The goal of this research was to determine the effects of the growth of invasive plant Amur Honeysuckle (Lonicera maackii) on the rhizosphere bacterial community composition, and diversity in an urban wetland forest ecosystem. Bacterial communities from the rhizosphere of 5 L. maackii plants and control bulk soils that did not have any L. maackii were investigated at Nina Mason Pulliam EcoLab (NMPE) using a culture-independent pipeline. Bacterial communities were characterized by PCR amplification and cloning 16S rRNA gene fragments following total DNA isolation from the soil samples. Microbial communities associated with both L. maackii rhizosphere and control sites showed high bacterial diversity within each site and taxa unique to individual sites were observed. Phylogenetic analyses revealed 80% of 400 16S rDNA clones were classified as α-, β- and γ-Proteobacteria, Acidobacteria, Actinobacteria, Cytophaga-Flexibacter-Bacteroides (CFB) group, and Verrucomicrobia. Members of the Proteobacteria and Acidobacterium represented 66.5% and 14.5% of the clone library, respectively, whereas the remaining bacterial divisions each comprised less than 7% of the clone library. Twenty-five 16S rDNA clones could not be classified into any known bacterial divisions. Statistical analyses showed significant differences in the presence of L. maackii on the proportions of 16S rDNA clones affiliated with Proteobacteria and Acidobacterium, suggesting bacterial community composition and structure does significantly change in the presence of L. maackii. However, sequence-based community analysis and the corresponding lack of intact microbial cultures limit understanding of the potential influences of enriched microbial taxa on plant hosts and their roles in ecosystem functioning.
America is becoming increasingly diverse. Discrimination against minority groups persists and contributes to negative disparate outcomes for patients and healthcare professionals. Healthcare professionals have a responsibility to address inequity in the medical system. This activity defines the terms "diversity" and "discrimination" and highlights the interprofessional team's role in improving care for patients from diverse backgrounds.
* Define the terms "diversity" and "discrimination" and discuss their implications in healthcare.
* Explain the different levels on which bias and discrimination occur.
* Summarize relationships between bias and negative patient outcomes.
* Outline actions that healthcare systems can take to increase diversity and reduce disparities.
The treatment of Cushing’s disease (CD) has been advanced well with the introduction of treatment options like transsphenoidal surgery, radiosurgery, bilateral adrenalectomy, and various classes of medication; however, many patients still fail to achieve disease remission. Osilodrostat, an orally bioavailable adrenal steroidogenesis inhibitor, was approved in the USA and EU in 2020 for the treatment of CD.
This review provides an overview of Cushing’s disease and the newly FDA approved 11β-hydroxylase inhibitor, osilodrostat, for CD with a focus on pharmacodynamics, pharmacokinetics, safety and efficacy data, and phase 2 and 3 clinical trials.
Osilodrostat has proven clinical efficacy and tolerability in phase 2 and 3 trials with CD patients who had an inadequate or reoccurring response to transsphenoidal surgery (TSS) and conventional first-line treatment. The phase 3 trial (LINC3) had 86% of the treatment group respond with normal urinary free cortisol (UFC) level compared to 29% in the placebo group (p < 0.001). Deemed as well-tolerated in all current pivotal trials, oral osilodrostat provides a noninvasive option for patients who cannot undergo surgery or patients who have reoccurring hypercortisolemia.
The authors present a stereotypical case presentation of X-linked hypophosphatemia (XLH) and provide a review of the pathophysiology and related pharmacology of this condition, primarily focusing on the FDA-approved medication burosumab. XLH is a renal phosphate wasting disorder caused by loss of function mutations in the PHEX gene (phosphate-regulating gene with homologies to endopeptidases on the X chromosome). Typical biochemical findings include elevated serum levels of bioactive/intact fibroblast growth factor 23 (FGF23) which lead to (i) low serum phosphate levels, (ii) increased fractional excretion of phosphate, and (iii) inappropriately low or normal 1,25-dihydroxyvitamin D (1,25-vitD). XLH is the most common form of heritable rickets and short stature in patients with XLH is due to chronic hypophosphatemia. Additionally, patients with XLH experience joint pain and osteoarthritis from skeletal deformities, fractures, enthesopathy, spinal stenosis, and hearing loss. Historically, treatment for XLH was limited to oral phosphate supplementation, active vitamin D supplementation, and surgical intervention for cases of severe bowed legs. In 2018, the United States Food and Drug Administration (FDA) approved burosumab for the treatment of XLH and this medication has demonstrated substantial benefit compared with conventional therapy. Burosumab binds circulating intact FGF23 and blocks its biological effects in target tissues, resulting in increased serum inorganic phosphate (Pi) concentrations and increased conversion of inactive vitamin D to active 1,25-vitD.
I believe this article emphasizes how emotionally valuable receiving patients' trust is to the practicing physician. It also gives new insight into understanding the emotional loss a physician may experience when leaving private practice, even if they remain active in medicine. Finally, for those entering medicine, it explains the profound personal satisfaction they can experience from long term trusting relationships with patients.
