Journal Description
Pathophysiology
Pathophysiology
is an international, peer-reviewed, open access journal on the etiology, development, and elimination of pathological processes. Pathophysiology is the official journal of the International Society for Pathophysiology (ISP) and is published quarterly online by MDPI (from Volume 27, Issue 1 - 2020).
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within ESCI (Web of Science), Scopus, PMC, PubMed, and other databases.
- Journal Rank: CiteScore - Q2 (Pathology and Forensic Medicine)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 37.2 days after submission; acceptance to publication is undertaken in 2.7 days (median values for papers published in this journal in the first half of 2023).
- Recognition of Reviewers: APC discount vouchers, optional signed peer review, and reviewer names published annually in the journal.
Latest Articles
Clinical Characteristics of 6102 Asymptomatic and Mild Cases for Patients with COVID-19 in Indonesia
Pathophysiology 2023, 30(3), 366-376; https://doi.org/10.3390/pathophysiology30030028 - 04 Aug 2023
Abstract
Background: The COVID-19 pandemic has led to a rise in confirmed cases, making epidemiological studies crucial for identifying the source of transmission and developing effective treatment methods. We conducted a study on the clinical characteristics of patients with asymptomatic and mild symptoms of
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Background: The COVID-19 pandemic has led to a rise in confirmed cases, making epidemiological studies crucial for identifying the source of transmission and developing effective treatment methods. We conducted a study on the clinical characteristics of patients with asymptomatic and mild symptoms of COVID-19 at a rescue hospital in Indonesia. Methods: This is an epidemiological study involving 6102 patients who were admitted to the Indrapura forefront hospital in Surabaya from May 2020 to February 2021. We described demographic data, clinical signs and symptoms, laboratory data, therapy, and clinical outcomes. Results: A total of 6102 patients were involved in this study, with 3664 (60.04%) being male and 2438 (39.95%) being female. The age range of 21–30 years was the most prevalent, accounting for 31.1% (1898 patients). The population had 1476 patients (24.2%) with comorbid conditions. The most prevalent comorbidity observed among these patients was hypertension, affecting 1015 individuals (16.6%). Out of the total 6006 patients observed, 40.7% (n = 2486) were asymptomatic, 54.6% (n = 3329) had mild symptoms, and 3.1% (n = 191) had moderate symptoms. All patients were administered supportive therapy without the use of antiviral medication. Out of the 6102 patients included in the study, 5923 patients (97.1%) achieved a cure, 36 patients (0.6%) are currently undergoing treatment, 142 patients (2.3%) were referred for desaturation indications (SpO2 < 94%), and one patient died due to a suspected cardiovascular event. Out of the total number of patients, 74.5% (4529 patients) had an average length of stay (LOS) of less than 10 days, while 25.6% (1563 patients) had an average length of stay of more than 10 days. Conclusion: The clinical presentation of asymptomatic and mild COVID-19 patients at a rescue hospital varies significantly based on the age and sex of patients. Cough and hyposmia are commonly observed symptoms. Supportive therapy is effective, and strict implementation of social distancing is crucial in preventing the spread of this disease from individuals who are asymptomatic or have mild symptoms.
Full article
(This article belongs to the Special Issue Hot Topics in Internal Medicine: Moving Forward from the Pandemic Era)
Open AccessReview
Myc beyond Cancer: Regulation of Mammalian Tissue Regeneration
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Pathophysiology 2023, 30(3), 346-365; https://doi.org/10.3390/pathophysiology30030027 - 02 Aug 2023
Abstract
Myc is one of the most well-known oncogenes driving tumorigenesis in a wide variety of tissues. From the brain to blood, its deregulation derails physiological pathways that grant the correct functioning of the cell. Its action is carried out at the gene expression
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Myc is one of the most well-known oncogenes driving tumorigenesis in a wide variety of tissues. From the brain to blood, its deregulation derails physiological pathways that grant the correct functioning of the cell. Its action is carried out at the gene expression level, where Myc governs basically every aspect of transcription. Indeed, in addition to its role as a canonical, chromatin-bound transcription factor, Myc rules RNA polymerase II (RNAPII) transcriptional pause–release, elongation and termination and mRNA capping. For this reason, it is evident that minimal perturbations of Myc function mirror malignant cell behavior and, consistently, a large body of literature mainly focuses on Myc malfunctioning. In healthy cells, Myc controls molecular mechanisms involved in pivotal functions, such as cell cycle (and proliferation thereof), apoptosis, metabolism and cell size, angiogenesis, differentiation and stem cell self-renewal. In this latter regard, Myc has been found to also regulate tissue regeneration, a hot topic in the research fields of aging and regenerative medicine. Indeed, Myc appears to have a role in wound healing, in peripheral nerves and in liver, pancreas and even heart recovery. Herein, we discuss the state of the art of Myc’s role in tissue regeneration, giving an overview of its potent action beyond cancer.
