Initial Stages Of Disease Research Articles

Yeni Tiyazolil-Hidrazin Türevlerinin Sentezi ve Asetilkolinesteraz (AChE) ve Bütirilkolinesteraz (BuChE) Aktivite Çalışmaları

Alzheimer hastalığı (AH), zamanla beyin hücrelerinin ölümüne bağlı olarak bilişsel işlevlerde azalma, hafıza kaybı ve bunama ile ilişkilendirilmiştir. Alzheimer hastalığının tedavisinde sınırlayıcı uygulamaların mevcut oluşu, hastalığın sağlık harcamalarında kanser ve kalp hastalıklardan sonra dünyada üçüncü sırada oluşu araştırmacıları AH üzerinde erken evrede tanıma ve yeni tedavi yöntemlerine yönlendirmektedir. Günümüzde kolinerjik anomalikler ile AH arasında doğrudan bir ilişki olduğu düşünülmektedir. Çalışmalar, asetilkolinesteraz (AChE) ve bütirilkolinesteraz (BuChE) inhibisyonunun asetilkolin (ACh) seviyesinde meydana gelen artışların Alzheimer hastalığının başlangıç evrelerindeki bilişsel yetmezliği iyileştirebileceğini kanıtlamıştır. Dolayısıyla ACh düzeylerini arttırmak için uygulanacak en iyi metot ise, ACh’yi yıkan AChE veya BuChE enzimlerinin baskılanmasıdır. Dolayısıyla yapılan bu çalışmada, sübstitüe edilmiş tiyazolilhidrazin türevleri tasarlanmış, sentezlenmiş ve AH’ ye karşı asetilkolinesteraz (AChE) ve bütirilkolinesteraz (BuChE) kolinesteraz enzimlerinin inhibisyon potansiyelleri araştırılmıştır. Hedef bileşiklerin yapıları 1H NMR/13C NMR analiz yöntemleri ile aydınlatılmıştır. Hedef bileşiklerin AChE ve BuChE enzimleri üzerindeki inhibisyon etkileri Ellman yöntemiile değerlendirilmiş ve hedef bileşiklerin enzim inhibisyon çalışmaları sonucunda 3d bileşiğinin orta düzeyde bütirilkolinesteraz enzimini inhibe ettiği tespit edilmiştir.

The Relationship Of The Anterior Dental Malocclusion With The Incidence Of Gingivitis In Students Of Medical Faculty in Surabaya

Introduction: Gingivitis is an inflammation of the gums, which is the initial stage of gum and periodontal tissue disease, characterized by red gingival tissue, bleeding easily, bad breath (halitosis), and the presence of debris on the teeth and cervical area. Misaligned tooth is said to be one of the predisposing factors for gingivitis. Purpose: To determine the relationship between the arrangement of the anterior mandibular teeth with the incidence of gingivitis in students of the Faculty of Medicine, Wijaya Kusuma University, Surabaya. Methods: This study used a purposive sampling method with a total population of 125 subjects. From this population, 56 people were taken who experienced anterior crowding with gingivitis. The degree of malocclusion, i.e. anterior crowding, was examined clinically and was associated with gingivitis. The data obtained were analyzed by Chi-square test. Results: There is a significant relationship between the anterior mandibular malocclusion and the incidence of gingivitis (p< 0,05). Conclusion: Anterior tooth arrangement affects the incidence of gingivitis among medical faculty students in Surabaya.

P1740: HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM) TREATED WITH IDECABTAGENE VICLEUCEL VS BELANTAMAB MAFODOTIN: A MATCHING-ADJUSTED INDIRECT COMPARISON STUDY

