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Vitamin C is known to stimulate procollagen, enhance collagen synthesis, and stimulate alkaline phosphatase activity, a marker for osteoblast formation. Studies of dietary vitamin C intake and the relation with [...]

Background: For many complex cardiovascular procedures the well-established link between volume and outcome has rested on the underlying assumption that experience leads to more reliable implementation of the processes of care which have been associated with better clinical outcomes. This study tested that assumption by examining the relationship between cardiovascular case volumes and the implementation of twelve basic evidence-based processes of cardiovascular care.Method and Results: Observational analysis of over 3000 US hospitals submitting cardiovascular performance indicator data to The Joint Commission on during 2005. Hospitals were grouped together based upon their annual case volumes and indicator rates were calculated for twelve standardized indicators of evidence-based processes of cardiovascular care (eight of which assessed evidenced-based processes for patients with acute myocardial infarction and four of which evaluated evidenced-based processes for heart failure patients). As case volume increased so did indicator rates, up to a statistical cut-point that was unique to each indicator (ranging from 12 to 287 annual cases). t-Test analyses and generalized linear mixed effects logistic regression were used to compare the performance of hospitals with case volumes above or below the statistical cut-point. Hospitals with case volumes that were above the cut-point had indicator rates that were, on an average, 10 percentage points higher than hospitals with case volumes below the cut-point (P < 0.05).Conclusion: Hospitals treating fewer cardiovascular cases were significantly less likely to apply evidence-based processes of care than hospitals with larger case volumes, but only up to a statistically identifiable cut-point unique to each indicator. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The authors report the association of balding or graying with BMD in older adults. METHOD: BMD was measured at the spine, hip, and total body in 1,207 participants. Of these, 508 women and 380 men responded to a 1986 survey about balding patterns; in 1994, all participants answered questions about graying. RESULTS: Among men, 10.7% reported graying, and 51.1%, balding; 9.9% of women reported graying, and 9.5%, balding. Models were adjusted for age, body mass index, alcohol consumption, smoking, exercise, calcium supplements, diuretics, glucocorticoids, thyroid hormone, and estrogen. CONCLUSION: Graying was not significantly associated with BMD in either group. Balding men averaged 5% lower total body BMD (p

Objective: To determine the effect of the timing of initiation and the duration of postmenopausal estrogen therapy on bone mineral density (BMD).Design: Cross-sectional study.Setting: White, middle-class to upper middle-class community-dwelling women.Participants: A total of 740 women aged 60 to 98 years who participated in a study of osteoporosis.Measurements: Questionnaire, validated medication use, and height and weight. Bone mineral density at the ultradistal radius and midshaft radius using single-photon absorptiometry (SPA) and at the hip and lumbar spine using dual-energy x-ray absorptiometry (DEXA).Results: Of the 740 women, 69% had used oral estrogen after menopause and 30% were current users. Five groups of estrogen use were identified: never users, past users who started at menopause, past users who started after age 60 years, current users who started after age 60 years, and current users who started at menopause. At all 4 bone sites, current users who started at menopause had the highest BMD levels, which were significantly higher than never users or past users who started at menopause (with 10 years' duration of use). These differences persisted after controlling for all major risk factors for osteoporosis. Among current users, there was no significant difference in BMD levels at any site between those who started estrogen at menopause (with 20 years of use) and those who started after age 60 years (with 9 years of use).Conclusions: Estrogen initiated in the menopausal period and continued into late life is associated with the highest bone density. Nevertheless, estrogen begun after age 60 years and continued appears to offer nearly equal bone-conserving benefit. [ABSTRACT FROM AUTHOR]

Objective: To determine the effect of long-term use of thyroid hormone on bone mineral density (BMD) in elderly women and the potential mitigating effects of estrogen replacement therapy.Design: Cross-sectional, community-based study.Setting: Rancho Bernardo, Calif.Participants: A total of 991 white women aged 50 to 98 years who participated in a study of osteoporosis.Main Outcome Measures: Bone mineral density at the ultradistal radius and midshaft radius using single-photon absorptiometry and at the hip and lumbar spine using dual-energy x-ray absorptiometry.Results: A total of 196 women taking thyroid hormone for a mean duration of 20.4 years were compared with 795 women who were not using thyroid hormone. Women taking daily thyroxine-equivalent doses of 200 micrograms or more had significantly lower BMD levels at the midshaft radius and hip compared with those taking less than 200 micrograms. Daily doses of 1.6 micrograms/kg and greater were associated with lower bone mass at all four sites compared with nonuse, whereas doses less than 1.6 micrograms/kg were not associated with lower BMD levels. These associations were independent of age, body mass index, smoking status, and use of thiazides, corticosteroids, and estrogen. Women taking both estrogen and a thyroid hormone dose of 1.6 micrograms/kg or greater had significantly higher BMD levels at all four sites than women taking the same thyroid hormone dose alone. Women taking both thyroid hormone and estrogen had BMD levels comparable with those observed in women taking only estrogen.Conclusions: Long-term thyroid hormone use at thyroxine-equivalent doses of 1.6 micrograms/kg or greater was associated with significant osteopenia at the ultradistal radius, midshaft radius, hip, and lumbar spine. Estrogen use appears to negate thyroid hormone-associated loss of bone density in postmenopausal women. [ABSTRACT FROM AUTHOR]

Purpose: This study examined the health-related quality of life (HRQoL) among ethnically diverse Black men (BM) with prostate cancer (CaP) in the United States., Methods: A convergent parallel mixed-methods design, employing both qualitative and quantitative research, involved recruiting Black CaP survivors through multiple channels. The target population was native-born BM (NBBM), African-born BM (ABBM), and Caribbean-born BM (CBBM). QoL for all men was assessed using The Functional Assessment Cancer Therapy-Prostate (FACT-P) measure, which includes five domains: physical- (PWB), emotional- (EWB), social-(SWB), and functional-wellbeing (FWB), and a CaP subscale (PCS). A subset of men completed qualitative interviews. Demographic and clinical characteristics were also collected., Results: Black CaP survivors aged 49-85 participated in the study (n = 108), with a subset (n = 31) completing a qualitative interview. Participants were mainly NBBM (72.2%) and treated with radiotherapy (51.9%). The FACT-P scale total mean score (± SD) was 114 ± 24.1 (theoretical range 0-156), with lower scores reported on the SWB, FWB, and EWB domains. The mixed-methods findings approach included meta-inferences derived from integrating the corresponding quantitative and qualitative data, covering all the domains within the FACT-P., Conclusion: Black CaP survivors experienced significant burdens that impacted their overall HRQoL. The analysis revealed impacts on physical, social, and emotional well-being, with variations among ethnic groups suggesting the need for culturally tailored interventions. EWB was also profoundly impacted by CaP treatment, with universal emotional burdens emphasized across all groups. Healthcare providers must recognize and address these multifaceted needs to promote better outcomes and HRQoL for Black CaP survivors., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Prostate cancer disproportionately affects Black men in the United States, leading to higher mortality rates and health disparities. In addition, based on historical mistreatment and discrimination and the resulting distrust of the medical system, Black populations are consistently underrepresented in health care-related research. Addressing these challenges requires community-driven approaches integrating diverse perspectives and fostering equitable health outcomes. This article describes the formation and impact of The Multidisciplinary Health Outcomes Research and Economics (MORE) Lab Community Advisory Board (CAB) at The University of Oklahoma Health Sciences. We purposefully recruited Black men with CaP and Black health care professionals to serve on a CAB and advise on ongoing research to address quality of life (QoL) issues in ethnically diverse Black CaP survivors. The CAB seeks to mitigate CaP disparities and improve health equity by empowering Black voices and promoting collaborative research practices. The MORE Lab CAB has successfully provided a venue for community members to contribute to designing a culturally relevant research program to improve the QoL in ethnically diverse Black men with CaP. The CAB has been instrumental in developing research goals and tools, implementing a series of town hall meetings to educate and support Black CaP survivors, and disseminating research findings. In conclusion, CABs are potentially critical in guiding research, enhancing community engagement, and advocating for culturally responsive health interventions., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Physiology is an important field for students to gain a better understanding of biological mechanisms. Yet, many students often find it difficult to learn from lectures, resulting in poor retention. Here, we utilize a learning workshop model to teach students at different levels ranging from middle school to undergraduate. We specifically designed a workshop to teach students about mitochondria - endoplasmic reticulum contact (MERC) sites. The workshop was implemented for middle school students in a laboratory setting that incorporated a pretest to gauge prior knowledge, instructional time, hands-on activities, interactive learning from experts, and a posttest. We observed that the students remained engaged during the session of interactive methods, teamed with their peers to complete tasks, and delighted in the experience. Implications for the design of future physiological workshops are further offered. NEW & NOTEWORTHY This manuscript offers a design for a workshop that utilizes blended learning to engage middle school, high school, and undergraduate students while teaching them about mitochondria-endoplasmic reticulum contact sites.

