Rehabilitation in Older Adults Affected by Immobility Syndrome, Aided by Virtual Reality Technology: A Narrative Review.

Individual mobility deficit in older adults induces a variety of medical conditions, diminishing their functional capacity in pursuing activities of daily living. In immobility syndrome patients, such conditions are prone further deterioration through a drastically reduced scope of physical activity, owing mostly to poor self-motivation and the monotonous character of conventional rehabilitation regimens. As evidenced by published research, virtual reality technology solutions in rehabilitation management actually add significantly to patients' self-motivation, while promoting their active involvement in therapy through visual, auditory, and kinaesthetic stimuli. Effective rehabilitation training aided by virtual reality solutions helps patients acquire specific physical and cognitive skills to be subsequently emulated in the real-world environment. The extra added advantage lies in facilitating such training within patients' own home environments, combined with online monitoring of their progress, when not personally supervised by a physiotherapist, which also boosts the overall cost effectiveness of the therapeutic management itself. This narrative review appears to be the very first one principally focused on critically comparing individual immobilisation with immobility syndrome, especially through the application of the Authors' own substantial hands-on therapeutic experience in managing various rehabilitation schemes, specifically aided by diverse virtual reality technology solutions.

The Evolution of Effort-Reward Imbalance in Workers during the COVID-19 Pandemic in France-An Observational Study in More than 8000 Workers.

(1) Background: The effects of lockdown repetition on work-related stress, expressed through Effort-Reward Imbalance (ERI), during the COVID-19 pandemic are poorly documented. We investigated the effect of repetitive lockdowns on the ERI in French workers, its difference across occupations, and the change in its influencing factors across time. (2) Methods: Participants were included in a prospective cross-sectional observational study from 30 March 2020 to 28 May 2021. The primary outcome was the ERI score (visual analog scale). The ERI score of the population was examined via Generalized Estimating Equations. For each period, the factors influencing ERI were studied by multivariate linear regression. (3) Results: In 8121 participants, the ERI score decreased in the first 2 lockdowns (53.2 ± 0.3, p < 0.001; 50.5 ± 0.7, p < 0.001) and after lockdown 2 (54.8 ± 0.8, p = 0.004) compared with the pre-pandemic period (59 ± 0.4). ERI was higher in medical than in paramedical professionals in the pre-pandemic and the first 2 lockdowns. Higher workloads were associated with better ERI scores. (4) Conclusions: In a large French sample, Effort-Reward Imbalance worsened during the COVID-19 pandemic until the end of the 2nd lockdown. Paramedical professionals experienced a higher burden of stress compared with medical professionals.

Physiotherapy Programmes Aided by VR Solutions Applied to the Seniors Affected by Functional Capacity Impairment: Randomised Controlled Trial.

Modern technologies are presently harnessed in response to a complex challenge of providing physiotherapeutic management in older adults. Fully immersive virtual reality (VR) solutions are acknowledged to viably enhance the overall effectiveness of traditional physiotherapeutic methods. A total of 60 community-dwelling older adults (over 75 years of age) were recruited for the study protocol. They were subsequently randomly split into four equally sized study groups (VR, CVR, OCULUS, and the classic programme group (OTAGO), and the physiotherapy sessions were pursued in the subjects' homes for 3 weeks, 3 times a week, for 30 min in each group. At the first measurement point, respective study groups differed significantly in functional performance, as expressed in gait (POMA G) and individual static balance. The post hoc analysis indicated significantly higher scores in POMA G for the classic programme group vs. the results of the VR and CVR groups. On the other hand, the OCULUS group held significantly higher scores in individual balance and TUG, as compared to the other groups (p < 0.001). Making use of a virtual reality (VR) environment in the physiotherapeutic management of community-dwelling older adults appreciably enhanced individual functional performance, especially in terms of static balance. Physiotherapy management aided by VR technology solutions offers a viable alternative to traditional physiotherapeutic regimens (e.g., OTAGO programme) in enhancing individual functional performance. The innovatively self-designed VIRTUAL REALITY COMPREHENSIVE REHABILITATION ROOMS (VRCRR) solution may help out in pursuing a complex physiotherapy programme on an individual basis within one's own home environment.

