Pharmacologic fibroblast reprogramming into photoreceptors restores vision.

Photoreceptor loss is the final common endpoint in most retinopathies that lead to irreversible blindness, and there are no effective treatments to restore vision1,2. Chemical reprogramming of fibroblasts offers an opportunity to reverse vision loss; however, the generation of sensory neuronal subtypes such as photoreceptors remains a challenge. Here we report that the administration of a set of five small molecules can chemically induce the transformation of fibroblasts into rod photoreceptor-like cells. The transplantation of these chemically induced photoreceptor-like cells (CiPCs) into the subretinal space of rod degeneration mice (homozygous for rd1, also known as Pde6b) leads to partial restoration of the pupil reflex and visual function. We show that mitonuclear communication is a key determining factor for the reprogramming of fibroblasts into CiPCs. Specifically, treatment with these five compounds leads to the translocation of AXIN2 to the mitochondria, which results in the production of reactive oxygen species, the activation of NF-κB and the upregulation of Ascl1. We anticipate that CiPCs could have therapeutic potential for restoring vision.

Safety and efficacy of COVID-19 vaccines: A systematic review and meta-analysis of controlled and randomized clinical trials.

Vaccines against coronavirus disease 2019 (COVID-19) have been discovered within a very small duration of time as compared to the traditional way for the development of vaccines, which raised the question about the safety and efficacy of the approved vaccines. The purpose of this study is to look at the effectiveness and safety of vaccine platforms against the incidence of COVID-19. The literature search was performed on PubMed/Medline, Cochrane, and clinical trials.gov databases for studies published between 1 January 2020 and 19 February 2022. Preferred Reporting Items for Systemic Review and Meta-Analysis Statement guidelines were followed. Among 284 articles received by keywords, a total of 11 studies were eligible according to the inclusion and exclusion criteria (studies in special populations, e.g., pregnant women, paediatric patients, editorials, case reports, review articles, preclinical and in vitro studies) of the study. A total of 247,186 participants were considered for randomisation at baseline, among them, 129,572 (52.42%) were provided with vaccine (Intervention group) and 117,614 (47.58%) with the placebo (Control group). A pooled fold change estimation of 0.19 (95% CI: 0.12-0.31, p < 0.0001) showed significant protection against the incidence of COVID-19 in the vaccines received group versus the placebo group. mRNA based, inactivated vaccines and non-replicating viral vector-based vaccines showed significantly protection against the incidence of COVID-19 compared to placebo with pooled fold change estimation was 0.08 (95% CI: 0.06-0.10), 0.20 (95% CI: 0.14-0.29) and 0.36 (95% CI: 0.28-0.46), respectively. Injection site discomfort and fatigue were the most common side effect observed in mRNA, non-replicating viral vector, inactivated, and protein subunit-based vaccines. All the approved vaccines were found safe and efficacious but mRNA-based vaccines were found to be more efficacious against SARS-CoV-2 than other platforms.

The 5-lipoxygenase/cyclooxygenase-2 cross-over metabolite, hemiketal E2, enhances VEGFR2 activation and promotes angiogenesis.

Consecutive oxygenation of arachidonic acid by 5-lipoxygenase and cyclooxygenase-2 yields the hemiketal eicosanoids, HKE2 and HKD2. Hemiketals stimulate angiogenesis by inducing endothelial cell tubulogenesis in culture; however, how this process is regulated has not been determined. Here, we identify vascular endothelial growth factor receptor 2 (VEGFR2) as a mediator of HKE2-induced angiogenesis in vitro and in vivo. We found that HKE2 treatment of human umbilical vein endothelial cells dose-dependently increased the phosphorylation of VEGFR2 and the downstream kinases ERK and Akt that mediated endothelial cell tubulogenesis. In vivo, HKE2 induced the growth of blood vessels into polyacetal sponges implanted in mice. HKE2-mediated effects in vitro and in vivo were blocked by the VEGFR2 inhibitor vatalanib, indicating that the pro-angiogenic effect of HKE2 was mediated by VEGFR2. HKE2 covalently bound and inhibited PTP1B, a protein tyrosine phosphatase that dephosphorylates VEGFR2, thereby providing a possible molecular mechanism for how HKE2 induced pro-angiogenic signaling. In summary, our studies indicate that biosynthetic cross-over of the 5-lipoxygenase and cyclooxygenase-2 pathways gives rise to a potent lipid autacoid that regulates endothelial cell function in vitro and in vivo. These findings suggest that common drugs targeting the arachidonic acid pathway could prove useful in antiangiogenic therapy.

