Search Results (63)

The Popeye domain-containing protein 1 (Popdc1), also known as Bves, plays a crucial role in maintaining skeletal muscle homeostasis, with its variants leading to limb–girdle muscular dystrophy type R25. Skeletal muscles of patients with the homozygous missense variant of Bves exhibit impaired membrane trafficking, while skeletal muscle fibers in bves^S191F homozygous mutant zebrafish are significantly reduced and disorganized. However, the mechanism by which the absence of bves induces skeletal muscle atrophy remains unclear. In this study, we discovered a novel mechanism whereby bves deficiency drives skeletal muscle atrophy by disrupting mitochondrial structure and function. Our findings indicate that bves knockout leads to a significant decrease in zebrafish’s ability to swim, atrophy of skeletal muscle tissue, loss of cell membrane localization signals, and abnormalities in mitochondrial structure and function. After an 8-week intervention of regular aerobic exercise, the symptoms of skeletal muscle atrophy in bves knockout zebrafish were significantly alleviated, and the expression levels of genes and proteins related to mitochondrial were effectively rescued. These findings establish a connection between bves deficiency-induced disruption of mitochondrial structure and function and the onset and progression of skeletal muscle tissue atrophy symptoms, thereby laying a molecular foundation for exercise rehabilitation strategies in atrophic myopathy. Full article

Eggplant (Solanum melongena L.) is highly susceptible to chilling injury (CI) during cold storage, with severity being strongly influenced by fruit maturity stage. At the tissue level, the peel acts as the primary site of cold-stress metabolic responses. This study evaluated the effect of pre-storage glycine betaine treatment (GB, 10 mM) on CI in purple eggplant at baby (BB, low sensitivity) and commercial (CC, high sensitivity) maturity stages stored at 4 °C for 20 days, integrating the use of ATR-FTIR spectroscopy as a rapid, non-destructive tool to monitor quality in the fruit peel. Physiological traits including chilling injury index (CII) and fruit rigidity were integrated with peel-specific ATR-FTIR spectroscopy combined with chemometric analysis to describe structural and metabolic behavior. BB fruit showed higher tolerance to CI, reaching a CII 23% lower than CC after 20 d, along with greater rigidity retention. GB treatment was significantly effective in reducing CI in both maturity stages by decreasing CII by 23% for BB and 32% for CC fruit, and delaying symptom onset. FTIR analysis revealed that the main peel spectral changes during storage occurred in the amide–phenolic (1653–1515 cm⁻¹) and polysaccharide (~1017 cm⁻¹) regions. Control fruit showed progressive shifts in these regions indicating structural disorganization, while GB-treated fruit delayed and attenuated spectral changes. Chemometric analysis (OPLS-DA) clearly discriminated samples according to maturity stage, treatment, and storage time. Overall, the results demonstrate that chilling susceptibility is determined by maturity stage, that the GB treatment enhanced CI tolerance—especially in sensitive CC fruit—and that ATR-FTIR coupled with chemometrics provides an effective approach for rapid non-destructive monitoring of postharvest quality changes in eggplant during cold storage. Full article

Sjögren’s Disease is an autoimmune epithelitis targeting the exocrine glands, predominantly the salivary and lacrimal glands, resulting in the major symptoms of dry mouth and dry eyes. The aim of this study is to review the pertinent literature on studies linking the oral manifestations of SjD patients, with the underlying molecular events driving SjD pathogenesis. These include mechanisms inducing innate sensing in salivary gland epithelial cells, activation of interferon signaling pathway, amplification of cytokines and chemokines, and orchestration of the inflammatory milieu in salivary glands, as well as mechanisms inducing salivary epithelial tissue destruction and secretory dysfunction, such as programmed cell death pathways, mitochondrial dysfunction, structural disorganization, loss of junctional integrity, and quantitative and qualitative aberrations in salivary secretory process. Full article

