Next Issue
Volume 13, September
Previous Issue
Volume 13, July
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
3.7
3.0
Journals
Diseases
Volume 13
Issue 8
share announcement

Diseases, Volume 13, Issue 8 (August 2025) – 45 articles

Cover Story (view full-size image): Pancreatic stone protein (PSP) is gaining recognition as a versatile biomarker with applications in areas ranging from critical care to oncology. Rising earlier than C-reactive protein or procalcitonin and less affected by non-infectious inflammation, PSP offers a valuable tool for timely diagnosis and risk stratification. This review integrates the current evidence on PSP in sepsis, intra-abdominal infections, burns, COVID-19, metabolic disorders, and cancer, detailing its pathophysiology, comparative performance, and prognostic power. By bridging molecular insights with clinical data, the article underscores PSP’s potential to enhance early intervention and improve patient outcomes across diverse healthcare settings. View this paper
  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Reader to open them.
Order results
Result details
Section
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
15 pages, 561 KiB  
Review
Considerations for Augmenting Aripiprazole Long-Acting Injectables with Other Antipsychotics: A Mini-Review
by Jonathan Shaw, Ethan Kim, Emily Ton, Charles Lai, Peter Bota and Tina Allee
Diseases 2025, 13(8), 274; https://doi.org/10.3390/diseases13080274 - 21 Aug 2025
Abstract
Aripiprazole is a third-generation antipsychotic, approved in 2002, notable for its partial agonism of the Dopamine D2 receptor and lower risk of metabolic and extrapyramidal adverse effects. It is available in a long-acting injectable formulation, which is very useful for maintaining medication compliance, [...] Read more.
Aripiprazole is a third-generation antipsychotic, approved in 2002, notable for its partial agonism of the Dopamine D2 receptor and lower risk of metabolic and extrapyramidal adverse effects. It is available in a long-acting injectable formulation, which is very useful for maintaining medication compliance, which is crucial for preventing recurrent psychotic episodes in patients. Additionally, the aripiprazole long-acting injectable is frequently combined with other antipsychotic medications in acute settings to manage refractory symptoms. However, there is limited literature regarding the psychopharmacology, efficacy, and adverse effect profiles of augmenting aripiprazole long-acting injectable with other antipsychotic medications. This narrative review intends to synthesize the existing literature on aripiprazole, its comparative affinity to the dopamine D2 receptor versus other antipsychotics, and the efficacy and side effect profiles of combining aripiprazole with other antipsychotics in the context of acute inpatient treatment for psychosis. Current literature on Ki values indicates that fluphenazine, pimozide, thiothixene, trifluoperazine, and perphenazine bind more strongly to dopamine D2 receptors than aripiprazole. However, there is a knowledge gap regarding antipsychotic polypharmacy with aripiprazole and these first generation antipsychotics, limiting the discussion of these drug combinations to theory. Additionally, the muscarinic effects of aripiprazole suggest the possibility of augmentation with clozapine or xanomeline-trospium, albeit the peer-reviewed literature on this was also limited. Overall, it is difficult to draw conclusions regarding best clinical practices for these scenarios, as the existing literature is contradictory. Nonetheless, the application of the dopamine and muscarinic pathway theories for schizophrenia opens venues for future research and consideration. Full article
(This article belongs to the Section Neuro-psychiatric Disorders)
►▼ Show Figures

Figure 1

15 pages, 950 KiB  
Review
Endobiliary Radiofrequency Ablation for Hepato-Biliary Diseases: A Narrative Review
by Tawfik Khoury, Wisam Sbeit, Andrea Lisotti and Bertrand Napoléon
Diseases 2025, 13(8), 273; https://doi.org/10.3390/diseases13080273 - 21 Aug 2025
Abstract
Background/Objectives: Malignant biliary diseases still represent a therapeutic challenge given its poor prognosis, and limited response to the available curative treatments. Recently, endobiliary radiofrequency ablation (RFA) has been increasingly reported as an adjunct therapeutic option for biliary diseases, especially malignant biliary obstruction (MBO), [...] Read more.
Background/Objectives: Malignant biliary diseases still represent a therapeutic challenge given its poor prognosis, and limited response to the available curative treatments. Recently, endobiliary radiofrequency ablation (RFA) has been increasingly reported as an adjunct therapeutic option for biliary diseases, especially malignant biliary obstruction (MBO), due to potentially improving survival and stent patency. Methods: Herein, we provide a comprehensive review article discussing the indication, procedural details, safety, and comparative efficacy of endobiliary RFA to aid in providing an in-depth understanding of the clinical indications and future implications of this specific option. Results: Overall, endobiliary RFA is technically feasible, being associated with a high safety profile, significantly improving biliary stent patency, and having a potential benefit in extending the survival of patients with MBO who were treated with endobiliary RFA combined with biliary stenting vs. stenting alone. Moreover, it has a promising role in the treatment of intraductal extension of ampullary tumors. Conclusions: Endobiliary RFA had a beneficial therapeutic effect in biliary strictures, with potential impact on patients outcome and survival. Full article
►▼ Show Figures

Figure 1

13 pages, 497 KiB  
Article
Dietary Fiber Intake Was Inversely Associated with All-Cause Mortality but Not with Cancer and Cardiovascular Disease Mortalities in the US
by Zoha Akbar, Sundus Fituri, Zumin Shi and Vijay Ganji
Diseases 2025, 13(8), 272; https://doi.org/10.3390/diseases13080272 - 21 Aug 2025
Abstract
Background: Evidence linking dietary fiber intake with cancer risk and mortality is equivocal. Objective: We investigated the relationship between dietary fiber intake and all-cause, cancer, and cardiovascular disease (CVD) mortalities in US adults ≥ 20 years. Methods: Data from the National Health and [...] Read more.
Background: Evidence linking dietary fiber intake with cancer risk and mortality is equivocal. Objective: We investigated the relationship between dietary fiber intake and all-cause, cancer, and cardiovascular disease (CVD) mortalities in US adults ≥ 20 years. Methods: Data from the National Health and Nutrition Examination Surveys (NHANES) from 2003 to 2016 were used. Seven two-year cycles were concatenated into one analytic data file, NHANES 2003–2016 (n = 25,868; age ≥ 20 years). Dietary fiber intakes were collected from one 24-h dietary recall. Fiber intakes were categorized into quartiles. Mortality information was obtained from data linkage. To determine mortality, subjects were followed up for 6.4 years. Association between dietary fiber and mortality from all causes, cancer, and CVD was determined with multivariable-adjusted Cox proportional hazards models. Multivariate-adjusted Cox proportional hazard regression was used to generate mortality survival rates. Results: During the follow-up period, out of 2520 deaths, 561 and 511 deaths were from cancer and CVD, respectively. Dietary fiber intake was inversely associated with all-cause mortality [RR (95% CI), 0.67 (0.56–0.80); p ≤ 0.001]. No relationship was observed between fiber intake and cancer mortality [RR (95% CI), 0.8 (0.55–1.17); p = 0.51] and CVD mortality [RR (95% CI), 0.84 (0.53–1.33); p = 0.67]. Conclusions: In the US population, dietary fiber intake was associated with decreased all-cause mortality, but not with cancer and CVD mortality. Full article
►▼ Show Figures

Figure 1

27 pages, 2349 KiB  
Review
The Role of Obesity in the Regulation of Immunosuppressive Cell Infiltration and Immunosurveillance in Cancers
by Chunye Zhang, Keyao Zhu, Jiazheng Liu and Ming Yang
Diseases 2025, 13(8), 271; https://doi.org/10.3390/diseases13080271 - 21 Aug 2025
Viewed by 63
Abstract
Cancer is a leading cause of death worldwide, causing about 10 million deaths annually. Obesity contributes to cancer progression by inducing chronic inflammation, immunosuppressive microenvironment, metabolic dysfunction, and therapeutic resistance. Accumulating evidence shows that obesity can advance the infiltration of immunosuppressive cells and [...] Read more.
Cancer is a leading cause of death worldwide, causing about 10 million deaths annually. Obesity contributes to cancer progression by inducing chronic inflammation, immunosuppressive microenvironment, metabolic dysfunction, and therapeutic resistance. Accumulating evidence shows that obesity can advance the infiltration of immunosuppressive cells and ameliorate the function and cytotoxicity of tumor-killing cells such as natural killer cells, natural killer T cells, macrophages, and CD8 T cells in cancer patients, resulting in cancer progression. Understanding the molecular signaling pathways involved in obesity-induced immunosuppression and cancer cell proliferation enables us to screen new biomarkers for cancer early diagnosis and improve anti-tumor therapeutic efficacy in obese patients with cancer. In this review, we first review the molecular mechanisms by which obesity induces the immunosuppressive landscape in the tumor microenvironment and some key obesity-associated factors causing immunotherapeutic suppression and metabolic dysfunction. Then, the application of natural products in the treatment of obesity and obesity-associated cancers is summarized. In addition, we discuss the contradictory functions of obesity in cancer risk and treatment outcome. The potent roles of precision medicine and artificial intelligence in the management of obesity-related cancers are highlighted. Full article
(This article belongs to the Topic Cellular and Molecular Mechanisms of Obesity-Associated Cancer Development and Treatments)
►▼ Show Figures