Frailty Syndrome-Fall Risk and Rehabilitation Management Aided by Virtual Reality (VR) Technology Solutions: A Narrative Review of the Current Literature.

Frailty, a physiological syndrome (FS) affecting primarily the older adults, manifests itself through significantly depleted bodily reserves, and appreciably higher (up to over threefold) individual exposure to fall risk. Concomitant medical conditions such as balance impairment, reduced visual acuity, limited mobility, and significantly diminished daily functional performance further exacerbate the patients' condition. Their resultant susceptibility to frequent hospitalisations makes their prognosis even worse. This narrative review aimed to provide an overview of published studies focused on rehabilitation management approaches aided by virtual reality (VR) technology in frail older adults. The authors had it also augmented with their own, evidence-based body of experience in rehabilitation. Making use of technologically advanced exercise machinery, specially adapted for rehabilitating frail older adults, combined with a structured exercise regimen, further aided by the application of select virtual reality (VR) technology solutions, clearly proved effective. Consequently, the patients were helped to move back from the frail to the pre-frail stage, as well as had their motor and cognitive functions appreciably enhanced. The application of modern technology in rehabilitating older adults over 65, affected by FS, when specifically aided by the select VR technology solutions, was also proven to complement successfully the conventional rehabilitation management. The overall versatility of the VR technology solutions, e.g., adaptation for home use allowing remote supervision, also makes this novel approach to rehabilitation far more appealing to the patients. They find it both very attractive and far more mentally engaging. Its considerable potential lies mostly in being appreciably more effective in bringing in desirable therapeutic outcomes.

Pisa syndrome: Pathophysiology, physical rehabilitation and falls risk.

BACKGROUND: Pisa syndrome (PS) is a postural disorder characterised by lateral flexion of the spine (> 10°), predisposing the affected individuals to falls, and contributing to increased mortality in neurodegenerative diseases. OBJECTIVE: An overview of currently applied therapeutic management options, primarily focused on specifically structured rehabilitation exercises, in conjunction with falls-risk assessment in the individuals affected by PS. METHODS: A narrative literature review, augmented with the authors' own experience in physical rehabilitation management. RESULTS: As individuals affected by PS are evidenced to be intrinsically exposed to higher falls-risk through acquired postural deformities, they often fall victims of traumatic accidents, occasionally also facing relocation into 24-hour nursing facilities due to the injuries sustained/resultant disability, consequently having overall quality of their life appreciably reduced. CONCLUSIONS: sA comprehensive approach is postulated in designing optimal therapeutic management, comprised of the exercises controlling postural stability, whilst reducing lower back pain, and the ones also promoting specific skills essential for coping unassisted after an accidental fall effectively. Rehabilitation of individuals affected by PS should be a fully integrated service, eliminating all identified risk factors for falls. As clinical PS symptoms tend to recur after completion of a full course of therapeutic management, all PS patients should continue the pursuit of therapeutic exercises on an individual basis, to effectively retard their recurrence. In view of overall scarcity of clinical studies completed on the large population samples of PS patients, further in-depth research is still required to ensure higher credence to overall efficacy of the presently proposed therapeutic solutions.

Selective downregulation of natural killer activating receptors on NK cells and upregulation of PD-1 expression on T cells in children with severe and/or recurrent Herpes simplex virus infections.

