The developing hippocampus: Microstructural evolution through childhood and adolescence.

The hippocampus is a structure in the medial temporal lobe which serves multiple cognitive functions. While important, the development of the hippocampus in the formative period of childhood and adolescence has not been extensively investigated, with most contemporary research focusing on macrostructural measures of volume. Thus, there has been little research on the development of the micron-scale structures (i.e., microstructure) of the hippocampus, which engender its cognitive functions. The current study examined age-related changes of hippocampal microstructure using diffusion MRI data acquired with an ultra-strong gradient (300 mT/m) MRI scanner in a sample of children and adolescents (N=88; 8-19 years). Surface-based hippocampal modelling was combined with established microstructural approaches, such as Diffusion Tensor Imaging (DTI) and Neurite Orientation Dispersion Density Imaging (NODDI), and a more advanced gray matter diffusion model Soma And Neurite Density Imaging (SANDI). No significant changes in macrostructural measures (volume, gyrification, and thickness) were found between 8-19 years, while significant changes in microstructure measures related to neurites (from NODDI and SANDI), soma (from SANDI), and mean diffusivity (from DTI) were found. In particular, there was a significant increase across age in neurite MR signal fraction and a significant decrease in extracellular MR signal fraction and mean diffusivity across the hippocampal subfields and long-axis. A significant negative correlation between age and MR apparent soma radius was found in the subiculum and CA1 throughout the anterior and body of the hippocampus. Further surface-based analyses uncovered variability in age-related microstructural changes between the subfields and long-axis, which may reflect ostensible developmental differences along these two axes. Finally, correlation of hippocampal surfaces representing age-related changes of microstructure with maps derived from histology allowed for postulation of the potential underlying microstructure that diffusion changes across age may be capturing. Overall, distinct neurite and soma developmental profiles in the human hippocampus during late childhood and adolescence are reported for the first time.

A comparison of several separation processes for eggshell membrane powder as a natural biomaterial for skin regeneration.

BACKGROUND: Numerous studies have focused on skin damage, the most prevalent physical injury, aiming to improve wound healing. The exploration of biomaterials, specifically eggshell membranes (ESMs), is undertaken to accelerate the recovery of skin injuries. The membrane must be separated from the shell to make this biomaterial usable. Hence, this investigation aimed to identify more about the methods for membrane isolation and determine the most efficient one for usage as a biomaterial. METHODS AND MATERIALS: For this purpose, ESM was removed from eggs using different protocols (with sodium carbonate, acetic acid, HCl, calcium carbonate, and using forceps for separation). Consequently, we have examined the membranes' mechanical and morphological qualities. RESULTS: According to the analysis of microscopic surface morphology, the membranes have appropriate porosity. MTT assay also revealed that the membranes have no cytotoxic effect on 3T3 cells. The results indicated that the ESM had acquired acceptable coagulation and was compatible with blood. Based on the obtained results, Provacol 4 (0.5-mol HCl and neutralized with 0.1-mol NaOH) was better than other methods of extraction and eggshell separation because it was more cell-compatible and more compatible with blood. CONCLUSION: This study demonstrates that ESMs can be used as a suitable biomaterial in medical applications.

Exploring Hydrogel Nanoparticle Systems for Enhanced Ocular Drug Delivery.

Drug delivery to the ocular system is affected by anatomical factors like the corneal epithelium, blinking reflex, aqueous blood barrier, and retinal blood barrier, which lead to quick removal from the site and inefficient drug delivery. Developing a drug delivery mechanism that targets specific eye tissue is a major hurdle for researchers. Our study examines the challenges of drug absorption in these pathways. Hydrogels have been researched as a suitable delivery method to overcome some obstacles. These are developed alone or in conjunction with other technologies, such as nanoparticles. Many polymer hydrogel nanoparticle systems utilizing both natural and synthetic polymers have been created and investigated; each has pros and cons. The complex release mechanism of encapsulated agents from hydrogel nanoparticles depends on three key factors: hydrogel matrix swelling, drug-matrix chemical interactions, and drug diffusion. This mechanism exists regardless of the type of polymer. This study provides an overview of the classification of hydrogels, release mechanisms, and the role of controlled release systems in pharmaceutical applications. Additionally, it highlights the integration of nanotechnology in ocular disease therapy, focusing on different types of nanoparticles, including nanosuspensions, nanoemulsions, and pharmaceutical nanoparticles. Finally, the review discusses current commercial formulations for ocular drug delivery and recent advancements in non-invasive techniques. The objective is to present a comprehensive overview of the possibilities for enhancing ocular medication delivery through hydrogel nanoparticle systems.

