30 results on '"Ward, Christopher"'
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2. PD: A professional deterrence? The financial cost and time commitment of professional development for VET practitioners in Western Australia
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Ward, Christopher and Rodd, Piper
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- 2024
3. The recent disappearance of a persistent Planktothrix bloom: Characterization of a regime shift in the phytoplankton of Sandusky Bay (USA)
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Wagner, Ryan S., Neudeck, Michelle J., Heath, Alexis E., Barker, Katelyn B., Brown, Katelyn M., Buchholz, Seth, Ward, Christopher S., and Bullerjahn, George S.
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- 2024
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4. Airway management in the paediatric difficult intubation registry: a propensity score matched analysis of outcomes over time
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Bruins, Benjamin, Stricker, Paul, Laverriere, Elizabeth, Lockman, Justin L., Struyk, Brian, Ward, Christopher, Nishisaki, Akira, Kodavatiganti, Ramesh, Guris, Rodrigo Daly, Sequera-Ramos, Luis, Teen, Mark, Oke, Ayodele, Hsu, Grace, Lingappan, Arul, Battles, Rhae, Bocanegra, Ashley, Goldfarb, Tally, Kiss, Edgar, Szmuk, Peter, Mireles, Sam, Murray, Andrea, Whyte, Simon, Jain, Ranu, Matuszczak, Maria, Holmes, Christopher, McCann, Alexander, Matava, Clyde, Dalesio, Nicholas, Greenberg, Robert, Lucero, Angela, Desai, Sapna, Rosander, Sondra, Samba, Sindhu, Schrock, Charles, Nykiel-Bailey, Sydney, Marsh, Jennifer, Peterson, Melissa Brooks, Lee, Amy, Bhattacharya, Somaletha, Burjek, Nicholas, Jagannathan, Narasimhan, Lardner, David, Crockett, Christy, Robetson, Sara, Patel, Jasmine, Sharma, Aarti, Templeton, Thomas, Marín, Piedad Echeverry, Pérez-Pradilla, Carolina, Singh, Neeta, Sommerfield, David, Hauser, Neil, Hesselink, Emily, Lewkowitz-Shpuntoff, Hilana, Castro, Pilar, Riveros Perez, N. Ricardo, Vega, Eduardo, González, Alejandro, Ostermann, Paola, Rubin, Kasia, Meserve, Jonathan, Lord, Charles, Lee, Angela, Valairucha, Songyos, Dalal, Priti, Tran, Thanh, Anspach, Taylor, Lee, Lisa K., Ayad, Ihab, Rehman, Mohamed, Fernandez, Allison, Zamora, Lillian, Ravula, Niroop, Shaik, Sadiq, Szolnoki, Judit, Mathew, Preethy, Yaddanapudi, Sandhya, Sen, Indu, Gupta, Aakriti, Handlogten, Kathryn, Sroka, J. Michael, Quintão, Vinícius Caldeira, Carlos, Ricardo Vieira, Leite, Fernanda, Stein, Mary Lyn, Sarmiento Argüello, Lina Andrea, Staffa, Steven J., Heunis, Julia, Egbuta, Chinyere, Flynn, Stephen G., Khan, Sabina A., Sabato, Stefano, Taicher, Brad M., Chiao, Franklin, Bosenberg, Adrian, Lee, Angela C., Adams, H. Daniel, von Ungern-Sternberg, Britta S., Park, Raymond S., Peyton, James M., Olomu, Patrick N., Hunyady, Agnes I., Garcia-Marcinkiewicz, Annery, Fiadjoe, John E., and Kovatsis, Pete G.
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- 2024
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5. Bile acids and the gut microbiome are involved in the hyperthermia mediated by 3,4-methylenedioxymethamphetamine (MDMA).
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Rana, Srishti, Canfield, Jeremy R., Ward, Christopher S., and Sprague, Jon E.
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GUT microbiome ,BILE acids ,ECSTASY (Drug) ,SYMPATHETIC nervous system ,FEVER - Abstract
Hyperthermia induced by phenethylamines, such as 3,4–methylenedioxymethamphetamine (MDMA), can lead to life-threatening complications and death. Activation of the sympathetic nervous system and subsequent release of norepinephrine and activation of uncoupling proteins have been demonstrated to be the key mediators of phenethylamine-induced hyperthermia (PIH). Recently, the gut microbiome was shown to also play a contributing role in PIH. Here, the hypothesis that bile acids (BAs) produced by the gut microbiome are essential to PIH was tested. Changes in the serum concentrations of unconjugated primary BAs cholic acid (CA) and chenodeoxycholic acid (CDCA) and secondary BA deoxycholic acid (DCA) were measured following MDMA (20 mg/kg, sc) treatment in antibiotic treated and control rats. MDMA-induced a significant hyperthermic response and reduced the serum concentrations of three BAs 60 min post-treatment. Pretreatment with antibiotics (vancomycin, bacitracin and neomycin) in the drinking water for five days resulted in the depletion of BAs and a hypothermic response to MDMA. Gut bacterial communities in the antibiotic-treated group were distinct from the MDMA or saline treatment groups, with decreased microbiome diversity and alteration in taxa. Metagenomic functions inferred using the bioinformatic tool PICRUSt2 on 16S rRNA gene sequences indicated that bacterial genes associated to BA metabolism are less abundant in the antibiotic-MDMA treated group. Overall, these findings suggest that gut bacterial produced BAs might play an important role in MDMA-induced hyperthermia. [ABSTRACT FROM AUTHOR]
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- 2024
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6. Distinct Effects of Respiratory Viral Infection Models on miR-149-5p, IL-6 and p63 Expression in BEAS-2B and A549 Epithelial Cells.
