Disease Damage Research Articles

Rhekiss-The German Register for Child Wish and Pregnancies in Inflammatory Rheumatic Diseases.

In pharmacoepidemiology, robust data are needed to judge the impact of drug treatment on pregnancy, pregnancy outcomes and breast-fed infants. As pregnant and breastfeeding women are usually excluded from randomised clinical trials, observational studies are required. One of those data sources are pregnancy registers specifically developed to focus on certain diseases or disease groups. The German Rhekiss register investigates pregnancies in women with chronic inflammatory rheumatic diseases (IRD). Rhekiss is a nationwide, multicentre, longitudinal study, in which women aged 18 years or older with an underlying IRD can be enrolled by a rheumatologist either when planning a pregnancy or in the first half of pregnancy. Data are collected prospectively at regular follow-up visits. Rheumatologists and patients provide information in a web-based system before conception (if enrolment was at the time of pregnancy planning), during and after pregnancy. A smartphone app is available for patients. Maternal and clinical information, general laboratory markers, treatment with antirheumatic and other drugs, adverse events, items related to course and outcome of pregnancy and the health of the child are uniformly assessed for all diseases. Individual information on the IRD includes classification criteria, diagnosis-specific laboratory parameters, clinical parameters and validated instruments to measure disease activity or damage. Furthermore, patient-reported outcome measures are captured. A total of 2013 individual patients have been enrolled in the register, and data on 1801 completed pregnancies are available. In summary, Rhekiss is a comprehensive and complex register that can answer various research questions about pregnancy in women with chronic IRDs.

The possibilities of ultrasound examination in the diagnosis of joint and peripheral nerve damage in vibration disease: a review of the literature

The possibilities of ultrasound examination in the diagnosis of joint and peripheral nerve damage in vibration disease: a review of the literature

Complex Interplay between DNA Damage and Autophagy in Disease and Therapy.

Cancer, a multifactorial disease characterized by uncontrolled cellular proliferation, remains a global health challenge with significant morbidity and mortality. Genomic and molecular aberrations, coupled with environmental factors, contribute to its heterogeneity and complexity. Chemotherapeutic agents like doxorubicin (Dox) have shown efficacy against various cancers but are hindered by dose-dependent cytotoxicity, particularly on vital organs like the heart and brain. Autophagy, a cellular process involved in self-degradation and recycling, emerges as a promising therapeutic target in cancer therapy and neurodegenerative diseases. Dysregulation of autophagy contributes to cancer progression and drug resistance, while its modulation holds the potential to enhance treatment outcomes and mitigate adverse effects. Additionally, emerging evidence suggests a potential link between autophagy, DNA damage, and caretaker breast cancer genes BRCA1/2, highlighting the interplay between DNA repair mechanisms and cellular homeostasis. This review explores the intricate relationship between cancer, Dox-induced cytotoxicity, autophagy modulation, and the potential implications of autophagy in DNA damage repair pathways, particularly in the context of BRCA1/2 mutations.

Achieving food security: Household perception and adoption of home gardening techniques in Ghana

As global food crises and high food prices continue to impact communities, there is a growing focus on strengthening local food systems and improving livelihoods. Home gardening techniques have gained renewed attention as a means of food production and enhancing household food security. However, there is a lack of empirical studies on the perception and adoption of home gardening techniques. This study therefore fills this gap by examining the perception and adoption of home gardening techniques among households in Ghana. A multistage sampling technique was used to select 348 households and data was collected through a structured questionnaire. Using a 5-point Likert scale, we analyzed the households' perception of home gardening techniques, and utilized a multivariate probit regression model to examine the factors influencing multiple adoption of home gardening techniques. The Kendall’s coefficient of concordance was used to test the level of agreement among ranked constraints in adopting home gardening techniques. The generalized Poisson regression was used to examine the number of adoption of home gardening techniques. The results revealed that most households perceived home gardening techniques as a way to improve household food security. Households were found to adopt multiple home gardening techniques, such as use of pots, sacks, and tires. Empirically, factors such as sex, education, occupation, income, technology cost, and social network had a significant influence on multiple adoption of home gardening techniques. Also, age, education, household size, income, technology cost, social network, inadequate space and insect and disease damages significantly influenced the number of adoptions of home gardening techniques. Furthermore, lack of time and inadequate space were the main constraints limiting the adoption of these techniques. We suggest government interventions to spur the adoption of home gardening techniques to improve household food nutrition.

