Distribution of ozone and its precursors over Bay of Bengal during winter 2009: role of meteorology

Measurements of ozone and NO₂ were carried out in the marine environment of the Bay of Bengal (BoB) during the winter months, December 2008–January 2009, as part of the second Integrated Campaign for Aerosols, gases and Radiation Budget conducted under the Geosphere Biosphere Programme of the Indian Space Research Organization. The ozone mixing ratio was found to be high in the head and the southeast BoB with a mean value of 61 ± 7 ppb and 53 ± 6 ppb, respectively. The mixing ratios of NO₂ and CO were also relatively high in these regions. The spatial patterns were examined in the light of airflow patterns, air mass back trajectories and other meteorological conditions and satellite retrieved maps of tropospheric ozone, NO₂, CO, and fire count in and around the region. The distribution of these gases was strongly associated with the transport from the adjoining land mass. The anthropogenic activities and forest fires/biomass burning over the Indo Gangetic Plains and other East Asian regions contribute to ozone and its precursors over the BoB. Similarity in the spatial pattern suggests that their source regions could be more or less the same. Most of the diurnal patterns showed decrease of the ozone mixing ratio during noon/afternoon followed by a nighttime increase and a morning high. Over this oceanic region, photochemical production of ozone involving NO₂ was not very active. Water vapour played a major role in controlling the variation of ozone. An attempt is made to simulate ozone level over the north and south BoB using the photochemical box model (NCAR-MM). The present observed features were compared with those measured during the earlier cruises conducted in different seasons

Hyptis suaveolens (L.) Poit. (Lamiaceae) a source of edible oil among tribals of Orissa, India

The tribal use of Hyptis suaveolens (Lamiaceae) as a source for edible oil purpose in cooking medium is reported for the first time from Gandhamardan hill areas of Bolan gil' district in Orissa, India. &nbsp

Hyptis suaveolens (L.) Poit. (Lamiaceae) a source of edible oil among tribals of Orissa, India

The tribal use of Hyptis suaveolens (Lamiaceae) as a source for edible oil purpose in cooking medium is reported for the first time from Gandhamardan hill areas of Bolan gil' district in Orissa, India. &nbsp

Hyptis suaveolens (L.) Poit. (Lamiaceae) a source of edible oil among tribals of Orissa, India

The tribal use of Hyptis suaveolens (Lamiaceae) as a source for edible oil purpose in cooking medium is reported for the first time from Gandhamardan hill areas of Bolan gil' district in Orissa, India. &nbsp

Association of Organochlorine Pesticides with Peripheral Neuropathy in Patients with Diabetes or Impaired Fasting Glucose

OBJECTIVE—Recent epidemiological studies have shown that background exposure to persistent organic pollutants (POPs)—xenobiotics accumulated in adipose tissue—is strongly associated with type 2 diabetes. Hyperglycemia is the cause of long-term complications of diabetes as well as diabetes itself, and POPs are well-known neurotoxicants. This study was performed to explore whether POPs are associated with peripheral neuropathy, a common long-term complication of diabetes, in people with glucose abnormalities

RNA-based therapies in inherited retinal diseases

Inherited retinal diseases (IRDs) are a genetically and phenotypically heterogeneous group of genetic eye disorders. There are more than 300 disease entities, and together this group of disorders affects millions of people globally and is a frequent cause of blindness or low-vision certification. However, each type is rare or ultra-rare. Characteristically, the impaired vision in IRDs is due to retinal photoreceptor dysfunction and loss resulting from mutation in a gene that codes for a retinal protein. Historically, IRDs have been considered incurable and individuals living with these blinding conditions could be offered only supportive care. However, the treatment landscape for IRDs is beginning to evolve. Progress is being made, driven by improvements in understanding of genotype-phenotype relationships, through advances in molecular genetic testing and retinal imaging. Alongside this expanding knowledge of IRDs, the current era of precision medicine is fueling a growth in targeted therapies. This has resulted in the first treatment for an IRD being approved. Several other therapies are currently in development in the IRD space, including RNA-based therapies, gene-based therapies (such as augmentation therapy and gene editing), cell therapy, visual prosthetics, and optogenetics. RNA-based therapies are a novel approach within precision medicine that have demonstrated success, particularly in rare diseases. Three antisense oligonucleotides (AONs) are currently in development for the treatment of specific IRD subtypes. These RNA-based therapies bring several key advantages in the setting of IRDs, and the potential to bring meaningful vision benefit to individuals living with inherited blinding disorders. This review will examine the increasing breadth and relevance of RNA-based therapies in clinical medicine, explore the key features that make AONs suitable for treating genetic eye diseases, and provide an overview of the three-leading investigational AONs in clinical trials

Measurement and Reproducibility of Preserved Ellipsoid Zone Area and Preserved Retinal Pigment Epithelium Area in Eyes With Choroideremia

