Prescribing patterns for hyperopia: an insight of the optometrist perspective and practice.

BACKGROUND: To investigate the current prescribing patterns for correcting hyperopia among optometrists in clinical practice in Saudi Arabia and compare those to current international guidelines. And explore the factors that influence practitioners' prescribing decision. METHOD: This cross-sectional study employed 30 items online survey that encompass demographic data, current practice and cycloplegia use, numerical response to indicate the minimum level of hyperopia at which optometrists would consider prescribing spectacles to non-strabismic children and determine the diopter value required for prescribing correction for hyperopia if present with other factors. RESULT: A total of 104 optometrists responded to the survey (52 females and 52 males). They recruited from 35 cities across Saudi Arabia. Out of total, 44% of them considered cycloplegic refraction essential under 12 years and 56% of them extended the range to 18 years. Large variation were found between the optometrists' responses and current guideline recommendations. Several factors influenced the decision-making of the practicing optometrist including signs and symptoms, bilateral hyperopia, average dioptric value, reading difficulty, and accommodative function. CONCLUSION: There are some matches between the international guidelines and the practice patterns that followed by optometrists in Saudi Arabia, however, the optometrists did not report that they are following them purposefully. These findings highlight the need to improve optometrists' practice about spectacle prescription in pediatric population.

The prevalence of post-traumatic stress disorder among emergency medical services personnel in Saudi Red Crescent Authority, Riyadh, Saudi Arabia.

Background: Determining the prevalence of PTSD and contributing variables among (EMS) specialists was the goal of the current investigation. Furthermore, limited evidence exists regarding the application of PCL-5 for EMT practitioners, and the incidence of PTSD among different age groups and genders in Saudi Arabia. Methods: This cross-sectional descriptive study includes 211 prehospital care providers of the Saudi Red Crescent Authority stations in Riyadh. The randomization was done using Google Forms into subgroups according to participants' gender, years of experience, occupations, and average working hours. The presence and severity of PTSD symptoms were evaluated using the 20-item PTSD Checklist for DSM-5 (PCL-5) self-report questionnaire. Data were analyzed using Pearson Chi-Square, Mann-Whitney and Kruskal-Wallis tests. The reliability statistics were calculated using Cronbach's Alpha for the 20-survey questionnaire. Results: The comparison of PCL-5 total scores indicated more PTSD symptomatology among females (1.61 + 0.799) as compared to male workers (1.13 + 0.642). The total score of PTSD demonstrated no statistically significant (P=0.79) differences between our age group classifications. In terms of the participants' city (Riyadh), the total PTSD score was less than the cutoff point which is 31. PTSD total score may not be affected by working experience as indicated by the non-significant difference in prevalence among EMT practitioners having <5 years, 5-10 years and above 10 years of working experience (P=0.215 with X2 = 3.076). PTSD incidence is affected by the type of occupation as statistically significant differences between groups (P=0.001) were recorded depending on the position and responsibilities of EMS practitioners. PTSD is also affected by average working hours per week, and there were statistically significant differences between groups (P=0.001). Conclusion: The total score of PTSD in the case of emergency service practitioners was found to be 33.7% among all the research participants, which may be regarded as a high prevalence when compared to the general population. Our investigations would contribute to a better understanding of the underlying factors of mental stress in EMS specialists in Saudi Arabia and to the development of adequate mental health practices.

Efficacy of hydroxypropyl-guar drops in improving tear film index and ocular surface dynamics using two treatment methods under a controlled desiccating environment.

AIM: This study aimed to assess the efficacy of hp-guar eye drops on tear film index and ocular surface dynamics under desiccating conditions using protection and relief treatment modalities. METHODOLOGY: The 12 normal, non-dry eye participants were subjected to adverse environmental conditions using a Controlled Environment Chamber (CEC) where the relative humidity (RH) was 5% and the ambient temperature was 21 °C. The participants were screened for ocular symptoms, tear osmolarity, ocular surface temperature (OST), tear production using the Ocular Surface Disease Index questionnaire (OSDI), OcuSense TearLab Osmometer, FLIR System ThermaCAM P620, and Schirmer strips. Tear production was calculated by the Tear Function Index test (TFI). RESULTS: The mean tear film osmolarity decreased significantly from 296 mOsm/L at 40% RH to 285 mOsm/L at 5% RH (p = 0.01). Conflicting responses were seen for osmolarity in protection and relief. Mean tear osmolarity was significantly higher in the protection method in comparison to the relief method (p = 0.005). The mean TFI increased from 557 at 40% to 854 at 5% (p = 0.02). A significant increase in TFI was observed in the relief method in comparison with both 40% (p = 0.001) and 5% (p = 0.04). In the relief method, the mean TFI score went up to 1139 when hp-guar was installed. A significant improvement in ocular comfort was experienced in both the protection (p = 0.041) and relief (p = 0.010) methods at 5% RH. The instillation of hp-guar drops in the relief method resulted in a significant reduction in OST. The mean OST dropped to 33.01 ºC, significantly lower than the recorded OST for both normal (p = 0.040) and dry (p = 0.014) environmental conditions. CONCLUSION: Hp-guar drops significantly improve tear film parameters under a desiccating environment, however, tear film parameters respond differently to the management modalities. In the protection method, tear film osmolarity was protected against a dry environment, while in the relief mode, an improvement in tear production and a decrease in ocular surface temperature were seen. Hp-guar performance could be maximized for the management of exposure to adverse environments by using a treatment protocol that targets the most affected parameters in each group of patients. Using CEC has the potential to provide researchers with a readily available method to evaluate the efficiency of tear supplementation.

