Take it or leave it: oophorectomy at the time of benign hysterectomy.

PURPOSE OF REVIEW: Previous modeling data suggest ovarian conservation up to age 65 for women without adnexal disease and at average risk of ovarian cancer because of an increase in mortality associated with ovarian removal. Recent modeling data challenges this practice. This review of recent literature will update providers regarding consideration for oophorectomy at time of benign hysterectomy. RECENT FINDINGS: Oophorectomy at time of hysterectomy for women less than 50 years with estrogen supplementation and greater than 50 years without estrogen supplementation is not associated with increased mortality. SUMMARY: Although not associated with increased mortality, the decision to remove the ovaries at time of hysterectomy in women older than 50 years is nuanced and requires careful shared decision-making, considering unique patient factors.

Incidence of Intrauterine Adhesions After Hysteroscopic Myomectomy in Patients Seeking Fertility.

STUDY OBJECTIVE: To study the incidence of intrauterine adhesions (IUAs) after hysteroscopic myomectomy. Previous studies report a range of incidence for IUAs after hysteroscopic myomectomy. DESIGN: A retrospective review study. SETTING: An academic community hospital in the Boston metropolitan area. PATIENTS: Patients undergoing hysteroscopic myomectomy at our institution from January 2019 to February 2022. Patients were excluded if they did not have plans for future fertility or had a new diagnosis of cancer. INTERVENTIONS: All patients underwent hysteroscopic myomectomy using bipolar resectoscope without postoperative medical or barrier treatment. All procedures were performed by 1 of 4 fellowship-trained high-volume gynecologic surgeons with resident and fellow assistance. Incidence of postoperative IUAs was assessed and treated using second-look office hysteroscopy. MEASUREMENTS AND MAIN RESULTS: A total of 44 patients without preoperative IUAs underwent hysteroscopic myomectomy during our study period, and 4 patients (9.1%) developed new IUAs. Among 9 patients who were found to have preoperative IUAs and underwent concurrent hysteroscopic myomectomy and lysis of adhesions, we found a recurrence of IUAs in 5 patients (55.6%). We found the number, size, and deepest type of myoma removed were not correlated to an increased risk of new IUA formation. In addition, removing myomas on opposing walls during the same operation did not increase the incidence of new IUAs. CONCLUSION: Formation of IUAs after hysteroscopic myomectomy is a well-documented consequence. Our reported incidence of 9.1% of new IUAs that are not affected by the number, size, deepest type of myoma resected, and resection of myomas on opposing uterine walls contributes to the current literature. In addition, our finding of 55.6% of recurrent IUAs in patients undergoing both hysteroscopic myomectomy and lysis of adhesions highlights a high-risk population requiring additional study.

Incidence and Clinical Implications of Placenta Accreta Spectrum after Treatment for Asherman Syndrome.

STUDY OBJECTIVE: To investigate the incidence, predictors, and clinical implications of placenta accreta spectrum (PAS) in pregnancies after hysteroscopic treatment for Asherman syndrome (AS). DESIGN: This is a retrospective cohort study, conducted through a telephone survey and chart review. SETTING: Minimally invasive gynecologic surgery center in an academic community hospital. PATIENTS: Database of 355 patients hysteroscopically treated for AS over 4 years. We identified patients who achieved pregnancy past the first trimester and evaluated the incidence and predictors for PAS as well as associated clinical implications. INTERVENTIONS: Telephone survey. MEASUREMENTS AND MAIN RESULTS: We identified 97 patients meeting the inclusion criteria. Among these patients, 23 (23.7%) patients had PAS. History of cesarean delivery was the only variable statistically significantly associated with having PAS (adjusted odds ratio 4.03, 95% confidence interval 1.31-12.39). PAS was diagnosed antenatally in 3 patients (14.3%), with patients having placenta previa more likely to be diagnosed (p <.01). Nine patients (39.13%) with PAS required cesarean hysterectomy, which is 9.3% of those with a pregnancy that progressed past the first trimester. Factors associated with cesarean hysterectomy were the etiology of AS (dilation and evacuation after the second trimester pregnancy or postpartum instrumentation, p <.01), invasive placenta (increta or percreta, p <.05), and history of morbidly adherent placenta in previous pregnancies (p <.05). Two patients with PAS (9.5%) had uterine rupture, and another 2 (9.5%) experienced uterine inversion. CONCLUSION: There is a high incidence of PAS and associated morbidity in pregnancies after hysteroscopic treatment for AS. There is a low rate of antenatal diagnosis as well as a lack of reliable clinical predictors, which both stress the importance of clinical awareness, careful counseling, and delivery planning.

