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A longstanding goal of translational neuroscience is the ability to noninvasively deliver therapeutic agents to specific brain regions at the right time. Focused ultrasound (FUS) is an emerging technology that can noninvasively deliver high amounts of energy with millimeter and millisecond resolution to any point in the human brain with FDA-approved hardware. Although FUS is clinically utilized primarily for focal ablation in conditions such as essential tremor, recent breakthroughs have enabled the use of FUS for drug delivery. In this review, we present strategies for image-guided FUS-mediated pharmacologic neurointerventions. First, we discuss blood-brain barrier opening to deliver therapeutic agents of a variety of sizes to the central nervous system. We then describe the use of ultrasound-sensitive nanoparticles to noninvasively deliver small molecules to millimeter-sized structures within the brain without the need for blood-brain barrier opening. We also consider the safety and potential complications of these techniques, with attention to temporal acuity. Finally, we close with a discussion of different methods for mapping the ultrasound field within the brain and describe future avenues of research in ultrasound-targeted drug therapies.

Multilevel Inverters (MLI) are a viable option for a filter-less and transformerless photovoltaic system for direct grid integration, reducing losses, space and cost provided the issues of control and reliability are resolved. A modified cascaded half-bridge MLI with polarity changer is proposed with a reduced number of switches, thereby reducing control complexity. The proposed converter is designed for both seven-level and nine-level topologies. Selective harmonic elimination has been adopted to switch converter and the transcendental equations are solved by the gravitational search algorithm. The THD for nine-level configuration is 7.94% and 5.86% with MPPT and DC source inputs, respectively. The analysis on the open-circuit fault of switches confirms the presence of only five critical switches irrespective of the number of increase in levels, thereby requiring only five redundant switches at the Polarity Changer. The output voltage waveform is subjected to multiresolution analysis for feature extraction of voltages under various irradiance and temperature conditions. A conditions based fault detection algorithm is developed based on the observations of energies of signals to detect the open circuit fault in switches. Based on the comparative analysis, the proposed converter has fewer controlled switches for nine levels or higher configurations than other topologies. Apart from this, the high reliability due to inherent fault isolation capability restricted to half-bridge compared to different MLI topologies shows its superiority. For a nine-level MLI proposed topology reduces the cost considering redundancies for FDI in range of 67–30% depending on the topology for comparision. The system is simulated using MATLAB –Simulink and further validated by experimental results.

Glucagon-like peptide 2 (GLP-2) is a 33-aa proglucagon-derived peptide produced by intestinal enteroendocrine cells. GLP-2 stimulates intestinal growth and up-regulates villus height in the small intestine, concomitant with increased crypt cell proliferation and decreased enterocyte apoptosis. Moreover, GLP-2 prevents intestinal hypoplasia resulting from total parenteral nutrition. However, the mechanism underlying these actions has remained unclear. Here we report the cloning and characterization of cDNAs encoding rat and human GLP-2 receptors (GLP-2R), a G protein-coupled receptor superfamily member expressed in the gut and closely related to the glucagon and GLP-1 receptors. The human GLP-2R gene maps to chromosome 17p13.3. Cells expressing the GLP-2R responded to GLP-2, but not GLP-1 or related peptides, with increased cAMP production (EC50=0.58 nM) and displayed saturable high-affinity radioligand binding (Kd= 0.57 nM), which could be displaced by synthetic rat GLP-2 (Ki= 0.06 nM). GLP-2 analogs that activated GLP-2R signal transduction in vitro displayed intestinotrophic activity in vivo. These results strongly suggest that GLP-2, like glucagon and GLP-1, exerts its actions through a distinct and specific novel receptor expressed in its principal target tissue, the gastrointestinal tract.

