Comparison of the effect of zinc oxide nanoparticles and extract of Acorus calamus applied topically on surgical wounds inflicted on the skin of rabbits.

Antibiotics are used for postsurgical wound healing purposes but unfortunately, resistance against them demands some alternatives for quick recovery. Sepsis of wounds is a challenge for medical as well as veterinary professionals. Nanoparticles have significant advantages in wound treatment and drug resistance reversal. This study was conducted to appreciate emerging alternates of antibiotics like zinc oxide nanoparticles and plant extracts in topical application. Zinc oxide is considered a good wound healer and its nanoparticles are easy to access. So, the efficacies of zinc oxide nanoparticles and sweet flag plant extract ointments were tested to compare modern and traditional therapeutics as sweet flag is considered a pure medicinal plant. Rabbits were selected for this study due to the healing properties of their skin. Wounds were inflicted on the thoracolumbar region and treated for 29 days post-surgically daily with normal saline and the ointment of zinc oxide nanoparticles and sweet flag extract ointment, prepared in a hydrophilic solvent. Wound shrinkage was observed daily and histopathological analysis was made and results were compared. Zinc oxide nanoparticles ointment showed the most satisfactory results for every parameter included in the study. No side effects of its topical application were observed. Healing was normal without any complications. The preparations of zinc oxide nanoparticles may help in the era of antibiotic resistance as topical drugs in the future.

Intestinal parasitic infections among type-2 diabetics seeking healthcare in Sana'a city, Yemen.

Intestinal parasitic infections (IPIs) are common in developing countries, particularly in countries witnessing conflicts and humanitarian crises like Yemen. Type-2 diabetics are among the population categories most vulnerable to a variety of infections, including IPIs. Therefore, this study determined the prevalence and risk factors associated with IPIs among Yemeni type-2 diabetics in Sana'a city. This hospital-based, cross-sectional study recruited 389 type-2 diabetics seeking healthcare in Sana'a from December 2019 to February 2020. Sociodemographic data and risk factors were collected from interviewed participants using a structured questionnaire. Stool samples were collected and examined for parasites using standard techniques. The association of sociodemographic characteristics and risk factors with IPIs was tested using univariate analysis, and a multivariable logistic regression model was developed to identify the independent predictors of IPIs at a significance level of <0.05. The overall prevalence of IPIs among diabetics was 38.6%. Entamoeba histolytica/dispar (30.3%) was the most frequent parasite, followed by Cryptosporidium species (8.2%). The significant independent predictors of IPIs were duration of diabetes mellitus > 10 years (AOR = 1.6; 95% CI: 1.10-2.47, P = 0.029), eating unwashed vegetables/fruits (AOR = 3.2; 95% CI: 1.44-6.92, P = 0.004) and not practicing handwashing before meals (AOR = 2.4; 95% CI: 1.10-5.48, P = 0.035). Over one-third of type-2 diabetics seeking healthcare in Sana'a city are infected with one or more IPIs, predominantly with E. histolytica/dispar, followed by Cryptosporidium species. Such infections cannot be predicted from the sociodemographic characteristics of diabetics. Nevertheless, prolonged duration of diabetes mellitus, eating unwashed vegetables/fruits and not practicing handwashing before meals are independent predictors of IPIs among type-2 diabetics. Large-scale studies are recommended for IPIs among type-2 diabetics with and without gastrointestinal complaints, preferably in comparison to non-diabetics.

An intrusive method for estimating speech intelligibility from noisy and distorted signals.

An objective metric that predicts speech intelligibility under different types of noise and distortion would be desirable in voice communication. To date, the majority of studies concerning speech intelligibility metrics have focused on predicting the effects of individual noise or distortion mechanisms. This study proposes an objective metric, the spectrogram orthogonal polynomial measure (SOPM), that attempts to predict speech intelligibility for people with normal hearing under adverse conditions. The SOPM metric is developed by extracting features from the spectrogram using Krawtchouk moments. The metric's performance is evaluated for several types of noise (steady-state and fluctuating noise), distortions (peak clipping, center clipping, and phase jitters), ideal time-frequency segregation, and reverberation conditions both in quiet and noisy environments. High correlation (0.97-0.996) is achieved with the proposed metric when evaluated with subjective scores by normal-hearing subjects under various conditions.

Foramen magnum decompression in adults with Chiari type 1 malformation: use of intraoperative ultrasound to guide extent of surgery.

