Pathophysiology最新文献

{"title":"Influence of Housing Temperature and Genetic Diversity on Allogeneic T Cell-Induced Tissue Damage in Mice.","authors":"Josue Enriquez, Brianyell McDaniel Mims, Stephanie Stroever, Andrea Pires Dos Santos, Yava Jones-Hall, Kathryn L Furr, Matthew B Grisham","doi":"10.3390/pathophysiology30040039","DOIUrl":"10.3390/pathophysiology30040039","url":null,"abstract":"<p><p>The objective of this study was to determine how housing temperature and genetic diversity affect the onset and severity of allogeneic T cell-induced tissue damage in mice subjected to reduced intensity conditioning (RIC). We found that adoptive transfer of allogeneic CD4⁺ T cells from inbred donors into sub-lethally irradiated inbred recipients (I→I) housed at standard housing temperatures (ST; 22-24 °C) induced extensive BM and spleen damage in the absence of injury to any other tissue. Although engraftment of T cells in RIC-treated mice housed at their thermo-neutral temperature (TNT; 30-32 °C) also developed similar BM and spleen damage, their survival was markedly and significantly increased when compared to their ST counterparts. In contrast, the adoptive transfer of allogeneic T cells into RIC-treated outbred CD1 recipients failed to induce disease in any tissue at ST or TNT. The lack of tissue damage was not due to defects in donor T cell trafficking to BM or spleen but was associated with the presence of large numbers of B cells and myeloid cells within these tissues that are known to contain immunosuppressive regulatory B cells and myeloid-derived suppressor cells. These data demonstrate, for the first time, that housing temperature affects the survival of RIC-treated I→I mice and that RIC-conditioned outbred mice are resistant to allogeneic T cell-induced BM and spleen damage.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"30 4","pages":"522-547"},"PeriodicalIF":0.0,"publicationDate":"2023-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10661280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138177002","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}

{"title":"Impact of Prematurity on Auditory Processing in Children","authors":"Maria Y. Boboshko, Irina V. Savenko, Ekaterina S. Garbaruk, Veronika M. Knyazeva, Marina J. Vasilyeva","doi":"10.3390/pathophysiology30040038","DOIUrl":"https://doi.org/10.3390/pathophysiology30040038","url":null,"abstract":"Prematurity is one of the most crucial risk factors negatively affecting the maturation of the auditory system. Children born preterm demonstrate high rates of hearing impairments. Auditory processing difficulties in preterm children might be a result of disturbances in the central auditory system development and/or sensory deprivation due to peripheral hearing loss. To investigate auditory processing in preterm children, we utilized a set of psychoacoustic tests to assess temporal processing and speech intelligibility. A total of 241 children aged 6–11 years old (136 born preterm and 105 healthy full-term children forming the control group) were assessed. The preterm children were divided into three groups based on their peripheral hearing status: 74 normal hearing (NH group); 30 children with bilateral permanent sensorineural hearing loss (SNHL group) and 32 children with bilateral auditory neuropathy spectrum disorder (ANSD group). The results showed significantly worse performance in all tests in premature children compared with full-term children. NH and SNHL groups showed significant age-related improvement in speech recognition thresholds in noise that might signify a “bottom-up” auditory processing maturation effect. Overall, all premature children had signs of auditory processing disorders of varying degrees. Analyzing and understanding the auditory processing specificity in preterm children can positively contribute to the more effective implementation of rehabilitation programs.","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"45 9","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136263086","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}

