Dual optical elastography detects TGF - ß -induced alterations in the biomechanical properties of skin scaffolds.

Significance: The skin's mechanical properties are tightly regulated. Various pathologies can affect skin stiffness, and understanding these changes is a focus in tissue engineering. Ex vivo skin scaffolds are a robust platform for evaluating the effects of various genetic and molecular interactions on the skin. Transforming growth factor-beta ( TGF - ß ) is a critical signaling molecule in the skin that can regulate the amount of collagen and elastin in the skin and, consequently, its mechanical properties. Aim: This study investigates the biomechanical properties of bio-engineered skin scaffolds, focusing on the influence of TGF - ß , a signaling molecule with diverse cellular functions. Approach: The TGF - ß receptor I inhibitor, galunisertib, was employed to assess the mechanical changes resulting from dysregulation of TGF - ß . Skin scaffold samples, grouped into three categories (control, TGF - ß -treated, and TGF - ß + galunisertib-treated), were prepared in two distinct culture media-one with aprotinin (AP) and another without. Two optical elastography techniques, namely wave-based optical coherence elastography (OCE) and Brillouin microscopy, were utilized to quantify the biomechanical properties of the tissues. Results: Results showed significantly higher wave speed (with AP, p < 0.001 ; without AP, p < 0.001 ) and Brillouin frequency shift (with AP, p < 0.001 ; without AP, p = 0.01 ) in TGF - ß -treated group compared with the control group. The difference in wave speed between the control and TGF - ß + galunisertib with ( p = 0.10 ) and without AP ( p = 0.36 ) was not significant. Moreover, the TGF - ß + galunisertib-treated group exhibited lower wave speed without and with AP and reduced Brillouin frequency shift than the TGF - ß -treated group without AP, further strengthening the potential role of TGF - ß in regulating the mechanical properties of the samples. Conclusions: These findings offer valuable insights into TGF - ß -induced biomechanical alterations in bio-engineered skin scaffolds, highlighting the potential of OCE and Brillouin microscopy in the development of targeted therapies in conditions involving abnormal tissue remodeling and fibrosis.

A Prospective Study on Perfusion MRI Changes in Intracranial Meningiomas Following Gamma Knife Therapy.

BACKGROUND: Radiosurgery plays an important role as a treatment modality for intracranial meningiomas. Perfusion MR imaging can be performed by using arterial spin-labeling (ASL) which is a relatively new and advanced technique. OBJECTIVES: To assess the changes in perfusion parameters on ASL perfusion MRI in intracranial meningioma after radiosurgery and correlate with histopathological grade of meningioma. MATERIALS AND METHODS: In this Prospective study done at the our institute over a period of 20 months (Jan 2016-Aug 2017), patients with intracranial meningiomas had perfusion MRI with ASL sequence on GE Optima 450W®, 1.5T MRI (GE Medical Systems) prior to GKT and at 6 months after GKT were included in the study. RESULTS: Twenty-seven patients were included in this study. Mean cerebral blood flow (CBF) was higher in angiomatous meningiomas. Though mean values of average CBF, maximum, minimum, and SD derived from the ASL MR perfusion were relatively higher in post GKT group as compared to those obtained in pre-GKT but it was not clinically significant. Mean baseline volume of whole cohort was 5.71 cm3 and decreased significantly post GKT in a follow up of 6 months to 5.59 cm3 (P value 0.0018). On comparing volumes of primary and secondary group, volumes were not found be significantly decreased in primary group (P value = 0.1361), 0.1361), but significantly reduced in secondary group (7.13 vs 7.034 cm3) (P value of = 0.0038). CONCLUSION: Our preliminary observations support ASL as a sensitive MRI sequence for the evaluation of meningioma perfusion patterns.

Effect of loss-of-function CYP2C19 variants on clinical outcomes in coronary artery disease patients treated with clopidogrel: A systematic meta-analysis approach.

