The suppression of MAPK/NOX/MMP signaling prompts renoprotection conferred by prenatal naproxen in weaning preeclamptic rats.

Although nonsteroidal antiinflammatory drugs (NSAIDs) are frequently used for fever and pain during pregnancy, their possible interaction with perinatal renal injury induced by preeclampsia (PE) has not been addressed. Here, studies were undertaken in the N(gamma)-nitro-L-arginine methyl ester (L-NAME) PE model to assess the influence of gestational NSAIDs on renal damage in weaning dams. PE-evoked increments and decrements in urine protein and creatinine clearance, respectively, were intensified by celecoxib and weakened by diclofenac or naproxen. Naproxen also improved renal cloudy swelling, necrosis, and reduced glomerular area evoked by PE. The concomitant rises in renal expression of markers of oxidative stress (NOX2/4), extracellular matrix metaloproteinase deposition (MMP9), and prostanoids (PGE2, PGF2α, TXA2) were all more effectively reduced by naproxen compared with celecoxib or diclofenac. Western blotting showed tripled expression of mitogen-activated protein kinases (MAPKs; p-p38, p-JNK1, p-ERK1, p-ERK2) in PE kidneys that was overturned by all NSAIDs, with naproxen producing the largest drop in p-ERK2 expression. The PE-provoked elevation in renal expression of autophagic marker LC3 was reduced by naproxen and diclofenac, but not celecoxib. The data suggests superior effect for naproxen over other NSAIDs in rectifying preeclamptic renal injury and predisposing inflammatory, oxidative, autophagic, and fibrotic signals.

Gestational NSAIDs distinctly reprogram cardiac injury in preeclamptic rats: Roles of cyclooxygenase, apoptotic and autophagic trails.

AIMS: Considering the role of cyclooxygenases (COX) in placental programming induced by preeclampsia (PE), we investigated whether gestational exposure to nonsteroidal antiinflammatory drugs (NSAIDs) with different COX-1/2 selectivity would variably modulate pre- and postnatal (weaning time, i.e. 3 weeks after delivery) cardiovascular manifestations of PE. MATERIALS AND METHODS: PE was induced by oral administration of Nω-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg/day for 7 days) to pregnant rats starting from day 14 of gestation. Rats were treated simultaneously with celecoxib (10 mg/kg/day), diclofenac (0.5 mg/kg/day), or naproxen (1 mg/kg/day). KEY FINDINGS: Tail-cuff measurements revealed a higher systolic blood pressure (SBP) in PE mothers at gestational day 20 (GD20). More exaggerated rises in prenatal SBP were noted in PE rats treated with celecoxib but not diclofenac or naproxen. Higher levels of serum creatine and kinase MB (CK-MB), a biomarker of cardiac damage, were demonstrated in weaning PE rats and this effect was suppressed by naproxen only. Additionally, naproxen was the most effective among all 3 NSAIDs in diminishing the PE-induced surges in (i) cardiomyocyte cross-sectional area, (ii) cardiac COX-1/COX-2 activities, (iii) arachidonate metabolites (PGE2, PGF2α, and TXA2), (iv) caspase-3 and beclin-1 expressions. By contrast, the PE-related increments in cardiac expression of antiangiogenic (sFlt-1, and endoglin-1) and inflammatory (nuclear factor kappa B, NF-κB) factors were indiscriminately reduced by all NSAIDs. SIGNIFICANCE: Compared with celecoxib or diclofenac, naproxen appears to be the most advantageous in minimizing cardiac damage in weaning PE rats due to its synchronized downregulatory effects on cyclooxygenase, apoptotic, and autophagic pathways.

Metformin and omega-3 fish oil elicit anti-inflammatory effects via modulation of some dysregulated micro RNAs expression and signaling pathways in experimental induced arthritis.