Women in medicine have made progress since Elizabeth Blackwell: the first women to receive her medical degree in the United States in 1849. Yet although women currently represent just over one-half of medical school applicants and matriculates, they continue to face many challenges that hinder them from entering residency, achieving leadership positions that exhibit final decision-making and budgetary power, and, in academic medicine, being promoted. Challenges include gender bias in promotion, salary inequity, professional isolation, bullying, sexual harassment, and lack of recognition, all of which lead to higher rates of attrition and burnout in women physicians. These challenges are even greater for women from groups that have historically been marginalized and excluded, in all aspects of their career and especially in achieving leadership positions. It is important to note that, in several studies, it was indicated that women physicians are more likely to adhere to clinical guidelines, provide preventive care and psychosocial counseling, and spend more time with their patients than their male peers. Additionally, some studies reveal improved clinical outcomes with women physicians. Therefore, it is critical for health care systems to promote workforce diversity in medicine and support women physicians in their career development and success and their wellness from early to late career.
Successful fracture healing requires the simultaneous regeneration of both the bone and vasculature; mesenchymal stem cells (MSCs) are directed to replace the bone tissue, while endothelial progenitor cells (EPCs) form the new vasculature that supplies blood to the fracture site. In the elderly, the healing process is slowed, partly due to decreased regenerative function of these stem and progenitor cells. MSCs from older individuals are impaired with regard to cell number, proliferative capacity, ability to migrate, and osteochondrogenic differentiation potential. The proliferation, migration and function of EPCs are also compromised with advanced age. Although the reasons for cellular dysfunction with age are complex and multidimensional, reduced expression of growth factors, accumulation of oxidative damage from reactive oxygen species, and altered signaling of the Sirtuin-1 pathway are contributing factors to aging at the cellular level of both MSCs and EPCs. Because of these geriatric-specific issues, effective treatment for fracture repair may require new therapeutic techniques to restore cellular function. Some suggested directions for potential treatments include cellular therapies, pharmacological agents, treatments targeting age-related molecular mechanisms, and physical therapeutics. Advanced age is the primary risk factor for a fracture, due to the low bone mass and inferior bone quality associated with aging; a better understanding of the dysfunctional behavior of the aging cell will provide a foundation for new treatments to decrease healing time and reduce the development of complications during the extended recovery from fracture healing in the elderly.
Bone morphogenetic proteins (BMPs) constitute the largest subdivision of the transforming growth factor-? family of ligands. BMPs exhibit widespread utility and pleiotropic, context-dependent effects, and the strength and duration of BMP pathway signaling is tightly regulated at numerous levels via mechanisms operating both inside and outside the cell. Defects in the BMP pathway or its regulation underlie multiple human diseases of different organ systems. Yet much remains to be discovered about the BMP pathway in its original context, i.e., the skeleton. In this review, we provide a comprehensive overview of the intricacies of the BMP pathway and its inhibitors in bone development, homeostasis, and disease. We frame the content of the review around major unanswered questions for which incomplete evidence is available. First, we consider the gene regulatory network downstream of BMP signaling in osteoblastogenesis. Next, we examine why some BMP ligands are more osteogenic than others and what factors limit BMP signaling during osteoblastogenesis. Then we consider whether specific BMP pathway components are required for normal skeletal development, and if the pathway exerts endogenous effects in the aging skeleton. Finally, we propose two major areas of need of future study by the field: greater resolution of the gene regulatory network downstream of BMP signaling in the skeleton, and an expanded repertoire of reagents to reliably and specifically inhibit individual BMP pathway components.
Bone morphogenetic proteins (BMPs) constitute the largest subdivision of the transforming growth factor (TGF)-? family of ligands and exert most of their effects through the canonical effectors Smad1, 5, and 8. Appropriate regulation of BMP signaling is critical for the development and homeostasis of numerous human organ systems. Aberrations in BMP pathways or their regulation are increasingly associated with diverse human pathologies, and there is an urgent and growing need to develop effective approaches to modulate BMP signaling in the clinic. In this review, we provide a wide perspective on diseases and/or conditions associated with dysregulated BMP signal transduction, outline the current strategies available to modulate BMP pathways, highlight emerging second-generation technologies, and postulate prospective avenues for future investigation.
Osteoporosis, a disease of low bone mass, places individuals at enhanced risk for fracture, disability, and death. In the USA, hospitalizations for osteoporotic fractures exceed those for heart attack, stroke, and breast cancer and, by 2025, the number of fractures due to osteoporosis is expected to rise to nearly three million in the USA alone. Pharmacological treatments for osteoporosis are aimed at stabilizing or increasing bone mass. However, there are significant drawbacks to current pharmacological options, particularly for long-term management of this chronic condition. Moreover, the drug development pipeline is relatively bereft of new strategies. Consequently, there is an urgent and unmet need for developing new strategies and targets for treating osteoporosis. Casual observation led us to hypothesize that much of the bone remodeling research literature focused on relatively few molecular pathways. This led us to perform bibliometric analyses to determine the relative popularity of bone remodeling pathways in publications and US National Institutes of Health funding of the last 10 years. In this review article, we discuss these findings and highlight several less-examined signaling pathways that may hold promise for future therapies.