Prevalence of spinal deformity development after surgical management of a congenital heart disease among children: a systematic review and meta-analysis.

INTRODUCTION: Open heart surgery is the most common treatment for congenital heart disease. Thoracotomy, sternotomy, or a combination of both are the main approaches used in open heart surgeries. In cardiac surgery, there have been concerns that these surgeries increase the likelihood of spinal deformities. Therefore, this systematic review and meta-analysis provided updated evidence on the prevalence of spinal deformities following congenital heart surgery. METHOD: EMBASE, Medline, ScienceDirect, and Google Scholar were used to search for studies published until 2022. We include randomized clinical trials and observational studies that reported the prevalence of spinal deformities (scoliosis and kyphosis) after congenital heart surgery among participants without these deformities before surgery. Two independent reviewers independently screened literature identified from the databases. Two reviewers independently conducted screening of studies identified during the search, data extraction, and quality assessment of the included studies. RESULTS: In total, 688 studies were screened; 13 retrospective and one prospective cohort studies were included, encompassing 2294 participants. The pooled prevalence of spinal deformities (scoliosis and kyphosis) after open heart surgery performed on skeletally immature patients was 23.1% (95% confidence interval [CI] = 23.1-35.3; I2 = 97.5%). CONCLUSION: This review suggests that the prevalence of spinal deformities was high among patients who underwent sternotomy or thoracotomy.

Effect of endo-1,4-beta-xylanase supplementation to low-energy diets on performance, blood constituents, nutrient digestibility, and gene expressions related growth of broiler chickens.

The presence of soluble and insoluble non-starch polysaccharides (NSP) was reported to reduce nutrient utilisation, and adversely impact the broilers' growth performance; accordingly, NSP-degrading enzymes are essential supplements to cereal-based diets. Therefore, the current trial was conducted to characterise the impacts of supplemental xylanase (Xyl) to diets with low-ME levels on performance, carcass traits, blood parameters, nutrient digestibility and some genes expressions in broiler chickens. A total of 600 1-day-old Ross 308 male broiler chicks were randomly assigned to 6 treatments with 10 replications of 10 birds each per group in a completely randomised design. The 6 treatments were as follow: (1) basal diets with balanced ME content served as control (positive control, PC), (2) low-energy diet (negative control 1 [NC1]; ME content reduced by 70 kcal/kg compared with PC), (3) low-energy diet (negative control 2 [NC2]; ME content reduced by 140 kcal/kg compared with PC), (4) NC1 + 100 g/ton xylanase (NC1 + 100Xyl), (5) NC2 + 100 g/ton xylanase (NC2 + 100Xyl), and (6) NC1 + 50 g/ton xylanase (NC1 + 50Xyl). At the end of the experiment (35 days of age), the reduction of energy in the NC diets yielded lower live body weight (BW) and total body weight gain (BWG) (p ˂ 0.001); however, it significantly increased feed intake (p ˂ 0.05), leading to worst feed conversion ratio (FCR) and European production efficiency factor (EPEF) (p ˂ 0.01) than PC. There was non-significant variation in final BW, BWG, FCR, or EPEF between the PC group and the NC groups supplemented with Xyl. Carcass yield, gizzard, liver and, muscle relative weights were not influenced by dietary treatments; while broilers fed diet with low-energy diets with or without Xyl addition had lower abdominal fat (p ˂ 0.01) than PC. Furthermore, broilers fed on low-ME diets supplemented with Xyl showed a reduction in plasma total cholesterol (p ˂ 0.05) and low density lipoprotein (p ˂ 0.01) levels. Greater antibody titre against Newcastle disease (p ˂ 0.05) was recorded in the NC1 + 100Xyl and NC2 + 100Xyl groups. The addition of Xyl to low-energy diets significantly improved (p ˂ 0.05) fibre digestibility compared to the PC group. Moreover, enzyme supplementation increased muscle total lipids content and decreased muscle thiobarbituric acid retroactive substance content. In addition, enzyme supplementation increased gene expression related to growth and gene expression related to fatty acid synthesis. It was concluded that a low-ME diet might diminish broiler performance, whereas Xyl supplementation to low-ME diets beneficially affected growth performance, abdominal fat percentage, nutrient digestibility and immunity for broilers, and gene expressions related to growth and fatty acid synthesis in broiler chickens fed low-energy diets.

Zinc Oxide Nanoparticles Promise Anticancer and Antibacterial Activity in Ovarian Cancer.

