Development Of Disease Research Articles

Ocular effects of eye cosmetic formulations

Objective To study the ocular effects seen among eye cosmetic wearers in the Indian Population. Methods This cross-sectional study was conducted on female participants who had fulfilled the inclusion and exclusion criteria. A detailed history was obtained and thorough ophthalmic evaluation was done. Mann Whitney U test was used. Statistical analysis was done using IBM SPSS. p < .05 was taken as the level of statistical significance. Results Among a total of 225 participants in our study, the mean age was 24.23 ± 1.8, which comprised of young student females. Majority of the females used one eye cosmetic with Kajal (n = 156) being the most predominant. Most frequently encountered symptom upon using eye cosmetics was watering from eyes and ocular pain was the least encountered symptom. Anterior segment examination showed- allergic conjunctivitis and meibomian gland dysfunction being the most and least predominant, respectively. Our study highlights that Kajal predisposes the eyes to significant ocular morbidity with p = .039 for dry eye disease, p = .041 for allergic conjunctivitis, p = .036 for conjunctival pigmentation. Prolonged use of such formulations for more than 4 times a week (p = .046) or even daily (p = .031) for a duration of either 1–5 years (p = .033) or greater than 5 years (p = .027) was found to be statistically significant in causing ocular signs. Non removal of eye cosmetics at the end of the day was significant in causing allergic conjunctivitis (p = .035) and conjunctival pigmentation (p = .021). Plain tap water has been found to be the least effective technique in the removal of such ocular cosmetics with a statistical significance of p = .031 in causing ocular signs. Conclusions Eye cosmetics are a significant contributor to the development of ocular surface diseases. Removal of products along with decreased usage seems to be a significant contributor in dampening unwanted adverse effects.

Gastrointestinal stromal tumour (GIST): British Sarcoma Group clinical practice guidelines.

British Sarcoma Group guidelines for the management of GIST were initially informed by those published by the European Society of Clinical Oncology. This update was written by a group of experts to includes a discussion of the highlight improvements in our knowledge of the disease and recent treatment developments. The guidelines include sections on Incidence, Aetiology, Diagnosis, including risk assessment, Treatment and Follow-up. A careful review of the literature was performed to ensure that wherever possible recommendations are supported by the results of clinical trials or substantive retrospective reports. Areas of uncertainty are indicated appropriately. Guidelines represent a consensus view of current best clinical practice. Where appropriate, key recommendations are given and the levels of evidence and strength of recommendation gradings are those used by the European Society for Medical Oncology (ESMO).

The immune system in Parkinson's disease: what we know so far.

Parkinson's disease (PD) is characterised neuropathologically by the degeneration of dopaminergic neurons in the ventral midbrain, the accumulation of α-synuclein (α-syn) aggregates in neurons, and chronic neuroinflammation. In the past two decades, in vitro, ex vivo and in vivo studies have consistently shown the involvement of inflammatory responses mediated by microglia and astrocytes, which may be elicited by pathological α-syn or signals from affected neurons and other cell types, and are directly linked to neurodegeneration and disease development. Besides the prominent immune alterations seen in the central nervous system (CNS), including the infiltration of T-cells into the brain, more recent studies have demonstrated important changes in the peripheral immune profile within both the innate and adaptive compartments, particularly involving monocytes, CD4+ and CD8+ T-cells. This review aims to integrate the consolidated understanding of immune-related processes underlying the pathogenesis of PD, focusing on both central and peripheral immune cells, neuron-glia crosstalk as well as the central-peripheral immune interaction during the development of PD. Our analysis seeks to provide a comprehensive view of the emerging knowledge of the mechanisms of immunity in PD and the implications of this for better understanding the overall pathogenesis of this disease.

INFLUENCE OF PROFESSIONAL FACTORS ON THE DEVELOPMENT OF GYNECOLOGICAL PATHOLOGY IN FLIGHT ATTENDANCE IN CIVIL AVIATION

The literature review reflects the main possible gynecological pathologies in flight attendants, as well as the causes of their occurrence. These diseases are a serious problem for all women, but professionals working in the aviation industry are at a higher risk of developing them. The article focuses on the study of various factors that can contribute not only to the development of gynecological diseases, but also to breast cancer, as well as venous thrombosis in flight attendants. Risk factors include long-term exposure to ionizing radiation, static stress, jet lag, and chronic stress. The review includes an analysis of existing studies related to the impact of occupational exposure on the health of flight attendants, and also suggests possible measures for the prevention and treatment of emerging pathology, which can serve as a basis for the development of effective programs to preserve the health of women working in civil aviation.

