Duration of Cochlear Microphonics in Click and Toneburst-Evoked Auditory Brainstem Response in Individuals With Auditory Neuropathy Spectrum Disorder and Normal Hearing.

The presence of ringing cochlear microphonics (CM) with an absence of auditory brainstem response (ABR) is an indicator of auditory neuropathy spectrum disorder (ANSD). The duration of CM may vary based on the stimuli used to elicit the response. Generally, ABR is recorded using clicks with very limited use of tonebursts. Thus, this study aims to understand the duration of CM in individuals with ANSD and normal hearing in response to clicks, 500 Hz toneburst, and 4000 Hz toneburst using ABR. Results show that individuals with ANSD have a longer duration of CM than those with normal hearing. The presence of CM was more evident in response to toneburst stimuli than clicks, with 500 Hz being commonly eliciting more CM in both groups. The difference in duration of CM was statistically significant in individuals with ANSD with longer duration obtained for 500 Hz followed by clicks and 4000 Hz toneburst. The duration of the stimuli used plays an important role in revealing the CM while recording ABR. This indicates that the use of toneburst, particularly low frequency such as 500 Hz, will be clinically useful in identifying ANSD especially when otoacoustic emissions are compromised.

Bluish-white Light-emitting 2D Sheets of Lead-free Perovskite Cesium Titanium Bromide (CsTiBr3) by a Two-stage Deposition Technique.

Bluish-white light-emitting materials are commonly used in LED lighting because they produce natural-looking light. Here we report the photoluminescent emission (PL) of novel, two-dimensional lead-free CsTiBr3 perovskite prepared via a two-stage deposition process. The formation of two-dimensional nanosheets of CsTiBr3 perovskite is confirmed by XRD, EDAX, and FESEM analysis. The height of the cesium bromide thin film substrate from the titanium bromide vapor source plays an important role in the formation of two-dimensional CsTiBr3. The CsTiBr3 perovskite nanosheets exhibit unique exciton- luminescence at 440 nm and self-trapped exciton emission at 595 nm which are the characteristics of two-dimensional halide structure, along with the band-to-band emission at 400 nm at an excitation wavelength of 340 nm. The resulting bluish-white light PL emission makes two-dimensional CsTiBr3 perovskite an alternative material to the traditional lead-based perovskite in LEDs, display technology, solid-state lighting, and various optoelectronic devices, addressing environmental concerns.

Gracilis Flap Reconstruction After Proctocolectomy for Malignancy and Inflammatory Bowel Disease.

BACKGROUND: Gracilis flap reconstruction (GFR) following abdominoperineal resection (APR) or proctocolectomy (PC) can reduce pelvic wound complications but has not been adequately assessed in the setting of immunosuppression, fistulous disease, and neoadjuvant chemoradiation. METHODS: Patients undergoing APR/PC with GFR were retrospectively analyzed with regard to perioperative characteristics, and morbidity was assessed. RESULTS: Patients underwent GFR for rectal cancer (n = 28), anal cancer (n = 3), inflammatory bowel disease (n = 13), or benign fistulizing disease (n = 1). 22.2% were chronically immunosuppressed, and 66.7% underwent preoperative chemoradiation. Twenty (44.4%) patients had minor wound complications, all treated nonoperatively. Nine patients had major complications with 4 patients requiring reoperation. The 4 threatened flaps were unilateral, and all were salvaged. Donor site morbidity was minimal. Patients with major complications were older (56 vs. 71 years, P = .030), and less likely to have pelvic drains (P = .018). CONCLUSION: In high-risk perineal wounds, GFR offers durable reconstruction with acceptably low morbidity.

Overexpression of RCAN1 isoform 4 in mouse neurons leads to a moderate behavioral impairment.

