Drug use pattern for emergency psychiatric conditions in a tertiary care hospital: A prospective observational study.

PURPOSE: Psychiatric emergencies (PEs) are defined as acute disturbances of thought, mood, behavior, or social relationships requiring immediate interventions. The common emergency psychiatrics are attempted suicide, severe anxiety, schizophrenia, acute psychosis, substance abuse, acute panic attacks, drug toxicities, and extrapyramidal reactions. Emergency physicians in the general hospital may face the challenge of assessing and managing patients in PEs. This study was conducted to evaluate the clinical pattern and drug use pattern for PEs at a tertiary care hospital. MATERIALS AND METHODS: This was a cross-sectional, observational study where patients presenting to emergency medical services of a tertiary care hospital were recruited after approval from Institutional Ethics Committee and written informed consent. Demographic details, diagnosis, medication details, cost of the treatment, and adherence to guidelines in the management of emergency psychiatric conditions were assessed using a validated questionnaire. Descriptive statistics was applied to analyze the data. RESULTS: In 110 patients, a total number of drugs prescribed were 463 (mean: 4.21 drugs/prescription). The most commonly used psychotropic drug in emergency setting was found to be risperidone (19.39%), followed by lorazepam (13.60%) and clonazepam (4.28%). The most common diagnoses were substance abuse (32.72%) and schizophrenia (21.81%). About 74.5% of the physicians prescribed drugs abiding by the standard guidelines. The average total cost incurred by patients was about Rs. 366. CONCLUSION: The most commonly used drugs in emergency treatment found in this study are risperidone, followed by lorazepam and haloperidol.

Impact of climate change on navel orangeworm, a major pest of tree nuts in California.

California's agricultural sector is the highest valued agricultural sector in the United States. It is also a global leader in the production of various specialty crops, including three major tree nuts - almond, walnut, and pistachio. These three nut crops accounted for approximately 16% of the state's total agricultural economy. Current and future changes in climate pose many challenges in agriculture and impacts related to increased pest pressure in agriculture due to elevated temperatures are significant. The navel orangeworm, Amyelois transitella (Walker), is the most challenging pest of tree nuts in California and often cause a significant economic loss despite the careful implementation of multiple pest control tactics. Temperature variations can directly affect the developmental rates, behavior, and overall population dynamics of this pest, and it is critically important to understand these dynamics with respect to climate change. The objective of this study was to quantify changes in the timing and number of navel orangeworm generations in almonds, walnuts, and pistachios for the entire Central Valley of California using projections from ten general circulation models (GCMs) under two emission scenarios. The results suggest that navel orangeworm is likely to complete its life cycle much faster under climate change due to projected temperature increases. The results also suggest that under future climate change, navel orangeworm can complete one additional generation within the growing season and likely going to pose significant risks to these major nut industries in the future. Quantifying navel orangeworm generations and assessing risks to tree nuts under climate change can help facilitate and strategize integrated pest management (IPM) practices to the sustainability of the production systems by minimizing risks.

Practical challenges in conducting respiratory studies.

Respiratory studies are complex on account of specific therapeutic knowledge that is needed and various instruments that are used for the management of this condition. Monitoring a respiratory study requires knowledge of the specific disease and associated guidelines. The intent of this article is to help clinical research professionals understand the technicalities, challenges, and the nuances of performing respiratory studies.

Halobetasol propionate-loaded solid lipid nanoparticles (SLN) for skin targeting by topical delivery.

