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5. Systematic rare variant analyses identify RAB32 as a susceptibility gene for familial Parkinson’s disease

Author

Hop, Paul J., Lai, Dongbing, Keagle, Pamela J., Baron, Desiree M., Kenna, Brendan J., Kooyman, Maarten, Shankaracharya, Halter, Cheryl, Straniero, Letizia, Asselta, Rosanna, Bonvegna, Salvatore, Soto-Beasley, Alexandra I., Wszolek, Zbigniew K., Uitti, Ryan J., Isaias, Ioannis Ugo, Pezzoli, Gianni, Ticozzi, Nicola, Ross, Owen A., Veldink, Jan H., Foroud, Tatiana M., Kenna, Kevin P., and Landers, John E.

Published
2024
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9. The parasitic lifestyle of an archaeal symbiont

Author

Hamm, Joshua N., Liao, Yan, von Kügelgen, Andriko, Dombrowski, Nina, Landers, Evan, Brownlee, Christopher, Johansson, Emma M. V., Whan, Renee M., Baker, Matthew A. B., Baum, Buzz, Bharat, Tanmay A. M., Duggin, Iain G., Spang, Anja, and Cavicchioli, Ricardo

Published
2024
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10. Author Correction: The SOD1-mediated ALS phenotype shows a decoupling between age of symptom onset and disease duration

Author

Opie-Martin, Sarah, Iacoangeli, Alfredo, Topp, Simon D., Abel, Olubunmi, Mayl, Keith, Mehta, Puja R., Shatunov, Aleksey, Fogh, Isabella, Bowles, Harry, Limbachiya, Naomi, Spargo, Thomas P., Al-Khleifat, Ahmad, Williams, Kelly L., Jockel-Balsarotti, Jennifer, Bali, Taha, Self, Wade, Henden, Lyndal, Nicholson, Garth A., Ticozzi, Nicola, McKenna-Yasek, Diane, Tang, Lu, Shaw, Pamela J., Chio, Adriano, Ludolph, Albert, Weishaupt, Jochen H., Landers, John E., Glass, Jonathan D., Mora, Jesus S., Robberecht, Wim, Damme, Philip Van, McLaughlin, Russell, Hardiman, Orla, van den Berg, Leonard, Veldink, Jan H., Corcia, Phillippe, Stevic, Zorica, Siddique, Nailah, Silani, Vincenzo, Blair, Ian P., Fan, Dong-sheng, Esselin, Florence, de la Cruz, Elisa, Camu, William, Basak, Nazli A., Siddique, Teepu, Miller, Timothy, Brown, Robert H., Al-Chalabi, Ammar, and Shaw, Christopher E.

Published
2024
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12. Expression of ALS-PFN1 impairs vesicular degradation in iPSC-derived microglia

Author

Funes, Salome, Jung, Jonathan, Gadd, Del Hayden, Mosqueda, Michelle, Zhong, Jianjun, Shankaracharya, Unger, Matthew, Stallworth, Karly, Cameron, Debra, Rotunno, Melissa S., Dawes, Pepper, Fowler-Magaw, Megan, Keagle, Pamela J., McDonough, Justin A., Boopathy, Sivakumar, Sena-Esteves, Miguel, Nickerson, Jeffrey A., Lutz, Cathleen, Skarnes, William C., Lim, Elaine T., Schafer, Dorothy P., Massi, Francesca, Landers, John E., and Bosco, Daryl A.

Published
2024
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13. Policy, system and service design influence on healthcare inequities for people with end-of-life chronic obstructive airways disease, their support people and health professionals

Author

Amanda Landers, Suzanne G. Pitama, Suetonia C. Green, and Lutz Beckert

Subjects
Chronic obstructive pulmonary disease, Healthcare network, Quality healthcare, Healthcare systems, Equity, Public aspects of medicine, RA1-1270
Abstract

Abstract Background People with end-of-life chronic obstructive pulmonary disease (COPD) experience debilitating physical limitations, with a high mortality rate. Our research has shown health system design and delivery leads to inequitable outcomes. Enabling people with end-of-life COPD, their support people, and health professionals to partner in setting the agenda for resource allocation may inform health service improvement. Design Qualitative methodology utilising focus groups including patients, family, friends, informal support people, health care workers and professionals. Methods The analysis, utilising critical theory and Actor-Network theory, positioned people with severe COPD, their support people and health professionals as experts in end-of-life care. Analyses triangulated these perspectives, and were reviewed by the research investigators and an expert reference group. Results Participants (n=74) in seven focus groups reported their experiences of inequity within the healthcare system. Equity was an overarching phenomenon identified by participants, with three specific themes being described: policy design, system design, and service design. Conclusion Experiences of patients, their support people and health professionals as experts in end-of-life COPD care can inform health systems and health service design to address current inequities in funding and delivery of care for end-of-life COPD.

Published
2024
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14. Perceptions of Middle School Science Teachers Use of Technology: A Qualitative Exploratory Case Study

Author

LaToya S. Landers

Abstract

The problem in this study is that the teachers do not implement various technologies as instructional tools. The purpose of this qualitative exploratory case study was to examine the perceptions of teachers implementing technology in middle school science classes. The overarching research question was, "How do middle school science teachers perceive their use of implementing technology in middle school science?" The findings from this study can contribute to other research on teacher education programs and their preparation of new teachers' technology use entering the classroom. Education leaders need to learn more about the use of technology and how it is implemented in middle school science. This research can lead to other methods and designs for future studies on implementing technology in middle school science. This study population consisted of 15 middle school science teachers. All participants were interviewed individually, five participants were interviewed in a focus group, and a questionnaire was completed to collect data for this study. Data were analyzed by reviewing patterns in participant responses, which were then categorized in the data collection results. The results indicated that teachers believe implementing technology streamlines instruction, technology is significant when specifically planned for instruction, and technology actively promotes student engagement. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]

Published
2024

16. Rural adolescent attitudes and use of helmets while riding ATVs, motorcycles and dirt bikes

Author

Charles A. Jennissen, Sehansa R. Karunatilaka, Brianna J. Iverson, Devin E. Spolsdoff, Kristel M. Wetjen, Brenda Vergara, Shannon R. Landers, and Pam J. Hoogerwerf

Subjects
Adolescent, All-terrain vehicle, Dirt bike, Farm, Helmet, Head injury, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9, Public aspects of medicine, RA1-1270
Abstract

Abstract Background Head injuries are the most common cause of death in some motorized vehicles for which helmet use can significantly decrease the risk. Our objective was to determine rural adolescents’ attitudes regarding helmets and their use while riding ATVs, motorcycles and dirt bikes. Methods A convenience sample of 2022 Iowa FFA (formerly Future Farmers of America) Leadership Conference attendees were surveyed. After compilation, data were imported into the statistical program, R ( https://www.R-project.org/ ). Descriptive statistics, contingency table, logistic regression and non-parametric alternatives to ANOVA analyses were performed. Results 1331 adolescents (13–18 years) participated. One half lived on a farm, 21% lived in the country/not on a farm and 28% were from towns. Nearly two-thirds (65%) owned an ATV with 77% of all having ridden one in the past year. Farm residents had the highest ATV ownership (78%) and having ridden (80%) proportions, both p

Published
2024
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17. Arterial function in response to a 50 km ultramarathon in recreational athletes

Author

Sushant M. Ranadive, Cynthia M. Weiner, Lauren E. Eagan, Odessa Addison, Rian Q. Landers‐Ramos, and Steven J. Prior

Subjects
endothelial function, flow‐mediated dilatation, inflammation, wave‐reflection, Physiology, QP1-981
Abstract

