Pathophysiology最新文献

{"title":"In Vitro Chronic Hyperinsulinemia Induces Remodelling of Vascular Smooth Muscle Cells from Young Men and Women in a Sex Hormone Independent Manner.","authors":"Ashley Jazzar, Danielle Jacques, Amira Abou-Aichi, Ghassan Bkaily","doi":"10.3390/pathophysiology32010012","DOIUrl":"10.3390/pathophysiology32010012","url":null,"abstract":"<p><p>Elevated circulating insulin levels between 80 and 100 µU/mL characterize hyperinsulinemia, which often leads to metabolic disorders such as obesity, insulin resistance, and type 2 diabetes (T2D). Elevated circulating insulin levels can directly affect vascular function and contribute to the pathophysiology of the cardiovascular system, including secondary arterial hypertension (SAH) and atherosclerosis. It is well known that hyperinsulinemia induced remodeling of the heart. However, there is no information on whether intrinsic differences exist between human vascular smooth muscle cells (VSMCs) and if in vitro mimicking hyperinsulinemia induces human VSMCs morphological and intracellular homeostasis remodeling in a sex- and sex hormones-dependent manner. Our in vitro cultured human VSMCs, coupled with quantitative 3D confocal imaging results, show that intrinsic differences exist between VSMCs from young men and women. Chronic hyperinsulinemia (80 µU/mL, 48 h treatment) increases cell and nuclear volumes associated with increased intracellular calcium (Ca²⁺) and ROS and decreased glutathione. In the absence of hyperinsulinemia, pretreatment with testosterone in VSMCs from men and oestradiol in VSMCs from women had no effect. Both sex hormones partially but not completely prevented hyperinsulinemia-induced remodeling of VSMCs from young men and women. The increase in VSMC volume may increase the thickness of the tunica media, leading to a decrease in the lumen of the blood vessel, which promotes the development of SAH and atherosclerosis in a sex-dependent manner.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"32 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MRI Voxel Morphometry Shows Brain Volume Changes in Breast Cancer Survivors: Implications for Treatment.","authors":"Alexandra Nikolaeva, Maria Pospelova, Varvara Krasnikova, Albina Makhanova, Samvel Tonyan, Aleksandr Efimtsev, Anatoliy Levchuk, Gennadiy Trufanov, Mark Voynov, Matvey Sklyarenko, Konstantin Samochernykh, Tatyana Alekseeva, Stephanie E Combs, Maxim Shevtsov","doi":"10.3390/pathophysiology32010011","DOIUrl":"10.3390/pathophysiology32010011","url":null,"abstract":"<p><p>Chemotherapy-related cognitive impairment termed «chemobrain» is a prevalent complication in breast cancer survivors that requires early detection for the development of novel therapeutic approaches. Magnetic resonance voxel morphometry (MR morphometry), due to its high sensitivity, might be employed for the evaluation of the early changes in the volumes of brain structures in order to explore the «chemobrain» condition.</p><p><strong>Methods: </strong>The open, prospective, single-center study enrolled 86 breast cancer survivors (43.3 ± 4.4 years) and age-matched 28 healthy female volunteers (44.0 ± 5.68). Conventional MR sequences (T1- and T2-weighted, TIRM, DWI, MPRAGE) were obtained in three mutually perpendicular planes to exclude an organ pathology of the brain. Additionally, the MPRAGE sequence was performed for subsequent MR morphometry of the volume of brain structures using the open VolBrain program. The evaluation was performed at two follow-up visits 6 months and 3 years after the completion of BC treatment.</p><p><strong>Results: </strong>According to the MR morphometry, breast cancer survivors presented with significantly decreased volumes of brain structures (including total brain volume, cerebellum volume, subcortical gray matter, etc.) as compared to healthy volunteers. Evaluation over the follow-up period of 3 years did not show the restoration of brain volume structures.</p><p><strong>Conclusions: </strong>The data obtained employing MR morphometry revealed significant reductions (that were not detected on the conventional MR sequences) in both gray and white matter in breast cancer survivors following chemotherapy. This comprehensive analysis indicated the utility of MR morphometry in detecting subtle yet statistically significant neuroanatomical changes associated with cognitive and motor impairments in patients, which can in turn provide valuable insights into the extent of structural brain alterations, helping to identify specific regions that are most affected by treatment.