between several braced conditions are relatively small, they are clinically significant knowing that the maximum barefoot inversion whilst standing is less than 17 degrees.


The influence of geopolitical change on the well-being of a population: the Berlin Wall.
Social cohesion is recognized as a fundamental condition for healthy populations, but social cohesion itself arises from political unity. The history of the Berlin Wall provides a unique opportunity to examine the effects of partition on social cohesion and, by inference, on health. This ethnographic study consisted of examination of the territory formerly occupied by the Wall, formal and informal interviews with Berlin residents, and collection of cultural documents related to the Wall. Transcripts, field notes, and documents were examined by means of a keyword-in-context analysis. The separation of Berlin into 2 parts was a traumatic experience for the city's residents. After partition, East and West Germany had divergent social, cultural, and political experiences and gradually grew apart. The demolition of the Wall--the symbol and the instrument of partition--makes possible but does not ensure the reintegration of 2 populations that were separated for 40 years. The evolution of a new common culture might be accelerated by active attempts at cultural and social exchange.


Herpes viruses and tumours in kidney transplant recipients. The role of immunosuppression.
Herpes virus infections are frequent in renal transplant recipients. Some herpes viruses are not only responsible for life-threatening infections and renal graft injury but can also increase the risk of malignancy. Three herpes viruses, namely cytomegalovirus (CMV) or human herpes virus 5, Epstein-Barr virus (EBV) or herpes virus 4 and human herpes virus 8 (HHV8), may play an oncogenic role. The oncogenic role of CMV is controversial. However, there is growing evidence showing that CMV can infect cancer cells and favour their resistance to the immune system and chemotherapy. B cells infected by EBV can have uncontrolled proliferation eventually resulting in polyclonal polymorphic or monomorphic post-transplant lymphoproliferative diseases (PTLD), which are particularly frequent in children and in EBV-negative recipients. In some ethnicities, the carriers of HHV8 are susceptible to develop Kaposi's sarcoma after transplantation. The intensity of immunosuppression therapy plays a critical role in mediating infections from oncogenic herpes viruses. However, the type of immunosuppressive drugs can also influence the risk of virus-mediated neoplasias. An aggressive induction therapy aimed at depleting lymphocytes may favour the reactivation and dissemination of oncogenic herpes viruses, while anti-CD25 monoclonal antibodies have little impact on virus reactivation. Calcineurin inhibitors can increase the risk of viral infections and malignancy. Mycofenolate salts may perhaps protect from EBV-related PTLD. Finally, the inhibitors of the mammalian target of rapamycine may reduce the risk of viral disease by inhibiting the cascade of kinases that govern the proliferation and replication of oncogenic herpes viruses.


Prospect evaluation as a function of numeracy and probability denominator.
This study examines how numeracy and probability denominator (a direct-ratio probability, a relative frequency with denominator 100, a relative frequency with denominator 10,000) affect the evaluation of prospects in an expected-value based pricing task. We expected that numeracy would affect the results due to differences in the linearity of number perception and the susceptibility to denominator neglect with different probability formats. An analysis with functional measurement verified that participants integrated value and probability into an expected value. However, a significant interaction between numeracy and probability format and subsequent analyses of the parameters of cumulative prospect theory showed that the manipulation of probability denominator changed participants' psychophysical response to probability and value. Standard methods in decision research may thus confound people's genuine risk attitude with their numerical capacities and the probability format used.


A Brief Parenting Intervention to Enhance the Parent-Child Relationship in Hong Kong: Harmony@Home.
There is a dearth of high-level evidence for brief programs designed to promote positive parent-child relationships in nonwestern cultures. We present a pilot randomized controlled trial of a four-session intervention to enhance the parenting skills that promote a positive relationship with pre-adolescent children in Hong Kong. Our intervention, Harmony@Home, utilized Cunningham's culturally appropriate coping modeling, problem-solving approach to change parental behavior. Our objective was to evaluate the feasibility, acceptability and initial evidence of benefit of the intervention. We blindly randomized 150 Hong Kong parents of children 10-13 years of age to (a) a Harmony@Home intervention group, (b) a waitlist control group, or (c) a third active intervention which shared the control group. Immediately following the intervention, we report increases in satisfaction with the parent-child relationship, one of the targeted parenting behaviors and family harmony, for the Harmony@Home group versus control group. However, only the results from satisfaction with the parent-child relationship were significant at 3-months post intervention. Most respondents reported high levels of program satisfaction. The results provide preliminary evidence that this parenting intervention is culturally acceptable for a nonwestern general population, is feasible for implementation in a community setting and shows evidence of benefit. This intervention is concordant with public health priorities because of the global importance of the parent-child relationship as a protective factor for adolescent outcomes, the need for culturally-appropriate interventions for nonwestern populations, and design characteristics that promote dissemination.


Experimental evaluation of spectral efficiency from a circular array antenna producing a Laguerre-Gauss mode.
We present the four-dimensional volumetric electromagnetic field measurements (x, y, z and frequency) of the complex radiated field produced by an 8-element circular antenna array. The array is designed to produce a Laguerre-Gauss (LG) mode l = +1 over the frequency range of 9-10 GHz. We evaluate our findings in terms of far-field LG mode purity and spectral efficiency in terms of the quadrature amplitude modulation (QAM) modulation scheme that can be supported. The application of LG modes in radio systems is as a means of multiplexing several data streams onto the same frequency, polarization and time slot, thus making a highly spectrally efficient transmission system or enhancing radar systems by means of exploiting mode behaviour as an additional degree of freedom. Our results show that for the circular antenna array, we find that mode purity is sufficient to support binary phase shift keying or quadrature phase shift keying modulation over a 0.3 GHz bandwidth, which corresponds to a spectral efficiency of 1.5 b s-1 Hz-1 per mode. Closer to the antennas' design frequency, 256QAM modulation may be supported over a 0.05 GHz band, and which corresponds to a spectral efficiency of 11 b s-1 Hz-1 per mode. We anticipate the practical insights provided in this paper contribute to the successful design of such systems.


Alcohol and suicidal behavior: what is known and what can be done.
Research on associations between substances of abuse and suicidal behaviors is a large, complex area. Herein, alcohol, the most commonly abused intoxicant worldwide, is examined with a focus on two topics: (1) acute use of alcohol (AUA) shortly prior to suicidal behavior; and (2) more chronic alcohol use disorder (AUD) and suicidal behavior. First, a brief summary of what is known about AUA, AUD, and suicidal behavior is provided. Next, we draw on preliminary evidence, practical considerations, and our own experience to offer recommendations for intervention research that may lower risk associated with AUA and AUD. The literature on AUD and suicidal behavior is more developed, thus we discuss separately research designed to: (1) prevent individuals with AUD with suicidal ideation from engaging in suicidal behavior; and (2) prevent individuals with AUD who have made a suicide attempt from reattempting. Our focus is on clinical intervention strategies for individuals at risk for suicidal behavior that use alcohol or have developed AUD. We also focus on applied research that may directly lead to practical prevention efforts. Although clinical interventions are important components of a comprehensive suicide prevention strategy, they should be complemented with primary prevention efforts.


Graft-vs-host disease as a cause of enlargement of the epiglottis in an immunocompromised child.
We report a rare case of dyspnea due to enlargement of the epiglottis in a severely immunocompromised patient. The child underwent a previous tracheostomy at another hospital because of respiratory distress under the diagnosis of acute epiglottitis. The patient was subsequently decannulated without incident. One year later, the child developed a new episode of dyspnea with inspiratory stridor. A new tracheostomy was neccessary, and a biopsy specimen of the enlarged epiglottis was taken to confirm the diagnosis of graft-vs-host disease. The therapeutic measures in these situations are discussed below, and a review of the current literature concerning the etiology and management of epiglottic enlargement is performed.


