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A protein panel in cerebrospinal fluid for diagnostic and predictive assessment of alzheimer’s disease
(American Association for the Advancement of Science, 2023) Haque, Rafi; Watson, Caroline M.; Liu, Jiaqi; Carter, E. Kathleen; Duong, Duc M.; Lah, James J.; Wingo, Aliza P.; Roberts, Blaine R.; Johnson, Erik C. B.; Saykin, Andrew J.; Shaw, Leslie M.; Seyfried, Nicholas T.; Wingo, Thomas S.; Levey, Allan I.; Radiology and Imaging Sciences, School of Medicine
Alzheimer's disease (AD) is a neurodegenerative disease with heterogenous pathophysiological changes that develop years before the onset of clinical symptoms. These preclinical changes have generated considerable interest in identifying markers for the pathophysiological mechanisms linked to AD and AD-related disorders (ADRD). On the basis of our prior work integrating cerebrospinal fluid (CSF) and brain proteome networks, we developed a reliable and high-throughput mass spectrometry-selected reaction monitoring assay that targets 48 key proteins altered in CSF. To test the diagnostic utility of these proteins and compare them with existing AD biomarkers, CSF collected at baseline visits was assayed from 706 participants recruited from the Alzheimer's Disease Neuroimaging Initiative. We found that the targeted CSF panel of 48 proteins (CSF 48 panel) performed at least as well as existing AD CSF biomarkers (Aβ42, tTau, and pTau181) for predicting clinical diagnosis, FDG PET, hippocampal volume, and measures of cognitive and dementia severity. In addition, for each of those outcomes, the CSF 48 panel plus the existing AD CSF biomarkers significantly improved diagnostic performance. Furthermore, the CSF 48 panel plus existing AD CSF biomarkers significantly improved predictions for changes in FDG PET, hippocampal volume, and measures of cognitive decline and dementia severity compared with either measure alone. A potential reason for these improvements is that the CSF 48 panel reflects a range of altered biology observed in AD/ADRD. In conclusion, we show that the CSF 48 panel complements existing AD CSF biomarkers to improve diagnosis and predict future cognitive decline and dementia severity.
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Defining minimal invasive surgical therapy for benign prostatic obstruction surgery: Perspectives from a global knowledge, attitude, and practice survey
(Elsevier, 2024) Kwun-Chung Cheng, Bryan; Kar-Kei Yuen, Steffi; Castellani, Daniele; Langer Wroclawski, Marcelo; Zhao, Hongda; Chiruvella, Mallikarjuna; Chua, Wei-Jin; Tiong, Ho-Yee; Tanidir, Yiloren; de la Rosette, Jean; Rijo, Enrique; Misrai, Vincent; Krambeck, Amy; Elterman, Dean S.; Somani, Bhaskar K.; Yuen-Chun Teoh, Jeremy; Gauhar, Vineet; Urology, School of Medicine
Objective: To scrutinize the definitions of minimal invasive surgical therapy (MIST) and to investigate urologists' knowledge, attitudes, and practices for benign prostatic obstruction surgeries. Methods: A 36-item survey was developed with a Delphi method. Questions on definitions of MIST and attitudes and practices of benign prostatic obstruction surgeries were included. Urologists were invited globally to complete the online survey. Consensus was achieved when more than or equal to 70% responses were "agree or strongly agree" and less than or equal to 15% responses were "disagree or strongly disagree" (consensus agree), or when more than or equal to 70% responses were "disagree or strongly disagree" and less than or equal to 15% responses were "agree or strongly agree" (consensus disagree). Results: The top three qualities for defining MIST were minimal blood loss (n=466, 80.3%), fast post-operative recovery (n=431, 74.3%), and short hospital stay (n=425, 73.3%). The top three surgeries that were regarded as MIST were Urolift® (n=361, 62.2%), Rezum® (n=351, 60.5%), and endoscopic enucleation of the prostate (EEP) (n=332, 57.2%). Consensus in the knowledge section was achieved for the superiority of Urolift®, Rezum®, and iTIND® over transurethral resection of the prostate with regard to blood loss, recovery, day surgery feasibility, and post-operative continence. Consensus in the attitudes section was achieved for the superiority of Urolift®, Rezum®, and iTIND® over transurethral resection of the prostate with regard to blood loss, recovery, and day surgery feasibility. Consensus on both sections was achieved for EEP as the option with the better symptoms and flow improvement, lower retreatment rate, and better suitable for prostate more than 80 mL. Conclusion: Minimal blood loss, fast post-operative recovery, and short hospital stay were the most important qualities for defining MIST. Urolift®, Rezum®, and EEP were regarded as MIST by most urologists.
