Many clinicians and patients believe that endometriosis-associated pain is due to the lesions. Yet causality remains an enigma, because pain symptoms attributed to endometriosis occur in women ...without endometriosis and because pain symptoms and severity correlate poorly with lesion characteristics. Most research and reviews focus on the lesions, not the pain. This review starts with the recognition that the experience of pain is determined by the central nervous system (CNS) and focuses on the pain symptoms.
Comprehensive searches of Pubmed, Medline and Embase were conducted for current basic and clinical research on chronic pelvic pain and endometriosis. The information was mutually interpreted by a basic scientist and a clinical researcher, both in the field of endometriosis. The goal was to develop new ways to conceptualize how endometriosis contributes to pain symptoms in the context of current treatments and the reproductive tract.
Endometriotic lesions can develop their own nerve supply, thereby creating a direct and two-way interaction between lesions and the CNS. This engagement provides a mechanism by which the dynamic and hormonally responsive nervous system is brought directly into play to produce a variety of individual differences in pain that can, in some women, become independent of the disease itself.
Major advances in improving understanding and alleviating pain in endometriosis will likely occur if the focus changes from lesions to pain. In turn, how endometriosis affects the CNS would be best examined in the context of mechanisms underlying other chronic pain conditions.
As of 2020, 20% of people residing in the United States of America (U.S.) lived in rural communities. Despite rural residents tending to be older, poorer, and having greater disease burden than their ...urban counterparts, the number of rural primary care providers continues to decline. Nearly 66% of U.S. Primary Care Health Professional Shortage Areas are designated as rural. Pharmacists can help address this shortage of rural primary care providers, often serving as providers of first-contact care; however, only 12% of U.S. pharmacists practice in rural communities. To help address this gap, in 2022 an elective Rural Pharmacy course was created at the University of Minnesota College of Pharmacy by a faculty member who has rural practice experience.
The course combines formal lectures, guest presentations by rural pharmacists and student interviews with additional rural pharmacists. For the 42 students enrolled in the course in 2022 and 2023, non-parametric statistics were used to compare the percentage of students who were raised in rural communities or who otherwise had extensive exposure to rural, and compare student interest ratings (1 to 7) about practicing/living rural at the beginning and end of the course. Students also wrote end-of-course reflection papers, commenting on the course and their interviews with rural pharmacists.
Across both years, 45% of the enrolled students had previous experience in rural communities. The net change in Rural Interest scores among students completing both questionnaires was + 5 in 2022 and + 2 in 2023, both non-significant differences. The largest shifts in student interest were from "Not Sure" at the start of the course to "Interested" or "Not Interested" at the end of the course, and from "Interested" to "Very Interested." In their reflection papers nearly 60% of students reported being most impressed by their interviews with rural pharmacists.
A course addressing the benefits and challenges of practicing pharmacy in rural communities was well-received by pharmacy students. Even students who have little interest in living in a rural community can benefit from being introduced to rural culture, enabling them to provide more culturally-responsive care for patients from rural communities.
Concise Total Synthesis of Herqulines B and C He, Chi; Stratton, Thomas P; Baran, Phil S
Journal of the American Chemical Society,
01/2019, Letnik:
141, Številka:
1
Journal Article
Recenzirano
Odprti dostop
A simple total synthesis of herqulines B and C is reported, modeled on the reductive biosynthesis reported previously by other researchers. Commencing from tyrosine, these alkaloids were fashioned ...through a dimerization, macrocyclization, and four consecutive reductions. Emerging from these studies are strategic insights on the synthesis of these strained alkaloids, as well as mild conditions for the exhaustive reduction of diketopiperizines.
Conspectus Total synthesisthe ultimate proving ground for the invention and field-testing of new methods, exploration of disruptive strategies, final structure confirmation, and empowerment of ...medicinal chemistry on natural productsis one of the oldest and most enduring subfields of organic chemistry. In the early days of this field, its sole emphasis focused on debunking the concept of vitalism, that living organisms could create forms of matter accessible only to them. Emphasis then turned to the use of synthesis to degrade and reconstitute natural products to establish structure and answer questions about biosynthesis. It then evolved to not only an intricate science but also a celebrated form of art. As the field progressed, a more orderly and logical approach emerged that served to standardize the process. These developments even opened up the possibility of computer-aided design using retrosynthetic analysis. Finally, the elevation of this field to even higher levels of sophistication showed that it was feasible to synthesize any natural product, regardless of complexity, in a laboratory. During this remarkable evolution, as has been reviewed elsewhere, many of the principles and methods of organic synthesis were refined and galvanized. In the modern era, students and practitioners are still magnetically attracted to this field due to the excitement of the journey, the exhilaration of creation, and the opportunity to invent solutions to challenges that still persist. Contemporary total synthesis is less concerned with demonstrating a proof of concept or a feasible approach but rather aims for increased efficiency, scalability, and even “ideality.” In general, the molecules of Nature are created biosynthetically with levels of practicality that are still unimaginable using the tools of modern synthesis. Thus, as the community strives to do more with less (i.e., innovation), total synthesis is now focused on a pursuit for simplicity rather than a competition for maximal complexity. In doing so, the practitioner must devise outside-the-box strategies supplemented with forgotten or newly invented methods to reduce step count and increase the overall economy of the approach. The downstream applications of this pursuit not only empower students who often go on to apply these skills in the private sector but also lead to new discoveries that can impact numerous disciplines of societal importance. This account traces some select case studies from our laboratory over the past five years that vividly demonstrate our own motivation for dedicating so much effort to this classic field. In aiming for simplicity, we focus on the elusive goal of achieving ideality, a term that, when taken in the proper context, can serve as a guiding light to point the way to furthering progress in organic synthesis.