Evaluation of therapeutic efficacy of Emustil drops for ocular discomfort and tear film osmolarity using different treatment management modes under dry environmental conditions.

BACKGROUND: We aimed to check the efficacy of Emustil (oil in water emulsion) drops on tear film index and ocular surface dynamics in dry environments through protection and relief treatment modalities. METHODS: The subjects were exposed to a dry environment using a Controlled Environment Chamber (CEC) where the relative humidity (RH) was 5% and the temperature was 21 °C and screened for ocular symptoms, tear osmolarity, ocular surface temperature (OST) and tear production using ocular Surface Disease Index questionnaire (OSDI), OcuSense TearLab Osmometer, FLIR System ThermaCAM P620 and Schirmer strips/phenol red test respectively. Tear production was calculated by the Tear Function Index test (TFI). RESULTS: The mean tear film osmolarity decreased significantly from 296.8 mOsm/l at 40% RH to 291 mOsm/l at 5%. (p = 0.01). Instillation of Emustil resulted in a significant increase in tear osmolarity in the relief method compared with osmolarity seen at 5% RH when no drop was used. The mean PRT value decreased from 26 ± 9 in normal conditions (40% RH) to 22 ± 4 mm in dry conditions (5% RH). Emustil drops did not induce any significant change in tear production in the PRT test. No significant change was found in OST following exposure to 5% RH. OST did not show a statistically significant change with the emulsion when used for relief (p > 0.05). The mean score of ocular discomfort observed was 70 at 5% RH. Still, the instillation of the oil-in-water emulsion (Emustil) resulted in a noticeable decrease in visual discomfort to 37 (p = 0.00) in protection and 59 in relief (p = 0.05). Emustil drops substantially improved tear film parameters under a desiccating environment, however, tear film parameters respond differently to the management modalities. In the protection method, tear film osmolarity was protected against a dry environment, while in the relief mode, tear production was improved. CONCLUSION: CEC allows for a thorough evaluation of tear film parameters and dry eye treatment protocols in labs, providing greater confidence when applying them to patients. In addition, our study showed that Emustil not only provides protection and relief for dry eyes but also helps to maintain ocular homeostasis in desiccating environments. This indicates a promising potential for improving dry eye treatment protocols.

SIRT1 inhibits mitochondrial hyperfusion associated mito-bulb formation to sensitize oral cancer cells for apoptosis in a mtROS-dependent signalling pathway.

SIRT1 (NAD-dependent protein deacetylase sirtuin-1), a class III histone deacetylase acting as a tumor suppressor gene, is downregulated in oral cancer cells. Non-apoptotic doses of cisplatin (CDDP) downregulate SIRT1 expression advocating the mechanism of drug resistance. SIRT1 downregulation orchestrates inhibition of DNM1L-mediated mitochondrial fission, subsequently leading to the formation of hyperfused mitochondrial networks. The hyperfused mitochondrial networks preserve the release of cytochrome C (CYCS) by stabilizing the mitochondrial inner membrane cristae (formation of mitochondrial nucleoid clustering mimicking mito-bulb like structures) and reducing the generation of mitochondrial superoxide to inhibit apoptosis. Overexpression of SIRT1 reverses the mitochondrial hyperfusion by initiating DNM1L-regulated mitochondrial fission. In the overexpressed cells, inhibition of mitochondrial hyperfusion and nucleoid clustering (mito-bulbs) facilitates the cytoplasmic release of CYCS along with an enhanced generation of mitochondrial superoxide for the subsequent induction of apoptosis. Further, low-dose priming with gallic acid (GA), a bio-active SIRT1 activator, nullifies CDDP-mediated apoptosis inhibition by suppressing mitochondrial hyperfusion. In this setting, SIRT1 knockdown hinders apoptosis activation in GA-primed oral cancer cells. Similarly, SIRT1 overexpression in the CDDP resistance oral cancer-derived polyploid giant cancer cells (PGCCs) re-sensitizes the cells to apoptosis. Interestingly, synergistically treated with CDDP, GA induces apoptosis in the PGCCs by inhibiting mitochondrial hyperfusion.