Abstract This study was performed to determine whether prolonged endurance running results in acute endothelial dysfunction and wave‐reflection, as endothelial dysfunction and arterial stiffness are cardiovascular risk factors. Vascular function (conduit artery/macrovascular and resistance artery/microvascular) was assessed in 11 experienced runners (8 males, 3 females) before, during and after a 50 km ultramarathon. Blood pressure (BP), heart rate (HR), wave reflection, augmentation index (AIx) and AIx corrected for HR (AIx75) were taken at all time points—Baseline (BL), following 10, 20, 30 and 40 km, 1 h post‐completion (1HP) and 24 h post‐completion (24HP). Flow‐mediated dilatation (FMD) and inflammatory biomarkers were examined at BL, 1HP and 24HP. Reactive hyperaemia area under the curve (AUC) and shear rate AUC to peak dilatation were lower (∼75%) at 1HP compared with BL (P

Published
2024
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18. The parasitic lifestyle of an archaeal symbiont

Author

Joshua N. Hamm, Yan Liao, Andriko von Kügelgen, Nina Dombrowski, Evan Landers, Christopher Brownlee, Emma M. V. Johansson, Renee M. Whan, Matthew A. B. Baker, Buzz Baum, Tanmay A. M. Bharat, Iain G. Duggin, Anja Spang, and Ricardo Cavicchioli

Subjects
Science
Abstract

Abstract DPANN archaea are a diverse group of microorganisms characterised by small cells and reduced genomes. To date, all cultivated DPANN archaea are ectosymbionts that require direct cell contact with an archaeal host species for growth and survival. However, these interactions and their impact on the host species are poorly understood. Here, we show that a DPANN archaeon (Candidatus Nanohaloarchaeum antarcticus) engages in parasitic interactions with its host (Halorubrum lacusprofundi) that result in host cell lysis. During these interactions, the nanohaloarchaeon appears to enter, or be engulfed by, the host cell. Our results provide experimental evidence for a predatory-like lifestyle of an archaeon, suggesting that at least some DPANN archaea may have roles in controlling host populations and their ecology.

Published
2024
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19. Mutations in the tail and rod domains of the neurofilament heavy‐chain gene increase the risk of ALS

Author

Heather Marriott, Thomas P. Spargo, Ahmad Al Khleifat, Peter M Andersen, Nazli A. Başak, Johnathan Cooper‐Knock, Philippe Corcia, Philippe Couratier, Mamede deCarvalho, Vivian Drory, Marc Gotkine, John E. Landers, Russell McLaughlin, Jesús S. Mora Pardina, Karen E. Morrison, Susana Pinto, Christopher E. Shaw, Pamela J. Shaw, Vincenzo Silani, Nicola Ticozzi, Philip vanDamme, Leonard H. van denBerg, Patrick Vourc'h, Markus Weber, Jan H. Veldink, Project MinE ALS Sequencing Consortium, Richard J. Dobson, Patrick Schwab, Ammar Al‐Chalabi, and Alfredo Iacoangeli

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Objective Neurofilament heavy‐chain gene (NEFH) variants are associated with multiple neurodegenerative diseases, however, their relationship with ALS has not been robustly explored. Still, NEFH is commonly included in genetic screening panels worldwide. We therefore aimed to determine if NEFH variants modify ALS risk. Methods Genetic data of 11,130 people with ALS and 7,416 controls from the literature and Project MinE were analysed. We performed meta‐analyses of published case–control studies reporting NEFH variants, and variant analysis of NEFH in Project MinE whole‐genome sequencing data. Results Fixed‐effects meta‐analysis found that rare (MAF

Published
2024
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20. Capsid protein mediated evasion of IRAK1-dependent signalling is essential to Sindbis virus neuroinvasion and virulence in mice

Author

V Douglas Landers, Milton Thomas, Cierra M. Isom, Deepa Karki, and Kevin J. Sokoloski

Subjects
Alphavirus, Sindbis virus, capsid, IRAK1, neurovirulence, pathogenesis, Infectious and parasitic diseases, RC109-216, Microbiology, QR1-502
Abstract

Alphaviruses are arthropod-borne, single-stranded positive-sense RNA viruses that are recognized as rapidly emerging pathogens. Despite being exquisitely sensitive to the effects of the innate immune response alphaviruses can readily replicate, disseminate, and induce pathogenesis in immunologically competent hosts. Nonetheless, how alphaviruses evade the induction of an innate immune response prior to viral gene expression, or in non-permissive infections, is unknown. Previously we reported the identification of a novel host/pathogen interaction between the viral Capsid (CP) protein and the host IRAK1 protein. The CP/IRAK1 interaction was determined to negatively impact IRAK1-dependent PAMP detection in vitro, however, the precise importance of the CP/IRAK1 interaction to alphaviral infection remained unknown. Here we detail the identification of the CP/IRAK1 interaction determinants of the Sindbis virus (SINV) CP protein and examine the importance of the interaction to alphaviral infection and pathogenesis in vivo using an interaction deficient mutant of the model neurotropic strain of SINV. Importantly, these interaction determinants are highly conserved across multiple Old-World alphaviruses, including Ross River virus (RRV), Mayaro virus (MAYV), Chikungunya virus (CHIKV), and Semliki Forest virus (SFV). In the absence of a functional CP/IRAK1 interaction, SINV replication is significantly restricted and fails to disseminate from the primary site of inoculation due to the induction of a robust type-I Interferon response. Altogether these data indicate that the evasion of IRAK1-dependent signalling is critical to overcoming the host innate immune response and the in vivo data presented here demonstrate the importance of the CP/IRAK1 interaction to neurovirulence and pathogenesis.

Published
2024
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21. Magnetically Guided Microcatheter for Targeted Injection of Magnetic Particle Swarms

Author

Harun Torlakcik, Semih Sevim, Pedro Alves, Michael Mattmann, Joaquim Llacer‐Wintle, Maria Pinto, Rosa Moreira, Andreas D. Flouris, Fabian C. Landers, Xiang‐Zhong Chen, Josep Puigmartí‐Luis, Quentin Boehler, Tiago Sotto Mayor, Minsoo Kim, Bradley J. Nelson, and Salvador Pané

Subjects
magnetic catheter, magnetic control, magnetic nanoparticle swarm, magnetic nanoparticles, targeted delivery, Science
Abstract

Abstract The initial delivery of small‐scale magnetic devices such as microrobots is a key, but often overlooked, aspect for their use in clinical applications. The deployment of these devices within the dynamic environment of the human body presents significant challenges due to their dispersion caused by circulatory flows. Here, a method is introduced to effectively deliver a swarm of magnetic nanoparticles in fluidic flows. This approach integrates a magnetically navigated robotic microcatheter equipped with a reservoir for storing the magnetic nanoparticles. The microfluidic flow within the reservoir facilitates the injection of magnetic nanoparticles into the fluid stream, and a magnetic field gradient guides the swarm through the oscillatory flow to a target site. The microcatheter and reservoir are engineered to enable magnetic steering and injection of the magnetic nanoparticles. To demonstrate this approach, experiments are conducted utilizing a spinal cord phantom simulating intrathecal catheter delivery for applications in the central nervous system. These results demonstrate that the proposed microcatheter successfully concentrates nanoparticles near the desired location through the precise manipulation of magnetic field gradients, offering a promising solution for the controlled deployment of untethered magnetic micro‐/nanodevices within the complex physiological circulatory systems of the human body.