For many years, clopidogrel has been a commonly utilised antiplatelet drug in the management of coronary artery disease (CAD). It's thought that the CYP2C19 loss of function (LoF) polymorphism causes clopidogrel's poor metabolism, which eventually leads to resistance. Previous research produced extremely divergent and inconsistent results, making it impossible to draw definitive conclusions. Therefore, current, investigation was carried out to obtain definitive evidence from an updated meta-analysis on the connection between CYP2C19 LoF polymorphism and coronary artery event in patients treated with clopidogrel. 52,542 individuals with coronary artery disease who were receiving clopidogrel treatment were included in 87 carefully chosen trials from reliable databases that we used for our meta-analysis. According to our data, those who carry one or more CYP2C19 LoF alleles worldwide are much more likely to experience composite events and coronary artery events than people who do not carry these alleles, especially in Asian populations. Our meta-analysis observed that the global population, particularly Asians receiving clopidogrel treatment, is at risk of recurrent coronary artery events and composite events if they carry the CYP2C19 LoF alleles. Additional research is essential on alternative antiplatelet therapies for individuals who exhibit poor or intermediate metabolic activity. OBJECTIVES: 1.To systematically analyze the current evidence regarding the association of CYP2C19 variants with coronary artery disease (CAD). 2.To conduct a meta-analysis to investigate the association between loss of function (LoF) CYP2C19 modifications and CAD.

Palbociclib in HR-Positive, HER2-Negative Advanced/Metastatic Breast Cancer: A Systematic Scoping Review of Real-World Evidence from Countries Outside of Western Regions that Are Underrepresented in Clinical Trials.

INTRODUCTION: Limited awareness exists regarding real-world data (RWD) for palbociclib in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced/metastatic breast cancer in populations from certain countries outside of Western regions. METHODS: A systematic scoping review was conducted using PubMed and Embase to evaluate RWD for palbociclib from countries outside of Western regions that are underrepresented in clinical trials. Search criteria were aligned with our research question for relevant English-language publications, without restrictions on publication date, followed by Phase 1 (title and abstract) and Phase 2 (full-text) screening of retrieved citations as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data analyses of eligible studies were done separately for abstracts and full-text publications to enhance the precision and reliability of the results. RESULTS: Database search yielded 1485 non-duplicate records, 46 qualified for inclusion, of which 47.8% were published as full text. The analysis of outcomes, based exclusively on full-text publications that collectively included 2048 patients treated with palbociclib, revealed the median progression-free survival (PFS) of 20.2-36.7 months, overall survival (OS) of 39.9 months (reported in one publication) and objective response rate (ORR) of 45.3-80.0% with first-line treatment. In ≥ second line, the median PFS, OS and ORR ranged from 7.0 to 24.2 months, 11 to 19.6 months, and 13.9% to 47.9%, respectively. The safety profile of palbociclib was similar to that reported in pivotal clinical studies, and no new safety concerns were identified. CONCLUSIONS: A comprehensive volume of evidence demonstrates that palbociclib's effectiveness and safety profile in real-world settings align with those observed in clinical trials, offering valuable insights for clinical decision-making in countries outside of Western regions underrepresented in clinical trials.

Serum Vascular Endothelial Growth Factor and Endostatin as an Adjunct to Clinical Decision Making in Managing Radiation-induced Changes Post Gamma Knife Radiosurgery in Spetzler Martin Grade 3 Arteriovenous Malformations Patients: A Pilot Study.

BACKGROUND: Radiation induced changes (RIC) are the most common complications observed post Gamma Knife radiosurgery (GKRS) and may be observed within 6-18 months post procedure. It has been observed that almost one-third of RICs are symptomatic and half of them are persistent. There is no way to predict which patients will develop these changes and to what extent. METHODS: This was a prospective analytical pilot study with the aim of understanding the role of serum vascular endothelial growth factor (VEGF) and endostatin as predictive factors for clinically symptomatic RIC in intracranial arteriovenous malformations (AVMs) of Spetzler Martin (SM) grade 3 being managed with primary GKRS. RESULTS: A total of 15 patients were analyzed; 60% of them had a history of bleed. The median volume of AVM nidus was 4.36 mL. One-third of the patients had no imaging changes suggestive of RIC at 1 year follow-up and 2 of the patients had symptomatic RIC needing intervention. Before GKRS, the median values of serum concentration of endostatin and VEGF were 34.98 ng/mL and 168.37 pg/mL, respectively. The serum values of VEGF at 1 month post GKRS was much lower than the pre-GKRS values but not found to be predictive of RIC. No correlation could be observed with the levels of serum endostatin and RIC. CONCLUSIONS: Some patients may develop resistant edema and necrosis post GKRS for intracranial AVMs, which may warrant medical and surgical intervention. Serum biomarkers like VEGF and endostatin may vary in the post GKRS period and can be used to identify at-risk cases, however more studies are needed to decide on appropriate time of sampling and identify clinically relevant predictive factors.

