Genetic risk factors for endometriosis near estrogen receptor 1 and coexpression of genes in this region in endometrium.

The etiology and pathogenesis of endometriosis are complex with both genetic and environmental factors contributing to disease risk. Genome-wide association studies (GWAS) have identified multiple signals in the estrogen receptor 1 (ESR1) region associated with endometriosis and other reproductive traits and diseases. In addition, candidate gene association studies identified signals in the ESR1 region associated with endometriosis risk suggesting genetic regulation of genes in this region may be important for reproductive health. This study aimed to investigate hormonal and genetic regulation of genes in the ESR1 region in human endometrium. Changes in serum oestradiol and progesterone concentrations and expression of hormone receptors ESR1 and progesterone receptor (PGR) were assessed in endometrial samples from 135 women collected at various stages of the menstrual cycle. Correlation between hormone concentrations, receptor expression and expression of genes in the ESR1 locus was investigated. The effect of endometriosis risk variants on expression of genes in the region was analyzed to identify gene targets. Hormone concentrations and receptor expression varied significantly across the menstrual cycle. Expression of genes in the ESR1 region correlated with progesterone concentration; however, they were more strongly correlated with expression of ESR1 and PGR suggesting coregulation of genes. There was no evidence that endometriosis risk variants directly regulated expression of genes in the region. Limited sample size and cellular heterogeneity in endometrial tissue may impact the ability to detect significant genetic effects on gene expression. Effects of these variants should be validated in a larger dataset and in relevant individual cell types.

Physical outcome measures for conductive and mixed hearing loss treatment: A systematic review.

BACKGROUND: The number of potential options for rehabilitation of patients with conductive or mixed hearing loss is continually expanding. To be able to inform patients and other stakeholders, there is a need to identify and develop patient-centred outcomes for treatment of hearing loss. OBJECTIVE OF REVIEW: To identify outcome measures in the physical core area used when reporting the outcome after treatment of conductive and mixed hearing loss in adult patients. TYPE OF REVIEW: Systematic review. SEARCH STRATEGY: Systematic review of the literature related to reported physical outcome measures after treatment of mixed or conductive hearing loss without restrictions regarding type of intervention, treatment or device. EVALUATION METHOD: Any measure reporting the physical outcome after treatment or intervention of mixed or conductive hearing loss was sought and categorised. The physical outcome measures that had been extracted were then grouped into domains. RESULTS: The literature search resulted in the identification of 1434 studies, of which 153 were selected for inclusion in the review. The majority (57%) of papers reported results from middle ear surgery, with the remainder reporting results from either bone conduction hearing devices or middle ear implants. Outcomes related to complications were categorised into 17 domains, whereas outcomes related to treatment success was categorised into 22 domains. CONCLUSIONS: The importance of these domains to patients and other stakeholders needs to be further explored in order to establish which of these domains are most relevant to interventions for conductive or mixed hearing loss. This will allow us to then assess which outcome measures are most suitable for inclusion in the core set.

Dienogest mediates midkine suppression in endometriosis.

STUDY QUESTION: What are the effects of dienogest (DNG) on midkine (MK) production in women with endometriosis? SUMMARY ANSWER: DNG-mediated down-regulation of MK in vivo and in vitro. WHAT IS KNOWN ALREADY: DNG is an oral progestin that alleviates painful symptoms of women with endometriosis with a favourable tolerability and safety profile. Its effects on MK, a growth factor that plays an important role in endometriosis, have not yet been investigated. STUDY DESIGN, SIZE, DURATION: Prospective in vivo study on 283 patients subjected to laparoscopy for benign pathologies in a University hospital and in vitro cultures of primary endometrial stromal cells (ESC) from 6 of these women with histologically confirmed endometriosis. PARTICIPANTS/MATERIALS, SETTING, METHODS: MK concentrations in the peritoneal fluid (PF) of women were measured by ELISA and compared based on endometriosis status and the use of DNG. A subsequent in vitro analysis with ESC was used to confirm the direct influence of DNG and other progestins including, norethisterone acetate (NETA) and medroxyprogesterone acetate (MPA) on MK mRNA production. MAIN RESULTS AND THE ROLE OF CHANCE: The final study population consisted of 253 women. Of these, 165 suffered from endometriosis, with 62 of them taking DNG (DNG group) and 103 taking no hormone treatment (non-DNG group) during at least 3 months before surgery. Another 88 women were endometriosis free (non-endometriosis group). The concentration of MK was highest in the PF of women in the non-DNG group (median 5.26 ng/ml, IQR 2.74-8.46). Significantly lower concentrations were found in the non-endometriosis group (median 3.51 ng/ml, IQR: 1.90-7.53, P = 0.028). The lowest concentrations were found in the DNG group (median 2.44 ng/ml, IQR: 1.12-4.70, P < 0.0001 versus non-DNG group, P = 0.048 versus non-endometriosis group). The treatment of primary cultured ESC with DNG (10(-5) M) suppressed MK mRNA production (P = 0.016), whereas MPA (P = 0.109) and NETA (P = 0.422) at same concentrations did not show a similar effect. LIMITATIONS, REASONS FOR CAUTION: The non-randomized design of the study. WIDER IMPLICATIONS OF THE FINDINGS: These findings could indicate a direct effect of DNG on endometriotic cells that could contribute to its effectiveness in the treatment of this disease. STUDY FUNDING/COMPETING INTERESTS: Funding was received from Swiss National Science Foundation (Grant No. 320030_140774). M.D.M. has received fees for speaking at scientific meetings from Bayer. The other authors have no conflicts of interest to declare.The authors state that the manufacturer of dienogest has in no way influenced the performance or outcomes of this study.