Identity matters in science, technology, engineering, mathematics, and medicine (STEMM) because it can affect an individual's long-term sense of belonging, which may in turn affect their persistence in STEMM. Early K-12 science classes often teach students about the foundational discoveries of the field, which have been predominately made, or at least published, by White men. This homogeneity can leave underrepresented individuals in STEMM feeling isolated, and underrepresented K-12 students may feel as though they cannot enter STEMM fields. This study aimed to examine these feelings of inclusivity in STEMM through an interactive workshop that asked middle schoolers to identify scientists from images of individuals with various racial and gender identities. We found that a plurality of students had a positive experience discussing diversity in science and recognizing underrepresented individuals as scientists. NEW & NOTEWORTHY We observed positive sentiments from middle school students following a workshop that showcased diversity in science. This workshop uniquely encourages students to recognize that physiologists and scientists today are much more diverse than textbooks typically demonstrate and can be adapted for middle schoolers, high schoolers, and college students.

Purpose: Prostate cancer (CaP) is the most common cancer in Black men (BM), and the number of Black CaP survivors is rapidly increasing. Although Black immigrants are among the fastest-growing and most heterogeneous ethnic groups in the USA, limited data exist regarding their CaP experiences. Therefore, this study aimed to explore and model the experiences of ethnically diverse Black men with CaP., Methods: In-depth interviews were conducted with 34 participants: native-born BM (NBBM) (n = 17), African-born BM (ABBM) (n = 11), and Caribbean-born BM (CBBM) (n = 6) CaP survivors recruited through QR code-embedded flyers posted in Black businesses, clinics, social media platforms, and existing research networks within the USA. Guided by Charmaz's constructivist grounded theory methodology, the interviews were analyzed using constant comparison following key stages of initial, focused, and theoretical coding using Atlas.ti v23., Results: Participants were thirty-four men aged 49-84 years (mean ± SD, 66 ± 8). Most were married (77%), likely to be diagnosed at stage I (35%), and treated with radiotherapy (56%). Our study findings explored the complex trajectory of Black prostate cancer (CaP) survivors, unveiling a comprehensive model termed "Journeying through Unfamiliar Terrain." Comprising three phases and 11 sub-phases, this model uniquely captures the pre-diagnosis awareness and post-treatment adaptation among survivors., Conclusion: The resulting theoretical model delineates the entire CaP survivorship process among BM, providing contextual and conceptual understanding for developing interventions and enhancing patient-centered care for ethnically diverse CaP survivors, pivotal in bridging the gaps in survivorship research and healthcare practices., Implications for Cancer Survivors: Black CAP survivors experience significant burdens and challenges that impact their overall quality of life. Understanding the factors that impact the complex survivorship journey can inform design and implementation of interventions to address the multiple challenges and thus improve quality of life., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Chronic kidney disease (CKD) is associated with adverse outcomes and higher costs after lower extremity arthroplasty from higher rates of infection, aseptic loosening, and transfusion and longer hospital length of stay (LOS). The purpose of this study was to compare health care utilization and 90-day encounter charges after shoulder arthroplasty (SA) in patients with and without renal disease. A secondary aim was to define the characteristics of patients with renal disease., Methods: We conducted a retrospective cohort study of all patients who underwent primary SA from January 2015 to December 2019 by a single surgeon at a single institution. Patients without a baseline glomerular filtration rate (GFR) were excluded. We evaluated results for patients with CKD (GFR ≤59 mL/min/1.73 m 2 ) and without CKD (GFR ≥60 mL/min/1.73 m 2 ). Univariate regression was performed to assess the influence of CKD on health care utilization, including LOS, transfusion, and risk for emergency department (ED) revisit or readmission during the 90-day postoperative period. In addition, 90-day encounter charges, revisit charges, and ED charges for patients with CKD were compared with those for patients with normal renal function. Last, multivariable linear regression models were used to assess the effect of estimated GFR on total 90-day encounter charges., Results: A total of 514 patients met the study inclusion criteria, with 125 having CKD and 389 having normal GFR. Patients with CKD were more likely to require transfusion (odds ratio: 16.2 [confidence interval: 1.9, 139.7], P = .011) despite similar intraoperative estimated blood loss (156.9 ± 132.5 mL vs. 153.8 ± 89.7 mL; P = .768). In addition, patients with CKD had longer LOS (2.8 ± 1.3 days vs. 2.3 ± 1.0 days; P < .001), had higher 90-day readmission rates (P = .001), were more likely to visit the ED within 90 days after SA (P = .018), and had higher total 90-day encounter charges ($37,769 ± $6901 vs. $35,684 ± $5312; P = .001). Each unit increase in eGFR independently reduced total encounter charges by $67 (-$132, -$2; P = .043); dialysis patients incurred higher total 90-day encounter charges compared with patients with less severe renal disease ($42,733 ± $8985 vs. $37,531 ± $6749; P = .002). Also, patients with CKD were older (73.2 ± 8.9 vs. 68.1 ± 9.4 years; P < .001); had a lower preoperative hemoglobin level (12.4 ± 1.5 g/dL vs. 13.4 ± 1.5 g/dL; P < .001), higher American Society of Anesthesiologists score (P < .001), and more preoperative comorbidities (5.9 ± 2.9 vs. 5.0 ± 3.1; P < .001); and were more likely to use opioids preoperatively (P = .043)., Conclusion: Patients with CKD have a higher risk for blood transfusion, ED visits, and readmission after SA, with higher total 90-day encounter charges. Identifying and optimizing this patient population before surgery can reduce costs and improve outcomes, which benefits patients, physicians, institutions, and payors., (Copyright © 2023. Published by Elsevier Inc.)

There remains a clear deficiency in recruiting middle school students in science, technology, engineering, mathematics, and medicine fields, especially for those students entering physiology from underrepresented backgrounds. A large part of this may be arising from a disconnect between how science is typically practiced at a collegiate and K-12 level. Here, we have envisioned mitochondria and their diverse subcellular structures as an involver for middle school students. We present the framework for a workshop that familiarizes students with mitochondria, employing three-dimensional visual-spatial learning and real-time critical thinking and hypothesis forming. This workshop had the goal of familiarizing middle school students with the unique challenges the field currently faces and better understanding the actuality of being a scientist through critical analysis including hypothesis forming. Findings show that middle school students responded positively to the program and felt as though they had a better understanding of mitochondria. Future implications for hands-on programs to involve underrepresented students in science are discussed, as well as potential considerations to adapt it for high school and undergraduate students. NEW & NOTEWORTHY Here we employ a workshop that utilizes blended and tactile learning to teach middle schoolers about mitochondrial structure. By creating an approachable and fun workshop that can be utilized for middle school students, we seek to encourage them to join a career in physiology.

