Neural contribution to the effect of glucagon-like peptide-1-(7-36) amide on arterial blood pressure in rats.
This study was designed to determine the contribution of the central nervous system (CNS) to the effects of glucagon-like peptide-1-(7-36) amide (tGLP-1) on arterial blood pressure and heart rate in rats. Accordingly, intracerebroventricular administration of the peptide produced an increase in cardiovascular parameters, which was blocked by previous administration of exendin-(9-39) through the same route, but not when it was intravenously injected. Intravenous administration of tGLP-1 produced a significant increase in arterial blood pressure and heart rate, which was blocked by the previous intracerebroventricular or intravenous administration of exendin-(9-39). Bilateral vagotomy blocked the stimulating effect of intracerebroventricular tGLP-1 administration on arterial blood pressure and heart rate. Also, bilateral vagotomy prevented the blocking effect of intracerebroventricular but not of intravenous exendin-(9-39) on cardiovascular parameters after intravenous administration of tGLP-1. These findings suggest that the action of tGLP-1 on cardiovascular parameters is under a dual control generated in the CNS and in peripheral structures and that the neural information emerging in the brain is transmitted to the periphery through the vagus nerve.


Using Illumina next generation sequencing technologies to sequence multigene families in de novo species.
The advent of Next Generation Sequencing Technology (NGST) has revolutionized molecular biology research, allowing for rapid gene/genome sequencing from a multitude of diverse species. As high throughput sequencing becomes more accessible, more efficient workflows must be developed to deal with the amounts of data produced and better assemble the genomes of de novo lineages. We combine traditional laboratory methods with Illumina NGST to amplify and sequence the largest mammalian multigene family, the Olfactory Receptor gene family, for species with and without a reference genome. We develop novel assembly methods to annotate and filter these data, which can be utilized for any gene family or any species. We find no significant difference between the ratio of genes within their respective gene families of our data compared with available genomic data. Using simulated data we explore the limitations of short-read sequence data and our assembly in recovering this gene family. We highlight the benefits and shortcomings of these methods. Compared with data generated from traditional polymerase chain reaction, cloning and Sanger sequencing methodologies, sequence data generated using our pipeline increases yield and sequencing efficiency without reducing the number of unique genes amplified. A cloning step is not required, therefore shortening data generation time. The novel downstream methodologies and workflows described provide a tool to be utilized by many fields of biology, to access and analyze the vast quantities of data generated. By combining laboratory and in silico methods, we provide a means of extracting genomic information for multigene families without complete genome sequencing.


Photon management to reduce energy loss in perovskite solar cells.
Despite the rapid development of perovskite solar cells (PSCs) over the past few years, the conversion of solar energy into electricity is not efficient enough or cost-competitive yet. The principal energy loss in the conversion of solar energy to electricity fundamentally originates from the non-absorption of low-energy photons ascribed to Shockley-Queisser limits and thermalization losses of high-energy photons. Enhancing the light-harvesting efficiency of the perovskite photoactive layer by developing efficient photo management strategies with functional materials and arrays remains a long-standing challenge. Here, we briefly review the historical research trials and future research trends to overcome the fundamental loss mechanisms in PSCs, including upconversion, downconversion, scattering, tandem/graded structures, texturing, anti-reflection, and luminescent solar concentrators. We will deeply emphasize the availability and analyze the importance of a fine device structure, fluorescence efficiency, material proportion, and integration position for performance improvement. The unique energy level structure arising from the 4fn inner shell configuration of the trivalent rare-earth ions gives multifarious options for efficient light-harvesting by upconversion and downconversion. Tandem or graded PSCs by combining a series of subcells with varying bandgaps seek to rectify the spectral mismatch. Plasmonic nanostructures function as a secondary light source to augment the light-trapping within the perovskite layer and carrier transporting layer, enabling enhanced carrier generation. Texturing the interior using controllable micro/nanoarrays can realize light-matter interactions. Anti-reflective coatings on the top glass cover of the PSCs bring about better transmission and glare reduction. Photon concentration through perovskite-based luminescent solar concentrators offers a path to increase efficiency at reduced cost and plays a role in building-integrated photovoltaics. Distinct from other published reviews, we here systematically and hierarchically present all of the photon management strategies in PSCs by presenting the theoretical possibilities and summarizing the experimental results, expecting to inspire future research in the field of photovoltaics, phototransistors, photoelectrochemical sensors, photocatalysis, and especially light-emitting diodes. We further assess the overall possibilities of the strategies based on ultimate efficiency prospects, material requirements, and developmental outlook.


Nucleotide sequence of the 16S - 23S spacer region in an rRNA gene cluster from tobacco chloroplast DNA.
The nucleotide sequence of a spacer region between 16S and 23S rRNA genes from tobacco chloroplasts has been determined. The spacer region is 2080 bp long and encodes tRNAIle and tRNAAla genes which contain intervening sequences of 707 bp and 710 bp, respectively. Strong homology between the two intervening sequences is observed. These spacer tRNAs are synthesized as part of an 8.2 kb precursor molecule containing 16S and 23S rRNA sequences.


Total bilirubin in athletes, determination of reference range.
The purpose of this study was to determine a typical reference range for the population of athletes. Results of blood tests of 339 athletes (82 women and 257 men, aged 18-37 years) were retrospectively analysed. The subjects were representatives of different sports disciplines. The measurements of total bilirubin (BIT), iron (Fe), alkaline phosphatase (ALP), alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) were made using a Pentra 400 biochemical analyser (Horiba, France). Red blood cell count (RBC), reticulocyte count and haemoglobin concentration measurements were made using an Advia 120 haematology analyser (Siemens, Germany). In groups of women and men the percentage of elevated results were similar at 18%. Most results of total bilirubin in both sexes were in the range 7-14 μmol·L-1 (49% of women and 42% of men). The highest results of elevated levels of BIT were in the range 21-28 μmol·L-1 (12% of women and 11% of men). There was a significant correlation between serum iron and BIT concentration in female and male athletes whose serum total bilirubin concentration does not exceed the upper limit of the reference range. Elevated concentrations of total bilirubin appear to be due to changes caused by regular exercise. The obtained upper limit of the reference range for total bilirubin concentration in the group of athletes is 29.0 μmol·L-1. It seems reasonable to use dedicated reference values for total bilirubin concentration in relation to the group of athletes.


Induction of melanoma phenotypes in human skin by growth factors and ultraviolet B.
Exposure to UV radiation likely plays a key role in melanoma development, whereas other etiologic agents remain unknown. Here we show that in normal human skin an increased expression of a combination of three growth factors, basic fibroblast growth factor, stem cell factor, and endothelin-3, along with exposure to UVB can transform normal melanocytes into a melanoma phenotype within 4 weeks. Invasion of melanoma lesions was found in skin from newborn donors, whereas melanomas in adult skin were of a noninvasive in situ type only. This suggests that susceptibility of skin to exogenous tumor promoters is dependent on age. This is the first report on human cancer initiation in vivo in which an imbalance of physiological factors combined with an environmental carcinogen can lead to transformation of normal tissue.


[Conditional shared confidentiality with regard to the exchange of information between members of a team or network; ethical advice needs to be updated].
Care-givers not only work as a team, but increasingly they also participate in networks. This development represents an ethical challenge to the exchange of information and to confidentiality. To revise and update earlier advice formulated by the Ethics Committee for Mental Health Care of the Brothers of Charity in Flanders, in particular concerning the question of whether shared confidentiality can be extended from a team to a network. The Ethics Committee applied an appropriate method which combined ethical discussion and literature research. The earlier advice is no longer adequate because of certain practical and theoretical grounds. The Ethics Committee chooses to take a positive view of the developing cooperation between care-givers and networks. Consequently, the committee proposes shared confidentiality, but links this to five conditions: (1) the care-givers should participate in a clearly defined and identifiable team or network, (2) they should have a caring task in common, (3) they should be pledged to confidentiality, (4) they should consult with the patient and obtain his/her informed consent, (5) they should apply 'the filter of relevance'. Care-givers can exchange information with members of a team or network, but this should be done on the basis of conditional shared confidentiality.


Anti-Infective Effect of Adhesive Probiotic Lactobacillus in Fish is Correlated With Their Spatial Distribution in the Intestinal Tissue.
In this study, we tested the distribution of 49 Lactobacillus strains in the mucus and mucosa of the intestine tissue of zebrafish. We observed a progressive change in the spatial distribution of Lactobacillus strains, and suggested a division of the strains into three classes: mucus type (>70% in mucus), mucosa type (>70% in mucosa) and hybrid type (others). The hybrid type strains were more efficient in protection of zebrafish against Aeromonas hydrophila infection. Three strains representing different distribution types (JCM1149, CGMCC1.2028, and JCM 20300) were selected. The mucosa type strain JCM1149 induced higher intestinal expression of inflammatory cytokines and Hsp70 than the other strains. Furthermore, we used L. rhamnosus GG and its mutant (PB22) lacking SpaCBA pili to investigate the influence of pili on spatial distribution. LGG showed a mucosa type distribution, while PB22 revealed a hybrid distribution and the disease protection was accordingly improved. The different protection ability between LGG and PB22 did not involve the intestinal microbiota, however, LGG induced injury to the mucosa of zebrafish. Collectively, the disease protection activity of Lactobacillus in zebrafish is correlated with their spatial distribution in the intestinal tissue, with strains showing a balanced distribution (hybrid type) more efficient in protection.


Ankyrin-G regulated epithelial phenotype is required for mouse lens morphogenesis and growth.
Epithelial cell polarity, adhesion, proliferation, differentiation and survival are essential for morphogenesis of various organs and tissues including the ocular lens. The molecular mechanisms regulating the lens epithelial phenotype however, are not well understood. Here we investigated the role of scaffolding protein ankyrin-G (AnkG) in mouse lens development by conditional suppression of AnkG expression using the Cre-LoxP recombination approach. AnkG, which serves to link integral membrane proteins to the spectrin/actin cytoskeleton, was found to distribute predominantly to the lateral membranes of lens epithelium with several isoforms of the protein being detected in the mouse lens. Conditional deficiency of AnkG impaired mouse lens morphogenesis starting from embryonic stage E15.5, with neonatal (P1) AnkG cKO lenses exhibiting overt abnormalities in shape, size, epithelial cell height, sheet length and lateral membrane assembly together with defective fiber cell orientation relative to lenses from littermate AnkG floxed or Cre expressing mice. Severe disruptions in E-cadherin/β-catenin-based adherens junctions, and the membrane organization of spectrin-actin cytoskeleton, ZO-1, connexin-50 and Na+-K+-ATPase were noted in AnkG deficient lenses, along with detection in lens epithelium of α-smooth muscle actin, a marker of epithelial to mesenchymal transition. Moreover, lens epithelial cell proliferation and survival were severely compromised while differentiation appears to be normal in AnkG deficient mouse lenses. Collectively, these results indicate that AnkG regulates establishment of the epithelial phenotype via lateral membrane assembly, stabilization of E-cadherin-based cell-cell junctions, polarity and membrane organization of transport and adhesion proteins and the spectrin-actin skeleton, and provide evidence for an obligatory role for AnkG in lens morphogenesis and growth.


