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Atrophy patterns of deep gray matter nuclei in Alzheimer's disease and frontotemporal dementia
No full textBackgroundWhile cortical atrophy has been widely studied in dementia, emerging evidence highlights the role of subcortical degeneration, particularly in deep gray matter structures such as the thalamus, claustrum, and basal nuclei, in both Alzheimer's disease (AD) and frontotemporal dementia (FTD). However, disease-specific subcortical patterns remain undercharacterized.ObjectiveTo quantify deep gray matter atrophy across the AD continuum (mild cognitive impairment and AD) and three FTD subtypes (bvFTD, svFTD, PNFA), and to assess longitudinal atrophy, cognitive associations, and diagnostic classification.MethodsWe applied a novel segmentation pipeline (sTHOMAS) to T1-weighted MRI data from 380 participants in the ADNI cohort and 274 participants in the FTLDNI cohort, with longitudinal follow-up available for 237 participants. Group differences were assessed using ANCOVA (adjusted for age and sex), followed by post hoc comparisons and effect size estimation (Cohen's d). Neuropsychological associations were examined using partial correlations. A hierarchical Random Forest model was trained to classify diagnostic groups.ResultsPronounced atrophy was observed in the mediodorsal, anteroventral, pulvinar thalamic nuclei, and nucleus accumbens, and claustrum in both AD and FTD, but was significantly greater in bvFTD. Longitudinal analysis revealed the fastest progression in bvFTD. Classification achieved 96.8% accuracy (AUC = 0.99) for AD versus FTD and 77.7% accuracy (AUC = 0.83) for PNFA versus svFTD. Subcortical atrophy correlated to executive, language, and semantic deficits.ConclusionsAtrophy in the mediodorsal, pulvinar, anteroventral thalamic nuclei, nucleus accumbens, and claustrum distinguishes AD from FTD and differentiates FTD subtypes. These subcortical structures represent promising biomarkers for diagnosis and monitoring of neurodegeneration.No embarg
Assessment of Family Involvement as A Determinant of Rehabilitative Therapy Administration, Change in Depression Severity, and Risk of Pressure Injuries Development in U.S. Nursing Home Residents
No full textABSTRACT
Background: As older adults transition to nursing homes from the community, their health and quality of life in nursing homes are significantly influenced by various factors, including family involvement in care planning. Family involvement is associated with better health outcomes in older adults, yet its impact on specific conditions like therapy administration, depression, and pressure injuries among nursing home residents remains understudied. This dissertation addresses these gaps by examining the role of family involvement in these key areas.
Methods: Using national data from the Minimum Data Set (MDS) 3.0, this dissertation explores the influence of family involvement on nursing home care and health outcomes from 2014 to 2019. The study includes three aims: 1) assessing the association between family involvement and rehabilitative therapy administration among newly admitted residents transferred from acute care in 2019; 2) examining the relationship between perceived family involvement and changes in depression severity in long-stay residents from 2014 to 2019, and 3) evaluating the impact of family involvement on the risk of developing stage 2 or higher pressure injuries in long-term care residents from 2014 to 2019. Statistical methods included linear regression, Poisson regression, and generalized estimating equations (GEEs).
Results: The first study included 2,112,330 residents aged 50 years and older. In Aim 1, residents who reported family involvement as "Very Important" received an average of 247 minutes of individual physical therapy and 236 minutes of individual occupational therapy, compared to 222 minutes of individual physical therapy and 215 minutes of individual occupational therapy among those who found it "Important, but no choice." Adjusted analyses showed that residents who rated family involvement as "Not Important at All" received 21 fewer therapy minutes (95% CI: -27, -15) compared to those who valued it as "Very Important." In Aim 2, among 2,043,308 long-stay nursing home residents, those with none-to-low baseline depression who perceived family involvement as "Not Important at All" had a 10% higher risk of significant worsening of depression symptoms (RR: 1.10, 95% CI: 1.06, 1.14) after adjusting for confounders, compared to those who considered it "Very Important." Conversely, among residents with moderate to moderately severe baseline depression, those who perceived family involvement as "Not Important at All" had a 33% higher risk of significant worsening (RR: 1.33, 95% CI: 1.10, 1.61) compared to the "Very Important" group, after adjusting for covariates. In Aim 3, among 579,958 residents, the relative risk of developing stage 2 or higher-pressure injuries was 0.97 (95% CI: 0.78, 1.22) for those who rated family involvement as "Not Important at All," compared to those who viewed it as "Very Important." Subgroup analysis revealed a higher risk for residents with severe physical impairments (RR: 1.34, 95% CI: 0.94, 1.93) and those with no urine output/ostomy (RR: 1.59, 95% CI: 0.88, 2.86).
