Nanoemulsions for enhanced skin permeation and controlled delivery of chlorohexidine digluconate.

Chlorhexidine digluconate (CHG) is a widely used antiseptic for skin disinfection, as it exhibits poor skin permeability. Therefore, aim of the present study was preparation and evaluation of CHG nanoemulsions (NEs) using high-speed homogenisation (HSH) combined with ultra-probe sonication to improve skin permeability. CHG-NEs were prepared using eucalyptus oil (EO) and olive oil (OO), with a surfactant-to-cosurfactant ratio of 2:1. Optimised NEs had a mean droplet diameter of 257.5 ± 12.4 nm and PDI of 0.56 ± 0.13. In In vitro permeation studies EO based NEs delivered more CHG into the skin, 6.15 ± 0.12 µg/mg compared to 3.01 ± 0.02 µg/mg for a control solution. Additionally NEs were incorporated into an in situ forming dressing and results showed controlled delivery of CHG within skin. Together, these findings bring new possibilities for topical antimicrobial treatment and prophylactic strategies in wound management.

Design and development of essential oil based nanoemulsion for topical application of triclosan for effective skin antisepsis.

The skin acts as a physical barrier to protect the body from the external physical and chemical environment. When skin is infected, the outer epidermal barrier is compromised and colonized with microbial growth. Wound infection presents an immense burden on healthcare costs and decreased the quality of life for patients. The topical application of nanoemulsions (NE) at pathological sites offers the potential advantage of direct drug delivery to the skin including the potential for follicular targeting. This may have application in the improvement of skin antisepsis. In this study, NEs of triclosan (TSN) were prepared using hot high shear homogenization followed by ultrasonication. The oil phases comprised eucalyptus oil (EO) and olive oil (OO) and pseudo-ternary phase diagrams were used to select optimum concentrations of surfactant. EO-based NEs had smaller droplet sizes and higher entrapment efficiency compared to OO-based NEs. Skin permeation was higher for EO-containing formulations, likely due to the higher solubility of TSN in EO, smaller droplet size, low viscosity, and permeation enhancement effects of EO. Significantly, TSN was retained within the skin, demonstrating the potential of NEs for targeting hair follicular delivery within the skin, which may help improve the success of topical antisepsis.

Comparison of root surface roughness produced by air polishing combined with hand instrumentation or ultrasonic instrumentation: an in vitro study.

The aim of this study was to examine the surface roughness produced by root debridement during periodontal maintenance therapy. The root surface roughness produced by hand scaling and subsequent glycine powder air polishing (GPAP) was compared with that produced by ultrasonic scaling and subsequent GPAP. Fifty extracted incisor and premolar teeth were collected and randomly allocated to the following 5 groups (n = 10 per group): 1, hand scaling followed by GPAP; 2, ultrasonic scaling followed by GPAP; 3, hand scaling alone; 4, ultrasonic scaling alone; and 5, no treatment. After the initial scaling procedure, specimens in groups 1 and 2 were incubated at 37°C for 3 days. The specimens then underwent GPAP for 5 seconds. All specimens were examined under a profilometer, and the root surface roughness was measured in micrometers. The specimens in groups 1 (hand scaling with GPAP) and 2 (ultrasonic scaling with GPAP) were studied in detail under a scanning electron microscope. The different protocols produced the following mean root surface roughness values: group 1, 2.31 µm; group 2, 4.33 µm; group 3, 5.84 µm; group 4, 6.32 µm; and group 5, 9.20 µm. The difference between groups 1 and 2 was statistically significant (P < 0.05). In this in vitro study, hand scaling with curettes produced smoother root surfaces than ultrasonic scaling. Adjunctive use of GPAP for 5 seconds along with hand scaling or ultrasonic scaling resulted in improved root surface smoothness during periodontal maintenance therapy.

Solid lipid nanoparticles for targeted delivery of triclosan into skin for infection prevention.

