14809 research outputs found
Sort by
Association between cardiac autonomic dysfunction, cognitive impairment, and survival in patients with amyotrophic lateral sclerosis
Full text linkPurpose: The aim of this study was to investigate the relationship between cardiac autonomic dysfunction, cognitive impairment, and survival in patients with amyotrophic lateral sclerosis (ALS).
Methods: The heart activity of 65 patients with ALS (28 with normal cognition [ALS-CN]; 37 with impaired cognition [ALS-CI]) and 38 healthy controls (HCs) was measured by 24-h Holter monitoring. Heart rate (HR) measures and heart rate variability (HRV) parameters were compared between the three study groups and, additionally, correlated with five Edinburgh Cognitive and Behavioral ALS Screen (ECAS) domains in the ALS subgroups. Age, gender, and educational level were adjusted. Factors associated with cognitive status were assessed using logistic regression. Survival predictors in patients with ALS were analyzed using the Kaplan-Meier estimator and Cox regression.
Results: Compared to the HCs, patients with ALS-CI exhibited lower RRI (R-R-interval; P = 0.017), SDNN (standard deviation of all normal RR intervals; P = 0.013), SDNN Index (P = 0.044), and VLF power (very low-frequency power; P = 0.012). Total power was reduced in the ALS-CI group compared to the HCs (P = 0.036) and ALS-CN group (P = 0.048). In patients with ALS-CN, language negatively correlated with mean HR (P = 0.001) and positively with the RRI (P = 0.003), SDNN (P = 0.001), SDANN (standard deviation of the average NN intervals; P = 0.005), total power (P = 0.006), VLF power (P = 0.011), and low-frequency power (P = 0.026). Visuospatial function correlated positively with the SDNN Index (P = 0.041). In patients with ALS-CI, executive function (P = 0.015) and ECAS total score (P = 0.009) negatively correlated with the RMSSD (square root of mean sum-of-squares of differences between adjacent NN intervals), while visuospatial function correlated positively with normalized LF value (LFnu; P = 0.049). No associations were observed between the other cognitive domains and any of the 14 HRV/HR measures in patients with either ALS-CI or ALS-CN. SDNN ≤ 100 ms was linked to cognitive impairment (P = 0.039) and also showed a borderline association (P = 0.066) with poorer survival, while cognitive impairment (P = 0.010) was significantly linked to worse outcomes.
Conclusions: Patients with ALS with cognitive impairment demonstrated reduced cardiac autonomic modulations and altered cognitive autonomic associations. Cognitive impairment was linked to reduced survival, with baseline SDNN ≤ 100 ms identified as a potential marker.the National Natural Science Foundation of ChinaVoRSUNY DownstateNeurologyN/
Given a scenario, select the most appropriate response.
Full text linkPoetryFriends of Rochester Public LibraryVoRSUNY BrockportN/
Efficacy of a Novel BCL-xL Degrader, DT2216, in Preclinical Models of JAK2-mutated Post-MPN AML
Full text linkAcute myeloid leukemia (AML) that evolves from myeloproliferative neoplasm (MPN) is known as post-MPN AML. Current treatments don't significantly extend survival beyond 12 months. BCL-xL has been found to be overexpressed in leucocytes from MPN patients, making it a potential therapeutic target. We investigated the role of BCL-xL in post-MPN AML and tested the efficacy of DT2216, a platelet-sparing BCL-xL proteolysis-targeting chimera (PROTAC), in preclinical models of post-MPN AML. We found that BCL2L1, the gene encoding BCL-xL, is expressed at higher levels in post-MPN AML patients compared to those with de novo AML. Single-cell multi-omics analysis revealed that leukemia cells harboring both MPN-driver and TP53 mutations exhibited higher BCL2L1 expression, elevated scores for leukemia stem cell, megakaryocyte development, and erythroid progenitor than wild-type cells. BH3 profiling confirmed a strong dependence on BCL-xL in post-MPN AML cells. DT2216 alone, or in combination with standard AML/MPN therapies, effectively degraded BCL-xL, reduced the apoptotic threshold, and induced apoptosis in post-MPN AML cells. DT2216 effectively eliminated viable cells in JAK2-mutant AML cell lines, induced pluripotent stem cell-derived hematopoietic progenitor cells (iPSC-HPCs), primary samples, and reduced tumor burden in cell line-derived xenograft model in vivo by degrading BCL-xL. DT2216, either as a single agent or in combination with azacytidine, effectively inhibited the clonogenic potential of CD34+ leukemia cells from post-MPN AML patients. In summary, our data indicate that the survival of post-MPN AML is BCL-xL dependent, and DT2216 may offer therapeutic advantage in this high-risk leukemia subset with limited treatment options.VoRSUNY DownstateMedicineN/
The Bok-IP3R interaction and the impact it has on apoptosis, Bok stability, and IP3R-mediated calcium mobilization
Full text linkBcl-2-related ovarian killer, Bok, is often considered a pro-apoptotic Bcl-2 family member due to its ability to induce mitochondrial outer membrane permeabilization (MOMP) when over-expressed. However, there are many conflicting reports regarding endogenous Bok's apoptotic function and stability. Some studies claim that endogenous Bok is constitutively a MOMP-mediator but is very unstable and kept at very low levels via ubiquitin proteasome pathway (UPP)-mediated degradation. On the other hand, many studies, including those from the Wojcikiewicz Lab, indicate that endogenous Bok is a stable protein constitutively bound to inositol 1,4,5-trisphosphate receptors (IP3Rs), a calcium (Ca2+) release channel in the endoplasmic reticulum (ER) membrane, where it would be unable to induce MOMP. In fact, Bok KO mice have no developmental of phenotypical abnormalities, further suggesting that Bok's "killer" characterization needs to be reconsidered.
