Parvifoline Derivatives as Tubulin Polymerization Inhibitors.

A series of functionalized sesquiterpenoids derived from benzocyclooctene, including natural parvifoline (1), isoparvifoline (3), epoxyparvifoline (5), epoxyisoparvifoline (7), 8,12-oxyparfivoline (9), 8,14-oxyparvifoline (11), and the respective benzoyl derivatives 2, 4, 6, 8, 10, and 12, were prepared and tested for their inhibitory effect on the in vitro α,ß-tubulin polymerization process. The structural analysis and characterization of the new compounds 5-7 and 9-12 were achieved by 1D and 2D NMR spectroscopy, mass spectrometry, and X-ray diffraction analysis of 6, 7, and 9. Preparation of 9 and 12 involved molecular rearrangements of the epoxide group with transannular 1,5-hydride shifts. At 10 µM compounds 1, 5, and 8 inhibited the polymerization of the α,ß-tubulin heterodimer by 24%, 49%, and 90% as compared to colchicine. These compounds were subjected to docking analysis that supported their interactions in a colchicine binding site located in the α-tubulin subunit, in the pocket formed by Phe296, Pro298, Pro307, His309, Tyr312, Lys338, Thr340, Ile341, and Gln342. Competitive inhibition assays with colchicine were also performed for the three compounds, which supported their binding at the colchicine secondary site in α-tubulin. Also, evaluations of their cytotoxicity on MCF7 breast carcinoma, HeLa cervix carcinoma, and HCT 116 colon carcinoma cell lines were carried out and showed that 8 is active against the HeLa and HCT 116 cell lines with IC50 3.3 ± 0.2 and 5.0 ± 0.5 µM, respectively.

Processing of fallopian tube, ovary, and endometrial surgical pathology specimens: A survey of U.S. laboratory practices.

OBJECTIVE: Many high-grade serous carcinomas initiate in fallopian tubes as serous tubal intraepithelial carcinoma (STIC), a microscopic lesion identified with specimen processing according to the Sectioning and Extensive Examination of the Fimbria protocol (SEE-Fim). Given that the tubal origin of these cancers was recently recognized, we conducted a survey of pathology practices to assess processing protocols that are applied to gynecologic surgical pathology specimens in clinical contexts in which finding STIC might have different implications. METHODS: We distributed a survey electronically to the American Society for Clinical Pathology list-serve to determine practice patterns and compared results between practice types by chi-square (χ2) tests for categorical variables. Free text comments were qualitatively reviewed. RESULTS: Survey responses were received from 159 laboratories (72 academic, 87 non-academic), which reported diverse specimen volumes and percentage of gynecologic samples. Overall, 74.1% of laboratories reported performing SEE-Fim for risk-reducing surgical specimens (82.5% academic versus 65.7% non-academic, p < 0.05). In specimens from surgery for benign indications in which initial microscopic sections showed an unanticipated suspicious finding, 75.9% of laboratories reported using SEE-Fim to process the remainder of the specimen (94.8% academic versus 76.4% non-academic, p < 0.01), and 84.6% submitted the entire fimbriae. CONCLUSIONS: Changes in the theories of pathogenesis of high-grade serous carcinoma have led to implementation of pathology specimen processing protocols that include detailed analysis of the fallopian tubes. These results have implications for interpreting trends in cancer incidence data and considering the feasibility of developing a bank of gynecologic tissues containing STIC or early cancer precursors.

The American Society for Clinical Pathology 2022 Vacancy Survey of medical laboratories in the United States.

OBJECTIVES: To determine the extent and distribution of laboratory workforce shortages within the nation's medical laboratories. METHODS: The Vacancy Survey was conducted through collaboration between the American Society for Clinical Pathology (ASCP) Institute for Science, Technology and Public Policy in Washington, DC, and the Evaluation, Measurement, and Assessment Department and ASCP Board of Certification in Chicago, IL. Data were collected through an internet survey distributed to individuals who were able to report on staffing and certifications for their laboratories. RESULTS: Results of the ASCP 2022 Vacancy Survey show increased overall vacancy rates for laboratory positions in all departments compared with 2020. Overall retirement rates for laboratory professionals increased across most departments. CONCLUSIONS: Current Vacancy Survey data show continued increases in the numbers of laboratory vacancies and retirements as well as changes in certification requirements, with trends amplified during the pandemic continuing into the present. Qualitative analysis results showed that there is an urgent need to focus not only on recruitment but-equally important-on retention of laboratory professionals.

