Pub Date : 2024-05-09DOI: 10.21203/rs.3.rs-4344179/v1
Giuseppe Cullaro, Andrew S. Allegretti, Kavish R. Patidar, Elizabeth C. Verna, Jennifer C. Lai
Abstract Methods A case-control study of 97 patients hospitalized at our institution. We performed aptamer-based proteomics and metabolomics on serum biospecimens obtained within 72 hours of admission. We compared the proteome and metabolome by the AKI phenotype (i.e., HRS-AKI, ATN) and by AKI recovery (decrease in sCr within 0.3 mg/dL of baseline) using ANCOVA analyses adjusting for demographics and clinical characteristics. We completed Random Forest (RF) analyses to identify metabolites and proteins associated with AKI phenotype and recovery. Lasso regression models were developed to highlight metabolites and proteins could improve diagnostic accuracy. Results: ANCOVA analyses showed no metabolomic or proteomic differences by AKI phenotype while identifying differences by AKI recovery status. Our RF and Lasso analyses showed that metabolomics can improve the diagnostic accuracy of both AKI diagnosis and recovery, and aptamer-based proteomics can enhance the diagnostic accuracy of AKI recovery. Discussion: Our analyses provide novel insight into pathophysiologic pathways, highlighting the metabolomic and proteomic similarities between patients with cirrhosis with HRS-AKI and ATN while also identifying differences between those with and without AKI recovery.
摘要 方法 对在我院住院的 97 名患者进行病例对照研究。我们对入院 72 小时内获得的血清生物样本进行了基于适配体的蛋白质组学和代谢组学研究。我们使用方差分析比较了AKI表型（即HRS-AKI、ATN）和AKI恢复（sCr比基线下降0.3 mg/dL以内）的蛋白质组和代谢组，并对人口统计学和临床特征进行了调整。我们完成了随机森林（RF）分析，以确定与 AKI 表型和恢复相关的代谢物和蛋白质。我们还开发了拉索回归模型，以突出可提高诊断准确性的代谢物和蛋白质。结果方差分析显示，AKI 表型与代谢组学或蛋白质组学无差异，而 AKI 恢复状态则存在差异。我们的 RF 和 Lasso 分析表明，代谢组学能提高 AKI 诊断和恢复的诊断准确性，而基于适配体的蛋白质组学能提高 AKI 恢复的诊断准确性。讨论：我们的分析提供了对病理生理途径的新见解，突出了肝硬化伴 HRS-AKI 和 ATN 患者之间代谢组学和蛋白质组学的相似性，同时也发现了 AKI 恢复和未恢复患者之间的差异。
{"title":"Applying Metabolomics and Aptamer-based Proteomics to Determine Pathophysiologic Differences in Decompensated Cirrhosis Patients Hospitalized with Acute Kidney Injury","authors":"Giuseppe Cullaro, Andrew S. Allegretti, Kavish R. Patidar, Elizabeth C. Verna, Jennifer C. Lai","doi":"10.21203/rs.3.rs-4344179/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-4344179/v1","url":null,"abstract":"Abstract Methods A case-control study of 97 patients hospitalized at our institution. We performed aptamer-based proteomics and metabolomics on serum biospecimens obtained within 72 hours of admission. We compared the proteome and metabolome by the AKI phenotype (i.e., HRS-AKI, ATN) and by AKI recovery (decrease in sCr within 0.3 mg/dL of baseline) using ANCOVA analyses adjusting for demographics and clinical characteristics. We completed Random Forest (RF) analyses to identify metabolites and proteins associated with AKI phenotype and recovery. Lasso regression models were developed to highlight metabolites and proteins could improve diagnostic accuracy. Results: ANCOVA analyses showed no metabolomic or proteomic differences by AKI phenotype while identifying differences by AKI recovery status. Our RF and Lasso analyses showed that metabolomics can improve the diagnostic accuracy of both AKI diagnosis and recovery, and aptamer-based proteomics can enhance the diagnostic accuracy of AKI recovery. Discussion: Our analyses provide novel insight into pathophysiologic pathways, highlighting the metabolomic and proteomic similarities between patients with cirrhosis with HRS-AKI and ATN while also identifying differences between those with and without AKI recovery.","PeriodicalId":21039,"journal":{"name":"Research Square","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140996978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-09DOI: 10.21203/rs.3.rs-4307935/v1
Yen-Tung Liu, Novera H. Khan, Krista M. Nicklaus, Marie Karen Bravo Moix, Chi Liu, Gregory P. Reece, Ashleigh M. Francis, Margaret J. Roubaud, Mia K. Markey
Abstract Purpose Breast cancer surgery, even with reconstruction, can make it difficult for patients to find a bra that fits properly, is comfortable, and meets their aesthetic standards. We explored breast cancer survivors’ experiences with bras over time to identify preferences, needs, and challenges throughout their journeys. Methods Fifteen women who had undergone mastectomy and either delayed or immediate breast reconstruction participated in the study. Focus groups were conducted to explore the participants’ current experiences with bras. They were also prompted to recall their experiences before mastectomy and immediately after reconstruction. The discussion included bra materials, styles, construction techniques, color, quality, and price. Results Thematic analysis generated five major themes: “Sense of normalcy and personal well-being,” “Struggles immediately following surgery,” “Transitions in bra experiences and preference,” “Practicality with outfit,” and “Association between quality and price”. Conclusion Breast cancer survivors' well-being is linked to their experiences with bras and the associated purchasing process, and bra needs change throughout the cancer care journey. Survivors’ experiences with bras impact their sense of normalcy and sense of control over significant bodily changes arising from cancer and its treatment. The study underscores the importance of future research on examining the relationship between survivors' quality of life and garment experiences, including factors such as color choices, closure options, and adjustability for individual needs.
