Diseases

15 pages, 1470 KB

Open AccessArticle

Exploring Mitochondrial DNA Copy Number in Italian Children with ADHD: Implications for Neurobiological Mechanisms

by Luigi Citrigno, Annamaria Cerantonio, Ludovico Neri, Pierluigi Sebastiani, Alessia Colanardi, Gabriele Turacchio, Tiziana Del Beato, Beatrice Marziani and Anna Aureli

Diseases 2025, 13(11), 378; https://doi.org/10.3390/diseases13110378 - 19 Nov 2025

Abstract

Background: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition frequently accompanied by behavioral dysregulation. While genetic factors involving monoaminergic systems have been implicated, emerging evidence suggests a role for mitochondrial dysfunction in ADHD pathophysiology. Mitochondrial DNA copy number (mtDNA-cn), a surrogate marker of mitochondrial [...] Read more.

Background: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition frequently accompanied by behavioral dysregulation. While genetic factors involving monoaminergic systems have been implicated, emerging evidence suggests a role for mitochondrial dysfunction in ADHD pathophysiology. Mitochondrial DNA copy number (mtDNA-cn), a surrogate marker of mitochondrial biogenesis and cellular energy demand, may reflect underlying neurobiological alterations and oxidative stress-related mechanisms relevant to ADHD. Methods: We assessed mtDNA-cn in the peripheral blood of 56 Italian children and adolescents with ADHD and 27 age- and sex-matched healthy controls. ADHD symptoms and aggressive behavior were evaluated using DSM-5 criteria and the Conners’ 3 Rating Scales. Genotyping was performed for MAOA (rs6323, rs1137070) and 5-HTT (rs4795541) polymorphisms. Results: ADHD patients showed significantly higher mtDNA-cn than controls (p = 0.002), supporting mitochondrial dysregulation. Comparing the ADHD patient subgroups with aggressive behavior and those without, a non-significant reduction in mtDNA-cn was observed in the first subgroup. Notably, individuals with the TT genotype (rs6323) or CC genotype (rs1137070) had significantly higher mtDNA-cn compared to controls with the same genotypes (p = 0.031). Similar increases were seen across all 5-HTT rs4795541 genotypes in ADHD patients. Conclusions: Our findings suggest that mitochondrial alterations may contribute to ADHD pathophysiology. The association between mtDNA-cn and monoaminergic gene variants highlights a potential link between neurotransmitter metabolism, oxidative stress, and mitochondrial function. Thus, mtDNA-cn may serve as a peripheral biomarker and therapeutic target in ADHD. Full article

(This article belongs to the Section Neuro-psychiatric Disorders)

► Show Figures

Figure 1

19 pages, 526 KB

Open AccessReview

Reframing Dental Anxiety: Cognitive Behavioral Therapy and Its Role in Phobia Treatment—A Narrative Review

by Dorina Stan, Dragoș Voicu, Pușica Zainea, Alexandra Toma and Anamaria Ciubară

Diseases 2025, 13(11), 377; https://doi.org/10.3390/diseases13110377 - 18 Nov 2025

Abstract

Dental phobia is a disabling yet underdiagnosed condition that prevents many patients from seeking essential oral healthcare, leading to avoidable pain, disease progression, and reduced quality of life. Cognitive Behavioral Therapy (CBT) is the most widely supported psychological intervention for specific phobias and [...] Read more.

Dental phobia is a disabling yet underdiagnosed condition that prevents many patients from seeking essential oral healthcare, leading to avoidable pain, disease progression, and reduced quality of life. Cognitive Behavioral Therapy (CBT) is the most widely supported psychological intervention for specific phobias and has demonstrated significant efficacy in reducing dental anxiety and avoidance. This narrative review synthesizes recent evidence on CBT applications for phobia management, with particular emphasis on dental settings. In addition to reviewing established mechanisms of CBT, this paper highlights emerging adjunctive approaches such as virtual reality, eye movement desensitization and reprocessing (EMDR), and hypnosis. Special attention is given to pediatric populations, trauma-exposed individuals, and patients with neurodevelopmental disorders, who are often underrepresented in clinical research. The findings underscore the central role of CBT in addressing dental phobia while identifying gaps in standardized protocols, long-term outcomes, and accessibility across diverse healthcare contexts. Future research should prioritize controlled trials, cultural adaptations, and the integration of psychological training into dental curricula to enhance the translation of evidence into everyday practice. Full article

(This article belongs to the Special Issue Mental Health—Management and Care, Multidisciplinary Approaches and Perspectives)

► Show Figures

Figure 1

10 pages, 914 KB

Open AccessCase Report

Toxic Shock Syndrome in a 45-Year-Old Woman Possibly Associated with Tampon Use: A Case Report of Multiorgan Failure Due to Streptococcus agalactiae

by Tina Zavidić, Ema Dejhalla and David Zahirović

Diseases 2025, 13(11), 376; https://doi.org/10.3390/diseases13110376 - 16 Nov 2025

Abstract

Background: Toxic shock syndrome (TSS) is a rare but potentially fatal condition most often caused by Staphylococcus aureus or Streptococcus pyogenes. However, other streptococcal species, including Streptococcus agalactiae (group B Streptococcus (GBS)), can also cause TSS, sometimes leading to severe complications, [...] Read more.