Comparative Analysis of Supratentorial Intraventricular Tumors in Adults and Pediatrics in a Developing Country: Clinicopathological Features, Surgical Management, and Outcomes.

BACKGROUND: Supratentorial intraventricular tumors, encompassing lateral and third ventricular tumors, are uncommon intracranial neoplasms, typically slow-growing and benign, manifesting symptoms only upon reaching a substantial size. This study aims to identify optimal surgical approaches, assess the prevalence and characteristics of these tumors, and evaluate postoperative outcomes among pediatric and adult age groups. METHODS: A retrospective comparative study at a tertiary care hospital from January 2014 to June 2020 included 165 patients (68 pediatrics, 97 adults) meeting inclusion criteria for intraventricular tumor management. Data covered demographic factors, clinical history, neurological assessments, neuroimaging, surgical approaches, histopathological diagnoses, immunohistochemical features, adjuvant therapies, follow-up status, postoperative complications, and morbidity/mortality. RESULTS: Ventricular tumor incidence showed male preponderance in both adults (M:F = 1.2:1) and pediatrics (M:F = 3:1). Lateral ventricles were the most common location. Pediatric cases exhibited more frequent calcifications on computed tomography scans (35.6% vs. 29.5%). Grade II and III tumors were more prevalent in adults within the lateral ventricle (27.1 and 1.9%) compared with pediatrics (6.5 and 8.4%). The third ventricle predominantly featured benign lesions, with pediatric patients experiencing significantly longer hospital stays (16.12 ± 21.94 days vs. 9.58 ± 6.21 days) (p = 0.006). Adults and pediatric patients showed a significant difference in high-grade lateral ventricle tumors (p-value = 0.002*). CONCLUSIONS: Supratentorial ventricular tumors are relatively more prevalent in children than adults, presenting challenges due to size and bleeding risks. Surgical resection is the primary treatment, with a focus on the optimal approach for gross total excision to reduce recurrence risk.

Surgical Management of Extradural Tumors at the Craniovertebral Junction - Insights from a Tertiary Care Center.

BACKGROUND: Craniovertebral junction (CVJ) tumors are challenging due to their unique anatomical location. This study aimed to evaluate the complexities in dealing with such precarious CVJ extradural lesions over the decade. METHODS: Twenty-seven patients of extradural CVJ tumors operated between 2009 and 2018 were included. The demographic details, neurological status, surgical approach, extent of resection, type of fixation, complications, and outcome at final follow-up were recorded for each patient. RESULTS: The mean age of the patients was 39.5 ± 20 years. Most (17/27) of the patients had involvement of a single level. Clivus was the most common (9/17) involved region followed by atlas (7/17) vertebrae. Majority of the patients (13/27) were operated through the posterior-only approach. About 15 patients (55.5%) had instability or extensive lesions that necessitated posterior fixation. None of the patients underwent anterior fixation. Gross and near total excision were achieved in 10 patients (37%) and 3 patients (11%) respectively while 14 patients underwent subtotal excision of tumor. On histopathological analysis, clival chordoma (8/27) was found to be the most common pathology followed by giant cell tumor (6/27), plasmacytoma (4/27), and multiple myeloma (2/27). Most patients (13 out of 27) had the same neurological status after the surgery. Six patients (22%) improved post-operatively with decreased weakness and spasticity. Thirteen (48%) patients underwent adjuvant radiotherapy. CONCLUSIONS: This retrospective study provides valuable insights into managing extradural CVJ tumors and highlights the importance of individualized approaches for optimal outcome.

Dolutegravir induces FOLR1 expression during brain organoid development.

