Randomized, controlled study of the safety and immunogenicity of Peru-15, a live attenuated oral vaccine candidate for cholera, in adult volunteers in Bangladesh.
A live oral Vibrio cholerae O1 El Tor vaccine candidate, Peru-15, was studied for safety, immunogenicity, and excretion in phase 1 (inpatient) and phase 2 (outpatient) studies of Bangladeshi adults.METHODs. The study was conducted among adults, by use of a double-blind, randomized, placebo-controlled design. A single dose of Peru-15 (approximately 2 x 108 cfu) or placebo (buffer only) was given in standard bicarbonate and ascorbic acid buffer.RESULTS. Study treatment did not elicit any major adverse events in the volunteers, during either the inpatient or the outpatient phases, and there were no reports of diarrhea. V. cholerae was isolated from the stool of only 1 volunteer and was found to be genetically identical to the vaccine strain. Vibriocidal antibody responses were seen in 30 (75%) of 40 vaccine recipients and in 3 (10%) of 30 placebo recipients. Peripheral blood immunoglobulin (Ig) A and IgM antibody-secreting cell responses to lipopolysaccharide were seen in the majority of vaccine recipients (response rate, 78%--88%). Seroconversion for lipopolysaccharide-specific IgA antibodies was seen in 88% of vaccine recipients. The response in vaccine recipients was significantly higher than that in placebo recipients, in all of the immunological assays (P=.036 to <.001). A lower immunological response against cholera toxin B subunit was detected.CONCLUSIONS. The safety and immunogenicity of this Peru-15 vaccine candidate indicates the usefulness of future studies in Bangladesh, where cholera is endemic.


Psychiatrists' responses to failure of maintenance therapy with antidepressants.
Some patients being treated for recurrent major depression experience a return of depressive symptoms despite a constant maintenance dose of an antidepressant, a phenomenon known as breakthrough depression. A total of 145 psychiatrists who were members of the Massachusetts Psychiatric Society responded to a survey about intervention in hypothetical cases of breakthrough depression if the patient was taking either 20 mg of fluoxetine, 100 mg of sertraline, 100 mg of nortriptyline, or 40 mg of fluoxetine. For all drugs and dosages, the most popular choice was increasing the dosage, followed by augmenting with lithium or another antidepressant or changing to a different drug.


The missing graphical user interface for genomics.
The Galaxy package empowers regular users to perform rich DNA sequence analysis through a much-needed and user-friendly graphical web interface. See research article http://genomebiology.com/2010/11/8/R86 RESEARCH HIGHLIGHT: With the advent of affordable and high-throughput DNA sequencing, sequencing is becoming an essential component in nearly every genetics lab. These data are being generated to probe sequence variations, to understand transcribed, regulated or methylated DNA elements, and to explore a host of other biological features across the tree of life and across a range of environments and conditions. Given this deluge of data, novices and experts alike are facing the daunting challenge of trying to analyze the raw sequence data computationally. With so many tools available and so many assays to analyze, how can one be expected to stay current with the state of the art? How can one be expected to learn to use each tool and construct robust end-to-end analysis pipelines, all while ensuring that input formats, command-line options, sequence databases and program libraries are set correctly? Finally, once the analysis is complete, how does one ensure the results are reproducible and transparent for others to scrutinize and study?In an article published in Genome Biology, Jeremy Goecks, Anton Nekrutenko, James Taylor and the rest of the Galaxy Team (Goecks et al. 1) make a great advance towards resolving these critical questions with the latest update to their Galaxy Project. The ambitious goal of Galaxy is to empower regular users to carry out their own computational analysis without having to be an expert in computational biology or computer science. Galaxy adds a desperately needed graphical user interface to genomics research, making data analysis universally accessible in a web browser, and freeing users from the minutiae of archaic command-line parameters, data formats and scripting languages. Data inputs and computational steps are selected from dynamic graphical menus, and the results are displayed in intuitive plots and summaries that encourage interactive workflows and the exploration of hypotheses. The underlying data analysis tools can be almost any piece of software, written in any language, but all their complexity is neatly hidden inside of Galaxy, allowing users to focus on scientific rather than technical questions.


Pharmacological or genetic inhibition of LTCC promotes cardiomyocyte proliferation through inhibition of calcineurin activity.
Cardiomyocytes (CMs) lost during ischemic cardiac injury cannot be replaced due to their limited proliferative capacity, which leads to progressive heart failure. Calcium (Ca2+) is an important signal transducer that regulates key cellular processes, but its role in regulating CM proliferation is incompletely understood. A drug screen targeting proteins involved in CM calcium cycling in human embryonic stem cell-derived cardiac organoids (hCOs) revealed that only the inhibition of L-Type Calcium Channel (LTCC), but not other Ca2+ regulatory proteins (SERCA or RYR), induced the CM cell cycle. Furthermore, overexpression of Ras-related associated with Diabetes (RRAD), an endogenous inhibitor of LTCC, induced CM cell cycle activity in vitro, in human cardiac slices, and in vivo. Mechanistically, LTCC inhibition by RRAD induces the cell cycle in CMs by modulating calcineurin activity and translocating Hoxb13 to the CM nucleus. Together, this represents a robust pathway for regenerative strategies.


Intent to Build Hepatitis C Treatment Capacity Within Family Medicine Residencies: A Nationwide Survey of Program Directors: A CERA Study.
In the current interferon-free era, family medicine is in a unique position to deliver hepatitis C (HCV) treatment with adequate training. Little is known about attitudes of family medicine program directors (PDs) toward capacity building within their residency programs. We report the results of a nationwide survey of family medicine PDs to examine these attitudes. This study was part of a CERA (Council of Academic Family Medicine Educational Research Alliance) omnibus survey administered to family medicine PDs between February 2015 and March 2015. Attitudes were assessed using a Likert scale ranging from 1=strongly disagree to 6=strongly agree. We surveyed 452 physicians, with 273 responses (response rate 61%). The majority of PDs (78%) believed that chronic HCV represented a significant problem for primary care, and 61.9% believed their program should take steps to build capacity in HCV treatment. There was no effect of regional HCV prevalence, residency program context, or PD characteristics on intent to build capacity. This is the first report to examine PDs intent to build capacity in HCV treatment in this interferon-free, direct antiviral era. Our findings highlight a historic opportunity to train family physicians and position them on the frontline as HCV treatment providers.


Self-reflection and positive schizotypy in the adolescent brain.
Clinical and phenomenological accounts of schizophrenia suggest that impairments in self-reflective processes significantly contribute to psychopathological expression. Recent imaging studies observe atypical cerebral activation patterns during self-reflection, especially around the cortical midline structures, both in psychosis-prone adults and individuals with schizophrenia. Given that self-reflection processes consolidate during adolescence, and that early transient expression of psychosis (positive schizotypy) also arises during this period, the present study sought to examine whether atypical cerebral activation during self-reflection task could be associated with early schizotypic expression during adolescence. Forty-two neurotypical adolescent participants (19 females) aged from 12 to 19 (15.92±1.9) underwent a self-reflection task using functional neuroimaging (fMRI), where they had to evaluate trait adjectives (1 to 4 ratings) about themselves or their same sex best friend. The Schizotypal Personality Questionnaire (SPQ) was employed to assess positive schizotypic expression. Results showed that positive schizotypy in adolescents significantly correlated with cortical midline activation patterns in the dorsomedial prefrontal cortex (dmPFC) and the posterior cingulate cortex (PCC), as well as the dorsolateral PFC and the lingual gyrus. The results are consistent with previous imaging literature on self-reflection and schizophrenia. They further highlight that the relationship between self-reflection processes and positive schizotypy operates at the trait level of expression and can be observed as early as adolescence.


Effect of long-term treatment with insulin and/or acarbose on glomerular basement membrane thickening in alloxan-diabetic rats.
Acarbose is a competitive inhibitor of the intestinal alpha-glycosidases, that can delay absorption of intestinal carbohydrates causing their malabsorption. In the present paper we studied the effects of insulin, acarbose and their association on glomerular basement membrane thickening in alloxan-diabetic rats. Twenty-five male and female Wistar rats, approximately 3 months old at the beginning of the experiment, were assigned randomly to each of five experimental groups: normal control rats, alloxan-diabetic control rats, alloxan-diabetic rats treated with acarbose, alloxan-diabetic rats treated with insulin, and alloxan-diabetic rats treated with insulin plus acarbose. Alloxan was administered in a single i.v. dose of 442 mg/kg body weight. Insulin was given subcutaneously at doses of 18 to 30 IU/kg corrected daily on the basis of glycosuria and ketonuria. Acarbose was given mixed with rat chow in a dose of 50 mg/100 g chow. Body weight, water and food intake and diuresis, as well as blood and urine glucose were determined after 1, 3, 6, 9, and 12 months of treatment. Glomerular basement membrane (GBM) thickening was determined by electron microscopy at the same times. Clear clinical and laboratory signs of severe diabetes, with blood glucose levels above 200 mg/dl and urine glucose above 3000 mg/dl, were observed in all alloxan-diabetic control rats, in all periods of follow-up, whereas administration of insulin or acarbose reduced the blood glucose levels of treated groups. The most satisfactory control of blood and urine glucose was observed in animals treated with both insulin and acarbose. However, diarrhea was observed in diabetic rats treated with acarbose associated or not with insulin. GBM thickening was correlated with age in all groups. Beginning at six months after diabetes induction, the GBM of untreated diabetic rats was significantly thicker (mean +/- SEM, 4.446 +/- 0.45 mm) than that of normal rats (2.977 +/- 0.63mm). Both insulin and acarbose prevented GBM thickening and their combination induced thickening similar to the age dependent thickening observed for normal rats of the same age. We conclude that acarbose when combined with insulin may be a good option in the control of diabetes and its renal complications.


Communal Behaviors and Psychological Adjustment of Family Caregivers and Persons With Spinal Cord Injury.
OBJECTIVE: Examined the influence of mutual communal behaviors on the adjustment reported by persons with spinal cord injury (SCI) and their family caregivers. Previous research has found that persons who have a history of mutually communal behaviors in relationships may react differently to relationship changes after an acquired physical disability than dyads with few communal behaviors. METHOD: Family caregivers and persons with SCI were administered measures of mutual communal behaviors, depression, and life satisfaction. Structural equation modeling was used to test the relations among caregivers' communal behaviors and care recipients' communal behaviors, depression, and life satisfaction. RESULTS: Caregiver and care recipient reports of communal behaviors were not significantly correlated. Significant paths indicated that care recipients' communal behavior scores were positively associated with their life satisfaction, and care recipients' depression was inversely associated with their life satisfaction. Caregivers' communal behavior scores were unrelated to their self-reported adjustment. CONCLUSIONS: Caregiver-care recipient dyads may differ in their perceptions of communal behaviors in their relationships. Although care recipient reports of communal behavior may be related to their life satisfaction, communal behaviors may not serve a similar function among caregivers of persons with SCI.