Healthcare-associated infections (HAIs) are a concern for health service providers, exacerbated by poor delivery of antimicrobials to target sites within the skin. The dermal route is attractive for local and systemic delivery of drugs, however; permeation, penetration, and access to deeper skin layers are restricted due to the barrier function of the stratum corneum (SC). Solid lipid nanoparticles present several benefits for topical delivery for therapeutic applications, especially via the follicular route. Hair follicles, surrounded by a close network of blood capillaries and dendritic cells, are an important target for delivery of antimicrobials and present a unique microbial nidus for endogenous infections in situations where the barrier is disrupted, such as after surgery, for example, triclosan, a broad-spectrum antimicrobial agent, was encapsulated into nanoparticles using glyceryl behenate and glyceryl palmitostearate (GP) solid lipids, and incorporating Transcutol P, a known permeation enhancer at different ratios. Optimised formulation was stable over 90 d and in vitro permeation studies using full thickness porcine ear skin showed that the lipid-based nanoparticles enhanced delivery of triclosan into the skin and could direct the agent towards hair follicles, indicating their potential as a carrier system for antiseptic dermal delivery.

Salivary Neutrophil-to-Lymphocyte Ratio as a Prognostic Predictor of Oral Premalignant and Malignant Disorders: A Prospective Study.

INTRODUCTION: Inflammation is a definitive characteristic of carcinogenesis. The neutrophil-to-lymphocyte ratio (NLR) is an easy and efficient indicator of inflammation and a valuable marker in individuals with malignancies. The present study was performed to ascertain NLR values in salivary samples collected from individuals with oral premalignant disorders (OPMDs) and to assess the prognostic significance of NLR in distinguishing OPMDs from oral malignancies. MATERIALS AND METHODS: This study was conducted on 50 patients histopathologically diagnosed with OPMDs with mild dysplasia. The patients were provided with standard medicinal treatment, encouraged to quit their habits, and followed up for one year at three-month regular intervals. During the follow-up, 29 (67.4%) patients completely recovered, whereas 14 (32.6%) developed oral malignancies. Salivary samples were collected at baseline (T0) and one-year follow-up (T1). The total salivary neutrophils and lymphocytes were counted using an improved cell counting method with a Neubauer chamber. The NLR values were calculated at T0 and T1. The paired t-test was used to compare the NLR values at T0 and T1. The cutoff value of the NLR was determined using the receiver operating characteristic (ROC) curve. The Youden index was used to determine the optimal cutoff NLR values in the groups. Statistical significance was set at p ≤0.05. RESULTS: OPMDs were predominantly observed in males, with leukoplakia being the most prevailing one. Erythroplakia exhibited the highest propensity for malignant transformation, and habitual consumption of alcohol and tobacco was identified as a risk factor for this transformation. NLR increased in both premalignant and malignant conditions. NLR value equal to or exceeding 4 was determined to be a reliable indicator for the occurrence of oral cancer in patients with OPMDs. The ROC curve analysis yielded a sensitivity and specificity of 92%, with an area under the curve (AUC) of 0.928. CONCLUSION: The poor prognosis of oral cancers was associated with higher NLR values. NLR values in salivary samples can serve as an independent reliable predictor in oral cancer and OPMDs.

Do rainfed production systems have lower environmental impact over irrigated production systems?: On -farm mitigation strategies.

The intensive agriculture practices improved the crop productivity but escalated energy inputs (EI) and carbon foot print (CF) which contributes to global warming. Hence designing productive, profitable crop management practices under different production systems with low environmental impact (EI and CF) is the need of the hour. To identify the practices, quantification of baseline emissions and the major sources of emissions are required. Indian agriculture has diversified crops and production systems but there is dearth of information on both EI and CF of these production systems and crops. Hence the present study was an attempt to find hot spots and identify suitable strategies with high productivity, energy use efficiency (EUE) and carbon use efficiency (CUE). Energy and carbon balance of castor, cotton, chickpea, groundnut, maize, rice (both rainfed and irrigated), wheat, sugarcane (only irrigated), pigeon pea, soybean, sorghum, pearl millet (only rainfed) in different production systems was assessed. Field specific data on different crop management practices as well as grain and biomass yields were considered. Rainfed production systems had lower EI and CF than irrigated system. The nonrenewable sources of energy like fertilizer (64 %), irrigation (78 %), diesel fuel (75 %) and electricity (67 %) are the major source of energy input. Rainfed crops recorded higher CUE over irrigated condition. Adoption of technologies like efficient irrigation strategies (micro irrigation), enhancing fertilizer use efficiency (site specific nutrient management or slow release fertilizer), conservation agriculture (conservation or reduced tillage) rice cultivation methods (SRI or Direct seeded rice) were the mitigation strategies. These results will help policy makers and stake holders in adoption of suitable strategies for sustainable intensification.

