A Monte Carlo simulation of tracer diffusion in amorphous polymers.

Tracer diffusion in amorphous polymers is a sought-after quantity for a range of technological applications. In this regard, a quantitative description of the so-called decoupling from the reverse proportionality between viscosity and diffusion coefficient into a fractional one remains a challenge requiring a deeper insight. This work employs a Monte Carlo simulation framework in 3 dimensions to investigate the consequences of different scenarios for estimating this fractional exponent on the diffusion coefficient of tracers in polymers near glass transition. To this end, we adopted a continuous-time random walk model for tracer diffusion in the supercooled liquid state. The waiting time distribution of the diffusants was computed based on the rotational correlation times of the polymer. This proposed procedure is of particular interest because it brings the quantity of waiting time (and its statistics) in connection with the measurable observable of rotational times. In the framework of our simulations the aforementioned fractional exponent appears in the relation between the diffusant's waiting time and the rotational time of the diffusion medium. A limited comparison with experimental diffusivities from the literature revealed a reasonable agreement with a fractional exponent on the basis of the molar volumes of the diffusant and the monomeric unit. Finally, an analysis of time-averaged mean squared displacement pointed to normal Brownian dynamics for tracer diffusion in polymers above the glass transition temperature.

Fatal Oedipism: A Case Report and Literature Review.

PURPOSE: To describe a unique case of a fatal self-enucleation and review previously published cases. METHODS: The authors describe a unique case of a complete unilateral self-enucleation while under the influence of drugs, which resulted in severe intracranial hemorrhages, right internal carotid artery opacification, and death. A literature review was performed by searching articles published before January 2023 in the Pubmed/MEDLINE database using the keywords "auto-enucleation or self-enucleation." Cases of self-inflicted damage to the globe without severing any connections were excluded. RESULTS: A literature review identified a total of 54 articles and 75 patients who had self-enucleated at least one globe completely (84.0%). Their average age was 37 years and 50.7% were male. At the time of auto-enucleation, 64.0% of these patients had known psychiatric disorders, and 28.0% were found to be under the influence of illicit drugs or alcohol. Auto-enucleation resulted in intracranial complications in 26.7% of cases. There has been 1 prior case, which, like the authors' case, resulted in death due to intracranial complications. However, this occurred in a patient who partially enucleated one eye after a self-inflicted injury to the fellow eye. The current case is unique as these complications resulted from a complete unilateral auto-enucleation. CONCLUSIONS: The severity of this case's presentation and outcome highlights the importance of prompt neuroimaging and a thorough assessment. Prompt psychiatric assessment and treatment are also required.

Effectiveness of telemedicine diabetic retinopathy screening in the USA: a protocol for systematic review and meta-analysis.

BACKGROUND: Diabetic retinopathy (DR) is the leading cause of vision loss among adults in the USA. Vision loss associated with diabetic retinopathy can be prevented with timely ophthalmologic care, and therefore, it is recommended that individuals with diabetes have annual retinal examinations. There is limited evidence on whether using telemedicine to screen for DR in primary care clinics in the USA effectively leads to increased DR screening rates. The objective of this systematic review is to collate evidence from existing studies to investigate the effectiveness of telemedicine DR screening (TDRS) in primary care clinics on DR screening rates. METHODS: Relevant studies will be identified through searching MEDLINE/PubMed interface, Scopus, and Web of Science from their inception until November 2021, as well as searching reference lists of included studies and previous related review articles or systematic reviews. There will be no restrictions on study design. Eligible studies will include subjects with either type 1 or type 2 diabetes, will evaluate telemedicine technology for screening of DR, will have been conducted in the USA, and will report DR screening rates or data necessary for calculating such rates. Two reviewers will screen search results independently. Risk-of-bias assessment and data extraction will be carried out by two reviewers. The version 2 of the Cochrane risk-of-bias tool (RoB 2) and the Newcastle-Ottawa scale (NOS) tool will be used to assess the quality and validity of individual studies. If feasible, we will conduct random-effects meta-analysis where appropriate. If possible, we will conduct subgroup analyses to explore potential heterogeneity sources (setting, socio-economic status, age, ethnicity, study design, outcomes). We will disseminate the findings through publications and relevant networks. DISCUSSION: This protocol outlines the methods for systematic review and synthesis of evidence of TDRS and its effect on DR screening rates. The results will be of interest to policy makers and program managers tasked with designing and implementing evidence-based services to prevent and manage diabetes and its complications in similar settings. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021231067.

