Searched for: All
Exploring the Molecular Link Between Diabetes and Erectile Dysfunction Through Single-Cell Transcriptome Analysis
Begum, Mahmuda; Choubey, Mayank; Tirumalasetty, Munichandra Babu; Arbee, Shahida; Sadik, Sibly; Mohib, Mohammad Mohabbulla; Srivastava, Shivani; Minhaz, Naofel; Alam, Riffat; Mohiuddin, Mohammad Sarif
Erectile dysfunction (ED) is a pathophysiological condition in which the patients cannot achieve an erection during sexual activity, and it is often overlooked yet prevalent among diabetic men, globally affecting approximately 35-75% of diabetic individuals. The precise mechanisms through which diabetes contributes to ED remain elusive, but the existing literature suggests the potential involvement of nerve and vascular damage that affects the penile supply. In the present review, we reanalyze the existing human single-cell transcriptomic data from patients having diabetes mellitus-associated ED with normal erections. The analysis validates the expression of genes associated with antioxidative pathways, growth factors, adipokines, angiogenesis, vascular functions, penile erection, sexual function, and inflammation in diverse cell types from healthy individuals and those with ED. Our transcriptomic analysis reveals alterations in the expression of adiponectin receptors in the pathogenesis of ED compared to their counterparts in healthy subjects. This comprehensive review sheds light on the molecular underpinnings of ED in the context of diabetes, providing an in-depth understanding of the biological and cellular alterations involved and paving the way for possible targeted therapeutic discoveries in the field of diabetes-associated male infertility.
PMCID:11675191
PMID: 39766863
ISSN: 2073-4425
CID: 5779312
Higher abdominal fat area associates with lower donor kidney function before and after living kidney donation
Westenberg, Lisa B; van Londen, Marco; Zorgdrager, Marcel; McAdams-DeMarco, Mara A; Segev, Dorry L; Bakker, Stephan J L; Viddeleer, Alain R; Pol, Robert A
Central body fat distribution affects kidney function. Abdominal fat measurements using computed tomography (CT) may prove superior in assessing body composition-related kidney risk in living kidney donors. This retrospective cohort study including 550 kidney donors aimed to determine the association between CT-measured abdominal fat areas and kidney function before and after donor nephrectomy. Donors underwent glomerular filtration rate measurements (125I-Iothalamate, mGFR) before and 3 months after donation. Linear regression analyses with body surface area (BSA)-standardized and crude mGFR were performed to assess the association of height-indexed tomographic fat measurements with kidney function. In age-, and sex-adjusted analyses higher levels of total abdominal, visceral, subcutaneous, and intramuscular adipose tissue index were significantly associated with lower mGFR levels before donation (BSA-standardized mGFR: visceral adipose tissue index: Βeta=-0.11, p < 0.001, subcutaneous: Βeta=-0.10, p < 0.001, intramuscular: Βeta=-1.18, p < 0.001, total abdominal: Βeta=-0.07, p < 0.001). Higher tomographic abdominal fat is associated with lower BSA-standardized mGFR after donation and a greater decrease in mGFR between screening and 3 months post-donation. This study shows that CT-measured abdominal fat area is associated with kidney function before and after living kidney donation.
PMCID:11682065
PMID: 39733114
ISSN: 2045-2322
CID: 5779192
Tips and Tricks for Image-Guided Breast Biopsies: Technical Factors for Success
Dodelzon, Katerina; Grimm, Lars; Coffey, Kristen; Reig, Beatriu; Mullen, Lisa; Dashevsky, Brittany Z; Bhole, Sonya; Parikh, Jay
Image-guided biopsy is an integral step in the diagnosis and management of suspicious image-detected breast or axillary lesions, allowing for accurate diagnosis and, if indicated, treatment planning. Tissue sampling can be performed under guidance of a full spectrum of breast imaging modalities, including stereotactic, tomosynthesis, sonographic, and MRI, each with its own set of advantages and limitations. Procedural planning, which includes consideration of technical, patient, and lesion factors, is vital for diagnostic accuracy and limitation of complications. The purpose of this paper is to review and provide guidance for breast imaging radiologists in selecting the best procedural approach for the individual patient to ensure accurate diagnosis and optimal patient outcomes. Common patient and lesion factors that may affect successful sampling and contribute to postbiopsy complications are reviewed and include obesity, limited patient mobility, patient motion, patients prone to vasovagal reactions, history of anticoagulation, and lesion location, such as proximity to vital structures or breast implant.