Background: Toxic shock syndrome (TSS) is a rare but potentially fatal condition most often caused by Staphylococcus aureus or Streptococcus pyogenes. However, other streptococcal species, including Streptococcus agalactiae (group B Streptococcus (GBS)), can also cause TSS, sometimes leading to severe complications, such as multiorgan failure. Case Description: We report the case of a 45-year-old woman who developed TSS associated with tampon use. She presented with fever, chills, hypotension, and leg pain, progressing rapidly to septic shock and multiorgan failure. Blood and urine cultures revealed S. agalactiae group B, while a gynecological examination identified Ureaplasma urealyticum and S. agalactiae. Imaging demonstrated bilateral pneumonic infiltrates and pleural effusion. The patient required intensive care, vasopressor support, and broad-spectrum antibiotic therapy, leading to full clinical recovery. Discussion: Despite advances in tampon design, menstrual TSS remains a significant clinical concern. Early symptoms may be nonspecific, but rapid progression highlights the need for timely recognition and intervention. Although S. agalactiae is an uncommon cause of TSS, it should be considered in relevant clinical scenarios. Prompt empirical antibiotic therapy, followed by targeted treatment based on culture results, along with supportive intensive care, is essential to improve outcomes. Conclusions: Menstrual TSS continues to pose a serious health risk. Physicians should maintain a high index of suspicion in tampon users presenting with fever, rash, and shock. Early diagnosis and rapid initiation of appropriate therapy are crucial to reducing morbidity and mortality. Full article

► Show Figures

Figure 1

16 pages, 1304 KB

Open AccessArticle

Causal Graphical Model of Bacterial Vaginosis in Pregnant Women

by Maricela García-Avalos, Juana Canul-Reich, Lil María Xibai Rodríguez-Henríquez and Erick Natividad De la Cruz-Hernández

Diseases 2025, 13(11), 375; https://doi.org/10.3390/diseases13110375 - 15 Nov 2025

Abstract

Background: This study developed a Causal Graphical Model (CGM) to analyze Bacterial Vaginosis (BV), a condition caused by an imbalance in the vaginal microbiota, whose bacterial composition varies among women. While previous studies used variable selection, clustering, and association rules to identify BV-associated [...] Read more.

Background: This study developed a Causal Graphical Model (CGM) to analyze Bacterial Vaginosis (BV), a condition caused by an imbalance in the vaginal microbiota, whose bacterial composition varies among women. While previous studies used variable selection, clustering, and association rules to identify BV-associated bacteria, these approaches lack visual tools to explore causal relationships and determine which are the most relevant. In contrast, the CGM generated in this study allows visualization of associated bacteria and their causal links, thereby identifying those most influential. Methods: Path Analysis (PA), a statistical structural equation modeling method, was used to construct the CGM, with emphasis on observable variables and to assess direct and indirect effects through correlations and covariances. PA was applied to an already-collected third-party dataset related to BV diagnosis, consisting of data from 132 pregnant women between 4 and 24 weeks of gestation. Results: The CGM, built using a theoretical model based on the Spearman correlation matrix, was validated through statistical metrics and by a clinical-biological expert. The resultant model highlights bacteria influencing BV diagnosis, specifically Mycoplasma hominis (Mh), Atopobium vaginae (Av), Gardnerella vaginalis (Gv), Megasphaera Type 1 (MT1), and Bacteria Associated with Bacterial Vaginosis Type 2 (BVAB2). Among them, MT1 and BVAB2 showed the strongest association with BV. Conclusions: The CGM effectively identifies causal associations among bacteria related to BV. Full article

► Show Figures

Graphical abstract

13 pages, 3681 KB

Open AccessArticle

T Helper and Cytotoxic T Cells Play an Important Role in Acute Gastric Injury

by Irfan F. Corovic, Jelena M. Pantic, Isidora A. Stanisavljevic, Sladjana M. Pavlovic, Nemanja U. Jovicic, Ivan P. Jovanovic, Gordana D. Radosavljevic and Bojana J. Simovic Markovic

Diseases 2025, 13(11), 374; https://doi.org/10.3390/diseases13110374 - 15 Nov 2025

Abstract

Background: Inflammation plays a central role in the formation of peptic ulcers, yet the contribution of cellular immunity remains poorly defined. This study aimed to clarify the contribution of cellular immunity to acute gastric mucosal injury. Methods: BALB/c mice received 80% ethanol via [...] Read more.

Background: Inflammation plays a central role in the formation of peptic ulcers, yet the contribution of cellular immunity remains poorly defined. This study aimed to clarify the contribution of cellular immunity to acute gastric mucosal injury. Methods: BALB/c mice received 80% ethanol via oral gavage to induce acute gastric injury. Stomachs were examined macroscopically and histologically, and gastric tissues were analyzed by qPCR, ELISA, and flow cytometry for cytokine expression, immune cell infiltration, and apoptosis. Results: Administration of ethanol exacerbated acute gastric injury in mice, as evidenced by extensive macroscopic lesions and severe disruption of mucosal architecture. This damage was accompanied by marked infiltration of CD11c⁺ dendritic cells, together with an increased frequency of CD86-expressing and IL-12-producing dendritic cells. In addition, there was greater accumulation of both CD4⁺ and CD8⁺ T lymphocytes, including elevated numbers of CD4⁺ and CD8⁺ cells producing IFN-γ and IL-17, as well as CD8⁺CD107a⁺ cytotoxic cells. Alongside these cellular alterations, ethanol exposure was accompanied by elevated levels of pro-inflammatory cytokines (IL-1β, TNF-α, IL-17, and IFN-γ) in gastric tissue. In parallel, ethanol exposure also promoted epithelial cell apoptosis, further contributing to mucosal deterioration. Conclusions: Our findings reveal for the first time that both CD4⁺ and CD8⁺ T cells participate in sterile ethanol-induced acute gastric injury, emphasizing cellular immunity as an important yet insufficiently studied contributor to mucosal damage and highlighting the necessity for further mechanistic and translational research. Full article

(This article belongs to the Special Issue Diseases: From Molecular to the Clinical Perspectives)

► Show Figures

Figure 1

27 pages, 1422 KB

Open AccessArticle

Stress, Anxiety, and Self-Efficacy in Hypertension: Evidence from a Romanian Case—Control Study

by Lucia Bubulac, Mirela Zivari, Irina Anca Eremia, Constantin Erena, Consuela-Mădălina Gheorghe, Iuliana-Raluca Gheorghe, Viorica Tudor, Claudia Florina Bogdan-Andreescu, Emin Cadar and Cristina-Crenguța Albu

Diseases 2025, 13(11), 373; https://doi.org/10.3390/diseases13110373 - 13 Nov 2025

Abstract

Background: Hypertension and psychological distress often coexist, though evidence from Eastern Europe is still limited. Stress, anxiety, and self-efficacy influence blood pressure control and treatment adherence. Their effect on hypertension prevention and treatment has not been systematically evaluated in Romania. Aim: This study [...] Read more.