Published
2024
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24. Shame

Author

Landers, Mitchell, Sznycer, Daniel, Al-Shawaf, Laith, Al-Shawaf, Laith, book editor, and Shackelford, Todd K., book editor

Published
2024
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27. Sync fast and solve things—best practices for responsible digital health

Author

Constantin Landers, Alessandro Blasimme, and Effy Vayena

Subjects
Computer applications to medicine. Medical informatics, R858-859.7
Abstract

Abstract Digital health innovation is expected to transform healthcare, but it also generates ethical and societal concerns, such as privacy risks, and biases that can compound existing health inequalities. While such concerns are widely recognized, existing regulatory principles, oversight methods and ethical frameworks seem out of sync with digital health innovation. New governance and innovation best practices are thus needed to bring such principles to bear with the reality of business, innovation, and regulation. To grant practical insight into best practices for responsible digital health innovation, we conducted a qualitative study based on an interactive engagement methodology. We engaged key stakeholders (n = 46) operating at the translational frontier of digital health. This approach allowed us to identify three clusters of governance and innovation best practices in digital health innovation: i) inclusive co-creation, ii) responsive regulation, and iii) value-driven innovation. Our study shows that realizing responsible digital health requires diverse stakeholders’ commitment to adapt innovation and regulation practices, embracing co-creation as the default modus operandi for digital health development. We describe these collaborative practices and show how they can ensure that innovation is neither slowed by overregulation, nor leads to unethical outcomes.

Published
2024
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28. A global exploration of operating theatre temperatures during severe burn repair

Author

Zehra Palejwala, Karen E Wallman, Shane K Maloney, Grant J Landers, Mark W Fear, and Fiona M Wood

Subjects
Ambient temperature, Operating theatre, Clinical practice, Severe burns, Patient hypothermia, Dermatology, RL1-803, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

The perioperative maintenance of a patient’s core temperature is a challenge during burn care. While patient warming devices are sometimes used to prevent intraoperative hypothermia, raising the ambient temperature of the theatre is the most common practice. Theatre temperature can impact on the performance and comfort of surgery staff but standards for theatre temperatures in burn care are poorly defined. Therefore, in this study we investigated the current, global, clinical practices in burn care with respect to the ambient temperature of theatres that are used to treat severe burn injuries. An internet-based, descriptive, QualtricsXM survey was distributed electronically to 81 burn professionals to identify the temperatures at which the surgical teams operate on severe burn injuries. The survey was completed by 33 participants from 15 countries and revealed that there is a wide range of temperatures (24–45°C) at which burn injuries are treated. The prevention of hypothermia was the clinical justification most reported for those theatre temperatures. Temperatures between 26 and 30°C appear to be most comfortable for the staff. One respondent mentioned that surgeries are often limited to 5 h to avoid hypothermia in patients, however, others noted surgery durations of up to 8–12 h in raised temperatures, which may impact the physiology and performance of the team, potentially impacting the safety of the patients. The adoption of an optimal theatre temperature to address the surgical team’s comfort levels, their performance, and patient hypothermia, may improve outcomes in cases of severe burn injury.

Published
2024
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29. Federal Support for Reproductive Health Services: Frequently Asked Questions

Author

DeBoth, Alexa C., Baumrucker, Evelyne P., Forsberg, Vanessa C., Heisler, Elayne J., James, Nathan, Kolker, Abigail F., Landers, Patrick A., Mendez, Bryce H.P., Mickler, Alexandria K., Morgan, Paulette C., Rosso, Ryan J., Sussman, Jared S., and Tollestrup, Jessica

Subjects
United States. Government Accountability Office -- Political activity, United States. Administration for Children and Families -- Political activity, United States. Veterans Health Administration -- Political activity, United States. Department of Homeland Security -- Political activity, United States. Department of Health and Human Services -- Political activity, United States. Centers for Medicare and Medicaid Services -- Political activity, United States. Department of Justice -- Political activity, United States. Coast Guard -- Political activity, United States. Department of Defense -- Political activity, United States. Food and Drug Administration -- Political activity, United States. Indian Health Service -- Political activity, United States. Health Resources and Services Administration -- Political activity, United States. Supreme Court -- Political activity, Reproductive Health Services -- Political activity, Health insurance industry -- Political activity -- Political aspects, Bills, Legislative -- Political aspects, Health care industry -- Political activity -- Political aspects, Reproductive health -- Political aspects, Abortion -- Political aspects, Medical screening -- Political aspects, Health care industry, Government, Pregnancy Discrimination Act of 1978, HealthCare.gov (Online service) -- Political aspects
Abstract

Updated October 4, 2024 Contents Introduction General Questions What Are Reproductive Health Services? What Are Contraceptive Services? What Are Abortions and Abortion Counseling Services? Can Federal Funds Be Used to [...]

Published
2024

30. The impact of multiple exposures and movement on the fear response of poultry

Author

Alexandra Jackson, Marcela Quino, Anusha Gautam, Melissa Gilpin, Katie Still, Denise Landers, and Bethany Baker-Cook

Subjects
Novel object, Voluntary human approach, Fearfulness, Broilers, Welfare assessments, Animal culture, SF1-1100
Abstract

Fear tests are a common research method to assess the affective state of an animal. This study aimed to assess: 1) the impact of repeated exposure to fear tests on fear response and, 2) how the addition of movement to fear stimuli during a novel object test impacts bird fear response. Over two trials, a total of 3,600 Ross 308 birds (1800 birds/trial) were raised until 42 days of age. At 23d, 30d, and 37d, three fear tests were performed, novel object, human approach, and response to observer tests. The novel object test was split into three movement treatments, stationary, intermittent, and continuous. The response to observer test was performed before and after the other tests. Data from the human approach test was analyzed for age effect by ANOVA. Novel object data was analyzed as repeated measures ANOVA for the effect of movement. Differences in response to observer were analyzed using a paired T-test. Repeated exposure to fear test within the same day decreased the fear response, with response to observer results before fear testing (66%) differing from after (42%, P

Published
2025
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33. A citizen science approach to develop a digital intervention to reduce HIV stigma and promote HIV self‐testing among adolescents and young adults: a mixed methods analysis from Kazakhstan

Author

Davis, Alissa, Rosenthal, Susan L., Tucker, Joseph D., Balabekova, Olga, Nyblade, Laura, Sun, Yihang, Gryazev, Denis, Lunze, Karsten, Landers, Sara E., Tang, Weiming, Kuskulov, Azamat, Gulyayev, Valera, Terlikbayeva, Assel, Primbetova, Sholpan, and Mergenova, Gaukhar

Subjects
Crowdsourcing -- Research -- Analysis -- Methods, HIV (Viruses) -- Research, HIV testing -- Rankings, Discrimination against AIDS virus carriers -- Methods -- Research -- Analysis, Citizen scientists -- Methods -- Analysis -- Research, Local government -- Kazakhstan, Teenagers -- Research -- Analysis -- Methods, Youth -- Research -- Analysis -- Methods, Health
Abstract

: Introduction: Kazakhstan has one of the fastest‐growing HIV epidemics in the world, with increasing rates among adolescents and young adults (AYA). Innovative strategies are needed to increase HIV testing uptake and decrease HIV stigma among AYA. Citizen science, defined as the active engagement of the general public in scientific research tasks, promotes and facilitates community engagement throughout the research process. This citizen science study used crowdsourcing to engage AYA in Kazakhstan to develop a digital intervention to reduce HIV stigma and promote HIV self‐testing. Our objectives in this paper are to describe the approach used, its feasibility and acceptability, and AYA motivations for and lessons learned collaborating on the study. Methods: From October 2021 to July 2022, in collaboration with a Community Collaborative Research Board and a Youth Advisory Board, we developed an open call requesting multimedia submissions to reduce HIV testing stigma. Eligible submissions were separated by age group (13−19 or 20−29 years) and judged by a panel composed of AYA (n = 23), healthcare professionals (n = 12), and representatives from the local government and non‐governmental organizations (n = 17). Each entry was reviewed by at least four judges and ranked on a 5‐point scale. The top 20 open call contestants were asked to submit self‐recordings sharing their motivation for and experience participating in the contest and lessons learned. Descriptive statistics were calculated for quantitative data. Qualitative data were coded using open coding. Results: We received 96 submissions from 77 youth across Kazakhstan. Roughly, three‐quarters (n = 75/96) of entries met judging eligibility criteria. Of the eligible entries, over half (n = 39/75) scored 3.5 or higher on a 5‐point scale (70.0%). The most frequent types of entries were video (n = 36/96, 37.5%), image (n = 28/96, 29.2%) and text (n = 24/96, 25.0%). AYA's primary motivations for collaborating on the study included a desire to improve society and help youth. The main challenges included creating content to address complex information using simple language, finding reliable information online and technological limitations. Conclusions: Crowdsourcing was feasible and highly acceptable among AYA in Kazakhstan. Citizen science approaches hold great promise for addressing the increasingly complex health and social challenges facing communities today., INTRODUCTION Eastern Europe and central Asia (EECA) has the world's fastest‐growing HIV epidemic with a 43.0% increase in incident cases of HIV acquisition from 2010 to 2020 [1] and for [...]

