Expression of chicken epidermal growth factor (cEGF) in Escherichia coli regulates the microflora structure of the duodenum to improve growth performance and intestinal morphogenesis in broilers.

1. A study used gene synthesis to obtain the functional domains of chicken epidermal growth factor (cEGF) and examined their impact on broiler growth performance, small intestinal morphology, digestive enzyme activities in the intestinal contents and the structure of duodenal microflora.2. The pET-32a-cEGF recombinant expression vector was constructed. The specific band at 26 KDa was shown by SDS-PAGE analysis and WB results. The purified protein content was shown to be 1687 µg/ml by assay.3. A total of 180 healthy, one-day-old Arbor Acres male, white-feathered broilers were randomly divided into three dietary treatment groups (six replicate pens, 10 birds per replicate): A control diet (ND); cEGF diet (cEGF), control supplemented with 250 mg/kg cEGF and the control diet (CD) supplemented with 250 mg/kg chlortetracycline.4. The results showed that feeding the cEGF and CD diet reduced FCR of broilers aged 1-21 d, average daily feed intake (ADFI) at 22-42 d, and the FCR in the whole period (1-42 d; p < 0.05). Compared with the ND group, the cEGF diet increased duodenal α-amylase and alkaline phosphatase activities in the 1-21 d, duodenal lipase, alkaline phosphatase, and ileal alkaline phosphatase activities in the post-period and increased villus height in the duodenum and ileum (p < 0.05). In addition, the ACE and Chao1 index for the birds fed cEGF were higher than the ND group (p < 0.05). At the phyla level, Firmicutes and Proteobacteria were dominant in all groups. At the genus level, the dominant genus was Lactobacillus. The LEfSe analysis showed that the cEGF group was enriched by 11 species including Brevibacillus, Eisenbergiella, Cloacibacterium, Butyricoccus spp.5. The addition of 250 mg/kg cEGF to the diet can increase growth performance by improving intestinal development and digestive enzyme activity, which may be related to the duodenal intestinal microflora. Therefore, cEGF is an effective alternative to antibiotics in broiler farming.

Cannabinoid exposure in rat adolescence reprograms the initial behavioral, molecular, and epigenetic response to cocaine.

The initial response to an addictive substance can facilitate repeated use: That is, individuals experiencing more positive effects are more likely to use that drug again. Increasing evidence suggests that psychoactive cannabinoid use in adolescence enhances the behavioral effects of cocaine. However, despite the behavioral data, there is no neurobiological evidence demonstrating that cannabinoids can also alter the brain's initial molecular and epigenetic response to cocaine. Here, we utilized a multiomics approach (epigenomics, transcriptomics, proteomics, and phosphoproteomics) to characterize how the rat brain responds to its first encounter with cocaine, with or without preexposure to the synthetic cannabinoid WIN 55,212-2 (WIN). We find that in adolescent (but not in adult) rats, preexposure to WIN results in cross-sensitization to cocaine, which correlates with histone hyperacetylation and decreased levels of HDAC6 in the prefrontal cortex (PFC). In the PFC, we also find that WIN preexposure blunts the typical mRNA response to cocaine and instead results in alternative splicing and chromatin accessibility events, involving genes such as Npas2 Moreover, preexposure to WIN enhances the effects of cocaine on protein phosphorylation, including ERK/MAPK-targets like gephyrin, and modulates the synaptic AMPAR/GluR composition both in the PFC and the nucleus accumbens (NAcc). PFC-NAcc gene network topological analyses, following cocaine exposure, reveal distinct top nodes in the WIN preexposed group, which include PACAP/ADCYAP1. These preclinical data demonstrate that adolescent cannabinoid exposure reprograms the initial behavioral, molecular, and epigenetic response to cocaine.

Dephosphorylation of Y228 and Y217 and phosphorylation of Y335 in p120 catenin activate convergent extension during zebrafish gastrulation.