The impact of ADHD symptom severity on reinforcement and punishment learning among adults.

Introduction: Aberrations in feedback learning are hypothesised to contribute to the behavioural disruptions and impairment of attention-deficit/hyperactivity disorder (ADHD). However, few studies have evaluated the relation of reward/punishment feedback and ADHD symptom severity on learning. The current study evaluates the differential effects of reward and punishment feedback on learning among adults with elevated ADHD. Methods: One hundred five participants self-reported their level of current ADHD symptoms and completed an innovative instrumental learning task. Results: Consistent with predictions, participants with low self-reported ADHD symptom severity benefitted equally from reward and punishment feedback during the learning task, whereas participants with high self-reported symptom severity performed better (indexed by accuracy on learning task) from reward than punishment feedback trials. Conclusions: Overall, adults with high self-reported symptom severity of ADHD learned more from reward-based feedback, which provides critical implications for motivational theories about ADHD, as well as for treatment protocols. Future work should examine the translatability of results within a treatment setting.

National Strength and Conditioning Association Position Statement on Weightlifting for Sports Performance.

ABSTRACT: Comfort, P, Haff, GG, Suchomel, TJ, Soriano, MA, Pierce, KC, Hornsby, WG, Haff, EE, Sommerfield, LM, Chavda, S, Morris, SJ, Fry, AC, and Stone, MH. National Strength and Conditioning Association position statement on weightlifting for sports performance. J Strength Cond Res 37(6): 1163-1190, 2023-The origins of weightlifting and feats of strength span back to ancient Egypt, China, and Greece, with the introduction of weightlifting into the Olympic Games in 1896. However, it was not until the 1950s that training based on weightlifting was adopted by strength coaches working with team sports and athletics, with weightlifting research in peer-reviewed journals becoming prominent since the 1970s. Over the past few decades, researchers have focused on the use of weightlifting-based training to enhance performance in nonweightlifters because of the biomechanical similarities (e.g., rapid forceful extension of the hips, knees, and ankles) associated with the second pull phase of the clean and snatch, the drive/thrust phase of the jerk and athletic tasks such as jumping and sprinting. The highest force, rate of force development, and power outputs have been reported during such movements, highlighting the potential for such tasks to enhance these key physical qualities in athletes. In addition, the ability to manipulate barbell load across the extensive range of weightlifting exercises and their derivatives permits the strength and conditioning coach the opportunity to emphasize the development of strength-speed and speed-strength, as required for the individual athlete. As such, the results of numerous longitudinal studies and subsequent meta-analyses demonstrate the inclusion of weightlifting exercises into strength and conditioning programs results in greater improvements in force-production characteristics and performance in athletic tasks than general resistance training or plyometric training alone. However, it is essential that such exercises are appropriately programmed adopting a sequential approach across training blocks (including exercise variation, loads, and volumes) to ensure the desired adaptations, whereas strength and conditioning coaches emphasize appropriate technique and skill development of athletes performing such exercises.

Predictors of Patient Return to a Tertiary Neurofibromatosis Subspecialty Clinic.

