Nevin Manimala

Int Ophthalmol. 2023 Mar 1. doi: 10.1007/s10792-023-02661-x. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare tear fluid levels of matrix metalloproteinase 9 (MMP-9) and IL-1ß cytokines between healthcare workers wearing facial masks and controls with correlations in clinical findings.

METHODS: In a prospective, controlled clinical trial tear fluid was analyzed for MMP-9 and IL-1ß levels using a commercially available test (Invitrogen; Thermo Fisher Scientific Inc. Waltham, Massachusetts, USA). Symptoms and signs of dry eye disease (DED) were evaluated using the ocular surface disease index (OSDI), noninvasive tear break-up time (NIBUT), tear meniscus height (TMH), Oxford corneal staining, meibomiography, and clinical findings of meibomian gland dysfunction (MGD).

RESULTS: In the 38 eyes of healthcare workers and 30 eyes of controls, there was no statistically significant difference between the groups in terms of age and sex (p > 0.05). The mean OSDI score, daily mask wear time, meibomiography degree, and rate of positive clinical findings of MGD were higher in group 1 than in group 2, and the mean NIBUT was higher in group 2. (p > 0.05). The mean values of IL-1ß and MMP-9 were higher in group 1 (p = 0.036 and p = 0.001, respectively). The TMH and Oxford score percentages were similar between the two groups (p > 0.05).

CONCLUSIONS: Elevated levels of IL-1ß and MMP-9 in the basal tear fluid reveal increased ocular inflammation in healthcare professionals. Lower NIBUT values with higher OSDI and meibomian gland loss scores support ocular surface disturbance depending on regular mask use.

PMID:36856985 | DOI:10.1007/s10792-023-02661-x

Ophthalmol Ther. 2023 Mar 1. doi: 10.1007/s40123-023-00669-1. Online ahead of print.

ABSTRACT

Meibomian gland dysfunction (MGD) is highly prevalent and is the leading cause of evaporative dry eye disease (DED). MGD is characterized by a reduction in meibum secretion and/or a change in meibum composition that results in the disruption of the tear film lipid layer and an increase in the tear film evaporation rate. Excessive evaporation causes tear film instability, desiccation, tear hyperosmolarity, inflammation, and apoptosis of ocular surface cells, resulting in a continuous cycle of DED. The primary treatment goal for DED associated with MGD is to restore the tear film lipid layer and decrease evaporation, thereby reducing ocular signs and symptoms. The management of MGD includes home care options (eyelid hygiene, warming eye masks, ocular lubricants) and office-based treatments (manual expression, microblepharoexfoliation, thermal pulsation, intense pulsed light, intraductal probing). Topical ophthalmic prescription medications attempt to alter various factors that may contribute to DED (e.g., inflammation, bacterial growth, inadequate tear production). In this review, clinical evidence regarding available treatments and emerging therapies from randomized studies in patients with DED associated with MGD is summarized. Although some treatment modalities have been evaluated specifically for DED patients with MGD, large-scale randomized controlled trials are needed to confirm efficacy and safety in this patient population. Currently, there are no approved prescription pharmacologic treatments specifically indicated for DED associated with MGD, and those medications approved for the treatment of DED do not target the key driver of the disease (i.e., excessive evaporation). NOV03 (perfluorohexyloctane; under review with the US Food and Drug Administration) is the most advanced emerging therapy for DED associated with MGD and has demonstrated statistically significant improvements in both signs and symptoms in randomized controlled trials. Development of novel pharmacotherapies will improve therapeutic options and allow for a more individualized approach for patients with DED associated with MGD.

PMID:36856980 | DOI:10.1007/s40123-023-00669-1

Health Commun. 2023 Mar 1:1-13. doi: 10.1080/10410236.2023.2184452. Online ahead of print.

