Pub Date : 2023-05-10DOI: 10.3390/pathophysiology30020018
Liudmila Gerasimova-Meigal, Alexander Meigal, Maria Gerasimova, Anna Sklyarova, Ekaterina Sirotinina
The primary aim of the study was to assess cerebral circulation in healthy young subjects during an ultra-short (45 min) session of ground-based microgravity modeled by "dry" immersion (DI), with the help of a multifunctional Laser Doppler Flowmetry (LDF) analyzer. In addition, we tested a hypothesis that cerebral temperature would grow during a DI session. The supraorbital area of the forehead and forearm area were tested before, within, and after a DI session. Average perfusion, five oscillation ranges of the LDF spectrum, and brain temperature were assessed. Within a DI session, in the supraorbital area most of LDF parameters remained unchanged except for a 30% increase in respiratory associated (venular) rhythm. The temperature of the supraorbital area increased by up to 38.5 °C within the DI session. In the forearm area, the average value of perfusion and its nutritive component increased, presumably due to thermoregulation. In conclusion, the results suggest that a 45 min DI session does not exert a substantial effect on cerebral blood perfusion and systemic hemodynamics in young healthy subjects. Moderate signs of venous stasis were observed, and brain temperature increased during a DI session. These findings must be thoroughly validated in future studies because elevated brain temperature during a DI session can contribute to some reactions to DI.
{"title":"Cerebral Circulation and Brain Temperature during an Ultra-Short Session of Dry Immersion in Young Subjects.","authors":"Liudmila Gerasimova-Meigal, Alexander Meigal, Maria Gerasimova, Anna Sklyarova, Ekaterina Sirotinina","doi":"10.3390/pathophysiology30020018","DOIUrl":"https://doi.org/10.3390/pathophysiology30020018","url":null,"abstract":"<p><p>The primary aim of the study was to assess cerebral circulation in healthy young subjects during an ultra-short (45 min) session of ground-based microgravity modeled by \"dry\" immersion (DI), with the help of a multifunctional Laser Doppler Flowmetry (LDF) analyzer. In addition, we tested a hypothesis that cerebral temperature would grow during a DI session. The supraorbital area of the forehead and forearm area were tested before, within, and after a DI session. Average perfusion, five oscillation ranges of the LDF spectrum, and brain temperature were assessed. Within a DI session, in the supraorbital area most of LDF parameters remained unchanged except for a 30% increase in respiratory associated (venular) rhythm. The temperature of the supraorbital area increased by up to 38.5 °C within the DI session. In the forearm area, the average value of perfusion and its nutritive component increased, presumably due to thermoregulation. In conclusion, the results suggest that a 45 min DI session does not exert a substantial effect on cerebral blood perfusion and systemic hemodynamics in young healthy subjects. Moderate signs of venous stasis were observed, and brain temperature increased during a DI session. These findings must be thoroughly validated in future studies because elevated brain temperature during a DI session can contribute to some reactions to DI.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10204427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9568951","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 : 2023-05-09DOI: 10.3390/pathophysiology30020017
Nhi Dao, Colette Cozean, Oleg Chernyshev, Clete Kushida, Jonathan Greenburg, Jonathan S Alexander
In addition to mandibular advancement devices, dental expansion appliances are an important clinical approach for achieving an increased intra-oral space that promotes airflow and lessens the frequency or severity of apneic events in patients diagnosed with obstructive sleep apnea (OSA). It has been thought that dental expansion in adults must be preceded by oral surgery; however, in this paper, we examine the results of a new technique for slow maxillary expansion without any surgical procedures. The palatal expansion device, DNA (Daytime-Nighttime Appliance), was reviewed in this retrospective study, particularly regarding its effects on measurements of transpalatal width, airway volume, and apnea-hypopnea indices (AHI) as well as its common modalities and complications. The DNA effectively reduced AHI by 46% (p = 0.00001) and significantly increased both airway volume and transpalatal width (p < 0.00001). After DNA treatment, 80% of patients showed some improvement in AHI scores with 28% of patients having their OSA symptoms completely resolved. Compared to the use of mandibular appliances, this approach is intended to create a sustained improvement in airway management that can reduce or eliminate dependence on continuous positive airway pressure (CPAP) or other OSA treatment devices.