Xenoestrogen concentration in women with endometriosis or leiomyomas: A case-control study.

Xenoestrogens are synthetic or naturally occurring chemicals capable of altering the endocrine system of humans and animals owing to their molecular similarity to endogenous hormones. There is limited data regarding their effects on women´s health. Chronic exposure to xenoestrogens can promote the development of estrogen-related diseases. To examine xenoestrogen concentration (TEXB-α) differences between women with leiomyomas or endometriosis and control women, and to study the relationship between the clinical and sociodemographic characteristics of these patients and their xenoestrogen levels. Prospective case-control study. We selected 221 women who underwent surgery at Quironsalud Madrid University Hospital between 2017 and 2021. The cases included 117 patients: 74 women who underwent surgery for uterine leiomyomas, 21 with endometriosis, and 22 with both pathologies. The control group comprised 104 healthy women who underwent surgical procedures for other reasons. TEXB-α was determined in the omental fat of all patients. Using a questionnaire and reviewing the patients' medical records, we collected sociodemographic data and other relevant variables. A significant majority of study participants (68.8%) had detectable levels of xenoestrogens. We found no association between TEXB-α levels in omental fat and the presence of myomas or endometriosis. In the case group, women living or working in Madrid Community exhibited, on average, 3.12 Eeq pM/g higher levels of TEXB-α compared to those working in other areas (p = 0.030). Women who referred to the use of estrogen-containing hormonal contraceptives had, on average, 3.02 Eeq pM/g higher levels of TEXB-α than those who had never used them (p = 0.022). This study found no association between omental xenoestrogen levels and leiomyomas or endometriosis. However, their presence in most participants and their association with highly polluted areas emphasizes the importance of limiting environmental exposure to these substances. We also identified an association between hormonal contraceptive use and xenoestrogen concentration.

Modern approach to pharmacotherapy of chronic insomnia in childhood

Aim. Insomnia is a widespread problem in the pediatric population. The prevalence of insomnia in childhood varies from 5 to 50%. The lack of adequate therapy can lead to chronicity of the disease, impairment of the child’s cognitive and motor functions, and in the long term – the development of cardiovascular and metabolic diseases, diabetes, gastrointestinal and mental disorders. Thus, timely identification and treatment of childhood insomnia is important. The goal is to summarize and systematize current information about the modern approach to pharmacotherapy of chronic insomnia in childhood. Materials and methods: an analysis of modern and foreign publications, randomized controlled trials over the past 10 years was carried out. Results. Treatment of chronic insomnia includes non-pharmacological and pharmacological approaches. Behavioral strategies are recommended as first-line treatment for childhood insomnia. The presence of different pharmacological groups of drugs allows for a personalized approach to treatment. The use of “off-label” drugs requires justified prescription. Conclusion. The lack of large-scale clinical studies on the effectiveness, tolerability, dosing and safety profile of drugs dictates the need for further research to better understand the risks (negative side effects) and benefits of using medications for sleep disorders in children.

The interplay of hydrogen sulfide and microRNAs in cardiovascular diseases: insights and future perspectives.

Hydrogen sulfide (H2S) is recognized as the third gasotransmitter, after nitric oxide (NO) and carbon monoxide (CO). It is known for its cardioprotective properties, including the relaxation of blood vessels, promotion of angiogenesis, regulation of myocardial cell apoptosis, inhibition of vascular smooth muscle cell proliferation, and reduction of inflammation. Additionally, abnormal H2S generation has been linked to the development of cardiovascular diseases (CVD), such as pulmonary hypertension, hypertension, atherosclerosis, vascular calcification, and myocardial injury. MicroRNAs (miRNAs) are non-coding, conserved, and versatile molecules that primarily influence gene expression by repressing translation and have emerged as biomarkers for CVD diagnosis. Studies have demonstrated that H2S can ameliorate cardiac dysfunction by regulating specific miRNAs, and certain miRNAs can also regulate H2S synthesis. The crosstalk between miRNAs and H2S offers a novel perspective for investigating the pathophysiology, prevention, and treatment of CVD. The present analysis outlines the interactions between H2S and miRNAs and their influence on CVD, providing insights into their future potential and advancement.

