Brain Connectivity Signature Extractions from TMS Invoked EEGs.

(1) Background: The correlations between brain connectivity abnormality and psychiatric disorders have been continuously investigated and progressively recognized. Brain connectivity signatures are becoming exceedingly useful for identifying patients, monitoring mental health disorders, and treatment. By using electroencephalography (EEG)-based cortical source localization along with energy landscape analysis techniques, we can statistically analyze transcranial magnetic stimulation (TMS)-invoked EEG signals, for obtaining connectivity among different brain regions at a high spatiotemporal resolution. (2) Methods: In this study, we analyze EEG-based source localized alpha wave activity in response to TMS administered to three locations, namely, the left motor cortex (49 subjects), left prefrontal cortex (27 subjects), and the posterior cerebellum, or vermis (27 subjects) by using energy landscape analysis techniques to uncover connectivity signatures. We then perform two sample t-tests and use the (5 × 10-5) Bonferroni corrected p-valued cases for reporting six reliably stable signatures. (3) Results: Vermis stimulation invoked the highest number of connectivity signatures and the left motor cortex stimulation invoked a sensorimotor network state. In total, six out of 29 reliable, stable connectivity signatures are found and discussed. (4) Conclusions: We extend previous findings to localized cortical connectivity signatures for medical applications that serve as a baseline for future dense electrode studies.

Dementia Detection from Speech Using Machine Learning and Deep Learning Architectures.

Dementia affects the patient's memory and leads to language impairment. Research has demonstrated that speech and language deterioration is often a clear indication of dementia and plays a crucial role in the recognition process. Even though earlier studies have used speech features to recognize subjects suffering from dementia, they are often used along with other linguistic features obtained from transcriptions. This study explores significant standalone speech features to recognize dementia. The primary contribution of this work is to identify a compact set of speech features that aid in the dementia recognition process. The secondary contribution is to leverage machine learning (ML) and deep learning (DL) models for the recognition task. Speech samples from the Pitt corpus in Dementia Bank are utilized for the present study. The critical speech feature set of prosodic, voice quality and cepstral features has been proposed for the task. The experimental results demonstrate the superiority of machine learning (87.6 percent) over deep learning (85 percent) models for recognizing Dementia using the compact speech feature combination, along with lower time and memory consumption. The results obtained using the proposed approach are promising compared with the existing works on dementia recognition using speech.

Convolution-Based Encoding of Depth Images for Transfer Learning in RGB-D Scene Classification.

Classification of indoor environments is a challenging problem. The availability of low-cost depth sensors has opened up a new research area of using depth information in addition to color image (RGB) data for scene understanding. Transfer learning of deep convolutional networks with pairs of RGB and depth (RGB-D) images has to deal with integrating these two modalities. Single-channel depth images are often converted to three-channel images by extracting horizontal disparity, height above ground, and the angle of the pixel's local surface normal (HHA) to apply transfer learning using networks trained on the Places365 dataset. The high computational cost of HHA encoding can be a major disadvantage for the real-time prediction of scenes, although this may be less important during the training phase. We propose a new, computationally efficient encoding method that can be integrated with any convolutional neural network. We show that our encoding approach performs equally well or better in a multimodal transfer learning setup for scene classification. Our encoding is implemented in a customized and pretrained VGG16 Net. We address the class imbalance problem seen in the image dataset using a method based on the synthetic minority oversampling technique (SMOTE) at the feature level. With appropriate image augmentation and fine-tuning, our network achieves scene classification accuracy comparable to that of other state-of-the-art architectures.

A hospital based study on reference range of serum prostate specific antigen levels.

BACKGROUND & OBJECTIVES: Serum prostate specific antigen (PSA) levels are known to vary with race and ethnicity, environmental factors, lifestyle, metabolic and physiologic changes and advancing age. This study was designed to determine age specific serum PSA level in healthy Indian men and its comparison with that reported in different populations of the world. METHODS: A total of 1300 adult men who attended Executive Health Check-up programme in a tertiary care hospital in Haryana, India, were included in the study. Forty seven men were excluded from the analysis because of urological conditions affecting PSA values. Overall, 1253 men were analyzed for age specific PSA values. RESULTS: The age specific reference range of serum PSA values was 0.71 ng/ml in those younger than 40 yr; 0.85 ng/ml in 40-49 yr; 1.13 ng/ml in 50-59 yr group; 1.45 ng/ml in 60-69 yr group; 1.84 ng/ml in 70-79 yr group and 2.35 ng/ml in men older than 80 yr. INTERPRETATION & CONCLUSIONS: Our study provided the age-specific reference range of serum PSA in healthy men in India. The data suggested that the PSA levels were associated with increasing age.