Soil bacterial community structure and functioning in a long-term conservation agriculture experiment under semi-arid rainfed production system.

Soil microbial communities are important drivers of biogeochemical cycling of nutrients, organic matter decomposition, soil organic carbon, and Greenhouse gas emissions (GHGs: CO2, N2O, and CH4) and are influenced by crop and soil management practices. The knowledge on the impact of conservation agriculture (CA) on soil bacterial diversity, nutrient availability, and GHG emissions in semi-arid regions under rainfed conditions is vital to develop sustainable agricultural practices, but such information has not been systemically documented. Hence, studies were conducted for 10 years in rainfed pigeonpea (Cajanus cajan L.)-castor bean (Ricinus communis L.) cropping system under semi-arid conditions to assess the effects of tillage and crop residue levels on the soil bacterial diversity, enzyme activity (Dehydrogenase, urease, acid phosphatase, and alkaline phosphatase), GHG emissions, and soil available nutrients (Nitrogen, phosphorus, and potassium). Sequencing of soil DNA through Illumina HiSeq-based 16S rRNA amplicon sequencing technology has revealed that bacterial community responded to both tillage and residue levels. The relative abundance of Actinobacteria in terms of Operational Taxonomic Unit (OTUs) at phyla, class as well as genera level was higher in CA (NTR1: No Tillage + 10 cm anchored residue and NTR2 NT + 30 cm anchored residue) over CT (conventional tillage without crop residues). CA resulted in higher enzyme activities (dehydrogenase, urease, acid phosphatase, and alkaline phosphatase) and reduction in GHG emissions over CT. CA recorded 34% higher and 3% lower OC, as compared to CT, and CTR1, respectively. CA recorded 10, 34, and 26% higher available nitrogen, phosphorus, and potassium over CT and CTR1, respectively. NTR1 recorded 25 and 38% lower N2O emissions as compared to CTR1 and CTR2, respectively. Whereas only NT recorded 12% higher N2O emissions as compared to CT. Overall, the results of the study indicate that CA improves the relative abundance of soil bacterial communities, nutrient availability, and enzyme activities, and may help to contribute to the mitigation of climate change, and sustainability in rainfed areas.

Pest scenario of Helicoverpa armigera (Hub.) on pigeonpea during future climate change periods under RCP based projections in India.

Gram pod borer, Helicoverpa armigera (Hub.) is the major insect pest of pigeonpea and prediction of number of generations (no. of gen.) and generation time (gen. time) using growing degree days (GDD) approach during three future climate change periods viz., Near (NP), Distant (DP) and Far Distant (FDP) periods at eleven major pigeonpea growing locations of India was attempted. Multi-model ensemble of Maximum (Tmax) and Minimum (Tmin) temperature data of four Representative Concentration Pathways viz., RCP 2.6, 4.5, 6.0 and 8.5 of Coupled Model Inter comparison Project 5 (CMIP5) models was adopted here. The increase in projected Tmax and Tmin are significant during 3 climate change periods (CCPs) viz., the NP, DP and FDP over base line (BL) period under four RCP scenarios at all locations and would be higher (4.7-5.1 °C) in RCP 8.5 and in FDP. More number of annual (10-17) and seasonal (5-8) gens. are expected to occur with greater percent increase in FDP (8 to 38%) over base line followed by DP (7 to 22%) and NP (5to 10%) periods with shortened annual gen. time (4 to 27%) across 4 RCPs. The reduction of crop duration was substantial in short, medium and long duration pigeonpeas at all locations across 4 RCPs and 3 CCPs. The seasonal no.of gen. is expected to increase (5 to 35%) with shortened gen. time (4 to 26%) even with reduced crop duration across DP and FDP climate periods of 6.0 and 8.5 RCPs in LD pigeonpea. More no. of gen. of H. armigera with reduced gen. time are expected to occur at Ludhiana, Coimbatore, Mohanpur, Warangal and Akola locations over BL period in 4 RCPs when normal duration of pigeonpeas is considered. Geographical location (66 to 72%), climate period (11 to 19%), RCPs (5-7%) and their interaction (0.04-1%) is vital and together explained more than 90% of the total variation in future pest scenario. The findings indicate that the incidence of H. armigera would be higher on pigeonpea during ensuing CCPs in India under global warming context.