During the first month of pregnancy, the brain and spinal cord are formed through a process called neurulation. However, this process can be altered by low serum levels of folic acid, environmental factors, or genetic predispositions. In 2018, a surveillance study in Botswana, a country with a high incidence of human immunodeficiency virus (HIV) and lacking mandatory food folate fortification programs, found that newborns whose mothers were taking dolutegravir (DTG) during the first trimester of pregnancy had an increased risk of neural tube defects (NTDs). As a result, the World Health Organization and the U.S. Food and Drug Administration have issued guidelines emphasizing the potential risks associated with the use of DTG-based antiretroviral therapies during pregnancy. To elucidate the potential mechanisms underlying the DTG-induced NTDs, we sought to assess the potential neurotoxicity of DTG in stem cell-derived brain organoids. The gene expression of brain organoids developed in the presence of DTG was analyzed by RNA sequencing, Optical Coherence Tomography (OCT), Optical Coherence Elastography (OCE), and Brillouin microscopy. The sequencing data shows that DTG induces the expression of the folate receptor (FOLR1) and modifies the expression of genes required for neurogenesis. The Brillouin frequency shift observed at the surface of DTG-exposed brain organoids indicates an increase in superficial tissue stiffness. In contrast, reverberant OCE measurements indicate decreased organoid volumes and internal stiffness.

Beyond Traditional Training: Exploring the Benefits of Virtual Reality Simulator in Lumbar Pedicle Screw Insertion - A Randomized Controlled Trial.

INTRODUCTION: This study compares the effectiveness of virtual reality simulators (VRS) and a saw bone model for learning lumbar pedicle screw insertion (LPSI) in neurosurgery. METHODS: A single-center, cross-sectional, randomized controlled laboratory investigation was conducted involving residents and fellows from a tertiary care referral hospital. Participants were divided into two groups (A and B). Group A performed 3 LPSI tasks: the first on a saw bone model, the second on VRS, and the third on another saw bone model. Group B completed 2 LPSI tasks: the first on a saw bone model and the second on another saw bone model. The accuracy of LPSI was evaluated through noncontrast computed tomography scans for the saw bone models, while the in-built application of VRS was utilized to check for accuracy of screw placement using the simulator. RESULTS: The study included 38 participants (19 in each group). Group A participants showed reduced mean entry point error (0.11 mm, P 0.024), increased mean purchase length (4.66 cm, P 0.007), and no cortical breaches (P 0.031) when placing the second saw bone model screw. Similar improvements were observed among group A participants in PGY 1-3 while placing the second saw bone model screws. CONCLUSIONS: Virtual reality simulators (VRS) prove to be an invaluable tool for teaching complex neurosurgical skills, such as LPSI, to trainees. This technology investment can enhance the learning curve while maintaining patient safety.

Acute alcohol consumption modulates corneal biomechanical properties as revealed by optical coherence elastography.

Acute alcohol ingestion has been found to impact visual functions, including eye movement, but its effects on corneal biomechanical properties remain unclear. This study aimed to investigate the influence of acute alcohol consumption on corneal biomechanical properties using optical coherence elastography (OCE). An air-coupled ultrasound transducer induced elastic waves in mice corneas in vivo, and a high-resolution phase-sensitive optical coherence tomography (OCT) system tracked the mechanical waves to quantify the elastic wave speed. In vivo measurements were performed on three groups of age- and gender-matched mice: control, placebo (administered saline), and alcohol (administered ethanol) groups. Longitudinal measurements were conducted over a one-hour period to assess acute temporal changes in wave speeds, which are associated with inherent biomechanical properties of the cornea. The results showed a significant decrease in wave speed for the alcohol group after 10 min of ingestion in comparison to pre-ingestion values (p = 0.0096), whereas the temporal wave speed changes for the placebo group were statistically insignificant (p = 0.076). In contrast, the control group showed no significant changes in elastic wave speed and corneal thickness. Furthermore, a significant difference was observed between the wave speeds of the placebo and alcohol groups at each measurement time point between 10 and 50 min (p < 0.05), though both groups exhibited a similar trend in corneal thickness change. The findings of this study have important implications for clinical assessments and research in corneal disorders, highlighting the potential of OCE as a valuable tool for evaluating such changes.

Rathke's Cleft Cyst and Craniopharyngioma: A Continuum of the Same Spectrum? Insights from an Interesting Case and Previous Literature.