GABA and glycine-like immunoreactivity at axoaxonic synapses on 1a muscle afferent terminals in the spinal cord of the rat.
The object of this study was to analyze the synaptic interactions of identified muscle spindle afferent axon terminals in the spinal cord of the rat. Group 1a muscle afferents supplying the gastrocnemius muscle were impaled with microelectrodes in the dorsal white matter of the spinal cord and stained by intracellular injection with Neurobiotin. Postembedding immunogold techniques were used to reveal GABA- and glycine-like immunoreactivity in boutons presynaptic to afferent terminals in the ventral horn and the deep layers of the dorsal horn. Serial-section reconstruction was used to reveal the distribution of synaptic contacts of different types on the afferent terminals. The majority of afferent boutons received axoaxonic and made axodendritic or axosomatic synaptic contacts. In the ventral horn, 91% of boutons presynaptic to the afferent terminals were immunoreactive for GABA alone and 9% were immunoreactive for both GABA and glycine. The mean number of axo-axonic contacts received per terminal was 2.7, and the mean number of synaptic contacts at which the terminal was the presynaptic element was 1.4. In the deep layers of the dorsal horn, 58% of boutons presynaptic to afferent terminals were immunoreactive for GABA alone, 31% were immunoreactive for GABA and glycine, and 11% for glycine alone. The mean number of axoaxonic contacts received per afferent terminal in this region was 1.6 and the mean number of synaptic contacts at which the terminal was the presynaptic element was 0.86. This clearly establishes the principle that activity in 1a afferents is modulated by several neurochemically distinct populations of presynaptic neuron.


The relationship between the rapid rejection of Haemonchus contortus larvae with cells and mediators in abomasal tissues in immune sheep.
Rapid rejection or immune exclusion of challenge larvae is a well recognised phenomenon in sheep hypersensitised by repeated infection with gastrointestinal nematodes. While mast cells and globule leukocytes (GLs) are typically associated with this rapid rejection response, the exact mechanisms and mediators involved are not known. This study has adapted a recently developed ex vivo tissue explant model to examine in more detail the cells and mediators involved in preventing establishment of Haemonchus contortus L3s in abomasal tissue of sensitised sheep. Hypersensitisation of sheep by repeated larval infection resulted in a significant inhibition of larval establishment in abomasal tissue cultures and the extent of inhibition was dependent on the sensitisation dose. Both mast cells and GLs, but not eosinophils, were increased in abomasal tissues of hypersensitised sheep. Globule leucocyte numbers decreased significantly after 3h of culture, independent of the addition of L3s. In contrast, mast cell numbers only decreased after addition of L3s to the tissue cultures and this was associated with an increased release of histamine in tissue washes after incubation with L3s. Although, there was no significant difference in the number of tissue eosinophils between the groups, there was a marked increase in the eosinophil-specific protein, galectin-14, in tissue washes of the hypersensitised sheep after culture, suggesting eosinophils and their products may play a hitherto unrecognised role in the rapid rejection response. Further studies using specific inhibitors in this ex vivo tissue explant model may delineate the relative role of each cell population and mediator in the rapid rejection process.


Prevention of postoperative nausea and vomiting with granisetron and dolasetron in relation to CYP2D6 genotype.
We investigated the efficacy of granisetron and dolasetron in preventing postoperative nausea and vomiting. Because the metabolism of the various antiemetic 5-hydroxytryptamine type 3 (5-HT3) antagonists involves different isoforms of the hepatic cytochrome P450 system, we examined the relationship between the clinical efficacy of these drugs and polymorphic cytochrome P450 2D6 (CYP2D6) genotype. This prospective, randomized, double-blind study involved 150 adult patients with a moderate to high risk for postoperative nausea and vomiting. All subjects received dexamethasone at induction of anesthesia followed by either 12.5 mg of dolasetron or 1 mg of granisetron. We analyzed the number of complete responders (no vomiting or rescue medication) during the first 24 hours after surgery. CYP2D6 genotyping was performed using a TaqMan real-time polymerase chain reaction. A complete response was more frequent in the granisetron group (54.7%) compared with the dolasetron group (38.7%, P < 0.05). In subjects receiving dolasetron, carriers of the duplication of the CYP2D6 allele predicting ultrarapid metabolizer status had more frequent vomiting episodes (P < 0.05) than patients in the granisetron group. It is postulated that the difference in the antiemetic efficacy between two investigated 5-HT3 receptor antagonists may be associated with differences in the carrier status for the duplication of the CYP2D6 allele.


Time-reversal symmetry breaking superconductivity between twisted cuprate superconductors.
Twisted interfaces between stacked van der Waals (vdW) cuprate crystals present a platform for engineering superconducting order parameters by adjusting stacking angles. Employing a cryogenic assembly technique, we construct twisted vdW Josephson junctions (JJ) at atomically sharp interfaces between Bi2Sr2CaCu2O8+x crystals with quality approaching the limit set by intrinsic JJ. Near 45° twist angle, we observe fractional Shapiro steps and Fraunhofer patterns, consistent with the existence of two degenerate Josephson ground states related by time-reversal symmetry (TRS). By programming the JJ current bias sequence, we controllably break TRS to place the JJ into either of the two ground states, realizing reversible Josephson diodes without external magnetic fields. Our results open a path to engineering topological devices at higher temperatures.


Simultaneous measurement of multiple ear proteins with multiplex ELISA assays.
A recent advancement in enzyme-linked immunosorbent assay (ELISA) technology is the multiplex antibody array that measures multiple proteins simultaneously within a single sample. This allows reduction in sample volume, time, labor, and material costs, while increasing sensitivity over single ELISA. Current multiplex platforms include planar-based systems using microplates or slides, or bead-based suspension assay with microspheres. To determine the applicability of this technology for ear research, we used 3 different multiplex ELISA-based immunoassay arrays from 4 different companies to measure cytokine levels in mouse middle and inner ear tissue lysate extracts 24 h following transtympanic Haemophilus influenzae inoculation. Middle and inner ear tissue lysates were analyzed using testing services from Quansys Biosciences, Aushon Biosystems SearchLight (both microplate-based), MILLIPLEX MAP Sample (bead-based), and a RayBiotech, Inc (slide-based) kit. Samples were assayed in duplicate or triplicate. Results were compared to determine their relative sensitivity and reliability for measures of cytokines related to inflammation. The cytokine pg/ml amounts varied among the multiplex assays, so a comparison also was made of the mean fold increase in cytokines from untreated controls. Several cytokines and chemokines were elevated, the extent dependent upon the assay sensitivity. Those most significantly elevated were IL-1α, IL-1β, IL-6, TNFα, VEGF, and IL-8/MIP-2. The results of the multiplex systems were compared with single ELISA kits (IL-1β, IL-6) to assess sensitivity over the traditional method. Overall, the Quansys Biosciences and SearchLight arrays showed the greatest sensitivity, both employing the same multiplex methodology of a spotted array within a microplate well with chemiluminescent detection. They also were more sensitive than the traditional single ELISA performed with commercial kits and matched gene expression changes determined by quantitative RT-PCR. The Quansys array showed a limit of detection for ear IL-6 down to 2-4 pg/ml, indicating it is sufficiently sensitive to detect ear proteins present in low concentrations. Thus, the multiplex ELISA procedures appear suitable and reliable for the study of hearing related proteins, providing accurate, quantitative, reproducible results with considerable improvement in sensitivity and economy.


[Dynamics of coronary artery lumina during tests with cold and with intracoronary and sublingual administration of nitroglycerin in patients with different clinical forms of stenocardia].
Cold tests and those using intracoronary or sublingual nitroglycerin administration were applied during coronarography to 50 coronary patients with varying clinical manifestations of angina pectoris. The quantitative assessment of angiographic patterns showed the cold and nitroglycerin tests to change significantly the extent of stenosis in patients with spontaneous angina (by +13.3 and -30.8%, respectively) and those with angina of effort and at rest (by +5.6 and -12.0%, respectively) and have no such effect in patients with angina of effort. The change in the stenosed coronary arterial lumen was more marked in cases of excentric localization of the atherosclerotic patch inside the coronary artery, as compared to the concentric arterial narrowing. The data obtained demonstrate the variability of coronary arterial lumen at the site of atherosclerotic stenosis in a certain population of patients.


Herpes simplex virus recovery in neural tissues after ocular HSV shedding induced by epinephrine iontophoresis to the rabbit cornea.
Ocular HSV-1 shedding from latently infected rabbits was induced by iontophoresis of 0.01% epinephrine into the eye. Anodal Iontophoresis of epinephrine was performed at 0.8 mAmps for 8 min once a day for 3 consecutive days. Shedding was determined by the presence of HSV-1 in the preocular tear film obtained via eye swabs. Bilateral epinephrine iontophoresis performed on selected days during 220-280 days after inoculation resulted in HSV-1 shedding in 75% of the eyes (30/40) and 100% of the rabbits (20/20). Following the induction of ocular HSV-1 shedding, rabbits were killed and selected neural tissues were homogenized. Cell-free preparations were assayed for the presence of infectious virions using primary rabbit kidney cell monolayers. When the tissues were homogenized immediately after death, virus was detected in only one neural tissue, the trigeminal ganglia. However, when the tissues were incubated in vitro for 18-24 hours prior to the homogenization, infectious HSV-1 was recovered from homogenates of the trigeminal ganglion, superior cervical ganglion, the ophthalmic branch of the trigeminal nerve, and the root entry zone of the trigeminal nerve. A relationship was noted between the time of the last ocular shedding and recovery of infectious HSV from the tissue homogenates. Furthermore, a positive correlation in 11 eyes between the recovery of HSV-1 from the perocular tear film and HSV-1 recovery from one or more corresponding neural tissues was found. These results suggested that epinephrine iontophoresis to the cornea triggered an "alteration" in the state of the virus in the neural tissues of the latently infected rabbits and that the change can be related to the induced ocular shedding.


Differences in conformation of type 3 poliovirus antigenic sites on non-infectious empty particles and infectious virus.
A panel of monoclonal antibodies which react with empty non-infectious type 3 poliovirus particles (C antigen) but not infectious virus (D antigen) were characterized for their reactivity with C antigen particles derived from neutralization-resistant virus strains which had single amino acid substitutions at each of the antigenic sites. Antibodies were identified which failed to bind to variant viruses with modifications at each of antigenic sites 2b, 3b and 4 indicating that the same amino acid sequences involved in the neutralization of infectious virus are also present on the surface of non-infectious particles but in different configurations.