BACKGROUND: Foramen magnum decompression (FMD) is an established technique for patients with Chiari-1 malformation. However, the extent of decompressive surgery is controversial, in particular whether dural opening is undertaken. OBJECTIVE: In this study, we report outcomes with our technique utilising intraoperative ultrasound (iOU) findings. Decision to proceed for further decompression was based on CSF flow around foramen magnum and visualisation of tip of tonsils. METHODS: Review of adults with CM-1 undergoing FMD 2013-2018. Patients underwent a suboccipital craniectomy ± partial C1 superior laminectomy ± duraplasty in a stepwise manner. Favourable iOU findings of CSF flow around the foramen magnum and pulsation of the tonsillar tips were sought at each step. Post-operative outcomes were assessed using the Chicago Chiari Outcome Score (CCOS). RESULTS: Fifty-seven patients were included. The mean age was 47 years (range 18-77 years). There was a strong female preponderance (48 females to nine males). The mean follow-up was 3.2 years (range 1-5 years). Surgery included: suboccipital craniectomy (52/57, 91%), plus partial C1 superior laminectomy (2/57, 4%), and plus duraplasty (3/57, 6%). Redo surgery was undertaken in 7/57 patients (12%). At final follow-up, 56/57 (98%) patients achieved a good (CCOS 13-16) or satisfactory (CCOS 9-12) outcome based on COSS. CONCLUSIONS: A patient centred approach to surgery utilising findings from iOU can achieve favourable outcomes. Dural opening is not routinely required.

Are extracellular vesicles new hope in clinical drug delivery for neurological disorders?

Cells secrete extracellular vesicles (EVs) for intercellular communication. EVs are natural nanovesicles that are surrounded by lipid bilayer for delivery of assorted cargoes for therapeutic purposes. In addition to their therapeutic roles, these vesicles are potential drug delivery systems. Exosomes are the most studied EVs as the delivery carriers that can cross the blood-brain barrier (BBB) because of their nanosize. BBB is a diffusion barrier that is selective for small molecules to transit from blood to the brain. This barrier has been an obstacle for the delivery of drugs to the brain for the treatment of neurological disorders (NDs). For efficient drug delivery, synthetic vesicles such as liposomes have been employed as carriers for delivery of therapeutic molecules in clinical practice. However, these delivery systems are not without drawbacks. Among the limitations of these drug carriers include recognition by the body as foreign particles that encounter multiple defence systems that could recognize, neutralize and eliminate them. EVs are natural vesicles that may circumvent the body defence system to remain in systemic circulation for a long time. This unique property made them excellent drug delivery vehicles for clinical application. Here I discuss the progress, challenges and future directions of EVs (especially exosomes) as vehicles for targeted delivery of drug and at the same time deliver their cargoes for regenerative purposes in NDs. Recent developments in bioengineering and microfluidic technologies, which hold promise for clinical-grade production of EVs as drug delivery systems for NDs are also highlighted.

Identification of New Chromenone Derivatives as Cholinesterase Inhibitors and Molecular Docking Studies.

BACKGROUND: Alzheimer's Disease (AD) is the leading cause of dementia among the aging population. This devastating disorder is generally associated with the gradual memory loss, specified by a decrease of acetylcholine level in the cortex hippocampus of the brain due to hyperactivation of cholinesterases (acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)). OBJECTIVE: Therefore, inactivation of AChE and BChE by inhibitors can increase the acetylcholine level and hence may be an encouraging strategy for the treatment of AD and related neurological problems. METHOD: In this contribution, two series of chromenone-based derivatives were tested by Ellmann's calorimetric method for AChE and BChE inhibition. RESULTS: All the compounds showed inhibitory activity against cholinesterases and some of them exhibited dual inhibition of AChE as well as BChE. The most potent inhibitor of AChE was 2l having an IC50 value of 0.08 ± 0.03 µM, while 3q inhibited the BChE with an IC50 value of 0.04 ± 0.01 µM. In case of dual inhibition, 3h showed an inhibitory concentration of 0.15 ± 0.01 µM for AChE, and 0.09 ± 0.01 µM for BChE. Molecular docking studies were performed to explore the probable binding modes of the most potent dual inhibitors. CONCLUSION: It can be hypothesized that the inhibitors are able to target cholinesterase pathways and may emerge as a suitable outset for the further development process.

A phenomenological model of the synapse between the inner hair cell and auditory nerve: Implications of limited neurotransmitter release sites.