Evolution of the surgical management of neonatal ovarian cysts: laparoscopic-assisted transumbilical extracorporeal ovarian cystectomy (LATEC).
Since its first detailed description in 1995, the laparoscopic management of neonatal ovarian cysts has typically required multiple incisions, specialized equipment, and advanced laparoscopic skills. After some initial frustration with neonatal laparoscopy, we developed a simplified single-incision laparoscopic-assisted transumbilical extracorporeal cystectomy (LATEC). This paper reviews our experience with this technique and compares outcomes to those of our other surgically managed neonatal ovarian cyst patients. A retrospective record review of 20 patients treated surgically between 1992 and 2006. Student's t-tests were used for comparisons (P<0.05 was significant). Means were: age, 11 days; weight, 3.7 kg; and cyst diameter, 5.0 cm. Nineteen patients were diagnosed prenatally, at the mean gestational age of 33 weeks. Twelve of 20 (60%) had torsed cysts (1 bilateral). Three of 13 torsed cysts (23%) were less than 4 cm diameter (range, 2.9-3.5). Laparotomies were transverse lower abdominal incisions. Laparoscopic operations used 2 (3 patients) or 3 incisions (2 patients). LATEC involved transumbilical laparoscopy, complete cyst aspiration, and then cyst evisceration through the umbilicus for either ovarian cystectomy (simple cysts) or salpingo-oophorectomy (torsed cysts). Laparoscopic patients had similar time to feeds, length of stay, and postoperative narcotic requirements, when compared to laparotomy patients (P=nonsignificant). LATEC patients had shorter surgical times, more rapid advancement to full enteral feedings, shorter length of hospital stay, and equal ovarian preservation, when compared to laparoscopy. Cosmetic results with LATEC were outstanding. Both laparoscopic and "open" approaches have acceptable perioperative morbidity and rapid recovery. LATEC is a relatively simple procedure, which combines laparoscopy and traditional extracorporeal surgery, and may be successfully performed by experienced pediatric surgeons and with a single incision.


Off-axis reference beam for full-field swept-source OCT and holoscopy.
In numerous applications, Fourier-domain optical coherence tomography (FD-OCT) suffers from a limited imaging depth due to signal roll-off, a limited focal range, and autocorrelation noise. Here, we propose a parallel full-field FD-OCT imaging method that uses a swept laser source and an area camera in combination with an off-axis reference, which is incident on the camera at a small angle. As in digital off-axis holography, this angle separates autocorrelation signals and the complex conjugated mirror image from the actual signal in Fourier space. We demonstrate that by reconstructing the signal term only, this approach enables full-range imaging, i.e., it increases the imaging depth by a factor of two, and removes autocorrelation artifacts. The previously demonstrated techniques of inverse scattering and holoscopy can then numerically extend the focal range without loss of lateral resolution or imaging sensitivity. The resulting, significantly enhanced measurement depth is demonstrated by imaging a porcine eye over its entire depth, including cornea, lens, and retina. Finally, the feasibility of in vivo measurements is demonstrated by imaging the living human retina.


Hormonal control of fructose 2,6-bisphosphate concentration in isolated rat hepatocytes.
The ability of glucagon and of adrenaline to affect the concentration of fructose 2,6-bisphosphate in isolated hepatocytes was re-investigated because of important discrepancies existing in the literature. We were unable to detect a significant difference in the sensitivity of the hepatocytes with regard to the effect of glucagon to initiate the interconversion of phosphorylase, pyruvate kinase, 6-phosphofructo-2-kinase and fructose 2,6-bisphosphatase, and also to cause the disappearance of fructose 2,6-bisphosphate. In contrast, we have observed differences in the time-course of these various changes, since the interconversions of phosphorylase and of pyruvate kinase were at least twice as fast as those of 6-phosphofructo-2-kinase and of fructose 2,6-bisphosphatase. When measured in a cell-free system in the presence of MgATP, the cyclic AMP-dependent interconversion of pyruvate kinase was 5-10-fold more rapid than those of 6-phosphofructo-2-kinase and of fructose 2,6-bisphosphatase. These data indicate that 6-phosphofructo-2-kinase and fructose 2,6-bisphosphatase are relatively poor substrates for cyclic AMP-dependent protein kinase; they also support the hypothesis that the two catalytic activities belong to a single protein. Adrenaline had only a slight effect on the several parameters under investigation, except for the activation of phosphorylase. In the absence of Ca2+ ions from the incubation medium, however, adrenaline had an effect similar to that of glucagon.


Intrauterine growth retardation: obstetrical aspects.
We have just begun our study of fetal growth retardation. Prenatal influences upon fetal growth are poorly understood and little studied. One may list multiple etiologies, catalogue numerous physiologic processes, and still not know in any given child what went wrong. The questions far exceed our preliminary answers. How does maternal undernutrition significantly effect the fetal "parasite?" Is the syndrome of intrauterine growth retardation a manifestation of a host versus graft phenomenon, with "runting" in the offspring? Are deficits in cell number and size unalterable? Can these deficits be overcome with good postnatal care? How can we better detect the fetus who is undergoing deprivation in utero? What altered biochemical processes exist? Can we reverse such abnormal influences in utero and prevent their consequences to the fetus? Certainly there are numerous additional areas for investigation and thought.


A case of three rare uterine neoplasms in the same surgical specimen.
Uterine sarcomas are mesenchymal tumors; they are rare, representing less than 2-3% of all uterine malignancies. Among them, we can define four types: leiomyosarcoma (LMS), endometrial stromal sarcoma (ESS), Adenosarcoma and Carcinosarcoma. This last type was recently reclassified by FIGO as a Mullerian type of the endometrial adenocarcinoma. Therefore, today only the first three types are histologically considered. In this paper, we reported a case of simultaneous presence of three different rare neoplasms in the same surgical specimen, resulting from a hysterectomy of a premenopausal woman. The woman presented to the ED with a six-months history of vaginal bleeding. Given the complexity of the clinical picture, we suggested hospitalization in our Department of Gynecology, to perform appropriate diagnostic tests. Because of the persistent hemorrhage and the absence of required fertility preservation, a laparotomic hysterectomy with bilateral annessiectomy was performed. The postoperative histology of the specimen described the myoma at the fundus as a leiomyosarcoma. The myoma of the uterine anterior wall appeared as an endometrial stromal sarcoma of low-grade. Moreover, an intramural cavernous hemangioma of 3 cm in diameter was reported at the uterine corpus. All these described pathologies have no specific clinic characteristics; the most common symptom is abnormal uterine bleeding. To date, hysterectomy and bilateral salpingo-oophorectomy are the standards of care in the management of all early stage uterine sarcomas. To our knowledge, cases of LMS, ESS and cavernous haemangioma coexisting in the same patient have not been reported in literature to date. The pathogenesis of this combination remains to be elucidated. Key words: Cavernous hemangioma, Endometrial stromal sarcoma, Leiomyosarcoma, Uterine sarcomas.


Statin Use and Severe Acute Liver Injury Among Patients with Elevated Alanine Aminotransferase.
While serious liver injury among statin users is extremely rare, baseline liver enzyme testing is still recommended prior to initiating therapy. The benefit of such screening should be reevaluated based on empirical evidence. This study compared the risk of severe acute liver injury (SALI) between statin initiators with an elevated ALT (>35U/L) matched to statin initiators with a normal ALT level (≤35U/L). Statin initiators with an elevated ALT were additionally compared against matched non-users. The study created cohorts from Optum and MarketScan claims data. Exposed and comparison cohorts were propensity score (PS) matched in each dataset and findings were pooled using meta-analysis. Proportional hazards regression was used to estimate hazard ratios (HRs), and a prespecified non-inferiority margin for SALI was set at a HR of 1.8. 232,889 patients with elevated ALT were PS-matched to 232,889 with normal ALT level. The overall incidence rate of SALI was about 19/100,000 person-years among statin initiators. Statin initiators with elevated ALT had no meaningfully increased risk of SALI compared to those with normal ALT (HR=1.15; 95% CI 0.75 to 1.75). Comparing statin initiators with non-initiators with elevated ALT values equally yielded no increased risk (HR=0.76; 95% CI 0.52 to 1.11). In this large population-based study, SALI in statin users was rare. Importantly, the results showed no evidence that baseline ALT status is a reliable indicator for an increased risk of severe liver injury among statin initiators.


Supervision and responsibility: The Royal College of Anaesthetists National Audit.
The Royal College of Anaesthetists audited consultant supervision and responsibility in anaesthesia in the UK during 2003. Consultants (supervising) and non-consultants (supervised) were surveyed on their attitudes to supervision, experience of their own hospital system for supervision and of induction for new starters. Local coordination was achieved through anaesthesia audit coordinators who provided information on local policies, induction programmes and anaesthesia charts. Supervision was audited over a 5-day period. 135 departments of anaesthesia took part (43% of 315 departments), questionnaires being returned by 2297 anaesthetists. Anaesthesia record charts in use do not meet criteria considered desirable locally. Most trainees, but less than half staff grade/associate specialists, received an induction programme, often not supported by written documentation. Consultants find conflicting demands of service and supervision difficult. Many work in systems which do not permit providing direct, immediate support to those supervised. Most anaesthetists think supervision is very important. Around half disagree with national guidance that every NHS patient should have a named consultant. Two per cent of non-consultants during the audit period reported assistance from consultants not being obtainable soon enough. This audit found departure from standards and the potential for risk and failure. New standards may be needed regarding anaesthesia record sheets, induction, accountability, when to seek help and care of sick patients. Supervision systems in over 40% of hospitals need review to ensure they provide a named consultant and immediate direct support for elective lists.


