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What Is the Institutional Financial Impact of an md-phd program Without Extramural Funding?

TEACHING AND LEARNING IN MEDICINE 2010年第1期22卷 56-59页

作者： Byrne, Margaret M. Losso, Izidore S. Koniaris, Leonidas G. Univ Miami Miller Sch Med Dept Epidemiol & Publ Hlth Miami FL 33136 USA Univ Miami Miller Sch Med MD PhD Program Miami FL 33136 USA

Background: Training in the form of md-phd programs is an important part of the academic mission of medical schools, yet the costs incurred in providing these programs may be considerable. This research explores the financial impacts on a university of supporting an md-phd program. Summary: We estimate the net financial impact of an md-phd program under a variety of assumptions about the financial gain that the school obtains through md-phd students' contributions to externally funded research. Under certain assumptions, the net financial impact of the md-phd program is positive, and under the most unfavorable assumptions the cost per student year is less than $30,000. Conclusions: The apparent costs of an md-phd program are ameliorated or even turned into gains when one considers the resources generated by md-phd students. Thus, such programs can serve as a means of increasing external awards and improving the overall quality in graduate schools.

关键词： MEDICAL students HEALTH occupations students INTERNS (Medicine) PRACTICUMS EXPERIENTIAL learning PRACTICUM supervision OCCUPATIONAL training HEALTH occupations practicums INTERNSHIP programs TRAINING of

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Metabolic constraint of human telomere length by nucleotide salvage efficiency

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NATURE COMMUNICATIONS 2025年第1期16卷 1-14页

作者： Mannherz, William Crompton, Andrew Lampl, Noah Agarwal, Suneet Boston Childrens Hosp Oncol & Stem Cell Program Div Hematol Boston MA 02115 USA Dana Farber Canc Inst Pediat Oncol Boston MA 02215 USA Harvard Med Sch Harvard Stem Cell Inst Dept Pediat Harvard Initiat RNA Med Boston MA 02215 USA Harvard Med Sch Biol & Biomed Sci PhD Program Biol & Biomed Sci PhD Program Boston MA 02215 USA Harvard Med Sch Harvard MIT MD PhD Program Boston MA 02215 USA

Human telomere length is tightly regulated and associated with diseases at either extreme, but how these bounds are established remains incompletely understood. Here, we developed a rapid cell-based telomere synthesis assay and found that nucleoside salvage bidirectionally constrains human telomere length. Metabolism of deoxyguanosine (dG) or guanosine via purine nucleoside phosphorylase (PNP) and hypoxanthine-guanine phosphoribosyltransferase to form guanine ribonucleotides strongly inhibited telomerase and shortened telomeres. Conversely, salvage of dG to its nucleotide forms via deoxycytidine kinase drove potent telomerase activation, the extent of which was controlled by the dNTPase SAMHD1. Circumventing limits on salvage by expressing Drosophila melanogaster deoxynucleoside kinase or augmenting dG metabolism using the PNP inhibitor ulodesine robustly lengthened telomeres in human cells, including those from patients with lethal telomere diseases. Our results provide an updated paradigm for telomere length control, wherein telomerase reverse transcriptase activity is actively and bidirectionally constrained by the availability of its dNTP substrates, in a manner that may be therapeutically actionable.

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The elevated stroke and death rates among asymptomatic patients undergoing carotid stenting in the Pacific Northwest are associated with high-risk patient selection

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JOURNAL OF VASCULAR SURGERY 2025年第4期81卷 929-937.e12页

作者： Ghosh, Rahul Elizaga, Norma Murphy, Blake Cornett, Carrie Tran, Nam Zettervall, Sara L. Dansey, Kirsten D. Univ Washington Div Vasc Surg 1959 NE Pacific StBox 358811 Seattle WA 98195 USA Texas A&M Coll Med MD PhD Program College Stn TX USA

