Amelioration of Endotoxin-Induced Uveitis in Rabbit by Topical Administration of Tacrolimus Proglycosome Nano-Vesicles

This work was aimed to improve the efficacy of tacrolimus in the treatment of endotoxin-induced uveitis (EIU) using propylene glycol modified lipid vesicles termed as proglycosome nano-vesicles (PNVs). PNVs were prepared by modified film hydration method. Experimental uveitis in rabbit eye was induced by an intravitreal injection of 20 μL of the endotoxin solution containing 100 ng of lipopolysaccharide endotoxin. In vivo efficacy of PNVs was determined by studying clinical symptoms of uveitis using slit lamp examination and by quantitatively measuring levels of tumor necrosis factor-alpha, interleukin-6, leukocytes and total proteins in aqueous humor, 24 h after intravitreal injection of endotoxin. Comparison was made with healthy, untreated and tacrolimus solution treated eyes. PNVs developed were nano-sized, deformable and showed sustained release of tacrolimus over period of 12 h. In vivo results indicated statistically significant difference between the effects of PNVs in the treatment of EIU compared to tacrolimus. PNV treatment not only subsides clinical symptoms of uveitis but also prevented breakdown of blood aqueous barrier. Tacrolimus loaded PNVs are potential new topical treatment for uveitis.     

Angiopoietins as promising biomarkers and potential therapeutic targets in brain injury

Traumatic brain injury (TBI) and sub-arachnoid hemorrhage (SAH) are major causes of long-term disability, mortality, and enormous economic costs to society. The full spectrum of neurological damage created by TBI or SAH is not usually manifested at the time of injury, but evolves gradually over the course of hours to days (or weeks) following these injuries. Angiopoietins, important regulators of vascular structure and function, are hallmark indicators of vascular injury and may therefore represent promising targets in the treatment of SAH and TBI. In animal models and human tissues, normal intracerebral and pial vessels show strong expression of Angiopoietin-1 (Ang-1), but only minimal expression or presentation of Angiopoietin-2 (Ang-2). After several types of neurotrauma, the ratios of Ang-1 and Ang-2 expression in brain microvessel are disturbed and appear to contribute to the remarkable loss of blood–brain barrier (BBB) in these injuries. Angiopoietins levels, and perhaps more importantly, Angiopoietin ratios (1:2) may have novel and important diagnostic and prognostic uses in TBI and SAH brain injury. Ang-1/2 evaluation in plasma, serum and cerebrospinal fluid may provide new therapeutic modalities which can modify ‘secondary’ forms of brain injury after TBI and SAH.     

Poverty indicators and mental health functioning among adults living with HIV in Delhi,India

Poor mental health functioning among persons living with HIV (PLHIV) has gained considerable attention particularly in low-income countries that disproportionately carry the global HIV/AIDS burden. Fewer studies, however, have examined the relationship between poverty indicators and mental health among PHLIV in India. Based on this cross-sectional study of 196 HIV-seropositive adults who received medical services at Shalom AIDS Project in Delhi, India, structural equation modeling and mediation analysis were employed to estimate the associations between poverty indices (household asset index, food security, unemployment, water treatment, sanitation), HIV-health factors (illness in the past 3 months, co-morbid medical conditions), and psychological distress. In the final model, ownership of fewer household assets was associated with higher levels of food insecurity, which in turn was associated with higher psychological distress. Also, the household asset index, food insecurity, and unemployment had a larger effect on psychological distress than new opportunistic infections. These findings build on increasing evidence that support concerted efforts to design, evaluate, and refine HIV mental health interventions that are mainstreamed with livelihood programming in high poverty regions in India.     

Magnetic,structural and magnetocaloric properties of Ni-Si and Ni-Al thermoseeds for self-controlled hyperthermia

Self-controlled hyperthermia is a non-invasive technique used to kill or destroy cancer cells while preserving normal surrounding tissues. We have explored bulk magnetic Ni-Si and Ni-Al alloys as a potential thermoseeds. The structural, magnetic and magnetocaloric properties of the samples were investigated, including saturation magnetisation, Curie temperature (T_C), and magnetic and thermal hysteresis, using room temperature X-ray diffraction and magnetometry. The annealing time, temperature and the effects of homogenising the thermoseeds were studied to determine the functional hyperthermia applications. The bulk Ni-Si and Ni-Al binary alloys have Curie temperatures in the desired range, 316?K–319?K (43?°C–46?°C), which is suitable for magnetic hyperthermia applications. We have found that T_C strictly follows a linear trend with doping concentration over a wide range of temperature. The magnetic ordering temperature and the magnetic properties can be controlled through substitution in these binary alloys.     

Influence of copy number on the expression levels of pandemic influenza hemagglutinin recombinant protein in methylotrophic yeast Pichia pastoris

The hemagglutinin (HA) gene of novel Swine Origin Influenza A/California/04/2009 (H1N1) was engineered for expression in Pichia pastoris as a soluble secreted protein. The full length HA-synthetic gene having ?? secretory tag under the control of AOX1 promoter was integrated into P. pastoris genome through homologous recombination. The resultant Pichia clones having single and multiple copy integrants of the expression cassettes were screened for the expression of full length HA protein in the culture supernatant. In order to completely exploit the expression potential of the P. pastoris expression system, a systematic investigation on the influence of gene copy number on the expression of the recombinant protein was made. A panel of Pichia clones carrying increasing copies of the heterologous gene was selected based on Geneticin resistance and SYBR green-based quantitative real-time PCR approach. Using these strategies, recombinant Pichia transformants carrying up to a maximum of four to six copies of the transgene were identified. After optimising the expression conditions for shaker flask culture, the resultant clones demonstrated that the increase in copy number results in a proportional elevation in the expression level of H1N1HA recombinant protein. Our findings clearly suggest that the gene dosage effect play a vital role in high level expression of the pandemic Influenza HA protein in yeast system.     

Music enjoyment with cochlear implantation

Since the advent of cochlear implant (CI) surgery in the 1960s, there have been remarkable technological and surgical advances enabling excellent speech perception in quiet with many CI users able to use the telephone. However, many CI users struggle with music perception, particularly with the pitch-based and melodic elements of music. Yet remarkably, despite poor music perception, many CI users enjoy listening to music based on self-report questionnaires, and prospective studies have suggested a disassociation between music perception and enjoyment. Music enjoyment is arguably a more functional measure of one’s listening experience, and thus enhancing one’s listening experience is a worthy goal. Recent studies have shown that re-engineering music to reduce its complexity may enhance enjoyment in CI users and also delineate differences in musical preferences from normal hearing listeners.     

Antesternal Colonic Interposition for Corrosive Esophageal Stricture

Restoration of swallowing in a patient with dysphagia due to nondilatable corrosive stricture of esophagus remains a surgical challenge. Organs available for replacement are stomach, jejunum, or colon. Jejunum is useful to replace a small segment, whereas stomach and colon are required for a long-segment replacement. In cases where the stomach is also injured, colon remains the only option. The route of colonic interposition has also been a subject of debate over the years. Antesternal, retrosternal, or esophageal bed passage are the routes described. In the present series, the data of antesternal colonic interposition (ACI) performed for nondilatable benign esophageal strictures in 32 patients (1988–2011) have been retrospectively analyzed. The results indicate that ACI for corrosive strictures is a quick and simple procedure. Thoracotomy is avoided and anastomosis is easily performed in the neck, and mortality rate due to anastomotic failure or graft failure is diminished. This retrospective analysis discusses the ease, effectiveness, quality of life, morbidity, and mortality of ACI and compares the pros and cons of ACI with other procedures described in the literature.