The European Glaucoma Prevention Study and the Ocular Hypertension Treatment Study: why do two studies have different results?
To understand the results of the Ocular Hypertension Treatment Study and the European Glaucoma Prevention Study and to explain differences in their findings and recommendations. The value of lowering intraocular pressure with medical therapy to delay or prevent the progression from ocular hypertension to primary open-angle glaucoma has been the subject of two recently completed large clinical trials, the Ocular Hypertension Treatment Study and the European Glaucoma Prevention Study. In the Ocular Hypertension Treatment Study, patients were randomized to either medical treatment to achieve a 20% reduction in intraocular pressure or to careful observation. European Glaucoma Prevention Study patients were randomized to receive either topical dorzolamide or the vehicle for the commercially available solution without a specific intraocular pressure goal. The apparent difference in benefit of reducing the conversion rate by lowering intraocular pressure in these two studies may be explained by understanding the methodological differences in study design. The benefit of lowering intraocular pressure to reduce the rate of progression from ocular hypertension to primary open-angle glaucoma has been established in the Ocular Hypertension Treatment Study. Failure to demonstrate a comparable benefit in the European Glaucoma Prevention Study relates to the selective drop-out of treated and untreated patients with higher intraocular pressure levels and to the failure to achieve sufficient lowering of intraocular pressure. The evidence that the placebo effect was responsible for progressive intraocular pressure-lowering over the 5-year study is not convincing and is likely a result of the regression to the mean phenomenon.


[Basic mechanism of the histotoxic action of chelating agents].
Chelant injections in animals cause intravital histochemical reactions with zinc thus deranging this metal metabolism and disturbing the cellular structure with subsequent changes in the main histochemical components. The degree of alterations depends on the intensity and persistence of the intravital reaction. The basic mechanism of the chevant histotoxic action consists in the damage it produces in the mechanical structure of the cells.


Light-triggered and cysteine-mediated nitric oxide release from a biodegradable starch-based film.
A new nitric oxide-releasing material produced with cassava starch is described. The ruthenium nitrosyl complex trans-[Ru(NH3)4(isn)NO](BF4)3 (RuNOisn; isn = isonicotinamide) is able to release NO upon either photolysis or chemical reduction. Impregnating this complex under mild conditions into cassava starch (CS) films produced a NO-delivery platform (CSx-RuNOisn). Spectroscopic analysis of CSx-RuNOisn indicates that the coordination sphere of RuNOisn remains intact during film production. Exposure of CSx-RuNOisn to long wave UV-light (λirr = 355 nm) leads to NO release and formation of the paramagnetic photoproduct trans-[RuIII(NH3)4isn(H2O)]3+ in the CS film. Reaction of this aquaruthenium(iii) complex with aqueous nitrite regenerates RuNOisn in the film. Delivery of NO upon photolysis of CSx-RuNOisn was verified by trapping with oxymyoglobin. Moreover, NO release upon chemical reduction was carried out using l-cysteine as a reductant. Cysteine-mediated NO delivery from CSx-RuNOisn persisted for more than 7 h, during which physiologically relevant NO concentrations were liberated. These results suggest that CSx-RuNOisn is a promising candidate for use in biological applications.


Lifetime Ultraviolet Radiation Exposure and DNA Methylation in Blood Leukocytes: The Norwegian Women and Cancer Study.
Ultraviolet radiation (UVR) exposure is a leading cause of skin cancers and an ubiquitous environmental exposure. However, the molecular mechanisms relating UVR exposure to melanoma is not fully understood. We aimed to investigate if lifetime UVR exposure could be robustly associated to DNA methylation (DNAm). We assessed DNAm in whole blood in three data sets (n = 183, 191, and 125) from the Norwegian Woman and Cancer cohort, using Illumina platforms. We studied genome-wide DNAm, targeted analyses of CpG sites indicated in the literature, global methylation, and accelerated aging. Lifetime history of UVR exposure (residential ambient UVR, sunburns, sunbathing vacations and indoor tanning) was collected by questionnaires. We used one data set for discovery and the other two for replication. One CpG site showed a genome-wide significant association to cumulative UVR exposure (cg01884057) (pnominal = 3.96e-08), but was not replicated in any of the two replication sets (pnominal ≥ 0.42). Two CpG sites (cg05860019, cg00033666) showed suggestive associations with the other UVR exposures. We performed extensive analyses of the association between long-term UVR exposure and DNAm. There was no indication of a robust effect of past UVR exposure on DNAm.


4-vinyl-substituted pyrimidine nucleosides exhibit the efficient and selective formation of interstrand cross-links with RNA and duplex DNA.
The formation of interstrand cross-links in nucleic acids can have a strong impact on biological function of nucleic acids; therefore, many cross-linking agents have been developed for biological applications. Despite numerous studies, there remains a need for cross-linking agents that exhibit both efficiency and selectivity. In this study, a 4-vinyl-substituted analog of thymidine (T-vinyl derivative) was designed as a new cross-linking agent, in which the vinyl group is oriented towards the Watson-Crick face to react with the amino group of an adenine base. The interstrand cross-link formed rapidly and selectively with a uridine on the RNA substrate at the site opposite to the T-vinyl derivative. A detailed analysis of cross-link formation while varying the flanking bases of the RNA substrates indicated that interstrand cross-link formation is preferential for the adenine base on the 5'-side of the opposing uridine. In the absence of a 5'-adenine, a uridine at the opposite position underwent cross-linking. The oligodeoxynucleotides probe incorporating the T-vinyl derivative efficiently formed interstrand cross-links in parallel-type triplex DNA with high selectivity for dA in the homopurine strand. The efficiency and selectivity of the T-vinyl derivative illustrate its potential use as a unique tool in biological and materials research.


Modelling tendon excursions and moment arms of the finger flexors: anatomic fidelity versus function.
A detailed musculoskeletal model of the human hand is needed to investigate the pathomechanics of tendon disorders and carpal tunnel syndrome. The purpose of this study was to develop a biomechanical model with realistic flexor tendon excursions and moment arms. An existing upper extremity model served as a starting point, which included programmed movement of the index finger. Movement capabilities were added for the other fingers. Metacarpophalangeal articulations were modelled as universal joints to simulate flexion/extension and abduction/adduction while interphalangeal articulations used hinges to represent flexion. Flexor tendon paths were modelled using two approaches. The first method constrained tendons with control points, representing annular pulleys. The second technique used wrap objects at the joints as tendon constraints. Both control point and joint wrap models were iteratively adjusted to coincide with tendon excursions and moment arms from a anthropometric regression model using inputs for a 50th percentile male. Tendon excursions from the joint wrap method best matched the regression model even though anatomic features of the tendon paths were not preserved (absolute differences: mean<0.33 mm, peak<0.74 mm). The joint wrap model also produced similar moment arms to the regression (absolute differences: mean<0.63 mm, peak<1.58 mm). When a scaling algorithm was used to test anthropometrics, the scaled joint wrap models better matched the regression than the scaled control point models. Detailed patient-specific anatomical data will improve model outcomes for clinical use; however, population studies may benefit from simplified geometry, especially with anthropometric scaling.


[Prediction of ETA oligopeptides antagonists from Glycine max based on in silico proteolysis].
Oligopeptides are one of the the key pharmaceutical effective constituents of traditional Chinese medicine(TCM). Systematic study on composition and efficacy of TCM oligopeptides is essential for the analysis of material basis and mechanism of TCM. In this study, the potential anti-hypertensive oligopeptides from Glycine max and their endothelin receptor A (ETA) antagonistic activity were discovered and predicted based on in silico technologies.Main protein sequences of G. max were collected and oligopeptides were obtained using in silico gastrointestinal tract proteolysis. Then, the pharmacophore of ETA antagonistic peptides was constructed and included one hydrophobic feature, one ionizable negative feature, one ring aromatic feature and five excluded volumes. Meanwhile, three-dimensional structure of ETA was developed by homology modeling methods for further docking studies. According to docking analysis and consensus score, the key amino acid of GLN165 was identified for ETA antagonistic activity. And 27 oligopeptides from G. max were predicted as the potential ETA antagonists by pharmacophore and docking studies.In silico proteolysis could be used to analyze the protein sequences from TCM. According to combination of in silico proteolysis and molecular simulation, the biological activities of oligopeptides could be predicted rapidly based on the known TCM protein sequence. It might provide the methodology basis for rapidly and efficiently implementing the mechanism analysis of TCM oligopeptides.