Focused Ultrasound for Neurodegenerative Diseases.

Neurodegenerative diseases are a leading cause of death and disability and pose a looming global public health crisis. Despite progress in understanding biological and molecular factors associated with these disorders and their progression, effective disease modifying treatments are presently limited. Focused ultrasound (FUS) is an emerging therapeutic strategy for Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. In these contexts, applications of FUS include neuroablation, neuromodulation, and/or blood-brain barrier opening with and without facilitated intracerebral drug delivery. Here, the authors review preclinical evidence and current and emerging applications of FUS for neurodegenerative diseases and summarize future directions in the field.

Acute toxicity of some expired insecticides on rats and their effects on some vital parameters and residues in the liver and kidney.

Little information is available on the adverse effects of expired pesticides on the environment, so it is essential to characterize the risk of these chemicals to non-target organisms. Therefore, this work aims to estimate and compare the acute toxicity (LD50) of unexpired and expired formulations of malathion, chlorpyrifos, and lambda-cyhalothrin in rats and to determine their residues in the liver and kidneys of treated rats. This is the first study to investigate the toxic effects of expired pesticides on rats. The acute toxicity of expired lambda-cyhalothrin was higher than that of non-expired rats, while the opposite was observed in rats treated with malathion and chlorpyrifos. All formulations tested caused clinical signs of toxicity in the treated rats. The data showed that some expired formulations significantly affected body weight and estimated vital signs compared to non-expired pesticides. The data showed that the highest residues were found in the liver and kidneys of rats treated with both malathion formulations, followed by chlorpyrifos; however, the lowest residues were found in rats treated with lambda-cyhalothrin, which can be referred to as LD50 values of the insecticides tested. The residues detected after the 10th dose gradually decreased at the end of the recovery period, and their losses ranged from 80.0 to 95.4% in the liver and from 92.3 to 99.99% (undetectable). The results show that the toxic effects of expired and non-expired formulations are different. This underlines the need to dispose of expired compounds carefully to prevent their discharge into the ecosystem.

The Role of Serology in the Diagnosis of Ocular Predominant Mucous Membrane Pemphigoid and the Search for an Ocular-Specific Autoantigen.

Ocular predominant mucous membrane pemphigoid (oMMP) is a severe subtype of MMP that can lead to scarring and blindness. While conjunctival biopsy for direct immunofluorescence (DIF) is considered the gold standard for diagnosis, limited sensitivity results in a false-negative rate upwards of 40%. Likewise, it remains unclear to what extent a negative biopsy, whether false-negative or true-negative, results in a different prognosis, with patients previously termed "pseudopemphigoid" demonstrating comparable disease progression. Serologic testing allows for a less invasive means to demonstrate circulating autoantibodies against known autoantigens in pemphigoid diseases. Patients with MMP, particularly oMMP, however, typically demonstrate low titers of circulating autoantibodies, limiting the diagnostic utility of these tests. The autoantigen integrin ß4 has been previously reported to be a specific marker of pure ocular MMP, while in the majority of patients with oMMP, the identified target antigens are BP180 (type XVII collagen) and laminin 332. Recent studies have, however, demonstrated inconsistent reactivity and specificity for integrin ß4 as an ocular-specific marker in MMP. Herein, we review the role of serologic testing in the diagnosis and prognosis of oMMP, as well as the current understanding of autoantigens in oMMP.Abbreviations: BMZ - basement membrane zone, DIF - direct immunofluorescence, IIF - indirect immunofluorescence, MMP - mucous membrane pemphigoid, oMMP - ocular predominant mucous membrane pemphigoid.

Changes in physiological signal entropy in patients with obstructive sleep apnoea: a systematic review.