Role of corneal collagen cross-linking in pseudophakic bullous keratopathy: a clinicopathological study.

OBJECTIVE: To evaluate the clinical and histopathologic changes induced by collagen cross-linking (CXL) in pseudophakic bullous keratopathy (PBK). DESIGN: Randomized, prospective, interventional study. PARTICIPANTS: Twenty-four patients with PBK were included in the study. METHODS: Twenty-four patients with PBK underwent CXL followed by keratoplasty at 1 or 3 months. Twelve patients underwent penetrating keratoplasty 1 month after CXL (group A) and the remaining 12 patients underwent penetrating keratoplasty 3 months after CXL (group B). The main outcome measures were assessed at 1 week and 1 month for all patients and at 3 months for 12 patients only. The corneal buttons underwent histopathologic and immunofluorescence evaluation. MAIN OUTCOME MEASURES: Visual acuity, ocular discomfort (tearing, redness, pain), corneal haze, central corneal thickness, histopathologic evaluation, and immunofluorescent microscopy. RESULTS: Mean visual acuity showed a significant improvement after CXL, from 1.925 ± 0.173 before surgery to 1.75±0.296 at 1 month after surgery (P = 0.010), but deteriorated to 1.81 ± 0.23 at 3 months. Symptomatic relief after CXL was at a maximum at 1 month, with a worsening trend at 3 months. Eighteen patients showed a reduction in corneal haze 1 month after CXL. The effect was maintained in 9 of 12 patients at 3 months. The mean central corneal thickness decreased significantly from 846.46 ± 88.741 to 781.0 ± 98.788 µm at 1 month (P<0.01) after CXL, but increased to 805.08±136.06 µm at 3 months. Immunofluorescence microscopy revealed anterior stromal compaction in 7 of 12 patients (58.3%) in group A and in 5 of 12 patients (41.6%) in group B. Staining of keratocyte nuclei with 4',6-diaminido-2-phenylindole dihydrochloride (Molecular Probes, Carlsband, CA) revealed a relative uniform distribution throughout the stroma. CONCLUSIONS: Collagen cross-linking causes symptomatic relief and a decrease in central corneal thickness and anterior stromal compaction in PBK. However, the effect decreases with time and depends on disease severity.

Results of corneal collagen cross-linking in pediatric patients.

PURPOSE: To evaluate the safety and efficacy of corneal collagen cross-linking (CXL) in the treatment of keratoconus in pediatric patients. METHODS: Epithelium-off CXL using the standard protocol was performed in 15 eyes from 15 patients (age range: 10 to 15 years) with moderate keratoconus in 1 eye and advanced disease in the fellow eye. Principal outcomes included uncorrected and corrected distance visual acuity (CDVA), refraction, and topography-derived outcomes of maximum and average keratometry (K). RESULTS: Mean uncorrected distance visual acuity improved significantly from 1.00 ± 0.30 (20/200) to 0.72 ± 0.29 (20/100) logMAR (P=.035) and mean CDVA from 0.56 ± 0.21 (20/70) to 0.30 ± 0.15 (20/40) logMAR (P=.003) at the end of 12 months. Mean change in apical K (1.01 ± 2.40 diopters) was also significant (P=.004). No significant complications were noted. CONCLUSIONS: Corneal collagen CXL was found to be safe and effective in the first 12 months for keratoconus in children with similar initial efficacy as in adults in terms of improvement in visual and topographic outcomes.

Voriconazole versus natamycin as primary treatment in fungal corneal ulcers.