Omalizumab in the treatment of bullous pemphigoid: A single-center series of 15 cases.

Bullous pemphigoid (BP) is a chronic autoimmune disease affecting the elderly population and characterized by the formation of subepidermal tense bullae. Treatment options include topical steroids, systemic steroids, immunosuppressants, and antimicrobials, and there is emerging evidence of the efficacy of omalizumab. In this study, we aimed to demonstrate omalizumab's efficacy for treating BP, and we also reported treatment-related adverse events. The retrospective cohort study included patients with BP who were followed up in our clinic's bullous diseases department between 2016 and 2023. Patients who received omalizumab were included in the study. Treatment responses of all patients were assessed by BP Disease Area Index activity and damage scores, treatment scale scoring, steroid dose reduction, and the presence/absence of pruritus. Also, total IgE levels of patients before the treatment onset and at the last visit were compared. There were 15 (male/female = 8/7) BP patients receiving omalizumab treatment. Omalizumab therapy allowed steroid dose reduction at a median of 1 month. Omalizumab (25.5 mg, 95% confidence interval 17.2-33.9, P < .001) provided a significant steroid dose reduction at the last visit compared to the beginning of treatment. Omalizumab resulted in a decrease in BP Disease Area Index activity score of 80.8 (95% confidence interval 71.8-89.8, P < .001). Also, omalizumab caused significant decline in IgE levels compared to baseline (1102.5 ± 834.5 vs 834.6 ± 613.6, P = .002). In this study, omalizumab treatment was an effective and safe option in BP patients with high baseline IgE levels who are refractory to or cannot tolerate other immunosuppressive therapies.

Effects of Fast Food Consumption on Adolescent Health: A Literature Review

Ready-to-eat food is food that can be easily and quickly prepared as a substitute for home-cooked food. The popularity of fast food or fast food among teenagers is increasing, along with the increase in portions and energy contained in it. Several factors that support the consumption of fast food by teenagers include knowledge, peer influence, a comfortable place to gather, good taste, convenience and practicality, pocket money, affordable prices, and fast food brands. This research aims to determine the negative impacts that can be caused by consuming fast food on teenagers. This research was conducted using qualitative analysis methods through literature studies obtained from Google Scholar relating to the influence of fast food consumption among teenagers. Research results show that consumption of fast food by teenagers can cause dangerous diseases such as high cholesterol, diabetes, heart disease, kidney problems and liver damage. Apart from that, excessive consumption of fast food can also increase the risk of obesity in teenagers.

Identification of deregulated lncRNAs in Alzheimer's disease: an integrated gene co-expression network analysis of hippocampus and fusiform gyrus RNA-seq datasets.

The deregulation of lncRNAs expression has been associated with neuronal damage in Alzheimer's disease (AD), but how or whether they can influence its onset is still unknown. We investigated 2 RNA-seq datasets consisting, respectively, of the hippocampal and fusiform gyrus transcriptomic profile of AD patients, matched with non-demented controls. We performed a differential expression analysis, a gene correlation network analysis (WGCNA) and a pathway enrichment analysis of two RNA-seq datasets. We found deregulated lncRNAs in common between hippocampus and fusiform gyrus and deregulated gene groups associated to functional pathways related to neurotransmission and memory consolidation. lncRNAs, co-expressed with known AD-related coding genes, were identified from the prioritized modules of both brain regions. We found common deregulated lncRNAs in the AD hippocampus and fusiform gyrus, that could be considered common signatures of AD pathogenesis, providing an important source of information for understanding the molecular changes of AD.

