Smartphone-based, rapid, wide-field fundus photography for diagnosis of pediatric retinal diseases

PurposeAn important, unmet clinical need is for cost-effective, reliable, easy-to-use, and portable retinal photography to evaluate preventable causes of vision loss in children. This study presents the feasibility of a novel smartphone-based retinal imaging device tailored to imaging the pediatric fundus.MethodsSeveral modifications for children were made to our previous device, including a child-friendly 3D printed housing of animals, attention-grabbing targets, enhanced image stitching, and video-recording capabilities. Retinal photographs were obtained in children undergoing routine dilated eye examination. Experienced masked retina-specialist graders determined photograph quality and made diagnoses based on the images, which were compared to the treating clinician's diagnosis.ResultsDilated fundus photographs were acquired in 43 patients with a mean age of 6.7 years. The diagnoses included retinoblastoma, Coats' disease, commotio retinae, and optic nerve hypoplasia, among others. Mean time to acquire five standard photographs totaling 90-degree field of vision was 2.3 ± 1.1 minutes. Patients rated their experience of image acquisition favorably, with a Likert score of 4.6 ± 0.8 out of 5. There was 96% agreement between image-based diagnosis and the treating clinician's diagnosis.ConclusionsWe report a handheld smartphone-based device with modifications tailored for wide-field fundus photography in pediatric patients that can rapidly acquire fundus photos while being well-tolerated.Translational relevanceAdvances in handheld smartphone-based fundus photography devices decrease the technical barrier for image acquisition in children and may potentially increase access to ophthalmic care in communities with limited resources

Embedding low loss polymer optical fibre Bragg gratings:two different approaches

In this paper, we present two different ways to embed polymer fibre Bragg gratings (FBGs) into polymer matrices. In the first experiment, we embedded the FBG into a 3D printed polymer structure, whereas in the second experiment, the coating was polymerized around the fibre. In both cases, the response of the grating was unchanged, without any loss or distortion of the FBG signal compared with the bare fibre response. The design of the polymer coating was optimised for the measurement of a single measurand. We highlighted two possible applications: surface bend deformation monitoring and improved-sensitivity temperature sensing

Methods of cognitive status research in patients with glioblastoma

Introduction: Glioblastoma is a high-grade, aggressive central nervous system tumor with predominantly astrocytic differentiation, characterized by fast invasive growth into the surrounding brain parenchyma and aggressive clinical course. The short life expectancy of patients diagnosed with glioblastoma necessitates the need to maximize their quality of remaining life. One of the most common reasons for quality of life impairment in these patients is the cognitive deficit accompanying the disease. There is a lack of a unified and standardized method for the assessment of cognitive functions in these patients, which meets all the necessary criteria to be convenient and usable in the wide clinical practice.Aim: The aim of the present study is to compare the Montreal cognitive assessment (MoCA) brief screening test with an extended neuropsychological examination to determine its applicability in patients diagnosed with glioblastoma. Material and methods: The study includes 27 patients undergoing neurosurgical intervention for histologically proven IDH-wildtype glioblastoma in the Department of Neurosurgery, “St. Marina” University Hospital – a tertiary healthcare center, for the period January 2019 to December 2022. Preoperatively, patients were examined with the short MoCA screening test and an extended neuropsychological examination including the following subtests: Issac set test, Trail making test A and B, Luria test, Raven‘s color matrices, Stroop test and Bender test.Results: Of all the patients studied, those with a MoCA score below 26 points present at least one negative test of the extended neuropsychological examination. MoCA patients with scores of 26 or more do not demonstrate cognitive impairment in the extended neuropsychological impairment.Conclusion: The obtained results support the claim that the MoCA short screening test is applicable for preoperative diagnosis of cognitive disorders in patients with glioblastoma. Due to the study‘s small sample size, further research is needed to definitively prove this claim

Age as a factor for cognitive decline in patients with glial tumors

Introduction: Cognitive impairment appears in almost all patients with glial tumors during the course of this neuro-oncological disease. There are various reasons for this in regards to the glial tumor: grade of malignancy, rate of growth, molecular nature, mass effect, and presence of perifocal edema. But these factors do not always correlate with the degree of patient’s cognitive impairment. The present study’s aim is to account for age as a factor in the occurrence of cognitive decline in patients with glial tumors.Materials and methods: The study includes thirty two patients diagnosed with a glial tumor, treated operatively in the Neurosurgery Clinic of University hospital „St. Marina“ in Varna between 2019 and 2022 year. Twenty nine of those patients are diagnosed with glioblastoma, two are diagnosed with diffuse astrocytoma and one with astrocytoma grade 3 according to WHO. The mean age of the patients is 58.4 ± 11.4 years. The youngest patient is 25 years old and the oldest is 78 years old. Preoperatively, all patients are subjected to a series of cognitive tests.Results: From the studied sample, patients diagnosed with glioblastoma showed lower cognitive scores compared to the patients diagnosed with other glial tumors. Patients diagnosed with glioblastoma are significantly older than the patients diagnosed with other glial tumors.Conclusion: The older age of patients affected by glioblastoma may be an additional reason beside tumor factors for lower cognitive test outcome compared to patients affected by lower-grade gliomas