The clinical use of halobetasol propionate (HP) is related to some adverse effects like irritation, pruritus and stinging. The purpose of this work was to construct HP-loaded solid lipid nanoparticles (HP-SLN) formulation with skin targeting to minimizing the adverse side effects and providing a controlled release. HP-SLN were prepared by solvent injection method and formula was optimized by the application of 3(2) factorial design. The nanoparticulate dispersion was evaluated for particle size and entrapment efficiency (EE). Optimized batch was characterized for differential scanning calorimetry (DSC), scanning electron microscopy, X-ray diffraction study and finally incorporated into polymeric gels of carbopol for convenient application. The nanoparticulate gels were evaluated comparatively with the commercial product with respect to ex-vivo skin permeation and deposition study on human cadaver skins and finally skin irritation study. HP-SLN showed average size between 200 nm and 84-94% EE. DSC studies revealed no drug-excipient incompatibility and amorphous dispersed of HP in SLN. Ex vivo study of HP-SLN loaded gel exhibited prolonged drug release up to 12 h where as in vitro drug deposition and skin irritation studies showed that HP-SLN formulation can avoid the systemic uptake, better accumulative uptake of the drug and nonirritant to the skin compared to marketed formulation. These results indicate that the studied HP-SLN formulation represent a promising carrier for topical delivery of HP, having controlled drug release, and potential of skin targeting with no skin irritation.

Self-ignited high temperature synthesis and enhanced super-exchange interactions of Ho(3+)-Mn(2+)-Fe(3+)-O(2-) ferromagnetic nanoparticles.

The present work is focused on the effect of Fe(3+) replacement by rare earth-Ho(3+) ions and their influence on the properties of MnFe2O4 ferrite. The Ho(3+) substituted MnFe2O4 ferrite samples with chemical formula MnHoxFe2-xO4 were synthesized where substitution concentration of Ho(3+) was 0.0, 0.05, 0.1 and 0.15. The samples were synthesized by the self-ignited sol-gel method using the nitrates of the respective elements. Powder X-ray diffraction, transmission electron microscopy, infrared spectroscopy, vibrating sample magnetometer (VSM) and electrical measurements were employed to characterize the structural, magnetic and electrical properties of these ferrite nanoparticles. The cations distribution between the tetrahedral (A-site) and octahedral sites (B-site) has been estimated by XRD analysis. It is found that substitution of Ho(3+) ions favorably influenced the magnetic and electrical properties. Magnetic measurements were carried out at 77 and 300 K. Saturation magnetization and coercivity increased from 54.57 to 71.6 emu g(-1) and 172 to 766 Oe, respectively, with increasing the Ho(3+) substitution. The change in magnetic properties may be explained with the increase of A-O-B (FeA(3+)-O(2-)-HoB(3+)) super exchange interactions and the anisotropy constant. The electrical properties show that the pure sample has lower resistivity with respect to any Ho(3+) doped one. The conduction mechanism is used to interpret electrical measurements. Results of the presently investigated samples with enhanced saturation magnetization, coercivity and remanence ratio indicate that the Ho(3+) doped MnFe2O4 nanoparticles can be a useful candidate for the application in high density recording media.

Genotoxicity of different nanocarriers: possible modifications for the delivery of nucleic acids.

The prevention of cyto- and genotoxicity of nanocarriers is an important task in nanomedicine. In the present investigation, we, at the first time using similar experimental conditions, compared genotoxicity of nanocarriers with different composition, architecture, size, molecular weight and charge. Poly(ethylene glycol) polymers, neutral and cationic liposomes, micelles, poly(amindo amine) and poly(propyleneimine) dendrimers, quantum dots, mesoporous silica, and supermagnetic iron oxide (SPIO) nanoparticles were studied. All nanoparticles were used in non-cytotoxic concentrations. However, even in these concentrations, positively charged cationic liposomes, dendrimers, and SPIO nanoparticles induced genotoxicity leading to the significant formation of micronuclei in cells. Negatively charged and neutral nanocarriers were not genotoxic. A strong positive correlation was found between the number of formed micronuclei and the positive charge of nanocarriers. We proposed modifications of both types of dendrimers and SPIO nanoparticles that substantially decreased their genotoxicity and allowed for an efficient intracellular delivery of nucleic acids.

Multifunctional triblock Nanocarrier (PAMAM-PEG-PLL) for the efficient intracellular siRNA delivery and gene silencing.