Magnetically Actuated Nanomaterials in Biomedical Applications

Magnetic nanomaterials, distinguished by their unique magnetic phenomena, particularly their magnetically actuated capabilities, have found widespread application in the field of nanomedicine. Compared with alternative driving mechanisms, magnetic actuation as a remote, highly permeable, and precisely controllable driving strategy endows nanomaterials with temporal and spatia mobility, making it possible to initiate and cease multiple forms of movement in vivo at will. When coupled with cutting‐edge diagnostic and treating techniques including but not limited to magnetic resonance imaging, magnetothermal therapy, and magnetoelectric stimulation, magnetically actuated nanomaterials offer the potential for visual analysis, provision of reliable molecular information, and effective disease or tissue damage intervention. This review comprehensively outlines the synthesis methodologies, functional strategies, and biomedical applications of magnetically actuated nanomaterials within nanomedicine. Additionally, the future developments and applications of biocompatible magnetically actuated nanomaterials, especially in response to time‐varying magnetic fields, are anticipated.

Neutrophils in Ocular Diseases.

Neutrophils, traditionally viewed as first responders to infection or tissue damage, exhibit dynamic and diverse roles in ocular health and disease. This review elaborates on previous findings that showed how neutrophils contribute to ocular diseases. In ocular infections, neutrophils play a pivotal role in host defense by orchestrating inflammatory responses to combat pathogens. Furthermore, in optic nerve neuropathies and retinal degenerative diseases like age-related macular degeneration (AMD) and diabetic retinopathy (DR), neutrophils are implicated in neuroinflammation and tissue damage owing to their ability to undergo neutrophil extracellular trap formation (NETosis) and secretion of inflammatory molecules. Targeting neutrophil-dependent processes holds promise as a therapeutic strategy, offering potential avenues for intervention in ocular infections, cancers, and retinal degenerative diseases. Understanding the multifaceted roles of neutrophils in ocular diseases is crucial for developing targeted therapies to improve patient outcomes.

Molecular docking and proteomics approaches for the identification of neuroprotective effects of IL15.5 peptide against oxidative stress-induced apoptosis in SH-SY5Y neurons

Amyloid-β (Aβ) aggregation is central to Alzheimer’s disease (AD), causing oxidative and synaptic damage. We developed IL15.5, a peptide-base inhibitor derived from IL15, a natural peptide from Siamese crocodile hemoglobin. Computational and molecular assays confirm IL15.5 effectively inhibits Aβ42 aggregation, evident in thioflavin T assay results. IL15.5 also demonstrates acetylcholinesterase inhibition and antioxidant activity. It protects SH-SY5Y cells from oxidative stress and apoptosis, influencing caspase 3/MAPK pathways. Proteomic analysis reveals the role of IL15.5 in oxidative stress mitigation, affecting proteins linked to DNA repair, inflammation, and cell migration, with a significant association with Ubiquitin C. These findings suggest the potential of IL15.5 as an anti-amyloidogenic agent for AD treatment, offering neuronal protection and highlighting its therapeutic promise.

IP-GCN: A deep learning model for prediction of insulin using graph convolutional network for diabetes drug design

Insulin is a kind of protein that regulates the blood sugar levels is significant to prevent complications associated with diabetes, such as cancer, neurodegenerative disorders, cardiovascular disease, and kidney damage. Insulin protein (IP) plays an active role in drug discovery, medicine, and therapeutic methods. Unlike experimental protocols, computational predictors are fast and can predict IP accurately. This work introduces a model, called IP-GCN for IP prediction. The patterns from IP are extracted by K-spaced position specific scoring matrix (KS-PSSM) and the model training is accomplished using powerful deep learning tool, called Graph Convolutional Network (GCN). Additionally, we implemented Pseudo Amino Acid Composition (PseAAC) and Dipeptide Composition (DPC) for feature encoding to assess the predictive performance of GCN. To evaluate the efficacy of our novel approach, we compare its performance with well-known deep/machine learning algorithms such as Convolutional Neural Network (CNN), Extremely Randomized Tree (ERT), and Support Vector Machine (SVM). Predictive results demonstrate that the proposed predictor (IP-GCN) secured the best performance on both training and testing datasets. The novel computational would be fruitful in diabetes drug discovery and contributes to research for therapeutic interventions in various Insulin protein associated diseases.

Research topics in occupational medicine, 1990-2022: A text-mining-applied bibliometric study.