BACKGROUND: The cadherin-associated protein p120 catenin regulates convergent extension through interactions with cadherin proteins, Cdc42, and Rac1, as we previously showed in zebrafish (Danio rerio). Phosphorylation of p120 catenin changes the nature of its activity in vitro but is virtually unexplored in embryos. We used our previously developed antisense RNA splice-site morpholino targeted to endogenous p120 catenin-δ1 to cause defects in axis elongation probing the functions of three p120 catenin tyrosine-phosphorylation sites in gastrulating zebrafish embryos. RESULTS: The morpholino-induced defects were rescued by co-injections with mouse p120 catenin-δ1-3A mRNAs mutated at residues Y228 and Y217 to a non-phosphorylatable phenylalanine (F) or mutated at residue Y335 to a phosphomimetic glutamic acid (E). Co-injection of the complementary mutations Y228E, Y217E, or Y335F mRNAs partially rescued embryos whereas dual mutation to Y228E-Y217E blocked rescue. Immunopurification showed Y228F mutant proteins preferentially interacted with Rac1, potentially promoting cell migration. In contrast, the phosphomimetic Y228E preferentially interacted with E-cadherin increasing adhesion. Both Y228F and Y335F strongly bind VAV2. CONCLUSIONS: p120 catenin serves dual roles during gastrulation of zebrafish. Phosphorylation and dephosphorylation of tyrosine residues Y217, Y228, and Y335 precisely balance cell adhesion and cell migration to facilitate somite compaction and axis elongation.

[Disseminated nocardiosis caused by Nocardia otitidiscaviarum in an immunocompetent host: a case report].

Nocardiosis can be caused by various Nocardia spp., including Nocardia asteroides, Nocardia brasiliensis, Nocardia cyriacigeorgica, Nocardia farcinica and Nocardia otitidiscaviarum. As compared with the other Nocardia spp., Nocardia otitidiscaviarum appears to be rare which can spread through the bloodstream and affect multiple organs. The disease is usually seen in immunocompromised patients' but may also occur in immunocompetent patients. The clinical symptoms and laboratory and imaging examinations of the disease are nonspecific.Here, we reported a case of disseminated nocardiosis caused by infection with Nocardiosis otitidiscaviarum in an immunocompetent host to improve the knowledge and diagnosis of nocardiosis.

[A pedigree study of Loeys-Dietz syndrome type 4 with skeletal deformity related to a novel TGFß2 mutation].

Objective: Loeys-Dietz syndrome is a rare type of hereditary connective tissue disease. This study was aimed to analyze the clinical characteristics and gene mutations in a family of Loeys-Dietz syndrome with skeletal deformity. Methods: Clinical data of the proband and family members were collected and biochemical measurements and radiological examinations were conducted. Genomic DNA was extracted from peripheral blood of the family members. Whole-exome sequencing was performed to determine the mutation sites in the proband, and Sanger sequencing was applied to verify the candidate mutation in the other family members. Results: The proband is a 34-year-old man with deformities of lower extremities for more than 30 years. Physical examinations showed dolichostenomelia, pes planus, joint laxity and scoliosis. Echocardiography revealed the dilatation of aortic root at the level of the sinuses of Valsalva. A heterozygous missense mutation (c. 220A>C, p.Thr74Pro) in exon 1 of TGFß2 gene was identified in the proband. The same mutation was detected in his sister and niece with similar clinical features such as deformities of lower extremities and pes planus. This novel mutation has not been reported in ExAC or 1000G and was predicted to be deleterious, supporting a diagnosis of Loeys-Dietz syndrome type 4. Conclusions: Loeys-Dietz syndrome type 4 is caused by TGFß2 mutations. Skeletal deformity is one of the distinctive features. Genetic testing is helpful for the early diagnosis and differential diagnosis from other connective tissue diseases.

CrY2H-seq: a massively multiplexed assay for deep-coverage interactome mapping.