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(This article belongs to the Special Issue MYC in Regeneration and Tumorigenesis)
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Open AccessReview
Pathophysiology of Red Blood Cell Dysfunction in Diabetes and Its Complications
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Pathophysiology 2023, 30(3), 327-345; https://doi.org/10.3390/pathophysiology30030026 - 02 Aug 2023
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Diabetes Mellitus (DM) is a complex metabolic disorder associated with multiple microvascular complications leading to nephropathy, retinopathy, and neuropathy. Mounting evidence suggests that red blood cell (RBC) alterations are both a cause and consequence of disturbances related to DM-associated complications. Importantly, a significant
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Diabetes Mellitus (DM) is a complex metabolic disorder associated with multiple microvascular complications leading to nephropathy, retinopathy, and neuropathy. Mounting evidence suggests that red blood cell (RBC) alterations are both a cause and consequence of disturbances related to DM-associated complications. Importantly, a significant proportion of DM patients develop varying degrees of anemia of confounding etiology, leading to increased morbidity. In chronic hyperglycemia, RBCs display morphological, enzymatic, and biophysical changes, which in turn prime them for swift phagocytic clearance from circulation. A multitude of endogenous factors, such as oxidative and dicarbonyl stress, uremic toxins, extracellular hypertonicity, sorbitol accumulation, and deranged nitric oxide metabolism, have been implicated in pathological RBC changes in DM. This review collates clinical laboratory findings of changes in hematology indices in DM patients and discusses recent reports on the putative mechanisms underpinning shortened RBC survival and disturbed cell membrane architecture within the diabetic milieu. Specifically, RBC cell death signaling, RBC metabolism, procoagulant RBC phenotype, RBC-triggered endothelial cell dysfunction, and changes in RBC deformability and aggregation in the context of DM are discussed. Understanding the mechanisms of RBC alterations in DM provides valuable insights into the clinical significance of the crosstalk between RBCs and microangiopathy in DM.
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Open AccessArticle
Hemodynamic, Oxygenation and Lymphocyte Parameters Predict COVID-19 Mortality
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Pathophysiology 2023, 30(3), 314-326; https://doi.org/10.3390/pathophysiology30030025 - 02 Aug 2023
Abstract
The mortality of COVID-19 patients has left the world devastated. Many scoring systems have been developed to predict the mortality of COVID-19 patients, but several scoring components cannot be carried out in limited health facilities. Herein, the authors attempted to create a new
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The mortality of COVID-19 patients has left the world devastated. Many scoring systems have been developed to predict the mortality of COVID-19 patients, but several scoring components cannot be carried out in limited health facilities. Herein, the authors attempted to create a new and easy scoring system involving mean arterial pressure (MAP), PF Ratio, or SF ratio-respiration rate (SF Ratio-R), and lymphocyte absolute, which were abbreviated as MPL or MSLR functioning, as a predictive scoring system for mortality within 30 days for COVID-19 patients. Of 132 patients with COVID-19 hospitalized between March and November 2021, we followed up on 96 patients. We present bivariate and multivariate analyses as well as the area under the curve (AUC) and Kaplan–Meier charts. From 96 patients, we obtained an MPL score of 3 points: MAP < 75 mmHg, PF Ratio < 200, and lymphocyte absolute < 1500/µL, whereas the MSLR score was 6 points: MAP < 75 mmHg, SF Ratio < 200, lymphocyte absolute < 1500/µL, and respiration rate 24/min. The MPL cut-off point is 2, while the MSLR is 4. MPL and MSLR have the same sensitivity (79.1%) and specificity (75.5%). The AUC value of MPL vs. MSLR was 0.802 vs. 0.807. The MPL ≥ 2 and MSLR ≥ 4 revealed similar predictions for survival within 30 days (p < 0.05). Conclusion: MPL and MSLR scores are potential predictors of mortality in COVID-19 patients within 30 days in a resource-limited country.