{"title":"Retrospective Analysis of Real-World Data for the Treatment of Obstructive Sleep Apnea with Slow Maxillary Expansion Using a Unique Expansion Dental Appliance (DNA).","authors":"Nhi Dao, Colette Cozean, Oleg Chernyshev, Clete Kushida, Jonathan Greenburg, Jonathan S Alexander","doi":"10.3390/pathophysiology30020017","DOIUrl":"https://doi.org/10.3390/pathophysiology30020017","url":null,"abstract":"<p><p>In addition to mandibular advancement devices, dental expansion appliances are an important clinical approach for achieving an increased intra-oral space that promotes airflow and lessens the frequency or severity of apneic events in patients diagnosed with obstructive sleep apnea (OSA). It has been thought that dental expansion in adults must be preceded by oral surgery; however, in this paper, we examine the results of a new technique for slow maxillary expansion without any surgical procedures. The palatal expansion device, DNA (Daytime-Nighttime Appliance), was reviewed in this retrospective study, particularly regarding its effects on measurements of transpalatal width, airway volume, and apnea-hypopnea indices (AHI) as well as its common modalities and complications. The DNA effectively reduced AHI by 46% (<i>p</i> = 0.00001) and significantly increased both airway volume and transpalatal width (<i>p</i> < 0.00001). After DNA treatment, 80% of patients showed some improvement in AHI scores with 28% of patients having their OSA symptoms completely resolved. Compared to the use of mandibular appliances, this approach is intended to create a sustained improvement in airway management that can reduce or eliminate dependence on continuous positive airway pressure (CPAP) or other OSA treatment devices.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10204354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9870976","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 : 2023-05-04DOI: 10.3390/pathophysiology30020016
Muhammad Vitanata Arfijanto, Tri Pudy Asmarawati, Bramantono Bramantono, Musofa Rusli, Brian Eka Rachman, Bagus Aulia Mahdi, Nasronudin Nasronudin, Usman Hadi
Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) ribonucleic acid (RNA) shedding is an important parameter for determining the optimal length of isolation period required for coronavirus disease 2019 (COVID-19) patients. However, the clinical (i.e., patient and disease) characteristics that could influence this parameter have yet to be determined. In this study, we aim to explore the potential associations between several clinical features and the duration of SARS-CoV-2 RNA shedding in patients hospitalized with COVID-19. A retrospective cohort study involving 162 patients hospitalized for COVID-19 in a tertiary referral teaching hospital in Indonesia was performed from June to December 2021. Patients were grouped based on the mean duration of viral shedding and were compared based on several clinical characteristics (e.g., age, sex, comorbidities, COVID-19 symptoms, severity, and therapies). Subsequently, clinical factors potentially associated with the duration of SARS-CoV-2 RNA shedding were further assessed using multivariate logistic regression analysis. As a result, the mean duration of SARS-CoV-2 RNA shedding was found to be 13 ± 8.44 days. In patients with diabetes mellitus (without chronic complications) or hypertension, the duration of viral shedding was significantly prolonged (≥13 days; p = 0.001 and p = 0.029, respectively). Furthermore, patients with dyspnea displayed viral shedding for longer durations (p = 0.011). The multivariate logistic regression analysis reveals that independent risk factors associated with the duration of SARS-CoV-2 RNA shedding include disease severity (adjusted odds ratio [aOR] = 2.94; 95% CI = 1.36-6.44), bilateral lung infiltrates (aOR = 2.79; 95% CI = 1.14-6.84), diabetes mellitus (aOR = 2.17; 95% CI = 1.02-4.63), and antibiotic treatment (aOR = 3.66; 95% CI = 1.74-7.71). In summary, several clinical factors are linked with the duration of SARS-CoV-2 RNA shedding. Disease severity is positively associated with the duration of viral shedding, while bilateral lung infiltrates, diabetes mellitus, and antibiotic treatment are negatively linked with the duration of viral shedding. Overall, our findings suggest the need to consider different isolation period estimations for specific clinical characteristics of patients with COVID-19 that affect the duration of SARS-CoV-2 RNA shedding.
严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)核糖核酸(RNA)脱落是确定2019冠状病毒病(COVID-19)患者最佳隔离时间的重要参数。然而,可能影响这一参数的临床(即患者和疾病)特征尚未确定。在这项研究中,我们的目的是探讨一些临床特征与COVID-19住院患者SARS-CoV-2 RNA脱落持续时间之间的潜在关联。2021年6月至12月,在印度尼西亚一家三级转诊教学医院进行了一项回顾性队列研究,涉及162名因COVID-19住院的患者。根据病毒脱落的平均持续时间对患者进行分组,并根据几种临床特征(如年龄、性别、合并症、COVID-19症状、严重程度和治疗方法)进行比较。随后,使用多因素logistic回归分析进一步评估可能与SARS-CoV-2 RNA脱落持续时间相关的临床因素。结果发现,SARS-CoV-2 RNA脱落的平均持续时间为13±8.44天。在糖尿病(无慢性并发症)或高血压患者中,病毒脱落的持续时间明显延长(≥13天;P = 0.001和P = 0.029)。此外,呼吸困难患者的病毒脱落持续时间更长(p = 0.011)。多因素logistic回归分析显示,与SARS-CoV-2 RNA脱落持续时间相关的独立危险因素包括疾病严重程度(校正优势比[aOR] = 2.94;95% CI = 1.36-6.44),双侧肺浸润(aOR = 2.79;95% CI = 1.14-6.84),糖尿病(aOR = 2.17;95% CI = 1.02-4.63),抗生素治疗(aOR = 3.66;95% ci = 1.74-7.71)。总之,几个临床因素与SARS-CoV-2 RNA脱落的持续时间有关。疾病严重程度与病毒脱落持续时间呈正相关,而双侧肺浸润、糖尿病和抗生素治疗与病毒脱落持续时间呈负相关。总体而言,我们的研究结果表明,需要考虑对影响SARS-CoV-2 RNA脱落持续时间的COVID-19患者的特定临床特征进行不同的隔离期估计。