Protecting Tear-Film Stability under Adverse Environmental Conditions Using a Mucomimetic with a Non-Newtonian Viscosity Agent.

Background and Objectives: Tamarind-seed polysaccharide (TSP) and hyaluronic acid (HA) have mucoadhesive properties that improve drug absorption and delay in drug elimination from the ocular surface. We aimed to evaluate TSP/HA-containing formulation for its efficiency in dry-eye symptoms induced by adverse environments and the interaction between mucomimic polymer and tear-film parameters. Materials and Methods: The participants were exposed to 5% relative humidity (RH) in a Controlled Environment Chamber (CEC) under constant room temperature (21 °C). Tear-film parameters were assessed at 40% RH and 5% RH. Rohto Dry Eye Relief drops were used in the two treatment modalities, protection (drops instilled before exposure to the dry environment) and relief (drops instilled after exposure to the dry environment). The HIRCAL grid, Servomed EP3 Evaporimeter, and Keeler's TearScope-Plus were used to screen for non-invasive tear break-up time (NITBUT), tear evaporation rate, and lipid-layer thickness (LLT) using protection and relief treatment methodology. Results: LLT was found to be significantly thinner at 5% RH compared with at 40% RH (p = 0.007). The median LLT dropped from 50-70 nm (grade 3) at 40% RH to 10-50 nm (grade 2) at 5% RH. TSP/HA eye drops significantly augment LLT in both treatment modalities, protection (p = 0.01) and relief (p = 0.004) at 5% RH. The mean evaporation rate doubled from 40.93 at 40% RH to 82.42 g/m2/h after exposure to 5% RH. In protection mode, the TSP/HA allowed the average evaporation rate to be much lower than when no TSP/HA was used at 5% RH (p < 0.008). No alteration in evaporation rate was recorded when the TSP/HA drop was used after exposure (relief). The mean NITBUT was reduced from 13 s in normal conditions to 6 s in the dry environment. Instillation of TSP/HA eye drops resulted in significant improvement (p = 0.006) in tear stability, where the NITBUT increased to 8 s in both protection (before exposure) and relief (after exposure) (p = 0.001). Although improved, these values were still significantly lower than NITBUT observed at 40% RH. Conclusions: Significant protection of tear-film parameters was recorded post instillation of TSP/HA eye drop under a desiccating environment. Both treatment methods (protection and relief) were shown to be effective. The presence of TSP/HA enhances the effectiveness of teardrops in protecting the tear-film parameters when exposed to adverse environments.

Synthesis, in-vitro inhibition of cyclooxygenases and in silico studies of new isoxazole derivatives.

Isoxazole belongs to the class of five-membered heterocyclic compounds. The process of developing new drugs has significantly gained attention due to inadequate pharmacokinetic and safety attributes of the available drugs. This study aimed to design a new diverse array of ten novel isoxazole derivatives via Claisen Schmidt condensation reaction. In vitro COX-1/2 anti-inflammatory assay, in silico molecular docking of potent compounds, Molecular docking simulation, and SwissADME pharmacokinetic profile were investigated in this research. The in vitro COX-1 and COX-2 enzyme inhibitory assay showed that almost all the tested compounds exhibited anti-inflammatory effects whereas C6, C5, and C3 were found to be the most potent COX-2 enzyme inhibitors among the tested compounds and are good candidates for selective COX-2 inhibitors. In silico molecular docking studies coupled with molecular dynamic simulation has been done to rationalize the time-evolved mode of interaction of selected inhibitor inside the active pockets of target COX-2. The binding orientations and binding energy results also showed the selectivity of compounds towards COX-2. Physicochemical properties, pharmacokinetic profile, lipophilicity, water solubility, drug metabolism, drug-likeness properties, and medicinal chemistry of the synthesized isoxazole derivatives were assessed. The SwissADME (absorption, distribution, metabolism, and excretion) database was used to assess the physicochemical properties and drug-likeness properties of the synthesized isoxazole derivatives. All the compounds were shown high GI absorption except Compound 7 (C7). Compound 1 (C1) and Compound 2 (C2) were found to cross the blood-brain barrier (BBB). Lipinski's rule of five is not violated by any of the ten synthesized isoxazole derivatives. It was predicted with the SwissADME database that C2, C5, C6, C7, and C8 are potent inhibitors of cytochrome (CYP) subtype CYP-2C19. A subtype of CYP-2C9 was inhibited by C4 and C7. The medicinal chemistry of all the compounds C1-C10 showed no PAIN (Pan assay interference compounds) alerts. The improved gastrointestinal (GI) absorption and BBB permeability of C1 and C2 can provide a future prospective for new researchers in the medicinal field to investigate the compounds for the management of chronic diseases. The synthesized isoxazole compounds showed excellent in vitro COX-1/2 enzymes anti-inflammatory investigations, in silico studies, good physicochemical properties, and improved pharmacokinetic profile which will be further investigated via in vivo anti-inflammatory activities. Moreover, to further support our findings of the computational research and in vitro studies, an in-vivo pharmacokinetic profile is suggested in the future.