Rapidly Dissolving Trans-scleral Microneedles for Intraocular Delivery of Cyclosporine A.

Cyclosporine A (CsA) is a cyclic peptide immunosuppressant drug that is beneficial in the treatment of various ocular diseases. However, its ocular bioavailability in the posterior eye is limited due to its poor aqueous solubility. Conventional CsA formulations such as a solution or emulsion permeate poorly across the eye due to various static and dynamic barriers of the eye. Dissolvable microneedle (MN)-based patches can be used to overcome barrier properties and, thus, enhance the ocular bioavailability of CsA in the posterior eye. CsA-loaded dissolvable MN patches were fabricated using polyvinylpyrrolidone (PVP) and characterized for MN uniformity and sharpness using SEM. Further characterization for its failure force, penetration force, and depth of penetration were analyzed using a texture analyzer. Finally, the dissolution time, ex vivo permeation, and ocular distribution of cyclosporine were determined in isolated porcine eyes. PVP MNs were sharp, uniform with good mechanical properties, and dissolved within 5 min. Ocular distribution of CsA in a whole porcine eye perfusion model showed a significant increase of CsA levels in various posterior segment ocular tissues as compared to a topically applied ophthalmic emulsion (Restasis®) (P < 0.001). Dissolving MNs of CsA were prepared, and the MN arrays can deliver CsA to the back of the eye offering potential for treating various inflammatory diseases.

Microbial community structure and exploration of bioremediation enzymes: functional metagenomics insight into Arabian Sea sediments.

Deep-sea sediments provide important information on oceanic biogeochemical processes mediated by the microbiome and their functional roles which could be unravelled using genomic tools. The present study aimed to delineate microbial taxonomic and functional profiles from Arabian Sea sediment samples through whole metagenome sequencing using Nanopore technology. Arabian Sea is considered as a major microbial reservoir with significant bio-prospecting potential which needs to be explored extensively using recent advances in genomics. Assembly, co-assembly, and binning methods were used to predict Metagenome Assembled Genomes (MAGs) which were further characterized by their completeness and heterogeneity. Nanopore sequencing of Arabian Sea sediment samples generated around 1.73 tera basepairs of data. Proteobacteria (78.32%) was found to be the most dominant phylum followed by Bacteroidetes (9.55%) and Actinobacteria (2.14%) in the sediment metagenome. Further, 35 MAGs from assembled and 38 MAGs of co-assembled reads were generated from long-read sequence dataset with major representations from the genera Marinobacter, Kangiella, and Porticoccus. RemeDB analysis revealed a high representation of pollutant-degrading enzymes involved in hydrocarbon, plastic and dye degradation. Validation of enzymes with long nanopore reads using BlastX resulted in better characterization of complete gene signatures involved in hydrocarbon (6-monooxygenase and 4-hydroxyacetophenone monooxygenase) and dye degradation (Arylsulfatase). Enhancing the cultivability of deep-sea microbes predicted from the uncultured WGS approaches by I-tip method resulted in isolation of facultative extremophiles. This study presents a comprehensive insight into the taxonomic and functional profiles of Arabian Sea sediments, indicating a potential hotspot for bioprospection.

Vertical Microbial Profiling of Arabian Sea Oxygen Minimal Zone Reveals Complex Bacterial Communities and Distinct Functional Implications.