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(This article belongs to the Special Issue Hot Topics in Internal Medicine: Moving Forward from the Pandemic Era)
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Open AccessArticle
Shift of N-MYC Oncogene Expression in AML Patients Carrying the FLT3-ITD Mutation
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, , , , , , and
Pathophysiology 2023, 30(3), 296-313; https://doi.org/10.3390/pathophysiology30030024 - 01 Aug 2023
Abstract
Mutations in the FLT3 gene not only lead to abnormalities in its structure and function, but also affect the expression of other genes involved in leukemogenesis. This study evaluated the expression of genes that are more characteristic of neuroblastoma but less studied in
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Mutations in the FLT3 gene not only lead to abnormalities in its structure and function, but also affect the expression of other genes involved in leukemogenesis. This study evaluated the expression of genes that are more characteristic of neuroblastoma but less studied in leukemia. N-MYC oncogene expression was found to be more than 3-fold higher in primary AML patients carrying the FLT3-ITD mutation compared to carriers of other mutations as well as patients with normal karyotype (p = 0.03946). In contrast to the expression of several genes (C-MYC, SPT16, AURKA, AURKB) directly correlated to the allelic load of FLT3-ITD, the expression of the N-MYC oncogene is extremely weakly related or independent of it (p = 0.0405). Monitoring of N-MYC expression in some patients with high FLT3-ITD allelic load receiving therapy showed that a decrease in FLT3-ITD allelic load is not always accompanied by a decrease in N-MYC expression. On the contrary, N-MYC expression may remain elevated during the first three months after therapy, which is additional evidence of the emergence of resistance to therapy and progression of AML.
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(This article belongs to the Special Issue MYC in Regeneration and Tumorigenesis)
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Sex Differences in Immune Cell Infiltration and Hematuria in SCI-Induced Hemorrhagic Cystitis
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Pathophysiology 2023, 30(3), 275-295; https://doi.org/10.3390/pathophysiology30030023 - 11 Jul 2023
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Rats manifest a condition called hemorrhagic cystitis after spinal cord injury (SCI). The mechanism of this condition is unknown, but it is more severe in male rats than in female rats. We assessed the role of sex regarding hemorrhagic cystitis and pathological chronic
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Rats manifest a condition called hemorrhagic cystitis after spinal cord injury (SCI). The mechanism of this condition is unknown, but it is more severe in male rats than in female rats. We assessed the role of sex regarding hemorrhagic cystitis and pathological chronic changes in the bladder. We analyzed the urine of male and female Sprague-Dawley and Fischer 344 rats after experimental spinal cord contusion, including unstained microscopic inspections of the urine, differential white blood cell counts colored by the Wright stain, and total leukocyte counts using fluorescent nuclear stains. We examined bladder histological changes in acute and chronic phases of SCI, using principal component analysis (PCA) and clustered heatmaps of Pearson correlation coefficients to interpret how measured variables correlated with each other. Male rats showed a distinct pattern of macroscopic hematuria after spinal cord injury. They had higher numbers of red blood cells with significantly more leukocytes and neutrophils than female rats, particularly hypersegmented neutrophils. The histological examination of the bladders revealed a distinct line of apoptotic umbrella cells and disrupted bladder vessels early after SCI and progressive pathological changes in multiple bladder layers in the chronic phase. Multivariate analyses indicated immune cell infiltration in the bladder, especially hypersegmented neutrophils, that correlated with red blood cell counts in male rats. Our study highlights a hitherto unreported sex difference of hematuria and pathological changes in males and females’ bladders after SCI, suggesting an important role of immune cell infiltration, especially neutrophils, in SCI-induced hemorrhagic cystitis.