Cord blood transplantation from unrelated donors: a preliminary report from the Japanese Cord Blood Bank Network.
As a source for hematopoietic stem cell transplantation (HSCT), cord blood transplantation from unrelated donors (UCBT) is now considered as an acceptable alternative to patients who need unrelated HSCT. To confirm the findings that mismatched UCBT is feasible, we discussed here the results for 477 patients with hematologic malignancies and non-malignancies who were subjected to UCBT coordinated by the Japanese Cord Blood Bank Network (JCBBN). From February 1997 to October 2001, 411 patients with malignancies and 66 with non-malignancies had UCBT through the cord blood bank in the JCBBN; 311 patients had HLA 0-1 mismatched UCBT; 165, had a 2-4 HLA mismatch. The Kaplan-Meier estimates for 3-year disease-free survival rate (DFS) were 35.2 +/- 2.8% in malignant diseases, and 33.6 +/- 7.2% in patients with non-malignant diseases. The HLA disparity had no effect on DFS, incidence of acute graft-versus-host disease, or engraftment. As reported previously, we also noted the importance of graft cell dose in determining survival in UCBT. Major advantages of UCBT include its rapid availability compared with unrelated donor bone marrow, and tolerance of an HLA mismatch at 2 loci, which will enable extension of the donor pool. This review outlines the latest UCBT progress, with emphasis on practical considerations in HLA-mismatched umbilical cord blood selection.


Anterior cruciate ligament reconstruction in skeletally immature patients : a systematic review.
Different methods of anterior cruciate ligament (ACL) reconstruction have been described for skeletally immature patients before closure of the growth plates. However, the outcome and complications following this treatment remain unclear. The aim of this systematic review was to analyse the outcome and complications of different techniques which may be used for reconstruction of the ACL in these patients. We performed a systematic review of the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. This involved a comprehensive search of PubMed, Medline, CINAHL, Cochrane, Embase and Google Scholar databases using the following combinations of keywords, "knee", "anterior cruciate ligament", "reconstruction", "injury", "children", "adolescent", "skeletally immature", "open physis" and "surgery". A total of 53 studies met the inclusion criteria and were included for analysis. The overall rate of disturbance of growth after ACL reconstruction was 2.6%, with no statistical difference between transphyseal and physeal-sparing techniques. Physeal-sparing techniques had a lower rate of post-operative complications compared with transphyseal techniques (p = 0.0045). Outcomes assessed were Lysholm score, International Knee Documentation Committee (IKDC) score, the IKDC grade, the Tegner score and the KT-1000. Both techniques had similar clinical outcomes. This review reveals low rates of disturbance of growth after ACL reconstruction in skeletally immature patients. Although limited, the available evidence did not support any particular surgical technique when considering disturbance of growth or clinical outcome. Further randomised controlled trials are needed to investigate the efficacy of differing surgical techniques on outcomes in skeletally immature patients. Cite this article: Bone Joint J 2017;99-B:1053-60.


Feasibility of the modified sequential organ function assessment score in a resource-constrained setting: a prospective observational study.
Sub-Saharan Africa has a great burden of critical illness with limited health care resources. We evaluated the feasibility and utility of the modified Sequential Organ Function Assessment (mSOFA) score in assessing morbidity and mortality in the National Referral Hospital's intensive care unit (ICU) for one year. We conducted a prospective, observational cohort study on patients above 12 years of age admitted to the ICU at Mulago Hospital (Kampala, Uganda). All SOFA scores were determined at admission and at 48 h. We modified the SOFA score by replacing the PaO2/FiO2 ratio with SPO2/FiO2. The primary outcome was ICU mortality. This ICU cohort of 118 patients had a mean age of 37 years and an ICU mortality rate of 46.6%. Non-survivors had higher initial (7.7 SD 3.8 vs. 5.5 SD 3.3; p = 0.007), mean (8.1 SD 3.9 vs 4.7 SD 2.6; p < 0.001) and highest mSOFA scores (9.4 SD 4.2 vs. 5.8 SD 3.2; p < 0.001), with an increase of 1.0 (SD 3.1) mSOFA on average after 48 h when compared to survivors (p < 0.001). The area under the receiver operating characteristic curves for each mSOFA category was: initial-0.68, mean-0.76, highest-0.76 and delta mSOFA-0.74. Multivariate logistic regression analysis showed no significant association between mSOFA scores and mortality. Our results confirm that calculation of the mSOFA score is feasible for an ICU population in a resource-limited country. More data are needed to test for an association between mSOFA and mortality.


Molecular Beams with Energies above One Electron Volt.
By using as sources supersonic jets of hydrogen or helium containing small concentrations of heavier molecules we have been able to obtain molecular beams with kinetic energies of the heavy molecules well into the range above I electron volt. A variety of molecules have been successfully accelerated. Intensities of 10(16) to 10(17) heavy molecules per steradian-second have been achieved at these high energies.


Identification of a novel member in the family Albulidae (bonefishes).
A novel Caribbean species Albula sp. cf. vulpes in the family Albulidae (bonefishes) was diagnosed through genetic and morphometric study. Phylogenies derived from 16S rRNA sequences revealed deeply separated lineages among Caribbean bonefishes. Mitochondrial DNA sequence divergences indicated a separation between 3.0 and 5.2 million years before present (b.p.). Cytochrome b phylogenies further supported the classification of A. sp. cf. vulpes as a novel albulid. Morphological variability revealed several differences between A. sp. cf. vulpes and other Caribbean species. A microsatellite library was developed to discern hybridization rates among the species. Microsatellite analyses revealed low levels of hybridization between some members in the complex. One instance of backcrossing was found between A. vulpesxA. sp. B and a pure A. sp. B, indicating that hybrids may have reduced fitness or may be reproductively isolated due to temporal-spatial spawning habitat differences.


Caritas--caring as an ethical conduct.
The aim of this theoretical study is to describe and analyze caritas by seeking the primary source for this phenomenon, which is used as a central motive in Eriksson's Caritative Theory. The search for the origin and the essence of caritas by critical analysis will create an opportunity to assimilate new meaning into the practice of caring science. This new meaning, based on interpretation, will also act as a solid base for the creation of future theories within caring science. Although this study does not intend to create a new theory for this domain, an attempt is made to shed light on new understandings to establish a deeper foundation for further discussion. Therefore, the methodological basis used is the hermeneutics phenomenology described by Nygren. The starting points refer to three basic assumptions, the former two of which present the core of caring science as an academic discipline; the latter borrows from philosophical creation theology. Therefore, the path for analyzing caritas and the significance of developing a deeper and meaningful understanding are based on the writing of Eriksson as well as through historical and philosophical sources from Judaism, such as the Bible and the Talmud. The results of this study have introduced a new meaning and created a 'space' for caritas. These results are related to the notion of attitudes, being driven by curiosity and questioning, that link faith and scientific investigation. Above all, these attitudes form a central motive profoundly linked to love. Hence, caritas as an attitude turns the concept of care into a more ethical act. However, these new understandings have given rise to ethical questions that obligate consideration towards further study.


A systematic review of pharmacoeconomic guidelines.
To review, summarize, and analyze both similarities and differences of pharmacoeconomic (PE) guidelines, to enable researchers to access their characteristics and the current state of PE guidelines; furthermore, to learn which methodological issues still remain contested and to promote the methodological development of PE guidelines. The authors performed a search for PE guidelines using PubMed, the Cochrane library database, and the websites of the International Society for Pharmacoeconomics and Outcomes Research. Information of each guideline was extracted using a pre-designed extraction template, which included 22 aspects; the guidelines were summarized in the forms of charts, and their characteristics have been described. A total of 40 PE guidelines were studied. The most common methodological issues include the types of analysis, sources for effectiveness, use of quality-adjusted life-years (QALYs) to measure outcomes, and use of incremental cost effectiveness ratios to present results. The majority of the guidelines preferred a cost utility analysis with outcomes expressed in terms of QALYs. Most of the guidelines preferred meta-analysis or meta-analysis of the randomized controlled trials, and required a systematic review of all evidence. Issues that varied most in the guidelines were the choice of the comparator, recommended costs to be included, methods related to indirect cost calculations, methods of sensitivity analysis, and discounting rate. A comparison of these guidelines revealed that a number of differences exist among them in several key aspects, and some critical methodological issues still exist, for which no best solution is available. Furthermore, efforts need to be made to develop harmonious methods for the PE, and to improve the transferability of the outcomes of PE evaluations.


LYSOSOMAL ENZYMES IN CELLS INFECTED WITH CYTOPATHIC AND NON-CYTOPATHIC VIRUSES.
In chick embryo cells infected with fowl plague virus, an avian strain of influenza A which produces cytopathic effects, lysosomal enzymes were released from the particulate to the supernatant fraction of homogenates within 6 hours of infection. This change occurred in the presence of high concentrations of parafluorophenylalanine, suggesting that the changes were due to redistribution of preformed enzymes rather than to de novo protein synthesis. No such changes were observed when the Melbourne strain of influenza A virus multiplied in the same cell system without cytopathic effects. The possible role of lysosomal enzymes in virus uncoating and in the genesis of cytopathic effects is discussed.


Marital status and mortality among middle age and elderly men and women in urban Shanghai.
Previous studies have suggested that marital status is associated with mortality, but few studies have been conducted in China where increasing aging population and divorce rates may have major impact on health and total mortality. We examined the association of marital status with mortality using data from the Shanghai Women's Health Study (1996-2009) and Shanghai Men's Health Study (2002-2009), two population-based cohort studies of 74,942 women aged 40-70 years and 61,500 men aged 40-74 years at the study enrollment. Deaths were identified by biennial home visits and record linkage with the vital statistics registry. Marital status was categorized as married, never married, divorced, widowed, and all unmarried categories combined. Cox regression models were used to derive hazard ratios (HR) and 95% confidence interval (CI). Unmarried and widowed women had an increased all-cause HR = 1.11, 95% CI: 1.03, 1.21 and HR = 1.10, 95% CI: 1.02, 1.20 respectively) and cancer (HR = 1.17, 95% CI: 1.04, 1.32 and HR = 1.18, 95% CI: 1.04, 1.34 respectively) mortality. Never married women had excess all-cause mortality (HR = 1.46, 95% CI: 1.03, 2.09). Divorce was associated with elevated cardiovascular disease (CVD) mortality in women (HR = 1.47, 95% CI: 1.01, 2.13) and elevated all-cause mortality (HR = 2.45, 95% CI: 1.55, 3.86) in men. Amongst men, not being married was associated with excess all-cause (HR = 1.45, 95% CI: 1.12, 1.88) and CVD (HR = 1.65, 95% CI: 1.07, 2.54) mortality. Marriage is associated with decreased all cause mortality and CVD mortality, in particular, among both Chinese men and women.