Background and Objective.Obstructive sleep apnoea (OSA) affects an estimated 936 million people worldwide, yet only 15% receive a definitive diagnosis. Diagnosis of OSA poses challenges due to the dynamic nature of physiological signals such as oxygen saturation (SpO2) and heart rate variability (HRV). Linear analysis methods may not fully capture the irregularities present in these signals. The application of entropy of routine physiological signals offers a promising method to better measure variabilities in dynamic biological data. This review aims to explore entropy changes in physiological signals among individuals with OSA.Approach.Keyword and title searches were performed on Medline, Embase, Scopus, and CINAHL databases. Studies had to analyse physiological signals in OSA using entropy. Quality assessment used the Newcastle-Ottawa Scale. Evidence was qualitatively synthesised, considering entropy signals, entropy type, and time-series length.Main results.Twenty-two studies were included. Multiple physiological signals related to OSA, including SpO2, HRV, and the oxygen desaturation index (ODI), have been investigated using entropy. Results revealed a significant decrease in HRV entropy in those with OSA compared to control groups. Conversely, SpO2and ODI entropy values were increased in OSA. Despite variations in entropy types, time scales, and data extraction devices, studies using receiver operating characteristic curves demonstrated a high discriminative accuracy (>80% AUC) in distinguishing OSA patients from control groups.Significance. This review highlights the potential of SpO2entropy analysis in developing new diagnostic indices for patients with OSA. Further investigation is needed before applying this technique clinically.

Executive function and cortical thickness in biomarker aMCI.

INTRODUCTION: Memory deficits are the primary symptom in amnestic Mild Cognitive Impairment (aMCI); however, executive function (EF) deficits are common. The current study examined EF in aMCI based upon amyloid status (A+/A-) and regional atrophy in signature areas of Alzheimer's disease (AD). METHOD: Participants included 110 individuals with aMCI (A+ = 66; A- = 44) and 33 cognitively healthy participants (HP). EF was assessed using four neuropsychological assessment measures. The cortical thickness of the AD signature areas was calculated using structural MRI data. RESULTS: A + had greater EF deficits and cortical atrophy relative to A - in the supramarginal gyrus and superior parietal lobule. A - had greater EF deficits relative to HP, but no difference in signature area cortical thickness. DISCUSSION: The current study found that the degree of EF deficits in aMCI are a function of amyloid status and cortical thinning in the parietal cortex.

Cortical Network Disruption Is Minimal in Early Stages of Psychosis.

Background and Hypothesis: Schizophrenia is associated with white matter disruption and topological reorganization of cortical connectivity but the trajectory of these changes, from the first psychotic episode to established illness, is poorly understood. Current studies in first-episode psychosis (FEP) patients using diffusion magnetic resonance imaging (dMRI) suggest such disruption may be detectable at the onset of psychosis, but specific results vary widely, and few reports have contextualized their findings with direct comparison to young adults with established illness. Study Design: Diffusion and T1-weighted 7T MR scans were obtained from N = 112 individuals (58 with untreated FEP, 17 with established schizophrenia, 37 healthy controls) recruited from London, Ontario. Voxel- and network-based analyses were used to detect changes in diffusion microstructural parameters. Graph theory metrics were used to probe changes in the cortical network hierarchy and to assess the vulnerability of hub regions to disruption. The analysis was replicated with N = 111 (57 patients, 54 controls) from the Human Connectome Project-Early Psychosis (HCP-EP) dataset. Study Results: Widespread microstructural changes were found in people with established illness, but changes in FEP patients were minimal. Unlike the established illness group, no appreciable topological changes in the cortical network were observed in FEP patients. These results were replicated in the early psychosis patients of the HCP-EP datasets, which were indistinguishable from controls in most metrics. Conclusions: The white matter structural changes observed in established schizophrenia are not a prominent feature in the early stages of this illness.

The lateral based nasopharyngeal flap: A novel vascularized flap for skull base reconstruction.

As the indications for endoscopic skull base approaches have increased, so has the need for more versatile vascularized flaps for skull base reconstruction. Here, we describe a novel lateral based nasopharyngeal flap (LNPF). Two cadaver heads were dissected to elucidate flap anatomy, dimensions, and technique. A retrospective review was performed on two cases where LNPF was used to repair CSF leaks in the nasopharyngeal area, and outcomes reported. The LNPF is an ascending pharyngeal artery myomucosal flap that includes the nasopharyngeal mucosa and the superior pharyngeal constrictor muscle. The flap was 1.2 × 2.2 cm in greatest dimensions. The LNPF was used for salvage CSF leak repair in two cases: one clival and one tubal. Both patients had resolution of leak at 7 months follow-up. The LNPF is a novel flap with reconstruction potential for the nasopharynx, including the lower clivus and the eustachian tube.