Background: Hypertension and psychological distress often coexist, though evidence from Eastern Europe is still limited. Stress, anxiety, and self-efficacy influence blood pressure control and treatment adherence. Their effect on hypertension prevention and treatment has not been systematically evaluated in Romania. Aim: This study evaluated the associations between stress, anxiety, and self-efficacy in Romanian adults with and without hypertension to identify modifiable psychological factors relevant for integrated cardiovascular management. Methods: A retrospective case–control study was conducted among 215 adults, including individuals with hypertension and normotensive controls. Participants completed validated questionnaires assessing stress vulnerability, perceived stress, state and trait anxiety, self-efficacy, and Type A behavior, together with demographic and occupational data. Results: Hypertensive participants reported higher stress vulnerability, perceived stress, and anxiety, as well as lower self-efficacy, compared with controls. Type A behavior showed no association with hypertension. These differences remained consistent after accounting for demographic characteristics. Conclusions: Hypertension in Romanian adults is associated with a distinct psycho-emotional profile characterized by elevated stress and anxiety and reduced self-efficacy. Type A personality showed no association. The results emphasize the importance of recognizing and addressing modifiable psychological determinants in hypertension care. Integrating psychosocial assessment with personalized interventions, including mindfulness-based approaches, digital health support, and nurse-led telemonitoring, could improve treatment adherence, reduce emotional burden, and contribute to overall cardiovascular health. This region-specific evidence supports expanding hypertension management to include psychological care alongside standard medical approaches. Full article

(This article belongs to the Special Issue Insights into the Management of Cardiovascular Disease Risk Factors)

► Show Figures

Figure 1

14 pages, 1132 KB

Open AccessArticle

Silicosis and Pulmonary Functions Among Residents Exposed to Dust in Saraburi Thailand

by Narongkorn Saiphoklang, Pitchayapa Ruchiwit, Apichart Kanitsap, Pichaya Tantiyavarong, Pasitpon Vatcharavongvan, Srimuang Palungrit, Kanyada Leelasittikul, Apiwat Pugongchai and Orapan Poachanukoon

Diseases 2025, 13(11), 372; https://doi.org/10.3390/diseases13110372 - 13 Nov 2025

Abstract

Background: Silicosis is a lung disease caused by inhalation of crystalline silica dust, leading to lung fibrosis, respiratory symptoms, and impaired lung function. This study aimed to determine the prevalence of silicosis, asthma, and chronic obstructive pulmonary disease (COPD), and to identify [...] Read more.

Background: Silicosis is a lung disease caused by inhalation of crystalline silica dust, leading to lung fibrosis, respiratory symptoms, and impaired lung function. This study aimed to determine the prevalence of silicosis, asthma, and chronic obstructive pulmonary disease (COPD), and to identify factors associated with abnormal pulmonary function among residents living in dust-exposed areas in Thailand. Methods: A cross-sectional study was conducted from March 2024 to July 2024 among adults aged 18 years or older in Saraburi, Thailand. Data collected included demographics, comorbidities, respiratory symptoms, risk of silicosis, chest radiographs, and spirometry (forced vital capacity (FVC), forced expiratory volume in one second (FEV₁), and bronchodilator responsiveness (BDR)). Silicosis was confirmed based on a history of significant silica exposure and characteristic chest radiographic findings. Results: Among 290 participants (55.9% female, mean age 47.6 ± 16.4 years), the prevalence of silicosis, asthma, and COPD was 0.3%, 4.5%, and 10.3%, respectively. Abnormal chest radiographs were observed in 8.3%, and abnormal lung function in 34.1%, including restrictive lung patterns (16.6%), airway obstruction (9.0%), mixed defects (2.8%), and small-airway disease (5.9%). BDR was observed in 4.8%. Logistic regression identified increasing age as a significant predictor of abnormal lung function. Conclusions: Silicosis prevalence was lower than that of asthma and COPD, but abnormal pulmonary function—especially restrictive defects—was common. Notably, the prevalence of asthma and COPD was higher than previously reported community-based diagnosis rates, suggesting potential underdiagnosis. Older age was associated with a higher likelihood abnormal lung function. These findings highlight the need for targeted surveillance, preventive measures, and public health interventions to mitigate the respiratory impacts of dust exposure in community settings Full article

► Show Figures

Figure 1

51 pages, 7121 KB

Open AccessCase Report

Total Reversal of ALS Confirmed by EMG Normalization, Structural Reconstitution, and Neuromuscular–Molecular Restoration Achieved Through Computerized Brain-Guided Reengineering of the 1927 Nobel Prize Fever Therapy: A Case Report

by M. Marc Abreu, Mohammad Hosseine-Farid and David G. Silverman

Diseases 2025, 13(11), 371; https://doi.org/10.3390/diseases13110371 - 12 Nov 2025

Abstract

Background: Neurological disorders are the leading cause of disability, affecting over three billion people worldwide. Amyotrophic lateral sclerosis (ALS) is among the most feared and uniformly fatal neurodegenerative diseases, with no therapy capable of restoring lost function. Methods: We report the first application [...] Read more.

