Estrogen and leptin have differential effects on FSH and LH release in female rats.
Prior experiments have shown that the adipocyte hormone leptin can advance puberty in mice. We hypothesized that it would also stimulate gonadotrophin secretion in adults. Since the secretion of follicle stimulating hormone (FSH) and luteinizing hormone (LH) is drastically affected by estrogen, we hypothesized that leptin might have different actions dependent on the dose of estrogen. Consequently in these experiments, we tested the effect of injection of leptin into the third cerebral ventricle of ovariectomized animals injected with either the oil diluent, 10 microg or 50 microg of estradiol benzoate 72 hr prior to the experiment. The animals were ovariectomized 3-4 weeks prior to implantation of a cannula into the third ventricle 1 week before the experiments. The day after implantation of an external jugular catheter, blood samples (0. 3 ml) were collected just before and every 10 min for 2 hr after 3V injection of 5 microl of diluent or 10 microg of leptin. Both doses of estradiol benzoate equally decreased plasma LH concentrations and pulse amplitude, but there was a graded decrease in pulse frequency. In contrast, only the 50-microg dose of estradiol benzoate significantly decreased mean plasma FSH concentrations without significantly changing other parameters of FSH release. The number of LH pulses alone and pulses of both hormones together decreased as the dose of estrogen was increased, whereas the number of pulses of FSH alone significantly increased with the higher dose of estradiol benzoate, demonstrating differential control of LH and FSH secretion by estrogen, consistent with alterations in release of luteinizing hormone releasing hormone (LHRH) and the putative FSH-releasing factor (FSHRF), respectively. The effects of intraventricularly injected leptin were drastically altered by increasing doses of estradiol benzoate. There was no significant effect of intraventricular injection of leptin (10 microg) on the various parameters of either FSH or LH secretion in ovariectomized, oil-injected rats, whereas in those injected with 10 microg of estradiol benzoate there was an increase in the first hr in mean plasma concentration, area under the curve, pulse amplitude, and maximum increase of LH above the starting value (Deltamax) on comparison with the results in the diluent-injected animals in which there was no alteration of these parameters during the 2 hr following injection. The pattern of FSH release was opposite to that of LH and had a different time-course. In the diluent-injected animals, probably because of the stress of injection and frequent blood sampling, there was an initial significant decline in plasma FSH at 20 min after injection, followed by a progressive increase with a significant elevation above the control values at 110 and 120 min. In the leptin-injected animals, mean plasma FSH was nearly constant during the entire experiment, coupled with a significant decrease below values in diluent-injected rats, beginning at 30 min after injection and progressing to a maximal difference at 120 min. Area under the curve, pulse amplitude, and Deltamax of FSH was also decreased in the second hour compared to values in diluent-injected rats. In contrast to the stimulatory effects of intraventricular injection of leptin on pulsatile LH release manifest during the first hour after injection, there was a diametrically opposite, delayed significant decrease in pulsatile FSH release. This differential effect of leptin on FSH and LH release was consistent with differential effects of leptin on LHRH and FSHRF release. Finally, the higher dose of E2 (50 microg) suppressed release of both FSH and LH, but there was little effect of leptin under these conditions, the only effect being a slight (P < 0.04) increase in pulse amplitude of LH in this group of rats. The results indicate that the central effects of leptin on gonadotropin release are strongly dependent on plasma estradiol levels. These effects are consistent w


Patch-clamp fluorometry recording of conformational rearrangements of ion channels.
Conformational rearrangements are commonly observed in membrane proteins and constitute the molecular mechanisms through which they contribute to signal transduction. Information on structural changes in membrane proteins has mostly been inferred from functional studies. Recently, site-specific fluorescence recordings have made it possible to directly observe such molecular events in real time within the membrane environment. Here, we describe the patch-clamp fluorometry (PCF) technique that records simultaneously the local structural changes and the functional states of ion channels in isolated cell membranes. Combined with fluorescence resonance energy transfer (FRET), the technique should shed new light on ion channel activation, regulation, and interaction with other membrane proteins.


Behavioural and emotional difficulties in students attending schools for children and adolescents with severe intellectual disability.
For several decades, researchers and clinicians have been aware of an increased prevalence of psychiatric disorder in children with intellectual disability. However, there are few research studies exploring this issue. The parents of 123 children attending schools for children with 'severe learning difficulties' completed the Developmental Behaviour Checklist (DBC) in order to identify those children with clinically significant behavioural and emotional problems. Comparisons were made with norms for the DBC and a range of child variables were investigated as possible correlates of disorder. Some 50.4% of the children scored above the cut-off on the DBC for psychiatric disorder. The child's severity of physical disability was related most strongly to parental ratings of behavioural and emotional problems. There were also effects for the child's age and the absence of Down's syndrome. The present study confirms previous research findings of a high prevalence of behavioural and emotional difficulties amongst children with intellectual disability, and identifies a number of correlates of disorder which require further investigation.


Transitioning Toward Evidence-Based Research in the Health Sciences for the XXI Century.
This article discusses some of the misconceptions of evidence-based research in the health sciences. It proposes that since not all treatments in medicine and dentistry can be evidence-based, clinical applications of the evidence-based process should become a specialty. The case is particularly evident in dentistry. Therefore dentistry is taken in this article as a model for discussion. We propose that to approach dentistry from the viewpoint of the patient-oriented evidence that matters (POEM) is perfectly acceptable so far as we also engage in the process of research evaluation and appraisal in dentistry (READ). We distinguish between dentistry based on the evidence, and evidence-based dentistry. We argue that when invoking an evidence-based approach to dentistry or medicine, it is not sufficient to establish the 'levels of evidence', but rather that all evidence-based clinical intervention must undergo the stringent process of evidence-based research so that clinical practice guidelines be revised based on the best available evidence.


Psychodynamic psychotherapy of ADHD: a review of the literature.
Contributions of psychodynamic psychotherapy to the treatment of children with attention deficit hyperactivity disorder (ADHD) have been sparse. However, mixed results of other interventions, including behavior therapy and medication, call for a systematic examination of psychodynamic contributions to treatment of ADHD children. A systematic review of the literature on psychodynamic psychotherapy with ADHD children yielded a combination of 23 case studies, research reports, and theoretical writings. Questions relevant to the practice of psychodynamic psychotherapy were the focus and included a review of psychodynamic diagnosis of ADHD, theoretical orientations of psychodynamic psychotherapy, identification of core treatment issues, clinical examples, and theoretical perspectives on therapeutic change as well as practice techniques. A review of 231 abstracts resulted from key word searches including ADHD, Psychotherapy, Psychodynamic, and Psychoanalytic. Once inclusion criteria were met, the information from the literature was organized according to categories reflecting the review's focus. Findings of the review are provided to guide psychodynamic psychotherapists in their treatment of ADHD children. Recommendations for future individual and group studies are discussed.


Open breast biopsy. A critical analysis.
A retrospective study of open breast biopsies performed from January 1, 1988 to December 31, 1988 was undertaken to compare the malignancy rate of the authors with that generally reported in the literature. This was done to determine if biopsy of mammographically demonstrated nonpalpable lesions had a favorable impact on outcome, and to identify factors with high relative risk or predictive value for malignancy. Office records of 518 patients who underwent breast biopsies were reviewed, 122 of which (23.6%) proved to be malignant. The malignancy rate for needle localized excisions of nonpalpable lesions was 17.5 per cent. Of these, 28 per cent were stage tumor in situ (TIS), 60 per cent stage 1, and 12 per cent stage 2. A higher percentage of palpable lesions were malignant than were nonpalpable lesions (29.0%). Of the palpable malignancies, 28 per cent were stage 1, 51 per cent stage 2, 13 per cent stage 3, and 8 per cent stage 4. Those who were older than 40 years of age yielded a significantly higher malignancy rate when compared with the less than 40 age group (28.6% versus 6.7%, P less than 0.001). Lesions that appeared on mammogram as nodules, calcium, or both had a higher malignancy rate than those where no lesion was identified (25.3% versus 14.2%, P less than 0.001). None of these factors alone or in combination ruled out malignancy. Biopsy of nonpalpable mammographically demonstrated lesions lead to detection of breast cancer at an earlier stage. Age greater than forty years, demonstrable lesion by mammogram, and palpable lesion were significant predictors of malignancy.(ABSTRACT TRUNCATED AT 250 WORDS)


Biomarker responses and decreasing contaminant levels in ringed seals (Pusa hispida) from Svalbard, Norway.
Blubber was analyzed for a wide range of contaminants from five sub-adult and eight adult male ringed seals sampled in 2004, namely, for polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), toxaphenes, chlordanes, dichlorodiphenyldichloroethylene (DDE), and polybrominated diphenylethers (PBDEs). Contaminant levels were compared to previously sampled animals from the same area, as well as data from literature for other arctic wildlife species from a wide variety of locations. Ringed seals sampled in 2004 showed 50-90% lower levels of legacy contaminants such as PCBs and chlorinated pesticides compared to animals sampled in 1996 of similar age (14 sub-adults and 7 adult males), indicating that the decline of chlorinated contaminants observed during the 1990s in a variety of arctic wildlife species is continuing into the 21st century. The results also indicated that PBDE declined in ringed seals; levels in 2004 were about 70-80% lower than in animals sampled in 1998. This is one of the first observations of reduced exposure to these compounds and might be a first indication that restrictions of production and use of these contaminants have resulted in lower exposures in the Arctic. The PCB pattern shifted toward the less chlorinated (i.e., less persistent) PCBs, especially in adult ringed seals, possibly as a result of reduced overall contaminant exposures and a consequently lower cytochrome P-450 (CYP) induction, which results in a slower metabolism of less persistent PCBs. The overall effect would be relative increases in the lower chlorinated PCBs and a relative decreases in the higher chlorinated PCB. Possibly due to low exposure and consequent low induction levels, ethoxyresorufin O-deethylation (EROD) activity proved to be a poor biomarker for contaminant exposure in ringed seals in the present study. The close negative correlation (r(2) = 70.9%)between EROD activity and percent blubber indicates that CYP might respond to increased bioavailability of the contaminant mixtures when they are mobilized from blubber during periods of reduced food intake.