Development of alginate/chitosan hydrogel loaded with obestatin and evaluation of collagen type I, III, VEGF and TGF-ß1 gene expression for skin repair in a rat model (in vitro and in vitro study).

BACKGROUND: Skin injuries have long been recognized as a prevalent type of physical injury. As a result, numerous research studies have been performed to discover an effective mechanism for wound healing. Therefore, tissue engineering of skin has developed as a potential solution for traditional methods of treating skin injuries. METHODS AND MATERIALS: Alginate/Chitosan hydrogel was mixed with 1, 10, 100, and 150 µM Obestatin, and evaluated the morphology, cumulative release, hemocompatibility and cytocompatibility, water absorption, cell viability, weight loss, and antibacterial characteristics of three-dimensional (3D) alginate (Alg) and chitosan (Cs) hydrogels during the process of wound curing. Various concentrations of Obestatin (Obes) were utilized for this purpose. Finally, the hydrogels that were made were tested on a full-thickness dermal wound in a Wistar rat model. The curative effects were determined by analyzing RNA expression and examining tissue stained with Masson's trichrome (MT) and hematoxylin-eosin (H&E). RESULTS: The biodegradability of this hydrogel was verified using weight loss testing, which demonstrated a reduction of around 90% after a period of 3 days. Furthermore, the MTT assay demonstrated that hydrogels have a beneficial effect on cell proliferation without inducing any harmful effects. Furthermore, the hydrogels produced demonstrated higher wound closure in vivo compared to the wounds treated with gauze (negative control group). Among the hydrogel groups, the chitosan/alginate/obestatin 100 µM group exhibited the apical percentage of wound closure, gene expression, and secondary epithelialization, but in 150 µM concentrations, we saw a lower rate of cell growth and proliferation and increase in hemolysis. In addition, RT-PCR analysis demonstrated that a concentration of 100 µM obestatin resulted in an upregulation in the expression of mRNA for vascular endothelial growth factor (VEGF), collagen type I & type III, and transforming growth factor-beta (TGF-ß). CONCLUSION: The present study suggests that 3D Alg/Cs hydrogels with a concentration of 100 µM obestatin have the potential for clinical application in the treatment of skin injuries.

Loss of cped1 does not affect bone and lean tissue in zebrafish.

Human genetic studies have nominated Cadherin-like and PC-esterase Domain-containing 1 (CPED1) as a candidate target gene mediating bone mineral density (BMD) and fracture risk heritability. Recent efforts to define the role of CPED1 in bone in mouse and human models have revealed complex alternative splicing and inconsistent results arising from gene targeting, making its function in bone difficult to interpret. To better understand the role of CPED1 in adult bone mass and morphology, we conducted a comprehensive genetic and phenotypic analysis of cped1 in zebrafish, an emerging model for bone and mineral research. We analyzed two different cped1 mutant lines and performed deep phenotyping to characterize more than 200 measures of adult vertebral, craniofacial, and lean tissue morphology. We also examined alternative splicing of zebrafish cped1 and gene expression in various cell/tissue types. Our studies fail to support an essential role of cped1 in adult zebrafish bone. Specifically, homozygous mutants for both cped1 mutant alleles, which are expected to result in loss-of-function and impact all cped1 isoforms, exhibited no significant differences in the measures examined when compared to their respective wildtype controls, suggesting that cped1 does not significantly contribute to these traits. We identified sequence differences in critical residues of the catalytic triad between the zebrafish and mouse orthologs of CPED1, suggesting that differences in key residues, as well as distinct alternative splicing, could underlie different functions of CPED1 orthologs in the two species. Our studies fail to support a requirement of cped1 in zebrafish bone and lean tissue, adding to evidence that variants at 7q31.31 can act independently of CPED1 to influence BMD and fracture risk.

Resolution of Plaque Keratopathy in a Patient with Atopic Keratoconjunctivitis After Treatment with Leflunomide.

PURPOSE: To report a case of resolution of corneal findings in a patient with atopic keratoconjunctivitis after treatment with leflunomide. METHODS: Case report. RESULTS: A 57-year-old male presented with ocular signs and symptoms consistent with severe atopic keratoconjunctivitis. His case was distinguished by impressive sub-epithelial Salzmann-like nodules in the shape of petaloid plaques in both eyes. These keratinized plaques persisted despite topical steroids, tacrolimus ointment, and routine subconjunctival triamcinolone injections. The patient was started on leflunomide 10 mg daily for seropositive rheumatoid arthritis with rapid subsequent improvement in his symptoms, vision, and keratopathy. The patient has remained stable on oral leflunomide. CONCLUSION: To the authors' knowledge, this is the first case report to describe rapid resolution of "plaque keratopathy" and improvement of AKC with leflunomide treatment. Further work remains to be done to elucidate the role of disease-modifying drugs in atopic keratoconjunctivitis.

Effectiveness of Hydrated Sodium Calcium Aluminosilicates and Discarded Date Pits as Dietary Adsorbents for Aflatoxin B1 in Enhancing Broiler Chicken Productive Performance, Hepatic Function, and Intestinal Health.

The research aimed to evaluate how effective hydrated sodium calcium aluminosilicates (HSCASs) and discarded date pits (DDPs) are as dietary adsorbents for aflatoxin B1 (AFB1) in enhancing the performance and health of broiler chickens aged 16 to 30 days. A total of 240 Ross 308 straight-run broilers were randomly allocated into four dietary groups, each with 10 replicates: a control diet, a control diet with 1000 ppb AFB1, an AFB1-contaminated diet with 0.5% HSCAS, and an AFB1-contaminated diet with 4% DDP. Incorporating HSCASs or DDPs into the AFB1-contaminated diet resulted in significant improvements across various parameters, involving increased body weight, improved feed conversion ratio, higher dressing percentage, decreased relative weights of kidney and spleen, elevated serum levels of total protein, globulin, and glucose, reduced serum alanine aminotransferase activity, and heightened hepatic protein concentration and glutathione peroxidase activity, along with diminished hepatic malondialdehyde content and glutamic oxaloacetic transaminase activity. Moreover, both supplements led to increased ileal villus height and surface area, enhanced apparent nitrogen-corrected metabolizable energy digestibility, and decreased AFB1 residues in the liver and kidney. Moreover, the dietary inclusion of DDPs significantly decreased relative liver weight, raised serum albumin concentration, lowered serum alkaline phosphatase activity, enhanced hepatic total antioxidant capacity level, and augmented ileal villus width. Conversely, the dietary addition of HSCASs significantly heightened apparent crude protein digestibility. In conclusion, the inclusion of HSCASs and DDPs in AFB1-contaminated diets can mitigate the toxic effects of AFB1 on broiler chickens, with DDPs exhibiting additional advantages in optimizing liver function and gut morphology.

Various Morphologies of Graphitic Carbon Nitride (g-C3N4) and Their Effect on the Thermomechanical Properties of Thermoset Epoxy Resin Composites.

This research aims to highlight the importance of diverse forms of graphitic carbon nitride (g-C3N4) as strengthening elements in epoxy composites. It explores the influence of three different forms of g-C3N4 and their concentrations on the mechanical properties of the epoxy composites. Various characterization techniques, such as scanning electron microscopy (SEM), dynamic light scattering (DLS), thermogravimetric analysis (TGA), and Fourier-transform infrared spectroscopy (FTIR), were utilized to comprehend the effects of g-C3N4 morphology and particle size on the physical and chemical characteristics of epoxy resin. Mechanical properties, such as tensile strength, strain, modulus, and fracture toughness, were determined for the composite samples. SEM analysis was performed to examine crack morphology in samples with different reinforcements. Findings indicate that optimal mechanical properties were achieved with a 0.5 wt% bulk g-C3N4 filler, enhancing tensile strength by 14%. SEM micrographs of fracture surfaces revealed a transition from brittle to rough morphology, suggesting increased toughness in the composites. While the TGA results showed no significant impact on degradation temperature, dynamic mechanical analysis demonstrated a 17% increase in glass transition temperature. Furthermore, the improvement in thermal breakdown up to 600 °C was attributed to reinforced covalent bonds between carbon and nitrogen, supported by FTIR results.