Preserved White Matter Integrity and Recovery After Brain Tumor Surgery: A Prospective Pilot Study on the Frontal Aslant Tract.
Introduction: Damage to white matter tracts can cause severe neurological deficits, which are often hardly predictable before brain tumor surgery. To explore the possibility of assessing white matter integrity and its preservation, we chose the frontal aslant tract (FAT) due to its involvement in multiple neurological functions such as speech and movement initiation. Methods: Right-handed patients with left hemispheric intracerebral tumors underwent FAT tractography within 7 days before and 3 days after surgery. Neurological performance score and aphasia score were assessed within 7 days before and after surgery, as well as at follow-up 3 months postoperatively. Results: Fifteen patients were prospectively analyzed. After multivariate analysis and receiver operating characteristic analysis, we found that preoperative fractional anisotropy (FA) of the left FAT indicated the preoperative aphasia score (cutoff 0.40, p = 0.015). Aphasia scores 3 months postoperatively were predicted by both postoperative FA of the left FAT (cutoff 0.35, p = 0.005) and postoperatively preserved FA of the left FAT (cutoff 95.8%, p = 0.017). Postoperatively preserved right FAT FA inversely predicted postoperative aphasia score (cutoff 95.1%, p = 0.016). Discussion: Assessment of white matter integrity preservation is possible and correlates with outcome after brain tumor surgery. It may be useful for patient counseling and assessment of rehabilitation potential, as well as to investigate relevant brain networks in the future. Clinical Trial Registration: The trial was prospectively registered at ClinicalTrials.gov (NCT04302857).


[The peroxidase activity of rat cerebral hemisphere neurons during hypoxia training].
Peroxidase activity (PA) was studied in the rat's brain cortex during a 2 months training to hypoxia according to the Barbashova method. PA was investigated histochemically by an ammonium--molibdate--benzidine method on blocks of surviving brain tissue, thereafter they were studied by the contact microscopy. PA was also determined biochemically in water-salt extracts of the brain tissue. A progressive increase of PA in the course of training was shown by both the techniques. The increase of activity is accounted for by the growing quantity of neurons developing the reaction as well as by the growing intensity of reaction in each neuron. The nature of PA of neurons and its adaptive significance in hypoxic conditions is discussed.


Systematic insertional mutagenesis of a streptomycete genome: a link between osmoadaptation and antibiotic production.
The model organism Streptomyces coelicolor represents a genus that produces a vast range of bioactive secondary metabolites. We describe a versatile procedure for systematic and comprehensive mutagenesis of the S. coelicolor genome. The high-throughput process relies on in vitro transposon mutagenesis of an ordered cosmid library; mutagenized cosmids with fully characterized insertions are then transferred by intergeneric conjugation into Streptomyces, where gene replacement is selected. The procedure can yield insertions in upward of 90% of genes, and its application to the entire genome is underway. The methodology could be applied to many other organisms that can receive DNA via RK2/RP4-mediated intergeneric conjugation. The system permits introduction of mutations into different genetic backgrounds and qualitative measurement of the expression of disrupted genes as demonstrated in the analysis of a hybrid histidine kinase and response regulator gene pair, osaAB, involved in osmoadaptation in Streptomyces. The independently transcribed response regulator gene, osaB, is essential for osmoadaptation; when grown with supplementary osmolyte, an osaB mutant cannot erect aerial hyphae and produces up to fivefold greater antibiotic yields than the wild-type strain.


The discovery of spectral opponency in visual systems and its impact on understanding the neurobiology of color vision.
The two principal theories of color vision that emerged in the nineteenth century offered alternative ideas about the nature of the biological mechanisms that underlie the percepts of color. One, the Young-Helmholtz theory, proposed that the visual system contained three component mechanisms whose individual activations were linked to the perception of three principal hues; the other, the Hering theory, assumed there were three underlying mechanisms, each comprising a linked opponency that supported contrasting and mutually exclusive color percepts. These competing conceptions remained effectively untested until the middle of the twentieth century when single-unit electrophysiology emerged as a tool allowing a direct examination of links between spectral stimulation of the eye and responses of individual cells in visual systems. This approach revealed that the visual systems of animals known to have color vision contain cells that respond in a spectrally-opponent manner, firing to some wavelengths of stimulation and inhibiting to others. The discovery of spectral opponency, and the research it stimulated, changed irrevocably our understanding of the biology of color vision.


Intersectionality research in counseling psychology.
This article introduces the special section on intersectionality research in counseling psychology. Across the 4 manuscripts that constitute this special section, a clear theme emerges: a need to return to the roots and politics of intersectionality. Importantly, the 2 empirical articles in this special section (Jerald, Cole, Ward, & Avery, 2017; Lewis, Williams, Peppers, & Gadson, 2017) are studies of Black women's experiences: a return, so to speak, to the subject positions and social locations from which intersectionality emanates. Shin et al. (2017) explore why this focus on Black feminist thought and social justice is so important by highlighting the persistent weaknesses in how much research published in leading counseling psychology journals has tended to use intersectionality as a way to talk about multiple identities, rather than as a framework for critiquing systemic, intersecting forms of oppression and privilege. Shin and colleagues also point to the possibilities intersectionality affords us when scholars realize the transformative potential of this critical framework. Answers to this call for transformative practices are foregrounded in Moradi and Grzanka's (2017) contribution, which surveys the interdisciplinary literature on intersectionality and presents a series of guidelines for using intersectionality responsibly. We close with a discussion of issues concerning the applications of intersectionality to counseling psychology research that spans beyond the contributions of each manuscript in this special section. (PsycINFO Database Record


Effect of pomegranate extract on vagina, skeleton, metabolic and endocrine profiles in an ovariectomized rat model.
Many women need estrogen therapy because of menopausal complaints. It is suggested that pomegranate plant has estrogenic effect. Aim of the study was to examine the effects of pomegranate seed extract on menopausal changes. This study was conducted in an experimental environment with 23 Wistar Albino genus female rats. Sixteen rats were divided into two groups after ovariectomy. One group (SG) was fed with standard food and the pomegranate extract was added to drinking water of the other group (PG). Seven rats were identified as the sham group for the detection of basal values. At the end of 90 days, follicle stimulating hormone (FSH), estradiol, total cholesterol, high-density lipoprotein cholesterol (HDL)-cholesterol, low-density lipoprotein cholesterol (LDL)-cholesterol, triglyceride, tibial bone cortex thickness and vaginal epithelium thickness of the groups were compared. FSH, total-cholesterol and HDL-cholesterol levels were similar among the three groups (P > 0.05), while others were different (P < 0.05). In binary comparisons (PG vs SG), estradiol level (average ± standard deviation [SD]: 252 ± 43 vs 154 ± 26 pg/mL), tibial bone cortex thickness (58 ± 7 vs 40 ± 2 μm) and vaginal epithelium thickness (21 ± 7 vs 10 ± 4 μm) were significantly higher in PG. In PG, triglyceride levels (103 ± 26 vs 87 ± 41 mg/dL) were higher and LDL-cholesterol levels were lower (20 ± 8 vs 27 ± 8 mg/dL), but these differences were not significant. In rats fed with pomegranate extract, estradiol levels increased and tibial bone cortex thickness and vaginal epithelium thickness also increased. Pomegranate itself or its formulation extracts may be a support or an alternative to the main treatment modalities in the preservation of bone density and the treatment of vaginal epithelial atrophy.


The Benefits and Challenges of Preconsent in a Multisite, Pediatric Sickle Cell Intervention Trial.
Enrollment of patients in sickle cell intervention trials has been challenging due to difficulty in obtaining consent from a legal guardian and lack of collaboration between emergency medicine and hematology. We utilized education and preconsent in a pediatric multisite sickle cell intervention trial to overcome these challenges. Overall, 48 patients were enrolled after being preconsented. Variable Institutional Review Board policies related to preconsent validity and its allowable duration decreased the advantages of preconsent at some sites. The utility of preconsent for future intervention trials largely depends on local Institutional Review Board policies. Preeducation may also benefit the consent process, regardless of site differences.


The functionality of a therapeutic antibody candidate restored by a single mutation from proline to threonine in the variable region.
mAbs play an essential role in the therapeutic arsenal. Our laboratory has patented the Rendomab-B49 mAb targeting the endothelin B receptor (ETB). This G protein-coupled receptor plays a driving role in the progression of numerous cancers. We chimerized our mAb (xiRB49) to evaluate its preclinical therapeutic efficacy in different ETB+ tumor models with an antibody drug conjugate approach. As previously reported, the chimerization process of an antibody can alter its functionality. In this article, we present the chimerization of RB49. xiRB49 purified by Protein A remained perfectly soluble and did not aggregate, but it lost all its ability to recognize ETB. A detailed analysis of its variable region using IMGT tools allowed us to identify an unusual proline at position 125. In silico mAb modeling and in vitro experiments were performed for a better understanding of xiRB49 structure-function relationships. Our results show that the proline in position 125 on the heavy chain alters the xiRB49 CDR3 light chain conformation and its mutation to threonine allows complete functional recovery.


The history of Crohn's perianal fistula treatment with mesenchymal stem cells: the story of darvadstrocel.
This study provides an overview of the development of the first drug authorized for use in cell therapy. We analyze the case of darvadstrocel, an example of a successful cell-therapy drug used worldwide to treat Crohn's perianal fistula. A bibliographic-historical analysis of the first cellular treatment approved by the EMA, including relevant aspects concerning the authors, who were involved in the whole process. We would like to highlight the following messages: Development: The article describes the development process of the drug, from initial concept through the clinical trial phases. Learning from failure: In describing the development of darvadstrocel, the authors highlight the importance of learning from failures, which is crucial to achieving successful outcomes. Collaboration: The article underscores the need for collaboration between public and private institutions to facilitate the advancement of cell-therapy drugs and ensure efficiency while adhering to regulatory guidelines. Regulatory requirements play a crucial role in the design and development of advanced therapies such as cell-therapy drugs. The findings of this study underscore the significance of appropriate disease application, meticulous donor selection, robust manufacturing processes, and proper therapy administration. Only by adopting these measures can cell-therapy drugs successfully complete all phases of the clinical trial process.