Induced maternal response to the Lyme disease spirochaete Borrelia burgdorferi sensu lato in a colonial seabird, the kittiwake Rissa tridactyla.
Mothers are predicted to invest in their offspring depending on the quality of their mate, their opportunity to invest in future reproduction and the characteristics of the habitat in which their offspring will be born. Recent studies have suggested a transfer of maternal immunity to offspring as an induced response to the local presence of parasites in the environment, but evidence has been indirect. Here, we show the presence of antibodies against the Lyme disease agent Borrelia burgdorferi sensu lato, a spirochaete transmitted by the seabird tick Ixodes uriae, in the eggs of kittiwakes Rissa tridactyla. We report higher prevalence of antibodies against Borrelia in eggs from breeding areas with higher prevalence and abundance of ticks. Further, high repeatabilities of antibody-positive eggs within clutches and between first and replacement clutches show that, within a breeding season, females differ consistently with respect to the expression of this induced maternal response. Our results suggest that mothers can alter investment in their young depending on local conditions. Such maternal effects clearly have implications for the ecology and evolution of host-parasite interactions.


Regulation of ANGPTL8 in liver and adipose tissue by nutritional and hormonal signals and its effect on glucose homeostasis in mice.
The angiopoietin-like protein (ANGPTL) family represents a promising therapeutic target for dyslipidemia, which is a feature of obesity and type 2 diabetes (T2DM). The aim of the present study was to determine the metabolic role of ANGPTL8 and to investigate its nutritional, hormonal, and molecular regulation in key metabolic tissues. The regulation of Angptl8 gene expression by insulin and glucose was quantified using a combination of in vivo insulin clamp experiments in mice and in vitro experiments in primary and cultured hepatocytes and adipocytes. The role of AMPK signaling was examined, and the transcriptional control of Angptl8 was determined using bioinformatic and luciferase reporter approaches. The metabolism of Angptl8 knockout mice (ANGPTL8-/-) was examined following chow and high-fat diets (HFD). Insulin acutely increased Angptl8 expression in liver and adipose tissue, which involved the CCAAT/enhancer-binding protein (C/EBPβ) transcription factor. In insulin clamp experiments, glucose further enhanced Angptl8 expression in the presence of insulin in adipose tissue. The activation of AMPK signaling antagonized the effect of insulin on Angptl8 expression in hepatocytes and adipocytes. The ANGPTL8-/- mice had improved glucose tolerance and displayed reduced fed and fasted plasma triglycerides. However, there was no change in body weight or steatosis in ANGPTL8-/- mice after the HFD. These data show that ANGPTL8 plays important metabolic roles in mice that extend beyond triglyceride metabolism. The finding that insulin, glucose, and AMPK signaling regulate Angptl8 expression may provide important clues about the distinct function of ANGPTL8 in these tissues.


Association of the DASH dietary pattern with insulin resistance and diabetes in US Hispanic/Latino adults: results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).
To examine the association between diet quality and both diabetes status and insulin resistance in Hispanic/Latino adults, and the extent to which differences in diet quality contribute to differences in outcomes across Hispanic/Latino heritage. Cross-sectional study. Data are from 15 942 individuals enrolled in the Hispanic Community Health Study/Study of Latinos. Diet was ascertained using two 24-hour dietary recalls, and diet quality was measured using the Dietary Approaches to Stop Hypertension (DASH) score (range: 0-80, lowest to highest). Diabetes status was defined based on self-reported diagnosis, use of antihyperglycemic medications, or unrecognized diabetes (determined by baseline laboratory measures). Insulin resistance was determined using homeostatic model assessment of β-cell function and insulin resistance (HOMA-IR). The association between DASH and diabetes status was examined using multinomial logistic regression. The association between DASH and HOMA-IR was assessed using linear regression, and we tested whether the association was modified by Hispanic/Latino heritage or diabetes status. DASH score was highest in those with self-reported diabetes (controlled) and no medications (44.8%). A higher DASH score was associated with a lower HOMA-IR, and the association was the same regardless of diabetes status (p>0.8 for the interaction). The association between DASH and diabetes status was strongest for those with controlled self-reported diabetes and who were not taking antihyperglycemic medications. A higher DASH score was associated with less insulin resistance among Hispanics/Latinos. Differences in DASH scores by Hispanic/Latino heritage did not explain the differences in prevalence of diabetes and insulin resistance reported in the diverse Hispanic/Latino population. NCT02060344.


Synthesis, axonal transport, and turnover of the high molecular weight microtubule-associated protein MAP 1A in mouse retinal ganglion cells: tubulin and MAP 1A display distinct transport kinetics.
Microtubule-associated proteins (MAPs) in neurons establish functional associations with microtubules, sometimes at considerable distances from their site of synthesis. In this study we identified MAP 1A in mouse retinal ganglion cells and characterized for the first time its in vivo dynamics in relation to axonally transported tubulin. A soluble 340-kD polypeptide was strongly radiolabeled in ganglion cells after intravitreal injection of [35S]methionine or [3H]proline. This polypeptide was identified as MAP 1A on the basis of its co-migration on SDS gels with MAP 1A from brain microtubules; its co-assembly with microtubules in the presence of taxol or during cycles of assembly-disassembly; and its cross-reaction with well-characterized antibodies against MAP 1A in immunoblotting and immunoprecipitation assays. Glial cells of the optic nerve synthesized considerably less MAP 1A than neurons. The axoplasmic transport of MAP 1A differed from that of tubulin. Using two separate methods, we observed that MAP 1A advanced along optic axons at a rate of 1.0-1.2 mm/d, a rate typical of the Group IV (SCb) phase of transport, while tubulin moved 0.1-0.2 mm/d, a group V (SCa) transport rate. At least 13% of the newly synthesized MAP 1A entering optic axons was incorporated uniformly along axons into stationary axonal structures. The half-residence time of stationary MAP 1A in axons (55-60 d) was 4.6 times longer than that of MAP 1A moving in Group IV, indicating that at least 44% of the total MAP 1A in axons is stationary. These results demonstrate that cytoskeletal proteins that become functionally associated with each other in axons may be delivered to these sites at different transport rates. Stable associations between axonal constituents moving at different velocities could develop when these elements leave the transport vector and incorporate into the stationary cytoskeleton.


Condom-associated erection problems: behavioural responses and attributions in young, heterosexual men.
Background Previous studies have associated men who experience condom-associated erection problems (CAEP) with incomplete condom use and/or foregoing using condoms altogether. However, how men respond to CAEP and what they attribute CAEP to, remains unclear. Understanding young men's CAEP responses and attributions could help improve sexually transmissible infections (STI)/HIV prevention programs and interventions. Behavioural responses to, and attributions for, CAEP during application (CAEP-Application) and/or during penile-vaginal intercourse (CAEP-PVI) were reported using an online questionnaire by 295 young, heterosexual men (aged 18-24 years) who were recruited via social media websites and university Listservs across major cities in the Midwestern USA. Behavioural responses to CAEP-Application included receiving oral or manual stimulation, stimulating a partner, self-stimulation, foregoing condom use and applying the condom after starting intercourse. Attributions for CAEP-Application included: distraction, fit and feel problems, application taking too long and having consumed too much alcohol. Behavioural responses to CAEP-PVI included increasing the intensity of intercourse, removing the condom to receive oral or manual stimulation and removing condom and continuing intercourse. Attributions for CAEP-PVI included: lack of sensation, taking too long to orgasm, not being 'turned on' enough, fit and feel problems and partner-related factors. Men who report CAEP respond with both STI/HIV risk-reducing and potentially risk-increasing behaviours (e.g. forgoing condom use). Men attribute their experiences to a wide range of individual- and partner-level factors. Addressing men's CAEP behavioural responses and attributions may increase the efficacious value of condom programs and STI/HIV prevention interventions - particularly among men who experience CAEP.


Inflammatory Bowel Disease Does Not Impact Mortality but Increases Length of Hospitalization in Patients with Acute Myocardial Infarction.
Inflammatory bowel diseases (IBD) have been associated with increased risk of cardiovascular events. We aimed to investigate the outcomes of myocardial infarction (MI) in patients with IBD. We performed a cross-sectional study utilizing data from the Nationwide Inpatient Sample from the years 1998 to 2010. ICD-9-CM codes were used to identify patients with Crohn's disease (CD) (555.X), ulcerative colitis (UC) (556.X), and acute MI (410.X). Outcomes in patients with MI with and without IBD were compared. Univariate analysis was performed. Multivariate logistic regression was used to determine the effect of UC and CD on in-hospital MI mortality after adjusting for confounders. A total of 2,629,161 MI, 3,607 UC and 3784 CD patients were analyzed. UC (odds ratio [OR], 1.12; 95% CI 0.98-1.29) and CD (OR 0.99; 95% CI 0.86-1.15) did not affect in-hospital mortality in patients with MI. There was no difference between in-hospital mortality in patients with MI with or without UC (7.75% vs. 7.05%; p = 0.25) or in patients with MI with or without CD (6.50% vs. 6.59%; p = 0.87). The length of stay (LOS) was higher in IBD patients and total charges were statistically higher in patients with UC as compared to non-IBD patients ($65,182 vs. $53,542; p < 0.001). This study shows that IBD does not impact in-hospital mortality from MI. However, patients with MI with IBD have longer LOS. Patients with UC have higher total hospitalization charges than patients with MI without IBD. Further prospective studies are needed to assess the outcomes of MI in IBD patients.


