A dynamic control algorithm based on physiological parameters and wearable interfaces for adaptive ventricular assist devices.

In this work we present an innovative algorithm for the dynamic control of ventricular assist devices (VADs), based on the acquisition of continuous physiological and functional parameters such as heart rate, blood oxygenation, temperature, and patient movements. Such parameters are acquired by wearable devices (MagIC & Winpack) and sensors implanted close to the VAD. The aim of the proposed algorithm is to dynamically control the hydraulic power of the VAD as a function of the detected parameters, patient's activity and emotional status. In this way, the cardiac dynamics regulated by the proposed autoregulation control algorithm for sensorized VADs, thus providing new therapy approaches for heart failure.

An autoregulation unit for enabling adaptive control of sensorized left ventricular assist device.

This paper describes an integrated system for facing heart failures (HF) in an innovative way. Existing left ventricular assist devices (LVAD or VAD) are usually devoted to blood pumping without the possibility to adapt the speed to patient conditions during everyday activities. This is essentially due to the lack of sensorization, bulkiness, and the need of relying on device-specific controllers with reduced computing ability for the existing ventricular assist systems. In this work, an innovative integrated and portable device, the ARU, is presented for enhancing VADs applicability as a long-term solution to HF. The ARU is an universal device able to fulfill with the needs of sensorized VADs in terms of data storing, continuous monitoring, autoregulation and adaptation to patient condition changes during daily activities. The ARU is able to wirelessly interface wearable devices for offering additional monitoring features from remote. The ARU functionalities on bench have been tested by the interfacing with a sensorized VAD platform in order to prove the feasibility of the approach. Experiments of local and remote VAD speed changes and autoregulation algorithms have been successfully tested showing response time of 1 s.

Experimental integration of Autoregulation Unit for left ventricular assist devices in a cardiovascular hybrid simulator.

In this paper, an Autoregulation Unit (ARU) for left ventricular sensorized assist devices (LVAD) has been used with a cardiovascular hybrid simulator mimicking physiological and pathological patient conditions. The functionalities of the ARU have been demonstrating for the successful receiving and visualization of system parameters, sending of commands for LVAD speed changes, and enabling of the autonomous flow control algorithm. Experiments of speed changes and autoregulation are reported, showing the feasibility of the approach for both local and remote control of a LVAD.

Absence of xenotropic murine leukemia virus-related virus in Italian patients affected by chronic fatigue syndrome, fibromyalgia, or rheumatoid arthritis.

The xenotropic murine leukemia virus-related virus (XMRV) has been recently linked to chronic fatigue syndrome in a US cohort in whom the virus was demonstrated in 67% patients vs 3.7% healthy controls. Albeit this finding was not substantiated by subsequent reports and eventually considered a laboratory contamination, the matter is still the object of intense debate and scrutiny in various cohorts of patients. In this work we examined well-clinically characterized Italian patients affected by chronic fatigue syndrome, and also fibromyalgia and rheumatoid arthritis, two chronic illnesses of basically unknown etiology which show quite a few symptoms in common with chronic fatigue syndrome. Although we used recently updated procedures and controls, the XMRV was not found in 65 patients with chronic fatigue syndrome diagnosis, 55 with fibromyalgia, 25 with rheumatoid arthritis, nor in 25 healthy controls. These results add to the ever-growing number of surveys reporting the absence of XMRV in chronic fatigue syndrome patients and suggest that the virus is also absent in fibromyalgia and rheumatoid arthritis.

High dynamic range CMOS image sensors in biomedical applications.

The biomedical environment is one of the most recent and interesting application fields for CMOS image sensors. Low power consumption, high sensitivity and a simple interface are the main required features; nevertheless high dynamic range can be considered one of the more interesting and less investigated aspects. High Dynamic range is one of the main research fields NeuriCam has been involved in since its incipit. This work is an excursus of NeuriCam's approaches to this topic.

HIV-1 NAT minipool during the pre-seroconversion window period: detection of a repeat blood donor.

