Crizanlizumab for retinal vasculopathy with cerebral leukoencephalopathy in a phase II clinical study.

BackgroundRetinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a rare, autosomal dominant, universally fatal disease without effective treatment options. This study explores the safety and preliminary efficacy of crizanlizumab, a humanized monoclonal antibody against P-selectin approved for the prevention of sickle cell crises, in slowing retinal nonperfusion and preserving vision in patients with RVCL-S.METHODSEleven patients with RVCL-S with confirmed exonuclease 3 prime repair exonuclease 1 (TREX1) mutations received monthly crizanlizumab infusions over 2 years. The study measured the nonperfusion index within 3 retinal zones and the total retina with fluorescein angiography, visual acuity, intraocular pressure (IOP), and optical coherence tomography central subfield thickness (CST) at baseline, 1 year, and 2 years. A mixed repeated-measures analysis was performed to assess the progression rates and changes from baseline.RESULTSEleven participants received crizanlizumab infusions. All of the participants tolerated crizanlizumab well, with 8 of 11 (72.7%) reporting mild adverse effects such as nausea, fatigue, and gastrointestinal symptoms. The change in total retinal nonperfusion was 7.22% [4.47, 9.97] in year 1 and -0.69% [-4.06, 2.68] in year 2 (P < 0.001). In the mid periphery, the change in nonperfusion was 10.6% [5.1, 16.1] in year 1 and -0.68% [-3.98, 5.35] in year 2 (P < 0.01), demonstrating a reduction in progression of nonperfusion in the second year of treatment. Visual acuity, IOP, and CST remained stable.CONCLUSIONCrizanlizumab has an acceptable safety profile. These results show promising potential for examining crizanlizumab in larger studies of RVCL-S and similar small-vessel diseases and for using the retina as a biomarker for systemic disease.Trial registrationClinicalTrials.gov NCT04611880.FUNDINGThe Clayco Foundation; DeNardo Education and Research Foundation Grant; Jeffrey T. Fort Innovation Fund; Siteman Retina Research Fund; unrestricted grant from Research to Prevent Blindness Inc.; National Heart,Lung, and Blood Institute (NHLBI), NIH (R01HL129241); National Institute of Neurological Disorders and Stroke (NINDS), NIH (RF1NS116565).

Longitudinal Assessment of Glymphatic Changes Following Mild Traumatic Brain Injury: Insights from PVS burden and DTI-ALPS Imaging.

Traumatic brain injury (TBI) even in the mild form may result in long-lasting post-concussion symptoms. TBI is also a known risk to late-life neurodegeneration. Recent studies suggest that dysfunction in the glymphatic system, responsible for clearing protein waste from the brain, may play a pivotal role in the development of dementia following TBI. Given the diverse nature of TBI, longitudinal investigations are essential to comprehending the dynamic changes in the glymphatic system and its implications for recovery. In this prospective study, we evaluated two promising glymphatic imaging markers, namely the enlarged perivascular space (ePVS) burden and Diffusion Tensor Imaging-based ALPS index, in 44 patients with mTBI at two early post-injury time points: approximately 14 days (14Day) and 6-12 months (6-12Mon) post-injury, while also examining their associations with post-concussion symptoms. Additionally, 37 controls, comprising both orthopedic patients and healthy individuals, were included for comparative analysis. Our key findings include: 1) White matter ePVS burden (WM-ePVS) and ALPS index exhibit significant correlations with age. 2) Elevated WM-ePVS burden in acute mTBI (14Day) is significantly linked to a higher number of post-concussion symptoms, particularly memory problems. 3) The increase in the ALPS index from acute (14Day) to the chronic (6-12Mon) phases in mTBI patients correlates with improvement in sleep measures. Furthermore, incorporating WM-ePVS burden and the ALPS index from acute phase enhances the prediction of chronic memory problems beyond socio-demographic and basic clinical information, highlighting their distinct roles in assessing glymphatic structure and activity. Early evaluation of glymphatic function could be crucial for understanding TBI recovery and developing targeted interventions to improve patient outcomes.