Historical origin and meaning of the term „glial tumor“

In everyday neurosurgical practice, the term „glial tumor“ is associated with astrocytomas, glioblastomas, and oligodendrogliomas, although historically this has not always been the case. The term „glial tumor“ was first given by Virchow in the 19th century as a term initially combining all primary brain tumors under this name. It derives from the name of the group of „supporting“ nerve cells - glia or neuroglia (from the Greek glia - glue), a group which for many years was wrongly ascribed only a cohesive or supporting function.In 1926, in their classification of glial tumors - A Classification of the Tumors of the Glioma Group on a Histogenetic Basis with a Correlated Study of Prognosis, one of the founding fathers of neuropathology Percival Bailey and the founding father of modern neurosurgery – Harvey Cushing ascribed several different tumors in this group: in addition to neuroepithelioma, spongioblastoma multiforme, astrocytoma and ependymoma, they also add medulloblastoma, astroblastoma, oligodendroglioma and unipolar spongioblastoma. Since then, the classification of glial tumors has undergone many changes to its current form. In the latest classification of brain tumors published in 2021, glial tumors are united in a common group together with glioneuronal and neuronal tumors. Their extensive group includes tumors with different prognosis, age presentation, molecular profile and therapeutic response. From a neurosurgical point of view, the term „glial tumor“ does not carry a prognostic value, but only determines the belonging of the tumor to the astrocyte, oligodendrocyte cell line or their precursor cells. In relation to that an interesting question arises- why the remaining tumors originating from glial cells other than astrocytic, such as ependymomas, lost their belonging to the group of glial tumors, or such as intracranial schwannomas, are not included in it at all

Cetuximab-Ag₂S quantum dots for fluorescence imaging and highly effective combination of ALA-based photodynamic/chemo-therapy of colorectal cancer cells

Colorectal cancer (CRC) has a poor prognosis and urgently needs better therapeutic approaches. 5-Aminolevulinic acid (ALA) induced protoprophyrin IX (PpIX) based photodynamic therapy (PDT) is already approved in the clinic for several cancers but not yet well investigated for CRC. Currently, systemic administration of ALA offers a limited degree of tumour selectivity, except for intracranial tumours, limiting its wider use in the clinic. Combination of effective ALA-PDT with chemotherapy may provide a promising alternative approach for CRC treatment. Herein, theranostic Ag2S quantum dots (AS-2MPA) optically trackable in near-infrared (NIR), conjugated with endothelial growth factor receptor (EGFR) targeting Cetuximab (Cet) and loaded with ALA for PDT monotherapy or ALA/5-fluorouracil (5FU) for the combination therapy is proposed for enhanced treatment of EGFR(+) CRC. AS-2MPA-Cet endowed excellent targeting of the high EGFR expressing cells and showed a strong intracellular signal for NIR optical detection in a comparative study performed on SW480, HCT116, and HT29 cells, which are high, medium and low EGFR expressers. Targeting provided enhanced uptake of the ALA loaded nanoparticles by strong EGFR expressing cells and formation of higher levels of PpIX. Cells also differ in their efficiency to convert ALA to PpIX, and SW480 was the best, followed by HT29, while HCT116 were determined as unsuitable for ALA-PDT. The therapeutic efficacy was evaluated in 2D cell cultures and 3D spheroids of SW480 and HT29 cells using AS-2MPA with either electrostatically loaded, hydrazone or amide linked ALA to achieve different levels of pH or enzyme sensitive release. Most effective phototoxicity was observed in SW480 cells using AS-2MPA-ALA-electrostatic-Cet due enhanced uptake of the particles, fast ALA release and effective ALA-to-PpIX conversion. Targeted delivery reduced the effective ALA concentration significantly which was further reduced with codelivery of 5FU. Delivery of ALA via covalent linkage was also effective for PDT, but required longer incubation time for the release of ALA in therapeutic doses. Phototoxicity was correlated with high levels of reactive oxygen species (ROS) and apoptotic/necrotic cell death. Hence, both AS-2MPA-ALA-Cet based PDT and AS-2MPA-ALA-Cet-5FU based Chemo/PDT combination therapy coupled with strong NIR tracking of the nanoparticles demonstrate an exceptional therapeutic effect on CRC cells and an excellent potential for synergistic multistage tumour targeting therapy

Alternating, private alternating, and quantum alternating realtime automata

We present new results on realtime alternating, private alternating, and quantum alternating automaton models. Firstly, we show that the emptiness problem for alternating one-counter automata on unary alphabets is undecidable. Then, we present two equivalent definitions of realtime private alternating finite automata (PAFAs). We show that the emptiness problem is undecidable for PAFAs. Furthermore, PAFAs can recognize some nonregular unary languages, including the unary squares language, which seems to be difficult even for some classical counter automata with two-way input. Regarding quantum finite automata (QFAs), we show that the emptiness problem is undecidable both for universal QFAs on general alphabets, and for alternating QFAs with two alternations on unary alphabets. On the other hand, the same problem is decidable for nondeterministic QFAs on general alphabets. We also show that the unary squares language is recognized by alternating QFAs with two alternations