Underrepresented faculty have higher burnout rates and lower grant attainment rates when compared with their non-minority counterparts. Many in science, technology, engineering, mathematics, and medicine (STEMM) disciplines, including underrepresented individuals, often have difficulty dedicating time to the writing process, with trainees often being relegated to laboratory tasks in their training years, resulting in a lack of practice in academic writing. Notably, past studies have shown that grant attainment rates of underrepresented individuals are lower than their majority counterparts. Here, we sought to consider a mechanism targeted to underrepresented individuals, although applicable to everyone, to help overcome traditional barriers to writing in STEMM. The authors have hosted a writing accountability group (WAG) that uniquely provides a format focused on physical activity and different forms of writing to strengthen both career development and award/funding attainment. Our objectives were to evaluate this unique format, thus creating a resource for individuals and institutions to learn about WAGs and expand upon the framework to formulate their own WAG. To do this, we performed a small pilot study (n = 21) to investigate attitudes towards the WAG. We present the results of a survey conducted among underrepresented WAG participants, which spanned different career stages and was highly diverse demographically. Our results show that following attendance of our WAG, individuals did not note a significant change in scales pertaining to John Henryism (high-effort coping), resilience, sense of belonging, or grit. However, significant increases were noted in the self-perceived ability to handle stress, confidence in applying for awards, appreciation for mentoring, and satisfaction of WAGs. Taken together, the results of this study suggest that our unique WAG format can have some positive results as a career and writing development opportunity and may be able to support underrepresented individuals in attaining funding at higher education institutions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Extranodal extension (ENE) is a pattern of cancer growth from within the lymph node (LN) outward into perinodal tissues, critically defined by disruption and penetration of the tumor through the entire thickness of the LN capsule. The presence of ENE is often associated with an aggressive cancer phenotype in various malignancies including head and neck squamous cell carcinoma (HNSCC). In HNSCC, ENE is associated with increased risk of distant metastasis and lower rates of locoregional control. ENE detected on histopathology (pathologic ENE; pENE) is now incorporated as a risk-stratification factor in human papillomavirus (HPV)-negative HNSCC in the eighth edition of the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC) TNM classification. Although ENE was first described almost a century ago, several issues remain unresolved, including lack of consensus on definitions, terminology, and widely accepted assessment criteria and grading systems for both pENE and ENE detected on radiological imaging (imaging-detected ENE; iENE). Moreover, there is conflicting data on the prognostic significance of iENE and pENE, particularly in the context of HPV-associated HNSCC. Herein, we review the existing literature on ENE in HNSCC, highlighting areas of controversy and identifying critical gaps requiring concerted research efforts., Competing Interests: HM reports grants from UK National Institute of Health research, Cancer Research UK, the UK Medical Research Council, and AstraZeneca; advisory board fees from AstraZeneca, MSD, Merck, Nanobiotix, and Seagen; and is Director of Warwickshire head neck clinic and Docpsert Health. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Henson, Abou-Foul, Morton, McDowell, Baliga, Bates, Lee, Bonomo, Szturz, Nankivell, Huang, Lydiatt, O’Sullivan and Mehanna.)

Maximizing Access to Research Careers (MARC) programs are aimed to increase diversity in science, technology, engineering, math, and medicine (STEMM) fields. However, limited programs and eligibility requirements limit the students who may apply to similar programs. At Winston-Salem State University, we piloted a series of workshops, collectively termed Project Strengthen, to emulate some of the key aspects of MARC programs. Following the workshop, Project Strengthen students showed a significant increase in their understanding of essential educational development skills, such as writing personal statements, applying to graduate school, studying for the GRE, and seeking summer internships. This suggests Project Strengthen may be a potential lower cost comparable option than MARC to make up for current deficiencies in preparedness for graduate school. We also provide educational materials from Project Strengthen, including a clear framework for this seminar series, six ready-made PowerPoints to share with trainees that have been demonstrated to be effective., Competing Interests: Authors declare that they have no competing interests., (© 2023 The Author(s).)

The Drosophila polyadenosine RNA binding protein Nab2, which is orthologous to a human protein lost in a form of inherited intellectual disability, controls adult locomotion, axon projection, dendritic arborization, and memory through a largely undefined set of target RNAs. Here, we show a specific role for Nab2 in regulating splicing of ~150 exons/introns in the head transcriptome and focus on retention of a male-specific exon in the sex determination factor Sex-lethal ( Sxl ) that is enriched in female neurons. Previous studies have revealed that this splicing event is regulated in females by N6-methyladenosine (m 6 A) modification by the Mettl3 complex. At a molecular level, Nab2 associates with Sxl pre-mRNA in neurons and limits Sxl m 6 A methylation at specific sites. In parallel, reducing expression of the Mettl3, Mettl3 complex components, or the m 6 A reader Ythdc1 rescues mutant phenotypes in Nab2 flies. Overall, these data identify Nab2 as an inhibitor of m 6 A methylation and imply significant overlap between Nab2 and Mettl3 regulated RNAs in neuronal tissue., Competing Interests: BJ, CL, JR, BB, SL, AB, DM, RB, MF, IK, MT, KM, AC, KM No competing interests declared, (© 2023, Jalloh, Lancaster et al.)

We are 52 Black scientists. Here, we establish the context of Juneteenth in STEMM and discuss the barriers Black scientists face, the struggles they endure, and the lack of recognition they receive. We review racism's history in science and provide institutional-level solutions to reduce the burdens on Black scientists., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Advanced squamous cell carcinoma (SCCa) of the oral cavity is often not amenable to curative-intent therapy due to tumor location, tumor size, or comorbidities., Case Presentation: A 51-year-old male patient with human immunodeficiency virus and on highly active antiretroviral therapy (HAART) presented with a cT4aN2c SCCa of the tongue. He received a preoperative single course of Quad-Shot radiation therapy to 14 Gy in 4 fractions followed by surgical resection. Patient had no residual carcinoma on surgical pathology and no evidence of disease on subsequent clinical and radiological exams., Conclusions: To our knowledge, this is the first case of pathologic complete response for a patient on HAART following a single cycle of the Quad-Shot regimen for advanced oral cavity SCCa. Protease inhibitors in HAART can induce spontaneous tumor regression via inhibition of proteasome function and activation of apoptosis, and thus act as a cancer therapeutic., (© 2022. The Author(s).)

Despite efforts to increase diversity, a glaring underrepresentation of minorities (URM) persists in the fields of science, technology, engineering, and mathematics (STEM). Graduate school can be a stressful step in the STEM pipeline, especially for students previously unaware of the structure and challenges of postgraduate education. To promote successful minority participation in STEM and prepare prospective students for the impending challenges of applying for and attending graduate school, we developed a workshop based on the mentoring and fostering of a champion-oriented mindset entitled, "The Trials and Tribulations of Graduate School: How Do You Make an Impact?." Students from the HBCU Winston-Salem State University attended the workshop, and a pre/post-a 10-point Likert scale-based survey was administered. The questions used in this seminar were newly designed by the authors as program evaluations. The results suggest that the workshop was well-received by the students and provided information that they considered helpful to help navigate the graduate school process., (© The Author(s) 2022. Published by Oxford University Press on behalf of FEMS.)

The success of mentoring derives from active and respectful listening and the willingness to learn and accept opportunities for personal growth. This shapes every trainee and their destined path in science, technology, engineering, and mathematics (STEM). The act of cultivating rapport, asking, and pondering meaningful questions, and receiving constructive feedback are critical to support a productive mentoring relationship. Successful mentoring in STEM can be established and allow mentees, especially underrepresented minorities (URMs), to flourish in an environment where they feel welcomed and supported. However, mentees from underrepresented groups often experience inadequate mentoring due to a mentor's lack of awareness, poor trainings themselves, or lack of understanding of the mentee's hardships. It is important for mentors and mentees to work together to promote diversity, equity, and inclusion (DEI) in STEM education through creativity, authenticity, and networking. We analyzed data obtained from students who attended a recent workshop that are interested in going to graduate school. Our results show that despite low initial expectations for the workshop, many students were satisfied in the knowledge they gleaned. The future and role of diversity in STEM within these underrepresented groups lies in community support and an important role that they can play in the lives of others through DEI initiatives and throughout their careers all of which involves positive mentoring., (© The Author(s) 2022. Published by Oxford University Press on behalf of FEMS.)