Background: Patients (pts) with RRMM who are triple-class exposed (TCE; to an immunomodulatory imide drug [IMiD® agent], proteasome inhibitor [PI], and anti-CD38 monoclonal antibody [mAb]) have poor clinical outcomes and poor health-related quality of life (HRQoL). The B-cell maturation antigen (BCMA)-directed CAR T cell therapy idecabtagene vicleucel (ide-cel, bb2121) received regulatory approval in the US for pts with RRMM with ≥4 prior lines of therapy (LOT), including an IMiD agent, PI, and anti-CD38 mAb, and in Europe and Japan for pts with RRMM with ≥3 prior LOTs including an IMiD agent, PI, and anti-CD38 mAb. Ide-cel showed frequent, deep, and durable responses in TCE pts with RRMM in KarMMa, a phase 2, single-arm trial (NCT03361748). Clinically meaningful improvements in HRQoL outcomes vs baseline were observed. The BCMA-targeted antibody-drug conjugate belantamab mafodotin (BM) was approved in the US and Europe for pts with RRMM with ≥4 prior LOTs including an IMiD agent, PI and anti-CD38 mAb, based on data from the phase 2, single-arm DREAMM-2 trial (NCT03525678). There is a paucity of evidence comparing HRQoL for different treatment options approved in RRMM. Aims: To compare HRQoL outcomes for TCE pts with RRMM treated with ide-cel vs BM. Methods: Data were analyzed using unanchored matching-adjusted indirect comparisons. Between-study differences in pt characteristics were adjusted using individual-level pt data from KarMMa to align with summary-level pt characteristics from DREAMM-2. The ide-cel-treated population (N=128; median follow-up 15.4 months) from KarMMa (of whom, 54 pts received the target dose of 450×106 CAR+ T cells) and the intention-to-treat population (N=97; median follow-up 13.0 months) from DREAMM-2 who received the 2.5 mg/kg dose of BM (Popat et al. HemaSphere 2020;4:S1. EP1746) were analyzed. Predefined outcomes of interest were differences in mean change from baseline scores for the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) pain, fatigue, and global health/QoL domains, and the QLQ-Multiple Myeloma (MY20) pain domain. Analyses were performed at 2, 3, 4, 6, 9, and 12 months of follow-up. Given differences in time points of evaluation between KarMMa and DREAMM-2, the nearest neighbor approach was used. Pt characteristics included as covariates in the propensity model included: age, sex, race, years from initial diagnosis, disease stage, and number of prior treatments. Sensitivity analyses included additional covariates: high-risk cytogenetics and extramedullary disease. Results: Ide-cel was associated with improved HRQoL vs BM at all evaluated time points for the QLQ-C30 global health status/QoL domain (Table). Improved HRQoL scores were statistically significant for ide-cel vs BM at 6 and 9 months for the QLQ-C30 fatigue domain (HRQoL scores were numerically better for ide-cel vs BM at all other time points). Similarly, HRQoL scores favored ide-cel vs BM at all evaluated time points for the QLQ-C30 pain and QLQ-MY20 pain domains, with statistically significant findings at 4, 6, and 9 months for QLQ-C30 and 3, 4, and 6 months for QLQ-MY20. Sensitivity analyses were consistent with the base case analyses. Image:Summary/Conclusion: While this analysis was limited by the availability of aggregate data from DREAMM-2, which may influence the outcomes of interest, results suggest that one-time treatment with ide-cel offers improved HRQoL vs BM across the QLQ-C30 pain, fatigue, and global health status/QoL domains, as well as the QLQ-MY20 pain domain.

Challenges of Diagnosis and Treatment Choice in Riedel‘s Fibrosing Thyroiditis: Clinical Case Examples

Background. Clinically distinct Riedel’s fibrosing thyroiditis is extremely rare, accounting for only 0.05 % of histologically verified thyroiditis cases, as follows from the real clinical practice and literature. Classic Riedel’s thyroiditis is typified by a marked compression syndrome, which may lack at initial disease stages. A problematic verification often conduces to a diagnostic and, especially, therapeutic malpractice, as illustrated by the two hereby analysed clinical cases.Materials and methods. The article presents two clinical cases of fibrosing thyroiditis, specifying the diagnosis and treatment choice in patients with this pathology. Diagnosis verification and therapy correction facilitated a favourable outcome.Results and discussion. Riedel’s fibrosing thyroiditis can be reluctant to diagnosis due to asymptomatic thyroid dysfunction, the lack of strict radiological diagnostic criteria and rarity in clinical practice. This provokes diagnostic and later therapeutic malpractices, which correction permitted a favourable outcome.Conclusion. Since treatment for compression syndrome-aggravated Riedel’s fibrosing thyroiditis is exclusively surgical, it continues posing a challenge as associated with likely severe complications. Essentially, the first treatment stage was inadequate in both cases. In the first case, the patient withdrew a thyroid hormone therapy already in 4 days, which precluded serious iatrogenic complications, while in the second case, the long-term drug misuse had conduced to cardiovascular pathology.