BACKGROUND: Ovarian cancer is the most lethal cancer in gynaecology. Surgery, chemotherapy, and radiotherapy are the most often used cancer-fighting strategies. Post-surgery infection is fairly prevalent, especially among people with insufficient immunity. Zinc oxide nanoparticles (ZnOnps) have amazing biomedical features as anticancer and antibacterial agents. METHODS: We investigated the behaviour of ZnOnps synthesized by green methods on ovarian cancers using established human ovarian cancer cell lines, besides the antibacterial action toward models of gram + ve and gram -ve bacteria. The cytotoxic effect of ZnOnps was calculated using a Sulforhodamine B (SRB) trial. Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) were tested as models for gram + ve and gram -ve bacteria. The selected bacteria were subjected to concentrations of 20, 40, 80, and 100 µg/ml. RESULTS: The synthesized ZnOnps induced 50% inhibitory concentration (IC50) at a concentration of 27.45 µg/ml. The diameter of inhibition ranged between 20.16 ± 0.16 and 27 ± 0.57 mm for S. aureus and 25.66 ± 0.33 to 31 ± 0.33 mm for E. coli. ZnOnps antagonistic effect statistically differed with neomycin, cefaclor, and cefadroxil. CONCLUSIONS: Green synthesis of ZnOnps is easily prepared, low cost, non-toxic, and eco-friendly. Their cytotoxic action on SKOV3 cells and their antibacterial characteristics pave the way to be an alternative therapy for ovarian cancer and S. aureus and E. coli infection.

Microencapsulation of Bifidobacterium bifidum F-35 via modulation of emulsifying technique and its mechanical effects on the rheological stability of set-yogurt.

Microencapsulation of B. bifidum F-35 was carried out through emulsification technique in order to increase the microbial load while maintaining the rheological functions of set-yogurt. To produce single-layer (SL) microcapsules of whey protein, the pH was adjusted to 6.4 within Transglutaminase-induced gelation. Sodium alginate was processed as the external layer using calcium-induced gelation (pH 5.5) to produce the double-layer (DL) microcapsule. Scanning electron microscopy revealed that SL and DL microcapsules had sizes of 10 and 280 µm, respectively. The highest microbial load was clearly visible in the DL sample. According to texture profile analysis, the DL sample had the highest levels of gumminess, chewiness, and adhesiveness. The free sample outperformed the encapsulated samples in terms of springiness and cohesiveness. Although the SL sample had the highest viscosity, it produced a deformed gel when firmness was measured. In terms of firmness, the DL sample performed quite well. The viability of encapsulated B. bifidum F-35 in DL was higher than SL microcapsules during storage. Microencapsulation of B. bifidum F-35 with whey protein and sodium alginate is a promising technique that could improve the rheological properties of set-yogurt as a popular vehicle for bioactive ingredients.

Post-burn scar malignancy: 5-year management review and experience.

The study spotlights a severe uncommon post-burn complication, Marjolin's ulcer, in upper Egypt plastic and wound care centres. This problem is mainly related to inadequate medical care and awareness. No community or race is immune. The underlying malignant transformation mechanism remains unclear. The study aims, according to our experience, to review the prognostic factors through the management protocol of Marjolin's ulcers. This prospective study was conducted in the Aswan University Plastic & Burn surgery department in South Egypt between 2013 and 2020 and investigated 226 patients with chronic post-burn ulceration. Nineteen cases were proved to have Marjolin's ulcer, and the other cases that had been excluded from being malignant went for reconstruction with split-thickness skin graft with/without flap after adequate ulcer debridement. The surgical, oncologic, radiologic indications, and prognostic factors were reviewed according to our management outcome-the assessment with follow-up period extended over 5 years. Histopathology of ulcers ranged among mild, moderate, and poorly differentiated squamous cell carcinoma. One scalp ulcer case showed basosquamous pathology. Most cases presented at age above 50, but no age was immune. The mean latent period was 29 years on average. The lesions' sites varied in their anatomic location where they involved the upper extremity, the scalp, and the lower extremity that had a predilection. Although surgical excision is the primary management line for tumour ablation, other factors may change the management course. During the follow-up period, neoplasm recurrence in the form of lymph node enlargement and/or locoregional metastasis was detected in eight cases. Within 1 year after the intervention, six recurrent cases died, and two were saved. In addition to the case study, this paper reviewed the literature and provided our team a good experience in light of the NCCN protocol for non-melanotic cutaneous carcinoma, although we suffered limited medical resources. It is concluded that early accurate diagnosis, low-grade malignancy, and well-planned individualised surgery with adjuvant radiotherapy were the best prognostic factors. The close follow-up for an early sign of disease recurrence is paramount.

Clinical and pathological patterns of non-epithelial malignant ovarian tumours in Western Saudi Arabia.