Published
2024
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34. Reproductive neuroendocrine defects programmed by prenatal testosterone treatment between gestational days 60–90 are amplified by postnatal obesity in sheep

Author

S. C. Gurule, J. F. Sustaita-Monroe, L. N. King, R. S. Landers, V. Garza, S. M. West, S. E. Bynum, L. Perry, V. Padmanabhan, and R. C. Cardoso

Subjects
androgens, neuroendocrine, obesity, PCOS (polycystic ovary syndrome), sheep, Physiology, QP1-981
Abstract

Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility in women of reproductive age, and obesity can increase the severity and development of the PCOS phenotype. Prenatal testosterone (T) treatment between gestational days 30–90 advanced puberty and disrupted the reproductive and metabolic phenotype in female sheep, recapitulating attributes of women with PCOS, with postnatal obesity amplifying its severity. On the other hand, prenatal T treatment from gestational days 60–90 led to a much milder phenotype. We hypothesized that reproductive neuroendocrine defects programmed by prenatal T treatment between gestational days 60–90 are amplified by postnatal obesity in sheep. Suffolk ewes received T propionate (T; 100 mg) or corn oil (C; vehicle) twice weekly from gestational days 60–90. At 5 months of age, T lambs were assigned to either a maintenance (100% of NRC requirements) or overfed (130% NRC) diet and C lambs were fed the maintenance diet. We compared the timing of puberty (n = 15/group) determined by twice weekly measurement of progesterone concentrations, estradiol positive feedback responsiveness (n = 8/group) determined by assessing LH secretion in response to exogenous estradiol, periovulatory LH dynamics during the second breeding season (n = 8/group) following synchronization with two injections of PGF2α, and progesterone negative feedback (n = 8/group) determined by characterizing LH pulses during the mid-luteal phase between C, T-maintenance and T-overfed groups. Our findings indicate that postnatal obesity: 1) exacerbated reproductive defects and further deteriorated reproductive cyclicity during the second breeding season (adulthood); 2) did not amplify the impairment in estradiol positive feedback in delaying the timing and amplitude of the LH surge, although it reduced the total amount of LH secreted during the preovulatory LH surge; 3) amplified the reduced responsiveness to progesterone negative feedback manifested as an increase in LH pulse amplitude and peak. These observations, in addition to supporting our previous findings that prenatal T treatment results in reproductive neuroendocrine dysfunction and periovulatory disruptions, provide evidence that these neuroendocrine defects programmed between gestational days 60–90 are amplified by postnatal obesity in female sheep.

Published
2024
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35. Long-term impact of COVID-19 hospitalisation among individuals with pre-existing airway diseases in the UK: a multicentre, longitudinal cohort study – PHOSP-COVID