Background: Neurological disorders are the leading cause of disability, affecting over three billion people worldwide. Amyotrophic lateral sclerosis (ALS) is among the most feared and uniformly fatal neurodegenerative diseases, with no therapy capable of restoring lost function. Methods: We report the first application of therapeutic fever to ALS using Computerized Brain-Guided Intelligent Thermofebrile Therapy (CBIT²). This fully noninvasive treatment, delivered through an FDA-approved computerized platform, digitally reengineers the 1927 Nobel Prize-recognized malarial fever therapy into a modern treatment guided by the Brain–Eyelid Thermoregulatory Tunnel. CBIT² induces therapeutic fever through synchronized hypothalamic feedback, activating heat shock proteins, which are known to restore proteostasis and neuronal function. Case presentation: A 56-year-old woman was diagnosed with progressive ALS at the Mayo Clinic, with electromyography (EMG) demonstrating fibrillation and fasciculation indicative of denervation corroborated by neurological and MRI findings; the patient was informed that she had an expected survival of three to five years. A neurologist from Northwestern University confirmed the diagnosis and thus maintained the patient on FDA-approved ALS drugs (riluzole and edaravone). Her condition rapidly worsened despite pharmacological treatment, and she underwent CBIT², resulting in (i) electrophysiological reversal with complete disappearance of denervation; (ii) biomarker correction, including reductions in neurofilament and homocysteine, IL-10 normalization (previously linked to mortality), and robust HSP70 induction; (iii) restoration of gait, swallowing, respiration, speech, and cognition; (iv) reconstitution of tongue structure; and (v) return to complex motor tasks, including golf, pickleball, and swimming. Discussion: This case provides the first documented evidence that ALS can be reversed through digitally reengineered fever therapy aligned with thermoregulation, which induces heat shock response and upregulates heat shock proteins, resulting in the patient no longer meeting diagnostic criteria for ALS and discontinuation of ALS-specific medications. Beyond ALS, shared protein-misfolding pathology suggests that CBIT² may extend to Alzheimer’s, Parkinson’s, and related disorders. By modernizing this Nobel Prize-recognized therapeutic principle with computerized precision, CBIT² establishes a framework for large-scale clinical trials. A century after fever therapy restored lost brain function and so decisively reversed dementia paralytica such that it earned the 1927 Nobel Prize in Medicine, CBIT² now safely harnesses the therapeutic power of fever through noninvasive, intelligent, brain-guided thermal modulation. Amid a global brain health crisis, fever-based therapies may offer a path to preserve thought, memory, movement, and independence for the more than one-third of humanity currently affected by neurological disorders. Full article

(This article belongs to the Special Issue Research Progress in Neurodegenerative Diseases)

► Show Figures

Graphical abstract

9 pages, 344 KB

Open AccessArticle

The Diagnostic Utility of the Triptorelin Stimulation Test Compared to the Standard Gonadotropin-Releasing Hormone Stimulation Test in Children with Idiopathic Central Precocious Puberty

by Giorgio Sodero

Diseases 2025, 13(11), 370; https://doi.org/10.3390/diseases13110370 - 12 Nov 2025

Abstract

Background: Central precocious puberty (CPP) is diagnosed through a combination of clinical, auxological, and biochemical parameters, with pharmacological stimulation tests considered the diagnostic gold standard. In recent years, triptorelin, a long-acting Gonadotropin-Releasing Hormone (GnRH) analog, has been increasingly adopted in clinical practice due [...] Read more.

Background: Central precocious puberty (CPP) is diagnosed through a combination of clinical, auxological, and biochemical parameters, with pharmacological stimulation tests considered the diagnostic gold standard. In recent years, triptorelin, a long-acting Gonadotropin-Releasing Hormone (GnRH) analog, has been increasingly adopted in clinical practice due to limited availability of native GnRH. Objective: To compare the clinical, auxological, and hormonal profiles of girls diagnosed with idiopathic CPP using either the classical GnRH stimulation test or the triptorelin test. Methods: This retrospective study included 136 female patients diagnosed with CPP and followed for at least two years at a single pediatric endocrinology unit. Of these, 101 underwent a GnRH stimulation test, and 35 were assessed using the triptorelin test. Baseline and stimulated hormonal parameters, growth data, and IGF-1 levels were collected. A multivariate linear regression model was used to explore the influence of age, test type, and other covariates on the LH peak response. Results: Anthropometric and baseline hormonal parameters were comparable between the two groups. The LH peak was significantly higher in the GnRH group (9.8 ± 3.1 IU/L at 60 min) than in the triptorelin group (6.8 ± 2.4 IU/L at 4 h). FSH levels were also significantly lower following triptorelin stimulation (p = 0.004), while the LH/FSH ratio did not differ significantly. Multivariate analysis confirmed that triptorelin was associated with a lower LH peak (β = −2.2, p = 0.008), particularly in younger patients, with a significant interaction between age and test type (β = 0.6, p = 0.022). Conclusions: Both GnRH and triptorelin stimulation tests are valid tools for CPP diagnosis. However, the GnRH test appears to elicit a more robust LH response, especially in younger patients, whereas the triptorelin test is associated with delayed and lower LH peaks. Full article

(This article belongs to the Special Issue Recent Therapeutic Advances in Gynecological Diseases and Clinical Management)

► Show Figures

Figure 1

12 pages, 6117 KB

Open AccessCase Report

Treatment of Neglected Elbow Dislocation with Secondary Heterotopic Ossification

by Mihai Tudor Gavrilă, Vlad Cristea and Cristea Stefan

Diseases 2025, 13(11), 369; https://doi.org/10.3390/diseases13110369 - 11 Nov 2025

Abstract

A traumatic elbow dislocation that remains unreduced for more than three weeks is considered a neglected elbow dislocation. We report a case of a patient with a neglected elbow dislocation combined with a terrible triad injury (elbow dislocation with fractures of the coronoid [...] Read more.

A traumatic elbow dislocation that remains unreduced for more than three weeks is considered a neglected elbow dislocation. We report a case of a patient with a neglected elbow dislocation combined with a terrible triad injury (elbow dislocation with fractures of the coronoid process and radial head). Initially, the patient was managed with three weeks of cast immobilization followed by physiotherapy. However, six months after the trauma, he presented to our clinic with severe heterotopic ossification, significant pain, and nearly complete elbow stiffness. An open surgical intervention was performed, involving excision of the heterotopic bone, reduction in the dislocation, and suturing of the anterior capsule to the coronoid process. Given the irreparable fracture of the radial head, radial head arthroplasty was also performed. At 18-month follow-up, the elbow was stable and pain-free, with flexion–extension of 80°, pronation of 85°, and supination of 80°. This case underscores the critical importance of early diagnosis and intervention to prevent long-term complications in neglected elbow dislocations. Full article

► Show Figures

Figure 1

16 pages, 720 KB

Open AccessArticle

Risk Factors and Predictive Parameters of Necrotizing Enterocolitis in Preterm Infants—A Single-Center Retrospective Study

by Tamas Toth, Angela Borda, Reka Borka-Balas, Manuela Cucerea, Emoke Andrea Szasz, Horea Gozar and Radu-Alexandru Prisca

Diseases 2025, 13(11), 368; https://doi.org/10.3390/diseases13110368 - 10 Nov 2025

Abstract

Background and Objectives: Necrotizing enterocolitis (NEC) represents a severe gastrointestinal emergency in preterm infants. The aim of this study was to identify risk factors and predictive parameters for NEC requiring surgery and to evaluate associated short-term outcomes. Materials and Methods: We [...] Read more.