A Review on Enhancing the Life of Teeth by Toothpaste Containing Bioactive Glass Particles.

Purpose of Review: Dental caries or tooth decay is one of the communal problems in the world which can affect not only the oral health but also the general health conditions. The main objective of this systematic review is to explore the efficacy of bioactive glass-based toothpastes against cariogenic bacteria. Recent Findings: Bioactive glass particulates containing toothpaste show better remineralization potential on demineralized enamel and dentin when compared with toothpaste containing various bioactive constituents such as fluoride and potassium chloride. These constituents in conventional toothpaste can rapidly streak off due to acidic impact in the oral environment as the bioactive glass provides minerals for demineralized enamel and dentin by forming a strong hydroxyapatite (HAp) layer on its surface. Further, the therapeutic ions present in the bioglass can resist plaque formation by raising the pH of the surrounding environment or saliva and create amicable media for healthier teeth. Summary: Toothpaste containing bioactive glass particles undoubtedly displayed the remineralizing potentiality of the dental hard tissues. Dynamics of the mineralization through different bioactive glass materials needs further investigations. In order to prevent dental cavities and improve oral health, it is important to identify and study different effective bioglass particles in toothpaste.

Multimodal Structural and Functional Characterization of Retinal Vasculopathy with Cerebral Leukoencephalopathy.

OBJECTIVE: To describe and quantify the structural and functional consequences of retinal vasculopathy with cerebral leukoencephalopathy (RVCL) on the neurosensory retina. DESIGN: Cross sectional descriptive study from December 2021 to December 2022. PARTICIPANTS: Retinal vasculopathy with cerebral leukoencephalopathy patients (n = 9, 18 eyes) recruited from the RVCL Research Center at Washington University in St. Louis. METHODS: Retinal vasculopathy with cerebral leukoencephalopathy patients underwent comprehensive ophthalmological evaluation including OCT, OCT angiography (OCTA), ultrawidefield fundus imaging, retinal autofluorescence, dark adaptation, electroretinography (ERG), Goldmann kinetic perimetry, and fluorescein angiography (FA). MAIN OUTCOME MEASURES: Comprehensive characterization from various modalities including best-corrected visual acuity, central subfield thickness (µm) from OCT, foveal avascular zone (mm2) from OCTA, dark adaptation rod intercept (seconds), cone response in ERG, and presence or absence of vascular abnormalities, leakage, neovascularization, and nonperfusion on FA. RESULTS: A total of 18 eyes from 9 individuals were included in this study. The best-corrected visual acuity ranged from 20/15 to 20/70. The mean central subfield thickness from OCT was 275.8 µm (range, 217-488 µm). The mean foveal avascular zone (FAZ) from OCTA was 0.65 (range, 0.18-1.76) mm2. On dark adaptometry, the mean time was 5.02 (range, 2.9-6.5) minutes, and 1 individual had impaired dark adaptation. Electroretinography demonstrated mild cone response impairment in 4 eyes. On FA, there was evidence of macular and peripheral capillary nonperfusion in 16 of 18 eyes and notable areas of vascular leakage and retinal edema in 5 of the 18 eyes. CONCLUSIONS: This study illustrates the phenotypic spectrum of disease and may be clinically valuable for aiding diagnosis, monitoring disease progression, and further elucidating the pathophysiology of RVCL to aid in the development of therapies. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Rescue splenic artery embolization in an adult patient of sickle cell disease presented with acute splenic sequestration crisis.