PMID: 39313444
ISSN: 2631-6129
CID: 5778172
Application of a Heuristic Framework for Multilevel Interventions to Eliminate the Impact of Unjust Social Processes and Other Harmful Social Determinants of Health
Guilamo-Ramos, Vincent; Thimm-Kaiser, Marco; Benzekri, Adam; Johnson, Celia; Williams, Desiree; Wilhelm-Hilkey, Nash; Goodman, Melody; Hagan, Holly
There is consensus about the importance of developing a strong cadre of effective multilevel interventions to eliminate the impacts of unjust social processes, such as structural racism and other harmful social determinants of health (SDOH), on health inequities in the USA. However, the available cadre of rigorously evaluated evidence-based interventions for SDOH mitigation remains underdeveloped relative to the magnitude of historic and current health inequities. The proposed manuscript addresses this gap in two ways: first, by introducing a heuristic framework to inform decisions in multilevel intervention development, study design, and selection of analytic methods and, second, by providing a roadmap for future applications of the framework in multilevel intervention research through an exemplar application using the ongoing NIH-funded evaluation study of the Nurse-Community-Family Partnership (NCFP) intervention. NCFP leverages individual, family, institutional, and system factors to shape COVID-19 mitigation outcomes at the individual and household levels. NCFP takes an approach informed by the heuristic framework to addressing and mitigating unjust social processes and other harmful SDOH. We discuss the application of a two-arm parallel explanatory group randomized trial to evaluate the efficacy of NCFP in improving the primary (COVID-19 testing uptake) and secondary (adoption of COVID-19 control measures, COVID-19 vaccine uptake, mutual aid capacity, etc.) outcomes at the individual and household levels. The analysis approach relies on random-intercept models, and we calculate the variance partitioning coefficient to estimate the extent to which household- and individual-level variables contribute to the outcome, allowing examination of NCFP effects at multiple levels.
PMCID:11239765
PMID: 38607535
ISSN: 1573-6695
CID: 5779512
Crystallization by microwave energy: Effects on the survival probability of lithia-based glass ceramics
Diamantino, Pedro Santos; Rodrigues, Camila da Silva; Carvalho, Ana Beatriz Gomes de; Tribst, João Paulo Mendes; Riquieri, Hilton; Ramos, Nathália de Carvalho; Viegas, Diogo Miguel da Costa Cabecinha Pacheco; Bergamo, Edmara Tatiely Pedroso; Bonfante, Estevam Augusto; Saavedra, Guilherme de Siqueira Ferreira Anzaloni
This study evaluated the survival probabilities of two lithia-based glass-ceramics after final crystallization in a microwave furnace using conventional crystallization as a reference. Disc-shaped samples of a lithium silicate (LS, Celtra Duo) and a lithium disilicate (LD, e.max CAD) were prepared and divided into two groups according to the crystallization method (n = 30): microwave (M) or conventional furnaces (C). The biaxial flexural strength test was used to determine the fatigue test profile and its parameters. Then, specimens were submitted to an accelerated life test (step stress) using three profile levels - mild, moderate, and aggressive - varying the load increments and the number of cycles until fracture (4 Hz). Survival data were used to calculate Weibull's beta (β) value and reliability of the assigned missions. Scanning electron microscopy was employed to analyze surface morphology, fracture characteristics, and failure patterns. Beta (β) values for the LS-C, LS-M, LD-C, and LD-M groups were 2.65, 0.25, 0.62, and 0.3, respectively. Similar reliability was observed in all groups after 50,000 cycles at 100 and 150 Mpa. At 200 Mpa, the crystallization method did not affect the reliability within LS or LD. However, LD showed greater reliability than LS when crystallized by microwave energy. Thus, microwave energy can be suggested as an alternative to the process of conventional lithia-based glass-ceramics crystallization without damaging their survival probabilities.