A novel triblock poly(amido amine)-poly(ethylene glycol)-poly-l-lysine (PAMAM-PEG-PLL) nanocarrier was designed, synthesized, and evaluated for the delivery of siRNA. The design of the nanocarrier is unique and provides a solution to most of the common problems associated with the delivery and therapeutic applications of siRNA. Every component in the triblock nanocarrier plays a significant role and performs multiple functions: (1) tertiary amine groups in the PAMAM dendrimer work as a proton sponge and play a vital role in the endosomal escape and cytoplasmic delivery of siRNA; (2) PEG, a linker connecting PLL and PAMAM dendrimers renders nuclease stability and protects siRNA in human plasma; (3) PLL provides primary amines to form polyplexes with siRNA through electrostatic interaction and also acts as penetration enhancer; and (4) conjugation to PEG and PAMAM reduced toxicity of PLL and the entire triblock nanocarrier PAMAM-PEG-PLL. The data obtained show that the polyplexes resulted from the conjugation of siRNA, and the proposed nanocarriers were effectively taken up by cancer cells and induced the knock down of the target BCL2 gene. In addition, triblock nanocarrier/siRNA polyplexes showed excellent stability in human plasma.

Enantioselective Wacker-type cyclization of 2-alkenyl-1,3-diketones promoted by Pd-SPRIX catalyst.

An enantioselective intramolecular Wacker-type cyclization of 2-alkenyl-1,3-diketones catalyzed by a Pd(II)-SPRIX complex was developed. The reaction proceeded in a 6-endo-trig mode to give the desired chromene derivatives with moderate to good enantioselectivity. Isomerization of C-C double bonds via a pi-allyl Pd intermediate was involved as the key step.

LHRH-targeted nanoparticles for cancer therapeutics.

Synthesis and evaluation of a novel cancer cell's receptor-targeted internally quaternized and surface neutral poly(amidoamine) (PAMAM) generation four dendrimer as well as PAMAM-paclitaxel conjugate are described. The advantages of developed nanocarriers include but are not limited to (1) internal cationic charges for the complexation with small interfering RNA or antisense oligonucleotides and their protection from the degradation in systemic circulation; (2) neutral-modified surface for low cytotoxicity of empty unloaded dendrimers; (3) efficient internalization by cancer cells; and (4) preferential accumulation in the tumor and the prevention of adverse side effects of chemotherapy.

Internally cationic polyamidoamine PAMAM-OH dendrimers for siRNA delivery: effect of the degree of quaternization and cancer targeting.

A novel cancer targeted, internally cationic and surface neutral polyamidoamine (PAMAM) dendrimer, was designed, synthesized, and evaluated as a nanocarrier for the targeted intracellular delivery of siRNA. The dendrimer contained a synthetic analog of Luteinizing hormone-releasing hormone as cancer targeting moiety. The proposed delivery system possesses the following advantages: (1) internal cationic charges for complexation with siRNA and enhanced siRNA protection; (2) low cytotoxicity; (3) lesser degree of quaternization offering free tertiary amines for potential proton sponge effect; and (4) targeting specifically to cancer cells for enhancing siRNA uptake and efficiency and potential limitation of adverse side effects of chemotherapy on healthy organs. Both nontargeted and targeted dendrimer-siRNA complexes formed compact nanometer size spherical particles, exhibited very low cytotoxicity even at the higher concentration, and efficiently penetrated cancer cells in vitro. However, only the targeted dendrimer-siRNA complex was able to substantially decrease the expression of a targeted BCL2 gene.

Surface-modified and internally cationic polyamidoamine dendrimers for efficient siRNA delivery.