OBJECTIVE: To evaluate sociodemographic and medical predictors of patient return to a neurofibromatosis subspecialty clinic. STUDY DESIGN: Data were collected from the Washington University Neurofibromatosis Clinical Program electronic medical records. A total of 713 subjects with initial visits to the Washington University Neurofibromatosis Clinical Program between July 1, 2005 and December 18, 2020 were included. Variables collected included sex, race, ethnicity, age, date of first visit, place of residence, diagnosis, insurance payer, physician recommendation for return, and subject return. Return rates for each demographic group were calculated. Bivariate analyses were performed to inform variable inclusion in the model, and a binary logistic regression model was calculated to predict subject return. RESULTS: The overall return rate was 76%. The binary logistic regression model was statistically significant (χ29 = 131.094; P < .001) and showed that subjects who self-identified as Black and/or African American, presented with or received a diagnosis of café-au-lait macules at their initial visit, were from a rural area, were older, or who lived farther from the Washington University Neurofibromatosis Clinical Program were less likely to return to clinic. CONCLUSIONS: These findings support the implementation of tailored communication and monitoring interventions to improve the care for children with neurofibromatosis type 1.

Adenomyosis and fertility: does adenomyosis impact fertility and does treatment improve outcomes.

PURPOSE OF REVIEW: Adenomyosis has recently been associated with infertility. Relief of bleeding and pain has been demonstrated with medical and surgical therapy. Less is known about reproductive outcomes after treatment. RECENT FINDINGS: Imaging findings during infertility evaluation can be suggestive of adenomyosis without pathologic evaluation. Among women with infertility undergoing assisted reproductive technologies (ART), adenomyosis is associated with lower live birth rates and clinical pregnancy rates. Treatment with gonadotropin releasing hormone (GnRH) modulators prior to frozen embryo transfer may increase the live birth rate and clinical pregnancy rate among women with adenomyosis. Pregnancy has been documented following image-guided adenomyosis ablation; however, the reproductive impact is not well established. Pregnancy following excisional procedures appears to be well tolerated, although may carry a higher risk of uterine rupture compared with pregnancy following myomectomy. It is not clear if ablative therapy or resection increases pregnancy rates. SUMMARY: Adenomyosis is associated with lower embryo implantation rates and ongoing pregnancy rates. Adenomyotic changes in the uterus can be seen by ultrasound and MRI. GnRH modulators may be useful for women with adenomyosis undergoing ART. Additional prospective data is warranted to determine the optimal medical or surgical therapy for women with adenomyosis desiring conception.Video abstract Supplementary digital content, http://links.lww.com/COOG/A78.

Dose-dependent seizure control with MEK inhibitor therapy for progressive glioma in a child with neurofibromatosis type 1.

BACKGROUND: Low-grade gliomas (LGGs) occurring in children can result in many different neurologic complications, including seizures. MEK inhibitors are increasingly being used to treat LGG, but their effect on associated neurologic symptoms has not been established. RESULTS: Here, we report a patient with neurofibromatosis type 1 (NF1), medically refractory epilepsy (MRE), and an extensive optic pathway glioma (OPG) who developed dose-dependent seizure control while being treated with selumetinib. Seizure frequency rebounded after dose reduction for cardiac toxicity, then improved, and finally ceased after restarting full dosing, allowing confidence in the cause of improvement. CONCLUSION: Selumetinib may have promise in epilepsy management in other children with NF1 or LGG.

Social prescribing during the COVID-19 pandemic: a qualitative study of service providers' and clients' experiences.

BACKGROUND: COVID-19 public health restrictions, such as social distancing and self-isolation, have been particularly challenging for vulnerable people with health conditions and/or complex social needs. Link worker social prescribing is widespread in the UK and elsewhere and is regarded as having the potential to provide support to vulnerable people during the pandemic. This qualitative study explores accounts of how an existing social prescribing service adapted to meet clients' needs in the first wave of the pandemic, and of how clients experienced these changes. METHODS: Data were collected in a deprived urban area of North East England via remote interviews with clients (n = 44), link workers (n = 5) and service provider managerial staff (n = 8) from May-September 2020. Thematic data analysis was conducted. RESULTS: The research found that service providers quickly adapted to remote intervention delivery aiming to serve existing clients and other vulnerable groups. Service providers experienced improved access to some existing clients via telephone in the first months of remote delivery and in some cases were able to engage clients who had previously not attended appointments at GP surgeries. However, link workers also experienced challenges in building rapport with clients, engaging clients with the aims of the intervention and providing a service to digitally excluded people. Limited link worker capacity meant clients experienced variable contact with link workers with only some experiencing consistent support that was highly valued for helping to manage their conditions and mental wellbeing. Limited access to linked services also adversely affected clients. Clients living in less affluent circumstances and/or with worse health were more likely to experience negative impacts on their long-term condition. Some found their health and progress with social prescribing was 'on hold' or 'going backwards', which sometimes negatively affected their health. CONCLUSIONS: Social prescribing offered valued support to some during the pandemic, but remote support sometimes had limited impact for clients and findings highlight the vulnerability of social prescribing's success when linked services are disrupted. Findings also show the need for more to be done in the upscaling of social prescribing to provide support to digitally excluded populations.