Background: Cataract is a progressive lens opacity. According to the World Health Organization, about 45 million people in the world are blind, with about half of these cases attributable to cataracts. Due to the complexity of cataract disease, current research on cataracts is far from sufficient, so it is especially important to understand the development process and the pathogenic factors of cataracts. Myodes rufocanus (M. rufocanus) is an animal of the M. rufocanus of the hamster family Volinae. In developing M. rufocanus, we found an individual of M. rufocanus with a congenital cataract phenotype. We confirmed the symptoms of cataract under natural light and using a slit lamp. Methods: Therefore, we analyzed the mechanism of congenital cataract in M. rufocanus from the aspects of pathological histology, physiology and biochemistry, and gene level, aiming to explore the feasibility of its development into an animal model of cataract. Cataract is a progressive lens opacity and a leading cause of visual impairment. Understanding its pathogenesis requires appropriate animal models. In a laboratory-bred colony of M. rufocanus, we identified individuals with a spontaneous congenital cataract phenotype, confirmed by gross observation and slit lamp examination. To characterize this phenotype and explore its potential as an animal model, we performed pathological, physiological, biochemical, and transcriptomic analyses using three cataract-affected and three normal age-matched male individuals (8 weeks old per group). Results: Blood tests revealed significantly lower white blood cell and lymphocyte counts in the cataract group, while blood glucose and other biochemical parameters showed no significant differences. Histologically, cataractous lenses exhibited eosinophilic aggregation in the nuclear region with disorganized fiber cells. Transcriptome analysis identified 6544 differentially expressed genes, including downregulation of crystallin genes (CRYBB2, CRYBA4, CRYGS) known to be associated with congenital cataract. KEGG pathway enrichment analysis highlighted retinol metabolism, tyrosine metabolism, and cytochrome P450-related pathways. RT-qPCR confirmed reduced CRYBB2 expression in cataractous eyes. Conclusions: This study provides the first transcriptome dataset for M. rufocanus ocular tissues and offers preliminary evidence that this naturally occurring cataract phenotype may serve as a potential model for congenital cataract research. Full article

Attention Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder that is found in both children and adults. While this disorder often continues in adulthood, diagnosis can be challenging, particularly in females. Unlike males, who are often diagnosed with ADHD due to their externalizing behaviors (i.e., impulsive nature), most females show inattentive symptoms (i.e., in focusing, disorganization), which makes this disorder hard to detect. This paper proposes a machine learning approach to detect ADHD among females. The Wids Datathon 2025 provides three datasets: categorical data, quantitative data, and function connectomes. It contains information on 1213 participants who are seeking to take a test to detect ADHD. Categorical data includes 10 attributes, quantitative data has 19 attributes, and functional connectomes contain 19,901 attributes which are relevant to studying the participants’ overall condition. By combining both XGBoost and Random Forest, an accuracy of 79.42% was achieved. The results show that machine learning algorithms can help in improving ADHD detection in females, leading to better diagnoses in future. Full article

Urinary bladder hamartoma is an exceptionally rare benign lesion composed of disorganized yet mature tissue elements native to the bladder, including urothelium, fibrous stroma, smooth muscle, and occasionally adipose tissue. Unlike malignant tumors, it lacks cytological atypia, mitotic activity, or necrosis. Patients most often present with lower urinary tract symptoms (LUTS) or hematuria, though some cases are incidental findings. Associations with syndromic conditions such as Peutz–Jeghers, Beckwith–Wiedemann, Goldenhar, and Loeys–Dietz have been reported. Transurethral resection is the preferred treatment and has generally been curative. We report the first case in Germany—and the 16th worldwide—of urinary bladder hamartoma, occurring in a young adult male with bothersome LUTS. Because of its proximity to both ureteral orifices, only partial transurethral resection was performed, which provided durable symptom relief at 14 months of follow-up. This case highlights partial TUR as a pragmatic, organ-preserving alternative when complete resection is anatomically unsafe, while emphasizing that TURBT remains the standard of care. We provide a detailed discussion of the histopathological features, differential diagnosis, treatment considerations, and an updated narrative review of all reported cases. Full article