{"title":"Undergarment Needs and Challenges for Breast Cancer Survivors: A Qualitative Study","authors":"Yen-Tung Liu, Novera H. Khan, Krista M. Nicklaus, Marie Karen Bravo Moix, Chi Liu, Gregory P. Reece, Ashleigh M. Francis, Margaret J. Roubaud, Mia K. Markey","doi":"10.21203/rs.3.rs-4307935/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-4307935/v1","url":null,"abstract":"Abstract Purpose Breast cancer surgery, even with reconstruction, can make it difficult for patients to find a bra that fits properly, is comfortable, and meets their aesthetic standards. We explored breast cancer survivors’ experiences with bras over time to identify preferences, needs, and challenges throughout their journeys. Methods Fifteen women who had undergone mastectomy and either delayed or immediate breast reconstruction participated in the study. Focus groups were conducted to explore the participants’ current experiences with bras. They were also prompted to recall their experiences before mastectomy and immediately after reconstruction. The discussion included bra materials, styles, construction techniques, color, quality, and price. Results Thematic analysis generated five major themes: “Sense of normalcy and personal well-being,” “Struggles immediately following surgery,” “Transitions in bra experiences and preference,” “Practicality with outfit,” and “Association between quality and price”. Conclusion Breast cancer survivors' well-being is linked to their experiences with bras and the associated purchasing process, and bra needs change throughout the cancer care journey. Survivors’ experiences with bras impact their sense of normalcy and sense of control over significant bodily changes arising from cancer and its treatment. The study underscores the importance of future research on examining the relationship between survivors' quality of life and garment experiences, including factors such as color choices, closure options, and adjustability for individual needs.","PeriodicalId":21039,"journal":{"name":"Research Square","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140996731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-09DOI: 10.21203/rs.3.rs-3280283/v1
Guangyu Wang
Transient receptor potential vanilloid-1 (TRPV1) is a capsaicin receptor and employs the use-dependent desensitization to protect mammals from noxious heat damage in response to repeated or constant heat stimuli. However, the underlying structural factor or motif has not been resolved precisely. In this computational study, the graph theory-based grid thermodynamic model was used to reveal how the temperature-dependent noncovalent interactions as identified in the 3D structures of rat TRPV1 could develop a well-organized fluidic grid-like mesh network, featuring various topological grids constrained as the thermo-rings that range in size from the biggest to the smallest to govern distinct structural and functional traits of the channel in response to varying temperature degrees. Following the findings that the heat unfolding of three specific biggest grids, one in the closed state and two in the open state, was respectively responsible for the reversible activation at 43 °C and thermal inactivation from 56 °C to 61 °C, a random smaller grid was further identified for the irreversible inactivation and the relevant use-dependent desensitization from the pre-open closed state between 43 °C and 61 °C. Thus, these two distinct inactivation pathways of TRPV1 may be involved in protecting mammals against noxious heat damages.