Heat inactivation of beta-lactam antibiotics in milk.
The presence of residues of antimicrobial substances in milk is one of the main concerns of the milk industry, as it poses a risk of toxicity to public health, and can seriously influence the technological properties of milk and dairy products. Moreover, the information available on the thermostability characteristics of these residues, particularly regarding the heat treatments used in control laboratories and the dairy industry, is very scarce. The aim of the study was, therefore, to analyze the effect of different heat treatments (40 degrees C for 10 min, 60 degrees C for 30 min, 83 degrees C for 10 min, 120 degrees C for 20 min, and 140 degrees C for 10 s) on milk samples fortified with three concentrations of nine beta-lactam antibiotics (penicillin G: 3, 6, and 12 microg/liter; ampicillin: 4, 8, and 16 microg/liter; amoxicillin: 4, 8, and 16 microg/liter; cloxacillin: 60, 120, and 240 microg/liter; cefoperazone: 55, 110, and 220 microg/liter; cefquinome: 100, 200, and 400 microg/liter; cefuroxime: 65, 130, and 260 microg/liter; cephalexin: 80, 160, and 220 microg/ liter; and cephalonium: 15, 30, and 60 microg/liter). The method used was a bioassay based on the inhibition of Geobacillus stearothermophilus var. calidolactis. The results showed that heating milk samples at 40 degrees C for 10 min hardly produced any heat inactivation at all, while the treatment at 83 degrees C for 10 min caused a 20% loss in penicillin G, 27% in cephalexin, and 35% in cefuroxime. Of the three dairy industry heat treatments studied in this work, low pasteurization (60 degrees C for 30 min) and treatment at 140 degrees C for 10 s only caused a small loss of antimicrobial activity, whereas classic sterilization (120 degrees C for 20 min) showed a high level of heat inactivation of over 65% for penicillins and 90% for cephalosporins.


[Current trends of using evidence based medicine principles in urgent surgical service development in Adjara].
Ongoing social and economic processes in Georgia had a strong influence on the basic health indicators of the population. Change of usual lifestyle, poor living conditions, worsening of communications and unemployment leads to condition of the chronic stress and development of related pathologies. According to the current statistics there is a great increase in the cases of surgical pathology. Taking into account the existing realities the serious problem is a provision of and accessibility to the health services designated for this groups of the population. Based on the advanced methods of research the author of the article studied in Adjara the social environment, working and living conditions and effectiveness of preventive, curative and rehabilitative surgical care rendered to the patients with severe surgical pathologies. There have been carried out the analysis of the processes, characterising health and medical activities of the population of Autonomous Republic. The author believes, that despite the number of problems in health system, introduction of well organised primary health care will make possible to provide the majority of patients with timely and qualified care.


Pharmacist Provision of Medication Abortion: A Pilot Study.
To perform a 'proof of concept' pilot and assess patient satisfaction of pharmacist provision of medication abortion utilizing an implementation toolkit STUDY DESIGN: Pharmacists completed an online and in-person training followed by an online assessment prior to participating in the pilot. Pharmacists provided medication abortion care using a "no-test" protocol and an implementation toolkit. Participants were administered 200 mg of mifepristone orally on the day of their abortion visit and instructed to take 800 mcg of misoprostol buccally 24-48 hours later (with an additional 800 mcg buccally four hours after the first dose for patients 63-70 days gestation). Visits were completed in person in a private room adjacent to the pharmacy. We assessed the rate of completed abortions and any complications. Following their abortion, patients completed a brief interviewer-administered survey and semi-structured qualitative interview. Ten patients completed medication abortion visits. Nine out of 10 participants had complete abortions. One participant identified that she did not pass her pregnancy and underwent an in-office aspiration. One participant visited an Emergency Department for pain and received pain medication. No serious adverse events occurred. All patients completed the post-abortion survey, and all were "very satisfied" with their abortion experience. Nine patients completed post-abortion interviews. In this pilot study, pharmacists were successful at providing medication abortion to patients. Satisfaction was high and complications were uncommon. Patients were highly satisfied with pharmacist provision of medication abortion and are likely to utilize this service if available.


World assumptions and the role of trauma in borderline personality disorder.
The present study tested whether borderline personality disorder (BPD) is characterized by specific worldviews as hypothesized by cognitive models, using Janoff-Bulman's [(1989) Social Cognition, 7, 113-136] world assumptive model of negative effects of trauma. A second aim of this study was to investigate the role of trauma in the content of worldviews of BPD patients. Fifteen BPD patients, 14 patients with Cluster C personality disorders (PD), 19 patients with axis-I psychopathology and 21 non-patients filled out the World Assumptions Scale, the Personality Disorder Belief Questionnaire, a childhood trauma checklist (assessing physical, emotional and sexual abuse) and the BPD Checklist (severity of BPD psychopathology). BPD patients appear to view the world as malevolent and perceive less luck independent of trauma but dependent of BPD psychopathology. Furthermore, BPD patients have low self-worth and persist in specific beliefs independent of trauma or severity of BPD psychopathology. Pretzer's theory of BPD can be largely supported through Janoff-Bulman's world assumptive model. World assumptions of BPD patients can better be explained by the severity of BPD psychopathology than by the presence of trauma.


Measurement of electronic states of PbS nanocrystal quantum dots using scanning tunneling spectroscopy: the role of parity selection rules in optical absorption.
We study the structure of electronic states in individual PbS nanocrystal quantum dots by scanning tunneling spectroscopy (STS) using one-to-two monolayer nanocrystal films treated with 1, 2-ethanedithiols (EDT). Up to six individual valence and conduction band states are resolved for a range of quantum dot sizes. The measured states' energies are in good agreement with calculations using the k · p four-band envelope function formalism. A comparison of STS and optical absorption spectra indicates that some of the absorption features can only be explained by asymmetric transitions involving the states of different symmetries (e.g., S and P or P and D), which points towards the relaxation of the parity selection rules in these nanostructures. STS measurements also reveal a midgap feature, which is likely similar to one observed in previous charge transport studies of EDT-treated quantum dot films.


The warburg effect in leukemia-stroma cocultures is mediated by mitochondrial uncoupling associated with uncoupling protein 2 activation.
In 1956, Otto Warburg proposed that the origin of cancer cells was closely linked to a permanent respiratory defect that bypassed the Pasteur effect (i.e., the inhibition of anaerobic fermentation by oxygen). Since then, permanent defects in oxygen consumption that could explain the dependence of cancer cells on aerobic glycolysis have not been identified. Here, we show that under normoxic conditions exposure of leukemia cells to bone marrow-derived mesenchymal stromal cells (MSC) promotes accumulation of lactate in the culture medium and reduces mitochondrial membrane potential (DeltaPsiM) in both cell types. Notably, the consumption of glucose was not altered in cocultures, suggesting that the accumulation of lactate was the result of reduced pyruvate metabolism. Interestingly, the decrease in DeltaPsiM was mediated by mitochondrial uncoupling in leukemia cells and was accompanied by increased expression of uncoupling protein 2 (UCP2). HL60 cells fail to increase UCP2 expression, are not uncoupled after coculture, and do not exhibit increased aerobic glycolysis, whereas small interfering RNA-mediated suppression of UCP2 in OCI-AML3 cells reversed mitochondrial uncoupling and aerobic glycolysis elicited by MSC. Taken together, these data suggest that microenvironment activation of highly conserved mammalian UCPs may facilitate the Warburg effect in the absence of permanent respiratory impairment.


Association of C677T and A1298C polymorphisms of the MTHFR gene with maternal risk for Down syndrome: A meta-analysis of case-control studies.
Several studies around the world support the hypothesis that genetic polymorphisms involved in folate metabolism could be related to the maternal risk for Down syndrome (DS). Most of them investigated the role of MTHFR C677T and/or A1298C polymorphisms as maternal risk factors for DS, but their results are often conflicting and still inconclusive. We conducted a systematic review and meta-analysis to clarify the association of MTHFR C677T and/or A1298C polymorphisms with the maternal risk of DS. Our search strategy selected 42 eligible case control studies for a total of 4131 case mothers and 5452 control mothers. The Newcastle-Ottawa Scale was used to assess the methodological quality of the selected studies. To assess the confidence of statistically significant associations we applied false positive report probability test, and we performed the trial sequential analysis to minimize the type I error and random error. We observed significant associations between the MTHFR C677T polymorphism and maternal risk for DS for each of the genetic models investigated (dominant, recessive, codominant, and allelic contrast). Subgroup analysis by region revelated significant association in the Asian population for all the genetic models investigated. Significant associations were also found for certain genetic models in North American, South American, and Middle Eastern populations, while no association was observed in Europeans. The MTHFR A1298C polymorphism did not show any association with the maternal risk of DS, either alone or in combination with the C677T one. The results of false positive report probability to verify the confidence of a significant association suggest that the association between the MTHFR C677T polymorphism and the maternal risk for DS is noteworthy, with high confidence in Asians. The results of this meta-analysis support that the MTHFR C677T polymorphism, but not the A1298C one, is associated with the maternal risk for DS. Further studies are required to better characterize the contribution of gene-gene and gene-nutrient interactions as well as those of other regional or ethnic factors that could explain the observed different effect size in different populations.


BDPCA plus LDA: a novel fast feature extraction technique for face recognition.
Appearance-based methods, especially linear discriminant analysis (LDA), have been very successful in facial feature extraction, but the recognition performance of LDA is often degraded by the so-called "small sample size" (SSS) problem. One popular solution to the SSS problem is principal component analysis (PCA) + LDA (Fisherfaces), but the LDA in other low-dimensional subspaces may be more effective. In this correspondence, we proposed a novel fast feature extraction technique, bidirectional PCA (BDPCA) plus LDA (BDPCA + LDA), which performs an LDA in the BDPCA subspace. Two face databases, the ORL and the Facial Recognition Technology (FERET) databases, are used to evaluate BDPCA + LDA. Experimental results show that BDPCA + LDA needs less computational and memory requirements and has a higher recognition accuracy than PCA + LDA.


Confocal microscopic estimation of GABAergic nerve terminals in the central nervous system.
We describe a method for estimating the average proportion of GABAergic terminal area relative to total nerve terminal area with confocal microscopy. Nerve terminal regions were identified with dual colour immunofluorescence on Vibratome sections with an antibody to synaptophysin (SYN), and GABAergic processes, including axon terminals, were identified with an antibody to glutamic acid decarboxylase (GAD). Sections were viewed in an Olympus AX70 microscope attached to a Biorad 1024 MRC scanning confocal system. Images were collected with a 100 x objective from the same tissue locations and imported into the NIH-Image program, where black and white binary images were obtained for co-localisation and quantitation. Measurements were made separately of areas of SYN/GAD (GABAergic terminals) and SYN labelling (all terminals). The relative proportion of GABAergic terminal areas in visual cortex (6.1+/-1%; mean +/- SE), CA1 hippocampus (2.6+/-0.5%) and deep cerebellar nuclei (46.6+/-3%) are consistent with what is known of the relative levels of inhibitory input to these structures. The assumptions that SYN labelling is restricted to axon terminals, and that SYN labels all axon terminals was tested by ultrastructural localisation of SYN in the three brain regions examined. Only 7.4+/-0.4% of SYN-labelled profiles could not be positively identified as synaptic vesicle-containing axon terminals, and between 93.4 and 99.2% of vesiculated axon profiles were SYN-positive. These results suggest that SYN is a very reliable marker for axon terminals, and validates the confocal analytical approach. The confocal method allows rapid sampling of many brain regions and would be suitable for examining terminals containing any neurotransmitter that can be detected immunocytochemically.


