Search Results (202)

Tomato (Solanum lycopersicum) is an essential vegetable crop cultivated worldwide, but its production is highly vulnerable to tomato yellow leaf curl disease (TYLCD), which is transmitted by whiteflies (Bemisia tabaci). Management strategies typically focus on controlling either the virus or its vector. This study evaluates the effectiveness of multi-disease and insect-resistant tomato lines, developed by the World Vegetable Center (WorldVeg), which integrate Ty-1/Ty-3 genes for virus resistance and WF2-10 and WF3-09 genes for whitefly resistance. Virus accumulation, whitefly settling behavior, and adult mortality were assessed among multi-resistant lines, a Ty-resistant line, a whitefly-resistant line, and a susceptible check using preference bioassays, controlled inoculation experiments, and acylsugar quantification. Multi-resistant lines exhibited significantly higher acylsugar concentrations, reduced whitefly preference for settling, and increased whitefly adult mortality. Additionally, these lines displayed less severe disease symptoms and lower virus accumulation over time than Ty-resistant, whitefly-resistant, and susceptible controls. These findings highlight the superior efficacy of combined virus and vector resistance in mitigating tomato yellow leaf curl Thailand virus (TYLCTHV) transmission. This research underscores the importance of integrated genetic resistance as a key element of sustainable integrated pest management strategies, offering an environmentally friendly solution for safeguarding global tomato production. Full article

Rapid, safe, and field-deployable molecular diagnostics are crucial for the effective management of infectious disease outbreaks, particularly those involving highly infectious pathogens, which can produce clinical symptoms similar to less infectious pathogens, thus raising potential biosafety concerns. In this study, we evaluated DNA/RNA Defend Pro (DRDP) buffer, a novel viral-inactivating transport medium designed to stabilize nucleic acids and allow direct PCR without nucleic acid extraction. To ensure critical qPCR parameters were not compromised by using DRDP, we conducted serial dilution tests using herpes simplex viruses 1 and 2 (HSV-1, HSV-2) and varicella-zoster virus (VZV), comparing DRDP to standard universal transport medium (UTM). Detection sensitivity, determined by cycle quantification (Cq) values, favored DRDP, as UTM samples required a 2–3-fold dilution to mitigate PCR inhibition. DRDP maintained reliable PCR compatibility at reaction volumes containing up to 25% buffer. At higher DRDP concentrations (30–35%), PCR inhibition occurred due to EDTA content but was fully reversible by adding supplemental magnesium. Furthermore, DRDP samples did not require an initial 95 °C thermal lysis step, thus simplifying the procedure without reducing PCR sensitivity or efficiency. Full article