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Shahdab, Nafeesa, Ward, Christopher, Hansbro, Philip M., Cummings, Stephen, Young, John S., and Moheimani, Fatemeh
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GENE expression , *EPITHELIAL cells , *INTERLEUKIN-6 , *VIRUS diseases , *RESPIRATORY infections , *PORCINE reproductive & respiratory syndrome - Abstract
Respiratory viruses cause airway inflammation, resulting in epithelial injury and repair. miRNAs, including miR-149-5p, regulate different pathological conditions. We aimed to determine how miR-149-5p functions in regulating pro-inflammatory IL-6 and p63, key regulators of airway epithelial wound repair, in response to viral proteins in bronchial (BEAS-2B) and alveolar (A549) epithelial cells. BEAS-2B or A549 cells were incubated with poly (I:C, 0.5 µg/mL) for 48 h or SARS-CoV-2 spike protein-1 or 2 subunit (S1 or S2, 1 μg/mL) for 24 h. miR-149-5p was suppressed in BEAS-2B challenged with poly (I:C), correlating with IL-6 and p63 upregulation. miR-149-5p was down-regulated in A549 stimulated with poly (I:C); IL-6 expression increased, but p63 protein levels were undetectable. miR-149-5p remained unchanged in cells exposed to S1 or S2, while S1 transfection increased IL-6 expression in BEAS-2B cells. Ectopic over-expression of miR-149-5p in BEAS-2B cells suppressed IL-6 and p63 mRNA levels and inhibited poly (I:C)-induced IL-6 and p63 mRNA expressions. miR-149-5p directly suppressed IL-6 mRNA in BEAS-2B cells. Hence, BEAS-2B cells respond differently to poly (I:C), S1 or S2 compared to A549 cells. Thus, miR-149-5p dysregulation may be involved in poly (I:C)-stimulated but not S1- or S2-stimulated increased IL-6 production and p63 expression in BEAS-2B cells. [ABSTRACT FROM AUTHOR]
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- 2024
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7. Bacterial community and cyanotoxin gene distribution of the Winam Gulf, Lake Victoria, Kenya.
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Brown, Katelyn M., Barker, Katelyn B., Wagner, Ryan S., Ward, Christopher S., Sitoki, Lewis, Njiru, James, Omondi, Reuben, Achiya, James, Getabu, Albert, McKay, R. Michael, and Bullerjahn, George S.
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CYANOBACTERIAL toxins ,AGRICULTURE ,ALGAL blooms ,RIBOSOMAL RNA ,WASTEWATER treatment ,SUMMER - Abstract
The Winam Gulf (Kenya) is frequently impaired by cyanobacterial harmful algal blooms (cHABs) due to inadequate wastewater treatment and excess agricultural nutrient input. While phytoplankton in Lake Victoria have been characterized using morphological criteria, our aim is to identify potential toxin‐producing cyanobacteria using molecular approaches. The Gulf was sampled over two successive summer seasons, and 16S and 18S ribosomal RNA gene sequencing was performed. Additionally, key genes involved in production of cyanotoxins were examined by quantitative PCR. Bacterial communities were spatially variable, forming distinct clusters in line with regions of the Gulf. Taxa associated with diazotrophy were dominant near Homa Bay. On the eastern side, samples exhibited elevated cyrA abundances, indicating genetic capability of cylindrospermopsin synthesis. Indeed, near the Nyando River mouth in 2022, cyrA exceeded 10 million copies L−1 where there were more than 6000 Cylindrospermopsis spp. cells mL−1. In contrast, the southwestern region had elevated mcyE gene (microcystin synthesis) detections near Homa Bay where Microcystis and Dolichospermum spp. were observed. These findings show that within a relatively small embayment, composition and toxin synthesis potential of cHABs can vary dramatically. This underscores the need for multifaceted management approaches and frequent cyanotoxin monitoring to reduce human health impacts. [ABSTRACT FROM AUTHOR]
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- 2024
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8. Rail-wheel friction quantification and its variability under lab and field trial conditions.
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White, Ben, Lewis, Roger, Fletcher, David, Harrison, Tim, Hubbard, Peter, and Ward, Christopher
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Friction forces (often referred to as adhesion or traction forces) at the wheel/rail interface can vary dramatically due to changing environmental and contact conditions. The causes of this variance are partially documented, but it is not fully understood. Friction forces affect wheel and rail wear, traction energy usage, vehicle dynamics and safety through braking performance. A range of different portable railhead tribometers are used in the field to measure friction, but until recently have been limited in their performance, being unable to measure low friction situations or have made use of an unrealistic contact geometry. Recent developments have improved this situation but there is currently a lack of published field data which is required for validation, benchmarking and comparison between other studies and test rigs, as well as for input to multi-body dynamics simulations of railway vehicles. Friction studies in general are often undertaken for a specific period of time or under closely controlled conditions which makes it difficult to understand the true range of conditions occurring in the wheel/rail contact. In this paper an extensive dataset of railhead measurements is presented, using two types of measuring devices and three railhead conditions throughout a 4-week test period. Confidence in tribometer results was gained by comparing between established laboratory friction test rigs and methodologies. The results provide an insight into the friction variance and transient conditions that would occur on the railhead during operational use. [ABSTRACT FROM AUTHOR]
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- 2024
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9. Clinical Decision Making in Inflammatory Bowel Disease Mimics: Practice Management from Inflammatory Bowel Disease LIVE.