Rathke's Cleft Cysts (RCCs) and Craniopharyngiomas (CPs) may represent disease entities on the same etio-pathological spectrum. We report the case of a 36-year-old female presenting with vision loss and menstrual irregularities, imaging shows a predominantly cystic lesion in the sellar region with suprasellar extension. She underwent a microscopic transnasal resection of the lesion. She later presented with recurrent symptoms and increased residual lesion size on imaging, a transcranial excision of the lesion was performed. Histopathology from the initial operative specimen revealed RCC with squamous metaplasia which was BRAF negative, while the specimen from the second surgery revealed BRAF positive papillary stratified squamous architecture suggestive of Papillary CP. This case adds to the evidence that both RCCs and papillary CPs may be the spectrum of the same disease. Further, papillary CPs may be an evolution from the RCCs.

Tunable Macroscopic Alignment of Self-Assembling Peptide Nanofibers.

Progress in the design and synthesis of nanostructured self-assembling systems has facilitated the realization of numerous nanoscale geometries, including fibers, ribbons, and sheets. A key challenge has been achieving control across multiple length scales and creating macroscopic structures with nanoscale organization. Here, we present a facile extrusion-based fabrication method to produce anisotropic, nanofibrous hydrogels using self-assembling peptides. The application of shear force coinciding with ion-triggered gelation is used to kinetically trap supramolecular nanofibers into aligned, hierarchical macrostructures. Further, we demonstrate the ability to tune the nanostructure of macroscopic hydrogels through modulating phosphate buffer concentration during peptide self-assembly. In addition, increases in the nanostructural anisotropy of fabricated hydrogels are found to enhance their strength and stiffness under hydrated conditions. To demonstrate their utility as an extracellular matrix-mimetic biomaterial, aligned nanofibrous hydrogels are used to guide directional spreading of multiple cell types, but strikingly, increased matrix alignment is not always correlated with increased cellular alignment. Nanoscale observations reveal differences in cell-matrix interactions between variably aligned scaffolds and implicate the need for mechanical coupling for cells to understand nanofibrous alignment cues. In total, innovations in the supramolecular engineering of self-assembling peptides allow us to decouple nanostructure from macrostructure and generate a gradient of anisotropic nanofibrous hydrogels. We anticipate that control of architecture at multiple length scales will be critical for a variety of applications, including the bottom-up tissue engineering explored here.

Optical coherence tomography-guided Brillouin microscopy highlights regional tissue stiffness differences during anterior neural tube closure in the Mthfd1l murine mutant.

Neurulation is a highly synchronized biomechanical process leading to the formation of the brain and spinal cord, and its failure leads to neural tube defects (NTDs). Although we are rapidly learning the genetic mechanisms underlying NTDs, the biomechanical aspects are largely unknown. To understand the correlation between NTDs and tissue stiffness during neural tube closure (NTC), we imaged an NTD murine model using optical coherence tomography (OCT), Brillouin microscopy and confocal fluorescence microscopy. Here, we associate structural information from OCT with local stiffness from the Brillouin signal of embryos undergoing neurulation. The stiffness of neuroepithelial tissues in Mthfd1l null embryos was significantly lower than that of wild-type embryos. Additionally, exogenous formate supplementation improved tissue stiffness and gross embryonic morphology in nullizygous and heterozygous embryos. Our results demonstrate the significance of proper tissue stiffness in normal NTC and pave the way for future studies on the mechanobiology of normal and abnormal embryonic development.

Redefining the Role of Medical Affairs Professionals as Innovators and Leaders in Industry-Led Medical Education.

Medical affairs professionals are pivotal players at the intersection of medical innovation and practice in the pharmaceutical industry. They are uniquely positioned to translate complex medical knowledge into actionable insights for internal and external stakeholders. Industry-led continuing medical education (CME) programs, guided by these professionals, hold the potential to markedly improve clinicians' application of evidence-based medicine (EBM) in clinical settings, thereby elevating patient care outcomes. However, current CME techniques often overlook the integration of diverse disciplines such as educational theories, cognitive psychology, information mastery, and implementation science, which are important for effective real-time decision-making in patient care. This gap in integrating implementation science is vital, as it is key in ensuring that medical innovations are not just developed but also effectively implemented and efficiently utilized in clinical settings. In this opinion article, we aim to highlight the crucial yet often underrecognized role of medical affairs professionals in shaping robust and practical CME programs within the industry. We explore emerging trends and approaches in medical education and CME based on the principles of adult education. Additionally, we explore how medical affairs professionals can effectively drive the adoption of EBM in clinical practice. This exploration aims to provide insights into enhancing CME programs, with medical affairs professionals at the forefront of innovation and leadership in bridging gaps in clinical practice.