Author

Omer Elneima, John R. Hurst, Carlos Echevarria, Jennifer K. Quint, Samantha Walker, Salman Siddiqui, Petr Novotny, Paul E. Pfeffer, Jeremy S. Brown, Manu Shankar-Hari, Hamish J.C. McAuley, Olivia C. Leavy, Aarti Shikotra, Amisha Singapuri, Marco Sereno, Matthew Richardson, Ruth M. Saunders, Victoria C. Harris, Linzy Houchen-Wolloff, Neil J. Greening, Ewen M. Harrison, Annemarie B. Docherty, Nazir I. Lone, James D. Chalmers, Ling-Pei Ho, Alex Horsley, Michael Marks, Krisnah Poinasamy, Betty Raman, Rachael A. Evans, Louise V. Wain, Aziz Sheikh, Chris E. Brightling, Anthony De Soyza, Liam G. Heaney, J.K. Baillie, N.I. Lone, E. Pairo-Castineira, N. Avramidis, K. Rawlik, S Jones, L. Armstrong, B. Hairsine, H. Henson, C. Kurasz, A. Shaw, L. Shenton, H. Dobson, A. Dell, S. Fairbairn, N. Hawkings, J. Haworth, M. Hoare, V. Lewis, A. Lucey, G. Mallison, H. Nassa, C. Pennington, A. Price, C. Price, A. Storrie, G. Willis, S. Young, K. Poinasamy, S. Walker, I. Jarrold, A. Sanderson, K. Chong-James, C. David, W.Y. James, P. Pfeffer, O. Zongo, A. Martineau, C. Manisty, C. Armour, V. Brown, J. Busby, B. Connolly, T. Craig, S. Drain, L.G. Heaney, B. King, N. Magee, E. Major, D. McAulay, L. McGarvey, J. McGinness, T. Peto, R. Stone, A. Bolger, F. Davies, A. Haggar, J. Lewis, A. Lloyd, R. Manley, E. McIvor, D. Menzies, K. Roberts, W. Saxon, D. Southern, C. Subbe, V. Whitehead, A. Bularga, N.L. Mills, J. Dawson, H. El-Taweel, L. Robinson, L. Brear, K. Regan, D. Saralaya, K. Storton, S. Amoils, A. Bermperi, I. Cruz, K. Dempsey, A. Elmer, J. Fuld, H. Jones, S. Jose, S. Marciniak, M. Parkes, C. Ribeiro, J. Taylor, M. Toshner, L. Watson, J. Worsley, L. Broad, T. Evans, M. Haynes, L. Jones, L. Knibbs, A. McQueen, C. Oliver, K. Paradowski, R. Sabit, J. Williams, I. Jones, L. Milligan, E. Harris, C. Sampson, E. Davies, C. Evenden, A. Hancock, K. Hancock, C. Lynch, M. Rees, L. Roche, N. Stroud, T. Thomas-Woods, S. Heller, T. Chalder, K. Shah, E. Robertson, B. Young, M. Babores, M. Holland, N. Keenan, S. Shashaa, H. Wassall, L. Austin, E. Beranova, T. Cosier, J. Deery, T. Hazelton, H. Ramos, R. Solly, S. Turney, H. Weston, M. Ralser, L. Pearce, S. Pugmire, W. Stoker, A. Wilson, W. McCormick, E. Fraile, J. Ugoji, L. Aguilar Jimenez, G. Arbane, S. Betts, K. Bisnauthsing, A. Dewar, N. Hart, G. Kaltsakas, H. Kerslake, M.M. Magtoto, P. Marino, L.M. Martinez, M. Ostermann, J. Rossdale, T.S. Solano, M. Alvarez Corral, A. Arias, E. Bevan, D. Griffin, J. Martin, J. Owen, S. Payne, A. Prabhu, A. Reed, W. Storrar, N. Williams, C. Wrey Brown, T. Burdett, J. Featherstone, C. Lawson, A. Layton, C. Mills, L. Stephenson, Y. Ellis, P. Atkin, K. Brindle, M.G. Crooks, K. Drury, N. Easom, R. Flockton, L. Holdsworth, A. Richards, D.L. Sykes, S. Thackray-Nocera, C. Wright, S. Coetzee, K. Davies, R. Hughes, R. Loosley, H. McGuinness, A. Mohamed, L. O'Brien, Z. Omar, E. Perkins, J. Phipps, G. Ross, A. Taylor, H. Tench, R. Wolf-Roberts, L. Burden, E. Calvelo, B. Card, C. Carr, E.R. Chilvers, D. Copeland, P. Cullinan, P. Daly, L. Evison, T. Fayzan, H. Gordon, S. Haq, R.G. Jenkins, C. King, O. Kon, K. March, M. Mariveles, L. McLeavey, N. Mohamed, S. Moriera, U. Munawar, J. Nunag, U. Nwanguma, L. Orriss-Dib, A. Ross, M. Roy, E. Russell, K. Samuel, J. Schronce, N. Simpson, L. Tarusan, D.C. Thomas, C. Wood, N. Yasmin, D. Altmann, L.S. Howard, D. Johnston, A. Lingford-Hughes, W.D-C. Man, J. Mitchell, P.L. Molyneaux, C. Nicolaou, D.P. O'Regan, L. Price, J. Quint, D. Smith, R.S. Thwaites, J. Valabhji, S. Walsh, C.M. Efstathiou, F. Liew, A. Frankel, L. Lightstone, S. McAdoo, M. Wilkins, M. Willicombe, R. Touyz, A-M. Guerdette, M. Hewitt, R. Reddy, K. Warwick, S. White, A. McMahon, M. Malim, K. Bramham, M. Brown, K. Ismail, T. Nicholson, C. Pariante, C. Sharpe, S. Wessely, J. Whitney, O. Adeyemi, R. Adrego, H. Assefa-Kebede, J. Breeze, S. Byrne, P. Dulawan, A. Hoare, C.J. Jolley, A. Knighton, S. Patale, I. Peralta, N. Powell, A. Ramos, K. Shevket, F. Speranza, A. Te, A. Shah, A. Chiribiri, C. O'Brien, A. Hayday, A. Ashworth, P. Beirne, J. Clarke, C. Coupland, M. Dalton, C. Favager, J. Glossop, J. Greenwood, L. Hall, T. Hardy, A. Humphries, J. Murira, D. Peckham, S. Plein, J. Rangeley, G. Saalmink, A.L. Tan, E. Wade, B. Whittam, N. Window, J. Woods, G. Coakley, L. Turtle, L. Allerton, A.M. Allt, M. Beadsworth, A. Berridge, J. Brown, S. Cooper, A. Cross, S. Defres, S.L. Dobson, J. Earley, N. French, W. Greenhalf, K. Hainey, H.E. Hardwick, J. Hawkes, V. Highett, S. Kaprowska, A.L. Key, L. Lavelle-Langham, N. Lewis-Burke, G. Madzamba, F. Malein, S. Marsh, C. Mears, L. Melling, M.J. Noonan, L. Poll, J. Pratt, E. Richardson, A. Rowe, M.G. Semple, V. Shaw, K.A. Tripp, L.O. Wajero, S.A. Williams-Howard, D.G. Wootton, J. Wyles, S.N. Diwanji, S. Gurram, P. Papineni, S. Quaid, G.F. Tiongson, E. Watson, A. Briggs, M. Marks, C. Hastie, N. Rogers, N. Smith, D. Stensel, L. Bishop, K. McIvor, P. Rivera-Ortega, B. Al-Sheklly, C. Avram, J. Blaikely, M. Buch, N. Choudhury, D. Faluyi, T. Felton, T. Gorsuch, N.A. Hanley, A. Horsley, T. Hussell, Z. Kausar, N. Odell, R. Osbourne, K. Piper Hanley, K. Radhakrishnan, S. Stockdale, T. Kabir, J.T. Scott, P.J.M. Openshaw, I.D. Stewart, D. Burn, A. Ayoub, G. Burns, G. Davies, A. De Soyza, C. Echevarria, H. Fisher, C. Francis, A. Greenhalgh, P. Hogarth, J. Hughes, K. Jiwa, G. Jones, G. MacGowan, D. Price, A. Sayer, J. Simpson, H. Tedd, S. Thomas, S. West, M. Witham, S. Wright, A. Young, M.J. McMahon, P. Neill, D. Anderson, N. Basu, H. Bayes, A. Brown, A. Dougherty, K. Fallon, L. Gilmour, D. Grieve, K. Mangion, A. Morrow, R. Sykes, C. Berry, I.B. McInnes, K. Scott, F. Barrett, A. Donaldson, E.K. Sage, D. Bell, R. Hamil, K. Leitch, L. Macliver, M. Patel, J. Quigley, A. Smith, B. Welsh, G. Choudhury, S. Clohisey, A. Deans, A.B. Docherty, J. Furniss, E.M. Harrison, S. Kelly, A. Sheikh, J.D. Chalmers, D. Connell, C. Deas, A. Elliott, J. George, S. Mohammed, J. Rowland, A.R. Solstice, D. Sutherland, C.J. Tee, J. Bunker, R. Gill, R. Nathu, K. Holmes, H. Adamali, D. Arnold, S. Barratt, A. Dipper, S. Dunn, N. Maskell, A. Morley, L. Morrison, L. Stadon, S. Waterson, H. Welch, B. Jayaraman, T. Light, I. Vogiatzis, P. Almeida, C.E. Bolton, A. Hosseini, L. Matthews, R. Needham, K. Shaw, A.K. Thomas, J. Bonnington, M. Chrystal, C. Dupont, P.L. Greenhaff, A. Gupta, W. Jang, S. Linford, A. Nikolaidis, S. Prosper, A. Burns, N. Kanellakis, V.M. Ferreira, C. Nikolaidou, C. Xie, M. Ainsworth, A. Alamoudi, A. Bloss, P. Carter, M. Cassar, J. Chen, F. Conneh, T. Dong, R.I. Evans, E. Fraser, J.R. Geddes, F. Gleeson, P. Harrison, M. Havinden-Williams, L.P. Ho, P. Jezzard, I. Koychev, P. Kurupati, H. McShane, C. Megson, S. Neubauer, D. Nicoll, G. Ogg, E. Pacpaco, M. Pavlides, Y. Peng, N. Petousi, J. Pimm, N.M. Rahman, B. Raman, M.J. Rowland, K. Saunders, M. Sharpe, N. Talbot, E.M. Tunnicliffe, A. Korszun, S. Kerr, R.E. Barker, D. Cristiano, N. Dormand, P. George, M. Gummadi, S. Kon, K. Liyanage, C.M. Nolan, B. Patel, S. Patel, O. Polgar, P. Shah, S. Singh, J.A. Walsh, M. Gibbons, S. Ahmad, S. Brill, J. Hurst, H. Jarvis, L. Lim, S. Mandal, D. Matila, O. Olaosebikan, C. Singh, C. Laing, H. Baxendale, L. Garner, C. Johnson, J. Mackie, A. Michael, J. Newman, J. Pack, K. Paques, H. Parfrey, J. Parmar, A. Reddy, M. Halling-Brown, P. Dark, N. Diar-Bakerly, D. Evans, E. Hardy, A. Harvey, D. Holgate, S. Knight, N. Mairs, N. Majeed, L. McMorrow, J. Oxton, J. Pendlebury, C. Summersgill, R. Ugwuoke, S. Whittaker, W. Matimba-Mupaya, S. Strong-Sheldrake, P. Chowienczyk, J. Bagshaw, M. Begum, K. Birchall, R. Butcher, H. Carborn, F. Chan, K. Chapman, Y. Cheng, L. Chetham, C. Clark, Z. Coburn, J. Cole, M. Dixon, A. Fairman, J. Finnigan, H. Foot, D. Foote, A. Ford, R. Gregory, K. Harrington, L. Haslam, L. Hesselden, J. Hockridge, A. Holbourn, B. Holroyd-Hind, L. Holt, A. Howell, E. Hurditch, F. Ilyas, C. Jarman, A. Lawrie, J-H. Lee, E. Lee, R. Lenagh, A. Lye, I. Macharia, M. Marshall, A. Mbuyisa, J. McNeill, S. Megson, J. Meiring, L. Milner, S. Misra, H. Newell, T. Newman, C. Norman, L. Nwafor, D. Pattenadk, M. Plowright, J. Porter, P. Ravencroft, C. Roddis, J. Rodger, S.L. Rowland-Jones, P. Saunders, J. Sidebottom, J. Smith, L. Smith, N. Steele, G. Stephens, R. Stimpson, B. Thamu, A.A.R. Thompson, N. Tinker, K. Turner, H. Turton, P. Wade, J. Watson, I. Wilson, A. Zawia, L. Allsop, K. Bennett, P. Buckley, M. Flynn, M. Gill, C. Goodwin, M. Greatorex, H. Gregory, C. Heeley, L. Holloway, M. Holmes, J. Hutchinson, J. Kirk, W. Lovegrove, T.A. Sewell, S. Shelton, D. Sissons, K. Slack, S. Smith, D. Sowter, S. Turner, V. Whitworth, I. Wynter, J. Tomlinson, L. Warburton, S. Painter, S. Palmer, D. Redwood, J. Tilley, C. Vickers, T. Wainwright, G. Breen, M. Hotopf, R. Aul, D. Forton, M. Ali, A. Dunleavy, M. Mencias, N. Msimanga, T. Samakomva, S. Siddique, V. Tavoukjian, J. Teixeira, R. Ahmed, R. Francis, L. Connor, A. Cook, G.A. Davies, T. Rees, F. Thaivalappil, C. Thomas, M. McNarry, K.E. Lewis, M. Coulding, S. Kilroy, J. McCormick, J. McIntosh, V. Turner, J. Vere, A. Butt, H. Savill, S.S. Kon, G. Landers, H. Lota, S. Portukhay, M. Nasseri, A. Daniels, A. Hormis, J. Ingham, L. Zeidan, M. Chablani, L. Osborne, S. Aslani, A. Banerjee, R. Batterham, G. Baxter, R. Bell, A. David, E. Denneny, A.D. Hughes, W. Lilaonitkul, P. Mehta, A. Pakzad, B. Rangelov, B. Williams, J. Willoughby, M. Xu, N. Ahwireng, D. Bang, D. Basire, J.S. Brown, R.C. Chambers, A. Checkley, R. Evans, M. Heightman, T. Hillman, J. Jacob, R. Jastrub, M. Lipman, S. Logan, D. Lomas, M. Merida Morillas, H. Plant, J.C. Porter, K. Roy, E. Wall, T. Treibel, N. Ahmad Haider, C. Atkin, R. Baggott, M. Bates, A. Botkai, A. Casey, B. Cooper, J. Dasgin, C. Dawson, K. Draxlbauer, N. Gautam, J. Hazeldine, T. Hiwot, S. Holden, K. Isaacs, T. Jackson, V. Kamwa, D. Lewis, J.M. Lord, S. Madathil, C. McGhee, K. McGee, A. Neal, A. Newton-Cox, J. Nyaboko, D. Parekh, Z. Peterkin, H. Qureshi, L. Ratcliffe, E. Sapey, J. Short, T. Soulsby, J. Stockley, Z. Suleiman, T. Thompson, M. Ventura, S. Walder, C. Welch, D. Wilson, S. Yasmin, K.P. Yip, N. Chaudhuri, C. Childs, R. Djukanovic, S. Fletcher, M. Harvey, M.G. Jones, E. Marouzet, B. Marshall, R. Samuel, T. Sass, T. Wallis, H. Wheeler, R. Steeds, P. Beckett, C. Dickens, U. Nanda, M. Aljaroof, N. Armstrong, H. Arnold, H. Aung, M. Bakali, M. Bakau, E. Baldry, M. Baldwin, C. Bourne, M. Bourne, C.E. Brightling, N. Brunskill, P. Cairns, L. Carr, A. Charalambou, C. Christie, M.J. Davies, E. Daynes, S. Diver, R. Dowling, S. Edwards, C. Edwardson, O. Elneima, H. Evans, R.A. Evans, J. Finch, S. Finney, S. Glover, N. Goodman, B. Gooptu, N.J. Greening, K. Hadley, P. Haldar, B. Hargadon, V.C. Harris, L. Houchen-Wolloff, W. Ibrahim, L. Ingram, K. Khunti, A. Lea, D. Lee, H.J.C. McAuley, G.P. McCann, P. McCourt, T. McNally, G. Mills, W. Monteiro, M. Pareek, S. Parker, A. Prickett, I.N. Qureshi, A. Rowland, R. Russell, M. Sereno, A. Shikotra, S. Siddiqui, A. Singapuri, S.J. Singh, J. Skeemer, M. Soares, E. Stringer, S. Terry, T. Thornton, M. Tobin, T.J.C. Ward, F. Woodhead, T. Yates, A.J. Yousuf, B. Guillen Guiio, O.C. Leavy, L.V. Wain, M. Broome, P. McArdle, D. Thickett, R. Upthegrove, D. Wilkinson, P. Moss, D. Wraith, J. Evans, E. Bullmore, J.L. Heeney, C. Langenberg, W. Schwaeble, C. Summers, J. Weir McCall, D. Adeloye, D.E. Newby, R. Pius, I. Rudan, M. Shankar-Hari, C.L. Sudlow, M. Thorpe, S. Walmsley, B. Zheng, L. Allan, C. Ballard, A. McGovern, J. Dennis, J. Cavanagh, S. MacDonald, K. O'Donnell, J. Petrie, N. Sattar, M. Spears, E. Guthrie, M. Henderson, R.J. Allen, M. Bingham, T. Brugha, R. Free, D. Jones, L. Gardiner, A.J. Moss, E. Mukaetova-Ladinska, P. Novotny, C. Overton, J.E. Pearl, T. Plekhanova, M. Richardson, N. Samani, J. Sargent, M. Sharma, M. Steiner, C. Taylor, C. Tong, E. Turner, J. Wormleighton, B. Zhao, K. Ntotsis, R.M. Saunders, D. Lozano-Rojas, D. Cuthbertson, G. Kemp, A. McArdle, B. Michael, W. Reynolds, L.G. Spencer, B. Vinson, M. Ashworth, K. Abel, H. Chinoy, B. Deakin, M. Harvie, C.A. Miller, S. Stanel, P. Barran, D. Trivedi, H. McAllister-Williams, S. Paddick, A. Rostron, J.P. Taylor, D. Baguley, C. Coleman, E. Cox, L. Fabbri, S. Francis, I. Hall, E. Hufton, S. Johnson, F. Khan, P. Kitterick, R. Morriss, N. Selby, L. Wright, C. Antoniades, A. Bates, M. Beggs, K. Bhui, K. Breeze, K.M. Channon, D. Clark, X. Fu, M. Husain, X. Li, E. Lukaschuk, C. McCracken, K. McGlynn, R. Menke, K. Motohashi, T.E. Nichols, G. Ogbole, S. Piechnik, I. Propescu, J. Propescu, A.A. Samat, Z.B. Sanders, L. Sigfrid, M. Webster, L. Kingham, P. Klenerman, H. Lamlum, G. Carson, M. Taquet, L. Finnigan, L.C. Saunders, J.M. Wild, P.C. Calder, N. Huneke, G. Simons, D. Baldwin, S. Bain, L. Daines, E. Bright, P. Crisp, R. Dharmagunawardena, M. Stern, L. Bailey, A. Reddington, A. Wight, A. Ashish, J. Cooper, E. Robinson, A. Broadley, L. Barman, C. Brookes, K. Elliott, L. Griffiths, Z. Guy, K. Howard, D. Ionita, H. Redfearn, C. Sarginson, and A. Turnbull