Examining the role of diversity, equity, and inclusion in mitigating workforce burnout in laboratory medicine.

OBJECTIVES: The clinical laboratory workforce plays a crucial role in health care delivery, yet little is known about the unique pressures and challenges this workforce faces. The objective of this study was to identify factors that contribute to burnout, discrimination, exclusion, and inequity in pathology and laboratory medicine. METHODS: A nationwide survey was conducted in 2 phases. In phase 1, 2391 laboratory professionals were surveyed over a 1-week period about their experiences with burnout, discrimination, and work-related stress. In phase 2, the survey was extended to 1 month and questions were added to elicit more detailed information about diversity, equity, and inclusion (DEI) as well as wellness. RESULTS: Results showed a high prevalence of burnout, discrimination, and stress among laboratory professionals, with significant differences among certain demographic groups. Women, Black, indigenous, or people of color individuals and those with disabilities reported higher rates of discrimination. The study also showed a need for mentorship and resources to address educational barriers. CONCLUSIONS: Findings from this study highlight the urgent need for interventions to address burnout, discrimination, exclusion, and inequity in the laboratory workforce. Initiatives to increase workforce diversity, promote mentorship and diversity training programs, and improve recognition of the laboratory workforce are recommended. The results underscore the pressing need to addressing the challenges and apprehensions laboratory professionals face, including enhancing recognition of their role in patient care, tackling systemic problems related to discrimination and equity, and enhancing the provision of support and resources for managing burnout and fostering well-being.

Feeding sows milk biofortified with n-6 and n-3 modulates immune status of sows and drives positive transgenerational effects.

The risk of chronic diseases such as cardiovascular disease, cancer, inflammation, obesity, and autoimmune disease is linked to the quality of dietary fats, with lower intake of saturated and higher intake of n-6 and n-3 polyunsaturated fatty acids (PUFA) considered beneficial to health. This study investigated the effect of supplementing sows' diets with cow's milk biofortified with n-6 or n-3 PUFA, at varying n-6/n-3 ratios (8.26, 7.92, and 2.72) during their growing phase and throughout gestation and lactation on their reproductive performance and immune-inflammatory status. Specifically, we analyzed circulating cholesterol and fatty acid profiles of serum, colostrum and milk, sow body weight, and neonate colostrum intake, Apgar scores, muscle composition, and embryo viability. Analysis of circulating immunoglobulins (Ig), interleukins, and eicosanoids and complement system hemolytic activity were used to evaluate inflammatory and immune responses of sows and piglets. Expression of lipolysis and lipogenic genes in the liver were investigated in sows and piglets, with additional investigation of hypothalamus genes regulating appetite in sows. Feeding sows milk biofortified with n-6 and n-3 PUFA altered serum fatty acid profiles, reduced triglycerides (TG), increased embryo total number, increased early gestation backfat, and reduced colostrum IgG. Piglets of biofortified sow had higher circulating IgA, IgM and TNF-α, and lower IL-10. Sows fed n-3 biofortified milk had higher very low-density lipoproteins (VLDL) and TNF-α in circulation. Offspring from sows fed n-6 versus n-3 biofortified milk had lower IL-10 and expression levels of SREBP-1. N-3 versus n-6 also lowered arachidonic acid (ARA) levels in sow's milk and piglet viability 1. Findings offer insights into the potential health benefits of dietary supplementation with biofortified milk in swine, which serve as good model of diet-nutrition studies of humans, and therefore can potentially be considered in dietary recommendations both human and animal populations.

The American Society for Clinical Pathology's 2021 Wage Survey of Medical Laboratories in the United States.