TMPRSS2 Activates Hemagglutinin-Esterase Glycoprotein of Influenza C Virus.
Influenza C virus (ICV) has only one kind of spike protein, the hemagglutinin-esterase (HE) glycoprotein. HE functions similarly to hemagglutinin (HA) and neuraminidase of the influenza A and B viruses (IAV and IBV, respectively). It has a monobasic site, which is cleaved by some host enzymes. The cleavage is essential to activating the virus, but the enzyme or enzymes in the respiratory tract have not been identified. This study investigated whether the host serine proteases, transmembrane protease serine S1 member 2 (TMPRSS2) and human airway trypsin-like protease (HAT), which reportedly cleave HA of IAV/IBV, are involved in HE cleavage. We established TMPRSS2- and HAT-expressing MDCK cells (MDCK-TMPRSS2 and MDCK-HAT). ICV showed multicycle replication with HE cleavage without trypsin in MDCK-TMPRSS2 cells as well as IAV did. The HE cleavage and multicycle replication did not appear in MDCK-HAT cells infected with ICV without trypsin, while HA cleavage and multistep growth of IAV appeared in the cells. Amino acid sequences of the HE cleavage site in 352 ICV strains were completely preserved. Camostat and nafamostat suppressed the growth of ICV and IAV in human nasal surface epithelial (HNE) cells. Therefore, this study revealed that, at least, TMPRSS2 is involved in HE cleavage and suggested that nafamostat could be a candidate for therapeutic drugs for ICV infection. IMPORTANCE Influenza C virus (ICV) is a pathogen that causes acute respiratory illness, mostly in children, but there are no anti-ICV drugs. ICV has only one kind of spike protein, the hemagglutinin-esterase (HE) glycoprotein on the virion surface, which possesses receptor-binding, receptor-destroying, and membrane fusion activities. The HE cleavage is essential for the virus to be activated, but the enzyme or enzymes in the respiratory tract have not been identified. This study revealed that transmembrane protease serine S1 member 2 (TMPRSS2), and not human airway trypsin-like protease (HAT), is involved in HE cleavage. This is a novel study on the host enzymes involved in HE cleavage, and the result suggests that the host enzymes, such as TMPRSS2, may be a target for therapeutic drugs of ICV infection.


Intra-arterial chemotherapy for head and neck cancer: experiences from three continents.
Intra-arterial infusion of chemotherapy agents for cancer of the head and neck has been used for several decades. This article provides the rationale, historical background, and current state of investigations for patients treated in this manner. The experience with this route of drug delivery comes from three geographic regions: Europe, Japan, and North America. While the results of the trials have yet to establish the approach as being superior to intravenous infusions, continued research is warranted.


Phase response curve and light-induced fos expression in the suprachiasmatic nucleus and adjacent hypothalamus of Arvicanthis niloticus.
This article describes the phase response curve (PRC), the effect of light on Fos immunoreactivity (Fos-IR) in the suprachiasmatic nucleus (SCN), and the effect of SCN lesions on circadian rhythms in the murid rodent, Arvicanthis niloticus. In this species, all individuals are diurnal when housed without a running wheel, but running in a wheel induces a nocturnal pattern in some individuals. First, the authors characterized the PRC in animals with either the nocturnal or diurnal pattern. Both groups of animals were less affected by light during the middle of the subjective day than during the night and were phase delayed and phase advanced by pulses in the early and late subjective night, respectively. Second, the authors characterized the Fos response to light at circadian times 5, 14, or 22. Light induced an increase in Fos-IR within the SCN during the subjective night but not subjective day; this effect was especially pronounced in the ventral SCN, where retinal inputs are most concentrated, but was also evident in other regions. Both light and time influenced Fos-IR within the lower subparaventricular area. Third, SCN lesions caused animals to become arrhythmic when housed in a light-dark cycle as well as constant darkness. In summary, Arvicanthis appear to be very similar to nocturnal rodents with respect to their PRC, temporal patterns of light-induced Fos expression in the SCN, and the effects of SCN lesions on activity rhythms.


Nerve terminal remodeling visualized in living mice by repeated examination of the same neuron.
The distribution of presynaptic endings on the surfaces of autonomic ganglion cells was mapped in living mice after intravenous administration of a styryl pyridinium dye. The staining and imaging techniques did not appear to damage the ganglion cells, or the synapses on them; these procedures could therefore be repeated after an arbitrary period. Observations of the same neurons at intervals of up to 3 weeks indicate that the pattern of preganglionic terminals on many of these nerve cells gradually changes.


Hydroxypalladation precedes the rate-determining step in the Wacker oxidation of ethene.
The complete reaction mechanism and kinetics of the Wacker oxidation of ethene in water under low [Cl(-)], [Pd(II)], and [Cu(II)] conditions are investigated in this work by using ab initio molecular dynamics. These extensive simulations shed light on the molecular details of the associated individual steps, along two different reaction routes, starting from a series of ligand-exchange processes in the catalyst precursor PdCl4(2-) to the final aldehyde-formation step and the reduction of Pd(II). Herein, we report that hydroxylpalladation is not the rate-determining step and is, in fact, in equilibrium. The newly proposed rate-determining step involves isomerization and follows the hydroxypalladation step. The mechanism proposed herein is shown to be in excellent agreement with the experimentally observed rate law and rate. Moreover, this mechanism is in consensus with the observed kinetic isotope effects. This report further confirms the outer-sphere (anti) hydroxypalladation mechanism. Our calculations also ratify that the final product formation proceeds through a reductive elimination, assisted by solvent molecules, rather than through β-hydride elimination.


The Speed of Increasing milk Feeds: a randomised controlled trial.
In the UK, 1-2% of infants are born very preterm (<32 weeks of gestation) or have very low birth weight (<1500 g). Very preterm infants are initially unable to be fed nutritional volumes of milk and therefore require intravenous nutrition. Milk feeding strategies influence several long and short term health outcomes including growth, survival, infection (associated with intravenous nutrition) and necrotising enterocolitis (NEC); with both infection and NEC being key predictive factors of long term disability. Currently there is no consistent strategy for feeding preterm infants across the UK. The SIFT trial will test two speeds of increasing milk feeds with the primary aim of determining effects on survival without moderate or severe neurodevelopmental disability at 24 months of age, corrected for prematurity. The trial will also examine many secondary outcomes including infection, NEC, time taken to reach full feeds and growth. Two thousand eight hundred very preterm or very low birth weight infants will be recruited from approximately 30 hospitals across the UK to a randomised controlled trial. Infants with severe congenital anomaly or no realistic chance of survival will be excluded. Infants will be randomly allocated to either a faster (30 ml/kg/day) or slower (18 ml/kg/day) rate of increase in milk feeds. Data will be collected during the neonatal hospital stay on weight, infection rates, episodes of NEC, length of stay and time to reach full milk feeds. Long term health outcomes comprising vision, hearing, motor and cognitive impairment will be assessed at 24 months of age (corrected for prematurity) using a parent report questionnaire. Extensive searches have found no active or proposed studies investigating the rate of increasing milk feeds. The results of this trial will have importance for optimising incremental milk feeding for very preterm and/or very low birth weight infants. No additional resources will be required to implement an optimal feeding strategy, and therefore if successful, the trial results could rapidly be adopted across the NHS at low cost. ISRCTN Registry; ISRCTN76463425 on 5 March, 2013.


Haemoptysis from a Dacron graft aneurysm 21 years post repair of coarctation of the aorta.
We report an unusual complication of a Dacron graft in a 31-year-old woman who had undergone extra-anatomical bypass for coarctation of the aorta aged 11 years. She presented with haemoptysis, and imaging confirmed an aneurysm of the Dacron graft at the proximal anastomosis with the aorta, eroding into the right upper lobe, as well as a smaller aneurysm at the anastomosis with the descending aorta. She underwent a median sternotomy and refashioning of the bypass, and a re-do right thoracotomy with removal of the Dacron graft and a right upper and middle lobectomy.