{"title":"Duration of SARS-CoV-2 RNA Shedding Is Significantly Influenced by Disease Severity, Bilateral Pulmonary Infiltrates, Antibiotic Treatment, and Diabetic Status: Consideration for Isolation Period.","authors":"Muhammad Vitanata Arfijanto, Tri Pudy Asmarawati, Bramantono Bramantono, Musofa Rusli, Brian Eka Rachman, Bagus Aulia Mahdi, Nasronudin Nasronudin, Usman Hadi","doi":"10.3390/pathophysiology30020016","DOIUrl":"https://doi.org/10.3390/pathophysiology30020016","url":null,"abstract":"<p><p>Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) ribonucleic acid (RNA) shedding is an important parameter for determining the optimal length of isolation period required for coronavirus disease 2019 (COVID-19) patients. However, the clinical (i.e., patient and disease) characteristics that could influence this parameter have yet to be determined. In this study, we aim to explore the potential associations between several clinical features and the duration of SARS-CoV-2 RNA shedding in patients hospitalized with COVID-19. A retrospective cohort study involving 162 patients hospitalized for COVID-19 in a tertiary referral teaching hospital in Indonesia was performed from June to December 2021. Patients were grouped based on the mean duration of viral shedding and were compared based on several clinical characteristics (e.g., age, sex, comorbidities, COVID-19 symptoms, severity, and therapies). Subsequently, clinical factors potentially associated with the duration of SARS-CoV-2 RNA shedding were further assessed using multivariate logistic regression analysis. As a result, the mean duration of SARS-CoV-2 RNA shedding was found to be 13 ± 8.44 days. In patients with diabetes mellitus (without chronic complications) or hypertension, the duration of viral shedding was significantly prolonged (≥13 days; <i>p</i> = 0.001 and <i>p</i> = 0.029, respectively). Furthermore, patients with dyspnea displayed viral shedding for longer durations (<i>p</i> = 0.011). The multivariate logistic regression analysis reveals that independent risk factors associated with the duration of SARS-CoV-2 RNA shedding include disease severity (adjusted odds ratio [aOR] = 2.94; 95% CI = 1.36-6.44), bilateral lung infiltrates (aOR = 2.79; 95% CI = 1.14-6.84), diabetes mellitus (aOR = 2.17; 95% CI = 1.02-4.63), and antibiotic treatment (aOR = 3.66; 95% CI = 1.74-7.71). In summary, several clinical factors are linked with the duration of SARS-CoV-2 RNA shedding. Disease severity is positively associated with the duration of viral shedding, while bilateral lung infiltrates, diabetes mellitus, and antibiotic treatment are negatively linked with the duration of viral shedding. Overall, our findings suggest the need to consider different isolation period estimations for specific clinical characteristics of patients with COVID-19 that affect the duration of SARS-CoV-2 RNA shedding.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10204499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9568952","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 : 2023-04-26DOI: 10.3390/pathophysiology30020015
Elena Zelikovna Golukhova, Inessa Viktorovna Slivneva, Inga Yur'evna Farulova, Ivan Ivanovich Skopin, Damir Ildarovich Marapov, Dar'ya Vladimirovna Murysova, Yuliya Dmitrievna Pirushkina, Irina Vasilyevna Volkovskaya
Aim of the study: The aim of this study was to perform a comparative analysis of severity of discordant aortic stenosis (AS) assessment using multiposition scanning and the standard apical window.
Materials and methods: All patients (n = 104) underwent preoperative transthoracic echocardiography (TTE) and were ranked according to the degree of AS severity. The reproducibility feasibility of the right parasternal window (RPW) was 75.0% (n = 78). The mean age of the patients was 64 years, and 40 (51.3%) were female. In 25 cases, low gradients were identified from the apical window not corresponding to the visual structural changes in the aortic valve, or disagreement between the velocity and calculated parameters was detected. Patients were divided into two groups: concordant AS (n = 56; 71.8%) and discordant AS (n = 22; 28.2%). Three individuals were excluded from the discordant AS group due to the presence of moderate stenosis.
Results: Based on the comparative analysis of transvalvular flow velocities obtained from multiposition scanning, the concordance group showed agreement between the velocity and calculated parameters. We observed an increase in the mean transvalvular pressure gradient (ΔPmean) and peak aortic jet velocity (Vmax), ΔPmean in 95.5% of patients, velocity time integral of transvalvular flow (VTI AV) in 90.9% of patients, and a decrease in aortic valve area (AVA) and indexed AVA in 90.9% of patients after applying RPW in all patients with discordant AS. The use of RPW allowed the reclassification of AS severity from discordant to concordant high-gradient AS in 88% of low-gradient AS cases.
Conclusion: Underestimation of flow velocity and overestimation of AVA using the apical window may lead to misclassification of AS. The use of RPW helps to match the degree of AS severity with the velocity characteristics and reduce the number of low-gradient AS cases.