{"title":"Thermo-ring basis for heat unfolding-induced inactivation in TRPV1.","authors":"Guangyu Wang","doi":"10.21203/rs.3.rs-3280283/v1","DOIUrl":"10.21203/rs.3.rs-3280283/v1","url":null,"abstract":"<p><p>Transient receptor potential vanilloid-1 (TRPV1) is a capsaicin receptor and employs the use-dependent desensitization to protect mammals from noxious heat damage in response to repeated or constant heat stimuli. However, the underlying structural factor or motif has not been resolved precisely. In this computational study, the graph theory-based grid thermodynamic model was used to reveal how the temperature-dependent noncovalent interactions as identified in the 3D structures of rat TRPV1 could develop a well-organized fluidic grid-like mesh network, featuring various topological grids constrained as the thermo-rings that range in size from the biggest to the smallest to govern distinct structural and functional traits of the channel in response to varying temperature degrees. Following the findings that the heat unfolding of three specific biggest grids, one in the closed state and two in the open state, was respectively responsible for the reversible activation at 43 °C and thermal inactivation from 56 °C to 61 °C, a random smaller grid was further identified for the irreversible inactivation and the relevant use-dependent desensitization from the pre-open closed state between 43 °C and 61 °C. Thus, these two distinct inactivation pathways of TRPV1 may be involved in protecting mammals against noxious heat damages.</p>","PeriodicalId":21039,"journal":{"name":"Research Square","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10479453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10213335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-08DOI: 10.21203/rs.3.rs-4343683/v1
Jonas Schluter, Grant A. Hussey, João Valeriano, Chenzhen Zhang, Alexis Sullivan, David Fenyö
Abstract The human gut microbiome is a promising therapeutic target, but interventions are hampered by our limited understanding of microbial ecosystems. Here, we present a platform to develop, evaluate, and score approaches to learn ecological interactions from microbiome time series data. The microbiome time series inference standardized test (MTIST) comprises: a simulation framework for the in silico generation of microbiome study data akin to what is obtained with quantitative next-generation sequencing approaches, a compilation of a large curated data set generated by the simulation framework representing 648 simulated microbiome studies containing 18,360 time series, with a total of 2,182,800 species abundance measurements, and a scoring method to rank ecological inference algorithms. We use the MTIST platform to rank five implementations of microbiome inference approaches, revealing that while all algorithms performed well on ecosystems with few species (3 and 10), all algorithms failed to infer most interaction in a large ecosystem with 100 member species. However, we do find that the strongest interactions within a large ecosystem are inferred with higher success by all algorithms. Finally, we use the MTIST platform to compare different microbiome study designs, characterizing tradeoffs between samples per subject and number of subjects. Interestingly, we find that when only few samples can be collected per subject, ecological inference is most successful when these samples are collected with highest feasible temporal frequency. Taken together, we provide a computational tool to aid the development of better microbiome ecosystem inference approaches, which will be crucial towards the development of reliable and predictable therapeutic approaches that target the microbiome ecosystem.
{"title":"The MTIST platform: a microbiome time series inference standardized test","authors":"Jonas Schluter, Grant A. Hussey, João Valeriano, Chenzhen Zhang, Alexis Sullivan, David Fenyö","doi":"10.21203/rs.3.rs-4343683/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-4343683/v1","url":null,"abstract":"Abstract The human gut microbiome is a promising therapeutic target, but interventions are hampered by our limited understanding of microbial ecosystems. Here, we present a platform to develop, evaluate, and score approaches to learn ecological interactions from microbiome time series data. The microbiome time series inference standardized test (MTIST) comprises: a simulation framework for the in silico generation of microbiome study data akin to what is obtained with quantitative next-generation sequencing approaches, a compilation of a large curated data set generated by the simulation framework representing 648 simulated microbiome studies containing 18,360 time series, with a total of 2,182,800 species abundance measurements, and a scoring method to rank ecological inference algorithms. We use the MTIST platform to rank five implementations of microbiome inference approaches, revealing that while all algorithms performed well on ecosystems with few species (3 and 10), all algorithms failed to infer most interaction in a large ecosystem with 100 member species. However, we do find that the strongest interactions within a large ecosystem are inferred with higher success by all algorithms. Finally, we use the MTIST platform to compare different microbiome study designs, characterizing tradeoffs between samples per subject and number of subjects. Interestingly, we find that when only few samples can be collected per subject, ecological inference is most successful when these samples are collected with highest feasible temporal frequency. Taken together, we provide a computational tool to aid the development of better microbiome ecosystem inference approaches, which will be crucial towards the development of reliable and predictable therapeutic approaches that target the microbiome ecosystem.","PeriodicalId":21039,"journal":{"name":"Research Square","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141000117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-08DOI: 10.21203/rs.3.rs-4323878/v1
Asha K. Nabirye, I. Munabi, A. Mubuuke, Sarah Kiguli
Abstract Introduction: Caring for dying patients is associated with psychological trauma, strong emotions and enormous stress for nursing staff and nursing students who are relied on by patients and relatives in such difficult situations. Although nurses have an ability of self-control and calm approach towards death, there are still some emotions they need to “work through”. Research studies have documented limited exposure of nursing students to end-of-life care and inadequate understanding of the psychological and emotional experiences they encounter during clinical placements. This study explored the psychological and emotional experiences of Ugandan student nurses on caring for the dying patients at Mulago national referral hospital during clinical placement. Methods A qualitative phenomenological study was conducted among fifteen undergraduate nursing students of Makerere University in clinical placement at Mulago hospital. An In-depth interview guide was used to gather data on nursing students’ emotional and psychological experiences and coping mechanisms. Data was audio recorded, verbatim transcribed and thematically analyzed using Atlas. ti version 6 software. Results The nursing students emotional and psychological experiences when caring for dying patients were emerged into two themes; (1) Psychological and emotional reactions, (2) Coping mechanisms. The sub themes were; anger, anxiety and depression which is triggered by a combination of issues of pressure from relatives, failure to save the dying patient, thoughts of wasted efforts to reverse the dying process, limited resources, limited technical and emotional support. The students cope by seeking help from peers, engagement in problem solving, distancing from patients, spirituality and engaging in personal stress reducing activities. Conclusion Insights from this study provide educators with a snapshot of student encounters, emotions, and coping strategies when facing dying patients and their families. Nursing students experience various negative emotional and psychological stressors triggered by a combination of issues that need to be addressed during care of dying patients. However, they devise different coping mechanisms to continue with provision of necessary end of life care as the clinical placement contributes to their learning, experience and builds confidence among student nurses.
