Neutralization, effector function and immune imprinting of Omicron variants.

Currently circulating SARS-CoV-2 variants have acquired convergent mutations at hot spots in the receptor-binding domain1 (RBD) of the spike protein. The effects of these mutations on viral infection and transmission and the efficacy of vaccines and therapies remains poorly understood. Here we demonstrate that recently emerged BQ.1.1 and XBB.1.5 variants bind host ACE2 with high affinity and promote membrane fusion more efficiently than earlier Omicron variants. Structures of the BQ.1.1, XBB.1 and BN.1 RBDs bound to the fragment antigen-binding region of the S309 antibody (the parent antibody for sotrovimab) and human ACE2 explain the preservation of antibody binding through conformational selection, altered ACE2 recognition and immune evasion. We show that sotrovimab binds avidly to all Omicron variants, promotes Fc-dependent effector functions and protects mice challenged with BQ.1.1 and hamsters challenged with XBB.1.5. Vaccine-elicited human plasma antibodies cross-react with and trigger effector functions against current Omicron variants, despite a reduced neutralizing activity, suggesting a mechanism of protection against disease, exemplified by S309. Cross-reactive RBD-directed human memory B cells remained dominant even after two exposures to Omicron spikes, underscoring the role of persistent immune imprinting.

Therapeutic and vaccine-induced cross-reactive antibodies with effector function against emerging Omicron variants.

Currently circulating SARS-CoV-2 variants acquired convergent mutations at receptor-binding domain (RBD) hot spots. Their impact on viral infection, transmission, and efficacy of vaccines and therapeutics remains poorly understood. Here, we demonstrate that recently emerged BQ.1.1. and XBB.1 variants bind ACE2 with high affinity and promote membrane fusion more efficiently than earlier Omicron variants. Structures of the BQ.1.1 and XBB.1 RBDs bound to human ACE2 and S309 Fab (sotrovimab parent) explain the altered ACE2 recognition and preserved antibody binding through conformational selection. We show that sotrovimab binds avidly to all Omicron variants, promotes Fc-dependent effector functions and protects mice challenged with BQ.1.1, the variant displaying the greatest loss of neutralization. Moreover, in several donors vaccine-elicited plasma antibodies cross-react with and trigger effector functions against Omicron variants despite reduced neutralizing activity. Cross-reactive RBD-directed human memory B cells remained dominant even after two exposures to Omicron spikes, underscoring persistent immune imprinting. Our findings suggest that this previously overlooked class of cross-reactive antibodies, exemplified by S309, may contribute to protection against disease caused by emerging variants through elicitation of effector functions.

Climate change and neurodegenerative diseases.

The climate change induced global warming, and in particular the increased frequency and intensity of heat waves, have been linked to health problems. Among them, scientific works have been reporting an increased incidence of neurological diseases, encompassing also neurodegenerative ones, such as Dementia of Alzheimer's type, Parkinson's Disease, and Motor Neuron Diseases. Although the increase in prevalence of neurodegenerative diseases is well documented by literature reports, the link between global warming and the enhanced prevalence of such diseases remains elusive. This is the main theme of our work, which aims to examine the connection between high temperature exposure and neurodegenerative diseases. Firstly, we evaluate the influence of high temperatures exposure on the pathophysiology of these disorders. Secondly, we discuss its effects on the thermoregulation, already compromised in affected patients, and its interference with processes of excitotoxicity, oxidative stress and neuroinflammation, all of them related with neurodegeneration. Finally, we investigate chronic versus acute stressors on body warming, and put forward a possible interpretation of the beneficial or detrimental effects on the brain, which is responsible for the incidence or progression of neurological disorders.

Energy cost and psychological impact of robotic-assisted gait training in people with spinal cord injury: effect of two different types of devices.

BACKGROUND: In the last years, there has been an intense technological development of robotic devices for gait rehabilitation in spinal cord injury (SCI) patients. The aim of the present study was to evaluate energy cost and psychological impact during a rehabilitation program with two different types of robotic rehabilitation systems (stationary system on a treadmill, Lokomat, and overground walking system, Ekso GT). METHODS: Fifteen SCI patients with different injury levels underwent robot-assisted gait training sessions, divided into 2 phases: in the first phase, all subjects completed 3 sessions both Lokomat and Ekso GT. Afterwards, participants were randomly assigned to Lokomat or the Ekso for 17 sessions. A questionnaire, investigating the subjective psychological impact (SPI) during gait training, was administered. The functional outcome measures were oxygen consumption (VO2), carbon dioxide production (VCO2), metabolic equivalent of task (MET), walking economy, and heart rate (HR). RESULTS: The metabolic responses (7.73 ± 1.02 mL/kg/min) and MET values (3.20 ± 1.01) during robotic overground walking resulted to be higher than those during robotic treadmill walking (3.91 ± 0.93 mL/kg/min and 1.58 ± 0.44; p < 0.01). Both devices showed high scores in emotion and satisfaction. Overground walking resulted in higher scores of fatigue, mental effort, and discomfort while walking with Lokomat showed a higher score in muscle relaxation. All patients showed improvements in walking economy due to a decrease in energy cost with increased speed and workload. CONCLUSIONS: Overground robotic-assisted gait training in rehabilitation program needs higher cognitive and cardiovascular efforts than robot-assisted gait training on a treadmill.

Exercise training in ad libitum and food-restricted old rats: effects on metabolic and physiological parameters.