Objective: To report a single-center experience in non-epithelial malignant ovarian tumours (NEMOT), by presenting different clinical and pathological characteristics, management and outcomes. Methods: We retrospectively reviewed electronic files of all female patients who underwent surgery for NEMOT at the Gynecology Department of King Abdulaziz University Hospital, Jeddah, Saudi Arabia, from July 2003 to July 2019. We collected baseline demographic, anthropomorphic and clinical data; pathological characteristics; management and follow-up data; and outcomes including residual disease, recurrence and last follow-up status (deceased or alive). Results: Thirty-three women were included; mean (standard deviation) age = 33.24 (17.72) years, range = 4, 86 years. Granulosa cell tumor was the most frequent subtype diagnosed in 17 (51.5%) patients, followed by germ cell tumours 13 (39.4%). The majority of patients were diagnosed at FIGO Stage I (22, 66.7%) and with tumor Grade 1 (23, 69.7%), while 8 (24.2%) were diagnosed with Grade 3 tumors. Granulosa cell and Sertoli-Leydig cell tumours were diagnosed at an older age (mean age = 39.30 vs. 23.92 years) compared to germ cell tumours, respectively (P = 0.012). Two-third of the patients benefited from conservative surgery including oophorectomy + staging, and 16 (48.5%) benefited from chemotherapy with bleomycin, etoposide and platinum being the most common protocol (13, 39.4%) for germ cell tumours. Postoperatively, only 2 (6.1%) patients had residual disease. Recurrence and mortality were reported in one and four patients, respectively, resulting in recurrence rate = 3.0% (95% confidence interval [CI] = 0.01%, 15.8%) and mortality rate = 12.1% (95% CI = 3.4%, 28.2%). Conclusions: The present series of NEMOT was predominated by sex cord-stromal cell tumors, which were diagnosed in patients with older age, while germ cell tumours were underrepresented. Although survival rates were comparable to those reported internationally, more consideration should be given to following up patients regarding fertility outcomes to provide a more comprehensive evaluation of treatment success and quality of care.

Stress resistance associated with multi-host transmission and enhanced biofilm formation at 42 °C among hyper-aerotolerant generalist Campylobacter jejuni.

One of the emerging conundrums of Campylobacter food-borne illness is the bacterial ability to survive stressful environmental conditions. We evaluated the heterogeneity among 90 C. jejuni and 21 C. coli isolates from different sources in Egypt with respect to biofilm formation capabilities (under microaerobic and aerobic atmosphere) and resistance to a range of stressors encountered along the food chain (aerobic stress, refrigeration, freeze-thaw, heat, peracetic acid, and osmotic stress). High prevalence (63%) of hyper-aerotolerant (HAT) isolates was observed, exhibiting also a significantly high tolerance to heat, osmotic stress, refrigeration, and freeze-thaw stress, coupled with high biofilm formation ability which was clearly enhanced under aerobic conditions, suggesting a potential link between stress adaptation and biofilm formation. Most HAT multi-stress resistant and strong biofilm producing C. jejuni isolates belonged to host generalist clonal complexes (ST-21, ST-45, ST-48 and ST-206). These findings highlight the potential role of oxidative stress response systems in providing cross-protection (resistance to other multiple stress conditions) and enhancing biofilm formation in Campylobacter and suggest that selective pressures encountered in hostile environments have shaped the epidemiology of C. jejuni in Egypt by selecting the transmission of highly adapted isolates, thus promoting the colonization of multiple host species by important disease-causing lineages.

Microbes on the Mobile Phones of Healthcare Workers in Palestine: Identification, Characterization, and Comparison.