Background and Objectives: Necrotizing enterocolitis (NEC) represents a severe gastrointestinal emergency in preterm infants. The aim of this study was to identify risk factors and predictive parameters for NEC requiring surgery and to evaluate associated short-term outcomes. Materials and Methods: We conducted a retrospective study in preterm neonates diagnosed with NEC admitted to a tertiary neonatal intensive care unit (NICU) between January 2015 and May 2025. Demographic data, perinatal events, risk factors, clinical signs, imaging findings, and outcomes were analyzed, with a particular focus on surgically managed cases. Descriptive and inferential statistical methods were applied. Results: Forty-four infants met the inclusion criterion. The mean gestational age (GA) was 29.34 ± 4.3 weeks, and the mean birth weight was 1100 ± 563 g. According to Bell’s severity index, 45.5% had Bell Stage I, 36.4% Stage II, and 18.2% Stage III. Eleven patients (25%) required surgery. All surgical patients had abdominal distension, and 63.6% had bilious gastric residue. Abdominal X-ray showed pneumoperitoneum in 72.7% and pneumatosis intestinalis in 27.3% of cases. Laboratory abnormalities, including thrombocytopenia, elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH), and hyponatremia (45.5%; 133 ± 6.95 mmol/L), were frequently associated with surgical NEC. A lower GA and birth weight correlated with a higher Bell stage (p = 0.0085 and p = 0.0291). Overall mortality was 29.5% (13/44); surgical mortality was 9.1% (1/11). Conclusions: In this single-center lot, low gestational age and birth weight, abdominal distension with bilious residuals, systemic inflammation, and hyponatremia were frequent among infants who required surgery. Selected infants may benefit from early surgery even without perforation, but inferences are limited by this study’s sample size and retrospective design. Prospective multi-center studies are needed to validate predictors and refine surgical timing. Full article

► Show Figures

Figure 1

17 pages, 259 KB

Open AccessArticle

Psychological and Psychosocial Effects of Cancer on Young Patients and Survivors in Italy: A Mixed-Methods Study on the Challenges and Meaning-Making Factors

by Martina Gentile, Lucia Ronconi, Marco Romeo, Ciro De Vincenzo, Elena Burattini, Chiara Rutigliano, Nicola Santoro, Giulia Zucchetti, Franca Fagioli and Ines Testoni

Diseases 2025, 13(11), 367; https://doi.org/10.3390/diseases13110367 - 10 Nov 2025

Abstract

Background: Pediatric oncological diagnoses and treatments pose complex biopsychosocial challenges for both patients and their families. These experiences can significantly disrupt daily life, evoke intense emotional responses, and raise concerns about the future, often leading to long-term psychological implications. Objective: This study aimed [...] Read more.

Background: Pediatric oncological diagnoses and treatments pose complex biopsychosocial challenges for both patients and their families. These experiences can significantly disrupt daily life, evoke intense emotional responses, and raise concerns about the future, often leading to long-term psychological implications. Objective: This study aimed to assess the emotional functioning of children undergoing cancer treatment and to explore the lasting psychological effects reported by young adult survivors of pediatric cancer. Methods: A mixed-methods approach was employed. In total, 52 minors and their caregivers were recruited from two pediatric oncology units in Italy (Turin and Bari), while 18 young adults diagnosed during childhood were recruited from clinical and community settings in Ancona and Bari. Standardized instruments were used to evaluate emotional symptoms and broader psychological functioning in the pediatric sample, while self-report measures assessed psychological well-being and quality of life in the young adult group. To complement these data, semi-structured interviews were conducted with the young adult survivors to investigate the long-term psychosocial and psychological impacts of pediatric cancer. Results: The quantitative results indicate generally low levels of psychological distress in both groups. However, the qualitative findings reveal the complexity of post-cancer identity, highlighting experiences of resilience, emotional ambivalence, and redefinition of self. Conclusions: These results underscore the importance of addressing the psychological well-being of pediatric oncology patients and young adult survivors beyond the medical treatment phase, with a focus on long-term psychosocial support and individualized care. Full article

(This article belongs to the Special Issue Mental Health—Management and Care, Multidisciplinary Approaches and Perspectives)

10 pages, 1332 KB

Open AccessArticle

In Vitro Activity of Silver-Bound Titanium Dioxide (TiAB) Against Multidrug-Resistant Vaginal Pathogens

by Lorenzo Drago, Luigi Regenburgh De La Motte, Erika Stefàno, Vincenzo Minasi, Loredana Deflorio, Sofia Benedetti and Fabiana Giarritiello

Diseases 2025, 13(11), 366; https://doi.org/10.3390/diseases13110366 - 10 Nov 2025

Abstract

Background: Gynecological infections, including bacterial vaginosis, vulvovaginal candidiasis, and recurrent urinary tract infections, represent a major clinical burden and are often complicated by biofilm formation and antimicrobial resistance. Novel non-antibiotic strategies are urgently needed. We previously demonstrated the antimicrobial activity of silver-bound titanium [...] Read more.