Arabian Sea harbours one of the largest oxygen minimal zones (OMZs) among the global oceans wherein biogeochemical cycles are regulated through dominant and complex microbial processes. The present study investigated the bacterial communities at various depths of the Arabian Sea OMZ using high-throughput sequencing of the v3-v4 hyper variable region of 16S rRNA gene. A total of 10 samples which included water samples from 8 different depths and 2 sediment samples were analyzed in this study. About 2.7 million sequences were obtained from all the samples. The sequence analysis revealed high bacterial diversity at deep waters and sediment samples and comparatively less species richness at the core OMZ depths. Number of OTUs ranged from 114 to 14441.Taxonomic assignments of the obtained OTUs showed dominant presence of Proteobacteria, Bacteriodetes, and Chloroflexi across all the samples. The identified OTUs were further affiliated to the phyla Marinimicrobia, Colwellia, Nitrospina, Tepidicaulis, Shewanella, Pseudoalteromonas, Woeseia at various depths along the water column. Correlation with abiotic factors suggested distinct variation in bacterial community composition with change in depth and dissolved oxygen (DO) levels. Predictive functional annotation based on bacterial phylotypes suggested presence of active nitrogen, sulphur, carbon, and methane metabolic cycles along the vertical transect of the studied region. Presence of nitrogen reduction bacterial group below the core OMZ depths may potentially provide insight into the expansion of OMZ region in Arabian Sea. Functional profiling further revealed presence of genes related to xenobiotic degradation in the water and sediment samples indicating a potential hotspot for bio-prospection.

Percutaneous absorption and Skin accumulation of Lorazepam-Diphenhydramine- Haloperidol Carbopol gel in Porcine Ear Skin.

This study presents the formulation and evaluation of an ABH Carbopol gel containing lorazepam (Ativan®), diphenhydramine hydrochloride (Benadryl®), and haloperidol (Haldol®) for treating chemotherapy-induced nausea and vomiting (CINV) in hospice patients. ABH PLO gel is widely used for this purpose due to its low cost and presumed efficacy. However, previous studies, including one conducted by the authors, have reported insufficient drug absorption from the ABH PLO gel. Here we hypothesized that the ABH Carbopol gel would provide superior percutaneous absorption of the drugs. ABH Carbopol gel was characterized for pH, viscosity, thermal properties, and infrared spectroscopy. The percutaneous absorption and skin retention of the gel was evaluated across porcine ear skin using Franz diffusion cells, and the drug concentrations were determined by high-performance liquid chromatography. The pH of the ABH Carbopol gel was found to be 6.80 ± 0.33, and the retention time of diphenhydramine, haloperidol, and lorazepam were 4.73, 7.11, and 18.69 minutes, respectively. The thermogram of the ABH Carbopol gel indicates the drugs were present in the dissolved state. Based on the flux data, the estimated steady-state concentration (Css) of diphenhydramine, haloperidol, and lorazepam were found to be 44.64 ng/ml, 2.58 ng/ml, and 20.1 ng/ml, respectively. These values were significantly higher than those obtained from the ABH PLO gel. In conclusion, the ABH Carbopol gel provides a promising alternative to the ABH PLO gel for treating CINV in hospice patients. Further studies are required to validate these findings in clinical settings.

3D-Printed Capsaicin-Loaded Injectable Implants for Targeted Delivery in Obese Patients.

