Development of olmesartan medoxomil optimized nanosuspension using the Box-Behnken design to improve oral bioavailability.

The aim of the present investigation was to enhance the oral bioavailability of olmesartan medoxomil by improving its solubility and dissolution rate by preparing nanosuspension (OM-NS), using the Box-Behnken design. In this, four factors were evaluated at three levels. Independent variables include: concentration of drug (X1), concentration of surfactant (X2), concentration of polymer (X3) and number of homogenization cycles (X4). Based on preliminary studies, the size (Y1), zeta potential (ZP) (Y2) and % drug release at 5 min (Y3) were chosen as dependent responses. OM-NS was prepared by high pressure homogenization method. The size, PDI, ZP, assay, in vitro release and morphology of OM-NS were characterized. Further, the pharmacokinetic (PK) behavior of OM-NS was evaluated in male wistar rats. Statistically optimized OM-NS formulation exhibited mean particle size of 492 nm, ZP of -27.9 mV and 99.29% release in 5 min. OM-NS showed more than four times increase in its solubility than pure OM. DSC and XRD analyses indicated that the drug incorporated into OM-NS was in amorphous form. The morphology of OM-NS was found to be nearly spherical with high dispersity by scanning electron microscopic studies. The PK results showed that OM lyophilized nanosuspension (NS) exhibited improved PK properties compared to coarse powder suspension and marketed tablet powder suspension (TS). Oral bioavailability of lyophilized NS was increased by 2.45 and 2.25 folds when compared to marketed TS and coarse powder suspension, respectively. Results of this study lead to conclusion that NS approach was effective in preparing OM formulations with enhanced dissolution and improved oral bioavailability.

Study of sleep microstructure in patients of migraine without aura.

PURPOSE: Although the relationship between sleep and migraine has been widely reported, studies on sleep microstructure are few. The aim was to study and compare microstructural polysomnographic characteristics in patients of "migraine without aura" (MOA) with controls. METHODS: Twenty-five patients of MOA and 25 age- and gender-matched healthy controls were subjected to overnight polysomnography. Microstructural sleep analysis, including arousal and cyclic alternating pattern (CAP) analysis was performed. Arousals and CAP parameters were compared between the two groups using the Mann-Whitney U test (p ≤ 0.05). RESULTS: The overall arousal index (p = 0.528) and that during non-rapid eye movement (NREM) sleep (p = 0.503) were comparable between the two groups. However, the arousal index was lower in migraineurs during rapid eye movement (REM) sleep (p = 0.001). The overall CAP rate (p = 0.020) as well as the number of CAP cycles and sequences (p = 0.032) was lower among migraineurs. The total phase A duration (p < 0.0001) was increased, and conversely, phase B duration (p = 0.001) was decreased in migraineurs. The phase A1 duration (p = 0.036) was higher in migraineurs. Finally, phase A1 (p = 0.357) index was comparable, and conversely, A2 (p < 0.0001) and A3 (p = 0.020) indices were decreased in migraineurs. CONCLUSIONS: This study showed a decreased REM arousability as well as a decreased overall CAP rate and CAP cycling in patients with migraine as compared to controls. This indicates that there is probably an alteration of the arousal mechanisms in patients with migraine that may facilitate the occurrence of headache paroxysms during sleep.

Predictive models of lameness in dairy cows achieve high sensitivity and specificity with force measurements in three dimensions.

Lameness remains a significant cause of production losses, a growing welfare concern and may be a greater economic burden than clinical mastitis . A growing need for accurate, continuous automated detection systems continues because US prevalence of lameness is 12.5% while individual herds may experience prevalence's of 27.8-50.8%. To that end the first force-plate system restricted to the vertical dimension identified lame cows with 85% specificity and 52% sensitivity. These results lead to the hypothesis that addition of transverse and longitudinal dimensions could improve sensitivity of lameness detection. To address the hypothesis we upgraded the original force plate system to measure ground reaction forces (GRFs) across three directions. GRFs and locomotion scores were generated from randomly selected cows and logistic regression was used to develop a model that characterised relationships of locomotion scores to the GRFs. This preliminary study showed 76 variables across 3 dimensions produced a model with greater than 90% sensitivity, specificity, and area under the receiver operating curve (AUC). The result was a marked improvement on the 52% sensitivity, and 85% specificity previously observed with the 1 dimensional model or the 45% sensitivities reported with visual observations. Validation of model accuracy continues with the goal to finalise accurate automated methods of lameness detection.

Quick and Easy Placement of Coil Spring.

A tooth displaced palatally in an arch often demands placement of an open coil spring for gaining space. Ligation of an archwire with compressed coil spring is a cumbersome process. We have made use of 0.010 supreme AJ Wilcock sectional wire to compress the open coil spring and place it on the required dental arch.