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"32 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered Production and Cellular Levels of Hydrogen Sulfide (H₂S) in Placental Trophoblasts from Pregnancies Affected by Pre-Eclampsia.","authors":"Xiaodan Chu, Jie Xu, Xinggui Shen, Wenji Sheng, Jingxia Sun, Yang Gu, David F Lewis, Danielle Cooper, Dani Zoorob, Yuping Wang","doi":"10.3390/pathophysiology32010010","DOIUrl":"10.3390/pathophysiology32010010","url":null,"abstract":"<p><strong>Background/objectives: </strong>Hydrogen sulfide (H₂S) is a vasorelaxant gas and exerts anti-oxidative, anti-inflammatory, and cytoprotective effects. H₂S has been implicated in regulating placental vaso-activity and angiogenesis. It is believed that abnormal trophoblast production of vasodilators and angiogenic factors contributes to pre-eclampsia development. However, little is known about whether aberrant H₂S production is present in placental trophoblasts from pre-eclamptic pregnancies.</p><p><strong>Methods: </strong>Trophoblasts were isolated from normal and pre-eclamptic placentas. After incubation, cell production of H₂S in the culture medium and the cellular levels of H₂S were analyzed by reversed phase high-performance liquid chromatography (RP-HPLC). Expression levels of the three key H₂S converting enzymes, cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST), were determined by immunohistochemistry. The protein expression of CBS and CSE was assessed by Western blot analysis.</p><p><strong>Results: </strong>(1) Trophoblast production and cellular levels of H₂S were significantly reduced in cells from pre-eclamptic vs. normal placentas; (2) free H₂S production was increased in a time-dependent manner in cultured trophoblasts from normal, but not from pre-eclamptic, placentas; and (3) strong CBS and CSE expression was seen in trophoblasts from normal, as opposed to pre-eclamptic, placentas. Reduced CBS and CSE expression in trophoblasts from pre-eclamptic vs. normal placentas were confirmed by Western blot analysis; and (4) 3-MST expression was undetachable in both normal and pre-eclamptic placentas, but 3-MST expression was strongly expressed in the first and second trimester placentas.</p><p><strong>Conclusions: </strong>These data provide plausible evidence that downregulation of CBS and CSE, but not 3-MST, expression may be responsible for reduced free H₂S production and decreased cellular H₂S levels in pre-eclamptic placentas. Our data provide further evidence that expression of 3-MST in placental trophoblasts is likely gestational age (developmental)-dependent.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"32 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial Dysfunction in Diabetes: Shedding Light on a Widespread Oversight.","authors":"Franklyn Nonso Iheagwam, Amarachi Joy Joseph, Eniola Deborah Adedoyin, Olawumi Toyin Iheagwam, Samuel Akpoyowvare Ejoh","doi":"10.3390/pathophysiology32010009","DOIUrl":"https://doi.org/10.3390/pathophysiology32010009","url":null,"abstract":"<p><p>Diabetes mellitus represents a complicated metabolic condition marked by ongoing hyperglycemia arising from impaired insulin secretion, inadequate insulin action, or a combination of both. Mitochondrial dysfunction has emerged as a significant contributor to the aetiology of diabetes, affecting various metabolic processes critical for glucose homeostasis. This review aims to elucidate the complex link between mitochondrial dysfunction and diabetes, covering the spectrum of diabetes types, the role of mitochondria in insulin resistance, highlighting pathophysiological mechanisms, mitochondrial DNA damage, and altered mitochondrial biogenesis and dynamics. Additionally, it discusses the clinical implications and complications of mitochondrial dysfunction in diabetes and its complications, diagnostic approaches for assessing mitochondrial function in diabetics, therapeutic strategies, future directions, and research opportunities.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"32 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low Serum Methylglyoxal Levels Correlate with Psoriasis Severity and Inflammatory Response Indices.","authors":"Aleksandra Damasiewicz-Bodzek, Agnieszka Nowak, Maciej Maciejczyk, Sławomir Waligóra, Brygida Przywara-Chowaniec","doi":"10.3390/pathophysiology32010008","DOIUrl":"10.3390/pathophysiology32010008","url":null,"abstract":"<p><p>Psoriasis is a multifactorial inflammatory disease. Methylglyoxal (MG) is a highly reactive dicarbonyl compound responsible for dicarbonyl stress in some inflammatory conditions, and it may play a role in the etiopathogenesis of psoriasis. <b>Methods:</b> A total of 50 patients with psoriasis and 35 healthy individuals participated in this study. The following indices were assessed in patients: Body Surface Area (BSA), Psoriasis Area and Severity Index (PASI), and Dermatology Life Quality Index (DLQI). MG concentration was evaluated in blood samples. The following inflammatory response indices were calculated: Systemic Inflammation Response Index (SIRI), Systemic Immuno-inflammation Index (SII), and Aggregate Index of Systemic Inflammation (AISI). <b>Results:</b> An analysis of the obtained data showed a statistically significant decrease in the mean serum MG concentration in patients with psoriasis when compared to the healthy individuals (1.19 ± 0.4 μg/mL vs. 1.75 ± 0.6 μg/mL; <i>p</i> = 0.000002). In the patients, MG concentration correlated negatively with psoriasis disease severity indicators (BSA and PASI), C-reactive protein (CRP) concentration, and inflammatory response indicators (SII and AISI). <b>Conclusions:</b> The decreased concentration of MG may be attributed to an increased accumulation of its derivatives (advanced glycation end-products) in the inflamed skin and/or scavenging by polyamines.