Occupational health has been influenced by societal and industrial changes. This study aimed to clarify topic trends in occupational health research in 1990-2022. We conducted a text-mining-adjusted bibliometric study using research titles in occupational health. Data on research titles and the years of publication were collected from 26 peer-reviewed journals on PubMed. Using morphological and correspondence analyses in text mining, we structured research topics into multiple categories and visualized the relationship between all categories and publication years. Statistical analyses were conducted using the text mining software - KH Coder 3.0. We obtained 48 645 articles containing 714 890 words in their titles. The research topics were classified into 4 categories and 17 subcategories, of which those of occupations; countries; non-intervention; psychosocial factors; lifestyle factors; safety; symptoms; therapy and care; and productivity have recently shown an increasing trend. In contrast, the subcategories of risk, chemical factors, disease, and organ damage showed decreasing trends. Chemical factors, which were the main topics in the 1990s, included risk, organ damage, and disease. Productivity, the main topic in the 2020s, co-occurred with lifestyle factors, symptoms, and intervention. Focal areas in occupational-health research shift according to societal trends. Occupational-health research has primarily analyzed issues in developed countries with capitalist values and may not have sufficiently covered issues in developing countries. It is imperative for policymakers and public funding bodies to determine priorities for investigation in the field.

Pathophysiology of hypereosinophilia-associated heart disease.

Cardiac complications in patients with hypereosinophilia cause significant morbidity and mortality. However, mechanisms of how eosinophilic inflammation causes heart damage are poorly understood. We developed a model of hypereosinophilia-associated heart disease by challenging hypereosinophilic mice with peptide from the cardiac myosin heavy chain. Disease outcomes were measured by histology, immunohistochemistry, flow cytometry, and measurement of cells and biomarkers in peripheral blood. Eosinophil dependence was determined by using eosinophil-deficient mice (ΔdblGATA). Single cells from heart were subjected to single cell RNA sequencing to assess cell composition, subtypes and expression profiles. Mice challenged with myocarditic and control peptide had peripheral blood leukocytosis, but only those challenged with myocarditic peptide had heart inflammation. Heart tissue was infiltrated by eosinophil-rich inflammatory infiltrates associated with cardiomyocyte damage. Disease penetrance and severity were dependent on the presence of eosinophils. Single cell RNA sequencing showed enrichment of myeloid cells, T-cells and granulocytes (neutrophils and eosinophils) in the myocarditic mice. Macrophages were M2 skewed, and eosinophils had an activated phenotype. Gene enrichment analysis identified several pathways potentially involved in pathophysiology of disease. Eosinophils are required for heart damage in hypereosinophilia-associated heart disease. Additionally, myeloid cells, granulocytes and T-cell cooperatively or independently participate in the pathogenesis of hypereosinophilia-associated heart disease.

Monogenic interferon-mediated diseases: novel phenotype and genotype characteristics from a Saudi population.

IFN-mediated diseases are mendelian innate immunodysregulatory disorders that present early in life with fevers, sterile organ inflammation, and a high type-I IFN-response gene signature in peripheral blood cells. To date, monumental discoveries of novel genetic variants with various phenotypic features have been recognised. We aimed to describe the genotype and phenotype findings in Saudi children diagnosed with autoinflammatory interferonopathy and to report novel findings. This is a descriptive retrospective cohort study of children with genetically confirmed type I interferonopathies. Medical records were reviewed for demographic, family history, clinical and laboratory data. All patients underwent genetic testing. A total of 20 patients (11 females) were included in the study. Sixteen patients (80%) presented within the first 2 years. The median age of disease onset was 0.87 years (IQR: 0.5-2) and the median age of diagnosis was 4.5 years (IQR: 2-7.5). The rates of consanguinity and family history of affected members were high (88% and 47%, respectively). Among the cohort of patients, whole exome sequencing was conducted for 15 patients. Three patients underwent targeted gene tests, and 2 patients had a leukoencephalopathy genetic panel. Eight patients were diagnosed with Aicardi-Goutières syndrome, attributed to variants in the RNASEH2A, RNASEH2C, and IFIH1 genes. Additionally, 2 patients were identified with STING-associated vasculopathy with onset in infancy linked to the TMEM173 variant. One patient exhibited chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature due to PSMB8, and another patient had DNase II. Moreover, 8 patients presented with rare interferonopathy conditions, including three with ISG15, 3 with ZNFX1, 1 with the SOCS1 variant, and 1 the STAT1 variant. Of 12 variants, six (50%) found to have novel genetic variants. The most frequent features were fever (75%), neurology (70%), mucocutaneous (60%), gastrointestinal (50%), and pulmonary (50%). Hypogammaglobinaemia and recurrent infections were seen in (45%) and (20%), respectively. Fifteen patients (75%) had elevated inflammatory markers. The majority of patients received intensive treatment, including corticosteroids, JAK inhibitors, IVIG, and various immunosuppressive agents. Despite these interventions, a partial response to treatment was observed, and cumulative disease damage primarily manifested as growth failure and developmental delay. Our findings support the previous reports; early-onset fever, neurology, and respiratory features should raise the suspicion of interferonopathies. However, there is eminent evidence of phenotypic variability. Our data also expanded the spectrum of clinical findings in relation to novel genetic variants.