BACKGROUND: Healthcare workers (HCWs) may be using their mobile phones (MPs) to carry microbes that cause hospital-acquired and community infections in general. With antibiotic resistance problem emergence, these infections can be challenging to eradicate. Hence, this study aimed to determine the microbial contamination of HCW MPs and identify and classify bacterial isolates in Palestine. METHODS: This was a 7-month comparative cross-sectional analysis of 200 HCW MPs from 2 hospitals and 100 MPs from university students (non-HCWs). Data collection was done using a self-administrated questionnaire, and a swab sample from both HCW and non-HCW MPs was obtained and transferred to An-Najah National University (NNU) microbiology lab for bacterial identification and antibiotic susceptibility. Data were analyzed using Social Sciences Statistical Package (SPSS) version 22.0. RESULT: Among HCWs, the microbial contamination was 87.5%. Coagulase-negative staphylococci (CoNS; 67.3%), methicillin-sensitive Staphylococcus aureus (MSSA; 17.5%), Gram-positive bacilli (4.1%), methicillin-resistant Staphylococcus aureus (MRSA; 1.6%), and Gram-negative species (1.6%) were the most predominant bacterial isolates. More than half of staphylococci isolates were resistant to penicillin and erythromycin. Male gender, using a mobile phone in the bathroom, and entry to the operating theatre were associated with mobile phone contamination and increased resistance against specific antibiotics. Among non-HCWs, the contamination was 86%. The most predominant bacterial isolates were CoNS, MSSA, and Gram-positive bacilli, with a contamination of 66.8%, 28.5%, and 2.6%, respectively. No MRSA or Gram-negative species were detected in this group. Antibiotic resistance percentage of staphylococci was nearly half of that yielded in the HCW group against each antibiotic. CONCLUSION: Significant numbers of bacteria have been isolated from HCW MPs. Working in a hospital environment frequently raises the probability of presence of antibiotic-resistant bacteria on a MP. Therefore, infection control teams should discuss methods to prevent the transmission of drug-resistant pathogens from HCW MPs.

Methanolic extract of Chlorella vulgaris protects against sodium nitrite-induced reproductive toxicity in male rats.

The current study aimed to investigate the protective potential of Chlorella Vulgaris (CV) extract against the reproductive dysfunction induced by sodium nitrite toxicity. Forty-five male Wistar albino rats were assigned into five groups (n = 9). Control group received normal saline orally for 3 months, CV-treated: administered CV extract (70 mg/kg.BW) orally for 3 months, sodium nitrite-treated: received sodium nitrite (80 mg/kg.BW) orally for 3 months, co-treated: simultaneously received CV along with sodium nitrite treatment, orally, daily for 3 months, and CV-pre-treated: pre-treated with CV extract for 4 weeks followed by simultaneous treatment with sodium nitrite and CV extract for additional 8 weeks. Treatment with sodium nitrite significantly decreased serum testosterone and follicle-stimulating hormone concentrations, sperm count, motility, and viability. Besides, it decreased testicular superoxide dismutase and glutathione peroxidase activities while increased malondialdehyde concentration. This effect of sodium nitrite was associated with degenerative, necrotic, vascular, and inflammatory changes in testicular tissues. Treatment of sodium nitrite-intoxicated rats with CV in co-treated and pre-treated groups significantly prevented sodium nitrite-induced alterations of sperm parameters, hormonal concentrations, testicular oxidative-antioxidant status, and histological architecture. This study indicates that CV extract ameliorates the reproductive dysfunction induced by sodium nitrite toxicity via improving reproductive hormonal levels and testicular antioxidant activities.

Presumed tuberculous uveitis in a university-based tertiary referral center in Saudi Arabia.

PURPOSE: To describe clinical characteristics and outcomes of treatment in patients with presumed tuberculous uveitis (PTU). METHODS: All patients diagnosed with PTU between January 1996 and March 2013 were reviewed. The diagnosis was made when clinical findings were consistent with possible intraocular tuberculosis, strongly positive purified protein derivative (PPD) skin test result, and response to anti-tuberculous therapy with no other cause of uveitis as suggested by history, symptoms, or ancillary testing. RESULTS: Ninety patients (141 eyes) were identified. There were 43 males (47.3%) and 47 females (52.7%). Mean age was 48.2 ± 14.4 years. Mean duration of symptoms prior to presentation was 6.7 ± 8.3 months. Ten eyes (7.1%) had anterior uveitis, 18 eyes (12.8%) had intermediate uveitis, 34 eyes (24.1%) had posterior uveitis, and 79 eyes (56%) had panuveitis. Macular edema was present in 33.3% of the eyes at presentation. All patients received anti-tuberculous therapy and systemic corticosteroids. Mean follow-up after completion of therapy was 36 ± 2.5 months. Only 2 eyes developed recurrent inflammation after treatment completion. At last follow-up, all eyes showed resolution of inflammation, associated with significant improvement in visual acuity. There was a significant positive correlation between initial and final VA. Eyes that had macular edema at presentation showed a significant reduction in central macular thickness at final follow-up. CONCLUSIONS: There is delay in presentation of patients with PTU. The most common anatomic diagnosis was panuveitis. Treatment with anti-tuberculous therapy combined with systemic corticosteroids resulted in resolution of inflammation and macular edema with significant improvement in visual acuity.

Protective potential of royal jelly against cadmium-induced infertility in male rats.