Background/Objectives: The opioid epidemic and adverse childhood experiences (ACEs) are two major concerns for child welfare systems. Little is known, however, regarding the mechanisms that perpetuate intergenerational cycles of ACEs and insecure/disorganized parent–young child attachment patterns in the context of parents’ opioid use. Methods: A high-risk sample of 101 parents (75 mothers and 26 fathers) who were opioid-involved, who had a child in the 0- to 5-year age range, and who were receiving medication-assisted treatment in the United States of America participated in this study. Parents were mostly White/Caucasian and single. Direct pathways between parents’ reported ACEs and their perceived parent–young child attachment patterns, as well as indirect pathways through substance use severity, depression, and trauma symptoms, were examined. Results: PROCESS analyses suggested that mothers’ ACEs significantly predicted their ratings of disorganized attachment patterns with their young children, with depression and trauma symptoms explaining greater variance than ACEs alone. The results indicated that fathers’ ACEs were not predictive of insecure/disorganized attachment patterns with their young children. Substance use severity was not predictive of parent–child attachment patterns for mothers or fathers. Conclusions: Generally, these findings highlighted different patterns among mothers and fathers’ ACEs, their ratings of parent–young child insecure/disorganized attachment, and their psychological sequelae. These findings further suggested the utility of trauma- and attachment-informed parenting interventions for high-risk mothers and fathers in breaking intergenerational cycles of risk. Full article

Background: Tendon structure is related to the magnitude of load and its management, rather than directly predicting pain incidence. Although pain symptoms frequently persist until they severely impact performance, function, and tendon structure, professional basketball players often manage patellar tendon pain alongside high training and competition loads. The aim of this study was to investigate patellar tendon structural adaptations over 8 months of training and competition in professional female and male basketball players. Methods: The primary outcome of this study was defined as the change in the percentage of echo-type II structure from baseline to 8 months. A prospective cohort study was conducted where 43 professional basketball players (20 male, 23 female) were followed during 8 months of training and competition. A bilateral patellar tendon ultrasound tissue characterization (UTC) scan was conducted, and jumping leg (jumping/non-jumping), presence of pain (yes/no), and exposure time (hours) were recorded at baseline, and at 4 and 8 months in the competitive season. Results: The mid-tendon exhibited negative adaptations (decreased alignment), represented by echo-type II, after 8 months of competition (left; p = 0.001; ES = 2.16; right; p = 0.001; ES = −1.35). Positive adaptations (increased alignment], were observed in echo-types III (p = 0.004; ES = −1.04) and IV (p = 0.001; ES = −0.15), after 4 and 8 months. Tendon structure showed differences between female and male professional basketball players throughout the 8 months (echo-type II; p = 0.00; ES = 0.34). Conclusions: The study demonstrated that the tendon structure undergoes significant adaptations, supporting the concept that the patellar tendon adapts to compensate for areas of structure disorganization. Female professional basketball players appeared to maintain a more organized tendon structure than their male counterparts. Jumping leg and presence of pain did not show significant differences in tendon structure over the study period. This research has significant implications for elite sport, as a better understanding of tendon load capacity throughout a competitive season is needed. Full article

Background: A large number of substance use disorders are increasingly associated with complex clinical presentations and unknown mental and medical risks, presenting a growing challenge for mental health worldwide. Research exploring the interplay between substance use and psychiatric disorders remains limited in Eastern Europe. Objectives: We investigated the demographic and clinical features of 203 patients admitted to a major Romanian psychiatric hospital, aiming to clarify the patterns of dual diagnosis and symptomatology within this vulnerable population. Results: Cannabis, novel psychoactive substances and unknown substances were the most commonly used drugs. Psychiatric comorbidity was rather the rule than the exception within our group. Cluster analysis revealed three distinct symptom profiles: manic/psychotic, negative affective and disorganized. While individual drug type did not independently predict symptom severity or readmission risk, a significant interaction effect between drug use and psychiatric comorbidity influenced symptom cluster membership. Conclusions: These findings highlight the complexity and heterogeneity of dual diagnoses and underline the importance of an integrated, multidisciplinary approach in addiction medicine. Full article