OBJECTIVES: To inform the pathology and laboratory field of the most recent national wage data. Historically, the results of this biennial survey have served as a basis for additional research on laboratory recruitment, retention, education, marketing, certification, and advocacy. METHODS: The 2021 Wage Survey was conducted through collaboration between the American Society for Clinical Pathology (ASCP) Institute of Science, Technology, and Policy in Washington, DC, and the ASCP Board of Certification in Chicago, IL. RESULTS: Compared with 2019, results show that mean hourly wage for staff-level personnel increased for only two occupations-cytologist and medical laboratory scientist/medical technologist/clinical laboratory scientist-after adjusting for inflation. Geographically, laboratory professionals from urban areas continue to earn more than their rural counterparts. Most respondents reported no change in their salaries during the coronavirus disease 2019 pandemic. CONCLUSIONS: The pandemic had a significant effect on staffing, workload, and work-life balance of many laboratory professionals. Even with the salary increases reported from the results of this survey, it is evident that the increases have not kept up with the current inflation. Focus on visibility, recruitment and retention, and diversity are essential to develop long- and short-term solutions.

The American Society for Clinical Pathology 2020 Vacancy Survey of Medical Laboratories in the United States.

OBJECTIVES: To determine the extent and distribution of workforce shortages within the nation's medical laboratories. METHODS: The survey was conducted through collaboration between the American Society for Clinical Pathology Institute for Science, Technology, and Public Policy in Washington, DC, and the Evaluation, Measurement, and Assessment Department and Board of Certification in Chicago, IL. Data were collected via an internet survey distributed to individuals who were able to report on staffing and certifications for their laboratories. RESULTS: The coronavirus disease 2019 (COVID-19) pandemic disrupted the staffing of clinical laboratories and the stream of incoming graduates entering the workforce. Results show decreased vacancy rates for the majority of laboratory positions across all departments surveyed. The overall anticipated retirement rates continue to decline, which suggests that the field has already lost personnel with vast amounts of experience. CONCLUSIONS: Addressing the current and future needs of the laboratory workforce requires a collective effort by numerous groups of stakeholders at all levels, including the laboratory employers, laboratory training programs, health care executives/hospital administrators, and professional organizations. The time is now to address the future shortage of laboratory professionals and to create a resilient clinical laboratory professional workforce.

American Society for Clinical Pathology's 2019 Wage Survey of Medical Laboratories in the United States.

OBJECTIVES: To inform the pathology and laboratory field of the most recent national wage data. Historically, the results of this biennial survey have served as a basis for additional research on laboratory recruitment, retention, education, marketing, certification, and advocacy. METHODS: The 2019 Wage Survey was conducted through collaboration of the American Society for Clinical Pathology (ASCP) Institute of Science, Technology, and Policy in Washington, DC, and the ASCP Board of Certification in Chicago, Illinois. RESULTS: Compared with 2017, results show an overall increase in salaries for most laboratory occupations surveyed except cytogenetic technologists, laboratory information systems personnel, and performance improvement or quality assurance personnel. Geographically, laboratory professionals from urban areas earned more than their rural counterparts. CONCLUSIONS: As retirement rates continue to increase, the field needs to intensify its efforts on recruiting the next generation of laboratory personnel. To do so, the report urged the field to highlight advocacy for better salaries for laboratory personnel at the local and national levels when developing recruitment and retention strategies.

Revised Reporting (Issuing Addenda and Amendments) in Pathology.

OBJECTIVES: The purpose of this study was to align the current experiences and best practices in revised reporting (issuing of addenda and amendments) in pathology. Pathology specialties explored in the survey include anatomic pathology, surgical pathology, cytopathology, and hematopathology. METHODS: The study used a cross-sectional design in which an online revised reporting survey was deployed to a large national sample represented by pathologists, pathology residents, pathology fellows, pathology managers, and laboratory directors. RESULTS: Qualitative and quantitative results from this survey highlight significant variation in standards for creating, issuing, and tracking quality indicators related to addenda and amendments. The most notable findings were a lack of standardization and the potential for widespread adoption of revised reporting best practices within and between pathology services. CONCLUSIONS: Survey insight provides the potential for improving patient safety outcomes, engaging with consumers of our reports, providing a current state view of revised reporting, and assessing the attitudes of pathologists and laboratory professionals on how their individual approaches and team-based workflows achieve revised reports. The data generated from this survey will provide patient safety opportunities associated with accurate pathology reporting and will encourage further development of optimal pathology revised reporting guidelines.

Job Stress, Burnout, Work-Life Balance, Well-Being, and Job Satisfaction Among Pathology Residents and Fellows.

