Echovirus Epidemics, Autoimmunity, and Type 1 Diabetes

Role of echovirus infections in organ-specific autoimmunity and diabete

Treatment of Severe Post-traumatic Bone Defects With Autologous Stem Cells Loaded on Allogeneic Scaffolds.

Mesenchymal stem cells may differentiate into angiogenic and osteoprogenitor cells. The effectiveness of autologous pluripotent mesenchymal cells for treating bone defects has not been investigated in humans. We present a case series to evaluate the rationale of using nucleated cells from autologous bone marrow aspirates in the treatment of severe bone defects that failed to respond to traditional treatments. Ten adult patients (mean age, 49.6-years-old) with severe bone defects were included in this study. Lower limb bone defects were >or=5 cm3 in size, and upper limb defects .or=2 cm3. Before surgery, patients were tested for antibodies to common pathogens. Treatment consisted of bone allogeneic scaffold enriched with bone marrow nucleated cells harvested from the iliac crest and concentrated using an FDA-approved device. Postsurgery clinical and radiographic follow-up was performed at 1, 3, 6, and 12 months. To assess viability, morphology, and immunophenotype, bone marrow nucleated cells were cultured in vitro, tested for sterility, and assayed for the possible replication of adventitious (contaminating) viruses. In 9 of 10 patients, both clinical and radiographic healing of the bone defect along with bone graft integration were observed (mean time, 5.6 months); one patient failed to respond. No post-operative complications were observed. Bone marrow nucleated cells were enriched 4.49-fold by a single concentration step, and these enriched cells were free of microbial contamination. The immunophenotype of adherent cells was compatible with that of mesenchymal stem cells. We detected the replication of Epstein-Barr virus in 2/10 bone marrow cell cultures tested. Hepatitis B virus, cytomegalovirus, parvovirus B19, and endogenous retrovirus HERV-K replication were not detected. Overall, 470 to 1,150 million nucleated cells were grafted into each patient. This case series, with a mean follow-up of almost 2 years, demonstrates that an allogeneic bone scaffold enriched with concentrated autologous bone marrow cells obtained from the iliac crest provides orthopedic surgeons a novel option for treating important bone defects that are unresponsive to traditional therapies

Culture of skeletal myoblasts from human donors aged over 40 years: dynamics of cell growth and expression of differentiation markers

BACKGROUND: Local myogenesis, neoangiogenesis and homing of progenitor cells from the bone marrow appear to contribute to repair of the infarcted myocardium. Implantation into heart tissues of autologous skeletal myoblasts has been associated with improved contractile function in animal models and in humans with acute myocardial ischemia. Since heart infarction is most prevalent in individuals of over 40 years of age, we tested whether culture methods available in our laboratory were adequate to obtain sufficient numbers of differentiated skeletal myoblasts from muscle biopsy specimens obtained from patients aged 41 to 91. METHODS AND RESULTS: No matter of donor age, differentiated skeletal muscle cells could be produced in vitro in amounts adequate for cellular therapy (≥300 millions). Using desmin as a cytoplasmic marker, about 50% cultured cells were differentiated along myogenic lineages and expressed proteins proper of skeletal muscle (myosin type I and II, actin, actinin, spectrin and dystrophin). Cytogenetic alterations were not detected in cultured muscle cells that had undergone at least 10 population doublings. Molecular methods employed for the screening of persistent viral infections evidenced that HCV failed to replicate in muscle cells cultured from one patient with chronic HCV infection. CONCLUSION: The proposed culture methods appear to hold promise for aged patients not only in the field of cardiovascular medicine, but also in the urologic and orthopedic fields

TRPV4 channels dominant role in the temperature modulation of intrinsic contractility and lymph flow of rat diaphragmatic lymphatics

The lymphatic system drains and propels lymph by extrinsic and intrinsic mechanisms. Intrinsic propulsion depends upon spontaneous rhythmic contractions of lymphatic muscles in the vessel walls, and is critically affected by changes in the surrounding tissue like osmolarity and temperature. Lymphatics of the diaphragm display a steep change in contraction frequency in response to changes in temperature, and this, in turn, affects lymph flow. In the present work we demonstrated, in an ex vivo diaphragmatic tissue rat model, that diaphragmatic lymphatics express transient receptor potential channels of the vanilloid 4 subfamily (TRPV4), and that their blockade by both the non-selective antagonist, Ruthenium Red and by the selective antagonist, HC-067047, abolished the response of lymphatics to temperature changes. Moreover, the selective activation of TRPV4 channels by means of GSK1016790A mirrored the behavior of vessels exposed to increasing temperatures, pointing out the critical role played by these channels in sensing the temperature of the lymphatic vessels environment and thus inducing a change in contraction frequency and lymph flow

