Electrostatic interactions mediated defibrillation of ß-lactoglobulin fibrils using Keggin Polyoxometalates.

The whey protein ß-lactoglobulin (ßLG) forms fibrils similar to the amyloid fibrils in the neurodegenerative diseases due to its higher predisposition of ß-sheets. This study shed light on the understanding different inorganic Keggin polyoxometalates (POMs) interaction with the protein ßLG fibrils. POMs such as Phosphomolybdic acid (PMA), silicomolybdic acid (SMA), tungstosilicic acid (TSA), and phosphotungstic acid (PTA) were used due to their inherent higher anionic charges. The interaction studies were monitored with fluorescence spectra and Thioflavin T assay for both the ßLG monomers and the fibrils initially to elucidate the binding ability of the POMs. The binding of POMs and ßLG is also demonstrated by molecular docking studies. Zeta potential studies showed the electrostatic mediated higher interactions of the POMs with the protein fibrils. Isothermal titration calorimetry (ITC) studies showed that the molybdenum containing POMs have higher affinity to the protein fibrils than the tungsten. This study could help understanding formation of food grade protein fibrils which have profound importance in food industries.

Non-thermal plasma modulated l-tyrosine self-assemblies: a potential avenue for fabrication of supramolecular self-assembled biomaterials.

Aromatic amino acids (AAs) have garnered particular interest due to their pivotal roles in numerous biological processes and disorders. Variations in AA self-assembly not only affect protein structures and functions, but their non-covalent interactions such as hydrogen bonding, van der Waals forces, and π-π stacking, yield versatile assemblies vital in bio-inspired material fabrication. Tyrosine (Tyr), a non-essential aromatic amino acid, holds multifaceted significance in the body as a protein building block, neurotransmitter precursor, thyroid hormone contributor, and melanin synthesis regulator. The proficiency of Cold Atmospheric Plasma (CAP) in generating a spectrum of reactive oxygen and nitrogen species has spurred innovative research avenues in the studies of biomolecular components, including its potential for targeted cancer cell ablation and biomolecule modification. In this work, we have assessed the chemical as well as the structural changes in Tyrosine-derived self-assembled structures arising from the CAP-induced reactive species. For a comprehensive understanding of the mechanism, different treatment times, feed gases, and the role of solvent acidification are compared using various spectroscopic and microscopic techniques. LC-ESI-QQQ mass spectra unveiled the emergence of oxygenated and nitro derivatives of l-tyrosine following its interaction with CAP-derived ROS/RNS. SEM and TEM images demonstrated an enhanced surface size of self-assembled structures and the formation of novel nanomaterial-shaped assemblies following CAP treatment. Overall, this study aims to explore CAP's interaction with a single-amino acid, hypothesizing the creation of novel supramolecular structures and scrutinizing CAP-instigated transformations in l-tyrosine self-assembled structures, potentially advancing biomimetic-attributed nanomaterial fabrication which might present a novel frontier in the field of designing functional biomaterials.

Machine learning for cognitive behavioral analysis: datasets, methods, paradigms, and research directions.

Human behaviour reflects cognitive abilities. Human cognition is fundamentally linked to the different experiences or characteristics of consciousness/emotions, such as joy, grief, anger, etc., which assists in effective communication with others. Detection and differentiation between thoughts, feelings, and behaviours are paramount in learning to control our emotions and respond more effectively in stressful circumstances. The ability to perceive, analyse, process, interpret, remember, and retrieve information while making judgments to respond correctly is referred to as Cognitive Behavior. After making a significant mark in emotion analysis, deception detection is one of the key areas to connect human behaviour, mainly in the forensic domain. Detection of lies, deception, malicious intent, abnormal behaviour, emotions, stress, etc., have significant roles in advanced stages of behavioral science. Artificial Intelligence and Machine learning (AI/ML) has helped a great deal in pattern recognition, data extraction and analysis, and interpretations. The goal of using AI and ML in behavioral sciences is to infer human behaviour, mainly for mental health or forensic investigations. The presented work provides an extensive review of the research on cognitive behaviour analysis. A parametric study is presented based on different physical characteristics, emotional behaviours, data collection sensing mechanisms, unimodal and multimodal datasets, modelling AI/ML methods, challenges, and future research directions.