Surfactant Penetration into Human Skin from Sodium Dodecyl Sulfate and Lauramidopropyl Betaine Mixtures.

Surfactant mixtures are used in a variety of personal care and cosmetic applications but are known to be harsh on the skin. The purpose of this study was to examine anionic surfactant penetration into human skin from nonideal surfactant mixtures under short-time exposure conditions that are relevant to realistic exposure scenarios. This was done by measuring the penetration of a radiolabeled probe (14C-SDS) into human cadaver skin in Franz diffusion cells in vitro from the mixtures of sodium dodecyl sulfate (SDS) and lauramidopropyl betaine (LAPB). Monomer and micelle concentrations in the SDS/LAPB/14C-SDS mixtures were predicted using a regular solution theory approximation. We confirmed that the mixtures of SDS and LAPB exhibit nonideal behavior with a net attraction between the two surfactants. Penetration of 14C-SDS into excised human skin from the mixtures of SDS and LAPB was found to decrease in a log-linear manner with increasing mole fraction of LAPB in the bulk solution (R2 = 0.97, p < 0.001). Additionally, the penetration of 14C-SDS into excised human skin from the mixtures of SDS and LAPB was found to correlate linearly and strongly with the predicted values of 14C-SDS monomer concentration in SDS/LAPB/14C-SDS mixtures (R2 = 0.95, p < 0.01). 14C-SDS penetration from the mixed surfactant composition could be quantitatively reconciled with that from an SDS-only composition by postulating a secondary, positive contribution from LAPB related to its own penetration and binding to skin components that increased SDS penetration at low concentrations. This research therefore supports a monomer penetration theory of surfactant penetration into the skin, combined with a measurable impact of favorable surfactant interactions within the tissue.

Effects of Asherman Syndrome on Maternal and Neonatal Morbidity with Evaluation by Conception Method.

STUDY OBJECTIVE: Create a comprehensive summary of maternal and neonatal morbidities from patients previously treated for Asherman syndrome and evaluate for differences in perinatal outcomes based on conception method. DESIGN: Retrospective cohort. SETTING: Community teaching hospital affiliated with a large academic medical center. PATIENTS: Total of 43 singleton births identified from 40 patients previously treated at our institution for Asherman syndrome. INTERVENTIONS: Review of fertility and obstetric data to summarize the maternal and neonatal outcomes in singleton births from patients with Asherman syndrome who had been treated with hysteroscopic adhesiolysis. MEASUREMENTS AND MAIN RESULTS: Primary outcomes of maternal morbidity (i.e., hypertensive disease, gestational diabetes, ruptured membranes, postpartum hemorrhage, morbidly adherent placenta [MAP]) and secondary outcomes of neonatal morbidity (i.e., gestational age at birth, method of delivery, weight, length, 1- and 5-minute Apgar score oxygen requirement, anatomic malformations, length of neonatal admission) were evaluated. We identified 40 patients who completed successful treatment of Asherman syndrome and went on to carry a singleton gestation within our institution: 20 (50%) with mild disease, 18 (45%) with moderate disease, and 2 (5%) with severe disease under the March classification system. In total, 43 singleton births were examined, with 27 of 43 (62.8%) conceived without in vitro fertilization (IVF) (group A: non-IVF conception) and 16 of 43 (37.2%) conceived through IVF (group B: IVF conception). The overall rate of preterm birth in Asherman pregnancies was 11.6%, with no difference between the 2 conception groups. We documented 9.3% cases with intrauterine growth restriction, with no difference based on conception groups. The rate of MAP in patients with Asherman syndrome was 14.0%, and the rate of postpartum hemorrhage was 32.6%, with no differences between the conception groups. Newborn anatomic malformations of any cause were documented in 18.6% of all singleton births, with no difference between the conception groups. CONCLUSION: Our series indicates a higher incidence of intrauterine growth restriction, MAP, postpartum hemorrhage, and newborn anatomic malformations in Asherman syndrome pregnancies than that reported in pregnancies within the general population. However, we found no significant differences in the maternal and neonatal outcomes of patients with Asherman syndrome who conceived with or without IVF after being treated with hysteroscopic adhesiolysis.