Background and Objectives: While α1-blockers like silodosin are the mainstay for treating lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH), combination therapy with phytotherapeutics may provide enhanced symptom control. Xipag^® is a novel formulation containing Graminex^® G96 (pollen extract) and Teupol^® 25P (teupolioside), offering anti-inflammatory and antiandrogenic effects. This study aimed to evaluate the efficacy of Xipag^® versus hexanic extract of Serenoa repens (HESr), both in combination with silodosin, in patients with LUTS/BPH. Materials and Methods: We conducted a single-center, prospective, observational, comparative study involving male patients with moderate-to-severe LUTSs undergoing treatment with silodosin. Patients were allocated to receive either Xipag^® or HESr in addition to silodosin, with follow-up every 3 months for 12 months. Primary outcomes included changes in symptom scores such as IPSS, QoL, and functional improvements such as peak urinary flow rate (Qmax). Multivariable regression analyses were used to assess predictors of the response. Results: Patients receiving Xipag^® showed significantly greater improvements in Qmax at all follow-up points (p < 0.05), with earlier and more sustained benefits compared to the HESr group. QoL index scores and PSA levels were also significantly better in the Xipag^® group starting from month six onward. IPSS scores improved in both groups but were significantly lower in the Xipag^® group only at 12 months (p = 0.04). No differences in erectile function (IIEF-5) or adverse events were observed. Conclusions: Xipag^® in combination with silodosin provides superior improvement in urinary flow, symptom-related QoL, and PSA reduction compared to HESr plus silodosin, with a favorable safety profile. These findings support the use of multi-target nutraceuticals like Xipag^® as a valuable adjunct in the management of LUTS/BPH. Larger randomized trials are warranted to confirm these results and explore underlying mechanisms. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder leading to movement impairment, cognitive decline, and psychiatric symptoms. Key manifestations of PD include bradykinesia (the slowness of movement), changes in voice or speech, and gait disturbances. The quantification of neurological disorders through voice analysis has emerged as a rapidly expanding research domain, offering the potential for non-invasive and large-scale monitoring. This review explores existing research on the application of machine learning (ML) in speech, voice, and language processing for the diagnosis of PD. It comprehensively analyzes current methodologies, highlights key findings and their associated limitations, and proposes strategies to address existing challenges. A systematic review was conducted following PRISMA guidelines. We searched four databases: PubMed, Web of Science, Scopus, and IEEE Xplore. The primary focus was on the diagnosis, detection, or identification of PD through voice, speech, and language characteristics. We included 34 studies that used ML techniques to detect or classify PD based on vocal features. The most used approaches involved free speech and reading-speech tasks. In addition to widely used feature extraction toolkits, several studies implemented custom-built feature sets. Although nearly all studies reported high classification performance, significant limitations were identified, including challenges in comparability and incomplete integration with clinical applications. Emerging trends in this field include the collection of real-world, everyday speech data to facilitate longitudinal tracking and capture participants’ natural behaviors. Another promising direction involves the incorporation of additional modalities alongside voice analysis, which may enhance both analytical performance and clinical applicability. Further research is required to determine optimal methodologies for leveraging speech and voice changes as early biomarkers of PD, thereby enhancing early detection and informing clinical intervention strategies. Full article

Background/Objectives: Fabry disease (FD) is a lysosomal storage disorder often associated with early-onset neuropathic pain, attributed to small fibre neuropathy (SFN). The dorsal root ganglion (DRG) has emerged as a critical site of early pathophysiological involvement in FD, with structural and functional alterations implicated in the development of neuropathic symptoms. This exploratory study introduces DRG proton density (DRG-PD) as a novel MRI-derived biomarker and evaluates its association with SFN. Methods: Eighty genetically confirmed FD patients underwent high-resolution 3T MRI with DRG-PD quantification at the lumbosacral levels L5 and S1. DRG-PD was derived from B1-corrected multi-echo spin echo sequences and normalised to cerebrospinal fluid intensity. All patients underwent clinical, biochemical and histological evaluation to determine SFN status. Associations between DRG imaging parameters and clinical variables were analysed using correlation and regression models. Diagnostic performance was evaluated using receiver operating characteristic curve analysis. Results: DRG-PD values were significantly increased in patients with classical FD and SFN, demonstrating a large effect size (Cliff’s δ = 0.92) and excellent discriminatory performance (AUC = 0.96). In contrast, DRG volume and T2 relaxation time were not significantly associated with SFN status. DRG-PD remained an independent predictor of SFN in multivariable logistic regression (p = 0.019). Conclusions: DRG-PD is a non-invasive correlate of SFN in classical FD. It may provide superior diagnostic value compared to existing MRI metrics and reflects proximal ganglionic pathology not captured by distal histological assessments. Full article