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Fiske, Hannah W, Ward, Christopher, Shah, Samir A, Holubar, Stefan D, Al-Bawardy, Badr, Barnes, Edward L, Binion, David, Bohm, Matthew, Brand, Myron, Clarke, Kofi, Cohen, Benjamin L, Cross, Raymond K, Dueker, Jeffrey, Engels, Michael, Farraye, Francis A, Fine, Sean, Forster, Erin, Gaidos, Jill, Ginsburg, Philip, and Goyal, Alka
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- 2024
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10. Difficult intubation in syndromic versus nonsyndromic forms of micrognathia in children.
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Hunyady, Agnes I., Sergeeva, Vera, Kovatsis, Pete G., Evans, Kelly N., Staffa, Steven J., Zurakowski, David, Fiadjoe, John E., Jimenez, Nathalia, von Ungern‐Sternberg, Britta S, Sommerfield, David, Hauser, Neil, Taicher, Brad M, Dalesio, Nicholas M, Matuszczak, Maria, Garcia‐Marcinkiewicz, Annery G., Bruins, Benjamin B., Kodavatiganti, Ramesh, Hsu, Grace, Ward, Christopher, and Struyk, Brian
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TRACHEA intubation ,MICROGNATHIA ,INTUBATION ,PROPENSITY score matching ,CRANIOFACIAL abnormalities - Abstract
Background: We investigated how syndromic versus nonsyndromic forms of micrognathia impacted difficult intubation outcomes in children. Primary outcome was the first‐attempt success rate of tracheal intubation, secondary outcomes were number of intubation attempts and complications. We hypothesized that syndromic micrognathia would be associated with lower first‐attempt success rate. Methods: In micrognathic patients enrolled in the Pediatric Difficult Intubation Registry (08/2012–03/2019) we retrospectively compared demographic and clinical characteristics between children with nonsyndromic and syndromic micrognathia using standardized mean differences (SMD) and assessed the association of the presence of syndrome with the primary and secondary outcomes using propensity score matching analysis with and without matching for airway assessment findings. Results: Nonsyndromic patients (628) were less likely to have additional airway abnormalities. Syndromic patients (216) were less likely to have unanticipated difficult intubation (2% vs. 20%, SMD 0.59). First‐attempt success rates of intubation were: 38% in the syndromic versus 34% in the nonsyndromic group (odds ratio [OR] 1.18; 95% confidence intervals [95% CI] 0.74, 1.89; p =.478), and 37% versus 37% (OR 0.99; 95% CI 0.66, 1.48; p =.959). Median number of intubation attempts were 2 (interquartile range [IQR]: 1, 3; range: 1, 8) versus 2 (IQR: 1, 3; range 1, 12) (median regression coefficient = 0; 95% CI: −0.7, 0.7; p =.999) and 2 (IQR: 1, 3; range: 1, 12) versus 2 (IQR: 1, 3; range 1, 8) (median regression coefficient = 0; 95% CI: −0.5, 0.5; p =.999). Complication rates were 14% versus 22% (OR 0.6; 95% CI 0.34, 1.04; p =.07) and 16% versus 21% (OR 0.71; 95% CI 0.43, 1.17; p =.185). Conclusions: Presence of syndrome was not associated with lower first‐attempt success rate on intubation, number of intubation attempts, or complication rate among micrognathic patients difficult to intubate, despite more associated craniofacial abnormalities. Nonsyndromic patients were more likely to have unanticipated difficult intubations, first attempt with direct laryngoscopy. [ABSTRACT FROM AUTHOR]
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- 2024
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11. Volume loss during muscle reinnervation surgery is correlated with reduced CMAP amplitude but not reduced force output in a rat hindlimb model.
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Lowe, Alexis L., Santana, Maria V. Rivera, Bopp, Taylor, Quinn, Kiara N., Johnson, Johnnie, Ward, Christopher, Tae Hwan Chung, Tuffaha, Sami, and Thakor, Nitish V.
