The BONSAI (Brain and Optic Nerve Study with Artificial Intelligence) deep learning system can accurately identify pediatric papilledema on standard ocular fundus photographs.

BACKGROUND: Pediatric papilledema often reflects an underlying severe neurologic disorder and may be difficult to appreciate, especially in young children. Ocular fundus photographs are easy to obtain even in young children and in nonophthalmology settings. The aim of our study was to ascertain whether an improved deep-learning system (DLS), previously validated in adults, can accurately identify papilledema and other optic disk abnormalities in children. METHODS: The DLS was tested on mydriatic fundus photographs obtained in a multiethnic pediatric population (<17 years) from three centers (Atlanta-USA; Bucharest-Romania; Singapore). The DLS's multiclass classification accuracy (ie, normal optic disk, papilledema, disks with other abnormality) was calculated, and the DLS's performance to specifically detect papilledema and normal disks was evaluated in a one-vs-rest strategy using the AUC, sensitivity and specificity, with reference to expert neuro-ophthalmologists. RESULTS: External testing was performed on 898 fundus photographs: 447 patients; mean age, 10.33 (231 patients ≤10 years of age; 216, 11-16 years); 558 normal disks, 254 papilledema, 86 other disk abnormalities. Overall multiclass accuracy of the DLS was 89.6% (range, 87.8%-91.6%). The DLS successfully distinguished "normal" from "abnormal" optic disks (AUC 0.99 [0.98-0.99]; sensitivity, 87.3% [84.9%-89.8%]; specificity, 98.5% [97.6%-99.6%]), and "papilledema" from "normal and other" (AUC 0.99 [0.98-1.0]; sensitivity, 98.0% [96.8%-99.4%]; specificity, 94.1% (92.4%-95.9%)]. CONCLUSIONS: Our DLS reliably distinguished papilledema from normal optic disks and other disk abnormalities in children, suggesting it could be utilized as a diagnostic aid for the assessment of optic nerve head appearance in the pediatric age group.

Quality standards for the care of people with giant cell arteritis in secondary care.

OBJECTIVE: GCA is the commonest primary systemic vasculitis in adults, with significant health economic costs and societal burden. There is wide variation in access to secondary care GCA services, with 34% of hospitals in England not having any formal clinical pathway. Quality standards provide levers for change to improve services. METHODS: The multidisciplinary steering committee were asked to anonymously put forward up to five aspects of service essential for best practice. Responses were qualitatively analysed to identify common themes, subsequently condensed into domain headings, and ranked in order of importance. Quality standards and metrics for each domain were drafted, requiring a minimum 75% agreement. RESULTS: 13 themes were identified from the initial suggestions. Nine quality standards with auditable metrics were developed from the top 10 themes. Patient Access, glucocorticoid use, pathways, ultrasonography, temporal artery biopsy, PET scan access, rheumatology/ophthalmology expertise, education, multidisciplinary working have all been covered in these quality standards. Access to care is a strand that has run through each of the developed standards. An audit tool was developed as part of this exercise. CONCLUSION: These are the first consensus auditable quality standards developed by clinicians from rheumatology and ophthalmology, nursing representatives and involvement of a patient charity. We hope that these standards will be adopted by commissioning bodies to provide levers for change from the improvement of patient care of individuals with GCA.

Artificial intelligence in ophthalmology: an insight into neurodegenerative disease.

PURPOSE OF REVIEW: The aging world population accounts for the increasing prevalence of neurodegenerative diseases such as Alzheimer's and Parkinson's which carry a significant health and economic burden. There is therefore a need for sensitive and specific noninvasive biomarkers for early diagnosis and monitoring. Advances in retinal and optic nerve multimodal imaging as well as the development of artificial intelligence deep learning systems (AI-DLS) have heralded a number of promising advances of which ophthalmologists are at the forefront. RECENT FINDINGS: The association among retinal vascular, nerve fiber layer, and macular findings in neurodegenerative disease is well established. In order to optimize the use of these ophthalmic parameters as biomarkers, validated AI-DLS are required to ensure clinical efficacy and reliability. Varied image acquisition methods and protocols as well as variability in neurogenerative disease diagnosis compromise the robustness of ground truths that are paramount to developing high-quality training datasets. SUMMARY: In order to produce effective AI-DLS for the diagnosis and monitoring of neurodegenerative disease, multicenter international collaboration is required to prospectively produce large inclusive datasets, acquired through standardized methods and protocols. With a uniform approach, the efficacy of resultant clinical applications will be maximized.