Despite an increase in programming to promote persons excluded by their ethnicity or race (PEER) scholars, minorities remain underrepresented in many STEM programs. The academic pipeline is largely leaky for underrepresented minority (URM) scholars due to a lack of effective mentorship. Many URM students experience microaggressions and discrimination from their mentors due to a lack of quality mentorship training. In this workshop, we provide a framework to show trainees what effective mentoring looks like. Mentees, especially URM trainees, can flourish in effective mentoring environments where they feel welcomed and can comfortably develop new ideas without feeling threatened by external factors. Effective mentoring environments provide motivational support, empathy, cultural competency, and training. This workshop explains facets of effective mentoring to students, as well as highlights to URM trainees why mentors can serve as valuable resources., (© The Author(s) 2022. Published by Oxford University Press on behalf of FEMS.)

Working with multiple mentors is a critical way for students to expand their network, gain opportunities, and better prepare for future scholastic or professional ventures. However, students from underrepresented groups (UR) are less likely to be mentored or have access to mentors, particularly in science, technology, engineering, and mathematics (STEM) fields. We developed and implemented a workshop, to provide the necessary foundation for students to be better prepared for establishing future mentorships throughout graduate and professional school. Faculty well-versed in the area of effective mentorship from multiple universities developed and delivered a 1.5-hour workshop to address the roles of a mentor, especially when it comes to UR students, and how students may effectively work with multiple mentors. This workshop was delivered to a group of students from, the Historically Black College and University (HBCU), Winston-Salem State University, and a pre/post-10-point Likert scale-based survey was administered where 1 represented strongly disagree and 10 was strongly agree. The questions used in this seminar were newly designed by the authors as program evaluations. We analyzed the raw data with nonparametric tests for comparison within paired samples. Wilcoxon matched-pairs and signed-rank tests showed statistically significant growth in student self-ratings related to the workshop learning objectives. The 'How to Handle More than One Mentor to Achieve Excellence' workshop was well-received as a component of pregraduate and preprofessional training. Incorporating workshops like this may increase student preparedness around developing and cultivating healthy mentorship relationships throughout STEM training., (© The Author(s) 2022. Published by Oxford University Press on behalf of FEMS.)

The goal of this article is to provide guidance for those who have decided to apply to graduate school with the plan to obtain a PhD in biomedical science. Choosing an appropriate graduate school and program can seem like a daunting choice. There are numerous graduate training programs that offer excellent training with multiple specific program choices at any given institution. Thus, identifying a program that provides an optimal training environment, which aligns with the applicant's training and career goals, can be daunting. There is no single training program that is ideal for all applicants, and, fortunately, there is no sole perfect place for any individual applicant to obtain a PhD. This article presents points to consider at multiple phases of this process as collected from the authors, including a senior faculty member, a junior faculty member, and four current graduate students who all made different choices for their graduate training (Fig. 1). In Phase I of the process, the vast number of choices must be culled to a reasonable number of schools/programs for the initial application. This is one of the most challenging steps because the number of training programs is very large, and most applicants will rely primarily on information readily available on the internet. Phase II is the exciting stage of visiting the program for an interview where you can ask questions and get a feel for the place. Finally, Phase III suggests information to collect following the interview when comparing choices and making a final decision. While the process may feel long and can be stressful, the good news is that making informed decisions along the way should result in multiple options that can support excellent training and career development. © 2022 Wiley Periodicals LLC., (© 2022 Wiley Periodicals LLC.)

Experimental evolution with Drosophila melanogaster has been used extensively for decades to study aging and longevity. In recent years, the addition of DNA and RNA sequencing to this framework has allowed researchers to leverage the statistical power inherent to experimental evolution to study the genetic basis of longevity itself. Here, we incorporated metabolomic data into to this framework to generate even deeper insights into the physiological and genetic mechanisms underlying longevity differences in three groups of experimentally evolved D. melanogaster populations with different aging and longevity patterns. Our metabolomic analysis found that aging alters mitochondrial metabolism through increased consumption of NAD + and increased usage of the TCA cycle. Combining our genomic and metabolomic data produced a list of biologically relevant candidate genes. Among these candidates, we found significant enrichment for genes and pathways associated with neurological development and function, and carbohydrate metabolism. While we do not explicitly find enrichment for aging canonical genes, neurological dysregulation and carbohydrate metabolism are both known to be associated with accelerated aging and reduced longevity. Taken together, our results provide plausible genetic mechanisms for what might be driving longevity differences in this experimental system. More broadly, our findings demonstrate the value of combining multiple types of omic data with experimental evolution when attempting to dissect mechanisms underlying complex and highly polygenic traits such as aging.