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NERVE grafting ,ANIMAL disease models ,ACTION potentials ,PERONEAL nerve ,MUSCLE mass ,TISSUE analysis - Abstract
Introduction: Muscle reinnervation (MR) surgery offers rehabilitative benefits to amputees by taking severely damaged nerves and providing them with new denervated muscle targets (DMTs). However, the influence of physical changes to muscle tissue during MR surgery on long-term functional outcomes remains understudied. Methods: Our rat hindlimb model of MR surgery utilizes vascularized, directly neurotized DMTs made from the lateral gastrocnemius (LG), which we employed to assess the impact of muscle tissue size on reinnervation outcomes, specifically pairing the DMT with the transected peroneal nerve. We conducted MR surgery with both DMTs at full volume and DMTs with partial volume loss of 500 mg at the time of surgery (n = 6 per group) and measured functional outcomes after 100 days of reinnervation. Compound motor action potentials (CMAPs) and isometric tetanic force production was recorded from reinnervated DMTs and compared to contralateral naïve LG muscles as positive controls. Results: Reinnervated DMTs consistently exhibited lower mass than positive controls, while DMTs with partial volume loss showed no significant mass reduction compared to full volume DMTs (p = 0.872). CMAP amplitudes were lower on average in reinnervated DMTs, but a broad linear correlation also exists between muscle mass and maximum CMAP amplitude irrespective of surgical group (R2 = 0.495). Surprisingly, neither MR group, with or without volume loss, demonstrated decreased force compared to positive controls. The average force output of reinnervated DMTs, as a fraction of the contralateral LG's force output, approached 100% for both MR groups, a notable deviation from the 9.6% (±6.3%) force output observed in our negative control group at 7 days post-surgery. Tissue histology analysis revealed few significant differences except for a marked decrease in average muscle fiber area of reinnervated DMTs with volume loss compared to positive controls (p = 0.001). Discussion: The results from our rat model of MR suggests that tissue electrophysiology (CMAPs) and kinesiology (force production) may recover on different time scales, with volumetric muscle loss at the time of MR surgery not significantly reducing functional outcome measurements for the DMTs after 100 days of reinnervation. [ABSTRACT FROM AUTHOR]
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- 2024
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12. Coexisting Primary Sclerosing Cholangitis and Autoimmune Hepatitis: Overlapping Challenges in Diagnosis and Treatment.
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Fiske, Hannah W., Saeed, Firrah, Ward, Christopher, Sinayuk, Boris, Ulici, Veronica, Curry, Michael, Feller, Edward, and Shah, Samir A.
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AUTOIMMUNE hepatitis ,CHOLANGITIS ,DIAGNOSIS ,BILIOUS diseases & biliousness ,LIVER diseases ,ULCERATIVE colitis - Abstract
Introduction: Hepatobiliary overlap syndromes describe the coinciding presentation of more than one immune-mediated biliary and liver disease in a single patient and present complex challenges in diagnosis and treatment. We report a case of ulcerative colitis with primary sclerosing cholangitis and autoimmune hepatitis overlap syndrome responsive to vancomycin. Case Presentation: The patient is a 30-year-old female with known ulcerative pancolitis and autoimmune hepatitis. She presented to the emergency department with a constellation of gastrointestinal symptoms, including diffuse lower abdominal pain, bloody diarrhea, and nausea with bilious vomiting. Subsequent imaging revealed the additional diagnosis of primary sclerosing cholangitis, and she was diagnosed with overlap syndrome. Multiple treatment regimens were trialed with minimal improvement. She eventually achieved normalization of both clinical status and biochemical markers after the addition of vancomycin. Conclusion: Vancomycin is an underutilized therapy; its potential role in primary sclerosing cholangitis and autoimmune hepatitis overlap syndrome has not been previously reported. [ABSTRACT FROM AUTHOR]
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- 2024
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13. President's Column.
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Ward, Christopher A.
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TASK forces - Abstract
This document is a column written by the President of the American Bankruptcy Institute (ABI). The President expresses gratitude to past Presidents and acknowledges the important role of the organization's staff. They outline their goals for the coming year, which include strengthening the bond between members and the organization, developing ties between older and younger members, and promoting mentorship and inclusion. The President also mentions specific initiatives that will be implemented, such as the ABI Resident Scholar Program and a new podcast series. The article discusses various initiatives and updates within ABI, including virtual town halls, the "40 Under 40" program, and the work of the Diversity and Inclusion Working Group. It also emphasizes the strategic planning efforts and the significance of the ABI Endowment for the organization's sustainability. The article concludes with a tribute to Judge Carey, a dedicated colleague who recently passed away. [Extracted from the article]
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- 2024
14. P396: Circadian and behavioral differences with Rai1 haploinsufficiency in the setting of hyperphagia-induced weight gain
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Agrons, Kenyon, Hufft, Gracie, Elsea, Sarah, Ward, Christopher, and McDowell-Takahashi, Kathleen
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- 2024
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15. Editor's Note.
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Ward, Christopher J.
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The second issue of the Soviet & Post-Soviet Review for 2024 focuses on the ongoing war between Russia and Ukraine. Despite the challenging circumstances, the journal features four articles that provide valuable insights into different aspects of the conflict. The articles cover topics such as the representation of victims and victimizers in recent Russian films, the impact of the war on the Finnish-Russian border region, the memorialization of victims of political repressions in Belarus, and personal recollections of noncombatants during the Second World War in the Kursk Oblast region. The journal aims to shed light on these complex issues and contribute to a better understanding of the conflict. [Extracted from the article]
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- 2024
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16. MP-470551-006 INHIBITION OF LYSOSOMAL CA2+ RELEASE ABOLISHES CA2+-BASED ARRHYTHMIAS.
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Kaplan, Aaron, Boyman, Liron, Ward, Christopher W., Lederer, W. Jonathan, and Greiser, Maura
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- 2024
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17. PO-CES-02 INHIBITION OF LYSOSOMAL CA2+ RELEASE ABOLISHES CA2+-BASED ARRHYTHMIAS
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Kaplan, Aaron, Boyman, Liron, Ward, Christopher W., Lederer, W. Jonathan, and Greiser, Maura
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- 2024
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18. 817 Trans-placental transport of a novel fluorescent lipid nanoparticle in a pre-clinical fetal therapy murine model
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Zietsman, Maryshe S., Shanahan, Matthew A., Barrozo, Enrico R., Seferovic, Maxim D., Bhavane, Rohan, Bhandari, Prajwal, Ghaghada, Ketan, Cortes, Magdalena Sanz, Ward, Christopher, Belfort, Michael A., and Aagaard, Kjersti M.