Ischemic Optic Neuropathies: Current Concepts.

Ischemic optic neuropathy (ION) is the term ascribed to optic nerve disease that is the result of a transient or permanent interruption of the blood supply to any portion of the optic nerve. Anterior ischemic optic neuropathy (AION) refers to ischemia of the optic nerve head, whereas posterior ischemic optic neuropathy (PION) indicates ischemia of the posterior optic nerve. IONs are primarily classified as arteritic ION and non-arteritic ION. A subset of ION that occurs around the time of surgery is termed peri-operative ION. These phenomena will be discussed as distinct entities.

Elemental and Thermo-gravimetric Characterization of Trace Metals in Leaves and Soils as Bioindicators of Pollution in Kyiv City.

In this study, leaf and soil samples were used as bio-monitors for different alkali and heavy metals at six different locations in Kyiv city. Using x-y plots of the inductively coupled plasma optical emission spectroscopy (ICP-OES) data measured the discrepancy level in elemental composition between the different investigated areas; the correlation between the concentrations in tree leaves and the samples from the surrounding soils were investigated. While the concentration of essential mineral elements and metals was found to be similar in several leaf and soil samples, in other samples, their concentration spread up to more than one order of magnitude. The concentration of metals was found to be higher in soil samples than in leaves. Thermo-gravimetric analysis (TGA) data helped to further characterize both types of samples. The metal removal during the incineration of the leaves was investigated by coupling a thermo-gravimetric analyzer to an inductively coupled plasma optical emission spectrometer (TGA-ICP-OES). The release of Cd, K, Na, Pb, and Zn during incineration at temperatures up to 960 °C was online monitored, and some insights were drawn about the behavior of such metals and the chemistry involved in the volatilization process.

Central retinal artery occlusion during vitrectomy: Immediate retinal revascularization following induction of posterior vitreous detachment.

PURPOSE: To describe a patient with acute central retinal artery occlusion (CRAO) during vitrectomy surgery and the possible role of vitrectomy in acute CRAO management. OBSERVATIONS: An 84-year-old man presented with broad vitreomacular traction and epiretinal membrane in the right eye. Preoperative assessment clearly showed normal retinal vasculature. On starting vitrectomy, complete CRAO with marked segmentation of all retinal vessels was noted. Vitrectomy was performed in the usual manner and once the posterior hyaloid detached from the disc, immediate complete revascularization of the retinal vessels was noted. The patient had a complete visual recovery. CONCLUSIONS AND IMPORTANCE: Immediate vitrectomy with induction of posterior vitreous detachment may have a role in selected cases of acute CRAO, particularly if performed within a short window.

Ribosomal Protein S3 Negatively Regulates Unwinding Activity of RecQ-like Helicase 4 through Their Physical Interaction.

Human RecQ-like helicase 4 (RECQL4) plays crucial roles in replication initiation and DNA repair; however, the contextual regulation of its unwinding activity is not fully described. Mutations in RECQL4 have been linked to three diseases including Rothmund-Thomson syndrome, which is characterized by osteoskeletal deformities, photosensitivity, and increased osteosarcoma susceptibility. Understanding regulation of RECQL4 helicase activity by interaction partners will allow deciphering its role as an enzyme and a signaling cofactor in different cellular contexts. We became interested in studying the interaction of RECQL4 with ribosomal protein S3 (RPS3) because previous studies have shown that RPS3 activity is sometimes associated with phenotypes mimicking those of mutated RECQL4. RPS3 is a small ribosomal protein that also has extraribosomal functions, including apurnic-apyrimidinic endonuclease-like activity suggested to be important during DNA repair. Here, we report a functional and physical interaction between RPS3 and RECQL4 and show that this interaction may be enhanced during cellular stress. We show that RPS3 inhibits ATPase, DNA binding, and helicase activities of RECQL4 through their direct interaction. Further domain analysis shows that N-terminal 1-320 amino acids of RECQL4 directly interact with the C-terminal 94-244 amino acids of RPS3 (C-RPS3). Biochemical analysis of C-RPS3 revealed that it comprises a standalone apurnic-apyrimidinic endonuclease-like domain. We used U2OS cells to show that oxidative stress and UV exposure could enhance the interaction between nuclear RPS3 and RECQL4. Regulation of RECQL4 biochemical activities by RPS3 along with nuclear interaction during UV and oxidative stress may serve to modulate active DNA repair.