Background & objectives: Chikungunya virus (CHIKV), a mosquito-borne arthritogenic virus causes infections ranging from febrile illness to debilitating polyarthralgia in humans. Re-emergence of the virus has affected millions of people in Africa and Asia since 2004. During the outbreak, a new lineage of the virus has evolved as an adaptation for enhanced replication and transmission by Aedes albopictus mosquito. A study was designed to compare the susceptibility of four vertebrate cell lines, namely Vero E6 (African green monkey kidney), BHK-21 (Baby hamster kidney), RD (human rhabdomyosarcoma), A-549 (human alveolar basal epithelial cell) and C6/36 (Ae. albopictus) to Asian genotype and two lineages of East, Central and South African (E1:A226 and E1:A226V) of CHIKV. Methods: One-step growth kinetics of different CHIKV strains was carried out in the above five cell lines to determine the growth kinetics and virus yield. Virus titre was determined by 50 per cent tissue culture infectious dose assay and titres were calculated by the Reed and Muench formula. Growth and virus yield of the three strains in Ae. aegypti mosquitoes was studied by intrathoracic inoculation and virus titration in Vero E6 cell line. Results: Virus titration showed Vero E6, C6/36 and BHK-21 cell lines are high virus yielding with all the three lineages while RD and A-549 yielded low virus titres. C6/36 cell line was the most sensitive and yielded the maximum titre. Ae. aegypti mosquitoes, when inoculated with high titre virus, yielded an almost equal growth with the three strains while rapid growth of E1:A226V and Asian strain was observed with 1 log virus. Interpretation & conclusions: C6/36 cell line was found to be the most sensitive and high yielding for CHIKV irrespective of lineages while Vero E6 and BHK-21 cell lines yielded high titres and may find application for vaccine/diagnostic development. Infection of Ae. aegypti mosquitoes with the three CHIKV strains gave almost identical pattern of growth.

The whole-plant, Pergularia daemia (Family: Asclepediaceae), extract (50% alcohol) was investigated for its antiurolithiatic and diuretic activity. Ethylene glycol (0.75% in water) feeding resulted in hyperoxaluria as well as increased renal excretion of calcium and phosphate. Alcoholic extract (400 mg/kg) of P. daemia was given orally in curative and preventive regimens over a period of 28 days. Supplementation with extract significantly (P < 0.001) lowered the urinary excretion and kidney retention levels of oxalate, calcium and phosphate. Furthermore, high serum levels of urea nitrogen, creatinine and uric acid were significantly (P < 0.001) reduced by the extract. The results were comparable with the standard drug, cystone (750 mg/kg). The reduction of stone-forming constituents in urine and their decreased kidney retention reduces the solubility product of crystallizing salts such as calcium oxalate and calcium phosphate, which could contribute to the antiurolithiatic property of the extract. The extract exhibited significant diuretic activity at dose of 400 mg/kg body weight as evidenced by increased total urine volume and the urine concentration of Na(+), and K(+). These findings affirm assertions made regarding the effectiveness of the extract of this plant against urinary pathologies in the Indian folk medicine.

Background: Sciatic nerve is a mixed nerve which provide sensory and motor supply for skin and muscles of the lower limb by tibial and common peroneal nerve. Anatomical variations of sciatic nerve at high division have been reported by various authors. The path of the sciatic nerve is important while administration of intramuscular injection to prevent nerve injury and nerve blockage failure during anesthesia. This knowledge of high division helps in different surgical approach for sciatic nerve injury or hip dislocation. Aims and Objectives: The aim of the study was to describe incidences of high division variation of Sciatic nerve and different types in cadavers during routine dissection schedule. Materials and Methods: The study was conducted during routine dissection schedule in anatomy department for first MBBS students to observe sciatic nerve course in 30 gluteal regions from 15 adult cadavers fixed by formalin. Location of sciatic nerve in relation to piriformis muscle and its division whether in single nerve sheath or separate sheath and types was recorded. Results: In 12 cadavers (80%), sciatic nerve course found normal which leaves pelvis at inferior border of piriformis muscle and bifurcate in terminal branches tibial nerve and common peroneal nerve as it approaches at the apex of popliteal fossa. In 3 cadavers (20%), two male and one female, we found high division of sciatic nerve where terminal branches, tibial nerve, and common peroneal nerve leave the pelvis below piriformis separately in different sheaths. Conclusion: Knowledge of variations-related high division of sciatic nerve would help surgeons during different interventions related to sciatic nerve and for preventing further complications.

An important component of assessing the hazards of anticoagulant rodenticides to non-target wildlife is observations in exposed free-ranging individuals. The objective of this study was to determine whether environmentally realistic, sublethal first-generation anticoagulant rodenticide (FGAR) exposures via prey can result in direct or indirect adverse effects to free-flying raptors. We offered black-tailed prairie dogs ( Cynomys ludovicianus ) that had fed on Rozol® Prairie Dog Bait (Rozol, 0.005% active ingredient chlorophacinone, CPN) to six wild-caught red-tailed hawks (RTHA, Buteo jamaicensis ), and also offered black-tailed prairie dogs that were not exposed to Rozol to another two wild-caught RTHAs for 7 days. On day 6, blood was collected to determine CPN’s effects on blood clotting time. On day 7, seven of the eight RTHAs were fitted with VHF radio telemetry transmitters and the RTHAs were released the following day and were monitored for 33 days. Prothrombin time (PT) and Russell’s viper venom time confirmed that the CPN-exposed RTHAs were exposed to and were adversely affected by CPN. Four of the six CPN-exposed RTHAs exhibited ptiloerection, an indication of thermoregulatory dysfunction due to CPN toxicity, but no signs of intoxication were observed in the reference hawk or the remaining two CPN-exposed RTHAs. Of note is that PT values were associated with ptiloerection duration and frequency; therefore, sublethal CPN exposure can directly or indirectly evoke adverse effects in wild birds. Although our sample sizes were small, this study is a first to relate coagulation times to adverse clinical signs in free-ranging birds.