Measurement of the 1H(γ, p)π0 reaction using a novel nucleon spin polarimeter.

We report the first large-acceptance measurement of polarization transfer from a polarized photon beam to a recoiling nucleon. The measurement pioneers a novel polarimetry technique, which can be applied to many other nuclear and hadron physics experiments. The commissioning reaction of 1H(γ, p)π0 in the range 0.4

Vibrant soundbridge in aural atresia: does severity matter?

Congenital aural atresia (CAA) poses significant challenges to surgical remediation. Both bone anchored hearing aids (BAHA) and the Vibrant Soundbridge (VSB) have been considered as alternatives or adjuncts to conventional atresiaplasty. A consensus statement on VSB implantation in children and adolescents recommended against implantation when the Jahrsdoerfer score was less than 8. More recent publications suggest that patients with Jahrsdoerfer scores between three and seven may benefit from VSB implantation. The purpose of this study was to further investigate the outcomes of VSB implantation in CAA. The study was a multi-center, retrospective review. A retrospective review of data (patient's demographic, clinical, implant and audiological information) from four collaborating centers that have performed VSB implantation in CAA was performed. Outcomes based on severity of the atresia using the Jahrsdoerfer and Yellon-Branstetter scoring systems were also evaluated. Data from 28 patients from the four centers revealed no iatrogenic facial nerve injuries or change in bone thresholds. Post-operative speech threshold and speech recognition was, respectively, 39 dB and 94%. Jahrsdoerfer and Yellon scores ranged from 4 to 9 and 4 to 12, respectively. The scores did not correlate to or predict outcomes. Three individual elements of the scores did correlate to initial, but not long-term outcomes. Atresiaplasty and BAHA in the management of CAA are not complete solutions. VSB may offer an alternative in these surgically complex patients for achieving amplification, though better metrics for patient selection need to be developed. LEVEL OF EVIDENCE : IV.

Modeling Intracochlear Magnetic Stimulation: A Finite-Element Analysis.

This study models induced electric fields, and their gradient, produced by pulsatile current stimulation of submillimeter inductors for cochlear implantation. Using finite-element analysis, the lower chamber of the cochlea, scala tympani, is modeled as a cylindrical structure filled with perilymph bounded by tissue, bone, and cochlear neural elements. Single inductors as well as an array of inductors are modeled. The coil strength (~100 nH) and excitation parameters (peak current of 1-5 A, voltages of 16-20 V) are based on a formative feasibility study conducted by our group. In that study, intracochlear micromagnetic stimulation achieved auditory activation as measured through the auditory brainstem response in a feline model. With respect to the finite element simulations, axial symmetry of the inductor geometry is exploited to improve computation time. It is verified that the inductor coil orientation greatly affects the strength of the induced electric field and thereby the ability to affect the transmembrane potential of nearby neural elements. Furthermore, upon comparing an array of micro-inductors with a typical multi-site electrode array, magnetically excited arrays retain greater focus in terms of the gradient of induced electric fields. Once combined with further in vivo analysis, this modeling study may enable further exploration of the mechanism of magnetically induced, and focused neural stimulation.

Highly Flexible Silicone Coated Neural Array for Intracochlear Electrical Stimulation.