Background: Gynecological infections, including bacterial vaginosis, vulvovaginal candidiasis, and recurrent urinary tract infections, represent a major clinical burden and are often complicated by biofilm formation and antimicrobial resistance. Novel non-antibiotic strategies are urgently needed. We previously demonstrated the antimicrobial activity of silver-bound titanium dioxide (TiAB) against multidrug-resistant bacteria isolated from dermatological infections. Objectives: We evaluated whether TiAB, at concentrations used in marketed medical devices, exerts antibacterial and antifungal effects against clinically relevant vaginal isolates by determining Minimum Inhibitory Concentration/ Minimum Bactericidal and Fungicidal Concentration (MIC, MBC/MFC), and time–kill kinetics. Methods: A total of 73 clinical isolates were collected from vaginal swabs, including Staphylococcus aureus (MSSA, MRSA), Escherichia coli (ESBL+ and non-ESBL), Klebsiella pneumoniae, Enterococcus spp., Streptococcus agalactiae, and Candida albicans. Minimum inhibitory concentrations (MICs) and minimum bactericidal/fungicidal concentrations (MBCs/MFCs) were determined by broth microdilution, and bactericidal activity was confirmed by time-kill assays. Results: TiAB exhibited potent activity against Gram-negative bacteria, with median MIC values of 1–2% (w/v) for E. coli and K. pneumoniae. Gram-positive isolates, including S. agalactiae and Enterococcus spp., showed higher MIC values (2–4%). Candida albicans displayed fungistatic inhibition at 4%. Time-kill assays confirmed rapid bactericidal effects for Gram-negative isolates within 8 h at 2× MIC, while Gram-positive bacteria required prolonged exposure. Conclusions: These findings extend previous evidence of TiAB’s antimicrobial properties to gynecological pathogens, supporting its potential as a topical, non-antibiotic option for managing vaginal infections in an era of rising antimicrobial resistance. Further in vivo validation is warranted. Full article

► Show Figures

Figure 1

17 pages, 647 KB

Open AccessArticle

Residual Platelet Reactivity and Dyslipidemia in Post-CABG Patients Undergoing Repeat Revascularization: Insights from Kazakhstan

by Aisulu Mussagaliyeva, Sholpan Zhangelova, Laura Danyarova, Friba Nurmukhammad, Dina Kapsultanova, Orazbek Sakhov, Farida Rustamova, Akhmetzhan Sugraliyev and Dana Akhmentayeva

Diseases 2025, 13(11), 365; https://doi.org/10.3390/diseases13110365 - 9 Nov 2025

Abstract

Background: Coronary artery bypass grafting (CABG) remains a standard revascularization strategy for patients with advanced coronary artery disease (CAD). However, a considerable proportion of patients experience recurrent ischemia requiring repeat revascularization. Residual platelet reactivity (RPR) and dyslipidemia are recognized as key factors contributing [...] Read more.

Background: Coronary artery bypass grafting (CABG) remains a standard revascularization strategy for patients with advanced coronary artery disease (CAD). However, a considerable proportion of patients experience recurrent ischemia requiring repeat revascularization. Residual platelet reactivity (RPR) and dyslipidemia are recognized as key factors contributing to graft failure and disease progression. Methods: This observational study was conducted at a tertiary cardiology center in Kazakhstan. A total of 195 post-CABG patients who underwent repeat coronary angiography between 2023 and 2024 recruitment period for recurrent ischemic symptoms within 6–36 months after surgery were included. Clinical characteristics, comorbidities, lipid profiles, and antiplatelet response were analyzed. RPR was measured using the VerifyNow P2Y12 assay when available. Dyslipidemia was defined according to the 2019 and 2021 European guidelines. Results: Elevated RPR was identified in 45% of patients (n = 90) despite dual antiplatelet therapy (p < 0.01). Poor lipid control was frequent among those who underwent repeat percutaneous coronary intervention (PCI), particularly elevated levels of low-density lipoprotein cholesterol (LDL-C) and total cholesterol (p < 0.05). Both elevated RPR and dyslipidemia were independently associated with native coronary disease progression and graft failure (RPR: OR = 2.8; 95% CI 1.4–5.6; p = 0.003; dyslipidemia: OR = 2.2; 95% CI 1.1–4.3; p = 0.02). The use of ezetimibe was independently associated with a significantly lower risk of repeat stenting (OR = 0.12; 95% CI 0.02–0.75; p = 0.023). Smokers were younger, had lower blood pressure, and less frequently presented with diabetes or chronic kidney disease, demonstrating a pattern consistent with the “smoker’s paradox.” Conclusions: Residual platelet reactivity and dyslipidemia are common and clinically relevant predictors of repeat revascularization after CABG. Optimization of antiplatelet and lipid-lowering therapy should be prioritized in secondary prevention for this high-risk population. These findings are particularly important in Kazakhstan, where post-CABG management strategies warrant further improvement. Full article

(This article belongs to the Section Cardiology)

► Show Figures

Graphical abstract

21 pages, 734 KB

Open AccessArticle

Clinical Profiles, Management, and Outcomes of Complicated Pneumonia in Children: A Retrospective Study from Tertiary Centers in Jordan

by Lina Alshadfan, Muna Kilani, Saleh Abualhaj, Osama Abu-Salah, Mohammad Ghassab Deameh, Ahmad Nidal Al-Faouri, Mustafa Elayyan, Randa Othman and Reem Abuzraiq

Diseases 2025, 13(11), 364; https://doi.org/10.3390/diseases13110364 - 8 Nov 2025

Abstract

Background: Complicated pneumonia (CP) in children presents in various forms—including empyema, necrotizing pneumonia (NP), necrotizing pneumonia with pleural effusion (NP + PE), and parapneumonic pleural effusion (PPE)—and is associated with significant morbidity despite advances in antimicrobial therapy. This study aimed to describe and [...] Read more.

