Anti-SARS-CoV-2 antibody levels and kinetics of vaccine response: potential role for unresolved inflammation following recovery from SARS-CoV-2 infection

The immune response after SARS-CoV-2 vaccine administration appears to be characterized by high inter-individual variation, even in SARS-CoV-2 positive subjects, who could have experienced different post-infection, unresolved conditions. We monitored anti-SARS-CoV-2 IgG levels and kinetics along with circulating biomarkers in a cohort of 175 healthcare workers during early immunization with COVID-19 mRNA-LNP BNT162b2 vaccine, to identify the associated factors. Subjects with a previous SARS-CoV-2 infection were characterized by higher BMI and CRP levels and lower neutrophil count with respect to na\uefve subjects. Baseline IgG levels resulted associated with CRP independently on BMI and inflammatory diseases. Among 137 subjects undergoing vaccination and monitored after the first and the second dose, three kinetic patterns were identified. The pattern showing a rapid growth was characterized by higher IgG levels at baseline and higher CRP and MCHC levels than negative subjects. Subjects previously exposed to SARS-CoV-2 showed higher levels of CRP, suggesting persistence of unresolved inflammation. These levels are the main determinant of IgG levels at baseline and characterized subjects belonging to the best performing, post-vaccine antibody kinetic pattern

Evaluation of anti-photoaging effects of a novel cosmeceutical containing a retinoids mixture using in vitro cell models

11noopenPhysiological ageing due to the passing of time and prolonged exposure to harmful sun rays generate wrinkles and reduce skin elasticity. These visible and clinical signs can be prevented or reversed by known strategies, such as the daily use of cosmetic products with antioxidant combina-tions or retinoids. A new dermocosmetic formulation enriched with a complex of retinoids, called RETINOIDS SERUM, was investigated through in vitro assays using human skin cells. The experiments were carried out to assess the anti-ageing activity in normal human dermal fibroblasts (NHDF) and epidermal keratinocytes (HaCaT). After the preliminary MTT assay, the proliferation together with the synthesis of collagen and elastin fibers was performed on NHDF cells after 24 h treatment with the two non-cytotoxic concentrations. Using UVB-irradiated HaCaT cells, the measurement of matrix metalloproteinase-1 (MMP-1) levels was also investigated. In vitro studies show that the dermocosmetic product improves collagen and elastin synthesis and the renewal of dermal fibrob-lasts. Moreover, a reduction in the MMP-1 secretion was also highlighted in UVB-irradiated HaCaT cells. These results suggest that the cosmetic formulation containing functional compounds such as retinoids can be useful to prevent the natural sign of ageing.openZerbinati N.; Sommatis S.; Maccario C.; Capillo M.C.; Di Francesco S.; Liga E.; Rauso R.; D'este E.; Dalla Gasperina D.; Guida S.; Mocchi R.Zerbinati, N.; Sommatis, S.; Maccario, C.; Capillo, M. C.; Di Francesco, S.; Liga, E.; Rauso, R.; D'Este, E.; Dalla Gasperina, D.; Guida, S.; Mocchi, R

Detection of Torquetenovirus and Redondovirus DNA in Saliva Samples from SARS-CoV-2-Positive and -Negative Subjects

Torquetenovirus (TTV) and Redondovirus (ReDoV) are the most prevalent viruses found in the human respiratory virome in viral metagenomics studies. A large-scale epidemiological study was performed to investigate their prevalence and loads in saliva samples according to SARS-CoV-2 status

Kidney, kidney-pancreas and liver-kidney transplantation in HIV infected individuals: the Italian experience

Until a few years ago, HIV infection was considered an exclusion criteria for organ transplantation. However, more recently, because of the significant increase in life expectancy of HIV-infected persons with highly active antiretroviral therapy (HAART), kidney, kidney-pancreas, heart, lung and liver transplantation have been introduced in this patients population in several centers around the world. To evaluate the possible extension of the indications of kidney transplantation to HIV-infected individuals, the Italian National Centre for Transplantation has designed a protocol to be applied on a national basis. Inclusion criteria required a CD4 count ≥200/mm3 and undetectable HIV viral load for at least 3 months for patients on HAART.The program was voluntarily adopted by 4 transplant centres. From January 2006 through November 2007 a total of 13 HIV infected patients (9 male and 4 female, mean age 46.4 years, range 35-56) underwent cadaveric kidney transplantation (including two kidney-pancreas and two liver-kidney) after a median waiting time of 142 days (range 58-650). Median CD4 cells count at the time of transplantation was 449 (range 210-782) and the HIV-RNA was undetectable in all recipients. HAART was started in all recipients after transplantation and HIV-RNA remain undetectable in all patients. Five patients (38.4%) experienced an episode of biopsy proven acute rejection (steroid resistant in one). Drug-drug interactions between antiretrovirals and immunosuppressive agents required frequent dosage modifications. Graft and patient survival was 100% at a median follow-up of 161 days after transplantation (range 8-669). Despite the limited number of patients and the shortness of the follow-up, our study confirms excellent short term results of kidney transplantation in HIV-infected individuals