Subjects
Medicine
Abstract

Background The long-term outcomes of COVID-19 hospitalisation in individuals with pre-existing airway diseases are unknown. Methods Adult participants hospitalised for confirmed or clinically suspected COVID-19 and discharged between 5 March 2020 and 31 March 2021 were recruited to the Post-hospitalisation COVID-19 (PHOSP-COVID) study. Participants attended research visits at 5 months and 1 year post discharge. Clinical characteristics, perceived recovery, burden of symptoms and health-related quality of life (HRQoL) of individuals with pre-existing airway disease (i.e., asthma, COPD or bronchiectasis) were compared to the non-airways group. Results A total of 615 out of 2697 (22.8%) participants had a history of pre-existing airway diseases (72.0% diagnosed with asthma, 22.9% COPD and 5.1% bronchiectasis). At 1 year, the airways group participants were less likely to feel fully recovered (20.4% versus 33.2%, p

Published
2024
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36. A citizen science approach to develop a digital intervention to reduce HIV stigma and promote HIV self‐testing among adolescents and young adults: a mixed methods analysis from Kazakhstan

Author

Alissa Davis, Susan L. Rosenthal, Joseph D. Tucker, Olga Balabekova, Laura Nyblade, Yihang Sun, Denis Gryazev, Karsten Lunze, Sara E. Landers, Weiming Tang, Azamat Kuskulov, Valera Gulyayev, Assel Terlikbayeva, Sholpan Primbetova, Gaukhar Mergenova, and the JasSpark Study Team

Subjects
adolescents, stigma, intervention, testing, low‐ and middle‐income countries, HIV, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Introduction Kazakhstan has one of the fastest‐growing HIV epidemics in the world, with increasing rates among adolescents and young adults (AYA). Innovative strategies are needed to increase HIV testing uptake and decrease HIV stigma among AYA. Citizen science, defined as the active engagement of the general public in scientific research tasks, promotes and facilitates community engagement throughout the research process. This citizen science study used crowdsourcing to engage AYA in Kazakhstan to develop a digital intervention to reduce HIV stigma and promote HIV self‐testing. Our objectives in this paper are to describe the approach used, its feasibility and acceptability, and AYA motivations for and lessons learned collaborating on the study. Methods From October 2021 to July 2022, in collaboration with a Community Collaborative Research Board and a Youth Advisory Board, we developed an open call requesting multimedia submissions to reduce HIV testing stigma. Eligible submissions were separated by age group (13−19 or 20−29 years) and judged by a panel composed of AYA (n = 23), healthcare professionals (n = 12), and representatives from the local government and non‐governmental organizations (n = 17). Each entry was reviewed by at least four judges and ranked on a 5‐point scale. The top 20 open call contestants were asked to submit self‐recordings sharing their motivation for and experience participating in the contest and lessons learned. Descriptive statistics were calculated for quantitative data. Qualitative data were coded using open coding. Results We received 96 submissions from 77 youth across Kazakhstan. Roughly, three‐quarters (n = 75/96) of entries met judging eligibility criteria. Of the eligible entries, over half (n = 39/75) scored 3.5 or higher on a 5‐point scale (70.0%). The most frequent types of entries were video (n = 36/96, 37.5%), image (n = 28/96, 29.2%) and text (n = 24/96, 25.0%). AYA's primary motivations for collaborating on the study included a desire to improve society and help youth. The main challenges included creating content to address complex information using simple language, finding reliable information online and technological limitations. Conclusions Crowdsourcing was feasible and highly acceptable among AYA in Kazakhstan. Citizen science approaches hold great promise for addressing the increasingly complex health and social challenges facing communities today.

Published
2024
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41. Mechanism-free repurposing of drugs for C9orf72-related ALS/FTD using large-scale genomic data