Multiscale in silico knowledge-based model predicts tumor growth in advanced EGFR+ NSCLC patients on gefitinib.

e20565 Background: Tumor heterogeneity and treatment resistance remains a continued threat to patients with advanced non-small cell lung cancer (NSCLC), despite the emergence of targeted medicines, e.g. against epidermal growth factor receptor (EGFR) alterations. We developed an in silico EGFR mutated lung adenocarcinoma (EGFR+ LUAD) model to predict the effect of known oncogenic EGFR mutations (common EGFR mutations, EGFR exon 20 insertions). The model provides mechanistic representation of tumor progression, including response to gefitinib and captures tumor heterogeneity, patient age, gender, initial clinical disease stage, and smoking status. Methods: 5-step in silico model development: Model building: biology of EGFR+LUAD was characterized by extracting biological features and their functional relationships from > 300 published papers and translating them into ordinary differential equations (ODEs). Mutational burden, EGFR-downstream-pathways, tumor growth and heterogeneity, gefitinib-PK/PD, treatment-induced resistance and clinical outcome were incorporated into a knowledge-based model containing 27-97 variables, 108-258 parameters and 13-83 ODEs reflecting intra-tumor clonal heterogeneity in a mechanistic manner. Calibration: published spheroid, xenograft and clinical data were used for stepwise calibration to find the correct parameter values. Relevant virtual populations (VPOPs) matching real patients baseline characteristics were generated for model benchmarking and validation. Benchmarking against a published data-based model: coverage of experimental interquartile range (IQR) with simulated IQR (precision) assesses model fit with experimental data, coverage of simulated IQR with experimental IQR (overlap) assesses model fit with experimental variability. Validation: a VPOP with comparable baseline characteristics was simulated and results compared against a published patient dataset that wasn’t used in any step during calibration. Matching of prediction over clinical data was done using both coverage and bootstrapped log-rank metrics. Results: Our model provides comparable outputs to the data-based model without having access to the exact original data (our model: precision of 62%, overlap of 91% VS data-based model: precision of 72% and an overlap of 86%). Besides, as a validation criterion, our model also successfully reproduces the time to progression observed in an independent clinical trial (coverage > 99%, negative log-rank tests > 98%). Conclusions: We simulated tumor growth and treatment response in advanced EGFR+ LUAD patients and successfully validated results both against an existing data-based model and a published clinical data. Our model highlights the potential of in silico modeling to better understand complex diseases progression and support efficient development of innovative therapies.

Analysis of the relationship between social determinants of health and survival outcomes in gestational trophoblastic neoplasia in the United States.

e17537 Background: Gestational trophoblastic neoplasia (GTN) is a rare disease with a reported incidence of 1 in 40,000 pregnancies. There have been no studies evaluating the impact of social determinants of health (SDH) on outcomes in GTN. This study seeks to examine the influence of social and biologic prognostic factors related to survival among women with GTN. We hypothesized that older age at diagnosis, lower household income, and marginalized, racial/ethnic groups are associated with worse prognosis. Methods: In this retrospective study, the Surveillance, Epidemiology, and End Results (SEER) database was used to identify women with GTN diagnosed from 2010-2018. Clinical-pathologic characteristics were described including initial stage of disease, presence of brain metastases at diagnosis, treatment with chemotherapy or surgery, and treatment at a Commission on Cancer (CoC) accredited center. Demographic factors were collected, including race/ethnicity, age at diagnosis, marital status, median household income, and rural or urban location. Log-logistic regression models were used to estimate the association between various prognostic factors and the odds of survival. We compared overall survival distributions across race/ethnicity using the log-rank test. Results: Of the 1,149 eligible patients (pts), 36% were non-Hispanic White (NHW), 21% non-Hispanic Black (NHB), 28% Hispanic, and 14% Other (Native American, Alaska Native, Asian, Pacific Islander). Mean age was 33.8 years (range 14-87 years). The majority was in the 21-35 age group (51%). Compared to NHW pts, Hispanic pts had over two times the odds of increased survival (OR 2.11; 95% CI 1.08-3.27; p = 0.032). NHB pts had similar survival compared to NHW pts (OR 1.06; 95% CI 0.50-1.76; p = 0.860). Poor prognostic factors demonstrating decreased odds of survival included age ≥40 years (OR 0.139; 95% CI 0.025-0.478; p < 0.001) and widowed status (OR 0.09; 95% CI 0.018-0.375; p < 0.001). Localized stage (OR 2.94; 95% CI 1.13-5.53; p = 0.03), the absence of brain metastases (OR 4.58; 95% CI 1.96-7.91; p = 0.002), and rural location (OR 5.62; 95% CI 1.25-15.2; p = 0.028) were significantly associated with increased odds of survival. Household income and race/ethnicity were not independent predictors of survival. Conclusions: Compared to NHW pts, Hispanic pts have an increased cause-specific survival for GTN. NHB pts and NHW pts have similar survival. Additionally, rural location was significantly associated with greater odds of survival. Further research is needed to investigate the underlying mechanisms linking race/ethnicity and survival outcomes, considering structural racism, bias, and discrimination. Our findings highlight the importance of recognizing the role of racism and SDH on health disparities and call to attention the need for addressing social inequities in GTN.