OBJECTIVE: Rheumatoid arthritis is a progressive inflammatory disease with multiple dysfunctional intracellular signaling pathways that necessitate new approaches for its management. Hence, the study aimed to inspect the ability of the combination therapy of metformin and omega-3 to modulate different signaling pathways and micro RNAs such as (miR-155, miR-146a and miR-34) as new targets in order to mitigate adjuvant-induced arthritis and compare their effect to that of methotrexate. METHODS: Fourteen days post adjuvant injection, Sprague-Dawley rats were treated orally with metformin (200 mg/kg/day) and/or omega-3 (300 mg/kg/day) or intraperitoneally with methotrexate (2 mg/kg/week) for 4 weeks. RESULTS AND CONCLUSION: All drug treatments amended the arthrogram score and hind paw swelling as well as decreased serum tumor necrosis factor (TNF)-α and interleukin (IL)-1ß levels. On the molecular level, all therapies activated phospho-5'adenosine monophosphate-activated protein kinase (p-AMPK) and protein phosphatase 2A (PP2A), while they inhibited phospho-mammalian target of rapamycin (p-mTOR), phospho-signal transducers and activators of transcription (p-STAT3), nuclear factor (NF)-κB p65 subunit, phosho38 mitogen-activated protein kinase (p38 MAPK) and phospho- c-Jun N-terminal kinase (p-JNK). In addition, they decreased the elevated expression level of miRNA-155, 146a and increased the expression level of miRNA-34 and they decreased the expression level of retinoic acid receptor related orphan receptor γT (RORγT) and increased that of fork head box P3 (FOXP3), correcting Th17/Treg cells balance. On most of the aforementioned parameters, the effect of the combination therapy was comparable to that of methotrexate, emphasizing that this combination possesses better additive anti-inflammatory effect than either drug when used alone. In addition, the combination was capable of normalizing the serum transaminases levels as compared to untreated group offering hepatoprotective effect and suggesting the possibility of its use as a replacement therapeutic strategy for MTX in rheumatoid arthritis.

Ocular manifestations of dermatological diseases part II: genodermatoses.

Skin and eyes share a common embryological origin from the embryonic surface ectoderm. Ocular manifestations in dermatological diseases are common and have diagnostic value. At present, there are a limited number of comprehensive reviews emphasizing the ocular manifestations of dermatological diseases. More than 40 published articles about ocular findings in dermatology were reviewed. The search included Pubmed, Google Scholar, and Cochrane databases from 2014 to 2019. This review was divided into three parts including: I. infectious and inflammatory disorders; II. genodermatoses; III. connective tissue, autoimmune, neoplasms, and drug-related disorders. We excluded metabolic, endocrine, and nutrition-related dermatological diseases. In this part, we summarized the most common and important ocular findings in dermatology-related genetic disorders with appropriate referral recommendations to ophthalmology.

Ocular manifestations of dermatological diseases part I: infectious and inflammatory disorders.

Skin and eyes share a common embryological origin from the embryonic surface ectoderm. Ocular manifestations are one of the most important and common associations of dermatological diseases. Currently, there are few comprehensive reviews of the ocular manifestations of dermatological diseases. We have reviewed more than 40 published articles related to the ocular manifestations of the most important dermatological diseases. The search included Pubmed, Google Scholar, and Cochrane databases from 2014 to 2019. This review was divided into three parts including infections, inflammatory, genetics, connective tissue, autoimmune, neoplasms, and drug-related disorders. We excluded metabolic, endocrine, and nutrition-related dermatological diseases. The relationship of ocular manifestations and dermatological diseases is important to recognize for appropriate management since many dermatological diseases can manifest initially with ocular findings. In this part, we summarized the most common and significant ocular findings in infectious and inflammatory dermatological disorders with appropriate referral recommendations to ophthalmology.

Combined effects of soft drinks and nicotine on Streptococcus mutans metabolic activity and biofilm formation.

