The parvocellular vasotocin system of Japanese quail: a developmental and adult model for the study of influences of gonadal hormones on sexually differentiated and behaviorally relevant neural circuits.

Vasotocin (VT; the antidiuretic hormone of birds) is synthesized by diencephalic magnocellular neurons projecting to the neurohypophysis. A sexually dimorphic system of VT-immunoreactive (ir) parvocellular elements has been described within the male medial preoptic nucleus (POM) and the nucleus of the stria terminalis, pars medialis (BSTm). VT-ir fibers are present in many diencephalic and extradiencephalic locations, and quantitative morphometric analyses demonstrated their sexually dimorphic distribution in regions involved in the control of different aspects of reproduction. Moreover, systemic or intracerebroventricular injections of VT markedly inhibit the expression of some aspects of male sexual behavior. In adult animals, circulating levels of testosterone (T) have a profound influence on the VT immunoreactivity within BSTm, POM, and lateral septum. Castration markedly decreases the immunoreaction, whereas T-replacement therapy restores a situation similar to the intact birds. We observed no changes in gonadectomized females treated with T. These changes parallel similar changes in male copulatory behavior (not present in castrated male quail, fully expressed in castrated, T-treated males). The restoration by T of the VT immunoreactivity in castrated male quail could be fully mimicked by a treatment with estradiol (E(2)), suggesting that the aromatization of T into E(2) may play a key limiting role in both the activation of male sexual behavior and the induction of VT synthesis. This dimorphism has an organizational nature: administration of E(2) to quail embryos (a treatment that abolishes male sexual behavior) results in a dramatic decrease of the VT immunoreactivity in sexually dimorphic regions. Conversely, the inhibition of E(2) synthesis during embryonic life (a treatment that stimulates the expression of male copulatory behavior in treated females exposed in adulthood to T) results in a malelike distribution of VT immunoreactivity. The VT parvocellular system of the Japanese quail can therefore be considered an accurate marker of the sexual differentiation of brain circuits mediating copulatory behavior and could be a very sensitive indicator of the activity of estrogenlike substances on neural circuits

Simultaneous determination of wave speed and arrival time of reflected waves using the pressure-velocity loop

This is the post print version of the article. The official published version can be found at the link below.In a previous paper we demonstrated that the linear portion of the pressure–velocity loop (PU-loop) corresponding to early systole could be used to calculate the local wave speed. In this paper we extend this work to show that determination of the time at which the PU-loop first deviates from linearity provides a convenient way to determine the arrival time of reflected waves (Tr). We also present a new technique using the PU-loop that allows for the determination of wave speed and Tr simultaneously. We measured pressure and flow in elastic tubes of different diameters, where a strong reflection site existed at known distances away form the measurement site. We also measured pressure and flow in the ascending aorta of 11 anaesthetised dogs where a strong reflection site was produced through total arterial occlusion at four different sites. Wave speed was determined from the initial slope of the PU-loop and Tr was determined using a new algorithm that detects the sampling point at which the initial linear part of the PU-loop deviates from linearity. The results of the new technique for detecting Tr were comparable to those determined using the foot-to-foot and wave intensity analysis methods. In elastic tubes Tr detected using the new algorithm was almost identical to that detected using wave intensity analysis and foot-to-foot methods with a maximum difference of 2%. Tr detected using the PU-loop in vivo highly correlated with that detected using wave intensity analysis (r 2 = 0.83, P < 0.001). We conclude that the new technique described in this paper offers a convenient and objective method for detecting Tr, and allows for the dynamic determination of wave speed and Tr, simultaneously

Absence of system xc⁻ on immune cells invading the central nervous system alleviates experimental autoimmune encephalitis