Assessment of macular pigment optical density in Arab population and its relationship to people's anthropometric data: a cross-sectional study.

Background: Anthropometry facilitates the evaluation of risks associated with reduced macular pigment optical density (MPOD). Objectives: To investigate the predictors and anthropometric indices associated with MPOD in healthy adult in Arab population. Design: This is a cross-sectional study. Methods: The MPOD was measured at 0.5° from fovea using a heterochromatic flicker photometer. Healthy participants aged between 20 and 40 years were recruited. The study evaluated the following data of the participants: height, weight, body mass index, body fat percentage, basal metabolic rate, visceral fat level, muscle mass, bone mineral content, and percentage of protein and body water. The correlation between MPOD with anthropometrics and demographic data was evaluated using Spearman's correlation test. The differences among genders were investigated using the Mann-Whitney U test. The smoking effect on MPOD was analyzed using the Friedman test. Results: In all, 143 participants were recruited. The median ± interquartile range was calculated for age (23 ± 4 years), visual acuity (0.00 ± 0.00 logMAR), and MPOD (0.41 ± 0.18). The average MPOD was higher in males than in females but it was not statistically significant (p > 0.05); on the other hand, they were statistically significantly different in most of the anthropometric data. A significant relationship was found between MPOD and percentage of body fat, protein, and body water (r = 0.30, p < 0.05). The observed median MPOD value was higher in this study than that found in previous studies in white populations, but lower than that found in studies investigating Asian populations. Conclusion: One of the most important risk factors of age-related macular degeneration is associated with a relative absence of macular pigment. This study brought into focus percentage of protein and body water for further studies as well as the well-established links with body fat and obesity. Unknown predictors of MPOD remain uncovered. The study also provided first report on normative values of MPOD for Arab population and confirmed the differences from other ethnicities.

Multidrug resistance pattern and molecular epidemiology of pathogens among children with diarrhea in Bangladesh, 2019-2021.

Antimicrobial and multidrug resistance (MDR) pathogens are becoming one of the major health threats among children. Integrated studies on the molecular epidemiology and prevalence of AMR and MDR diarrheal pathogens are lacking. A total of 404 fecal specimens were collected from children with diarrhea in Bangladesh from January 2019 to December 2021. We used conventional bacteriologic and molecular sequence analysis methods. Phenotypic and genotypic resistance were determined by disk diffusion and molecular sequencing methods. Fisher's exact tests with 95% confidence intervals (CIs) was performed. Prevalence of bacterial infection was 63% (251 of 404) among children with diarrhea. E. coli (29%) was the most prevalent. E. coli, Shigella spp., V. cholerae, and Salmonella spp., showed the highest frequency of resistance against ceftriaxone (75-85%), and erythromycin (70-75%%). About 10-20% isolates of E. coli, V. cholerae and Shigella spp. showed MDR against cephem, macrolides, and quinolones. Significant association (p value < 0.05) was found between the phenotypic and genotypic resistance. The risk of diarrhea was the highest among the patients co-infected with E. coli and rotavirus [OR 3.6 (95% CI 1.1-5.4) (p = 0.001)] followed by Shigella spp. and rotavirus [OR 3.5 (95% CI 0.5-5.3) (p = 0.001)]. This study will provide an integrated insight of molecular epidemiology and antimicrobial resistance profiling of bacterial pathogens among children with diarrhea in Bangladesh.