PMID: 39775416
ISSN: 1807-3107
CID: 5779442
Barriers and Facilitators to Vaccine Equity Amidst the COVID-19 Vaccine Rollout in the United States
Piltch-Loeb, Rachael; Nuñez Sahr, Josefina; Nelson, LaRon E; Vlahov, David; Gershon, Robyn R
State and local health departments were responsible for ensuring equitable distribution of the COVID-19 vaccine. This qualitative study aimed to identify the challenges, strategies, disappointments, and successes in achieving equity for hard-to-reach and at-risk populations. Using a purposive sampling strategy, 16 individuals affiliated with health departments across nine states, each holding leadership roles in vaccine distribution, were interviewed between late 2021 and mid-2022. The key factors promoting vaccine equity included (1) inviting community members to serve on vaccine advisory groups to participate in decision-making; (2) utilizing pre-existing community relationships and spaces to facilitate the planning and distribution of the vaccine; and (3) establishing and building upon community outreach to support accessibility and uptake of the vaccine. The barriers included (1) a lack of clarity on vaccine prioritization criteria; (2) language/communication access; and (3) the initial focus on mass vaccination sites for vaccine delivery. The stakeholders also highlighted potential facilitators for increasing equity in future vaccine rollouts. Overall, community engagement emerged as a critical factor in ensuring equity during disaster response efforts.
PMCID:11675886
PMID: 39767429
ISSN: 1660-4601
CID: 5779422
ARTHRITIS CARE & RESEARCH [Letter]
Gupta, Nishant; Carsons, Steven E.; Carteron, Nancy L.; Scofield, Robert Hal; Lee, Augustine S.; Thomas, Donald E.; Moua, Teng; Ussavarungsi, Kamonpun; St Clair, E. William; Meehan, Richard; Dunleavy, Kieron; Makara, Matt; Hammitt, Katherine Morland
ISI:001383081700001
ISSN: 2151-464x
CID: 5778782
Diversity-Related, Student-Led National Medical Organizations: Leadership Opportunities for Learners
Brutus, Nicholas N; Spencer, Dennis J; Huell, Derek; Astudillo, Yaritzy M; Ott, Austen; Lee, Joyce H; Calac, Alex; Sánchez, John P
INTRODUCTION/UNASSIGNED:In light of the lack of diversity in academic medicine leadership, diversity-related, student-led national medical organizations (NMOs) provide a space for solace and reprieve among common peers while providing an opportunity to develop leadership competencies in a supportive environment. Despite the impact NMOs have had on cultivating generations of leaders in medicine, trainees may not identify opportunities for leadership development that are transferable to future careers in academic medicine. METHODS/UNASSIGNED:We designed and implemented a dynamic 60-minute workshop with an interactive PowerPoint presentation, author-owned video testimonials (from past student leaders of NMOs), two case presentations, and reflection exercises. We assessed learner self-perceived confidence via workshop surveys. The target audience of this module was medical trainees, including medical students, residents, and fellows. RESULTS/UNASSIGNED:Forty-three workshop attendees across three sites submitted partial or complete survey evaluations. Respondents included medical students (77%), with the remainder self-identified as either postbaccalaureate students, residents/fellows, academic faculty, or physicians. A comparison of pre- and postresponses showed a statistically significant increase in confidence in addressing each of the four educational objectives. Participants felt the case presentations offered relevant applicable examples. DISCUSSION/UNASSIGNED:For many trainees, the role that diversity-related NMOs play in developing leadership competencies may be unclear and not articulated in traditional medical curricula. In this module, we provide examples of how NMOs facilitate leadership development and may encourage our diverse trainees to eventually become academic faculty.