Objective: Current guidelines recommend treatment of patients with asymptomatic carotid stenosis when stroke/death rates less than 3% can be achieved. However, in the Pacific Northwest region of the Vascular Quality Initiative, elevated stroke/death rates have been reported. This study aims to characterize regional and center-specific outcomes for transcarotid artery revascularization (TCAR) and transfemoral carotid artery stenting (TF-CAS) and investigate potential underlying drivers. Methods: A retrospective review of asymptomatic patients undergoing TCAR and TF-CAS in the Vascular Quality Initiative for the Pacific Northwest region from 2016 to 2022 was performed. The primary outcome was the composite of stroke or death within 30 days of index hospitalization. Overall regional outcomes and center-specific outcomes were assessed. A high stroke/death rate was defined as greater than 3%. Demographics, comorbidities, and operative risk factors were then compared between centers with high and low stroke/death rates. Results: A total of 1154 asymptomatic patients across 27 centers underwent carotid stenting in the Pacific Northwest from 2016 to 2022, of which 886(76.8%) underwent TCAR and 268(23.2%) underwent TF-CAS. The overall stroke/death rates were 2.5% and 3.0% for TCAR and TF-CAS, respectively. Among centers with stroke/death rates above 3%, for both TCAR and TF-CAS, all were in the top one-half of centers by volume. When patients undergoing TCAR were assessed, those treated at centers with high stroke/ death rate underwent revascularization at higher volume centers (12 vs 7 cases per year;P = .03), which treated fewer patients with >80% stenosis (42.1% vs 52.2%;P < .01) and more patients with high-risk anatomy (42.3% vs 35.3%;P = .01), and high-risk physiology as defined by an American Society of Anesthesiologists (ASA) class of 4 or 5 (25.5% vs 17.5%;P < .01). Among patients undergoing TF-CAS, those treated at centers with a high stroke/death rate were more lik

关键词： Asymptomatic Carotid artery stenting Patient selection Perioperative outcomes Transcarotid artery revascularization Transfemoral carotid artery stenting

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Telehealth virtual reality intervention reduces chronic pain in a randomized crossover study

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NPJ DIGITAL MEDICINE 2025年第1期8卷 1-8页

作者： Colloca, Luana Han, Anna Massalee, Rachel Raghuraman, Nandini Cundiff-O'Sullivan, Rachel L. Colloca, Giancarlo Wang, Yang Univ Maryland Sch Nursing Dept Pain & Translat Symptom Sci Baltimore MD 21201 USA Univ Maryland Ctr Adv Chron Pain Res Baltimore MD 21201 USA Univ Maryland Sch Med Dept Anesthesiol & Psychiat Baltimore MD 21201 USA Univ Maryland Sch Nursing Placebo Opin Ctr Baltimore MD 21201 USA Towson Univ Dept Comp & Informat Sci Informat Technol PhD Program Towson MD USA

The efficacy of telehealth Virtual Reality (VR) for chronic pain, a promising digital intervention, remains underexplored due to methodological challenges. In a 5-week crossover trial, we compared VR to matched audio content control in individuals with chronic pain. VR significantly reduced pain intensity, anxiety, and pain interference while improving mood and sleep quality. Findings highlight the potential of telehealth-based VR for addressing real-world challenges in managing chronic pain. ISRCTN12473220 (07/18/2023).

关键词： eHealth

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Carcinogenetic mechanisms employed by the oral microbiome: A narrative review

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American Journal of the Medical Sciences 2025年第5期369卷 556-561页

作者： Menghani, Sanjay V. University of Arizona College of Medicine – Tucson AZ United States Medical Scientist Training MD-PhD Program University of Arizona College of Medicine Tucson AZ United States

Cancers of the oral cavity, lip, salivary gland, and oropharynx cause substantial global disease burden. While tobacco-use and alcohol use are highly associated with oral cancers, the rising incidence of disease in patients who do not use tobacco or alcohol points to additional carcinogenic risk factors. Chronic inflammation, disruption of the oral microbiome, and dysbiosis are becoming more widely implicated in the pathogenesis of oral cancer. Several studies have identified specific bacterial species enriched in patients with oral cancer, including Porphyromonas gingivalis and Fusobacterium nucleatum. In this narrative review, we describe potential carcinogenic mechanisms exhibited by these species and other microbes in the development of oral cancer. © 2025

关键词： Carcinogenesis Fusobacterium nucleatum Immunology Oral cancer Oral microbiome Porphyromonas gingivalis

