Rodent models have been fundamental to understand chronic pain (CP) pathophysiology and to test for potential treatments. Pain assessment in CP models is most frequently based on the evaluation of allodynia or hyperalgesia. However, these correspond only to a part of CP-related problems which include ongoing pain, depression, anxiety, disrupted sleep and attentional deficits. A growing number of preclinical studies have been assessing these manifestations in CP rodent models. We reviewed and systematized this information by behavioral domain. Observational studies in ethologically relevant conditions, paradigms of anxiety- and depressive-like behavior as well as of memory and executive function were selected. A considerable number of studies reported deficits similar to those observed in CP patients. These behavioral alterations are informative regarding ongoing maladaptive plasticity in multiple brain regions and its use as pain proxies has the potential to greatly improve the predictive value of CP models. However, the inclusion of female and/or older rodents is rare which is in clear dissonance with the clinical representation of CP.Aggressive behavior (AB) represents a public health concern often associated with severe psychiatric disorders. Although most psychiatric patients are not aggressive, untreated psychiatric illness, including bipolar disorder (BD), may associate with an increased risk of AB. Accurate predictive models of AB are still lacking and it is crucial to delineate AB biomarkers state of the art in BD. We performed a systematic review according to PRISMA guidelines to identify biological correlates of AB in BD. Final results included 20 studies 10 involving genetic and 10 other biological AB biomarkers (total sample size N = 5,181). Our results pointed to a serotoninergic hypoactivation in violent suicidal BD patients. Similarly, BD violent suicide attempters had a blunted hypothalamic-pituitary-adrenal (HPA) activity. Violent behavior in BD was associated with a chronic inflammatory state. While the role of lipids as biomarkers for AB remains equivocal, uric acid appears as a potential biomarker for hetero-AB in BD. Available data can be useful in the fulfill of specific biomarkers of AB in BD, ultimately leading to the development of accurate predictive models.The impact of two mouse models is reviewed, the Four Core Genotypes and XY* models. The models are useful for determining if the causes of sex differences in phenotypes are either hormonal or sex chromosomal, or both. Used together, the models also can distinguish between the effects of X or Y chromosome genes that contribute to sex differences in phenotypes. To date, the models have been used to uncover sex chromosome contributions to sex differences in a wide variety of phenotypes, including brain and behavior, autoimmunity and immunity, cardiovascular disease, metabolism, and Alzheimer’s Disease. In some cases, use of the models has been a strategy leading to discovery of specific X or Y genes that protect from or exacerbate disease. Sex chromosome and hormonal factors interact, in some cases to reduce the effects of each other. Future progress will come from more extensive application of these models, and development of similar models in other species.Tourette syndrome (TS) and chronic motor/vocal tic disorder (CTD) are neurodevelopmental conditions defined by the occurrence of multiple tics. Besides the well-known association with attention deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD), rage attacks (RA) represent common and detrimental symptoms for patients. Inorder to explore prevalence of RA in tic disorders, relation to tic severity/comorbidities and available treatments, we performed a systematic literature review based on PRISMA Guidelines. 32 studies published between January 2008 – December 2019 were deemed suitable for the analysis and provided a prevalence of 20-67 %. Most findings showed a direct correlation with tic severity and a significant impact on psychosocial functioning. Although apparently related to comorbid ADHD, RA also frequently occur as independent manifestations. Association with other comorbidities, such as OCD, impulse control and mood disorders has also been reported, not yet fully established. Behavioral interventions appear to be effective, whereas there is limited evidence concerning the efficacy of medication. In TS/CTD, RA may be regarded as a major comorbidity that requires clinical investigation in order to develop personalized treatments.Ophthalmic surgeons have been overwhelmed by the influx of multifocal intraocular lens (IOL) options in recent years, with close to 100 IOLs on the market in 2020. This practical and technical update on a representative group of established as well as newly launched multifocal IOLs on the market focuses on multifocal IOLs, including extended depth-of-focus lenses. We also describe the optical basis of lens platforms used and thorough preoperative planning to aid decision making. This allows the surgeon the knowledge base to deliver the required relative customized spectacle independence with the least photic phenomenon and loss of contrast possible while achieving high individual patient satisfaction. Data of reviewed IOLs displayed in tabular format include mean monocular uncorrected distance, intermediate, and near visual acuities (logarithm of the minimum angle of resolution), with standard deviations and ranges where available. The range of vision targeted, pupil dependence, toric availability, as well as type of optical platform, are provided as a practical guide to demystify existing terminology on the market that may create interest around a seemingly new design that is actually not novel at all. Halos and glare experienced, levels of patient satisfaction, and spectacle independence achieved also are summarized. A wide range of multifocal IOLs options are available on the market to surgeons. Comprehensive patient selection and examination, combined with knowledge of the most recent options and adequate patient counseling, including neuroadaptation, can avoid dissatisfaction. Many recently available IOLs are awaiting formal results, but the methods by which we label and compare these types of IOLs must also be standardized.