BACKGROUND: Splenic sequestration crisis is a potentially fatal complication of sickle cell disease, mainly seen in young children. Only a few case series describe the acute splenic sequestration crisis in adults and its management, which primarily consists of supportive care and, in some cases, splenectomy. Splenic artery embolization has seldom been described in sickle cell disease. This is probably the first case in which an adult with sickle cell disease presented with an acute splenic sequestration crisis was managed successfully through splenic artery embolization. RESULTS: This 22-year-old female, a known case of sickle cell disease, presented with severe pain in the abdomen and low-grade intermittent fever for two days, secondary to an acute splenic sequestration crisis. The diagnosis of acute splenic sequestration was made based on clinical and blood parameters, ultrasonography, and computed tomography. Even with adequate supportive care and blood transfusions, the patient's condition worsened with a rapid fall in the hemoglobin and total platelet count. Considering splenectomy to be a high-risk procedure for this patient, a decision of rescue splenic artery embolization was taken, which was successful. CONCLUSION: Splenic artery embolization may be considered a lifesaving procedure in patients with acute splenic sequestration, where the risk of splenectomy can be high. Adequate post-procedure supportive care is vital for preventing complications.

Downstaging with Atezolizumab-Bevacizumab: A Case Series.

Background/aims: Hepatocellular carcinoma (HCC) is generally diagnosed at an advanced stage, which limits curative treatment options for these patients. Locoregional therapy (LRT) is the standard approach to bridge and downstage unresectable HCC (uHCC) for liver transplantation (LT). Atezolizumab-bevacizumab (atezo-bev) can induce objective responses in nearly one-third of patients; however, the role and outcomes of downstaging using atezobev remains unknown. Methods: In this retrospective single-center study, we included consecutive patients between November 2020 and August 2023, who received atezo-bev with or without LRT and were subsequently considered for resection/LT after downstaging. Results: Of the 115 patients who received atezo-bev, 12 patients (10.4%) achieved complete or partial response and were willing to undergo LT; they (age: 58.5 years; women-17%; Barcelona Clinic Liver Cancer Stage System B/C:5/7) had received 3-12 cycles of atezo-bev, and 4 of them had received prior LRT. Three patients died before LT, while three were awaiting LT. Six patients underwent curative therapies: four underwent living donor LT after a median of 79.5 (54-114) days following the last atezo-bev dose, one underwent deceased donor LT 38 days after the last dose, and one underwent resection. All but one patient had complete pathologic response with no viable HCC. Three patients experienced wound healing complications, and one required re-exploration and succumbed to sepsis. After a median follow-up of 10 (4-30) months, none of the alive patients developed HCC recurrence or graft rejection. Conclusions: Surgical therapy, including LT, is possible after atezo-bev therapy in wellselected patients after downstaging.

APASL clinical practice guidelines on the management of acute kidney injury in acute-on-chronic liver failure.

Acute-on-chronic liver failure (ACLF) is a syndrome that is characterized by the rapid development of organ failures predisposing these patients to a high risk of short-term early death. The main causes of organ failure in these patients are bacterial infections and systemic inflammation, both of which can be severe. For the majority of these patients, a prompt liver transplant is still the only effective course of treatment. Kidneys are one of the most frequent extrahepatic organs that are affected in patients with ACLF, since acute kidney injury (AKI) is reported in 22.8-34% of patients with ACLF. Approach and management of kidney injury could improve overall outcomes in these patients. Importantly, patients with ACLF more frequently have stage 3 AKI with a low rate of response to the current treatment modalities. The objective of the present position paper is to critically review and analyze the published data on AKI in ACLF, evolve a consensus, and provide recommendations for early diagnosis, pathophysiology, prevention, and management of AKI in patients with ACLF. In the absence of direct evidence, we propose expert opinions for guidance in managing AKI in this very challenging group of patients and focus on areas of future research. This consensus will be of major importance to all hepatologists, liver transplant surgeons, and intensivists across the globe.

An artificial intelligence-generated model predicts 90-day survival in alcohol-associated hepatitis: A global cohort study.