Background: Multiple sclerosis (MS) is an autoimmune demyelinating disease that affects the central nervous system (CNS), leading to neurodegeneration and chronic disability. Accumulating evidence points to a key role for neuroinflammation, oxidative stress, and excitotoxicity in this degenerative process. System x(c)- or the cystine/glutamate antiporter could tie these pathological mechanisms together: its activity is enhanced by reactive oxygen species and inflammatory stimuli, and its enhancement might lead to the release of toxic amounts of glutamate, thereby triggering excitotoxicity and neurodegeneration. Methods: Semi-quantitative Western blotting served to study protein expression of xCT, the specific subunit of system x(c)-, as well as of regulators of xCT transcription, in the normal appearing white matter (NAWM) of MS patients and in the CNS and spleen of mice exposed to experimental autoimmune encephalomyelitis (EAE), an accepted mouse model of MS. We next compared the clinical course of the EAE disease, the extent of demyelination, the infiltration of immune cells and microglial activation in xCT-knockout (xCT(-/-)) mice and irradiated mice reconstituted in xCT(-/-) bone marrow (BM), to their proper wild type (xCT(+/+)) controls. Results: xCT protein expression levels were upregulated in the NAWM of MS patients and in the brain, spinal cord, and spleen of EAE mice. The pathways involved in this upregulation in NAWM of MS patients remain unresolved. Compared to xCT(+/+) mice, xCT(-/-) mice were equally susceptible to EAE, whereas mice transplanted with xCT(-/-) BM, and as such only exhibiting loss of xCT in their immune cells, were less susceptible to EAE. In none of the above-described conditions, demyelination, microglial activation, or infiltration of immune cells were affected. Conclusions: Our findings demonstrate enhancement of xCT protein expression in MS pathology and suggest that system x(c)- on immune cells invading the CNS participates to EAE. Since a total loss of system x(c)- had no net beneficial effects, these results have important implications for targeting system x(c)- for treatment of MS

Congenital epulis of the jaw: a series of five cases and review of literature

This article describes five cases of congenital epulis, a rare and benign swelling in the mouth of a newborn, which is not widely known. We present five cases: four cases presented as single pedunculated nodules of the gingiva and in one case two nodules were present. Of all, 50% were located at the maxilla. Excision was performed in four of the five cases and in one case, spontaneous regression was awaited. No recurrence was reported. The characteristic features of congenital epulis are a pedunculated, flesh-pink coloured tumour with a predominant occurrence on the anterior maxillary alveolar ridge in a female newborn. Although the aetiology is unknown, most authors suggest a mesenchymal, rather than an odontogenic, origin. Endogenous hormonal factors might influence growth prenatally. Histological findings include granular cells with eosinophilic cytoplasm and small, eccentric nuclei. Despite the fact that the lesion can be a striking sight, spontaneous regression is possible and can be awaited. Indications for non-radical excision under local anaesthesia are severe upper airway obstruction and interference with feeding technique. In conclusion, we provide clinical and histological information about congenital epulis, so that this entity will be more easily recognised and relevant information given to parent

International Veterinary Epilepsy Task Force consensus proposal: Medical treatment of canine epilepsy in Europe

In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown considerably over the last years. Nevertheless, the same questions remain, which include, 1) when to start treatment, 2) which drug is best used initially, 3) which adjunctive AED can be advised if treatment with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors’ experience. With this paper it is aimed to provide a consensus for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible

Help-seeking behaviour for pelvic floor dysfunction in women over 55: drivers and barriers

Objective: Our aim was to identify drivers of and barriers to help-seeking behaviour of older women with pelvic floor dysfunction (PFD) living independently in Australia . Methods: Women aged =55 years were recruited to this cross-sectional study during July and August 2016. Bladder, bowel, pelvic organ prolapse (POP) and sexual dysfunction were assessed with the Australian Pelvic Floor Questionnaire (APFQ). Drivers and barriers were based on the Barriers to Incontinence Care Seeking Questionnaire. Univariate analyses were used to assess any significant relationships between PFD, age, education level, self-reported PFD, barriers and drivers. Results: Of the 376 study participants [mean, standard deviation (SD) age 68.6 (10.5) years], 67% reported symptoms of PFD and 98.7% scored &gt; 0 on the APFQ. Women were more likely to seek help if they scored higher on the APFQ (p &lt; 0.001). The main barrier to seeking help was the perception that PFD was a normal part of ageing (22.4%). Of those who did seek help (50%), the main factor was increased level of symptom bother (51.4%). There was no difference in age or education level between women who did and did not seek help. Conclusion: Women are more likely to seek help for PFD if scoring higher on the APFQ or symptoms are becoming more bothersome. They are less likely to seek help if they view their symptoms as normal. Future direction should be taken to raise awareness of normal pelvic floor function as well as the availability of help for PFD

Safety of bazedoxifene in a randomized, double-blind, placebo- and active-controlled phase 3 study of postmenopausal women with osteoporosis