{"title":"Emotional and Psychological Experiences of Nursing students caring for Dying Patients: A phenomenology study at Mulago National Hospital, Uganda","authors":"Asha K. Nabirye, I. Munabi, A. Mubuuke, Sarah Kiguli","doi":"10.21203/rs.3.rs-4323878/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-4323878/v1","url":null,"abstract":"Abstract Introduction: Caring for dying patients is associated with psychological trauma, strong emotions and enormous stress for nursing staff and nursing students who are relied on by patients and relatives in such difficult situations. Although nurses have an ability of self-control and calm approach towards death, there are still some emotions they need to “work through”. Research studies have documented limited exposure of nursing students to end-of-life care and inadequate understanding of the psychological and emotional experiences they encounter during clinical placements. This study explored the psychological and emotional experiences of Ugandan student nurses on caring for the dying patients at Mulago national referral hospital during clinical placement. Methods A qualitative phenomenological study was conducted among fifteen undergraduate nursing students of Makerere University in clinical placement at Mulago hospital. An In-depth interview guide was used to gather data on nursing students’ emotional and psychological experiences and coping mechanisms. Data was audio recorded, verbatim transcribed and thematically analyzed using Atlas. ti version 6 software. Results The nursing students emotional and psychological experiences when caring for dying patients were emerged into two themes; (1) Psychological and emotional reactions, (2) Coping mechanisms. The sub themes were; anger, anxiety and depression which is triggered by a combination of issues of pressure from relatives, failure to save the dying patient, thoughts of wasted efforts to reverse the dying process, limited resources, limited technical and emotional support. The students cope by seeking help from peers, engagement in problem solving, distancing from patients, spirituality and engaging in personal stress reducing activities. Conclusion Insights from this study provide educators with a snapshot of student encounters, emotions, and coping strategies when facing dying patients and their families. Nursing students experience various negative emotional and psychological stressors triggered by a combination of issues that need to be addressed during care of dying patients. However, they devise different coping mechanisms to continue with provision of necessary end of life care as the clinical placement contributes to their learning, experience and builds confidence among student nurses.","PeriodicalId":21039,"journal":{"name":"Research Square","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141000928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-08DOI: 10.21203/rs.3.rs-4331250/v1
Adarsha Koirala, Ann Marshak-Rothstein, Bruce R. Ksander, M. Gregory-Ksander
Abstract Neovascular age-related macular degeneration (AMD), results from choroidal neovascularization (CNV), retinal edema and loss of photoreceptors. Previous studies suggested that Fas Ligand (FasL) on retinal pigment epithelial cells inhibited CNV by inducing apoptosis of infiltrating Fas + vascular endothelial cells. However, induction of apoptosis depends on membrane-bound (mFasL) while the FasL cleavage product (sFasL) is neuroprotective. To better understand how FasL regulates the development of CNV, we used a mouse model of laser CNV to evaluate the development of CNV in mice with a FasL cleavage site mutation (ΔCS) and can only express the membrane-bound form of FasL. There was no significant difference in CNV size and area of vascular leakage in homozygous FasL ΔCS/ΔCS mice when compared to wild type mice. Unexpectedly, heterozygous FasL ΔCS/WT mice developed significantly less vascular leakage and showed accelerated neovessel maturation. However, CNV was not prevented in heterozygous FasL ΔCS/WT mice if the Fas receptor was deleted in myeloid cells (FasL ΔCS/+ Fas flox/flox Cre LysM ). Thus, FasL-mediated CNV inhibition depends on the extent of FasL cleavage, and on FasL engagement of Fas + myeloid cells. Moreover, accelerated neovessel maturation prevents vascular leakage in AMD.