Evaluation of Therapeutic Capability of Emustil Drops against Tear Film Complications under Dry Environmental Conditions in Healthy Individuals.

Background and Objectives: Dry eye disease (DED) is a multifactorial ailment of the tears and ocular surface. The purpose of this study was to assess the tear film physiology under controlled dry environmental conditions and compare the efficacy of oil-in-water emulsion drops on tear film parameters in protection and relief treatment modalities under low-humidity conditions. Emustil eye drops were used after exposure to a low-humidity environment in the relief method, whereas, in the protection method, the drops were applied before exposure to low humidity. Materials and Methods: 12 normal male subjects (mean age 34.0 ± 7.0 years) were exposed to ultra-dry environmental conditions. A number of tear film measurements were carried out under desiccating environmental conditions in a controlled environment chamber (CEC), where the chamber temperature sat at 21 °C with a relative humidity (RH) of 5%. Keeler's TearScope Plus and an HIRCAL grid were used to assess the tear break-up time and lipid layer thickness (LLT), and the evaporation rate was evaluated using a Servomed EP3 Evaporimeter. Results: LLT measurements showed that the dry environment affected LLT significantly (p = 0.031). The median grade of LLT dropped from grade 3 (50-70 nm) at 40% RH to grade 2 (13-50 nm) at 5% RH. A significant increase in LLT was seen after both modes of treatment, with a median LLT grade of 3 when the Emustil was used for both protection (p = 0.004) and relief (p = 0.016). The mean tear evaporation rate in normal environmental conditions (40%) was 40.46 ± 11.80 g/m2/h (0.11 µL/min) and increased sharply to 83.77 ± 20.37 g/m2/h (0.25 µL/min) after exposure to the dry environment. A minimal decrease in tear film evaporation rate was seen in relief; however, statistical tests showed that the decrease in tear film evaporation rate was not significant. Mean NITBUT dropped from 13.6 s at 40% RH to 6.6 s at 5% RH (p = 0.002). All NITBUT measurements at 5% RH (with or without the instillation of Emustil) were significantly lower than those at 40%. The instillation of Emustil at 5% RH resulted in a significant improvement in NITBUT for protection (p = 0.016) but this was not the case for relief (p = 0.0.56). Conclusions: A control environmental chamber (CEC) enables the analysis of tear film parameters comparable to those found in dry eye patients. This enables us to examine the capability of oil in emulsion drops to manage tear film disruption in healthy individuals. This study suggests that using Emustil oil-in-water emulsion before exposure to a dry environment should be advocated for people who work in dry environments.

New Ways to Protect the Host from SARS-CoV-2? Lung Microbiome Metabolites Inhibit STAT3 and Modulate the Immunological Network.

COVID-19 caused by the SARS-CoV-2 infection is a systemic disease that affects multiple organs, biological pathways, and cell types. A systems biology approach would benefit the study of COVID-19 in the pandemic as well as the endemic state. Notably, patients with COVID-19 have dysbiosis of lung microbiota whose functional relevance to the host is largely unknown. We carried out a systems biology investigation of the impact of lung microbiome-derived metabolites on host immune system during COVID-19. RNAseq was performed to identify the host-specific pro- and anti-inflammatory differentially expressed genes (DEGs) in bronchial epithelium and alveolar cells during SARS-CoV-2 infection. The overlapping DEGs were harnessed to construct an immune network while their key transcriptional regulator was deciphered. We identified 68 overlapping genes from both cell types to construct the immune network, and Signal Transducer and Activator of Transcription 3 (STAT3) was found to regulate the majority of the network proteins. Furthermore, thymidine diphosphate produced from the lung microbiome had the highest affinity with STAT3 (-6.349 kcal/mol) than the known STAT3 inhibitors (n = 410), with an affinity ranging from -5.39 to 1.31 kcal/mol. In addition, the molecular dynamic studies showed distinguishable changes in the behavior of the STAT3 complex when compared with free STAT3. Overall, our results provide new observations on the importance of lung microbiome metabolites that regulate the host immune system in patients with COVID-19, and may open up new avenues for preventive medicine and therapeutics innovation.

Evaluation of different treatment modalities on the efficacy of hydroxypropyl Guar (HP-Guar) formulation on tear film stability (TFS) in subjects exposed to adverse environmental conditions.