Figure 1

10 pages, 684 KiB  
Article
Cardiovascular Manifestations and Outcomes in Patients with Scrub Typhus Admitted to a Tertiary Care Center in the Coastal Karnataka Region in India
by Mugula Sudhakar Rao, Jyothi Samanth, Swathi Poojary, Krishnananda Nayak, Shubha Srinivas and Thrupthi Naik
Diseases 2025, 13(8), 270; https://doi.org/10.3390/diseases13080270 - 20 Aug 2025
Viewed by 216
Abstract
Introduction: Scrub typhus is a mite-borne infectious disease caused by “Orientia tsutsugamushi”, a bacterium that was formerly classified under the genus Rickettsia. It is transmitted to humans through the bites of infected chigger mites (larval trombiculid mites). However, clinical data [...] Read more.
Introduction: Scrub typhus is a mite-borne infectious disease caused by “Orientia tsutsugamushi”, a bacterium that was formerly classified under the genus Rickettsia. It is transmitted to humans through the bites of infected chigger mites (larval trombiculid mites). However, clinical data on the cardiac manifestations of scrub typhus and their outcomes remain limited. Methods: This research was retrospectively conducted at a tertiary care hospital in South India. The study included all patients admitted from January 2016 to September 2021 who fulfilled the clinical criteria for a diagnosis of scrub typhus. Data were collected for 426 patients. Patients with previously diagnosed heart disease and mixed infections (leptospirosis, dengue fever, blood culture positivity, and COVID-19 positivity) were excluded. Comprehensive assessments of clinical presentation, electrocardiography (ECG), 2D echocardiography, and outcomes, including all-cause mortality and probable myocarditis, were performed. Multivariate regression analysis was performed to identify independent predictors of all-cause mortality and probable myocarditis. Results: Out of 426 patients, 200 (46.9%) were male and 226 (53.1%) were female. The mean age at presentation was 49.29 ± 14.43 years. A total of 108 (25.4%) patients had diabetes and 82 (19.25%) had hypertension. Sinus tachycardia (29.3%) was the most frequent ECG finding. Echocardiographic evidence of probable myocarditis was observed in 20 (4.7%) patients, while 6 (1.4%) patients had isolated RV dysfunction, 4 (0.9%) had biventricular dysfunction, 7 (1.6%) had significant pulmonary hypertension, and 40 (9.4%) had trivial pericardial effusion. A total of 78 (18.3%) patients had acute respiratory distress syndrome. All-cause mortality was observed in 12 (2.8%) patients. A total of 56 (13.1%) patients developed multiorgan dysfunction syndrome (MODS) during their hospitalization. A total of 78 (18.3%) patients were documented to have acute kidney injury (AKI), and 22 (5.2%) patients underwent hemodialysis. Multivariable binary logistic regression analysis revealed that probable myocarditis and MODS were independent predictors of mortality among patients with scrub typhus, and age, female gender, and LV systolic dysfunction were identified as predictors of overall complications, including mortality, probable myocarditis, congestive heart failure, MODS, AKI, and the need for hemodialysis. Conclusions: Probable myocarditis was the most frequent cardiac manifestation noted in patients with scrub typhus, and in addition to MODS, probable myocarditis was an independent predictor of mortality in this cohort. Thus, it is crucial to maintain clinical vigilance regarding the cardiac status of such patients. Full article
►▼ Show Figures

Figure 1

11 pages, 1177 KiB  
Article
Investigating the Relationships Between COVID-19 Cases, Public Health Interventions, Vaccine Coverage, and Mean Temperature in Ontario and Toronto
by Melinaz Barati Chermahini and Vernon Hoeppner
Diseases 2025, 13(8), 269; https://doi.org/10.3390/diseases13080269 - 19 Aug 2025
Viewed by 132
Abstract
Background/Objectives: We aimed to examine the relationship between COVID-19 cases and Public Health Interventions (PHIs), vaccine coverage, and temperature. We compared our findings with those of other studies that used different methodologies, such as mathematical models. Methods: We developed monthly PHI scores [...] Read more.
Background/Objectives: We aimed to examine the relationship between COVID-19 cases and Public Health Interventions (PHIs), vaccine coverage, and temperature. We compared our findings with those of other studies that used different methodologies, such as mathematical models. Methods: We developed monthly PHI scores using the Oxford COVID-19 Government Response Tracker from May 2020 to May 2021. We calculated PHI scores by summing the highest monthly score of each intervention and expressed the PHI score as a percentage of the maximum. We obtained vaccine coverage and temperature data from January 2021 to September 2023. We calculated Spearman’s rank-order correlation coefficients to examine correlations. Results: The correlation between cases and PHI was positive (ρ = 0.947, p < 0.0001). The correlation between cases and vaccine coverage was approximately zero (ρ = 0.0165, p = 0.957) from January 2021 to January 2022 and was negative from February 2022 to September 2023 (ρ= −0.816, p < 0.0001). The correlation for cases and temperature was negative from January 2021 to January 2022 (ρ = −0.676, p = 0.0112) and was almost zero from February 2022 to September 2023 (ρ = −0.162, p = 0.494). The models showed a negative correlation between PHI and vaccine coverage, and mixed results for temperature. Conclusions: There was a positive correlation between cases and PHI. Prior to reaching the vaccine threshold coverage, there was no correlation for vaccination and a negative correlation for temperature. Post-vaccine threshold, there was a negative correlation for vaccination and no correlation for temperature. Correlation results for PHI and temperature differed from those of the mathematical models. Full article
►▼ Show Figures

Figure 1

10 pages, 222 KiB  
Communication
Prevalence, Symptoms, and Associated Risk Factors for Depressive Symptoms Among Undergraduate Students of Non-Medical Universities in Mwanza, Tanzania
by Stanley Mwita, Mathew Ouma, Warren Edwin, Deogratias Katabalo and Karol Marwa
Diseases 2025, 13(8), 268; https://doi.org/10.3390/diseases13080268 - 19 Aug 2025
Viewed by 147
Abstract
Background: University students are vulnerable to depression due to the transitional nature of their life stage, which often involves increased academic pressures and social changes. This study aims to examine the prevalence, symptoms, and associated risk factors for depressive symptoms among undergraduate students [...] Read more.
Background: University students are vulnerable to depression due to the transitional nature of their life stage, which often involves increased academic pressures and social changes. This study aims to examine the prevalence, symptoms, and associated risk factors for depressive symptoms among undergraduate students at non-medical universities. Methods: This cross-sectional study was conducted at non-medical universities in Mwanza Region, Tanzania. A self-administered, structured questionnaire was used to collect the data. The presence and severity of depressive symptoms were assessed using the Beck Depression Inventory (BDI-II). Results: A total of 768 students participated in the study. The prevalence of depressive symptoms was 35.7%. A significant proportion experienced loss of interest and pleasure (n = 516; 67.2%), felt easily tired (n = 373; 48.6%), and had difficulty making decisions (n = 303; 39.4%). A significant relationship was observed between age and depressive symptoms, with participants aged 25 and above reporting higher rates of depressive symptoms (53.2%) compared to those aged 18–24 (28.8%) (p < 0.001). Similarly, the year of study was significantly associated with depressive symptoms; fourth-year students had the highest proportion of depressive symptoms (64.3%), while first-year students had the lowest proportion (26.2%) (p < 0.001). Conclusion: This study found that over one-third of undergraduate students in non-medical universities suffer from depressive symptoms. This high prevalence rate highlights an urgent need for targeted mental health interventions within university settings to prevent long-term academic, social, and psychological consequences. Campus counseling services should prioritize screening for key symptoms while developing stress-management programs tailored to academic progression challenges. Full article
(This article belongs to the Section Neuro-psychiatric Disorders)
22 pages, 2424 KiB  
Review
Impact of Obesity on Immunity to the Influenza Virus: Gut Microbiota, Mechanisms, and Novel Therapeutic Strategies
by Xiaoyue Ji and Jing Sun
Diseases 2025, 13(8), 267; https://doi.org/10.3390/diseases13080267 - 19 Aug 2025
Viewed by 270
Abstract
Obesity affects millions of individuals globally, and a deeper understanding of its associated physiological disturbances is essential for addressing key public health concerns. It has been demonstrated that the influenza virus possesses substantial global epidemic potential, with higher incidence rates observed in obese [...] Read more.
Obesity affects millions of individuals globally, and a deeper understanding of its associated physiological disturbances is essential for addressing key public health concerns. It has been demonstrated that the influenza virus possesses substantial global epidemic potential, with higher incidence rates observed in obese individuals and prolonged recovery times. Obese individuals exhibit impaired immune organ function, decreased immune cell activity, disrupted metabolism characterized by mitochondrial dysfunction, and an imbalance in gut microbiota associated with intestinal mucosal barrier damage. The gut microbiota and their metabolic composition in obese patients differ from those in non-obese individuals, potentially promoting viral replication and exacerbating disease severity. These factors collectively contribute to more severe tissue damage and heightened immune responses in obese patients during influenza infection. Therefore, understanding the impact of obesity on influenza virus infection dynamics enables the development of strategies promoting healthy lifestyles to manage body weight and enhance immunity against viral infections. Additionally, given that this special population may not respond optimally to antimicrobial drugs and vaccination, it is necessary to consider how treatment strategies for this group are managed. This review illustrates findings concerning the impact of obesity on the immune response to influenza virus infection, including potential underlying mechanisms. Full article
►▼ Show Figures