Treatment of a high angle class II malocclusion with severe crowding and enlarged adenoids: a case report.

AIM: The aim is to present the treatment of an 11-year-old, hyperdivergent, Class II division I, female patient with a history of enlarged adenoids and severe arch length discrepancies. METHODS: The malocclusion was treated by upper right molar distalisation and first premolar extractions. Accurate diagnosis, meticulous treatment planning and an unexpectedly favourable growth pattern lead to a highly satisfactory outcome. RESULTS: There was a significant improvement in facial profile, overjet and occlusion. A significant decrease in the mandibular plane angle was recorded, without the use of any extra-oral appliance. CONCLUSION: The treatment results remained stable after six years of retention following maintenance of the favourable growth pattern.

Prosthodontic Management of HIV/AIDS Subjects: An Overview.

Provision for high standard of oral health care is a fundamental requirement for any individual and dentists constantly strive to provide optimal treatment to their patients. However, when it comes to treating subjects with infectious diseases particularly those attached with social stigma like HIV/AIDS, there remains doubts and hesitations. This may lead the practitioners to breach the ethical responsibility by denying or not providing adequate treatment to these patients. Such situations can easily be avoided with thorough knowledge and awareness among the oral health care providers including prosthodontists regarding the disease process, its implications and measures to be taken during their treatment. This article summarises key points in prosthodontic management of HIV/AIDS patients which in the opinion of the author may be easily incorporated in routine dental practice.

Acceptable Deviation between Facial and Dental Midlines in Dentate Population.

The success of the dental restorations largely depends on its esthetics, although various literature reviews recommend that anterior teeth midline be placed coinciding the facial midline, the amount of acceptable deviation between facial and dental midline has not been fully investigated. To observe the acceptable deviation between the dental and facial midline. Facial photographs of 200 students aged about 18-30 years of both sexes, without any missing teeth, with complete alignment of anterior teeth, were selected and scanned on to computer screen. Using specialized programme, the crown width of the central incisor in the mouth and on photograph was ensured constant. The distance between the facial midline, (obtained by bisecting intercanthal line) and the mesial surfaces of the central incisors were read on the computer. 44.4 % Boys and 55 % of Girls showed deviation between dental and facial midline in the range of 0-1 mm. while, 54 % of boys and 33 % of girls showed deviation of the dental and facial midline in the range 1-2 mm. 37 % of boys and 8 % of girls showed deviation of dental midline with facial midline with the range of 2-3 mm. 80 % of the study population showed maxillary and mandibular dental midlines never coincide. Majority of the study population showed deviation between facial midline and anterior teeth midline within the range of 0-1 mm.

Colorimetric chemosensors for the selective detection of arsenite over arsenate anions in aqueous medium: Application in environmental water samples and DFT studies.

Novel organic receptors N3R1- N3R3 were developed for the selective colorimetric recognition of arsenite ions in the organo-aqueous media. In the 50% aq. acetonitrile media and 70% aq. DMSO media, receptors N3R2 and N3R3 showed specific sensitivity and selectivity towards arsenite anions over arsenate anions. Receptor N3R1 showed discriminating recognition of arsenite in the 40% aq. DMSO medium. All three receptors formed a 1:1 complex with arsenite and stable for a pH range of 6-12. The receptors N3R2 and N3R3 achieved a detection limit of 0.008 ppm (8 ppb) and 0.0246 ppm, respectively, for arsenite. Initial hydrogen bonding on binding with the arsenite followed by the deprotonation mechanism was well supported by the UV-Vis titration, 1H- NMR titration, electrochemical studies, and the DFT studies. Colorimetric test strips were fabricated using N3R1- N3R3 for the on-site detection of arsenite anion. The receptors are also employed for sensing arsenite ions in various environmental water samples with high accuracy.

Sample size determination for alternate periods of use study designs with binary responses.

In this article, we consider several study designs that arise in practice, which are variations of standard crossover designs. Often, they may result from modifications made to a standard crossover design due to practical considerations. Characteristic features of the studies we are concerned with are (a) treatments consist of external use of products with little or no possibility of carry over effects, and (b) the periods of use are dictated by the subjects or by some specific event, such as diaper leakage or menstrual flow. We consider a number of such study designs for estimating the difference in the efficacy of two treatments or test products. We provide brief descriptions of studies to motivate the study design, the underlying data structure, and computations of the variances of the usual unbiased estimators of the difference in efficacy, and the sample size formulas. The situations considered here cover a number of popular crossover designs. The objective of our work is to provide guidance to members of a wide audience on how to answer the sample size question for their own nonstandard situations. We conclude the article with a brief report on a simulation study we conducted to investigate the impact of estimation on the sample size determination and consequently on the actual power realized in an effort to promote the "best practice" of checking whether the recommended sample sizes indeed achieve the desired level of power.