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"32 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overweight-Related Hypertension in Middle-Aged Men Is Linked to Elevated Leptin, TNF-α, IL-6, Cholesterol, and Reduced Testosterone.","authors":"Shalan Alaamri, Abdulhalim S Serafi, Zahir Hussain, Shouq K Bafail, Mohammed A Bafail, Lusine Demirkhanyan, Christopher S Gondi, Sumera Sohail","doi":"10.3390/pathophysiology32010007","DOIUrl":"10.3390/pathophysiology32010007","url":null,"abstract":"<p><strong>Background/objectives: </strong>One of the major causes of hypertension (HT) is the transition of normal weight (NW) status to overweight (OW) status and obesity in a population, which leads to cardiovascular disease (CVD) and other disorders. A variety of factors/variables are involved in the development of HT and OW-related hypertension (OHT). However, we planned to investigate the pathophysiological role of serum leptin (Lep), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), total cholesterol (TC) and serum testosterone (ST) in OHT in middle-aged men.</p><p><strong>Methods: </strong>We consulted three groups of middle-aged men (age: 51-60 years)-an HT group (n: 97, high normal weight (HNW), body mass index (BMI): 23-24.9 kg/m²); an OHT group (n: 97, high overweight (HOW), BMI: 28-29.9 kg/m²) and a normal control group (NC, n: 98, HNW)-to investigate the variations in and correlations of Lep, IL-6, TNF-α, ST, TC and other variables.</p><p><strong>Results: </strong>Significant variations were obtained for the comparisons of TNF-α, Lep, ST and TC for the patient groups. OHT vs. NC showed a significant difference for ST. OHT vs. NC and OHT vs. HT had significant variations for IL-6. Significant changes were obtained for the serum levels of TNF-α, Lep, IL-6, ST and TC among groups. Significant and positive linear associations were obtained for TNF-α, Lep, TC and IL-6. Significant and negative linear associations were found for ST plotted against Lep, TNF-α and IL-6.</p><p><strong>Conclusions: </strong>The current report provides pathophysiological evidence of the interactive role of serum Lep, TNF-α, ST, TC and IL-6 in middle-aged men with HT and OHT. We suggest that the changes we noted in the present study would be helpful for further BMI-based studies in various subcategories of NW, OW and obese subjects with/without HT.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"32 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Vitamin D Receptor BsmI Polymorphism and Low Bone Mineral Density in Postmenopausal Women in the MENA Region.","authors":"Tara Al-Barazenji, Asma Allouch, Nedhal Al Husaini, Sondos Yousef, Wisam Nabeel Ibrahim, Amal Al-Haidose, Hatem Zayed, Atiyeh M Abdallah","doi":"10.3390/pathophysiology32010006","DOIUrl":"10.3390/pathophysiology32010006","url":null,"abstract":"<p><strong>Background/objectives: </strong>Low bone mineral density increases the risk of bone fractures, and this condition is especially common in postmenopausal women. Genetic factors significantly influence bone mineral density. This meta-analysis examined the relationship between vitamin D receptor (VDR) gene polymorphisms (BsmI, ApaI, and TaqI) and bone mineral density in postmenopausal women in the Middle East and North Africa (MENA) region.</p><p><strong>Methods: </strong>The PubMed, Embase, Scopus, and Web of Science databases were searched from inception to March 2024 for case-control studies on VDR BsmI, ApaI, and TaqI polymorphisms and their relationship with low bone density. Associations with low bone mineral density were tested with respect to different genetic models (dominant, recessive, allelic) using RevMan v5.3.</p><p><strong>Results: </strong>The meta-analysis included seven studies for BsmI, six for ApaI, and seven for TaqI, representing 704/689 cases/controls for BsmI, 914/711 for ApaI, and 974/895 for TaqI. No significant association was found between VDR polymorphisms and low bone mineral density in postmenopausal women, except in the dominant model (CC + CG vs. GG) for the BsmI variant (OR = 1.27, 95% CI: 1.01-1.59, <i>p</i> = 0.04).