Using Natural Language Processing on Electronic Health Records to Enhance Detection and Prediction of Psychosis Risk

BackgroundUsing novel data mining methods such as natural language processing (NLP) on electronic health records (EHRs) for screening and detecting individuals at risk for psychosis. MethodThe study included all patients receiving a first index diagnosis of nonorganic and nonpsychotic mental disorder within the South London and Maudsley (SLaM) NHS Foundation Trust between January 1, 2008, and July 28, 2018. Least Absolute Shrinkage and Selection Operator (LASSO)-regularized Cox regression was used to refine and externally validate a refined version of a five-item individualized, transdiagnostic, clinically based risk calculator previously developed (Harrell’s C = 0.79) and piloted for implementation. The refined version included 14 additional NLP-predictors: tearfulness, poor appetite, weight loss, insomnia, cannabis, cocaine, guilt, irritability, delusions, hopelessness, disturbed sleep, poor insight, agitation, and paranoia. ResultsA total of 92 151 patients with a first index diagnosis of nonorganic and nonpsychotic mental disorder within the SLaM Trust were included in the derivation (n = 28 297) or external validation (n = 63 854) data sets. Mean age was 33.6 years, 50.7% were women, and 67.0% were of white race/ethnicity. Mean follow-up was 1590 days. The overall 6-year risk of psychosis in secondary mental health care was 3.4 (95% CI, 3.3–3.6). External validation indicated strong performance on unseen data (Harrell’s C 0.85, 95% CI 0.84–0.86), an increase of 0.06 from the original model. ConclusionsUsing NLP on EHRs can considerably enhance the prognostic accuracy of psychosis risk calculators. This can help identify patients at risk of psychosis who require assessment and specialized care, facilitating earlier detection and potentially improving patient outcomes.     

Amiodarone-associated optic neuropathy: a critical review

Although amiodarone is the most commonly prescribed anti-arrhythmic drug, its use is limited by serious toxicities, including optic neuropathy. Current reports of amiodarone-associated optic neuropathy identified from the Food and Drug Administration's Adverse Event Reporting System and published case reports were reviewed. A total of 296 reports were identified: 214 from the Adverse Event Reporting System, 59 from published case reports, and 23 from adverse events reports for patients enrolled in clinical trials. Mean duration of amiodarone therapy before vision loss was 9 months (range 1-84 months). Insidious onset of amiodarone-associated optic neuropathy (44%) was the most common presentation, and nearly one third were asymptomatic. Optic disk edema was present in 85% of cases. Following drug cessation, 58% had improved visual acuity, 21% were unchanged, and 21% had further decreased visual acuity. Legal blindness (<20/200) was noted in at least one eye in 20% of cases. Close ophthalmologic surveillance of patients during the tenure of amiodarone administration is warranted.     

Multiple idiopathic cervical resorption: a diagnostic dilemma

Multiple idiopathic cervical resorption is an uncommon condition, the etiology of which remains unknown. The case of a 36-year-old woman with idiopathic resorption in the cervical areas of multiple teeth is presented. Her medical history was noncontributory, but her dental history was valuable in reaching a diagnosis. Hematologic and endocrinal investigations were unremarkable, but a computed tomography scan revealed relevant information. The progression of the lesion and involvement of multiple teeth without any pattern or chronology are challenges faced when diagnosing and treating this condition.     

Reserpine modulates neurotransmitter release to extend lifespan and alleviate age-dependent Aβ proteotoxicity in Caenorhabditis elegans