Food-Derived β-Carboline Alkaloids Ameliorate Lipid Droplet Accumulation in Human Hepatocytes.

Lipid droplet accumulation (LDA) in hepatocytes is the initial stage of nonalcoholic fatty liver disease (NAFLD). In the search for natural compounds for the prevention of NAFLD, a series of β-carboline alkaloid derivatives, inspired by flazin and its derivative, newly identified in Crassostrea gigas Thunberg. extracts, were examined for LDA inhibition (LDAI) activity in oleic acid–loaded hepatocytes (HepG2). Eight compounds with a piperidine or pyridine C-ring were chemically synthesized (1–8). Among them, compounds 2 and 4 (flazin) with a carboxy group at C-3 and furfuryl alcohol moiety at C-1 showed low cytotoxicity and they exhibited significant LDAI activity. Compound 2 with piperidine C-ring was identified for the first time in C. gigas extract, and ameliorated the lipid accumulation with the LDAI value of 25.4%. Active compounds 2 and 4 significantly inhibited triacylglycerol species accumulation in cells. These compounds upregulated ATGL and downregulated SREBP1, FASN, and SCD1 genes, suggesting that they activated lipolysis and suppressed lipogenesis, respectively. These results suggest that β-carboline alkaloids, especially compounds 2 and 4, might be potentially useful for preventing NAFLD.

When and which patients should receive remdesivir?

When and which patients should receive remdesivir?

Comparative analysis of cardio-cerebrovascular complications in immigrants and native-born Koreans with diabetes: Risk factors and perspectives

BackgroundGiven the rapidly increasing number of immigrants, it is crucial to address health care issues involving immigrants to facilitate their safe and secure settlement. Especially for common chronic diseases, such as diabetes, immigrants face more complex obstacles to manage their chronic conditions than do native-born residents. Therefore, we aimed to assess differences in the incidence and associated risk factors of cardio-cerebrovascular (CCV) complications of immigrants compared with native-born Koreans with diabetes.MethodsImmigrants and native-born Koreans who had new diagnosis of diabetes and simultaneously received anti-diabetic prescriptions in 2012 were defined by using Korean National Health Insurance Claim Database(KNHICD). CCV complications were assessed at a 3-year follow-up from the index date. We assessed differences in the CCV complications and risk factors using multiple cox regression models.ResultsIn total, 4,008 patients (668 of immigrants and 3,340 of native-born Koreans) who had newly diagnosed diabetes and simultaneously received anti-diabetic prescriptions in 2012 were selected. Immigrants with diabetes were at a 1.39 times higher risk of having CCV complications than native-born Koreans with diabetes (95% CI: 1.021–1.881). Patients who had a usual sources of care (USC) presented a significantly reduced risk of cardio-cerebrovascular complication (HR: 0.452; 95% CI: 0.342–0.598) in both immigrants and native Koreans. In subgroup analysis in immigrants, patients having USC showed decreased risk of CCV incidence (HR: 0.35, 95% CI: 0.175–0.703), whereas >60 years old and Charlson comorbidity index (CCI) score >1 presented increased risk of CCV complications.ConclusionImmigrants with diabetes have a higher risk of CCV complications than native-born Koreans with diabetes. However, having a USC significantly decreased the risk of CCV complications. Therefore, the utilization of USC will benefit to reduce diabetic complications in immigrants as well as reduction of overall health care cost burden, it would be necessary to implement USC in diabetes care at the initial disease stage.

Aberrant miR-339-5p/neuronatin signaling causes prodromal neuronal calcium dyshomeostasis in mutant presenilin mice.