OBJECTIVES: The study explored job stress, burnout, work-life balance, well-being, and job satisfaction among pathology residents and fellows. The aims were to examine the prevalence and sources of stress and burnout, as well as identify resources to promote work-life balance and well-being and prevent burnout. METHODS: The study used a cross-sectional survey deployed online to a large national sample of pathology residents and fellows. RESULTS: Job stress and burnout were prevalent, with more than a third of the respondents reporting that they were currently experiencing burnout. The respondents, particularly residents, were struggling with academics, and higher percentages were struggling with work-life balance and emotional well-being. Overall, the majority of respondents who rated their work-life balance indicated that it was poor or fair. Among the factors contributing to job stress and burnout and detracting from work-life balance, workload was the leading factor. CONCLUSIONS: The factors contributing to job stress and burnout included organizational factors such as workload, value, and aspects of the learning environment, as well as personal factors such as work-life integration. One of the overarching implications is the need to address a range of interdependent considerations in designing resources to reduce job stress, promote work-life balance, and prevent burnout.

The American Society for Clinical Pathology's Job Satisfaction, Well-Being, and Burnout Survey of Laboratory Professionals.

OBJECTIVES: To examine job satisfaction, well-being, job stress, and burnout among laboratory professionals. METHODS: The study utilized a cross-sectional survey design. The survey was administered online via the American Society for Clinical Pathology's survey tool, to elicit information about job satisfaction, well-being, job stress, and burnout among medical laboratory professionals. RESULTS: Although this survey shows high job satisfaction among respondents, overall job-related stress is high and burnout is prevalent. The majority of the respondents rated their work-life balance as "fair." The main contributing factors to job stress, burnout, and work-life balance are quantity of workload and understaffing. CONCLUSIONS: Based on the results of this survey, creating targeted interventions may help improve the quality of well-being programs for laboratory professionals. A comprehensive wellness program developed at the institutional, local, and national levels may improve morale and alleviate the recruitment and retention challenges faced by medical laboratory professionals.

The American Society for Clinical Pathology's Job Satisfaction, Well-Being, and Burnout Survey of Pathologists.

OBJECTIVES: To examine job satisfaction, well-being, job stress, and burnout among pathologists. METHODS: The study utilized a cross-sectional survey design. The survey was administered online via the American Society for Clinical Pathology's (ASCP's) survey tool to elicit information about job satisfaction, well-being, job stress, and burnout among pathologists. RESULTS: Job satisfaction is high and well-being is rated fair to good by most respondents. However, feelings of anxiety or worry about work, high levels of stress, and burnout are prevalent among pathologists. The main contributing factor to job stress, burnout, and work-life balance is quantity of workload. CONCLUSIONS: Creating targeted interventions based on the results of this survey may help improve the type and quality of wellness programs for pathologists. Trust among team members, managers and clinicians, and institutions can help reduce stress and increase collaboration, engagement, and motivation.

Effect of anticoagulant adjustment on prothrombin time test using two different PT reagents in patients with elevated hematocrit.

The recommendations for adjustment of citrate volume in sample tubes with high hematocrit (Ht) are based on indirect studies of underfilled tubes or artificially constructed Ht values. The aim of this study was to evaluate the effect of citrate volume adjustment in sample tubes from patients with hematocrit >55% using two different prothrombin time (PT) tests. METHODS: Paired citrate-adjusted and unadjusted blood specimens were obtained from 181 patients from the pulmonary hypertension ambulatory with high Ht values and on warfarin therapy. The samples were tested using recombinant human tissue factor (RTF) and reagents extracted from rabbit brain (HS Plus). The results are expressed as the international normalized ratio (INR). The correlation and percent change (% change) between sample pairs were calculated. RESULTS: INR-RTF results from adjusted and unadjusted citrate blood specimens showed a strong correlation (R2 â€‹= â€‹0.8226, p â€‹< â€‹0.0001). The INR median was 2.25 (95% CI 2.10 to 2.41) for citrate-adjusted samples and was 2.22 (95% CI 2.06 to 2.38) for citrate-unadjusted samples. For samples with Ht >62%, the % change between sample pairs was >10%. Results using HS Plus showed a moderate correlation between citrate-adjusted and unadjusted samples (R2 â€‹= â€‹0.4267, p â€‹< â€‹0.0001). The INR median was 2.51 (95% CI 2.35 to 2.68) for citrate-adjusted samples and 3.45 (95% CI 3.11 to 3.80) for citrate-unadjusted samples. For samples with Ht>55%, the % change between sample pairs was higher than 10%. CONCLUSION: Our data demonstrate that in patients with polycythemia on warfarin therapy, INR-RTF does not require anticoagulant adjustment for assessment of samples with Ht <62%.