To apply a deep learning algorithm for automated, objective, and comprehensive quantification of OCT scans to a large real-world dataset of eyes with neovascular age-related macular degeneration (AMD) and make the raw segmentation output data openly available for further research.

Retrospective analysis of OCT images from the Moorfields Eye Hospital AMD Database.

A total of 2473 first-treated eyes and 493 second-treated eyes that commenced therapy for neovascular AMD between June 2012 and June2017.

A deep learning algorithm was used to segment all baseline OCT scans. Volumes were calculated for segmented features such as neurosensory retina (NSR), drusen, intraretinal fluid (IRF), subretinal fluid (SRF), subretinal hyperreflective material (SHRM), retinal pigment epithelium (RPE), hyperreflective foci (HRF), fibrovascular pigment epithelium detachment (fvPED), and serous PED (sPED). Analyses included comparisons between first- and second-treated eyes by visual acuity (VA) and race/ethnicity and correleal-world care and the detection of novel structure-function correlations. These data will be made publicly available for replication and future investigation by the AMD research community.

We report the results of large-scale automated quantification of a novel range of baseline features in neovascular AMD. Major differences between first- and second-treated eyes, with increasing age, and between ethnicities are highlighted. In the coming years, enhanced, automated OCT segmentation may assist personalization of real-world care and the detection of novel structure-function correlations. These data will be made publicly available for replication and future investigation by the AMD research community.Acute exposure to arsenic is known to cause bone marrow depression and result in anemia, in which the dusfunction of cells in the bone marrow niche such as mesenchymal stem cells (MSCs) is vital. However, the mechanism underlying response of MSCs to arsenic challange is not fully understood. In the present study, we investigated the role of nuclear factor erythroid 2-related factor (NRF) 1 (NRF1), a sister member of the well-known master regulator in antioxidative response NRF2, in arsenite-induced cytotoxicity in mouse bone marrow-derived MSCs (mBM-MSCs). We found that arsenite exposure induced significant increase in the protein level of long-isoform NRF1 (L-NRF1). Though short-isoform NRF1 (S-NRF1) was induced by arsenite at mRNA level, its protein level was not obviously altered. Silencing L-Nrf1 sensitized the cells to arsenite-induced cytotoxicity. L-Nrf1-silenced mBM-MSCs showed decreased arsenic efflux with reduced expression of arsenic transporter ATP-binding cassette subfamily C member 4 (ABCC4), as well as compromised NRF2-mediated antioxidative defense with elevated level of mitochondrial reactive oxygen species (mtROS) under arsenite-exposed conditions. A specific mtROS scavenger (Mito-quinone) alleviated cell apoptosis induced by arsenite in L-Nrf1-silenced mBM-MSCs. Taken together, these findings suggest that L-NRF1 protects mBM-MSCs from arsenite-induced cytotoxicity via suppressing mtROS in addition to facilitating cellular arsenic efflux.Eravacycline has been shown to have broad-spectrum activity against Gram-negative bacteria, including carbapenem-resistant Enterobacteriaceae (CRE). We compared the activity of eravacycline with that of tigecycline in CRE isolates cultured from patients at an academic medical centre. Eravacycline was more potent than tigecycline [mean minimum inhibitory concentration (MIC) ratio = 0.76, 95% confidence interval 0.66-0.87]; however, the MIC90 observed for eravacycline was higher than previously reported at 4 μg/mL. Future studies are necessary to elucidate the mechanism driving this difference.New classes of therapeutic peptides are being developed to prosecute biological targets which have been inaccessible to other modalities. Higher potency and longer half-life peptides have given rise to multiuse injectable formulations that enable convenient, low volume, and self-administered dosing; however, inclusion of antimicrobial preservatives to meet bactericidal requirements can impact other attributes of peptide formulations. Peptide-preservative interactions influencing solution-phase self-association of a non-insulin, linear, palmitoylated 31 amino acid peptide and two structurally similar peptides were assessed via turbidity, intrinsic fluorescence shifts and quenching, isothermal titration calorimetry, and 1H NMR. Meta-cresol and phenol specifically interact with the peptide, result in increased hydrophobicity near the tryptophan residue, and induce conformational changes, while benzyl alcohol does not impact tryptophan fluorescence, demonstrate any interaction enthalpy, or induce conformational changes. These same trends did not hold true for the other palmitoylated peptides evaluated, reinforcing the impacts of unique peptide sequences. Importantly, the presence of benzyl alcohol does increase the physical stability and solubility of the linear, 31 amino acid peptide under salt stress. We report new insights into the physical interactions of peptides with antimicrobial excipients, demonstrating a reversible association phenomenon and highlighting practical implications for formulation design and excipient selection.