Prevalence and Factors Associated with Myopia Among High School Students in Hawassa City, South Ethiopia, 2019.

Purpose: Myopia is one of the avoidable causes of visual impairment. Twenty-seven percent of the world population were myopic in 2010 and after 30 years it is expected half of the peoples in the planet will become myopic. The aim of this study was to determine the prevalence and factors associated with myopia among high school students. Materials and Methods: A cross-sectional school-based study design using stratified simple random sampling technique was used to select 349 high school students from 21 high schools in Hawassa city. The study was conducted from April 24 to May 7, 2019. Structured questionnaire, six meter Snellen visual acuity chart, trial frame, trial set, retinoscope and cyclopentolate 1% eye drops were used to collect data. Data were analyzed using Statistical Package for Social Science (SPSS) version 20 computer software. Variables having p-value <0.05 in multivariate logistic regression were considered as statistically significant. Results: A total of 349 participants having a response rate of 97% were involved with the mean age of 16.90±1.32 years. Prevalence of myopia was 16.05% (95%CI: 12.6, 20.1). Early age of schooling (adjusted odds ratio, AOR=3.14; 95%CI: 1.16, 10.06), parents being myopic (AOR=8.46; 95%CI: 7.11, 12.08), prolonged near work (AOR=11.65; 95%CI: 2.11, 64.5), short working distance (AOR=10.90; 95%CI: 0.57, 20.55), lack of outdoor sport activities (AOR=7.37; 95%CI: 2.71, 20.03) and visual display unit (VDU) usage (AOR=8.36; 95%CI: 2.39, 29.33) were variables significantly associated with myopia. Conclusion and Recommendations: The prevalence of myopia was high in the study area. Early age of schooling, parents being myopic, prolonged near work, short working distance, lack of outdoor sport activities, and visual display unit usage were variables significantly associated with myopia. There should be strategies to prevent visual impairments secondary to myopia with affordable optical corrections and appropriate use of visual display units.

Bipolar Disorder after COVID-19 Infection: A Case Report from an Ethiopian Perspective.

Introduction: COVID-19 has been a sudden public health crisis since January 2020, spreading from the city of Wuhan, China, to the whole country within a month and posing serious threats to lives. The pandemic has a profound effect on all aspects of society, including mental health and physical health. The actual effect of the virus on the brain and possible psychiatric manifestations is still an area of study and further investigation. There are also several case reports showing manic like symptoms after COVID-19 infection. We describe the case of a 55-year-old patient who presented with behavioral and mood symptoms after a COVID-19 infection. Case Presentation. The patient presented with behavioral disturbance after a diagnosis of COVID-19. He exhibited symptoms including irritability, verbal and physical aggressiveness, increased goal-directed activity, elated and expansive mood, increased energy, grandiosity and inflated self-esteem, and decreased need for sleep. Findings on psychiatric evaluation encompassing detailed history and mental state examination suggested bipolar disorder due to COVID-19 infections. For this, he was put on sodium valproate 1000 mg per day and later, and he was discharged after 21 days with improvement. Conclusions: This case highlights the importance of paying attention to psychiatric symptoms in patients with COVID-19 and the early intervention and involvement of psychiatrists especially in critically ill patients. In the present scenario, we urge physicians to pay attention to those cases and be open-minded for such a possible new diagnosis. We also recommend performing antibody tests for CSF and RNA tests for patients with mental abnormalities following COVID-19. Further studies can be performed to identify the relationship between COVID-19 and bipolar disorders.

Profile of Amblyopia Among Children Aged from 5 to 15 Years at Hawassa University Comprehensive Specialized Hospital Pediatric Eye Clinic, South Ethiopia, 2020/21.

Purpose: Functional visual impairment in children is mostly caused by amblyopia. Permanent visual impairment is caused by belated treatment of amblyopia and underlying causes, mostly due to the lack of awareness. Amblyopia affects children's school performance, social interaction and motor skills. This study was aimed to assess the profile of amblyopia among children aged from 5 to 15 years. Methods and Materials: A hospital-based, cross-sectional study was done from November to April 2020/21. Data were collected from all children who came to Hawassa university comprehensive specialized hospital pediatric eye out patient department in the data collection period. Visual acuity measurement, slit lamp examination, cycloplegic refraction, cover test and dilated fundus examination were conducted. Data was entered in Epi-info version 7 and analyzed by Statistical Package for Social Science version 20. Descriptive statistics were conducted to estimate the proportion of amblyopia and its causes. Results: The proportion of amblyopia was 23.8% (18.3-29.7). Most of the participants were within the age range of 5-9 years (55.4%) and males (51.5%). Anisometropia was the commonest cause of amblyopia (31.25%), followed by meridional (20.83), mixed (16.67%), isometropia (12.50%), sensory deprivation (10.42%) and strabismus (8.33%). Conclusion: The proportion of amblyopia was 23.8%. Anisometropia, meridional, sensory deprivation, isometropia, mixed type and strabismus were the identified causes of amblyopia.