Since endogenous Bok is an ER protein, studying its MOMP-like properties seems futile. Therefore, focusing on the significance of the Bok-IP3R interaction has been the priority of the Wojcikiewicz Lab since we discovered the complex. Over the years, we found that Bok protects IP3Rs from proteolytic cleavage and that Bok stability is dependent on its ability to bind to IP3Rs. However, surprisingly, there is no clear evidence to date that Bok influences the Ca2+ mobilizing activity of IP3Rs.
Here, I study in detail the Bok-IP3R interaction and the impact it has on apoptosis, Bok stability, and IP3R-mediated Ca2+ mobilization. I resolve the controversy surrounding the apoptotic function of exogenous and endogenous Bok and hypothesize why there is a discrepancy between the two. Also, I show that IP3R binding in the ER membrane is essential for Bok stability, and without them Bok is rapidly degraded by the UPP. This demonstrates that the Bok-IP3R interaction is critical to Bok function, likely including its newly emerged non-apoptotic roles, such as regulating mitochondrial dynamics and mitochondria associated-ER membranes. Finally, for the first time, I reveal that Bok has suppressive effects on IP3R-mediated Ca2+ mobilization and describe how these effects are reversed when Bok is phosphorylated at serine-8. Overall, this thesis demonstrates the importance of the Bok-IP3R interaction on both Bok and IP3R function.NAUpstate Medical UniversityPharmacologyPhDWojcikiewicz, Richar
In the Webs of Globalization: Anna Tsing’s Friction and the Dynamics of Local-Global Encounters
Full text linkNASUNY OswegoAnthropologyN/
How salmonid fish hatcheries have negatively affected the fitness and long-term survival of wild populations
No full textNASUNY OswegoBiological SciencesN/
Effects of Induced Myopia on Inner Peripapillary Retinal Layer Structures
Full text link"Purpose: Myopic eye growth exerts mechanical stretching that can reshape the retinal architecture. This study investigates the longitudinal impact of induced myopia on peripapillary retinal layer structures in the common marmoset (Callithrix jacchus), a non-human primate model with close anatomical and developmental similarities to the human eye.
Methods: Thirteen juvenile marmosets were reared under binocular negative lens defocus for 23 weeks to induce myopia (six controls and seven treated). Serial measurements of cycloplegic refractive error and vitreous chamber depth were conducted alongside spectral domain optical coherence tomography (SD-OCT) imaging to assess regional peripapillary retinal layer thickness. Segmentation of OCT scans were used to quantify changes in total and individual retinal layers across four quadrants.
Results: Control animals exhibited age-related peripapillary thickening, particularly in the temporal quadrant of multiple inner retinal layers. In contrast, myopic eyes showed reduced thickening, and thinning at times, especially in the inferior and temporal regions. In particular, a significant thinning was observed in the inferior quadrants of the ganglion cell and inner plexiform layer in treated eyes. A regression analysis identified the inferior total retinal thickness and ganglion cell layer thickness to be the strongest predictors of vitreous chamber depth.
Conclusions: Induced myopia in marmosets leads to regional thinning of inner peripapillary retinal layers, suggesting early remodeling due to asymmetric retinal expansion. These findings contribute to understanding structural biomarkers of myopic progression and support the use of the marmoset model in translational vision science research."NASUNY College of OptometryM
The effect of therapeutic music playlists as a sleep aid on perceived sleep quality for college students: a pilot research protocol
Full text linkSleep is essential for our wellness and everyday performance. Poor sleep quality is highly prevalent among college students, with over 60% of them experiencing poor sleep quality (Becker et al., 2018). Multiple factors lead to poor sleep quality among college students, including academic stress, substance misuse, and unstable routines (Phillips et al., 2017; Summer, 2024a). A therapeutic playlist consists of songs in a specially arranged order to elicit desired response (McFerran & Grocke, 2022). To assist the client in achieving a restful state, it is recommended to choose music with the appropriate musical elements. These musical elements may include moderate tempos, soothing instrumentation, and the absence of sudden dynamic changes (Gaston, 1968; McFerran & Grocke, 2022). This research protocol aims to explore the use of therapeutic playlists as a sleep aid for college students experiencing sleep disturbances. The proposed research study will focus on how a therapeutic playlist will impact the perceived sleep quality of four college students, utilizing a multiple baseline design. In addition, it seeks to provide recommendations for music therapists and healthcare professionals using music with clients experiencing sleep disturbances. Key words: Sleep disturbances, Sleep deprivation, Therapeutic Playlists, Sedative music, Music
and Sleep, Music Listening and SleepNASUNY College at New PaltzMusic therapyMSZhang, JingwenMurphy, KathleenStuart-Rohm, Kary
Printmaking and the performing object: MFA Thesis - Printmaking
No full textThere were three objects on display in my thesis exhibit at the Dorsky Museum:
A Theater
A Book
A Cross between a Book and a Theater
After three years working the presses in the print studio at SUNY new Paltz, I have become
attuned to printmaking as a mediated process. The rollers, the press beds, the silkscreen
frames, the light tables have all been reminders that many phases separate the artist’s
intention from the finished product. Printmaking is a medium in the truest sense, I have found
– something that lies between the hand and the artwork – and the more time I have spent in
the studio, the more my focus has shifted away from the fine art image as an outcome and
towards printmaking itself as a technology. With this appreciation of printmaking not as an
autonomous art form but as a medium, I have chosen to direct its myriad capacities towards
developing a project in a domain not usually associated with fine art – puppet theater.NASUNY College at New PaltzPrintmakingMFAHoussart, EmilieDe Armendi Sobrino, Auror