Smaller total brain volume but not subcortical structure volume related to common genetic risk for ADHD.

BACKGROUND: Mechanistic endophenotypes can inform process models of psychopathology and aid interpretation of genetic risk factors. Smaller total brain and subcortical volumes are associated with attention-deficit hyperactivity disorder (ADHD) and provide clues to its development. This study evaluates whether common genetic risk for ADHD is associated with total brain volume (TBV) and hypothesized subcortical structures in children. METHODS: Children 7-15 years old were recruited for a case-control study (N = 312, N = 199 ADHD). Children were assessed with a multi-informant, best-estimate diagnostic procedure and motion-corrected MRI measured brain volumes. Polygenic scores were computed based on discovery data from the Psychiatric Genomics Consortium (N = 19 099 ADHD, N = 34 194 controls) and the ENIGMA + CHARGE consortium (N = 26 577). RESULTS: ADHD was associated with smaller TBV, and altered volumes of caudate, cerebellum, putamen, and thalamus after adjustment for TBV; however, effects were larger and statistically reliable only in boys. TBV was associated with an ADHD polygenic score [ß = -0.147 (-0.27 to -0.03)], and mediated a small proportion of the effect of polygenic risk on ADHD diagnosis (average ACME = 0.0087, p = 0.012). This finding was stronger in boys (average ACME = 0.019, p = 0.008). In addition, we confirm genetic variation associated with whole brain volume, via an intracranial volume polygenic score. CONCLUSION: Common genetic risk for ADHD is not expressed primarily as developmental alterations in subcortical brain volumes, but appears to alter brain development in other ways, as evidenced by TBV differences. This is among the first demonstrations of this effect using molecular genetic data. Potential sex differences in these effects warrant further examination.

Large epigenome-wide association study of childhood ADHD identifies peripheral DNA methylation associated with disease and polygenic risk burden.

Epigenetic variation in peripheral tissues is being widely studied as a molecular biomarker of complex disease and disease-related exposures. To date, few studies have examined differences in DNA methylation associated with attention-deficit hyperactivity disorder (ADHD). In this study, we profiled genetic and methylomic variation across the genome in saliva samples from children (age 7-12 years) with clinically established ADHD (N = 391) and nonpsychiatric controls (N = 213). We tested for differentially methylated positions (DMPs) associated with both ADHD diagnosis and ADHD polygenic risk score, by using linear regression models including smoking, medication effects, and other potential confounders in our statistical models. Our results support previously reported associations between ADHD and DNA methylation levels at sites annotated to VIPR2, and identify several novel disease-associated DMPs (p < 1e-5), although none of them were genome-wide significant. The two top-ranked, ADHD-associated DMPs (cg17478313 annotated to SLC7A8 and cg21609804 annotated to MARK2) are also significantly associated with nearby SNPs (p = 1.2e-46 and p = 2.07e-59), providing evidence that disease-associated DMPs are under genetic control. We also report a genome-wide significant association between ADHD polygenic risk and variable DNA methylation at a site annotated to the promoter of GART and SON (p = 6.71E-8). Finally, we show that ADHD-associated SNPs colocalize with SNPs associated with methylation levels in saliva. This is the first large-scale study of DNA methylation in children with ADHD. Our results represent novel epigenetic biomarkers for ADHD that may be useful for patient stratification, reinforce the importance of genetic effects on DNA methylation, and provide plausible molecular mechanisms for ADHD risk variants.

Evaluating chronic emotional dysregulation and irritability in relation to ADHD and depression genetic risk in children with ADHD.