Stabilizing the Naphthalenediimide Radical within a Tetracationic Cyclophane.
Organic radicals are of importance in developing smart materials that have paramagnetic and/or near-infrared optical properties. Their practical applications, however, are limited by the labile nature of the radicals. Here, we demonstrate that by using a tetracationic cyclophane, namely, cyclobis(4,4'-(1,4-phenylene)bispyridine-p-phenylene) (ExBox4+), to encapsulate a naphthalenediimide (NDI) guest, the redox properties of NDI can be modulated. In organic solvents such as MeCN or DMF, ExBox4+ is able to provide the surrounding Coulombic attraction to the NDI•- radical anion and therefore enhance its stability toward oxidation. In water, NDI•- is prone to dimerization, forming its (NDI•-)2 dimer. Under UV-light irradiation, the (NDI•-)2 dimer is observed to disproportionate and yield the dianionic NDI2-. ExBox4+ is able to encapsulate the NDI•- radical anion and prevent its dimerization, and as a consequence, the radical anion is protected from further reduction in a noncovalent manner. We believe that our strategy of modulating the redox properties of NDI by either host-guest recognition or mechanical interlocking can aid and abet the development of radical-based materials, which could be employed in pursuit of applications in many areas, such as transporting spin and charges.


Catalytic Fast Pyrolysis of Soybean Straw Biomass for Glycolaldehyde-Rich Bio-oil Production and Subsequent Extraction.
In this study, soybean straw (SS) as a promising source of glycolaldehyde-rich bio-oil production and extraction was investigated. Proximate and ultimate analysis of SS was performed to examine the feasibility and suitability of SS for thermochemical conversion design. The effect of the co-catalyst (CaCl2 + ash) on glycolaldehyde concentration (%) was examined. Thermogravimetric-Fourier-transform infrared (TG-FTIR) analysis was applied to optimize the pyrolysis temperature and biomass-to-catalyst ratio for glycolaldehyde-rich bio-oil production. By TG-FTIR analysis, the highest glycolaldehyde concentration of 8.57% was obtained at 500 °C without the catalyst, while 12.76 and 13.56% were obtained with the catalyst at 500 °C for a 1:6 ratio of SS-to-CaCl2 and a 1:4 ratio of SS-to-ash, respectively. Meanwhile, the highest glycolaldehyde concentrations (%) determined by gas chromatography-mass spectrometry (GC-MS) analysis for bio-oils produced at 500 °C (without the catalyst), a 1:6 ratio of SS-to-CaCl2, and a 1:4 ratio of SS-to-ash were found to be 11.3, 17.1, and 16.8%, respectively. These outcomes were fully consistent with the TG-FTIR results. Moreover, the effect of temperature on product distribution was investigated, and the highest bio-oil yield was achieved at 500 °C as 56.1%. This research work aims to develop an environment-friendly extraction technique involving aqueous-based imitation for glycolaldehyde extraction with 23.6% yield. Meanwhile, proton nuclear magnetic resonance (1H NMR) analysis was used to confirm the purity of the extracted glycolaldehyde, which was found as 91%.


Laser computed-tomography microscope.
The computed tomography (CT) technique is implemented in an optical transmission microscope with a laser as a light source. A rotational Pechan prism is used in the illumination optics of the microscope for projecting a thick 3-D sample onto a 2-D array detector in different directions. A minicomputer is employed for 3-D reconstruction from the observed image data. Energy throughput efficiency and signal-to-noise ratio in the developed CT microscope are higher than those of our previously developed CT microscope [J. Opt. Soc. Am. A 4, 292 (1987)]. Instrumentation of this microscope is described and some experimental results are shown with biological samples.


DNA condensing effects and sequence selectivity of DNA binding of antitumor noncovalent polynuclear platinum complexes.
The noncovalent analogues of antitumor polynuclear platinum complexes represent a structurally discrete class of platinum drugs. Their chemical and biological properties differ significantly from those of most platinum chemotherapeutics, which bind to DNA in a covalent manner by formation of Pt-DNA adducts. In spite of the fact that these noncovalent polynuclear platinum complexes contain no leaving groups, they have been shown to bind to DNA with high affinity. We report here on the DNA condensation properties of a series of noncovalent analogues of antitumor polynuclear platinum complexes described by biophysical and biochemical methods. The results demonstrate that these polynuclear platinum compounds are capable of inducing DNA condensation at more than 1 order of magnitude lower concentrations than conventional spermine. Atomic force microscopy studies of DNA condensation confined to a mica substrate have revealed that the DNA morphologies become more compact with increasing concentration of the platinum complexes. Moreover, we also found that the noncovalent polynuclear platinum complex [{Pt(NH3)3}2-μ-{trans-Pt(NH3)2(NH2(CH2)6NH2)2}](6+) (TriplatinNC-A) binds to DNA in a sequence-dependent manner, namely, to A/T-rich sequences and A-tract regions, and that noncovalent polynuclear platinum complexes protect DNA from enzymatic cleavage by DNase I. The results suggest that mechanisms of antitumor and cytotoxic activities of these complexes may be associated with their unique ability to condense DNA along with their sequence-specific DNA binding. Owing to their high cellular accumulation, it is also reasonable to suggest that their mechanism of action is based on the competition with naturally occurring DNA condensing agents, such as polyamines spermine, spermidine, and putrescine, for intracellular binding sites, resulting in the disturbance of the correct binding of regulatory proteins initiating the onset of apoptosis.


Pre-ischemia electro-acupuncture potentiates the expression of Bcl-2 and transforming growth factor-beta 1 in rat brains.
The expression of the anti-apoptotic molecules Bcl-2 and transforming growth factor-beta 1 is known to confer protective effects on the cerebral ischemia-reperfusion injury. The current study investigated the expression levels of Bcl-2 and transforming growth factor-beta 1 in response to multiple pre-ischemia electro-acupuncture at acupoints Zusanli (ST36) and Fengchi (GB20) stimulation. Rats were divided into five groups: uninjured, control, non-acupoint, GB20 and ST36. Rats in the non-acupoint, GB20 and ST36 groups received 30 minutes (3 times or 18 times) of electro-acupuncture stimulation before experimental cerebral ischemia was induced. Bcl-2 and transforming growth factor-beta 1 were found to be significantly increased in the ST36 groups with either 3 or 18 electro-acupuncture treatments (P < 0.05). The production was higher with 18 electro-acupuncture treatments in the ST36 groups (P < 0.05). In the GB20 groups, significant increase was only observed in transforming growth factor-beta 1 with 18 electro-acupuncture treatments (P < 0.05). No significant elevation of the level of transforming growth factor-beta 1 was observed in the non-acupoint groups. However, the production of Bcl-2 increased with 18 treatments in the non-acupoint groups (P < 0.05). The data suggest that multiple pre-ischemia electro-acupuncture at ST36 was effective in conferring neuroprotective effect on the brain by means of upregulation of Bcl-2 and transforming growth factor-beta 1 and the effect was increase with the number of treatment.


Conventional pituitary irradiation in acromegaly. Effect on growth hormone and TSH secretion.
Thirty-one patients who had been treated for acromegaly for 1-21 years with conventional pituitary irradiation were re-examined. Immunoreactive growth hormone (GH) was measured in connection with an oral glucose load. Adrenal and gonadal functions were assessed on the basis of plasma cortisol and the urinary excretion of 17-ketogenic steroids, 17-ketosteroids and gonadotrophins. In evaluating the thyroid-pituitary axis the thyrotrophin-releasing hormone stimulation test (TRH) was used. Initially 30 patients had experienced definite benefit from the treatment but at the time of re-examination 10 still had clinically active disease and required another type of treatment. Normal GH levels (less than 5 ng/ml/1) were seen in only 12 patients. Skin thickness was normal in 15 out of 30. Thus the remission rate can be evaluated as being 67% as regards clinical activity, 50% with regard to skin thickness and 39% in terms of GH levels. Hypogonadism occurred in 12 patients (39%) and adrenal and thyroid failure in 5 patients each (16%). The response to TRH was within the normal range in 2 of the hypothyroid patients. In 22 euthyroid patients the mean increment in serum TSH in response to 200 mug of synthetic TRH was only 5.8 mU/1 which was significantly below the normal mean 12.5 mU/1. Furthermore, in 7 of these patients (32%) the response was absent or subnormal (less than 3.0 mU/1). This indicated that the pituitary is capable of secreting enough TSH for maintenance of an euthyroid state but that its capacity is limited. Conventional pituitary irradiation is not a very effective treatment in acromegaly but may still be recommended in selected cases.


Cytochrome b Mutations F129L and G143A Confer Resistance to Azoxystrobin in Cercospora nicotianae, the Frogeye Leaf Spot Pathogen of Tobacco.
Azoxystrobin is the only synthetic, systemic fungicide labeled in the United States for management of frogeye leaf spot (FLS) of tobacco (Nicotiana tabacum L.), caused by Cercospora nicotianae. Though traditionally considered a minor disease in the United States, FLS has recently become yield and quality limiting. In 2016 and 2017, 100 C. nicotianae isolates were collected from symptomatic tobacco from eight counties in Kentucky, United States. Prior to azoxystrobin sensitivity testing, some C. nicotianae isolates were found to utilize the alternative oxidase pathway and, after assay comparisons, conidial germination was utilized to evaluate sensitivity in C. nicotianae as opposed to mycelial growth. Azoxystrobin sensitivity was determined by establishing the effective concentration to inhibit 50% conidial germination (EC50) for 47 (in 2016) and 53 (in 2017) C. nicotianae isolates. Distributions of C. nicotianae EC50 values indicated three qualitative levels of sensitivity to azoxystrobin. Partial cytochrome b sequence, encompassing the F129L and G143A mutation sites, indicated single-nucleotide polymorphisms (SNPs) conferring the F129L mutation in C. nicotianae of moderate resistance (azoxystrobin at 0.177 ≤ EC50 ≤ 0.535 µg/ml) and the G143A mutation in isolates with an azoxystrobin-resistant phenotype (azoxystrobin EC50 > 1.15 µg/ml). Higher frequencies of resistant isolates were identified from greenhouse transplant (4 of 17) and conventionally produced (58 of 62) tobacco samples, as compared with field-grown tobacco (<4 weeks prior to harvest; 4 of 62) or organically produced samples (1 of 7), respectively. Together, these results suggest that resistance to azoxystrobin in C. nicotianae occurs broadly in Kentucky, and generate new hypotheses about selection pressure affecting resistance mutation frequencies.