Background: Baseline health conditions can negatively impact cost of care and risk of complications after joint replacement, necessitating additional care and incurring higher costs. Bundled payments have been used for hip and knee replacement and the Centers for Medicare & Medicaid Services (CMS) is testing bundled payments for upper extremity arthroplasty. The purpose of this study was to determine the impact of predefined modifiable risk factors (MRFs) on total encounter charges, hospital length of stay (LOS), related emergency department (ED) visits and charges, and related hospital readmissions within 90 days after shoulder arthroplasty., Methods: We queried the electronic medical record (EPIC) for all shoulder arthroplasty cases under DRG 483 within a regional 7-hospital system between October 2015 and December 2019. Data was used to calculate mean LOS, total 90-day charges, related emergency department (ED) visits and charges, and related hospital readmissions after shoulder arthroplasty. Data for patients who had 1 or more MRFs, defined as anemia (hemoglobin < 10 g/dL), malnutrition (albumin < 3.4 g/dL), obesity (BMI > 40), uncontrolled diabetes (random glucose > 180 mg/dL or glycated hemoglobin > 8.0%), tobacco use (International Classification of Diseases, Tenth Revision, code indicating patient is a smoker), and opioid use (opioid prescription within 90 days of surgery), were evaluated as potential covariates to assess the relationship between MRFs and total encounter charges, LOS, ED visits, ED charges, and hospital readmissions., Results: A total of 1317 shoulder arthroplasty patients were identified. Multivariable analysis demonstrated that anemia (+$19,847, confidence interval [CI] $15,743, $23,951; P < .001), malnutrition (+$5850, CI $3712, $7988; P < .001), and obesity (+$2762, CI $766, $4758, P = .007) independently contributed to higher charges after shoulder arthroplasty. Mean LOS was higher in patients with anemia (5.0 ± 4.0 days vs. 2.2 ± 1.6 days, P < .001), malnutrition (3.7 ± 2.8 days vs. 2.2 ± 1.5 days, P < .001), and uncontrolled diabetes (2.8 ± 2.8 days vs. 2.3 ± 1.7 days, P = .019). Univariate risk factors associated with a significant increase in total 90-day encounter charges included anemia (+$19,345, n = 37, P < .001), malnutrition (+$6971, n = 116, P < .001), obesity (+$2615, n = 184, P = .011), and uncontrolled diabetes (+$4377, n = 66, P = .011). Univariate risk for readmission within 90 days was higher in patients with malnutrition (odds ratio 3.0, CI 1.8, 4.9; P < .001)., Conclusion: Malnutrition, obesity, and anemia contribute to significantly higher costs after shoulder arthroplasty. Medical strategies to optimize patients before shoulder arthroplasty are warranted to reduce total 90-day encounter charges, length of stay, and risk of readmission within 90 days of surgery. Optimizing patient health before shoulder surgery will positively impact outcomes and cost containment for patients, institutions, and payors after shoulder arthroplasty., (Copyright © 2021 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Background: The opioid crisis has illuminated the risks of opioid use for pain management, with renewed interest in reducing opioid consumption after common orthopedic procedures. Anti-inflammatory medication is an important component of multimodal pain management for patients undergoing orthopedic surgery. The purpose of this study was to evaluate the effect of celecoxib on pain control and opioid use after shoulder surgery., Methods: Patients scheduled for either total shoulder replacement (group 1) or rotator cuff repair (group 2) were candidates for the study. The exclusion criteria included allergy to celecoxib, coagulopathy, use of anticoagulants, baseline use of long-acting opioids, and a history of medical conditions such as myocardial infarction or stroke. Consenting patients were randomized by type of procedure using block randomization to receive either placebo or celecoxib 1 hour prior to the procedure and for 3 weeks postoperatively. The primary outcome measure assessed was opioid utilization as measured by morphine-equivalent dose (MED). Secondary outcome measures included pain scores at 3 and 6 weeks postoperatively. Data were analyzed using multiple linear regression., Results: Of 1081 patients scheduled for either total shoulder replacement or rotator cuff repair from February 2014 to February 2018, 78 were enrolled for arthroplasty (group 1, with 39 receiving celecoxib and 39 receiving placebo) and 79 were enrolled for rotator cuff repair (group 2, with 40 receiving celecoxib and 39 receiving placebo). Compared with the placebo arm, patients prescribed celecoxib took fewer MEDs by -168 (95% confidence interval [CI], -272 to -64; P < .01) at 3 weeks in the total population and by -197.7 (95% CI, -358 to -38; P = .02) in the arthroplasty group. Similarly, at 6 weeks, total MEDs used was -199 (95% CI, -356 to -42; P < .01) in the total population and -270 (95% CI, -524 to -16; P = .04) in the arthroplasty group. No statistically significant differences in opioid consumption were found between study arms in the cuff repair group, at either 3 or 6 weeks. Of note, preoperative opioid use was statistically associated with higher levels of opioid use in the total population and group 1 at 3 and 6 weeks (P < .01 for all) but not in group 2 (P > .05 for both)., Conclusions: Use of morphine equivalents was statistically significantly less at 3 and 6 weeks in patients who took celecoxib in the total population and in the arthroplasty group. Patients prescribed celecoxib for 3 weeks after shoulder surgery took less opioid medication for pain at 3 and 6 weeks. Multimodal pain control using celecoxib is an effective way to reduce postoperative opioid use in shoulder arthroplasty patients. Preoperative opioid use is associated with higher levels of opioid use after shoulder arthroplasty., (Copyright © 2020 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Background: Use of anti-inflammatory medications (NSAIDs) is an important component of multimodal pain control after orthopedic procedures to avoid opioid overutilization and abuse. However, the deleterious effects of NSAIDs on tendon healing are of particular concern in rotator cuff repair (RCR). The purpose of this study was to evaluate the effect of celecoxib or placebo on healing rates after RCR when administered in the perioperative and immediate postoperative period using MRI evaluation at one year postoperatively. A secondary aim was to determine whether clinical differences existed between patients with intact or non-intact repairs., Methods: Patients aged ≤65 years with partial- or full-thickness rotator cuff tear (<25x25 mm) were randomized to receive celecoxib 400 mg or placebo 1 hour before the procedure and 200mg bid for 3 weeks postoperatively. All patients were treated as clinically indicated at the time of surgery and followed standard postoperative protocol. Repair integrity was evaluated with MRI using the Sugaya classification for repair integrity. Data were analyzed using multivariable logistic regression by intent to treat., Results: Seventy-nine patients were enrolled; 21 were lost to follow-up, 6 did not have cuff repair, 5 were revised, and 2 declined follow-up, leaving 45 patients with one-year follow-up. Five of these patients did not complete MRI, leaving 40 patients for review. Eighteen of 20 patients (90%) who received celecoxib completed all doses of study medication as did 15 of 20 patients (75%) who received placebo. The patient groups were similar for demographics, clinical results, and healing rate. After adjusting for tear size, no statistically significant difference in healing rate was found between groups, with 10 of 20 celecoxib patients (50%) having intact repair at 1 year compared with 14 of 20 placebo patients (70%) (OR = 0.53, 95% CI: 0.14, 2.08, P  = 0.35)., Conclusion: Half of the patients who received celecoxib had an intact repair compared with 70% intact repair for patients receiving placebo. Although not statistically significant in this small study, larger studies are needed to clarify this important clinical concern. The authors do not recommend use of celecoxib for postoperative pain control after RCR., (© 2020 The Authors.)

Background: Emergency departments (EDs) have experienced an increase in annual patient visits and length of stay over the past decade. Management of frequent-user patients with pain-related diagnoses are challenging in a time-limited setting., Objective: The purpose of this study was to describe characteristics of frequent ED users with pain-related diagnoses., Methods: This was a retrospective longitudinal cohort study of hospital ED visits from two EDs in using encounters from September 2016 to August 2018. Frequent users were characterized as having four or more visits in a 1-year period and were further classified into three categories based on the number of pain-related visits in the study period. Descriptive statistics and regression analysis results are reported for all demographic and clinical characteristics for index encounters, patient level data, and pain subgroups., Results: Of all patients, 11.3% (n = 5174) were identified as frequent users, accounting for 38.9% (n = 91,114) of all ED visits. Overall, frequent pain users were more likely to be of middle age (odds ratio [OR] 1.70, 95% confidence interval [CI] 0.80-1.72), female (OR 2.43, 95% CI 1.79-3.29), have commercial insurance (OR 1.91, 95% CI 1.37-2.66), and have 10 or more ED encounters (super user status) in a 12-month period (OR 23.66, 95% CI 17.12-32.71)., Conclusion: Understanding characteristics of ED frequent users with pain-related diagnoses may inform community-based interventions designed to reduce episodic care and thereby improve care coordination and management., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The RNA exosome is an evolutionarily-conserved ribonuclease complex critically important for precise processing and/or complete degradation of a variety of cellular RNAs. The recent discovery that mutations in genes encoding structural RNA exosome subunits cause tissue-specific diseases makes defining the role of this complex within specific tissues critically important. Mutations in the RNA exosome component 3 (EXOSC3) gene cause Pontocerebellar Hypoplasia Type 1b (PCH1b), an autosomal recessive neurologic disorder. The majority of disease-linked mutations are missense mutations that alter evolutionarily-conserved regions of EXOSC3. The tissue-specific defects caused by these amino acid changes in EXOSC3 are challenging to understand based on current models of RNA exosome function with only limited analysis of the complex in any multicellular model in vivo. The goal of this study is to provide insight into how mutations in EXOSC3 impact the function of the RNA exosome. To assess the tissue-specific roles and requirements for the Drosophila ortholog of EXOSC3 termed Rrp40, we utilized tissue-specific RNAi drivers. Depletion of Rrp40 in different tissues reveals a general requirement for Rrp40 in the development of many tissues including the brain, but also highlight an age-dependent requirement for Rrp40 in neurons. To assess the functional consequences of the specific amino acid substitutions in EXOSC3 that cause PCH1b, we used CRISPR/Cas9 gene editing technology to generate flies that model this RNA exosome-linked disease. These flies show reduced viability; however, the surviving animals exhibit a spectrum of behavioral and morphological phenotypes. RNA-seq analysis of these Drosophila Rrp40 mutants reveals increases in the steady-state levels of specific mRNAs and ncRNAs, some of which are central to neuronal function. In particular, Arc1 mRNA, which encodes a key regulator of synaptic plasticity, is increased in the Drosophila Rrp40 mutants. Taken together, this study defines a requirement for the RNA exosome in specific tissues/cell types and provides insight into how defects in RNA exosome function caused by specific amino acid substitutions that occur in PCH1b can contribute to neuronal dysfunction., Competing Interests: The authors have declared that no competing interests exist.