BACKGROUND AND AIMS: Alcohol-associated hepatitis (AH) poses significant short-term mortality. Existing prognostic models lack precision for 90-day mortality. Utilizing artificial intelligence in a global cohort, we sought to derive and validate an enhanced prognostic model. APPROACH AND RESULTS: The Global AlcHep initiative, a retrospective study across 23 centers in 12 countries, enrolled patients with AH per National Institute for Alcohol Abuse and Alcoholism criteria. Centers were partitioned into derivation (11 centers, 860 patients) and validation cohorts (12 centers, 859 patients). Focusing on 30 and 90-day postadmission mortality, 3 artificial intelligence algorithms (Random Forest, Gradient Boosting Machines, and eXtreme Gradient Boosting) informed an ensemble model, subsequently refined through Bayesian updating, integrating the derivation cohort's average 90-day mortality with each center's approximate mortality rate to produce posttest probabilities. The ALCoholic Hepatitis Artificial INtelligence Ensemble score integrated age, gender, cirrhosis, and 9 laboratory values, with center-specific mortality rates. Mortality was 18.7% (30 d) and 27.9% (90 d) in the derivation cohort versus 21.7% and 32.5% in the validation cohort. Validation cohort 30 and 90-day AUCs were 0.811 (0.779-0.844) and 0.799 (0.769-0.830), significantly surpassing legacy models like Maddrey's Discriminant Function, Model for End-Stage Liver Disease variations, age-serum bilirubin-international normalized ratio-serum Creatinine score, Glasgow, and modified Glasgow Scores ( p < 0.001). ALCoholic Hepatitis Artificial INtelligence Ensemble score also showcased superior calibration against MELD and its variants. Steroid use improved 30-day survival for those with an ALCoholic Hepatitis Artificial INtelligence Ensemble score > 0.20 in both derivation and validation cohorts. CONCLUSIONS: Harnessing artificial intelligence within a global consortium, we pioneered a scoring system excelling over traditional models for 30 and 90-day AH mortality predictions. Beneficial for clinical trials, steroid therapy, and transplant indications, it's accessible at: https://aihepatology.shinyapps.io/ALCHAIN/ .

A CROSS-SECTIONAL STUDY ON COVID-19 VACCINATION HESITATION AMONG UNIVERSITY STUDENTS.

Students serve as ambassadors, conveying effective messages to encourage the adoption of promotes healthy behaviors. Recognizing their consciousness about corona illness 2019 (COVID-19), desires to utilize the COVID-19 vaccines, and other associated variables will aid in developing viable vaccination promotion tactics for the present COVID-19 pandemic. A transverse-segment internet poll of university students in the healthcare and non-healthcare industries was conducted to analyze their motivations to be vaccinated against the coronavirus. To recruit research participants, a random snowball sampling approach was utilized using digital media sites and mails. The contestants were chosen from throughout India, including several main geographic areas, between Nov-2020 and Jan-2021, prior to the release of the COVID-19 vaccination. There were descriptive metrics utilized to illustrate the research participants' socio-demographics and vaccine-related behaviors. Using logistic regression modeling, key characteristics that are expected to influence vaccination uptake among students were modeled. p 0.06 was judged substantial in each study. 656 students participated in the study, with 48.4% coming from the healthcare sector & 51.5% from other fields. Of these 655 students, 43.6 and 22.4% came from India's northern and eastern areas. Graduate students accounted for 41.1% of the total population, and graduates for around 43.2%. The age range of 56.0% of the students was 18 to 25. Women made up 62% of the population, and 69.5% of them were unmarried. Seventy-eight percent of the students were from the medium socioeconomic level. Concerns about side effects and safety, distrust of government officials, and questions about the vaccine's efficacy were among the reasons given by students in this study for their reluctance to get vaccinated. It is essential to remember that these investigations were carried out at various times and in various nations; thus, the conclusions may not apply to all college students throughout the globe. According to the findings of this research, Indian university students showed rather a great deal of motivating desire to acquire COVID-19 immunizations. The people were either doubtful or reluctant to get the vaccination, which suggests possible vaccine aversion. There is a need for information campaigns and other actions to lessen vaccine hesitancy in order to promote the usage of COVID-19 vaccines.