{"title":"Fas Ligand enhances vessel maturation and inhibits vascular leakage associated with age-related macular degeneration","authors":"Adarsha Koirala, Ann Marshak-Rothstein, Bruce R. Ksander, M. Gregory-Ksander","doi":"10.21203/rs.3.rs-4331250/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-4331250/v1","url":null,"abstract":"Abstract Neovascular age-related macular degeneration (AMD), results from choroidal neovascularization (CNV), retinal edema and loss of photoreceptors. Previous studies suggested that Fas Ligand (FasL) on retinal pigment epithelial cells inhibited CNV by inducing apoptosis of infiltrating Fas + vascular endothelial cells. However, induction of apoptosis depends on membrane-bound (mFasL) while the FasL cleavage product (sFasL) is neuroprotective. To better understand how FasL regulates the development of CNV, we used a mouse model of laser CNV to evaluate the development of CNV in mice with a FasL cleavage site mutation (ΔCS) and can only express the membrane-bound form of FasL. There was no significant difference in CNV size and area of vascular leakage in homozygous FasL ΔCS/ΔCS mice when compared to wild type mice. Unexpectedly, heterozygous FasL ΔCS/WT mice developed significantly less vascular leakage and showed accelerated neovessel maturation. However, CNV was not prevented in heterozygous FasL ΔCS/WT mice if the Fas receptor was deleted in myeloid cells (FasL ΔCS/+ Fas flox/flox Cre LysM ). Thus, FasL-mediated CNV inhibition depends on the extent of FasL cleavage, and on FasL engagement of Fas + myeloid cells. Moreover, accelerated neovessel maturation prevents vascular leakage in AMD.","PeriodicalId":21039,"journal":{"name":"Research Square","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141000494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-08DOI: 10.21203/rs.3.rs-3442966/v1
Tom Murungi, Irene Kunihira, Pamela Oyella, M. Mugerwa, Peruth Gift, Mercy Jane Aceng, Lydia Abolo, Sean Steven Puleh
Abstract Background: Currently, 410,000 new HIV infections among youth occur worldwide, which is a significant public health issue. Members of the clergy can be trustworthy allies in the reduction of HIV infections among the youth. However, little is known regarding their knowledge as well as the perceptions they hold towards HIV prevention among young people. Thus, we explored the knowledge and perceptions of religious leaders regarding HIV prevention among young people (15–24 years) in Lira district. Methods: This was a cross-sectional qualitative study conducted among 20 religious leaders in March 2021 in Lira district. Religious leaders were sampled purposively and recruited from modern religions (beliefs influenced by Christianity or Islam) in Lira district. Guides for key informant interviews were utilized to gather information. Each interview was audio recorded, transcribed, and entered into NVivo version 12 software, and the data was then ready for analysis. The main themes were determined using thematic analysis. Results: Although a few individuals had some misconceptions, the majority of participants had good knowledge about the transmission and prevention of HIV. Participants knew awareness creation, abstinence, and faithfulness in marriage as HIV prevention strategies and held positive perceptions. Perceived barriers to HIV prevention involvement were lack of knowledge and training, and inadequate resources whereas motivating factors were; being respected, and trusted, and having easy access to young people. Conclusion: In conclusion, religious leaders show limited HIV prevention knowledge due to religious beliefs, but understand the importance of measures like abstinence. Despite challenges, their involvement is crucial. Addressing knowledge gaps and providing support is vital. Future efforts should emphasize both behavioral measures and interventions like condom use, Post Exposure Prophylaxis, and Pre-Exposure Prophylaxis.