Aging is accompanied by a decline in the healthy function of multiple organs, leading to increased incidence and mortality from diseases such as cancer and inflammatory, cardiovascular and neurodegenerative diseases. Dietary restriction is the most effective experimental intervention known to consistently slow the aging process and with positive effects on health span in different organisms, from invertebrates to mammals. Age is also associated with progressive decline in physical activity levels in a wide range of animal species: therefore, regular physical exercise could represent a safe intervention to antagonize aging. In this research we explore the effects of exercise training initiated in late middle aged rats fed with different lifelong dietary regimens: one group was fed ad libitum and the second group was subjected to every-other-day fasting. These two groups might represent examples of "normal" aging and "successful" aging. The study shows the effects of exercise and food restriction and their interaction on plasma levels of total antioxidant capacity, lactate, amino acids, and on products of protein oxidation in soleus and tibialis anterior muscles. In addition, we evaluated body composition measurement by bioelectrical impedance analysis and muscle strength by grasping test. Results show that late-onset exercise training has the potential to improve some metabolic and physiological parameters in rats with the same "chronological age" but different "biological age", without negative effects, and highlight the relevance of a personalised and selected exercise protocol, since the responsiveness to exercise may depend on the individual's "biological age".

Whole body vibration and treadmill training in Parkinson's disease rehabilitation: effects on energy cost and recovery phases.

BACKGROUND: Although physical treatment is recognized as being beneficial for patients with Parkinson's disease (PD), there is scant literature on the type of rehabilitation program most useful for patients with PD. The aim of the present study was to investigate the effects of two different training protocols (aerobic treadmill training, AER and whole body vibration training, WBVT) on energy cost and adaptations after exercise and recovery phases, by means of the oxygen consumption measurement and the assay of metabolic biochemical substrates. METHODS: Twenty male patients with idiopathic Parkinson's disease, aged 51-66 years, were enrolled. Patients were randomly assigned to the training groups. The total work time was 20 min per group for 4 weeks, four times a week. In both groups, training intensity was monitored by the ratings of perceived exertion (RPE). Workload was gradually increased until patients worked up to the exertion level of 13 to 15 on the 20-point Borg scale RPE. The outcome measures were oxygen consumption, free fatty acid (FFA), and amino acid (AA) levels. RESULTS: The oxygen consumption during exercises does not show significant differences between the two training groups. Instead, only in the AER group, excess post-exercise oxygen consumption measurements increased significantly (p < 0.01) as well as FFA availability (p < 0.01). CONCLUSION: The WBVT does not appear to require a long time of recovery and leads to less feeling of fatigue, whereas AER needs an appropriate recovery time after the training session.

Muscle modifications in fibromyalgic patients revealed by surface electromyography (SEMG) analysis.

BACKGROUND: Several studies have been carried out in order to investigate surface electromyography (SEMG) response on fibromyalgic (FM) patients. Some studies failed to demonstrate differences between FM patients and healthy individuals while others found differences in SEMG parameters. Different muscular region have been analyzed in FM patients and heterogeneity is also produced because of the different ways in which the SEMG technique is used. The aims of this study were to evaluate muscle modifications by SEMG analysis in FM women with respect to a sample of healthy controls and to investigate the relationships between SEMG parameters and the clinical aspects of the disease. METHODS: SEMG was recorded in 100 FM women (48.10 +/- 11.96 yr) and in 50 healthy women (48.60 +/- 11.18 yr), from the tibialis anterior and the distal part of vastus medialis muscle during isometric contraction. Initial values and rate of change of median spectral frequency (MDF) and conduction velocity (CV) of the SEMG signal were calculated.The clinical parameters "Fibromyalgia Impact Questionnaire", pain, tender points, tiredness were evaluated and the relationships between these data and the SEMG results were also studied. For the statistical analysis Mann-Whitney test, chi-square test and Spearman correlation were used. RESULTS: MDF absolute values and the so-called Fatigue Index (FI) were significantly lower (p < 0.001) in both muscles studied in FM patients (MDF: 93.2 microV; FI: 1.10, 0.89) with respect to healthy controls (MDF: 138.2 microV; FI: 2.41, 1.66) and a smaller reduction in the percentage values of MDF was observed in FM patients vs controls (22% vs 38%). A significant correlation was found between the SEMG parameter decrement of normalized median frequency (MNF) (%) and seriousness of FM (evaluated by means of tender points). CONCLUSION: We have found some interesting muscle modifications in FM patients with respect to healthy controls, regarding MDF, CV and FI values which resulted significantly lower in FM. Patients might have a different fiber recruitment or a possible atrophy of type II fibers suggesting that they are not able to reach muscle relaxation.

Anthropic agency: a multiagent system for physiological processes.

Multiagent systems are powerful and flexible tools for modelling and regulating complex phenomena. In fact, a way to manage the complexity of a phenomenon is to decompose it in such a way that each agent embeds the control model for a portion of the phenomenon. In this perspective, the cooperative interaction among the agents results in the controller for the whole phenomenon. Since the portions in which the phenomenon is decomposed may overlap, the actions the single agents undertake to regulate these portions may conflict; hence a balanced negotiation is required. A class of complex phenomena that present several difficulties in their satisfactory modelling and controlling is the class of physiological processes. The purpose of this paper is to introduce a general multiagent architecture, called anthropic agency, for the modelling and the regulation of complex physiological phenomena.

Gemella morbillorum deep brain abscess successfully treated with combined stereotactic, medical, and imaging approach.

A rare case of brain abscess due to Gemella morbillorum, a normal inhabitant of the oral cavity, is presented. The aim of this report is to draw the attention of radiology literature readers to this little known pathogen, which caused a potentially life-threatening condition in an immunocompetent young man, and to emphasise the usefulness of a combined stereotactic, medical, and imaging approach to deep-located brain abscesses.