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Open AccessArticle
Elevated Levels of Serum Biomarkers Associated with Damage to the CNS Neurons and Endothelial Cells Are Linked with Changes in Brain Connectivity in Breast Cancer Patients with Vestibulo-Atactic Syndrome
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Pathophysiology 2023, 30(2), 260-274; https://doi.org/10.3390/pathophysiology30020022 - 15 Jun 2023
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Vestibulo-atactic syndrome (VAS), which represents a combination of motor and vestibular disorders, can be manifested as a clinical complication of breast cancer treatment and has a significant impact on patients’ quality of life. The identification of novel potential biomarkers that might help to
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Vestibulo-atactic syndrome (VAS), which represents a combination of motor and vestibular disorders, can be manifested as a clinical complication of breast cancer treatment and has a significant impact on patients’ quality of life. The identification of novel potential biomarkers that might help to predict the onset of VAS and its progression could improve the management of this group of patients. In the current study, the levels of intercellular cell adhesion molecule 1 (ICAM-1), platelet/endothelial cell adhesion molecule 1 (PECAM-1), NSE (neuron-specific enolase), and the antibodies recognizing NR-2 subunit of NMDA receptor (NR-2-ab) were measured in the blood serum of BC survivor patients with vestibulo-atactic syndrome (VAS) and associated with the brain connectome data obtained via functional magnetic resonance imaging (fMRI) studies. A total of 21 patients were registered in this open, single-center trial and compared to age-matched healthy female volunteers (control group) (n = 17). BC patients with VAS demonstrated higher serum levels of ICAM-1, PECAM-1, and NSE and a lower value of NR-2-ab, with values of 654.7 ± 184.8, 115.3 ± 37.03, 49.9 ± 103.9, and 0.5 ± 0.3 pg/mL, respectively, as compared to the healthy volunteers, with 230.2 ± 44.8, 62.8 ± 15.6, 15.5 ± 6.4, and 1.4 ± 0.7 pg/mL. According to the fMRI data (employing seed-to-voxel and ROI-to-ROI methods), in BC patients with VAS, significant changes were detected in the functional connectivity in the areas involved in the regulation of postural-tonic reflexes, the coordination of movements, and the regulation of balance. In conclusion, the detected elevated levels of serum biomarkers may reveal damage to the CNS neurons and endothelial cells that is, in turn, associated with the change in the brain connectivity in this group of patients.
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Open AccessArticle
Myocardial Glutathione Synthase and TRXIP Expression Are Significantly Elevated in Hypertension and Diabetes: Influence of Stress on Antioxidant Pathways
Pathophysiology 2023, 30(2), 248-259; https://doi.org/10.3390/pathophysiology30020021 - 12 Jun 2023
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Antioxidant protection is one of the key reactions of cardiomyocytes (CMCs) in response to myocardial damage of various origins. The thioredoxin interacting protein (TXNIP) is an inhibitor of thioredoxin (TXN). Over the recent few years, TXNIP has received significant attention due to its
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Antioxidant protection is one of the key reactions of cardiomyocytes (CMCs) in response to myocardial damage of various origins. The thioredoxin interacting protein (TXNIP) is an inhibitor of thioredoxin (TXN). Over the recent few years, TXNIP has received significant attention due to its wide range of functions in energy metabolism. In the present work, we studied the features of the redox-thiol systems, in particular, the amount of TXNIP and glutathione synthetase (GS) as markers of oxidative damage to CMCs and antioxidant protection, respectively. This study was carried out on 38-week-old Wistar-Kyoto rats with insulin-dependent diabetes mellitus (DM) induced by streptozotocin, on 38- and 57-week-old hypertensive SHR rats and on a model of combined hypertension and DM (38-week-old SHR rats with DM). It was found that the amount of TXNIP increased in 57-week-old SHR rats, in diabetic rats and in SHR rats with DM. In 38-week-old SHR rats, the expression of TXNIP significantly decreased. The expression of GS was significantly higher compared with the controls in 57-week-old SHR rats, in DM rats and in the case of the combination of hypertension and DM. The obtained data show that myocardial damage caused by DM and hypertension are accompanied by the activation of oxidative stress and antioxidant protection.