{"title":"NO Addition during Gas Oxygenation Reduces Liver and Kidney Injury during Prolonged Cardiopulmonary Bypass.","authors":"Aleksey Maksimovich Radovskiy,&nbsp;Andrey Evgenevich Bautin,&nbsp;Alexander Olegovich Marichev,&nbsp;Victor Vasilyevich Osovskikh,&nbsp;Natalia Yuryevna Semenova,&nbsp;Zoya Evgenyevna Artyukhina,&nbsp;Lada Aleksandrovna Murashova,&nbsp;Vsevolod Alexandrovich Zinserling","doi":"10.3390/pathophysiology30040037","DOIUrl":"10.3390/pathophysiology30040037","url":null,"abstract":"<p><p><b>Objective</b>. To evaluate the effect of NO added to the sweep gas of the oxygenator during cardiopulmonary bypass (CPB) on the liver and kidneys in pigs. <b>Methods</b>. An experiment was carried out on 10 pigs undergoing cardiac surgery using CPB. NO was added to the sweep gas of the oxygenator at a concentration of 100 ppm for the animals in the experimental group (CPB-NO, <i>n</i> = 5). Animals in the control group (CPB-contr, <i>n</i> = 5) did not receive NO in the sweep gas of the oxygenator. The CPB lasted 4 h, followed by postoperative monitoring for 12 h. To assess the injury to the liver and kidneys, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, creatinine, and neutrophil gelatinase-associated lipocalin (NGAL) were determined initially, at weaning from the CPB, and 6 and 12 h after weaning from the CPB. The glomerular filtration rate (GFR) was evaluated initially, at weaning from the CPB, and 6 and 12 h after weaning from the CPB. A pathomorphological study of the liver and kidneys was performed using semiquantitative morphometry. <b>Results</b>. The long four-hour period of CPB deliberately used in our experiment caused liver and kidney injury. In the CPB-contr group, an increase in the ALT concentration was found: 43 (34; 44) U/L at baseline to 82 (53; 99) U/L 12 h after CPB, <i>p</i> < 0.05. The AST concentration in the CPB-contr group increased from 25 (17; 26) U/L at baseline to 269 (164; 376) U/L 12 h after CPB, <i>p</i> < 0.05. We found no significant increase in the ALT and AST concentrations in the CPB-NO group. There were no significant differences in ALT and AST concentrations between the CPB-NO and CPB-contr groups at all the study time-points. In the CPB-contr group, an increase in the creatinine level was found from 131 (129; 133) µmol/L at baseline to 273 (241; 306) µmol/L 12 h after CPB, <i>p</i> < 0.05. We found no significant increase in creatinine level in the CPB-NO group. Creatinine levels in the CPB-NO group were significantly lower than in the CPB-contr group 12 h after weaning from CPB: 183 (168; 196) vs. 273 (241; 306) µmol/L; <i>p</i> = 0.008. The GFR in the CPB-NO group was significantly higher than in the CPB-contr group 6 h after weaning from CPB: 78.9 (77.8; 82.3) vs. 67.9 (62.3; 69.2) mL/min; <i>p</i> = 0.016. GFR was significantly higher in the CPB-NO group than in the CPB-contr group 12 h after weaning from CPB: 67.7 (65.5; 68.0) vs. 50.3 (48.7; 54.9) mL/min; <i>p</i> = 0.032. We found no significant differences between the study groups in the level of NGAL. We found several differences between the groups in the pathomorphological study. <b>Conclusions</b>. NO added to the sweep gas of the oxygenator reduces creatinine levels and increases GFR during prolonged CPB injury. Further research is required.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"30 4","pages":"484-504"},"PeriodicalIF":0.0,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10594502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49691877","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}

{"title":"Reply to Singh, G.D. Comment on \"Dao et al. Retrospective Analysis of Real-World Data for the Treatment of Obstructive Sleep Apnea with Slow Maxillary Expansion Using a Unique Expansion Dental Appliance (DNA). <i>Pathophysiology</i> 2023, <i>30</i>, 199-208\".","authors":"Nhi Dao,&nbsp;Colette Cozean,&nbsp;Oleg Chernyshev,&nbsp;Clete Kushida,&nbsp;Jonathan Greenburg,&nbsp;Jonathan S Alexander","doi":"10.3390/pathophysiology30040036","DOIUrl":"10.3390/pathophysiology30040036","url":null,"abstract":"<p><p>In response to the commentary \"Response to 'Retrospective analysis of real-world data for the treatment of obstructive sleep apnea with slow maxillary expansion'\" [...].</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"30 4","pages":"482-483"},"PeriodicalIF":0.0,"publicationDate":"2023-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10594429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49691878","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}

{"title":"Comment on Dao et al. Retrospective Analysis of Real-World Data for the Treatment of Obstructive Sleep Apnea with Slow Maxillary Expansion Using a Unique Expansion Dental Appliance (DNA). <i>Pathophysiology</i> 2023, <i>30</i>, 199-208.","authors":"G Dave Singh","doi":"10.3390/pathophysiology30040035","DOIUrl":"10.3390/pathophysiology30040035","url":null,"abstract":"<p><p>I found the recent article by Dao et al. titled \"Retrospective analysis of real-world data for the treatment of obstructive sleep apnea with slow maxillary expansion using a unique expansion dental appliance (DNA)\" [...].</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"30 4","pages":"480-481"},"PeriodicalIF":0.0,"publicationDate":"2023-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10594413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49691876","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}