Severe, recurrent or atypical Herpes simplex virus (HSV) infections are still posing clinical and diagnostic problem in clinical immunology facilities. However, the molecular background of this disorder is still unclear. The aim of this study was to investigate the expression of activating receptors on NK cells (CD16, NKp46, NKG2D, NKp80, 2B4, CD48 and NTB-A) and checkpoint molecule PD-1 on T lymphocytes and NK cells, in patients with severe and/or recurrent infections with HSV and age-matched healthy control subjects. As a result, we noticed that patients with severe and/or recurrent infection with HSV had significantly lower percentage of CD16brightCD56dim and higher percentage of CD16dimCD56bright NK cell subsets, when compared to control subjects, which may be associated with abnormal NK cell maturation during chronic HSV infection. Patients had also significantly downregulated expression of CD16 receptor on CD16bright NK cells. The expression of activating receptors was significantly reduced on patients' NK cells - either both the percentage of NK cells expressing the receptor and MFI of its expression (NKp46, NKp80 and 2B4 on CD16brightCD56dim cells and NKp46 on CD16dimCD56bright cells) or only MFI (NKG2D on both NK cell subsets). It should be noted that the reduction of receptor expression was limited to NK cells, since there was no differences in the percentage of receptor-positive cells or MFI on T cells. However, NTB-A receptor was the only one which expression was not only simultaneously changed in patients' NK and T cells, but also significantly upregulated on CD16dimCD56bright NK cell and CD8+ cell subsets. Patients had also upregulated proportion of CD4+ T cells expressing PD-1. Thus, we suggest that an increased percentage of PD-1+ cells may represent an independent indirect mechanism of downregulation of antiviral response, separate from the reduction of NK cell activating receptors expression. Altogether, our studies indicate two possible mechanisms which may promote perpetuation of HSV infection: 1) selective inhibition of activating receptors on NK cells, but not on T cells, and 2) upregulation of checkpoint molecule PD-1 on CD4+ T cells.

Intravenously administered contact allergens coupled to syngeneic erythrocytes induce in mice tolerance rather than effector immune response.

Constantly increasing prevalence of allergic diseases determines the attempts to elaborate the therapeutic strategies activating immune tolerance to particular allergen. Our current research focuses on the antigen-specific action of CD8+ suppressor T (Ts) lymphocytes induced in mice by intravenous administration of a high dose of haptenated syngeneic erythrocytes. While the regulatory activity of Ts cells mediated by exosome-delivered miRNA-150 is well de ned, the mechanism of their induction remained unclear. Therefore, the current studies investigated the immune e ects induced in mice by intravenous administration of contact allergens coupled to syngeneic erythrocytes. In mouse models of hapten-induced contact hypersensitivity (CHS) and delayed-type hypersensitivity to ovalbumin, we have shown that intravenous administration of hapten-coupled erythrocytes failed to induce CHS effector cells. Moreover, hapten-induced CHS reaction occurred to be suppressed in mice intravenously administered with syngeneic erythrocytes coupled with protein allergen. Finally, we have demonstrated that intravenously administered allergen induces immune tolerance only when bound to syngeneic erythrocytes, proving that intravenously delivered allergens are deprived of their immunizing properties when coupled with membrane of self cells. Altogether, our current studies suggest that alteration of self cell membrane by allergen binding is enough to induce Ts cell-mediated immune tolerance to nonpathogenic agents, which express a great translational potential in such conditions as allergies and hypersensitivity-related autoimmune disorders.

Smoking status in relation to obstructive sleep apnea severity (OSA) and cardiovascular comorbidity in patients with newly diagnosed OSA.

INTRODUCTION: the relationship between smoking and sleep disturbance has been well documented. Smoking is a common risk factor for both obstructive sleep apnea (OSA) and cardiovascular diseases. The study aimed to: 1) evaluate the incidence of newly diagnosed OSA in patients presenting with symptoms suggestive of a sleep disorder, 2) assess the relation between smoking status and OSA severity; and 3) compare the prevalence of cardiovascular comorbidities in ever- and never smokers with newly diagnosed OSA. MATERIAL AND METHODS: a retrospective analysis of 5,353 patients suspected of OSA was performed. OSA was diagnosed on the basis of polysomnography. The influence of smoking status on indices of OSA severity was evaluated and the incidence of self-reported cardiovascular diseases and diabetes mellitus type 2 was analyzed in relation to smoking history. RESULTS: OSA was diagnosed in 3,613 patients (67.5%); of these, 21.6% were ever-smokers. Smokers with OSA had a higher apnea-hypopnea index [AHI; 31 (18.4-53.29) vs 29 (18.3-47.7), p = 0.03], lower mean oxygenation during sleep [92 (90-93) vs 92 (91-94), p < 0.01] and a higher daytime sleepiness (Epworth Sleepiness Scale score 11.7 ± 5.5 vs 11.0 ± 5.5, p < 0.001). The most frequent comorbidity was hypertension, followed by obesity, diabetes mellitus type 2 and coronary artery disease, with a statistically higher incidence of hypertension in non-smokers (59.2 vs 64.7 %, p = 0.005). CONCLUSION: smoking is related with OSA severity and increased daytime sleepiness. Our study confirmed the elevated frequency of cardiovascular comorbidities in OSA patients in general but did not show an increased incidence of these comorbidities in smokers.