Background: Complicated pneumonia (CP) in children presents in various forms—including empyema, necrotizing pneumonia (NP), necrotizing pneumonia with pleural effusion (NP + PE), and parapneumonic pleural effusion (PPE)—and is associated with significant morbidity despite advances in antimicrobial therapy. This study aimed to describe and compare the clinical characteristics, laboratory findings, antibiotic use, and outcomes across different CP subtypes in hospitalized children and to assess the impact of prior antibiotic use on presentation and treatment outcomes. Methods: This retrospective observational study included 58 children admitted with CP to tertiary hospitals in Jordan. Patients were categorized into four subtypes: empyema (n = 4), NP (n = 4), NP + PE (n = 17), and PPE (n = 33). Demographic data, clinical features, laboratory results, antibiotic regimens, and clinical outcomes were analyzed. Multivariable regression was used to identify predictors of prior antibiotic use. Results: Fever and cough were the most common symptoms (96.6%). Over 40% of patients had received antibiotics prior to admission. Those pre-treated had significantly longer symptom duration (8.2 vs. 4.5 days, p < 0.001), longer hospitalization (18.2 vs. 14.6 days, p = 0.023), and more frequent chest tube insertion (66.7% vs. 35.3%, p = 0.019). Streptococcus pneumoniae was the most common organism isolated in culture-positive cases. Vancomycin-based regimens were the most frequently used treatments. Univariate regression analysis showed that patients with prior antibiotic use had significantly higher odds of longer hospitalization duration (OR = 1.11, p = 0.028) and chest tube insertion (OR = 3.67, p = 0.021). Conclusions: Complicated pneumonia in children remains a diverse and clinically significant condition. The findings demonstrate that prolonged symptom duration prior to hospitalization and certain clinical interventions were associated with prior antibiotic exposure. These results provide insight into local disease patterns and prescribing behaviors, which may help inform strategies to optimize antimicrobial stewardship and improve care pathways for affected children. Full article

(This article belongs to the Section Respiratory Diseases)

► Show Figures

Figure 1

38 pages, 2695 KB

Open AccessReview

Research Progress on the Efficacy and Mechanism of Acupuncture in Treating Chronic Gastritis

by Jing He, Hongye Wang, Cong Che, Anjie Wang, Ru Nie, Jinghong Tan, Jialin Jia, Zijian Liu, Tie Li and Guojuan Dong

Diseases 2025, 13(11), 363; https://doi.org/10.3390/diseases13110363 - 7 Nov 2025

Abstract

Chronic gastritis (CG) is a prevalent digestive disorder. It progresses through multiple stages, has an insidious onset, and can lead to severe complications if untreated. Modern treatments primarily aim to eradicate Helicobacter pylori and relieve symptoms. However, drug resistance and adverse effects often [...] Read more.

Chronic gastritis (CG) is a prevalent digestive disorder. It progresses through multiple stages, has an insidious onset, and can lead to severe complications if untreated. Modern treatments primarily aim to eradicate Helicobacter pylori and relieve symptoms. However, drug resistance and adverse effects often limit their effectiveness. As a primary traditional Chinese medicine (TCM) therapy, acupuncture treats CG through multi-target mechanisms. This review systematically outlines the classification and pathology of CG. It also comprehensively analyzes animal and clinical studies on acupuncture for CG from the past decade. The study summarizes the mechanisms of acupuncture and related therapies for CG, covering gastric mucosal function, metabolism, intestinal flora, gastrointestinal hormones, apoptosis, inflammation, and oxidative stress. It further explores the relationships among diseases, interventions, acupoints, and molecular pathways. Additionally, it compares the therapeutic profiles of different external therapies. The review also examines the current state of clinical research, including the selection of acupoints, treatment duration, and outcome assessment. The results demonstrate that external therapies effectively alleviate common CG symptoms such as abdominal distension, acid reflux, and stomach pain. These treatments also improve gastric mucosal health and modulate serum levels of inflammatory factors, oxidative stress markers, and gastrointestinal hormones. In vivo experiments using chronic non-atrophic gastritis (CNAG) and chronic atrophic gastritis (CAG) models confirm these benefits, showing changes in key biomarkers and elucidating potential mechanisms. Nevertheless, future high-quality, large-sample clinical trials are still needed to firmly establish efficacy. Further mechanistic studies are also needed to validate the interconnections among relevant signaling pathways. Full article

► Show Figures

Figure 1

13 pages, 696 KB

Open AccessArticle

Blood Urea/Creatinine Ratio and Mortality in Ambulatory Patients with Heart Failure with Reduced Ejection Fraction

by Andrew S. Oswald, Muhammad S. Hussain, Mohsin H. K. Roshan, Filippo Pigazzani, Anna-Maria Choy, Faisel Khan, Ify R. Mordi and Chim C. Lang

Diseases 2025, 13(11), 362; https://doi.org/10.3390/diseases13110362 - 7 Nov 2025

Abstract

Background: Chronic heart failure with reduced ejection fraction (HFrEF) is associated with high mortality, and renal dysfunction is common in these patients. Blood urea/creatinine ratio (UCR) has been identified as a potential prognostic marker, reflecting both renal function and neurohormonal activity. We assessed [...] Read more.

Background: Chronic heart failure with reduced ejection fraction (HFrEF) is associated with high mortality, and renal dysfunction is common in these patients. Blood urea/creatinine ratio (UCR) has been identified as a potential prognostic marker, reflecting both renal function and neurohormonal activity. We assessed whether a UCR ≥ 95 at discharge from an outpatient service was associated with increased mortality. Methods: This retrospective study reviewed 337 patients (age 72.7 ± 14.3 years; 64.7% Male; Mean LVEF 33.2 ± 8.9%) with HFrEF referred to the Heart Failure Nurse Service at NHS Tayside for optimisation of heart failure medication. Cox proportional hazards models were used to assess the association between UCR and all-cause mortality. Results: Receiver operating characteristic (ROC) analysis identified a UCR threshold of 95 (area under the curve [AUC] 0.701) as predictive of mortality. Results demonstrated that a UCR ≥ 95 was independently associated with increased mortality (HR 1.85, 95% CI 1.09–3.14, p = 0.022). A high UCR was associated with increased mortality even in patients with preserved eGFR, a group typically considered at lower risk (HR 4.03, 95% CI 1.50–10.9, p = 0.006). Conclusions: These findings suggest that UCR could be a useful addition for identifying high-risk patients who may benefit from closer monitoring and more aggressive intervention following optimisation of heart failure medication. Full article

(This article belongs to the Special Issue Insights into the Management of Cardiovascular Disease Risk Factors)

► Show Figures

Figure 1

9 pages, 414 KB

Open AccessArticle

Psychiatric Comorbidities in Parkinson’s Disease: A Moroccan Perspective on Anxiety and Depression

by Khaoula Elcadi, Oussama Cherkaoui Rhazouani, Nissrine Louhab, Najib Kissani and Mohamed Chraa

Diseases 2025, 13(11), 361; https://doi.org/10.3390/diseases13110361 - 6 Nov 2025

Abstract

Background/Objectives: An individual’s quality of life is greatly impacted by the motor and non-motor symptoms of Parkinson’s disease (PD), which include anxiety and depression. Using the Hospital Anxiety and Depression Scale (HADS), this study sought to determine the prevalence of anxiety and depression [...] Read more.