Background Status epilepticus is a neurological emergency and is refractory to standard treatment at times. New antiepileptic drugs have been introduced but the place of application of these drugs in status is yet to be established. Objective To compare efficacy and adverse effects of intravenous Valproate and intravenous Levetiracetam as second line anti-epileptic drugs in status epilepticus to intravenous Phenytoin. Methodology 42 patients between 6 months to 12 years presenting with status epilepticus were included in the study and randomly distributed in three groups depending on the day of admission and each group was assigned one of three drugs under study as second line anti-epileptic drug. The ability of the drug to stop convulsions as well as time taken to stop convulsions and adverse effects were noted. Analysis of the data was done using chi square test. Results 57% patients studied for phenytoin(12/21), 63% for valproate(7/11) and 80% for levitracetam(8/10) became non convulsive after the use of respective drugs. But on applying chi-square test, p value showed that the comparison was not significant. The average time taken to stop convulsions by phenytoin is 10 min, valproate is 10 min and by levetiracetam is 11 min, which again was not statistically significant. Only 2 out of 42(4.7%) developed minor adverse effects from phenytoin in the form of excessive drowsiness and irritability. Conclusion Clinically the efficacy of i.v. levetiracetam and i.v. valproate was found to be better than i.v. phenytoin but no statistically significant difference was observed. So phenytoin remains the preferred second-line anti-convulsant in status epilepticus with minimal side-effects.

Aims: To analyze the results of balloon dilatation for short segment male urethral strictures. Materials and Methods: Retrospective analysis was done of 120 patients undergoing urethral balloon dilatation since January 2004 to January 2012. The inclusion criteria for analysis was a short segment (less than 1.5 cm) stricture, exclusion criteria were pediatric, long (more than 1.5 cm), traumatic, malignant strictures. The parameters analyzed included presentation of patients, ascending urethrogram (AUG) and descending urethrogram findings, pre- and postoperative International prostate symptoms score (IPSS), uroflowmetry (Q max ), and post-void residue (PVR). Need for self calibration/ancillary procedures were assessed. Failure was defined as requirement for a subsequent endoscopic or open surgery. A urethral balloon catheter (Cook Urological, Spencer, Indiana) is passed over a guide wire after on table AUG and inflated till 180 psi for 5 minutes under fluoroscopy till waist disappears. Dilatation is followed by insertion of a Foley catheter. Patients were followed up at 1, 3, and 6 months. Results: Mean age was 49.86 years. Mean follow-up was 6 (2-60) months. IPSS improved from 21.6 preoperative to 5.6 postoperatively. Q max increased from 5.7 to 19.1 and PVR decreased from 90.2 to 28.8 (P < 0.0001FNx01) postoperatively. At 1, 3, and at 6 monthly follow-up, 69.2% ( n = 82) patients were asymptomatic. Conclusions: Balloon dilation is a safe, well-tolerated procedure with minimal complications. Further randomized studies comparing balloon dilatation with direct internal visual urethrotomy are warranted.

Although holistic processing has been documented extensively for upright faces, it is unclear whether it occurs for other visual categories with more extensive substructure, such as body postures. Like faces, body postures have high social relevance, but they differ in having fine-grain organization not only of basic parts (e.g., arm) but also subparts (e.g., elbow, wrist, hand). To compare holistic processing for whole bodies and body parts, we employed a novel stereoscopic depth manipulation that creates either the percept of a whole body occluded by a set of bars, or of segments of a body floating in front of a background. Despite sharing low-level visual properties, only the stimulus perceived as being behind bars should be holistically “filled in” via amodal completion. In two experiments, we tested for better identification of individual body parts within the context of a body versus in isolation. Consistent with previous findings, recognition of body parts was better in the context of a whole body when the body was amodally completed behind occluders. However, when the same bodies were perceived as floating in strips, performance was significantly worse, and not significantly different, from that for amodally completed parts, supporting holistic processing of body postures. Intriguingly, performance was worst for parts in the frontal depth condition, suggesting that these effects may extend from gross body organization to a more local level. These results provide suggestive evidence that holistic representations may not be “all-or-none,” but rather also operate on body regions of more limited spatial extent.