Delayed-Type Hypersensitivity Underlying Casein Allergy Is Suppressed by Extracellular Vesicles Carrying miRNA-150.

In patients with non-IgE-mediated milk allergy, a cellular mechanism of delayed-type hypersensitivity (DTH) is considered. Recent findings prove that cell-mediated reactions can be antigen-specifically inhibited by extracellular vesicles (EVs) carrying miRNA-150. We sought to establish a new mouse model of DTH to casein and test the possibility of antigen-specific suppression of the inflammatory reaction. To produce soluble antigenic peptides, casein was subjected to alkaline hydrolysis. DTH reaction to casein was induced in CBA, C57BL/6, and BALB/c mice by intradermal (id) injection of the antigen. Cells collected from spleens and lymph nodes were positively or negatively selected and transferred to naive recipients intravenously (iv). CBA mice were tolerized by iv injection of mouse erythrocytes conjugated with casein antigen and following id immunization with the same antigen. Suppressive EVs were harvested from cell cultures and serum of tolerized donors by means of ultrafiltration and ultracentrifugation for further therapeutic utilization. The newly established mouse model of DTH to casein was mediated by CD4+ Th1 cells and macrophages, while EVs produced by casein-tolerized animals effectively suppressed effector cell response, in an miRNA-150-dependent manner. Altogether, our observations contribute to the current understanding of non-IgE-mediated allergy to casein and of the possibilities to downregulate this reaction.

Regulatory B cell phenotype and mechanism of action: the impact of stimulating conditions.

A diverse population of regulatory B (Breg) cells reportedly exhibits significant immunomodulatory effects in various models of inflammatory responses and infectious diseases caused by bacteria, viruses or parasites. Breg cells contribute to maintenance of homeostasis via IL-10 production and multiple IL-10-independent mechanisms. The current review describes various phenotypic and functional subsets of Breg cells in autoimmune and infectious diseases and discusses the impacts of experimental conditions that have been found to drive Breg cell differentiation.

Data supporting the understanding of modulatory function of opioid analgesics in mouse macrophage activity.

The data presented herein expand the current understanding of the modulatory function of opioid drugs in mouse macrophage activity described in our relevant research article (Filipczak-Bryniarska et al., 2017) [1], in which we characterize the influence of morphine, buprenorphine and oxycodone on humoral and cell-mediated immune response in mice. Among other things, we have shown the effects of treatment with assayed analgesics on macrophage ability to induce antigen-specific B-cell response to sheep red blood cells as well as to generate reactive oxygen intermediates and nitric oxide. The current data demonstrate the effects of morphine, buprenorphine or oxycodone administration on phagocytosis of sheep red blood cells and zymosan by mouse macrophages, supplementing the data on immune modulatory capacities of assayed drugs, recently reported by us (Filipczak-Bryniarska et al., 2017; Kozlowski et al., 2017) [1,2].

In contrast to morphine, buprenorphine enhances macrophage-induced humoral immunity and, as oxycodone, slightly suppresses the effector phase of cell-mediated immune response in mice.