研究目的本研究旨在对使用多位置扫描和标准心尖窗评估主动脉瓣狭窄(AS)不一致的严重程度进行比较分析:所有患者(104 人)均在术前接受了经胸超声心动图(TTE)检查,并根据 AS 的严重程度进行排序。右胸骨旁窗(RPW)的再现性为 75.0%(78 人)。患者的平均年龄为64岁,其中40人(51.3%)为女性。在 25 例患者中,从心尖窗发现的低梯度与主动脉瓣的直观结构变化不符,或发现速度参数与计算参数不一致。患者被分为两组:一致的强直性脊柱炎(n = 56;71.8%)和不一致的强直性脊柱炎(n = 22;28.2%)。不一致强直性脊柱炎组中有三人因存在中度狭窄而被排除在外:根据对多位置扫描获得的跨瓣血流速度的比较分析,一致组的血流速度与计算参数一致。在对所有不一致的强直性脊柱炎患者应用 RPW 后,我们观察到平均跨瓣压力梯度(ΔPmean)和主动脉喷射速度峰值(Vmax)、ΔPmean 在 95.5% 的患者中增加,跨瓣血流速度时间积分(VTI AV)在 90.9% 的患者中增加,主动脉瓣面积(AVA)和指数化 AVA 在 90.9% 的患者中减少。在88%的低梯度AS病例中,使用RPW可将AS严重程度从不一致性重新分类为一致的高梯度AS:结论:使用心尖窗低估血流速度和高估AVA可能会导致AS分类错误。使用 RPW 有助于将 AS 的严重程度与流速特征相匹配,并减少低梯度 AS 病例的数量。
{"title":"Advantages of Multiposition Scanning in Echocardiographic Assessment of the Severity of Discordant Aortic Stenosis.","authors":"Elena Zelikovna Golukhova, Inessa Viktorovna Slivneva, Inga Yur'evna Farulova, Ivan Ivanovich Skopin, Damir Ildarovich Marapov, Dar'ya Vladimirovna Murysova, Yuliya Dmitrievna Pirushkina, Irina Vasilyevna Volkovskaya","doi":"10.3390/pathophysiology30020015","DOIUrl":"10.3390/pathophysiology30020015","url":null,"abstract":"<p><strong>Aim of the study: </strong>The aim of this study was to perform a comparative analysis of severity of discordant aortic stenosis (AS) assessment using multiposition scanning and the standard apical window.</p><p><strong>Materials and methods: </strong>All patients (<i>n</i> = 104) underwent preoperative transthoracic echocardiography (TTE) and were ranked according to the degree of AS severity. The reproducibility feasibility of the right parasternal window (RPW) was 75.0% (<i>n</i> = 78). The mean age of the patients was 64 years, and 40 (51.3%) were female. In 25 cases, low gradients were identified from the apical window not corresponding to the visual structural changes in the aortic valve, or disagreement between the velocity and calculated parameters was detected. Patients were divided into two groups: concordant AS (<i>n</i> = 56; 71.8%) and discordant AS (<i>n</i> = 22; 28.2%). Three individuals were excluded from the discordant AS group due to the presence of moderate stenosis.</p><p><strong>Results: </strong>Based on the comparative analysis of transvalvular flow velocities obtained from multiposition scanning, the concordance group showed agreement between the velocity and calculated parameters. We observed an increase in the mean transvalvular pressure gradient (ΔP<sub>mean</sub>) and peak aortic jet velocity (V<sub>max</sub>), ΔP<sub>mean</sub> in 95.5% of patients, velocity time integral of transvalvular flow (VTI AV) in 90.9% of patients, and a decrease in aortic valve area (AVA) and indexed AVA in 90.9% of patients after applying RPW in all patients with discordant AS. The use of RPW allowed the reclassification of AS severity from discordant to concordant high-gradient AS in 88% of low-gradient AS cases.</p><p><strong>Conclusion: </strong>Underestimation of flow velocity and overestimation of AVA using the apical window may lead to misclassification of AS. The use of RPW helps to match the degree of AS severity with the velocity characteristics and reduce the number of low-gradient AS cases.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10204481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9870975","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 : 2023-04-22DOI: 10.3390/pathophysiology30020014
Gatot Soegiarto, Dewajani Purnomosari
In recent years, the elderly has become a rapidly growing proportion of the world's population as life expectancy is extending. Immunosenescence and inflammaging contribute to the increased risk of chronic non-communicable and acute infectious diseases. Frailty is highly prevalent in the elderly and is associated with an impaired immune response, a higher propensity to infection, and a lower response to vaccines. Additionally, the presence of uncontrolled comorbid diseases in the elderly also contributes to sarcopenia and frailty. Vaccine-preventable diseases that threaten the elderly include influenza, pneumococcal infection, herpes zoster, and COVID-19, which contribute to significant disability-adjusted life years lost. Previous studies had shown that conventional vaccines only yielded suboptimal protection that wanes rapidly in a shorter time. This article reviews published papers on several vaccination strategies that were developed for the elderly to solve these problems: more immunogenic vaccine formulations using larger doses of antigen, stronger vaccine adjuvants, recombinant subunit or protein conjugated vaccines, newly developed mRNA vaccines, giving booster shots, and exploring alternative routes of administration. Included also are several publications on senolytic medications under investigation to boost the immune system and vaccine response in the elderly. With all those in regard, the currently recommended vaccines for the elderly are presented.