Background/Objectives: An individual’s quality of life is greatly impacted by the motor and non-motor symptoms of Parkinson’s disease (PD), which include anxiety and depression. Using the Hospital Anxiety and Depression Scale (HADS), this study sought to determine the prevalence of anxiety and depression in Moroccan patients with Parkinson’s disease (PD) and investigate any possible associations with clinical characteristics and pharmacological treatment. Methods: The HADS was used to assess 100 PD patients in total. Clinical and demographic information, including prescription drug use, was gathered. The relationships between HADS scores and clinical factors were evaluated using Pearson’s correlation. Results: According to the HADS assessment, 20% of respondents had no anxiety symptoms, 17% had borderline symptoms, and 63% of patients reported definite anxiety symptoms. Of those with depression, 24% showed no symptoms, 14% were borderline, and 62% were certain. The average HADS-A and HADS-D scores were 2.34 and 2.43, respectively. L-DOPA alone was used to treat half of the patients, while combinations of Trivastal, Sifrol, anticholinergics, or antidepressants were given to the other half. There were no discernible correlations between HADS scores and clinical or demographic traits. Conclusions: The HADS is a useful instrument for assessing anxiety and depression in PD patients. Regardless of the method of treatment or stage of the disease, psychiatric symptoms are prevalent. For PD patients to benefit from early interventions and achieve an improved quality of life, routine screening is crucial. Full article

(This article belongs to the Special Issue Research Progress in Neurodegenerative Diseases)

► Show Figures

Figure 1

20 pages, 3826 KB

Open AccessArticle

MicroRNA Signatures in Serous Ovarian Cancer: A Comparison of Prognostic Marker Targets in African Americans and Caucasians

by Jane M. Muinde, Celina Romi Yamauchi, Joseph Cruz, Alena A. McQuarter, Kyah Miller, Umang Sharma, Skyler Schiff, Isaac Kremsky, Saied Mirshahidi, Cody S. Carter and Salma Khan

Diseases 2025, 13(11), 360; https://doi.org/10.3390/diseases13110360 - 6 Nov 2025

Abstract

Background: Ovarian cancer (OC) is the second most common gynecologic malignancy in the United States and remains the leading cause of death among cancers of the female reproductive system. Alarmingly, mortality rates have risen disproportionately among women of African ancestry compared to those [...] Read more.

Background: Ovarian cancer (OC) is the second most common gynecologic malignancy in the United States and remains the leading cause of death among cancers of the female reproductive system. Alarmingly, mortality rates have risen disproportionately among women of African ancestry compared to those of European or Asian descent. Identifying microRNA (miRNA) signatures that contribute to these disparities may enhance prognostic accuracy and inform personalized therapeutic strategies. Methods: In this study, we identified prognostic markers of overall survival in serous ovarian cancer (SOC) using data from The Cancer Genome Atlas (TCGA) and the Human Protein Atlas. Integrative bioinformatic analyses revealed three key prognostic genes—TIMP3 (Tissue Inhibitor of Metalloproteinases-3), BRAF (v-raf murine sarcoma viral oncogene homolog B), and ITGB1 (Integrin Beta-1)—as critical molecular determinants associated with survival in patients with SOC. Candidate miRNAs regulating these genes were predicted using TargetScanHuman v8.0, identifying a core regulatory set comprising miR-192, miR-30d, miR-16-5p, miR-143-3p, and miR-20a-5p. To validate their clinical relevance, formalin-fixed, paraffin-embedded (FFPE) and fresh SOC tumor samples were obtained from African American and Caucasian patients who underwent surgery at Loma Linda University (LLU) between 2010 and 2023. Results and Discussion: Among all these, ITGB1 (p = 0.00033), TIMP3 (p = 0.0035), and BRAF (p = 0.026) emerged as statistically significant predictors. Following total RNA extraction, cDNA synthesis, and quantitative reverse transcription PCR (qRT-PCR), the expression levels of these miRNAs and their target genes were quantified. In the LLU cohort, ITGB1 and TIMP3 were significantly upregulated in African American patients compared to Caucasian patients (p < 0.01 and p < 0.02, respectively). Among the miRNAs, miR-192-5p was particularly noteworthy, showing marginally differential expression in LLU samples (p = 0.0712) but strong statistical significance in the TCGA cohort (p = 0.00013), where elevated expression correlated with poorer overall survival (p = 0.021). Pathway enrichment and gene ontology analyses (miRTargetLink2.0, Enrichr) revealed interconnected regulatory networks linking miR-192, miR-16-5p, miR-143-3p, and miR-20a-5p to ITGB1; miR-143-3p/miR-145-5p to BRAF; and miR-16-5p and miR-30c/d to TIMP3. Conclusions: Collectively, these findings identify distinct miRNA–mRNA regulatory signatures—particularly the miR-192-5p–ITGB1/TIMP3 axis—as potential clinically relevant biomarkers that may contribute to racial disparities and disease progression in ovarian cancer. Full article

► Show Figures

Figure 1

Journal Description

Diseases

Latest Articles

Journal Menu

Journal Browser

Highly Accessed Articles

Latest Books

E-Mail Alert

News

Topics

Conferences

Special Issues

Topical Collections

Further Information

Guidelines

MDPI Initiatives

Follow MDPI