Diet-induced obesity and hyperlipidemia are a growing public health concern leading to various metabolic disorders. Capsaicin, a major bioactive compound obtained from natural chili peppers, has demonstrated its numerous beneficial roles in treating obesity and weight loss. Current treatment involves either administration of antiobesity drugs or surgical procedures such as Roux-en-Y-gastric bypass or sleeve gastrectomy, both of which are associated with serious side effects and poor patient acceptance. Capsaicin, a pungent molecule, has low oral bioavailability. Therefore, there is a need for the development of site-specific drug delivery system for capsaicin. The present study is aimed at preparing and characterizing 3D-printed capsaicin-loaded rod-shaped implants by thermoplastic extrusion-based 3D printing technology. The implants were printed with capsaicin-loaded into a biodegradable polymer, polycaprolactone, at different drug loadings and infill densities. The surface morphology revealed a smooth and uniform external surface without any capsaicin crystals. DSC thermograms showed no significant changes/exothermic events among the blends suggesting no drug polymer interactions. The in vitro release studies showed a biphasic release profile for capsaicin, and the release was sustained for more than three months (~ 85% released) irrespective of drug loading and infill densities. The HPLC method was stability-indicating and showed good resolution for its analogs, dihydrocapsaicin and nordihydrocapsaicin. The implants were stable for three months at accelerated conditions (40°C) without any significant decrease in the assay of capsaicin. Therefore, capsaicin-loaded implants can serve as a long-acting injectable formulation for targeting the adipose tissue region in obese patients.

Cardiolipin for Enhanced Cellular Uptake and Cytotoxicity of Thermosensitive Liposome-Encapsulated Daunorubicin toward Breast Cancer Cell Lines.

Daunorubicin (DNR) and cardiolipin (CL) were co-delivered using thermosensitive liposomes (TSLs). 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1-myristoyl-2-stearoyl-sn-glycero-3-phosphocholine (MSPC), cholesterol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] or DSPE-mPEG (2000) and CL were used in the formulation of liposomes at a molar ratio of 57:40:30:3:20, respectively. CL forms raft-like microdomains that may relocate and change lipid organization of the outer and inner mitochondrial membranes. Such transbilayer lipid movement eventually leads to membrane permeabilization. TSLs were prepared by thin-film hydration (drug:lipid ratio 1:5) where DNR was encapsulated within the aqueous core of the liposomes and CL acted as a component of the lipid bilayer. The liposomes exhibited high drug encapsulation efficiency (>90%), small size (~115 nm), narrow size distribution (polydispersity index ~0.12), and a rapid release profile under the influence of mild hyperthermia. The liposomes also exhibited ~4-fold higher cytotoxicity against MDA-MB-231 cells compared to DNR or liposomes similar to DaunoXome® (p < 0.001). This study provides a basis for developing a co-delivery system of DNR and CL encapsulated in liposomes for treatment of breast cancer.

Lysinated Multiwalled Carbon Nanotubes with Carbohydrate Ligands as an Effective Nanocarrier for Targeted Doxorubicin Delivery to Breast Cancer Cells.

Multiwalled carbon nanotubes (MWCNTs) are elongated, hollow cylindrical nanotubes made of sp2 carbon. MWCNTs have attracted significant attention in the area of drug delivery due to their high drug-loading capacity and large surface area. Furthermore, they can be linked to bioactive ligands molecules via covalent and noncovalent bonds that allow for the targeted delivery of anticancer drugs such as doxorubicin. The majority of methodologies reported for the functionalization of MWCNTs for drug delivery are quite complex and use expensive linkers and ligands. In the present study, we report a simple, cost-effective approach for functionalizing MWCNTs with the carbohydrate ligands, galactose (GA), mannose (MA) and lactose (LA), using lysine as a linker. The doxorubicin (Dox)-loaded functionalized MWCNTs were characterized using FT-IR, NMR, Raman, XRD and FE-SEM. The drug-loaded MWCNTs were evaluated for drug loading, drug release and cell toxicity in vitro, in breast cancer cells. The results indicated that the carbohydrate-modified lysinated MWCNTs had greater Dox loading capacity, compared to carboxylated MWCNTs (COOHMWCNTs) and lysinated MWCNTs (LyMWCNTs). In vitro drug release experiments indicated that the carbohydrate functionalized LyMWCNTs had higher Dox release at pH 5.0, compared to the physiological pH of 7.4, over 120 h, indicating that they are suitable candidates for targeting the tumor microenvironment as a result of their sustained release profile of Dox. Doxorubicin-loaded galactosylated MWCNTs (Dox-GAMWCNTs) and doxorubicin loaded mannosylated MWCNTs (Dox-MAMWCNTs) had greater anticancer efficacy and cellular uptake, compared to doxorubicin-loaded lactosylated MWCNTs (Dox-LAMWCNTs) and pure Dox, in MDA-MB231 and MCF7 breast cancer cells. However, neither the ligand conjugated multiwall blank carbon nanotubes (GAMWCNTs, MAMWCNTs and LAMWCNTs) nor the lysinated multiwalled blank carbon nanotubes produced significant toxicity in the normal cells. Our results suggest that sugar-tethered multiwalled carbon nanotubes, especially the galactosylated (Dox-GAMWCNTs) and mannosylated (Dox-MAMWCNTs) formulations, may be used to improve the targeted delivery of anticancer drugs to breast cancer cells.