The study aimed to assess the efficacy of hydroxypropyl guar (HP) formulation (Systane) to protect tear film parameters under desiccating environment using protection and relief treatment modalities. The subjects were exposed to adverse environmental conditions using a Controlled Environment Chamber (CEC) where the relative humidity (RH) was 5% and the ambient temperature was 21 °C and screened for Tear break-up time (TBUT), Tear film evaporation rate (TFER) and lipid layer thickness (LLT) using the HIRCAL grid, Servomed EP3 Evaporimeter and Keeler's TearScope-Plus respectively. Significant improvement in LLT was noticed in the protection modality. The mean tear film evaporation rate doubled after exposure to the humidity of 5% to a value of 105.37 g/m2/h (0.29 µl/min). All subjects displayed a significant reduction in non-invasive tear break-up time (NITBUT) with a mean NITBUT of 7.7 s after exposure to a desiccating environment for 15 min. A significant increase in NITBUT after the instillation of the drops was recorded in both methods. The results obtained from this study showed that a solution containing HP-Guar significantly improves tear film parameters under a desiccating environment. Apart from the tear evaporation rate, all tear parameters showed improvement after the use of HP-Guar eye drops. It is evident that tear film parameters respond differently to the management modalities and using CEC has the potential to provide researchers with a readily available method to evaluate the efficiency of tear supplementation.

Biophysical, histological, and bioaccumulation properties of Tilapia muscle affected by water pollution with heavy elements and microbes at the El-Rahawy drain in Egypt.

The leakage of sewage and agricultural drains has led to the contamination of freshwater branches with toxic heavy elements. This raises concerns about their toxic effects on aquatic ecosystems, especially on fish. Tilapia is regarded as an important protein source in Egypt and many other countries. The biophysical, nutritional, and histological aspects of water pollution in the El-Rahawy and Al-Qatta locations of the Nile on Nilotic tilapia muscle were evaluated by assessing the level of contamination of Nilotic tilapia fish. The current study showed that water of the Rosetta branch water was polluted with a very high level at El-Rahawy Drain discharge (RD) location, and with a high level at Al-Qatta (Q) location, while El-Rahawy (R) location was polluted with a lower level. The study traced the pollution effects on Tilapia (Nilotic) muscles in the previous locations. Bioaccumulation factor (BAF) showed a high value of all heavy metals in Tilapia muscle at the Q and R locations. Contrary to what was expected, discharge (RD) location contamination caused BAF increment of heavy metals in Tilapia muscles at upstream R location. All these results were compared with measured dielectric parameters of Tilapia muscle samples in the frequency range (0.02-1000) kHz. There was an increase in conductivity (σac), dielectric constant (ε'), dielectric loss (ε″), penetration depth (dp), and dissipated power (PD) values of Tilapia muscle, with increasing pollution level. The values of permittivity at low and high frequencies (ε's & ε'∞) for Tilapia muscle decreased by increasing pollution. Finally, the variation of these parameters, based on that proportionality relationship, can be considered as a physical indicator for fish contamination affected by their environment pollution, although these parameters need further studies in a controlled (qualitatively and quantitatively) polluted media.

Analyzing the Differential Impact of Semen Preparation Methods on the Outcomes of Assisted Reproductive Techniques.

Sperm separation plays a critical role in assisted reproductive technology. Based on migration, density gradient centrifugation and filtration, a properly selected sperm could help in increasing assisted reproductive outcomes in teratozoospermia (TZs). The current study aimed to assess the prognostic value of four sperm selection techniques: density gradient centrifugation (DGC), swim-up (SU), DGC-SU and DGC followed by magnetic-activated cell sorting (DGC-MACS). These were evaluated using spermatozoa functional parameters. A total of 385 infertile couples underwent the procedure of intracytoplasmic sperm injection (ICSI), with an isolated teratozoospermia in the male partner. Semen samples were prepared by using one of the mentioned sperm preparation techniques. The improvements in the percentage of normal mature spermatozoa, rate of fertilization, cleavage, pregnancy and the number of live births were assessed. The normal morphology, spermatozoa DNA fragmentation (SDF) and chromatin maturity checked by using chromomycin A3 (CMA3) with DGC-MACS preparation were better compared to the other three methods. Embryo cleavage, clinical pregnancy and implantation were better improved in the DGC-MACS than in the other tested techniques. The DGC-MACS technique helped in the selection of an increased percentage of normal viable and mature sperm with intact chromatin integrity in patients with teratozoospermia.

Investigation of UTR Variants by Computational Approaches Reveal Their Functional Significance in PRKCI Gene Regulation.