A suite of genome-engineered hepatic cells provide novel insights into the spatiotemporal metabolism of APOB and APOB-containing lipoprotein secretion.

APOB-containing very-low-density lipoprotein (VLDL) production, secretion, and clearance by hepatocytes is a central determinant of hepatic and circulating lipid levels. Impairment of any of the aforementioned processes is associated with the development of multiple diseases. Despite the discovery of genes and processes that govern hepatic VLDL metabolism, our understanding of the different mechanistic steps involved is far from complete. An impediment to these studies is the lack of tractable hepatocyte-based systems to interrogate and follow APOB in cells, which the current study addresses. To facilitate the cellular study of VLDL metabolism, we generated human hepatic HepG2 and Huh-7 cell lines in which CRISPR/Cas9-based genome engineering was used to introduce the fluorescent protein mNeonGreen into the APOB gene locus. This results in the production of APOB100-mNeon that localizes predominantly to the endoplasmic reticulum (ER) and Golgi by immunofluorescence and electron microscopy imaging. The production and secretion of APOB100-mNeon can be quantitatively followed in medium over time, and results in production of lipoproteins that are taken up via the LDLR pathway. Importantly, the production and secretion of APOB-mNeon is sensitive to established pharmacological and physiological treatments, and to genetic modifiers known to influence VLDL production in humans. As a showcase, we used HepG2-APOBmNeon cells to interrogate ER-associated degradation (ERAD) of APOB. Using a dedicated sgRNA library targeting all established membrane-associated ER-resident E3 ubiquitin ligases led to identification of SYNV1 as the E3 responsible for degradation of poorly-lipidated APOB in HepG2 cells. In summary, the engineered cells reported here allow the study of hepatic VLDL assembly and secretion, and facilitate spatiotemporal interrogation induced by pharmacologic and genetic perturbations.

Pre-Procedural Predictors of Successful Endoscopic Sleeve Gastroplasty: A Retrospective Study

Objective: Obesity is a major risk factor for the morbidity and mortality of cardiovascular disease and predicts the development of hypertension, diabetes mellitus and other various diseases. Methods: A retrospective study evaluated predictors for higher total body weight loss following endoscopic sleeve gastroplasty (ESG). Adults (&gt;18 years old) with BMI &gt; 30 kg/m2 who underwent ESG from January 2019 to July 2022 were included. Patients under the age of 18 were excluded from the study. Results: This retrospective cohort included 76 patients, of whom 62 women (81.6%) and 14 were men (18.4%) with a mean age of 46.3 ± 10.4. The mean BMI baseline was 36.6 ± 4.21. Out of the included patients, 10% were lost to follow-up at 1 month, 33% at 3 months, 50% after 6 months, and only 30% met 12 months follow-up. During the follow-up period, no mortality was documented. Three major adverse events (3.9%) were documented (one mediastinal abscess, one lower gastrointestinal bleeding and one pulmonary embolism), all of them in female patients. Among the demographic clinical and laboratory data examined, smoking (N = 6, p &lt; 0.001) was associated with successful ESG, which was determined as total body weight loss (TBWL) above 15%. The rest of the variables examined were not shown to be statistically significant to sleeve success. Overall, 65 of the 76 patients which were studied in this research had more than 5% TBWL, 42 patients had more than 10% TBWL, 21 patients had more than 15% TBWL and 7 patients lost more than 20% of their weight during 1 year of follow-up. Maximal TBWL was achieved 3 months following the procedure. During the first month following ESG, the average weight lost was 8.6% (N = 69); at 3 months, it was 12.3% (N = 48); at 6 months, it was 11.3% (N = 33); and at 12 months, it was 9.8% (N = 13). Smoking was associated with higher weight loss. Conclusions: The current study showed a positive correlation between ESG weight loss above 15% and smoking. Older patients (&gt;50) gained weight earlier, within 3 months, and by 1 year of follow-up almost returned back to their original weight. Females sustained weight loss over 1 year of follow-up compared to males. Patients with lower BMI continued losing weight during the follow-up period (12 months). This study tries to summarize pre-procedural prediction of ESG success.

Porphyromonas gingivalis Vaccine: Antigens and Mucosal Adjuvants.