A Role for the Microbiota in the Immune Phenotype Alteration Associated with the Induction of Disease Tolerance and Persistent Asymptomatic Infection of Salmonella in the Chicken.
Previous studies have shown a tissue immune phenotype-altering event occurring on days 2 and 4 in the ceca post-Salmonella challenge. To evaluate the involvement of the cecal microbiota in the phenotype reprogramming, we hypothesized that the addition of subtherapeutic bacitracin (BMD) will affect the cecal microbiota. Therefore, the objective of this study was to determine if the antibiotic-mediated changes in the microbiota composition influenced the immune phenotype induced by Salmonella enteritidis infection of the chicken cecum. A total of 112 fertile eggs were obtained for each experiment, repeated for a total of three separate times. The ceca and cecal contents were collected on days 2 and 4 post-infection for mRNA expression TaqMan assay and 16S rRNA gene microbiota sequencing. The results demonstrate the effects of bacitracin on cecal composition and its interaction with Salmonella enteritidis in young chicks. There is a preliminary indication of phenotype change in the Salmonella-challenged group provided subtherapeutic BMD due to the shifting cecal microbiota and cecal immune response, indicating the addition of bacitracin during infection altered the cecal phenotype. These data demonstrate the potential involvement of the microbiota in reprogramming immune phenotype (disease resistance to disease tolerance) induced by Salmonella in the chicken cecum.


Smoking, season, and detection of Chlamydia pneumoniae DNA in clinically stable COPD patients.
The prevalence and role of Chlamydia pneumoniae in chronic obstructive pulmonary disease (COPD) remain unclear, and molecular methods of detection may help clarify this relationship. Consecutive clinically stable patients with smoking-related COPD attending a tertiary care outpatient clinic were enrolled in this cross-sectional study. Peripheral blood mononuclear cells were obtained from 100 patients, and induced sputum was obtained in 62 patients. C. pneumoniae DNA was detected in blood or sputum by nested polymerase chain reaction (PCR). Patients had mean age (standard deviation) of 65.8 (10.7) years, mean forced expiratory volume in one second (SD) of 1.34 (0.61) L, and 61 (61.0%) were male. C. pneumoniae nucleic acids were detected in 27 (27.0%) patients. Among 62 patients with both blood and sputum available, blood specimens were superior to induced sputum for detection of C. pneumoniae DNA (21 versus 7 detected, P=0.003). Current smoking (odds ratio [OR]=2.6, 95 % confidence interval [CI]: 1.1, 6.6, P=0.04), season (November to April) (OR=3.6, 95% CI: 1.4, 9.2, P=0.007), and chronic sputum production (OR=6.4, 95% CI: 1.8, 23.2, P=0.005) were associated with detection of C. pneumoniae DNA. C. pneumoniae DNA prevalence was higher among current smokers, and during winter/spring months. Prospective molecular studies are needed to examine the role of C. pneumoniae detection in COPD disease symptoms and progression.


What would they do? Latino church leaders and domestic violence.
Understanding what Latino church leaders believe about domestic violence, and what they do when they confront it, is a key step in developing programs to help them engage in domestic violence prevention and intervention activities in their congregations. This article presents the findings from an exploratory study of 28 Latino church leaders. The study surveyed respondents' beliefs about domestic violence and asked for their reactions to three domestic violence vignettes they might encounter. We found that study participants were willing to respond to cases of domestic violence in what we would define as constructive ways. However, some responses suggested potentially unsafe and ill-advised reactions to the vignettes. We discuss our study's implications for practice and suggest future directions for additional research.


Investigating personality and conceptualising allied health as person or technique oriented.
Allied health (AH) includes many diverse professions, each with a unique contribution to healthcare, making it possible to consider these professions as person oriented (PO) or technique oriented (TO). This paper explored the personality traits of AH professionals from the perspective of both the PO or TO orientation and the individual professions. AH professionals (n=562) provided demographic data and completed the Temperament and Character Inventory. Examination of the literature and a consultation process resulted in nine professions classified as PO and 10 classified as TO. Multivariate analyses compared levels of personality traits and demographic variables between the PO (n=492) and TO (n=70) groups, and the professions within the groups. Professionals in the PO group showed significantly higher levels of traits that emphasise person orientation attributes, such as being sociable, empathic and cooperative, compared with AH professionals in professions with an emphasis on TO. Trends in personality traits among AH professionals were congruent with the PO and TO aspects of their chosen profession. This supports the usefulness of the PO and TO concepts in describing AH professions and may provide new clues for policy aiming to enhance job satisfaction, retention and career development. WHAT IS KNOWN ABOUT THE TOPIC? The literature suggests that certain medical specialities can be classified as person (PO) or technique oriented (TO) and that individuals attracted to those specialties display traits that are similar to that orientation. There is scant information on the AH professions regarding similar person or technique orientations. WHAT DOES THIS PAPER ADD? The diversity of professions within AH allows a new approach to describing each profession as either PO (socially dependent, cooperative and relationship focused), or TO (focused on skills and procedures). The trend in personality traits of individuals in certain AH professions is compatible with the orientation of that profession. Findings suggest that individuals may be attracted to professions that favour a similar personality pattern to their own. WHAT ARE THE IMPLICATIONS FOR PRACTITIONERS? Gaining an improved understanding of the AH professions and individuals who are attracted to them in a climate of workforce shortage and increasing multidisciplinary service demand. The findings provide a new approach to understanding the characteristics of AH professions according to the personalities they attract. This information could guide recruitment and retention policy, and assist in career counselling by providing greater insight into personality profiles that are best suited to certain professions.


Monocyte-derived dendritic cells activated by bacteria or by bacteria-stimulated epithelial cells are functionally different.
Dendritic cells (DCs) are able to open the tight junctions between adjacent epithelial cells (ECs) and to take up both invasive and noninvasive bacteria directly from the intestinal lumen. In this study, we describe a tight cross talk between ECs and human monocyte-derived DCs (MoDCs) in bacterial handling across epithelial monolayers. We show that the release of proinflammatory mediators by ECs in response to bacteria is dependent on bacterial invasiveness and on the presence of flagella. This correlates with the capacity of EC-derived factors to modulate MoDC function. MoDCs incubated with supernatants of bacteria-treated ECs are "noninflammatory" as they release interleukin-10 (IL-10) but not IL-12 and can drive only T helper (Th)-2 type T cells. Moreover, noninflammatory MoDCs release chemokines aimed at recruiting Th2 and T-regulatory cells. In contrast, when MoDCs are incubated with ECs and bacteria in a transwell coculture system, and can contact directly the bacteria across stimulated EC monolayers, they are more inflammatory as they release IL-12 and IL-10 and induce both Th1 and Th2 responses. These results suggest that ECs are not simply a barrier to bacteria entering via the oral route, but they actively influence the activating properties of DCs.


Diagnostic evaluation of rhabdomyolysis.
Rhabdomyolysis is characterized by severe acute muscle injury resulting in muscle pain, weakness, and/or swelling with release of myofiber contents into the bloodstream. Symptoms develop over hours to days after an inciting factor and may be associated with dark pigmentation of the urine. Serum creatine kinase and urine myoglobin levels are markedly elevated. Clinical examination, history, laboratory studies, muscle biopsy, and genetic testing are useful tools for diagnosis of rhabdomyolysis, and they can help differentiate acquired from inherited causes of rhabdomyolysis. Acquired causes include substance abuse, medication or toxic exposures, electrolyte abnormalities, endocrine disturbances, and autoimmune myopathies. Inherited predisposition to rhabdomyolysis can occur with disorders of glycogen metabolism, fatty acid β-oxidation, and mitochondrial oxidative phosphorylation. Less common inherited causes of rhabdomyolysis include structural myopathies, channelopathies, and sickle-cell disease. This review focuses on the differentiation of acquired and inherited causes of rhabdomyolysis and proposes a practical diagnostic algorithm. Muscle Nerve 51: 793-810, 2015.