Single nucleotide polymorphisms (SNPs) are associated with many diseases including neurological disorders, heart diseases, diabetes, and different types of cancers. In the context of cancer, the variations within non-coding regions, including UTRs, have gained utmost importance. In gene expression, translational regulation is as important as transcriptional regulation for the normal functioning of cells; modification in normal functions can be associated with the pathophysiology of many diseases. UTR-localized SNPs in the PRKCI gene were evaluated using the PolymiRTS, miRNASNP, and MicroSNIper for association with miRNAs. Furthermore, the SNPs were subjected to analysis using GTEx, RNAfold, and PROMO. The genetic intolerance to functional variation was checked through GeneCards. Out of 713 SNPs, a total of thirty-one UTR SNPs (three in 3' UTR region and twenty-nine in 5' UTR region) were marked as ≤2b by RegulomeDB. The associations of 23 SNPs with miRNAs were found. Two SNPs, rs140672226 and rs2650220, were significantly linked with expression in the stomach and esophagus mucosa. The 3' UTR SNPs rs1447651774 and rs115170199 and the 5' UTR region variants rs778557075, rs968409340, and 750297755 were predicted to destabilize the mRNA structure with substantial change in free energy (∆G). Seventeen variants were predicted to have linkage disequilibrium with various diseases. The SNP rs542458816 in 5' UTR was predicted to put maximum influence on transcription factor binding sites. Gene damage index(GDI) and loss of function (o:e) ratio values for PRKCI suggested that the gene is not tolerant to loss of function variants. Our results highlight the effects of 3' and 5' UTR SNP on miRNA, transcription and translation of PRKCI. These analyses suggest that these SNPs can have substantial functional importance in the PRKCI gene. Future experimental validation could provide further basis for the diagnosis and therapeutics of various diseases.

Pathogenicity of PKCγ Genetic Variants-Possible Function as a Non-Invasive Diagnostic Biomarker in Ovarian Cancer.

Ovarian cancer has the highest mortality rate among gynecologic malignancies, owing to its misdiagnosis or late diagnosis. Identification of its genetic determinants could improve disease outcomes. Conventional Protein Kinase C-γ (PKCγ) dysregulation is reported in several cancers. Similarly, its variant rs1331262028 is also reported to have an association with hepatocellular carcinoma. Therefore, the aim of the present study was to analyze the variant rs1331262028 association with ovarian cancer and to determine its impact on PKCγ's protein interactions. Association of variation was determined through genotyping PCR (cohort size:100). Protein-protein docking and molecular dynamic simulation were carried out to study the variant impact of PKCγ interactions. The study outcome indicated the positive association of variant rs1331262028 with ovarian cancer and its clinicopathological features. Molecular dynamics simulation depicted the potential influence of variation on PKCγ molecular signaling. Hence, this study provided the foundations for assessing variant rs1331262028 as a potential prognostic marker for ovarian cancer. Through further validation, it can be applied at the clinical level.

Evaluation of Tear Evaporation Rate in Subjects with a High Body Mass Index.

AIM: This study evaluated the tear evaporation rate (TER) in subjects with a high body mass index (BMI) and tested the correlation between BMI and dry eye. METHODS: Thirty male subjects aged 18 - 38 years (26.4 ± 4.0 years) with a high BMI (26.4 - 47.0 kg/m2) were enrolled in the study. In addition, a control group of 30 males aged 20 - 36 years (24.0 ± 3.6 years) with a normal BMI (< 25 kg/m2) participated in the study for comparison. Each subject completed the ocular surface disease index (OSDI), followed by the TER measurement using a handheld VapoMeter. RESULTS: Significant differences (Wilcoxon test; p = 0.002 and 0.001) were found between the median scores of the OSDI (10.3 [3.7] vs. 5.9 [7.2]) and TER (35.5 [13.1] vs. 15.5 [12.8] g/m2 h) in the study and control groups, respectively. The OSDI indicated dry eye in 60.0% of subjects in the study group (n = 18). The TER measurements showed that 76.7% of subjects in the study group (n = 23) had dry eyes. A medium correlation (r = 0.569; p = 0.001) was found between the OSDI scores and TER measurements. CONCLUSIONS: The means of the tear evaporation rate and the ocular surface disease index scores are significantly higher in subjects with a high BMI compared with the control group. Therefore, a high BMI is considered a risk factor for dry eye. The measurement of the tear evaporation rate using a handheld VapoMeter is a simple and rapid method to detect dry eyes in combination with other tools.

Unraveling Catechol-O-Methyltransferase rs4680 SNP's Role in Patients' Response to Tramadol and Its Adverse Effects: A Pharmacogenetics Insight into Postoperative Pain Management.