Objective: The aim of this study is to investigate uterine prolapse (UP) among women attending a semi-urban health center for routine gynecological examinations. Specifically, the study explores the potential association between UP and various established or suspected risk factors, including age, menopausal status, number and mode of deliveries, birth weight, smoking habits, and body mass index (BMI). Furthermore, it examines the relationship between the presence or severity of UP and the scores of specific questionnaires and their subscales. Finally, the study seeks to develop a predictive model for the likelihood of UP based on questionnaire responses. Methods: A quantitative study was conducted at the gynecological department of a health center in Greece from January 2021 to October 2022. A total of 134 women were recruited using convenience sampling during routine gynecological visits. The degree of prolapse was classified according to the International Continence Society (ICS) Pelvic Organ Prolapse Quantification (POP-Q) classification system. Data collection also included the use of validated instruments: the Australian Pelvic Floor Questionnaire (APFQ), the Urogenital Distress Inventory-6 (UDI-6), the Pelvic Floor Distress Inventory-20 (PFDI-20), and the Pelvic Floor Impact Questionnaire-7 (PFIQ-7). The data were processed with the Statistical Package for the Social Sciences (SPSS) v25. Results: Of the 134 participants, 21 (15.7%) aged 21 to 82 showed signs of UP, while 113 women (84.3%) did not. The average age of the women with UP was 55 years. Fourteen (10.4%) of these women were diagnosed with UP stage I, three of them (2.2%) with stage II, and four of them (3%) with stage III UP. There were no stage IV UP incidents. The risk factors associated with the disease include age, mode of delivery, parity, and duration of menopause. Regarding parity, every subsequent birth after the first one increases the likelihood of a UP incident by approximately 125%. Conclusions: Most women with UP did not exhibit severe symptoms, as UP typically does not manifest symptoms until it reaches a final stage. Considering the population aging and the increase in morbidity, a regular pelvic organ prolapse (POP) checkup should be established to facilitate early recognition, prevention, and treatment of symptoms. This study offers a potential tool for non-invasive screening to facilitate identifying UP in women early, which has not been previously reported. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, heterogeneous at the molecular level and characterized by diverse and complex pathological features. Such features are known to accumulate silently in the brain over years or even decades before the onset of detectable symptoms. Despite long years of intense research activities, the disease remains orphaned of either disease-modifying therapies or a specific blood test capable of predicting the disease in the pre-symptomatic stages. This disappointing outcome of such efforts can be attributed to a number of factors. One of these factors is the failure of earlier research to capture the heterogeneity of the disease. Such failure has the direct consequence of poor patient stratification, which in turn impacts negatively on the development of specific and effective therapy. The second factor is the absence of detailed and accurate information on proteins and associated post-translational modifications, which may influence the initiation and progress of the disease. Recent studies have demonstrated that the quantification of various isoforms of phosphorylated tau protein in plasma and other biofluids can be considered as potential biomarkers for the early detection of Alzheimer’s disease. Mass spectrometry-based proteomics and immunoassay-based multiplex proteomics are the two technologies in current use for probing the human proteome, both in tissues and biofluids. In the present review, we discuss the contribution of MS-based proteomics to efforts aimed at the identification and eventual characterization of the heterogeneity of the disease, and the key role of the same technique in the analysis of protein post-translational modifications associated with the disease is also discussed. Full article

Background and aims: Recent advances in acute stroke interventions have highlighted the importance of accurate determination of infarct volume in the evaluation of acute stroke patients, carrying important prognostic and therapeutic implications for treatment planning, outcome prediction, and evaluation of the success of therapeutic interventions. However, there is no consensus on the methodologies employed to measure cerebral infarct volume. We aimed to assess the reproducibility and reliability of methods employed in the clinical determination of infarct volume in acute ischaemic stroke. Methods: We carried out a systematic review of studies assessing methodologies for the determination of infarct volume in the acute phase (<24 h). We searched Medline PubMed, Scopus, Cinahl, Cochrane Library, Web of Science, and Embase for studies examining image-based diagnosis of acute ischaemic stroke < 24 h by CT or MRI. Data on patient cohorts, imaging type, time from symptoms onset, methodologies and quantification strategies, rater reliability, accuracy, sensitivity, and specificity were compared. Results: We identified eighteen eligible studies with a total of 3298 ischaemic stroke patients assessing a variety of manual, semi-automated, and fully-automated methods. The ABC/2 method was found to be highly reliable, reproducible, and accurate, and provides the best manual estimate of infarction, but has a tendency to under- or overestimate infarct volume. Semi-automated and automated approaches with user refinement showed excellent inter-rater and intra-rater correlation. However, differences in operating algorithms and lack of standardisation of image acquisition parameters, quality, and format may impact performance and reproducibility. Conclusions: Of all methods, automated and semi-automated approaches utilising rater judgment and refinement represent the most robust approaches, with semi-automated tools demonstrating consistent and repeatable results. We recommend a standardised reporting of study methodologies for the accurate interpretation and comparison of efficacy of therapeutic interventions and patient outcomes, especially in a multi-centre setting. This may allow for more effective evaluation of stroke therapies and accelerate ischaemic stroke treatment decisions. Full article