{"title":"Challenges in the Vaccination of the Elderly and Strategies for Improvement.","authors":"Gatot Soegiarto, Dewajani Purnomosari","doi":"10.3390/pathophysiology30020014","DOIUrl":"https://doi.org/10.3390/pathophysiology30020014","url":null,"abstract":"<p><p>In recent years, the elderly has become a rapidly growing proportion of the world's population as life expectancy is extending. Immunosenescence and inflammaging contribute to the increased risk of chronic non-communicable and acute infectious diseases. Frailty is highly prevalent in the elderly and is associated with an impaired immune response, a higher propensity to infection, and a lower response to vaccines. Additionally, the presence of uncontrolled comorbid diseases in the elderly also contributes to sarcopenia and frailty. Vaccine-preventable diseases that threaten the elderly include influenza, pneumococcal infection, herpes zoster, and COVID-19, which contribute to significant disability-adjusted life years lost. Previous studies had shown that conventional vaccines only yielded suboptimal protection that wanes rapidly in a shorter time. This article reviews published papers on several vaccination strategies that were developed for the elderly to solve these problems: more immunogenic vaccine formulations using larger doses of antigen, stronger vaccine adjuvants, recombinant subunit or protein conjugated vaccines, newly developed mRNA vaccines, giving booster shots, and exploring alternative routes of administration. Included also are several publications on senolytic medications under investigation to boost the immune system and vaccine response in the elderly. With all those in regard, the currently recommended vaccines for the elderly are presented.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10204411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9870511","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 : 2023-04-18DOI: 10.3390/pathophysiology30020013
Nicole Hall, Nhi Dao, Cameron Hewett, Sara Oberle, Andrew Minagar, Kariann Lamon, Carey Ford, Bruce E Blough, J Steven Alexander, Kevin S Murnane
To avoid criminal prosecution, clandestine chemists produce designer stimulants that mimic the pharmacological and psychoactive effects of conventional stimulants, such as methamphetamine. Following persistent or high-dose exposure, both acute vasoconstriction and loss of vascular homeostasis are reported dangers of conventional stimulants, and designer stimulants may pose even greater dangers. To compare the effects of a conventional stimulant and two designer stimulants on vascular contraction, this study examined the direct effects of 1,3-benzodioxolylbutanamine (BDB) and N-butylpentylone in comparison to methamphetamine on the function of human brain vascular smooth muscle cells (HBVSMCs). HBVSMCs suspended in collagen gels were exposed to varying concentrations of each drug, and the degree of constriction was assessed over one week. The MTT assay was used to measure the impact of the three drugs on the cellular metabolic activity as a marker of cellular toxicity. The highest concentration tested of either methamphetamine or N-butylpentylone produced a loss of HBVSMC contractility and impaired cellular metabolism. BDB showed a similar pattern of effects, but, uniquely, it also induced vasoconstrictive effects at substantially lower concentrations. Each drug produced direct effects on HBVSMC contraction that may be a mechanism by which the cardiovascular system is damaged following high-dose or persistent exposure, and this could be exacerbated by any sympathomimetic effects of these compounds in whole organisms. BDB appears to impact HBVSMC function in ways distinct from methamphetamine and N-butylpentylone, which may present unique dangers.