Figure 1

15 pages, 1010 KiB  
Article
Anxiety and Depression in Mild and Moderate COPD Patients: An Observational, Cross-Sectional Study in Greece
by Effimia Kamariotou, Diamantis Chloros, Dionisios Spyratos, Dionisia Michalopoulou, Ioanna Tsiouprou and Lazaros Sichletidis
Diseases 2025, 13(8), 266; https://doi.org/10.3390/diseases13080266 - 17 Aug 2025
Viewed by 225
Abstract
Background: In this study, we investigated patients in the early stages of COPD to support the hypothesis that symptoms of anxiety and depression are related to mild and moderate COPD and not only to the chronic complications that accompany severe disease. Methods: A [...] Read more.
Background: In this study, we investigated patients in the early stages of COPD to support the hypothesis that symptoms of anxiety and depression are related to mild and moderate COPD and not only to the chronic complications that accompany severe disease. Methods: A total of 250 mild to moderate COPD patients were randomly selected from a population of 5239 individuals who were part of a study on early COPD detection and smoking cessation that was carried out in Central Macedonia, Greece. An age-matched control group of three hundred current or former smokers was also included. A questionnaire was used for demographic data collection, along with the Hospital Anxiety and Depression Scale (HADS) questionnaire for the evaluation of anxiety (HADS-A) and depressive (HADS-D) symptoms. Results: The COPD and non-COPD groups were similar in age, gender, and socioeconomic background. The majority of COPD patients were classified as Grade 1 or 2 and belonged to Group A or B according to the GOLD classification. Among the COPD patients, 19.6% had a score greater than 7 in the HADS-A subscale, 14% in the HADS-D subscale, and 10.8% in both, compared with 6%, 5%, and 5%, respectively, for the non-COPD individuals (p < 0.01). A regression analysis showed that the presence of at least one comorbidity (β = 0.43, p < 0.001) and the presence of at least one respiratory symptom (β = 0.49, p < 0.001) significantly predicted the total HADS score in the COPD group. Conclusions: The prevalence of depression and anxiety symptoms in early COPD patients was greater in comparison to non-COPD smokers. Implementing routine screening for mood disorders using the HADS in mild to moderate COPD outpatients may improve overall disease management and patients’ quality of life. Full article
(This article belongs to the Section Respiratory Diseases)
►▼ Show Figures

Figure 1

17 pages, 2265 KiB  
Article
Is There a Role for the Neutrophil-to-Lymphocyte Ratio for Rebleeding and Mortality Risk Prediction in Acute Variceal Bleeding? A Comparative 5-Year Retrospective Study
by Sergiu Marian Cazacu, Dragos Ovidiu Alexandru, Alexandru Valentin Popescu, Petrica Popa, Ion Rogoveanu and Vlad Florin Iovanescu
Diseases 2025, 13(8), 265; https://doi.org/10.3390/diseases13080265 - 16 Aug 2025
Viewed by 302
Abstract
(1) Background: Acute variceal bleeding (AVB) represents an important cause of upper gastrointestinal bleeding (UGIB). Several prognostic scores may be useful for assessing mortality and rebleeding risk, with the Glasgow-Blatchford score (GBS) and Rockall score being the most commonly used for non-variceal bleeding. [...] Read more.
(1) Background: Acute variceal bleeding (AVB) represents an important cause of upper gastrointestinal bleeding (UGIB). Several prognostic scores may be useful for assessing mortality and rebleeding risk, with the Glasgow-Blatchford score (GBS) and Rockall score being the most commonly used for non-variceal bleeding. Scores assessing liver failure (MELD and Child) do not reflect bleeding severity. The neutrophil-to-lymphocyte ratio (NLR) increases in UGIB and can predict survival and rebleeding. (2) Methods: We analyzed the predictive role of NLR, GBS, Rockall, AIMS65, Child, and MELD for mortality (48 h, 5-day, in-hospital, and 6-week) and rebleeding in AVB patients admitted to our hospital from 2017 to 2021. ROC analysis was performed, and a multivariate analysis with logistic regression was used to construct a simplified model. (3) Results: A total of 415 patients were admitted. NLR exhibited fair accuracy for 48-h mortality (AUC 0.718, 95% CI 0.597–0.839, p < 0.0001), with limited predictive value for medium-term mortality. The NLR accuracy was better than that of the GBS and Rockall score, similar to that of the AIMS65 and Child scores, but inferior to that of MELD. The value for all scores in predicting rebleeding was poor, with the highest AUC for the NLR. (4) Conclusions: The NLR exhibited reasonable accuracy in predicting short-term mortality in AVB. Our model (including NLR, age, creatinine, bilirubin, albumin, INR, platelet count, HCC, and etiology) demonstrated 80.72% accuracy in predicting 6-week mortality. Full article
►▼ Show Figures

Figure 1

12 pages, 3382 KiB  
Article
Histoanatomic Features Distinguishing Aganglionosis in Hirschsprung’s Disease: Toward a Diagnostic Algorithm
by Emma Fransson, Maria Evertsson, Tyra Lundberg, Tebin Hawez, Gustav Andersson, Christina Granéli, Magnus Cinthio, Tobias Erlöv and Pernilla Stenström
Diseases 2025, 13(8), 264; https://doi.org/10.3390/diseases13080264 - 16 Aug 2025
Viewed by 171
Abstract
Background/Objectives: Intraoperative frozen biopsies are essential during surgery for Hirschsprung’s disease (HD). However, this method has several limitations with the need for a faster and real-time diagnostic alternative. For this, consistent histoanatomical and morphometric differences between aganglionic and ganglionic bowel must be established. [...] Read more.
Background/Objectives: Intraoperative frozen biopsies are essential during surgery for Hirschsprung’s disease (HD). However, this method has several limitations with the need for a faster and real-time diagnostic alternative. For this, consistent histoanatomical and morphometric differences between aganglionic and ganglionic bowel must be established. The primary objective was to compare dimensions of bowel wall layers between aganglionic and ganglionic segments histopathologically in resected rectosigmoid specimens from children with HD. Secondary objectives were to design a diagnostic algorithm to distinguish aganglionosis from ganglionosis and assess whether full bowel wall thickness correlates with patient weight and age. Methods: Each histoanatomic bowel wall layer—mucosa, submucosa, and muscularis propria’s layers—was delineated manually on histopathological images. Mean thicknesses were calculated automatically using an in-house image analysis software. Paired parametric tests compared measurements in aganglionic and ganglionic segments. Results: Resected specimens from 30 children with HD were included. Compared to aganglionic bowel, ganglionic bowel showed a thicker muscularis interna (mean 0.666 mm versus 0.461 mm, CI −0.257–(−0.153), p < 0.001), and a higher muscularis interna/muscularis externa ratio (2.047 mm versus 1.287 mm, CI −0.954–(−0.565), p < 0.001). An algorithm based on these features achieved 100% accuracy in distinguishing aganglionosis from ganglionosis. No significant difference in full bowel wall thickness was found between aganglionic and ganglionic segments, nor any correlation with patient weight or age. Conclusions: Histoanatomic layer thickness differs between aganglionic and ganglionic bowel, forming the basis of a diagnostic algorithm. Full bowel wall thickness was independent of patient weight and age. Full article
►▼ Show Figures

