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One seventh of the world's population lives in the Indo-Gangetic Plain (IGP) and the fertile region sustains agricultural food crop production for much of South Asia, yet it remains one of the most under-studied regions of the world in terms of atmospheric composition and chemistry. In particular, the emissions and chemistry of volatile organic compounds (VOCs) that form surface ozone and secondary organic aerosol through photochemical reactions involving nitrogen oxides are not well understood. In this study, ambient levels of VOCs such as methanol, acetone, acetaldehyde, acetonitrile and isoprene were measured for the first time in the IGP. A new atmospheric chemistry facility that combines India's first high-sensitivity proton transfer reaction mass spectrometer, an ambient air quality station and a meteorological station, was used to quantify in situ levels of several VOCs and air pollutants in May 2012 at a suburban site in Mohali (northwest IGP). Westerly winds arriving at high wind speeds (5–20 m s−1) in the pre-monsoon season at the site were conducive for chemical characterization of regional emission signatures. Average levels of VOCs and air pollutants in May~2012 ranged from 1.2 to 2.7 nmol mol−1 for aromatic VOCs, 5.9 to 37.5 nmol mol−1 for the oxygenated VOCs, 1.4 nmol mol−1 for acetonitrile, 1.9 nmol mol−1 for isoprene, 567 nmol mol−1 for carbon monoxide, 57.8 nmol mol−1 for ozone, 11.5 nmol mol−1 for nitrogen oxides, 7.3 nmol mol−1 for sulfur dioxide, 104 μg m−3 for PM2.5 and 276 μg m−3 for PM10. By analyzing the one-minute in situ data with meteorological parameters and applying chemical tracers (e.g., acetonitrile for biomass burning) and inter-VOC correlations, we were able to constrain major emission source activities on both temporal and diel scales. Wheat residue burning caused massive increases (> 3 times the baseline values) for all the measured VOCs and primary pollutants. Other forms of biomass burning at night were also a significant source of oxygenated VOCs and isoprene (r2 with acetonitrile 0.5 for nighttime data), which is remarkable in terms of atmospheric chemistry implications. Surface ozone exceeded the 8 h national ambient air quality limit of 100 μg O3 m−3 (~50 ppbv) on a daily basis, except for 17 May 2012, when a severe dust storm event (PM2.5 > 800 μg m−3; PM10 > 2700 μg m−3) characterized by long-range transport from the west impacted the site. The novel data set and results point to the occurrence of high primary emissions of reactive VOCs. They also highlight the urgent need for establishing more comprehensive observational facilities in the IGP to constrain the spatial and seasonal variability of atmospheric chemical constituents. Such efforts will enable a mechanistic-level understanding of the in situ chemical processes controlling the formation of surface ozone, a necessary step for effective ozone mitigation and improvement of the regional air quality.

In this study we use a high-quality data set of in situ ozone measurements at a suburban site called Mohali in the state of Punjab to estimate ozone-related crop yield losses for wheat, rice, cotton and maize for Punjab and the neighbouring state Haryana for the years 2011–2013. We intercompare crop yield loss estimates according to different exposure metrics, such as AOT40 (accumulated ozone exposure over a threshold of 40) and M7 (mean 7-hour ozone mixing ratio from 09:00 to 15:59), for the two major crop growing seasons of kharif (June–October) and rabi (November–April) and establish a new crop-yield–exposure relationship for southern Asian wheat, maize and rice cultivars. These are a factor of 2 more sensitive to ozone-induced crop yield losses compared to their European and American counterparts. Relative yield losses based on the AOT40 metrics ranged from 27 to 41 % for wheat, 21 to 26 % for rice, 3 to 5 % for maize and 47 to 58 % for cotton. Crop production losses for wheat amounted to 20.8 ± 10.4 million t in the fiscal year of 2012–2013 and 10.3 ± 4.7 million t in the fiscal year of 2013–2014 for Punjab and Haryana taken together. Crop production losses for rice totalled 5.4 ± 1.2 million t in the fiscal year of 2012–2013 and 3.2 ± 0.8 million t in the year 2013–2014 for Punjab and Haryana taken together. The Indian National Food Security Ordinance entitles ~ 820 million of India's poor to purchase about 60 kg of rice or wheat per person annually at subsidized rates. The scheme requires 27.6 Mt of wheat and 33.6 Mt of rice per year. The mitigation of ozone-related crop production losses in Punjab and Haryana alone could provide > 50 % of the wheat and ~ 10 % of the rice required for the scheme. The total economic cost losses in Punjab and Haryana amounted to USD 6.5 ± 2.2 billion in the fiscal year of 2012–2013 and USD 3.7 ± 1.2 billion in the fiscal year of 2013–2014. This economic loss estimate represents a very conservative lower limit based on the minimum support price of the crop, which is lower than the actual production costs. The upper limit for ozone-related crop yield losses in all of India currently amounts to 3.5–20 % of India's GDP. The mitigation of high surface ozone would require relatively little investment in comparison to the economic losses incurred presently. Therefore, ozone mitigation can yield massive benefits in terms of ensuring food security and boosting the economy. The co-benefits of ozone mitigation also include a decrease in the ozone-related mortality and morbidity and a reduction of the ozone-induced warming in the lower troposphere.

