The Frontal Area with Higher Frequency Response Is the Principal Feature of Laser-Evoked Potentials in Rats with Chronic Inflammatory Pain: A Parallel Factor Analysis Study

Chronic pain is a pathological developing course of pain. In clinic, an objective indicator is needed for diagnosing and better controlling chronic pain. The abnormal neural responses in chronic pain are reflected by multiple event-related potentials (ERPs) in time, frequency, and location domain, respectively. However, multiple changes in ERPs are not applicable in clinic. So, the principal feature covered the most informative changes extracted from these three domains of ERP during the development of chronic pain is needed. In the present study, a parallel factor analysis method was employed to extract time–frequency–channel features of laser-evoked potential (LEP) simultaneously from rats with chronic inflammatory pain. Results showed that the main feature of LEP in channel domain locates in the frontal brain region in rats with chronic inflammatory pain while in the parietal brain region in control rats. In the frequency domain, the main frequency of LEP was significantly higher in chronic inflammatory pain rats than that in control rats. These findings indicate that the frontal region with higher frequency response to nociceptive information is the principal feature in the chronic pain state. Our study provided not only a principal feature of LEP but also a promising strategy for chronic pain, which is potential for clinic application

Elevated Resting State Gamma Oscillatory Activities in Electroencephalogram of Patients With Post-herpetic Neuralgia

In acute and ongoing pain, the spontaneous oscillatory activity of electroencephalogram (EEG) has been characterized by suppression of alpha band oscillations and enhancement of gamma band oscillations. In pathological chronic pain which is more severe and common in clinic practice, it is of great interest to investigate the oscillatory activity especially at the broad gamma frequency bands. Our present study explored the resting state oscillatory activities of EEG in patients with post-herpetic neuralgia (PHN) over 3 months which is a typical neuropathic pain model in clinical researches. It was found that the PHN patients showed anxiety and depression revealed by Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) examinations. Power spectrum analysis revealed that the power at gamma frequency band (from 40 to 70 Hz) of EEG was significantly higher in the PHN patients, and positively correlated with pain intensity, anxiety, and depression indexes. Further, increased gamma activity derived from the prefrontal cortex and the cerebellum were revealed by cluster-based sensor level and the beamforming source level analyses. These results suggest the enhanced gamma oscillatory activity in the prefrontal cortex and cerebellum is a characteristic marker in chronic neuropathic pain patients

The Protective Efficacy of a SARS-CoV-2 Vaccine Candidate B.1.351V against Several Variant Challenges in K18-hACE2 Mice

The emergence of SARS-CoV-2 variants of concern (VOCs) with increased transmissibility and partial resistance to neutralization by antibodies has been observed globally. There is an urgent need for an effective vaccine to combat these variants. Our study demonstrated that the B.1.351 variant inactivated vaccine candidate (B.1.351V) generated strong binding and neutralizing antibody responses in BALB/c mice against the B.1.351 virus and other SARS-CoV-2 variants after two doses within 28 days. Immunized K18-hACE2 mice also exhibited elevated levels of live virus-neutralizing antibodies against various SARS-CoV-2 viruses. Following infection with these viruses, K18-hACE2 mice displayed a stable body weight, a high survival rate, minimal virus copies in lung tissue, and no lung damage compared to the control group. These findings indicate that B.1.351V offered protection against infection with multiple SARS-CoV-2 variants in mice, providing insights for the development of a vaccine targeting SARS-CoV-2 VOCs for human use

Multinational patterns of second line antihyperglycaemic drug initiation across cardiovascular risk groups:federated pharmacoepidemiological evaluation in LEGEND-T2DM

Objective: To assess the uptake of second line antihyperglycaemic drugs among patients with type 2 diabetes mellitus who are receiving metformin.Design: Federated pharmacoepidemiological evaluation in LEGEND-T2DM.Setting: 10 US and seven non-US electronic health record and administrative claims databases in the Observational Health Data Sciences and Informatics network in eight countries from 2011 to the end of 2021.Participants: 4.8 million patients (≥18 years) across US and non-US based databases with type 2 diabetes mellitus who had received metformin monotherapy and had initiated second line treatments.Exposure: The exposure used to evaluate each database was calendar year trends, with the years in the study that were specific to each cohort.Main outcomes measures: The outcome was the incidence of second line antihyperglycaemic drug use (ie, glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, dipeptidyl peptidase-4 inhibitors, and sulfonylureas) among individuals who were already receiving treatment with metformin. The relative drug class level uptake across cardiovascular risk groups was also evaluated.Results: 4.6 million patients were identified in US databases, 61 382 from Spain, 32 442 from Germany, 25 173 from the UK, 13 270 from France, 5580 from Scotland, 4614 from Hong Kong, and 2322 from Australia. During 2011-21, the combined proportional initiation of the cardioprotective antihyperglycaemic drugs (glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors) increased across all data sources, with the combined initiation of these drugs as second line drugs in 2021 ranging from 35.2% to 68.2% in the US databases, 15.4% in France, 34.7% in Spain, 50.1% in Germany, and 54.8% in Scotland. From 2016 to 2021, in some US and non-US databases, uptake of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors increased more significantly among populations with no cardiovascular disease compared with patients with established cardiovascular disease. No data source provided evidence of a greater increase in the uptake of these two drug classes in populations with cardiovascular disease compared with no cardiovascular disease.Conclusions: Despite the increase in overall uptake of cardioprotective antihyperglycaemic drugs as second line treatments for type 2 diabetes mellitus, their uptake was lower in patients with cardiovascular disease than in people with no cardiovascular disease over the past decade. A strategy is needed to ensure that medication use is concordant with guideline recommendations to improve outcomes of patients with type 2 diabetes mellitus.</p

Carbon-Nanotube-Embedded Hydrogel Sheets for Engineering Cardiac Constructs and Bioactuators

We engineered functional cardiac patches by seeding neonatal rat cardiomyocytes onto carbon nanotube (CNT)-incorporated photo-cross-linkable gelatin methacrylate (GelMA) hydrogels. The resulting cardiac constructs showed excellent mechanical integrity and advanced electrophysiological functions. Specifically, myocardial tissues cultured on 50 μm thick CNT-GelMA showed 3 times higher spontaneous synchronous beating rates and 85% lower excitation threshold, compared to those cultured on pristine GelMA hydrogels. Our results indicate that the electrically conductive and nanofibrous networks formed by CNTs within a porous gelatin framework are the key characteristics of CNT-GelMA leading to improved cardiac cell adhesion, organization, and cell–cell coupling. Centimeter-scale patches were released from glass substrates to form 3D biohybrid actuators, which showed controllable linear cyclic contraction/extension, pumping, and swimming actuations. In addition, we demonstrate for the first time that cardiac tissues cultured on CNT-GelMA resist damage by a model cardiac inhibitor as well as a cytotoxic compound. Therefore, incorporation of CNTs into gelatin, and potentially other biomaterials, could be useful in creating multifunctional cardiac scaffolds for both therapeutic purposes and in vitro studies. These hybrid materials could also be used for neuron and other muscle cells to create tissue constructs with improved organization, electroactivity, and mechanical integrity.United States. Army Research Office. Institute for Soldier NanotechnologiesNational Institutes of Health (U.S.) (HL092836)National Institutes of Health (U.S.) (EB02597)National Institutes of Health (U.S.) (AR057837)National Institutes of Health (U.S.) (HL099073)National Science Foundation (U.S.) (DMR0847287)United States. Office of Naval Research (ONR PECASE Award)United States. Office of Naval Research (Young Investigator award)National Research Foundation of Korea (grant (NRF-2010-220-D00014)