Graphical abstract

13 pages, 1509 KiB  
Review
PIEZO Channels in Mechano-Inflammation: Gatekeepers of Neuroimmune Crosstalk
by Carmelo Pirri
Diseases 2025, 13(8), 263; https://doi.org/10.3390/diseases13080263 - 15 Aug 2025
Viewed by 284
Abstract
Mechanical forces shape immune responses in both health and disease. PIEZO1 and PIEZO2, two mechanosensitive ion channels, have emerged as critical transducers of these forces, influencing inflammation, pain, fibrosis, and neuroimmune regulation. This review aims to synthesize the current evidence on the role [...] Read more.
Mechanical forces shape immune responses in both health and disease. PIEZO1 and PIEZO2, two mechanosensitive ion channels, have emerged as critical transducers of these forces, influencing inflammation, pain, fibrosis, and neuroimmune regulation. This review aims to synthesize the current evidence on the role of PIEZO channels in mechano-inflammation, with a specific focus on their regulatory function in neuroimmune crosstalk. A comprehensive narrative synthesis was performed using the literature from PubMed, Scopus, and Web of Science up to June 2025. Experimental, translational, and mechanistic studies involving PIEZO channels in inflammatory, fibrotic, and neuroimmune processes were included. PIEZO1 is broadly expressed in immune cells, fibroblasts, and endothelial cells, where it regulates calcium-dependent activation of pro-inflammatory pathways, such as NF-kB and STAT1. PIEZO2, enriched in sensory neurons, contributes to mechanosensory amplification of inflammatory pain. Both channels are mechanistically involved in neuroinflammation, glial activation, blood–brain barrier dysfunction, connective tissue fibrosis, and visceral hypersensitivity. PIEZO channels act as integrators of biomechanical and immunological signaling. Their roles as context-dependent gatekeepers of neuroimmune crosstalk make them attractive targets for novel therapies. Full article
►▼ Show Figures

Figure 1

23 pages, 676 KiB  
Review
Current Neuroethical Perspectives on Deep Brain Stimulation and Neuromodulation for Neuropsychiatric Disorders: A Scoping Review of the Past 10 Years
by Jonathan Shaw, Sagar Pyreddy, Colton Rosendahl, Charles Lai, Emily Ton and Rustin Carter
Diseases 2025, 13(8), 262; https://doi.org/10.3390/diseases13080262 - 14 Aug 2025
Viewed by 235
Abstract
Background: The use of neuromodulation for the treatment of psychiatric disorders has become increasingly common, but this emerging treatment modality comes with ethical concerns. This scoping review aims to synthesize the neuroethical discourse from the past 10 years on the use of neurotechnologies [...] Read more.
Background: The use of neuromodulation for the treatment of psychiatric disorders has become increasingly common, but this emerging treatment modality comes with ethical concerns. This scoping review aims to synthesize the neuroethical discourse from the past 10 years on the use of neurotechnologies for psychiatric conditions. Methods: A total of 4496 references were imported from PubMed, Embase, and Scopus. The inclusion criteria required a discussion of the neuroethics of neuromodulation and studies published between 2014 and 2024. Results: Of the 77 references, a majority discussed ethical concerns of patient autonomy and informed consent for neuromodulation, with neurotechnologies being increasingly seen as autonomy enablers. Concepts of changes in patient identity and personality, especially after deep brain stimulation, were also discussed extensively. The risks and benefits of neurotechnologies were also compared, with deep brain stimulation being seen as the riskiest but also possessing the highest efficacy. Concerns about equitable access and justice were raised regarding the rise of private transcranial magnetic stimulation clinics and the current experimental status of deep brain stimulation. Conclusions: Neuroethics discourse, particularly for deep brain stimulation, has continued to focus on how post-intervention changes in personality and behavior influence patient identity. Multiple conceptual frameworks have been proposed, though each faces critiques for addressing only parts of this complex phenomenon, prompting calls for pluralistic models. Emerging technologies, especially those involving artificial intelligence through brain computer interfaces, add new dimensions to this debate by raising concerns about neuroprivacy and legal responsibility for actions, further blurring the lines for defining personal identity. Full article
(This article belongs to the Section Neuro-psychiatric Disorders)
►▼ Show Figures

Figure 1

19 pages, 11123 KiB  
Article
Establishment and Characterization of Behavioral Changes in the Nuclear Localization Human α-Synuclein Transgenic Mice
by Ziou Wang, Mengchen Wei, Shengtao Fan, Zheli Li, Weihu Long, Haiting Wu, Yiwei Zhang and Zhangqiong Huang
Diseases 2025, 13(8), 261; https://doi.org/10.3390/diseases13080261 - 14 Aug 2025
Viewed by 255
Abstract
Objectives: This study aimed to establish a transgenic mouse model expressing nucleus-localized human α-synuclein (α-syn) to investigate its impact on the central nervous system and behavior and the underlying mechanisms involved. Methods: A nuclear localization sequence (NLS) was added to the end of [...] Read more.
Objectives: This study aimed to establish a transgenic mouse model expressing nucleus-localized human α-synuclein (α-syn) to investigate its impact on the central nervous system and behavior and the underlying mechanisms involved. Methods: A nuclear localization sequence (NLS) was added to the end of the human SNCA (hSNCA) gene. Subsequently, an empty vector and a mammalian lentiviral vector of the hSNCA-NLS were constructed. Transgenic mice were generated via microinjection, with genotyping and protein expression confirmed by PCR and western blotting. Only male mice were used in subsequent behavioral and molecular experiments. Immunofluorescence identified the colocalization of human α-syn with the cell nucleus in mouse brain tissues. Behavioral changes in transgenic mice were assessed using open field, rotarod, and O-maze tests. qPCR and Western blotting detected expression levels of genes and proteins related to inflammation, endoplasmic reticulum stress (ERS), and apoptosis. Bulk RNA sequencing was used to screen for differentially expressed genes and signaling pathways. Results: We successfully constructed a transgenic mouse model expressing human α-syn. Human α-syn was widely expressed in the heart, liver, spleen, kidneys, and brain of the mice, with distinct nuclear localization observed. Behavioral assessments demonstrated that, by 2 months of age, the mice exhibited motor dysfunction alongside astrocyte proliferation and neuroinflammation. At 6 months, the elevated expression of ERS-related genes (ATF6, PERK, and IRE1) and activation of the PERK-Beclin1-LC3II pathway indicated progressive ERS. By 9 months, apoptotic events had occurred, accompanied by significant anxiety-like behaviors. Bulk RNA sequencing further identified key differentially expressed genes, including IL-1α, TNF, PERK, BECLIN, GABA, IL-6α, P53, LC3II, NOS, and SPAG, suggesting their involvement in the observed pathological and behavioral phenotypes. Conclusions: The nuclear localization human α-syn transgenic mice were successfully established. These findings demonstrate that nucleus-localized α-syn induces early motor deficits, which are likely mediated by neuroinflammation, whereas later anxiety-like behaviors may result from ERS-induced apoptosis. This model provides a valuable tool for elucidating the role of nuclear α-syn in Parkinson’s disease and supports further mechanistic and therapeutic research. Full article
(This article belongs to the Special Issue Research Progress in Neurodegenerative Diseases)
►▼ Show Figures

Figure 1

21 pages, 691 KiB  
Article
The High Prevalence of Oncogenic HPV Genotypes Targeted by the Nonavalent HPV Vaccine in HIV-Infected Women Urgently Reinforces the Need for Prophylactic Vaccination in Key Female Populations Living in Gabon
by Marcelle Mboumba-Mboumba, Augustin Mouinga-Ondeme, Pamela Moussavou-Boundzanga, Jeordy Dimitri Engone-Ondo, Roseanne Mounanga Mourimarodi, Abdoulaye Diane, Christ Ognari Ayoumi, Laurent Bélec, Ralph-Sydney Mboumba Bouassa and Ivan Mfouo-Tynga
Diseases 2025, 13(8), 260; https://doi.org/10.3390/diseases13080260 - 14 Aug 2025
Viewed by 267
Abstract
Background/Objectives. Women living with human immunodeficiency virus (WLWH) have a six-fold higher risk of developing cervical cancer associated with high-risk human Papillomavirus (HR-HPV) than HIV-negative women. We herein assessed HR-HPV genotype distribution and plasma levels of the cancer antigen 125 (CA-125) in WLWH [...] Read more.
Background/Objectives. Women living with human immunodeficiency virus (WLWH) have a six-fold higher risk of developing cervical cancer associated with high-risk human Papillomavirus (HR-HPV) than HIV-negative women. We herein assessed HR-HPV genotype distribution and plasma levels of the cancer antigen 125 (CA-125) in WLWH in a rural town in Gabon, in Central Africa. Methods. Adult WLWH attending the local HIV outpatient center were prospectively enrolled and underwent cervical visual inspection and cervicovaginal and blood sampling. HIV RNA load and CA-125 levels were measured from plasma using the Cepheid® Xpert® HIV-1 Viral Load kit and BioMérieux VIDAS® CA-125 II assay, respectively. HPV detection and genotyping were performed via a nested polymerase chain reaction (MY09/11 and GP5+/6+), followed by sequencing. Results. Fifty-eight WLWH (median age: 52 years) were enrolled. Median CD4 count was 547 cells/µL (IQR: 412.5–737.5) and HIV RNA load 4.88 Log10 copies/mL (IQR: 3.79–5.49). HPV prevalence was 68.96%, with HR-HPV detected in 41.37% of women. Among HR-HPV-positive samples, 87.5% (21/24) were genotypes targeted by the Gardasil vaccine, while 12.5% (3/24) were non-vaccine types. Predominant HR-HPV types included HPV-16 (13.8%), HPV-33 (10.34%), HPV-35 (5.17%), HPV-31, and HPV-58 (3.45%). Most participants had normal cervical cytology (62.07%), and a minority (14.29%) had elevated CA-125 levels, with no correlation to cytological abnormalities. Conclusions. In the hinterland of Gabon, WLWH are facing an unsuspected yet substantial burden of cervical HR-HPV infection and a neglected risk for cervical cancer. Strengthening cervical cancer prevention through targeted HPV vaccination, sexual education, and accessible screening strategies will help in mitigating associated risk. Full article
►▼ Show Figures