Melphalan alone prior to allogeneic bone marrow transplantation from HLA-identical sibling donors for hematologic malignancies: alloengraftment with potential preservation of fertility in women.
Melphalan has rarely been used as a single agent for conditioning prior to allogeneic marrow transplantation. Twenty-eight patients (median age 19.5 years) undergoing allogeneic BMT for acute leukemia (n = 26) or lymphoblastic lymphoma (n = 2) in first remission (n = 10) or beyond (n = 18) from HLA-identical siblings received 240 mg/m2 melphalan. Death due to primary graft failure was seen in two patients. Sustained hematopoietic recovery was seen in all the others (n = 22) not dying early due to toxicity (n = 2) or persistent active disease (n = 2). The 3-year probabilities of transplant-related mortality and relapse were 35% and 62%, respectively. Seven patients are alive and well at 103-163 months (median 136) with Karnofsky scores of 100% (10-year disease-free survival, 25%). Of the 16 patients with donors of the opposite sex, seven underwent cytogenetic studies after BMT and showed complete chimerism with donor cells. Amongst the four women who were 15-30 years at the time of the transplant, there were seven pregnancies over 297 months of follow-up beyond 2 years from transplant. In contrast, no pregnancies were seen in 53 women with hematologic malignancies who were conditioned with other regimens over 3524 months of follow-up beyond 2 years from transplant. The pregnancy rate was significantly higher (P < 0.001) for women conditioned with melphalan alone (three of four) than for those conditioned with other regimens (0 of 53). We conclude that pre-transplant conditioning with melphalan alone permits alloengraftment of marrow from HLA-identical siblings, and may preserve fertility better than other regimens in some women.


Characteristics of Dexmedetomidine Postconditioning in the Field of Myocardial Ischemia-Reperfusion Injury.
Timing and onset of myocardial ischemia are mostly unpredictable. Therefore, postconditioning could be an effective cardioprotective intervention. Because ischemic postconditioning is an invasive and not practicable treatment, pharmacological postconditioning would be a more suitable alternative cardioprotective measure. For the α2-adrenoreceptor agonist, dexmedetomidine postconditioning has been shown. However, data on a concentration-dependent effect of dexmedetomidine are lacking. Furthermore, it is unclear whether the time point and/or duration of dexmedetomidine administration in the reperfusion period is of relevance. We set out to determine whether infarct size reduction by dexmedetomidine is concentration dependent and whether time point and/or duration of dexmedetomidine application has an impact on the effect size of cardio protection. Hearts of male Wistar rats were randomized and placed on a Langendorff system perfused with Krebs-Henseleit buffer at a constant pressure of 80 mm Hg. All hearts were subjected to 33 minutes of global ischemia and 60 minutes of reperfusion. In part I of the study, a concentration-response effect was determined by perfusing hearts with various concentrations of dexmedetomidine (0.3-100 nM) at the onset of reperfusion. Based on these results, part II of the study was conducted with 3 nM dexmedetomidine. Application of dexmedetomidine started directly at the onset of reperfusion (Dex60) and 15 minutes (Dex15), 30 minutes (Dex30), or 45 minutes (Dex45) after the start of reperfusion and lasted always until the end of the reperfusion period. Infarct size was determined by triphenyltetrazolium chloride staining. In part I, infarct size in control (Con) hearts was 62% ± 4%. Three-nanometer dexmedetomidine was the lowest most effective cardioprotective concentration and reduced infarct size to 24% ± 7% (P < .0001 versus Con). Higher concentrations did not confer stronger protection. Infarct size in control hearts from part II was 66% ± 6%. Different starting times and/or durations of application resulted in similar infarct size reduction (all P < .0001 versus Con). Postconditioning by dexmedetomidine is concentration dependent in ranges between 0.3 and 3 nM. Increased concentrations above 3 nM do not further enhance this cardioprotective effect. This cardioprotective effect is independent of time point and length of application in the reperfusion period.


Exposure to bullying behaviours, resilience, and return to work self-efficacy in patients on or at risk of sick leave.
The study investigated relationships between exposure to bullying behaviours, return to work self-efficacy (RTW-SE) and resilience, and if resilience moderates the bullying-RTW-SE relationship among patients on sick leave or at risk of sick leave due to common mental disorders (CMD). A sample of 675 patients treated in an outpatient clinic was analysed using regressions and moderation analyses by employing SPSS and the Process macro SPSS supplement. The results showed a negative relationship between exposure to bullying behaviours and RTW-SE. There was also a positive main effect for resilience, as patients with high resilience score significantly higher on RTW-SE than patients with low resilience irrespective of levels of bullying. Further, the resilience sub-dimension personal resilience moderated the bullying-RTW-SE relationship, while the sub-dimension interpersonal resilience did not. Patients high on personal resilience showed relatively lower RTW-SE scores when exposed to bullying behaviours, compared to those that were not bullied with high personal resilience levels. Hence, one should take note of the fact that even if resilience may strengthen RTW-SE, bullying is an adverse event which particularly affects individuals who present with relatively high levels of resilience resources, at least when it comes to RTW-SE.


Analysis of cyanogen bromide peptides of type I collagen from a patient with lethal osteogenesis imperfecta.
The CNBr peptides of type I collagen from bone of a patient with lethal osteogenesis imperfecta and age-matched controls were isolated by molecular-sieve chromatography and their amino acid compositions were determined. No differences were found between the compositions of the peptides from the patient and those from the controls, except for an increase in the degree of hydroxylation of lysine in all peptides from the patient. Type I collagen CNBr peptides from chick-embryo skin [Barnes, Constable Morton & Kodicek (1971) Biochem. J. 125, 925--928] and guinea-pig scar tissue [Shuttleworth, Forrest & Jackson (1975) Biochim. Biophys. Acta 379, 207--216] also have an increased degree of hydroxylation of lysine with an otherwise normal amino acid composition, and it was believed that this could be an embryonic form of collagen. As a similar collagen was present in the bones of the patient studied, it seems possible that the same 'embryonic' collagen is synthesized during development, in repair process and also in genetic disorders of collagen metabolism.


Influence of age on dynamic position sense: evidence using a sequential movement task.
Age related changes to the nervous system are well documented. The main objectives of this study were to examine age-associated changes in dynamic position sense and relate these changes to measures of balance and physical function. Two groups of individuals (young <30 years; elderly >60 years) performed an upper extremity movement sequence triggered by a pre-determined target angle during passive rotations of the ankle joint at ten random velocities (10-90 degrees s(-1)). Balance was assessed with a series of timed standing tests. Physical function was assessed with the SF 36 questionnaire. Muscle activity was recorded from the ankle dorsiflexors and plantarflexors during the dynamic position tests. Increased error in the elderly group suggested that dynamic position sense declines with age. Moreover, this decline in dynamic position sense was associated with decreased balance and an impaired perception of physical function. The elderly also co-contracted the ankle plantarflexors and dorsiflexors during the proprioceptive testing, perhaps as a strategy to "gain up" spindle sensitivity. These findings suggest that impaired dynamic position sense of the ankle contributes to alterations in the overall physical function and balance in the elderly. Rehabilitative training methods that improve dynamic position sense of the ankles may improve physical function and balance in the elderly.


The influence of intermolecular coupling on electron and ion transport in differently substituted phthalocyanine thin films as electrochromic materials: a chemistry application of the Goldilocks principle.
The transport of both electrons and ions in organic mixed ionic and electronic conductors such as phthalocyanines, is essential to allow redox reactions of entire films and, hence, to impart electrochromism. Thin films of a new type, tetrakis-perfluoroisopropyl-perfluoro phthalocyanine, F40PcCu of different thicknesses were obtained via vapor deposition. The extent of the intermolecular coupling within the F40PcCu films established by van der Waals interactions was investigated by in situ optical spectroscopy during film growth. The transfer of electrons and diffusion of counter cations in these films, as well as their electrochromic performance were characterized by electrochemical and spectroelectrochemical measurements with an aqueous solution of KCl as electrolyte. A moderate degree of intermolecular interaction of the F40PcCu molecules in the solid state was observed, compared to non-fluoroalkylated perfluoro phthalocyanine, F16PcCu and octakis-perfluoroisopropyl-perfluorophthalocyanine, F64PcCu, which exhibit stronger and weaker coupling, respectively. The replacement of F by perfluoroisopropyl is, thereby, established as a valuable approach to tune this coupling of chromophores and, hence, the transport coefficients of electrons and ions in the solid films. Reversible changes of the films upon reduction and intercalation of K+ counter ions and re-oxidation and expulsion of the counter ions were confirmed by simultaneously measured optical absorption spectra. Thin films of F40PcCu showed a well-balanced, equally fast transport of electrons and ions. The films provided a fast and reversible switching process over at least 200 cycles indicating the stability of these materials.


Flux coupling in a neuronal glutamate transporter.
Synaptic transmission is commonly terminated by diffusion and reuptake of neurotransmitter from the synaptic cleft. Glutamate reuptake prevents neurotoxicity and sets the lower limit for the concentration of extracellular glutamate, so it is important to understand the thermodynamics of this process. Here we use voltage clamping with a pH-sensitive fluorescent dye to monitor electrical currents and pH changes associated with flux of glutamate mediated by the human neuronal glutamate transporter EAAT3. In contrast to a previous model, we find that three sodium ions and one proton are cotransported with each glutamate ion into the cell, while one potassium ion is transported out of the cell. This coupling can support a transmembrane glutamate concentration gradient ([Glu]in/[Glu]out) exceeding 10(6) under equilibrium conditions, and would allow the transporter to continue removing glutamate over a wide range of ionic conditions.


Radiation-induced lipid peroxidation and membrane-bound enzymes in liver microsomes.
Changes in lipid peroxidation and enzymes in liver microsomes were examined after alpha-irradiation. The radiation-induced lipid peroxidation was increased with increasing radiation dose, with decreasing dose-rate and also with decreasing concentration of microsomes. The content of P-450 was decreased with decreasing dose-rate and inversely with radiation dose, while NADPH-cytochrome c reductase and cytochrome b5 were less affected by alpha-irradiation. Both the lipid peroxidation and the inactivation of microsomal enzymes induced by alpha-irradiation were mardedly reduced by radical scavengers. Hexobarbital hydroxylating activity and binding capacity of P-450 for hexobarbital, which were strikingly decreased after alpha-irradiation were less protected by radical scavengers, in contrast to the case of the lipid peroxidation and of the enzymes. These results suggest that intrinsic enzymes are more damaged through radiation-induced peroxidation of membrane lipids as compared with extrinsic enzymes.