Nontypeable strains of Haemophilus influenzae (NTHi) are one of the most common cause of otitis media and the most frequent infection associated with exacerbations of chronic obstructive pulmonary disease; there is currently no vaccine in the U.S. to prevent NTHi. Using bioinformatics and structural vaccinology, we previously identified several NTHi species-conserved and sequence-conserved peptides that mediate passive protection in the rat model of infection. Using these, and similar peptides, we designed Hi Poly 1, a Bacterial Vaccine Polypeptide, comprising 9 unique peptides from 6 different surface proteins. Recombinant Hi Poly 1 was purified by affinity chromatography. Forty chinchillas were immunized three times with 200 µg of Hi Poly 1 with alum adjuvant; similarly, 41 controls were immunized with adjuvant alone. The average Log 2 IgG titer among immunized animals was 17.04, and IgG antibodies against each component peptide were detected. In the infant rat model, antisera from immunized chinchillas provided significant passive protection compared to PBS (p = 0.01) and pre-immune sera (p = 0.03). In the established chinchilla model of NTHi otitis media, the vaccinated group cleared infection faster than the control group as indicated by significantly decreased positive findings on video-otoscopy (p < 0.0001) and tympanometry (p = 0.0002) on day 7, and for middle ear fluid obtained by aspiration (p = 0.0001) on day 10 post-infection. Using 12 representative NTHi strains in a Live-Cell ELISA, greater antibody binding to each strain was detected with post Hi Poly 1 than the pre-immune chinchilla antisera. The data from this proof-of-principle study demonstrate the effectiveness of Hi Poly 1 against the NTHi in two relevant preclinical models of bacteremia and otitis media as well as surface antibody binding across the species. The Bacterial Vaccine Polypeptide approach to a vaccine against NTHi also serves as a paradigm for development of similar vaccines to protect against other bacteria., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [PWW, DJM and TLS have submitted patent applications related to the Bacterial Vaccine Polypeptide approach]. LM and HJM declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper]., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Exosomopathies are a collection of rare diseases caused by mutations in genes that encode structural subunits of the RNA exosome complex (EXOSC). The RNA exosome is critical for both processing and degrading many RNA targets. Mutations in individual RNA exosome subunit genes (termed EXOSC genes) are linked to a variety of distinct diseases. These exosomopathies do not arise from homozygous loss-of-function or large deletions in the EXOSC genes likely because some level of RNA exosome activity is essential for viability. Thus, all patients described so far have at least one allele with a missense mutation encoding an RNA exosome subunit with a single pathogenic amino acid change linked to disease. Understanding how these changes lead to the disparate clinical presentations that have been reported for this class of diseases necessitates investigation of how individual pathogenic missense variants alter RNA exosome function. Such studies will require access to patient samples, a challenge for these very rare diseases, coupled with modeling the patient variants. Here, we highlight five recent studies that model pathogenic variants in EXOSC3, EXOSC2, and EXOSC5., Competing Interests: Conflicting Interest The authors have declared that no conflict of interest exists.

The evolutionarily conserved RNA exosome is a multisubunit ribonuclease complex that processes and/or degrades numerous RNAs. Recently, mutations in genes encoding both structural and catalytic subunits of the RNA exosome have been linked to human disease. Mutations in the structural exosome gene EXOSC2 cause a distinct syndrome that includes retinitis pigmentosa, hearing loss, and mild intellectual disability. In contrast, mutations in the structural exosome genes EXOSC3 and EXOSC8 cause pontocerebellar hypoplasia type 1b (PCH1b) and type 1c (PCH1c), respectively, which are related autosomal recessive, neurodegenerative diseases. In addition, mutations in the structural exosome gene EXOSC9 cause a PCH-like disease with cerebellar atrophy and spinal motor neuronopathy. Finally, mutations in the catalytic exosome gene DIS3 have been linked to multiple myeloma, a neoplasm of plasma B cells. How mutations in these RNA exosome genes lead to distinct, tissue-specific diseases is not currently well understood. In this chapter, we examine the role of the RNA exosome complex in human disease and discuss the mechanisms by which mutations in different exosome subunit genes could impair RNA exosome function and give rise to diverse diseases.

Purpose: To determine the cost-effectiveness of knotted (KT) versus knotless (KL) methods for rotator cuff surgical repair and to assess differences in patients' outcomes., Methods: We retrospectively identified all patients who underwent arthroscopic rotator cuff repair at 1 institution by 1 surgeon over 2 6-month periods of time (KT technique from August 1, 2013, through January 31, 2014; and KL technique from December 1, 2014, through May 31, 2015) to calculate the direct and indirect costs associated with arthroscopic KT or KL suture bridge rotator cuff repair. Patient demographics, number of anchors used, tendons repaired, procedure time, operative time, and clinical results were also evaluated. We used univariate generalized linear models with a Gaussian distribution for assessment scores and total and implant cost data., Results: We identified 87 patients for inclusion during the 2 time frames (35 KT, 54 KL). After excluding patients for tear size < 4 cm 2 (n = 42), ≤ 3 anchors (n = 5), revision surgery (n = 1), and those in whom additional procedures were performed (n = 2), 37 eligible subjects remained (n KT  = 15, n KL  = 22). Median implant costs were statistically significantly higher in the KL group than in the KT group (M KL  = $2,127, M KT  = $1,520, β = 413.7, 95% CI: 242.8, 584.6, P < .01), and more anchors were used in the KL group, with KT requiring a median of 4 anchors (IQR: 4, 5) and KL requiring a median of 5 anchors (IQR: 5, 5, P  = .02). Procedure time was cut in half with KL repair (estimated 43.5 minutes) versus KT repair (80 minutes) (β = 0.5, 95% CI: 0.4, 0.6, P < .001). Operating room time also was reduced by approximately 40% (79.5 minutes for KL; 121 minutes for KT [β = 0.6, CI: 0.6, 0.7, P < .001]). Once operating room costs were considered, median costs were found to be significantly lower in the KL group (M KL  = $3788.40, M KT  = $4262.90, β = -492.1, 95% CI: -840.0, -144.1, P < .01). No statistically significant differences were found between groups in mean preoperative, postoperative or postpreoperative differences in the visual analog scale, Simple Shoulder Test, American Shoulder and Elbow Surgeons, or University of California at Los Angeles scores ( P > 0.05 for all)., Conclusions: Despite using more anchors and incurring higher implant costs, the KL technique for rotator cuff repair required less surgical procedure time and cost less overall than the KT technique and resulted in equivalent clinical results., Level of Evidence: Level IV Economic and Decision Analyses., (© 2019 by the Arthroscopy Association of North America. Published by Elsevier Inc.)

Background: Reported blood transfusion rates after total shoulder arthroplasty (TSA) range from 4.5% to 43%, and reported risk factors include race, female sex, prosthesis type (reverse), revision, age, anemia, low preoperative hemoglobin, and number of comorbidities. The purpose of this study was to develop a predictive model for transfusion in anatomic/hemi and reverse shoulder arthroplasty patients and to estimate the transfusion rate in a community hospital setting., Methods: A retrospective cohort of 265 shoulder arthroplasties (79 anatomic, 182 reverse, and 4 hemiarthroplasties) performed consecutively by 1 surgeon at 1 institution from May 2013 to May 2016 was assembled. Two patients were excluded for insufficient data, leaving 263 patients for analysis. Sensitivity, specificity, area under the curve, and cut points using estimated blood loss (EBL), history of anemia, and preoperative hemoglobin level were calculated, based on a logistic regression model., Results: The overall transfusion rate was 2.3% (6/265). Higher EBL ( P  = .003), lower preoperative hemoglobin level ( P  = .030), and history of anemia ( P  = .088) were predictive of transfusion with a sensitivity of 80.0% and a specificity of 99.6%. In this cohort, patients with a history of anemia had transfusion risk when an EBL of ≥300 mL was combined with a preoperative hemoglobin level <10.9, resulting in a sensitivity of 1.0 and a specificity of 0.96. Factors associated with transfusion in univariate models included arthroplasty for fracture ( P < .001), cemented stem ( P < .001), length of stay ( P < .001), EBL ( P < .001), operative time ( P < .001), and preoperative hemoglobin ( P  = .004) and hematocrit levels ( P  = .004)., Conclusion: Patients with a history of anemia, a preoperative hemoglobin level <10.9, and an intraoperative EBL ≥300 mL are at high risk for transfusion after TSA., (© 2019 The Authors.)