Transfer Deep Learning for Dental and Maxillofacial Imaging Modality Classification: A Preliminary Study.
To apply the technique of transfer deep learning on a small data set for automatic classification of X-ray modalities in dentistry. For solving the problem of classification, the convolution neural networks based on VGG16, NASNetLarge and Xception architectures were used, which received pre-training on ImageNet subset. In this research, we used an in-house dataset created within the School of Dental Medicine, Tel Aviv University. The training dataset contained anonymized 496 digital Panoramic and Cephalometric X-ray images for orthodontic examinations from CS 8100 Digital Panoramic System (Carestream Dental LLC, Atlanta, USA). The models were trained using NVIDIA GeForce GTX 1080 Ti GPU. The study was approved by the ethical committee of Tel Aviv University. The test dataset contained 124 X-ray images from 2 different devices: CS 8100 Digital Panoramic System and Planmeca ProMax 2D (Planmeca, Helsinki, Finland). X-ray images in the test database were not pre-processed. The accuracy of all neural network architectures was 100%. Following a result of almost absolute accuracy, the other statistical metrics were not relevant. In this study, good results have been obtained for the automatic classification of different modalities of X-ray images used in dentistry. The most promising direction for the development of this kind of application is the transfer deep learning. Further studies on automatic classification of modalities, as well as sub-modalities, can maximally reduce occasional difficulties arising in this field in the daily practice of the dentist and, eventually, improve the quality of diagnosis and treatment.


Detoxification: the basis of current practice.
With chronic use of a psychoactive drug the central nervous system undergoes a series of changes. These changes vary both in nature and in extent with each drug, but in general, they alter the responsiveness of the nervous system to the drug so as to reduce the perceived clinical effect, and also alter the innate responsiveness of the affected neurons to various stimuli. With cessation of drug use the nervous system undergoes a natural healing which consists of a restoration of normal responsiveness, but this process takes some time during which the patient's responses are abnormal and they are vulnerable to a variety of stressors. Detoxification is the safe negotiation of this period.


Professionals' perception of intimate partner violence in young people: a qualitative study in northern Spain.
Intimate partner violence (IPV) is a public health problem with devastating effects on young women's health. These negative effects increase when the exposure to IPV lasts for a long time and exposure at an early age increases the risk of adult IPV. Despite efforts made in the last few decades, data show little progress has been made towards its reduction. Thus, the aim of the study reported here is to explore professionals' perceptions regarding intimate partner violence (IPV) among young people, focusing on the characteristics of the phenomenon and their perceptions about existing programmes and campaigns aimed at addressing it. Twelve professionals from education, health and municipal social services were interviewed. All but one of the interviews were recorded and transcribed verbatim. Data were analysed according to the methodology of inductive thematic analysis, with the support of Atlas.ti software. The transcripts were read several times and coded line by line. Afterwards, codes were grouped into themes. The developed themes were refined into two phases with the participation of all the authors. From the analysis, the following three themes were identified: "A false sense of gender equity", "IPV among young people: subtle, daily and normalized", and "Mass media campaigns do not fit young people's needs". According to the participants, psychological abuse in the form of controlling behaviour by their partners is the most common type of IPV young women are exposed to, although exposure to other types of IPV was also acknowledged. This violence was described as something subtle, daily and normalized and, consequently, not something that is easy to recognize for the girls that are exposed to it, nor for adults working with young people. The study participants showed good knowledge of the characteristics IPV has among young people. This knowledge was reflected in locally implemented IPV prevention projects, which they considered successful in addressing young people's needs. However, these interventions lacked formal evaluation, political support and continuation. The study participants did not believe that nationwide mass media campaigns realistically reflected the specific characteristics of IPV among young people. Thus, participants perceived these campaigns to be ineffective.


The use of saliva specimens for detection of influenza A and B viruses by rapid influenza diagnostic tests.
Diagnostic tests for influenza infection commonly use nasopharyngeal swabs (NPS) even though these are invasive to obtain. As an alternative specimen, we evaluated the diagnostic usefulness of saliva samples with rapid influenza diagnostic tests (RIDTs). Both NPS and saliva samples were collected from 385 influenza suspected patients and analyzed using Sofia Influenza A+B Fluorescence Immunoassay (Quidel Corporation, San Diego, CA, USA), ichroma TRIAS Influenza A+B (Boditech, Chuncheon, Korea), SD Bioline Influenza Ag (Standard Diagnostic, Yonggin, Korea), BinaxNOW Influenza A/B antigen kit (Alere Inc., Waltham, MA, USA), and real-time reverse transcriptase PCR (RT-PCR). Of the 385 patients, 31.2% (120/385) were positive for influenza A, and 7.5% (29/385) were positive for influenza B virus with saliva or NPS by RT-PCR. The diagnostic sensitivity was slightly higher in NPS than in saliva samples for both influenza A and B by all of the four RIDTs. The diagnostic sensitivities of Sofia and ichroma TRIAS were significantly superior to those of the other conventional influenza RIDTs with both types of sample. The sensitivities of Sofia and ichroma TRIAS with saliva specimens were comparable to the sensitivities of the other two conventional RIDTs with NPS specimens. The simultaneous use of saliva and NPS samples exhibited improved sensitivity from 10.0% to 13.3% for influenza A and from 10.3% to 17.2% for influenza B compared to using NPS alone. This study demonstrates that saliva is a useful specimen for influenza detection, and that the combination of saliva and NPS could improve the sensitivities of influenza RIDTs.


Actinopolymorpha pittospori sp. nov., an endophyte isolated from surface-sterilized leaves of an apricot tree (Pittosporum phylliraeoides).
A member of the genus Actinopolymorpha, designated PIP 143(T), was isolated from the leaves of an Australian native apricot tree (Pittosporum phylliraeoides). The isolate was a Gram-reaction-positive, aerobic actinobacterium, with a well-developed substrate mycelium that fragmented into small rods. Phylogenetic evaluation based on 16S rRNA gene sequences placed the isolate in the family Nocardioidaceae. Strain PIP 143(T) was most closely related to Actinopolymorpha cephalotaxi I06-2230(T) (98.7 %) and Actinopolymorpha rutila YIM 45725(T) (98.1 %). Chemotaxonomic data, including cell-wall components, menaquinones and fatty acids, confirmed the affiliation of strain PIP 143(T) to the genus Actinopolymorpha. Phylogenetic analysis and physiological and biochemical studies, in combination with DNA-DNA hybridization studies, allowed the differentiation of strain PIP 143(T) from its closest phylogenetic neighbours with validly published names. Therefore, a novel species is proposed, with the name Actinopolymorpha pittospori sp. nov. The type strain is PIP 143(T) ( = DSM 45354(T) = ACM 5288(T) = NRRL B-24810(T)).


Primary pulmonary MALT-lymphoma mimicking pulmonary infection: a case report and overview on the pertinent literature.
Primary pulmonary extra-nodal MALT-lymphomas are very uncommon. Clinical-radiological pattern is variable and usually non-specific and a correct diagnosis usually requires the histopathological examination. Herein we report a case of a 59-year-old man presented with dyspnea at the slightest effort and dry cough. At imaging multiple pulmonary consolidations with interlobular septal thickenings and ground-glass opacities were disclosed, defining a crazy paving pattern. The surgical approach was necessary to reach the diagnosis of primary pulmonary low-grade marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT-lymphoma). Immunotherapy (Rituximab) and chemotherapy (Bendamustine) were started leading to a progressive improvement of the disease. (Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 260-263).


Targeted deletion of matrix metalloproteinase-9 attenuates left ventricular enlargement and collagen accumulation after experimental myocardial infarction.
Matrix metalloproteinase-9 (MMP-9) is prominently overexpressed after myocardial infarction (MI). We tested the hypothesis that mice with targeted deletion of MMP9 have less left ventricular (LV) dilation after experimental MI than do sibling wild-type (WT) mice. Animals that survived ligation of the left coronary artery underwent echocardiographic studies after MI; all analyses were performed without knowledge of mouse genotype. By day 8, MMP9 knockout (KO) mice had significantly smaller increases in end-diastolic and end-systolic ventricular dimensions at both midpapillary and apical levels, compared with infarcted WT mice; these differences persisted at 15 days after MI. MMP-9 KO mice had less collagen accumulation in the infarcted area than did WT mice, and they showed enhanced expression of MMP-2, MMP-13, and TIMP-1 and a reduced number of macrophages. We conclude that targeted deletion of the MMP9 gene attenuates LV dilation after experimental MI in mice. The decrease in collagen accumulation and the enhanced expression of other MMPs suggest that MMP-9 plays a prominent role in extracellular matrix remodeling after MI.


Multicenter phase II trial of vitamin K(2) monotherapy and vitamin K(2) plus 1alpha-hydroxyvitamin D(3) combination therapy for low-risk myelodysplastic syndromes.
We performed an open-labeled single-arm prospective phase II clinical trial of vitamin K(2) (menatetrenone: VK2) monotherapy and VK2 plus 1alpha-hydroxyvitamin D(3) (alfacalcidol: VD3) combination therapy for myelodysplastic syndromes (MDS) with refractory anemia and refractory cytopenia with multilineage dysplasia, having either low or intermediate-1 risks of the IPSS. The overall response rate to VK2 monotherapy (45mg/day) after 16 weeks was 13% (5/38) including 4 cases with improvement of both anemia and thrombocytopenia and 1 case with thrombocytopenia. We then enrolled and evaluated 20 out of 33 VK2-monotherapy non-responders for VK2 plus VD3 (0.75microg/day) combination therapy. The overall response rate at 16 weeks after initiation of VK2 plus VD3 was 30% (6/20). HI for hemoglobin (Hb) was observed in 6 out of 11 patients (55%) and for thrombocytopenia in 3 out of 11 patients (27%), respectively. No HI was observed for neutropenia in VK2 monotherapy and VK2 plus VD3 combination therapy. It was suggested that IPSS scores and absolute neutrophil counts positively correlated, and Hb levels inversely correlated with the response to VK2 plus VD3 combination therapy. Our study demonstrated that VK2 plus VD3 combination therapy appears to be promising for improvement of anemia and thrombocytopenia with low/intermediate-1 MDS.