Niosomal formulation of hydroxytyrosol, a polyphenolic antioxidant, for enhancing transdermal delivery across human cadaver skin.

Hydroxytyrosol (HT), a naturally occurring polyphenol from the olive plant, is a potent antioxidant, cardioprotective, neuroprotective, and anti-inflammatory agent. Upon oral administration, HT undergoes rapid elimination within minutes and thus limiting its therapeutic utility. Due to its hydrophilic nature, percutaneous absorption and transdermal delivery of HT are very low. The aim of this research was to enhance the skin permeation of hydroxytyrosol using a niosome gel formulation. The formulations prepared with Span 60 as surfactant showed uniform particle size and high encapsulation efficiency (>90%). The niosome formulations showed a pseudoplastic behavior for topical application within the lipid/surfactant composition of 45-50%. The formulations showed a controlled release of HT compared to the HT solution. The flux of HT across human skin was increased by 28 and 4.4 fold compared to aqueous and ethanolic HT solutions, respectively (p < 0.001). The presence of lecithin lowered the flux and increased the retention of the formulations compared to HT solutions (p < 0.001). The formulations containing lecithin showed two-fold higher skin retention of hydroxytyrosol (p < 0.05). In conclusion, this study demonstrates niosome gel as a promising alternative to oral delivery of HT, providing sustained delivery and greater efficacy.

Weighted estimators of the complier average causal effect on restricted mean survival time with observed instrument-outcome confounders.

A major concern in any observational study is unmeasured confounding of the relationship between a treatment and outcome of interest. Instrumental variable (IV) analysis methods are able to control for unmeasured confounding. However, IV analysis methods developed for censored time-to-event data tend to rely on assumptions that may not be reasonable in many practical applications, making them unsuitable for use in observational studies. In this report, we develop weighted estimators of the complier average causal effect (CACE) on the restricted mean survival time in the overall population as well as in an evenly matchable population (CACE-m). Our method is able to accommodate instrument-outcome confounding and adjust for covariate-dependent censoring, making it particularly suited for causal inference from observational studies. We establish the asymptotic properties and derive easily implementable asymptotic variance estimators for the proposed estimators. Through simulation studies, we show that the proposed estimators tend to be more efficient than instrument propensity score matching-based estimators or IPIW estimators. We apply our method to compare dialytic modality-specific survival for end stage renal disease patients using data from the U.S. Renal Data System.

The Physical Compatibility of Clinically Used Concentrations of Diltiazem Hydrochloride With Heparin Sodium.