Mucosal immune response after the booster dose of the BNT162b2 COVID-19 vaccine

Background: To date, only a few studies reported data regarding the development of mucosal immune response after the BNT162b2-booster vaccination. Methods: Samples of both serum and saliva of 50 healthcare workers were collected at the day of the booster dose (T3) and after two weeks (T4). Anti-S1-protein IgG and IgA antibody titres and the neutralizing antibodies against the Wuhan wild-type Receptor-Binding Domain in both serum and saliva were measured by quantitative and competitive ELISA, respectively. Data were compared with those recorded after the primary vaccination cycle (T2). Neutralizing antibodies against the variants of concern were measured in those individuals with anti-Wuhan neutralizing antibodies in their saliva. Findings: After eight months from the second dose, IgG decreased in both serum (T2GMC: 23,838.5 ng/ml; T3GMC: 1473.8 ng/ml) and saliva (T2GMC: 12.9 ng/ml; T3GMC: 0.3 ng/ml). Consistently, serum IgA decreased (T2GMC: 48.6 ng/ml; T3GMC: 6.4 ng/ml); however, salivary IgA showed a different behaviour and increased (T2GMC: 0.06 ng/ml; T3GMC: 0.41 ng/ml), indicating a delayed activation of mucosal immunity. The booster elicited higher titres of both IgG and IgA when compared with the primary cycle, in both serum (IgG T4GMC: 98,493.9 ng/ml; IgA T4GMC: 187.5 ng/ml) and saliva (IgG T4GMC: 21.9 ng/ml; IgA T4GMC: 0.65 ng/ml). Moreover, the booster re-established the neutralizing activity in the serum of all individuals, not only against the Wuhan wild-type antigen (N = 50; INH: 91.6%) but also against the variants (Delta INH: 91.3%; Delta Plus INH: 89.8%; Omicron BA.1 INH: 85.1%). By contrast, the salivary neutralizing activity was high against the Wuhan antigen in 72% of individuals (N = 36, INH: 62.2%), but decreased against the variants, especially against the Omicron BA.1 variant (Delta N = 27, INH: 43.1%; Delta Plus N = 24, INH: 35.2%; Omicron BA.1 N = 4; INH: 4.7%). This was suggestive for a different behaviour of systemic immunity observed in serum with respect to mucosal immunity described in saliva (Wald chi-square test, 3 df of interaction between variants and sample type = 308.2, p < 0.0001). Interpretation: The BNT162b2-booster vaccination elicits a strong systemic immune response but fails in activating an effective mucosal immunity against the Omicron BA.1 variant. Funding: This work was funded by the Department of Medicine and Surgery, University of Insubria, and supported by Fondazione Umberto Veronesi (COVID-19 Insieme per la ricerca di tutti, 2020), Italy

Use of colistin in adult patients: A cross-sectional study

Objectives: The aim of this study was to assess colistin use in a country endemic for multidrug-resistant Gram-negative bacteria (MDR-GNB). Methods: Colistin prescription patterns were evaluated in 22 Italian centres. Factors associated with use of colistin in combination with other anti-MDR-GNB agents were also assessed. Results: A total of 221 adults receiving colistin were included in the study. Their median age was 64 years (interquartile range 52\u201373 years) and 134 (61%) were male. Colistin was mostly administered intravenously (203/221; 92%) and mainly for targeted therapy (168/221; 76%). The most frequent indications for colistin therapy were bloodstream infection and lower respiratory tract infection. Intravenous colistin was administered in combination with at least another anti-MDR-GNB agent in 80% of cases (163/203). A loading dose of 9 MU of colistimethate was administered in 79% of patients receiving i.v. colistin and adequate maintenance doses in 85%. In multivariable analysis, empirical therapy [odds ratio (OR) = 3.25, 95% confidence interval (CI) 1.24\u20138.53;P = 0.017] and targeted therapy for carbapenem-resistant Enterobacterales infection (OR = 4.76, 95% CI 1.69\u201313.43; P = 0.003) were associated with use of colistin in combination with other agents, whilst chronic renal failure (OR = 0.39, 95% CI 0.17\u20130.88; P = 0.024) was associated with use of colistin monotherapy. Conclusion: Colistin remains an important option for severe MDR-GNB infections when other treatments are not available. Despite inherent difficulties in optimising its use owing to peculiar pharmacokinetic/pharmacodynamic characteristics, colistin was mostly used appropriately in a country endemic for MDR-GNB