Concomitant Adenomyosis among Patients with Asherman Syndrome.

STUDY OBJECTIVE: To characterize obstetric outcomes for concomitant Asherman syndrome and adenomyosis. DESIGN: A retrospective cohort study. SETTING: A community teaching hospital affiliated with a large academic medical center. PATIENTS: A total of 227 patients with Asherman syndrome with available hysteroscopy and pelvic ultrasound reports. INTERVENTIONS: Telephone survey to assess and compare the obstetric outcomes of patients with Asherman syndrome with concomitant adenomyosis (Group A) vs patients with Asherman syndrome without concomitant adenomyosis (Group B). MEASUREMENTS AND MAIN RESULTS: A telephone survey and confirmatory chart review were conducted to obtain information on patients' demographics, gynecologic and obstetric history, past medical and surgical history, and Asherman syndrome management. Adenomyosis was a common sonographic finding, detected in 39 patients with Asherman syndrome (17.2%). In this cohort, 77 patients attempted pregnancy and produced 87 pregnancies. Age (odds ratio [OR] 0.67; 95% confidence intervals [CI], 0.52-0.86) was negatively associated with a pregnancy outcome. Age (OR 0.83; 95% CI, 0.73-0.95) and severe Asherman disease (OR 0.06; 95% CI, <0.01-0.99) were negatively associated with a live birth outcome. Adenomyosis was not an independent predictor of pregnancy rate, miscarriage rate, or live birth rate among patients with Asherman syndrome. CONCLUSION: Adenomyosis is relatively common in patients with Asherman syndrome. Adenomyosis does not seem to add any distinct detriment to fertility among patients with Asherman syndrome.

A scoping review of qualitative research on perceptions of one's own alcohol use.

BACKGROUND: This scoping review aims to map the extent, range and nature of qualitative research on people's 'perceptions' of their own alcohol consumption. METHODS: A systematic search of five electronic databases was conducted. A total of 915 abstracts were screened and 452 full texts examined, of which 313 papers met the inclusion criteria (including a report of qualitative data on perceptions, experiences or views of people's own drinking in peer-reviewed journals published in English). RESULTS: This study maps the available literature assembled over approximately 30 years, which was found to be extensive and diverse. Many existing studies are focused largely on people's 'experiences' of their own drinking behaviours, particularly when they were drinking in ways commonly understood as heavy, risky or problematic. Fewer studies focused on populations whose drinking was not heavy or was risky in less obvious ways, such as older adults prescribed medications for chronic health conditions. Most studies were conducted since 2010, with the rate of publications increasing since 2014. CONCLUSIONS: This review identifies gaps in the evidence regarding people's perceptions of their own drinking and opportunities for qualitative studies to make valuable contributions to alcohol research. Gaps discussed include patterns of drinking that are less obviously problematic, and in relation to consumption of alcohol in those parts of the world where overall consumption and harms from alcohol are high. Such studies could usefully be informed by existing studies in the evidence mapping.

Community pharmacy and public health: preserving professionalism by extending the pharmacy gaze?