PMCID:11671812
PMID: 39735709
ISSN: 2374-8265
CID: 5779202
Predicting Robotic Hysterectomy Incision Time: Optimizing Surgical Scheduling with Machine Learning
Shah, Vaishali; Yung, Halley C; Yang, Jie; Zaslavsky, Justin; Algarroba, Gabriela N; Pullano, Alyssa; Karpel, Hannah C; Munoz, Nicole; Aphinyanaphongs, Yindalon; Saraceni, Mark; Shah, Paresh; Jones, Simon; Huang, Kathy
BACKGROUND AND OBJECTIVES/UNASSIGNED:Operating rooms (ORs) are critical for hospital revenue and cost management, with utilization efficiency directly affecting financial outcomes. Traditional surgical scheduling often results in suboptimal OR use. We aim to build a machine learning (ML) model to predict incision times for robotic-assisted hysterectomies, enhancing scheduling accuracy and hospital finances. METHODS/UNASSIGNED:A retrospective study was conducted using data from robotic-assisted hysterectomy cases performed between January 2017 and April 2021 across 3 hospitals within a large academic health system. Cases were filtered for surgeries performed by high-volume surgeons and those with an incision time of under 3 hours (n = 2,702). Features influencing incision time were extracted from electronic medical records and used to train 5 ML models (linear ridge regression, random forest, XGBoost, CatBoost, and explainable boosting machine [EBM]). Model performance was evaluated using a dynamic monthly update process and novel metrics such as wait-time blocks and excess-time blocks. RESULTS/UNASSIGNED: < .001, 95% CI [-329 to -89]), translating to approximately 52-hours over the 51-month study period. The model predicted more surgeries within a 15% range of the true incision time compared to traditional methods. Influential features included surgeon experience, number of additional procedures, body mass index (BMI), and uterine size. CONCLUSION/UNASSIGNED:The ML model enhanced the prediction of incision times for robotic-assisted hysterectomies, providing a potential solution to reduce OR underutilization and increase surgical throughput and hospital revenue.
PMCID:11741200
PMID: 39831273
ISSN: 1938-3797
CID: 5778432
Malate initiates a proton-sensing pathway essential for pH regulation of inflammation
Chen, Yu-Jia-Nan; Shi, Rong-Chen; Xiang, Yuan-Cai; Fan, Li; Tang, Hong; He, Gang; Zhou, Mei; Feng, Xin-Zhe; Tan, Jin-Dong; Huang, Pan; Ye, Xiao; Zhao, Kun; Fu, Wen-Yu; Li, Liu-Li; Bian, Xu-Ting; Chen, Huan; Wang, Feng; Wang, Teng; Zhang, Chen-Ke; Zhou, Bing-Hua; Chen, Wan; Liang, Tao-Tao; Lv, Jing-Tong; Kang, Xia; Shi, You-Xing; Kim, Ellen; Qin, Yin-Hua; Hettinghouse, Aubryanna; Wang, Kai-di; Zhao, Xiang-Li; Yang, Ming-Yu; Tang, Yu-Zhen; Piao, Hai-Long; Guo, Lin; Liu, Chuan-Ju; Miao, Hong-Ming; Tang, Kang-Lai
Metabolites can double as a signaling modality that initiates physiological adaptations. Metabolism, a chemical language encoding biological information, has been recognized as a powerful principle directing inflammatory responses. Cytosolic pH is a regulator of inflammatory response in macrophages. Here, we found that L-malate exerts anti-inflammatory effect via BiP-IRF2BP2 signaling, which is a sensor of cytosolic pH in macrophages. First, L-malate, a TCA intermediate upregulated in pro-inflammatory macrophages, was identified as a potent anti-inflammatory metabolite through initial screening. Subsequent screening with DARTS and MS led to the isolation of L-malate-BiP binding. Further screening through protein‒protein interaction microarrays identified a L-malate-restrained coupling of BiP with IRF2BP2, a known anti-inflammatory protein. Interestingly, pH reduction, which promotes carboxyl protonation of L-malate, facilitates L-malate and carboxylate analogues such as succinate to bind BiP, and disrupt BiP-IRF2BP2 interaction in a carboxyl-dependent manner. Both L-malate and acidification inhibit BiP-IRF2BP2 interaction, and protect IRF2BP2 from BiP-driven degradation in macrophages. Furthermore, both in vitro and in vivo, BiP-IRF2BP2 signal is required for effects of both L-malate and pH on inflammatory responses. These findings reveal a previously unrecognized, proton/carboxylate dual sensing pathway wherein pH and L-malate regulate inflammatory responses, indicating the role of certain carboxylate metabolites as adaptors in the proton biosensing by interactions between macromolecules.
PMCID:11683149
PMID: 39737965
ISSN: 2059-3635
CID: 5779222