Background: Acute treatment of atrial fibrillation often requires concomitant intravenous (IV) continuous infusions of unfractionated heparin and diltiazem. Concomitantly infusing these medications through the same IV line minimizes multiple IV sites. Diltiazem and heparin visual compatibility have been previously investigated but with limited drug dwell times and differing drug concentrations leading to inconsistent published results. Objective: To investigate the physical compatibility of diltiazem hydrochloride at concentrations of 5 and 1 mg/mL combined with an equal volume of heparin sodium 100 units/mL. Methods: Using a 0.22-µm filter, 15 mL of heparin sodium were placed into a polyvinyl chloride infusion bag followed by 15 mL of either diltiazem hydrochloride 5 or 1 mg/mL. Admixtures were prepared in triplicate. Each admixture was investigated for visual precipitation, spectrophotometric absorbance, and pH change at baseline and 1, 5, 8, and 24 hours after mixing. Physical incompatibility was determined by visual observation, increased spectrophotometric absorbance, and demonstrative pH changes. Results: Each diltiazem 5 mg/mL admixture exhibited a slight haze and enhanced absorbance readings indicating turbidity while none revealed a demonstrative pH change. None of the diltiazem 1 mg/mL assessments revealed visual precipitation or suggested turbidity. Only one pH reading at 5 hours revealed a demonstrative change from baseline. Conclusions: Our findings indicate that infusing diltiazem hydrochloride 5 mg/mL with heparin sodium 100 units/mL in the same IV line cannot be advocated. In contrast, our findings suggest that heparin sodium 100 units/mL infused with diltiazem hydrochloride 1 mg/mL is physically compatible but chemical stability was not assessed.

Inhibition of Noncanonical Murine Double Minute 2 Homolog Abrogates Ocular Inflammation through NF-κB Suppression.

Uveitis is estimated to account for 10% of all cases of blindness in the United States, including 30,000 new cases of legal blindness each year. Intraocular and oral corticosteroids are the effective mainstay treatment, but they carry the risk of serious long-term ocular and systemic morbidity. New noncorticosteroid therapies with a favorable side effect profile are necessary for the treatment of chronic uveitis, given the paucity of existing treatment choices. We have previously demonstrated that Nutlin-3, a small-molecule inhibitor of murine double minute 2 (MDM2) homolog, suppresses pathologic retinal angiogenesis through a p53-dependent mechanism, but the noncanonical p53-independent functions have not been adequately elucidated. Herein, we demonstrate an unanticipated function of MDM2 inhibition, where Nutlin-3 potently abrogates lipopolysaccharide-induced ocular inflammation. Furthermore, we identified a mechanism by which transcription and translation of NF-κB is mediated by MDM2, independent of p53, in ocular inflammation. Small-molecule MDM2 inhibition is a novel noncorticosteroid strategy for inhibiting ocular inflammation, which may potentially benefit patients with chronic uveitis.

Evaluation of topical econazole nitrate formulations with potential for treating Raynaud's phenomenon.

The purpose of this work was to design and characterize a topical formulation of econazole nitrate (EN) with potential for treating Raynaud's phenomenon (RP). Four topical dosage forms (F1_topical solution, F2_HPMC or hydroxypropyl methylcellulose dispersion, F3_VersaBase® cream, and F4_Lipoderm® Activemax™ Cream) containing 3% w/w EN were prepared and characterized for drug content, pH, viscosity, spreadability, drug crystallinity, stability, and in vitro permeation using Franz cells across pig ear skin, and results were compared to the 1% marketed EN cream. All four formulations had acceptable physical and visual characteristics required for topical application, with 3% w/w EN. The order of amount of drug permeated from highest to lowest was F2 (10.27%) > F4 (2.47%) > F1 (2.28%) > F3 (1.47%) > marketed formulation (0.22%). Formulation F2 showed better penetration of the drug into the stratum corneum, epidermis, and dermis layers. The drug concentration in the stratum corneum and epidermis was approximately 10-20 times higher with F2 compared to the marketed formulation. All formulations were found to be stable for up to 6 months. All four EN formulations were found to be better than the 1% marketed cream. Formulation F2_HPMC dispersion could be further explored as a treatment option for RP.

Honeycomb micro-textures for light trapping in multi-crystalline silicon thin-film solar cells.

The liquid phase crystallization (LPC) of silicon is an emerging technology for fabricating 10 - 20 µm thin multi-crystalline silicon layers on glass. LPC silicon solar cells exhibit similar electronic performance to multi-crystalline wafer-based devices. Due to the reduced absorber thickness, however, effective measures for light trapping have to be taken. We present tailor-made micro-structures for light trapping at the LPC silicon back-side, whereby a nano-imprinted resist layer serves as a three-dimensional etching mask in subsequent reactive ion etching. Contrary to state-of-the-art random pyramid textures produced by wet-chemical etching, this method allows to produce tailor-made textures independent of grain orientation. Differently shaped micro-textures were replicated in LPC silicon. Absorptance and external quantum efficiency of periodic honeycomb patterns and random pyramids were found to be equivalent. Thus, the method enables the potential to further optimize light trapping in LPC silicon solar cells.