BACKGROUND: A central nosological problem concerns the etiological relationship of emotional dysregulation with ADHD. Molecular genetic risk scores provide a novel method for informing this question. METHODS: Participants were 514 community-recruited children of Northern European descent age 7-11 defined as ADHD or non-ADHD by detailed research evaluation. Parents-rated ADHD on standardized ratings and child temperament on the Temperament in Middle Childhood Questionnaire (TMCQ) and reported on ADHD and comorbid disorders by semi-structured clinical interview. Categorical and dimensional variables were created for ADHD, emotional dysregulation (implicating disruption of regulation of both anger-irritability and of positive valence surgency-sensation seeking), and irritability alone (anger dysregulation). Genome-wide polygenic risk scores (PRS) were computed for ADHD and depression genetic liability. Structural equation models and computationally derived emotion profiles guided analysis. RESULTS: The ADHD PRS was associated in variable-centered analyses with irritability (ß = .179, 95% CI = 0.087-0.280; ΔR2  = .034, p < .0002), but also with surgency/sensation seeking (B = .146, 95%CI = 0.052-0.240, ΔR2 =.022, p = .002). In person-centered analysis, the ADHD PRS was elevated in the emotion dysregulation ADHD group versus other ADHD children (OR = 1.44, 95% CI = 1.03-2.20, Nagelkerke ΔR2  = .013, p = .033) but did not differentiate irritable from surgent ADHD profiles. All effects were independent of variation in ADHD severity across traits or groups. The depression PRS was related to oppositional defiant disorder but not to ADHD emotion dysregulation. CONCLUSIONS: Irritability-anger and surgency-sensation seeking, as forms of negative and positively valenced dysregulated affect in ADHD populations, both relate principally to ADHD genetic risk and not mood-related genetic risk.

Global Data Sharing in Alzheimer Disease Research.

Many investigators recognize the importance of data sharing; however, they lack the capability to share data. Research efforts could be vastly expanded if Alzheimer disease data from around the world was linked by a global infrastructure that would enable scientists to access and utilize a secure network of data with thousands of study participants at risk for or already suffering from the disease. We discuss the benefits of data sharing, impediments today, and solutions to achieving this on a global scale. We introduce the Global Alzheimer's Association Interactive Network (GAAIN), a novel approach to create a global network of Alzheimer disease data, researchers, analytical tools, and computational resources to better our understanding of this debilitating condition. GAAIN has addressed the key impediments to Alzheimer disease data sharing with its model and approach. It presents practical, promising, yet, data owner-sensitive data-sharing solutions.

MRI-based brain atrophy rates in ADNI phase 2: acceleration and enrichment considerations for clinical trials.

The goal of this work was to assess statistical power to detect treatment effects in Alzheimer's disease (AD) clinical trials using magnetic resonance imaging (MRI)-derived brain biomarkers. We used unbiased tensor-based morphometry (TBM) to analyze n = 5,738 scans, from Alzheimer's Disease Neuroimaging Initiative 2 participants scanned with both accelerated and nonaccelerated T1-weighted MRI at 3T. The study cohort included 198 healthy controls, 111 participants with significant memory complaint, 182 with early mild cognitive impairment (EMCI) and 177 late mild cognitive impairment (LMCI), and 155 AD patients, scanned at screening and 3, 6, 12, and 24 months. The statistical power to track brain change in TBM-based imaging biomarkers depends on the interscan interval, disease stage, and methods used to extract numerical summaries. To achieve reasonable sample size estimates for potential clinical trials, the minimal scan interval was 6 months for LMCI and AD and 12 months for EMCI. TBM-based imaging biomarkers were not sensitive to MRI scan acceleration, which gave results comparable with nonaccelerated sequences. ApoE status and baseline amyloid-beta positron emission tomography data improved statistical power. Among healthy, EMCI, and LMCI participants, sample size requirements were significantly lower in the amyloid+/ApoE4+ group than for the amyloid-/ApoE4- group. ApoE4 strongly predicted atrophy rates across brain regions most affected by AD, but the remaining 9 of the top 10 AD risk genes offered no added predictive value in this cohort.