Mushroom spine loss and calcium dyshomeostasis are early hallmark events of age-related neurodegeneration, such as Alzheimer’s disease (AD), that are connected with neuronal hyperactivity in early pathology of cognitive brain areas. However, it remains elusive how these key events are triggered at the molecular level for the neuronal abnormality that occurs at the initial stage of disease. Here, we identify downregulated miR-339-5p and its upregulated target protein, neuronatin (Nnat), in cortex neurons from the presenilin-1 M146V knockin (PSEN1-M146V KI) mouse model of familial AD (FAD). Inhibition of miR-339-5p or overexpression of Nnat recapitulates spine loss and endoplasmic reticulum calcium overload in cortical neurons with the PSEN1 mutation. Conversely, either overexpression of miR-339-5p or knockdown of Nnat restores spine morphogenesis and calcium homeostasis. We used fiber photometry recording during the object-cognitive process to further demonstrate that the PSEN1 mutant causes defective habituation in neuronal reaction in the retrosplenial cortex and that this can be rescued by restoring the miR-339-5p/Nnat pathway. Our findings thus reveal crucial roles of the miR-339-5p/Nnat pathway in FAD that may serve as potential diagnostic and therapeutic targets for early pathogenesis.

Novel Concepts of q -Rung Orthopair Fuzzy Topology and WPM Approach for Multicriteria Decision-Making

A q -rung orthopair fuzzy set (q-ROFS) is a robust approach for fuzzy modeling, computational intelligence, and multicriteria decision-making (MCDM) problems. The aim of this paper is to study the topological structure on q-ROFSs and define the idea of q -rung orthopair fuzzy topology (q-ROF topology). The characterization of q-ROF α -continuous mappings between q-ROF topological spaces and q-ROF connectedness is investigated. Some relationships of different types of q -rung orthopair fuzzy connectedness are also investigated. Additionally, the “ q -rung orthopair fuzzy weighted product model” (q-ROF WPM) is developed for MCDM of a hierarchical healthcare system. Due to limited and insufficient resources, a hierarchical healthcare system (HHS) is very effective to deal with the increasing problems of healthcare. Recognizing the stage of a disease with the symptoms, ranking the critical condition of patients, and referring patients to feasible hospitals are key features of HHS. A HHS will provide healthcare services in three levels, a primary health centers for initial stage of disease, secondary hospitals for secondary stage of disease, and tertiary hospital for the third-order stage. A numerical example is illustrated to demonstrate the efficiency of q-ROF WPM and advantages of HHS.

ПРИМЕНЕНИЕ ОРГАНИЧЕСКИХ СОЕДИНЕНИЙ В ТЕРАПЕВТИЧЕСКОЙ ПРАКТИКЕ ПРИ НАРУШЕНИЯХ ФУНКЦИИ ПЕЧЕНИ

Introduction. The nonspecificity of the clinical manifestations of the initial stage of non-alcoholic fatty liver disease (NAFLD) - the stage of steatosis, is the reason for the untimely correction and progression of this disease. Aim. The aim of the study was to conduct a randomized open comparative study to determine the effectiveness of the use of the food supplement FanDetox as a source of organic compounds in liver function disorders. Material and methods. This study was a single-center randomized open one and included the study of the possibility of using the herbal product FanDetox in the complex therapy of NAFLD in patients aged 18 to 75 years with a verified diagnosis of obesity and the presence of signs of steatohepatosis, against the background of basic therapy with Carsil Forte. The study was conducted with the involvement of 68 people matched by sex and age, 34 of whom made up the main observation group, whose participants took the study product 1 sachet 2 times a day after meals, in the form of a suspension obtained after mixing the powder in 100 ml of water. The rest 34 patients made up the comparison group. Carsil Forte was chosen as a background drug for both groups. The duration of therapy for each study participant was 3 months. The follow-up process included patient visits with a detailed medical history, therapeutic examination, and laboratory and instrumental examinations. Statistical analysis was carried out using the IBM SPSS Statistics 23 program. Results and discussion. As a result, an improvement in the subjective well-being of patients, a decrease in the echoscopic manifestations of fatty hepatosis, a decrease in the longitudinal size of the liver, a decrease in the manifestations of the cytolysis syndrome and bilirubin levels, as well as a significant positive dynamics of the lipid spectrum in the blood of patients who received complex therapy, including the use of the FanDetox biologically active additive, compared with the comparison group undergoing therapy with the background drug Carsil Forte, were shown. Conclusion. It has been established that taking the food supplement FanDetox helps to reduce the manifestations of fatty hepatosis, reduce the longitudinal size of the liver, blood biochemistry indicators and the general well-being of patients.