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- 2024
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19. BIOLOGICS AND SMALL MOLECULES USED IN IBD MIMICS: HIGHLIGHTING THE IMPORTANCE OF DIAGNOSIS CONFIRMATION.
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Fiske, Hannah, Ward, Christopher, Shah, Samir, Clarke, Kofi, Williams, Emmanuelle, Farraye, Francis, Siegel, Corey, Cross, Raymond, Hull, Tracy, Binion, David, Wexner, Steven, Goyal, Alka, Lazarev, Mark, Dueker, Jeffrey, Hanson, John, Watson, Andrew, Al-Bawardy, Badr, Barnes, Edward, Brand, Myron, and Melia, Joanna
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- 2024
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20. Results from the randomized phase III DREAMM-7 study of belantamab mafodotin (belamaf) + bortezomib, and dexamethasone (BVd) vs daratumumab, bortezomib, and dexamethasone (DVd) in relapsed/refractory multiple myeloma (RRMM).
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Mateos, Maria-Victoria, Robak, Pawel, Hus, Marek, Xia, Zhongjun, Zherebtsova, Vera, Ward, Christopher, Ho, P. Joy, Hajek, Roman, Kim, Kihyun, Dimopoulos, Meletios A., Cerchione, Claudio, Riccio, Antonio, McKeown, Astrid, Rogers, Rachel, Baig, Hena, Eccersley, Lydia, Roy-Ghanta, Sumita, Opalinska, Joanna, and Hungria, Vania
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- 2024
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21. Scanning WAXS microscopy of regenerated cellulose fibers at mesoscopic resolution.
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Johansson S, Scattarella F, Kalbfleisch S, Johansson U, Ward C, Hetherington C, Sixta H, Hall S, Giannini C, and Olsson U
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In this work, regenerated cellulose textile fibers, Ioncell-F, dry-wet spun with different draw ratios, have been investigated by scanning wide-angle X-ray scattering (WAXS) using a mesoscopic X-ray beam. The fibers were found to be homogeneous on the 500 nm length scale. Analysis of the azimuthal angular dependence of a crystalline Bragg spot intensity revealed a radial dependence of the degree of orientation of crystallites that was found to increase with the distance from the center of the fiber. We attribute this to radial velocity gradients during the extrusion of the spin dope and the early stage of drawing. On the other hand, the fiber crystallinity was found to be essentially homogeneous over the fiber cross section., (open access.)
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- 2024
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22. Acute microtubule changes linked to DMD pathology are insufficient to impair contractile function or enhance contraction-induced injury in healthy muscle.
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Vanegas C, Ursitti J, Kallenbach JG, Pinto K, Harriot A, Coleman AK, Shi G, and Ward CW
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Duchenne muscular dystrophy (DMD) is marked by the genetic deficiency of the dystrophin protein in striated muscle whose consequence is a cascade of cellular changes that predispose the susceptibility to contraction injury central to DMD pathology. Recent evidence identified the proliferation of microtubules enriched in post-translationally modified tubulin as a consequence of dystrophins absence that increases the passive mechanics of the muscle fiber and the excess mechanotransduction elicited reactive oxygen species and calcium signals that promote contraction injury. Motivated by evidence that acutely normalizing the disease microtubule alterations reduced contraction injury in murine DMD muscle ( mdx ), here we sought the direct impact of these microtubule alterations independent of dystrophins absence and the multitude of other changes consequent to dystrophic disease. To this end we used acute pharmacologic (epithiolone-D, EpoD; 4 hours) or genetic (vashohibin-2 and small vasohibin binding protein overexpression via AAV9; 2 weeks) strategies to effectively model the proliferation of detyrosination enriched microtubules in the mdx muscle. Quantifying in vivo nerve evoked plantarflexor function we find no alteration in peak torque nor contraction kinetics in WT mice modeling these DMD relevant MT alterations. Quantifying the susceptibility to eccentric contraction injury we show EpoD treatment proffered a small but significant protection from contraction injury while VASH/SVBP had no discernable impact. We conclude that the disease dependent MT alterations act in concert with additional cellular changes to predispose contraction injury in DMD., Competing Interests: Conflicts of Interest Christopher W. Ward is the Chief Scientific Officer of Myologica, LLC. All other authors declare no conflicts of interest.
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- 2024
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23. High throughput cell mechanotyping of cell response to cytoskeletal modulations using a microfluidic cell deformation system.
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Smith IM, Ursitti JA, Majeti P, Givpoor N, Stemberger MB, Hengen A, Banerjee S, Stains J, Martin SS, Ward C, and Stroka KM
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Cellular mechanical properties influence cellular functions across pathological and physiological systems. The observation of these mechanical properties is limited in part by methods with a low throughput of acquisition or with low accessibility. To overcome these limitations, we have designed, developed, validated, and optimized a microfluidic cellular deformation system (MCDS) capable of mechanotyping suspended cells on a population level at a high throughput rate of ∼300 cells pers second. The MCDS provides researchers with a viable method for efficiently quantifying cellular mechanical properties towards defining prognostic implications of mechanical changes in pathology or screening drugs to modulate cytoskeletal integrity.