A novel internally quaternized and surface-acetylated poly(amidoamine) generation four dendrimer (QPAMAM-NHAc) was synthesized and evaluated for intracellular delivery of siRNA. The proposed dendrimer as a nanocarrier possesses the following advantages: (1) modified neutral surface of the dendrimer for low cytotoxicity and enhanced cellular internalization; (2) existence of cationic charges inside the dendrimer (not on the outer surface) resulting in highly organized compact nanoparticles, which can potentially protect nucleic acids from degradation. The properties of this dendrimer were compared with PAMAM-NH 2 dendrimer, possessing surface charges, and with an internally quaternized charged and hydroxyl-terminated QPAMAM-OH dendrimer. Atomic force microscopy studies revealed that internally charged and surface neutral dendrimers, QPAMAM-OH and QPAMAM-NHAc, formed well-condensed, spherical particles (polyplexes) with siRNA, while PAMAM-NH 2 resulted in the formation of nanofibers. The modification of surface amine groups to amide significantly reduced cytotoxicity of dendrimers with QPAMAM-NHAc dendrimer showing the lowest toxicity. Confocal microscopy demonstrated enhanced cellular uptake and homogeneous intracellular distribution of siRNA delivered by the proposed QPAMAM-NHAc nanocarrier. The results clearly demonstrated distinct advantages of developed QPAMAM-NHAc/siRNA polyplexes over the existing nucleic acid dendrimeric carriers.

Recent developments on chiral ionic liquids: design, synthesis, and applications.

The recent progress in chiral ionic liquids with respect to their syntheses and applications in enantioselective reactions and chiral recognition is described. In addition to the conventional chiral ionic liquids derived from chiral natural products, a library of novel chiral spiro compounds, including spiro bis(pyridinium) and spiro bis(imidazolium) salt, is also described.

Design and synthesis of novel chiral spiro ionic liquids.

[reaction: see text] Novel chiral imidazolium salts have been synthesized as examples of chiral ionic liquids with a spiro skeleton. Effects of N-substituents and counteranions on the melting point of spiro imidazolium salts and their chiral discrimination abilities are described.

Possible role of polyamines in gyrate atrophy.

PURPOSE: Gyrate atrophy (GA) is marked by hyperornithinemia and lowered ornithine amino transferase (OAT). However there are patients of GA without hyperornithinemia and those with hyperornithinemia without GA. Some cases of GA have been reported to have low lysine. The purpose of the study was to determine if polyamines, the metabolites of ornithine, and lysine have any diagnostic role in GA. METHODS: Ornithine in plasma was estimated by two-dimensional paper chromatography, with elution of the coloured spot, and the absorbance measured using a spectrophotometer at 560 nm. OAT assay in lymphocytes was done spectrophotometrically using ornithine as substrate. Blood and urinary polyamines were extracted with n-butanol, benzoylated and analysed with HPLC; putrescine, spermine, spermidine, and cadaverine were assayed individually at 254 nm with the UV detector using ODS, G18 column with 63% methanol as solvent. RESULTS: Of the 7 patients investigated, 6 had features typical of GA. One was diagnosed to have atypical retinitis pigmentosa (case 3). The first five cases had elevated ornithine and diminished OAT, but cases 6 and 7 had near-normal ornithine and case 7 had near-normal OAT. However, all 7 patients had increased levels of total polyamines in urine compared to normals. Five had increased putrescine and three had increased spermine. All the 7 had decreased cadaverine in urine. Thus, though there were inconsistencies with ornithine and OAT, all the 7 patients had elevated polyamines from ornithine and decreased cadaverine. CONCLUSION: In addition to estimating ornithine and OAT in GA, it is suggested that urinary polyamines may be analysed as the latter appears to correlate better with the clinical condition and help in the diagnosis to a greater extent. Moreover, while ornithine is an innocuous amino acid, polyamines are known to damage DNA and proteins.

Lid swelling and diplopia as presenting features of orbital sarcoid.

Sarcoid is an idiopathic multisystem non-caseating granulomatous disease with protean clinical manifestations. In the eye, the common sites of involvement are the skin of eyelid, conjunctiva, uveal tract, retina, optic nerve and lacrimal gland.