The American Society for Clinical Pathology's 2017 Wage Survey of Medical Laboratories in the United States.

Objectives: To inform the pathology and laboratory field of the most recent national wage data. Historically, the results of this biennial survey have served as a basis for additional research on laboratory recruitment, retention, education, marketing, certification, and advocacy. Methods: The 2017 Wage Survey was conducted through collaboration between the American Society for Clinical Pathology's (ASCP's) Institute of Science, Technology, and Policy in Washington, DC, and the ASCP Board of Certification in Chicago, IL. Results: Compared with 2015, results show an overall increase in salaries for most of the laboratory occupations surveyed except histotechnologists and pathologists' assistants. Geographically, laboratory professionals from urban areas earn more than their rural counterparts. Conclusions: Survey results encourage laboratory professionals to be actively engaged in advocating for the profession in the workforce and educational training programs. Awareness of the career opportunities and value of the profession is needed to strengthen the future of the field.

The American Society for Clinical Pathology's 2018 Vacancy Survey of Medical Laboratories in the United States.

OBJECTIVES: To determine the extent and distribution of workforce shortages within the nation's medical laboratories. METHODS: The survey was conducted through collaboration between the American Society for Clinical Pathology's Institute of Science, Technology, and Policy in Washington, DC, and the Evaluation, Measurement, and Assessment Department and Board of Certification in Chicago, IL. Data were collected via an internet survey distributed to individuals who were able to report on staffing and certifications for their laboratories. RESULTS: Results show increased vacancy rates for laboratory positions across all departments surveyed. The overall retirement rates are at its lowest, suggesting that the field has already experienced loss of personnel with a vast amount of experience. CONCLUSIONS: Focus on retention of qualified and certified laboratory professionals would be crucial factors in addressing the needs of the laboratory workforce. The field also needs to intensify its efforts on recruiting the next generation of laboratory personnel.

CARDIOMETABOLIC RISK FACTORS ASSOCIATED WITH ACTIVE COMMUTING TO SCHOOL.

OBJECTIVE: To verify if there is an association between cardiometabolic risk factors and active daily commuting to school among children and adolescents. METHODS: A total of 1,743 schoolchildren aged 7 to 17 years old were evaluated in the city of Santa Cruz do Sul (RS). The way of commuting to school was investigated with a questionnaire, and the cardiometabolic risk factors analyzed were body mass index (BMI), waist circumference (WC), systolic (SBP) and diastolic (DBP) blood pressure, blood glucose, triglycerides, total cholesterol (TC) and fractions, LDL and HDL. RESULTS: The prevalence of active commuting among schoolchildren was 48.0% (95%CI 45.7-50.4), and it was associated, in the crude analysis, with blood glucose and LDL cholesterol levels. Passive schoolchildren had a 1.1 higher prevalence ratio of high glucose and LDL cholesterol levels. However, when sociodemographic variables were included in the model, these associations were not maintained. CONCLUSIONS: The prevalence of active commuting in the sample studied is low and it was shown to have a crude association with glucose and LDL cholesterol levels in students. However, sociodemographic factors seem to influence these associations.

The American Society for Clinical Pathology's 2016-2017 Vacancy Survey of Medical Laboratories in the United States.

OBJECTIVES: To determine the extent and distribution of workforce shortages within the nation's medical laboratories. METHODS: The 2016-2017 Vacancy Survey was conducted through collaboration between the American Society for Clinical Pathology's Institute of Science, Technology, & Policy in Washington, DC, and the Evaluation, Measurement, and Assessment division and Board of Certification in Chicago, Illinois. Data were collected via an internet survey that was distributed to individuals who were able to report on staffing and certifications for their laboratories. RESULTS: Results of the 2016-2017 Vacancy Survey shows decreased vacancy rates for laboratory positions across all departments surveyed compared with 2014. While overall, the data show that vacancy rates are decreasing, overall retirement rates and certification requirements are higher. CONCLUSIONS: Focus on the qualifications and certification status of laboratory professionals would be crucial factors in addressing the needs of the laboratory workforce. The field needs to intensify its efforts on recruiting the next generation of laboratory personnel.