Health-related profile and quality of life among nursing home residents: does pain matter?
The purpose of this exploratory cross-sectional study was to explore the health-related profile and quality of life among older persons living with and without pain in nursing homes. Ten nursing homes were approached, and 535 older persons were invited to join the study from 2009 to 2011. The nursing home residents' demographic information and information regarding their pain situation and the use of oral analgesic drug and nondrug therapy among the older residents with chronic pain were also collected. Residents' physical health (using the Barthel Activities of Daily Living (ADL) and Elderly Mobility Scores); psychologic health, including happiness, life satisfaction, depression, and loneliness (using the Happiness Scale, the Life Satisfaction Scale, the Geriatric Depression Scale, and the UCLA Loneliness Scale); and quality of life were investigated. Among the 535 nursing home residents, 396 (74%) of them suffered from pain, with mean pain scores of 4.09 ± 2.19, indicating medium pain intensity a remaining 139 (26%) reported no pain. The location of pain was mainly in the knees, back and shoulders. Our results demonstrated that, with the exception of the no-pain group (p < .05), nursing home residents' pain affected both their psychologic health, including happiness, life satisfaction, and depression, and their physical quality of life. Nevertheless, only one-half of the older persons with pain used oral analgesic drug or nondrug therapy to relieve their pain. Pain had a significant impact on their mobility and ADL, was positively correlated with happiness and life satisfaction, and was negatively correlated with loneliness and depression. Pain management is a high priority in elderly care; as such, innovative and interdisciplinary strategies are necessary to enhance quality of life particularly for older persons living in nursing homes.


Midterm Results of Arthroscopic Treatment for Recalcitrant Lateral Epicondylitis of the Elbow.
An effective treatment for the elbow recalcitrant lateral epicondylitis is arthroscopic surgery. This study evaluated the midterm results of treating recalcitrant lateral epicondylitis with arthroscopic surgery. A total of 40 subjects with recalcitrant lateral epicondylitis prepared for arthroscopic surgery on their elbows participated in this study. The elbow function was evaluated using the Quick disabilities of the arm, shoulder, and hand (Quick DASH) score. Pain intensity was assessed before and after the surgery by the visual analog scale (VAS). Grip and pinch strengths were assessed by a dynamometer. In this study, the mean age of the participants was 42.9±6.4 years. The average follow-up time was 42 months. The mean of VAS (pain intensities) were 7.05 and 3.20 before and after the surgery, respectively (P=0.001). The Quick DASH score decreased from 63.18 to 25.68 from before to after the surgery (P=0.001). The mean grip strength of the operated and nonoperated sides was not significantly different after the surgery. Arthroscopic surgery seems to be an effective method with few complications in patients suffering from an elbow recalcitrant lateral epicondylitis in the midterm follow-up.


When the perpetrator gets killed: effects of observing the death of a handgun user in a televised public service announcement.
This study evaluates the cognitive effects of an anti-handgun violence public service announcement (PSA) on sixth-, seventh-, and eighth-grade students (N = 294). Participants were randomly assigned to a treatment group, which viewed a PSA depicting the death of an aggressive handgun user, or a comparison group, which viewed identical content except that the PSA showed no negative consequence for the handgun user. Logistic regression analysis, adjusting for race and gender, revealed that the treatment group was more likely to report negative expected outcomes for aggressively using a handgun and lower behavioral intentions to aggressively use a handgun compared with the comparison group. These findings suggest that observing handgun violence on television that depicts death as a negative physical consequence for the perpetrator may produce lower handgun-encouraging beliefs compared with observing no consequence for the perpetrator--the norm for most televised violence today.


Phase I trial to evaluate the tumor and normal tissue uptake, radiation dosimetry and safety of (111)In-DTPA-human epidermal growth factor in patients with metastatic EGFR-positive breast cancer.
The safety, pharmacokinetics, biodistribution and radiation dosimetry of (111)In-DTPA-hEGF, an Auger electron-emitting radiopharmaceutical, were evaluated in a first-in-human trial. Dose escalation was performed in patients with EGFR-positive metastatic breast cancer who had received ≥2 prior courses of systemic treatment. (111)In-DTPA-hEGF (0.25 mg) was administered once intravenously (i.v.). Blood was collected for biochemistry/hematology testing and pharmacokinetic and immunogenicity analyses at selected times post injection (p.i.). Whole body planar images were acquired at 1, 4-6, 24 and 72 h p.i. and SPECT images at 24 and/or 72 h p.i. Macrodosimetry (MIRD) for the whole body and organs was estimated using OLINDA. Correlative radiological imaging was obtained at baseline, 1 and 3 months and then 6 monthly. Toxicity was scored using Common Terminology Criteria for Adverse Events (CTCAE)v2.0. Sixteen patients, median age 47 yr (range, 35-59), received (111)In-DTPA-hEGF as follows: 357-434 MBq (7), 754-805 MBq (3), 1,241-1,527 MBq (3) and 2,030-2,290 MBq (3). Fifteen were evaluable for toxicity. The commonest adverse events (AE) were flushing, chills, nausea, and vomiting occurring during or immediately p.i. One patient experienced Grade 3 thrombocytopenia (attributed to bone marrow infiltration by cancer). There were no other Grade 3 or 4 AEs. Maximum tolerated dose was not reached. Clear accumulation of radiopharmaceutical in at least one known site of disease was observed in 47% of patients. (111)In-DTPA-hEGF was cleared biexponentially from the blood with α-phase T½ of 0.16 ± 0.03 h and β-phase T½ of 9.41 ± 1.93 h. (111)In-DTPA-hEGF was not immunogenic. The mean radiation dose estimates in mGy/MBq for whole body, liver, kidneys, spleen and thyroid were 0.08, 0.86, 0.74, 0.37 and 0.30, respectively. No objective antitumor responses were observed at the doses studied. In summary, administered amounts of up to 2,290 MBq (0.25 mg) of (111)In-DTPA-hEGF were well tolerated as a single i.v. injection.


Real-world data of immunotherapy from China in recurrent or metastatic head and neck squamous cell carcinoma.
Immune checkpoint inhibitors (ICIs) have become a standard therapy for recurrent or metastatic head and neck squamous cell carcinoma (R/MHNSCC), however, there are still unanswered questions about immunotherapy. Furthermore, immunotherapy for R/MHNSCC of the mainland Chinese population are lacking. The aim of this study is to evaluate the efficacy and safety of ICIs in real-world settings in China. We retrospectively reviewed 59 patients with R/MHNSCC who received immunotherapy between May 2019 and December 2021. We assessed demographics, efficacy, survival and safety. Fifty-nine patients were included in the study, all of whom had R/MHNSCC affecting the oral cavity, oropharynx, hypopharynx, larynx, nasal cavity, paranasal sinuses and metastatic cancer in the neck with an unknown primary. The objective response rate (ORR) for all patients was found to be 40.6 %. Out of these patients, 11 patients achieved a complete response and 13 achieved a partial response. The median progression-free survival (PFS) was calculated to be 10.64 months (range: 1.15-29.24 months), while the median overall survival (OS) was 21.75 months (range 2.0-37.55 months). The addition of local radiotherapy resulted in higher ORR and PFS compared to previous reports. Notably, patients with R/MHNSCC in the paranasal sinuses and nasal cavity also showed benefits from immunotherapy. Additionally, patients who achieved stable disease (SD) had similar survival rates to those who achieved partial response (PR), indicating that SD is also an indicator of clinical benefit from immunotherapy. The overall incidence of immune-related adverse reactions in this study was low, with fatigue and rash being the most common side effects. These findings highlight the effectiveness and safety of immunotherapy for R/MHNSCC in a real-world setting in China. Further investigation is warranted to explore the potential benefits of incorporating local radiotherapy into the treatment of R/MHNSCC.