Stomatognathic dysfunctions, particularly bruxism, orofacial pain, and temporomandibular joint (TMJ) disorders, are frequently associated with anxiety and depression. However, the reverse hypothesis that these dysfunctions may act as peripheral stressors contributing to neuropsychological imbalance by activating the hypothalamic–pituitary–adrenal (HPA) axis remains underexplored. Objective: To assess the relationship between the severity of stomatognathic symptoms and both physiological and psychological stress markers to determine whether such dysfunctions may influence or exacerbate anxiety and depressive disorders. Methods: A cross-sectional observational study was conducted on 120 adult patients. Clinical assessment was included evaluation of TMJ function, bruxism, and orofacial pain. Psychological screening was performed using validated questionnaires (GAD-7 for anxiety and PHQ-9 for depression). Electromyographic (EMG) analysis of the masseter and temporalis muscles was conducted, along with the quantification of salivary cortisol using an enzyme-linked immunosorbent assay (ELISA). Multiple regression models were applied to identify statistically significant correlations (p < 0.05). Results: A positive correlation was found between the severity of stomatognathic dysfunction and scores on anxiety and depression measures, along with elevated salivary cortisol levels and increased masticatory muscle activity. Conclusions: These findings suggest a bidirectional relationship between stomatognathic dysfunctions and neuropsychological status, underscoring the potential value of integrated therapeutic approaches that combine dental care with psychological support. Full article

Most DNA damage caused by oxidative metabolism consists of single lesions that can accumulate in tissues. This review focuses on two classes of lesions: the two 8-oxopurine (8-oxo-Pu) lesions that are repaired by the base excision repair (BER) enzyme and the four 5′,8-cyclopurine (cPu) lesions that are repaired exclusively by the nucleotide excision repair (NER) enzyme. The aim is to correlate the simultaneous quantification of these two classes of lesions in the context of neurological disorders. The first half is a summary of reactive oxygen species (ROS) with particular attention to the pathways of hydroxyl radical (HO^•) formation, followed by a summary of protocols for the quantification of six lesions and the biomimetic chemistry of the HO^• radical with double-stranded oligonucleotides (ds-ODN) and calf thymus DNA (ct-DNA). The second half addresses two neurodegenerative diseases: xeroderma pigmentosum (XP) and Cockayne syndrome (CS). The quantitative data on the six lesions obtained from genomic and/or mitochondrial DNA extracts across several XP and CS cell lines are discussed. Oxidative stress contributes to oxidative DNA damage by resulting in the accumulation of cPu and 8-oxo-Pu in DNA. The formation of cPu is the postulated culprit inducing neurological symptoms associated with XP and CS. Full article

Objective: This study introduces a novel method for the automated detection and quantification of meibomian gland morphology using gray value distribution profiles. The approach addresses limitations in traditional manual and deep learning-based meibography analysis, which are often time-consuming and prone to variability. Methods: This study enrolled 100 volunteers (mean age 40 ± 16 years, range 18–85) who suffered from dry eye and responded to the Ocular Surface Disease Index questionnaire for scoring ocular discomfort symptoms and infrared meibography for capturing imaging of meibomian glands. By leveraging pixel brightness variations, the algorithm provides real-time detection and classification of long, medium, and short meibomian glands, offering a quantitative assessment of gland atrophy. Results: A novel parameter, namely “atrophy index”, a quantitative measure of gland degeneration, is introduced. Atrophy index is the first instrumental measurement to assess single- and multiple-gland morphology. Conclusions: This tool provides a robust, scalable metric for integrating quantitative meibography into clinical practice, making it suitable for real-time screening and advancing the management of dry eyes owing to meibomian gland dysfunction. Full article

