Interaction between sleep and the immune response in Drosophila: a role for the NFkappaB relish

STUDY OBJECTIVES: The regulation of sleep is poorly understood. While some molecules, including those involved in inflammatory/immune responses, have been implicated in the control of sleep, their role in this process remains unclear. The Drosophila model for sleep provides a powerful system to identify and test the role of sleep-relevant molecules. DESIGN: We conducted an unbiased screen for molecular candidates involved in sleep regulation by analyzing genome-wide changes in gene expression associated with sleep deprivation in Drosophila. To further examine a role of immune-related genes identified in the screen, we performed molecular assays, analysis of sleep behavior in relevant mutant and transgenic flies, and quantitative analysis of the immune response following sleep deprivation. RESULTS: A major class of genes that increased expression with sleep deprivation was that involved in the immune response. We found that immune genes were also upregulated during baseline conditions in the cyc01 sleep mutant. Since the expression of an NFkappaB, Relish, a central player in the inflammatory response, was increased with all manipulations that reduced sleep, we focused on this gene. Flies deficient in, but not lacking, Relish expression exhibited reduced levels of nighttime sleep, supporting a role for Relish in the control of sleep. This mutant phenotype was rescued by expression of a Relish transgene in fat bodies, which are the major site of inflammatory responses in Drosophila. Finally, sleep deprivation also affected the immune response, such that flies deprived of sleep for several hours were more resistant to bacterial infection than those flies not deprived of sleep. CONCLUSION: These results demonstrate a conserved interaction between sleep and the immune system. Genetic manipulation of an immune component alters sleep, and likewise, acute sleep deprivation alters the immune response.     

A novel device for safe exteriorization of haptic in scleral fixation intraocular lens surgery

The aim of this study was to describe a novel device that has been designed to facilitate anterior segment and novice surgeons to perform extraocular needle-guided haptic insertion technique (X-NIT) for scleral fixation intraocular lens surgery (SFIOL). We performed SFIOL surgery using X-NIT device in 21 eyes of 21 patients. The mean preoperative best-corrected visual acuity (BCVA) was 0.5 ± 0.2 logarithm of minimum angle of resolution (log MAR), which improved by one or more lines postoperatively in all eyes. There were no intraoperative complications. Postoperatively, we noted minimal corneal edema in one patient and dispersed vitreous hemorrhage in one patient. The sharpness and angulation of the needle and the haptic holding ability of silicone stopper were found to be satisfactory. The X-NIT device may potentially improve the safety of SFIOL procedures by minimizing intraocular maneuvers.     

Integrating binocular vision assessment in refractive surgery work-up: Proposition and protocol

Refractive surgeries are one of most commonly performed surgeries for correcting visual impairment due to refractive errors. With the increase in demand for refractive surgeries, there is an enormous strain on the operating surgeon for delivering ideal outcomes i.e 20/20 visual acuity. Regression, under-correction and ectasia are the most dreaded complications post-refractive correction, for the surgeon as well as the patient. They have significant effects on the quantity of the vision and most importantly on the quality of life of the patient. With the advent of digital era and jobs requiring the eyes being glued to the screen for hours there has been a surge in the patients presenting with complaints of asthenopia, glare, halos, and difficulty in focusing; pointing towards diagnosis of non-strabismic binocular vision anomalies (NSBVA). NSBVA in a postrefractive surgery patient may masquerade as regression or under-correction. However, timely diagnosis of NSBVA in such patients would prevent the greater harm caused by wrongful re-correction. Home- and office-based vision therapy results in improvement in visual acuity in a large majority of these patients. This preferred practice pattern intends to guide the refractive surgeons to diagnose and treat the postrefractive surgery NSBVA following a case-based and algorithmic approach. It also emphasizes the inclusion of the binocular vision assessment as a part of the pre-operative workup for patients undergoing refractive procedures.     

Synthesis,antitubercular and anticancer activity of new Baylis–Hillman adduct-derived N-cinnamyl-substituted isatin derivatives

Baylis–Hillman adduct-derived N-cinnamyl-substituted isatin derivatives were synthesized and evaluated for their antitubercular activity on Mycobacterium tuberculosis H₃₇Rv strain ATCC 27294 by agar dilution method. Anticancer activity for the same compounds was also screened on four different cell lines: Chinese hamster ovary (CHO cells), Colo 205 (human colon cancer), Sup-T1 (human lymphoma) and C6 glioma (rat glioma) by MTT assay method. The compounds (3j–l) have shown significant activity against Mycobacterium strain and the compound 3l has shown specific cytotoxic activity.     