Intercropping for management of insect pests of castor, Ricinus communis, in the semi-arid tropics of India.

Intercropping is one of the important cultural practices in pest management and is based on the principle of reducing insect pests by increasing the diversity of an ecosystem. On-farm experiments were conducted in villages of semi-arid tropical (SAT) India to identify the appropriate combination of castor (Ricinus communis L.) (Malpighiales: Euphorbiaceae) and intercropping in relation to pest incidence. The diversity created by introducing cluster bean, cowpea, black gram, or groundnut as intercrops in castor (1:2 ratio proportions) resulted in reduction of incidence of insect pests, namely semilooper (Achaea janata L.), leaf hopper (Empoasca flavescens Fabricius), and shoot and capsule borer (Conogethes punctiferalis Guenee). A buildup of natural enemies (Microplitis, coccinellids, and spiders) of the major pests of castor was also observed in these intercropping systems and resulted in the reduction of insect pests. Further, these systems were more efficient agronomically and economically, and were thus more profitable than a castor monocrop.

Tardive dyskinesia.

OPINION STATEMENT: Tardive dyskinesia (TD) is iatrogenic (drug-induced); hence the best strategy is prevention. Try to limit exposure to any dopamine receptor blocking agents (DRBAs) if possible. These agents may be unavoidable in some psychiatric conditions such as schizophrenia, but alternative therapies can be used in many situations, such as in the treatment of depression, anxiety, gastrointestinal conditions, and other neurologic conditions, including migraines and sleep disorders. When DRBAs are necessary, physicians should prescribe the smallest possible dose and try to taper and stop the drug at the earliest signs of TD. Abrupt cessation should be avoided, as this can worsen symptoms of TD. Always discuss and document the possibility of TD as an adverse effect when starting patients on DRBAs. If TD is mild and tolerable, the withdrawal of the offending agent is possible, and exposure to DRBAs was short, physicians should consider avoiding treatment and waiting for spontaneous recovery. When treatment is necessary, tetrabenazine (TBZ) is considered a potential first-line agent and is known to be one of the most effective drugs in treating TD, but it is expensive and adverse effects such as depression, akathisia and parkinsonism frequently occur. Therefore, second-line agents with better tolerability profiles are often tried first in practice. These include amantadine, benzodiazepines, beta-blockers, and levetiracetam. When using TBZ, adverse effects should be aggressively monitored. (Depression often can be managed with antidepressants, for instance). In patients with psychosis, withdrawal of the antipsychotic may not be possible. Switching to clozapine or quetiapine is one option to minimize TD. When these agents are contraindicated and the patient must continue using other atypical antipsychotic drugs, try to add dopamine-depleting agents such as TBZ or reserpine, but watch for the development of parkinsonism. When the symptoms are focal, such as tongue protrusion or blepharospasm, botulinum toxin injections can be very effective if spontaneous recovery does not occur. As a last resort, when disabling, life-threatening symptoms of TD persist despite all of the above-mentioned methods, some advocate resuming treatment with the DRBA to suppress symptoms of TD. This has the potential to worsen TD in the long run.

Drug Delivery Approaches for Managing Overactive Bladder (OAB): A Systematic Review.

Overactive bladder syndrome (OAB) is characterised by urgency symptoms, with or without urgency incontinence, usually with frequency and nocturia and severely affects the quality of life. This systematic review evaluates the various drug delivery strategies used in practice to manage OAB. Advanced drug delivery strategies alongside traditional strategies were comprehensively analysed and comparatively evaluated. The present review was conducted according to the preferred reporting items for systematic reviews and meta-analyses guidelines. A total of 24 studies reporting the development of novel formulations for the treatment of OAB were considered eligible and were further categorised according to the route of drug administration. The review found that various drug delivery routes (transdermal, intravesicular, oral, vaginal and intramuscular) are used for the administration of drugs for managing OAB, however, the outcomes illustrated the marked potential of transdermal drug delivery route. The findings of the current review are expected to be helpful for pharmaceutical scientists to better comprehend the existing literature and challenges and is anticipated to provide a basis for designing and fabricating novel drug delivery systems to manage OAB.

Root resection - Exploring ways beyond extraction.