Modified transpalatal arch for molar intrusion.

We have modified transpalatal arch (TPA) to intrude the extruded molar. The appliance is fabricated from 0.036 inch stainless steel wire which has a palatal and buccal arm. The appliance is activated by stretching an elastomeric chain from the palatal to the buccal arm such that the stretched chain lies across the occlusal surface of extruded second molar with an intensive force of 50 grams. The advantages of this appliance include reduced chair side time, patient comfort and cost effectiveness.

Diversity in the magnitude of hind limb unloading occurs with similar forms of lameness in dairy cows.

The objective of the study was to evaluate the relationship of veterinary clinical assessments of lameness to probability estimates of lameness predicted from vertical kinetic measures. We hypothesized that algorithm-derived probability estimates of lameness would accurately reflect vertical measures in lame limbs even though vertical changes may not inevitably occur in all lameness. Kinetic data were collected from sound (n=179) and unilaterally lame (n=167) dairy cattle with a 1-dimensional, parallel force plate system that registered vertical ground reaction force signatures of all four limbs as cows freely exited the milking parlour. Locomotion was scored for each hind limb using a 1-5 locomotion score system (1=sound, 5=severely lame). Pain response in the interdigital space was quantified with an algometer and pain response in the claw was quantified with a hoof tester fitted with a pressure gage. Lesions were assigned severity scores (1=minimal pathology to 5=severe pathology). Lameness diminished the magnitude of peak ground reaction forces, average ground reaction forces, Fourier transformed ground reaction forces, stance times and vertical impulses in the lame limbs of unilaterally lame cows. The only effect of lameness on the opposite sound limb was increased magnitude of stance times and vertical impulses in unilaterally lame cows. Symmetry measures of the peak ground reaction forces, average ground reaction forces, Fourier transformed ground reaction forces, stance times and vertical impulses between the left and right hind limbs were also affected in unilateral lameness. Paradoxically, limbs with clinically similar lesion and locomotion scores and pain responses were associated with a broad range of load-transfer off the limb. Substantial unloading and changes in the vertical limb variables occurred in some lameness while minimal unloading and changes in vertical limb variables occurred in other lameness. Corresponding probability estimates of lameness accurately reflected changes in the vertical parameters of limbs and generated low probability estimates of lameness when minimal unloading occurred. Failure to transfer load off limbs with pain reactions, locomotion abnormalities and lesions explained much of the limited sensitivity in lameness detection with vertical limb variables.

Alignment of an ectopic canine with mini-implant anchorage: a case report.

AIMS: To describe the treatment of an ectopic maxillary left canine and Class II molar relationship in a 12 year-old girl. METHODS: A pendulum appliance was used in a first phase of treatment to distalise the maxillary molars to a Class I molar relationship. In the second phase of treatment, a mini-implant, inserted between the roots of the left maxillary central and lateral incisors, provided anchorage to move an ectopic maxillary left canine into position. RESULTS: The implant remained stable throughout treatment and a maxillary canine - first premolar transposition was corrected. Good overjet and overbite were achieved and have been maintained one year after completion of active treatment.

Stainless hooks to bond lower lingual retainer.

We introduced a simple and economical technique for precise placement of lower lingual retainers. Two stainless steel hooks made of 0.6mm wire are placed interdentally in the embrasure area between canine and lateral incisor bilaterally to lock the retainer wire in the correct position. Etch, rinse and dry the enamel surfaces with the retainer passively in place, then bond the retainer with light-cured adhesive. Hooks are simple to fabricate and eliminate the need for a transfer tray.

Gingival biotype - Prosthodontic perspective.

During treatment planning it is important to recognize different gingival biotypes and forms, because they can affect the esthetic outcome of the treatment. This review provides an insight into the different gingival biotypes, their response to inflammation and trauma; significance in different prosthodontic modalities like esthetic rehabilitation and implant therapy.

Utilisation of Anganwadi services among pregnant women in rural Telangana: A cross sectional study.

BACKGROUND: Anganwadi centers were providing integrated services comprising supplementary nutrition, immunization, health check-up, and referral services to children below six years of age and expectant and nursing mothers. After more than three decades of implementation, the success of Integrated Child Development Services (ICDS) program in tackling maternal and childhood problems still remains a matter of concern. OBJECTIVES: To estimate the proportion of pregnant women utilizing various services provided by the anganwadi centre. To assess the association between demographic factors and utilization of anganwadi services by pregnant women. METHODS: A cross-sectional study with a sample size of 135 was conducted in three villages attached to a medical college. Pregnant women enrolled in anganwadi the center were included in the study. Data was collected by a predesigned pretested semi-structured questionnaire. Data was presented in proportions, odds ratio with confidence interval, and Chi-square test, Fisher test was applied to find the association between variables by using SPSS ver. 23. RESULTS: The study showed 86.66% utilized supplementary nutrition services, 62.96% received health education, 85.92% took vaccines from anganwadi centre, 40.74% utilized referral services, and 82.22% utilized health checkups services provided by anganwadi centre. Distance from the centre was found to be an important determinant of the utilization of anganwadi services. CONCLUSIONS: There is a need to sensitize and motivate beneficiaries to utilize the services offered by anganwadi center.