BACKGROUND: To evaluate the efficacy of topical 1% voriconazole versus 5% natamycin in treatment of fungal corneal ulcers. DESIGN: A prospective, randomized pilot study in a tertiary care hospital. PARTICIPANTS: Thirty patients of microbiologically proven fungal keratitis divided randomly in two groups of 15 patients each. METHODS: Two groups were treated with either 5% natamycin (group A) or 1% voriconazole (group B) topically as a primary treatment for fungal keratitis. The mean size, depth of infiltrate and LogMAR visual acuity at presentation were comparable in both groups (P > 0.05). Patients were followed up for minimum of 10 weeks or till complete resolution of ulcer, whichever was later. Cultures to identify the causative organisms were performed. MAIN OUTCOME MEASURE: Time of resolution of the ulcer. RESULTS: Twenty-nine of the total 30 patients showed complete resolution. Average time of resolution and gain in LogMAR visual acuity was 24.3 days and 1.12 in group A and 27.2 days and 0.77 in group B. These were comparable in the two groups (P > 0.05%). Aspergillus spp. (40%) and Curvularia spp. (30.0%) were found to be most common isolates. CONCLUSION: Topical 1% voriconazole was found to be safe and effective drug in primary management of fungal keratitis, its efficacy matching conventional natamycin. There was no added advantage of using topical 1% voriconazole over topical natamycin as primary treatment in fungal keratitis.

Synthesis, antifungal and antibacterial activity of novel 1,2,4-triazole derivatives.

A large number of 1,2,4-triazole-containing ring system have been incorporated into a wide variety of therapeutically interesting drug candidates including anti-inflammatory, central nervous system stimulants, antianxiety, and antimicrobial agents. To overcome the rapid development of drug resistance, new agents should preferably have chemical characteristics that clearly differ from those of existing agents. Thus led to the design and synthesize the new antimicrobial agents. A novel series of Schiff bases based on of 4-(benzylideneamino)-5-phenyl-4H-1,2,4-triazole-3-thiol scaffold was prepared by heating thiocarbohydrazide and substituted benzoic acid and subsequently, treating with substituted benzaldehydes. Seventeen derivatives were synthesized and were biologically screened for antifungal and antibacterial activity. The newly synthesized derivatives of triazole showed antifungal activity against fungal species, Microsporum gypseum; and antibacterial activity against bacterial species, Staphylococcus aureus. It was observed that none of the compounds tested showed positive results for fungi Candida albicans fungi Aspergillus niger, nor against bacterial strain Escherichia coli. Strong antifungal effects were obtained for the synthesized compounds against M. gypseum and were superior or comparable to standard drug ketoconazole. Similarly, all of the synthesized compounds exhibit strong antibacterial activity against S. aureus and were superior or comparable to standard drug streptomycin. It was found that among the triazole derivatives so synthesized, six of them, showed antifungal activity superior to ketoconazole while one of them, showed antibacterial activity superior to streptomycin. Thus, these can be the potential new molecule as an antimicrobial agent.

Chalcone derivatives as potential antifungal agents: Synthesis, and antifungal activity.

Much research has been carried out with the aim to discover the therapeutic values of chalcone derivatives. Chalcones possess wide range of pharmacological activity such as antibacterial, antimalarial, antiprotozoal, antitubercular, anticancer, and antifungal agents etc. The presence of reactive α,ß-unsaturated keto group in chalcones is found to be responsible for their biological activity. The rapid developments of resistance to antifungal agents, led to design, and synthesize the new antifungal agents. The derivatives of chalcones were prepared using Claisen-Schmidt condensation scheme with appropriate tetralone and aldehyde derivatives. Ten derivatives were synthesized and were biologically screened for antifungal activity. The newly synthesized derivatives of chalcone showed antifungal activity against fungal species, Microsporum gypseum. The results so obtained were superior or comparable to ketoconazole. It was observed that none of the compounds tested showed positive results for fungi Candida albicans nor against fungi Aspergillus niger. Chalcone derivatives showed inhibitory effect against M. gypseum species of fungus. It was found that among the chalcone derivatives so synthesized, two of them, that is, 4-chloro derivative, and unsubstituted derivative of chalcone showed antifungal activity superior to ketoconazole. Thus, these can be the potential new molecule as antifungal agent.

Tailored stromal expansion with a refractive lenticule for crosslinking the ultrathin cornea.