One of the crucial challenges that any present-day general dentist confronts is the treatment determination between extracting a tooth and placement of a dental implant or by conserving the natural tooth with an interdisciplinary approach. The rising concern amongst the patients towards preserving their dentition has driven the clinicians towards providing treatment options that are more appropriate and conservative and at the same time does not hamper its functional needs. This report highlights one such way of preserving the periodontally compromised natural tooth with just resecting the diseased part of it and also conserving the proprioceptive capacity of the tooth. One-year of regular follow up and maintenance paving way to a healthy periodontium and complete resolution of mobility concerning the affected tooth is described. This report also provides information on root resection in a mandibular molar as a viable and a definitive treatment modality, providing better access to the remaining tooth structure and thereby enabling successive prosthetic rehabilitation.

Predicted equations for ventilatory function among Kuching (Sarawak, Malaysia) population.

Spirometry data of 869 individuals (males and females) between the ages of 10 to 60 years were analyzed. The analysis yielded the following conclusions: 1. The pattern of Forced Vital Capacity (FVC) and Forced Expiratory Volume in One Second (FEV1) for the selected subgroups seems to be gender dependant: in males, the highest values were seen in the Chinese, followed by the Malay, and then the Dayak; in females, the highest values were seen in the Chinese, followed by the Dayak, and then the Malay. 2. Smoking that did not produce respiratory symptom was not associated with a decline in lung function, in fact we noted higher values in smokers as compared to nonsmokers. 3. Prediction formulae (54 in total) are worked out for FVC & FEV1 for the respective gender and each of the selected subgroups.

Lipid nanoparticles for dermal drug delivery.

Lipid based drug delivery systems have been widely studied and reported over the past decade and offer a useful alternative to other colloidal drug delivery systems. Skin is a popular route of drug delivery for locally and systemically acting drugs and nanoparticles are reported as a potential formulation strategy for dermal delivery. Although the skin acts as a natural physical barrier against penetration of foreign materials, including particulates, opportunities exist for the delivery of therapeutic nanoparticles, especially in diseased and damaged skin and via appendageal routes such as the openings of hair follicles. The extent and ability of nanoparticles to penetrate into the underlying viable tissue is still the subject of debate although recent studies have identified the follicular route as the most likely route of entry; this influences the potential applications of these dosage forms as a drug delivery strategy. This paper reviews present state of art of lipid-based nanocarriers focussing on solid lipid nanoparticles, nanostructured lipid carriers and nanoemulsions, their production methods, potential advantages and applications in dermal drug delivery.

Rotavirus immunoglobulin levels among Indian mothers of two socio-economic groups and occurrence of rotavirus infections among their infants up to six months.

Rotavirus specific immunoglobulin levels were estimated and compared between mothers undergoing delivery from two socio-economic groups (n = 56 each) by direct/capture ELISA. IgG geometric mean titers (GMTs) of cord blood/mothers serum at delivery were significantly higher in the higher socio-economic group (HSG) as compared to the lower socio-economic group (LSG) (P < 0.01). Thirty-four mother-infant pairs (17 from each group) were followed-up up to 6 months for the occurrence of rotavirus infections. All follow-up LSG infants were low birth weight as against none from the HSG. Detection of virus by ELISA/RT-PCR and considering IgM/IgA seroconversion as an index of infection, 11 and 17 infants from HSG and LSG respectively had rotavirus infections. Two infants from LSG were hospitalized for severe rotavirus diarrhea but none from the HSG. Lower IgG levels in the LSG mother-infant pairs as compared to those of HSG, suggests a possible role of under nutrition in development of antibodies and immunity. Infants from the HSG who did not have rotavirus infections had significantly higher IgG GMTs in cord blood and serum samples at 6 months, than those HSG infants who had symptomatic/asymptomatic rotavirus infections (P < 0.05). In conclusion, fewer rotavirus infections occur when cord blood contains higher level of IgG antibodies, suggesting a role of protective immunity.

Measurement of antirotavirus IgM/IgA/IgG responses in the serum samples of Indian children following rotavirus diarrhoea and their mothers.