Diabetic kidney disease (DKD) displays a high prevalence of cardiovascular and cerebrovascular disease. Both the kidney and the brain share common pathogenic mechanisms, such as inflammation, endothelial dysfunction, oxidative stress, and mitochondrial dysfunction. The aim of this study was to establish a potential association of cerebral vessel remodeling and its related functional impairment with biomarkers of inflammation, oxidative stress, and mitochondrial dysfunction in the early stages of DKD in type 2 diabetes mellitus (DM) patients. A cohort of 184 patients and 39 healthy controls was assessed concerning serum and urinary stromal cell-derived factor-1 (SDF-1), P-selectin, advanced oxidation protein products (AOPPs), urinary synaptopodin, podocalyxin, kidney injury molecule-1 (KIM-1), and N-acetyl-β-(D)-glucosaminidase (NAG). The quantification of the mitochondrial DNA copy number (mtDNA-CN) and nuclear DNA (nDNA) in urine and peripheral blood was conducted using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Using TaqMan tests, the beta-2 microglobulin nuclear gene (B2M) and the cytochrome b (CYTB) gene, which encodes subunit 2 of NADH dehydrogenase (ND2), were evaluated. The MtDNA-CN is the ratio of mitochondrial DNA to nuclear DNA copies, ascertained through the examination of the CYTB/B2M and ND2/B2M ratios. The intima-media thickness (IMT) measurements of the common carotid arteries (CCAs), along with the pulsatility index (PI) and resistivity index (RI) of the internal carotid arteries (ICAs) and middle cerebral arteries (MCAs), were obtained through cerebral Doppler ultrasonography (US). Additionally, the breath-holding index (BHI) was also measured by cerebral Doppler US. PI-ICAs, PI-MCAs, CCAs-IMT, RI-MCAs, and RI-ICAs demonstrated direct relationships with SDF-1, P-selectin, AOPPs, urine mtDNA, podocalyxin, synaptopodin, NAG, and KIM-1 while showing indirect correlations with serum mtDNA and the eGFR. In contrast, the BHI had negative correlations with SDF-1, P-selectin, AOPPs, urine mtDNA, synaptopodin, podocalyxin, KIM-1, and NAG while showing direct associations with serum mtDNA and the eGFR. In conclusion, a causative association exists among SDF-1, P-selectin, and AOPPs, as well as mitochondrial dysfunction, in early diabetic kidney disease (DKD) and significant cerebrovascular alterations in patients with type 2 diabetes mellitus and normoalbuminuric DKD, with no neurological symptoms. Full article

Chagas disease (CD) is endemic in Latin America, with its pathogenesis linked to Trypanosoma cruzi (Tc) persistence and autoimmune responses. This study investigates the role of LINE-1 (L1) activation in inflammation and loss of self-tolerance during Tc infection. In vitro assays evaluated the expression of genes involved in L1 regulation and interferon signaling under basal conditions and following L1 suppression via CRISPR/dCas9. In vivo analyses in a murine model included L1 and IFN expression profiling, autoantibody quantification, and histopathological assessments of liver, spleen, intestine, and heart. Tc infection induced L1 upregulation, correlating with an increased expression of its inhibitors, MOV-10 and APOBEC-3, suggesting host-driven regulatory mechanisms. L1 activation was also associated with the upregulation of DNA repair pathways (MMR and NHEJ) and RNA-sensing pathways (MDA-5 and RIG-I), leading to type I interferon responses. In the murine model, L1 expression was highest in the intestine and heart, independent of parasite burden, and correlated with increased interferon gene expression and autoantibody production. Our findings suggest that CD pathogenesis involves L1-induced chronic inflammation, which may contribute to late-stage symptoms. This highlights self-recognition mechanisms in disease severity and reveals potential therapeutic targets for novel treatments. Full article