{"title":"Methamphetamine and Designer Stimulants Modulate Tonic Human Cerebrovascular Smooth Muscle Contractility: Relevance to Drug-Induced Neurovascular Stress.","authors":"Nicole Hall, Nhi Dao, Cameron Hewett, Sara Oberle, Andrew Minagar, Kariann Lamon, Carey Ford, Bruce E Blough, J Steven Alexander, Kevin S Murnane","doi":"10.3390/pathophysiology30020013","DOIUrl":"10.3390/pathophysiology30020013","url":null,"abstract":"<p><p>To avoid criminal prosecution, clandestine chemists produce designer stimulants that mimic the pharmacological and psychoactive effects of conventional stimulants, such as methamphetamine. Following persistent or high-dose exposure, both acute vasoconstriction and loss of vascular homeostasis are reported dangers of conventional stimulants, and designer stimulants may pose even greater dangers. To compare the effects of a conventional stimulant and two designer stimulants on vascular contraction, this study examined the direct effects of 1,3-benzodioxolylbutanamine (BDB) and N-butylpentylone in comparison to methamphetamine on the function of human brain vascular smooth muscle cells (HBVSMCs). HBVSMCs suspended in collagen gels were exposed to varying concentrations of each drug, and the degree of constriction was assessed over one week. The MTT assay was used to measure the impact of the three drugs on the cellular metabolic activity as a marker of cellular toxicity. The highest concentration tested of either methamphetamine or N-butylpentylone produced a loss of HBVSMC contractility and impaired cellular metabolism. BDB showed a similar pattern of effects, but, uniquely, it also induced vasoconstrictive effects at substantially lower concentrations. Each drug produced direct effects on HBVSMC contraction that may be a mechanism by which the cardiovascular system is damaged following high-dose or persistent exposure, and this could be exacerbated by any sympathomimetic effects of these compounds in whole organisms. BDB appears to impact HBVSMC function in ways distinct from methamphetamine and N-butylpentylone, which may present unique dangers.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10123609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9394657","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 : 2023-04-06DOI: 10.3390/pathophysiology30020012
Stefanus Gunawan Kandinata, Soebagijo Adi Soelistijo, Agung Pranoto, Erwin Astha Triyono
Previous studies have yielded inconsistent results on whether glycated hemoglobin (HbA1c) and random blood glucose (RBG) are associated with mortality of coronavirus disease 2019 (COVID-19) patients with type 2 diabetes mellitus (T2DM). This study aimed to assess the association of HbA1c and RBG with mortality among COVID-19 patients with T2DM. A retrospective study was conducted on 237 patients with COVID-19 and T2DM (survival (n = 169) and non-survival groups (n = 68)). Data on socio-demography, comorbidities, clinical symptoms, laboratory examination, and mortality were collected. Patients in the non-survival group had an older age range as compared with those in the survival group (60 (52.3-65.0) vs. 56.0 (48.5-61.5) years, p = 0.009). There was no statistical gender difference between the two groups. After matching was done, chronic kidney disease, NLR, d-dimer, procalcitonin, and random blood glucose were higher in the non-survival group compared to the survival group (p < 0.05). HbA1c levels were similar in survivors and non-survivors (8.7% vs. 8.9%, p=0.549). The level of RBG was independently associated with mortality of COVID-19 patients with T2DM (p = 0.003, adjusted OR per 1-SD increment 2.55, 95% CI: 1.36-4.76). In conclusion, RBG was associated with the mortality of COVID-19 patients with T2DM, but HbA1c was not.
{"title":"Random Blood Glucose, but Not HbA1c, Was Associated with Mortality in COVID-19 Patients with Type 2 Diabetes Mellitus-A Retrospective Study.","authors":"Stefanus Gunawan Kandinata, Soebagijo Adi Soelistijo, Agung Pranoto, Erwin Astha Triyono","doi":"10.3390/pathophysiology30020012","DOIUrl":"10.3390/pathophysiology30020012","url":null,"abstract":"<p><p>Previous studies have yielded inconsistent results on whether glycated hemoglobin (HbA1c) and random blood glucose (RBG) are associated with mortality of coronavirus disease 2019 (COVID-19) patients with type 2 diabetes mellitus (T2DM). This study aimed to assess the association of HbA1c and RBG with mortality among COVID-19 patients with T2DM. A retrospective study was conducted on 237 patients with COVID-19 and T2DM (survival (<i>n</i> = 169) and non-survival groups (<i>n</i> = 68)). Data on socio-demography, comorbidities, clinical symptoms, laboratory examination, and mortality were collected. Patients in the non-survival group had an older age range as compared with those in the survival group (60 (52.3-65.0) vs. 56.0 (48.5-61.5) years, <i>p</i> = 0.009). There was no statistical gender difference between the two groups. After matching was done, chronic kidney disease, NLR, d-dimer, procalcitonin, and random blood glucose were higher in the non-survival group compared to the survival group (<i>p</i> < 0.05). HbA1c levels were similar in survivors and non-survivors (8.7% vs. 8.9%, p=0.549). The level of RBG was independently associated with mortality of COVID-19 patients with T2DM (<i>p</i> = 0.003, adjusted OR per 1-SD increment 2.55, 95% CI: 1.36-4.76). In conclusion, RBG was associated with the mortality of COVID-19 patients with T2DM, but HbA1c was not.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10123645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9388831","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 : 2023-04-04DOI: 10.3390/pathophysiology30020011
Lacee K Collins, Matthew W Cole, Timothy L Waters, Michael Iloanya, Patrick A Massey, William F Sherman
Aging causes a reduction in testosterone and estrogen, which is linked to diminished bone mineral density. Hormone replacement therapy and its effect on the outcome of joint arthroplasties is unclear. The purpose of this study was to analyze the impact of testosterone replacement therapy (TRT) and estrogen replacement therapy (ERT) on the medical and joint outcomes of total hip (THA) and total knee arthroplasties (TKA). A retrospective cohort study was conducted using the PearlDiver database. Patients who received TRT or ERT perioperatively were matched to controls. Rates of 90-day medical complications and 2-year joint complications were queried. Patients who received TRT had an increased risk of revision, periprosthetic joint infection, and pooled joint complications within 2 years following a THA and increased rates of septic and aseptic revisions, and aseptic loosening after TKA compared to the control cohort. Patients receiving ERT had increased rates of aseptic loosening and pooled joint complications within 2 years following THA and increased rates of all-cause revisions and pooled joint complications after TKA. Patients who received TRT demonstrated significantly higher rates of revision rates and PJI. Patients who received perioperative ERT were significantly more likely to have increased risks of revision rates and joint infections.