Evaluation of effects of Zingiber officinale on salivation in rats.
There are some herbal plants in Iranian traditional system of medicine which are believed to be excellent remedies to alleviate the symptoms of xerostomia. The aim of the present study was to evaluate the effect of systemic administration of seven different herbal extracts on the rate of salivation in rats. The extracts of 7 herbs; Zingiber officinale Roscoe (Zingiberaceae), Citrus sinensis (L.) Osbeck (Rutaceae), Artemisia absinthium L. (Asteraceae), Cichorium intybus L. (Asteraceae), Pimpinella anisum L.(Apiaceae), Portulaca oleracea L.(Portulacaceae), Tribulus terrestris L. (Zygophyllaceae) were prepared. Nine groups of animals (including negative and positive control groups) were used and seven rats were tested in each group. After the injection of extracts, saliva volume was measured gravimetrically in four continuous seven-minute intervals. The results showed that after injection of ginger extracts salivation was significantly higher as compared to the negative control group and other herbal extracts in all of the four intervals (P<0.01). The peak action of the ginger was during the first 7-minute interval and following this, salivation decreased to some extent. The present study suggests that the extract of Zingiber offiicianle can increase the rate of salivation significantly in animal model. Further investigations on different constituents of ginger seem to be essential to identify the responsible constituent for stimulation of saliva secretion.


Amygdala hyperreactivity in borderline personality disorder: implications for emotional dysregulation.
Disturbed interpersonal relations and emotional dysregulation are fundamental aspects of borderline personality disorder (BPD). The amygdala plays important roles in modulating vigilance and generating negative emotional states and is often abnormally reactive in disorders of mood and emotion. The aim of this study was to assess amygdala reactivity in BPD patients relative to normal control subjects. We hypothesized that amygdala hyperreactivity contributes to hypervigilance, emotional dysregulation, and disturbed interpersonal relations in BPD. Using functional magnetic resonance imaging, we examined neural responses to 20-sec blocks of neutral, happy, sad, and fearful facial expression (or a fixation point) in 15 BPD and 15 normal control subjects. The DSM IV-diagnosed BPD patients and the normal control subjects were assessed by a clinical research team in a medical school psychiatry department. Borderline patients showed significantly greater left amygdala activation to the facial expressions of emotion (vs. a fixation point) compared with normal control subjects. Post-scan debriefing revealed that some borderline patients had difficulty disambiguating neutral faces or found them threatening. Pictures of human emotional expressions elicit robust differences in amygdala activation levels in borderline patients, compared with normal control subjects, and can be used as probes to study the neuropathophysiologic basis of borderline personality disorder.


Semenogelins I and II bind zinc and regulate the activity of prostate-specific antigen.
In semen, the gel proteins SgI and SgII (semenogelins I and II) are digested by PSA (prostate-specific antigen), resulting in liquefaction and release of motile spermatozoa. Semen contains a high concentration of Zn2+, which is known to inhibit the protease activity of PSA. We characterized the binding of Zn2+ to SgI and SgII and found evidence that these proteins are involved in regulating the activity of PSA. Intact SgI and SgII and synthetic semenogelin peptides were used in the experiments. Binding of Zn2+ was studied by radioligand blotting, titration with a zinc (II) fluorophore chelator and NMR analysis. A chromogenic substrate was used to measure the enzymatic activity of PSA. SgI and SgII bound Zn2+ with a stoichiometry of at least 10 mol (mol of protein)(-1) and with an average dissociation constant of approx. 5 microM per site. Moreover, Zn2+-inhibited PSA was activated by exposure to SgI or SgII. Since both proteins have high affinity for Zn2+ and are the dominating proteins in semen, they probably represent the major Zn2+ binders in semen, one function of which may be to regulate the activity of PSA. The system is self-regulating, and PSA is maintained in an active state by its substrate.


Antioxidant activities of astaxanthin and related carotenoids.
The antioxidant activities of astaxanthin and related carotenoids have been measured by employing a newly developed fluorometric assay. This assay is based on 4,4-difluoro-3,5-bis(4-phenyl-1, 3-butadienyl)-4-bora-3a,4a-diaza-s-indacene (BODIPY 665/676) as an indicator; 2,2'-azobis-2,4-dimethylvaleronitrile (AMVN) as a peroxyl radical generator; and 6-hydroxy-2,5,7, 8-tetramethylchroman-2-carboxylic acid (Trolox) as a calibrator in an organic and liposomal media. By employing this assay, three categories of carotenoids were examined: namely, the hydrocarbon carotenoids lycopene, alpha-carotene, and beta-carotene; the hydroxy carotenoid lutein; and the alpha-hydroxy-ketocarotenoid astaxanthin. The relative peroxyl radical scavenging activities of Trolox, astaxanthin, alpha-tocopherol, lycopene, beta-carotene, lutein, and alpha-carotene in octane/butyronitrile (9:1, v/v) were determined to be 1.0, 1.0, 1.3, 0.5, 0.4, 0.3, and 0.2, respectively. In dioleoylphosphatidyl choline (DOPC) liposomal suspension in Tri-HCl buffer (pH 7.4 at 40 degrees C), the relative reactivities of astaxanthin, beta-carotene, alpha-tocopherol, and lutein were found to be 1.00, 0.9, 0.6, and 0.6, respectively. When BODIPY 665/676 was replaced by 4,4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a, 4a-diaza-s-indacene-3-undecanoic acid (BODIPY 581/591 C(11)) as an indicator, astaxanthin showed the highest antioxidant activity toward peroxyl radicals. The relative reactivities of Trolox, astaxanthin, alpha-tocopherol, alpha-carotene, lutein, beta-carotene, and lycopene were determined to be 1.0, 1.3, 0.9, 0.5, 0.4, 0.2, and 0.4, respectively.


Amyloid burden and neural function in people at risk for Alzheimer's Disease.
To determine the relationship between amyloid burden and neural function in healthy adults at risk for Alzheimer's Disease (AD), we used multimodal imaging with [C-11]Pittsburgh compound B positron emission tomography, [F-18]fluorodeoxyglucose, positron emission tomography , and magnetic resonance imaging, together with cognitive measurement in 201 subjects (mean age, 60.1 years; range, 46-73 years) from the Wisconsin Registry for Alzheimer's Prevention. Using a qualitative rating, 18% of the samples were strongly positive Beta-amyloid (Aβ+), 41% indeterminate (Aβi), and 41% negative (Aβ-). Aβ+ was associated with older age, female sex, and showed trends for maternal family history of AD and APOE4. Relative to the Aβ- group, Aβ+ and Aβi participants had increased glucose metabolism in the bilateral thalamus; Aβ+ participants also had increased metabolism in the bilateral superior temporal gyrus. Aβ+ participants exhibited increased gray matter in the lateral parietal lobe bilaterally relative to the Aβ- group, and no areas of significant atrophy. Cognitive performance and self report cognitive and affective symptoms did not differ between groups. Amyloid burden can be identified in adults at a mean age of 60 years and is accompanied by glucometabolic increases in specific areas, but not atrophy or cognitive loss. This asymptomatic stage may be an opportune window for intervention to prevent progression to symptomatic AD.


Molecular Serotype-Specific Identification of Non-type b Haemophilus influenzae by Loop-Mediated Isothermal Amplification.
Over the past four decades, the incidence of meningitis caused by Haemophilus influenzae in children has decreased due to widespread vaccination against H. influenzae type b (Hib). The incidence of invasive diseases due to H. influenzae types not included in the vaccines, however, has increased. At present, there are a limited number of diagnostics available to detect non-type b H. influenzae. To address this issue, we developed a rapid, simple, and cost-effective method for detecting serotypes of H. influenzae. We designed LAMP primer sets based on published sequences for H. influenzae capsular types a, c, d, e, and f. The assay was evaluated to determine test reactivity, specificity, and sensitivity. To support its use in patients with suspected meningitis, we evaluated the detection limit of the non-Hib serotype specific LAMP assay using bacterial genomic DNA-spiked cerebrospinal fluid (CSF) specimens. The reactivity and specificity of the LAMP assays were confirmed using six serotypes and non-typeable H. influenzae strains, plus eight strains of other Haemophilus species and non-Haemophilus genera. The detection limits of the LAMP assay for capsular types a, c, d, e, and f were 102, 102, 102, 103, and 10 copies per reaction, while those of the PCR assay were 104, 104, 103, 103, and 104 genome copies per reaction, respectively. Using DNA-spiked CSF specimens, the detection limit of the LAMP assay was equivalent to that using purified DNA as the template. However, the detection limit of the PCR was reduced from 103 to 104 genome copies per reaction for serotype d and from 103 to 105 genome copies per reaction for serotype e. To the best of our knowledge, this is the first report of a serotype-specific identification assay for H. influenzae using the LAMP method. Our results suggest the potential of LAMP methods for patients with suspected meningitis in resource-limited laboratories or public health surveillance systems.


The impact of Medicaid expansion on trauma-related emergency department utilization: A national evaluation of policy implications.
The impact of the 2014 Affordable Care Act (ACA) upon national trauma-related emergency department (ED) utilization is unknown. We assessed ACA-related changes in ED use and payer mix, hypothesizing that post-ACA ED visits would decline and Medicaid coverage would increase disproportionately in regions of widespread policy adoption. We queried the National Emergency Department Sample (NEDS) for those with a primary trauma diagnosis, aged 18 to 64. Comparing pre-ACA (2012) to post-ACA (10/2014 to 09/2015), primary outcomes were change in ED visits and payer status; secondary outcomes were change in costs, discharge disposition and inpatient length of stay. Univariate and multivariate analyses were performed, including difference-in-differences analyses. We compared changes in ED trauma visits by payer in the West (91% in a Medicaid expansion state) versus the South (12%). Among 21.2 million trauma-related ED visits, there was a 13.3% decrease post-ACA. Overall, there was a 7.2% decrease in uninsured ED visits (25.5% vs. 18.3%, p < 0.001) and a 6.6% increase in Medicaid coverage (17.6% vs. 24.2%, p < 0.001). Trauma patients had 40% increased odds of having Medicaid post-ACA (vs. pre-ACA: aOR 1.40, p < 0.001). Patients in the West had 31% greater odds of having Medicaid (vs. South: aOR 1.31, p < 0.001). The post-ACA increase in Medicaid was greater in the West (vs. South: aOR 1.60, p < 0.001). Post-ACA, inpatients were more likely to have Medicaid (vs. ED discharge: aOR 1.20, p < 0.001) and there was a 25% increase in inpatient discharge to rehabilitation (aOR 1.24, p < 0.001). Post-ACA, there was a significant increase in insured trauma patients and a decrease in injury-related ED visits, possibly resulting from access to other outpatient services. Ensuring sustainability of expanded coverage will benefit injured patients and trauma systems. Economic, level III.