Broad-scale protein-protein interaction mapping is a major challenge given the cost, time, and sensitivity constraints of existing technologies. Here, we present a massively multiplexed yeast two-hybrid method, CrY2H-seq, which uses a Cre recombinase interaction reporter to intracellularly fuse the coding sequences of two interacting proteins and next-generation DNA sequencing to identify these interactions en masse. We applied CrY2H-seq to investigate sparsely annotated Arabidopsis thaliana transcription factors interactions. By performing ten independent screens testing a total of 36 million binary interaction combinations, and uncovering a network of 8,577 interactions among 1,453 transcription factors, we demonstrate CrY2H-seq's improved screening capacity, efficiency, and sensitivity over those of existing technologies. The deep-coverage network resource we call AtTFIN-1 recapitulates one-third of previously reported interactions derived from diverse methods, expands the number of known plant transcription factor interactions by three-fold, and reveals previously unknown family-specific interaction module associations with plant reproductive development, root architecture, and circadian coordination.

Detection of different degree traumatic vertebral bone marrow oedema by virtual non-calcium technique of dual-source dual-energy CT.

AIM: To evaluate the diagnostic performance of dual-energy computed tomography (DECT) using the virtual non-calcium (VNCa) technique for the detection of different degrees of vertebral bone marrow oedema. MATERIALS AND METHODS: The present prospective study was approved by the institutional ethics committee. Informed consent was obtained from all patients. Twenty patients underwent both DECT and MRI. Vertebral bodies on VNCa images were graded visually by two blinded, independent radiologists using a three-point classification system (0=normal bone marrow, 2=distinct abnormal bone marrow attenuation). DECT values obtained from VNCa images were calculated by a third radiologist. Vertebral bodies on MRI images were graded by a forth radiologist using the same classification as DECT; magnetic resonance imaging (MRI) served as the reference standard. RESULTS: The agreement between VNCa and MRI images for the grading of bone marrow oedema was substantial (κ=0.694). If MRI at grade 2 was regarded as positive for bone marrow oedema, VNCa images achieved an overall sensitivity of 85%, specificity of 97.5%, positive predictive value of 81%, negative predictive value of 98.1%. Receiver operating characteristic analysis based on CT values for the diagnosis of distinct bone marrow oedema revealed an area under the curve of 0.950. A cut-off value of -11.80 HU provided a sensitivity of 95% and specificity of 86.3% for the diagnosis of distinct bone marrow oedema at DECT. CONCLUSION: DECT images of VNCa showed excellent diagnostic performance for the detection of distinct vertebral bone marrow oedema.

[Clinicopathological characteristics and prognosis of diffuse midline gliomas with histone H3K27M mutation: an analysis of 30 cases].

Objective: To analyze the clinicopathological characteristics and prognosis of diffuse midline glioma (DMG) with H3K27M mutation. Methods: Thirty cases of DMG were collected in Guangdong Sanjiu Brain Hospital from October 2016 to May 2018. The patients' clinicopathological data including age, tumor site and histological grade, treatment and follow-up data were collected and analyzed. Results: There were 21 males and 9 females, with a mean age of 26 years (range 5-53 years). Fourteen tumors were located in thalamus, 12 in brainstem (one involved both thalamus and brainstem), and one each in hypothalamus, fourth ventricle, and sellar region, respectively. Two cases presented as diffuse intracranial lesions. Three cases (10.0%) were of WHO grade Ⅰ, 10 cases (33.3%) were grade Ⅱ, eight cases (26.7%) were grade Ⅲ, and nine cases (30.0%) were grade Ⅳ.All patients with gradeⅠ tumors were older than 20 years. Histologically, all were pilocytic astrocytoma-like. Immunohistochemical staining demonstrated that all tumors were IDH1 negative. Twenty-eight tumors showed diffuse expression of H3K27M, and two showed focal expression. Twenty-one tumors(100.0%, 21/21) showed absent expression of H3K27me3. Sixteen tumors (57.1%, 16/28) showed strongly positive expression of p53, and ATRX was negative in eight tumors (38.1%, 8/21). The Ki-67 proliferation index ranged from 5% to 40%. Eight cases (including two cases of H3K27M expression of individual cells) showed K27M mutation in H3F3A gene. Intracranial and spinal cord dissemination occurred in six cases (20.0%, 6/30). Median progression-free survival (PFS) was 9.5 months and median overall survival (OS) was 34 months. Mean PFS was 11.2 months and mean OS was 24.3 months. Compared with adults (>20 years old), children/adolescents (no more than 20 years old) had significantly shorter median OS (8 months vs. 34 months, P=0.013). There was no significant difference in PFS and OS between DMGs located in the brain stem/thalamus and other sites within midline (P>0.05). There was no significant difference in PFS and OS between WHO grade ⅠDMGs and WHO grade Ⅱ-Ⅳ DMGs (P>0.05). Conclusions: DMGs occur more commonly in children and adolescents with male predominance. DMGs present with WHO Ⅰ-Ⅳ tumors morphologically, and pilocytic astrocytoma-like lesions with WHO Ⅰ are more common in adults. Expression of H3K27M but not H3K27me3 is helpful for diagnosis of DMG. The prognosis of children/adolescents is significantly worse than that of adults, whereas histological grade and tumor location do not affect prognosis.