Isoniazid urine spectrophotometry for prediction of serum pharmacokinetics in adults with TB.

BACKGROUND: Isoniazid (INH) is an important drug in many TB regimens, and unfavorable treatment outcomes can be caused by suboptimal pharmacokinetics. Dose adjustment can be personalized by measuring peak serum concentrations; however, the process involves cold-chain preservation and laboratory techniques such as liquid chromatography (LC)/mass spectrometry (MS), which are unavailable in many high-burden settings. Urine spectrophotometry could provide a low-cost alternative with simple sampling and quantification methods. METHODS: We enrolled 56 adult patients on treatment for active TB. Serum was collected at 0, 1, 2, 4, 6, and 8 h for measurement of INH concentrations using validated LC-MS/MS methods. Urine was collected at 0-4, 4-8, and 8-24 h intervals, with INH concentrations measured using colorimetric methods. RESULTS: The median peak serum concentration and total serum exposure over 24 h were 4.8 mg/L and 16.4 mg*hour/L, respectively. Area under the receiver operator characteristic curves for urine values predicting a subtherapeutic serum concentration (peak <3.0 mg/L) were as follows: 0-4 h interval (AUC 0.85, 95% CI 0.7-0.96), 0-8 h interval (AUC 0.85, 95% CI 0.71-0.96), and 0-24 h urine collection interval (AUC 0.84, 95% CI 0.68-0.96). CONCLUSION: Urine spectrophotometry may improve feasibility of personalized dosing in high TB burden regions but requires further study of target attainment following dose adjustment based on a urine threshold.

CONTEXTE: L'isoniazide (INH) est un médicament important dans de nombreux schémas thérapeutiques contre la TB, et des résultats thérapeutiques défavorables peuvent être dus à une pharmacocinétique sous-optimale. L'ajustement de la dose peut être personnalisé en mesurant les concentrations sériques maximales ; cependant, le processus implique la conservation de la chaîne du froid et des techniques de laboratoire telles que la chromatographie liquide (LC)/spectrométrie de masse (MS), qui ne sont pas disponibles dans de nombreuses régions à forte charge de morbidité. La spec-trophotométrie urinaire pourrait constituer une alternative peu coûteuse avec des méthodes d'échantillonnage et de quantification simples. MÉTHODES: Nous avons recruté 56 patients adultes sous traitement pour une TB active. Le sérum a été prélevé à 0, 1, 2, 4, 6 et 8 h pour mesurer les concentrations d'INH à l'aide de méthodes LC-MS/MS validées. L'urine a été prélevée à des intervalles de 0­4, 4­8 et 8­24 h, et les concentrations d'INH ont été mesurées à l'aide de méthodes colorimétriques. RÉSULTATS: La concentration sérique maximale médiane et l'exposition sérique totale sur 24 h étaient respectivement de 4,8 mg/L et de 16,4 mg*heure/L. L'aire sous les courbes caractéristiques de l'opérateur récepteur a été mesurée à l'aide de méthodes color-imétriques. Les aires sous les courbes caractéristiques des récepteurs pour les valeurs urinaires prédisant une concentration sérique sous-thérapeutique (pic <3,0 mg/L) étaient les suivantes : intervalle 0­4 h (AUC 0,85 ; IC 95% 0,7­0,96), intervalle 0­8 h (AUC 0,85 ; IC 95% 0,71­0,96), et intervalle de collecte d'urine 0­24 h (AUC 0,84 ; IC 95% 0,68­0,96). CONCLUSION: La spectrophotométrie urinaire peut améliorer la faisabilité d'un dosage personnalisé dans les régions à forte charge de TB, mais nécessite une étude plus approfondie de l'atteinte de la cible après l'ajustement de la dose sur la base d'un seuil urinaire.

A comprehensive review of the mechanism, changes, and effect of deep fat frying on the characteristics of restructured foods.