Therapeutic approach to the management of HER2-positive breast cancer metastatic to the brain.

HER2 positive breast cancers have been shown to have a greater propensity to metastasise to the brain. This may be due to several reasons, including the creation of a "sanctuary-site" for tumour in the brain following trastuzumab therapy. Elucidating the mechanism of this phenomenon may aid the prevention or intervention and treatment of such metastases, but research is limited by the deficiency and diminished access of CNS tissue. However, CNS penetrable HER2 receptor antagonists such as lapatinib and intrathecal administration of trastuzumab might benefit patients, and are worthy of further investigation. New avenues of molecular approach have focused on manipulating signal transduction system involved in HER2 function. The importance of systemic therapies and those targeted to metastatic lesions is emphasised and evaluated here.

Diosgenin from Dioscorea bulbifera: novel hit for treatment of type II diabetes mellitus with inhibitory activity against α-amylase and α-glucosidase.

Diabetes mellitus is a multifactorial metabolic disease characterized by post-prandial hyperglycemia (PPHG). α-amylase and α-glucosidase inhibitors aim to explore novel therapeutic agents. Herein we report the promises of Dioscorea bulbifera and its bioactive principle, diosgenin as novel α-amylase and α-glucosidase inhibitor. Among petroleum ether, ethyl acetate, methanol and 70% ethanol (v/v) extracts of bulbs of D. bulbifera, ethyl acetate extract showed highest inhibition upto 72.06 ± 0.51% and 82.64 ± 2.32% against α-amylase and α-glucosidase respectively. GC-TOF-MS analysis of ethyl acetate extract indicated presence of high diosgenin content. Diosgenin was isolated and identified by FTIR, 1H NMR and 13C NMR and confirmed by HPLC which showed an α-amylase and α-glucosidase inhibition upto 70.94 ± 1.24% and 81.71 ± 3.39%, respectively. Kinetic studies confirmed the uncompetitive mode of binding of diosgenin to α-amylase indicated by lowering of both Km and Vm. Interaction studies revealed the quenching of intrinsic fluorescence of α-amylase in presence of diosgenin. Similarly, circular dichroism spectrometry showed diminished negative humped peaks at 208 nm and 222 nm. Molecular docking indicated hydrogen bonding between carboxyl group of Asp300, while hydrophobic interactions between Tyr62, Trp58, Trp59, Val163, His305 and Gln63 residues of α-amylase. Diosgenin interacted with two catalytic residues (Asp352 and Glu411) from α-glucosidase. This is the first report of its kind that provides an intense scientific rationale for use of diosgenin as novel drug candidate for type II diabetes mellitus.

Phytochemical analysis and free radical scavenging activity of medicinal plants Gnidia glauca and Dioscorea bulbifera.

Gnidia glauca and Dioscorea bulbifera are traditional medicinal plants that can be considered as sources of natural antioxidants. Herein we report the phytochemical analysis and free radical scavenging activity of their sequential extracts. Phenolic and flavonoid content were determined. Scavenging activity was checked against pulse radiolysis generated ABTS(•+) and OH radical, in addition to DPPH, superoxide and hydroxyl radicals by biochemical methods followed by principal component analysis. G. glauca leaf extracts were rich in phenolic and flavonoid content. Ethyl acetate extract of D. bulbifera bulbs and methanol extract of G. glauca stem exhibited excellent scavenging of pulse radiolysis generated ABTS(•+) radical with a second order rate constant of 2.33 × 10(6) and 1.72 × 10(6), respectively. Similarly, methanol extract of G. glauca flower and ethyl acetate extract of D. bulbifera bulb with second order rate constants of 4.48 × 10(6) and 4.46 × 10(6) were found to be potent scavengers of pulse radiolysis generated OH radical. G. glauca leaf and stem showed excellent reducing activity and free radical scavenging activity. HPTLC fingerprinting, carried out in mobile phase, chloroform: toluene: ethanol (4: 4: 1, v/v) showed presence of florescent compound at 366 nm as well as UV active compound at 254 nm. GC-TOF-MS analysis revealed the predominance of diphenyl sulfone as major compound in G. glauca. Significant levels of n-hexadecanoic acid and octadecanoic acid were also present. Diosgenin (C27H42O3) and diosgenin (3á,25R) acetate were present as major phytoconstituents in the extracts of D. bulbifera. G. glauca and D. bulbifera contain significant amounts of phytochemicals with antioxidative properties that can be exploited as a potential source for herbal remedy for oxidative stress induced diseases. These results rationalize further investigation in the potential discovery of new natural bioactive principles from these two important medicinal plants.