[Comparison on the 10 years risk for ischemic cardiovascular disease among Han, Uygur, Kazak population from Xinjiang Uygur Autonomous Region].

Objective: To compare the 10 years risk for ischemic cardiovascular disease among Han, Uygur, Kazak nationality residents of Xinjiang Uygur Autonomous Region. Methods: From October 2007 to October 2010,14 618 adult (aged ≥35 years) Han (n=5 757),Uygur (n=4 767) and Kazak (n=4 094) residents were selected to join this study through the four-stage stratified cluster sampling method from 7 cities and regions of Xinjiang Uygur Autonomous Region. The 10 years risk for ischemic cardiovascular disease was calculated according to the 10 years ischemic cardiovascular disease risk assessment form modified with Chinese characteristics and compared among the residents of 3 nationalities. Results: (1) There were significant differences in age, body mass index, systolic blood pressure, diastolic blood pressure,fasting blood glucose,triglycerides,total cholesterol,low-density lipoprotein,high-density lipoprotein cholesterol, smoking history, and drinking history among Han, Uygur, Kazak nationality population (all P< 0.001). (2) There were significant differences in 10 years risk for ischemic cardiovascular disease between different gender and age group including 35-39, 40-44, 45-49, 50-54, 55-59, and ≥60 years old between Han, Uygur, Kazak nationality population (all P<0.001). (3) There were significant differences in rates of 10%-20% and>20% of 10 years risk for ischemic cardiovascular disease between different gender in Han, Uygur, Kazak nationality population (P values were 0.013 and <0.001, respectively). There were no significant differences in rates of <5% and 5%-9% of 10 years risk for ischemic cardiovascular disease between different gender in Han,Uygur,Kazak nationality population (all P>0.05).(4) There were significant differences in detection rates of diabetes,hypertension,smoking,hypertriglyceridemia,and obesity in male and female Han,Uygur,Kazak nationality population with 10 years risk for ischemic cardiovascular disease ≥10% (P<0.01 or 0.05). Meanwhile,there was significant difference in detection rates of hypercholesteremia in male Han, Uygur, Kazak nationality adults(P<0.001). There were no significant differences in detection rates of elevated low density lipoprotein cholesterol and reduced high density lipoprotein cholesterol in male and female Han,Uygur,Kazak nationality adults (all P>0.05). Conclusion: There are gender and age differences in the 10 years risk for ischemic cardiovascular disease in ≥35 years old Han,Uygur,Kazak nationality adults from Xinjiang Uygur Autonomous Region.

Consensus recommendations for trabecular meshwork cell isolation, characterization and culture.

Cultured trabecular meshwork (TM) cells are a valuable model system to study the cellular mechanisms involved in the regulation of conventional outflow resistance and thus intraocular pressure; and their dysfunction resulting in ocular hypertension. In this review, we describe the standard procedures used for the isolation of TM cells from several animal species including humans, and the methods used to validate their identity. Having a set of standard practices for TM cells will increase the scientific rigor when used as a model, and enable other researchers to replicate and build upon previous findings.

Disinfection of Tonometers: A Report by the American Academy of Ophthalmology.