Stability of methacholine chloride solutions under different storage conditions over a 9 month period.
Methacholine chloride solutions, routinely used for testing bronchial hyperreactivity, have been shown to degrade over time. The data published addressing the optimal conditions for methacholine chloride storage are conflicting and incomplete. This study investigated the effects of a variety of conditions on the stability of methacholine chloride. Methacholine chloride, dissolved in phosphate buffered saline (PBS) or sodium chloride (NaCl) at 50 and 0.39 g x L(-1), was subjected to various light and temperature conditions for 9 months. Methacholine chloride degradation was determined by high performance liquid chromatography, and all solutions underwent bacterial and pH testing. By 9 months, all 50 g x L(-1) solutions of methacholine chloride had degraded by 65+/-0.8%. All 0.39 g x L(-1) solutions in NaCl had degraded by 11.0+/-0.33%. The 0.39 g x L(-1) solutions in PBS which had been frozen, refrigerated or stored at room temperature had degraded by 8.0%, 16.0+/-0.3% and 63.8+/-0.5%, respectively. The pH of methacholine chloride was 7.2 in PBS at 0.39 g x L(-1), 5.8 in PBS at 50 g x L(-1), 3.9 in NaCl at 0.39 and 2.7 in NaCl at 50 g x L(-1). Bacterial contamination was minimal. The results of this study demonstrate that methacholine chloride is more stable at the higher concentration. However, the pH of the more concentrated solutions of methacholine chloride in sodium chloride could cause bronchoconstriction in some subjects. We therefore recommend storing methacholine chloride at 50 g x L(-1) in phosphate-buffered saline.


Physiologic remodeling annuloplasty to retain the shape of the anterior leaflet: a new concept in mitral valve repair.
The Carpentier-Edwards (CE) ring was developed to restore the normal 3:4 ratio between the anteroposterior and transverse diameters of the mitral valve orifice during systole. It is difficult to use in patients in whom the ratio is more than 3:4. To overcome this problem, we developed an adjustable obturator, the ratio of which may be changed by sliding apart its two components. Remodeling annuloplasty was performed using part of a flexible Duran ring or autologous pericardium and the adjustable obturator in 17 patients with severe MR, including two with high anterior leaflet. Physiologic remodeling annuloplasty was easily accomplished in all cases. Intraoperative echocardiography was performed in 14 patients, and it showed no regurgitant jet in 11 cases and only trivial jet in three. Physiologic remodeling annuloplasty to retain the natural shape of the anterior leaflet by using an adjustable obturator is a very useful technique that enables annuloplasty to be performed in all cases, irrespective of the shape of the anterior leaflet.


Combining Evolutionary Information and an Iterative Sampling Strategy for Accurate Protein Structure Prediction.
Recent work has shown that the accuracy of ab initio structure prediction can be significantly improved by integrating evolutionary information in form of intra-protein residue-residue contacts. Following this seminal result, much effort is put into the improvement of contact predictions. However, there is also a substantial need to develop structure prediction protocols tailored to the type of restraints gained by contact predictions. Here, we present a structure prediction protocol that combines evolutionary information with the resolution-adapted structural recombination approach of Rosetta, called RASREC. Compared to the classic Rosetta ab initio protocol, RASREC achieves improved sampling, better convergence and higher robustness against incorrect distance restraints, making it the ideal sampling strategy for the stated problem. To demonstrate the accuracy of our protocol, we tested the approach on a diverse set of 28 globular proteins. Our method is able to converge for 26 out of the 28 targets and improves the average TM-score of the entire benchmark set from 0.55 to 0.72 when compared to the top ranked models obtained by the EVFold web server using identical contact predictions. Using a smaller benchmark, we furthermore show that the prediction accuracy of our method is only slightly reduced when the contact prediction accuracy is comparatively low. This observation is of special interest for protein sequences that only have a limited number of homologs.


Onfield assessment of concussion in the adult athlete.
The onfield assessment of concussion in the adult athlete is challenging, given the elusiveness of injury, the sensitivity and specificity of the sideline assessment tools and the evolving nature of concussive injury. This paper reviews the evidence related to the onfield assessment and considers questions related to same day return to play, what to do when no physician is available onsite, as well as the benefit of remote notification of potential concussive events. To review the evidence regarding the onfield assessment of concussion in the adult athlete. Additional key issues to consider include same day return to play for the adult athlete with concussion, what to do in a community setting when no doctor is present and whether there is any benefit with remote notification of potential concussive events that occur on the playing field. Systematic literature review of concussion assessment and management. PubMed, MEDLINE, Psych Info and Cochrane Library databases were reviewed using the MeSH key words concussion and mild traumatic brain injury combined with athletic injuries. Each was refined by adding the key words 'adult', 'sideline assessment', 'onfield assessment' and 'return to play'. For the MEDLINE search, using 'concussion' and 'athletic injuries' as key words, there were 880 results, and refining by 'adult' there were 292 results. When 'traumatic brain injury' and 'athletic injuries' were combined, there were 210 results. When refining by 'adult', there were 89 results. Many of these results overlapped. Following an initial review, these articles form the basis of the discussion. The onfield evaluation of sport-related concussion is often a challenge, given the elusiveness and variability of presentation, difficulty in making a timely diagnosis, specificity and sensitivity of the sideline assessment tools and the reliance on symptoms. Despite these challenges, the sideline evaluation is based on recognition of injury, assessment of symptoms, cognitive and cranial nerve function and balance. Serial assessments are often necessary and, since signs and symptoms may be delayed, erring on the side of caution (keeping an athlete out of participation when there is any suspicion for injury) is important. A standardised assessment of concussion is useful in the assessment of the athlete with suspected concussion but should not take the place of the clinician's judgement.


Neuronal Adenosine A2A Receptors Are Critical Mediators of Neurodegeneration Triggered by Convulsions.
Neurodegeneration is a process transversal to neuropsychiatric diseases and the understanding of its mechanisms should allow devising strategies to prevent this irreversible step in brain diseases. Neurodegeneration caused by seizures is a critical step in the aggravation of temporal lobe epilepsy, but its mechanisms remain undetermined. Convulsions trigger an elevation of extracellular adenosine and upregulate adenosine A2A receptors (A2AR), which have been associated with the control of neurodegenerative diseases. Using the rat and mouse kainate model of temporal lobe epilepsy, we now tested whether A2AR control convulsions-induced hippocampal neurodegeneration. The pharmacological or genetic blockade of A2AR did not affect kainate-induced convulsions but dampened the subsequent neurotoxicity. This neurotoxicity began with a rapid A2AR upregulation within glutamatergic synapses (within 2 h), through local translation of synaptic A2AR mRNA. This bolstered A2AR-mediated facilitation of glutamate release and of long-term potentiation (LTP) in CA1 synapses (4 h), triggered a subsequent synaptotoxicity, heralded by decreased synaptic plasticity and loss of synaptic markers coupled to calpain activation (12 h), that predated overt neuronal loss (24 h). All modifications were prevented by the deletion of A2AR selectively in forebrain neurons. This shows that synaptic A2AR critically control synaptic excitotoxicity, which underlies the development of convulsions-induced neurodegeneration.


Effects of prenatal steroids on water and sodium homeostasis in extremely low birth weight neonates.
We sought to determine if prenatal steroid (PNS) treatment affects water and sodium (Na) balance in extremely low birth weight infants (<1000 g). PNS treatment enhances lung maturation in preterm infants and induces maturation of renal tubular function and adenylate cyclase activity in animals. We compared water and Na homeostasis for the first week of life in those infants whose mothers received steroids before delivery (PNS: n = 16) to those who did not (nonsteroid group [NSG]: n = 14). The data were collected prospectively, but PNS treatment was not given in a randomized manner. Fluids were initiated at 100 to 125 mL/kg/d and adjusted every 8 to 12 hours to allow a daily weight loss of </=4% of birth weight and to maintain normal serum electrolytes. Weight, serum and urine electrolytes, and urine output were frequently measured and fluid intake was adjusted by increasing the amount of free water to achieve these goals. When using our fluid management protocol, the percent weight loss in both groups was equivalent during each of the 7 days (15% PNS vs 17% NSG maximum loss) as well as the cumulative urine output at 1 week of age (663 mL/kg/wk PNS vs 681 mL/kg/wk NSG). PNS infants had a higher urine output on the first 2 days of life and a lower daily fluid intake for the first week. PNS infants also had significantly less insensible water loss for each of the first 4 days of life. The PNS group had a significantly lower mean peak serum Na of 138 +/- 1 mmol/L vs 144 +/- 2 mmol/L and none had a peak serum Na >150 mmol/L compared with 36% of the NSG infants. PNS infants had a higher cumulative Na excretion at day 2 of life (10 +/- 2 mmol/kg vs 6 +/- 1 mmol/kg) but a less negative cumulative Na balance at 1 week (-10 mmol/kg vs -14 mmol/kg). PNS treatment was associated with lower estimated insensible water loss, a decreased incidence of hypernatremia, and an earlier diuresis and natriuresis in extremely low birth weight neonates. We speculate that PNS effects these changes through enhancement of epithelial cell maturation improving skin barrier function. PNS treatment may also enhance lung Na, K-ATPase activity leading to an earlier postnatal reabsorption of fetal lung fluid increasing extracellular volume expansion to help prevent hypernatremia.