The role of Janus kinase 2 (JAK2) activation in pneumococcal EstA protein-induced inflammatory response in RAW 264.7 macrophages.

In a previous study, we demonstrated pneumococcal EstA-induced inflammatory response through NF-κB and MAPK-dependent pathways. Herein, we tested the hypothesis that the Janus kinase 2 (JAK2) activation and associated signaling cascades may also be involved in EstA-induced inflammatory process in RAW 264.7 macrophages. Our immunoblot analysis indicated EstA-induced activation of JAK2, with the phosphorylated protein detected from 1 to 24 h post-stimulation. As type I interferon (IFN) signaling requires the JAK/STAT pathway, we investigated EstA-induced expression of INF-α4 and INF-ß by semi-quantitative and quantitative RT PCR. Our results indicated both concentration- and time-dependent increases in both IFN-α4 and IFN-ß mRNA expression after EstA challenge, with the highest fold-increases observed at 4 h and 6 h post-stimulation for IFN-α4 and IFN-ß mRNA, respectively. Furthermore, we applied a pharmacological approach to demonstrate the effect of JAK2 inhibition on EstA-induced nitric oxide (NO) and pro-inflammatory cytokine production. The JAK2 inhibitor AG-490 reduced significantly (P < 0.05) EstA-induced NO production and the expression of iNOS mRNA in a concentration-dependent manner. Similarly, EstA-induced IL-1ß and IL-6 production and their respective mRNA expression were markedly suppressed by AG-490. However, AG-490 had no inhibitory effect on both mRNA and protein levels of TNF-α. Taken together, we demonstrate that JAK2 activation and IFN I signaling are integral parts of EstA-induced inflammatory process. Further studies will elucidate the interaction of the different signaling pathways, the specific downstream targets of JAK2, the kinetics of cytokine release, and if EstA could induce the pro-inflammatory mediators to the same extent in alveolar macrophages.

Immunomodulatory activities and subacute toxicity of a novel ß-glucan from Paenibacillus polymyxa JB115 in rats.

Subacute toxicity and immunopharmacological activities of ß-glucan from P. polymyxa JB115 was evaluated in a 28-day feeding study in rats. The white blood cell count, red blood cell count, hematocrit, hemoglobin, thrombocytes (THR) and thrombocytocrit were significantly higher in male fed with ß-glucan than control rats and the insignificant lower eosinophil count, mean corpuscular volume, mean cell hemoglobin and uninfected THR (uTHR) levels were observed in male whereas no marked changes in female rats. No other significant differences in serum chemistry and liver, kidney, and spleen weights were observed. The pathological changes and other abnormal indicators were not detected in urine. Female rats fed with diet supplemented with 0.01% ß-glucan also showed marked increase in the percentage of blood cytotoxic T-lymphocytes compared to that of the control group while not significant differences in the percentage of blood B-lymphocytes. No adverse effects on general condition and behavior, growth, feed and water consumption and feed conversion efficiency were found. The results suggest that consumption of the novel ß-1, 3/1, 6-glucan from P. polymyxa JB115 was not associated with any obvious toxic effects in rats, indicating its safety as a potential immunostimulant or as an adjuvant of some animal vaccines.

Pharmacokinetics of a florfenicol-tylosin combination after intravenous and intramuscular administration to beagle dogs.

A pharmacokinetic study of a commercial florfenicol-tylosin (2:1) combination product was conducted in six beagle dogs after intravenous (IV) and intramuscular (IM) administration at doses of 10 mg/kg (florfenicol) and 5 mg/kg (tylosin). Serum drug concentrations were determined by a validated high performance liquid chromatography (HPLC) using UV detection. A rapid and nearly complete absorption of both drugs with a mean IM bioavailability of 103.9% (florfenicol) and 92.6% (tylosin), prolonged elimination half-life, and high tissue penetration with steady state volume of distribution of 2.63 l/kg (florfenicol) and 1.98 l/kg (tylosin) were observed. Additional studies, including pharmacodynamic and toxicological evaluation are required before recommendations can be made regarding the clinical application of the product in dogs.