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Open AccessSystematic Review
Risk Factors and Clinical Characteristics of Acute Kidney Injury in Patients with COVID-19: A Systematic Review and Meta-Analysis
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Pathophysiology 2023, 30(2), 233-247; https://doi.org/10.3390/pathophysiology30020020 - 15 May 2023
Cited by 1
Abstract
Acute kidney injury (AKI) is associated with a worse prognosis in coronavirus disease 2019 (COVID-19) patients. Identification of AKI, particularly in COVID-19 patients, is important for improving patients’ management. The study aims to assess risk factors and comorbidities of AKI in COVID-19 patients.
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Acute kidney injury (AKI) is associated with a worse prognosis in coronavirus disease 2019 (COVID-19) patients. Identification of AKI, particularly in COVID-19 patients, is important for improving patients’ management. The study aims to assess risk factors and comorbidities of AKI in COVID-19 patients. We systematically searched PubMed and DOAJ databases for relevant studies involving confirmed COVID-19 patients with data on risk factors and comorbidities of AKI. The risk factors and comorbidities were compared between AKI and non-AKI patients. A total of 30 studies involving 22385 confirmed COVID-19 patients were included. Male (OR: 1.74 (1.47, 2.05)), diabetes (OR: 1.65 (1.54, 1.76)), hypertension (OR: 1.82 (1.12, 2.95)), ischemic cardiac disease (OR: 1.70 (1.48, 1.95)), heart failure (OR: 2.29 (2.01, 2.59)), chronic kidney disease (CKD) (OR: 3.24 (2.20, 4.79)), chronic obstructive pulmonary disease (COPD) (OR: 1.86 (1.35, 2.57)), peripheral vascular disease (OR: 2.34 (1.20, 4.56)), and history of nonsteroidal anti-inflammatory drugs (NSAID) (OR: 1.59 (1.29, 1.98)) were independent risk factors associated with COVID-19 patients with AKI. Patients with AKI presented with proteinuria (OR: 3.31 (2.59, 4.23)), hematuria (OR: 3.25 (2.59, 4.08)), and invasive mechanical ventilation (OR: 13.88 (8.23, 23.40)). For COVID-19 patients, male gender, diabetes, hypertension, ischemic cardiac disease, heart failure, CKD, COPD, peripheral vascular disease, and history of use of NSAIDs are associated with a higher risk of AKI.
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(This article belongs to the Special Issue Hot Topics in Internal Medicine: Moving Forward from the Pandemic Era)
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Trends in Drug Tests among Children: A 22-Year Retrospective Analysis
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Pathophysiology 2023, 30(2), 219-232; https://doi.org/10.3390/pathophysiology30020019 - 12 May 2023
Abstract
There are several pathophysiological outcomes associated with substance abuse including metabolic disbalance, neurodegeneration, and disordered redox. Drug use in pregnant women is a topic of great concern due to developmental harm which may occur during gestation and the associated complications in the neonate
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There are several pathophysiological outcomes associated with substance abuse including metabolic disbalance, neurodegeneration, and disordered redox. Drug use in pregnant women is a topic of great concern due to developmental harm which may occur during gestation and the associated complications in the neonate after delivery. We sought to determine what the trajectory of drug use is like in children aged 0–4 years and mothers of neonates. Urine drug screen (UDS) results were obtained of our target demographic during 1998–2011 and 2012–2019 from LSU Health Sciences Center in Shreveport (LSUHSC-S). Statistical analysis was performed using R software. We observed an increase in cannabinoid-positive UDS results in both Caucasian (CC) and African American (AA) groups between 1998–2011 and 2012–2019 periods. Cocaine-positive UDS results decreased in both cohorts. CC children had higher UDS positive results for opiates, benzodiazepines, and amphetamines, while AA children had a higher percentage for illicit drugs such as cannabinoids and cocaine. Neonate’s mothers had similar UDS trends to that in children during 2012–2019. Overall, while percentage of positive UDS results for both AA and CC 0–4 year old children started to decline for opiate, benzodiazepine, and cocaine during 2012–2019, cannabinoid- and amphetamine (CC)-positive UDS steadily increased. These results suggest a shift in the type of drug use by mothers from opiates, benzodiazepines, and cocaine to cannabinoids and/or amphetamines. We also observed that 18-year-old females who tested positive for opiates, benzodiazepine, or cocaine had higher than average chances of testing positive for cannabinoids later in life.