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Do People With Schizophrenia Enjoy Social Activities as Much as Everyone Else? A Meta-analysis of Consummatory Social Pleasure
(Oxford University Press, 2023) Abel, Danielle B.; Rand, Kevin L.; Salyers, Michelle P.; Myers, Evan J.; Mickens, Jessica L.; Minor, Kyle S.; Psychology, School of Science
Background: The "emotion paradox" of schizophrenia suggests people with schizophrenia demonstrate deficits when reporting anticipated and retrospective pleasure; yet, in-the-moment, consummatory pleasure is largely intact. It is uncertain how these findings extend to social situations. This meta-analysis aimed to (1) determine the mean difference in consummatory social pleasure between people with schizophrenia and healthy controls, and (2) examine moderators of this effect, including study design and clinical characteristics of participants. Design: A literature search using PsycINFO, Web of Science, Pubmed, and EMBASE databases was conducted. Studies measuring consummatory social pleasure using experience sampling methods and laboratory social simulations were included. Random effects meta-analyses were conducted using Hedge's g. Results: Meta-analysis of 26 studies suggests people with schizophrenia exhibited a small, significant deficit in consummatory social pleasure (g = -0.38, 90% CI [-0.53, -0.22]). There was significant heterogeneity in effect sizes; magnitude was moderated by study design and type of measure used to assess social pleasure. Conclusions: Overall, people with schizophrenia seem to exhibit less consummatory social pleasure than controls. However, this deficit is smaller than in studies of anticipated and retrospective pleasure. Thus, consummatory social pleasure may not be quite as impaired in people with schizophrenia as traditional anhedonia research suggests. Moreover, pleasure deficits observed in people with schizophrenia may result from differences in the quality of their daily social experiences rather than differences in their capacity for social pleasure. Results have important implications for clinical interventions that address barriers to social engagement, low-pleasure beliefs, and cognitive remediation to treat schizophrenia.
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IgG4‐related inflammatory pancreatic head pseudotumor mirrors pancreatic head tumor: A novel case series with a review of the literature
(Wiley, 2024-02-04) Khan, Faheemullah; Shahid, Jehanzeb; Saleem, Amna; Khawaja, Uzzam Ahmed; Memon, Wasim Ahmed; Zafar, Uffan; Hameed, Tariq Abdul; Ahmed, Khabab Abbasher Hussien Mohamed; Radiology and Imaging Sciences, School of Medicine
Key clinical message: In this noteworthy case series regarding pancreatic pseudo tumors, we intend to spread knowledge among physicians for the diagnostic and therapeutic approach and eventual disease prognosis. Abstract: Inflammatory pseudotumor of pancreatic head greatly mimics pancreatic head tumor. One of them is IgG4-related pancreatic disease, which is commonly mistaken as neoplastic disease on imaging. In our novel case series, we report three cases of IgG4-related pancreatic head pseudotumor with patients ranging from 35 to 72 years of age. Patients presented with jaundice and abdominal pain. Alongside initial laboratory workup, abdominal CTs and serum IgG4 levels were also obtained. Imaging features in conjunction with IgG4 levels confirmed the diagnosis of IgG4-related autoimmune pancreatitis. Pancreatic pseudotumors are notorious for being often reported as real tumors. Through our noteworthy case series, we intend to highlight the imaging features and laboratory markers that are crucial in such cases to avoid invasive procedures.
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Mechanical loading is required for initiation of extracellular matrix deposition at the developing murine myotendinous junction
(Elsevier, 2023) Lipp, Sarah N.; Jacobson, Kathryn R.; Colling, Haley A.; Tuttle, Tyler G.; Miles, Dalton T.; McCreery, Kaitlin P.; Calve, Sarah; Medicine, School of Medicine
The myotendinous junction (MTJ) contributes to the generation of motion by connecting muscle to tendon. At the adult MTJ, a specialized extracellular matrix (ECM) is thought to contribute to the mechanical integrity of the muscle-tendon interface, but the factors that influence MTJ formation during mammalian development are unclear. Here, we combined 3D imaging and proteomics with murine models in which muscle contractility and patterning are disrupted to resolve morphological and compositional changes in the ECM during MTJ development. We found that MTJ-specific ECM deposition can be initiated via static loading due to growth; however, it required cyclic loading to develop a mature morphology. Furthermore, the MTJ can mature without the tendon terminating into cartilage. Based on these results, we describe a model wherein MTJ development depends on mechanical loading but not insertion into an enthesis.