{"title":"Knowledge and perceptions of religious leaders toward HIV prevention among young people in a resource-limited setting: A qualitative study","authors":"Tom Murungi, Irene Kunihira, Pamela Oyella, M. Mugerwa, Peruth Gift, Mercy Jane Aceng, Lydia Abolo, Sean Steven Puleh","doi":"10.21203/rs.3.rs-3442966/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-3442966/v1","url":null,"abstract":"Abstract Background: Currently, 410,000 new HIV infections among youth occur worldwide, which is a significant public health issue. Members of the clergy can be trustworthy allies in the reduction of HIV infections among the youth. However, little is known regarding their knowledge as well as the perceptions they hold towards HIV prevention among young people. Thus, we explored the knowledge and perceptions of religious leaders regarding HIV prevention among young people (15–24 years) in Lira district. Methods: This was a cross-sectional qualitative study conducted among 20 religious leaders in March 2021 in Lira district. Religious leaders were sampled purposively and recruited from modern religions (beliefs influenced by Christianity or Islam) in Lira district. Guides for key informant interviews were utilized to gather information. Each interview was audio recorded, transcribed, and entered into NVivo version 12 software, and the data was then ready for analysis. The main themes were determined using thematic analysis. Results: Although a few individuals had some misconceptions, the majority of participants had good knowledge about the transmission and prevention of HIV. Participants knew awareness creation, abstinence, and faithfulness in marriage as HIV prevention strategies and held positive perceptions. Perceived barriers to HIV prevention involvement were lack of knowledge and training, and inadequate resources whereas motivating factors were; being respected, and trusted, and having easy access to young people. Conclusion: In conclusion, religious leaders show limited HIV prevention knowledge due to religious beliefs, but understand the importance of measures like abstinence. Despite challenges, their involvement is crucial. Addressing knowledge gaps and providing support is vital. Future efforts should emphasize both behavioral measures and interventions like condom use, Post Exposure Prophylaxis, and Pre-Exposure Prophylaxis.","PeriodicalId":21039,"journal":{"name":"Research Square","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141000065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-08DOI: 10.21203/rs.3.rs-4324566/v1
Sudhir Sri, Elizabeth T. Jensen, Michael E. Msall, Joe Yi, Vasyl Zhabotynsky, Robert Joseph, Karl Kuban, Jean A. Frazier, Stephen Hooper, Hudson Santos, S. Gogcu, Jeffrey S Shenberger, Rebecca C Fry, T. O'Shea
Abstract Objective In a cohort of 10-year-old children born extremely preterm, we evaluated the hypothesis that increasing severity of retinopathy of prematurity (ROP) is associated with increasing frequency of unfavorable neurodevelopmental and quality of life outcomes. Study Design Study participants were classified according to the severity of ROP. At 10 years of age, their neurocognitive abilities, academic achievement, and gross motor function were assessed, and they were evaluated for autism spectrum disorder, anxiety, depression, and quality of life. Results After adjustment for sample attrition and confounders, only the association with lower quality of life persisted. Increasing severity of visual impairment was associated with worse neurodevelopmental outcomes and lower quality of life. Conclusion Among extremely preterm children, severity of visual impairment, but not severity of ROP, was associated with adverse neurodevelopmental outcomes at 10 years of age. Both severe ROP and more severe visual impairment were associated with lower quality of life.
{"title":"Retinopathy of prematurity and neurodevelopmental outcome and quality of life at 10 years of age","authors":"Sudhir Sri, Elizabeth T. Jensen, Michael E. Msall, Joe Yi, Vasyl Zhabotynsky, Robert Joseph, Karl Kuban, Jean A. Frazier, Stephen Hooper, Hudson Santos, S. Gogcu, Jeffrey S Shenberger, Rebecca C Fry, T. O'Shea","doi":"10.21203/rs.3.rs-4324566/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-4324566/v1","url":null,"abstract":"Abstract Objective In a cohort of 10-year-old children born extremely preterm, we evaluated the hypothesis that increasing severity of retinopathy of prematurity (ROP) is associated with increasing frequency of unfavorable neurodevelopmental and quality of life outcomes. Study Design Study participants were classified according to the severity of ROP. At 10 years of age, their neurocognitive abilities, academic achievement, and gross motor function were assessed, and they were evaluated for autism spectrum disorder, anxiety, depression, and quality of life. Results After adjustment for sample attrition and confounders, only the association with lower quality of life persisted. Increasing severity of visual impairment was associated with worse neurodevelopmental outcomes and lower quality of life. Conclusion Among extremely preterm children, severity of visual impairment, but not severity of ROP, was associated with adverse neurodevelopmental outcomes at 10 years of age. Both severe ROP and more severe visual impairment were associated with lower quality of life.","PeriodicalId":21039,"journal":{"name":"Research Square","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140999067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-08DOI: 10.21203/rs.3.rs-4350949/v1