Figure 1

29 pages, 4115 KiB  
Article
In Silico Design of a Multiepitope Vaccine Against Intestinal Pathogenic Escherichia coli Based on the 2011 German O104:H4 Outbreak Strain Using Reverse Vaccinology and an Immunoinformatic Approach
by Eman G. Youssef, Khaled Elnesr and Amro Hanora
Diseases 2025, 13(8), 259; https://doi.org/10.3390/diseases13080259 - 13 Aug 2025
Viewed by 224
Abstract
Background: While most Escherichia coli strains are harmless members of the gastrointestinal microbiota, certain pathogenic variants can cause severe intestinal and extraintestinal diseases. A notable outbreak of E. coli O104:H4, involving both enteroaggregative (EAEC) and enterohemorrhagic (EHEC) strains, occurred [...] Read more.
Background: While most Escherichia coli strains are harmless members of the gastrointestinal microbiota, certain pathogenic variants can cause severe intestinal and extraintestinal diseases. A notable outbreak of E. coli O104:H4, involving both enteroaggregative (EAEC) and enterohemorrhagic (EHEC) strains, occurred in Europe, resulting in symptoms ranging from bloody diarrhea to life-threatening colitis and hemolytic uremic syndrome (HUS). Since treatment options remain limited and have changed little over the past 40 years, there is an urgent need for an effective vaccine. Such a vaccine would offer major public health and economic benefits by preventing severe infections and reducing outbreak-related costs. A multiepitope vaccine approach, enabled by advances in immunoinformatics, offers a promising strategy for targeting HUS-causing E. coli (O104:H4 and O157:H7 serotypes) with minimal disruption to normal microbiota. This study aimed to design an immunogenic multiepitope vaccine (MEV) construct using bioinformatics and immunoinformatic tools. Methods and Results: Comparative proteomic analysis identified 672 proteins unique to E. coli O104:H4, excluding proteins shared with the nonpathogenic E. coli K-12-MG1655 strain and those shorter than 100 amino acids. Subcellular localization (P-SORTb) identified 17 extracellular or outer membrane proteins. Four proteins were selected as vaccine candidates based on transmembrane domains (TMHMM), antigenicity (VaxiJen), and conservation among EHEC strains. Epitope prediction revealed ten B-cell, four cytotoxic T-cell, and three helper T-cell epitopes. Four MEVs with different adjuvants were designed and assessed for solubility, stability, and antigenicity. Structural refinement (GALAXY) and docking studies confirmed strong interaction with Toll-Like Receptor 4 (TLR4). In silico immune simulations (C-ImmSim) indicated robust humoral and cellular immune responses. In Conclusions, the proposed MEV construct demonstrated promising immunogenicity and warrants further validation in experimental models. Full article
►▼ Show Figures

Figure 1

19 pages, 1277 KiB  
Article
Association Between Dietary Patterns and Lifestyle Habits with Vascular Inflammatory Responses in Individuals with Hypertension Living in PM2.5-Polluted Areas: A Cross-Sectional Pilot Study in Chiang Mai Province, Thailand
by Wason Parklak, Kanokwan Kulprachakarn, Sawaeng Kawichai, Puriwat Fakfum, Putita Jiraya, Praporn Kijkuokool, Wiritphon Khiaolaongam and Hataichanok Chuljerm
Diseases 2025, 13(8), 258; https://doi.org/10.3390/diseases13080258 - 13 Aug 2025
Viewed by 617
Abstract
Background/Objectives: Exposure to fine particulate matter (PM2.5) is linked to increased cardiovascular risk, particularly in individuals with hypertension. This study examined the association between dietary patterns, lifestyle factors, and vascular inflammation among individuals with hypertension living in rural and peri-urban areas [...] Read more.
Background/Objectives: Exposure to fine particulate matter (PM2.5) is linked to increased cardiovascular risk, particularly in individuals with hypertension. This study examined the association between dietary patterns, lifestyle factors, and vascular inflammation among individuals with hypertension living in rural and peri-urban areas of Chiang Mai Province, Thailand. Methods: A cross-sectional pilot study was conducted among 47 participants (23 rural, 24 peri-urban). Data on dietary intake, smoking, alcohol use, anthropometry, and blood chemistry were collected. Serum intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and interleukin-6 (IL-6) were measured. Partial correlation analysis was used to examine associations with lifestyle factors, adjusting for relevant covariates. Results: Peri-urban participants had significantly higher levels of ICAM-1 [83.0 vs. 50.1 ng/mL], VCAM-1 [639.3 vs. 376.5 ng/mL], and IL-6 [4.80 vs. 1.02 pg/mL] compared to rural participants. Rural individuals reported higher intakes of antioxidant-related nutrients (selenium, β-carotene, niacin, vitamins A, B6, and C), while peri-urban individuals had higher sugar intake. Sugar intake was positively associated with ICAM-1 and VCAM-1, whereas selenium and vitamin C were inversely associated with both ICAM-1 and VCAM-1, while vitamin B6 was inversely associated with VCAM-1 only. Although rural participants had a higher rate of current smoking (34.8% vs. 4.4%), smoking and alcohol use were not significantly associated with inflammatory markers. Conclusion: Rural dietary patterns may be linked to reduced vascular adhesion molecule levels. Further studies with larger samples are warranted to clarify these associations and guide lifestyle strategies for managing vascular inflammation in PM2.5-exposed individuals with hypertension. Full article
(This article belongs to the Special Issue Dietary Effects on Health Status in South-East Asia Population)
►▼ Show Figures

Graphical abstract

3 pages, 1977 KiB  
Correction
Correction: Amin et al. Hepatocellular Carcinoma: A Comprehensive Review. Diseases 2025, 13, 207
by Nisar Amin, Javaria Anwar, Abdullahi Sulaiman, Nadia Nikolaeva Naumova and Nadeem Anwar
Diseases 2025, 13(8), 257; https://doi.org/10.3390/diseases13080257 - 13 Aug 2025
Viewed by 124
Abstract
In the original publication [...] Full article
(This article belongs to the Special Issue Viral Hepatitis: Diagnosis, Treatment and Management)
►▼ Show Figures