We present an effective method for tailoring the flexibility of a commercial thin-film polymer electrode array for intracochlear electrical stimulation. Using a pneumatically driven dispensing system, an average 232 ± 64 µm (mean ± SD) thickness layer of silicone adhesive coating was applied to stiffen the underside of polyimide multisite arrays. Additional silicone was applied to the tip to protect neural tissue during insertion and along the array to improve surgical handling. Each array supported 20 platinum sites (180 µm dia., 250 µm pitch), spanning nearly 28 mm in length and 400 µm in width. We report an average intracochlear stimulating current threshold of 170 ± 93 µA to evoke an auditory brainstem response in 7 acutely deafened felines. A total of 10 arrays were each inserted through a round window approach into the cochlea's basal turn of eight felines with one delamination occurring upon insertion (preliminary results of the in vivo data presented at the 48th Annual Meeting American Neurotology Society, Orlando, FL, April 2013, and reported in Van Beek-King 2014). Using microcomputed tomography imaging (50 µm resolution), distances ranging from 100 to 565 µm from the cochlea's central modiolus were measured. Our method combines the utility of readily available commercial devices with a straightforward postprocessing step on the order of 24 hours.

Pitfalls in the use of the Pavlik harness for treatment of congenital dysplasia, subluxation, and dislocation of the hip.

We reviewed the records of treatment of eighteen infants with congenital dysplasia, subluxation, or dislocation of the hip who had problems with the involved hip following treatment with the Pavlik harness. The most common problem (seen in twelve patients with a dislocated hip) was failure to obtain reduction. This failure was attributed primarily to improper use of the harness by the physician. In some patients, three to five months elapsed before the physician recognized the lack of reduction. In nine patients, a Pavlik harness of poor quality and construction added to both the physician's and the patient's problems, and in six patients, poor patient compliance with the use of the harness was partially responsible for the failure. In three patients who were initially treated in the Pavlik harness, avascular necrosis of the hip subsequently developed, in two following open reduction and in one after closed reduction and cast application. The physician's indications for use and application of the harness must be appropriate. The child must be examined frequently out of the harness both clinically and roentgenographically. Failure to achieve reduction or adductor relaxation must be recognized promptly and dealt with immediately.

Saccharomyces cerevisiae mannoproteins that protect wine from protein haze: their release during fermentation and lees contact and a proposal for their mechanism of action.

A fraction containing the mannoproteins released during fermentation from the winemaking strain of Saccharomyces cerevisiae, Maurivin PDM, was able to reduce the visible protein haze in white wine. This fraction of haze protective mannoprotein material (HPM) could be recovered by either ultrafiltration or ethanol precipitation. The kinetics of the release of both mannose- and glucose-containing polymers during the growth cycle of PDM were determined as a guide to the release of HPM. Active HPM was first detected in the culture supernatant when the cells were exponentially growing. HPM was also released into the medium under an environment simulating winemaking conditions by PDM cells during fermentation as well as during storage on yeast lees. Since the amounts of HPM released during fermentation are greater than those subsequently extracted from the cell wall, fermentation would be a more viable procedure than extraction from yeast cells for the commercial production of HPM. Yeast invertase, a mannoprotein with haze protective activity, was used as a model substrate to investigate the mechanism of haze protection. Invertase was found to reduce visible turbidity but not prevent protein precipitation. Invertase itself did not precipitate but remained soluble in the wine. On the basis of these observations, we propose that the mechanism of haze protection may be one of competition between HPM and wine proteins for unknown wine component(s), the latter being required for the formation of large insoluble aggregates of denatured protein. As the available concentration of these components decreases, due to the presence of HPM, the particle size of the haze decreases and thus visible turbidity declines.

Evaluation of flow rates for six disposable infusion devices.

The accuracy of flow was studied for six disposable infusion devices: Eclipse (Block Medical), Homepump (Block Medical), Intermate (Baxter Healthcare), MedFlo (Secure Medical), ReadyMED (McGaw), and SideKick (I-Flow). Each infusion device had a preset delivery rate of 100 mL/hr. Either 48 or 50 units of each device were filled with 100 mL of 0.9% sodium chloride injection. Flow was measured in a 60-mL syringe set 100 cm above the infusion device. The volume infused was recorded over 60 minutes at 5-minute intervals. Of the six devices tested, Homepump demonstrated the least variability in flow. The mean percentage of initial volume infused at 60 minutes was 93.7% for the Homepump, 92.4% for the MedFlo, 91.9% for the SideKick, 88.7% for the ReadyMED, 87.3% for the Eclipse, and 83.4% for the Intermate. The Intermate was the only device with a mean overall infusion rate outside the manufacturer's specifications of +/- 15%. The SideKick's mean infusion rate exceeded the +/- 15% range during the first half of the infusion. None of six disposable infusion devices delivered 100% of the volume to be infused within 60 minutes. Of the devices tested, the Homepump demonstrated the least variability in flow and the most complete volume delivery.