Disruption of Fuz in mouse embryos generates hypoplastic hindbrain development and reduced cranial nerve ganglia.

BACKGROUND: The brain and spinal cord formation is initiated in the earliest stages of mammalian pregnancy in a highly organized process known as neurulation. Environmental or genetic interferences can impair neurulation, resulting in clinically significant birth defects known collectively as neural tube defects. The Fuz gene encodes a subunit of the CPLANE complex, a macromolecular planar polarity effector required for ciliogenesis. Ablation of Fuz in mouse embryos results in exencephaly and spina bifida, including dysmorphic craniofacial structures due to defective cilia formation and impaired Sonic Hedgehog signaling. RESULTS: We demonstrate that knocking Fuz out during embryonic mouse development results in a hypoplastic hindbrain phenotype, displaying abnormal rhombomeres with reduced length and width. This phenotype is associated with persistent reduction of ventral neuroepithelial stiffness in a notochord adjacent area at the level of the rhombomere 5. The formation of cranial and paravertebral ganglia is also impaired in these embryos. CONCLUSIONS: This study reveals that hypoplastic hindbrain development, identified by abnormal rhombomere morphology and persistent loss of ventral neuroepithelial stiffness, precedes exencephaly in Fuz ablated murine mutants, indicating that the gene Fuz has a critical function sustaining normal neural tube development and neuronal differentiation.

The role of susceptibility-weighted imaging & contrast-enhanced MRI in the diagnosis of primary CNS vasculitis: a large case series.

Primary CNS Vasculitis (PCNSV) is a rare, diverse, and polymorphic CNS blood vessel inflammatory condition. Due to its rarity, clinical variability, heterogeneous imaging results, and lack of definitive laboratory markers, PCNSV diagnosis is challenging. This retrospective cohort analysis identified patients with histological diagnosis of PCNSV. Demographic data, clinical presentation, neuroimaging studies, and histopathologic findings were recorded. We enrolled 56 patients with a positive biopsy of CNS vasculitis. Most patients had cerebral hemisphere or brainstem symptoms. Most brain MRI lesions were bilateral, diffuse discrete to confluent white matter lesions. Frontal lobe lesions predominated, followed by inferior cerebellar lesions. Susceptibility-weighted imaging (SWI) hemorrhages in 96.4% (54/56) of patients, either solitary microhemorrhages or a combination of micro and macrohemorrhages. Contrast-enhanced T1-WIs revealed parenchymal enhancement in 96.3% (52/54 patients). The most prevalent pattern of enhancement observed was dot-linear (87%), followed by nodular (61.1%), perivascular (25.9%), and patchy (16.7%). Venulitis was found in 19 of 20 individuals in cerebral DSA. Hemorrhages in SWI and dot-linear enhancement pattern should be incorporated as MINOR diagnostic criteria to diagnose PCNSV accurately within an appropriate clinical context. Microhemorrhages in SWI and venulitis in DSA, should be regarded as a potential marker for PCNSV.

Tunable Macroscopic Alignment of Self-Assembling Peptide Nanofibers.

Fibrous proteins that comprise the extracellular matrix (ECM) guide cellular growth and tissue organization. A lack of synthetic strategies able to generate aligned, ECM-mimetic biomaterials has hampered bottom-up tissue engineering of anisotropic tissues and led to a limited understanding of cell-matrix interactions. Here, we present a facile extrusion-based fabrication method to produce anisotropic, nanofibrous hydrogels using self-assembling peptides. The application of shear force coinciding with ion-triggered gelation is used to kinetically trap supramolecular nanofibers into aligned, hierarchical structures. We establish how modest changes in phosphate buffer concentration during peptide self-assembly can be used to tune their alignment and packing. In addition, increases in the nanostructural anisotropy of fabricated hydrogels are found to enhance their strength and stiffness under hydrated conditions. To demonstrate their utility as an ECM-mimetic biomaterial, aligned nanofibrous hydrogels are used to guide directional spreading of multiple cell types, but strikingly, increased matrix alignment is not always correlated with increased cellular alignment. Nanoscale observations reveal differences in cell-matrix interactions between variably aligned scaffolds and implicate the need for mechanical coupling for cells to understand nanofibrous alignment cues. In total, innovations in the supramolecular engineering of self-assembling peptides allow us to generate a gradient of anisotropic nanofibrous hydrogels, which are used to better understand directed cell growth.