The purpose of this study was to explore the effects of nicotine on the activity of Streptococcus mutans (S. mutans) in soft drinks. Regular soft drinks contain large proportions of high-fructose corn syrup (HFCS), which increases the activity of S. mutans resulting in high-caries risk compared with sugar-free soft drinks. Nicotine use exhibits a strong correlation with increased S. mutans biofilm formation. The soft drinks chosen were (Coca-Cola Classic, Diet Coke, Coca-Cola Zero Sugar, Caffeine-Free Coca-Cola, Caffeine-Free Diet Coke, Caffeine-Free Coca-Cola Zero Sugar). S. mutans was grown overnight in tryptic soy broth; nicotine was diluted in tryptic soy broth supplemented with 1.0% sucrose followed by soft drinks in dilution of 1:3. Total growth absorbance and biofilm growth were determined by spectrophotometry, absorbance measured to determine biofilm formation, and metabolic activity quantified. One-way ANOVA showed a considerable effect for HFCS and caffeine in the presence of nicotine and their interaction in all measures. Results showed sugar-free caffeinated colas demonstrated significant effect in inhibiting S. mutans biofilm formation and metabolic activity with nicotine. Nicotine-induced S. mutans increased biofilm formation and metabolic activity in the presence of HFCS and caffeine in soft drinks. In conclusion, smokers should consider sugar-free caffeinated versions to minimize the chance of developing dental caries dut to the reduction of biofilm formation.

The effects of charcoal dentifrices on Streptococcus mutans biofilm development and enamel demineralization.

PURPOSE: To evaluate the in vitro effects of commercially available charcoal dentifrices on Streptococcus mutans biofilm development and their ability to prevent enamel demineralization. METHODS: Streptococcus mutans biofilm was formed on polished bovine enamel specimens (n= 9 per treatment), and treated twice-daily for 120 seconds over the course of 5 days with: charcoal dentifrice containing fluoride (1,000 ppm F) (CF+), fluoride-free charcoal dentifrice (CF-), regular fluoride (1,100 ppm F) dentifrice (F+ ), or regular fluoride-free dentifrice (F-). Chlorhexidine (CHX, 0.12%) and deionized water (DIW) were used as positive and negative controls, respectively. Biofilms were analyzed for bacterial viability (colony-forming units, CFU). The pH of the medium was measured daily. Enamel specimens were analyzed using Vickers microhardness ( HV) and transversal microradiography (TMR). Data were analyzed using one-way ANOVA followed by post-hoc tests (α= 0.05). RESULTS: F+ showed higher pH values than CF+ and CF-, and CF- presented higher pH than CF+, showing that CF+ did not have inhibitory effects on the acidogenicity of cariogenic biofilms. CFU was significantly decreased when specimens were treated with CF+, CF- and F+, compared to specimens treated with DIW (P≤ 0.035) or F- (P≤ 0.001), respectively. However, the reduction observed was minimal (approximately 1 log). CF+ and CF- were less effective than F+ in preventing enamel demineralization as determined using HV (P= 0.041 and P= 0.003, respectively) and TMR ( P≤ 0.001). Both charcoal dentifrices (CF+, CF-) did not show relevant inhibition of S. mutans biofilm growth. Additionally, neither product prevented enamel demineralization compared to a regular fluoride-containing dentifrice. CLINICAL SIGNIFICANCE: The tested charcoal dentifrices did not exhibit anticaries potential.

Evaluation of chamomile oil and nanoemulgels as a promising treatment option for atopic dermatitis induced in rats.

Background: Atopic dermatitis is a chronic inflammatory skin disease that remarkably affects the quality-of-life of patients. Chamomile oil is used to treat skin inflammations. We evaluated the efficacy of chamomile oil and nanoemulgel formulations as a natural alternative therapeutic option for atopic dermatitis.Research design and methods: Formulations were developed comprising chamomile oil: olive oil (1:1), Tween 20/80 or Gelucire 44/14 as surfactant-cosurfactant mixtures, propylene glycol (10%w/w), water and hydroxypropyl methylcellulose (3%w/w). In-vitro physicochemical characterization, stability testing and in-vivo assessment of inflammatory biomarkers and histopathological examination of skin lesions were conducted in rats induced with atopic dermatitis.Results: Nanoemulgels G1 and X1 which displayed the smallest particle size of 137.5 ± 2.04 and 207.1 ± 5.44 nm, good homogeneity and high zeta-potential values of -26.4 and -32.7 mV were selected as the optimized emulgel. Nanoemulgels were nonirritating of pH value 5.56, readily spreadable, and were physically stable following 10 heating-cooling cycles. Treatment with nanoemulgels showed a two-fold decrease in duration of skin healing and no spongiosis compared to chamomile oil. Levels of biomarkers were reduced after topical application of both nanoemulgels and chamomile oil.Conclusion: Nanoemulgels are a potential cost effective, safe topical carrier system for chamomile in treating atopic dermatitis.