Peterson and Heil [Hear. Res., In Press] have argued that the statistics of spontaneous spiking in auditory nerve fibers (ANFs) can be best explained by a model with a limited number of synaptic vesicle docking (release) sites (∼4) and a relatively-long average redocking time (∼16-17 ms) for each of the sites. In this paper we demonstrate how their model can be: i) generalized to also describe sound-driven ANF responses and ii) incorporated into a well-established and widely-used model of the entire auditory periphery [Zilany et al., J. Acoust. Soc. Am. 135, 283-286, 2014]. The responses of the new model exhibit substantial improvement in several measures of ANF spiking statistics, and predicted physiological forward-masking and rate-level functions from the new model structure are shown to also better match published physiological data.

Modeling Responses in the Superior Paraolivary Nucleus: Implications for Forward Masking in the Inferior Colliculus.

A phenomenological model of the responses of neurons in the superior paraolivary nucleus (SPON) of the rodent is presented in this study. Pure tones at the characteristic frequency (CF) and broadband noise stimuli evoke offset-type responses in these neurons. SPON neurons also phase-lock to the envelope of sinusoidally amplitude-modulated (SAM) stimuli for a range of modulation frequencies. Model SPON neuron received inhibitory input that was relayed by the ipsilateral medial nucleus of the trapezoid body from the contralateral model ventral cochlear nucleus neuron. The SPON model response was simulated by detecting the slope of its inhibitory postsynaptic potential. Responses of the proposed model to pure tones at CF and broadband noise were offset-type independent of the duration of the input stimulus. SPON model responses were also synchronized to the envelope of SAM stimuli with precise timing for a range of modulation frequencies. Modulation transfer functions (MTFs) obtained from the model response to SAM stimuli resemble the physiological MTFs. The output of the proposed SPON model provides an input for models of physiological responses at higher levels of the ascending auditory pathway and can also be utilized to infer possible mechanisms underlying gap detection and duration encoding as well as forward masking at the level of the auditory midbrain.

Reference-Free Assessment of Speech Intelligibility Using Bispectrum of an Auditory Neurogram.

Sensorineural hearing loss occurs due to damage to the inner and outer hair cells of the peripheral auditory system. Hearing loss can cause decreases in audibility, dynamic range, frequency and temporal resolution of the auditory system, and all of these effects are known to affect speech intelligibility. In this study, a new reference-free speech intelligibility metric is proposed using 2-D neurograms constructed from the output of a computational model of the auditory periphery. The responses of the auditory-nerve fibers with a wide range of characteristic frequencies were simulated to construct neurograms. The features of the neurograms were extracted using third-order statistics referred to as bispectrum. The phase coupling of neurogram bispectrum provides a unique insight for the presence (or deficit) of supra-threshold nonlinearities beyond audibility for listeners with normal hearing (or hearing loss). The speech intelligibility scores predicted by the proposed method were compared to the behavioral scores for listeners with normal hearing and hearing loss both in quiet and under noisy background conditions. The results were also compared to the performance of some existing methods. The predicted results showed a good fit with a small error suggesting that the subjective scores can be estimated reliably using the proposed neural-response-based metric. The proposed metric also had a wide dynamic range, and the predicted scores were well-separated as a function of hearing loss. The proposed metric successfully captures the effects of hearing loss and supra-threshold nonlinearities on speech intelligibility. This metric could be applied to evaluate the performance of various speech-processing algorithms designed for hearing aids and cochlear implants.

Structural modeling and analysis of dengue-mediated inhibition of interferon signaling pathway.

Dengue virus (DENV) belongs to the family Flaviviridae and can cause major health problems worldwide, including dengue fever and dengue shock syndrome. DENV replicon in human cells inhibits interferon α and ß with the help of its non-structural proteins. Non-structural protein 5 (NS5) of DENV is responsible for the proteasome-mediated degradation of signal transducer and activator of transcription (STAT) 2 protein, which has been implicated in the development of resistance against interferon-mediated antiviral effect. This degradation of STAT2 primarily occurs with the help of E3 ubiquitin ligases. Seven in absentia homologue (SIAH) 2 is a host protein that can mediate the ubiquitination of proteins and is known for its interaction with NS5. In this study, comprehensive computational analysis was performed to characterize the protein-protein interactions between NS5, SIAH2, and STAT2 to gain insight into the residues and sites of interaction between these proteins. The objective of the study was to structurally characterize the NS5-STAT2, SIAH2-STAT2, and NS5-SIAH2 interactions along with the determination of the possible reaction pattern for the degradation of STAT2. Docking and physicochemical studies indicated that DENV NS5 may first interact with the host SIAH2, which can then proceed towards binding with STAT2 from the side of SIAH2. These implications are reported for the first time and require validation by wet-lab studies.