Restructured foods are a blend of various ingredients that are dried or fried to obtain a ready-to-eat product. Several frying techniques have been employed viz., deep fat, microwave, vacuum, air, and spray frying. Deep-fat frying is the most common technique used for products that have improved texture and sensory characteristics. It facilitates various transformations that include starch gelatinization, protein denaturation, nutrient loss, non-enzymatic browning, lipid oxidation, etc. This physicochemical change alters both the product and the fried oil quality. The frying conditions will also influence the product characteristics and affect the properties of the fried product. This review focuses on the mechanisms and transformations during deep fat frying. The properties, namely physical, chemical, sensory, thermal, rheological, and microstructural changes of restructured foods were discussed. Thus, a better understanding of mechanisms and properties at optimum frying conditions would yield the desired product quality.

Zirconia based composite scaffolds and their application in bone tissue engineering.

In the field of bone tissue engineering, biomimetic scaffold utilization is deemed an immensely promising method. The bio-ceramic material Zirconia (ZrO2) has garnered significant attention in the biomimetic scaffolds realm due to its remarkable biocompatibility, superior mechanical strength, and exceptional chemical stability. Numerous examinations have been conducted to investigate the properties and functions of biomimetic structures built from zirconia. Generally, nano-ZrO2 materials have showcased encouraging applications in bone tissue engineering, providing a blend of mechanical robustness, bioactivity, drug delivery capabilities, and antibacterial properties. This review aims to concentrate on the properties and preparations of ZrO2 and its composite materials, while emphasizing its role along with other materials as scaffolds for bone tissue repair applications. The study also discusses the constraints of materials and technology involved in this domain. Ongoing research and development in this area are anticipated to further augment the potential of nano-ZrO2 for advancing bone regeneration therapies.

Longitudinal Biochemical and Behavioral Alterations in a Gyrencephalic Model of Blast-Related Mild Traumatic Brain Injury.

Blast-related traumatic brain injury (bTBI) is a major cause of neurological disorders in the U.S. military that can adversely impact some civilian populations as well and can lead to lifelong deficits and diminished quality of life. Among these types of injuries, the long-term sequelae are poorly understood because of variability in intensity and number of the blast exposure, as well as the range of subsequent symptoms that can overlap with those resulting from other traumatic events (e.g., post-traumatic stress disorder). Despite the valuable insights that rodent models have provided, there is a growing interest in using injury models using species with neuroanatomical features that more closely resemble the human brain. With this purpose, we established a gyrencephalic model of blast injury in ferrets, which underwent blast exposure applying conditions that closely mimic those associated with primary blast injuries to warfighters. In this study, we evaluated brain biochemical, microstructural, and behavioral profiles after blast exposure using in vivo longitudinal magnetic resonance imaging, histology, and behavioral assessments. In ferrets subjected to blast, the following alterations were found: 1) heightened impulsivity in decision making associated with pre-frontal cortex/amygdalar axis dysfunction; 2) transiently increased glutamate levels that are consistent with earlier findings during subacute stages post-TBI and may be involved in concomitant behavioral deficits; 3) abnormally high brain N-acetylaspartate levels that potentially reveal disrupted lipid synthesis and/or energy metabolism; and 4) dysfunction of pre-frontal cortex/auditory cortex signaling cascades that may reflect similar perturbations underlying secondary psychiatric disorders observed in warfighters after blast exposure.

Simultaneous Measurement of GABA, Glutathione, and Glutamate-Glutamine in the Thalamus using Edited MR Spectroscopy: Feasibility and Applications in Traumatic Brain Injury.