This study aimed to investigate the protective potential of Royal jelly (RJ) against cadmium (Cd)-induced testicular dysfunction in rats. Thirty-five adult male Wistar rats were assigned into five groups. G I; (control) injected intraperitoneally with saline, G II injected intraperitoneally with a single dose of CdCl2 (1 mg/kg BW), G III received RJ (100 mg/kg BW/day) orally, G IV was pre-treated with RJ for 1 week then, treated with CdCl2 , and G V was co-treated with RJ and CdCl2 . After day 56, serum and tissue samples were collected and analysed. The results showed decreased serum testosterone, luteinising hormone (LH), follicle-stimulating hormone (FSH), superoxide dismutase, glutathione reductase, sperm motility and count while increased malondialdehyde, nitric oxide, tumour necrosis factor-α (TNF-α) and sperm abnormalities, along with a severely damaged seminiferous tubules epithelium with cytoplasmic and nuclear disruptions following Cd toxicity. Additionally, Cd stimulated testicular mRNA expression of TNF-α while inhibited those of steroidogenic acute regulatory protein, cytochrome P450 cholesterol side chain cleavage enzyme androgen binding protein, FSH-receptor, LH-receptor, androgen receptor, 3ß-hydroxysteroid dehydrogenase (HSD), 17ß-HSD, and cytochrome P450 17A1. These negative alterations of cadmium were greatly reduced by RJ treatment. This study concluded that RJ protects against Cd-induced testicular toxicity.

Reliability of sonoelastography in predicting pediatric cervical lymph node malignancy.

PURPOSE: Controversy exists as regards the best non-invasive diagnostic tool for pediatric cervical lymphadenopathy. The current work aimed to evaluate the reliability, sensitivity, specificity, and accuracy of sonoelastography in diagnosing benign and/or malignant pediatric cervical lymphadenopathy. METHODS: Prospective study took place over a period of 4 years from January 2013 to December 2016. A total of 177 lymph nodes (LNs) in 128 children with an age ranging from 11 months to 12 years were recruited in this study. Patients were 77 males and 51 females with a ratio of 3:2. All patients underwent a thorough history taking and clinical examination of the neck focusing on the cervical lymph nodes. After that, a B-mode sonography, Color Doppler ultrasound, and Sonoelastography were performed. Elastographic patterns of 1-5 were evaluated, whereas patterns of 3-5 (firm to hard) were suspected to have a malignant nature. Sonographic-guided aspiration cytology took place in 107 lymph nodes and excisional biopsy in 102 lymph nodes, whereas 13 lymph nodes responded adequately to conservative treatment. They proved to be benign reactive hyperplasia. RESULTS: The majority of LNs (87%) were of the malignant type that showed an elastographic pattern of 3-5. The same patterns were observed in only 6 (3.4%) of the benign LNs. Sonoelastography showed a sensitivity of 85.9%, specificity of 100%, PPV of 100%, NPV of 75.96%, and overall accuracy of 90.23% in distinguishing benign from malignant lymph nodes. Using the B-Mode ultrasound, an abnormal hilum was seen in 75%. The accuracy of color Doppler US reached 82.7%. CONCLUSIONS: Sonoelastography may be superior to other US modalities in elucidating different cervical lymph node biopsy helping to distinguish benign from malignant lesions. This may replace the lymph node biopsies in the future. Moreover, its use in the follow-up of patients with cervical malignancies may reduce the number of future biopsies. Further studies with more patients may be needed for a better assessment of results.

An evidence-based medicine audit of the ophthalmic emergency services unit of King Abdulaziz University Hospital (KAUH).

PURPOSE: To improve the interventions provided for patients presenting with acute ophthalmic conditions to the ophthalmic emergency unit through applying the best available evidences from quality literature for managing such conditions. METHODS: A retrospective cohort study at a tertiary eye care university hospital in Riyadh, Saudi Arabia, involving a two-phase audit of diagnosis-intervention was conducted. The first phase was done retrospectively for the duration from April 1 to May 30, 2014, after disseminating the results of the first phase to King Abdulaziz University Hospital ophthalmology department staff, and the second phase was done retrospectively for the duration from November 1 to December 30, 2015. The validity of outcomes was assessed through a literature search using Medline and the Cochrane Database of Systematic Reviews. The participants were masked on the study objectives to avoid Hawthorne's phenomenon (prescribing bias). RESULTS: In the first part of the audit, 73.2% out of 355 interventions were found to be evidence based. There was notable improvement of 80.9% in the number of evidence-based interventions in the second part of the audit. This improvement was statistically significant (p = 0.017). CONCLUSION: Evidence-based medicine audit can be a helpful tool to assess the performance and can lead to quality improve of the provided care by reducing the number of medical errors and refining medical decisions and interventions.