Electron diffraction studies of light-induced conformational changes in the Leu-93 → Ala bacteriorhodopsin mutant

We previously have presented evidence for prominent structural changes in helices F and G of bacteriorhodopsin during the photocycle. These changes were determined by carrying out electron diffraction analysis of illuminated two-dimensional crystals of wild-type bacteriorhodopsin or the Asp-96 → Gly mutant that were trapped at a stage in the photocycle after light-driven proton release, but preceding proton uptake from the aqueous medium. Here, we report structural analysis of the long-lived O intermediate observed in the photocycle of the Leu-93 → Ala mutant, which accumulates after the release and uptake of protons, but before the reisomerization of retinal to its initial all-trans state. Projection Fourier difference maps show that upon illumination of the Leu-93 → Ala mutant, significant structural changes occur in the vicinity of helices C, B, and G, and to a lesser extent near helix F. Our results suggest that (i) all four helices that line the proton channel (B, C, F, and G) participate in structural changes during the late stages of the photocycle, and (ii) completion of the photocycle involves significant conformational changes in addition to those that are associated with steps in proton transport.     

Estrogen-eluting, phosphorylcholine-coated stent implantation is associated with reduced neointimal formation but no delay in vascular repair in a porcine coronary model.

Estrogen can inhibit intimal proliferation and accelerate endothelial regeneration after angioplasty. This suggests that estrogen may prevent in-stent restenosis. Unlike other therapies to prevent restenosis, estrogen may also not delay endothelial regrowth, thereby avoiding the risk of late stent thrombosis. The purpose of this work was to determine the effect of a 17beta-estradiol-eluting stent on neointimal formation in a porcine model. Each artery of six pigs was randomized to either a control, low-dose, or high-dose 17beta-estradiol-eluting stent. All animals were sacrificed at 30 days for histopathological analysis. There was a 40% reduction in intimal area in the high-dose stents compared with control stents (2.54 +/- 1.0 vs. 4.13 +/- 1.1 mm(2), for high dose vs. control, respectively; P < 0.05). There was complete endothelial regeneration at 30 days and similar inflammatory response to stenting on histopathology in all the stent groups. This is the first study to show that 17beta-estradiol-eluting stents are associated with reduced neointimal formation without affecting endothelial regeneration in the pig model of in-stent restenosis. Estrogen-coated stents may have a potential benefit in the prevention and treatment of in-stent restenosis.     

Subtype B and subtype C HIV type 1 recombinants in the northeastern state of Manipur, India

The predominant HIV-1 strain circulating in India is subtype C. However, subtype A and B strains of HIV-1 have also been reported in India. In 1999, the first A/C recombinant strain was reported from Pune in India. Intravenous drug users (IVDUs) from the northeastern region of India have a high HIV-1 seroprevalence. Studies carried out in intravenous drug users in the northeastern region of India have shown that HIV-1 subtype C is the predominant strain infecting IVDUs. Fourteen blood samples were collected from HIV-1-infected individuals from the northeastern region of India and screened by env and gag heteroduplex mobility assays (HMA). Where the env and gag HMA results from a sample yielded different subtypes, sequencing of env and gag PCR products was carried out to confirm the presence of HIV-1 recombinants. Of the 14 samples subtyped, nine samples belonged HIV-1 subtype C (gag C/env C), one to HIV-1 subtype B (gag B/env B), and the remaining were B/C recombinants (gag C/env B). This is the first report of HIV-1 B/C recombinants from India.     

Predictors of thrombotic complications after placement of the flexible coil stent

The balloon-expandable, stainless steel, flexible coil stent is a useful device for managing acute or threatened closure after percutaneous transluminal coronary angioplasty.^1–5 Use of the device is associated with thrombosis of the stented vessel in a small but important group of patients.^3,6–10 The clinical, angiographic, and procedural factors associated with stent thrombosis with this device are still unknown. The objective of this study was to define predictors of stent thrombosis occurring within the ftrst month after stenting with this device.     

Cephalometric evaluation of the pharyngeal airway space after orthognathic surgery and distraction osteogenesis of the jaw bones

Objective:

Orthognathic surgeries and distraction osteogenesis (DO) of the jaw bones cause a change in the pharyngeal airway space (PAS). The aim of our study was to evaluate the magnitude of changes occurring in the pharyngeal airway after mandibular set-back surgeries and DO of maxilla/mandible.

Materials and Methods:

The study undertaken was a retrospective cephalometric study. Subjects included in our study had undergone mandibular set-back surgery or DO of maxilla/mandible. Lateral cephalograms of the subjects taken pre-operatively (T0), immediate post-operatively (T1) and after a minimum follow-up period of 6 months (T2) were studied. The cephalograms were traced manually and the following parameters were evaluated: Surface area of the PAS, pharyngeal airway width at the level of the base of the tongue, position of the hyoid bone and the tongue. Repeated measure ANOVA test was done to assess the presence of any significant changes in the proposed parameters at T0, T1 and T2. A correlation analysis was made between the mandibular/maxillary movements and the corresponding changes in the PAS.

Results:

Surgical movements of maxilla and mandible do have an effect on the pharyngeal airway.

Conclusion:

It was clearly evident that the effects of mandibular movements on the PAS and the hyoid bone is more significant than the maxillary movements.KEY WORDS: Distraction osteogenesis, orthognathic surgery, pharyngeal airway space