Measuring early pre-symptomatic changes in locomotion of SOD1-G93A rats--a rodent model of amyotrophic lateral sclerosis.

A locomotion analysis system for laboratory rats is presented. The system produces locomotion parameters (LPs) in 4 different domains: force, space, time and frequency. Video images of the walking rats are used to associate the system signals with individual limbs. Numerous LPs can be derived for every test run when the rat walks through the system on the way to sweets and a personal toy placed at the exit. This manuscript demonstrates that in order to differentiate SOD1-G93A mutant rat, a model of amyotrophic lateral sclerosis (ALS), from a Sprague Dawley (SD) control rat at a pre-symptomatic stage, one has only to use 8 key parameters. These 8 parameters are the bio-markers of ALS. The spline-based transformed values of these parameters are used as explanatory variables of a logistic regression model. This model predicts the probability that the examined rat belongs to the SOD1-G93A group. The model differentiates faultlessly between the SOD1 and control groups from the very first time the rats walked through the system at 51 days old. This system provides a new paradigm for ALS diagnosis, and it can have a significant impact on the development of new therapeutic procedures for ALS. The methodology presented in this manuscript can further address the development and validation of therapeutic procedures for other neurological diseases that affect locomotion.

Impacted maxillary central incisor, canine, and second molar with 2 supernumerary teeth and an odontoma.

This report describes the orthodontic treatment of a 14-year-old boy who had 3 impacted maxillary teeth (right canine, left central incisor, and left second molar), 2 supernumerary teeth, and an odontoma. The treatment protocol involved surgical intervention followed by sequential traction of the 3 impacted teeth. The patient's smile dramatically improved after orthodontic treatment. Good posterior occlusion was achieved. However, long-term monitoring of the stability and periodontal health is critical.

Dentoskeletal and soft tissue effects of mini-implants in Class II division 1 patients.

OBJECTIVE: To examine the skeletal, dental, and soft tissue treatment effects of retraction of maxillary anterior teeth with mini-implant anchorage in nongrowing Class II division 1 female patients. MATERIALS AND METHODS: Twenty-three patients (overjet > or =7 mm) were selected on the basis of predefined selection criteria. Treatment mechanics consisted of retraction of anterior teeth by placing mini-implants in the interdental bone between the roots of the maxillary first molar and second premolar. A force of 150 g was applied, bilaterally. Treatment effects were analyzed by taking lateral cephalograms and study casts at T1 (before initiation of retraction) and at T2 (after complete space closure). RESULTS: The upper anterior teeth showed significant retraction (5.18 +/- 2.74 mm) and intrusion (1.32 +/- 1.08 mm). The upper first molar also showed some distal movement and intrusion, but this was not significant (P > .05). The upper and lower lips were retracted by 2.41 mm and 2.73 mm, respectively, and the convexity angle reduced by over 2 degrees (P < .001). CONCLUSION: Mini-implants provided absolute anchorage to bring about significant dental and soft tissue changes in moderate to severe Class II division 1 patients and can be considered as possible alternatives to orthognathic surgery in select cases.

Clinical investigation of periodontal ligament distraction osteogenesis for rapid orthodontic canine retraction.

AIMS: To investigate rapid canine distalisation by periodontal ligament distraction and to determine the effects of periodontal ligament distraction on the canine root and pulpal vitality. METHODS: The sample consisted of 16 upper canines in eight patients who required first premolar extractions. The upper first premolars were extracted and the interseptal bone distal to each canine was thinned and undermined surgically. Custom-built distractors were placed and activated immediately to distract the canines into the extraction spaces. Radiographs were taken before canine distraction and at regular intervals thereafter. The upper canine pulps were tested with an electronic pulp tester before and after the distraction and the canines were examined on the post-distraction radiographs for evidence of apical and lateral root resorption. RESULTS: The canines were retracted to proximal contact with the second premolars in 20.33 +/- 1.87 days. The average amount of retraction was 5.25 mm and the canines tipped distally 15.33 degrees. Although the upper molars did not move mesially, they extruded almost 1 mm. Root resorption was minimal and there was no deterioration in pulp vitality. CONCLUSION: Canines can be rapidly retracted by periodontal ligament distraction without complications. However, the efficacy of the method depends upon the surgical procedure, which is technique sensitive. Resistance offered by the interseptal bone distal to the apex of the canine was thought to be the reason for the canine tipping during distraction.