BACKGROUND: Opioid receptors are commonly expressed on various immune cells, macrophages especially. Thus, these cells are prone to stimulation with opioids, which seems to be responsible for opioid-induced immunomodulatory effects. While morphine, fentanyl and methadone influence on mouse immune response was recently studied, little is known about the potential immunomodulatory impact of buprenorphine and oxycodone. AIM: The current research aimed to investigate the influence of buprenorphine and oxycodone on immune responses in mice under homeostatic conditions. METHODS AND RESULTS: Repeated administration of morphine led to intensification of CHS response in actively sensitized mice, while buprenorphine or oxycodone administration exerted the opposite effect. Further, hapten-conjugated macrophages from mice treated with morphine, when transferred into naive recipients, induced more potent CHS response. The enhanced generation of reactive oxygen intermediates and nitric oxide by macrophages from mice treated with buprenorphine, oxycodone or morphine was also shown, along with increased release of IL-6, TNFα and TGFß. Treatment with opioids altered expression of antigen phagocytosis and presentation markers. Finally, the inhibitory effect of morphine treatment on induction of humoral immunity by macrophages was demonstrated, while oxycodone failed to influence humoral immune response and buprenorphine actually enhanced B-cell activation. CONCLUSIONS: Current observations confirm that macrophages greatly contribute to immunomodulatory effects of opioids. Studies on immunomodulation by opioids have great importance related to the evaluation of its beneficial and adverse effects on patient condition. Our research showed that oxycodone exerts the weakest immunomodulatory properties, allowing us to assume this drug as safer than morphine during prolonged therapy.

The impact of advanced opioid drugs and analgesic adjuvants on murine macrophage oxygen burst.

Macrophages (Mf) are a versatile group of phagocytic cells responsible for fulfilling a variety of immune functions, most notably for mounting the initial anti-microbial response and for the clearance of cellular debris and apoptotic bodies. The key processes for fulfilling these functions include the production of reactive oxygen intermediates (ROIs) and nitric oxide (NO). Mf also express a variety of receptors, including opioid, serotonin, and norepinephrine receptors, and thus can react to various substances. Our study aimed to examine the effects of oxycodone and buprenorphine on the production ROIs and NO by Mf from intraperitoneally-treated mice, as compared to the previously studied morphine, fentanyl, and methadone, as well as the effects of the analgesic adjuvants gabapentin, amitriptyline, and venlafaxine. ROIs was estimated via luminol and lucigenin dependent chemiluminescence assay, and NO secretion was estimated via a colorimetric method utilizing a modified Griess reaction. We observed an overall decrease in both ROIs and NO production by Mf from adjuvant-treated mice, especially with amitriptyline. Opioids, however, resulted in enhanced ROIs production and mixed NO secretion, with oxycodone and buprenorphine have the least immunomodulatory effects. As ROIs and NO are potent mediators of Mf activity during the innate immune response, our current results express great translational potential. Our results suggest that OPs administration may boost Mf anti-microbial response. On the other hand, during sterile in ammation, enhanced generation of ROIs by Mf influenced by opioids may increase the risk of tissue damage, but co-administration of adjuvants could abolish this adverse effect.

Inhibition of myeloperoxidase activity have impact on the formation of DNA double-strand breaks induced by etoposide in HL-60 cell line.

Many studies have shown the role of myeloperoxidase (MPO) in leukemogenic activity of etoposide. The aim of our study was to determine whether inhibition of MPO activity has influence on the formation of double-stranded DNA breaks (DSBs) that may contribute to the characteristic of leukemia translocations. Studies were carried out on HL-60 cell line, which were preincubated with the MPO inhibitor 4-aminobenzoic acid hydrazide (ABAH), or antioxidant N-acetyl-L-cysteine (NAC), followed by incubation at different concentrations of etoposide (1-10 mM) for 4 hours. Cytotoxicity was investigated using propidium iodide staining. Marker of DSBs, a phosphorylated form of histone 2AX (gH2AX) was detected using immunocytochemical methods. Cells were analyzed by flow cytometry. ABAH significantly reduced the cytotoxicity and the gH2AX level induced by lower concentrations of etoposide (1 and 1.5 mM) and did not modify the action of higher concentration (10 mM) of this cytostatic drug. NAC exerted similar impact as ABAH on the level of gH2AX induced by etoposide. The results of this study suggest that MPO contributes to increase of the DSBs level induced by low concentrations of etoposide in myeloid cells.