OBJECTIVES: Recent evidence supports the involvement of RCAN1 in Down syndrome and Alzheimer's disease. To better assess this, we generated and analyzed transgenic mice overexpressing human RCAN1 isoform 4 in neurons. METHODS: Cognitive behavioral (Morris water maze, open field, zero maze, elevated plus maze assays); cognitive-associated proteins (CREB, ERK and Tau Western immunoblotting); motor coordination (Rotarod assay); structural abnormalities (immunohistological analyses), and proinflammatory cytokines (cytometric bead assay) were measured in young (2 month) and old (18 month) transgenics and compared with wild type controls. RESULTS: In old mice, male but not female transgenics exhibited a significant decrease in anxiety as compared with wild type controls, whereas female but not male transgenic mice exhibited significantly less motor coordination. No differences were observed in the Morris water maze (spatial learning). pERK levels were reduced in transgenic males but not females, while no differences were observed between genotypes for pCREB and pTau. In young mice, a modest learning and exploratory behavior was observed in transgenic mice using a limited number of mice, and at higher N values, pCREB and pERK (but not pTau) levels were reduced in transgenics. No macro- and micro-scopic structural abnormalities or proinflammatory cytokine level differences were observed. DISCUSSION: These results indicate that elevated RCAN1 isoform 4 in neurons leads to a modest cognition-related impairment that is overall stronger at 2 months, suggesting a compensatory adaptation over time. These RCAN1 isoform 4 effects may contribute to at least some of the observed phenotypes in individuals with Down syndrome and Alzheimer's.

Degraded mitochondrial DNA is a newly identified subtype of the damage associated molecular pattern (DAMP) family and possible trigger of neurodegeneration.

We previously showed a preferential degradation and down-regulation of mitochondrial DNA and RNA in hamster fibroblasts in response to hydrogen peroxide. Subsequent studies by others demonstrated that mitochondrial DNA can stimulate immune cells as a DAMP (damage associated molecular patterns) family member. However, the actual physical structure of this mitochondrial DNA DAMP and its importance in non-immune cell types are poorly understood. Here we report that transfected oxidant-initiated degraded mitochondrial polynucleotides, which we term "DeMPs", strongly induce the proinflammatory cytokines interleukin 6, monocyte chemotactic protein-1, and tumor necrosis factor α in mouse primary astrocytes. Additionally, proinflammatory IL1ß was induced, implicating DeMPs in inflammasome activation. Furthermore, human cerebrospinal fluid (CSF) and plasma were found to contain detectable DeMP signal. Finally, significant degradation of mitochondrial DNA was observed in response to either a bolus or steady state hydrogen peroxide. Combined, these studies demonstrate, all for the first time, that a pathophysiologically relevant form of mitochondrial DNA (degraded) can elicit a proinflammatory cytokine induction; that a brain cell type (astrocytes) elicits a proinflammatory cytokine induction in response to these DeMPs; that this induction includes the inflammasome; that astrocytes are capable of inflammasome activation by DeMPs; that DeMPs are detectable in CSF and plasma; and that hydrogen peroxide can stimulate an early stage cellular degradation of mitochondrial DNA. These results provide new insights and are supportive of our hypothesis that DeMPs are a newly identified trigger of neurodegenerative diseases such as Alzheimer's disease, which are known to be associated with early stage inflammation and oxidation.

Modeling of ATP-sensitive inward rectifier potassium channel 11 and inhibition mechanism of the natural ligand, ellagic acid, using molecular docking.

Diabetes mellitus is a disorder in which blood sugar (glucose) levels are abnormally high because the body does not produce enough insulin to meet its needs. Post-prandial hyperglycemia (PPHG) is an independent risk factor for the development of macro vascular complications. It is now recognized that normalizing post-prandial blood glucose is more difficult than normalizing fasting glucose. Potassium channels are the most widely distributed type of ion channel and are found in virtually all living organisms. The function of KATP channels is best understood in pancreatic beta cells, the membrane potential of which is responsive to external glucose concentration. Beta cells show a remarkably complex electrical bursting behavior in response to an increase in glucose level. Nateglinide and Glimepiride are a class of insulin secretagog agents that lowers blood glucose levels by stimulating insulin secretion from the pancreas. These compounds interact with the ATP-sensitive potassium (K+ATP) channel in pancreatic beta cells. However, the side effects of these drugs overpass their uses, and the need to identify compounds with less adverse effects is exigent. In our research study, we used the natural compound ellagic acid, which is an already proven anti-carcinogen, anti-mutagen, and anticancer initiator, for its anti-diabetic activity in comparison to the two commercial drugs (Nateglinide and Glimepiride). The drugs and the compounds were docked to the ATP-dependent potassium channel and their energy value showed that the compound had higher binding value than the commercial drugs. Then an ADME/Tox analysis for the compound was carried out which showed that ellagic can be a possible lead molecule.