A cross-sectional analysis of refractive error prevalence and associated factors among elementary school children in Hawassa, Ethiopia.

OBJECTIVE: This study assessed the prevalence of refractive error (RE) and its associated factors among elementary school children in Hawassa, Ethiopia. METHODS: In this school-based cross-sectional study, a random selection technique with proportional allocation was used to ensure a representative sample of students. Survey questionnaires were used to collect sociodemographic, environmental, and family history data. Clinical examinations were performed to assess RE and ocular health. Associations between dependent and independent variables were computed using adjusted odds ratios (AORs) and 95% confidence intervals (CIs). RESULTS: Overall, 529 children participated in this study, with a response rate of 95.5% (529/554). Most participants were aged ≥12 years (337 [63.7%]), in grade levels 5 to 8 (307 [58%]), and attended public schools (366 [69.2%]). RE prevalence was 12.9% (95% CI: 10.0-16.1). Higher grade level (AOR=3.18, 95% CI: 1.68-5.97), positive family history of RE (AOR=3.69, 95% CI: 1.57-8.67), lack of paternal formal education (AOR=3.25, 95% CI: 1.20-8.77), and public school attendance (AOR=3.33, 95% CI: 1.52-7.27) were factors significantly associated with RE. CONCLUSIONS: RE prevalence among elementary school children in Hawassa was higher than in previous reports. Grade level, family history, paternal education level, and school type significantly influenced RE status.

Mechanism of macrophage activation induced by beta-glucan produced from Paenibacillus polymyxa JB115.

Beta-glucans are heterogeneous groups of glucose polymers found in the cell walls of fungi, plants and some bacteria. Our previous report showed that a novel beta-1,3/1,6-glucan produced from Paenibacillus (P.) polymyxa JB115 can induce nitric oxide (NO) production in RAW264.7 cells. In the present study, the beta-glucan significantly increased luciferase activity in cells transfected with NFkappaB or AP1, but not STAT1, reporter vector DNA, which contain their binding promoter site. All specific NFkappaB and MAPKs pathway inhibitors (pyrrolidine dithiocarbamate, AG490, U0126, SB203580 and SP600125) remarkably attenuated NO production induced by the beta-glucan. Furthermore, Western blot analysis revealed that the stimulation of Raw264.7 cells by beta-glucan induced phosphorylation of IkappaB and the consequent translocation of NFkappaB into the nucleus. Meanwhile, phosphorylation of ERK1/2, JNK/SAPK and p38 MAPKs in cytoplasm were also confirmed. All these results indicated that beta-glucan from P. polymyxa JB115 activates macrophages through MAPKs and NFkappaB signaling pathway.

Integration of pharmacokinetic and pharmacodynamic indices of orbifloxacin in beagle dogs after a single intravenous and intramuscular administration.

The pharmacokinetics (PK) and pharmacodynamics (PD) of orbifloxacin were studied in beagle dogs after intravenous (i.v.) and intramuscular (i.m.) administration at a dose of 2.5 mg/kg body weight. An absolute bioavailability of 100.1% +/- 4.76%, a terminal half-life of 4.23 +/- 0.2 h and 3.95 +/- 0.15 h after i.v. and i.m. administration, a steady-state volume of distribution of 1.61 +/- 0.13 liters/kg, and clearance of 0.31 +/- 0.03 liters/h/kg were observed. Orbifloxacin showed rapid, concentration-dependent killing against the Escherichia coli, Staphylococcus aureus, Staphylococcus intermedius, and Proteus mirabilis clinical isolates. Computations based on PK-PD analysis indicated that the recommended dose is unlikely to be clinically effective against some strains like S. intermedius. Therefore, a higher dose of orbifloxacin would be worthy of consideration for treatment of certain bacterial infections in dogs.

EstA protein, a novel virulence factor of Streptococcus pneumoniae, induces nitric oxide and pro-inflammatory cytokine production in RAW 264.7 macrophages through NF-kappaB/MAPK.