Association of HMGB1 with oxidative stress markers and regulators in PDR.

Purpose: We investigated the link among the proinflammatory cytokine high-mobility group box 1 (HMGB1) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a marker of oxidative DNA damage, the endothelial adhesion molecule and oxidase enzyme vascular adhesion protein-1 (VAP-1), and the inducible cytoprotective molecule heme oxygenase-1 (HO-1) in proliferative diabetic retinopathy (PDR). We correlated the levels of these molecules with clinical disease activity and studied the proinflammatory activities of HMGB1 on rat retinas and human retinal microvascular endothelial cells (HRMECs). Methods: Vitreous samples from 47 PDR and 19 non-diabetic patients, epiretinal membranes from 11 patients with PDR, human retinas (16 from diabetic patients and 16 from non-diabetic subjects), rat retinas, and HRMECs were studied by enzyme-linked immunosorbent assay, immunohistochemistry, western blot immunofluorescence, and RT-PCR analyses. In addition, we assessed the adherence of leukocytes to HMGB1-stimulated HRMECs. Results: HMGB1, 8-OHdG, and soluble VAP-1 (sVAP-1) levels were significantly higher in vitreous samples from PDR patients than in those from non-diabetics (p = 0.001, <0.0001, <0.0001, respectively). The HMGB1, 8-OHdG, sVAP-1, and HO-1 levels in PDR with active neovascularization were significantly higher than those in inactive PDR (p = 0.025, <0.0001, <0.0001, 0.012, respectively). Significant positive correlations were observed between the levels of HMGB1 and the levels of 8-OHdG (r = 0.422; p = 0.001) and sVAP-1 (r = 0.354; p = 0.004) and between the levels of 8-OHdG and the levels of sVAP-1 (r = 0.598; p<0.0001). In epiretinal membranes, VAP-1 and 8-OHdG were expressed in vascular endothelial cells and stromal cells. Significant increases in the VAP-1 mRNA and protein levels were detected in the RPE, but not in the neuroretina of diabetic patients. Treatment of HRMEC with HMGB1, diabetes induction, and an intravitreal injection of HMGB1 in normal rats induced a significant upregulation of the adhesion molecule intercellular adhesion molecule-1 (ICAM-1) in HRMECs and retinas. On the other hand, the expressions of vascular cell adhesion molecule-1 and VAP-1 were not affected. Oral administration of the HMGB1 inhibitor glycyrrhizin in rats attenuated the diabetes-induced upregulation of the retinal ICAM-1 expression. Treatment of HRMECs with HMGB1 increased leukocyte adhesion and induced the upregulation of 8-OHdG and HO-1 and the membranous translocation of VAP-1. Conclusions: Our results suggest a potential link among the proinflammatory cytokine HMGB1, VAP-1, oxidative stress, and HO-1 in the pathogenesis of PDR.

Macular Atrophy in Neovascular Age-Related Macular Degeneration with Monthly versus Treat-and-Extend Ranibizumab: Findings from the TREX-AMD Trial.

PURPOSE: To compare the enlargement rate of macular atrophy (ERMA) in eyes treated with ranibizumab monthly or using a treat-and-extend (TREX) regimen for neovascular age-related macular degeneration (AMD) or fellow control eyes, as well as analyze risk factors for macular atrophy (MA) development and progression. DESIGN: Eighteen-month, multicenter, randomized, controlled clinical trial. PARTICIPANTS: Sixty patients with treatment-naïve neovascular AMD in 1 eye randomized 1:2 to monthly or TREX ranibizumab. METHODS: Patients' study and fellow eyes were followed for 18 months using spectral-domain optical coherence tomography (SD OCT) and fundus autofluorescence (FAF) imaging. The MA was quantified on FAF images using Heidelberg Region Finder software (Heidelberg Engineering, Heidelberg, Germany), with suspected areas of atrophy confirmed by SD OCT and infrared reflectance imaging. For eyes without baseline MA yet developed MA by 18 months, intervening visits were assessed to determine the first visit at which MA appeared to define progression rates. Foveal choroidal thickness (FCT), subretinal hyperreflective material (SHRM), and pigment epithelial detachment (PED), were assessed at baseline to determine whether they influenced MA progression. MAIN OUTCOME MEASURES: Mean ERMA at 18 months. Relationship between visual acuity and MA, and the baseline risk factors for ERMA were also assessed. RESULTS: The final analysis cohort included 88 eyes in 3 groups: monthly (n = 19), TREX (n = 30), and control fellow eyes (n = 39). Mean ERMA over 18 months was 0.39±0.67 (monthly), 1.1±1.9 (TREX), and 0.49±1 mm2 (control, P = 0.12). Mean ERMA per group among the 40.9% (n = 36) of baseline patients with MA was 0.9±1, 1.9±2.2, and 1±1.3 mm2, respectively (P = 0.31). The incidence rate of MA in the 3 groups was 40%, 0%, and 8.3%, respectively. Mann-Whitney U test revealed a statistically significant association between baseline FCT (127±46 vs. 155±55 µm, P = 0.01) and SHRM thickness (106±131 vs. 50±85 µm, P = 0.02) on MA. In eyes with no baseline MA, presence of SHRM, SHRM, and PED thickness, and presence of baseline hemorrhage were all significant predictors of new MA development (P = 0.04, 0.01, 0.04, 0.004, 0.01, respectively). CONCLUSIONS: Ranibizumab did not show a statistically significant influence on new MA development in eyes with neovascular AMD, whether dosed monthly or per TREX regimen. The FCT, SHRM thickness, and hemorrhage at baseline were all significant predictors of new MA.