BACKGROUND: MR spectroscopy (MRS) is a noninvasive tool for evaluating biochemical alterations, such as glutamate (Glu)/gamma-aminobutyric acid (GABA) imbalance and depletion of antioxidative glutathione (GSH) after traumatic brain injury (TBI). Thalamus, a critical and vulnerable region post-TBI, is challenging for MRS acquisitions, necessitating optimization to simultaneously measure GABA/Glu and GSH. PURPOSE: To assess the feasibility and optimize acquisition and processing approaches for simultaneously measuring GABA, Glx (Glu + glutamine (Gln)), and GSH in the thalamus, employing Hadamard encoding and reconstruction of MEscher-GArwood (MEGA)-edited spectroscopy (HERMES). STUDY TYPE: Prospective. SUBJECTS: 28 control subjects (age: 35.9 ± 15.1 years), and 17 mild TBI (mTBI) patients (age: 32.4 ± 11.3 years). FIELD STRENGTH/SEQUENCE: 3T/T1-weighted magnetization-prepared rapid gradient-echo (MP-RAGE), HERMES. ASSESSMENT: We evaluated the impact of acquisition with spatial saturation bands and post-processing with spectral alignment on HERMES performance in the thalamus among controls. Within-subject variability was examined in five controls through repeated scans within a week. The HERMES spectra in the posterior cingulate cortex (PCC) of controls were used as a reference for assessing HERMES performance in a reliable target. Furthermore, we compared metabolite levels and fitting quality in the thalamus between mTBI patients and controls. STATISTICAL TESTS: Unpaired t-tests and within-subject coefficient-of-variation (CV). A P-value <0.05 was deemed significant. RESULTS: HERMES spectra, acquired with saturation bands and processed with spectral alignment, yielded reliable metabolite measurements in the thalamus. The mean within-subject CV for GABA, Glx, and GSH levels were 18%, 10%, and 16% in the thalamus (7%, 9%, and 16% in the PCC). GABA (3.20 ± 0.60 vs 2.51 ± 0.55, P < 0.01) and Glx (8.69 ± 1.23 vs 7.72 ± 1.19, P = 0.03) levels in the thalamus were significantly higher in mTBI patients than in controls, with GSH (1.27 ± 0.35 vs 1.22 ± 0.28, P = 0.65) levels showing no significant difference. DATA CONCLUSION: Simultaneous measuring GABA/Glx and GSH using HERMES is feasible in the thalamus, providing valuable insight into TBI. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Influence of the calcium voltage-gated channel auxiliary subunit (CACNA2D1) absence on intraocular pressure in mice.

The etiology of elevated intraocular pressure (IOP), a major risk factor for glaucoma (optic nerve atrophy), is poorly understood despite continued efforts. Although the gene variant of CACNA2D1 (encoding α2δ1), a calcium voltage-gated channel auxiliary subunit, has been reported to be associated with primary open-angle glaucoma, and the pharmacological mitigation of α2δ1 activity by pregabalin lowers IOP, the cellular basis for α2δ1 role in the modulation of IOP remains unclear. Our recent findings reveled readily detectable levels of α2δ1 and its ligand thrombospondin in the cytoskeletome fraction of human trabecular meshwork (TM) cells. To understand the direct role of α2δ1 in the modulation of IOP, we evaluated α2δ1 null mice for changes in IOP and found a moderate (∼10%) but significant decrease in IOP compared to littermate wild type control mice. Additionally, to gain cellular insights into α2δ1 antagonist (pregabalin) induced IOP changes, we assessed pregabalin's effects on human TM cell actin cytoskeletal organization and cell adhesive interactions in comparison with a Rho kinase inhibitor (Y27632), a known ocular hypotensive agent. Unlike Y27632, pregabalin did not have overt effects on cell morphology, actin cytoskeletal organization, or cell adhesion in human TM cells. These results reveal a modest but significant decrease in IOP in α2δ1 deficient mice, and this response appears to be not associated with the contractile and cell adhesive characteristics of TM cells based on the findings of pregabalin effects on isolated TM cells. Therefore, the mechanism by which pregabalin lowers IOP remains elusive.

Enhanced control over size, areal density, and shape of substrate-supported Au and Ag nanoparticles by solid-state dewetting and alloying.