Significant different Perceptions of the Viral Dynamics and the Immune System to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) Exposure

Aim: The knowledge of viral characteristics in addition immune reply to severe respiratory disorder (Sars Syndrome Coronavirus 2 (SARS-CoV-2) contamination still has significant gaps. Methods: In a retrospective longitudinal cohort analysis of 140 cases having PCR-established SARS-CoV-2 disease, researchers analyzed those parameters and demonstrated their correlation with symptom manifestations (mean age, 44 years; 54 percent male; 48 percent through comorbidities). Breathing models (n = 76) remained obtained for viral culture, serum specimens (n = 32) for IgM/IgG levels, and plasma samples (n = 82) for inflammatory cytokines and chemokines. The illness burden remained connected to the findings of viral culture, serologic tests, also immunological markers. Results: Fifty-eight (58%) cases established viral pneumonia, including 22 (18%) requiring supplementary oxygen and 14 (11%) requiring invasive mechanical ventilation. Twenty of the 77 individuals were positive for viral culture from respiratory samples (24 percent). When the PCR cycle threshold (Ct) value remained more than 31 or greater than 15 days following indication onset, no virus was recovered. Seroconversion happened at a median (IQR) of 13.6 (10–20) days for IgM and 16.1 (14–22) days for IgG; 56/63 patients (88.2 percent) seroconverted on day 15 or later. Health hazard appeared linked to quicker seroconversion as well as greater peak IgM and IgG levels. Conclusion: Researchers discovered that viral viability significantly related having such a lower PCR Ct charge in the initial stages of disease. The seriousness of the illness was linked to a greater antibody level. Overcharged pro-inflammatory immune markers provide marks for host-directed immunotherapy, that would have been investigated in randomized precise studies. Keywords: Coronavirus 2 (SARS-CoV-2), immune response, acute respiratory syndrome.

Vulnerability of the spinal motor neuron presynaptic terminal sub-proteome in ALS

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder, characterised by the loss of motor neurons and subsequent paralysis. Evidence indicates that synaptic alterations are associated with the early stages of ALS pathogenesis. A hallmark of ALS postmortem tissue is the presence of proteinaceous inclusions, indicative of disturbed protein homeostasis, particularly in spinal cord motor neurons. We recently demonstrated that spinal cord motor neurons contain a supersaturated proteome, as they possess proteins at concentrations that exceed their solubility limits, resulting in a metastable proteome conducive to protein misfolding and aggregation. Recent evidence indicates metastable sub-proteomes within neuronal compartments, such as the synapse, may be particularly vulnerable and underlie their involvement in the initial stages of neurodegenerative diseases. To investigate if the motor neuron presynaptic terminal possesses a metastable sub-proteome, we used human and mouse spinal cord motor neuron expression data to calculate supersaturation scores. Here, we found that both the human and mouse presynaptic terminal sub-proteomes have higher supersaturation scores than the entire motor neuron proteome. In addition, we observed that proteins down-regulated in ALS were over-represented in the synapse. These results provide support for the notion that the metastability of the sub-proteome within the motor neuron presynaptic terminal may be particularly susceptible to protein homeostasis disturbances in ALS, and may contribute to explaining the observed synaptic dysfunction in ALS.

Dry eye in Sjögren's syndrome - characteristics and therapy.

Sjögren's syndrome is an autoimmune disease, and its important feature is the lymphocyte infiltration of exocrine glands, including lacrimal glands. It contributes to defects of their activity and causes that one of the main manifestation of Sjögren's syndrome is dry eye. Unfortunately, the discrimination between dry eye related and non-related to Sjögren's syndrome is difficult at the initial stages of diseases. In addition, the available agents for the treatment of Sjögren's syndrome-related dry eye have limited efficacy. The purpose of this study was to describe and emphasize differences between Sjögren's Syndrome-related dry eye and non-Sjögren's Syndrome-related dry eye together with the determination of novel therapeutic options for Sjögren's Syndrome-related dry eye. A review of the relevant papers describing characteristics of Sjögren's Syndrome-related dry eye and its therapy was conducted. This article is based on both pre-clinical and clinical evidences. On the basis of our analysis, we indicated differences between Sjögren's Syndrome-related dry eye and non-Sjögren's Syndrome-related dry eye. Moreover, there are some novel markers that could be used in the diagnosis of Sjögren's Syndrome-related dry eye. In addition, expect artificial tear, other agents e.g. hydroxychloroquine can be effective in therapy of disease. Sjögren's Syndrome-related dry eye is a disorder, whose diagnosis may be difficult and mistaken for non-Sjögren's Syndrome-related dry eye. However, Sjögren's Syndrome-related dry eye has some specific features. In addition, the development of newer and safer therapeutic agents for Sjögren's syndrome-related dry eye is needed, and therefore further clinical, randomized studies are necessary.