Upper-Limb Exoskeletons for Stroke Rehabilitation

Upper-limb exoskeletons provide high-intensity, repetitive, task-specific, interactive and individualized training, making effective use of neuroplasticity for functional recovery in neurological patients. Most exoskeletons have robot axes aligned with the anatomical axes of the subject and provide direct control of individual joints. Recently, novel mechanical structures and actuation mechanisms have been proposed, but still result in bulky and heavy exoskeletons, limiting their applicability into clinical practice. Technological efforts are needed to promote light and wearable exoskeletons that implement active-assistive controllers, providing “assisted-as-needed” rehabilitation therapy, towards patient’s motivation and self-esteem. An overview of upper-limb exoskeletons, including mechanical design and control algorithms, will be provided. Special focus will be put on the current evidence about the efficacy of wearable robotic technologies on motor recovery and about other therapies that can be combined with exoskeletons to improve their therapeutic effects

Development and Electromyographic Validation of a Compliant Human-Robot Interaction Controller for Cooperative and Personalized Neurorehabilitation

Background: Appropriate training modalities for post-stroke upper-limb rehabilitation are key features for effective recovery after the acute event. This study presents a cooperative control framework that promotes compliant motion and implements a variety of high-level rehabilitation modalities with a unified low-level explicit impedance control law. The core idea is that we can change the haptic behavior perceived by a human when interacting with the rehabilitation robot by tuning three impedance control parameters. Methods: The presented control law is based on an impedance controller with direct torque measurement, provided with positive-feedback compensation terms for disturbances rejection and gravity compensation. We developed an elbow flexion-extension experimental setup as a platform to validate the performance of the proposed controller to promote the desired high-level behavior. The controller was first characterized through experimental trials regarding joint transparency, torque, and impedance tracking accuracy. Then, to validate if the controller could effectively render different physical human-robot interaction according to the selected rehabilitation modalities, we conducted tests on 14 healthy volunteers and measured their muscular voluntary effort through surface electromyography (sEMG). The experiments consisted of one degree-of-freedom elbow flexion/extension movements, executed under six high-level modalities, characterized by different levels of (i) corrective assistance, (ii) weight counterbalance assistance, and (iii) resistance. Results: The unified controller demonstrated suitability to promote good transparency and render both compliant and stiff behavior at the joint. We demonstrated through electromyographic monitoring that a proper combination of stiffness, damping, and weight assistance could induce different user participation levels, render different physical human-robot interaction, and potentially promote different rehabilitation training modalities. Conclusion: We proved that the proposed control framework could render a wide variety of physical human-robot interaction, helping the user to accomplish the task while exploiting physiological muscular activation patterns. The reported results confirmed that the control scheme could induce different levels of the subject's participation, potentially applicable to the clinical practice to adapt the rehabilitation treatment to the subject's progress. Further investigation is needed to validate the presented approach to neurological patients

Review on Patient-Cooperative Control Strategies for Upper-Limb Rehabilitation Exoskeletons

Technology-supported rehabilitation therapy for neurological patients has gained increasing interest since the last decades. The literature agrees that the goal of robots should be to induce motor plasticity in subjects undergoing rehabilitation treatment by providing the patients with repetitive, intensive, and task-oriented treatment. As a key element, robot controllers should adapt to patients’ status and recovery stage. Thus, the design of effective training modalities and their hardware implementation play a crucial role in robot-assisted rehabilitation and strongly influence the treatment outcome. The objective of this paper is to provide a multi-disciplinary vision of patient-cooperative control strategies for upper-limb rehabilitation exoskeletons to help researchers bridge the gap between human motor control aspects, desired rehabilitation training modalities, and their hardware implementations. To this aim, we propose a three-level classification based on 1) “high-level” training modalities, 2) “low-level” control strategies, and 3) “hardware-level” implementation. Then, we provide examples of literature upper-limb exoskeletons to show how the three levels of implementation have been combined to obtain a given high-level behavior, which is specifically designed to promote motor relearning during the rehabilitation treatment. Finally, we emphasize the need for the development of compliant control strategies, based on the collaboration between the exoskeleton and the wearer, we report the key findings to promote the desired physical human-robot interaction for neurorehabilitation, and we provide insights and suggestions for future works