Psychotherapy and religion: The emmanuel movement.
This paper reconsiders the significance of the Emmanuel movement, a pre- Freudian psychotherapeutic system founded by Dr. Elwood Worcester as a method of church-sponsored healing. Its significance lies in three areas: (1) Historically, it was a popular effort by Protestant clergy to claim religious authority over psychological and psychosomatic ailments, a struggle that the medical profession eventually won almost completely. (2) The Emmanuel movement was an effort to combat the scientific materialism and medical somaticism of its time, including the excessive use of drugs. It aimed at greater individual control over emotional wellbeing through a self-help movement taught by religious leaders using some Christian ideas. Significant parallels can be found with present-day holistic health efforts. (3) Theoretically, Worcester's conception of the "person" is of interest as an effort to construct a nonreductionist view of the interactions of body, mind, and spirit.


Eubiotic properties of rifaximin: Disruption of the traditional concepts in gut microbiota modulation.
Antibiotics are usually prescribed to cure infections but they also have significant modulatory effects on the gut microbiota. Several alterations of the intestinal bacterial community have been reported during antibiotic treatment, including the reduction of beneficial bacteria as well as of microbial alpha-diversity. Although after the discontinuation of antibiotic therapies it has been observed a trend towards the restoration of the original condition, the new steady state is different from the previous one, as if antibiotics induced some kind of irreversible perturbation of the gut microbial community. The poorly absorbed antibiotic rifaximin seem to be different from the other antibiotics, because it exerts non-traditional effects additional to the bactericidal/bacteriostatic activity on the gut microbiota. Rifaximin is able to reduce bacterial virulence and translocation, has anti-inflammatory properties and has been demonstrated to positively modulate the gut microbial composition. Animal models, culture studies and metagenomic analyses have demonstrated an increase in Bifidobacterium, Faecalibacterium prausnitzii and Lactobacillus abundance after rifaximin treatment, probably consequent to the induction of bacterial resistance, with no major change in the overall gut microbiota composition. Antibiotics are therefore modulators of the symbiotic relationship between the host and the gut microbiota. Specific antibiotics, such as rifaximin, can also induce eubiotic changes in the intestinal ecosystem; this additional property may represent a therapeutic advantage in specific clinical settings.


Evaluation of the World Health Organization criteria for chest radiographs for pneumonia diagnosis in children.
Our objective was to compare the inter-observer level of agreement in diagnosing pneumonia using the World Health Organization (WHO) guidelines for the interpretation of radiographs. We conducted a prospective study in a pediatric emergency room. Fifteen observers (13 pediatricians, 2 radiologists) interpreted 200 pediatric (<5 years old) chest radiographs using the WHO guidelines. Observers were blinded to the clinical presentation. RESULTS were analyzed for kappa values. Individual readings were compared to two "gold standard" teams: (1) radiologist and pediatrician and (2) two radiologists. Alveolar pneumonia, non-alveolar pneumonia, and no pneumonia were found (by radiologists) in 12.8%, 2.7%, and 78.6% of readings, respectively. The mean kappa values for alveolar pneumonia, non-alveolar pneumonia, and no pneumonia of observers versus the team consisting of a radiologist and a pediatrician were 0.73, 0.23, and 0.61, respectively. For non-alveolar pneumonia, the mean kappa value was higher for the gold standard consisting of a radiologist and a pediatrician when compared to the two-radiologist team. Pediatricians overdiagnosed "non-alveolar pneumonia" compared with radiologists. In contrast, for the alveolar pneumonia and no-pneumonia diagnoses, no significant differences were found. The WHO guidelines for interpretation of chest radiographs result in high level of agreement between readers for the definition of "alveolar pneumonia" and "no pneumonia" but poor agreement for non-alveolar pneumonia. The disagreement with regard to the latter was associated with overdiagnosis by pediatricians, which may lead to overtreatment. We believe that radiographic non-alveolar pneumonia should not be an endpoint for clinical trials and research, nor should it be implemented in clinical setting.


The epidemiology of spinal cord injuries in Papua New Guinea.
Thirty six patients with traumatic spinal cord injury were studied in Papua New Guinean hospitals. Road trauma and falls from trees each accounted for 1/3 of injuries. The mean age of patients, 80% of whom were male, was 26 years. Complications included pressure sores (69%), urinary tract infection (61%) and contractures (22%). Two thirds of patients failed to make any significant recovery and remained permanently in hospital. At present there are no special facilities for treating paraplegic patients in this country but as the number of cases is increasing it is recommended that major hospitals provide special units and a standard management protocol for these patients.


Can CT replace MRI in preoperative assessment of the circumferential resection margin in rectal cancer?
The surgical circumferential resection margin in total mesorectal excision surgery is defined by the relationship of the tumor to the mesorectal fascia. Patients with anticipated tumor invasion of the mesorectal fascia receive neoadjuvant therapy to downstage/downsize the tumor and to obtain tumor-free resection margins.Tumor relationship to the mesorectal fascia is accurately determined by MRI. Compared with MRI, multidetector-row computed tomography is more widely available, faster, less costly, and provides the ability to simultaneously assess the liver, peritoneum, and retroperitoneum for metastases. The objective of this study was to compare the accuracy of multidetector-row CT with conventional MRI in diagnosis of rectal cancer invasion of the mesorectal fascial envelope. During a 2-year period, all patients were enrolled in this study who had biopsy-proven rectal carcinoma and were referred, as a part of the routine preoperative staging workup, for a CT scan of the abdomen and pelvis and also an MRI of the pelvis.All examinations were reviewed independently by 2 radiologists who were blinded from one another, from the findings of the other modality, and from clinical information. Both observers were dedicated abdominal radiologists who are experienced in reading pelvic CT and MRI. Categorical agreement between MRI and multidetector-row CT for all the evaluated parameters of the tumor position, mesorectal fascia, and lymph nodes, as well as the interobserver agreement between CT and MRI, was determined by the intraclass correlation weighted kappa statistic to measure the data set's consistency. Among the study's 92 patients, the tumor characteristics suggested by multidetector-row CT agreed with those of MRI, with a weighted kappa ranging from 0.488 to 0.748 for the first reader and 0.577 to 0.800 for the second reader. Interobserver agreement ranged from 0.506 to 0.746.Agreement regarding mesorectal fascia characteristics differed significantly between multidetector-row CT and MRI, depending on the level of assessment. In the distal rectum, agreement was 0.207 for the first reader and 0.385 for the second reader. In the mid rectum, agreement was 0.420 and 0.527, respectively, and in the proximal rectum agreement was 0.508 and 0.520. Interobserver agreement was 0.737 at the distal level and 0.700 at the mid and proximal levels. Agreement regarding measurement of the distance from the tumor to the mesorectal fascia was 0.425 for the first reader and 0.723 for the second reader, with interobserver agreement of 0.766. Agreement in assessment of the number of lymph nodes ranged from 0.743 to 0.787 for the first reader and 0.754 to 0.840 for the second reader. Interobserver agreement ranged from 0.779 to 0.841. Agreement in assessment of the size of the lymph nodes ranged from 0.540 to 0.830 for the first reader and 0.850 to 0.940 for the second reader. Interobserver agreement ranged from 0.900 to 0.920. Agreement in assessment of the distance from nodes to the mesorectal fascia was 0.320 for the first reader and 0.401 for the second reader, with interobserver agreement of 0.950. The results of this study differ from previously published data by demonstrating substantial agreement between readers in multidetector-row CT assessment of the tumor, mesorectal fascia, and lymph nodes. With the exceptions of mesorectal fascia in the distal rectum and the distance from the nodes to mesorectal fascia, other evaluated parameters were assessed with moderate and substantial agreement between multidetector-row CT and MRI. However, our findings suggest that multidetector-row CT does not correlate well enough with MRI findings to replace it in rectal cancer staging.