Conclusions: This dissertation underscores the significant role of family involvement in enhancing the care and health outcomes of nursing home residents. Higher family engagement is associated with increased rehabilitative therapy use, reduced risk of worsening depression, and nuanced effects on pressure injury development, particularly among vulnerable subgroups. These findings highlight the need for nursing homes to foster family involvement in care planning as a strategy to improve residents' overall health and well-being. Implementing policies that encourage family engagement could lead to more personalized and effective care, ultimately enhancing the quality of life for older adults in nursing homes.Population Health Sciences2 years2027-05-0
Interpeduncular GABAergic neuron function controls threat processing and innate defensive adaptive learning
Full text linkThe selection of appropriate defensive behaviors in the face of potential threat is fundamental to survival. Equally important is learning to adjust and optimize defensive behaviors when there is no real danger. Despite extensive research on innate threat processing, little is known about the mechanisms by which individuals adapt their defensive behaviors in response to repeated threats that lack real danger. Insight into this process is critical as its dysregulation may contribute to neuropsychiatric conditions, such as anxiety disorders. Here, we used the visual looming stimulus (VLS) paradigm in mice to investigate innate threat processing and adaptive defensive learning. Repeated exposure to VLS over consecutive sessions reduced immediate freezing responses and time spent inside a sheltered area upon VLS events, leading to an increase in exploratory behaviors. Fiber photometry recordings and optogenetic manipulations revealed that VLS innate adaptive defensive learning is associated with reduced recruitment of the midbrain interpeduncular nucleus (IPN), a structure associated with fear and anxiety-related behaviors. Functional circuit-mapping identified a role for select IPN projections to the laterodorsal tegmental nucleus in gating defensive learning. Finally, we uncovered a subpopulation of IPN neurons that express the neuropeptide somatostatin and encode avoidance signals in response to VLS. These results identify critical behavioral signatures of innate defensive responses and a circuit that regulates the essential features of threat processing.No embarg
Physician as Good Samaritan: A Clinical Review of Responding to Motor Vehicle Collisions in the Community
No full textThere are over 6 million motor vehicle collisions (MVCs) in the United States per year, and it is likely clinicians will have the opportunity to assist victims of MVCs in the community as a bridge to prehospital care. This CME review prepares health care workers to respond appropriately when they encounter an MVC in the community. The management priorities for assisting in an MVC are: (1) scene safety, (2) notify EMS, (3) massive hemorrhage control, (4) airway, (5) respiration, (6) circulation, (7) head injuries and cervical spine immobilization, and (8) condition-specific management. Volunteer clinicians should continuously assess the scene for safety and plan escape routes. Extrication of passengers should only be performed if there is risk of the scene becoming unsafe or a need for emergency care. Massive hemorrhage may require the use of a commercial or makeshift tourniquet. There are special considerations for management in certain medical conditions, children, and pregnancy. Good Samaritan laws protect clinicians from legal liability when they perform good faith, volunteer assistance in community MVCs. Clinicians should be knowledgeable of the basic principles of MVC management to assist victims in the community and fulfill one of the purest expressions of their Hippocratic Oath.No embarg
UMCCTS Newsletter, December 2025
Full text linkThis is the December 2025 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.Supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grants UL1 TR001453, TL1 TR001454 and KL2 TR001455.No embarg
Characteristics and Medication Use Patterns of Pregnancies With COVID-19 Ending in Live-Birth in the Sentinel System
No full textBackground: Pregnant women are at high risk for developing severe illness related to COVID-19. We adapted the "COVID-19 infectiOn aNd medicineS In pregnancy" (CONSIGN) study protocol as part of an international collaboration to examine medication use patterns among pregnancies in the US.
Methods: We identified eligible women aged 12-55 years with documented live-birth deliveries in the Sentinel Distributed Database who had at least one qualifying diagnosis for COVID-19 or a positive-confirmed test for SARS-CoV-2, by trimester of COVID-19 infection. We conducted two sets of analyses comparing medication groups and COVID-19 treatment utilization in the 30 days prior to or after COVID-19 among pregnancies with COVID-19 to: (1) pregnancies without COVID-19 during 6 months prior to or during pregnancy; and (2) non-pregnancy episodes with COVID-19.
Results: From 2020 to 2022, we identified 52 355 pregnancies with COVID-19 matched to 52 355 pregnancies without COVID-19 (assigned same matched COVID-19 date), and 40 518 matched non-pregnancy episodes with COVID-19. Outpatient medication use in the 30 days prior to or after the COVID-19 date (or matched date) was quite low (< 15%) among pregnancies with and without COVID-19. Non-pregnancy episodes with COVID-19 had higher use of all medication groups in 30 days prior to COVID-19. However, in the 30 days post-COVID-19, anti-bacterials, anti-inflammatories such as NSAIDs, and analgesics were more common, and COVID-19-specific medications were less frequently used (< 1%) among pregnancies with COVID-19. Assessing COVID-19 severity, more pregnancies had a non-severe COVID-19 diagnosis than non-pregnancy episodes with COVID-19 (87.2% vs. 79.9%).