Demonstration of acid and water recovery systems: Applicability and operational challenges in Indian metal finishing SMEs.
Diffusion dialysis, acid retardation and nanofiltration plants were acquired from Europe and demonstrated in several Indian metal finishing companies over a three year period. These companies are primarily small and medium enterprises (SMEs). Free acid recovery rate from spent pickling baths using diffusion dialysis and retardation was in the range of 78-86% and 30-70% respectively. With nanofiltration, 80% recovery rate of rinse water was obtained. The demonstrations created awareness among the metal finishing companies to reuse resources (acid/water) from the effluent streams. However, lack of efficient oil separators, reliable chemical analysis and trained personnel as well as high investment cost limit the application of these technologies. Local manufacturing, plant customization and centralized treatment are likely to encourage the uptake of such technologies in the Indian metal finishing sector.


Extrachromosomal telomeric circles contribute to Rad52-, Rad50-, and polymerase delta-mediated telomere-telomere recombination in Saccharomyces cerevisiae.
Telomere maintenance is required for chromosome stability, and telomeres are typically replicated by the telomerase reverse transcriptase. In both tumor and yeast cells that lack telomerase, telomeres are maintained by an alternative recombination mechanism. By using an in vivo inducible Cre-loxP system to generate and trace the fate of marked telomeric DNA-containing rings, the efficiency of telomere-telomere recombination can be determined quantitatively. We show that the telomeric loci are the primary sites at which a marked telomeric ring-containing DNA is observed among wild-type and surviving cells lacking telomerase. Marked telomeric DNAs can be transferred to telomeres and form tandem arrays through Rad52-, Rad50-, and polymerase delta-mediated recombination. Moreover, increases of extrachromosomal telomeric and Y' rings were observed in telomerase-deficient cells. These results imply that telomeres can use looped-out telomeric rings to promote telomere-telomere recombination in telomerase-deficient Saccharomyces cerevisiae.


C1 Inhibitor Activity and Angioedema Attacks in Patients with Hereditary Angioedema.
Hereditary angioedema (HAE) is caused by deficiency or dysfunction in the C1 inhibitor (C1-INH) protein. C1-INH replacement therapy is used to treat patients with HAE to restore the missing or dysfunctional protein. In vitro studies showed that C1-INH inhibits prekallikrein activation and bradykinin formation in a dose-dependent manner when added to the plasma of patients with HAE. HAE is highly variable in clinical presentation, and early studies suggested that there was not a clear relationship between functional C1-INH levels and disease activity. Later, a threshold of approximately 40% functional C1-INH was identified, above which patients' risk of an attack was diminished. Long-term prophylaxis with plasma-derived C1-INH effectively reduces attack frequency and severity. Pharmacokinetic modeling shows that functional C1-INH levels are associated with the relative risk of having an attack. Subcutaneous administration of C1-INH results in consistently high levels of functional C1-INH activity, whereas intravenous administration results in periods of low trough functional C1-INH activity before the next scheduled dose, increasing the risk of an angioedema attack. These studies suggest that measurement of functional C1-INH activity may be useful as a biomarker of the risk of an attack in patients with HAE who are receiving long-term prophylaxis with plasma-derived C1-INH.


Use of a condensation particle counter and an optical particle counter to assess the number concentration of engineered nanoparticles.
There is a need to evaluate nanoparticle (< 100 nm) exposures in occupational settings. However, portable instruments do not size segregate particles in that size range. A proxy method for determining nanoparticle count concentrations involves subtracting counts made with a condensation particle counter (CPC) from those of an optical particle counter/sizer (OPC), resulting in an estimation of "very fine" particles < 300 nm, where 300 nm is the OPC lower detection limit. However, to determine size distributions from which particles < 100 nm may be estimated, the resulting count of particles < 300 nm can be used as an additional channel of count data in addition to those obtained from the OPC. To test these methods, the very fine number concentrations determined using a CPC and OPC were compared with those from SMPS measurements and were used to verify the accuracy of a very fine particle number concentration determined by an OPC and CPC. Two "size-distribution" methods, weighted-average and log-probit, were applied to reproduce particle size distributions from OPC and CPC data and were then evaluated relative to their ability to accurately estimate the nanoparticle number concentrations. Various engineered nanoparticles were used to create test aerosols, including titanium dioxide (TiO(2)), silicon dioxide (SiO(2)), and iron oxide (Fe(2)O(3)). These materials were chosen because of their different refractive indices and therefore may be measured differently by the OPC. The count-difference method was able to estimate very fine particle number concentrations with an error between 10.9 to 58.4%. In estimating nanoparticle number concentrations using the size-distribution methods, the log-probit method resulted in the lowest percent errors that ranged from -42% to 1023%. Percent error was lower than the instrument manufacturer's indicated level of accuracy when the test aerosol refractive index was similar to that used for OPC calibration standards. Accuracy could be increased if there was an increase in the size resolution for number concentrations measured by the CPC of very fine particles and mitigation of optical effects.


Modulation of monocyte complement synthesis by interferons.
Recombinant Escherichia coli-derived gamma-interferon has been shown to stimulate synthesis of the second component of complement (C2), factor B and C1 inhibitor, but to inhibit synthesis of the third component (C3). alpha- and beta-interferons stimulate synthesis of factor B and C3 inhibitor, inhibit C5 synthesis but do not alter synthesis of C2. alpha- and beta-interferons act synergistically with gamma-interferon to enhance both factor B and C1-inhibitor synthesis.


A comparison of the antagonistic activities of tamsulosin and terazosin against human vascular alpha1-adrenoceptors.
Tamsulosin, a selective alpha1A-adrenoceptor antagonist, and terazosin, a non-selective one, are effective for the treatment of urinary disturbance due to benign prostatic hypertrophy. In the present study, their alpha1-adrenoceptor-blocking effects on blood vessels, which may cause orthostatic hypotension, were investigated in 10 healthy males. After the subjects took orally 0.2 mg of tamsulosin, 1 mg of terazosin or a lactate capsule as the control in a randomized cross-over fashion, their finger tip vasoconstrictor response to cold stimulation and vasoconstrictor response of the dorsal hand vein to increasing doses of phenylephrine were examined. The finger tip vasoconstrictor response was significantly reduced and the infusion rate of phenylephrine producing a half-maximal constriction was significantly increased by terazosin, but tamsulosin had no significant effect on these parameters. These data suggest that the usual dose of tamsulosin exerts little alpha1-adrenoceptor-blocking activity on blood vessels, and orthostatic episodes might be mild, if any, during the treatment with tamsulosin.


Multiple scattering of electromagnetic waves by an array of parallel gyrotropic rods.
We study multiple scattering of electromagnetic waves by an array of parallel gyrotropic circular rods and show that such an array can exhibit fairly unusual scattering properties and provide, under certain conditions, a giant enhancement of the scattered field. Among the scattering patterns of such an array at its resonant frequencies, the most interesting is the distribution of the total field in the form of a perfect self-similar structure of chessboard type. The scattering characteristics of the array are found to be essentially determined by the resonant properties of its gyrotropic elements and cannot be realized for arrays of nongyrotropic rods. It is expected that the results obtained can lead to a wide variety of practical applications.


"Child marriage" in context: exploring local attitudes towards early marriage in rural Tanzania.
A global campaign to end "child marriage" has emerged over the last decade as part of growing international commitments to address gender inequities and improve female wellbeing. Campaigns typically assert that young brides have negligible autonomy in the marriage process and that marrying under 18 years has resolutely negative impacts on wellbeing. Yet, surprisingly few studies explore local attitudes towards marriage and its timing within contexts where early marriage is most common. As such our understanding of motivations and potential conflicts of interest leading female adolescents into marriage remain poorly informed by viewpoints of people purportedly at risk. We present an exploratory study of attitudes to early marriage in northwestern Tanzania where marriage before or shortly after 18 years is normative. We use focus group discussions, complimented by a survey of 993 women, to investigate local views on marriage. We explore (i) why people marry, (ii) when marriage is deemed appropriate, and (iii) who guides the marriage process. Contrary to dominant narratives in the end child marriage movement, we find that women are frequently active rather than passive in the selection of when and who to marry. Furthermore, marriage is widely viewed as instrumental in acquiring social status within one's local community. Our conclusions illuminate why rates of early marriage remain high despite potential negative wellbeing consequences and increasingly restrictive laws. We discuss our results in relation to related qualitative studies in other cultural contexts and consider the policy implications for current efforts to limit early marriage in Tanzania and beyond.


[Enhancing efficiency of sanatorium treatment of patients with chronic pyelonephritis using hyperbaric oxygenation].
Clinical studies were made in 117 patients with chronic pyelonephritis at the stage of sanatorium-and-health-resort treatment using hyperbaric oxygenation. Supplementing the "traditional" naftusya-based balneotherapy with hyperbaric oxygenation has been shown to potentiate the effect of the water on the course of the illness, functional condition of the urinary organs, to strengthen the potential of those systems res responsible for homeostasis of the peroxide oxygenation of lipids in the body, which fact validates a high efficiency of their combined use.


Earlier use of systemic immunosuppression is associated with fewer ophthalmic surgeries in paediatric non-infectious uveitis.
There is a paucity of large trials investigating the effect of management strategies for paediatric non-infectious uveitis on complications requiring surgery. The purpose of our study is to investigate whether earlier initiation of systemic immunosuppression in paediatric non-infectious uveitis is associated with fewer ophthalmic surgeries. A retrospective review was conducted on 48 children with non-infectious uveitis assessed in 1998-2013. Patients were divided into uveitis diagnosed before December 2008 (group 1) and after January 2009 (group 2). Duration from uveitis onset to methotrexate initiation (U-MTX) and biological addition (U-Biologic) were reviewed. Follow-up visits with topical corticosteroids >3 times daily and active uveitis (≥1+ cells) during 3.5 years were documented. The main outcome measure was the need for ≥1 ophthalmic surgery at 3.5 years. In group 1, 69.5% of patients required ≥1 ophthalmic surgery at 3.5 years versus 26.9% in group 2 (p=0.005). U-MTX was 28.9±11.8 weeks and 14.2±10.0 weeks for groups 1 and 2 (p=0.028). U-Biologic was 134.6±46.0 weeks and 82.3±43.3 weeks for groups 1 and 2 (p=0.0016). Corticosteroid use >3 times daily was 85.9±52.7 weeks and 14.6±11.1 weeks for groups 1 and 2. Multivariate regression showed methotrexate initiation within 6 months of uveitis onset lowered the likelihood of needing ophthalmic surgery at 3.5 years (OR=6.2, 95% CI 1.2 to 33.4; p=0.033). Univariate regression demonstrated biological addition within 18 months of uveitis onset reduced the likelihood of requiring ophthalmic surgery (OR 12.57, 95% CI 1.28 to 123.48; p=0.030). Earlier control of uveitis by addition of immunosuppressive therapy reduced the need for ophthalmic surgery.