In the present study we characterized the molecular mechanism by which esterase A (EstA) protein, a novel virulence factor of Streptococcus pneumoniae induces inflammation. Stimulation of RAW 264.7 macrophages with purified EstA protein induced the expression of inducible nitrogen oxide synthase (iNOS) mRNA and nitrogen oxide (NO) production in a concentration-dependent manner. Inhibitors of iNOS, NF-kappaB, p38 and ERK 1/2 MAPK pathways significantly decreased (50-78%) EstA-induced NO production. Similarly, EstA induced TNF-alpha, IL-1 beta and IL-6 mRNA expression in RAW 264.7 macrophages in a dose-dependent manner, and pre-treatment of the cell cultures with specific NF-kappaB, p38 and ERK 1/2 MAPK pathway inhibitors significantly decreased EstA-induced TNF-alpha, IL-1 beta and IL-6 protein production. Furthermore, immunoblot analysis revealed the degradation of the inhibitory kappa B (IKB-alpha) in response to EstA stimulation. Taken together, our data suggests that EstA protein is a novel inducer of NO and pro-inflammatory cytokines by activating the NF-kappaB, p38 and ERK 1/2 MAPK pathways during inflammatory responses. Future studies on the upstream protein kinases of the MAPK/NF-kappaB pathways and the kinetics of cytokine production will provide further details into the mechanism of EstA-induced inflammatory response.

Comparative pharmacokinetics of tylosin or florfenicol after a single intramuscular administration at two different doses of tylosin-florfenicol combination in pigs.

Clinical pharmacokinetic profiles were investigated following intramuscular (i.m.) administration to pigs with a commercial tylosin-florfenicol combination product at a dose of 2.5 mg/kg tylosin and 5 mg/kg florfenicol or 10 mg/kg tylosin and 20 mg/kg florfenicol. The quantitation limit (QL) of florfenicol was 0.1 microg/ml, the inter-day and intra-day precision (CV%) were both beow 10%. The quantitation limit (QL) of tylosin was 0.05 microg/mL. The pharmacokinetic characteristics after i.m. doses were fitted by a one compartment open model. A fourfold decrease in the normal dose of each drug (20 mg/kg to 5 mg/kg for florfenicol, and 10 mg/kg to 2.5 mg/kg for tylosin) resulted in a corresponding two fold decrease in each drug of the maximum plasma concentration (C(max)) and the area under curve (AUC) values.

Mutant prevention concentration and phenotypic and molecular basis of fluoroquinolone resistance in clinical isolates and in vitro-selected mutants of Escherichia coli from dogs.

The antibacterial activity, selection of Escherichia coli (E. coli) mutants and mechanisms of fluoroquinolone resistance were investigated by integrating the minimum inhibitory concentration (MIC), mutant prevention concentration (MPC) and in vitro dynamic model approaches. Difloxacin and orbifloxacin, for which the above information has been scarce, were used. A range of area under curve over a 24h interval (AUC(24h))/MIC ratios and selected E. coli strains were investigated using the dynamic models. Continuous incubation for three days in the presence of difloxacin or orbifloxacin resulted in losses in E. coli susceptibility. An AUC(24h)/MIC (AUC(24h)/MPC)-dependent fluoroquinolone activity and selection of E. coli mutants was confirmed. Maximum losses in susceptibility occurred at AUC(24h)/MIC ratios of 54 (orbifloxacin) and 57.3 (difloxacin). AUC(24h)/MIC ratios of 169.8 (orbifloxacin) and 199.5 (difloxacin) were estimated to be protective against the selection of E. coli mutants, and the corresponding ratios based on AUC(24h)/MPC predictions were 34 (orbifloxacin) and 36.3 (difloxacin). When integrating our in vitro data with pharmacokinetic data in dogs, the conventional clinical doses of both drugs were found to be inadequate to attain the above protective values for 90% of the mutant subpopulation (AUC(24h)/MPC(90)). Both target mutations, esp. at codon 83 (Ser to Leu) of gyrA, and overexpression of efflux pumps contributed to resistance development, with mutants also showing decreased susceptibility to enrofloxacin and marbofloxacin. Additional studies would determine the role of mutations found outside the QRDR, at codon 24 of gyrA, and at codon 116 of parC, and establish the significance of these observations in vivo.

Mutant-prevention concentration and mechanism of resistance in clinical isolates and enrofloxacin/marbofloxacin-selected mutants of Escherichia coli of canine origin.