Rotavirus specific, serum IgM/IgA/IgG levels among hospitalized children and their respective mothers were determined. Children were grouped as having rotavirus diarrhoea (RVD) and non-rotavirus diarrhoea (NRVD) on the basis of fecal excretion measured by ELISA and RT-PCR. Although IgM seropositivity was observed among children of both the groups, it was significantly higher in the acute as well as convalescent phase serum samples (P < 0.05 for both) of RVD group. Five out of ten acute sera from the NRVD group were positive for IgM and seven showed IgA/IgG seroconversion indicating rotavirus infection among these children in the past. It was noted that, three out of 24 mothers' sera from RVD group, showed presence of IgM in the serum collected during convalescence of their children. The observation suggests, subclinical rotavirus infection among mothers probably contacted from their children. This is supported by the seroconversion for IgA/IgG among these three mothers. Such a phenomenon was not noticed among the mothers from NRVD group. In general, IgA positivity did not vary significantly among the children from both the groups. IgA seropositivity was significantly higher (P < 0.001) from children of RVD group as compared to healthy group of children following rotavirus infection. From RVD group, all the child patients and 12 mothers out of 24 (50%) showed IgA/IgG seroconversion. None of the mothers from NRVD group showed seroconversion. Serum samples of healthy children and adults, showed IgM positivity at equal level (10%), but a significant difference (P < 0.01) was observed in IgA positivity. In conclusion, subclinical transmission of rotavirus infection from children to their mothers may occur. Seroconversion alone cannot be considered as a marker of rotavirus diarrhoea in children. Moreover, about 40-50% of subjects lacked rotavirus specific IgA at protective levels, making them susceptible to rotavirus infection.

Prevalence of neutralizing antibodies against different rotavirus serotypes in children with severe rotavirus-induced diarrhea and their mothers.

Neutralizing antibody (NAb) responses to different rotavirus serotypes were compared in 64 convalescent-phase serum samples from hospitalized rotavirus-positive children less than 2 years of age and their mothers. Compared to the child patients, the mothers showed significantly higher NAb positivity to animal rotavirus serotypes G3 simian (96.88%), G6 bovine (85.94%), and G10 bovine (25.0%) and to human rotavirus serotypes G8 (79.69%) and G3 (57.81%) (P < 0.01 for each) but not to human serotypes G1, G2, G4, and G9 (P > 0.05). The overall prevalence of NAb among the child patients was low for human rotavirus serotypes G1 (20.31%) and G3 (21.8%). The comparative NAb response in individual mother-child paired serum samples was analyzed against each rotavirus serotype. A substantial number of child patients showed higher NAb titers than their mothers to serotypes G1, G2, G4, and G9, indicating that these serotypes are the major serotypes causing rotavirus diarrhea among the children of Pune, India. In these cases, the mothers were either negative or had lower titers of NAbs than their children. Correlation was observed between the infecting serotype and child patient serum that showed a homologous NAb response at a higher level than that of the mother. It appears that when the level of NAb to a particular serotype is higher among child patients than among their mothers, that serotype is the infecting serotype, and that low titers of NAb among the mothers predispose the children to infection with that serotype, if the serotype is in circulation.

Complications of anaesthesia and surgery for laryngotracheo-oesophageal cleft.

Laryngotracheo-oesophageal cleft presents great difficulty in airway management. Tracheostomy and/or bilateral endobronchial intubation to secure the airway and a feeding gastrostomy are essential to sustain life until major definitive surgery can be planned. We describe the anaesthesia for these emergency life saving procedures in a 1.1-kg, 2-day-old neonate of 29 weeks gestation with apnoeic spells. Endoscopy to diagnose the extent of cleft, probable tracheostomy and gastrostomy were planned. Oesophagoscopy and bronchoscopy revealed a grade 3-4 cleft. Inadequate spontaneous ventilation during these procedures necessitated positive pressure ventilation. This resulted in a gaseous distension of an intact stomach which could be decompressed into the oesophagus. After the bronchoscopy, the use of a 3-mm tracheal tube without a Murphy's eye minimized the distension during gastrostomy. There was an accidental extubation after gastrostomy. Emergency reintubation with a 4-mm tracheal tube with a Murphy's eye resulted in gastric distension which led to tension pneumoperitoneum with a disappearance of PECO2. Misdiagnosis of this as loss of airway led to repeated intubations and extubation until the pneumoperitoneum was suspected and decompressed. After this setback, the baby's condition deteriorated over the next few hours ending fatally. The problems and suggestions to avoid these complications are discussed.