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GHSR blockade, but not reduction of peripherally circulating ghrelin via β1-adrenergic receptor antagonism, decreases binge-like alcohol drinking in mice

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MOLECULAR PSYCHIATRY 2025年第3期30卷 1047-1056页

作者： Richardson, Rani S. Kryszak, Lindsay A. Vendruscolo, Janaina C. M. Koob, George F. Vendruscolo, Leandro F. Leggio, Lorenzo NIDA Clin Psychoneuroendocrinol & Neuropsychopharmacol Translat Addict Med Branch Intramural Res Program Baltimore MD 21224 USA NIAAA Div Intramural Clin & Biol Res NIH Bethesda MD 20892 USA NIDA Neurobiol Addict Sect Intramural Res Program NIH Baltimore MD USA Univ North Carolina Sch Med PhD Program Chapel Hill NC USA Univ North Carolina Dept Cell Biol & Physiol Chapel Hill NC USA NIDA Stress & Addict Neurosci Unit Intramural Res Program Baltimore MD 21224 USA NIDA Intramural Res Program Translat Analyt Core NIH Baltimore MD 21224 USA Brown Univ Ctr Alcohol & Addict Studies Dept Behav & Social Sci Providence RI 02912 USA NIDA Medicat Dev Program Intramural Res Program Mol Targets & Medicat Discovery Branch Baltimore MD 20852 USA Johns Hopkins Univ Sch Med Dept Med Div Addict Med Baltimore MD 21218 USA Georgetown Univ Med Ctr Dept Neurosci Washington DC 20057 USA

Alcohol use disorder (AUD) and binge drinking are highly prevalent public health issues. The stomach-derived peptide ghrelin, and its receptor, the growth hormone secretagogue receptor (GHSR), both of which are expressed in the brain and periphery, are implicated in alcohol-related outcomes. We previously found that systemic and central administration of GHSR antagonists reduced binge-like alcohol drinking, whereas a ghrelin vaccine did not. Thus, we hypothesized that central GHSR drives binge-like alcohol drinking independently of peripheral ghrelin. To investigate this hypothesis, we antagonized beta(1)-adrenergic receptors (beta(1)ARs), which are required for peripheral ghrelin release, and combined them with GHSR blockers. We found that both systemic beta(1)AR antagonism with atenolol (peripherally restricted) and metoprolol (brain permeable) robustly decreased plasma ghrelin levels. Also, ICV administration of atenolol had no effect on peripheral endogenous ghrelin levels. However, only metoprolol, but not atenolol, decreased binge-like alcohol drinking. The beta(1)AR antagonism also did not prevent the effects of the GHSR blockers JMV2959 and PF-5190457 in decreasing binge-like alcohol drinking. These results suggest that the GHSR rather than peripheral endogenous ghrelin is involved in binge-like alcohol drinking. Thus, GHSRs and beta(1)ARs represent possible targets for therapeutic intervention for AUD, including the potential combination of drugs that target these two systems.

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Amygdala subregion volumes and apportionment in preadolescents - Associations with age, sex, and body mass index

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DEVELOPMENTAL COGNITIVE NEUROSCIENCE 2025年 73卷 101554页

作者： Overholtzer, L. Nate Torgerson, Carinna Morrel, Jessica Ahmadi, Hedyeh Tyszka, J. Michael Herting, Megan M. USC Dept Populat & Publ Hlth Sci Keck Sch Med Los Angeles CA USA Univ Southern Calif Neurosci Grad Program Los Angeles CA USA USC USC Caltech MD PhD Program Keck Sch Med Los Angeles CA USA CALTECH Caltech Brain Imaging Ctr Pasadena CA USA