Conclusions: In this retrospective evaluation, selected medication utilization was higher post-COVID-19 among pregnancies with COVID-19, compared to those without COVID-19 and to non-pregnancy episodes with COVID-19. However, the low use of COVID-19-specific medications underscores the need for a safety evaluation of therapies used for COVID-19 management in the pregnant population.No embarg
Oral, Vaginal, and Gut Microbiome in Birthing Parents With and Without Preeclampsia
No full textPregnancy is a time of significant change to the microbiome, which can be influenced by medical intervention and parental disease states. Unhealthy parental microbiomes have been associated with adverse pregnancy outcomes including preterm birth and pregnancy loss. Recent data have shown differences in the gut microbiomes of birthing parents with and without preeclampsia (PE), but there are limited data on the birthing parent vaginal and oral microbiomes. Our objective was to comprehensively characterize and compare the oral, vaginal, and gut microbiome of birthing parents with and without PE during the third trimester of their pregnancy. Subjects planning for a vaginal birth were recruited in the third trimester of pregnancy at the time of admission for delivery. 16S rRNA gene sequencing and whole-genome sequencing (WGS) were performed on oral, vaginal, and gut samples. Within (alpha) and between (beta) subject diversity metrics were performed followed by discriminate taxa analysis. The vaginal microbiome samples were additionally classified into standard Community State Types (CSTs).
A total of 100 birthing parents were enrolled, 49 with PE and 51 without PE (controls). The oral microbiome diversity was significantly lower in birthing parents with, as compared to those without, PE (p=0.040). On the taxa level, individuals with PE showed enrichment of Rothia and depletion of Neisseria compared with controls, both of which are nitrate-reducing genera. Beta diversity was significantly different with greater inter-individual variability in the PE group (Bray-Curtis, p=0.020). Vaginal microbiome beta diversity was significantly greater in birthing parents with PE (p=0.014), and Lachnospiraceae, a taxon linked to vaginal dysbiosis, appeared exclusively in PE individuals. No significant differences between the PE and control groups were found in birthing parents' gut samples. We found that PE was associated with significant alterations in the oral and vaginal microbiome, but not in the gut microbiome, of birthing parents in the third trimester of pregnancy. Although future research is necessary to confirm and quantify the role of the microbiome in the development of PE, these initial findings suggest that the birthing parent microbiome may be a suitable target for identifying individuals as risk for PE and the development of microbiome-based therapies to prevent and treat hypertensive disorders of pregnancy (HDP).Master of Science in Clinical Investigation2 years2027-05-0
SAR Disease-focused Panel: Restaging Rectal Cancer MRI Synoptic Report-User Guide with Imaging Review
No full textNeoadjuvant therapy (NAT) for patients with rectal cancer is intended to reduce the risk of local recurrence and distant metastasis while preserving quality of life. Choosing the optimal approach after NAT is complex, requiring a personalized plan that considers the unique characteristics of each patient and their tumor, as well as the resources and capabilities of the treating institution. Advances in treatment, guided by insights from randomized clinical trials and increasing acceptance of organ preservation strategies, also known as nonoperative management or the watch-and-wait approach, emphasize the importance of precise treatment response assessment and multidisciplinary communication. A comprehensive evaluation using digital rectal examination, endoscopy, and MRI with a dedicated rectal cancer protocol ensures accurate clinical and locoregional response assessment. This integrative approach enables clinicians to make decisions regarding organ preservation, surgery, treatment de-escalation, or even additional NAT, with MRI having a critical role in surgical planning when resection is needed. The authors provide a comprehensive guide for interpreting postneoadjuvant rectal cancer MRI and applying the Society of Abdominal Radiology Colorectal and Anal Cancer Disease-focused Panel (SAR DFP) synoptic MRI restaging report template. The aim is to improve the quality, consistency, and clarity of MRI interpretations across different readers and institutions. Each section corresponds to the SAR DFP synoptic MRI restaging report template, addressing common areas of confusion and providing essential background material to ensure that clinically relevant information is clearly communicated to the treatment team, supporting effective decision making and enhancing patient outcomes. RSNA, 2025No embarg
Use and Effectiveness of Antidepressants for Depressive Symptoms and Agitation Among U.S. Nursing Home Residents With Alzheimer’s Disease and Related Dementias
No full textIn 2025, an estimated 7.1 million Americans were living with Alzheimer’s disease and related dementias (ADRD), with nursing homes serving as a major site of care. Antidepressants are the most commonly prescribed psychotropic medications for this population, yet prescribing patterns, indications, and comparative effectiveness for depressive symptoms and agitation remain poorly understood. This dissertation aimed to: (1) describe patterns of antidepressant prescribing by class, drug, and potential indications; (2) compare the effectiveness of selective serotonin reuptake inhibitors (SSRIs) versus serotonin–norepinephrine reuptake inhibitors (SNRIs) for depressive symptoms; and (3) compare SSRIs versus second-generation antipsychotics (SGAs) for agitation.