Namdev S Togre, Naveen Melaka, Priyanka Bhoj, Nikhita Mogadala, Malika Winfield, Jayshil Trivedi, Deborah Grove, Sudhir Kotnala, Slava Rom, Uma Sri, Yuri Persidsky
Abstract Alcohol consumption leads to neuroinflammation and blood‒brain barrier (BBB) damage, resulting in neurological impairment. We previously demonstrated that ethanol-induced disruption of barrier function in human brain endothelial cells was associated with mitochondrial injury, increased ATP and extracellular vesicle (EV) release, and purinergic receptor P2X7R activation. Therefore, we aimed to evaluate the effect of P2X7r blockade on peripheral and neuro-inflammation in EtOH-exposed mice. In a chronic intermittent ethanol (CIE)-exposed mouse model, P2X7R was inhibited by two different methods: Brilliant Blue G (BBG) or gene knockout. We assessed blood ethanol concentration (BEC), plasma P2X7R and P-gp, number of extra-cellular vesicles (EV), serum ATP and EV-ATP levels. Brain microvessel gene expression and EV mtDNA copy numbers were measured by RT2 PCR array and digital PCR, respectively. A RT2 PCR array of brain microvessels revealed significant upregulation of proinflammatory genes involved in apoptosis, vasodilation, and platelet activation in CIE-exposed animals, which were decreased 15–50-fold in BBG-treated CIE-exposed animals. Plasma P-gp levels and serum P2X7R shedding were significantly increased in CIE-exposed animals. Pharmacological or genetic suppression of P2X7R decreased P2X7R shedding to levels equivalent to those in control group. The increase in EV number and EV-ATP content in the CIE-exposed mice was significantly reduced by P2X7R inhibition. CIE mice showed augmented EV-mtDNA copy numbers which were reduced in EVs after P2X7R inhibition or receptor knockout. These observations suggested that P2X7R signaling plays a critical role in ethanol-induced brain injury. Increased eATP, EV-ATP, EV numbers, and EV-mtDNA copy numbers highlight a new mechanism of brain injury during alcohol exposure via P2X7R and biomarkers of such damage. In this study, for the first time, we report the in vivo involvement of P2X7R signaling in CIE-induced brain injury.
{"title":"Neuroinflammatory Responses and Blood–Brain Barrier Injury in Chronic Alcohol Exposure: Role of Purinergic P2X7 Receptor Signaling","authors":"Namdev S Togre, Naveen Melaka, Priyanka Bhoj, Nikhita Mogadala, Malika Winfield, Jayshil Trivedi, Deborah Grove, Sudhir Kotnala, Slava Rom, Uma Sri, Yuri Persidsky","doi":"10.21203/rs.3.rs-4350949/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-4350949/v1","url":null,"abstract":"Abstract Alcohol consumption leads to neuroinflammation and blood‒brain barrier (BBB) damage, resulting in neurological impairment. We previously demonstrated that ethanol-induced disruption of barrier function in human brain endothelial cells was associated with mitochondrial injury, increased ATP and extracellular vesicle (EV) release, and purinergic receptor P2X7R activation. Therefore, we aimed to evaluate the effect of P2X7r blockade on peripheral and neuro-inflammation in EtOH-exposed mice. In a chronic intermittent ethanol (CIE)-exposed mouse model, P2X7R was inhibited by two different methods: Brilliant Blue G (BBG) or gene knockout. We assessed blood ethanol concentration (BEC), plasma P2X7R and P-gp, number of extra-cellular vesicles (EV), serum ATP and EV-ATP levels. Brain microvessel gene expression and EV mtDNA copy numbers were measured by RT2 PCR array and digital PCR, respectively. A RT2 PCR array of brain microvessels revealed significant upregulation of proinflammatory genes involved in apoptosis, vasodilation, and platelet activation in CIE-exposed animals, which were decreased 15–50-fold in BBG-treated CIE-exposed animals. Plasma P-gp levels and serum P2X7R shedding were significantly increased in CIE-exposed animals. Pharmacological or genetic suppression of P2X7R decreased P2X7R shedding to levels equivalent to those in control group. The increase in EV number and EV-ATP content in the CIE-exposed mice was significantly reduced by P2X7R inhibition. CIE mice showed augmented EV-mtDNA copy numbers which were reduced in EVs after P2X7R inhibition or receptor knockout. These observations suggested that P2X7R signaling plays a critical role in ethanol-induced brain injury. Increased eATP, EV-ATP, EV numbers, and EV-mtDNA copy numbers highlight a new mechanism of brain injury during alcohol exposure via P2X7R and biomarkers of such damage. In this study, for the first time, we report the in vivo involvement of P2X7R signaling in CIE-induced brain injury.","PeriodicalId":21039,"journal":{"name":"Research Square","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140999133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-08DOI: 10.21203/rs.3.rs-4214768/v1
Victoria M. Brown, Emily A. Ogutu, Alexandra E. Kauffman, Shanika S. Kennedy, Rebecca A. Tenner, A. Wurcel, Chad J. Zawitz, Anne C Spaulding, Matthew J. Akiyama
