Revisiting Estrogen: Efficacy and Safety for Postmenopausal Bone Health

The rapid decline in endogenous estrogen production that occurs during menopause is associated with significant bone loss and increased risk for fragility fracture. While hormone therapy (HT) is an effective means to re-establish endogenous estrogen levels and reduce the risk of future fracture, its use can be accompanied by undesirable side effects such as stroke and breast cancer. In this paper, we revisit the issue of whether HT can be both safe and effective for the prevention of postmenopausal bone loss by examining standard and alternative doses and formulations of HT. The aim of this paper is to continue the dialogue regarding the benefits and controversies of HT with the goal of encouraging the dissemination of-up-to date evidence that may influence how HT is viewed and prescribed

Middle cerebral artery velocity dynamic response profile during exercise is attenuated following multiple ischemic strokes: A case report

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Blood flow regulation is impaired in people with stroke. However, the time course of change in middle cerebral artery velocity (MCAv) following repeated stroke at rest and during exercise remains unknown. In this case study, we provide novel characterization of the dynamic kinetic MCAv response profile to moderate‐intensity exercise before and after repeated ischemic MCA stroke. The initial stroke occurred in the left MCA. At 3 months poststroke, left MCAv amplitude (Amp) was ~50% lower than the right. At the 6‐month follow‐up visit, MCAv Amp declined in both MCA with the left MCAv Amp ~50% lower than the right MCAv Amp. Following a second right MCA stroke, we report further decline in Amp for the left MCA. At the 3‐ and 6‐month visit following the second stroke, the left MCAv Amp declined further (~10%). The right MCAv Amp dramatically decreased by 81.3% when compared to the initial study visit. The MCAv kinetic analysis revealed a marked impairment in the cerebrovascular response to exercise following stroke. We discuss potential pathophysiological mechanisms contributing to poststroke cerebrovascular dysfunction and the need to test therapeutic interventions (such as exercise) that might attenuate cerebrovascular decline in people following stroke.Eunice Kennedy Shriver National Institute of Child Health and Human Development (K01HD067318)CTSA grant from NCATS awarded to the University of Kansas for Frontiers: University of Kansas Clinical and Translational Science Institute (# UL1TR002366)CTSA Award # UL1TR000001 from NCRR and NCATSGeorgia Holland Endowment Fun

‘Even though you hate everything that\u27s going on, you know they are safer at home’: The role of Aboriginal and Torres Strait Islander families in methamphetamine use harm reduction and their own support needs

Introduction: First Nations people who use methamphetamine are overrepresented in regional and remote Australia and more likely to turn to family for support. This can place strain on families. The support needs of family members of individuals using methamphetamine are poorly understood. Methods: We conducted 19 focus groups and seven interviews with mostly First Nations community, family members and service providers. In total, 147 participants across six sites participated as part of a larger study investigating First Nations perspectives of how to address methamphetamine use and associated harms. We applied a social and emotional wellbeing framework to examine support needs and role of family in mitigating methamphetamine harms. Results: Findings highlighted the importance of families in providing support to people using methamphetamine and in reducing associated harms, often without external support. The support provided encompassed practical, social, emotional, financial, access to services and maintaining cultural connection. Providing support took a toll on family and negatively impacted their own social and emotional wellbeing. Discussion and Conclusions: First Nations families play an important and under-recognised role in reducing methamphetamine-related harms and greater efforts are required to support them. Professional resources are needed to deal with impacts of methamphetamine on families; these should be pragmatic, accessible, targeted and culturally appropriate. Support for families and communities should be developed using the social and emotional wellbeing framework that recognises wellbeing and healing as intrinsically connected to holistic health, kinship, community, culture and ancestry, and socioeconomic and historical influences on peoples\u27 lives

Influence of ERβ selective agonism during the neonatal period on the sexual differentiation of the rat hypothalamic-pituitary-gonadal (HPG) axis

<p>Abstract</p> <p>Background</p> <p>It is well established that sexual differentiation of the rodent hypothalamic-pituitary-gonadal (HPG) axis is principally orchestrated by estrogen during the perinatal period. Here we sought to better characterize the mechanistic role the beta form of the estrogen receptor (ERβ) plays in this process.</p> <p>Methods</p> <p>To achieve this, we exposed neonatal female rats to three doses (0.5, 1 and 2 mg/kg) of the ERβ selective agonist diarylpropionitrile (DPN) using estradiol benzoate (EB) as a positive control. Measures included day of vaginal opening, estrous cycle quality, GnRH and Fos co-localization following ovariectomy and hormone priming, circulating luteinizing hormone (LH) levels and quantification of hypothalamic kisspeptin immunoreactivity. A second set of females was then neonatally exposed to DPN, the ERα agonist propyl-pyrazole-triol (PPT), DPN+PPT, or EB to compare the impact of ERα and ERβ selective agonism on kisspeptin gene expression in pre- and post-pubescent females.</p> <p>Results</p> <p>All three DPN doses significantly advanced the day of vaginal opening and induced premature anestrus. GnRH and Fos co-labeling, a marker of GnRH activation, following ovariectomy and hormone priming was reduced by approximately half at all doses; the magnitude of which was not as large as with EB or what we have previously observed with the ERα agonist PPT. LH levels were also correspondingly lower, compared to control females. No impact of DPN was observed on the density of kisspeptin immunoreactive (-ir) fibers or cell bodies in the arcuate (ARC) nucleus, and kisspeptin-ir was only significantly reduced by the middle (1 mg/kg) DPN dose in the preoptic region. The second experiment revealed that EB, PPT and the combination of DPN+PPT significantly abrogated preoptic Kiss1 expression at both ages but ARC expression was only reduced by EB.</p> <p>Conclusion</p> <p>Our results indicate that selective agonism of ERβ is not sufficient to completely achieve male-typical HPG organization observed with EB or an ERα agonist.</p