The ability to manipulate the dimensions, areal density, and form of substrate-supported Au and Ag nanoparticles (NPs) is highly desirable for utilizing their plasmonic properties in biosensing, photovoltaics, and nanophotonic applications. The transformation of thin films into the substrate-supported nanostructures by solid-state dewetting (SSD), provides an avenue to manipulate the dimensional aspects of nanostructures simply and cost-effectively on a large scale. However, spontaneous agglomeration of the film produces randomly distributed and non-uniform nanostructures that must be controlled. Here, we have systematically studied the effect of annealing temperature, between 200 °C and 750 °C, on the dewetting morphology evolution of Au, Ag, and Au-Ag bilayer ultrathin films sputter deposited on thec-plane (0001) sapphire substrates. Regardless of the film thickness, Ag films dewet faster than Au films and produce spherical NPs, compared to faceted Au NPs, with broader size distribution. Whereas, by the SSD of Au-Ag bilayer ultrathin films, highly spherical and monodisperse AuAg bimetallic NPs can be fabricated. Furthermore, we have shown the possibility of fabricating the AuAg bimetallic NPs of varying compositions by adjusting the thickness of individual layers, thus enabling us to smoothly tune the spectral location of plasmonic resonance within the visible range.

Exploring the potential of Eu3+ ions doped heavy metal oxide containing germanium borate glasses for high efficiency red emitting solid-state lasers.

Glasses activated with europium show promising potential for use in applications relating to photonics, in particular solid-state laser generation. In the current work, Eu2O3 incorporated gemanium borate glasses were developed and explored their potentiality towards lasing active medium by probing physical, structural, optical and lasing properties in detail. The physical and structural features of each glass indicated the presence of non-bridging oxygens (NBOs) and an enhancement in network stability on account of the inclusion of europium ions into the GeO2 glass network. Optical energy band gaps, Ed, Eo, no, So, and λo values were obtained by absorption spectra and found to be increased with europium content. The sequence of Judd-Ofelt (JO) intensity parameters (Ω2, Ω4, and Ω6) exhibited the trend Ω2 > Ω4 > Ω6, and it confirmed the covalent nature of the as-developed glasses. 1 mol% Eu2O3 doped glasses exhibited the highest photoluminescence, quantum efficiency and fluorescence intensity ratio (R). The decay profiles showed single exponential nature for 5D0 state of Eu3+ ions and their lifetime values were calculated. The results amply demonstrated the viability of the manufactured glasses as a potential solid-state active laser medium, with the CIE diagram confirming the intense red color emission as seen from the PL spectra.

Predictive modelling of methane yield in biochar-amended cheese whey and septage co-digestion: Exploring synergistic effects using Gompertz and neural networks.

This study performed bench scale studies on anaerobic co-digestion of cheese whey and septage mixed with biochar (BC) as additive at various dosages (0.5 g, 1 g, 2 g and 4 g) and total solids (TS) concentrations (5%, 7.5%, 10%,12.5% and 15%). The experimental results revealed 29.58% increase in methane yield (486 ± 11.32 mL/gVS) with 27% reduction in lag phase time at 10% TS concentration and 50 g/L of BC loading. The mechanistic investigations revealed that BC improved process stability by virtue of its robust buffering capacity and mitigated ammonia inhibition. Statistical analysis indicates BC dosage had a more pronounced effect (P < 0.0001) compared to the impact of TS concentrations. Additionally, the results were modelled using Gompertz model (GM) and artificial neural network (ANN) algorithm, which revealed the outperformance of ANN over GM with MSE 17.96, R2 value 0.9942 and error 0.27%. These findings validated the practicality of utilizing a high dosage of BC in semi-solid anaerobic digestion conditions.

Recent Advances in the Diagnosis and Management of Congenital Heart Disease.

Congenital heart defects (CHDs) are structural abnormalities of the heart or blood vessels that occur while cardiac structures are being formed in utero [...].