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- 2024
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24. Belantamab Mafodotin, Bortezomib, and Dexamethasone for Multiple Myeloma.
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Hungria V, Robak P, Hus M, Zherebtsova V, Ward C, Ho PJ, Ribas de Almeida AC, Hajek R, Kim K, Grosicki S, Sia H, Bryant A, Pitombeira de Lacerda M, Aparecida Martinez G, Sureda Balarí AM, Sandhu I, Cerchione C, Ganly P, Dimopoulos M, Fu C, Garg M, Abdallah AO, Oriol A, Gatt ME, Cavo M, Rifkin R, Fujisaki T, Mielnik M, Pirooz N, McKeown A, McNamara S, Zhou X, Nichols M, Lewis E, Rogers R, Baig H, Eccersley L, Roy-Ghanta S, Opalinska J, and Mateos MV
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Background: Belantamab mafodotin had single-agent activity in patients with relapsed or refractory multiple myeloma, a finding that supports further evaluation of the agent in combination with standard-care therapies., Methods: In this phase 3, open-label, randomized trial, we evaluated belantamab mafodotin, bortezomib, and dexamethasone (BVd), as compared with daratumumab, bortezomib, and dexamethasone (DVd), in patients who had progression of multiple myeloma after at least one line of therapy. The primary end point was progression-free survival. Key secondary end points were overall survival, response duration, and minimal residual disease (MRD)-negative status., Results: In total, 494 patients were randomly assigned to receive BVd (243 patients) or DVd (251 patients). At a median follow-up of 28.2 months (range, 0.1 to 40.0), median progression-free survival was 36.6 months (95% confidence interval [CI], 28.4 to not reached) in the BVd group and 13.4 months (95% CI, 11.1 to 17.5) in the DVd group (hazard ratio for disease progression or death, 0.41; 95% CI, 0.31 to 0.53; P<0.001). Overall survival at 18 months was 84% in the BVd group and 73% in the DVd group. An analysis of the restricted mean response duration favored BVd over DVd (P<0.001). A complete response or better plus MRD-negative status occurred in 25% of the patients in the BVd group and 10% of those in the DVd group. Grade 3 or higher adverse events occurred in 95% of the patients in the BVd group and 78% of those in the DVd group. Ocular events were more common in the BVd group than in the DVd group (79% vs. 29%); such events were managed with dose modifications, and events of worsening visual acuity mostly resolved., Conclusions: As compared with DVd therapy, BVd therapy conferred a significant benefit with respect to progression-free survival among patients who had relapsed or refractory multiple myeloma after at least one line of therapy. Most patients had grade 3 or higher adverse events. (Funded by GSK; DREAMM-7 ClinicalTrials.gov number, NCT04246047; EudraCT number, 2018-003993-29.)., (Copyright © 2024 Massachusetts Medical Society.)
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- 2024
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25. Vglut2-based glutamatergic signaling in central noradrenergic neurons is dispensable for normal breathing and chemosensory reflexes.
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Chang Y, Lusk S, Chang A, Ward CS, and Ray RS
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Central noradrenergic (NA) neurons are key constituents of the respiratory homeostatic network. NA dysfunction is implicated in several developmental respiratory disorders including Congenital Central Hyperventilation Syndrome (CCHS), Sudden Infant Death Syndrome (SIDS) and Rett Syndrome. The current unchallenged paradigm in the field, supported by multiple studies, is that glutamate co-transmission in subsets of central NA neurons plays a role in breathing control. If true, NA-glutamate co-transmission may also be mechanistically important in respiratory disorders. However, the requirement of NA-derived glutamate in breathing has not been directly tested and the extent of glutamate co-transmission in the central NA system remains uncharacterized. Therefore, we fully characterized the cumulative fate maps and acute adult expression patterns of all three Vesicular Glutamate Transporters ( Slc17a7 (Vglut1), Slc17a6 (Vglut2), and Slc17a8 (Vglut3)) in NA neurons, identifying a novel, dynamic expression pattern for Vglut2 and an undescribed co-expression domain for Vglut3 in the NA system. In contrast to our initial hypothesis that NA derived glutamate is required to breathing, our functional studies showed that loss of Vglut2 throughout the NA system failed to alter breathing or metabolism under room air, hypercapnia, or hypoxia in unrestrained and unanesthetized mice. These data demonstrate that Vglut2-based glutamatergic signaling within the central NA system is not required for normal baseline breathing and hypercapnic, hypoxic chemosensory reflexes. These outcomes challenge the current understanding of central NA neurons in the control of breathing and suggests that glutamate may not be a critical target to understand NA neuron dysfunction in respiratory diseases.
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- 2024
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26. Beta-blockers or Placebo for Primary Prophylaxis (BOPPP) of oesophageal varices: study protocol for a randomised controlled trial.