Background/Objectives: Lumbosacral spinal stenosis (LSS) is a degenerative condition characterized by narrowing of the spinal canal and associated neuropathic pain. While mechanical compression is well-characterized, the molecular mechanisms contributing to symptom severity remain poorly understood. Neurturin (NRTN), a member of the glial cell line-derived neurotrophic factor family, has emerged as a potential mediator of neural plasticity and nociception, but its role in spinal stenosis is largely unexplored. Methods: We analyzed NRTN mRNA and protein expression in ligamentum flavum samples from 96 patients undergoing surgery for LSS and 85 non-degenerative postmortem controls. Quantification was performed using real-time quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), Western blotting, and immunohistochemistry. Pain severity Visual Analog Scale (VAS), body mass index (BMI), diabetes, smoking, and alcohol use were assessed as modulators of NRTN expression. Results: NRTN expression was significantly elevated in LSS patients versus controls at both transcript and protein levels (p < 0.05). NRTN levels positively correlated with pain intensity (VAS; ANOVA p = 0.032 for mRNA, p = 0.041 for protein). Multivariate regression identified BMI (β = 0.50, p = 0.015) and diabetes (β = 0.39, p = 0.017) as independent predictors of increased NRTN expression. Alcohol use also showed a positive association (p = 0.046), while smoking showed no significant independent effect. Conclusions: Neurturin is upregulated in ligamentum flavum tissue from LSS patients and correlates with pain severity and metabolic risk factors. These findings suggest NRTN as a potential biomarker and therapeutic target in degenerative spine disease. Further longitudinal and mechanistic studies are warranted to elucidate its role in chronic pain and neuroinflammation. Full article

Objective: The benign nature of perimesencephalic subarachnoid hemorrhage (pmSAH) can be challenged by the occurrence of complications. Given the limited prognostic value of established clinical parameters for the development of complications in patients with pmSAH, this study evaluates the potential of volumetric hemorrhage quantification for risk assessment and the evaluation of the clinical outcome. Material and Methods: In this retrospective single-center study, we analyzed all consecutive patients diagnosed with pmSAH between 2010 and 2023 at a tertiary care academic medical center in Germany. The volumetric quantification of the hemorrhage in cm³ was performed using non-contrast CT imaging. The occurrence of clinical complications, including hydrocephalus, vasospasm, and delayed cerebral ischemia (DCI), were assessed. Clinical outcomes were determined by the Glasgow Outcome Scale (GOS) at discharge. Multivariable logistic regression models were used to assess the correlation between quantified hemorrhage volumes and the occurrence of complications and clinical outcomes (GOS) controlled for other variables such as age, sex, cardiovascular risk factors, clinical symptoms, and the modified Fisher scale. Results: A total of 82 patients (58.5% male, 54.8 ± 12.1 years) were enrolled. The median World Federation of Neurosurgical Societies (WFNS) score for all patients at admission was 1.0 (IQR 1.0–1.0). During the clinical course, hydrocephalus occurred in 29%, vasospasm in 14.6%, and DCI in 8.5% of all patients. Hemorrhage volume quantification was found to be the strongest independent predictor for hydrocephalus (OR 1.28; 95% CI 1.02–1.61; p = 0.032) and vasospasm (OR 1.25; 95% CI 1.07–1.46; p = 0.007) and showed a high predictive accuracy in ROC analyses (AUC = 0.77 and 0.76, respectively). Conversely, neither clinical parameters nor the modified Fisher scale were associated with these complications. A higher hemorrhage volume was also significantly correlated with a worse functional outcome (GOS; β = –0.07, CI: −0.12–−0.02, p = 0.021). Conclusions: In patients with pmSAH, the volumetric quantification of hemorrhage may be an adequate prognostic parameter regarding the occurrence of hydrocephalus and vasospasm. In addition, the quantitative assessment of hemorrhage volumes was strongly associated with clinical outcomes in these patients. Despite the generally benign nature of pmSAH, this imaging biomarker could improve individualized clinical management strategies and inform about the risk for the occurrence of complications. Full article