Clinical Significance of Serum Cystatin C in SLE: A Potential Marker of Disease Damage Beyond Lupus Nephritis

Objective: This work aimed to assess the serum level of cystatin C in systemic lupus erythematosus (SLE) patients and to determine the relation to disease characteristics and damage. Methods: The study included 33 SLE patients presenting to the Internal Medicine and Rheumatology Department and Outpatient clinic, King Abdulaziz University, Saudi Arabia. The medical history, clinical examination, laboratory investigations and medications received by the patients were recorded. The systemic lupus international collaborating clinics damage index (SLICC-DI) was assessed. Serum cystatin C was measured using the immune-nephelometric method. Results: The mean age of the patients was 35.3±10.7 years; 28 females and 5 males (F:M 5.6:1), disease duration 5.5±3.1 years and their age at onset was 27.9±10.6 years. Serum cystatin C level was significantly higher in patients with lupus nephritis (LN) (2.47±1.57 mg/L vs v mg/L, p=0.003) and diabetes (4.92±0.05 mg/L vs 1.93±1.34 mg/L; p&lt;0.0001) and was lower in those with thyroid dysfunction (1.41±0.75 mg/L vs 2.3±1.59 mg/L, p=0.047). There was a significant correlation between the serum cystatin C level with proteinuria (r=0.57, p=0.011) and with the SLICC-DI (r=0.42,p=0.016). Serum cystatin C could discriminate patients with LN at cut-off value of 0.904 mg/L with area under the curve of 0.765, sensitivity 87% and specificity 50%; p=0.017. Conclusion: The remarkable association between cystatin C and LN is confirmed and an emerging role is noted in reflecting the extent of disease damage. The likely association with diabetes and thyroid dysfunction should also be taken into consideration when deciding treatment regimens for LN patients.

Revisiting Childhood-Onset Systemic Lupus Erythematosus.

Childhood-onset systemic lupus erythematosus (cSLE) is a chronic autoimmune disease with a multisystemic involvement diagnosed during childhood. The disease is marked by the production of autoantibodies targeting self-antigens, often before symptoms emerge. The presentation, clinical course, and outcome vary significantly among patients with cSLE. The onset of cSLE can be at any age during childhood while a diagnosis of cSLE before the age of 5 years is rare and raises a suspicion of monogenic lupus. Childhood-onset systemic lupus erythematosus affects various organs and systems, most frequently presenting with mucocutaneous, musculoskeletal, renal, and neuropsychiatric manifestations. Multiple disease flares can be seen during the disease course. Childhood-onset systemic lupus erythematosus causes significant morbidity and mortality. Children and adolescents with cSLE show higher disease activity and damage, and more aggressive immunosuppressive treatments are needed compared to adultonset SLE. Early diagnosis can be difficult due to the insidious onset with nonspecific symptoms. Disease activity and damage measures aim to ensure an accurate evaluation of disease status. A multidisciplinary approach and individualized disease management are important. Disease management is complex including the control of disease activity, the reduction of flares and damage, and a limitation of drug toxicity while improving the health-related quality of life in patients with cSLE.