Choroidal thinning and "stair-case" foveal sign in a patient with Alport syndrome.

PURPOSE: To quantitatively describe choroidal thickness in a patient with Alport syndrome and to qualitatively describe an unusual "stair-case" foveal sign. METHODS: Retrospective case report. RESULTS: This is the first case, to our knowledge, of the stair-case foveal sign. This is also the first case where choroidal thickness in a patient with Alport rsyndrome has been quantitatively described using enhanced depth imaging optical coherence tomography. CONCLUSION: Stair-case foveal sign and choroidal thinning are two new signs that clinicians can expect to encounter on optical coherence tomography imaging of patients with Alport syndrome.

Cucurbiturils substituted on the methylene bridge.

Cucurbit[6]uril (CB[6]) with a substituent attached solely to one methylene bridge was prepared for the first time. The monosubstituted CB[6] undergoes self-assembly to form a cyclic tetramer in the solid state. The affinity of the monosubstituted CB[6] to a series of alkylammonium salts was measured revealing a minor effect of the substituent on the binding properties of the macrocycle.

Suboptimal use of neural information in a mammalian auditory system.

Establishing neural determinants of psychophysical performance requires both behavioral and neurophysiological metrics amenable to correlative analyses. It is often assumed that organisms use neural information optimally, such that any information available in a neural code that could improve behavioral performance is used. Studies have shown that detection of amplitude-modulated (AM) auditory tones by humans is correlated to neural synchrony thresholds, as recorded in rabbit at the level of the inferior colliculus, the first level of the ascending auditory pathway where neurons are tuned to AM stimuli. Behavioral thresholds in rabbit, however, are ∼10 dB higher (i.e., 3 times less sensitive) than in humans, and are better correlated to rate-based than temporal coding schemes in the auditory midbrain. The behavioral and physiological results shown here illustrate an unexpected, suboptimal utilization of available neural information that could provide new insights into the mechanisms that link neuronal function to behavior.

Updated parameters and expanded simulation options for a model of the auditory periphery.

A phenomenological model of the auditory periphery in cats was previously developed by Zilany and colleagues [J. Acoust. Soc. Am. 126, 2390-2412 (2009)] to examine the detailed transformation of acoustic signals into the auditory-nerve representation. In this paper, a few issues arising from the responses of the previous version have been addressed. The parameters of the synapse model have been readjusted to better simulate reported physiological discharge rates at saturation for higher characteristic frequencies [Liberman, J. Acoust. Soc. Am. 63, 442-455 (1978)]. This modification also corrects the responses of higher-characteristic frequency (CF) model fibers to low-frequency tones that were erroneously much higher than the responses of low-CF model fibers in the previous version. In addition, an analytical method has been implemented to compute the mean discharge rate and variance from the model's synapse output that takes into account the effects of absolute refractoriness.

Effect of vitamins a, C, and e supplementation in the treatment of metabolic syndrome in albino rats.

Obesity and metabolic syndrome increase the risk of cardiovascular morbidity and mortality. Oxidative stress seems to be involved in the path physiology of cardiovascular complications of metabolic syndrome. In this study we investigated the effects of vitamins A, C, and E in the management of metabolic syndrome traits condition in albino rats fed with high salt diet. The rats were placed on 8% NaCl diet for 5 weeks and then supplemented with these vitamins for additional 4 weeks in the presence of salt diet. Supplementation with vitamins significantly (P < 0.01 ) decreased blood pressure of the rats as compared with the control. Supplementation also significantly (P < 0.05) reduced serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, and very-low-density lipoprotein cholesterol and increased high-density lipoprotein cholesterol, and total antioxidant status as compared with untreated group. The percentage protection of the supplemented groups against atherogenesis indicated 55.50 ± 3.75%. Percentage weight gain indicated significant positive correlation with triglyceride, insulin resistance, and malondialdehyde while total antioxidant status and nitric oxide showed significant negative correlation. Salt diet significantly (P < 0.05) induced features of metabolic syndrome. The result, therefore, indicated strong relationship between obesity and metabolic syndrome and underscores the role of these vitamins in the management of metabolic syndrome.