Ultrasound biomicroscopy for the assessment of early-stage nonalcoholic fatty liver disease induced in rats by a high-fat diet.

PurposeThe aim of this study was to assess the ability of ultrasound biomicroscopy (UBM) to diagnose the initial stages of nonalcoholic fatty liver disease (NAFLD) in a rat model.MethodsEighteen male Wistar rats were allocated to control or experimental groups. A high-fat diet (HFD) with 20% fructose and 2% cholesterol, resembling a common Western diet, was fed to animals in the experimental groups for up to 16 weeks; those in the control group received a regular diet. A 21 MHz UBM system was used to acquire B-mode images at specific times: baseline (T0), 10 weeks (T10), and 16 weeks (T16). The sonographic hepatorenal index (SHRI), based on the average ultrasound image gray-level intensities from the liver parenchyma and right renal cortex, was determined at T0, T10, and T16. The liver specimen histology was classified using the modified Nonalcoholic Steatohepatitis Clinical Research Network NAFLD activity scoring system.ResultsThe livers in the animals in the experimental groups progressed from sinusoidal congestion and moderate macro- and micro-vesicular steatosis to moderate steatosis and frequent hepatocyte ballooning. The SHRI obtained in the experimental group animals at T10 and T16 was significantly different from the SHRI of pooled control group. No significant difference existed between the SHRI in animals receiving HFD between T10 and T16.ConclusionSHRI measurement using UBM may be a promising noninvasive tool to characterize early-stage NAFLD in rat models.

The Outcome of Patients with Amyloid-Negative Amnestic Mild Cognitive Impairment.

Patients with amnestic mild cognitive impairment (aMCI) are usually at an initial stage of Alzheimer's disease (AD). However, some patients with aMCI do not present biomarkers of amyloid pathology characteristic of AD. The significance of amyloid-negative aMCI is not presently clear. To know the etiology and prognosis of amyloid-negative aMCI. Patients who fulfilled criteria for aMCI and were amyloid negative were selected from a large cohort of non-demented patients with cognitive complaints and were followed with clinical and neuropsychological assessments. Few amyloid-negative aMCI had evidence of neurodegeneration at the baseline, as reflected in cerebrospinal fluid elevated tau protein levels. About half of the patients remained essentially stable for long periods of time. Others manifested a psychiatric disorder that was not apparent at baseline, namely major depression or bipolar disorder. Remarkably, about a quarter of patients developed neurodegenerative disorders other than AD, mostly frontotemporal dementia or Lewy body disease. Amyloid-negative aMCI is a heterogeneous condition. Many patients remain clinically stable, but others may later manifest psychiatric conditions or evolve to neurodegenerative disorders. Prudence is needed when communicating to the patient and family the results of biomarkers, and clinical follow-up should be advised.

Assessment of fear among the general public of Kerala, India, following a surge of COVID-19 cases.

During the initial stages of the coronavirus disease 2019 (COVID-19) pandemic, the community spread of the virus had efficiently been prevented in Kerala, India. The present study aimed to assess fear and its predictors among the general public following the unforeseen surge of COVID-19 cases in July, 2020 using a reliable and validated tool, the 'Fear of COVID-19 Scale', administered through social media. Of 1,100 responses, 1,046 responses were included in the analysis. The majority of the respondents expressed mild fear 44.6%; moderate fear was found in 39.4% of the respondents, severe fear in 13.6% and very severe fear in 2.4% of the respondents. The mean fear score was found to be 15.93±5.81. Statistically significant (P≤0.05) associations were found between fear and sociodemographic variables, such as age, sex, education and occupation, along with predictors, such as the district of residence, healthcare stakeholders in the family, and the presence of an infected individual in the family. Women and students were found to be the most affected. On the whole, the present study provides sufficient insight into the fear associated with COVID-19. The findings presented herein may enable authorities to take adequate measures to prevent the aftermath.