Aims: To date, no study has demonstrated an improvement in postoperative outcomes following elective joint arthroplasty with a focus on nutritional intervention for patients with preoperative hypoalbuminaemia. In this prospective study, we evaluated differences in the hospital length of stay (LOS), rate of re-admission, and total patient charges for a malnourished patient study population who received a specific nutrition protocol before surgery., Patients and Methods: An analytical report was extracted from the electronic medical record (EMR; Epic, Verona, Wisconsin) of a five-hospital network joint arthroplasty patient data set between 2014 and 2017. A total of 4733 patients underwent joint arthroplasty and had preoperative measurement of albumin levels: 2220 at four hospitals and 2513 at the study hospital. Albumin ≤ 3.4 g/l, designated as malnutrition, was found in 543 patients (11.5%). A nutritional intervention programme focusing on a high-protein, anti-inflammatory diet was initiated in January 2017 at one study hospital. Hospital LOS, re-admission rate, and 90-day charges were compared for differential change between patients in study and control hospitals for all elective hip and knee arthroplasty patients, and for malnourished patients over time as the nutrition intervention was implemented., Results: Malnourished patients with nutritional intervention at the study hospital had shorter hospital LOS beginning in 2017 than malnourished patients at control hospitals during the same period (p = 0.04). Similarly, this cohort had significantly lower primary hospitalization charges, charges associated with hospital re-admissions, and 90-day total charges (p < 0.001). Inclusion of covariant potential confounders (age, anaemia, diabetes, and obesity) did not alter the conclusions of the primary statistical analysis., Conclusion: Joint arthroplasty outcomes were positively affected in study patients with low albumin when a high-protein, anti-inflammatory diet was encouraged. Elective surgery was neither cancelled nor delayed with a malnutrition designation. While the entire network population experienced improved postoperative outcomes, malnourished control patients did not experience this improvement. This study demonstrated that education on malnutrition can benefit patients. Cite this article: Bone Joint J 2019;101-B(7 Supple C):17-21.

Background: Risk factors in demographics and health status have been identified that increase the risk of complications after joint arthroplasty, necessitating additional care and incurring additional charges. The purpose of this study was to identify the number of patients in a hospital network database who had one or more predefined modifiable risk factors and determine their impact on average length of stay, need for additional care during the 90-day postoperative period, and the 90-day charges for care., Methods: An electronic hospital record query of 6968 lower extremity joint arthroplasty procedures under Diagnosis-Related Group 469/470 performed in 2014-2015 was reviewed, and total 90-day charges were calculated. The case mean was compared to charges for patients with modifiable risk factors: anemia (Hgb < 10 g/dL), malnutrition (albumin < 3.4 g/dL), obesity (body mass index > 45 kg/m 2 ), uncontrolled diabetes (random glucose >180 mg/dL or A1C > 8), narcotic use (prescription filled), and tobacco use (documented within 30 days before surgery). Length of stay, emergency room visits, and hospital readmission were compared., Results: Mean 90-day charges for Diagnosis-Related Group 469/470 were $36,647. Risk factors were associated with a significant increase in 90-day charges: anemia (+$ 15,869/126 patients), malnutrition (+$9270/592), obesity (+$2048/445), diabetes (+$5074/291), narcotic use (+$1801/1943), and tobacco use (+$2034/1882). Intensive care unit admission rate, emergency department visits, and hospital readmission were significantly increased for patients with each risk factor. Length of stay was higher in patients with anemia, malnutrition, diabetes, and tobacco use. When separated by elective vs fracture admission, 90-day charges were significantly higher for each risk factor., Conclusions: Medical strategies to optimize patients before joint arthroplasty are warranted to improve postoperative outcomes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Center for Medicare and Medicaid Services reimbursement is the same for hip arthroplasty performed electively for arthritis and urgently for femoral neck fracture., Methods: An analytic report of hip arthroplasty for a 5-hospital network identified 2362 cases performed from January 2014 to May 2016. Resource utilization was determined using 90-day charges., Results: The fracture population (623 hips) was older (P < .01), had more medical comorbidities (28.3% vs 3.8%, P < .01), and was more likely to be anemic and malnourished (P < .01), and had longer hospital stay (5.7 vs 3.0 days, P < .0001), more frequent intensive care unit admission (4.5% vs 0.5%, P < .01), less frequent discharge to home (16.2% vs 83.6%, P < .01), more emergency department visits (26.5% vs 10.7%, P < .01), and more readmissions after hospital discharge (25.2% vs 12.2%, P < .01). Utilization of services ($50,875 vs $38,705, P < .0001) and the standard deviation of these services ($22,509 vs $9,847, P < .0001), from 90-day charges, were significantly greater in the fracture population., Conclusion: This study supports exclusion of fracture care from the Comprehensive Care for Joint Replacement bundled payment program., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The RNA exosome is an evolutionarily conserved, ribonuclease complex that is critical for both processing and degradation of a variety of RNAs. Cofactors that associate with the RNA exosome likely dictate substrate specificity for this complex. Recently, mutations in genes encoding both structural subunits of the RNA exosome and its cofactors have been linked to human disease. Mutations in the RNA exosome genes EXOSC3 and EXOSC8 cause pontocerebellar hypoplasia type 1b (PCH1b) and type 1c (PCH1c), respectively, which are similar autosomal-recessive, neurodegenerative diseases. Mutations in the RNA exosome gene EXOSC2 cause a distinct syndrome with various tissue-specific phenotypes including retinitis pigmentosa and mild intellectual disability. Mutations in genes that encode RNA exosome cofactors also cause tissue-specific diseases with complex phenotypes. How mutations in these genes give rise to distinct, tissue-specific diseases is not clear. In this review, we discuss the role of the RNA exosome complex and its cofactors in human disease, consider the amino acid changes that have been implicated in disease, and speculate on the mechanisms by which exosome gene mutations could underlie dysfunction and disease., (© 2018 Morton et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.)