Effect of antioxidant mineral elements supplementation in the treatment of hypertension in albino rats.

Oxidative stress has been implicated in various pathologies, including hypertension, atherosclerosis, diabetes, and chronic renal disease. The current work was designed with the aim of investigating the potentials of antioxidants copper, manganese, and zinc in the treatment of hypertension in Wistar rats. The rats were fed 8% NaCl diet for 5 weeks and treatment with supplements in the presence of the challenging agent for additional 4 weeks. The supplementation significantly decreased the blood pressure as compared with hypertensive control. The result also indicated significant decreased in the levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol and very low-density lipoprotein cholesterol, malondialdehyde, insulin and increase in the high-density lipoprotein cholesterol, total antioxidant activities, and nitric oxide of the supplemented groups relative to the hypertensive control. The average percentage protection against atherogenesis indicated 47.13 ± 9.60% for all the supplemented groups. The mean arterial blood pressure showed significant positive correlation with glucose, total cholesterol, triglyceride, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, atherogenic index, insulin resistance and malondialdehyde while high density lipoprotein-cholesterol and total antioxidant activities showed negative correlation. The result therefore indicated strong relationship between oxidative stress and hypertension and underscores the role of antioxidant minerals in reducing oxidative stress, dyslipidemia, and insulin resistance associated with hypertension.

Semi-supervised spike sorting using pattern matching and a scaled Mahalanobis distance metric.

Sorting action potentials (spikes) from tetrode recordings can be time consuming, labor intensive, and inconsistent, depending on the methods used and the experience of the operator. The techniques presented here were designed to address these issues. A feature related to the slope of the spike during repolarization is computed. A small subsample of the features obtained from the tetrode (ca. 10,000-20,000 events) is clustered using a modified version of k-means that uses Mahalanobis distance and a scaling factor related to the cluster size. The cluster-size-based scaling improves the clustering by increasing the separability of close clusters, especially when they are of disparate size. The full data set is then classified from the statistics of the clusters. The technique yields consistent results for a chosen number of clusters. A MATLAB implementation is able to classify more than 5000 spikes per second on a modern workstation.

Supramolecular shuttle based on inclusion complex between cucurbit[6]uril and bispyridinium ethylene.

Cucurbit[6]uril (CB6) and bispyridinium ethylene form a stable inclusion complex. A rotaxane derived from this complex was prepared in which a CB6 wheel shuttles along an axle in an NMR time-resolved regime.

Power-law dynamics in an auditory-nerve model can account for neural adaptation to sound-level statistics.

Neurons in the auditory system respond to recent stimulus-level history by adapting their response functions according to the statistics of the stimulus, partially alleviating the so-called "dynamic-range problem." However, the mechanism and source of this adaptation along the auditory pathway remain unknown. Inclusion of power-law dynamics in a phenomenological model of the inner hair cell (IHC)-auditory nerve (AN) synapse successfully explained neural adaptation to sound-level statistics, including the time course of adaptation of the mean firing rate and changes in the dynamic range observed in AN responses. A direct comparison between model responses to a dynamic stimulus and to an "inversely gated" static background suggested that AN dynamic-range adaptation largely results from the adaptation produced by the response history. These results support the hypothesis that the potential mechanism underlying the dynamic-range adaptation observed at the level of the auditory nerve is located peripheral to the spike generation mechanism and central to the IHC receptor potential.

A phenomenological model of the synapse between the inner hair cell and auditory nerve: long-term adaptation with power-law dynamics.

There is growing evidence that the dynamics of biological systems that appear to be exponential over short time courses are in some cases better described over the long-term by power-law dynamics. A model of rate adaptation at the synapse between inner hair cells and auditory-nerve (AN) fibers that includes both exponential and power-law dynamics is presented here. Exponentially adapting components with rapid and short-term time constants, which are mainly responsible for shaping onset responses, are followed by two parallel paths with power-law adaptation that provide slowly and rapidly adapting responses. The slowly adapting power-law component significantly improves predictions of the recovery of the AN response after stimulus offset. The faster power-law adaptation is necessary to account for the "additivity" of rate in response to stimuli with amplitude increments. The proposed model is capable of accurately predicting several sets of AN data, including amplitude-modulation transfer functions, long-term adaptation, forward masking, and adaptation to increments and decrements in the amplitude of an ongoing stimulus.