Structured crowdsourcing enables convolutional segmentation of histology images.

MOTIVATION: While deep-learning algorithms have demonstrated outstanding performance in semantic image segmentation tasks, large annotation datasets are needed to create accurate models. Annotation of histology images is challenging due to the effort and experience required to carefully delineate tissue structures, and difficulties related to sharing and markup of whole-slide images. RESULTS: We recruited 25 participants, ranging in experience from senior pathologists to medical students, to delineate tissue regions in 151 breast cancer slides using the Digital Slide Archive. Inter-participant discordance was systematically evaluated, revealing low discordance for tumor and stroma, and higher discordance for more subjectively defined or rare tissue classes. Feedback provided by senior participants enabled the generation and curation of 20 000+ annotated tissue regions. Fully convolutional networks trained using these annotations were highly accurate (mean AUC=0.945), and the scale of annotation data provided notable improvements in image classification accuracy. AVAILABILITY AND IMPLEMENTATION: Dataset is freely available at: https://goo.gl/cNM4EL. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Surgical management of eumycetoma: experience from Gezira Mycetoma Center, Sudan.

BACKGROUND: In this study, we share our experience of different operative techniques undertaken on 584 eumycetoma patients in the Gezira Mycetoma Center. METHODS: This is a retrospective, descriptive, hospital-based study, conducted to review the surgical treatment of eumycetoma patients. We included all patients diagnosed with eumycetoma who underwent a surgical operation in the center during January 2013-December 2016. RESULTS: A total number of 1654 patients were seen during the study period, and their records were revised, while 584 (35.3%) of them underwent an operation and included in the study. There was a male predominance 446 (76.4%). Surgical excision of mycetoma was the commonest operation performed among 513 (87.8%) patients in comparison with amputation 71 (12.2%). Below-knee amputation and toe amputation are the commonest types of amputation in 36 (6.1%) and 14 (2.3%) patients, respectively. Clinical features determining the type of operation performed included the size of the lesion, whether or not a bone was involved, and the feasibility of primary closure. A wide surgical excision (WSE) is performed mainly when the bone is not involved and when moderate or primary closure is possible or reconstruction is feasible. Amputations will typically follow identifying bone involvement, secondary infection, and an already disabled patient. CONCLUSION: The commonest procedure in our series was WSE and primary skin closure undertaken when the lesion was small (< 5 cm); there was no bone involvement, and the skin closure was achievable. Larger lesions (> 10 cm) without bone involvement were treated with excision and flap/graft. Bone involvement and large primary lesions were more likely to be managed by amputation. Recurrent and relapse of mycetoma were observed in patients with bone involvements or presented with recurrent mycetoma for the second time.

SCLERAL SELF-INDENTATION DURING CHANDELIER-ASSISTED PERIPHERAL VITRECTOMY UNDER AIR FOR RHEGMATOGENOUS RETINAL DETACHMENT: A Retrospective Cohort Study.

PURPOSE: To evaluate incidence of iatrogenic retinal breaks in eyes for whom self-indentation during chandelier-assisted peripheral vitrectomy under air, for primary retinal detachment, had been performed compared with eyes for whom a nonindentation chandelier-assisted peripheral vitrectomy under air had been performed. METHODS: Retrospective cohort study. One hundred and thirty eyes with primary rhegmatogenous retinal detachment were identified. All the patients had undergone a chandelier-assisted peripheral vitrectomy under air. Scleral self-indentation had been used in 68 eyes (study group; indentation), whereas nonindentation had been used in 62 eyes (comparison; nonindentation). Outcome variables included the following: trimming-induced retinal breaks, retinal redetachment rate, final logMAR best-corrected visual acuity, and intraoperative complications. RESULTS: The number of eyes with trimming-induced retinal break was statistically less in indentation group than in nonindentation group (0/68 and 3/62 eyes, 0% and 4.8%, respectively) (P = 0.04). Redetachment was observed in one eye (indentation) (1/68) and in three eyes (nonindentation) (3/62) (P = 0.267). There was no statistically significant difference in logMAR best-corrected visual acuity between both groups (P = 0.229). Chandelier repositioning was needed in 22 eyes (indentation) compared with 46 eyes (nonindentation) (P < 0.001). CONCLUSION: Self-indentation, during chandelier-assisted peripheral vitrectomy under air, enables complete trimming of the vitreous base without causing iatrogenic retinal breaks, with a higher retinal reattachment rate, and with less need for chandelier repositioning than with nonindentation approach. By contrast with previous reports, we consider scleral self-indentation as an advantage for chandelier air vitrectomy.