Anesthetic exposure in the treatment of symptomatic urinary calculi in pregnant women.
To assess the duration and total number of anesthetic exposures required for the treatment of urolithiasis during pregnancy, specifically comparing temporizing measures with active treatment because urolithiasis and its management may pose potential theoretical risks for the mother and fetus. We retrospectively reviewed patients with a confirmed diagnosis of urolithiasis during pregnancy who underwent surgical intervention from 1997 to 2012 at our institution. The number and duration of anesthetic exposures were assessed. We identified 26 women with urolithiasis during pregnancy, of which 15 (58%) were treated with temporizing stents and 11 (42%) with ureteroscopic stone extraction. In the ureteroscopy group, the median number of anesthetic exposures was 1.18 (interquartile range [IQR], 1-2), and the median total anesthetic time was 80 minutes (IQR, 37-126 minutes). In the stent group, 6 (40%) required multiple stent exchanges for a median of 1.47 (IQR, 1-3) anesthetic events and a median total anesthetic time of 70 minutes (IQR, 29-208 minutes). In the ureteral stent group, 7 women (47%) were induced before spontaneous labor due to inability to tolerate the stent. There was no difference in the number of anesthetic events (P = .208) or anesthesia time (P = .503) between stenting and ureteroscopy. Women undergoing ureteroscopic surgical intervention during pregnancy were at no greater risk in the number or cumulative duration of anesthesia exposure than women managed with temporizing ureteral stent placement and subsequent exchanges.


Orientational order of a ferroelectric liquid crystal with small layer contraction.
We present spectroscopic and optical studies of a non-layer-shrinkage ferroelectric liquid crystal DSiKN65. The orientational order parameters S, measured with respect to the smectic layer normal using IR spectroscopy on a sample aligned homeotropically, does not exhibit any significant variation between the smectic-A∗ and smectic-C∗ phases. In contrast the birefringence of a planar homogenous sample abruptly increases at the smectic-A∗ to smectic-C∗ transition. This suggests a general increase in the orientational order, which can be described by the orientational order parameters S' defined with respect to the director. Simultaneous increase of S' and the director tilt Θ may explain the low shrinkage of smectic layers, which is consistent with recent theoretical models describing the smectic-A∗ to smectic-C∗ transition for such materials.


Major histocompatibility complex and non-major histocompatibility complex antigens on mouse ectoplacental cone and placental trophoblastic cells.
The expression of major histocompatibility complex and non-major histocompatibility complex antigens on mouse trophoblast cultured from two defined stages of development was investigated by the sensitive in vitro mixed haemadsorption assay. Outgrowths obtained 3 to 5 days after explanation of 7 1/2-day ectoplacental cones contained a mixed population of cells. Those with a giant cell morphology showed no haemadsorption with congenic H-2 antisera and were reactive with non H-2 antiserum only in the CBA strain. Other, smaller cells were reactive for both H-2 and non-H-2 in all strains examined except for C57BL, where the cells were nonreactive for H-2. Monolayer cultures of 13 to 14-day placental suspensions tested 24 hr after preparation were strongly reactive for both H-2 and non-H-2. The identity and alloantigenic status of the cells are discussed in relation to their function in maternal-foetal immunological interactions.


Sequencing data on the long control region of human papillomavirus type 16.
A one base change (adenine at position 7861) in the long control region (LCR) of the prototype sequence of human papillomavirus type 16 was reported. With this correction, a new E2-binding site was revealed, 111 bp and 143 bp upstream from the TATA box and P97, respectively, and 105 bp downstream of the keratinocyte-dependent enhancer. An A to C mutation at position 41 was found in a patient with invasive carcinoma. This mutation falls within an E2-binding site.


cgmanalysis: An R package for descriptive analysis of continuous glucose monitor data.
Continuous glucose monitoring (CGM) is an essential part of diabetes care. Real-time CGM data are beneficial to patients for daily glucose management, and aggregate summary statistics of CGM measures are valuable to direct insulin dosing and as a tool for researchers in clinical trials. Yet, the various commercial systems still report CGM data in disparate, non-standard ways. Accordingly, there is a need for a standardized, free, open-source approach to CGM data management and analysis. A package titled cgmanalysis was developed in the free programming language R to provide a rapid, easy, and consistent methodology for CGM data management, summary measure calculation, and descriptive analysis. Variables calculated by our package compare well to those generated by various CGM software, and our functions provide a more comprehensive list of summary measures available to clinicians and researchers. Consistent handling of CGM data using our R package may facilitate collaboration between research groups and contribute to a better understanding of free-living glucose patterns.


Smoking-attributable medical care costs in the USA.
Medical care costs attributable to cigarette smoking are estimated using an econometric model of annual individual expenditures for four types of medical services: ambulatory, hospital, prescription drug, and other (which includes home health and durable medical equipment and excludes dental and mental health). The model follows the two-part specification of Duan et al. (1983). Estimation is carried out using the 1987 National Medical Expenditure Survey. Fitted values are used to calculate smoking-attributable fractions (SAFs) of expense by type of service and by age and gender category. The overall weighted average SAF is 6.54%. SAFs are generally largest for ambulatory and smallest for hospital expenses. They are larger for males and for the older age categories. The model is analyzed for heteroscedasticity and goodness of fit. Additional analysis using the National Health Interview Survey is conducted to test for the possible effect of not being able to include alcohol consumption in the primary model. A balanced repeated replication analysis is conducted to evaluate the variance of the SAFs. Variances are found to be acceptably small. An extension of the model to support evaluation of smoking-attributable costs for special populations such as individual states, and special insurance pools such as Medicaid recipients, is described. Results for the fifty states are presented. Conclusions and subjects for further research are discussed.


Hippocampal up-regulation of NCAM expression and polysialylation plays a key role on spatial memory.
Memory formation has been associated with structural and functional modifications of synapses. Cell adhesion molecules are prominent modulators of synaptic plasticity. Here, we investigated the involvement of the cell adhesion molecules, NCAM, its polysialylated state (PSA-NCAM) and L1 in spatial learning-induced synaptic remodeling and memory storage. A differential regulation of these adhesion molecules was found in the hippocampus of rats submitted to one training session in the spatial, but not cued, version of the Morris water maze. Twenty-four hours after training, synaptic expression of NCAM and PSA-NCAM was increased, whereas L1 appeared markedly decreased. The regulation of these molecules was spatial learning-specific, except for L1 reduction, which could be attributed to swimming under stressful conditions rather than to learning. Subsequent psychopharmacological experiments were performed to address the functional role of NCAM and PSA-NCAM in the formation of spatial memories. Rats received an intracerebroventricular injection of either a synthetic peptide (C3d) aimed to interfere with NCAM function, or endoneuraminidase, an enzyme that cleaves polysialic acid from NCAM. Both treatments affected acquisition of spatial information and lead to impaired spatial memory abilities, supporting a critical role of the observed learning-induced up-regulation of synaptic NCAM expression and polysialylation on spatial learning and memory. Therefore, our findings highlight NCAM as a learning-modulated molecule critically involved in the hippocampal remodeling processes underlying spatial memory formation.


Vitamin D deficiency as a risk factor for osteoporotic fractures.
The evidence on the association between vitamin D deficiency and fracture incidence is contradictory. Therefore, the objective of this study was to examine whether low serum 25-hydroxyvitamin D (25(OH)D) levels are associated with osteoporotic fractures. The study was conducted among 1311 community-dwelling older men and women of the Longitudinal Aging Study Amsterdam (LASA), an ongoing multidisciplinary cohort study. Serum 25(OH)D was determined using a competitive protein binding assay. Fractures were assessed during six years of follow-up. The data were analyzed using Cox proportional hazards model. In total, 11.3% of the persons had a serum 25(OH)D below 10 ng/ml, 48.4% had a value below 20 ng/ml, and 82.4% had a value below 30 ng/ml. Furthermore, 115 persons (8.5%) had one or more osteoporotic fractures. Different cut points of serum 25(OH)D were examined with a cut point of 12 ng/ml giving the best discrimination between persons with and without fractures (17.5% of the persons fell below this cut point). The lowest percentage of fractures (5.6%) was found above 30 ng/ml. Because an interaction effect with age was found (p=0.04), further analyses were conducted separately for persons aged 65-75 years (n=656) and for persons aged 75-89 years (n=664) at baseline. After adjustment for age, sex, season of blood collection, body mass index, number of chronic diseases, serum creatinine, cognition, smoking and alcohol use, serum 25(OH)D below or equal to 12 ng/ml was associated with an increased fracture risk in the youngest age group (HR=3.1; 95% CI: 1.4-6.9), but not in the oldest age group (HR=1.3; 95% CI: 0.7-2.2). For commonly used cut points of serum 25(OH)D (<10 ng/ml, 10-19.9 ng/ml, 20-29.9 ng/ml, > or =30 ng/ml), no statistically significant associations were found after adjustment for confounding. Serum 25(OH)D levels below or equal to 12 ng/ml were associated with an increased fracture risk in persons aged 65-75 years. The relatively low cut point of serum 25(OH)D in our population is possibly caused by high calcium intake in the Netherlands.


Measurement of occlusal forces in the therapy of functional disorders with the use of botulinum toxin type A.
Functional disorders of the stomatognathic system include dysfunctions leading to pathological increase of the occlusal forces generated by mandibular adductors. High values of these forces are the cause of numerous disorders within the masticatory organ such as pathological abrasion of the teeth, tension headaches and pain in the region of the temporomandibular joints. The aim of this study was assessment of occlusal forces in the course of the therapy of painful types of functional disorders with the use of botulinum toxin type A - the drug causing muscle relaxation. The material for the study comprised adult patients aged 24-42 years who presented with a painful type of functional disorders in the University Hospital, Institute of Dentistry Jagiellonian University Medical College in Cracow. The patients were qualified to the study on the basis of the results of specialist functional examination of the masticatory organ in which additionally the VAS (Visual Analogue Scale) was used for pain assessment of the masseters and temporomandibular joints. The measurement of maximal occlusal forces in the examined patients was carried out in all patients in the region of the central incisors and first molars on the both side with the use of a special measuring instrument for dental examination, specially constructed (patent number P 334933). The examinations were performed before the beginning of the treatment, 10 days and 16 weeks after intramuscular administration of botulinum toxin type A at a dosage of 21 mouse units - U for one masseter. The results of the examination of maximal occlusal forces obtained in the first examination, that is, before the beginning of the treatment, markedly exceeded the physiological values. In the control examinations, significant, persistent decrease of the studied forces has been noted.