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(This article belongs to the Special Issue Effects of Drug Exposure on the Health of Women and Children)
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Cerebral Circulation and Brain Temperature during an Ultra-Short Session of Dry Immersion in Young Subjects
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Pathophysiology 2023, 30(2), 209-218; https://doi.org/10.3390/pathophysiology30020018 - 10 May 2023
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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
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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.
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Open AccessArticle
Retrospective Analysis of Real-World Data for the Treatment of Obstructive Sleep Apnea with Slow Maxillary Expansion Using a Unique Expansion Dental Appliance (DNA)
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Pathophysiology 2023, 30(2), 199-208; https://doi.org/10.3390/pathophysiology30020017 - 09 May 2023
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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
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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.
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Open AccessArticle
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
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Pathophysiology 2023, 30(2), 186-198; https://doi.org/10.3390/pathophysiology30020016 - 04 May 2023
Abstract
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
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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.
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(This article belongs to the Special Issue Hot Topics in Internal Medicine: Moving Forward from the Pandemic Era)
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Advantages of Multiposition Scanning in Echocardiographic Assessment of the Severity of Discordant Aortic Stenosis
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Pathophysiology 2023, 30(2), 174-185; https://doi.org/10.3390/pathophysiology30020015 - 26 Apr 2023
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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
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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.
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Open AccessReview
Challenges in the Vaccination of the Elderly and Strategies for Improvement
Pathophysiology 2023, 30(2), 155-173; https://doi.org/10.3390/pathophysiology30020014 - 22 Apr 2023
Abstract
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
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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.
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(This article belongs to the Special Issue Hot Topics in Internal Medicine: Moving Forward from the Pandemic Era)
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Methamphetamine and Designer Stimulants Modulate Tonic Human Cerebrovascular Smooth Muscle Contractility: Relevance to Drug-Induced Neurovascular Stress
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Pathophysiology 2023, 30(2), 144-154; https://doi.org/10.3390/pathophysiology30020013 - 18 Apr 2023
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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
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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.
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Open AccessBrief Report
Random Blood Glucose, but Not HbA1c, Was Associated with Mortality in COVID-19 Patients with Type 2 Diabetes Mellitus—A Retrospective Study
Pathophysiology 2023, 30(2), 136-143; https://doi.org/10.3390/pathophysiology30020012 - 06 Apr 2023
Abstract
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
[...] Read more.
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.
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(This article belongs to the Special Issue Hot Topics in Internal Medicine: Moving Forward from the Pandemic Era)
Open AccessFeature PaperArticle
Hormone Replacement Therapy Does Not Eliminate Risk Factors for Joint Complications following Total Joint Arthroplasty: A Matched Cohort Study
by
, , , , and
Pathophysiology 2023, 30(2), 123-135; https://doi.org/10.3390/pathophysiology30020011 - 04 Apr 2023
Cited by 1
Abstract
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
[...] Read more.
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.
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(This article belongs to the Special Issue Pathophysiology behind Orthopaedics Disorders: From Mechanisms to Novel Therapeutic and Surgical Approaches)
Open AccessArticle
Neurotrophin-3 (NT-3) as a Potential Biomarker of the Peripheral Nervous System Damage Following Breast Cancer Treatment
by
, , , , , , , , , , , , and
Pathophysiology 2023, 30(2), 110-122; https://doi.org/10.3390/pathophysiology30020010 - 03 Apr 2023
Abstract
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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
[...] Read more.
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.
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Open AccessArticle
The Expressions of NF−κB, COX−2, Sp1, and c−Jun in Pancreatic Ductal Adenocarcinoma and Their Associations with Patient Survival
by
, , , , , , , , , , , , , , , and
Pathophysiology 2023, 30(2), 92-109; https://doi.org/10.3390/pathophysiology30020009 - 25 Mar 2023
Abstract
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Show Figures
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
[...] Read more.
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.
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