The Global Alzheimer's Association Interactive Network.

INTRODUCTION: The Global Alzheimer's Association Interactive Network (GAAIN) is consolidating the efforts of independent Alzheimer's disease data repositories around the world with the goals of revealing more insights into the causes of Alzheimer's disease, improving treatments, and designing preventative measures that delay the onset of physical symptoms. METHODS: We developed a system for federating these repositories that is reliant on the tenets that (1) its participants require incentives to join, (2) joining the network is not disruptive to existing repository systems, and (3) the data ownership rights of its members are protected. RESULTS: We are currently in various phases of recruitment with over 55 data repositories in North America, Europe, Asia, and Australia and can presently query >250,000 subjects using GAAIN's search interfaces. DISCUSSION: GAAIN's data sharing philosophy, which guided our architectural choices, is conducive to motivating membership in a voluntary data sharing network.

Amyloidosis of the orbit and adnexae.

PURPOSE: To present a series of patients with orbital and adnexal amyloidosis and illustrate the diversity of disease and the challenges of managing such cases. METHODS: Descriptive case series of ten patients with biopsy proven amyloidosis involving the orbit, conjunctiva and eyelids. The presentation, clinical findings and management are discussed for each case. RESULTS: All patients had some form of eyelid abnormality or malposition. Presenting complaints included ptosis, epiphora and ocular discomfort. Other clinical findings included conjunctival lesions and proptosis. The majority of patients had localised amyloidosis and one patient had systemic disease. Conservative management included lubrication and the use of bandage contact lenses. Surgical management included debulking, ptosis or other lid surgery. CONCLUSION: Amyloidosis can present to an Occuloplastic clinic in a wide variety of ways. Definitive diagnosis is based on the histopathological findings. Management is often challenging. Multi-disciplinary team involvement is critical in view of its systemic associations.

Spontaneous perforation of the cornea in mild keratoconus.

PURPOSE: Spontaneous corneal perforation during acute hydrops in keratoconus is a very rare complication and has only been described in patients with advanced keratoconus. We describe a case of spontaneous corneal perforation in mild keratoconus in a patient with no identifiable risk factors. METHODS: We report retrospectively on a 34-year-old woman with mild keratoconus (Krumeich stage II) who presented with the spontaneous perforation of the cornea. A literature review was undertaken. RESULTS: The handful of previously reported cases included patients with advanced keratoconus. Our patient had none of the risk factors identified in previously reported cases (eye rubbing, topical steroid use, and raised intraocular pressures). Corneal gluing was performed to restore globe integrity. She retained a visual acuity of 6/9 even through the acute episode. With the resolution of the acute episode, her corneal astigmatism improved and she achieved a final best-corrected visual acuity of 6/6 with spectacles. CONCLUSIONS: To our knowledge, this is the first reported case of spontaneous perforation of the cornea in mild keratoconus. We demonstrate that in this event, a good visual prognosis is possible from gluing alone.

A modified technique for descemet membrane stripping automated endothelial keratoplasty to minimize endothelial cell loss.

In an attempt to enhance postoperative survival of donor endothelium, the conventional technique for Descemet membrane stripping automated endothelial keratoplasty (DSAEK) was modified using the prototype of a glide specially designed to facilitate graft delivery and minimize surgical trauma. Instead of using the so-called taco technique, the Busin glide is loaded with the donor lamella, and a microincision forceps is inserted into a temporal side entry and passed across the anterior chamber, exiting through a nasal clear cornea tunnel to grab the graft and drag it into the eye. In 10 patients who underwent DSAEK, mean (SD) postoperative endothelial cell loss was 20.0% (2.6%) at 6 months, 23.5% (2.8%) at 12 months, and 26.4% (2.7%) at 18 to 24 months. Reduced trauma to the graft using our modified technique limits endothelial cell loss after DSAEK to the level recorded after conventional penetrating keratoplasty (PK).