The antibacterial activity and selection of resistant bacteria, along with mechanisms of fluoroquinolone resistance, were investigated by integrating the static [MIC or mutant-prevention concentration (MPC)] and in vitro dynamic model approaches using Escherichia coli isolates from diseased dogs. Using the dynamic models, selected E. coli strains and enrofloxacin and marbofloxacin at a range of simulated area under concentration-time curve over a 24 h interval (AUC(24 h))/MIC ratios were investigated. Our results indicated increasing losses in susceptibility of E. coli upon continuous exposure to enrofloxacin and marbofloxacin in vitro. This effect was transferable to other fluoroquinolones, as well as to structurally unrelated drugs. Our results also confirmed an AUC(24 h)/MIC (AUC(24 h)/MPC)-dependent antibacterial activity and selection of resistant E. coli mutants, in which maximum losses in fluoroquinolone susceptibility occurred at simulated AUC(24 h)/MIC ratios of 40-60. AUC(24 h)/MPC ratios of 39 (enrofloxacin) and 32 (marbofloxacin) were considered protective against the selection of resistant mutants of E. coli. Integrating our MIC and MPC data with published pharmacokinetic information in dogs revealed a better effect of the conventional dosing regimen of marbofloxacin than that of enrofloxacin in restricting the selection of resistant mutants of E. coli. Target mutations, especially at codon 83 (serine to leucine) of gyrA, and overexpression of efflux pumps contributed to resistance development in both clinically resistant and in vitro-selected mutants of E. coli. We also report here a previously undescribed mutation at codon 116 of parC in two laboratory-derived resistant mutants of E. coli. Additional studies would determine the exact role of this mutation in fluoroquinolone susceptibility, as well as establish the importance of our findings in the clinical setting.

Allometric scaling of orbifloxacin disposition in nine mammal species: a retrospective analysis.

The objective of this study was to analyze the relationship between pharmacokinetic parameters and body weight (W) for orbifloxacin using reported pharmacokinetic data. The parameters of interest: clearance (Cl), volume of distribution at steady state (Vss) and elimination half-life were correlated across nine mammal species, including cattle, dog, rat, rabbit, goat, camel, horse, cat and sheep as a function of W using the conventional allometric equation Y = aW(b), where Y is the pharmacokinetic parameter, W is the body weight, a is the allometric coefficient (intercept) and b is the exponent that describes the relationship between the pharmacokinetic parameter and W. Our estimates (Cl=4.40 W(1.03); Vss=1.10W(1.05)) indicated that the increase in these parameters with W approximates a linear power relationship with slopes being very close to one. Overall, the results of this study indicated that it is possible to use allometry to predict pharmacokinetic variables of orbifloxacin based on W of mammal species.

In vitro antioxidant and anti-inflammatory activities of protocatechualdehyde isolated from Phellinus gilvus.

Although various biological activities of Phellinus gilvus (PG) have been reported, the active compounds responsible for these effects are not known. Here, we evaluated the activity of various solvent extracts of PG, and found the ethyl acetate extract (Fd) to be the most active fraction, showing a strong DPPH free radical scavenging activity, and inhibitory effects on LPS-induced nitric oxide (NO) production and COX-2 mRNA expression in RAW264.7 macrophages. Six major compounds were identified from the ethyl acetate extract of PG, and protocatechualdehyde (PCA) was supposed to be the major phenolic compound of PG responsible for its DPPH free radical scavenging activity and its inhibitory effects on LPS-induced NO production in RAW264.7 cells. Further in vitro and in vivo experiments are currently underway to confirm this observation and to investigate the detailed molecular mechanisms involved in the process as well as the biological activities of other fractions of Fd.

Mycoplasma hyopneumoniae induces pro-inflammatory cytokine and nitric oxide production through NFκB and MAPK pathways in RAW264.7 cells.

In the present study, we confirmed the ability of M. hyopneumoniae to induce the secretion of large amount of proinflammatory cytokine and nitric oxide (NO) in murine macrophage RAW 264.7 cells. Moreover, M. hyopneumoniae-induced activation of the MAPK and NF-кB pathways by phosphorylation of ERK1/2, p38 and JNK/SAPK and by dissociation of IκB from NF-κB. Translocation of transcription factor NF-κB and its binding was confirmed through western blot and electromobility shift assay. From these results, we further hypothesized that these signal proteins were involved in M. hyopneumoniae-induced proinflammatory cytokines and NO productions in macrophages. Hence, we utilized specific blockers of MAPK and NF-κB to investigate the signaling pathway involvement in cytokine and NO production through pharmacological approaches. The results demonstrated significant inhibition of TNF-α, IL-1ß, IL-6 and NO by MAPK inhibitors. NF-κB inhibitor PDTC significantly inhibited IL-1ß and NO production. These findings contribute to the understanding of the mechanisms of immune reactivity and may ultimately prove useful in the development of new therapeutic strategies. In summary, we found critical evidence for the involvement of NF-κB and MAPK signaling pathways in the upregulation of proinflammatory cytokine and NO induced by M. hyopneumoniae.