Figure 2

14 pages, 233 KiB  
Article
Ten-Year Trends in Hepatocellular Carcinoma Mortality: Examining the Interaction Between Fibrosis Score and Patient Age
by Ayrton Bangolo, Hadrian Hoang-Vu Tran, Budoor Alqinai, Rishabh Goyal, Shehwar Ahmed, Aamna Qasim, Gabriela Rojas, Shubham Madan, Helena Barbosa, Zainab Mustafa, Risham Waseem, Gabriel Ingersoll, Hamza Khan, Alison Guzzetti, Jonathan Daniel, Samiya Parkar, Aakriti Tiwari, Sarah Lafleur, Rajasekhar Cingapagu, Saliha Y. Amasyali, Eric Pin-Shiuan Chen and Simcha Weissmanadd Show full author list remove Hide full author list
Diseases 2025, 13(8), 256; https://doi.org/10.3390/diseases13080256 - 12 Aug 2025
Viewed by 315
Abstract
Background: Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality worldwide, with survival outcomes influenced by a range of demographic and pathological factors. While cirrhosis is a well-established risk factor, recent evidence shows that HCC can also develop in patients with only [...] Read more.
Background: Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality worldwide, with survival outcomes influenced by a range of demographic and pathological factors. While cirrhosis is a well-established risk factor, recent evidence shows that HCC can also develop in patients with only mild to moderate liver fibrosis. However, there is limited understanding of how fibrosis severity interacts with other clinical variables, such as patient age, to affect mortality. This study aims to explore how fibrosis scores relate to both overall and cancer-specific mortality in US HCC patients, with an emphasis on how this relationship may shift across different age groups. Methods: We utilized data from the Surveillance, Epidemiology, and End Results (SEER) database to identify 15,796 adult patients diagnosed with HCC between 2010 and 2021. Baseline demographics, disease characteristics, and treatment variables were examined. Mortality outcomes were evaluated using Cox proportional hazard regression. Variables significant at p < 0.1 in univariate analysis were included in multivariate models to identify independent predictors of mortality (with hazard ratios [HRs] > 1 signifying increased risk). A secondary analysis assessed how age modifies the association between fibrosis score and mortality. Results: The study population was predominantly male (77.2%), with most patients aged 60–79 (59.6%) and presenting with localized disease (61%). A majority had advanced liver fibrosis or cirrhosis (81.7%) and lived in large urban areas (62.9%). Crude comparisons indicated that male sex, older age, single status, advanced tumor stage, lower income, and cirrhosis were linked to worse outcomes. In adjusted models, independent predictors of increased mortality included male sex, older age, unmarried status, and more advanced disease stage. Receipt of surgery or chemotherapy was associated with a lower risk of death. Notably, the influence of fibrosis on mortality was found to be greater in older patients than in their younger counterparts. Conclusions: This analysis identifies key prognostic indicators in HCC and suggests that the relationship between fibrosis and survival is not uniform across age groups. These findings support the need for age-specific clinical management strategies and highlight the potential benefit of early detection and appropriate interventions, even in non-cirrhotic patients. Full article
13 pages, 1674 KiB  
Article
Epidemiology and Genetic Diversity of Human Metapneumovirus in Patients with Severe Acute Respiratory Infection from 2023 to 2024 in Ningxia, China
by Ting Mu, Jianxin Pei, Jingting Wang, Ling Niu and Zhonglan Wu
Diseases 2025, 13(8), 255; https://doi.org/10.3390/diseases13080255 - 11 Aug 2025
Viewed by 202
Abstract
Background: Human metapneumovirus (HMPV) is a major pathogen responsible for causing severe acute respiratory infections (SARI). Whole-genome sequencing can better identify transmission events and outbreaks. In this study, we aimed to investigate the epidemiology and genetic diversity of HMPV in SARI cases in [...] Read more.
Background: Human metapneumovirus (HMPV) is a major pathogen responsible for causing severe acute respiratory infections (SARI). Whole-genome sequencing can better identify transmission events and outbreaks. In this study, we aimed to investigate the epidemiology and genetic diversity of HMPV in SARI cases in Ningxia, China. Methods: We collected respiratory tract samples from hospitalized patients with SARI from October 2023 to September 2024 in Ningxia, China. Nasopharyngeal swabs were tested for respiratory viruses with qRT-PCR. Whole-genome sequences were determined for samples with high viral loads using an amplicon-based method. Results: We enrolled 2873 SARI patients from October 2023 to September 2024, and found an HMPV-positive proportion of 3.06% (88/2873). Children aged 4 years were particularly susceptible to HMPV infection, with a positive proportion of 10.92% (13/119). HMPV exhibits distinct seasonal characteristics, consistent with its established epidemiological pattern, with a peak incidence occurring during winter months. Sixteen complete HMPV genome sequences were obtained. Among these, 81.25% (13/16) were identified as genotype A (A2.2.2: 92.31%, 12/13; A2.2.1: 7.69%, 1/13) and 18.75% (3/16) as genotype B1. Notably, the dominant strain was 111nt-dup in genotype A2.2.2. Sequence analysis of HMPV genes revealed divergent G-gene sequence identities between different genotypes. Additionally, the potential glycosylation sites of the G protein varied across genotypes. Conclusions: In this study, we found that the 111nt-dup strain was the dominant one in genotype A, and multiple genotypes co-circulated in Ningxia from October 2023 to September 2024. The HMPV G protein exhibited the highest level of inter-strain diversity between genotypes. These findings provide valuable insights into the prevention and control of HMPV infections in China. Full article
(This article belongs to the Section Infectious Disease)
►▼ Show Figures

Figure 1

10 pages, 240 KiB  
Article
Differences in Metabolic Control Between Different Insulin Use Patterns in Pediatric Patients with Type 1 Diabetes Through Intermittent Glucose Monitoring
by Rocio Porcel-Chacón, Leopoldo Tapia-Ceballos, Ana-Belen Ariza-Jimenez, Ana Gómez-Perea, José Manuel Jiménez-Hinojosa, Juan-Pedro López-Siguero and Isabel Leiva-Gea
Diseases 2025, 13(8), 254; https://doi.org/10.3390/diseases13080254 - 9 Aug 2025
Viewed by 194
Abstract
Introduction: In healthcare centers with limited resources, or for patients who prefer to make continuous changes in their treatment themselves and do not want to rely solely on technology, intermittent glucose monitoring (isCGM) with an insulin pump is a viable option that warrants [...] Read more.
Introduction: In healthcare centers with limited resources, or for patients who prefer to make continuous changes in their treatment themselves and do not want to rely solely on technology, intermittent glucose monitoring (isCGM) with an insulin pump is a viable option that warrants further study. Material and methods: prospective single-center study that collected data at 3 months and after isCGM implantation in pediatric patients with Type 1 diabetes, categorized according to their insulin regimen. Results: We found statistically significant differences in the time in range (TIR) between 70 and 180 mg/dl at 3 months after using the sensor (p = 0.017), although these differences were not maintained at 1 year (p = 0.064). When stricter TIRs (70–140 mg/dl) were analyzed, statistically significant differences were observed at 3 months (p = 0.01) and at 1 year (p = 0.018) in favor of patients using CSII. While 75% of the patients in the CSII group had good control with HbA1c < 7% after one year of sensor use, only 34.6% in the MDI group achieved these values. However, the CSII group presented a higher coefficient of variation (62.31% at 3 months and 43.08% at 1 year) (p = 0.02), and a higher number of hypoglycemic episodes (7.38% and 7.32%, respectively) (p = 0.016). The CSII group also had a higher number of capillary blood glucose measurements at the beginning of the study (8.32/day) (p = 0.249), but this number became similar between both groups after one year. Conclusions: We found statistically significant differences in favor of CSII over MDI in terms of metabolic control after one year of isCGM use. However, the TIR values were still below the range considered to be indicative of good control. These findings lead us to question whether CSII should be initially considered in specific cases where HCL is not possible, or if it would be more effective to wait until the patient is ready, or the necessary resources are available to start directly CSII integrated in a closed loop system. Full article
(This article belongs to the Special Issue From Monitoring to Management: Addressing Challenges in Type 1 and Type 2 Diabetes Care)
10 pages, 1086 KiB  
Article
Clinical Practice Patterns of Assessment and Interventions for Elderly Patients with a Hip Fracture Who Are at Risk of Dysphagia—A Survey
by Stine Mølgaard Kristoffersen, Signe Westmark and Dorte Melgaard
Diseases 2025, 13(8), 253; https://doi.org/10.3390/diseases13080253 - 8 Aug 2025
Viewed by 309
Abstract
Objective: Dysphagia is common among elderly patients after hip fracture surgery and can lead to aspiration pneumonia, malnutrition, and delayed rehabilitation. This study aims to present current clinical practice patterns of assessment and intervention for dysphagia in this patient group. Methods: The study [...] Read more.
Objective: Dysphagia is common among elderly patients after hip fracture surgery and can lead to aspiration pneumonia, malnutrition, and delayed rehabilitation. This study aims to present current clinical practice patterns of assessment and intervention for dysphagia in this patient group. Methods: The study was conducted through a two-round online questionnaire targeting Danish occupational therapists with expertise in dysphagia post hip fracture. Results: A total of 71 therapists participated in round one, and 44 (62%) completed round two. Triggers for assessment included coughing, recurrent pneumonia, voice changes, altered eating habits, unplanned weight loss, functional decline, and comorbidities; age was rarely used. Frequently used assessment tools were Facio-Oral Tract Therapy (57.1%), the Minimal Eating Observation Form—Version II (40%) and the Volume–Viscosity Swallow Test (41.4%). Key interventions included texture modification, posture correction, patient education, oral hygiene optimization, compensatory strategies, and dysphagia training; oral screens and electrical stimulation were less common. Conclusions: This study provides a descriptive overview of current dysphagia assessment triggers, tools, and interventions used for elderly hip fracture patients in Denmark. The findings highlight clinical practice patterns that can inform future research on patient outcomes and the effectiveness of specific interventions in this population. Full article
►▼ Show Figures

Figure 1

14 pages, 1388 KiB  
Review
Cardiovascular Complications of COVID-19 Disease: A Narrative Review
by Andrea Denegri, Valeria Dall’Ospedale, Marco Covani, Michal Pruc, Lukasz Szarpak and Giampaolo Niccoli
Diseases 2025, 13(8), 252; https://doi.org/10.3390/diseases13080252 - 8 Aug 2025
Viewed by 515
Abstract
Background: The coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has had a profound impact on global health, extending beyond pulmonary complications. Cardiovascular involvement in COVID-19 is multifactorial and may be influenced by viral load, inflammatory response, and pre-existing comorbidities. Discussion: Acute complications include [...] Read more.
Background: The coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has had a profound impact on global health, extending beyond pulmonary complications. Cardiovascular involvement in COVID-19 is multifactorial and may be influenced by viral load, inflammatory response, and pre-existing comorbidities. Discussion: Acute complications include myocardial injury, arrhythmias, acute coronary syndromes (ACS), heart failure, Takotsubo cardiomyopathy, myopericarditis, and cardiac arrest. Notably, atrial fibrillation (AF) emerges as a frequent arrhythmic complication, particularly among critically ill patients, and is associated with increased mortality. COVID-19-patients with concomitant ACS present more severe clinical profiles and higher rates of thrombotic events, including stent thrombosis. Cardiac arrest predominantly presents with non-shockable rhythms and is associated with dismal outcomes. COVID-19 also exacerbates heart failure, both by aggravating existing cardiac dysfunction or by precipitating de novo heart failure. Takotsubo cardiomyopathy and myocarditis, although less frequent, have been reported and are often underdiagnosed due to subtle clinical presentations. Right ventricular dysfunction, linked to pulmonary involvement, has emerged as a key prognostic marker. Post-COVID-19 syndrome include persistent cardiac abnormalities such as reduced ventricular function and myocardial inflammation. Cardiac magnetic resonance imaging and strain echocardiography have proven useful in identifying subclinical cardiac involvement. Conclusions: Early recognition and monitoring of cardiovascular complications are crucial for improving outcomes in patients affected by COVID-19. This review summarizes current evidence regarding cardiovascular manifestations associated with COVID-19. Full article
►▼ Show Figures