Latent Sensitization in a Mouse Model of Ocular Neuropathic Pain.

PURPOSE: Chronic ocular pain is poorly understood and difficult to manage. We developed a murine model of corneal surface injury (CSI)-induced chronic ocular neuropathic pain. The study focuses on changes in corneal nerve morphology and associated short- and long-term pain-like behavior after CSI. METHODS: CSI was induced in mice by local application of an alkali solution (0.75 N NaOH). Corneal nerve architecture, morphology, density, and length were studied. Eye-wiping was evaluated before and after CSI in response to hypertonic saline (2 M NaCl). Naltrexone (NTX) or Naloxone-methiodide (NLX-me), opioid receptor antagonists, were given subcutaneously (s.c., 3 mg/kg) or topically (eye drop, 100 µM), and then an eye-wiping test was performed. RESULTS: CSI caused partial corneal deinnervation followed by gradual reinnervation. Regenerated nerves displayed increased tortuosity, beading, and branching. CSI enhanced hypertonic saline-induced eye-wiping behavior compared to baseline or sham-injury (P < 0.01). This hypersensitivity peaked at 10 days and subsided 14 days after CSI. Administration of NTX, or NLX-me, a selective peripheral opioid antagonist, reinstated eye-wiping behavior in the injury group, but not in the sham groups (P < 0.05). CONCLUSIONS: This study introduces a model of chronic ocular pain and corneal neuropathy following CSI. CSI induces central and peripheral opioid receptor-dependent latent sensitization (LS) that is unmasked by systemic or topical administration of opioid antagonists. TRANSLATIONAL RELEVANCE: This model of chronic ocular pain establishes LS as a new inhibitory mechanism in the oculotrigeminal system and may be used for potential diagnostic and therapeutic interventions for ocular neuropathy.

Antagonism of inhibitor of apoptosis proteins increases bone metastasis via unexpected osteoclast activation.

UNLABELLED: Inhibitor of apoptosis (IAP) proteins play a central role in many types of cancer, and IAP antagonists are in development as anticancer agents. IAP antagonists cause apoptosis in many cells, but they also activate alternative NF-κB signaling through NF-κB-inducing kinase (NIK), which regulates osteoclasts. In bone metastasis, a positive feedback loop between tumors and osteoclasts promotes tumor growth and osteolysis. We therefore tested the effect of IAP antagonists on the bone microenvironment for metastasis. In both drug-sensitive and drug-resistant tumors, growth in bone was favored, as compared with other sites during IAP antagonist treatment. These drugs also caused osteoporosis and increased osteoclastogenesis, mediated by NIK, and enhanced tumor-associated osteolysis. Cotreatment with zoledronic acid, a potent osteoclast inhibitor, reduced IAP antagonist-enhanced tumor growth in bone and osteolysis. Thus, IAP antagonist-based cancer treatment may be compromised by osteoporosis and enhanced skeletal metastasis, which may be prevented by antiresorptive agents. SIGNIFICANCE: Although IAP antagonists are a class of anticancer agents with proven efficacy in multiple cancers, we show that these agents can paradoxically increase tumor growth and metastasis in the bone by stabilizing NIK and activating the alternative NF-κB pathway in osteoclasts. Future clinical trials of IAP antagonist-based therapy may require detailed examination of this potential for enhanced bone metastasis and osteoporosis, as well as possible combination with antiresorptive agents.