Emergence of SARS-COV-2 Spike Protein Escape Mutation Q493R after Treatment for COVID-19

7noWe report in vivo selection of a severe acute respiratory syndrome coronavirus 2 spike mutation (Q493R) conferring simultaneous resistance to bamlanivimab and etesivimab. This mutation was isolated from a patient who had coronavirus disease and was treated with these drugs.openopenFocosi, Daniele; Novazzi, Federica; Genoni, Angelo; Dentali, Francesco; Gasperina, Daniela Dalla; Baj, Andreina; Maggi, FabrizioFocosi, Daniele; Novazzi, Federica; Genoni, Angelo; Dentali, Francesco; Gasperina, Daniela Dalla; Baj, Andreina; Maggi, Fabrizi

Post-poliomyelitis syndrome as a possible viral disease

Summary This review summarizes current concepts on post-polio syndrome (PPS), a condition that may arise in polio survivors after partial or complete functional recovery followed by a prolonged interval of stable neurological function. PPS affects 15–20 million people worldwide. Epidemiological data are reported, together with the pathogenic pathways that possibly lead to the progressive degeneration and loss of neuromuscular motor units. As a consequence of PPS, polio survivors experience new weakness, generalized fatigue, atrophy of previously unaffected muscles, and a physical decline that may culminate in the loss of independent life. Emphasis is given to the possible pathogenic role of persistent poliovirus infection and chronic inflammation. These factors could contribute to the neurological and physical decline in polio survivors. A perspective is then given on novel anti-poliovirus compounds and monoclonal antibodies that have been developed to contribute to the final phases of polio eradication. These agents could also be useful for the treatment or prevention of PPS. Some of these compounds/antibodies are in early clinical development. Finally, current clinical trials for PPS are reported. In this area, the intravenous infusion of normal human immunoglobulins appears both feasible and promising

A CLUSTER OF SARS-COV-2 DELTA VARIANT OF CONCERN ADDITIONALLY HARBORING F490S, NORTHERN LOMBARDY, ITALY

The Delta variant of concern (VOC) of SARS-CoV-2 has become dominant worldwide. We report here a cluster caused by B.1.617.2 harboring the additional mutation of concern (MOC) F490S. Infection occurred in 5 fully vaccinated subjects between the ages of 47 and 84. The immune escape mutation F490S, first identified in the Lambda VOI, appears to impair vaccine efficacy and is rapidly increasing in prevalence worldwide

TTV and other anelloviruses: The astonishingly wide spread of a viral infection

The broad family of viruses known as anelloviruses (AV) infects both humans and numerous animal species. They have a tiny, covalently closed single-stranded DNA genome and the astonishing capacity to infect a very high percentage of healthy and ill people with chronic infections that could last a lifetime. AV, and particularly the prototype Torquetenovirus, have established a successful interaction with the host's immune system and the rate at which they replicate is a gauge to measure overall immune function, even though many aspects of their life cycle and pathogenesis are still poorly understood

Ten Years of Experience With a Telemedicine Platform Dedicated to Health Care Personnel: Implementation Report

Background: Telemedicine, a term that encompasses several applications and tasks, generally involves the remote management and treatment of patients by physicians. It is known as transversal telemedicine when practiced among health care professionals (HCPs). Objective: We describe the experience of implementing our telemedicine Eumeda platform for HCPs over the last 10 years. Methods: A web-based informatics platform was developed that had continuously updated hypertext created using advanced technology and the following features: security, data insertion, dedicated software for image analysis, and the ability to export data for statistical surveys. Customizable files called "modules" were designed and built for different fields of medicine, mainly in the ophthalmology subspecialty. Each module was used by HCPs with different authorization profiles. Implementation (results): Twelve representative modules for different projects are presented in this manuscript. These modules evolved over time, with varying degrees of interconnectivity, including the participation of a number of centers in 19 cities across Italy. The number of HCP operators involved in each single module ranged from 6 to 114 (average 21.8, SD 28.5). Data related to 2574 participants were inserted across all the modules. The average percentage of completed text/image fields in the 12 modules was 65.7%. All modules were evaluated in terms of access, acceptability, and medical efficacy. In their final evaluation, the participants judged the modules to be useful and efficient for clinical use. Conclusions: Our results demonstrate the usefulness of the telemedicine platform for HCPs in terms of improved knowledge in medicine, patient care, scientific research, teaching, and the choice of therapies. It would be useful to start similar projects across various health care fields, considering that in the near future medicine as we know it will completely change