Automatic classification of heterogeneous slit-illumination images using an ensemble of cost-sensitive convolutional neural networks.
Lens opacity seriously affects the visual development of infants. Slit-illumination images play an irreplaceable role in lens opacity detection; however, these images exhibited varied phenotypes with severe heterogeneity and complexity, particularly among pediatric cataracts. Therefore, it is urgently needed to explore an effective computer-aided method to automatically diagnose heterogeneous lens opacity and to provide appropriate treatment recommendations in a timely manner. We integrated three different deep learning networks and a cost-sensitive method into an ensemble learning architecture, and then proposed an effective model called CCNN-Ensemble [ensemble of cost-sensitive convolutional neural networks (CNNs)] for automatic lens opacity detection. A total of 470 slit-illumination images of pediatric cataracts were used for training and comparison between the CCNN-Ensemble model and conventional methods. Finally, we used two external datasets (132 independent test images and 79 Internet-based images) to further evaluate the model's generalizability and effectiveness. Experimental results and comparative analyses demonstrated that the proposed method was superior to conventional approaches and provided clinically meaningful performance in terms of three grading indices of lens opacity: area (specificity and sensitivity; 92.00% and 92.31%), density (93.85% and 91.43%) and opacity location (95.25% and 89.29%). Furthermore, the comparable performance on the independent testing dataset and the internet-based images verified the effectiveness and generalizability of the model. Finally, we developed and implemented a website-based automatic diagnosis software for pediatric cataract grading diagnosis in ophthalmology clinics. The CCNN-Ensemble method demonstrates higher specificity and sensitivity than conventional methods on multi-source datasets. This study provides a practical strategy for heterogeneous lens opacity diagnosis and has the potential to be applied to the analysis of other medical images.


Measuring the illicit cigarette market in Mexico: a cross validation of two methodologies.
To compare two methods to estimate the magnitude of the illicit cigarette trade in Mexico and to contrast these results with tobacco industry figures. We used two survey methods: a smoker survey and a discarded pack survey. Data were collected in eight major cities in Mexico between November and December 2017. A total of 2396 face-to-face interviews to adult smokers were conducted and 8204 discarded packs were collected. To determine whether cigarette packs were intended for the Mexican market, we analysed pack features required by Mexican regulations and self-reported brands of the last purchase. Standard statistical tests to compare proportions were employed. Correlates of illicit cigarette use were also analysed. The share of cigarettes not intended for the Mexican market was 8.8% based on the analysis of discarded packs and 7.6% based on the survey of smokers, that is, the difference was small and only borderline significant overall (p=0.055). Also, both results were lower than those presented by the tobacco industry (16.6%). However, differences across methods were statistically significant for various cities. Our results suggest that the optimal practice for the study of illicit trade is to cross validate estimates using both the smoker survey and the littered pack survey. If resources are limited, however, our findings indicate that either method could be used because both yield similar overall results, as longs as the potential biases are considered. Also, consistent with findings from other studies, our results suggest that the tobacco industry exaggerates the scope of illicit cigarette trade.


The wheat WRKY transcription factors TaWRKY49 and TaWRKY62 confer differential high-temperature seedling-plant resistance to Puccinia striiformis f. sp. tritici.
WRKY transcription factors (TFs) play crucial roles in plant resistance responses to pathogens. Wheat stripe rust, caused by the fungal pathogen Puccinia striiformis f. sp. tritici (Pst), is a destructive disease of wheat (Triticum aestivum) worldwide. In this study, the two WRKY genes TaWRKY49 and TaWRKY62 were originally identified in association with high-temperature seedling-plant resistance to Pst (HTSP) resistance in wheat cultivar Xiaoyan 6 by RNA-seq. Interestingly, the expression levels of TaWRKY49 and TaWRKY62 were down- and up-regulated, respectively, during HTSP resistance in response to Pst. Silencing of TaWRKY49 enhanced whereas silencing TaWRKY62 reduced HTSP resistance. The enhanced resistance observed on leaves following the silencing of TaWRKY49 was coupled with increased expression of salicylic acid (SA)- and jasmonic acid (JA)-responsive genes TaPR1.1 and TaAOS, as well as reactive oxygen species (ROS)-associated genes TaCAT and TaPOD; whereas the ethylene (ET)-responsive gene TaPIE1 was suppressed. The decreased resistance observed on leaves following TaWRKY62 silencing was associated with increased expression of TaPR1.1 and TaPOD, and suppression of TaAOS and TaPIE1. Furthermore, SA, ET, MeJA (methyl jasmonate), hydrogen peroxide (H2O2) and abscisic acid (ABA) treatments increased TaWRKY62 expression. On the other hand, MeJA did not affect the expression of TaWRKY49, and H2O2 reduced TaWRKY49 expression. In conclusion, TaWRKY49 negatively regulates while TaWRKY62 positively regulates wheat HTSP resistance to Pst by differential regulation of SA-, JA-, ET and ROS-mediated signaling.


Analysis of delta-globin gene mutations in Greek cypriots.
We recently described four delta-globin gene mutations in Greek Cypriots studied by polymerase chain reaction (PCR) amplification and automated fluorescence-based DNA sequence analysis (Blood 78:3298, 1991). Selective restriction enzyme digestion of PCR products facilitated direct mutation detection. Twenty-eight additional samples from unrelated Cypriots with Hb A2 levels ranging from 0.6% to 3.6% were studied by PCR and showed the following: twelve had the delta 27 (ala-->ser) mutation, one was heterozygous for the delta IVS-2 AG-->GG change, and none had either the delta 116 (arg-->cys) or delta 141 (leu-->pro) mutations. The remaining samples were divided into two groups: 11 with borderline normal Hb A2 values that were not pursued; and four with abnormal Hb A2 values. The delta-globin genes from these four samples were sequenced and the same four changes identified in each: a C-->T at -199, a C-->T at codon 4 (thr-->ile), a silent C-->T at codon 97, and an AT deletion at position 722 in IVS-2. The codon 4 change abolishes a Ple I site whereas the codon 97 creates an Nla III site, thus facilitating rapid identification. All four changes are in cis position, suggesting that the -199 C-->T, the C-->T at codon 97, and the AT deletion in IVS-2 are neutral polymorphisms present on the codon 4 (thr-->ile) chromosome. DNA haplotype analysis suggests all five delta-globin gene mutant alleles arose independently on different chromosomal backgrounds.


A novel method to determine the natural course of unruptured brain arteriovenous malformations without the need for follow-up information.
OBJECTIVEThere is a strong clinical need to accurately determine the average annual hemorrhage risk in unruptured brain arteriovenous malformations (AVMs). This need motivated the present initiative to use data from a uniquely large patient population and design a novel methodology to achieve a risk determination with unprecedented accuracy. The authors also aimed to determine the impact of sex, pregnancy, AVM volume, and location on the risk for AVM rupture.METHODSThe present study does not consider any specific management of the AVMs, but only uses the age distribution for the first hemorrhage, the shape of which becomes universal for a sufficiently large set of patients. For this purpose, the authors collected observations, including age at first hemorrhage and AVM size and location, in 3425 patients. The average annual risk for hemorrhage could then be determined from the simple relation that the number of patients with their first hemorrhage at a specific age equals the risk for hemorrhage times the number of patients at risk at that age. For a subset of the patients, the information regarding occurrence of AVM hemorrhage after treatment of the first hemorrhage was used for further analysis of the influence on risk from AVM location and pregnancy.RESULTSThe age distribution for the first AVM hemorrhage was used to determine the average annual risk for hemorrhage in unruptured AVMs at adult ages (25-60 years). It was concluded to be 3.1% ± 0.2% and unrelated to AVM volume but influenced by its location, with the highest risk for centrally located AVMs. The hemorrhage risk was found to be significantly higher for females in their fertile years.CONCLUSIONSThe present methodology allowed the authors to determine the average annual risk for the first AVM hemorrhage at 3.1% ± 0.2% without the need for individual patient follow-up. This methodology has potential also for other similar types of investigations. The conclusion that centrally located AVMs carry a higher risk was confirmed by follow-up information. Follow-up information was also used to conclude that pregnancy causes a substantially greater AVM hemorrhage risk. The age distribution for AVM hemorrhage is incompatible with AVMs present at birth having the same hemorrhage risk as AVMs in adults. Plausibly, they instead develop in the early years of life, possibly with a lower hemorrhage risk during that time period.


Proteases in agricultural dust induce lung inflammation through PAR-1 and PAR-2 activation.
Workers exposed to aerosolized dust present in concentrated animal feeding operations (CAFOs) are susceptible to inflammatory lung diseases, such as chronic obstructive pulmonary disease. Extracts of dust collected from hog CAFOs [hog dust extract (HDE)] are potent stimulators of lung inflammatory responses in several model systems. The observation that HDE contains active proteases prompted the present study, which evaluated the role of CAFO dust proteases in lung inflammatory processes and tested whether protease-activated receptors (PARs) are involved in the signaling pathway for these events. We hypothesized that the damaging proinflammatory effect of HDE is due, in part, to the proteolytic activation of PARs, and inhibiting the proteases in HDE or disrupting PAR activation would attenuate HDE-mediated inflammatory indexes in bronchial epithelial cells (BECs), in mouse lung slices in vitro, and in a murine in vivo exposure model. Human BECs and mouse lung slice cultures stimulated with 5% HDE released significantly more of each of the cytokines measured (IL-6, IL-8, TNF-α, keratinocyte-derived chemokine/CXC chemokine ligand 1, and macrophage inflammatory protein-2/CXC chemokine ligand 2) than controls, and these effects were markedly diminished by protease inhibition. Inhibition of PARs also blunted the HDE-induced cytokine release from BECs. In addition, protease depletion inhibited HDE-induced BEC intracellular PKCα and PKCε activation. C57BL/6J mice administered 12.5% HDE intranasally, either once or daily for 3 wk, exhibited increased total cellular and neutrophil influx, bronchial alveolar fluid inflammatory cytokines, lung histopathology, and inflammatory scores compared with mice receiving protease-depleted HDE. These data suggest that proteases in dust from CAFOs are important mediators of lung inflammation, and these proteases and their receptors may provide novel targets for therapeutic intervention in CAFO dust-induced airways disease.