Figure 1

12 pages, 1524 KiB  
Case Report
An Uncharted Path of Metastasis: A Case Report of Sigmoid Colon Cancer with Synchronous Vaginal and Urethral Spread
by John Fernando Montenegro, Giovanna Patricia Rivas Tafur, Miguel Diaz, Diego Fernando Alzate, María Camila Faria, Daniel Florez, Richard Andrés Acuña, Cesar Eduardo and Yamil Liscano
Diseases 2025, 13(8), 251; https://doi.org/10.3390/diseases13080251 - 8 Aug 2025
Viewed by 287
Abstract
Background and Objective: Colorectal cancer (CRC) most commonly metastasizes to the liver and lungs; however, synchronous metastases to pelvic structures such as the vagina and urethra are extremely rare, posing a significant diagnostic and therapeutic challenge. This report describes an unusual case of [...] Read more.
Background and Objective: Colorectal cancer (CRC) most commonly metastasizes to the liver and lungs; however, synchronous metastases to pelvic structures such as the vagina and urethra are extremely rare, posing a significant diagnostic and therapeutic challenge. This report describes an unusual case of sigmoid colon adenocarcinoma with synchronous metastases to the vagina and urethra, highlighting its diagnostic evaluation and the value of a multidisciplinary approach. Methods: A 59-year-old woman with a history of deep vein thrombosis treated with apixaban presented with chronic constipation and pelvic bleeding. A gynecological evaluation revealed a vaginal lesion. A colonoscopy, biopsy, pelvic magnetic resonance imaging, and molecular profiling were performed. Treatment included chemotherapy (capecitabine and oxaliplatin), panitumumab, and pelvic radiotherapy. Results: The biopsy confirmed a moderately differentiated invasive adenocarcinoma in the sigmoid colon with synchronous metastases to the vagina and urethra. Molecular profiling identified a rat sarcoma virus oncogene and BRAF (B-Raf proto-oncogene), allowing for the use of targeted therapy. The patient achieved a complete response according to RECIST 1.1 criteria and significant symptomatic improvement, including pain reduction, although dosages were adjusted for thrombocytopenia. She is currently continuing palliative treatment with good tolerance and durable symptomatic improvement. Conclusions: This case underscores the need to consider unusual metastatic sites in patients with colorectal cancer presenting with gynecological symptoms. Early diagnosis, based on imaging and histology, alongside molecular characterization, is crucial for effective personalized therapy. Multidisciplinary coordination is key to optimizing clinical outcomes in these rare metastatic presentations. Full article
(This article belongs to the Section Gastroenterology)
►▼ Show Figures

Figure 1

24 pages, 1523 KiB  
Review
Host–Microbiome Interaction in the Intensive Care Unit
by Maria Adriana Neag, Andrei Otto Mitre, Irina Georgiana Pomana, Maria Amalia Velescu, Claudia Militaru, Georgiana Nagy and Carmen Stanca Melincovici
Diseases 2025, 13(8), 250; https://doi.org/10.3390/diseases13080250 - 7 Aug 2025
Viewed by 413
Abstract
Critical illness profoundly disrupts the gut microbiota leading to a state of dysbiosis characterized by reduced microbial diversity and overrepresentation of pathogenic taxa such as Enterobacteriaceae and Proteobacteria. This dysbiotic shift compromises gut barrier integrity and modulates immune responses, contributing to systemic inflammation [...] Read more.
Critical illness profoundly disrupts the gut microbiota leading to a state of dysbiosis characterized by reduced microbial diversity and overrepresentation of pathogenic taxa such as Enterobacteriaceae and Proteobacteria. This dysbiotic shift compromises gut barrier integrity and modulates immune responses, contributing to systemic inflammation and increasing susceptibility to nosocomial infections and multi-organ dysfunction. Nutritional strategies in the ICU significantly influence the composition and function of the gut microbiota. Enteral nutrition supports the maintenance of microbial diversity and gut mucosal health, whereas parenteral nutrition is associated with mucosal atrophy and further microbial imbalance. Emerging interventions, including the administration of probiotics, prebiotics, synbiotics, and fermented products like kefir, show promise in restoring microbial equilibrium and improving patient outcomes. This review presents current evidence on the alterations of the gut microbiota in critically ill patients, explores the systemic consequences of dysbiosis, and evaluates the impact of nutritional and microbiota-targeted therapies in improving patient outcomes. Full article
(This article belongs to the Special Issue Microbiota in Human Disease)
►▼ Show Figures

Figure 1

25 pages, 1689 KiB  
Review
Practical Considerations in the Management of Frail Older People with Diabetes
by Dima Abdelhafiz and Ahmed Abdelhafiz
Diseases 2025, 13(8), 249; https://doi.org/10.3390/diseases13080249 - 6 Aug 2025
Viewed by 540
Abstract
With increasing life expectancy, the number of older people living with comorbid diabetes and frailty is increasing. The development of frailty accelerates diabetes-related adverse outcomes. Frailty is a multidimensional syndrome with physical, mental and social aspects which is associated with increased risk of [...] Read more.
With increasing life expectancy, the number of older people living with comorbid diabetes and frailty is increasing. The development of frailty accelerates diabetes-related adverse outcomes. Frailty is a multidimensional syndrome with physical, mental and social aspects which is associated with increased risk of hypoglycaemia, dementia and hospitalisation. Therefore, regular screening for all aspects of frailty should be an integrated part of the care plans of older people with diabetes. In addition, every effort should be made for prevention, which includes adequate nutrition combined with regular resistance exercise training. In already frail older people with diabetes, metabolic targets should be relaxed and hypoglycaemic agents should be of low hypoglycaemic risk potential. Furthermore, the metabolic phenotype of frailty should be considered when choosing hypoglycaemic agents and determining targets. With increasing severity of frailty, proactive chronological plans of de-escalation, palliation and end-of-life care should be considered. These plans should be undertaken in a shared decision-making manner which involves patients and their families. This ensures that patients’ views, wishes and preferences are in the heart of these plans. Full article
►▼ Show Figures

Figure 1

22 pages, 1785 KiB  
Article
Regulatory Effects of Endometriosis-Associated Genetic Variants: A Multi-Tissue eQTL Analysis
by Asbiel Felipe Garibaldi-Ríos, Perla Graciela Rodríguez-Gutiérrez, Jesús Magdiel García-Díaz, Guillermo Moisés Zúñiga-González, Luis E. Figuera, Belinda Claudia Gómez-Meda, Ana María Puebla-Pérez, Ingrid Patricia Dávalos-Rodríguez, Blanca Miriam Torres-Mendoza, Itzae Adonai Gutiérrez-Hurtado and Martha Patricia Gallegos-Arreola
Diseases 2025, 13(8), 248; https://doi.org/10.3390/diseases13080248 - 6 Aug 2025
Viewed by 470
Abstract
Backgroud. Endometriosis is a chronic, estrogen-dependent inflammatory disease characterized by the ectopic presence of endometrial-like tissue. Although genome-wide association studies (GWAS) have identified susceptibility variants, their tissue-specific regulatory impact remains poorly understood. Objective. To functionally characterize endometriosis-associated variants by exploring their regulatory effects [...] Read more.
Backgroud. Endometriosis is a chronic, estrogen-dependent inflammatory disease characterized by the ectopic presence of endometrial-like tissue. Although genome-wide association studies (GWAS) have identified susceptibility variants, their tissue-specific regulatory impact remains poorly understood. Objective. To functionally characterize endometriosis-associated variants by exploring their regulatory effects as expression quantitative trait loci (eQTLs) across six physiologically relevant tissues: peripheral blood, sigmoid colon, ileum, ovary, uterus, and vagina. Methods. GWAS-identified variants were cross-referenced with tissue-specific eQTL data from the GTEx v8 database. We prioritized genes either frequently regulated by eQTLs or showing the strongest regulatory effects (based on slope values, which indicate the direction and magnitude of the effect on gene expression). Functional interpretation was performed using MSigDB Hallmark gene sets and Cancer Hallmarks gene collections. Results. A tissue specificity was observed in the regulatory profiles of eQTL-associated genes. In the colon, ileum, and peripheral blood, immune and epithelial signaling genes predominated. In contrast, reproductive tissues showed the enrichment of genes involved in hormonal response, tissue remodeling, and adhesion. Key regulators such as MICB, CLDN23, and GATA4 were consistently linked to hallmark pathways, including immune evasion, angiogenesis, and proliferative signaling. Notably, a substantial subset of regulated genes was not associated with any known pathway, indicating potential novel regulatory mechanisms. Conclusions. This integrative approach highlights the com-plexity of tissue-specific gene regulation mediated by endometriosis-associated variants. Our findings provide a functional framework to prioritize candidate genes and support new mechanistic hypotheses for the molecular pathophysiology of endometriosis. Full article
►▼ Show Figures