Author

Baloh, Robert H., Bowser, Robert, Brady, Christopher B., Brice, Alexis, Broach, James, Camu, William, Chia, Ruth, Chio, Adriano, Cooper-Knock, John, Cusi, Daniele, Ding, Jinhui, Drepper, Carsten, Drory, Vivian E., Dunckley, Travis L., Feldman, Eva, Floeter, Mary Kay, Fratta, Pietro, Gerhard, Glenn, Gibbs, J. Raphael, Gibson, Summer B., Glass, Jonathan D., Goutman, Stephen A., Hardy, John, Harms, Matthew B., Heiman-Patterson, Terry D., Jansson, Lilja, Kirby, Janine, Laaksovirta, Hannu, Landers, John E., Landi, Francesco, Le Ber, Isabelle, Lumbroso, Serge, Guissart, Claire, MacGowan, Daniel JL., Maragakis, Nicholas J., Mora, Gabriele, Mouzat, Kevin, Myllykangas, Liisa, Orrell, Richard W., Ostrow, Lyle W., Pickering-Brown, Stuart, Pioro, Erik P., Pulst, Stefan M., Ravits, John M., Renton, Alan E., Robberecht, Wim, Rogaeva, Ekaterina, Rothstein, Jeffrey D., Salvi, Erika, Scholz, Sonja W., Sendtner, Michael, Shaw, Pamela J., Sidle, Katie C., Simmons, Zachary, Stone, David J., Tienari, Pentti J., Traynor, Bryan J., Trojanowski, John Q., Troncoso, Juan C., Valori, Miko, Van Damme, Philip, Van Deerlin, Vivianna M., Van Den Bosch, Ludo, Zinman, Lorne, Angelocola, Stefania M., Ausiello, Francesco P., Barberis, Marco, Bartolomei, Ilaria, Battistini, Stefania, Bersano, Enrica, Bisogni, Giulia, Borghero, Giuseppe, Brunetti, Maura, Cabona, Corrado, Calvo, Andrea, Canale, Fabrizio, Canosa, Antonio, Cantisani, Teresa A., Capasso, Margherita, Caponnetto, Claudia, Cardinali, Patrizio, Carrera, Paola, Casale, Federico, Colletti, Tiziana, Conforti, Francesca L., Conte, Amelia, Conti, Elisa, Corbo, Massimo, Cuccu, Stefania, Bella, Eleonora Dalla, D'Errico, Eustachio, DeMarco, Giovanni, Dubbioso, Raffaele, Ferrarese, Carlo, Ferraro, Pilar M., Filippi, Massimo, Fini, Nicola, Floris, Gianluca, Fuda, Giuseppe, Gallone, Salvatore, Gianferrari, Giulia, Giannini, Fabio, Grassano, Maurizio, Greco, Lucia, Iazzolino, Barbara, Introna, Alessandro, La Bella, Vincenzo, Lattante, Serena, Lauria, Giuseppe, Liguori, Rocco, Logroscino, Giancarlo, Logullo, Francesco O., Lunetta, Christian, Mandich, Paola, Mandrioli, Jessica, Manera, Umberto, Manganelli, Fiore, Marangi, Giuseppe, Marinou, Kalliopi, Marrosu, Maria Giovanna, Martinelli, Ilaria, Messina, Sonia, Moglia, Cristina, Monsurrò, Maria Rosaria, Mosca, Lorena, Murru, Maria R., Origone, Paola, Passaniti, Carla, Petrelli, Cristina, Petrucci, Antonio, Pirisi, Angelo, Pozzi, Susanna, Pugliatti, Maura, Quattrini, Angelo, Ricci, Claudia, Riolo, Giulia, Riva, Nilo, Russo, Massimo, Sabatelli, Mario, Salamone, Paolina, Salivetto, Marco, Salvi, Fabrizio, Santarelli, Marialuisa, Sbaiz, Luca, Sideri, Riccardo, Simone, Isabella, Simonini, Cecilia, Spataro, Rossella, Tanel, Raffaella, Tedeschi, Gioacchino, Ticca, Anna, Torriello, Antonella, Tranquilli, Stefania, Tremolizzo, Lucio, Trojsi, Francesca, Vasta, Rosario, Vacchiano, Veria, Vita, Giuseppe, Volanti, Paolo, Zollino, Marcella, Zucchi, Elisabetta, Silani, Vincenzo, Fogh, Isabella, Ticozzi, Nicola, Ratti, Antonia, Tiloca, Cinzia, Peverelli, Silvia, Gellera, Cinzia, Pinter, Giuseppe Lauria, Taroni, Franco, Pensato, Viviana, Castellotti, Barbara, Comi, Giacomo P., Corti, Stefania, Del Bo, Roberto, Cereda, Cristina, Ceroni, Mauro, Gagliardi, Stella, Corrado, Lucia, Mazzini, Letizia, Sorarù, Gianni, Raggi, Flavia, Siciliano, Gabriele, Simoncini, Costanza, Lo Gerfo, Annalisa, Filosto, Massimiliano, Inghilleri, Maurizio, Ferlini, Alessandra, Corcia, Philippe, Couratier, Philippe, Vourc'h, Patrick, Hardiman, Orla, McLaughlin, Russell, Gotkine, Marc, Drory, Vivian, van den Veldink, Jan H., Berg, Leonard H., de Carvalho, Mamede, Mora Pardina, Jesus S., Povedano, Monica, Andersen, Peter, Weber, Markus, Başak, Ayşe Nazlı, Al-Chalabi, Ammar, Shaw, Chris, Morrison, Karen E., Adeleye, Adelani, Alba, Camille, Bacikova, Dagmar, Dalgard, Clifton L., Hupalo, Daniel N., McGrath Martinez, Elisa, Soltis, Anthony R., Sukumar, Gauthaman, Viollet, Coralie, Wilkerson, Matthew D., Saez-Atienzar, Sara, Souza, Cleide dos Santos, Beal, Selina N., Lorenzini, Ileana, Huang, Ruili, Levy, Jennifer, Burciu, Camelia, Jones, Ashley, Dewan, Ramita, van Vugt, Joke J.F.A., van Rheenen, Wouter, Tunca, Ceren, Bayraktar, Elif, Xia, Menghang, Iacoangeli, Alfredo, Shatunov, Aleksey, Verde, Federico, Kenna, Kevin, Al Khleifat, Ahmad, Opie-Martin, Sarah, Piccinelli, Stefano Cotti, Padovani, Alessandro, Galimberti, Daniela, Serpente, Maria, Fenoglio, Chiara, Scarpini, Elio, Curtis, Charles J., Lee, Sang Hyuck, Chung, Raymond, Patel, Hamel, Cooper-Knock, Johnathan, Breen, Gerome, Dobson, Richard J.B., van den Berg, Leonard H., D’Alfonso, Sandra, Chandran, Siddharthan, Pal, Suvankar, Johnson, Kory, Doucet-O’Hare, Tara, Pasternack, Nicholas, Wang, Tongguang, Nath, Avindra, Veldink, Jan H., Chiò, Adriano, Sattler, Rita, Shaw, Christopher E., and Ferraiuolo, Laura

Published
2024
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49. Expression of ALS-PFN1 impairs vesicular degradation in iPSC-derived microglia

Author

Salome Funes, Jonathan Jung, Del Hayden Gadd, Michelle Mosqueda, Jianjun Zhong, Shankaracharya, Matthew Unger, Karly Stallworth, Debra Cameron, Melissa S. Rotunno, Pepper Dawes, Megan Fowler-Magaw, Pamela J. Keagle, Justin A. McDonough, Sivakumar Boopathy, Miguel Sena-Esteves, Jeffrey A. Nickerson, Cathleen Lutz, William C. Skarnes, Elaine T. Lim, Dorothy P. Schafer, Francesca Massi, John E. Landers, and Daryl A. Bosco

Subjects
Science
Abstract

Abstract Microglia play a pivotal role in neurodegenerative disease pathogenesis, but the mechanisms underlying microglia dysfunction and toxicity remain to be elucidated. To investigate the effect of neurodegenerative disease-linked genes on the intrinsic properties of microglia, we studied microglia-like cells derived from human induced pluripotent stem cells (iPSCs), termed iMGs, harboring mutations in profilin-1 (PFN1) that are causative for amyotrophic lateral sclerosis (ALS). ALS-PFN1 iMGs exhibited evidence of lipid dysmetabolism, autophagy dysregulation and deficient phagocytosis, a canonical microglia function. Mutant PFN1 also displayed enhanced binding affinity for PI3P, a critical signaling molecule involved in autophagic and endocytic processing. Our cumulative data implicate a gain-of-toxic function for mutant PFN1 within the autophagic and endo-lysosomal pathways, as administration of rapamycin rescued phagocytic dysfunction in ALS-PFN1 iMGs. These outcomes demonstrate the utility of iMGs for neurodegenerative disease research and implicate microglial vesicular degradation pathways in the pathogenesis of these disorders.

Published
2024
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50. Influence of cardiorespiratory fitness and body composition on resting and post-exercise indices of vascular health in young adults

Author

Rian Q. Landers-Ramos, Kathleen Dondero, Ian Imery, Nicholas Reveille, Hannah A. Zabriskie, and Devon A. Dobrosielski

Subjects
Cardiorespiratory fitness, Flow mediated dilation, Augmentation index, Vascular, Acute exercise, Body composition, Medicine (General), R5-920
Abstract

Poor cardiorespiratory fitness may mediate vascular impairments at rest and following an acute bout of exercise in young healthy individuals. This study aimed to compare flow mediated dilation (FMD) and vascular augmentation index (AIx75) between young adults with low, moderate, and high levels of cardiorespiratory fitness before and after an acute bout of aerobic exercise. Forty-three participants (22 men; 21 women) between 18 and 29 years of age completed the study. Participants were classified into low, moderate, and high health-related cardiorespiratory fitness groups according to age- and sex-based relative maximal oxygen consumption (V˙O2 max) percentile rankings. FMD was performed using Doppler ultrasound and AIx75 was performed using pulse wave analysis at baseline and 60-min after a 30-min bout of treadmill running at 70% V˙O2 max. A significant interaction (p ​= ​0.047; ηp2 ​= ​0.142) was observed, with the moderate fitness group exhibiting a higher FMD post-exercise compared with baseline ([6.7% ​± ​3.1%] vs. [8.5% ​± ​2.8%], p ​= ​0.028; d ​= ​0.598). We found a significant main effect of group for AIx75 (p ​= ​0.023; ηp2 ​= ​0.168), with the high fitness group exhibiting lower AIx75 compared to low fitness group ([−10% ​± ​10%] vs. [2% ​± ​10%], respectively, p ​= ​0.019; g ​= ​1.07). This was eliminated after covarying for body fat percentage (p ​= ​0.489). Our findings suggest that resting FMD and AIx75 responses are not significantly influenced by cardiorespiratory fitness, but FMD recovery responses to exercise may be enhanced in individuals with moderate cardiorespiratory fitness levels.

Published
2024
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