Methicillin-resistant Staphylococcus aureus (MRSA) is considered a common colonizer of burn wound and accounts for high morbidity and mortality all across the globe. Systemic antibiotic therapy which is generally prescribed for these patients has a number of limitations. These include high drug dose, toxicity, and chances of development of drug resistance. However, local delivery of drug not only addresses these limitations but also provides better efficacy at the site of infection. In the present study, hydrogel preparations were developed for the topical delivery of moxifloxacin for the treatment of S. aureus–infected burn wound. Moxifloxacin was characterized by UV, FTIR, DSC, hot-stage microscopy, NMR, and HPLC and loaded into conventional and Boswellia-containing novel gels. Gels were characterized by visual examination, pH, UV spectroscopy, and release assays. In vivo studies showed that both gels were effective in eradicating the bacteria completely from the wound site when treatment was started during the early stage of infection. On the contrary, delayed treatment of planktonic and biofilm cells with novel gel showed better efficacy as compared with conventional gel in S. aureus–infected burn wound. Histopathological analysis also showed better skin healing efficacy of novel gel than conventional gel. Our results show that moxifloxacin can be efficiently used topically in the management of burn wound infections along with other antibacterial agents. Since biofilm-mediated infections are on the rise especially in chronic bacterial disease, therefore, a preparation containing antibiofilm agent-like Boswellia as one of the excipients would be more meaningful.

There is an unmet need to develop alternative therapeutic strategies to not only restrain seizures but also to alleviate the underlying pathologies and sequelae. Berberine (BBR), an isoquinoline alkaloid, has shown promising effect in the kindling model of epileptogenesis, but due to the poor oral bioavailability its clinical application is limited. So, the present study was designed to study the neuroprotective effect of BBR nanoparticles (enhanced bioavailability as compared to BBR) against seizures in pentylenetetrazole (PTZ) induced kindling model of epileptogenesis. Kindling model was established in male Wistar rats by intraperitoneal (i.p.) administration of PTZ (30 mg/kg) on every alternate day till the animal became fully kindled or till 6 weeks. Three doses of BBR (50, 100, and 200 mg/kg) and nano-BBR (25, 50, 100 mg/kg) were studied for seizure score, percentage of animal kindled, histopathological score, oxidative stress, inflammation, and apoptosis in PTZ treated rats by conducting cytokines, gene expression and protein expression analysis. BBR nanoparticles showed significant effect on the seizure score and percentage of animal kindled, histopathological score, neurobehavioral parameters (Forced swim test, Rotarod), oxidative (MDA, SOD, GSH, GPx) and inflammatory (IL-1beta, TNF-alpha) parameters, apoptotic parameters (Bax and iNOS), and gene (Nrf2, NQO1, HO1) and protein expression (Nrf2) as compared to both PTZ and BBR. BBR nanoparticles showed neuroprotective effect in PTZ induced kindling model of epileptogenesis and proves to be a promising antiepileptogenic therapy for the patients who are at high risk of developing seizures. Graphical Abstract

The aim of the study was to develop and optimise drug-in-adhesive (DIA) transdermal patch of duloxetine HCl for enhanced drug delivery. DIA patch so developed reduced the dose and dosing frequency by enhancing bio-performance of the drug. A transdermal DIA patch having Duro-Tak 87–2287 as DIA polymer and Transcutol P as permeation enhancer loaded with 40% drug previously complexed with MeβCD duly characterised (FTIR, DSC, and SEM) was developed for in vivo study. Pharmacokinetic parameters of developed formulation were assessed and compared with oral route of administration. Among various permeation enhancers (PEs), Transcutol P exhibited most enhanced permeation (ER ≈ 1.99) in terms of flux and Q 24 compared to control group having. Mean of maximum plasma concentration ( C max ) and area under time-concentration curve (AUC 0–72 ) in Wistar rats ( n  = 6) for transdermal patch (10 mg/kg) was found to be 70.31 ± 11.2 ng/ml and 2997.29 ± 387.4 ng/ml*h, respectively, and were considerably higher than oral dose of DLX (20 mg/kg and 10 mg/kg). Albeit, T 1/2 was higher in case of transdermal delivery, but this was due to sustained behaviour of delivery system. These findings highlight the significance of both inclusion complexation and transdermal delivery of DLX using DIA patch for efficient drug absorption.