Castration-resistant prostate cancer (CRPC) is the emergence of prostate cancer cells that have adapted to the androgen-depleted environment of the prostate. In recent years, targeting multiple chaperones and co-chaperones (e.g., Hsp27, FKBP52) that promote androgen receptor (AR) signaling and/or novel AR regulatory mechanisms have emerged as promising alternative treatments for CRPC. We have shown that inactivation of inhibitor of differentiation 4 (ID4), a dominant-negative helix loop helix protein, promotes de novo steroidogenesis and CRPC with a gene expression signature that resembles constitutive AR activity in castrated mice. In this study, we investigated the underlying mechanism through which loss of ID4 potentiates AR signaling. Proteomic analysis between prostate cancer cell line LNCaP (L+ns) and LNCaP lacking ID4 (L(-)ID4) revealed elevated levels of Hsp27 and FKBP52, suggesting a role for these AR-associated co-chaperones in promoting constitutively active AR signaling in L(-)ID4 cells. Interestingly, protein interaction studies demonstrated a direct interaction between ID4 and the 52-kDa FK506-binding protein (FKBP52) in vitro, but not with AR. An increase in FKBP52-dependent AR transcriptional activity was observed in L(-)ID4 cells. Moreover, pharmacological inhibition of FKBP52-AR signaling, by treatment with MJC13, attenuated the tumor growth, weight, and volume in L(-)ID4 xenografts. Together, our results demonstrate that ID4 selectively regulates AR activity through direct interaction with FKBP52, and its loss, promotes CRPC through FKBP52-mediated AR signaling., (© 2016 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)

Given that mutated p53 (50% of all human cancers) is over-expressed in many cancers, restoration of mutant p53 to its wild type biological function has been sought after as cancer therapy. The conformational flexibility has allowed to restore the normal biological function of mutant p53 by short peptides and small molecule compounds. Recently, studies have focused on physiological mechanisms such as acetylation of lysine residues to rescue the wild type activity of mutant p53. Using p53 null prostate cancer cell line we show that ID4 dependent acetylation promotes mutant p53 DNA-binding capabilities to its wild type consensus sequence, thus regulating p53-dependent target genes leading to subsequent cell cycle arrest and apoptosis. Specifically, by using wild type, mutant (P223L, V274F, R175H, R273H), acetylation mimics (K320Q and K373Q) and non-acetylation mimics (K320R and K373R) of p53, we identify that ID4 promotes acetylation of K373 and to a lesser extent K320, in turn restoring p53-dependent biological activities. Together, our data provides a molecular understanding of ID4 dependent acetylation that suggests a strategy of enhancing p53 acetylation at sites K373 and K320 that may serve as a viable mechanism of physiological restoration of mutant p53 to its wild type biological function.

Objectives: Compare quality ratings of accredited and nonaccredited nursing homes using the publicly available Centers for Medicare and Medicaid Services (CMS) Nursing Home Compare data set., Methods: This cross-sectional study compared the performance of 711 Joint Commission-accredited (TJC-accredited) nursing homes (81 of which also had Post-Acute Care Certification) to 14,926 non-Joint Commission-accredited (non-TJC-accredited) facilities using the Nursing Home Compare data set (as downloaded on April 2015). Measures included the overall Five-Star Quality Rating and its 4 components (health inspection, quality measures, staffing, and RN staffing), the 18 Nursing Home Compare quality measures (5 short-stay measures, 13 long-stay measures), as well as inspection deficiencies, fines, and payment denials. t tests were used to assess differences in rates for TJC-accredited nursing homes versus non-TJC-accredited nursing homes for quality measures, ratings, and fine amounts. Analysis of variance models were used to determine differences in rates using Joint Commission accreditation status, nursing home size based on number of beds, and ownership type. An additional model with an interaction term using Joint Commission accreditation status and Joint Commission Post-Acute Care Certification status was used to determine differences in rates for Post-Acute Care Certified nursing homes. Binary variables (eg, deficiency type, fines, and payment denials) were evaluated using a logistic regression model with the same covariates., Results: After controlling for the influences of facility size and ownership type, TJC-accredited nursing homes had significantly higher star ratings than non-TJC-accredited nursing homes on each of the star rating component subscales (P < .05) (but not on the overall star rating), and TJC-accredited nursing homes with Post-Acute Care Certification performed statistically better on the overall star rating, as well as 3 of the 4 subscales (P < .05). TJC-accredited nursing homes had statistically fewer deficiencies than non-TJC-accredited nursing homes (P < .001), were less likely to have immediate jeopardy or widespread deficiencies (P < .001), and had fewer payment denials (P < .001) and lower fines (P < .001)., Discussion: Despite recent changes made to the CMS NHC star-rating methodology, results confirm previous findings that demonstrate a consistent pattern of superior performance among nursing homes accredited by The Joint Commission when compared to non-TJC-accredited facilities across a broad range of indicators in the Nursing Home Compare data set. It is important to note, however, that a cross-sectional study cannot determine causation, so it is unclear if accreditation assists nursing homes in achieving better care, or if higher-performing nursing homes are more likely to pursue accreditation., Conclusions: Accreditation status remains a significant predictor of nursing home quality across multiple dimensions, independent of facility size and ownership type., (Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Deregulation of tumor suppressor genes is associated with tumorigenesis and the development of cancer. In prostate cancer, ID4 is epigenetically silenced and acts as a tumor suppressor. In normal prostate epithelial cells, ID4 collaborates with androgen receptor (AR) and p53 to exert its tumor suppressor activity. Previous studies have shown that ID4 promotes tumor suppressive function of AR whereas loss of ID4 results in tumor promoter activity of AR. Previous study from our lab showed that ectopic ID4 expression in DU145 attenuates proliferation and promotes AR expression suggesting that ID4 dependent AR activity is tumor suppressive. In this study, we examined the effect of ectopic expression of ID4 on highly malignant prostate cancer cell, PC3. Here we show that stable overexpression of ID4 in PC3 cells leads to increased apoptosis and decreased cell proliferation and migration. In addition, in vivo studies showed a decrease in tumor size and volume of ID4 overexpressing PC3 cells, in nude mice. At the molecular level, these changes were associated with increased androgen receptor (AR), p21, and AR dependent FKBP51 expression. At the mechanistic level, ID4 may regulate the expression or function of AR through specific but yet unknown AR co-regulators that may determine the final outcome of AR function., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Despite pain resolution in most patients after total knee arthroplasty (TKA), poor function persists in approximately 20% of patients and frequently is associated with patient dissatisfaction. Lumbar spine problems are a leading cause of functional disability. This study sought to determine the association between lower knee function scores and history of spine disability., Methods: Prospective demographic, health, and knee-specific data were collected for 1156 consecutive TKAs from July 2010 to July 2012. A spine questionnaire and Oswestry Disability Index (ODI) score were obtained from 691 knees., Results: Of 691 patients, 371 (54%) with TKA had daily back pain or back pain that limited activity. Oxford Knee Score was significantly worse in patients with vs without back problems preoperatively (36.9/34.8; P = .0006) and postoperatively (20.2/17.0; P < .0001), but not for improvement (16.7/17.8; P = .10). Knee Society (KS) pain scores were similar regardless of spine history. KS function scores were lower in patients with vs without back problems preoperatively (42.3/47.0; P = .0005), postoperatively (69.0/79.8; P < .0001), and for improvement (25.8/32.9; P < .0001). Lower KS function was associated with female gender, age, health, preoperative function, and ODI. ODI was associated with Oxford Knee Score (R = 0.57) and KS function score (R = 0.54)., Conclusion: Knee function scores were significantly worse in patients with a history of back problems and directly associated with ODI score. KS function scores indicated that TKA patients with back problems had worse function before and after TKA with less improvement. Poor TKA outcomes and dissatisfaction may reflect poor knee function, spine disability, or both. Awareness of coexisting spine disability should guide patient expectations and evaluation of TKA outcomes., (Copyright © 2016. Published by Elsevier Inc.)

The p53 protein is a stress response protein that functions primarily as a tetrameric transcription factor. A tumor suppressor p53 binds to a specific DNA sequence and transactivates target genes, leading to cell cycle apoptosis. Encoded by the human gene TP53, p53 is a stress response protein that functions primarily as a tetrameric transcription factor. This gene regulates a large number of genes in response to a variety of cellular functions, including oncogene activation and DNA damage. Mutations in p53 are common in human cancer types. Herein we mutate a wild-type p53, 1TSR with four of its mutated proteins. The energy for the wild-type and mutated proteins is calculated by using molecular dynamics simulations along with simulated annealing. Our results show significant differences in energy between hotspot mutations and the wild type. Based on the findings, we investigate the correlation between molar masses of the target residue and the relative energy with respect to the wild type. Our results indicate that the relative energy changes play a pivotal role in bioactivity, in conformity with observations in the rate of mutation in biology.