The amygdala, a key limbic structure, is critical to emotional, social, and appetitive behaviors that develop throughout adolescence. Composed of a heterogeneous group of nuclei, questions remain about potential differences in the maturation of its subregions during development. In 3953 9- and 10-year-olds from the Adolescent Brain Cognitive DevelopmentSM Study, the CIT168 Atlas was used to segment nine amygdala subregions. Linear mixed-effects models were used to examine the effects of age, sex, pubertal stage, and body mass index z-score (BMIz) on subregion volumes and their relative apportionment within the amygdala. Distinct associations were observed between age, sex, and BMIz with whole amygdala volume, subregion volumes, and subregion apportionment. Pubertal stage was not related to amygdala subregion volumes. Age was associated with near-global expansion of amygdala subregions during this developmental period. Female sex was linked to smaller volumes in most amygdala subregions, with larger relative apportionment in the dorsal subregions and smaller apportionment in the basolateral ventral paralaminar subregion. Higher BMIz was associated with smaller volumes in large basolateral subregions, with increased relative apportionment in smaller subregions. These findings provide a foundational context for understanding how developmental variables influence amygdala structure, with implications for understanding future risk for brain disorders.

关键词： Amygdala Obesity Sex differences Neuroimaging Puberty Adolescence

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Weighted cart pull: A novel outcome measure for sustained motor function in mice

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EXPERIMENTAL PHYSIOLOGY 2025年第0期 2025 Mar 28页

作者： Brennan, Charles D. Kerr, Nathan R. Viteri, Jose A. Williard, Zachary Snyder, Harper Meier, Gabriella Cairns, Sam Darvishi, Fereshteh B. Dashtmian, Anna R. Moore, Peter J. Ayyagari, Sindhuja N. Wang, Meifang Arnold, W. David Univ Missouri Sch Med Columbia MO USA Univ Missouri Tom & Anne Smith MD PhD Program Columbia MO USA Univ Missouri Sch Med Dept Phys Med & Rehabil Columbia MO 65201 USA Univ Missouri NextGen Precis Hlth Columbia MO USA

Sarcopenia, the pathological age-related decline in muscle mass and strength, compromises independence and quality of life in older adults. Currently, no effective treatments are available. To enhance translational research using aged mouse models, we developed and validated the weighted cart pull (WCP) as a novel assessment of sustained motor function. The WCP test involved attaching a weighted cart to the tail of a mouse as it climbed a ramp to a 'resting house'. Mass was increased incrementally until failure, defined as either five consecutive hindquarter pokes without progress or sliding backwards. In experiment 1, reliability (inter- and intra-rater) was evaluated in middle-aged mice (9 months, n = 10, 50% female). In experiment 2, young (n = 8, 50% female) and old (n = 8, 50% female) mice were tested on WCP, all-limb grip and rotarod. In experiment 3, middle-aged mice (7-9 months, n = 20, 50% female) underwent behavioural tests, in vivo electrophysiology and muscle physiology to correlate WCP with assessments of neuromuscular function. WCP showed high intra-rater repeatability [intraclass correlation coefficient = 0.611, P = 0.018, 95% confidence interval (CI) = (0.046, 0.885)]. WCP demonstrated phenotypic differences between young and old mice (Student's unpaired t-test, P < 0.0001). WCP was significantly correlated with all-limb grip [Pearson's r = 0.5820, P = 0.0071, 95% CI = (0.1878, 0.8147)], percentage decrement upon repetitive nerve stimulation at 50 Hz [Pearson's r = 0.4613, P = 0.0468, 95% CI = (0.008973, 0.7569)], twitch torque [Pearson's r = 0.6241, P = 0.0033, 95% CI = (0.2509, 0.8358)], tetanic torque [Pearson's r = 0.5100, P = 0.0216, 95% CI = (0.08718, 0.7771)] and bilateral gastrocnemius and soleus muscle mass [Pearson's r = 0.5878, P = 0.0064, 95% CI = (0.1964, 0.8177)]. The WCP provides a cost-effective, comprehensive measure of strength and sustained motor function, improving preclinical assessments.