Porphyromonas gingivalis (Pg), a Gram-negative anaerobic bacterium found in dental plaque biofilm within periodontal pockets, is the primary pathogenic microorganism responsible for chronic periodontitis. Infection by Pg significantly impacts the development and progression of various diseases, underscoring the importance of eliminating this bacterium for effective clinical treatment. While antibiotics are commonly used to combat Pg, the rise of antibiotic resistance poses a challenge to complete eradication. Thus, the prevention of Pg infection is paramount. Research suggests that surface antigens of Pg, such as fimbriae, outer membrane proteins, and gingipains, can potentially be utilized as vaccine antigens to trigger protective immune responses. This article overviews these antigens, discusses advancements in mucosal adjuvants (including immunostimulant adjuvants and vaccine-delivery adjuvants), and their application in Pg vaccine development. Furthermore, the review examines the advantages and disadvantages of different immune pathways and common routes of Pg vaccine immunization. By summarizing the current landscape of Pg vaccines, addressing existing challenges, and highlighting the potential of mucosal vaccines, this review offers new insights for the advancement and clinical implementation of Pg vaccines.

Risk for cardiovascular disease development in rheumatoid arthritis

BackgroundPatients with rheumatoid arthritis have significant cardiovascular mortality and morbidity.ObjectiveTo investigate the effects of chronic inflammation in rheumatoid arthritis on cardiovascular morbidity association with cardiovascular risk factors risk factors. Mortality report is secondary just to show trends without sufficient statistical power as it is accidental endpoint.MethodsA total of 201 individuals without previous cardiovascular disease, 124 with rheumatoid arthritis (investigation group) and 77 with osteoarthritis (control group), were included in the study and followed up for an average of 8 years to assess the development of fatal or non-fatal cardiovascular diseases. The incidence and prevalence of cardiovascular risk factors were also investigated.ResultsThe total incidence of one or more fatal or nonfatal cardiovascular events was 43.9% in the investigation group and 37.5% in the control group. Of these patients, 31.7% and 30.9% survived cardiovascular events in the investigation and control groups, respectively. The most common cardiovascular disease among participants who completed the study and those who died during the study was chronic heart failure. The results of the subgroup analysis showed that strict inflammation control plays a central role in lowering cardiovascular risk.ConclusionA multidisciplinary approach to these patients is of paramount importance, especially with the cooperation of immunologists and cardiologists for early detection, prevention, and management of cardiovascular risks and diseases.

The aryl hydrocarbon receptor pathway is a marker of lung cell activation but does not play a central pathologic role in engineered stone-associated silicosis.

Engineered stone-associated silicosis is characterised by a rapid progression of fibrosis linked to a shorter duration of exposure. To date, there is lack of information about molecular pathways that regulates disease development and the aggressiveness of this form of silicosis. Therefore, we compared transcriptome responses to different engineered stone samples and standard silica. We then identified and further tested a stone dust specific pathway (aryl hydrocarbon receptor [AhR]) in relation to mitigation of adverse lung cell responses. Cells (epithelial cells, A549; macrophages, THP-1) were exposed to two different benchtop stone samples, standard silica and vehicle control, followed by RNA sequencing analysis. Bioinformatics analyses were conducted, and the expression of dysregulated AhR pathway genes resulting from engineered stone exposure was then correlated with cytokine responses. Finally, we inhibited AhR pathway in cells pretreated with AhR antagonist and observed how this impacted cell cytotoxicity and inflammation. Through transcriptome analysis, we identified the AhR pathway genes (CYP1A1, CYP1B1 and TIPARP) that showed differential expression that was unique to engineered stones and common between both cell types. The expression of these genes was positively correlated with interleukin-8 production in A549 and THP-1 cells. However, we only observed a mild effect of AhR pathway inhibition on engineered stone dust induced cytokine responses. Given the dual roles of AhR pathway in physiological and pathological processes, our data showed that expression of AhR target genes could be markers for assessing toxicity of engineered stones; however, AhR pathway might not play a significant pathologic role in engineered stone-associated silicosis.