Using linked CMS data (2011–2018) and MDS 3.0 assessments, we identified long-stay nursing home residents aged ≥65 years with ADRD. Aim 1 used 2018 cross-sectional data. Aims 2 and 3 applied active-comparator new-user cohort designs with overlap propensity-score weighting, inverse probability of censoring weights, and generalized estimating equations to estimate adjusted effects for continuous and binary outcomes.
Among 232,543 residents, 51.6% used antidepressants, although 85% had no documented indication. SSRIs accounted for most use. In Aim 2 (10,832 SSRI and 1,454 SNRI initiators), both classes produced similar reductions in depressive symptoms, with no significant differences in adjusted mean change or clinically meaningful improvement. In Aim 3 (19,508 SSRI and 21,541 SGA initiators), SSRIs were associated with higher adjusted probabilities of minimal clinically significant improvement in agitation, particularly among residents with mild–moderate baseline agitation or cognitive impairment.
Over half of U.S. nursing home residents with ADRD received antidepressants, often without clear indications or depressive symptoms. SSRIs and SNRIs showed comparable effectiveness for depressive symptoms, while SSRIs performed favorably versus SGAs for agitation. Findings support individualized treatment decisions and highlight opportunities to improve dementia care in U.S. nursing homes.Population Health Sciences2 year
Investigation of Attenuation Correction Methods for Dual-Gated Single Photon Emission Computed Tomography (DG-SPECT)
Full text linkBackground: Cardiac-respiratory dual gating in SPECT (DG-SPECT) is an emergent technique for alleviating motion blurring artifacts in myocardial perfusion imaging (MPI) due to both cardiac and respiratory motions. Moreover, the attenuation artifact may arise from the spatial mismatch between the sequential SPECT and CT attenuation scans due to the dual gating of SPECT data and non-gating CT images.
Objectives: This study adapts a four-dimensional (4D) cardiac SPECT reconstruction with post-reconstruction respiratory motion correction (4D-RMC) for dual-gated SPECT. In theory, a respiratory motion-matched attenuation correction (MAC) method is expected to yield more accurate reconstruction results than the conventional motion-averaged attenuation correction (AAC) method. However, its potential benefit is not clear in the presence of practical imaging artifacts in DG-SPECT. In this study, we aim to quantitatively investigate these two attenuation methods for SPECT MPI: 4D-RMC (MAC) and 4D-RMC (AAC).
Methods: DG-SPECT imaging (eight cardiac gates and eight respiratory gates) of the NCAT phantom was simulated using SIMIND Monte Carlo simulation, with a lesion (20% reduction in uptake) introduced at four different locations of the left ventricular wall: anterior, lateral, septal, and inferior. For each respiratory gate, a joint cardiac motion-compensated 4D reconstruction was used. Then, the respiratory motion was estimated for post-reconstruction respiratory motion-compensated smoothing for all respiratory gates. The attenuation map averaged over eight respiratory gates was used for each respiratory gate in 4D-RMC (AAC) and the matched attenuation map was used for each respiratory gate in 4D-RMC (MAC). The relative root mean squared error (RMSE), structural similarity index measurement (SSIM), and a Channelized Hotelling Observer (CHO) study were employed to quantitatively evaluate different reconstruction and attenuation correction strategies.
Results: Our results show that the 4D-RMC (MAC) method improves the average relative RMSE by as high as 5.42% and the average SSIM value by as high as 1.28% compared to the 4D-RMC (AAC) method. Compared to traditional 4D reconstruction without RMC ("4D (MAC)"), these metrics were improved by as high as 11.23% and 27.96%, respectively. The 4D-RMC methods outperformed 4D (without RMC) on the CHO study with the largest improvement for the anterior lesion. However, the image intensity profiles, the CHO assessment, and reconstruction images are very similar between 4D-RMC (MAC) and 4D-RMC (AAC).
Conclusions: Our results indicate that the improvement of 4D-RMC (MAC) over 4D-RMC (AAC) is marginal in terms of lesion detectability and visual quality, which may be attributed to the simple NCAT phantom simulation, but otherwise suggest that AAC may be sufficient for clinical use. However, further evaluation of the MAC technique using more physiologically realistic digital phantoms that incorporate diverse patient anatomies and irregular respiratory motion is warranted to determine its potential clinical advantages for specific patient populations undergoing dual-gated SPECT myocardial perfusion imaging.No embarg