Background. We report the safety findings from a 3-year phase 3 study (NCT00205777) of bazedoxifene, a novel selective estrogen receptor modulator under development for the prevention and treatment of postmenopausal osteoporosis. Methods. Healthy postmenopausal osteoporotic women (N = 7,492; mean age, 66.4 years) were randomized to daily doses of bazedoxifene 20 or 40 mg, raloxifene 60 mg, or placebo for 3 years. Safety and tolerability were assessed by adverse event (AE) reporting and routine physical, gynecologic, and breast examination. Results. Overall, the incidence of AEs, serious AEs, and discontinuations due to AEs in the bazedoxifene groups was not different from that seen in the placebo group. The incidence of hot flushes and leg cramps was higher with bazedoxifene or raloxifene compared with placebo. The rates of cardiac disorders and cerebrovascular events were low and evenly distributed among groups. Venous thromboembolic events, primarily deep vein thromboses, were more frequently reported in the active treatment groups compared with the placebo group; rates were similar with bazedoxifene and raloxifene. Bazedoxifene showed a neutral effect on the breast and an excellent endometrial safety profile. The incidence of fibrocystic breast disease was lower with bazedoxifene 20 and 40 mg versus raloxifene or placebo. Reductions in total and low-density lipoprotein levels and increases in high-density lipoprotein levels were seen with bazedoxifene versus placebo; similar results were seen with raloxifene. Triglyceride levels were similar among groups. Conclusion. Bazedoxifene showed a favorable safety and tolerability profile in women with postmenopausal osteoporosis. © 2010 Christiansen et al; licensee BioMed Central Ltd.link_to_subscribed_fulltex

Eosinophilic Enteritis Confined to an Ileostomy Site

Eosinophilic enteritis is a rather rare condition that can manifest anywhere from esophagus to rectum. Its description in the literature is sparse, but associations have been made with collagen vascular disease, malignancy, food allergy, parasitic or viral infections, inflammatory bowel disease, and drug sensitivity. We present the case of a 41-year-old male diagnosed with ulcerative colitis who underwent proctocolectomy with ileal pouch anal anastomosis and loop ileostomy formation utilizing Seprafilm®, who later developed eosinophilic enteritis of the loop ileostomy site. This is the first report of eosinophilic enteritis and its possible link to the use of bioabsorbable adhesion barriers

Common cortical responses evoked by appearance, disappearance and change of the human face

<p>Abstract</p> <p>Background</p> <p>To segregate luminance-related, face-related and non-specific components involved in spatio-temporal dynamics of cortical activations to a face stimulus, we recorded cortical responses to face appearance (Onset), disappearance (Offset), and change (Change) using magnetoencephalography.</p> <p>Results</p> <p>Activity in and around the primary visual cortex (V1/V2) showed luminance-dependent behavior. Any of the three events evoked activity in the middle occipital gyrus (MOG) at 150 ms and temporo-parietal junction (TPJ) at 250 ms after the onset of each event. Onset and Change activated the fusiform gyrus (FG), while Offset did not. This FG activation showed a triphasic waveform, consistent with results of intracranial recordings in humans.</p> <p>Conclusion</p> <p>Analysis employed in this study successfully segregated four different elements involved in the spatio-temporal dynamics of cortical activations in response to a face stimulus. The results show the responses of MOG and TPJ to be associated with non-specific processes, such as the detection of abrupt changes or exogenous attention. Activity in FG corresponds to a face-specific response recorded by intracranial studies, and that in V1/V2 is related to a change in luminance.</p

Characterization of Clinically-Attenuated Burkholderia mallei by Whole Genome Sequencing: Candidate Strain for Exclusion from Select Agent Lists

is an understudied biothreat agent responsible for glanders which can be lethal in humans and animals. Research with this pathogen has been hampered in part by constraints of Select Agent regulations for safety reasons. Whole genomic sequencing (WGS) is an apt approach to characterize newly discovered or poorly understood microbial pathogens. genome. Therefore, the strain by itself is unlikely to revert naturally to its virulent phenotype. There were other genes present in one strain and not the other and vice-versa. was both avirulent in the natural host ponies, and did not possess T3SS associated genes may be fortuitous to advance biodefense research. The deleted virulence-essential T3SS is not likely to be re-acquired naturally. These findings may provide a basis for exclusion of SAVP1 from the Select Agent regulation or at least discussion of what else would be required for exclusion. This exclusion could accelerate research by investigators not possessing BSL-3 facilities and facilitate the production of reagents such as antibodies without the restraints of Select Agent regulation