Background: Tendinopathy is a degenerative condition caused by mechanical overload, accounting for approximately 30% of musculoskeletal healthcare cases. It progresses through a process characterized by collagen disorganization, altered vascularization, and neuronal ingrowth. Traditional conservative treatments, such as therapeutic exercises, non-steroidal anti-inflammatory drugs, and physical therapies, are useful, but their effectiveness is sometimes only partial and there is a need to search for new potential solutions. Recent interest in oxygen–ozone (O₂-O₃) therapy stems from preliminary observations suggesting potential anti-inflammatory and regenerative effects. Nevertheless, its clinical role remains speculative and warrants thorough investigation beyond anecdotal evidence. Considering the heterogeneity of clinical presentations and treatment responses among patients, O₂-O₃ therapy has been proposed as a promising tool for tailoring personalized treatment strategies for tendinopathy. This review critically appraises the available literature concerning the mechanistic rationale and clinical applications of O₂-O₃ therapy in tendinopathy, with attention to both its theoretical underpinnings and the quality of empirical evidence. Methods: A literature search was conducted on O₂-O₃ therapy for tendinopathy using PubMed, Cochrane, and Embase, filtering for full-text articles published between 2004 and 2024. Recent clinical trials were included irrespective of evidence level, while excluding systematic reviews, duplicates, and irrelevant studies. Results: Ozone has been shown to modulate oxidative stress, promote neovascularization, and suppress pro-inflammatory cytokines. Both clinical and in vivo studies indicate that O₂-O₃ therapy relieves pain, enhances tendon healing, and improves biomechanical properties. Some comparative studies suggest that O₂-O₃ therapy might provide more sustained symptoms control than corticosteroids, but the heterogeneity of follow-up durations and outcome measures prevents definitive conclusions. Conclusions: O₂-O₃ therapy emerges as a potentially valuable adjunct in the management of chronic tendinopathy, particularly in cases unresponsive to conventional treatments. However, its clinical role remains to be clearly defined and its possible role in personalized medicine needs further exploration, particularly in relation to patient stratification and individualized treatment protocols. Further high-quality randomized controlled trials are warranted to validate its efficacy, determine long-term outcomes, and standardize treatment protocols to ensure safety and reproducibility. Full article

Multiple genes within the DISC1 (Disrupted-in-Schizophrenia-1) interactome have been implicated in psychotic disorders, which are characterized by hallucinations, delusions, negative symptoms, and disorganized behavior. However, the genetic associations of specific psychotic symptoms remain poorly understood. Methods: We conducted a genetic association analysis of the DISC1 interactome for hallucinations and delusions in schizophrenia and bipolar disorder, using single-nucleotide polymorphism (SNP), gene, and gene-set approaches. Results: Our findings showed an association between the SNP rs6754640 in the NRXN1 gene and auditory hallucinations. Additionally, rs10263196 (EXOC4), rs7076156 (ZNF365), and nine NRXN1 SNPs were associated with delusions of reference, while rs17039676 (NRXN1) was linked to persecutory delusions. At the gene level, NRG1 and PCM1 were related to auditory hallucinations. The NRXN1, APP, EXOC4, and NUP210 genes were associated with delusions of reference, whereas NRG1 and APP were linked to persecutory delusions. Gene-set analysis indicated that pathways related to the regulation of neuronal structure and function were involved in auditory hallucinations, while cellular transport regulation pathways were associated with persecutory delusions. Conclusions: This study emphasizes the polygenic architecture of psychosis and suggests that distinct molecular mechanisms contribute to different types of hallucinations and delusions. Full article