The interplay of environmental factors and neuroscience: Investigating tissue damage in environmental diseases

The interplay of environmental factors and neuroscience: Investigating tissue damage in environmental diseases

The effect of crocin on movement disorders and oxidative DNA damage in Parkinson's disease: Insights from a randomized controlled trial

BackgroundParkinson's disease (PD), the second most prevalent neurological disorder in the elderly, manifests with distinctive movement disorders, including bradykinesia, resting tremor, and stiffness. With a progressive course, current treatment strategies primarily target symptomatic relief. Crocin is a chemical compound isolated from the dry stigma of Crocus sativus, and has demonstrated neuroprotective properties. ObjectivesThis study explores the impact of crocin on movement disorders and neuronal oxidative DNA damage in PD patients. MethodConducted as a randomized, blinded, and controlled trial, this research focused on patients aged 30 to 80 with idiopathic PD. Using the second and third parts of the movement disorder society-unified PD rating scale (MDS-UPDRS), aspects of daily life activity and movement disorders were assessed before and after an 8-week intervention. Patients in the crocin groups received capsules containing 30 mg of crocin twice daily. Additionally, the 8-hydroxy-2-deoxydiguanosine (8-OHdG) to urinary creatinine ratio (8-OHdG/uCr) was measured to evaluate neuronal oxidative DNA damage. ResultsOut of the initially evaluated 164 patients, 30 were randomly assigned to each group, with 53 subjects completing the study. Within-group analysis revealed a significant improvement in the second and third parts of MDS-UPDRS after 8 weeks of crocin intervention (P < 0.05). However, the 8-OHdG/uCr did not show significant changes. The well-tolerated daily dose of 60 mg of crocin demonstrated minimal side effects. ConclusionThis study establishes the efficacy of crocin in enhancing daily life activities and mitigating movement disorders, suggesting its potential as a supplementary intervention alongside conventional PD medications.

Coronary Artery Calcification Progression in Patients With Systemic Lupus Erythematosus.

To evaluate the progression of coronary artery calcification (CAC) and associated risk factors in a systemic lupus erythematosus (SLE) cohort. We reassessed the presence of CAC in patients with SLE who were screened 9 years before, using multidetector computed tomography. Clinical variables (cumulated disease activity and damage accrual), antiphospholipid syndrome and SLE serology, and cardiovascular (CV) risk factors (hypertension, BMI [kg/m2], modified Framingham risk score, lipid profile, menopausal status) were assessed longitudinally. We included 104 patients from the parent study. Most of them were women (94.2%), with a mean age of 41.0 (SD 8.3) years and mean disease duration of 14.8 (SD 2.9) years. We documented CAC in 17 patients (16.3%). Seven cases were from the parent study and 10 were incident cases. The cumulative incidence of CAC was 9% and the incidence density was 1 per 100 person-years. CAC occurred more frequently in the age groups 30-39 years and 40-44 years. All patients with previous CAC had worsening of their calcium indexes, and none developed clinical CV events. When comparing prevalent CAC cases (n = 17) vs patients without calcification (n = 87), both groups were similar in traditional CV risk factors, disease duration, Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) area under the curve (AUC), and Systemic Lupus International Collaborating Clinics (SLICC) score, but were more likely to be postmenopausal and have higher apolipoprotein B (apoB) levels. Patients with previous CAC had higher apoB levels, SLEDAI-2K AUC scores, and anticardiolipin IgG antibodies than incident cases. CAC in patients with SLE progressed over time but was not associated with adverse CV events during the first 9 years of follow-up. ApoB levels and postmenopausal status might be associated with this progression.

Peningkatan Kesadaran Kesehatan melalui Deteksi Dini Hipertensi dan Penyuluhan Kesehatan

Hypertension can lead to serious complications such as heart disease, stroke, and kidney damage. The prevalence of hypertension often goes undetected due to minimal symptoms, so many individuals are unaware of it. Early detection through routine blood pressure measurements and health education is important for risk identification and effective management of hypertension. Blood pressure checks and health education are important first steps in raising public health awareness. This activity aims to identify individual health conditions and provide the knowledge necessary to maintain optimal health. From the data obtained, 14% of participants showed symptoms of hypotension, 66% had normal blood pressure, and 20% already had hypertension. These results show the need for continuous efforts in blood pressure monitoring and health education to reduce the risk of blood pressure-related diseases. This service emphasizes the importance of early detection and increased public understanding of the importance of keeping blood pressure within the normal range to prevent further health complications.