{"title":"What Are the Causes of Death among Patients Admitted to a Contemporary Tertiary-Level Cardiology Department? An Analysis of 10 Years of Morbidity and Mortality Meetings.","authors":"Chun Shing Kwok,&nbsp;Jacopo Tafuro,&nbsp;Chun Wai Wong,&nbsp;Sadie Bennett,&nbsp;Donah Zachariah,&nbsp;Diane Barker,&nbsp;Adrian Morley-Davies,&nbsp;Duwarakan Satchithananda,&nbsp;Mark Gunning,&nbsp;Josip A Borovac","doi":"10.3390/pathophysiology30040034","DOIUrl":"10.3390/pathophysiology30040034","url":null,"abstract":"<p><p>Despite the efforts to deliver the best evidence-based care, in-hospital death is an inevitable event among some patients hospitalized in cardiology departments. We conducted a retrospective evaluation of mortality events from inpatient admissions to the cardiology department between 2010 and 2019. Data were collected from morbidity and mortality meeting presentations that evaluated comorbidities, medical history, treatments, and causes of death for the overall cohort and according to age group and sex. There were 1182 registered deaths. The most common causes of death among patients were acute myocardial infarction (AMI, 53.0%), heart failure (HF, 11.7%), cardiac arrest (CA, 6.6%), HF with complication/defined cardiomyopathy (6.3%), and sepsis (4.4%). We observed a decline in deaths from AMI from 61.9% in 2010 to 46.7% in 2019, while there was a clear increase in deaths from HF (11.1% in 2010 to 25.9% in 2019). Compared to patients ≥65 years, younger patients were more likely to have died from CA (15.7% vs. 4.3%, <i>p</i> < 0.001) and other cardiac reasons (3.0% vs. 0.4%, <i>p</i> < 0.001). The majority of deaths were due to AMI, HF, and CA. We observed a significant declining trend in the proportion of deaths due to AMI in recent years, with an increase in deaths due to HF.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"30 4","pages":"467-479"},"PeriodicalIF":0.0,"publicationDate":"2023-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10594450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49691879","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}

{"title":"CKD Urine Metabolomics: Modern Concepts and Approaches.","authors":"Elena Y Danilova,&nbsp;Anna O Maslova,&nbsp;Andrey N Stavrianidi,&nbsp;Alexander E Nosyrev,&nbsp;Larisa D Maltseva,&nbsp;Olga L Morozova","doi":"10.3390/pathophysiology30040033","DOIUrl":"10.3390/pathophysiology30040033","url":null,"abstract":"<p><p>One of the primary challenges regarding chronic kidney disease (CKD) diagnosis is the absence of reliable methods to detect early-stage kidney damage. A metabolomic approach is expected to broaden the current diagnostic modalities by enabling timely detection and making the prognosis more accurate. Analysis performed on urine has several advantages, such as the ease of collection using noninvasive methods and its lower protein and lipid content compared with other bodily fluids. This review highlights current trends in applied analytical methods, major discoveries concerning pathways, and investigated populations in the context of urine metabolomic research for CKD over the past five years. Also, we are presenting approaches, instrument upgrades, and sample preparation modifications that have improved the analytical parameters of methods. The onset of CKD leads to alterations in metabolism that are apparent in the molecular composition of urine. Recent works highlight the prevalence of alterations in the metabolic pathways related to the tricarboxylic acid cycle and amino acids. Including diverse patient cohorts, using numerous analytical techniques with modifications and the appropriate annotation and explanation of the discovered biomarkers will help develop effective diagnostic models for different subtypes of renal injury with clinical applications.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"30 4","pages":"443-466"},"PeriodicalIF":0.0,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10594523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49691875","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}

{"title":"Pathophysiology, Management, and Therapeutics in Subarachnoid Hemorrhage and Delayed Cerebral Ischemia: An Overview.","authors":"Henry W Sanicola,&nbsp;Caleb E Stewart,&nbsp;Patrick Luther,&nbsp;Kevin Yabut,&nbsp;Bharat Guthikonda,&nbsp;J Dedrick Jordan,&nbsp;J Steven Alexander","doi":"10.3390/pathophysiology30030032","DOIUrl":"https://doi.org/10.3390/pathophysiology30030032","url":null,"abstract":"<p><p>Subarachnoid hemorrhage (SAH) is a type of hemorrhagic stroke resulting from the rupture of an arterial vessel within the brain. Unlike other stroke types, SAH affects both young adults (mid-40s) and the geriatric population. Patients with SAH often experience significant neurological deficits, leading to a substantial societal burden in terms of lost potential years of life. This review provides a comprehensive overview of SAH, examining its development across different stages (early, intermediate, and late) and highlighting the pathophysiological and pathohistological processes specific to each phase. The clinical management of SAH is also explored, focusing on tailored treatments and interventions to address the unique pathological changes that occur during each stage. Additionally, the paper reviews current treatment modalities and pharmacological interventions based on the evolving guidelines provided by the American Heart Association (AHA). Recent advances in our understanding of SAH will facilitate clinicians' improved management of SAH to reduce the incidence of delayed cerebral ischemia in patients.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"30 3","pages":"420-442"},"PeriodicalIF":0.0,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10536590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41159968","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}