Recent documents from leading international pediatric respiratory societies have strongly encouraged the use of lung function tests in clinical practice and research. These tests can explore ventilatory function across its volumetric and temporal domains, providing information on the intrapulmonary location and extent of damage caused by respiratory diseases. The choice of which test to use in each case to investigate presenting respiratory symptoms depends on the patient’s symptoms and the diagnostic–therapeutic phase being addresse d. In the most common and representative chronic pediatric condition—bronchial asthma—lung function tests play an especially important role due to the disease’s complexity and the fluctuating nature of airway obstruction. This review aims to examine the potential of various lung function tests in asthma, helping clinicians and researchers to optimize diagnosis and follow-up with the most appropriate methodology. While spirometry and flow resistance measurements using the interrupter technique have historically been the cornerstones of diagnosis and clinical monitoring in childhood asthma, the advent of new technologies—such as multiple breath nitrogen washout (MBNW) and the forced oscillation technique (FOT)—is opening up the door to a more nuanced view of the disease. These tools allow for an evaluation of asthma as a structurally complex and topographically and temporally disorganized condition. FOT, in particular, facilitates measurement acceptability in less cooperative subjects, both in respiratory physiology labs and even at the patient’s home. Full article

Background and Clinical Significance: Herein, we describe the clinical case of a 17-year-old patient with psychotic disorder secondary to cerebral venous thrombosis due to primary thrombophilia, which was related to protein S deficiency and a heterozygous MTHFR gene mutation with the p.Ala222Val variant. Case presentation: A 17-year-old female, with no history of previous illnesses, was admitted to the emergency service department due to a psychotic break. Psychiatric evaluation detected disorganized thought, euphoria, ideas that were fleeting and loosely associated, psychomotor excitement, and deviant judgment. On the fifth day, an inflammatory process in the parotid gland was detected, pointing out a probable viral meningoencephalitis, prompting antiviral and antimicrobial treatment. One week after antiviral and steroidal anti-inflammatory treatments, the symptoms’ improvement was minimal, which led to further neurological workup. MRI venography revealed a filling defect in the transverse sinus, consistent with cerebral venous thrombosis. Consequently, anticoagulation treatment with enoxaparin was initiated. The patient’s behavior improved, revealing that the encephalopathic symptoms were secondary to thrombosis of the venous sinus. Hematological studies indicated the cause of the venous sinus thrombosis was a primary thrombophilia caused by a heterozygous MTHFR mutation variant p.Ala222Val and a 35% decrease in plasmatic protein S. Conclusions: This case highlights the possible relationship between psychiatric and thrombotic disorders, suggesting that both the MTHFR mutation and protein S deficiency could lead to psychotic disorders. Early detection of thrombotic risk factors in early-onset psychiatric disorders is essential for the comprehensive management of patients. Full article

Autism spectrum disorder (ASD) encompasses a range of neurodevelopmental conditions characterized by impairments in social abilities and communication. Studying appropriate animal models can enhance our understanding of the neural mechanisms underlying these conditions, potentially leading to improved treatment and intervention strategies. Modeling impairments in linguistic development and vocal communication caused by autism had been a challenging goal for a long time. Prenatal valproic acid (VPA) treatment has been successfully used to induce ASD-like behavioral symptoms in several vertebrate species including birds. Applying VPA-treatment on songbirds, therefore, offers a promising research paradigm to model ASD. In this study, we investigated the effect of embryonic VPA treatment on song learning in the highly social zebra finch (Taeniopygia guttata). Fertilized eggs were injected with either 0.45 µmol VPA or a saline solution on day 9 of incubation, and hatchlings were allowed to stay with their parents until day 35 post-hatching to facilitate song learning from the father. Once male offsprings reached adulthood, their songs were recorded and compared to those of their fathers. VPA-exposed males exhibited significantly greater similarity to their fathers’ songs compared to control males (74% vs. 31%, respectively), suggesting a reduced ability to modify and develop their own vocal patterns as subadults. Additionally, they showed higher entropy in their songs compared to controls (−1.4 vs. −1.7), indicating more disorganized vocalizations. These findings suggest that prenatal VPA exposure disrupts typical song learning and vocal development in zebra finches, likely by affecting neural mechanisms involved in vocal learning and crystallization of the songs. Our study suggests VPA treatment in songbirds provides a useful tool to model and investigate linguistic developmental disorders related to ASD in humans. Full article