Early and discrete changes in permeability of Escherichia coli and certain other gram-negative bacteria during killing by granulocytes.
Rapid killing of Escherichia coli by intact or disrupted rabbit granulocytes or by granulocyte fractions was found to be accompanied by an equally rapid increase in permeability of the E.coli envelope. This increase in permeability was detected by determining entry of substances that normally do not cross E.coli's permeability barrier, namely actinomycin D and o-nitrophenyl-beta-D-galactopyranoside (ONPG), a substrate for cytoplasmic beta-galactosidase. Because E.coli continue to incorporate radioactively labeled precursors into bacterial RNA and protein for at least 1 h, despite rapid killing by granulocytes, entry of actinomycin D could be measured by its inhibitory effect on macromolecular synthesis. Entry was evident within minutes after exposure to granulocytes or granulocyte fractions and is independent of pH over a range of 6.5-9.0. The effect of disrupted granulocytes or partially purified fractions on susceptibility of E.coli to actinomycin D and entry of ONPG is dose dependent. That the entry of actinomycin D and ONPG was not caused by gross destruction of the envelope is indicated by two sets of observations: (a) net influx of (42)K was maintained for at least 15 min, even though efflux of potassium was immediately accelerated upon addition of bactericidal concentrations of granulocyte fractions; (b) beta-galactosidase did not leak out of E.coli under conditions that produce maximal inhibition by actinomycin D. Different species of gram-negative bacteria exhibited different susceptibilities to the bactericidal and permeability effects of granulocyte fractions. Thus, three strains of E.coli and one strain of Salmonella typhimurium were highly susceptible to both the bactericidal and the permeability enhancing effects of granulocyte fractions, whereas two strains of Serratia marcescens and one strain of Pseudomonas aeruginosa were resistant to both effects. Another strain of P. aeruginosa was rendered susceptible to actinomycin D without being killed and two strains of S. typhimurium remained insensitive to actinomycin D while being killed by granulocytes.


Sensory hyperalgesia is characteristic of nonspecific arm pain: a comparison with cervical radiculopathy and pain-free controls.
Nonspecific arm pain (NSAP) is a common clinical entity, the pathophysiological mechanisms of which are poorly understood. The purpose of this study was to investigate sensory profiles in individuals with nonspecific arm pain compared with cervical radiculopathy and pain-free controls. Forty office workers with NSAP, 17 people with cervical radiculopathy, and 40 pain-free controls were assessed by means of quantitative sensory testing (thermal and vibration detection thresholds; thermal and pressure pain thresholds), tests for neural tissue sensitivity, and questionnaires. Between-group comparisons were conducted using Kruskal-Wallis tests. An exploratory factor analysis was used to determine characteristic features in NSAP. Both patient groups demonstrated cold and pressure pain sensitivity (P<0.003; P<0.05) and neural tissue sensitivity (P<0.001). The NSAP group also demonstrated heat pain sensitivity (P<0.001). Both patient groups demonstrated hypoaesthesia to vibration thresholds (P<0.05), whereas thermal hypoaesthesia was only evident in the cervical radiculopathy group (P<0.05). Exploratory factor analysis revealed pressure and thermal pain sensitivity as the key characteristics of this NSAP group. Sensory profiles in NSAP and cervical radiculopathy differ. NSAP is characterized by widespread sensitivity to thermal and pressure pain in the absence of thermal hypoaesthesia, whereas cervical radiculopathy is characterized by the presence of thermal and vibratory hypoaesthesia as well as more localized cold and pressure pain sensitivity. The identification of widespread sensory hypersensitivity in NSAP has important implications for clinical decision making.


GADD45 is induced in Alzheimer's disease, and protects against apoptosis in vitro.
Expression of the growth arrest DNA damage-inducible protein, GADD45, has recently been reported to be induced by a wide range of stimuli, especially those that produce a high level of base pair damage. We have investigated the expression of GADD45 in brain tissue obtained from patients suffering from Alzheimer's disease (AD). Our results demonstrate that many neurons express the GADD45 protein, and that expression of this protein in neurons is associated with expression of the anti-apoptotic protein Bcl-2, and the presence of DNA damage, but not closely associated with tangle-bearing neurons. Additionally, cell lines overexpressing this protein confer resistance to apoptosis induced by DNA damage agent, suggesting that this protein may participate in cell survival mechanisms.


[Polyneuropathies caused by glues in inhabitants of Montebelluna in the decade 1979-1988].
Sixty-seven incident cases of polyneuropathy (PNP) occurred among shoe workers exposed to solvents in the last ten years (1979-1988) in the Montebelluna area (Veneto region, northern Italy). They have been identified by the Occupational Health Service implementing a surveillance system. Around 700 shoe factories are active in this area with more than 6,000 workers. The disease has been diagnosed by means of neurological investigation and electroneuromyographical examination; it appears always as subclinical. The National Institute of Compensation (INAIL) confirmed the case series. In the present study data are discussed on the personal characteristics of the cases, including an evaluation of social and health consequences of the disease, and the work environment where PNP cases arose; attention is posed on the chemicals used, on jobs performed by the workers, and on duration of exposure. The study stresses the need to improve further the work conditions where solvents are used and to maintain a surveillance system for this occupational disease.


Clinical and virologic manifestations of primary Epstein-Barr virus (EBV) infection in Kenyan infants born to HIV-infected women.
Human immunodeficiency virus (HIV) infection is a risk factor for Epstein-Barr virus (EBV)-associated lymphomas. Characterizing primary infection may elucidate risk factors for malignancy. To describe clinical and virologic manifestations of primary EBV infection among infants born to HIV-infected women, specimens were utilized from a cohort study conducted in Nairobi, Kenya. HIV and EBV viral loads were measured serially in plasma. EBV serology was performed on EBV DNA-negative infants. Monthly clinical examinations were performed by pediatricians. The probability of EBV infection by 1 year of age was .78 (95% CI, .67-.88) in HIV-infected and .49 (95% CI, .35-.65) in HIV-uninfected infants (P < .0001). At 2 years, probability of EBV infection was .96 (95% CI, .89-.99) in HIV-infected infants. Peak EBV loads were higher in HIV-infected versus HIV-uninfected infants (median 2.6 vs 2.1 log10 copies/mL; P < .0001). The majority of HIV-infected infants had detectable EBV DNA for >3 months (79%). Primary EBV infection was associated with cough, fever, otitis media, pneumonia, hepatomegaly, splenomegaly, and hospitalization in HIV-infected infants; conjunctivitis and rhinorrhea in HIV-uninfected infants. EBV infection occurs early in infants born to HIV-infected women. HIV infection was associated with more frequent and higher quantity EBV DNA detection.


Dynamic aspects of antibody:oligosaccharide complexes characterized by molecular dynamics simulations and saturation transfer difference nuclear magnetic resonance.
Carbohydrates are likely to maintain significant conformational flexibility in antibody (Ab):carbohydrate complexes. As demonstrated herein for the protective monoclonal Ab (mAb) F22-4 recognizing the Shigella flexneri 2a O-antigen (O-Ag) and numerous synthetic oligosaccharide fragments thereof, the combination of molecular dynamics simulations and nuclear magnetic resonance saturation transfer difference experiments, supported by physicochemical analysis, allows us to determine the binding epitope and its various contributions to affinity without using any modified oligosaccharides. Moreover, the methods used provide insights into ligand flexibility in the complex, thus enabling a better understanding of the Ab affinities observed for a representative set of synthetic O-Ag fragments. Additionally, these complementary pieces of information give evidence to the ability of the studied mAb to recognize internal as well as terminal epitopes of its cognate polysaccharide antigen. Hence, we show that an appropriate combination of computational and experimental methods provides a basis to explore carbohydrate functional mimicry and receptor binding. The strategy may facilitate the design of either ligands or carbohydrate recognition domains, according to needed improvements of the natural carbohydrate:receptor properties.


A baseline understanding of state laws governing e-cigarettes.
Electronic cigarettes (e-cigarettes) have been available for purchase in the USA since 2007, and have grown rapidly in popularity. Currently, there are no federal restrictions on e-cigarettes; therefore, any regulations are under the purview of state and/or local governments. This study examines state laws governing e-cigarettes through youth access restrictions, smoke-free air requirements and/or excise taxation. Codified statutory and administrative laws, attorney general opinions, executive orders, and revenue notices and rulings effective as of 15 November 2013 for all 50 states and the District of Columbia, were compiled using Boolean searches in Lexis-Nexis and Westlaw. All laws were analysed by two study authors to determine the presence and components of relevant provisions. Two categories of laws were identified; (1) explicit e-cigarette laws and (2) laws focused on tobacco-derived and/or nicotine-containing products. Thirty-four states' laws address e-cigarettes either explicitly or as part of language applying to tobacco-derived or nicotine-containing products. Laws explicitly addressing e-cigarettes primarily focus on youth access (22 states) or smoke-free air (12 states); only Minnesota imposes an excise tax on e-cigarettes. Similarly, tobacco-derived or nicotine-containing products are primarily regulated through youth access restrictions (6 states), smoke-free air laws (5 states), or excise taxation (2 states). In the current absence of federal law governing e-cigarettes, more than one-half of the states have taken the initiative to regulate these products. The opportunity exists for the remaining states to incorporate e-cigarette-related restrictions into their pre-existing tobacco control laws.


Surface-bound phosphatase activity in living hyphae of ectomycorrhizal fungi of Nothofagus obliqua.
We determined the location and the activity of surface-bound phosphomonoesterase (SBP) of five ectomycorrhizal (EM) fungi of Nothofagus oblique. EM fungal mycelium of Paxillus involutus, Austropaxillus boletinoides, Descolea antartica, Cenococcum geophilum and Pisolithus tinctorius was grown in media with varying concentrations of dissolved phosphorus. SBP activity was detected at different pH values (3-7) under each growth regimen. SBP activity was assessed using a colorimetric method based on the hydrolysis of p-nitrophenyl phosphate (pNPP) to p-nitrophenol phosphate (pNP) + P. A new technique involving confocal laser-scanning microscopy (LSM) was used to locate and quantify SBP activity on the hyphal surface. EM fungi showed two fundamentally different patterns of SBP activity in relation to varying environmental conditions (P-concentrations and pH). In the cases of D. antartica, A. boletinoides and C. geophilum, changes in SBP activity were induced primarily by changes in the number of SBP-active centers on the hyphae. In the cases of P. tinctorius and P. involutus, the number of SBP-active centers per μm hyphal length changed much less than the intensity of the SBP-active centers on the hyphae. Our findings not only contribute to the discussion about the role of SBP-active centers in EM fungi but also introduce LSM as a valuable method for studying EM fungi.