Evaluating center performance in the competing risks setting: Application to outcomes of wait-listed end-stage renal disease patients.

It is often of interest to compare centers or healthcare providers on quality of care delivered. We consider the setting where evaluation of center performance on multiple competing events is of interest. We propose estimating center effects through cause-specific proportional hazards frailty models that allow correlation among a center's cause-specific effects. Estimation of our model proceeds via penalized partial likelihood and is implemented in R. To evaluate center performance, we also propose a directly standardized excess cumulative incidence (ECI) measure. Therefore, based on our proposed methods, practitioners can evaluate centers either through the cause-specific hazards or the cumulative incidence functions. We demonstrate, through simulations, the advantages of the proposed methods to detect outlying centers, by comparing the proposed methods and existing methods which assume uncorrelated random center effects. In addition, we develop a Correlation Score Test to test the null hypothesis that the competing event processes within a center are correlated. Using data from the Scientific Registry of Transplant Recipients, we apply our method to evaluate the performance of Organ Procurement Organizations on two competing risks: (i) receipt of a kidney transplant and (ii) death on the wait-list.

AMBULATORY BLOOD PRESSURE PATTERNS IN PATIENTS WITH RETINAL VEIN OCCLUSION.

PURPOSE: Failure of blood pressure (BP) to dip during sleep (nondipper pattern) is associated with cardiovascular disease and stroke. The prevalence and degree of nondipping and masked hypertension in patients with retinal vein occlusion (RVO), which is associated with stroke, has not been previously examined. METHODS: We measured clinic and 24-hour ambulatory BPs in 22 patients with RVO and 20 control participants without known eye disease matched by age and sex. Mean BP dipping, defined as the ratio of difference in mean awake and sleep systolic BPs to mean awake systolic BP, and masked and nocturnal hypertension were compared between groups. RESULTS: Mean 24-hour ambulatory BP was 144/79 mmHg among those with RVO and 136/77 mmHg among controls. Patients with RVO had an almost 2-fold higher prevalence of nondipping pattern (80.8% [95% confidence interval, 52.8-94.1] vs. 50.4% [95% confidence interval, 26.1-74.5]; P = 0.008). Average sleep systolic BP dip in patients with RVO was 6.1% versus 11.9% in controls (P = 0.004). More patients with RVO had masked hypertension by ambulatory BPs than controls (71% vs. 50%), but this difference was not statistically significant. CONCLUSION: Our data suggest an association between RVO and nondipper BP pattern. Ambulatory BP monitoring may be useful in the evaluation of patients with RVO by identifying those who may benefit from more aggressive BP control.

Thiamethoxam induces oxidative stress and antioxidant response in zebrafish (Danio Rerio) livers.

Thiamethoxam, a second-generation neonicotinoid insecticide, was found to be toxic to nontarget aquatic organisms. The purpose of this study was to investigate the toxicity of thiamethoxam (0.30, 1.25, and 5.00 mg/L) on zebrafish (Danio rerio) livers at the 7th, 14th, 21st, and 28th days. The reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), glutathione-s-transferase (GST), malondialdehyde (MDA) content, and DNA damage were used to evaluate the toxic effects of thiamethoxam on zebrafish. Compared to control groups, ROS levels were ascended in the exposure period; SOD and CAT activities were dramatically increased during early exposure and then inhibited. GST activity only increased on days 28. MDA content was slightly elevated on days 21 and 28. Additionally, a clear dose-response relationship was found for DNA damage. In conclusion, thiamethoxam could induce oxidative stress and DNA damage on the exposed zebrafish. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 2006-2015, 2016.