</p><p><strong>Conclusions: </strong>We found a modest association between the BsmI polymorphism and increased risk of low bone mineral density (BMD) in postmenopausal women from the MENA region, suggesting its potential as a biomarker. No associations were observed for ApaI or TaqI. These findings highlight the complex genetic-environmental interactions influencing BMD.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"32 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolocumab Reduces Oxidative Stress and Lipid Peroxidation in Obese Zucker Rats.","authors":"Martina Cebova, Radoslava Bulkova, Olga Pechanova","doi":"10.3390/pathophysiology32010005","DOIUrl":"10.3390/pathophysiology32010005","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Evolocumab inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9) binding to low-density lipoprotein (LDL) receptors, thus allowing more LDL receptors to remove LDL cholesterol from the blood. We aimed to determine the effects of evolocumab on the plasma lipid profile, reactive oxygen species (ROS), and nitric oxide (NO) generation in the heart of adult male obese Zucker rats. <b>Methods</b>: The rats were divided into lean and obese controls and obese rats treated with evolocumab subcutaneously at a dose of 10 mg/kg every two weeks. After 6 weeks, the lipid profile was determined in the plasma, and NO synthase (NOS) activity, thiobarbituric acid reactive substance (TBARS), conjugated diene (CD) concentration, and protein expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, nuclear factor kappaB (NF-κB), endothelial NOS (eNOS), and phosphorylated eNOS (peNOS) were measured in the heart. <b>Results</b>: Evolocumab treatment did not reduce body weight, relative heart weight, or systolic blood pressure in obese Zucker rats. Evolocumab treatment, however, reduced plasma LDL levels, TBARS, and CD concentrations along with decreasing expression of NADPH oxidase and NF-kappaB proteins in the heart. On the other hand, evolocumab had no effect on NOS activity or eNOS and peNOS protein expression. <b>Conclusions</b>: Besides its lipid-lowering effect, evolocumab may exert antioxidant properties and protect cardiomyocytes from lipid peroxidation while not affecting NO production.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"32 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Yamarthi et al. <i>Sepia pharaonis</i> Ink Mitigates Dehydroepiandrosterone-Induced Insulin Resistance in Mouse Model of Polycystic Ovarian Syndrome. <i>Pathophysiology</i> 2024, <i>31</i>, 408-419.","authors":"Prathyusha Yamarthi, Rama Satyasri Kotipalli, Samatasai Patnaik, Kv Veena, Muralidharan Kathirvel, Rajkumar Vutukuri, Manjula Bhanoori","doi":"10.3390/pathophysiology32010004","DOIUrl":"10.3390/pathophysiology32010004","url":null,"abstract":"<p><p><b>Error in Figure</b> [...].</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"32 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cause of Death Analysis in a 9½-Year-Old with COVID-19 and Dravet Syndrome.","authors":"Vedashree R Meher, Richard J Huntsman, Francis H Y Green, Jill C Wooff, Roland N Auer","doi":"10.3390/pathophysiology32010003","DOIUrl":"10.3390/pathophysiology32010003","url":null,"abstract":"<p><p><b>Background</b>: Cause of death analysis is fundamental to forensic pathology. We present the case of a 9½-year-old girl with a genetically confirmed diagnosis of Dravet syndrome who died in her sleep with no evidence of motor seizure. She also had a lifelong history of recurrent pneumonias and, along with her family, had tested positive for COVID-19 10 days before death. <b>Methods</b>: Long-term clinical history of Dravet Syndrome and respiratory infections were obtained from patient's medical charts and radiology reports. A Rapid-Antigen Test was used to confirm SARS-CoV2 infection days prior to death. At autopsy, brain, heart and lung tissues were obtained. Paraffin-embedded tissues were double-stained with H&E, and immunohistochemically stained using various antibodies. <b>Results</b>: Autopsy revealed evidence of previous seizure activity in the brain and cellular interstitial thickening in the lung. The brain showed edema and fibrillary gliosis without neuronal loss in neocortex and hippocampus. The lung showed inflammatory interstitial thickening with histiocytes, megakaryocytes, B-lymphocytes, and T-lymphocytes, including helper/suppressor cells and cytotoxic T-lymphocytes. Diffuse alveolar damage was observed as alveolar flooding with proteinaceous fluid. <b>Conclusions</b>: The cause of death may be attributed to Sudden Unexpected Death in Epilepsy (SUDEP) in Dravet syndrome, sudden death in viral pneumonia, or some combination of the two. When two independent risk factors for sudden unexpected death are identified due to co-pathology, it may not be possible to determine a single cause of death beyond a reasonable doubt.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"32 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023725","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}