We describe a technique for stromal expansion of thin and ultrathin corneas in keratoconus patients that uses refractive stromal lenticules of patients having small-incision lenticule extraction for myopic correction. The stromal lenticule is placed and spread over the host cornea following epithelial debridement so the thickest area of the 6.2 mm diameter lenticule corresponds to the thinnest area of the cone. The remaining collagen crosslinking (CXL) procedure is carried out in a routine manner. We believe tailored stromal expansion is a safe and effective technique for performing CXL in patients with thin corneas.

Comparative Analysis of Refractive and Topographic Changes in Early and Advanced Keratoconic Eyes Undergoing Corneal Collagen Crosslinking.

PURPOSE: To compare the refractive and topographic changes at 1 year in eyes with early and advanced keratoconus undergoing corneal collagen crosslinking (CXL). A prospective, nonrandomized comparative clinical intervention study. METHODS: Thirty eyes of patients with keratoconus underwent CXL. They were divided into 2 groups based on their mean central keratometry: group A [mean central K ≤ 53 diopters (D)] and group B (mean central K > 53 D). Uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), refraction, topography, pachymetry, and endothelial cell counts were evaluated at baseline and at 1, 3, 6, and 12 months of follow-up. RESULTS: The mean baseline logarithm of the minimum angle of resolution (logMAR) UCVA and logMAR BCVA in group A was 1.007 ± 0.30 and 0.566 ± 0.21, respectively. The values improved to 0.727 ± 0.29 (P = 0.001) and 0.306 ± 0.15 (P = 0.001) at 1-year post CXL. The mean baseline logMAR UCVA and logMAR BCVA in group B were 1.040 ± 0.24 and 0.641 ± 0.25, respectively. It changed to 0.953 ± 0.26 (P = 0.054) and 0.633 ± 0.27 (P = 0.891) at 1 year. The improvement in the UCVA and BCVA was statistically significant in group A as compared with that in group B. The mean baseline flattest, steepest, central, and apical keratometry in group A were 48.7 ± 2.5 D, 54.9 ± 3.3 D, 49.5 ± 1.4 D, and 57.3 ± 2.3 D, respectively. At 12 months, the values changed to 47.8 ± 2.4 D, 54.1 ± 3.0 D, 48.8 ± 1.8 D, and 56.2 ± 2.7 D, the change being statistically significant for mean flat and apical K only (P < 0.05). All the 4 indices did not show any statistically significant difference at 12 months in group B (P > 0.05). CONCLUSIONS: Corneal CXL is more effective in improving the refractive and topographical parameters at 1 year when it is performed early in the course of the disease.

Sterile keratitis after corneal collagen crosslinking in a child.

Corneal collagen crosslinking (CXL) is a non invasive technique used in halting the progression of keratoconus. Complications with this modality are rare. We report a case of an 8-year-old child who developed sterile infiltrates in the immediate postoperative period after uneventful corneal collagen crosslinking for keratoconus. The infiltrates resolved with topical steroid therapy. There was also present coexisting vernal keratoconjunctivitis (VKC) which was controlled with topical 2% cyclosporine A eye drops prior to crosslinking treatment. This case highlights importance of controlling VKC prior to CXL in keratoconus as it adds to the risk of developing post operative sterile keratitis.

Attenuation of endocrine-exocrine pancreatic communication in type 2 diabetes: pancreatic extracellular matrix ultrastructural abnormalities.

Ultrastructural observations reveal a continuous interstitial matrix connection between the endocrine and exocrine pancreas, which is lost due to fibrosis in rodent models and humans with type 2 diabetes mellitus (T2DM). Widening of the islet-exocrine interface appears to result in loss of desmosomes and adherens junctions between islet and acinar cells and is associated with hypercellularity consisting of pericytes and inflammatory cells in T2DM pancreatic tissue. Organized fibrillar collagen was closely associated with pericytes, which are known to differentiate into myofibroblasts-pancreatic stellate cells. Of importance, some pericyte cellular processes traverse both the connecting islet-exocrine interface and the endoacinar interstitium of the exocrine pancreas. Loss of cellular paracrine communication and extracellular matrix remodeling fibrosis in young animal models and humans may result in a dysfunctional insulino-acinar-ductal-incretin gut hormone axis, resulting in pancreatic insufficiency and glucagon-like peptide deficiency, which are known to exist in prediabetes and overt T2DM in humans.