OBJECTIVE: To examine the efficacy of various disinfection methods for reusable tonometer prisms in eye care and to highlight how disinfectants can damage tonometer tips and cause subsequent patient harm. METHODS: Literature searches were conducted last in October 2016 in the PubMed and the Cochrane Library databases for original research investigations. Reviews, non-English language articles, nonophthalmology articles, surveys, and case reports were excluded. RESULTS: The searches initially yielded 64 unique citations. After exclusion criteria were applied, 10 laboratory studies remained for this review. Nine of the 10 studies used tonometer prisms and 1 used steel discs. The infectious agents covered in this assessment include adenovirus 8 and 19, herpes simplex virus (HSV) 1 and 2, human immunodeficiency virus 1, hepatitis C virus, enterovirus 70, and variant Creutzfeldt-Jakob disease. All 4 studies of adenovirus 8 concluded that after sodium hypochlorite (dilute bleach) disinfection, the virus was undetectable, but only 2 of the 4 studies found that 70% isopropyl alcohol (e.g., alcohol wipes or soaks) eradicated all viable virus. All 3 HSV studies concluded that both sodium hypochlorite and 70% isopropyl alcohol eliminated HSV. Ethanol, 70% isopropyl alcohol, dilute bleach, and mechanical cleaning all lack the ability to remove cellular debris completely, which is necessary to prevent prion transmission. Therefore, single-use tonometer tips or disposable tonometer covers should be considered when treating patients with suspected prion disease. Damage to tonometer prisms can be caused by sodium hypochlorite, 70% isopropyl alcohol, 3% hydrogen peroxide, ethyl alcohol, water immersion, ultraviolet light, and heat exposure. Disinfectants can cause tonometer tips to swell and crack by dissolving the glue that holds the hollow tip together. The tonometer tip cracks can irritate the cornea, harbor microbes, or allow disinfectants to enter the interior of the tonometer tip. CONCLUSIONS: Sodium hypochlorite (dilute bleach) offers effective disinfection against adenovirus and HSV, the viruses commonly associated with nosocomial outbreaks in eye care. Tonometer prisms should be examined regularly for signs of damage.

An update on therapeutic modalities for the prevention of angle closure glaucoma.

PURPOSE OF REVIEW: Angle closure glaucoma is a prominent burden for the worldwide health system. Because this disorder is commonly asymptomatic, and can lead to irreversible blindness, the proper screening and early management of this disease can be critical. The definitions of angle closure and consequently its treatment guidelines have been dynamically modified and updated in the past decades. Surgical and laser techniques have been adapted to address the different mechanisms involved in the manifestation of the disease and properly prevent its progression in different stages. In this review, we will assess the most recent techniques and their indications in the prevention and management of angle closure disorders. RECENT FINDINGS: Recent trends in surgical and laser procedures in the management of angle closure glaucoma are often geared toward combination strategies, to target different mechanisms. Targeting the lens and the angle structures and adjacent tissues simultaneously may be a promising approach in both the prevention of further angle closure, modulating the pressure, and prevention of cataract progression. SUMMARY: Modifying your therapeutic modalities and thresholds for treatment based on updated angle closure disorder definitions and guidelines, as well as innovative screening techniques, may be beneficial to your patients, in regards to both prevention and reduction of disease progression.

Update on ciliary body laser procedures.

PURPOSE OF REVIEW: There are currently various options available for glaucoma treatment procedures ranging from laser to penetrating to nonpenetrating surgeries. Innovations in glaucoma surgical therapeutics include features such as external application, focused tissue effects, and minimal manipulation as these factors all help lower the risk of side-effects in addition to increasing the success rate of the treatment. Traditional diode laser transscleral cyclophotocoagulation (TSCPC) is invasive and destructive. This review aims to provide an overview of the latest ciliary body laser modalities, including micropulse diode laser transscleral cyclophotocoagulation (MP-TSCPC), as well as endoscopic cyclophotocoagulation. RECENT FINDINGS: MP-TSCPC and endoscopic cyclophotocoagulation, less invasive interventional procedures than filtering surgeries, have shown promise in having reduced postoperative complications while demonstrating reasonably good success rates. These modalities allow direct effects to the inflow system of the eye. The precision of these interventions has led to comparable or greater control of intraocular pressure (IOP) and lower inflammatory-fibrotic response in comparison to conventional TSCPC. Recent studies of these procedures have focused on their repeatability, long-term survival rate, and ability to be combined with cataract surgery. SUMMARY: The development of new minimally invasive surgical modalities such as MP-TSCPC and endoscopic cyclophotocoagulation has provided new options for treating glaucoma with a relatively safe side-effects profile as compared with filtration surgeries. These new treatments can lead to a significant decline in the number of postsurgical medications needed for IOP control.