{"title":"Hormone Replacement Therapy Does Not Eliminate Risk Factors for Joint Complications following Total Joint Arthroplasty: A Matched Cohort Study.","authors":"Lacee K Collins, Matthew W Cole, Timothy L Waters, Michael Iloanya, Patrick A Massey, William F Sherman","doi":"10.3390/pathophysiology30020011","DOIUrl":"https://doi.org/10.3390/pathophysiology30020011","url":null,"abstract":"<p><p>Aging causes a reduction in testosterone and estrogen, which is linked to diminished bone mineral density. Hormone replacement therapy and its effect on the outcome of joint arthroplasties is unclear. The purpose of this study was to analyze the impact of testosterone replacement therapy (TRT) and estrogen replacement therapy (ERT) on the medical and joint outcomes of total hip (THA) and total knee arthroplasties (TKA). A retrospective cohort study was conducted using the PearlDiver database. Patients who received TRT or ERT perioperatively were matched to controls. Rates of 90-day medical complications and 2-year joint complications were queried. Patients who received TRT had an increased risk of revision, periprosthetic joint infection, and pooled joint complications within 2 years following a THA and increased rates of septic and aseptic revisions, and aseptic loosening after TKA compared to the control cohort. Patients receiving ERT had increased rates of aseptic loosening and pooled joint complications within 2 years following THA and increased rates of all-cause revisions and pooled joint complications after TKA. Patients who received TRT demonstrated significantly higher rates of revision rates and PJI. Patients who received perioperative ERT were significantly more likely to have increased risks of revision rates and joint infections.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10123744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9394652","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 : 2023-04-03DOI: 10.3390/pathophysiology30020010
Samvel Tonyan, Maria Pospelova, Varvara Krasnikova, Olga Fionik, Tatyana Alekseeva, Konstantin Samochernykh, Nataliya Ivanova, Tatyana Vavilova, Elena Vasilieva, Albina Makhanova, Aleksandra Nikolaeva, Tatyana Bukkieva, Stephanie Combs, Maxim Shevtsov
Damage to the peripheral nervous system (PNS) is a common complication of breast cancer (BC) treatment, with 60 to 80% of breast cancer survivors experiencing symptoms of PNS damage. In the current study, the levels of brain-derived neurotrophic factor (BDNF), galectin-3 (Gal-3), and neurotrophin-3 (NT-3) were measured in the blood serum of BC patients by ELISA as potential biomarkers that might indicate the PNS damage. Sixty-seven patients were enrolled in this multi-center trial and compared to the aged-matched healthy female volunteers (control group) (n = 25). Intergroup comparison of biomarker levels (i.e., Gal-3 and BDNF) did not show significant differences in any of the studied subgroups. However, intriguingly, NT-3 levels were significantly higher in BC patients as compared to healthy volunteers, constituting 14.85 [10.3; 18.0] and 5.74 [4.56; 13.7] pg/mL, respectively (p < 0.001). In conclusion, NT-3 might be employed as a potential biomarker in BC patients with clinical manifestations of PNS damage. However, further studies to validate its correlation to the degree of peripheral nervous system lesions are of high value.
{"title":"Neurotrophin-3 (NT-3) as a Potential Biomarker of the Peripheral Nervous System Damage Following Breast Cancer Treatment.","authors":"Samvel Tonyan, Maria Pospelova, Varvara Krasnikova, Olga Fionik, Tatyana Alekseeva, Konstantin Samochernykh, Nataliya Ivanova, Tatyana Vavilova, Elena Vasilieva, Albina Makhanova, Aleksandra Nikolaeva, Tatyana Bukkieva, Stephanie Combs, Maxim Shevtsov","doi":"10.3390/pathophysiology30020010","DOIUrl":"https://doi.org/10.3390/pathophysiology30020010","url":null,"abstract":"<p><p>Damage to the peripheral nervous system (PNS) is a common complication of breast cancer (BC) treatment, with 60 to 80% of breast cancer survivors experiencing symptoms of PNS damage. In the current study, the levels of brain-derived neurotrophic factor (BDNF), galectin-3 (Gal-3), and neurotrophin-3 (NT-3) were measured in the blood serum of BC patients by ELISA as potential biomarkers that might indicate the PNS damage. Sixty-seven patients were enrolled in this multi-center trial and compared to the aged-matched healthy female volunteers (control group) (<i>n</i> = 25). Intergroup comparison of biomarker levels (i.e., Gal-3 and BDNF) did not show significant differences in any of the studied subgroups. However, intriguingly, NT-3 levels were significantly higher in BC patients as compared to healthy volunteers, constituting 14.85 [10.3; 18.0] and 5.74 [4.56; 13.7] pg/mL, respectively (<i>p</i> < 0.001). In conclusion, NT-3 might be employed as a potential biomarker in BC patients with clinical manifestations of PNS damage. However, further studies to validate its correlation to the degree of peripheral nervous system lesions are of high value.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10123681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9388832","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}