The relation between schizophrenia and the menstrual cycle has always been found attractive by researchers. It is still a question of debate whether the clinical picture changes during the menstrual cycle. Our study aimed to see whether there is any change of symptoms during different phases of menstrual cycle (premenstrual, menstrual, and postmenstrual) in patients suffering from schizophrenia. Over a period of 15 months, 40 female inpatients of a tertiary care psychiatric hospital with the diagnosis of schizophrenia were assessed by applying PANSS. Rating was done up to two menstrual cycles. Total scores, positive and negative subscale scores, and general psychopathology scores of PANSS in premenstrual, menstrual, and postmenstrual phases of those patients were compared with one another by applying paired t test. Symptoms in women suffering from schizophrenia frequently vary with the different phases of menstrual cycle. The positive symptoms improved significantly only during progesterone phase. Negative symptoms and general psychopathology subscale showed improvement on estrogen phases of menstrual cycle. So optimal treatment needs to be adjusted to the individual women suffering from schizophrenia.

The US Food and Drug Administration (FDA) public workshop, entitled “Application of Physiologically‐based Pharmacokinetic (PBPK) Modeling to Support Dose Selection focused on the role of PBPK in drug development and regulation. Representatives from industry, academia, and regulatory agencies discussed the issues within plenary and panel discussions. This report summarizes the discussions and provides current perspectives on the application of PBPK in different areas, including its utility, predictive performance, and reporting for regulatory submissions.

Despite the known biochemical production of a range of aromatic compounds by plants and the presence of benzenoids in floral scents, the emissions of only a few benzenoid compounds have been reported from the biosphere to the atmosphere. Here, using evidence from measurements at aircraft, ecosystem, tree, branch and leaf scales, with complementary isotopic labeling experiments, we show that vegetation (leaves, flowers and phytoplankton) emits a wide variety of benzenoid compounds to the atmosphere at substantial rates. Controlled environment experiments show that plants are able to alter their metabolism to produce and release many benzenoids under stress conditions. The functions of these compounds remain unclear but may be related to chemical communication and protection against stress. We estimate the total global secondary organic aerosol potential from biogenic benzenoids to be similar to that from anthropogenic benzenoids (~10 Tg y −1 ), pointing to the importance of these natural emissions in atmospheric physics and chemistry.

Hydroxyl radicals play a central role in the troposphere as they control the lifetime of many trace gases. Measurement of OH reactivity (OH loss rate) is important to better constrain the OH budget and also to evaluate the completeness of measured VOC budget. Total atmospheric OH reactivity was measured for the first time in an European Megacity: Paris and its surrounding areas with 12 million inhabitants, during the MEGAPOLI winter campaign 2010. The method deployed was the Comparative Reactivity Method (CRM). The measured dataset contains both measured and calculated OH reactivity from CO, NOx and VOCs measured via PTR-MS, GC-FID and GC-MS instruments. The reactivities observed in Paris covered a range from 10 s−1 to 130 s−1, indicating a large loading of chemical reactants. The present study showed that, when clean marine air masses influenced Paris, the purely local OH reactivity (20 s−1) is well explained by the measured species. Nevertheless, when there is a continental import of air masses, high levels of OH reactivity were obtained (120–130 s−1) and the missing OH reactivity measured in this case jumped to 75%. Using covariations of the missing OH reactivity to secondary inorganic species in fine aerosols, we suggest that the missing OH reactants were most likely highly oxidized compounds issued from photochemically processed air masses of anthropogenic origin.

Abstract Purpose: Bilastine is a novel second-generation antihistaminic. Very few studies in Indian population have compared the safety and efficacy of bilastine with other second-generation antihistaminic like cetirizine. Hence, the present study was planned. Materials and Methods: This was a randomized, open-label comparative parallel group study conducted on 70 patients of chronic spontaneous urticaria (CSU). Patients either received cetirizine 10 mg or bilastine 20 mg once daily for 6 weeks. The primary endpoint was to find out the difference in the mean total symptom score (MTSS) at baseline and 6 weeks. The secondary endpoint was to find out changes in the scale of the number of wheals, change in pruritus scale, scale for size of wheal, change for interference of wheals with sleep, change in visual analog scale (VAS) for sedation, change in scale for intensity of erythema, and change in Scale for Extent of Skin Area Involvement (SESI). Results: Bilastine and cetirizine offer a significant reduction in MTSS, mean number of wheals, and mean pruritus scale at baseline to 1, 3, and 6 weeks. The mean difference in MTSS was significantly more in bilastine. Cetirizine showed a significant increase in VAS score for sedation as compared to bilastine. Both the drugs were well tolerated and safe. Adverse events like headache, gastric irritation, dryness of mouth, and sedation were more reported in cetirizine group. Conclusion: Bilastine was more efficacious than cetirizine in patients of CSU and the efficacy was seen earlier at 1 week, which was not seen in the cetirizine group.