FDA safety alert: hazards of precipitation associated with parenteral nutrition.

In April 1994, the Food and Drug Administration issued a Safety Alert regarding the hazards of precipitation associated with parenteral nutrition in response to reports of two deaths and at least two cases of respiratory distress in patients receiving three-in-one admixtures. The admixtures were thought to contain a precipitate of calcium phosphate, and patient autopsies revealed diffuse microvascular pulmonary emboli. The American Society for Parenteral and Enteral Nutrition took an active role in informing its members of the alert and responding to their concerns. Release of the alert has caused nutrition practitioners to reevaluate their compounding practices, use of filters, prescribing practices for calcium and phosphate in parenteral nutrition solutions, and use of three-in-one admixtures.

The vascular anatomy and angiosome of the posterior auricular artery. A cadaver study.

BACKGROUND: Pedicled flaps based on the posterior auricular artery have been used for small auricular and mastoid cavity defects. OBJECTIVE: To precisely define the vascular anatomy and angiosome (cutaneous distribution) of the posterior auricular artery. METHODS: A fresh cadaver model was used for 3 separate investigations, studying the posterior auricular artery. Intra-arterial ink injections defined the angiosome, and subtraction angiography and latex injection defined the vascular anatomy in relation to bony and soft tissue landmarks. SUBJECTS: Eight fresh cadavers, 6 men and 2 women, were used, varying in age from 58 to 85 years. RESULTS: The posterior auricular artery has a predictable course in the posterior auricular sulcus. The branching pattern over the auricle and temporal bone and the artery's relationship to bony and soft tissue landmarks were consistent. The angiosome includes the anterior and posterior surfaces of the auricle and the periauricular skin superiorly, posteriorly, and inferiorly. CONCLUSIONS: The investigation documented the consistent vascular anatomy and angiosome of the posterior auricular artery. The cutaneous distribution suggests that a large pedicled or island flap based on the posterior auricular artery may be raised safely as a myocutaneous or myofasciocutaneous flap with temporalis fascia and/or periosteum, extending previously published dimensions. Further studies may extend the clinical application to include free flaps based on the posterior auricular artery.

Naproxen-associated sudden sensorineural hearing loss.

Naproxen is a commonly used nonsteroidal anti-inflammatory drug (NSAID) whose side effects include tinnitus and transient hearing loss. Sudden sensorineural hearing loss has rarely been reported as a result of NSAID use. This usually occurs in patients taking other ototoxic medications, with poor renal function, or with autoimmune disease. This article reports the case of an otherwise healthy patient who experienced permanent sensorineural hearing loss after a brief course of naproxen and reviews the literature on NSAID-related permanent sensorineural hearing loss.

Leadership: a means of empowering the nursing profession.

For too long now, nurses have assumed an obsequious role in their working relationship with other health professionals. The nursing profession holds the majority membership in the field of health care professions yet nurses continue to be cast into subordinate roles within professional relationships, failing to be recognised as peers. This is despite many nurses possessing unique but analogous knowledge, credentials and professionalism. It is time nurses were agitated to reflect upon their position and be reminded nursing is also a profession. Some suggestions and motivation are offered.

Regression of the inflammatory microenvironment of the peritoneal cavity in women with endometriosis by GnRHa treatment.

OBJECTIVE: To investigate the effect of gonadotropin-releasing hormone analogues (GnRHa) on the peritoneal fluid microenvironment in women with endometriosis. STUDY DESIGN: Peritoneal fluid was collected from 85 women with severe endometriosis (rAFS stage III and IV) during laparoscopic surgery during the proliferative phase. Prior to surgery clinical data were collected. The concentrations of specific markers for endometriosis in the peritoneal fluid were determined using an ELISA and a comparison between peritoneal fluid markers in women using GnRHa and no hormonal treatment was performed using a non-parametric Mann-Whitney U test. RESULTS: The study included peritoneal fluid from 39 patients who had been administered GnRHa (Zoladex(®)) in the three months prior to surgery and 46 from women with no hormonal treatment in this period. Concentrations of IL-8, PAPP-A, glycodelin-A and midkine were significantly reduced in the GnRHa treatment group compared to women receiving no hormonal treatment. RANTES, MCP-1, ENA-78, TNF-α, OPG, IP-10 and defensin showed no significant change between the two groups. CONCLUSIONS: GnRHa mediate a significant regression in the inflammatory nature of the peritoneal microenvironment in women with endometriosis.