Advances in understanding the pathogenesis of primary familial and congenital polycythaemia.
Primary familial and congenital polycythemia (PFCP) is an autosomal-dominant proliferative disorder characterized by erythrocytosis and hypersensitivity of erythroid progenitors to erythropoietin (Epo). Several lines of evidence suggest a causal role of truncated erythropoietin receptor (EpoR) in this disease. In this review, we discuss PFCP in the context of erythrocytosis and EpoR signalling. We focus on recent studies describing mechanisms underlying Epo-dependent EpoR down-regulation. One mechanism depends on internalization mediated through the p85 regulatory subunit of the Phosphoinositide 3-Kinase, and the other utilizes ubiquitin-based proteasomal degradation. Truncated PFCP EpoRs are not properly down-regulated upon stimulation, underscoring the importance of these mechanisms in the pathogenesis of PFCP.


Effects of volume-controlled equal ratio ventilation with recruitment maneuver and positive end-expiratory pressure in laparoscopic sleeve gastrectomy: a prospective, randomized, controlled trial
We compared the effects of volume-controlled equal ratio ventilation (VC-ERV) and volume-controlled conventional ratio ventilation (VC-CRV) on oxygenation, ventilation, respiratory mechanics, and hemodynamic status during mechanical ventilation with recruitment maneuver (RM) and positive end-expiratory pressure (PEEP) in patients undergoing laparoscopic sleeve gastrectomy. A total of 111 patients scheduled for laparoscopic sleeve gastrectomy were randomized to ventilation with inspiratory to expiratory ratio of 1:1 (Group VC-ERV) or 1:2 (Group VC-CRV) following tracheal intubation. RM (40 cmH2O, 15 s) and PEEP (10 cmH2O) were administered to all patients. Arterial blood gas samples were taken and peak airway pressure (Ppeak), mean airway pressure (Pmean), dynamic compliance (Cdyn), mean arterial pressure, heart rate, SpO2, and EtCO2 were recorded at 4 time points. Postoperative respiratory complications were recorded. Oxygenation, ventilation, Pmean levels, and hemodynamic variables were similar in both groups. VC-ERV significantly decreased Ppeak and increased Cdyn compared to VC-CRV at all time points of the operation (P < 0.05). No pulmonary complication was observed in any patients. VC-ERV provides significantly lower Ppeak and higher Cdyn with similar oxygenation, ventilation, hemodynamic parameters, and Pmean levels when compared to VC-CRV during mechanical ventilation with RM and PEEP in laparoscopic sleeve gastrectomy.


A finite mixture distribution model for data collected from twins.
Most analyses of data collected from a classical twin study of monozygotic (MZ) and dizygotic (DZ) twins assume that zygosity has been diagnosed without error. However, large scale surveys frequently resort to questionnaire-based methods of diagnosis which classify twins as MZ or DZ with less than perfect accuracy. This article describes a mixture distribution approach to the analysis of twin data when zygosity is not perfectly diagnosed. Estimates of diagnostic accuracy are used to weight the likelihood of the data according to the probability that any given pair is either MZ or DZ. The performance of this method is compared to fully accurate diagnosis, and to the analysis of samples that include some misclassified pairs. Conventional analysis of samples containing misclassified pairs yields biased estimates of variance components, such that additive genetic variance (A) is underestimated while common environment (C) and specific environment (E) components are overestimated. The bias is non-trivial; for 10% misclassification, true values of Additive genetic: Common environment: Specific Environment variance components of.6:.2:.2 are estimated as.48:.29:.23, respectively. The mixture distribution yields unbiased estimates, while showing relatively little loss of statistical precision for misclassification rates of 15% or less. The method is shown to perform quite well even when no information on zygosity is available, and may be applied when pair-specific estimates of zygosity probabilities are available.


The Influence of BRAF and KRAS Mutation Status on the Association between Aspirin Use and Survival after Colon Cancer Diagnosis.
Use of aspirin after diagnosis of colon cancer has been associated with improved survival. Identification of cancer subtypes that respond to aspirin treatment may help develop personalized treatment regimens. The aim of this study was to investigate the influence of BRAF and KRAS mutation status on the association between aspirin use and overall survival after colon cancer diagnosis. A random selection of 599 patients with colon cancer were analyzed, selected from the Eindhoven Cancer Registry, and BRAF and KRAS mutation status was determined. Data on aspirin use (80 mg) were obtained from the PHARMO Database Network. Parametric survival models with exponential (Poisson) distribution were used. Aspirin use after colon cancer diagnosis was associated with improved overall survival in wild-type BRAF tumors, adjusted rate ratio (RR) of 0.60 (95% CI 0.44-0.83). In contrast, aspirin use in BRAF mutated tumors was not associated with an improved survival (RR 1.11, 95% CI 0.57-2.16). P-value for interaction was non-significant. KRAS mutational status did not differentiate in the association between aspirin use and survival. Low-dose aspirin use after colon cancer diagnosis was associated with improved survival in BRAF wild-type tumors only. However, the large confidence interval of the rate ratio for the use of aspirin in patients with BRAF mutation does not rule out a possible benefit. These results preclude BRAF and KRAS mutation status to be used as a marker for individualized treatment with aspirin, if aspirin becomes regular adjuvant treatment for colon cancer patients in the future.


Chronic obstructive uropathy in severe combined immunodeficient (SCID) mice: lymphocyte infiltration is not required for progressive tubulointerstitial injury.
Progressive renal injury in humans and experimental animal models is characterized by tubular atrophy, infiltration of mononuclear inflammatory cells, and interstitial fibrosis. Permanent unilateral ureter ligation represents a reproducible model for investigating mechanisms of progressive kidney injury, and in the rat is characterized by tubular epithelial cell proliferation followed by apoptosis and progressive infiltration of monocytes and lymphocytes. Nevertheless, whether monocytes or lymphocytes play a dominant role in causing tubulointerstitial damage remains to be elucidated. In the current study, a model of chronic obstructive uropathy in the mouse is established and the role of lymphocyte infiltration in the evolution of the tubule and interstitial alterations is investigated. Permanent ligation of the left ureter in wild-type (C3H/HeJ) mice resulted in progressive atrophy of tubules and interstitial fibrosis compared with the contralateral kidney over a 30-d period. Immunoperoxidase studies on frozen sections taken from kidneys at 0, 3, 10, 20, and 30 d after ureter ligation showed that the tubulointerstitial injury was accompanied by a marked and progressive increase in interstitial macrophages and T lymphocytes, with no appreciable increase in B lymphocytes. No increase in inflammatory cells was detected in contralateral kidneys over the same time frame. The significance of T lymphocyte infiltration was examined by comparing the degree of tubular atrophy and interstitial fibrosis and the nature and quantity of the inflammatory infiltrate in wild-type mice and C3HSMn.C-Scid/J (SCID) mice subjected to permanent left ureter ligation. SCID mice have genetic defects in immunoglobulin and T cell receptor gene rearrangements and are devoid of circulating mature B and T lymphocytes. Wild-type and SCID mice developed tubular atrophy and interstitial volume expansion in the ligated kidney to the same degree and at the same rate. SCID mice developed a prominent and marked monocyte/macrophage infiltrate in the ligated kidney, which was essentially equal to that in wild-type mice. In contrast, consistent with the known absence of mature lymphocytes in SCID mice, there was essentially no T lymphocyte infiltration into the ligated kidney of SCID mice. These results demonstrate the effective establishment of the model of maintained unilateral ureter ligation in mice, which is readily applicable to genetic mutant strains thus allowing for specific investigation of the role of individual components of the inflammatory response in progressive tubulointerstitial injury. These studies further demonstrate that lymphocyte infiltration is not required for progressive tubular atrophy and increased interstitial fibrosis after maintained unilateral ureter ligation.


Feline immunodeficiency syndrome--a comparison between feline T-lymphotropic lentivirus and feline leukemia virus.
A feline T-lymphotrophic lentvirus (FTLV) has recently been isolated from a domestic cat free of feline leukemia virus (FeLV). This virus is distinct from FeLV (an oncornavirus), although they share a common denominator, namely, the ability to cause immunosuppression and induce lymphadenopathy and anemia. Their differences can be revealed by examining the following: the metal requirement for reverse transcriptase activity, the antigenic comparison by Western blot analysis, the different susceptibilities of a variety of feline cells, and the morphology based on electron microscopy. In the serological survey of 1,612 cats surveyed in the USA, 232 (14.4%) were seropositive for antibodies to FTLV, which was lower than for the 42 Canadian cats surveyed of which 8 (19%) were seropositive. Of the 61 cats positive for FeLV, 15 (25%) were also positive for FTLV, giving the impression that coinfection between these two retroviruses plays an important role in the cliniocpathological signs of what was previously thought to be solely an FeLV syndrome.


Early pregnancy metabolite profiling discovers a potential biomarker for the subsequent development of gestational diabetes mellitus.
Current early pregnancy screening tools to identify women at risk of developing gestational diabetes mellitus lack both specificity and sensitivity. As a result, the foetus and mother are often subjected to insult during disease progression, prior to diagnosis and treatment in later pregnancy. Metabolomics is an analytical approach, which allows for appraisal of small molecular mass compounds in a biofluid. The aim of this pilot study was to investigate the relationship between the early gestation serum metabolite profile and the subsequent development of gestational diabetes mellitus in the search for early pregnancy biomarkers and potential metabolic mechanisms. Our nested case-control study analysed maternal serum at 20 weeks' gestation, obtained from the New Zealand cohort of the Screening for Pregnancy Endpoints study. Metabolomic profiling was performed using gas chromatography coupled to mass spectrometry, and metabolites were identified using R software and an in-house mass spectral library. Statistical analysis was performed using SPSS version 21.0. Forty-eight metabolites were identified in the serum samples. Itaconic acid (P = 0.0003), with a false discovery rate of 0.012, was found to be significantly more abundant in women who subsequently developed gestational diabetes mellitus, when compared to controls with uncomplicated pregnancies. The current pilot study found that itaconic acid may have potential as a novel biomarker in early pregnancy to predict the subsequent development of gestational diabetes mellitus. However, the findings from this pilot study require validation with a larger, diverse population before translation into the clinical setting.