Respiratory viruses continue to present serious health challenges to human wellness. Growing evidence suggests that the more severe and damaging effects and symptoms of influenza, rhinovirus (RV), respiratory syncytial virus (RSV), and COVID-19 may primarily result from their common ability to disorganize the body’s healthy immune response. The simultaneous over-stimulation of several reactive oxygen species (ROS) pathways and concurrent suppression of bioavailable Nitic Oxide (NO) contribute to an immune disbalance that can lead to cellular oxidative distress and an excessive inflammatory response. This study evaluated the real-time, acute ability of a single, orally administered 50 mg encapsulated dose of a plant-based dietary supplement (“PB-Blend”), compared to 1000 mg of Vitamin C as a positive control, to modulate multiple ROS associated with a dampened immune response, as well as NO and other markers of inflammation, in a cohort recovering from a moderate course of COVID-19. This randomized, double-blind study was performed on 28 individuals 18–24 days after a moderate COVID-19 infection. Participants were orally supplemented with a single encapsulated dose of either 50 mg of PB-Blend or 1000 mg Vitamin C as a positive control. Changes in the levels of bioavailable NO (measured as circulating NOHb) were assessed, as well as the ex vivo cellular formation of mitochondrial, NOX2-, iNOS-, and TNFα-dependent ROS. All parameters were measured in real time before ingestion (baseline), and then at 30, 60, 120, and 180 min after administration. ROS were measured using a portable electron paramagnetic resonance (EPR) spectrometer. Inflammatory, immunity (hsCRP and TNFα plasma levels), interleukin (IL1, IL6, IL8, and IL10), cytokine (IFNγ, TNFα, and NF-κB), and immunoglobulin (IgA, IgM, IgG, and IgE) profiles were also followed. In addition to laboratory and cell function investigations, we performed clinical cardio ergometry, blood O₂ saturation, and respirometry examinations. As hypothesized, the collected baseline data from this study group confirmed that mitochondrial, NOX2, and iNOS enzymatic systems were strongly involved in the generation of ROS at 18–24 days following a positive COVID-19 PCR test. Acute single-dose supplementation of 50 mg PB-Blend had a multifunctional impact on ROS and significantly inhibited the following: (a.) mitochondrial ROS levels by up to 56%; (b.) iNOS by up to 60%; and (c.) NOX2-dependent ROS generation by up to 49%. Moreover, 1000 mg Vitamin C supplementation exhibited narrower ROS-mitigating activity by solely inhibiting NOX2-dependent ROS generation by 45%. Circulating NOHb levels were significantly increased after PB-Blend administration (33%), but not after Vitamin C administration. PB-Blend and Vitamin C exhibited similar potential to reduce ex vivo high dose TNFα (200 ng/mL)-induced H₂O₂ formation. These results suggest that 50 mg of PB-Blend has the potential to modulate disbalanced mitochondria, iNOS, and NOX2 enzymatic systems that can be engendered during respiratory viral infection and subsequent recovery. Moreover, PB-Blend, but not Vitamin C, showed potential to upregulate bioavailable NO, which is known to decline under these conditions. Based upon these observations, PB-Blend could be considered an alternative to, or to be used in tandem with Vitamin C in applications that promote immune support and recovery during seasons of heightened respiratory viral risk (e.g., “flu season”). Full article