Abstract Background Little guidance exists on best practices for implementing and sustaining wastewater-based surveillance (WBS) for SARS-CoV-2 in carceral settings. To ensure alignment with priorities of stakeholders, we aimed to understand the perspectives of persons with lived experience (PLE) of jail who were incarcerated during the height of the COVID-19 pandemic on infection control. Methods We recruited two PLE at each of four jails: Cook County (IL), Fulton County (GA), Middlesex County (MA), and Washington DC. Focus Group Discussion (FGD) guides followed the Consolidated Framework for Implementation Research (CFIR). Two FGDs focusing on lived experience with jail infection control protocol and WBS were conducted, and six Key Informant (KI) interviews followed to gain insights on communicating WBS results. We used a combination of deductive thematic analysis based on CFIR constructs and inductive analysis to capture emergent themes. Results Themes from FGDs included: (1) variable experiences with COVID-19 infection control protocols including intake processes, individual testing, isolation and quarantine, (2) the perceived attitudes of fellow residents and staff surrounding COVID-19 mitigation in a carceral setting; and (3) perceived benefits and challenges involving WBS implementation and messaging. KIs emphasized 1) The importance of straightforward health messaging and trustworthiness in the communication of WBS results, 2) Support for enhanced health education around outbreaks, and 3) Receptiveness to WBS being used as a tool to measure common infectious agents (i.e., influenza) but hesitancy regarding its application to conditions such as HIV and illicit drug use. PLE articulated support of robust infection control programs and receptiveness to expanding WBS if conducted in a non-stigmatizing manner. Conclusion Perspectives from PLE can help shape the infection control programs for future outbreaks and inform the expansion of WBS implementation in carceral facilities. It will be important to consider the voices of current and former residents, as receivers of care, to promote an environment conducive to comprehensive infection control. In addition to having infection control programs consistently execute set protocols and educate all stakeholders, PLE identified collaboration between jail staff and residents, and clear communication around program expectations as priorities. Findings from this qualitative study can be shared with jail decision makers and the perceived engagement of stakeholders can be measured.
{"title":"Guiding the Implementation of Wastewater-based Surveillance for Carceral Infection Control with Perspectives from People with Lived Experience of Incarceration during the COVID-19 Pandemic","authors":"Victoria M. Brown, Emily A. Ogutu, Alexandra E. Kauffman, Shanika S. Kennedy, Rebecca A. Tenner, A. Wurcel, Chad J. Zawitz, Anne C Spaulding, Matthew J. Akiyama","doi":"10.21203/rs.3.rs-4214768/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-4214768/v1","url":null,"abstract":"Abstract Background Little guidance exists on best practices for implementing and sustaining wastewater-based surveillance (WBS) for SARS-CoV-2 in carceral settings. To ensure alignment with priorities of stakeholders, we aimed to understand the perspectives of persons with lived experience (PLE) of jail who were incarcerated during the height of the COVID-19 pandemic on infection control. Methods We recruited two PLE at each of four jails: Cook County (IL), Fulton County (GA), Middlesex County (MA), and Washington DC. Focus Group Discussion (FGD) guides followed the Consolidated Framework for Implementation Research (CFIR). Two FGDs focusing on lived experience with jail infection control protocol and WBS were conducted, and six Key Informant (KI) interviews followed to gain insights on communicating WBS results. We used a combination of deductive thematic analysis based on CFIR constructs and inductive analysis to capture emergent themes. Results Themes from FGDs included: (1) variable experiences with COVID-19 infection control protocols including intake processes, individual testing, isolation and quarantine, (2) the perceived attitudes of fellow residents and staff surrounding COVID-19 mitigation in a carceral setting; and (3) perceived benefits and challenges involving WBS implementation and messaging. KIs emphasized 1) The importance of straightforward health messaging and trustworthiness in the communication of WBS results, 2) Support for enhanced health education around outbreaks, and 3) Receptiveness to WBS being used as a tool to measure common infectious agents (i.e., influenza) but hesitancy regarding its application to conditions such as HIV and illicit drug use. PLE articulated support of robust infection control programs and receptiveness to expanding WBS if conducted in a non-stigmatizing manner. Conclusion Perspectives from PLE can help shape the infection control programs for future outbreaks and inform the expansion of WBS implementation in carceral facilities. It will be important to consider the voices of current and former residents, as receivers of care, to promote an environment conducive to comprehensive infection control. In addition to having infection control programs consistently execute set protocols and educate all stakeholders, PLE identified collaboration between jail staff and residents, and clear communication around program expectations as priorities. Findings from this qualitative study can be shared with jail decision makers and the perceived engagement of stakeholders can be measured.","PeriodicalId":21039,"journal":{"name":"Research Square","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140999531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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