{"title":"Unraveling MYC's Role in Orchestrating Tumor Intrinsic and Tumor Microenvironment Interactions Driving Tumorigenesis and Drug Resistance.","authors":"Zinab O Doha, Rosalie C Sears","doi":"10.3390/pathophysiology30030031","DOIUrl":"10.3390/pathophysiology30030031","url":null,"abstract":"<p><p>The transcription factor MYC plays a pivotal role in regulating various cellular processes and has been implicated in tumorigenesis across multiple cancer types. MYC has emerged as a master regulator governing tumor intrinsic and tumor microenvironment interactions, supporting tumor progression and driving drug resistance. This review paper aims to provide an overview and discussion of the intricate mechanisms through which MYC influences tumorigenesis and therapeutic resistance in cancer. We delve into the signaling pathways and molecular networks orchestrated by MYC in the context of tumor intrinsic characteristics, such as proliferation, replication stress and DNA repair. Furthermore, we explore the impact of MYC on the tumor microenvironment, including immune evasion, angiogenesis and cancer-associated fibroblast remodeling. Understanding MYC's multifaceted role in driving drug resistance and tumor progression is crucial for developing targeted therapies and combination treatments that may effectively combat this devastating disease. Through an analysis of the current literature, this review's goal is to shed light on the complexities of MYC-driven oncogenesis and its potential as a promising therapeutic target.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"30 3","pages":"400-419"},"PeriodicalIF":0.0,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10537413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41147851","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}

{"title":"Acromegaly: Pathophysiological Considerations and Treatment Options Including the Evolving Role of Oral Somatostatin Analogs.","authors":"Charles P Daniel,&nbsp;Maxwell J Wagner,&nbsp;Grant E Borne,&nbsp;Connor J Plaisance,&nbsp;Shahab Ahmadzadeh,&nbsp;Alfonso Aquino,&nbsp;Sahar Shekoohi,&nbsp;Adam M Kaye,&nbsp;Elyse M Cornett,&nbsp;Alan D Kaye","doi":"10.3390/pathophysiology30030029","DOIUrl":"https://doi.org/10.3390/pathophysiology30030029","url":null,"abstract":"<p><p>Acromegaly is a condition most commonly diagnosed in the fifth decade of life and has numerous treatment options. In this regard, Mycapssa^® is the first FDA-approved oral octreotide capsule for treating acromegaly, combining the efficacy of the somatostatin receptor ligand, octreotide, with the ease of a twice-daily oral capsule. Where surgical treatment is not an option, somatostatin analogs, including octreotide, are the first line of medical treatment for acromegaly, requiring regular subcutaneous or intramuscular injections administered by a patient's healthcare provider. Octreotide capsules (Mycapssa^®) provide an alternative to these somatostatin receptor ligand injections by combining octreotide with other excipients to produce a transient permeability enhancer technology that improves paracellular transport of octreotide across the gastrointestinal wall into the small intestine. Across multiple trials, including open-label (CH-ACM-01), double-blind placebo-controlled (CHIASMA OPTIMAL), and open-label extension of the trial period (CHIASMA OPTIMAL OLE), Mycapssa^® octreotide capsules maintained a consistent biochemical normalization of IGF-1 and GH levels, safety profiles similar to injected somatostatin receptor ligands, and patient preference to continued treatment with octreotide capsules. While clinical trial data supports the use of octreotide capsules (Mycapssa^®) in the pharmacological management of GH and IGF-1 levels, very little data exist regarding the drug's efficacy, tolerability, and use in female or pediatric-specific populations. A better understanding of the efficacy, application, and role of oral octreotide capsules in the long-term medical management of acromegaly in a diversity of populations is imperative to best determine the risks/benefits for the clinician.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"30 3","pages":"377-388"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10537411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41147534","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}