Randomized Clinical Trial on Direct Composite and Indirect Ceramic Laminate Veneers in Multiple Diastema Closure Cases: Two-Year Follow-Up.

In recent years, laminate veneer restorations should be considered as a minimally invasive treatment option for several aesthetic reasons. This study compared direct composite veneers' and indirect ceramic laminate veneers' longevity in multiple diastema closures. A total of 28 patients with a mean age of 26 years received 60 direct resin composite (Estelite Asteria; n = 14) and 60 indirect ceramic veneers (IPS e.max Press; n = 14) on the maxillary anterior teeth with diastema closure. Veneers were evaluated at baseline and thereafter every 6 months for up to 2 years using USPHS criteria. Data were analyzed with Fisher's exact and chi-squared tests, while Kaplan-Meier curve was used to assess time to event. In total, three failures were observed in the form of debonding (n = 1) and fracture (n = 2) in the indirect ceramic veneers. No significant difference was observed between the survival rates of composite and ceramic veneers (Estelite Asteria: 93.4%, IPS e.max Press: 95%; p > 0.05). The overall survival rate was 94.2% (Kaplan-Meier). Staining (n = 11) and roughness (n = 14) were frequently observed for the resin composite veneers up to the final recall. Thereby, the preliminary results from this clinical trial comparing two veneer materials indicated that their survival rates were statistically similar. However, surface quality changes were more frequent in the composite veneer material.

Investigating the effect of levothyroxine replacement on cholesterol levels in hypothyroid patients.

Introduction: Effects of levothyroxine therapy on the lipid profile of hypothyroid patients lead to decrease in the risk of cardiovascular diseases and mortality. Objective: Overt or subclinical hypothyroid dysfunction has negative effects on lipid metabolism and leads to hypercholesterolemia that in turn increases the risk of cardiovascular diseases and mortality. In this matter, several interventional studies investigated the effects of levothyroxine therapy on the lipid profile of hypothyroid patients, and conflicting results have been obtained. The current research aims to investigate the effect of levothyroxine replacement on cholesterol levels in hypothyroid patients. Methods: The present prospective study examined 112 patients (mean age of 43.80 ± 14.36 years) with overt hypothyroidism. To do so, 72.3% of patients were females. Levothyroxine replacement therapy was prescribed for patients, and they were examined monthly to evaluate the effects of therapy on their lipid profiles. After reaching normal thyroid stimulating hormone (TSH), the patients' laboratory parameters, including TSH, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides, were surveyed. Results: After Levothyroxine therapy, there was a significant reduction in mean TSH (62.03 vs. 2.33 ± 1.95; P < 0.0001), triglycerides (145.57 ± 88.65 vs. 121.91 ± 59.52, P = 0.002), cholesterol (203.90 ± 53.73 vs. 166.65 ± 40.07, P < 0.0001), and serum LDL (123.61 ± 45.03 vs. 95.99 ± 24.20, P < 0.0001), but the mean value of serum HDL did not show any significant change (54.18 ± 16.60 vs. 51.59 ± 18.38, P = 0.274). Conclusions: Levothyroxine therapy has beneficial effects on lipid profile in patients with overt hypothyroidism because it decreases serum triglyceride, total cholesterol, and LDL. However, levothyroxine therapy does not significantly change HDL levels.

Infectious keratitis in pediatric population aged less than two years: a tertiary eye institute experience.