Community pharmacy faces ongoing challenges to its economic and social standing. A concern to legitimate professional status explains the attraction of public health. Interventions currently advocated by UK State-sponsored health care seek to reconcile the autonomous 'entrepreneurial' patient with market-driven solutions. Engaging critically with recent Foucauldian sociological work on pharmacy as a conduit for disciplinary power, we explore how professional ambiguity is exploited to 'manage' the subjectivities of community pharmacists. Locating our discussion in the observed empirical realities of pharmacy practice (the inclusion of alcohol and other 'healthy living' advice in the Medicines Use Review), we connect unresolved historical debates in community pharmacy with current ongoing (neoliberal) changes in policy and pharmacy business practices, drawing attention to the poor evidence base underpinning healthy living activities in community pharmacy. Our findings show how community pharmacists struggle to provide meaningful advice, valued by patients. Instead of enhancing professional status, 'add-on' public health roles created the risk of offering little more than an essentialised enactment of consumerist health care. Understanding how patients conceptualise drinking and 'healthy living' in relation to their long-term health, using more open discussions, including the negotiation (rather than provision) of information, could help community pharmacists challenge the current professional vulnerabilities they face.

Sorting nexin 27 (SNX27) variants associated with seizures, developmental delay, behavioral disturbance, and subcortical brain abnormalities.

Sorting nexin 27 (SNX27) influences the composition of the cellular membrane via regulation of selective endosomal recycling. Molecular analysis indicates that SNX27 regulates numerous cellular processes through promiscuous interactions with its receptor cargos. SNX27 deficient (Snx27 -/- ) mice exhibit reduced embryonic survival, marked postnatal growth restriction and lethality. Haploinsufficient mice (Snx27 +/- ) show a less severe phenotype, with deficits in learning, memory, synaptic transmission and neuronal plasticity. One family previously reported with a homozygous SNX27 frameshift variant (c.515_516del;p.His172Argfs*6), exhibited infantile intractable myoclonic epilepsy, axial hypotonia, startle-like movements, cardiac septal defects, global developmental delay, failure to thrive, recurrent chest infections, persistent hypoxemia and early death secondary to respiratory failure. Here, we report two additional patients with compound heterozygous SNX27 variants, that are predicted to be damaging: (a) c.510C>G;p.Tyr170* and c.1295G>A;p.Cys432Tyr, and (b) c.782dupT;p.Leu262Profs*6 and c.989G>A;p.Arg330His. They exhibit global developmental delay, behavioral disturbance, epilepsy, some dysmorphic features and subcortical white matter abnormalities. In addition, possible connective tissue involvement was noted. Epilepsy, developmental delays and subcortical white matter abnormalities appear to be core features of SNX27-related disorders. We correlate the observed phenotype with available in vitro, in vivo and proteomic data and suggest additional possible molecular mediators of SNX27-related pathology.

Endometrial thickness measurements among Asherman syndrome patients prior to embryo transfer.

STUDY QUESTION: Is there an association between endometrial thickness (EMT) measurement and clinical pregnancy rate among Asherman syndrome (AS) patients utilizing IVF and embryo transfer (ET)? SUMMARY ANSWER: EMT measurements may not be associated with successful clinical pregnancy among AS patients undergoing IVF. WHAT IS KNOWN ALREADY: Clinical pregnancy rate after IVF is significantly lower in patients with a thin endometrium, defined as a maximum EMT of <7 mm. However, AS patients often have a thin EMT measurement due to intrauterine scarring, with a paucity of data and no guidance on what EMT cutoff is appropriate when planning an ET among these patients. STUDY DESIGN, SIZE, DURATION: This is a retrospective cohort study of 45 AS patients treated at a specialized advanced hysteroscopic clinic from 1 January 2015, to 1 March 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Review of EMT measurements prior to a total of 90 ETs, among 45 AS patients. The impact of the maximum EMT measurement prior to ET on clinical pregnancy rate was analyzed. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 25/45 (55.6%) AS patients ultimately went on to have ≥1 clinical pregnancy following a mean ± SD of 2.00 ± 1.26 ET attempts. There was a total of 90 ETs among the 45 AS patients, with 29/90 (32.2%) ETs resulting in a clinical pregnancy. Younger patient age (P = 0.05) and oocyte donation (P = 0.01) were the only variables identified to be significant predictors for a positive clinical pregnancy outcome on bivariate analysis. The mean EMT measurement prior to all ETs among AS patients was 7.5 ± 1.6 mm. EMT measurement prior to ET did not predict a positive clinical pregnancy on either bivariate (P = 0.84) or multivariable analysis (odds ratio 0.91, P = 0.60). 31.8% of EMT measurements measured <7.0 mm. In this small cohort, no difference in the clinical pregnancy rate was detected when comparing ETs with EMT measurements of <7.0 mm versus ≥7.0 mm (P = 0.83). The mean EMT measurement decreased with increasing AS disease severity; 8.0 ± 1.6 mm for mild disease, 7.0 ± 1.4 mm for moderate disease and 5.4 ± 0.1 mm for severe disease. LIMITATIONS, REASONS FOR CAUTION: Our small sample size limits our ability to draw any definitive conclusions. In addition, patients utilized various infertility clinics. This limits our ability to evaluate the consistency of EMT measurements and the IVF care that was received. WIDER IMPLICATIONS OF THE FINDINGS: EMT measurement cutoff values should be used with caution if canceling a scheduled ET in AS patients. STUDY FUNDING/COMPETING INTEREST(S): This study was not funded. K.I. reports personal fees from Karl Stroz and personal fees from Medtronics outside the submitted work. The other authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Conventional and pioneer modes of glucocorticoid receptor interaction with enhancer chromatin in vivo.