Structural and functional analysis of domains mediating interaction between the bagpipe homologue, Nkx3.1 and serum response factor.
Nkx3.1 is a member of the NK2 class of homeodomain proteins and is expressed in development, being an early marker of the sclerotome and prostate gland. It has been shown to be a critical factor for prostate differentiation and function. Previous studies suggested that Nkx3.1 interacts with Serum Response Factor (SRF) to transactivate the Smooth Muscle gamma-Actin (SMGA) promoter. In studies presented here, we examined the molecular mechanisms underlying the functional synergy of these factors upon SMGA transcription. We demonstrate that full length Nkx3.1 physically interacts with SRF in the absence of DNA and that these factors are able to co-associate in cellular context using a mammalian two-hybrid system. The segment of SRF responsible for Nkx3.1 interaction was mapped to a approximately 30 amino acid region (AAs 142-171) at the N-terminal segment of the MADS box. Two separate regions of Nkx3.1 were found to mediate interactions with SRF. Interestingly, recognized domains of NK2 proteins, namely the TN, homeodomain DNA binding segment, and the NK2-SD do not participate in SRF interactions. One of the Nkx3.1 SRF binding domains was mapped to the N-terminal of the protein consistent with recent studies of these proteins using NMR spectroscopy by Gelmann and colleagues (1). A second SRF binding region was mapped to amino acids C-terminal to the homeodomain. Structural predictions indicate that both of the SRF interacting segments are largely hydrophobic in character and beta-strand in structure. With co-transfection transcriptional analyses we found that interaction between SRF and Nkx3.1 as well as DNA binding by both factors was required for the observed transcriptional synergy. Thus our studies have identified novel protein-protein interacting domains within Nkx3.1 and SRF that operate in concert with their respective DNA binding domains to mediate functional transcriptional synergy of these factors to regulate SMGA gene activation.


The Effect of Music on Auditory Hallucination and Quality of Life in Schizophrenic Patients: A Randomised Controlled Trial.
The study was conducted to determine the effects of music on auditory hallucination and quality of life in schizophrenic patients. The sample of this randomised controlled study consisted of 28 patients (14 experimental and 14 control groups) hospitalised with a diagnosis of schizophrenia (DSM-IV) and auditory hallucination. The study data were collected with the Information Form, The Scale for the Assessment of Positive Symptoms (SAPS), Characteristics of Auditory Hallucinations Questionnaire, and The World Health Organization Quality of Life Scale (WHOQOL-BREF). The hallucination, positive formal thought, and total SAPS scores of the patients in the experimental group obtained during their hospitalisation were determined to be higher than those obtained at discharge and at follow-ups after discharge. The characteristics of auditory hallucination questionnaire scores of the patients in the experimental and control groups decreased. The physical, mental, environmental, and national environmental domain scores of the quality of life in the experimental group increased at sixth month after discharge. Listening to music had positive effects on positive symptoms and the quality of life of patients with auditory hallucination. In line with these results, listening to music may be recommended to cope with auditory hallucinations and to provide positive quality of life.


Serum oncoproteins and growth factors in asbestosis and silicosis patients.
Levels of 9 different oncoproteins and growth factors were assayed by immunoblotting with monoclonal antibodies in 91 serum samples collected between March 1983 and August 1987 from 46 pneumoconiosis patients (36 asbestosis, 10 silicosis) at high risk for the development of cancer. Follow-up of these patients through June 1991 showed that 18 had developed cancer (11 lung, 2 pleural mesothelioma, 2 transitional-cell carcinomas of the urinary bladder, 1 osteosarcoma, 1 non-Hodgkin's lymphoma, 1 adenocarcinoma of the gallbladder). Increased serum levels of ras oncogene-related protein (p21) were found in 7 of the 18 patients who developed cancer (5 lung, 2 pleural mesothelioma) versus 2 of the 28 patients without cancer, a statistically significant difference (p = 0.012). In addition, 6 of the 7 p21-positive cancer cases had positive serum samples prior to clinical diagnosis of disease (average = 16.3 months, range = 3-26 months prior to diagnosis), suggesting that elevated serum p21 levels may be a useful marker for earlier detection in a significant percentage of respiratory malignancies. Finally, elevated serum levels of PDGF-related protein were detected significantly more frequently in advanced pneumoconiosis cases (ILO radiographic classification of 2/1 or greater) than in less advanced cases (80% vs. 41.9%; p = 0.016), and there was a tendency for these PDGF-positive patients to have progression of their disease (68.2% vs. 41.7%; p = 0.065), suggesting that elevated serum PDGF levels may be a marker for the development of severe and progressive pneumoconioses.


Family intervention for schizophrenia.
It has been showed that people with schizophrenia from families that express high levels of criticism, hostility, or over involvement, have more frequent relapses than people with similar problems from families that tend to be less expressive of their emotions. Psychosocial interventions designed to reduce these levels of expressed emotions within families now exist for mental health workers. These interventions are proposed as adjuncts rather than alternatives to drug treatments, and their main purpose is to decrease the stress within the family and also the rate of relapse. To estimate the effects of family psychosocial interventions in community settings for the care of those with schizophrenia or schizophrenia-like conditions compared to standard care. Electronic searches of the Cochrane Library (Issue 2, 1998), the Cochrane Schizophrenia Group's Register (June 1998), EMBASE (1981-1995) and MEDLINE (1966-1995) were undertaken and supplemented with reference searching of the identified literature. Randomised or quasi-randomised studies were selected if they focused on families of people with schizophrenia or schizoaffective disorder and compared community-orientated family-based psychosocial intervention of more than five sessions to standard care. Data were reliably extracted, and, where appropriate and possible, summated. Peto odds ratios (OR), their 95% confidence intervals (CI) and number needed to treat (NNT) were estimated. The reviewers assume that people who died or dropped out had no improvement and tested the sensitivity of the final results to this assumption. Family intervention may decrease the frequency of relapse (one year OR 0.57 CI 0.4-0.8, NNT 6.5 CI 4-14). The trend over time of this main finding is towards the null and some small but negative studies may not have been identified by the search. Family intervention may decrease hospitalisation and encourage compliance with medication but data are few and equivocal. Family intervention does not obviously effect the tendency of individuals/families to drop out of care. It may improve general social impairment and the levels of expressed emotion within the family. This review provides no data to suggest that family intervention either prevents or promotes suicide. Clinicians, researchers, policy makers and recipients of care cannot be confident of the effects of family intervention from the findings of this review. Further data from already completed trials could greatly inform practice and more trials are justified as long as their participants, interventions and outcomes are generalisable to routine care.


Exploring the role of 2-chloro-6-fluoro substitution in 2-alkylthio-6-benzyl-5-alkylpyrimidin-4(3H)-ones: effects in HIV-1-infected cells and in HIV-1 reverse transcriptase enzymes.
A comparison of the effects of the 6-(2-chloro-6-fluorobenzyl)-2-(alkylthio)pyrimidin-4(3H)-ones (2-Cl-6-F-S-DABOs) 7-12 and the related 6-(2,6-difluorobenzyl) counterparts 13-15 in HIV-1 infected cells and in the HIV-1 reverse transcriptase (RT) assays is here described. The new 2-Cl-6-F-S-DABOs showed up to picomolar activity against wt HIV-1. Against clinically relevant HIV-1 mutants and in enzyme assays, the simultaneous C5(methyl)/C6(methyl/ethyl) substitution in the 2-Cl-6-F- and 2,6-F2-benzyl series furnished compounds with the highest, wide-spectrum inhibitory activity against HIV-1. Three representative 2-Cl-6-F-S-DABOs carrying two (9c, 10c) or one (10a) stereogenic centers were resolved into their individual stereoisomers and showed a significant diastereo- and enantioselectivity in HIV-1 inhibition, the highest antiviral activity well correlating with the R absolute configuration to the stereogenic center of the C6-benzylic position in both cellular and enzymatic tests. Application of previously reported COMBINEr protocol on 9c and 10c confirmed the influence of the stereogenic centers on their binding modes in the HIV-1 RT.


Involvement of the epithelial sodium channel in initiation of mechanically evoked swallows in anaesthetized rats.
Afferents carried by the superior laryngeal nerve play a primary role in the initiation of laryngeal mechanically evoked swallows in anaesthetized rats. Amiloride and its analogues inhibit swallowing evoked by mechanical stimulation, but not swallowing evoked by chemical and electrical stimulation. The epithelial sodium channel is probably involved in the initiation of laryngeal mechanically evoked swallows. The swallowing reflex plays a critical role in airway protection. Because impaired laryngeal mechanosensation is associated with food bolus aspiration, it is important to know how the laryngeal sensory system regulates swallowing initiation. This study was performed to clarify the neuronal mechanism of mechanically evoked swallows. Urethane-anaesthetized Sprague-Dawley male rats were used. A swallow was identified by activation of the suprahyoid and thyrohyoid muscles on electromyography. The swallowing threshold was measured by von Frey filament and electrical stimulation of the larynx. The number of swallows induced by upper airway distension and capsaicin application (0.03 nmol, 3 μl) to the vocal folds was counted. The effects of topical application (0.3-30 nmol, 3 μl) of the epithelial sodium channel (ENaC) blocker amiloride and its analogues (benzamil and dimethylamiloride), acid-sensing ion channel (ASIC) inhibitors (mambalgine-1 and diminazene) and gadolinium to the laryngeal mucosa on swallowing initiation were evaluated. A nerve transection study indicated that afferents carried by the superior laryngeal nerve play a primary role in the initiation of laryngeal mechanically evoked swallows. The mechanical threshold of swallowing was increased in a dose-dependent manner by amiloride and its analogues and gadolinium, but not by ASIC inhibitors. The number of swallows by upper airway distension was significantly decreased by benzamil application. However, the initiation of swallows evoked by capsaicin and electrical stimulation was not affected by benzamil application. We speculate that the ENaC is involved in the initiation of laryngeal mechanically evoked swallows.


The impact of racial identity, ethnic identity, asian values and race-related stress on Asian Americans and Asian international college students' psychological well-being.
The current study investigated the direct and moderating effects of racial identity, ethnic identity, Asian values, and race-related stress on positive psychological well-being among 402 Asian American and Asian international college students. Results revealed that the racial identity statuses Internalization, Immersion-Emersion, Dissonance, Asian values and Ethnic Identity Affirmation and Belonging were significant predictors of well-being. Asian values, Dissonance and Conformity were found to moderate the relationship between race-related stress on well-being. Specifically, individuals in low race-related stress conditions who had low Asian values, high Conformity and low Dissonance attitudes started high on well being but decreased as race-related stress increased. These findings underscore the importance of how racial identity statuses, Asian values and ethnic identity jointly and uniquely explain and moderate the effects of race-related stress on positive well-being. Implications for future research and clinical practice are discussed.