ABSTRACT

Emerging communication technologies have seen the proliferation of misleading claims, untruthful narratives, and conspiracies. To understand how people perceive and act on different types of misinformation, this study examines how health misinformation varying in falsity (fabrication versus misuse) and evidence type (statistical versus narrative) affects sharing and verification intentions. Using COVID-19 vaccines as cases, the results from an online experiment showed that misused misinformation was perceived as less false than fabricated misinformation and resulted in higher sharing intentions for the issue of vaccine efficacy. Misinformation with narrative evidence, as compared to that with statistical evidence, was perceived as less false and led to lower verification intentions. These findings can be explained by psychological processes such as counterarguing and narrative engagement. Our results can help practitioners develop dedicated misinformation literacy programs.

PMID:36856056 | DOI:10.1080/10410236.2023.2184452

J Biomol Struct Dyn. 2023 Mar 1:1-18. doi: 10.1080/07391102.2023.2184172. Online ahead of print.

ABSTRACT

Over the past few decades, various inhibitors of PRMT5 have been developed because of its involvement in a variety of tumor development processes. As of now, no drugs targeting PRMT5 have been approved, and multiple drugs entering clinical trials have proven to have side effects. In this study, PRMT5 was used to perform virtual screening of 52119 marine natural compounds by combining various methods. We constructed 20 pharmacophore models based on multiple ligands. The best pharmacophore model AARR_2 was selected by analyzing the statistical parameters of the pharmacophore model and the binding characteristics of the ligand active site, and then 3552 compounds were screened out. Compared with the positive compound, 46 compounds were selected based on the molecular docking fraction and docking mode analysis. Then, 3D-QSAR was used to analyze the relationship between structure and activity of the compounds. Then, in addition to marine compounds 36404, 36405 and 14436, we selected compound 46 (the positive control compound) and used the CLC-Pred online Web server to predict their cytotoxicity to human cell lines, making cell experiments possible. Finally, we conducted the prediction of ADMET in order to better promote clinical trials. After comprehensive judgment, we screened out the marine natural compounds 36404 and 36405 as candidates for PRMT5 substrate competitive inhibitors.Communicated by Ramaswamy H. Sarma.

PMID:36856049 | DOI:10.1080/07391102.2023.2184172

Otolaryngol Head Neck Surg. 2023 Mar 1. doi: 10.1002/ohn.301. Online ahead of print.

ABSTRACT

OBJECTIVE: Determine if students with severe-to-profound hearing loss with cochlear implants (CIs) mainstream (transition to general education) more than students with hearing amplification at the population level.

STUDY DESIGN: Cross-sectional secondary analysis of data from the National Center of Education Statistics.

SETTING: Special education (SpEd) students in the United States who had severe to profound “hearing impairment” and were 6 to 16 years old at enrollment from 2000 to 2001.

METHODS: We weighted the data to produce national estimates, performed multiple imputations for missingness, and built a multivariate linear regression model, which was cross-validated with a multivariate Poisson regression model. We used a theory-based approach to model-building using a directed acyclic graph to identify the minimally sufficient adjustment set of variables, which included school district urbanicity, student’s age when they started SpEd, other disabilities, home language, and caregiver education.

RESULTS: We identified 7267 students with CIs and 28,794 students with hearing amplification. CI users mainstreamed more than peers using hearing amplification during secondary school (40.29% less daily time in special education, p = .004) but not during primary school (9.19% less daily time in SpEd, p = .155). Additional significant predictors of mainstreaming varied between the primary and secondary school cohorts and included school district urbanicity and the student’s age when they started SpEd.

CONCLUSION: CI status predicts daily time spent in SpEd among a secondary school cohort. These findings do not establish causation. The National Center of Education Statistics should consider linking to clinical databases in future studies.

PMID:36856033 | DOI:10.1002/ohn.301

Folia Med (Plovdiv). 2023 Feb 28;65(1):149-154. doi: 10.3897/folmed.65.e71970.

ABSTRACT

INTRODUCTION: Excessive lipoperoxidation is accompanied by accumulation of peroxidation products and depletion of antioxidant re-serves, which cause hyperenzymemia and the accumulation of toxic substances. The level of endotoxicosis is determined by the content of hydrophilic and hydrophobic products in the blood.

AIM: To define the pathogenetic role of endogenous intoxication in the dynamics of development of experimental periodontitis of bacterial-immune genesis.