Efficient solvent system containing malonamides in room temperature ionic liquids: actinide extraction, fluorescence and radiolytic degradation studies.

Solvent extraction studies of actinide metal ions such as Am(III), U(VI), Np(IV), Np(VI), Pu(IV) were carried out in a nitric acid medium using two diamides (L) viz. (DMDBTDMA (N,N'-dimethyl-N,N'-dibutyl-2-tetradecylmalonamide) and DMDOHEMA (N,N'-dimethyl-N,N'-dioctyl-2-(2'-(hexyloxy)ethyl)-malonamide) dissolved in different room temperature ionic liquids (RTILs). The use of RTILs as the diluent significantly enhanced metal ion extraction as compared to that observed in non polar diluent such as n-dodecane. The effects of parameters such as kinetics, aqueous phase acidity (0.01-3 M HNO(3)), metal ion oxidation states, diamide concentration on the extraction of metal ions were studied. The stoichiometry of the extracted Am(III) species using these diamides varied with ligand concentration viz. (Am.3L)(3+) ([L] = 0.005-0.02 M) and (Am.2-2.5L)(3+) ([L] = 0.05-0.1 M). Time resolved laser induced fluorescence spectroscopy (TRLFS) studies showed that the extracted species of Eu(III) in an ionic liquid medium had no coordinated water molecules, in contrast to the presence of 1-2 water molecules in the extracted species in a n-dodecane medium. The radiolytic degradation behavior of the diamides/RTIL system has been studied using IR spectroscopy and gas chromatography-mass spectrometry (GC-MS). The data revealed that a significantly lower ligand concentration is required for actinide extraction in ionic liquids as the extraction media as compared to nonpolar diluents.

Medical practice and related insurance.

The liability of a doctor as regards medical negligence is now a well accepted eventuality. However still many doctors and hospitals are unaware of their liability on account of negligence on the part of their junior doctors and hospital staff. Indemnity insurance specifically protects you against your liability to pay compensation including legal costs, fees or expenses. If court orders to pay compensation for negligence of patient and you have a valid insurance cover, the insurance company is supposed to pay the money. In the present text we are highlighting the medical practice related insurance such as personal indemnity insurance, error and omission policy for hospital and nursing homes and insurance policy related to damage to hospital building, damage to electrical and electronics appliances and also insurance for doctor's kit, signboard, burglary, fidelity guarantee and loss of money in transit. All this medical practice related insurance is explained with its present charges, terms and conditions and its importance in today's practice.

Dichotomy in cross-clade reactivity and neutralization by HIV-1 sera: Implications for active and passive immunotherapy.

The identification of broadly reactive and cross-clade neutralizing antibodies will facilitate the development of a more universally effective vaccine for human immunodeficiency virus (HIV). Antibodies in sera from individuals infected with Clade B HIV bind native primary viral isolates, and virus binding correlates with neutralization and stable clinical disease. In this study, we quantified cross-clade antibody reactivity and neutralization by Clades B and C sera. Primary viral isolates were captured by serum IgG bound to anti-human IgG and quantitated as p24 released by lysis of captured virus. Neutralization was determined using PHA-stimulated PBMC. Clade B antibodies reacted more frequently with Clade B R5 virus, but positive sera captured quantitatively more X4 virus than R5 and R5X4 virus. Clade B sera reacted less frequently and captured less Clade C virus than Clade B virus. Antibodies in Clade C sera captured Clades B and C isolates with equal frequency and quantity. There was no difference in neutralization of Clade B virus by either group of sera; however, Clade C sera neutralized Clade C virus, whereas Clade B sera were ineffective against Clade C virus. Thus, there are distinct differences in cross-clade reactivity of and neutralization by antibodies induced in response to Clade C infection compared to Clade B infection. Understanding antibody responses to native virions after Clade C infection and cross clade antibody behavior has implications for understanding pathogenesis and vaccine development.