Optimising nano-carbide precipitation in tool steels Stratton, P.F.
Materials science & engineering. A, Structural materials : properties, microstructure and processing,
03/2007, Letnik:
449
Journal Article, Conference Proceeding
Recenzirano
It is well known that the wear resistance of tools can be improved using deep cold treatment to produce nucleation sites for the nano-sized carbides that form in the martensite during low temperature ...tempering following the extended treatment times. However, inconsistencies in the processing techniques used, particularly the soaking time at very low temperature and the steel's previous thermal history, have led to different conclusions as to the exact mechanisms involved. This paper reviews current thinking and attempts to explain the different results obtained in terms of the processing parameters and to elucidate the implications for the practical application of the technique to obtain optimum properties. An optimised process route using liquid nitrogen as the coolant is recommended and a possible technique to make further improvements in the process is suggested.
Objective To standardize the recording of surgical phenotypic information on endometriosis and related sample collections obtained at laparoscopy, allowing large-scale collaborative research into the ...condition. Design An international collaboration involving 34 clinical/academic centers and three industry collaborators from 16 countries. Setting Two workshops were conducted in 2013, bringing together 54 clinical, academic, and industry leaders in endometriosis research and management worldwide. Patient(s) None. Intervention(s) A postsurgical scoring sheet containing general and gynecological patient and procedural information, extent of disease, the location and type of endometriotic lesion, and any other findings was developed during several rounds of review. Comments and any systematic surgical data collection tools used in the reviewers' centers were incorporated. Main Outcome Measure(s) The development of a standard recommended (SSF) and minimum required (MSF) form to collect data on the surgical phenotype of endometriosis. Result(s) SSF and MSF include detailed descriptions of lesions, modes of procedures and sample collection, comorbidities, and potential residual disease at the end of surgery, along with previously published instruments such as the revised American Society for Reproductive Medicine and Endometriosis Fertility Index classification tools for comparison and validation. Conclusion(s) This is the first multicenter, international collaboration between academic centers and industry addressing standardization of phenotypic data collection for a specific disease. The Endometriosis Phenome and Biobanking Harmonisation Project SSF and MSF are essential tools to increase our understanding of the pathogenesis of endometriosis by allowing large-scale collaborative research into the condition.
Truly personalized precision medicine combines pharmacogenomics (PGx), a person's lived medication experiences and ethics; person-centeredness lies at the confluence of these considerations. A ...person-centered perspective can help inform PGx-related treatment guidelines, shared decision-making for PGx-related therapeutics and PGx-related healthcare policy. This article examines the interplay between these components of person-centered PGx-related care. Ethics concepts addressed include privacy, confidentiality, autonomy, informed consent, fiduciary responsibility, respect, the burden of pharmacogenomics knowledge for both the patient and healthcare provider and the pharmacist's ethical role in PGx-testing. Incorporating the patient's lived medication experience and ethics principles into PGx-based discussions of treatment can optimize the ethical, person-centered application of PGx testing to patient care.
Clinical management of genital chronic GvHD Hamilton, B K; Goje, O; Savani, B N ...
Bone marrow transplantation (Basingstoke),
06/2017, Letnik:
52, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Chronic GvHD (cGvHD) of the genital tract is an underreported and infrequently recognized complication of allogeneic hematopoietic cell transplantation in both male and female long-term survivors. ...Its pathophysiology, clinical manifestations and management are not well understood, and studies are limited. We thus provide a comprehensive review of genital cGvHD in both men and women, as well as discuss related issues of sexual health and viral reactivation. We further provide guidance on screening, management and long-term follow-up, as well as future priority areas of study.
BACKGROUND: Women with endometriosis may also have associated disorders related to autoimmune dysregulation or pain. This study examined whether the prevalence of autoimmune, chronic pain and fatigue ...and atopic disorders is higher in women with endometriosis than in the general female population. METHODS AND RESULTS: A cross-sectional survey was conducted in 1998 by the Endometriosis Association of 3680 USA members with surgically diagnosed endometriosis. Almost all responders had pain (99%), and many reported infertility (41%). Compared with published rates in the general USA female population, women with endometriosis had higher rates of hypothyroidism (9.6 versus 1.5%, P < 0.0001), fibromyalgia (5.9 versus 3.4%, P < 0.0001), chronic fatigue syndrome (4.6 versus 0.03%, P < 0.0001), rheumatoid arthritis (1.8 versus 1.2%, P = 0.001), systemic lupus erythematosus (0.8 versus 0.04%, P < 0.0001), Sjögren’s syndrome (0.6 versus 0.03%, P < 0.0001) and multiple sclerosis (0.5 versus 0.07%, P < 0.0001), but not hyperthyroidism or diabetes. Allergies and asthma were more common among women with endometriosis alone (61%, P < 0.001 and 12%, P < 0.001 respectively) and highest in those with fibromyalgia or chronic fatigue syndrome (88%, P < 0.001 and 25%, P < 0.001 respectively) than in the USA female population (18%, P < 0.001 and 5%, P < 0.001 respectively). CONCLUSIONS: Hypothyroidism, fibromyalgia, chronic fatigue syndrome, autoimmune diseases, allergies and asthma are all significantly more common in women with endometriosis than in women in the general USA population.
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