Sex Differences in the Association of Diabetes With Cardiovascular Disease Outcomes Among African-American and White Participants in the Atherosclerosis Risk in Communities Study.
A sex × diabetes interaction in cardiovascular disease (CVD) has been established among white persons; however, it is unknown whether this interaction occurs among African Americans. We hypothesized that there was a multiplicative sex × diabetes interaction for CVD among African Americans participating in the Atherosclerosis Risk in Communities Study (1987-2013). Race-specific Cox models were run in three stages: Stage 1 examined baseline diabetes status; stage 2 examined baseline diabetes status with the competing risk of non-CVD death; and stage 3 examined time-varying diabetes status with a competing risk of non-CVD death. There were 1,073 incident CVD events among 3,767 African Americans and 2,475 among 10,291 white persons. Among African Americans, in stage 1 analysis, the hazard ratio for women with diabetes was 2.3 (95% confidence interval (CI): 2.0, 2.7) compared with women without diabetes after adjustment for age, and the corresponding hazard ratio for men was 1.8 (95% CI: 1.5, 2.1) (P for interaction = 0.014). After full adjustment, the diabetes hazard ratio was attenuated to 2.0 (95% CI: 1.8, 2.3) among women and remained 1.8 (95% CI: 1.5, 2.1) for men (P for interaction = 0.058). A synergistic influence on CVD risk between being a black woman and having diabetes was consistent across stage 2 and stage 3 analyses, with marginally significant interaction, mirroring sex differences seen in whites.


Network-based prediction of human tissue-specific metabolism.
Direct in vivo investigation of mammalian metabolism is complicated by the distinct metabolic functions of different tissues. We present a computational method that successfully describes the tissue specificity of human metabolism on a large scale. By integrating tissue-specific gene- and protein-expression data with an existing comprehensive reconstruction of the global human metabolic network, we predict tissue-specific metabolic activity in ten human tissues. This reveals a central role for post-transcriptional regulation in shaping tissue-specific metabolic activity profiles. The predicted tissue specificity of genes responsible for metabolic diseases and tissue-specific differences in metabolite exchange with biofluids extend markedly beyond tissue-specific differences manifest in enzyme-expression data, and are validated by large-scale mining of tissue-specificity data. Our results establish a computational basis for the genome-wide study of normal and abnormal human metabolism in a tissue-specific manner.


Repeated visual hallucinations in Parkinson's disease as disturbed external/internal perceptions: focused review and a new integrative model.
Visual hallucinations (VH) in Parkinson's disease (PD) are a chronic complication in 30 to 60% of treated patients and have a multifaceted phenomenology. Flickering, faultive impressions, and illusionary misperceptions precede the core syndrome of stereotyped, colorful images. The patient variably recognizes these images as hallucinations, being rarely irritated or frightened and more often amused as a bystander. Although studies on VH in PD focus on several research domains, no comprehensive, unified theory has been developed to study their pathophysiology. We have adapted Hobson's work on the states of consciousness and propose a model integrating seemingly disparate data on VH. We suggest that VH should be considered as a dysregulation of the gating and filtering of external perception and internal image production. Contributive elements and anatomical links for the model include poor primary vision, reduced activation of primary visual cortex, aberrant activation of associative visual and frontal cortex, lack of suppression or spontaneous emergence of internally generated imagery through the ponto-geniculo-occipital system, intrusion of rapid eye movement dreaming imagery into wakefulness, errative changes of the brainstem filtering capacities through fluctuating vigilance, and medication-related overactivation of mesolimbic systems. Different etiologies likely produce different phenomenologies and the prognosis may not be uniform. This new conceptual framework permits an anatomical view of VH and suggests new, testable hypotheses regarding their pathophysiology and therapy.


Keratinocytes exposed to ultraviolet radiation reveal three down-regulated genes with potential function in differentiation and cell cycle control.
The incidence of skin cancer is increasing in epidemic proportion. Although solar UV radiation is known to be the major risk factor, much information is lacking about the molecular mechanisms leading to skin cancer. To gain a deeper insight into these mechanisms, we have examined cells of a human keratinocyte cell line (HaCat) after exposure to 0.16 minimal erythema doses of UVB radiation. This dose led to an S-phase delay that was reversible 22 h postirradiation. To examine gene expression 10 h after UV irradiation, a nonradioactive differential display was employed. Three genes were identified as being down-regulated significantly. The first encodes for topoisomerase-IIbeta-binding protein 1 (expression level 5% 6 h after irradiation). This protein is associated with human topoisomerase IIbeta and appears to be necessary for DNA replication during the onset of S phase. The second gene product has previously been reported to be involved in differentiation and is therefore known as differentiation-dependent A4 protein (28% 8 h after irradiation). The third gene is XPO1 (also known as CRM1) (5% 8 h after irradiation), whose protein is involved in nuclear export of mRNA molecules. Differential expression of these genes after UV irradiation has not been reported. Because of their potential involvement in cell cycle control and differentiation, these proteins could be important for understanding the reaction of keratinocytes after exposure to UV radiation.


[OPERa Study].
On the whole, most European and international guidelines recommend prophylactic use of granulocyte-colony stimulating factors (G-CSFs) when the risk of chemotherapy-induced febrile neutropenia (FN) in cancer patients exceeds 20%. In patients treated with intermediate-risk chemotherapy regimens the recent EORTC guidelines recommend to consider supplementary patient-related adverse risk factors such as elderly age ( 65 years) prior to administrating each cycle of chemotherapy. The primary objective of our study is to describe the most important FN risk factors that underlie the use of pegfilgrastim PP in daily practice in the Czech Republic; secon-dary endpoints include FN incidence, chemotherapy dose intensity, anti-infective agents admini-stration, hospitalization length and safety of chemotherapy regimens. This prospective, multicenter, non-interventional study enrolled patients receiving a chemotherapy with high FN risk ( 20% according to EORTC guidelines) based on investigators` assessment. Data were collected on a total of 333 patients treated for breast cancer (69%), lymphoma (20%), ovarian (5%), lung (4%) and testicular cancer (1%). The most frequent indications for G-CSF prophylaxis were myelotoxic chemotherapy regimen (96%), elderly age (36%), advanced stage disease (35%), female gender (30%), cancer type (15%) and previous FN episode (12%). The overall FN incidence was 3% in patients receiving primary pegfilgrastim prophylaxis (n = 210) and 12% in patients with no pegfilgrastim PP (n = 123). The myelotoxicity of a chemotherapeutic regimen was the most significant FN risk factor identified by the inquired physicians. The second most compelling FN risk factor was elderly age and advanced stage disease. FN incidence in patients who received pegfilgrastim PP was relatively low in comparison to the commonly expected FN incidence in a population of patients receiving a chemotherapy regimen with high risk of FN.


Location-based prediction model for Crohn's disease regarding a novel serological marker, anti-chitinase 3-like 1 autoantibodies.
Defective neutrophil regulation in inflammatory bowel disease (IBD) is thought to play an important role in the onset or manifestation of IBD, as it could lead to damage of the intestinal mucosal barrier by the infiltration of neutrophils in the inflamed mucosa and the accumulation of pathogens. Like neutrophils in the context of innate immune responses, immunoglobulin A (IgA) as an acquired immune response partakes in the defense of the intestinal epithelium. Under normal conditions, IgA contributes to the elimination of microbes, but in connection with the loss of tolerance to chitinase 3-like 1 (CHI3L1) in IBD, IgA could participate in CHI3L1-mediated improved adhesion and invasion of potentially pathogenic microorganisms. The tolerance brake to CHI3L1 and the occurrence of IgA autoantibodies to this particular target, the exact role and underlying mechanisms of CHI3L1 in the pathogenesis of IBD are still unclear. To determine the predictive potential of Ig subtypes of a novel serological marker, anti-CHI3L1 autoantibodies (aCHI3L1) in determining the disease phenotype, therapeutic strategy and long-term disease course in a prospective referral cohort of adult IBD patients. Sera of 257 Crohn's disease (CD) and 180 ulcerative colitis (UC) patients from a tertiary IBD referral center of Hungary (Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen) were assayed for IgG, IgA, and secretory IgA (sIgA) type aCHI3L1 by enzyme-linked immunosorbent assay using recombinant CHI3L1, along with 86 healthy controls (HCONT). The IgA type was more prevalent in CD than in UC (29.2% vs 11.1%) or HCONT (2.83%; P < 0.0001 for both). However, sIgA subtype aCHI3L1 positivity was higher in both CD and UC patients than in HCONT (39.3% and 32.8% vs 4.65%, respectively; P < 0.0001). The presence of both IgA and sIgA aCHI3L1 antibodies was associated with colonic involvement (P < 0.0001 and P = 0.038, respectively) in patients with CD. Complicated disease behavior at sample procurement was associated with aCHI3L1 sIgA positivity (57.1% vs 36.0%, P = 0.009). IgA type aCH3L1 was more prevalent in patients with frequent relapse during the disease course in the CD group (46.9% vs 25.7%, P = 0.005). In a group of patients with concomitant presence of pure inflammatory luminal disease and colon involvement at the time of diagnosis, positivity for IgA or sIgA type aCH3L1 predicted faster progression towards a complicated disease course in time-dependent models. This association disappeared after merging subgroups of different disease locations. CHI3L1 is a novel neutrophil autoantigenic target in IBD. The consideration of antibody classes along with location-based prediction may transform the future of serology in IBD.


A septate uterus with double cervix during two pregnancies: pregnancy outcome before and after cervix sparing metroplasty. A case report.
In this case report we present a patient with different pregnancy outcomes after IVF treatments. After an extremely premature delivery in her first pregnancy, a vaginal 3D ultrasound scan revealed a correct diagnosis for her uterine anomaly: A complete uterine septum, double cervix and non-obstructive longitudinal vaginal septum, classified as U2bC2V1 according to the European Society of Human Reproduction and EmbryologyEuropean Society for Gynaecological Endoscopy (ESHRE-ESGE)-classification. She underwent a cervix sparing metroplasty and had a spontaneous vaginal birth at 41+2 weeks gesttation. For patients with otherwise unexplained infertility or earlier premature delivery, a diagnostic workup, oriented to the research of uterine malformations, should be taken into consideration.