MVComp toolbox: MultiVariate Comparisons of brain MRI features accounting for common information across measures

Introduction Multivariate approaches have recently gained in popularity to address the physiological unspecificity of neuroimaging measures and to better characterize the complexity of biological processes underlying behavior. However, commonly used approaches are biased by the intrinsic associations between variables, or they are computationally expensive and may be more complicated to implement than standard univariate approaches. Here, we propose using the Mahalanobis distance (D2), an individual-level measure of deviation relative to a reference distribution that accounts for covariance between measures. To facilitate its use, we introduce an open-source python-based tool for computing D2 relative to a reference group or within a single individual: the MultiVariate Comparison (MVComp) toolbox (https://github.com/neuralabc/mvcomp (https://github.com/neuralabc/mvcomp)). The toolbox allows different levels of analysis (i.e., group- or subject-level), resolutions (e.g., voxel-wise, ROI-wise) and dimensions considered (e.g., combining MRI measures or WM tracts). Several example cases are presented to showcase the wide range of possible applications of MVComp and to demonstrate the functionality of the toolbox. Methods &amp; Results The D2 framework was applied to the assessment of white matter (WM) microstructure at 1) the group-level, where D2 can be computed between a subject and a reference group to yield an individualized measure of deviation. We observed that clustering applied to D2 in the corpus callosum yields parcellations that highly resemble known topography based on neuroanatomy, suggesting that D2 provides an integrative index that meaningfully reflects the underlying microstructure. 2) At the subject level, D2 was computed between voxels to obtain a measure of (dis)similarity. The loadings of each MRI measure (i.e., its relative contribution to D2) were then extracted in voxels of interest to showcase a useful option of the MVComp toolbox. These relative contributions can provide important insights into the physiological underpinnings of differences observed. Discussion Integrative multivariate models are crucial to expand our understanding of the complex brain-behavior relationships and the multiple factors underlying disease development and progression. Our toolbox facilitates the implementation of a useful multivariate method, making it more widely accessible.

HPV16 Phylogenetic Variants in Anogenital and Head and Neck Cancers: State of the Art and Perspectives.

HPV16 is responsible for approximately 60% and 90% of global HPV-induced cervical and oropharyngeal cancers, respectively. HPV16 intratype variants have been identified by HPV genome sequencing and classified into four phylogenetic lineages (A-D). Our understanding of HPV16 variants mostly derives from epidemiological studies on cervical cancer (CC) in which HPV16 B, C, and D lineages (previously named "non-European" variants) were mainly associated with high-grade cervical lesions and cancer. Although a predominance of HPV16 lineage A (previously named "European variants") has been observed in head and neck squamous cell carcinoma (HNSCC), epidemiological and in vitro biological studies are still limited for this tumor site. Next Generation Sequencing (NGS) of the entire HPV genome has deepened our knowledge of the prevalence and distribution of HPV variants in CC and HNSCC. Research on cervical cancer has shown that certain HPV16 sublineages, such as D2, D3, A3, and A4, are associated with an increased risk of cervical cancer, and sublineages A4, D2, and D3 are linked to a higher risk of developing adenocarcinomas. Additionally, lineage C and sublineages D2 or D3 of HPV16 show an elevated risk of developing premalignant cervical lesions. However, it is still crucial to conduct large-scale studies on HPV16 variants in different HPV-related tumor sites to deeply evaluate their association with disease development and outcomes. This review discusses the current knowledge and updates on HPV16 phylogenetic variants distribution in HPV-driven anogenital and head and neck cancers.

Consideration of the Disease Complexes, the Missing Link to Correctly Analyze the Impact of Intercropping on Disease Development

Diversification at the plot level, through the use of intercropping (mixtures of crops), is an alternative to the conventional system of intensive agriculture, based on monospecific, usually single-variety canopies. Intercropping has been shown to provide benefits in terms of disease control. However, competition phenomena and the heterogeneity of the associated crops raise new ecological questions, particularly with regard to the dynamics and evolution of parasite populations. No study has assessed the potential impact of these associations on the dynamics of pathogenic species complexes. Changes in the nutritional status of plants and therefore in their physiological susceptibility to infection within intercropping systems could contribute to an increased diversity of ecological niches and thus affect the composition of the parasitic complex and its spatiotemporal dynamics. In this review, focusing on foliar diseases of fungal origin, and after outlining some elements of the biology and epidemiology of these fungal diseases, we will (i) describe the mechanisms that contribute to the composition of disease clusters and that drive interactions, but we will also review the strategies that these foliar diseases have adopted to deal with these co-infections; (ii) define how intercropping can lead to changes in epidemic dynamics, in particular by presenting the mechanisms that have a direct and indirect effect on disease evolution; and (iii) present the approach that should be adopted to properly study intercropping correctly in a multi-infection situation.