Adults' perspectives of experiences and preferences for end-of-life care.
Decisions about end-of-life care often raise clinical and ethical challenges, especially when the person's capacity to contribute in the decision making at the end of life is limited. This study aimed to explore Taiwanese adults' preferences associated with communication, healthcare planning, life-sustaining treatments and palliative care and experiences of end-of-life care. Semi-structured interviews were conducted with 16 adults aged 20 years and above. The sampling approach was a convenience strategy in a community centre located in a metropolitan area in the Southern region of Taiwan. A qualitative content analysis approach was used to elicit key themes from the data. Significant findings related to the two main themes of adults' experiences, including the observed distress of those who were dying and the distress experienced by the family. Other key findings pertain to personal preferences for end-of-life care, such as preferred end-of-life communication, preparing for the end-of-life and maintenance of quality of life. This exploratory study offers insight into 16 Taiwanese community-dwelling adults' views of preferences regarding end-of-life communication, preparation for the end of life and maintenance of quality of life, as well as their experiences of end-of-life care. A further exploration is suggested to elicit how personal end-of-life experiences shape individuals' health practices in advance care planning for end-of-life care.


A new peroral mother-baby endoscope system for biliary tract disorders.
To investigate a new mother-baby system, consisting of a peroral cholangioscope and a duodenoscope in patients regarding its feasibility. In the study period from January 2007 to February 2010, 76 consecutive patients (33 men, 43 women; mean age 63 years old) were included in this pilot series. Endoluminal images and biopsies were obtained from 55 patients with indeterminate strictures, while 21 patients had fixed filling defects. The diagnostic accuracy of peroral cholangioscopy (POCS) in the visualization of strictures and tissue sampling was evaluated, and therapeutic success was monitored. Follow-up was performed over at least 9 mo. A total of 55 patients had indeterminate strictures. Using the criteria "circular stenosis" and "irregular surface or margins", POCS correctly described 27 out of 28 malignant biliary strictures and 25 out of 27 benign lesions (sensitivity, 96.4%; specificity, 92.6%, diagnostic accuracy 94.5%). Visually targeted forceps biopsies were performed in 55 patients. Tissue sampling during POCS revealed malignancy in 18 of 28 cases (sensitivity: 64.3%). In 21 patients with fixed filling defects, 10 patients with bile duct stones were successfully treated with conventional stone removal. Nine patients with difficult stones (5 giant stones and 4 intrahepatic stones) were treated with visually guided laser lithotripsy. Two patients in the group with unclear fixed filling defects had bile duct adenoma or papillary tumors and were surgically treated. The new 95 cm POCS allows for accurate discrimination of strictures and fixed filling defects in the biliary tree, provides improved sensitivity of endoscopically guided biopsies and permits therapeutic approaches for difficult intrahepatic stones.


Identical inferences about correlated evolution arise from ancestral state reconstruction and independent contrasts.
Inferences about the evolution of continuous traits based on reconstruction of ancestral states have often been considered more error-prone than analysis of independent contrasts. Here we show that both methods in fact yield identical estimators for the correlation coefficient and regression gradient of correlated traits, indicating that reconstructed ancestral states are a valid source of information about correlated evolution. We show that the independent contrast associated with a pair of sibling nodes on a phylogenetic tree can be expressed in terms of the maximum likelihood ancestral state function at those nodes and their common parent. This expression gives rise to novel formulae for independent contrasts for any model of evolution admitting of a local likelihood function. We thus derive new formulae for independent contrasts applicable to traits evolving under directional drift, and use simulated data to show that these directional contrasts provide better estimates of evolutionary model parameters than standard independent contrasts, when traits in fact evolve with a directional tendency.


Etiological considerations for the growth of stroma in benign prostatic hyperplasia.
The finding that human benign prostatic hyperplasia (BPH) consisted primarily of fibromuscular tissue has led to basic research into the hormonal control of the growth of male accessory sex organ smooth muscle. By using the separated epithelium and muscle layers of the guinea pig seminal vesicle, it was determined that the epithelium exhibited only reversible androgen-induced growths, whereas the muscle proved to be a target tissue for both androgen and estrogen, and exhibited irreversible growth responses. It was of particular interest that the normal androgen-dependent pubertal development of the muscle involved an approximate twofold increase in DNA, followed by the development of a complete and relatively selective androgenic insensitivity in this parameter. An understanding of the factors leading to this apparently normal androgen-dependent loss of the proliferative response in muscle may allow for the development of specific hypotheses for the reawakened stromal growth in BPH. Research on other organ systems focusing on the various factors and mechanisms involved in muscle growth regulation is briefly discussed.


Corticosterone and growth hormone levels in shorebirds during spring and fall migration stopover.
Large numbers of shorebirds stop over at Delaware Bay during spring migration and undergo major mass increases within a two- to three-week period. We studied plasma levels of corticosterone and growth hormone in three species of migrants that use this site, sanderlings, Calidris alba, semipalmated plovers, Charadrius semipalmatus, and semipalmated sandpipers, Calidris pusilla. Semipalmated sandpipers were also studied at a fall migration stopover in Manomet, Massachusetts. These two hormones were chosen because they modulate the physiological processes of lipogenesis/lipolysis and promote increased feeding in birds. The stress response was not suppressed in the shorebirds studied, and plasma levels of corticosterone were elevated compared to other studies. We believe that the high levels of corticosterone relate to the rapid fat deposition that takes place at this stop-over site. There was a significant negative correlation between plasma growth hormone and body mass, indicating the lipolytic effects of the growth hormone. Because the lighter birds are recent arrivals to Delaware Bay they may have elevated plasma growth because of fat breakdown during flight to this stop-over site. High levels of growth hormone may also result in protein synthesis, replenishing tissues broken down during the previous migratory bout. J. Exp. Zool. 284:645-651, 1999.


Suppression of a squamous cell carcinoma (SCC)-related serpin, SCC antigen, inhibits tumor growth with increased intratumor infiltration of natural killer cells.
Squamous cell carcinoma (SCC) antigen (SCCA), a member of the ovalbumin serine proteinase inhibitor family, serves as a circulating marker of squamous cell carcinoma (SC). One of the SCCAs, SCCA1, has been suggested to play a role in the attenuation of apoptosis in vitro and in the augmentation of tumor growth in vivo. In the present study, the infection of a SCC cell line (SKG IIIa) with recombinant retrovirus that expressed the antisense SCCA mRNA suppressed expression of SCCA in vitro. Local administration of this retrovirus into tumors by inoculation in nude mice suppressed tumor growth. Treatment of tumor tissue in vivo is also associated with increased numbers of apoptotic tumor cells and large mononuclear cells in the tumor. To test the possible role of SCCA in the infiltration of large mononuclear cells, we analyzed the effect of SCCA1 on migration of natural killer (NK) cells induced by monocyte-chemoattractant protein-1 in vitro. SCCA1 suppressed migration of NK cells completely, and this inhibitory effect was lost by mutation of the reactive site loop of SCCA1. These results suggest that antisense SCCA may suppress the growth of SCC in vivo not only by the augmentation of intracellular apoptosis but also by the increased infiltration of NK cells into the tumor.


Safe household water treatment and storage using ceramic drip filters: a randomised controlled trial in Bolivia.
A randomised controlled field trial was conducted to evaluate the effectiveness of ceramic drip filters to improve the microbiological quality of drinking water in a low-income community in rural Bolivia. In four rounds of water sampling over five months, 100% of the samples were free of thermotolerant (faecal) coliforms (TTC) compared to an arithmetic mean TTC count of 1517, 406, 167 and 245 among control households which continued to use their customary sources of drinking water. The filter systems produced water that consistently met WHO drinking-water standards despite levels of turbidity that presented a challenge to other low-cost POU treatment methods. The filter systems also demonstrated an ability to maintain the high quality of the treated water against subsequent re-contamination in the home.


[Clinical and electrophysiological parameters of alcohol dependence and its comorbidity with affective disorders].
To identify characteristics of and possible differences in clinical and electroencephalographic parameters in patients with alcohol dependence with- and without comorbid affective disorders. Ninety-five patients, including 74 with an established diagnosis of alcohol dependence and 21 with alcohol dependence and affective disorders, were examined. Duration of alcohol dependence and affective disorder (years), number of hospitalizations and suicidal attempts were analyzed as anamnestic data. Hamilton's anxiety and depression scale (HDRS), the Alcohol Use Disorders Identification Test (AUDIT), the General clinical impression scale (CGI-s) were used as psychometric tools. The study of bioelectric activity of the brain was carried out using a 16-channel encephalograph. The background electroencephalogram was recorded, the values of absolute spectral power and coherence of theta, alpha and beta rhythms were analyzed. Patients with comorbidity of alcohol dependence and affective disorders have a significantly higher risk of suicidal behavior, a greater frequency of hospitalizations, higher levels of anxiety compared with patients without affective disorders. Electrophysiological data have shown that patients with comorbidity of alcohol dependence and affective disorders have higher values of spectral power of alpha-rhythm in all parts of the cerebral cortex (except for temporal lobes) and beta-rhythm in the occipital cortex, as well as an increase in interhemispheric coherence in all frequency ranges.


Where the road ends, yaws begins? The cost-effectiveness of eradication versus more roads.
A disabling and disfiguring disease that "begins where the road ends", yaws is targeted by WHO for eradication by the year 2020. The global campaign is not yet financed. To evaluate yaws eradication within the context of the post-2015 development agenda, we perform a somewhat allegorical cost-effectiveness analysis of eradication, comparing it to a counterfactual in which we simply wait for more roads (the end of poverty). We use evidence from four yaws eradication pilot sites and other mass treatment campaigns to set benchmarks for the cost of eradication in 12 known endemic countries. We construct a compartmental model of long-term health effects to 2050. Conservatively, we attribute zero cost to the counterfactual and allow for gradual exit of the susceptible (at risk) population by road (poverty reduction). We report mean, 5th and 95th centile estimates to reflect uncertainty about costs and effects. Our benchmark for the economic cost of yaws eradication is uncertain but not high -US$ 362 (75-1073) million in 12 countries. Eradication would cost US$ 26 (4.2-78) for each year of life lived without disability or disfigurement due to yaws, or US$ 324 (47-936) per disability-adjusted life year (DALY). Excluding drugs, existing staff and assets, the financial cost benchmark is US$ 213 (74-522) million. The real cost of waiting for more roads (poverty reduction) would be 13 (7.3-20) million years of life affected by early-stage yaws and 2.3 (1.1-4.2) million years of life affected by late-stage yaws. Endemic countries need financing to begin implementing and adapting global strategy to local conditions. Donations of drugs and diagnostics could reduce cost to the public sector and catalyze financing. Resources may be harnessed from the extractive industries. Yaws eradication should be seen as complementary to universal health coverage and shared prosperity on the post-2015 development agenda.