Skin resistance to UVB-induced oxidative stress and hyperpigmentation by the topical use of Lactobacillus helveticus NS8-fermented milk supernatant.

AIMS: In this study, we investigated the preventive properties of the supernatant of Lactobacillus helveticus NS8-fermented milk (NS8-FS) against UV light-induced skin oxidative damage and hyperpigmentation. METHODS AND RESULTS: NS8-FS exhibited significant radical scavenging activity in tests with ABST+ and DPPH scavenging methods, and as well strongly inhibited 3-morpholinosydnonimine (Sin-1)-induced ROS generation in HaCat keratinocytes. Unexpectedly, NS8-FS was found to inhibit melanin production in B16F10 melanoma cells and to exhibit inhibitory effects both to the enzymatic activity of tyrosinase (TYR) and the expression of proteins required for melanin synthesis. In SKH-1 hairless mice, topical application of NS8-FS alleviated UVB-induced skin photodamage, including the improvement of the appearance of epidermal thickness, transepidennal water loss and lipid peroxidation levels. In the tanning guinea pig model, the whitening effect of NS8-FS was demonstrated using Masson-Fontana staining and TYR staining. Furthermore, NS8-FS was shown to stimulate the nuclear translocation and activation of the Nrf2 protein, along with recovery of antioxidant enzyme activities. CONCLUSION: NS8-FS exhibits the protective capacities against UV light-induced skin oxidative damage and hyperpigmentation. SIGNIFICANCE AND IMPACT OF THE STUDY: Our findings indicate the potential of cell-free fermented products of lactic acid bacteria in topical photoprotection.

Effect of mitomycin c and 5-flurouracil adjuvant therapy on the outcomes of Ahmed glaucoma valve implantation.

BACKGROUND: To examine the effect of mitomycin c and 5-flurouracil on treatment outcomes following Ahmed glaucoma valve implantation. DESIGN: Retrospective consecutive case series. PARTICIPANTS: Fifty patients who received Ahmed glaucoma valve implantation from 1999 to 2013 in the San Francisco Veterans Administration Hospital. METHODS: The +INJECTION group received intraoperative mitomycin c followed by postoperative mitomycin c and/or 5-flurouracil, whereas the -INJECTION group did not. MAIN OUTCOME MEASURES: Primary outcome was treatment success at 1 year post-implantation. Intraocular pressure, hypertensive phase, and the number of glaucoma medications were also examined. RESULTS: Twenty-six patients/eyes in the +INJECTION group and 24 patients/eyes in the -INJECTION group were included. Treatment success was higher in the +INJECTION compared with the -INJECTION group (86 vs. 58%; P = 0.04). Intraocular pressure was lower in the +INJECTION compared with the -INJECTION group at 1, 3, 6 and 12 months (P ≪ 0.00001, P = 0.00003, 0.0008 and 0.024). Hypertensive phase occurred less often in the +INJECTION compared with the -INJECTION group (3.8 vs. 54%; P = 0.021). The +INJECTION group required fewer medications compared with the -INJECTION group (P = 0.02, 0.002, 0.003 and 0.008 at 1, 3, 6 and 12 months). Complication rates were comparable between groups (46.2 and 54.2%; P = 0.63). CONCLUSIONS: Adjuvant treatment with antifibrotics following Ahmed glaucoma valve implantation decreased the hypertensive phase and improved surgical outcomes without impacting complication rates at 1 year. This study postulates a role for antifibrotics in the postoperative management of Ahmed glaucoma valves.