PURPOSE: To identify valid and reproducible methods for quantifying anatomic outcome measures for eyes with choroideremia (CHM) in clinical trials. DESIGN: Reliability analysis study. METHODS: In this multicenter study, patients with confirmed genetic diagnosis of CHM were enrolled. All cases underwent spectral-domain optical coherence tomography (SDOCT) and fundus autofluorescence (FAF) imaging. Two graders independently delineated boundaries of preserved autofluorescence (PAF) and pre-served ellipsoid zone (EZ) on FAF and OCT images, respectively. The results of the 2 independent gradings of both FAF and OCT images were compared to assess the reproducibility of the grading methods. RESULTS: A total of 148 eyes from 75 cases were included. In 21% of eyes PAF and in 43% of eyes preserved EZ had extended beyond the image capture area. After exclusion of these eyes and low-quality images, 114 FAF and 77 OCT images were graded. The mean PAF areas from 2 independent gradings were 3.720 +/- 3.340 mm(2) and 3.692 +/- 3.253 mm2, respectively. Intraclass correlation coefficient (ICC) for these gradings was 0.996. The mean preserved EZ areas from 2 independent gradings were 2.746 +/- 2.319 mm2 and 2.858 2.446 mm2, respectively. ICC for these gradings was 0.991. CONCLUSIONS: Quantifying preserved retinal pigment epithelium and EZ areas on FAF and OCT images, respectively, in CHM patients is highly reproducible. These variables would be potential anatomic outcome measures for CHM clinical trials and could be studied and tracked longitudinally in choroideremia. (C) 2017 Elsevier Inc. All rights reserved.Peer reviewe

Durable Vision Improvement After a Single Intravitreal Treatment With Antisense Oligonucleotide in CEP290-Lca: Replication in Two Eyes

PURPOSE: An intravitreally injected antisense oligonucleotide, sepofarsen, was designed to modulate splicing within retinas of patients with severe vision loss due to deep intronic c.2991 + 1655A \u3e G variant in the OBSERVATIONS: Visual function was evaluated with best corrected standard and low-luminance visual acuities, microperimetry, dark-adapted chromatic perimetry, and full-field sensitivity testing. Retinal structure was evaluated with OCT imaging. At the fovea, all visual function measures and IS/OS intensity of the OCT showed transient improvements peaking at 3-6 months, remaining better than baseline at ∼2 years, and returning to baseline by 3-4 years after each single injection. CONCLUSIONS AND IMPORTANCE: These results suggest that sepofarsen reinjection intervals may need to be longer than 2 years

Intravitreal antisense oligonucleotide sepofarsen in Leber congenital amaurosis type 10: a phase 1b/2 trial

CEP290-associated Leber congenital amaurosis type 10 (LCA10) is a retinal disease resulting in childhood blindness. Sepofarsen is an RNA antisense oligonucleotide targeting the c.2991+1655A>G variant in the CEP290 gene to treat LCA10. In this open-label, phase 1b/2 (NCT03140969), 12-month, multicenter, multiple-dose, dose-escalation trial, six adult patients and five pediatric patients received ≤4 doses of intravitreal sepofarsen into the worse-seeing eye. The primary objective was to evaluate sepofarsen safety and tolerability via the frequency and severity of ocular adverse events (AEs); secondary objectives were to evaluate pharmacokinetics and efficacy via changes in functional outcomes. Six patients received sepofarsen 160 µg/80 µg, and five patients received sepofarsen 320 µg/160 µg. Ten of 11 (90.9%) patients developed ocular AEs in the treated eye (5/6 with 160 µg/80 µg; 5/5 with 320 µg/160 µg) versus one of 11 (9.1%) in the untreated eye; most were mild in severity and dose dependent. Eight patients developed cataracts, of which six (75.0%) were categorized as serious (2/3 with 160 µg/80 µg; 4/5 with 320 µg/160 µg), as lens replacement was required. As the 160-µg/80-µg group showed a better benefit–risk profile, higher doses were discontinued or not initiated. Statistically significant improvements in visual acuity and retinal sensitivity were reported (post hoc analysis). The manageable safety profile and improvements reported in this trial support the continuation of sepofarsen development

Phosphorylation of Syntaxin‐1a by casein kinase 2α (CK2α) regulates presynaptic vesicle exocytosis from the reserve pool

The t-soluble NSF-attachment protein receptor protein Syntaxin-1a (Stx-1a) is abundantly expressed at pre-synaptic terminals where it plays a critical role in the exocytosis of neurotransmitter-containing synaptic vesicles. Stx-1a is phosphorylated by Casein kinase 2α (CK2α) at Ser14, which has been proposed to regulate the interaction of Stx-1a and Munc-18 to control of synaptic vesicle priming. However, the role of CK2α in synaptic vesicle dynamics remains unclear. Here, we show that CK2α over-expression reduces evoked synaptic vesicle release. Furthermore, shRNA-mediated knockdown of CK2α in primary hippocampal neurons strongly enhanced vesicle exocytosis from the reserve pool, with no effect on the readily releasable pool of primed vesicles. In neurons in which endogenous Stx-1a was knocked down and replaced with a CK2α phosphorylation-deficient mutant, Stx-1a(D17A), vesicle exocytosis was also increased. These results reveal a previously unsuspected role of CK2α phosphorylation in specifically regulating the reserve synaptic vesicle pool, without changing the kinetics of release from the readily releasable pool