The role of retroelements of the human genome in the development of type 1 diabetes mellitus

Retroelements (retrotransposons and endogenous retroviruses) are a class of mobile genetic elements that move in the genome by inserting their own reverse transcribed transcripts. They serve as drivers of epigenetic regulation; therefore, individual characteristics of the distribution of retroelements in the genome influence the development of multifactorial diseases. Type 1 diabetes mellitus is a multifactorial disease with an immune response against pancreatic β cells. The role of heredity in the development of the disease is estimated at 88%, and the role of allelic variants of various genes is determined. There are also other specific types of diabetes mellitus, which account for more than 2% of cases of diabetes mellitus and are monogenic diseases with an autosomal dominant mode of inheritance due to germline mutations in the MODY genes, including HNF4A, GCK, HNF1A, HNF1B. Most patients with type 1 diabetes have the protein product and ribonucleic acid (RNA) of the insulin inhibitor HERV-W-Env, which is caused by abnormal expression of the human endogenous retrovirus (HERV). An assumption has been made about the role of retroelements in the development of type 1 diabetes mellitus. This is due to their involvement in the phylogenetic formation of the endocrine system, since in evolution retroelements turned out to be sources of regulatory sequences of hormone genes, nuclear hormone receptors and binding sites for them. Type 1 diabetes mellitus is associated with the integration of HERV into the HLA-DQ gene region, with allelic variants and sizes of VNTR variable tandem repeats (part of the SVA retroelements), which regulate the expression of the insulin gene and other hormones. For this reason, it is likely that the development of type 1 diabetes mellitus may be based on individual characteristics of the distribution of HERVs in the human genome and their dynamic changes in ontogenesis. HERVs also play a role in the etiopathogenesis of diabetes mellitus through the activation of an autoimmune response, the triggering factors of which are exogenous viral infections and stress. Thus, retroelements are involved in various mechanisms of the development of type 1 diabetes mellitus, which reflects their global regulatory influence on endocrine regulation.

ER stress inhibition enhances formation of triacylglcerols and protects endothelial cells from lipotoxicity

Elevated concentrations of palmitate in serum of obese individuals can impair endothelial function, contributing to development of cardiovascular disease. Although several molecular mechanisms of palmitate-induced endothelial dysfunction have been proposed, there is no consensus on what signaling event is the initial trigger of detrimental palmitate effects. Here we report that inhibitors of ER stress or ceramid synthesis can rescue palmitate-induced autophagy impairment in macro- and microvascular endothelial cells. Furthermore, palmitate-induced cholesterol synthesis was reverted using these inhibitors. Similar to cell culture data, autophagy markers were increased in serum of obese individuals. Subsequent lipidomic analysis revealed that palmitate changed the composition of membrane phospholipids in endothelial cells and that these effects were not reverted upon application of above-mentioned inhibitors. However, ER stress inhibition in palmitate-treated cells enhanced the synthesis of trilglycerides and restored ceramide levels to control condition. Our results suggest that palmitate induces ER-stress presumably by shift in membrane architecture, leading to impaired synthesis of triglycerides and enhanced production of ceramides and cholesterol, which altogether enhances lipotoxicity of palmitate in endothelial cells.

Sclerotia degradation by Trichoderma-mycoparasitic; an effective and sustainable trend in the drop lettuce disease control caused by Sclerotinia sclerotiorum.

Controlling the hazard of sclerotia produced by the Sclerotinia sclerotiorum is very complex, and it is urgent to adopt an effective method that is harmonious environmentally to control the disease. Among the six isolates isolated from the rhizosphere of lettuce, the isolate HZA84 demonstrated a high activity in its antagonism towards Sclerotinia sclerotiorum in vitro, and produces siderophore. By amplification of internal transcribed spacer (ITS), translation elongation factor 1-alpha (TEF1-α), and RNA polymerase II subunit (RPB2) genes, the isolate HZA84 was identified as Trichoderma asperellum, which was confirmed by analysis of phylogenetic tree. The Scanning electron microscope monitoring detected that the isolate HZA84 spread over the sclerotial surface, thus, damaging, decomposing, and distorting the globular cells of the outer cortex of the sclerotia. The Real-time polymerase chain reaction (RT-qPCR) analysis disclosed the overexpression of two genes (chit33 and chit37) encoding the endochitinase in addition to one gene (prb1) encoding the proteinase during 4 and 8days of the parasitism behavior of isolate HZA84 on the sclerotia surface. These enzymes aligned together in the sclerotia destruction by hyperparasitism. On the other hand, the pots trial revealed that spraying of isolate HZA84 reduced the drop disease symptoms of lettuce. The disease severity was decreased by 19.33 and the biocontrol efficiency was increased by 80.67% within the fourth week of inoculation. These findings magnify the unique role of Trichoderma in disrupting the development of plant diseases in sustainable ways.