MATERIALS AND METHODS: The experiment was conducted on rats. The animals were divided into three groups: group 1 – control group/intact; group 2 – model periodontitis at 7 days; group 3 – model periodontitis at 30 days. The experimental bacterial-immune periodon-titis was induced by injection into the tissue of the periodontal complex of the microorganisms’ mixture diluted with egg’s albumin. For the study, we selected the blood serum in which the content of middle molecular weight molecules and erythrocyte intoxication index were determined. The results were statistically analyzed by means of non-parametric indices methods.

RESULTS: The development of generalized periodontitis is characterized by the occurrence of oxidative stress, which leads to violation of the metabolism in the mucous membrane of the oral cavity resulting in the accumulation of toxic products and the development of endogenous intoxication. The results show that the content of middle molecular weight molecules (aromatic amino and chain amino acids) determined on day 7 of the experiment was 1.11 times higher than that of the control group (p<0.01) and by 1.16 times (p<0.01), respectively. Comparing the levels of the above hydrophilic components of endogenous intoxication at 30 days of experimental peri-odontitis, we found a probable increase in these indicators compared with those at 7 days of the experiment. Studying the level of eryth-rocyte intoxication index, we found that at 7 days of experimental periodontitis this index was 1.28 times higher (p<0.01) than that of the intact group and continued to increase at 30 days.

CONCLUSIONS: The dynamics of experimental periodontitis of bacterial-immune genesis show that the highest rates of endogenous intoxication are found in the late stages of the dynamics of the inflammatory process in the periodontium, namely at 30 days of the experiment, which may indicate chronic inflammation.

PMID:36855987 | DOI:10.3897/folmed.65.e71970

Folia Med (Plovdiv). 2023 Feb 28;65(1):140-148. doi: 10.3897/folmed.65.e72920.

ABSTRACT

INTRODUCTION: Peri-implantitis is a relatively new and difficult disease that is becoming more common. Of the different therapeutic options to manage this condition, lasers show certain advantages over other therapeutic alternatives because of their antibacterial potential.

AIM: The aim of the present study was to investigate the temperature rise of implant surfaces, soft tissues, and bone during irradiation with diode, CO2, and Er:YAG lasers.

MATERIALS AND METHODS: Ten implants inserted in biological models were irradiated with three laser systems with different parameters: a diode laser (980 nm) with power levels of 0.75 W and 1.6 W; a CO2 laser (10600 nm) with power levels of 252 W and 241 W; and an Er:YAG laser (2940 nm) with power levels of 1.5 W, 6.8 W, and 7.5 W. The temperature rise was measured using a specially designed thermal probe (type K thermocouple) with accuracy of ±0.1°C over the range from 20°C to 80°C. The temperature was measured at 5 points – in the implant body, in the mucosa, in the middle part of the implant, in the implant apex, and in the bone around the implant apex. Measurements were obtained at 1 minute working interval.

RESULTS: Diode and CO2 lasers with both parameters used increased significantly the temperature of more than 46°C, whereas the temperature in the Er:YAG laser group was less than 30°C. There was a statistically significant difference between diode, CO2, and Er:YAG lasers in favor of the erbium laser.

CONCLUSIONS: The Er:YAG laser demonstrates the best thermal properties during irradiation of the implant surface. The three working modes tested – 1.5 W, 6.8 W, and 7.5 W – provide safe intervention on both the soft and bone tissues of the implant interface and on the implant itself.

PMID:36855986 | DOI:10.3897/folmed.65.e72920

Folia Med (Plovdiv). 2023 Feb 28;65(1):93-98. doi: 10.3897/folmed.65.e77257.

ABSTRACT

INTRODUCTION: In situ fixation is the gold standard for mild and moderate slipped capital femoral epiphysis (SCFE) cases. The condition is associated with a low percentage of avascular necrosis and chondrolysis.[1] The present study examines the postoperative femoral neck remodelling and implant elongation in cases of therapeutic and prophylactic in situ fixation using the free-gliding screw system.

AIM: The aim of our study was to assess the postoperative femoral neck growth and evaluate the biomechanical evolution and complication’s rate for 19 therapeutic and 11 prophylactic in situ fixations with a free-gliding screw.