Clinical, serological and genetic predictors of response to immunotherapy in anti-IgLON5 disease.

Anti-IgLON5 disease is a newly defined clinical entity characterized by a progressive course with high disability and mortality rate. While precise pathogenetic mechanisms remain unclear, features characteristic of both autoimmune and neurodegenerative diseases were reported. Data on immunotherapy are limited, and its efficacy remains controversial. In this study, we retrospectively investigated an anti-IgLON5 disease cohort with special focus on clinical, serological and genetic predictors of the immunotherapy response and long-term outcome. Patients were recruited from the GENERATE (German Network for Research on Autoimmune Encephalitis) registry. Along with clinical parameters, anti-IgLON5 immunoglobulin (Ig)G in serum and CSF, anti-IgLON5 IgG1-4, IgA and IgM in serum, neurofilament light chain and glial fibrillary acidic protein in serum as well as human leukocyte antigen-genotypes were determined. We identified 53 patients (symptom onset 63.8 ± 10.3 years, female:male 1:1.5). The most frequent initial clinical presentations were bulbar syndrome, hyperkinetic syndrome or isolated sleep disorder [at least one symptom present in 38% (20/53)]. At the time of diagnosis, the majority of patients had a generalized multi-systemic phenotype; nevertheless, 21% (11/53) still had an isolated brainstem syndrome and/or a characteristic sleep disorder only. About one third of patients [28% (15/53)] reported subacute disease onset and 51% (27/53) relapse-like exacerbations during the disease course. Inflammatory CSF changes were evident in 37% (19/51) and increased blood-CSF-barrier permeability in 46% (21/46). CSF cell count significantly decreased, while serum anti-IgLON5 IgG titre increased with disease duration. The presence of human leukocyte antigen-DRB1*10:01 [55% (24/44)] was associated with higher serum anti-IgLON5 IgG titres. Neurofilament light chain and glial fibrillary acidic protein in serum were substantially increased (71.1 ± 103.9 pg/ml and 126.7 ± 73.3 pg/ml, respectively). First-line immunotherapy of relapse-like acute-to-subacute exacerbation episodes resulted in improvement in 41% (11/27) of patients and early initiation within the first 6 weeks was a predictor for therapy response. Sixty-eight per cent (36/53) of patients were treated with long-term immunotherapy and 75% (27/36) of these experienced no further disease progression (observation period of 20.2 ± 15.4 months). Long-term immunotherapy initiation during the first year after onset and low pre-treatment neurofilament light chain were significant predictors for a better outcome. In conclusion, subacute disease onset and early inflammatory CSF changes support the primary role of autoimmune mechanisms at least at initial stages of anti-IgLON5 disease. Early immunotherapy, prior to advanced neurodegeneration, is associated with a better long-term clinical outcome. Low serum neurofilament light chain at treatment initiation may serve as a potential biomarker of the immunotherapy response.

On a Correlation between the Results of In-Hospital Analysis of Biosamples from Children Performed Using Standard Methods and an Array of Piezosensors

A rapid procedure for obtaining information on changes in particular characteristics of urine as the most frequently taken biosample is presented. The relationship between the output data of an array of piezoelectric sensors based on different micro- and nanostructured phases and the standard characteristics of clinical urine analysis is discussed. Volatile organic compounds identified in an equilibrium headspace gas phase of the samples with deviations from normal characteristics of clinical urine analysis are considered. The tetrachoric correlation coefficients and associations between the parameters of a sensor array and standard characteristics were calculated. A minimum set of calculated parameters of an electronic nose for the rapid in-hospital monitoring of changes in the patient’s condition in the course of therapy or medical examination was recognized. A fast and economically affordable method was developed for the monitoring of body state characteristics using the profile of volatile urine compounds obtained with an electronic nose based on piezosensors. Two versions, a color scale and a table, were proposed for presenting the electronic nose data; they can be used even by specially untrained personnel for the rapid and easy assessment of the most important urine analysis data (protein, glucose, mucus, and bacteria). The method developed makes it possible to quickly (the time of a measurement is 120 s) perform the daily monitoring of patient’s condition to avoid an unnecessary burden on the laboratory and to increase the physician’s awareness of the dynamics of the patient’s condition and facilitate the choice of treatment tactics. This method can be used for clinical examinations in polyclinics and feldsher’s stations, and it will significantly shorten the time taken to obtain screening and diagnostic information on disruptions in the body, in particular, at the initial stages of diseases.