Optical coherence elastography measures the biomechanical properties of the ex vivo porcine cornea after LASIK.

Significance: The biomechanical impact of refractive surgery has long been an area of investigation. Changes to the cornea structure cause alterations to its mechanical integrity, but few studies have examined its specific mechanical impact. Aim: To quantify how the biomechanical properties of the cornea are altered by laser assisted in situ keratomileusis (LASIK) using optical coherence elastography (OCE) in ex vivo porcine corneas. Approach: Three OCE techniques, wave-based air-coupled ultrasound (ACUS) OCE, heartbeat (Hb) OCE, and compression OCE were used to measure the mechanical properties of paired porcine corneas, where one eye of the pair was left untreated, and the fellow eye underwent LASIK. Changes in stiffness as a function of intraocular pressure (IOP) before and after LASIK were measured using each technique. Results: ACUS-OCE showed that corneal stiffness changed as a function of IOP for both the untreated and the treated groups. The elastic wave speed after LASIK was lower than before LASIK. Hb-OCE and compression OCE showed regional changes in corneal strain after LASIK, where the absolute strain difference between the cornea anterior and posterior increased after LASIK. Conclusions: The results of this study suggest that LASIK may soften the cornea and that these changes are largely localized to the region where the surgery was performed.

Metabolic imaging in recurrent gliomas: comparative performance of 18F-FDOPA, 18F-fluorocholine and 18F-FDG PET/CT.

PURPOSE: The aim of this study was to directly evaluate glucose, amino-acid and membrane metabolism in tumor cells for diagnosis and prognostication of recurrent gliomas. METHODS: Fifty-five patients (median age = 36 years; 33 men) with histologically proven gliomas and suspected recurrence were prospectively recruited and underwent 18F-FDG (Fluorodeoxyglucose), 18F-FDOPA (fluorodopa) and 18F-Fluorocholine-PET/CT. Images were evaluated by two physicians visually and quantitatively [lesion-SUVmax, tumor (T) to gray-matter (G) and metabolically-active tumor volumes (MTV)]. After median follow-up of 51.5 months, recurrence was diagnosed in 49 patients. Thirty-one patients died with a median survival of 14 months. RESULTS: Diagnostic-accuracies for 18F-FDOPA, 18F-Fluorocholine,18F-FDG and contrast-enhanced-MRI were 92.7% (95% CI 82.7-97.1), 81.8% (69.7-89.8), 45.5% (33.0-58.5) and 44.7% (30.2-60.3), respectively. Among the 20 lesions, missed by MRI; 18F-FDOPA, 18F-Fluorocholine and 18F-FDG were able to detect 19, 14 and 4 lesions. Corresponding area-under-the-curves (T/G ratios) were 0.817 (0.615-1.000), 0.850 (0.736-0.963) and 0.814 (0.658-0.969), when differentiating recurrence from treatment-induced changes. In univariate-survival-analysis, 18F-FDOPA-T/G, visually detectable recurrence in 18F-FDG, 18F-FDOPA-MTV, cell-lineage and treatment-type were significant parameters. In Multivariate-Cox-regression analysis, 18F-FDOPA-MTV [HR = 1.009 (1.001-1.017); P  = 0.024 (~0.9% increase in hazard for every mL increase of MTV)] and cell-lineage [3.578 (1.447-8.846); P  = 0.006] remained significant. 18F-FDOPA-MTV cutoff <29.59 mL predicted survival higher than 2 years. At cutoff ≥29.59 mL, HR at 2 years was 2.759 (1.310-5.810). CONCLUSION: 18F-FDOPA-PET/CT can diagnose recurrence with high accuracy and MTV predicts survival. 18F-Fluorocholine is a good alternative. Higher 18F-FDG uptake is an adverse prognostic indicator.