[Malignant external otitis caused by Pseudomonas aeruginosa. Report of 3 cases].
The cases of three patients aged over sixty, diabetic for a long time and having clinical, otological, neurological and microbiological findings of malignant external otitis by Pseudomonas aeruginosa are registered. The first patient, a 62 years old woman, had important neurological alterations, such as proven P. aeruginosa meningitis and involvement of the 6th, 7th, 8th, 9th and 10th left cranial nerves. Although mortality and morbidity rates of cases with these characteristics are reported to be high, this patient survived. The second was a 64 years old male with the classical complaints of this condition consisting of persistent and intensive ear pain, serous purulent discharge and an emerging tumourous lesion in the left external ear canal. Good results were obtained with the surgical treatment administered along with an antimicrobial plan which remained incomplete because the patient has requested his discharge from the hospital. In less than one month, he was again hospitalized already presenting neurological manifestations (paralysis of the 6th cranial nerve) following a fatal course in a few days. The third was also a male patient, 70 years old, whose initial complaints occurred after a month a butterfly penetrated his right ear during his sleep. In spite of the presence of neurological troubles (facial paralysis and stupor) he survived with a prolonged antibiotic therapy. After a literature revision on this pathology, considerations are made concerning its pathogeny, clinical findings, diagnosis, therapy and prognosis.


Predictability of urodynamic findings based on the Urogenital Distress Inventory-6 questionnaire.
The Urogenital Distress Inventory (UDI-6) is a validated 6-item questionnaire that assesses lower urinary tract symptoms, including incontinence, in women. Similar indexes developed in men to evaluate symptoms of benign prostatic hyperplasia have failed to show a relationship with urodynamic (UD) parameters indicating bladder outlet obstruction (BOO). In this study, we sought to determine whether UDI-6 responses could predict information obtained during UD evaluations. All women referred to our clinic with lower urinary tract complaints who completed a UDI-6 questionnaire and subsequently underwent UD evaluation were included (n = 128). UD findings used for analysis included Valsalva leak point pressure (VLPP), maximum flow rate (Qmax), and detrusor pressure at Qmax (PdetQmax). BOO was defined as Qmax of 1 5 mL/s or less and PdetQmax of greater than 20 cm H2O; detrusor overactivity (DO) was defined as any rise in detrusor pressure associated with urge during filling. The most common chief complaints were incontinence (mixed, 26.6%; stress, 20.3%; and urge, 13.3%), urgency/frequency (14.1%), and symptomatic prolapse (10.1%). There was a moderate correlation between a positive response to question 3 (stress urinary incontinence [SUI]) and leakage with strain or cough during UD evaluation (correlation coefficient = 0.51). In fact, most patients answering that SUI was moderately or greatly bothersome were found to have stress-induced leakage during the UD evaluation (82%), which differed significantly from those who reported no bother (Fisher's exact test, P = 0.0006). Severity of leakage assessed by VLPP, however, did not correlate with the severity assessed by any question. With regard to BOO in women, most patients who answered that incomplete emptying was their most bothersome symptom had BOO (61%), and most women with a different main complaint were unobstructed (73%, P <0.002). Finally, 30 of 36 women who answered that leakage related to urgency was moderately or greatly bothersome were found to have DO, which was significantly different than the incidence of DO in women who did not report this complaint (correlation coefficient = 0.38, P <0.001). Unlike similar indexes used to assess lower urinary tract symptoms in men, specific items from the UDI-6 may provide predictive information regarding UD findings in women, particularly with regard to SUI, BOO, and DO. However, if VLPP is considered vital to planning treatment, UD studies will still be required, since no question could estimate the severity of incontinence as determined by serial VLPP measurement.


The p75 neurotrophin receptor regulates hippocampal neurogenesis and related behaviours.
Although changes to neural circuitry are believed to underlie behavioural characteristics mediated by the hippocampus, the contribution of neurogenesis to this process remains controversial. This is partially because the molecular regulators of neurogenesis remain to be fully elucidated, and experiments generically preventing neurogenesis have, for the most part, depended on paradigms involving irradiation. Here we show that mice lacking the p75 neurotrophin receptor (p75(NTR-/-)) have 25% fewer neuroblasts and 50% fewer newborn neurons in the dentate gyrus, coincident with increased rates of cell death of newly born cells and a significantly smaller granular cell layer and dentate gyrus, than those of p75(NTR+/+) mice. Whereas p75(NTR-/-) mice had increased latency to feed in a novelty-suppressed feeding paradigm they had increased mobility in another test of "depression", the tail-suspension test. p75(NTR-/-) mice also had subtle behavioural impairment in Morris water maze tasks compared to wild-type animals. No difference between genotypes was found in relation to anxiety or exploration behaviour based on the elevated-plus maze, light-dark, hole-board, T-maze or forced-swim tests. Overall, this study demonstrates that p75(NTR) is an important regulator of hippocampal neurogenesis, with concomitant effects on associated behaviours. However, the behavioural attributes of the p75(NTR-/-) mice may be better explained by altered circuitry driven by the loss of p75(NTR) in the basal forebrain, rather than direct changes to neurogenesis.


Are primary healthcare services culturally appropriate for Aboriginal people? Findings from a remote community.
This study explored the views of key stakeholders on cultural appropriateness of primary health care (PHC) services for Aboriginal people. A total of 78 participants, including healthcare providers, administrative team members (n=24, ~30% of study sample) and Aboriginal community members (n=54, ~70% of study sample) living in remote North West Queensland participated in the study. Outcome measures were assessed by administering survey questionnaires comprising qualitative questions and various subscales (e.g. provider behaviours and attitudes, communication, physical environment and facilities, and support from administrative staff). Descriptive statistics were used to present quantitative findings, whereas inductive thematic analysis was used for qualitative data. In contrast to the views of PHC providers, a significant number of Aboriginal people did not perceive that they were receiving culturally appropriate services. Although PHC providers acknowledged cultural awareness training for familiarising themselves with Aboriginal culture, they found the training to be general, superficial and lacking prospective evaluation. PHC providers should understand that culturally inappropriate clinical encounters generate mistrust and dissatisfaction. Therefore, a broad approach involving culturally respectful association between PHC providers, Aboriginal consumers and administrative staff is required to bring sustainable changes at the practice level to improve the health of Aboriginal people.


Coronary perfusion during acute myocardial infarction with a combined therapy of coronary angioplasty and high-dose intravenous streptokinase.
Two hundred and sixteen patients with acute myocardial infarction were treated with immediate infusion of high-dose (1.5 million units) intravenous streptokinase followed by emergency coronary angioplasty. The infarct lesion was crossed and dilated in 99% and persistent coronary perfusion after the procedure was achieved in 90% (including 3% with significant residual stenosis). Total in-hospital mortality was 12%. Multivariable analysis showed a higher hospital mortality with cardiogenic shock (41% vs 5% without shock), older age, lower left ventricular ejection fraction, and female sex. Final patency of the infarct-related vessel was determined by follow-up in-hospital cardiac catheterization. Coronary reocclusion occurred in 11% (symptomatic in 7%, treated with emergency angioplasty or bypass surgery; silent in 4%, treated medically). Of the surviving patients with successful initial establishment of infarct vessel patency, 94% were discharged from the hospital with an open infarct artery or a bypass graft to the infarct vessel. There was significant improvement in both ejection fraction (44% to 49%; p less than .0001) and regional wall motion in the infarct zone (-3.0 SD to -2.4 SD; p less than .0001) among patients with persistent coronary perfusion and insignificant residual stenosis at the time of the follow-up cardiac catheterization. Thus, a treatment strategy for acute myocardial infarction that includes immediate administration of streptokinase followed by emergency coronary angioplasty, and coronary bypass surgery when necessary, results in a high rate of early and sustained patency of the infarct-related vessel.


Correlation transfer function analysis as a biomarker for Alzheimer brain plasticity using longitudinal resting-state fMRI data.
Neural plasticity is the ability of the brain to alter itself functionally and structurally as a result of its experience. However, longitudinal changes in functional connectivity of the brain are still unrevealed in Alzheimer's disease (AD). This study aims to discover the significant connections (SCs) between brain regions for AD stages longitudinally using correlation transfer function (CorrTF) as a new biomarker for the disease progression. The dataset consists of: 29 normal controls (NC), and 23, 24, and 23 for early, late mild cognitive impairments (EMCI, LMCI), and ADs, respectively, along three distant visits. The brain was divided into 116 regions using the automated anatomical labeling atlas, where the intensity time series is calculated, and the CorrTF connections are extracted for each region. Finally, the standard t-test and ANOVA test were employed to investigate the SCs for each subject's visit. No SCs, along three visits, were found For NC subjects. The most SCs were mainly directed from cerebellum in case of EMCI and LMCI. Furthermore, the hippocampus connectivity increased in LMCI compared to EMCI whereas missed in AD. Additionally, the patterns of longitudinal changes among the different AD stages compared to Pearson Correlation were similar, for SMC, VC, DMN, and Cereb networks, while differed for EAN and SN networks. Our findings define how brain changes over time, which could help detect functional changes linked to each AD stage and better understand the disease behavior.


Convenient and efficient synthesis of Boc-/Z-/Fmoc-beta-amino acids employing N-protected alpha-amino acid fluorides.
A new and efficient method for the synthesis of N(alpha)-Fmoc-/Boc-/Z-beta-amino acids using the two-step Arndt-Eistert approach is described. Fmoc-/Boc-/Z-alpha-Amino acid fluorides were used for the acylation of diazomethane synthesizing Fmoc-/Boc-/Z-alpha-aminodiazoketones as crystalline solids with good yield and purity. They were then converted to the corresponding beta-amino acids using PhCOOAg/dioxane/H2O.


Cancer knowledge in the plural: queering the biopolitics of narrative and affective mobilities.
In this age of DIY Health-a present that has been described as a time of "ludic capitalism"-one is constantly confronted with the injunction to manage risk by means of making healthy choices and of informed participation in various self-surveillant technologies of bioinformatics. Neoliberal governmentality has been redacted by poststructuralist scholars of bioethics as defined by the two-fold emergence of, on the one hand, populations and on the other, the self-determining individual-as biopolitical entities. In this article, we provide a genealogical-phenomenological schematization (GPS analysis) of the narration of cancer in relation to "sexual minority populations." Canonical discourses concerning minority sexualities are articulated by means of a logic of "inclusion and reification" that organizes the interiorization of norms of embodied relationality, and a positive liaison with biomedical technologies and techniques in the taking up of a rhetorical style of biographical compliance. Neoliberal DIY Health logics conflate participation with agency, and institute norms of recognition that constrain visibility to: citizens who make healthy choices and manage risk, heroic cancer stories, stories of the reconstruction of states of normalcy, or of survival against all odds. Alternatively, we trace the performative articulations of queer narrative practices that constitute an ephemeral, nomadic praxiology-a doing of knowledge in cancer's queer narration. Queer cancer narrative practices represent a relationship to health and embodiment that is predicated, not on normalcy, but predicated on troubling norms, on artful failure, and on engaging in a kind of affective mapping that might be thought constitutive of a speculative bioethical relation to the self as other.