The comprehensive outcomes of hepatitis C virus infection: A multi-faceted chronic disease.
Treatment of hepatitis C virus (HCV) infection has been revolutionized with the introduction of pangenotypic, interferon- and ribavirin-free regimens associated with high cure rates and a low side effect profile. Additionally, there is evidence that HCV cure reduces HCV complications, improves patient-reported outcomes and is cost-saving in most western countries in the long term. This is a review of the comprehensive burden of HCV and the value of eliminating HCV infection. With the introduction of the interferon-free all-oral, once a day pill treatment regimen for the cure of HCV, the potential to eliminate HCV by 2030 has become a possibility for some regions of the world. Nevertheless, there are barriers to screening, linkage to care, and treatment in many countries that must be overcome in order to reach this goal. In conclusion, globally, work must continue to ensure national policies are in place to support screening, linkage to care and affordable treatment in order to eliminate HCV.


Strategy alternatives for homeland air and cruise missile defense.
Air and cruise missile defense of the U.S. homeland is characterized by a requirement to protect a large number of critical assets nonuniformly dispersed over a vast area with relatively few defensive systems. In this article, we explore strategy alternatives to make the best use of existing defense resources and suggest this approach as a means of reducing risk while mitigating the cost of developing and acquiring new systems. We frame the issue as an attacker-defender problem with simultaneous moves. First, we outline and examine the relatively simple problem of defending comparatively few locations with two surveillance systems. Second, we present our analysis and findings for a more realistic scenario that includes a representative list of U.S. critical assets. Third, we investigate sensitivity to defensive strategic choices in the more realistic scenario. As part of this investigation, we describe two complementary computational methods that, under certain circumstances, allow one to reduce large computational problems to a more manageable size. Finally, we demonstrate that strategic choices can be an important supplement to material solutions and can, in some cases, be a more cost-effective alternative.


Cannabinoids, hippocampal excitability and efficacy for the treatment of epilepsy.
Interest in cannabis and its related cannabinoids THC and CBD for use as anti-convulsant therapy has been progressively increasing. While the destigmatization of cannabis and cannabis related research have progressed in the last few decades, there are still many questions that remain unanswered. This review seeks to summarize the progress made in cannabis research in the past four decades and to identify possible directions for future research that are critical for the development of cannabinoid-based therapy in epilepsy.


Change in fruit and vegetable intake over 24 months in older adults: results of the SENIOR project intervention.
We test the efficacy of an intervention based on the transtheoretical model to increase the intake of fruits and vegetables and to describe differences in psychosocial variables based on the achievement of the 5 A Day Program target. This study is a randomized controlled trial comparing a 12-month fruit and vegetable intervention to a control condition with a 12-month follow-up. Participants included 1,277 community-residing persons who were 60 years of age or older; 834 provided dietary data at all three time points and are included in our outcome analyses. The intervention group increased intake by 0.5 to 1.0 serving more than the control group over 24 months as measured by the NCI Fruit and Vegetable Screener and the 5 A Day Program screener. The majority of the participants (58%) perceived that they maintained 5 or more servings per day for 24 months. These maintainers had a higher intake at each time point for all dietary measures and differed from those who failed to progress (11%) for most transtheoretical model variables. The intervention was effective in increasing the intake of fruits and vegetables in older adults. Those who maintained their level of perceived intake as 5 or more servings per day consumed 2-4 servings per day more than those who failed to progress.


Photo stories, Ricoeur, and experiences from practice: a hermeneutic dialogue.
The purpose of this article is to demonstrate how a particular narrative approach in nursing, namely the photo instrument can be connected with Ricoeur's hermeneutic philosophy. Ricoeur's concept of mimesis, when supplemented with the concept of performance, is shown relevant for understanding how patients construct and reformulate meaning in illness experiences. A single-case study is presented for a tentative exploration of how the key concepts of mimesis and performance can broaden our understanding of practice. More specifically it concerned the use of photographs in a group with psychiatric patients.


Antiviral activity of extracts from Morinda citrifolia leaves and chlorophyll catabolites, pheophorbide a and pyropheophorbide a, against hepatitis C virus.
The development of complementary and/or alternative drugs for treatment of hepatitis C virus (HCV) infection is still needed. Antiviral compounds in medicinal plants are potentially good targets to study. Morinda citrifolia is a common plant distributed widely in Indo-Pacific region; its fruits and leaves are food sources and are also used as a treatment in traditional medicine. In this study, using a HCV cell culture system, it was demonstrated that a methanol extract, its n-hexane, and ethyl acetate fractions from M. citrifolia leaves possess anti-HCV activities with 50%-inhibitory concentrations (IC(50)) of 20.6, 6.1, and 6.6 μg/mL, respectively. Bioactivity-guided purification and structural analysis led to isolation and identification of pheophorbide a, the major catabolite of chlorophyll a, as an anti-HCV compound present in the extracts (IC(50) = 0.3 μg/mL). It was also found that pyropheophorbide a possesses anti-HCV activity (IC(50) = 0.2 μg/mL). The 50%-cytotoxic concentrations (CC(50)) of pheophorbide a and pyropheophorbide a were 10.0 and 7.2 μg/mL, respectively, their selectivity indexes being 33 and 36, respectively. On the other hand, chlorophyll a, sodium copper chlorophyllin, and pheophytin a barely, or only marginally, exhibited anti-HCV activities. Time-of-addition analysis revealed that pheophorbide a and pyropheophorbide a act at both entry and the post-entry steps. The present results suggest that pheophorbide a and its related compounds would be good candidates for seed compounds for developing antivirals against HCV.


Lack of Associations between Female Hormone Levels and Visuospatial Working Memory, Divided Attention and Cognitive Bias across Two Consecutive Menstrual Cycles.
Background: Interpretation of observational studies on associations between prefrontal cognitive functioning and hormone levels across the female menstrual cycle is complicated due to small sample sizes and poor replicability. Methods: This observational multisite study comprised data of n = 88 menstruating women from Hannover, Germany, and Zurich, Switzerland, assessed during a first cycle and n = 68 re-assessed during a second cycle to rule out practice effects and false-positive chance findings. We assessed visuospatial working memory, attention, cognitive bias and hormone levels at four consecutive time-points across both cycles. In addition to inter-individual differences we examined intra-individual change over time (i.e., within-subject effects). Results: Estrogen, progesterone and testosterone did not relate to inter-individual differences in cognitive functioning. There was a significant negative association between intra-individual change in progesterone and change in working memory from pre-ovulatory to mid-luteal phase during the first cycle, but that association did not replicate in the second cycle. Intra-individual change in testosterone related negatively to change in cognitive bias from menstrual to pre-ovulatory as well as from pre-ovulatory to mid-luteal phase in the first cycle, but these associations did not replicate in the second cycle. Conclusions: There is no consistent association between women's hormone levels, in particular estrogen and progesterone, and attention, working memory and cognitive bias. That is, anecdotal findings observed during the first cycle did not replicate in the second cycle, suggesting that these are false-positives attributable to random variation and systematic biases such as practice effects. Due to methodological limitations, positive findings in the published literature must be interpreted with reservation.


Ultrasound-Guided Periadventitial Administration of Rapamycin-Fibrin Glue Attenuates Neointimal Hyperplasia in the Rat Carotid Artery Injury Model.
Arterial restenosis caused by intimal hyperplasia (IH) is a serious complication after vascular interventions. In the rat carotid balloon injury model, we injected phosphate buffer saline (PBS), rapamycin-phosphate buffer saline suspension (RPM-PBS), blank fibrin glue (FG) and rapamycin-fibrin glue (RPM-FG) around the injured carotid artery under ultrasound guidance and observed the inhibitory effect on IH. The properties of RPM-FG in vitro were verified by scanning electron microscopy (SEM) and determination of the drug release rate. FG metabolism in vivo was observed by fluorescence imaging. The rat carotid balloon injury models were randomly classified into 4 groups: PBS group (control group), RPM-PBS group, FG group, and RPM-FG group. Periadventitial administration was performed by ultrasound-guided percutaneous puncture on the first day after angioplasty. Carotid artery specimens were analyzed by immunostaining, Evans blue staining and hematoxylin-eosin staining. The RPM particles showed clustered distributions in the FG block. The glue was maintained for a longer time in vivo (> 14 days) than in vitro (approximately 7 days). Two-component liquid FG administered by ultrasound-guided injection completely encapsulated the injured artery before coagulation. The RPM-FG inhibited IH after carotid angioplasty vs. control and other groups. The proliferation of vascular smooth muscle cells (VSMCs) was significantly inhibited during neointima formation, whereas endothelial cell (EC) repair was not affected. Periadventitial delivery of RPM-FG contributed to inhibiting IH in the rat carotid artery injury model without compromising re-endothelialization. Additionally, FG provided a promising platform for the future development of a safe, effective, and minimally invasive perivascular drug delivery method to treat vascular disease.


Spin-flop and spin-Peierls transition in doped CuGeO3.
Ni++ ions doped inorganic CuGeO3 sample has been studied by using electron spin resonance (ESR) technique in the temperature range of 3-300 K. The ESR spectrum of Cu++ ion has been observed to be strongly temperature dependent for inorganic spin-Peierls (SP) Cu0.96Ni0.04GeO3 samples. The ESR line width and ESR amplitude exponentially vanishes below a critical temperature, Tsp=14 K. The one-dimensional (1D) antiferromagnetic (AF) spin chain formed of Cu++ is broken by Ni++ (spin-1) ion, giving uncoupled spins at the end of the chains that give extra contribution to the spectra at lower temperature and stabilizes a Néel state. The g-factor is much smaller than the expected value for isolated Cu++ and Ni++ ions and is much more anisotropic than for undoped samples [O. Yalçin, B. Aktaş, J. Magn. Magn. Mater. 258/259 (2003) 137 (reference therein)]. It is shown that the ground state of dimerized spins is singlet. The spin-flop (SF) phenomenon is obtained from AF state mixed condition and then ferromagnetic (FM) state. The spin-flop field slightly increases when increasing temperature in the temperature range 100-300 K. The SF transition is showed almost AF order for Cu0.96Ni0.04GeO3.