Changes in corneal sensitivity and tear physiology after phacoemulsification.

PURPOSE: To identify any changes in corneal sensitivity and tear physiology after phacoemulsification and to evaluate the effectiveness of the use of ophthalmic lubricants. METHODS: The design of the study was longitudinal, parallel, randomised and double masked. Eighteen patients (average age 70.83 +/- 10.66 years, 7 males and 11 females) undergoing phacoemulsification were recruited and divided into three groups of six. In addition to the prednisolone acetate 1% and chloramphenicol 0.5% routinely given to patients postoperatively, the first two groups were given a tear lubricant (Refresh Soothe and Protect, Allergan Inc., Irvine, CA, USA) and saline (Chauvin Pharmaceuticals Ltd, Essex, UK), respectively, and the third was a control group and did not receive any additional eye drops. Tear production, evaporation, lipid layer interferometry and osmolarity along with corneal sensitivity were measured before and 3 days, 2 weeks, 1 month and 3 months after the surgery. RESULTS: Statistically significant detrimental changes were seen in all parameters of corneal sensitivity and tear physiology immediately after phacoemulsification. Tear physiology recovered within 1 month. Corneal sensitivity did not return to normal levels in 3 months, but a trend towards full recovery was seen. Saline and the tear lubricant were not found to have an effect on the improvement of tear physiology and corneal sensitivity post-surgically. CONCLUSIONS: Deterioration in corneal sensitivity and tear physiology is seen immediately after phacoemulsification. Corneal sensitivity does not return to preoperative levels until 3 months postoperatively whereas the tear functions recover within 1 month.

Late detachment of donor graft after Descemet stripping automated endothelial keratoplasty.

We describe the case of an 85-year-old man with pseudophakic bullous keratopathy. Descemet stripping automated endothelial keratoplasty (DSAEK) was performed, and 6 weeks postoperatively, subtle separation of the 2 corneal layers was noted. To our knowledge, this case of post-DSAEK graft detachment involves the longest interval between surgery and successful reattachment. It provides new insight into the survival of detached grafts following DSAEK, as well as a possible treatment for this complication.

Peripheral ulcerative keratitis due to a 'long lost' hard contact lens.

Peripheral ulcerative keratitis (PUK) is a disorder consisting of a crescent-shaped destructive inflammation of the perilimbal corneal stroma. PUK can occur in a variety of ocular and systemic conditions including infections, lid abnormalities, dermatological disorders and connective tissue disorders. We present a case of PUK associated with a hard contact lens (CL) retained in the superior fornix for over 16 years. After removal of the embedded CL, a superior forniceal conjunctival pedicle graft was performed to prevent corneal perforation. The patient was managed postoperatively with a combination of topical steroids and antibiotics. The use of systemic immunosuppressive therapy was not necessary. Micro-trauma and micro-keratitis may have occurred as a result of the mechanical effect of the CL but if this was the sole mechanism, one would expect presentation at a much earlier date. We discuss the pathogenetic mechanisms which may have contributed to the development of this ulceration. This report highlights the importance of lid eversion when examining patients with anterior segment pathology.

A simple correction for congenital tarsal kink associated with distichiasis.

Congenital tarsal kink is a rare condition. The folded edge of the upper tarsus, or the inturned lashes, may traumatize the cornea causing ulceration. We describe a case of unilateral upper eyelid horizontal tarsal kink associated with distichiasis and congenital corneal ulceration. Several different surgical treatment options have been previously alluded to in the literature including lamellar tarsoplasty, full-thickness eyelid fracture, and rotation and excision of the kink with tarsal reapposition. Repair by means of eyelid everting sutures via an anterior lamellar approach is presented as a novel technique to correct this congenital anomaly.