- Author
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Patel VC, McPhail MJ, Uddin R, Jafari H, Lawrence V, Le Boutillier C, Shearer J, Yaziji N, Cape A, Ahmed H, Ward C, Walsh P, Besly K, Zamalloa A, Kelly J, and Carter B
- Subjects
- Adult, Humans, Adrenergic beta-Antagonists therapeutic use, Ascites drug therapy, Carvedilol therapeutic use, Gastrointestinal Hemorrhage diagnosis, Gastrointestinal Hemorrhage etiology, Gastrointestinal Hemorrhage prevention & control, Liver Cirrhosis complications, Liver Cirrhosis diagnosis, Liver Cirrhosis drug therapy, Multicenter Studies as Topic, Randomized Controlled Trials as Topic, Pragmatic Clinical Trials as Topic, Esophageal and Gastric Varices diagnosis, Esophageal and Gastric Varices etiology, Esophageal and Gastric Varices prevention & control, Hepatic Encephalopathy diagnosis, Hepatic Encephalopathy drug therapy, Hepatic Encephalopathy etiology, Hypertension, Portal complications, Hypertension, Portal diagnosis, Hypertension, Portal drug therapy
- Abstract
Background: Liver disease is within the top five causes of premature death in adults. Deaths caused by complications of cirrhosis continue to rise, whilst deaths related to other non-liver disease areas are declining. Portal hypertension is the primary sequelae of cirrhosis and is associated with the development of variceal haemorrhage, ascites, hepatic encephalopathy and infection, collectively termed hepatic decompensation, which leads to hospitalisation and mortality. It remains uncertain whether administering a non-selective beta-blocker (NSBB), specifically carvedilol, at an earlier stage, i.e. when oesophageal varices are small, can prevent VH and reduce all-cause decompensation (ACD)., Methods/design: The BOPPP trial is a pragmatic, multicentre, placebo-controlled, triple-blinded, randomised controlled trial (RCT) in England, Scotland, Wales and Northern Ireland. Patients aged 18 years or older with cirrhosis and small oesophageal varices that have never bled will be recruited, subject to exclusion criteria. The trial aims to enrol 740 patients across 55 hospitals in the UK. Patients are allocated randomly on a 1:1 ratio to receive either carvedilol 6.25 mg (a NSBB) or a matched placebo, once or twice daily, for 36 months, to attain adequate power to determine the effectiveness of carvedilol in preventing or reducing ACD. The primary outcome is the time to first decompensating event. It is a composite primary outcome made up of variceal haemorrhage (VH, new or worsening ascites, new or worsening hepatic encephalopathy (HE), spontaneous bacterial peritonitis (SBP), hepatorenal syndrome, an increase in Child-Pugh grade by 1 grade or MELD score by 5 points, and liver-related mortality. Secondary outcomes include progression to medium or large oesophageal varices, development of gastric, duodenal, or ectopic varices, participant quality of life, healthcare costs and transplant-free survival., Discussion: The BOPPP trial aims to investigate the clinical and cost-effectiveness of carvedilol in patients with cirrhosis and small oesophageal varices to determine whether this non-selective beta-blocker can prevent or reduce hepatic decompensation. There is clinical equipoise on whether intervening in cirrhosis, at an earlier stage of portal hypertension, with NSBB therapy is beneficial. Should the trial yield a positive result, we anticipate that the administration and use of carvedilol will become widespread with pathways developed to standardise the administration of the medication in primary care., Ethics and Dissemination: The trial has been approved by the National Health Service (NHS) Research Ethics Committee (REC) (reference number: 19/YH/0015). The results of the trial will be submitted for publication in a peer-reviewed scientific journal. Participants will be informed of the results via the BOPPP website ( www.boppp-trial.org ) and partners in the British Liver Trust (BLT) organisation., Trial Registration: EUDRACT reference number: 2018-002509-78. ISRCTN reference number: ISRCTN10324656. Registered on April 24 2019., (© 2024. The Author(s).)
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- 2024
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27. Eating and drinking experience in patients with idiopathic pulmonary fibrosis: a qualitative study.
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Alamer AA, Ward C, Forrest I, Drinnan M, and Patterson J
- Subjects
- Male, Adult, Humans, Female, Middle Aged, Aged, Aged, 80 and over, Communication, Qualitative Research, Idiopathic Pulmonary Fibrosis
- Abstract
Objective: To explore eating and drinking experiences of patients with idiopathic pulmonary fibrosis (IPF), the impact of any changes associated with their diagnosis and any coping mechanisms developed by patients., Setting: Pulmonary fibrosis support groups around the UK and the regional Interstitial Lung Diseases Clinic, Newcastle upon Tyne., Participants: 15 patients with IPF (9 men, 6 women), median age 71 years, range (54-92) years, were interviewed. Inclusion criteria included competent adults (over the age of 18 years) with a secure diagnosis of IPF as defined by international consensus guidelines. Patients were required to have sufficient English language competence to consent and participate in an interview. Exclusion criteria were a history of other lung diseases, a history of pre-existing swallowing problem of other causes that may be associated with dysphagia and individuals with significant communication or other memory difficulties that render them unable to participate in an interview., Design: A qualitative study based on semistructured interviews used purpose sampling conducted between February 2021 and November 2021. Interviews were conducted via video videoconferencing call platform or telephone call, transcribed and data coded and analysed using a reflexive thematic analysis., Results: Three main themes were identified, along with several subthemes, which were: (1) Eating, as such, is no longer a pleasure. This theme mainly focused on the physical and sensory changes associated with eating and drinking and their effects and the subsequent emotional and social impact of these changes; (2) It is something that happens naturally and just try and get on with it. This theme centred on the self-determined strategies employed to manage changes to eating and drinking; and (3) What is normal. This theme focused on patients seeking information to better understand the changes in their eating and drinking and the patients' beliefs about what has changed their eating and drinking., Conclusions: To our knowledge, this is the first study to report on IPF patients' lived experience of eating and drinking changes associated with their diagnosis. Findings demonstrate that some patients have substantial struggles and challenges with eating and drinking, affecting them physically, emotionally and socially. There is a need to provide better patient information for this area and further study., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2024
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28. Efficacy, Safety, and Cost-effectiveness of Bezlotoxumab in Preventing Recurrent Clostridioides difficile Infection : Systematic Review and Meta-analysis.