Aging is a debilitating process often associated with chronic diseases such as diabetes, cardiovascular and neurodegenerative diseases like Alzheimer's disease (AD). AD occurs at a very high incidence posing a huge burden to the society. Model organisms such as C. elegans become essential to understand aging or lifespan extension - the etiology, molecular mechanism and identification of new drugs against age associated diseases. The AD model, manifesting Aβ proteotoxicity, in C. elegans is well established and has provided valuable insights. Earlier, we have reported that Reserpine, an FDA-approved antihypertensive drug, increases C. elegans lifespan with a high quality of life and ameliorates Aβ toxicity in C. elegans. But reserpine does not seem to act through the known lifespan extension pathways or inhibition of its known target, vesicular monoamine transporter, VMAT. Reserpine's mode of action and the pathways it activates are not known. Here, we have evaluated the presynaptic neurotransmitter(s) release pathway and identified acetylcholine (ACh) as the crucial player for reserpine's action. The corroborating evidences are: i) lack of lifespan extension in the ACh loss of function (hypomorphic) - synthesis (cha-1) and transport (unc-17) mutants; ii) mitigation of chronic aldicarb effect; iii) lifespan extension in dopamine (cat-2) and dopamine and serotonin (bas-1) biosynthetic mutants; iv) no rescue from exogenous serotonin induced paralysis in the AD model worms; upon reserpine treatment. Thus, modulation of acetylcholine is essential for reserpine's action.     

A template free protocol for fabrication of a Ni(ii)-loaded magnetically separable nanoreactor scaffold for confined synthesis of unsymmetrical diaryl sulfides in water

In the present report, an environmentally benign magnetically recoverable nickel(ii)-based nanoreactor as a heterogeneous catalyst has been developed via a template free approach. The catalytic performance of the synthesized catalyst is assessed in the confined oxidative coupling of arenethiols with arylhydrazines to form unsymmetrical diaryl sulfides under aerobic conditions. The salient features of our protocol include oxidant- and ligand-free conditions, use of water as a green solvent, room temperature and formation of nitrogen and water as the only by-products. Moreover, a broad range of functional groups are tolerated well and provide the corresponding diaryl sulfides in moderate to good yields. Moreover, the heterogeneous nature of the catalyst permits facile magnetic recovery and reusability for up to seven runs, making the present protocol highly desirable from industrial and environmental standpoints.

An environmentally benign nickel(ii)-based magnetic nanoreactor has been developed for oxidative coupling of arenethiols with arylhydrazines to form unsymmetrical diaryl sulfides in water at room temperature.     

Novel non-mulberry silk fibroin nanoparticles with enhanced activity as potential candidate in nanocarrier mediated delivery system

Silk fibroin (SF) is well known for its excellent biocompatible properties facilitating its application in the field of biomedical engineering through different biomaterial fabrications in the recent era. Here in this study, novel nanoparticles from non-mulberry SF of Antheraea assamensis were fabricated, characterized and evaluated for its applicability as nanocarrier. Fabricated nanoparticles were initially compared with prevailing SF nanoparticles from Bombyx mori. Fabricated A. assamensis silk fibroin nanoparticles (AA-SFNps) were found to be lesser in size (80–300 nm in diameter) than B. mori silk fibroin nanoparticles (BM-SFNps) (120–500 nm in diameter). When checked for stability, AA-SFNps were found to be more stable than BM-SFNps in biological media. FTIR and XRD studies revealed persistence of structural properties even after fabrication. TGA and DSC studies showed AA-SFNps to be thermally more stable than BM-SFNps without any cytotoxicity (MTT assay). On loading with model drug Doxorubicin hydrochloride (DOX), AA-SFNps exhibited an encapsulation efficiency of 94.47% with 11.81% loading of the anticancer drug. Cumulative release study revealed highest percentage release of DOX (42.1 ± 0.4%) at pH 5.2 on day 7 in comparison to pH 7.4 and 8.0. Sustained release profile of the DOX loaded AA-SFNps (AA-SFNps-DOX) was clearly reflected and it was found to be highly cytotoxic against triple negative MDA-MB-231 cells in comparison to free DOX at different time points. Overall, this study showed the efficacy of the AA-SFNps as a nanocarrier for future drug delivery applications.

Novel Antheraea assamensis silk fibroin nanoparticles (AA-SFNps) exhibiting enhanced activity as doxorubicin hydrochloride (DOX) loaded nanocarriers for future drug delivery applications.