Perspectives of SLIT/ROBO signaling in placental angiogenesis.
A novel family of evolutionally conserved neuronal guidance cues, including ligands (i.e., Slit, netrin, epherin, and semaphorin) and their corresponding receptors (i.e., Robo, DCC/Unc5, Eph and plexin/ neuropilin), has been identified to play a crucial role in axon pathfinding and branching as well as neuronal cell migration. The presence of commonalities in both neural and vascular developments has led to some exciting discoveries recently, which have extended the functions of these systems to vascular formation (vasculogenesis) and development (angiogenesis). Some of these ligands and receptors have been found to be expressed in the vasculature and surrounding tissues in physiological and pathological conditions. It is postulated that they regulate the formation and integrity of blood vessels. In particular, it has been shown that the Slit/Robo pair plays a novel role in angiogenesis during tumorigenesis and vascular formation during embryogenesis. Herein we summarize briefly the characteristics of this family of neuronal guidance molecules and discuss the extra-neural expression and function of the Slit/Robo pair in angiogenesis in physiological and pathological settings. We report expression of Robo1 protein in capillary endothelium and co-expression of Slit2 and Robo1 proteins in syncytiotrophoblast in healthy term human placental villi. These cellular expression patterns implicate that the Slit/Robo signaling plays an autocrine and/or paracrine role in angiogenesis and trophoblast functions. We also speculate a possible role of this system in pathophysiological placental angiogenesis.


Is Bacillus Calmette-Guerin revaccination necessary for Japanese children?
Bacillus Calmette-Guerin (BCG) revaccination has been implemented in Japan among tuberculin-negative first grade primary and first grade junior high school students for decades. Controversies regarding the effectiveness of BCG revaccination and low incidence of tuberculosis (TB) among Japanese children prompted this study. Cost-effectiveness and cost-benefit analyses were conducted for a cohort of schoolchildren who underwent revaccination during 1996. The study population was a hypothetical cohort comprising 1.35 million first grade primary school and 1.51 million first grade junior high school students enrolled in 1996 at locations throughout Japan. Assuming 50% vaccine efficacy for revaccination, a 10-year duration of protection, and 5% annual discount rate, we calculated the total hypothetical number of TB cases averted, the cost and number of immunizations per TB case averted, and the benefit-cost ratio for the program. The revaccination program for 1996 schoolchildren cohort would prevent 296 TB cases over a 10-year period at a cost of US$ 108,378 per case averted. About 4,963 immunizations would be required to prevent one child from developing TB. The benefit-cost ratio remained at 0.13 with baseline assumptions and ranged from 0.05 to 0.29 and from 0.02 to 0.74 for one-way and two-way sensitivity analyses, respectively. BCG revaccination among schoolchildren is not supported by available scientific and economic data. Based on the results of this study, current BCG revaccination policies in Japan and other countries should be reexamined.


Parenteral administration of L-arginine prevents fetal growth restriction in undernourished ewes.
Intrauterine growth restriction (IUGR) is a major health problem worldwide that currently lacks an effective therapeutic solution. This study was conducted with an ovine IUGR model to test the hypothesis that parenteral administration of l-arginine (Arg) is effective in enhancing fetal growth. Beginning on d 28 of gestation, ewes were fed a diet providing 100% (control-fed) or 50% (underfed) of NRC-recommended nutrient requirements. Between d 60 of gestation and parturition, underfed ewes received i.v. infusions of saline or 155 micromol Arg-HCl/kg body weight 3 times daily, whereas control-fed ewes received only saline. The birth weights of lambs from saline-infused underfed ewes were 23% lower (P < 0.01) than those of lambs from control-fed dams. Administration of Arg to underfed ewes increased (P < 0.01) concentrations of Arg (69%), ornithine (55%), proline (29%), methionine (37%), leucine (36%), isoleucine (35%), cysteine (19%), and FFA (43%) in maternal serum, decreased maternal circulating levels of ammonia (18%) and triglycerides (32%), and enhanced birth weights of lambs by 21% compared with saline-infused underfed ewes. There was no difference in birth weights of lambs between the control-fed and the Arg-infused underfed ewes. These novel results indicate that parenteral administration of Arg to underfed ewes prevented fetal growth restriction and provide support for its clinical use to ameliorate IUGR in humans. The findings also lay a new framework for studying cellular and molecular mechanisms responsible for the beneficial effects of Arg in regulating conceptus growth and development.


Flavanols, the Kuna, cocoa consumption, and nitric oxide.
The Kuna Indians, who reside in an archipelago on the Caribbean Coast of Panama, have very low blood pressure (BP) levels, live longer than other Panamanians, and have a reduced frequency of myocardial infarction, stroke, diabetes mellitus, and cancer-at least on their death certificates. One outstanding feature of their diet includes a very high intake of flavanol-rich cocoa. Flavonoids in cocoa activate nitric oxide synthesis in healthy humans. The possibility that the high flavanol intake protects the Kuna against high BP, ischemic heart disease, stroke, diabetes mellitus, and cancer is sufficiently intriguing and sufficiently important that large, randomized controlled clinical trials should be pursued.


Gene classification using parameter-free semi-supervised manifold learning.
A new manifold learning method, called parameter-free semi-supervised local Fisher discriminant analysis (pSELF), is proposed to map the gene expression data into a low-dimensional space for tumor classification. Motivated by the fact that semi-supervised and parameter-free are two desirable and promising characteristics for dimension reduction, a new difference-based optimization objective function with unlabeled samples has been designed. The proposed method preserves the global structure of unlabeled samples in addition to separating labeled samples in different classes from each other. The semi-supervised method has an analytic form of the globally optimal solution, which can be computed efficiently by eigen decomposition. Experimental results on synthetic data and SRBCT, DLBCL, and Brain Tumor gene expression data sets demonstrate the effectiveness of the proposed method.


Hepatitis B vaccine and uveitis: an emerging hypothesis suggested by review of 32 case reports.
To report a possible association between hepatitis B vaccine and uveitis. Spontaneous reports from the National Registry of Drug-Induced Ocular Side Effects, the World Health Organization, and the Food and Drug Administration were collected on hepatitis B vaccine associated with uveitis between 1982 and 2009. In addition, we performed a Medline literature search using the keywords of uveitis, iritis, or vitritis, in combination with vaccines and hepatitis B vaccine. Data garnered from the spontaneous reports included age, gender, adverse drug reaction, temporal association of uveitis with vaccine doses, concomitant drugs, other systemic disease, recovery, and recurrence after repeat dosage. Thirty-two case reports of uveitis occurring after hepatitis B vaccine were reported to the spontaneous reporting databases. The mean age of the patients was 29 years (1-57 years), with 8 male and 24 female patients. The mean number of days until uveitis was reported after vaccination was 3 days (1-15 days). The uveitis was reported to occur after the first vaccination in 15 patients, after the second vaccination in 3 patients, and after the third vaccination in 3 patients; the duration of time to occurrence of uveitis was not reported for 9 patients. One patient had recurrent uveitis after both the second and third doses of vaccine. One patient had recurrent uveitis after the first and second doses of vaccine. Hepatitis B vaccine may have a possible association with the development of uveitis in some patients. Immune complex deposition and adjuvant effects are potential pathogenic mechanisms.