Glucocorticoid hormone plays a major role in metabolism and disease. The hormone-bound glucocorticoid receptor (GR) binds to a specific set of enhancers in different cell types, resulting in unique patterns of gene expression. We have addressed the role of chromatin structure in GR binding by mapping nucleosome positions in mouse adenocarcinoma cells. Before hormone treatment, GR-enhancers exist in one of three chromatin states: (i) Nucleosome-depleted enhancers that are DNase I-hypersensitive, associated with the Brg1 chromatin remodeler and flanked by nucleosomes incorporating histone H2A.Z. (ii) Nucleosomal enhancers that are DNase I-hypersensitive, marked by H2A.Z and associated with Brg1. (iii) Nucleosomal enhancers that are inaccessible to DNase I, incorporate little or no H2A.Z and lack Brg1. Hormone-induced GR binding results in nucleosome shifts at all types of GR-enhancer, coinciding with increased recruitment of Brg1. We propose that nucleosome-depleted GR-enhancers are formed and maintained by other transcription factors which recruit Brg1 whereas, at nucleosomal enhancers, GR behaves like a pioneer factor, interacting with nucleosomal sites and recruiting Brg1 to remodel the chromatin.

A Systematic Review of Tissue Sampling Techniques for the Diagnosis of Adenomyosis.

OBJECTIVE: Evaluate the accuracy of tissue sampling techniques for the diagnosis of adenomyosis. DATA SOURCES: Systematic Review via MEDLINE and the Cochrane Library searches. METHODS OF STUDY SELECTION: Review performed utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, utilizing MeSH terms and keywords including "Adenomyosis/diagnosis" or "Adenomyosis/pathology" or "Myometrium/pathology" and "Biopsy" or "Hysteroscopy" or "Laparoscopy." Articles initially screened by title and abstract to include relevant studies with reference lists cross-referenced to find additional studies. Articles related to the diagnosis of uterine malignancy or studies in which tissue sampling was obtained through excisional surgical procedures were excluded from the review. TABULATION, INTEGRATION, AND RESULTS: Fourteen studies were identified describing tissue sampling techniques to diagnose adenomyosis, with a total of 1909 patients, from 12 different countries, involving 6 different continents. Tissue sampling techniques were categorized based on (1) biopsy approach as either intrauterine and extrauterine and (2) techniques that were validated or not validated with a confirmatory hysterectomy pathology. Overall, there was significant heterogeneity in the tissue sampling techniques including intrauterine sampling obtained through hysteroscopic biopsy or resection and extrauterine tissue sampling obtained with needle biopsy by a percutaneous, transvaginal, laparoscopic, or ex-vivo approach. Sensitivity of these techniques varied significantly based on technique, tissue sampling location and the number of biopsies obtained, and was as low as 22.2% for an ultrasound-guided transvaginal biopsy of suspicious uterine lesions (4 biopsies per patient) and was as high as 97.8% for a laparoscopic guided myometrial biopsy of suspicious uterine lesions (10 biopsies per patient). Specificity for the identified tissue sampling techniques was more homogeneous ranging from 78.5% to 100% for all methods identified. The positive predictive value and negative predictive value ranges were 75.9% to 100% and 46.4% to 80% respectively among all tissue sampling techniques identified with confirmatory hysterectomy pathology. CONCLUSION: Because of the heterogeneity of the tissue sampling techniques, diverse patient populations, and significant conflicting recommendations, no conclusive recommendation on the optimal tissue sampling technique can be made. However, it would be reasonable to limit uterine tissue sampling for confirmatory diagnosis of adenomyosis in patients with a suspicion of adenomyosis based on both symptom profile and pelvic ultrasound, where a planned diagnostic laparoscopy for either infertility or pelvic pain has already been contemplated and scheduled, and where the confirmatory results may be of clinical benefit in discussing the prognosis of recurrent postoperative symptoms and guide any future treatment recommendations.