MATERIALS AND METHODS: We measured the preoperative and postoperative articulo-trochanteric distance (ATD), alpha angle (α angle) and screw elongation in symptomatic hips and in contralateral hips with prophylactic fixation. We compared the radiographic param-eters of 30 hips.

RESULTS: ATD remains approximately the same for symptomatic cases, whereas it increases for prophylactic fixated hip. Screw elongates in both group with statistically higher value for the prophylactic group. The alpha angle remains pathological in these cases with a mean value of 67.12±4.62°, but decreases for group II. Screw elongates by a mean value of 3.14±2.74 mm for group I and 6.78±8.81 mm for group II.

CONCLUSIONS: Prophylactic in situ fixation with free-gliding screws does not affect the proximal femoral growth (ATD), and does not decrease the alpha angle significantly. Screw elongates statistically in both groups, but more significantly for group II. For symptomatic hips, the in situ fixation allows the femoral neck to grow with ATD preserved, but significantly less than in group II. The alpha angle decreases but remains pathological.

PMID:36855980 | DOI:10.3897/folmed.65.e77257

Folia Med (Plovdiv). 2023 Feb 28;65(1):53-59. doi: 10.3897/folmed.65.e72448.

ABSTRACT

INTRODUCTION: Rheumatoid arthritis (RA) is the most common inflammatory joint disease. Various proinflammatory cytokines are involved in the pathogenesis of this chronic disorder. It is characterized by the presence of autoantibodies, such as rheumatoid factor and antibodies against citrullinated peptides. The present study focuses on investigation of possible association between the proinflammatory cytokine interleukin 17 and anti-CCP, anti-MCV, and anti-CarP antibodies seropositivity in RA patients.

AIM: To assess serum levels of interleukin 17 (IL-17) in patients with rheumatoid arthritis and healthy controls (HC) and to investigate the relationship between IL-17 and anti-cyclic citrullinated protein (anti-CCP) antibodies, antimutated citrullinated vimentin (anti-MCV) antibodies, and anti-carbamylated protein (anti-CarP) antibodies in patients with RA.

MATERIALS AND METHODS: Forty-seven patients diagnosed with rheumatoid arthritis and 44 healthy controls were included in the study. Serum IL-17 levels were examined in all participants. Anti-CCP, anti-MCV, and anti-CarP antibodies were tested in the group of RA patients.

RESULTS: The mean serum level of IL-17 in RA patients was higher (12.8 pg/ml) than that in healthy controls (7.9 pg/ml), but the difference was not statistically significant (p=0.276). No significant correlation was observed between anti-CCP (+/-) and IL-17 (rs=0.162, p=0.380), and between anti-MCV (+/-) and IL-17 (rs=0.157, p=0.340). A significant positive correlation of moderate value was reported between anti-CarP (+/-) and IL-17 (rs=0.388, p=0.015).

CONCLUSIONS: The present study demonstrated that the IL-17 serum levels in RA patients were increased compared to healthy controls. No correlation was found between ACPA immunological markers and IL-17 levels in patients with RA. A positive correlation was found between anti-CarP antibodies and IL-17 in the patients’ group. The increased level of IL-17 is suggestive of its possible role in the pathogenesis of CarP positive RA patients.

PMID:36855974 | DOI:10.3897/folmed.65.e72448

Stress. 2023 Mar 1:1-26. doi: 10.1080/10253890.2023.2186141. Online ahead of print.

ABSTRACT

Stress can have severe psychological and physiological consequences. Thus, inappropriate regulation of the stress response is linked to the etiology of mood and anxiety disorders. The generation and implementation of preclinical animal models represent valuable tools to explore and characterize the mechanisms underlying the pathophysiology of stress-related psychiatric disorders and the development of novel pharmacological strategies. In this commentary, we discuss the strengths and limitations of state-of-the-art molecular and computational advances employed in stress neurobiology research, with a focus on the ever-increasing spatiotemporal resolution in cell biology and behavioral science. Finally, we share our perspective on future directions in the fields of preclinical and human stress research.

PMID:36855966 | DOI:10.1080/10253890.2023.2186141