Systematic Review of Non-ASCP Choosing Wisely Recommendations Relevant to Pathology and Laboratory Medicine.

OBJECTIVES: To determine non-American Society for Clinical Pathology pathology- and laboratory-related Choosing Wisely recommendations that drive effective test utilization in the laboratory. METHODS: Data were collected via a two-part web-based survey distributed to a broad sample of pathologists and laboratory professionals from a variety of institutions. RESULTS: Pathologists' most relevant recommendation: "Do not transfuse more units of blood than absolutely necessary"; highest priority: "Do not transfuse more than the minimum number of RBC units necessary to relieve symptoms of anemia or to return a patient to a safe hemoglobin range (7-8 g/dL in stable, noncardiac inpatients)." Laboratory professionals' most relevant recommendation: "Avoid testing for a Clostridium difficile infection in the absence of diarrhea"; highest priority: "Do not routinely transfuse stable, asymptomatic hospitalized patients with a hemoglobin level greater than 7 to 8 g/dL." CONCLUSIONS: Most of the highest priority, most relevant recommendations among those surveyed concerned utilization of blood products and transfusion management.

Release of interleukin-10 and neurotrophic factors in the choroid plexus: possible inductors of neurogenesis following copolymer-1 immunization after cerebral ischemia.

Copolymer-1 (Cop-1) is a peptide with immunomodulatory properties, approved by the Food and Drug Administration of United States in the treatment of multiple sclerosis. Cop-1 has been shown to exert neuroprotective effects and induce neurogenesis in cerebral ischemia models. Nevertheless, the mechanism involved in the neurogenic action of this compound remains unknown. The choroid plexus (CP) is a network of cells that constitute the interphase between the immune and central nervous systems, with the ability to mediate neurogenesis through the release of cytokines and growth factors. Therefore, the CP could play a role in Cop-1-induced neurogenesis. In order to determine the participation of the CP in the induction of neurogenesis after Cop-1 immunization, we evaluated the gene expression of various growth factors (brain-derived neurotrophic factor, insulin-like growth factor 1, neurotrophin-3) and cytokines (tumor necrosis factor alpha, interferon-gamma, interleukin-4 (IL-4), IL-10 and IL-17), in the CP at 14 days after ischemia. Furthermore, we analyzed the correlation between the expression of these genes and neurogenesis. Our results showed that Cop-1 was capable of stimulating an upregulation in the expression of the genes encoding for brain-derived neurotrophic factor, insulin-like growth factor 1, neurotrophin-3 and IL-10 in the CP, which correlated with an increase in neurogenesis in the subventricular and subgranular zone. As well, we observed a downregulation of IL-17 gene expression. This study demonstrates the effect of Cop-1 on the expression of growth factors and IL-10 in the CP, in the same way, presents a possible mechanism involved in the neurogenic effect of Cop-1.

The American Society for Clinical Pathology's 2015 Wage Survey of Medical Laboratories in the United States.

OBJECTIVES: To inform the pathology and laboratory field of the most recent national wage data from the American Society for Clinical Pathology (ASCP). Historically, the results of this biennial survey have served as a basis for additional research on laboratory recruitment, retention, education, marketing, certification, and advocacy. METHODS: The 2015 wage survey was conducted through collaboration between the ASCP's Institute of Science, Technology, & Policy in Washington, DC, and the ASCP Board of Certification in Chicago, Illinois. Electronic survey invitations were sent to individuals who are currently practicing in the field. RESULTS: Data reveal increased salaries since 2013 for all staff-level laboratory professionals surveyed except phlebotomists and pathologists' assistants. Laboratory assistants and phlebotomists, regardless of level, continue to have lower salaries while pathologists' assistants and administration personnel have higher salaries than the rest of the laboratory professions surveyed. CONCLUSIONS: Survey results put emphasis on strategic recruitment and retention by laboratory training programs and institutions that hire laboratory professionals.