Effects of dihydroorotate dehydrogenase (DHODH) inhibitors on the growth of Theileria equi and Babesia caballi in vitro.

Theileria equi and Babesia caballi are the causative agents of equine piroplasmosis (EP), which affects equine production in various parts of the world. However, a safe and effective drug is not currently available for treatment of EP. Dihydroorotate dehydrogenase (DHODH) is the fourth enzyme in the de novo pyrimidine synthesis pathway and has been known as a novel drug target for several apicomplexan protozoan parasites. In this study, we evaluated four DHODH inhibitors; atovaquone (ATV), leflunomide (LFN), brequinar (Breq), and 7-hydroxy-5-[1,2,4] triazolo [1,5,a] pyrimidine (TAZ) on the growth of T. equi and B. caballi in vitro and compared them to diminacene aceturate (Di) as the control drug. The growth of T. equi and B. caballi was significantly hindered by all inhibitors except TAZ. The half maximal inhibitory concentration (IC50) of ATV, LFN, Breq and Di against T. equi was approximately 0.028, 109, 11 and 40 µM, respectively, whereas the IC50 of ATV, LFN, Breq and Di against B. caballi was approximately 0.128, 193, 5.2 and 16.2 µM, respectively. Using bioinformatics and Western blot analysis, we showed that TeDHODH was similar to other Babesia parasite DHODHs, and confirmed that targeting DHODHs could be useful for the development of novel chemotherapeutics for treatment of EP.

Toxicokinetics and toxicodynamics of chlorpyrifos is altered in embryos of Japanese medaka exposed to oil sands process-affected water: evidence for inhibition of P-glycoprotein.

Oil sands process-affected water (OSPW) is generated during extraction of bitumen in the surface mining oil sands industry in Alberta, Canada. Studies were performed in vitro by use of Caco-2 cells, and in vivo with larvae of Japanese medaka (Oryzias latipes) to determine if organic compounds from the aqueous phase of OSPW inhibit ATP binding cassette protein ABCB1 (permeability-glycoprotein, P-gp). Neutral and basic fractions of OSPW inhibited activity of P-gp in Caco-2 cells by 1.9- and 2.0-fold, respectively, while the acidic fraction had the least effect. The organophosphate pesticides chlorpyrifos (a substrate of P-gp) and malathion (not a substrate of P-gp), were used as model chemicals to investigate inhibition of P-gp in larvae. Co-exposure to chlorpyrifos and an extract of OSPW containing basic and neutral compounds reduced survival of larvae to 26.5% compared to survival of larvae exposed only to chlorpyrifos, which was 93.7%. However, co-exposure to malathion and the extract of OSPW did not cause acute lethality compared to exposure only to malathion. Accumulation and bioconcentration of chlorpyrifos, but not malathion, was greater in larvae co-exposed with the extract of OSPW. The terminal elimination half-life of chlorpyrifos in larvae exposed to chlorpyrifos in freshwater was 5 days compared with 11.3 days in larvae exposed to chlorpyrifos in OSPW. Results suggest that in non-acute exposures, basic and neutral organic compounds in the water-soluble fraction of OSPW inhibit activity of P-gp, which suggests that OSPW has the potential to cause adverse effects by chemosensitization. Copyright © 2016 John Wiley & Sons, Ltd.

Coexpression of heparanase activity, cathepsin L, tissue factor, tissue factor pathway inhibitor, and MMP-9 in proliferative diabetic retinopathy.