Cloning and expression of class I chitinases in Hami melon after Penicillium infection.

Chitinases are important disease-related proteins that play critical roles in plant defense against disease. To investigate the function of chitinases in the resistance of Hami melon to Penicillium infection, the gene encoding chitinases, HmCHT-2, was cloned and RT-PCR was used to measure expression levels of HmCHT-2. When the Hami melon was infected by Penicillium sp after 0, 12, 36, 48, 60, and 72 h. The results showed that comparing to the control group, the time of expression levels reaching to the peak delayed and the expression levels maintained at a significantly high level for a longer time. These results suggest that HmCHT-2 may contribute to the defense of Hami melon against fungal infection.

Oral Contraceptive Use and Prevalence of Self-Reported Glaucoma or Ocular Hypertension in the United States.

PURPOSE: To investigate the association between oral contraceptive (OC) use and glaucoma prevalence in the United States. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 3406 female participants, aged 40 years or older, from the 2005 to 2008 National Health and Nutrition Examination Survey, who reported a presence or absence of glaucoma or ocular hypertension completed both the vision and the reproductive health questionnaires and underwent eye examinations. METHODS: Multivariate regression analysis was used to assess the correlation between OC use and self-reported glaucoma or ocular hypertension (n = 231 cases), controlling for potential confounders, including age, ethnicity, systemic comorbidities such as hypertension and stroke, ocular diseases such as cataract and diabetic retinopathy, and reproductive health factors, including age at menopause, age at menarche, history of hormone replacement therapy, and gynecological surgical history. MAIN OUTCOME MEASURES: The outcome variable was self-reported glaucoma or ocular hypertension. RESULTS: After adjusting for confounders, those with ≥3 years of OC use had greater odds (odds ratio, 1.94; 95% confidence interval, 1.22-3.07) of self-reported glaucoma or ocular hypertension. Other factors associated with higher glaucoma or ocular hypertension prevalence included older age, African American race, and later age at menarche. CONCLUSIONS: Oral contraceptive use may be associated with increased risk of self-reported glaucoma or ocular hypertension.

A role for antimetabolites in glaucoma tube surgery: current evidence and future directions.

PURPOSE OF REVIEW: Glaucoma is the leading cause of irreversible blindness worldwide. The main treatment modality for glaucoma is the reduction and control of the intraocular pressure (IOP). Glaucoma filtration surgery, including trabeculectomy and/or implantation of a glaucoma drainage device (GDD), is warranted if IOP remains medically uncontrolled. However, postoperative scarring remains a critical determinant of long-term bleb survival and IOP control after drainage surgery. Antimetabolites, such as mitomycin C and 5-fluorouracil, have been used for many years to increase survival time of filtration surgeries by preventing bleb fibrosis and scarring. The aim of this study is to provide an overview of: the current usage of these antimetabolites in GDD, the recent advancements of these antimetabolites in combination with other technologies, and the role of future antimetabolites. RECENT FINDINGS: Mitomycin C and 5-fluorouracil have been used in GDD and trabeculectomy to prevent the exaggerated cellular reaction that leads to fibrosis. The adjunctive administration of these drugs intraoperatively and postoperatively has resulted in a lower rate of the hypertensive phase, and possibly a better long-term success rate in Ahmed valve surgeries. However, the application of these antimetabolites and their multiple-dosing applications are associated with nonspecific cytotoxicity and potentially severe complications such as bleb leak and conjunctival erosion over the tube. Recent studies are thus focusing on different medications, targeting new molecular pathways, and designing new delivery vehicles to minimize current antimetabolites side-effects and increase their efficacy. Promising results of these studies have led to development of new collaborative medications and advanced drug delivery systems for better modulation of GDD surgeries' predictable outcomes. SUMMARY: The development of small molecule therapeutics, combination therapies, and innovative drug vehicles to prevent postsurgical fibrosis and achieve better surgical outcome in glaucoma filtration surgeries is promising.