Investigation of the activity level and radiological impacts of naturally occurring radionuclides in blast furnace slag.
The activity level and possible radiological impacts of naturally occurring radionuclides on the health of workers and members of the public, as a result of utilisation of blast furnace slag (BFS) samples as a substitute for aggregate in road construction were investigated by using a gamma-ray spectrometer and potential exposure scenarios given in Radiation Protection 122. The mean activity concentrations of the (226)Ra, (232)Th and (40)K in BFS samples were found to be 152.4, 54.9 and 183.1 Bq kg(-1), respectively. These values are compared with typical values measured in BFS samples from the European Union countries, which are 270, 70 and 240 Bq kg(-1) for (226)Ra, (232)Th and (40)K, respectively. The values of radium equivalent activity index calculated for BFS samples were within the recommended safety limits. The highest total annual effective doses evaluated as 0.9 and 0.4 mSv y(-1) for members of the public and workers, respectively, were lower than the annual limit of 1 mSv y(-1).


[Interrelationship between metabolic and genetic regulation of alkaline and acid phosphatases in E. coli cells].
The effect of exogenous orthophosphate and mutations in regulatory genes of alkaline phosphatase on the level of nonspecific acid phosphatase was studied. The level of this enzyme as well as the level of alkaline phosphatase were shown to be regulated by exogenous orthophosphate being derepressed under phosphate starvation. The derepression of acid phosphatase is accompanied by more rapid secretion of enzyme from membranes to soluble fraction. Mutations in all the four regulatory genes decrease the level of enzyme in cells. Genes phoR and phoS, participating in regulation of alkaline phosphatase, are required for the derepression of acid phosphatase under the conditions of phosphate starvation.


Vitamin D deficiency associated with neurodevelopmental problems in 2-year-old Japanese boys.
While associations between vitamin D deficiency and neurodevelopmental disorders have been found, large studies on child vitamin D, neurodevelopment, and sex differences among the general population are lacking. This study aimed to investigate the association between child serum 25-hydroxyvitamin D (25(OH)D)) levels and neurodevelopmental problems (NDPs). Serum 25(OH)D and NDPs were measured at age two among the subcohort study of the Japan Environment and Children's Study. NDPs were assessed with the Kyoto Scale of Psychological Development 2001 (Kyoto scale). Adjusted odds ratios (aORs) for the Kyoto-scale developmental quotient scores <70 were calculated, for postural-motor, cognitive-adaptive, and language-social domains and overall scores, adjusted for test month, latitude, small for gestational age, maternal age, and daycare attendance. Among 2363 boys and 2290 girls, boys had higher 25(OH)D levels, but scored lower in the Kyoto scale. For boys in the vitamin D deficiency (<20 ng/mL) group, aORs of scoring the Kyoto-scale DQs <70 were 2.33 (p = 0.006) for overall DQs, 1.91 (p = 0.037) for cognitive-adaptive, and 1.69 (p = 0.024) for language-social domains. For girls, results were inconclusive. Only boys showed a clear and cross-modal association between vitamin D deficiency and NDPs.


The effect of sildenafil on rats with adenine-Induced chronic kidney disease.
The erectile dysfunction drug sildenafil has cardiopulmonary protective actions, and a nephroprotective action in cisplatin and ischemia-reperfusion-induced acute kidney injury. Here, we assessed its possible ameliorative action in a model of chronic kidney disease (CKD) using adenine feeding. Eight groups of rats were treated with saline (controls), adenine (0.25% w/w in feed daily for 5 weeks), and oral sildenafil (0.1, 0.5 or 2.5 mg/kg), either alone, or concomitantly with adenine. Urine was collected 24 h after the end of the treatments from all rats and blood pressure measured, followed by collection of blood and kidneys for the measurement of several functional, biochemical and histopathological parameters. Adenine treatment reduced body weight, creatinine renal clearance, and increased water intake and urine output, as well as the plasma concentrations of urea and creatinine, neutrophil gelatinase-associated lipocalin, and N-acetyl-β-D-glucosaminidase activity, and albumin in urine. Adenine also increased the concentrations of the uremic toxins indoxyl sulfate, uric acid and phosphate, and a number of proteins and inflammatory cytokines, and decreased that of several anti - oxidant indices. Renal histopathological markers of damage (inflammation and fibrosis) were significantly increased by adenine. Sildenafil, given simultaneously with adenine, induced a dose - dependent improvements in most of the above parameters, suggesting its possible use as adjunct treatment for CKD in humans.


Hand-assisted laparoscopic total proctocolectomy and ileal pouch-anal anastomosis after liver transplant for primary sclerosing cholangitis.
Chronic ulcerative colitis (CUC) is associated with extraintestinal manifestations such as primary sclerosing cholangitis (PSC). The onset of PSC can precede the diagnosis of CUC, and require liver transplantation in some patients. Surgical management of CUC posttransplant has traditionally been open total proctocolectomy and ileal pouch-anal anastomosis. Herein, we present a case of a woman with a previous liver transplant for PSC who subsequently developed CUC with dysplasia, successfully treated with hand-assisted laparoscopic total proctocolectomy and ileal pouch-anal anastomosis. Hand-assisted laparoscopic surgery is an excellent option for patients with previous complex abdominal surgery. It can be performed safely and expediently, providing the benefits of reduced hospital stay and early return of bowel function.


A multi-approach study to delineate interactions between carabid beetles and soybean aphids.
In recent years, the soybean aphid, Aphis glycines Matsumura, has become the most important exotic pest of soybean, Glycine max (L.) Merrill, in North America. Given the significant yield losses that are reported, considerable effort has been expended to characterize the natural enemy community associated with this pest. Several indigenous and naturalized predators have been identified as potential biological control agents, and these include carabid beetles, an abundant and important family of aphid predators. The objectives of this study were to assess the incidence of field predation by Pterostichus melanarius (Illiger), the most common carabid species in Québec soybeans, using molecular gut-content analysis, and to quantify its impact on A. glycines populations through laboratory and field cage experiments. Throughout the growing season between 16.8% (during low aphid density) and 33.7% (at times of high aphid density) of P. melanarius tested positive for aphid DNA. Furthermore, although laboratory feeding trials confirmed that P. melanarius prey on A. glycines, short-term field cage experiments failed to demonstrate a significant reduction of A. glycines populations by carabid beetles. These results suggest a relatively weak interaction between P. melanarius and A. glycines when pest densities are high, but the high predation rate when aphid densities are particularly low suggests these natural enemies may function as important early-season predators.


Factor 8 (F8) gene mutation profile of Turkish hemophilia A patients with inhibitors.
Factor VIII (FVIII) replacement therapy is ineffective in hemophilia A patients who develop alloantibodies (inhibitors) against FVIII. The type of factor 8 (F8) gene mutation, genes in the major histocompatibility complex loci, and also polymorphisms in IL-10 and tumor necrosis factor-alpha are the major predisposing factors for inhibitor formation. The present study was initiated to reveal the F8 gene mutation profile of 30 severely affected high-responder patients with inhibitor levels of more than 5 Bethesda U (BU)/ml and four low-responder patients with inhibitors less than 5 BU/ml. Southern blot and PCR analysis were performed to detect intron 22 and intron 1 inversions, respectively. Point mutations were screened by DNA sequence analysis of all coding regions, intron/exon boundaries, promoter and 3' UTR regions of the F8 gene. The prevalent mutation was the intron 22 inversion among the high-responder patients followed by large deletions, small deletions, and nonsense mutations. Only one missense and one splicing error mutation was seen. Among the low-responder patients, three single nucleotide deletions and one intron 22 inversion were found. All mutation types detected were in agreement with the severe hemophilia A phenotype, most likely leading to a deficiency of and predisposition to the development of alloantibodies against FVIII. It is seen that Turkish hemophilia A patients with major molecular defects have a higher possibility of developing inhibitors.


Nucleotide sequence of tobacco chloroplast gene for the alpha subunit of proton-translocating ATPase.
The tobacco chloroplast gene for the alpha subunit of proton-translocating ATPase has been cloned and sequenced. The coding region contains 1521 bp (507 codons). The nucleotide sequence and the deduced amino acid sequence show 55% and 54% homologies with those of the E. coli alpha subunit, respectively. The deduced amino acid composition is quite similar to that estimated for the spinach alpha subunit.


Body mass index, physical activity, and dietary behaviors among members of an urban community fitness center: a questionnaire survey.
Development of effective behavioral interventions to promote weight control and physical activity among diverse, underserved populations is a public health priority. Community focused wellness organizations, such as YMCAs, could provide a unique channel with which to reach such populations. This study assessed health behaviors and related characteristics of members of an urban YMCA facility. We surveyed 135 randomly selected members of an urban YMCA facility in Massachusetts to examine self-reported (1) physical activity, (2) dietary behaviors, (3) body mass index, and (4) correlates of behavior change among short-term (i.e., one year or less) and long-term (i.e., more than one year) members. Chi-square tests were used to assess bivariate associations between variables, and multivariate linear regression models were fit to examine correlates of health behaviors and weight status. Eighty-nine percent of short-term and 94% of long-term members reported meeting current physical activity recommendations. Only 24% of short-term and 19% of long-term members met fruit and vegetable consumption recommendations, however, and more than half were overweight or obese. Length of membership was not significantly related to weight status, dietary behaviors, or physical activity. Most respondents were interested in changing health behaviors, in the preparation stage of change, and had high levels of self-efficacy to change behaviors. Short-term members had less education (p = 0.02), lower household incomes (p = 0.02), and were less likely to identify as white (p = 0.005) than long-term members. In multivariate models, females had lower BMI than males (p = 0.003) and reported less physical activity (p = 0.008). Physical activity was also inversely associated with age (p = 0.0004) and education (p = 0.02). Rates of overweight/obesity and fruit and vegetable consumption suggested that there is a need for a weight control intervention among members of an urban community YMCA. Membership in such a community wellness facility alone might not be sufficient to help members maintain a healthy weight. The data indicate that YMCA members are interested in making changes in their dietary and physical activity behaviors. Targeting newer YMCA members might be an effective way of reaching underserved populations. These data will help inform the development of a weight control intervention tailored to this setting.