How do older people normalise their drinking?: An analysis of interviewee accounts.

Alcohol consumption has been linked to a wide range of social and health problems, and it is known that drinking among older age groups has been increasing. Relatively little qualitative research has examined how older drinkers make sense of their drinking practices, including how they seek to normalise their consumption when talking about it. This paper reports on a qualitative interview study with older drinkers (n = 25; aged 41-89), focusing on the various discursive strategies they use to rationalise their drinking. Discursive analysis of the interview transcripts highlights four key approaches used: strategic vagueness; reinforcing responsible restraint; self-serving comparisons; and downplaying drinking as mundane practice. Taken together, the efforts made to convey drinking in moderation suggest a concern among interviewees with being regarded as a good citizen, in control of their consumption and their lives generally. Some possible implications for health promotion, and ideas for further research, are discussed.

A pilot cluster randomised trial of the medicines and alcohol consultation (MAC): an intervention to discuss alcohol use in community pharmacy medicine review services.

BACKGROUND: Alcohol interventions are important to the developing public health role of community pharmacies. The Medicines and Alcohol Consultation (MAC) is a new intervention, co-produced with community pharmacists (CPs) and patients, which involves a CP practice development programme designed to integrate discussion of alcohol within existing NHS medicine review services. We conducted a pilot trial of the MAC and its delivery to investigate all study procedures to inform progression to a definitive trial. METHODS: This cluster pilot RCT was conducted in 10 community pharmacies in Yorkshire, UK, with a CP from each who regularly conducted Medicine Use Review (MUR) and New Medicine Service (NMS) consultations. Randomisation was conducted using a secure remote randomisation service. Intervention CPs (n = 5) were trained to deliver the MAC in MUR/NMS consultations. Control CPs (n = 5) provided these services as usual. Consecutive MUR/NMS patients were asked by CPs to participate, screened for eligibility (consumption of alcohol at least twice per week), and baseline data collected for those eligible. A two-month follow-up telephone interview was conducted. Blinding of CPs was not possible, but patients were blinded to the alcohol focus of the trial. Primary outcomes were total weekly UK units (8 g of ethanol per unit) of alcohol consumption in the week prior to follow-up, and confidence in medications management. Trial procedures were assessed by recruitment, attrition, and follow-up rates. RESULTS: 260 patients were approached by CPs to take part in the trial, 68% (n = 178) were assessed for eligibility and 30% (n = 54) of these patients were eligible. Almost all eligible patients (n = 51; 94%) consented to participate, of whom 92% (n = 47) were followed-up at 2 months; alcohol consumption was lower in the intervention arm and confidence in medication management reduced slightly for both groups. Exploration of recall issues at follow-up showed a high level of agreement between a two-item quantity/frequency measure and 7-day guided recall of alcohol consumption. CONCLUSIONS: The pilot trial demonstrates the feasibility of implementing the MAC in community pharmacy and trial recruitment and data collection procedures. However, decommissioning of MURs means that it is not possible to conduct a definitive trial of the intervention in this service. TRIAL REGISTRATION: ISRCTN57447996.