关键词： ageing motor function power sarcopenia weakness

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Rapid whole genome characterization of antimicrobial-resistant pathogens using long-read sequencing to identify potential healthcare transmission

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INFECTION CONTROL & HOSPITAL EPIDEMIOLOGY 2025年第2期46卷 129-135页

作者： Wu, Chin-Ting Shropshire, William C. Bhatti, Micah M. Cantu, Sherry Glover, Israel K. Anand, Selvalakshmi Selvaraj Liu, Xiaojun Kalia, Awdhesh Treangen, Todd J. Chemaly, Roy F. Spallone, Amy Shelburne, Samuel Univ Texas MD Anderson Canc Ctr Sch Hlth Profess Grad Program Diagnost Genet & Genom Houston TX USA Univ Texas MD Anderson Canc Ctr Dept Infect Dis Infect Control & Employee Hlth Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr Dept Lab Med Houston TX USA Univ Texas MD Anderson Canc Ctr Infect Control Chief Qual Off Houston TX USA Univ Texas MD Anderson Canc Ctr Dept Genom Med Houston TX 77030 USA Rice Univ PhD Program Synthet Biol Inst Syst Synthet & Phys Houston TX USA Rice Univ Dept Comp Sci Houston TX USA Rice Univ Dept Bioengn Houston TX USA

Objective: Whole genome sequencing (WGS) can help identify transmission of pathogens causing healthcare-associated infections (HAIs). However, the current gold standard of short-read, Illumina-based WGS is labor and time intensive. Given recent improvements in long-read Oxford Nanopore Technologies (ONT) sequencing, we sought to establish a low resource approach providing accurate WGS-pathogen comparison within a time frame allowing for infection prevention and control (IPC) interventions. Methods: WGS was prospectively performed on pathogens at increased risk of potential healthcare transmission using the ONT MinION sequencer with R10.4.1 flow cells and Dorado basecaller. Potential transmission was assessed via Ridom SeqSphere & thorn;for core genome multilocus sequence typing and MINTyper for reference-based core genome single nucleotide polymorphisms using previously published cutoff values. The accuracy of our ONT pipeline was determined relative to Illumina. Results: Over a six-month period, 242 bacterial isolates from 216 patients were sequenced by a single operator. Compared to the Illumina gold standard, our ONT pipeline achieved a mean identity score of Q60 for assembled genomes, even with a coverage rate as low as 40x. The mean time from initiating DNA extraction to complete analysis was 2 days (IQR 2-3.25 days). We identified five potential transmission clusters comprising 21 isolates (8.7% of sequenced strains). Integrating ONT with epidemiological data, > 70% (15/21) of putative transmission cluster isolates originated from patients with potential healthcare transmission links. Conclusions: Via a stand-alone ONT pipeline, we detected potentially transmitted HAI pathogens rapidly and accurately, aligning closely with epidemiological data. Our low-resource method has the potential to assist in IPC efforts. (Received 27 August 2024;accepted 1 November 2024)

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Assessment of regulating ecosystem services generated by green infrastructure: A case study of Bolzano, Italy

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URBAN CLIMATE 2025年 60卷

作者： Sokolova, Milena, V Fath, Brian D. Buonocore, Elvira Franzese, Pier Paolo Parthenope Univ Naples UNESCO Chair Environm Resources & Sustainable Dev Dept Sci & Technol Int PhD Programme Naples Italy Int Inst Appl Syst Anal Adv Syst Anal Program Laxenburg Austria Towson Univ Dept Biol Sci Towson MD USA Masaryk Univ Dept Environm Studies Brno Czech Republic

Sustainable cities is one of the key topics of the United Nations 2030 Agenda for Sustainable Development. SDG 11 promotes the goal that cities should be inclusive, safe, resilient and sustainable human settlements. In this context, urban ecosystems, namely, Green Infrastructure (GI) can play a key role to enhance ecosystem services. GI improves ecosystem functioning and resilience, protects biodiversity, promotes societal health and well-being. The concept of GI in cities is becoming increasingly important in the development of urban policies since it improves the quality of life while mitigating the adverse effects of climate change. In this paper, we integrate biophysical method and monetary methods using i-Tree Eco software with about 12,000 trees within Bolzano, Italy. Model results are given for five assessed ecosystem services: 1) carbon storage, 2) carbon sequestration, 3) oxygen production, 4) avoided runoff, and 5) air pollution removal. Thus, our results show the significance of urban trees as a key element for better urban planning considering specific species contribution. The findings of this study will increase the awareness on the important role GIs play in urban systems to improve human well-being, informing policy-makers in charge of developing strategies to achieve impelling conservation actions and sustainability goals.

关键词： Green infrastructure Ecosystem services i-Tree Eco software SDG 11 Bolzano Urban ecosystems

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