Effective postoperative pain management is essential for patient well-being and an efficient healthcare system. Variations in the Catechol O-Methyltransferase (COMT) gene, specifically rs4680, play a crucial role in pain perception and opioid response. This study seeks to elucidate the impact of rs4680 polymorphism on tramadol efficacy and adverse reactions in post-surgical patients. We performed an uncontrolled cohort pharmacogenetics study in which participants underwent postoperative tramadol administration. The frequencies of rs4680 alleles were determined and the association between rs4680 genotypes and the efficacy of tramadol analgesic as pain relief, measured by the Numeric Rating Scale (NRS), was analyzed. Secondary outcomes included tramadol-induced sedation levels, opioid-induced nausea and vomiting, and other adverse effects of tramadol. Data analysis, using IBM SPSS Statistics 23, focused on pain and side effect differences across genotypes, with statistical significance set to p ≤ 0.05. The COMT (rs4680) genotype distribution exhibited a 'G' allele frequency of 41.5% and an 'A' allele frequency of 58.5%, with the AA genotype present in 44% of individuals, adhering to the Hardy-Weinberg equilibrium (p = 0.788). Patients with the AA genotype reported lower pain scores post-tramadol administration across all times examined (p < 0.001), but also experienced statistically significant (p < 0.001) higher incidences of tramadol-induced nausea, vomiting, and sedation. However, GG genotype individuals experienced poor pain relief from tramadol, requiring more supplemental analgesia. These significant findings underscore the critical role of COMT rs4680 polymorphism in response to tramadol and the necessity of a personalized approach to postoperative pain management.

Measurements of Tear Evaporation Rate in Subjects with Refractive Errors Using a Portable Evaporimeter.

Dry eye symptoms are associated with refractive errors. We aimed to measure the tear evaporation rate (TER) in subjects with refractive errors (RE) using a portable evaporimeter. This nonrandomized, case-control, and observational study included 75 subjects, including 25 subjects aged 18-38 years (28.8 ± 6.8 years) with myopia (-0.75 to -3.75 D) and 25 subjects aged 18-39 years (27.7 ± 5.5 years) with hyperopia (+0.50 to +3.75 D). In addition, a control group of 25 subjects with emmetropic eyes aged 20-30 years (23.6 ± 2.6 years) was recruited. The ocular surface disease index (OSDI) was completed, followed by the TER measurements using a portable evaporimeter. The OSDI score and TER measurements showed dry eye symptoms in 36% and 48% of myopic subjects, respectively. For hyperopic participants, dry eye was observed in 24% and 56% of the subjects based on the OSDI and TER scores, respectively. Significant differences (Mann-Whitney U test; p < 0.001) were found among the OSDI and TER scores recorded within the study (myopic and hyperopic subjects) and control groups. Significant strong positive correlations were detected between the OSDI and TER scores in both myopic (p = 0.004; r = 0.559) and hyperopic (p = 0.001; r = 0.619) subjects. The TER scores were significantly higher in subjects with RE (myopic and hyperopic) as compared with individuals with normal eyes.

Improving tear ferning patterns collected from goats and camels after adding various electrolyte solutions.

BACKGROUND: Good quality of tear film is essential for healthy vision in both animals and humans. Therefore, improving the quality of tears through the addition of electrolytes is important. OBJECTIVES: To assess the effect of adding various electrolyte solutions on tear ferning (TF) patterns collected from goats and camels. MATERIAL AND METHODS: Tear samples (20 ƒÊL) were collected from 5 goats (2 males and 3 females; 3.4 }1.6 years) and 5 camels (2 males and 3 females; 4.0 }1.1 years) using microcapillary tubes. A tear sample (0.5 ƒÊL) from each animal was mixed with various volumes (0.5.5 ƒÊL) of each electrolyte solution to produce homogenous mixtures. A sample (1 ƒÊL) of each mixture was dried on a microscopic glass at 22°C with a humidity .40%. The obtained TF pattern was observed, graded and compared with those obtained for the corresponding pure tear samples. The effect of dilution using purified water on the TF patterns of animals was also tested. RESULTS: The TF grades of animals were generally enhanced when mixed with electrolyte solutions. Specifically, the TF grade for tears collected from a goat was improved from 1.4 to 0.7 and to 0.8 when magnesium chloride hexahydrate and calcium chloride were added, respectively. Similarly, the TF grade for tears collected from a camel was improved from 1.8 to 0.9 and to 1.1, when calcium chloride and sodium dihydrogen phosphate solutions were added, respectively. CONCLUSIONS: The TF grades of tears collected from both goats and camels were improved after adding electrolyte solutions, and they were most remarkably improved when divalent electrolyte solutions were added, followed by the hydrogenated electrolyte.