Figure 1

11 pages, 468 KiB  
Article
Association of Therapeutic Plasma Exchange-Treated Thrombotic Thrombocytopenic Purpura with Improved Mortality Outcome in End-Stage Renal Disease
by Brenna S. Kincaid, Kiana Kim, Jennifer L. Waller, Stephanie L. Baer, Wendy B. Bollag and Roni J. Bollag
Diseases 2025, 13(8), 247; https://doi.org/10.3390/diseases13080247 - 5 Aug 2025
Viewed by 268
Abstract
Background/Objectives: Thrombotic thrombocytopenic purpura (TTP) is a microangiopathic hemolytic anemia exhibiting 90% mortality without prompt treatment. The aim of this study was to investigate the association of therapeutic plasma exchange (TPE)-treated TTP in end-stage renal disease (ESRD) patients with mortality, demographics, and [...] Read more.
Background/Objectives: Thrombotic thrombocytopenic purpura (TTP) is a microangiopathic hemolytic anemia exhibiting 90% mortality without prompt treatment. The aim of this study was to investigate the association of therapeutic plasma exchange (TPE)-treated TTP in end-stage renal disease (ESRD) patients with mortality, demographics, and clinical comorbidities. We queried the United States Renal Data System for ESRD patients starting dialysis between 1 January 2005 and 31 December 2018, using International Classification of Diseases (ICD)-9 and ICD-10 codes for thrombotic microangiopathy, with a TPE procedure code entered within 7 days. Methods: Cox proportional hazards models were used to assess mortality, adjusting for demographic and clinical factors. Results: Among 1,155,136 patients, increased age [adjusted odds ratio (OR) = 0.96, 95% confidence interval (CI): 0.94–0.96]; black race (OR = 0.67, CI: 0.51–0.89); and Hispanic ethnicity (OR = 0.43, CI: 0.28–0.66) were associated with a lower risk of TPE-treated TTP diagnosis, whereas female sex (OR = 1.59, CI: 1.25–2.02) and tobacco use (OR = 2.08, CI: 1.58–2.75) had a higher risk. A claim for TPE-treated TTP carried a lower risk of death (adjusted hazard ratio = 0.024, CI: 0.021–0.028). Female sex, black race, Hispanic ethnicity, and hypothyroidism were also associated with decreased all-cause mortality. Conclusions: These findings suggest that ESRD patients with TPE-treated TTP are significantly protected from mortality compared with ESRD patients without this diagnosis. Full article
►▼ Show Figures

Figure 1

23 pages, 11168 KiB  
Article
Persistent Inflammation, Maladaptive Remodeling, and Fibrosis in the Kidney Following Long COVID-like MHV-1 Mouse Model
by Rajalakshmi Ramamoorthy, Anna Rosa Speciale, Emily M. West, Hussain Hussain, Nila Elumalai, Klaus Erich Schmitz Abe, Madesh Chinnathevar Ramesh, Pankaj B. Agrawal, Arumugam R. Jayakumar and Michael J. Paidas
Diseases 2025, 13(8), 246; https://doi.org/10.3390/diseases13080246 - 5 Aug 2025
Viewed by 534
Abstract
Background: Accumulating evidence indicates that SARS-CoV-2 infection results in long-term multiorgan complications, with the kidney being a primary target. This study aimed to characterize the long-term transcriptomic changes in the kidney following coronavirus infection using a murine model of MHV-1-induced SARS-like illness and [...] Read more.
Background: Accumulating evidence indicates that SARS-CoV-2 infection results in long-term multiorgan complications, with the kidney being a primary target. This study aimed to characterize the long-term transcriptomic changes in the kidney following coronavirus infection using a murine model of MHV-1-induced SARS-like illness and to evaluate the therapeutic efficacy of SPIKENET (SPK). Methods: A/J mice were infected with MHV-1. Renal tissues were collected and subjected to immunofluorescence analysis and Next Generation RNA Sequencing to identify differentially expressed genes associated with acute and chronic infection. Bioinformatic analyses, including PCA, volcano plots, and GO/KEGG pathway enrichment, were performed. A separate cohort received SPK treatment, and comparative transcriptomic profiling was conducted. Gene expression profile was further confirmed using real-time PCR. Results: Acute infection showed the upregulation of genes involved in inflammation and fibrosis. Long-term MHV-1 infection led to the sustained upregulation of genes involved in muscle regeneration, cytoskeletal remodeling, and fibrotic responses. Notably, both expression and variability of SLC22 and SLC22A8, key proximal tubule transporters, were reduced, suggesting a loss of segment-specific identity. Further, SLC12A1, a critical regulator of sodium reabsorption and blood pressure, was downregulated and is associated with the onset of polyuria and hydronephrosis. SLC transporters exhibited expression patterns consistent with tubular dysfunction and inflammation. These findings suggest aberrant activation of myogenic pathways and structural proteins in renal tissues, consistent with a pro-fibrotic phenotype. In contrast, SPK treatment reversed the expression of most genes, thereby restoring the gene profiles to those observed in control mice. Conclusions: MHV-1-induced long COVID is associated with persistent transcriptional reprogramming in the kidney, indicative of chronic inflammation, cytoskeletal dysregulation, and fibrogenesis. SPK demonstrates robust therapeutic potential by normalizing these molecular signatures and preventing long-term renal damage. These findings underscore the relevance of the MHV-1 model and support further investigation of SPK as a candidate therapy for COVID-19-associated renal sequelae. Full article
(This article belongs to the Special Issue COVID-19 and Global Chronic Disease 2025: New Challenges)
►▼ Show Figures

Figure 1

23 pages, 5695 KiB  
Article
Impact of miR-181a on SIRT1 Expression and Senescence in Hutchinson–Gilford Progeria Syndrome
by Eva-Maria Lederer, Felix Quirin Fenzl, Peter Krüger, Moritz Schroll, Ramona Hartinger and Karima Djabali
Diseases 2025, 13(8), 245; https://doi.org/10.3390/diseases13080245 - 4 Aug 2025
Viewed by 254
Abstract
Background/Objectives: Hutchinson–Gilford progeria syndrome (HGPS) is a rare and fatal genetic disease caused by a silent mutation in the LMNA gene, leading to the production of progerin, a defective prelamin A variant. Progerin accumulation disrupts nuclear integrity, alters chromatin organization, and drives systemic [...] Read more.
Background/Objectives: Hutchinson–Gilford progeria syndrome (HGPS) is a rare and fatal genetic disease caused by a silent mutation in the LMNA gene, leading to the production of progerin, a defective prelamin A variant. Progerin accumulation disrupts nuclear integrity, alters chromatin organization, and drives systemic cellular dysfunction. While autophagy and inflammation are key dysregulated pathways in HGPS, the role of microRNAs (miRNAs) in these processes remains poorly understood. Methods: We performed an extensive literature review to identify miRNAs involved in autophagy and inflammation. Through stem-loop RT-qPCR in aging HGPS and control fibroblast strains, we identified significant miRNAs and focused on the most prominent one, miR-181a-5p, for in-depth analysis. We validated our in vitro findings with miRNA expression studies in skin biopsies from an HGPS mouse model and conducted functional assays in human fibroblasts, including immunofluorescence staining, β-Galactosidase assay, qPCR, and Western blot analysis. Transfection studies were performed using an miR-181a-5p mimic and its inhibitor. Results: We identified miR-181a-5p as a critical regulator of premature senescence in HGPS. miR-181a-5p was significantly upregulated in HGPS fibroblasts and an HGPS mouse model, correlating with Sirtuin 1 (SIRT1) suppression and induction of senescence. Additionally, we demonstrated that TGFβ1 induced miR-181a-5p expression, linking inflammation to miRNA-mediated senescence. Inhibiting miR-181a-5p restored SIRT1 levels, increased proliferation, and alleviated senescence in HGPS fibroblasts, supporting its functional relevance in disease progression. Conclusions: These findings highlight the important role of miR-181a-5p in premature aging and suggest its potential as a therapeutic target for modulating senescence in progeroid syndromes. Full article
(This article belongs to the Section Rare Syndrome)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-45
Previous Issue
Next Issue
Back to TopTop