BACKGROUND: Infectious keratitis is a serious ocular condition, which can lead to corneal scarring, vision loss, and even blindness. Pediatric infectious keratitis accounts for about 13% of all cases, although there is a lack of comprehensive data regarding keratitis in less than two years of age population group. This study was aimed to determine predisposing factors, clinical characteristics, microbial profile, and management of infectious keratitis in a population of children aged less than two years. MATERIALS AND METHODS: A retrospective study was carried out in a tertiary eye institute over a period of 18 years from July 2005 to December 2022. Collected data was analyzed for demographics, predisposing factors, clinical features, and treatment methods. RESULTS: Fifty-seven cases of keratitis were identified. Age of the patients ranged from 1 to 24 months (Median: 6, interquartile range: 2-10). Thirty cases were male (52.6%). Predisposing factors were identified in 39 cases (68.4%): consisting of prior ocular trauma (n = 15), previous intraocular surgery (n = 11), ocular surface disease (n = 10), nasolacrimal duct obstruction (n = 4), prematurity (n = 3), developmental delay (n = 2), TORCH infection (n = 1), and contact lens (n = 1). Corneal thinning was observed in 29 eyes (50.9%), which progressed to perforation in 13 eyes (22.8%). Three patients developed endophthalmitis (95% CI, 1.5-13.4%). Most eyes had negative smear (60.4%) and culture (59.6%) results. Pseudomonas aeruginosa was the most common microorganism (11 of 21). Candida albicans was isolated in one case. In vitro susceptibility results showed good coverage of the combined ceftazidime and vancomycin regimen (100%). Surgical procedures were carried out in 35 eyes (61.4%) and 15 eyes required tectonic procedures (26.3%). CONCLUSION: Despite good coverage of medical treatment over cultured isolates, surgical tectonic intervention was required in nearly a quarter of cases to resolve the corneal infection. This finding indicates the necessity of prompt patient referring, corneal sampling and initiation of the treatment.

Increased mean diffusivity of the caudal motor SNc identifies patients with REM sleep behaviour disorder and Parkinson's disease.

Idiopathic rapid eye movement sleep behaviour disorder (iRBD)-a Parkinson's disease (PD) prodrome-might exhibit neural changes similar to those in PD. Substantia nigra pars compacta (SNc) degeneration underlies motor symptoms of PD. In iRBD and early PD (ePD), we measured diffusion MRI (dMRI) in the caudal motor SNc, which overlaps the nigrosome-1-the earliest-degenerating dopaminergic neurons in PD-and in the striatum. Nineteen iRBD, 26 ePD (1.7 ± 0.03 years), and 46 age-matched healthy controls (HCs) were scanned at Western University, and 47 iRBD, 115 ePD (0.9 ± 0.01 years), and 56 HCs were scanned through the Parkinson's Progression Markers Initiative, using 3T MRI. We segmented the SNc and striatum into subregions using automated probabilistic tractography to the cortex. We measured mean diffusivity (MD) and fractional anisotropy (FA) along white-matter bundles and subregional surfaces. We performed group-level and classification analyses. Increased caudal motor SNc surface MD was the only iRBD-HCs and ePD-HCs difference replicating across datasets (padj < 0.05). No iRBD-ePD differences emerged. Caudal motor SNc surface MD classified patient groups from HCs at the single-subject level with good-to-excellent balanced accuracy in an independent sample (0.91 iRBD and 0.86 iRBD and ePD combined), compared to fair performance for total SNc surface MD (0.72 iRBD and ePD). Caudal motor SNc surface MD correlated significantly with MDS-UPDRS-III scores in ePD patients. Using dMRI and automated segmentation, we detected changes suggesting altered microstructural integrity in iRBD and ePD in the nigrostriatal subregion known to degenerate first in PD. Surface MD of the caudal motor SNc presents a potential measure for inclusion in neuroimaging biomarkers of iRBD and PD.

Physiological network approach to prognosis in cirrhosis: A shifting paradigm.

Decompensated liver disease is complicated by multi-organ failure and poor prognosis. The prognosis of patients with liver failure often dictates clinical management. Current prognostic models have focused on biomarkers considered as individual isolated units. Network physiology assesses the interactions among multiple physiological systems in health and disease irrespective of anatomical connectivity and defines the influence or dependence of one organ system on another. Indeed, recent applications of network mapping methods to patient data have shown improved prediction of response to therapy or prognosis in cirrhosis. Initially, different physical markers have been used to assess physiological coupling in cirrhosis including heart rate variability, heart rate turbulence, and skin temperature variability measures. Further, the parenclitic network analysis was recently applied showing that organ systems connectivity is impaired in patients with decompensated cirrhosis and can predict mortality in cirrhosis independent of current prognostic models while also providing valuable insights into the associated pathological pathways. Moreover, network mapping also predicts response to intravenous albumin in patients hospitalized with decompensated cirrhosis. Thus, this review highlights the importance of evaluating decompensated cirrhosis through the network physiologic prism. It emphasizes the limitations of current prognostic models and the values of network physiologic techniques in cirrhosis.