PURPOSE: Heparanase cleaves heparan sulfate side chains of heparan sulfate proteoglycans, activity that is implicated in angiogenesis. Proteolytic cleavage of proheparanase by cathepsin L leads to the formation of catalytically active heparanase. We investigated the expression levels of heparanase enzymatic activity and correlated these with the levels of cathepsin L, the angiogenic factors tissue factor (TF) and matrix metalloproteinase-9 (MMP-9), and the angiostatic factor tissue factor pathway inhibitor (TFPI) in proliferative diabetic retinopathy (PDR). METHODS: Vitreous samples from 25 patients with PDR and 20 nondiabetic patients and epiretinal membranes from 12 patients with PDR were studied with enzyme-linked immunosorbent assay, western blot analysis, and immunohistochemistry. RESULTS: We observed a significant increase in the expression of heparanase activity in vitreous samples from patients with PDR compared to the nondiabetic controls (p=0.027). Significant positive correlations were found between the levels of heparanase activity and the levels of cathepsin L (r=0.51; p=0.001), TF (r=0.6; p<0.0001), and TFPI (r=0.49; p=0.001). The expression levels of cathepsin L (p=0.019), TF (p<0.0001), TFPI (p<0.0001), and MMP-9 (p=0.029) were significantly higher in the vitreous samples with detected heparanase activity compared to the vitreous samples with undetected heparanase activity. Western blot analysis demonstrated proteolytic cleavage of TFPI in the vitreous samples from patients with PDR. In the epiretinal membranes, cathepsin L, TF, and TFPI were expressed in vascular endothelial cells and CD45-expressing leukocytes. Significant positive correlations were detected between the number of blood vessels that expressed CD31 and the number of blood vessels that expressed TF (r=0.9; p<0.0001) and TFPI (r=0.81; p=0.001). CONCLUSIONS: The coexpression of these angiogenesis regulatory factors suggests cross-talk between these factors and pathogenesis of PDR angiogenesis.

Polymorphism rs7555523 in transmembrane and coiled-coil domain 1 (TMCO1) is not a risk factor for primary open angle glaucoma in a Saudi cohort.

BACKGROUND: We investigated whether polymorphism rs7555523 (A > C) in human transmembrane and coiled-coil domain 1 (TMCO1) gene is a risk factor for primary open angle glaucoma (POAG) in a Saudi cohort. METHODS: A cohort of 87 unrelated POAG cases and 94 control subjects from Saudi Arabia were genotyped using Taq-Man® assay. The association of genotypes with POAG and other glaucoma specific clinical indices was investigated. RESULTS: The genotype and allele frequency of polymorphism rs7555523 at TMCO1 did not show any statistically significant association with POAG as compared to controls. The minor allele frequency was 0.103 in cases and 0.085 in controls. Except for awareness of glaucoma (p = 0.036), no significant association of genotypes were seen with glaucoma specific clinical indices such as intraocular pressure (IOP), cup/disc ratio and number of anti-glaucoma medications used. Binary logistic regression analysis (adjusted for age and gender) showed that age was a significant indicator for the development of glaucoma in this group (adjusted odds ratio = 1.2; 95 % confidence interval = 1.078-1.157; p < 0.001). CONCLUSION: Our study was unable to replicate the findings of previously reported association for polymorphism rs7555523 in TMCO1 with POAG and related clinical indices such as IOP and cup/disc ratio indicating that this variant is not a risk factor for POAG in the Saudi cohort.

Microencapsulation of Oils: A Comprehensive Review of Benefits, Techniques, and Applications.

Microencapsulation is a process of building a functional barrier between the core and wall material to avoid chemical and physical reactions and to maintain the biological, functional, and physicochemical properties of core materials. Microencapsulation of marine, vegetable, and essential oils has been conducted and commercialized by employing different methods including emulsification, spray-drying, coaxial electrospray system, freeze-drying, coacervation, in situ polymerization, melt-extrusion, supercritical fluid technology, and fluidized-bed-coating. Spray-drying and coacervation are the most commonly used techniques for the microencapsulation of oils. The choice of an appropriate microencapsulation technique and wall material depends upon the end use of the product and the processing conditions involved. Microencapsulation has the ability to enhance the oxidative stability, thermostability, shelf-life, and biological activity of oils. In addition, it can also be helpful in controlling the volatility and release properties of essential oils. Microencapsulated marine, vegetable, and essential oils have found broad applications in various fields. This review describes the recognized benefits and functional properties of various oils, microencapsulation techniques, and application of encapsulated oils in various food, pharmaceutical, and even textile products. Moreover, this review may provide information to researchers working in the field of food, pharmacy, agronomy, engineering, and nutrition who are interested in microencapsulation of oils.