Botulinum Toxin for the Treatment of Gummv Smile.

AIM: The aim was to evaluate the effect of botulinum toxin (Botox) injections as a conservative treatment for gummy smile. MATERIALS AND METHODS: An experimental in vivo study was conducted at a dermatology clinic in Riyadh in January 2016. The study included 23 female patients who ranged from 20 to 50 years and were treated with Botox injections due to excessive maxillary gingival display. The patients with short clinical crowns or long maxilla, those who were pregnant or breastfeeding, and patients with neuromuscular disorders were excluded. Patients received Botox type I, injected 3 mm lateral to the alar-fascial groove at the level of the nostril opening at the insertion of the levator labii superioris alaeque nasi muscle. Photos were taken of the patient's smile before and after the treatment and were then uploaded to the SketchUp program to calculate improvements in gingival display. The distance from the lower margin of the upper lip to the gingival margin was calculated pre- and posttreatment. The amount of improvement was calculated as (pre-Botox treatment - post-Botox treatment/pre-Botox treatment × 100). The mean percentage of the total improvement was analyzed. RESULTS: A total of 23 female patients received treatment to improve their gummy smile. Improvement was clear 2 weeks after Botox injection. The mean percentage of improvement in the gingival display was 99.6%. CONCLUSION: Botox type I is an effective conservative technique to improve gummy smile caused by muscular hyperfunction. CLINICAL SIGNIFICANCE: Patients' retention highly indicated that they were satisfied with the provided treatment by Botox injections. Improving the quality of life with least painful experience and immediate results was the major advantage for Botox type I.

Effect of fluoride on the corrosion behavior of Ti and Ti6Al4V dental implants coupled with different superstructures.

The effect of fluoride ion concentration on the corrosion behavior of Ti and Ti6Al4V implant alloys, when coupled with either metal/ceramic or all-ceramic superstructure, was examined by different electrochemical methods in artificial saliva solutions. It was concluded that increased fluoride concentration leads to a decrease in the corrosion resistance of all tested couples. The type of the superstructure also showed a significant effect on the corrosion resistance of the couple.

[Lethal uropathies: prenatal diagnosis and feto-pathologic aspects]. / Les uropathies létales: diagnostic anténatal et aspects foetopathologiques.

Forty-three prenatal diagnoses of lethal urinary tract abnormalities were carried out during a five-year-period. The abnormalities were bilateral renal agenesis (56%), autosomal recessive polycystic kidney disease (16%), autosomal dominant polycystic kidney disease (14%), MECKEL-GRUBER syndrome and Prune-Belly syndrome (4%). The pregnancy was interrupted in thirty-five cases (81.4%).

[The Dalkon Shield, a forgotten device, responsible for actinomycosis]. / Le Delkon Shield un sterilet oublié responsable d'actinomycose.

The authors report a case of a Dalkon Shield, forgot in a 55 years old patient, responsible for actinomycosis infection. Basing on a review of the literature, diagnostic methods and management of this kind of complication are discussed.

[Value of fetal MRI in the prenatal diagnosis of renal polycystic disease: a case report]. / Apport de l'IRM foetale dans le diagnostic anténatal de la polykystose rénale: à propos d'une observation.

We present a case of foetal polycystic kidney disease diagnosed at 34 weeks of gesttion thanks to resonance imaging (MRI). MRI demonstrated enlarged foetal kidneys that were low signal intensity on T1 weighted images and high signal intensity on T2 weighted images. These MRI findings suggested a high water containing of the renal parenchyma.