- Author
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Mohamed MFH, Ward C, Beran A, Abdallah MA, Asemota J, and Kelly CR
- Abstract
Introduction: Clostridioides difficile infection (CDI) remains a global health challenge. Bezlotoxumab (BEZ) is a monoclonal antibody against C. difficile toxin B. Two randomized controlled trials (RCTs), MODIFY I and II, confirmed BEZ efficacy in preventing recurrent Clostridioides difficile infection (rCDI). However, there are safety concerns about its use in patients with a history of congestive heart failure. Observational studies have since been conducted, and it is important to explore the consistency of BEZ efficacy, cost-effectiveness, and its safety utilizing these real-world data., Methods: We performed a systematic review and meta-analysis to pool the rate of rCDI in patients receiving BEZ and explore its efficacy and safety in preventing rCDI compared with control. We searched PubMed, EMBASE, Cochrane Library, and Google Scholar from inception through April 2023 for relevant RCTs or observational studies assessing BEZ in preventing rCDI. Single-arm studies describing experience with BEZ in preventing rCDI were also included for proportion meta-analysis. A proportion meta-analysis with a random-effects model was used to pool the rCDI rate with its corresponding 95% CI. In a meta-analysis of efficacy, we generated the relative risk (RR) to compare BEZ versus control in preventing rCDI., Results: Thirteen studies including 2 RCTs and 11 observational studies totaling 2337 patients, of which 1472 received BEZ, were included in the analysis. Of the constituent studies, 5 (1734 patients) compared BEZ versus standard-of-care (SOC). Pooled rate of rCDI in patients receiving BEZ was 15.8% (95% CI: 14%-17.8%), and was 28.9% (95% CI: 24%-34.4%) in the SOC. BEZ significantly reduced rCDI risk compared with SOC [RR=0.57 (95% CI: 0.45-0.72, I2 =16%)]. There was no difference in the overall mortality or heart failure risk. Of the 9 included cost-effectiveness analyses, 8 demonstrated BEZ+SOC cost-effectiveness compared with SOC alone., Discussion: Our meta-analysis comprising real-world data revealed lower rCDI in patients receiving BEZ and supported its efficacy and safety when added to SOC therapy. The results were consistent across various subgroups. Available cost-effectiveness analyses mostly support BEZ+SOC cost-effectiveness compared with SOC alone., Competing Interests: C.R.K. was a site investigator for clinical trials of SER109 (Seres Health) and CP101 (Finch Therapeutics). She also has consulted for Sebela Pharmaceuticals. Otherwise, the authors declare that the research was conducted in the absence of significant commercial or financial relationships that could be construed as a potential conflict of interest. The remaining authors declare that they have nothing to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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29. Metagenome-assembled genome sequences of two cyanobacterial cultures from Homa Bay County, Kenya.
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Brown KM, Ward CS, and Bullerjahn GS
- Abstract
Metagenome-assembled genomes were generated for two xenic cyanobacterial strains collected from aquatic sources in Kenya and sequenced by NovaSeq S4. Here, we report the classification and genome statistics of Microcystis panniformis WG22 and Limnospira fusiformis LS22., Competing Interests: The authors declare no conflict of interest.
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- 2024
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30. Ryanodine Receptor Stabilization Therapy Suppresses Ca 2+ -Based Arrhythmias in a Novel Model of Metabolic HFpEF.
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Kaplan AD, Boyman L, Ward CW, Lederer WJ, and Greiser M
- Abstract
Heart Failure with preserved ejection fraction (HFpEF) is the most prevalent form of heart failure worldwide and its significant mortality is associated with a high rate of sudden cardiac death (SCD; 30% - 40%). Chronic metabolic stress is an important driver of HFpEF, and clinical data show metabolic stress as a significant risk factor for ventricular arrhythmias in HFpEF patients. The mechanisms of SCD and ventricular arrhythmia in HFpEF remain critically understudied and empirical treatment is ineffective. To address this important knowledge gap, we developed a novel preclinical model of metabolic-stress induced HFpEF using Western diet (High fructose and fat) and hypertension induced by nitric oxide synthase inhibition (with L-NAME) in wildtype C57BL6/J mice. After 5 months, mice display all clinical characteristics of HFpEF and present with stress-induced sustained ventricular tachycardia (VT). Mechanistically, we found a novel pattern of arrhythmogenic intracellular Ca
2+ handling that is distinct from the well-characterized changes pathognomonic for heart failure with reduced ejection fraction. In addition, we show that the transverse tubular system remains intact in HFpEF and that arrhythmogenic, intracellular Ca2+ mobilization becomes hyper-sensitive to ß- adrenergic activation. Finally, in proof-of-concept experiments we show in vivo that the clinically used intracellular calcium stabilizer dantrolene, which acts on the Ca2+ release channels of the sarcoplasmic reticulum (SR), the ryanodine receptors, acutely prevents stress-induced VT in HFpEF mice. Therapeutic control of SR Ca2+ leak may present a novel mechanistic treatment approach in metabolic HFpEF.- Published
- 2024
- Full Text
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