Establishment of a Posttraumatic Osteoarthritis Model in Mice Induced by Noninvasive Anterior Cruciate Ligament Tear.

Animal models that use open surgical transection of the anterior cruciate ligament (ACL) do not accurately simulate the clinical condition regarding the pivot-shift mechanism and the associated inflammatory response that occurs before reconstruction. The purpose was to characterize a reproducible manual, nonsurgical method to mimic an isolated ACL tear in a clinically relevant model and to evaluate the development of progressive posttraumatic osteoarthritis due to ACL injury. It was hypothesized that the ACL could be reproducibly torn with minimal damage to other ligaments and that there would be progressive development of degenerative joint disease after ACL injury. Controlled laboratory study. A total of 37 mice (strain C57BL/6) were used to compare the manual procedure with sham surgery (sham group; n = 10) and with the established surgical ACL transection (ACLT) procedure (surgical group; n = 27). In the sham group, a closed manual procedure was performed on the right knee and sham surgery on the left knee. In the surgical group, the closed manual procedure was performed on the right knee and surgical ACLT on the left knee. Dissection using India ink, histological assessment with safranin O and hematoxylin-eosin staining, radiological evaluation through radiographs and microfocus computed tomography scans, and gait analyses were performed to assess cartilage/ligament status. Osteoarthritis Research Society International (OARSI) and synovitis scores, anterior tibial translation, range of motion, bone microstructure, osteophyte volume, and pain were assessed at 2, 4, and 8 weeks postoperatively. The manual procedure successfully resulted in an ACL rupture and associated meniscal injury. The posterior cruciate, lateral collateral, and medial collateral ligaments were intact in all dissected knees. Two weeks after ACL tear, the surgical group showed a significantly higher synovitis score, whereas 8 weeks after ACL tear, the manual group showed a significantly higher volume of osteophytes. No significant differences were found between the groups in terms of OARSI score, anterior tibial translation, range of motion, bone microstructure computed tomography values, and stride distance/irregularity. This procedure can be used to create an ACL tear model without causing grossly evident injuries to other ligaments and avoiding the risk of cartilage damage from surgical instruments. This procedure offers a more clinically relevant ACL tear model and facilitates simple, inexpensive, and reproducible development of posttraumatic osteoarthritis.

Current challenges for therapy of comorbid patients: a new look at celecoxib. A review

The use of non-steroidal anti-inflammatory drugs (NSAIDs) for a wide range of diseases is increasing, in part due to an increasing elderly population. Elderly patients are more vulnerable to adverse drug reactions, including side effects and adverse effects of drug-drug interactions, often occurring in this category of patients due to multimorbidity and polypharmacy. One of the most popular NSAIDs in the world is celecoxib. It is a selective cyclooxygenase (COX)-2 inhibitor with 375 times more COX-2 inhibitory activity than COX-1. As a result, celecoxib has a better gastrointestinal tract safety profile than non-selective NSAIDs. Gastrointestinal tolerance is an essential factor that physicians should consider when selecting NSAIDs for elderly patients. Celecoxib can be used in a wide range of diseases of the musculoskeletal system and rheumatological diseases, for the treatment of acute pain in women with primary dysmenorrhea, etc. It is also increasingly used as part of a multimodal perioperative analgesia regimen. There is strong evidence that COX-2 is actively involved in the pathogenesis of ischemic brain damage, as well as in the development and progression of neurodegenerative diseases, such as Alzheimer's disease. NSAIDs are first-line therapy in the treatment of acute migraine attacks. Celecoxib is well tolerated in patients with risk factors for NSAID-associated nephropathy. It does not decrease the glomerular filtration rate in elderly patients and patients with chronic renal failure. Many meta-analyses and epidemiological studies have not confirmed the increased risk of cardiovascular events reported in previous clinical studies and have not shown an increased risk of cardiovascular events with celecoxib, irrespective of dose. COX-2 activation is one of the key factors contributing to obesity-related inflammation. Specific inhibition of COX-2 by celecoxib increases insulin sensitivity in overweight or obese patients. Combination therapies may be a promising new area of treatment for obesity and diabetes.