Chronic inflammation is a crucial driver of carcinogenesis in pancreatic ductal adenocarcinoma (PDAC). Several studies have investigated the prognostic significance of cyclooxygenase-2 (COX-2) expression in PDAC patients, obtaining conflicting results. Nuclear factor kappa-B (NF-κB), specificity protein 1 (Sp1), and c-Jun are known as the transcription factors of the COX2 gene. This exploratory observational study investigated the association of the NF-κB, COX-2, Sp1, and c-Jun expressions with patient survival in PDAC. We used the immunohistochemical method to detect the PDAC tissue expressions of NF-κB (RelA/p65), COX-2, Sp1, and c-Jun. The expressions of these proteins were correlated with the overall survival (OS) and other clinicopathological characteristics of PDAC patients. We obtained 53 PDAC specimens from resections and biopsies. There were significant correlations between the four proteins' expressions in the PDAC tissues. The expression of the cytoplasmic (aHR = 0.31; 95% CI 0.11-0.90; p = 0.032) or nuclear NF-κB (aHR = 0.22; 95% CI 0.07-0.66; p = 0.007) was independently associated with a better prognosis in the PDAC patients. COX-2, Sp1, and c-Jun showed no significant association with a prognosis in the PDAC patients. The PDAC patients who expressed NF-κB had a better prognosis than the other patients, which suggests that the role of inflammation in PDAC is more complex than previously thought.
慢性炎症是胰腺导管腺癌(PDAC)发生的关键驱动因素。一些研究调查了环氧化酶-2 (COX-2)表达在PDAC患者中的预后意义,但得到了相互矛盾的结果。核因子κ b (NF-κB)、特异性蛋白1 (Sp1)和c-Jun是COX2基因的转录因子。本探索性观察研究探讨了NF-κB、COX-2、Sp1和c-Jun表达与PDAC患者生存的关系。采用免疫组化方法检测PDAC组织中NF-κB (RelA/p65)、COX-2、Sp1、c-Jun的表达。这些蛋白的表达与PDAC患者的总生存期(OS)及其他临床病理特征相关。我们从切除和活检中获得53例PDAC标本。这四种蛋白在PDAC组织中的表达有显著相关性。细胞质表达量(aHR = 0.31;95% ci 0.11-0.90;p = 0.032)或核NF-κB (aHR = 0.22;95% ci 0.07-0.66;p = 0.007)与PDAC患者预后较好独立相关。COX-2、Sp1和c-Jun与PDAC患者的预后无显著相关性。表达NF-κB的PDAC患者预后优于其他患者,提示炎症在PDAC中的作用比之前认为的更为复杂。
{"title":"The Expressions of NF-κB, COX-2, Sp1, and c-Jun in Pancreatic Ductal Adenocarcinoma and Their Associations with Patient Survival.","authors":"Kaka Renaldi, Marcellus Simadibrata, Nur Rahadiani, Diah Rini Handjari, Alida Roswita Harahap, Kuntjoro Harimurti, Nasrul Zubir, Lianda Siregar, Imelda Maria Loho, Evlina Suzanna, Bonita Prawirodihardjo, Heriawaty Hidajat, Budi Widodo, Alphania Rahniayu, Renaningtyas Tambun, Andy William, Dadang Makmun","doi":"10.3390/pathophysiology30020009","DOIUrl":"https://doi.org/10.3390/pathophysiology30020009","url":null,"abstract":"<p><p>Chronic inflammation is a crucial driver of carcinogenesis in pancreatic ductal adenocarcinoma (PDAC). Several studies have investigated the prognostic significance of cyclooxygenase-2 (COX-2) expression in PDAC patients, obtaining conflicting results. Nuclear factor kappa-B (NF-κB), specificity protein 1 (Sp1), and c-Jun are known as the transcription factors of the <i>COX2</i> gene. This exploratory observational study investigated the association of the NF-κB, COX-2, Sp1, and c-Jun expressions with patient survival in PDAC. We used the immunohistochemical method to detect the PDAC tissue expressions of NF-κB (RelA/p65), COX-2, Sp1, and c-Jun. The expressions of these proteins were correlated with the overall survival (OS) and other clinicopathological characteristics of PDAC patients. We obtained 53 PDAC specimens from resections and biopsies. There were significant correlations between the four proteins' expressions in the PDAC tissues. The expression of the cytoplasmic (aHR = 0.31; 95% CI 0.11-0.90; <i>p</i> = 0.032) or nuclear NF-κB (aHR = 0.22; 95% CI 0.07-0.66; <i>p</i> = 0.007) was independently associated with a better prognosis in the PDAC patients. COX-2, Sp1, and c-Jun showed no significant association with a prognosis in the PDAC patients. The PDAC patients who expressed NF-κB had a better prognosis than the other patients, which suggests that the role of inflammation in PDAC is more complex than previously thought.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10123625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9388830","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}