Managing Opportunities and Challenges of Co-Authorship

Research with the largest impact on practice and science is often conducted by teams with diverse substantive, clinical, and methodological expertise. Team and interdisciplinary research has created authorship groups with varied expertise and expectations. Co-authorship among team members presents many opportunities and challenges. Intentional planning, clear expectations, sensitivity to differing disciplinary perspectives, attention to power differentials, effective communication, timelines, attention to published guidelines, and documentation of progress will contribute to successful co-authorship. Both novice and seasoned authors will find the strategies identified by the Western Journal of Nursing Research Editorial Board useful for building positive co-authorship experiences

Complete Genome Sequences of Paenibacillus Larvae Phages BN12, Dragolir, Kiel007, Leyra, Likha, Pagassa, PBL1c, and Tadhana

We present here the complete genomes of eight phages that infect Paenibacillus larvae, the causative agent of American foulbrood in honeybees. Phage PBL1c was originally isolated in 1984 from a P. larvae lysogen, while the remaining phages were isolated in 2014 from bee debris, honeycomb, and lysogens from three states in the USA

Frequency and significance of IgG4 immunohistochemical staining in liver explants from patients with primary sclerosing cholangitis

Dense tissue infiltrates of IgG4(+) plasma cells >50/high-powered field (HPF) are purportedly highly specific for IgG4-related disease. However, the frequency and significance of liver-infiltrating IgG4(+) plasma cells in primary sclerosing cholangitis (PSC) applying these cut-offs has not been determined. We sought to determine the incidence of intrahepatic IgG4-positive staining in PSC patients undergoing transplantation, correlating findings with clinical parameters. Immunohistochemical staining was performed on liver explants obtained between 1991 and 2009. Of 122 explants obtained, hilar IgG4(+) staining was found to be mild (10–29 IgG4(+) cells/HPF) in 23.0%, moderate (30–50/HPF) in 9.0% and marked (>50/HPF) in 15.6%. Marked hilar lymphoplasmacytic infiltration was significantly associated with marked hilar IgG4(+) staining (P < 0.001). No patient had marked peripheral IgG4(+) staining, although mild and moderate staining was observed in 24.5% and 3.3% respectively. Marked hilar IgG4(+) staining was significantly associated with the presence of dominant biliary strictures (P = 0.01) and need for biliary stenting (P = 0.001). There did not, however, exist any significant differences in the age at PSC diagnosis, presence of inflammatory bowel disease or extrahepatic autoimmune disease, frequency of cholangiocarcinoma, interval between diagnosis and transplantation, or post-transplant PSC recurrence or survival. Of 51 control liver sections (PBC = 18; HCV = 19; HBV = 8; AIH = 6), none had marked or moderate hilar IgG4(+) staining, whereas mild staining was seen in only 10% (P < 0.001). Marked (>50/HPF) hilar IgG4(+) lymphoplasmacytic infiltration is frequently observed in PSC and associated with the presence of dominant biliary strictures. However, unlike serum IgG4(+)(,) this does not seemingly associate with clinical disease course

Agonists of proteinase-activated receptor-2 affect transendothelial migration and apoptosis of human neutrophils

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73837/1/j.1600-0625.2007.00605.x.pd

Recent developments in frailty identification, management, risk factors and prevention : A narrative review of leading journals in geriatrics and gerontology

Funding The Frailty Epidemiology Research Network (EPI-FRAIL) is an international collaborative project aimed at filling knowledge gaps in the field of frailty epidemiology. The network was established as part of a NWO/ZonMw Veni fellowship awarded to E.O. Hoogendijk (Grant no. 91618067). P. Hanlon is funded through a Clinical Research Training Fellowship from the Medical Research Council (Grant reference: MR/S021949/1). Z. Liu was supported by the Soft Science Research Program of Zhejiang Province (2023KXCX-KT011). J. Jylhävä has received grant support from the Swedish Research Council (grant no. 2018-02077), the Academy of Finland (grant no. 349335), the Sigrid Jusélius Foundation, the Yrjö Jahnsson Foundation and the Instrumentarium Science Foundation. M. Sim is supported by a Royal Perth Hospital Research Foundation Career Advancement Fellowship and an Emerging Leader Fellowship from the Future Health Research and Innovation Fund (Department of Health, Western Australia). R. Ambagtsheer receives funding from the Australian Medical Research Future Fund (grant #MRF2016140). D. L. Vetrano receives financial support from the Swedish Research Council (2021-03324). S. Shi reports funding from the National Institute of Aging, R03AG078894-01. None of the funding agencies had any role in the conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript.Peer reviewedPublisher PD