BACKGROUND: The introduction of nucleic acid amplification technology (NAT) for screening pooled or individual donations remarkably improved the safety of blood products. The size of mini-pooled NAT is considered critical for identification of HIV-1 infected donors during preseroconversion phase of infection. We describe a case of HIV-1 infection in a serologically negative repeat blood donor identified by 16 minipool (MP) NAT. MATERIALS AND METHODS: The donation was tested by Roche Cobas AmpliScreen HIV-1 Test with manual extraction (MultiPrep Specimen Processing Procedure). The sensitivity of different MP sizes was observed. Serial samples of infected donor were examined with different third and fourth generation HIV-1 serological assays. RESULTS: In the index donation viral load was 515 copies/ml corresponding to about 50 IU when diluted in 16 MP. Abbott third and fourth generation EIA tests detected the seroconversion four days later the index donation. CONCLUSION: The report emphasizes the relevance of a very small size of MP to really reduce the window serologic phase of current EIA test by HIV-1 NAT test.

Relationships between TT virus infection and hepatitis C virus response to interferon therapy in doubly infected patients.

A group of 24 well-characterized patients doubly infected with hepatitis C virus (HCV) and TT virus (TTV) were studied to evaluate whether the loads and number or identity of the genogroups of TTV they carried could affect the response of HCV infection to interferon-alpha (IFN) treatment. The features of HCV infection in the study patients provided a fair representation of the variables that are usually found in considering patients for IFN treatment. The same was true for the features of TTV infection. In particular, plasma loads of TTV varied over a wide range in individual patients, and infection with multiple TTV genogroups was extremely frequent. TTV genogroups 1 and 3 were the most prevalent, followed by genogroups 4 and 5. The HCV response to IFN was evaluated by measuring plasma viraemia at 24 hours and 30 days after initiation of treatment. The results showed that the TTV parameters investigated had little or no impact on the response of HCV to therapy. Due to study design, these results do not exclude that the presence of a concomitant TTV infection can affect how HCV infection responds to treatment. However, they indicate that, should such effects exist, they would be independent on load and genetic features of the infecting TTV.

Dynamics of persistent TT virus infection, as determined in patients treated with alpha interferon for concomitant hepatitis C virus infection.

TT virus (TTV) is a recently identified widespread DNA virus of humans that produces persistent viremia in the absence of overt clinical manifestations. In an attempt to shed light on the dynamics of chronic infection, we measured the levels of TTV in the plasma of 25 persistently infected patients during the first 3 months of alpha interferon (IFN-alpha) treatment for concomitant hepatitis C virus (HCV) infection. The first significant decline of TTV loads was observed at day 3 versus day 1 for HCV. Subsequently, the loads of TTV became progressively lower in most patients, but some initial responders relapsed before the end of the follow-up, suggesting that at least in some subjects the effects of IFN on TTV can be very short-lived. No correlation between the responses of TTV and HCV to therapy was found. Fitting the viremia data obtained during the first week of treatment into previously developed mathematical models showed that TTV sustains very active chronic infections, with over 90% of the virions in plasma cleared and replenished daily and a minimum of approximately 3.8 x 10(10) virions generated per day. Low levels of TTV were occasionally detected in the peripheral blood mononuclear cells of patients who had cleared plasma viremia, thus corroborating previous results showing that these cells may support TTV replication and/or persistence.

Low prevalence of TT virus in the cerebrospinal fluid of viremic patients with central nervous system disorders.

TT virus (TTV) is a widespread infectious agent of humans identified in 1998. In infected individuals, TTV induces persistent viremia but its life cycle and pathogenic potential are still poorly understood. In the present study, the presence of TTV DNA in 32 consecutive paired serum and cerebrospinal fluid (CSF) samples from patients with neurological (mainly multiple sclerosis) disorders was investigated by means of a sensitive quantitative real-time PCR assay. Of the 24 patients who were found to carry TTV DNA in serum, 3 also had detectable TTV DNA in their CSF. Two TTV positive CSF samples had markers indicative of blood contamination or a disrupted blood-brain barrier and contained considerably lower TTV loads as compared with the corresponding serum samples, thus suggesting that the virus they contained was of plasma origin. These findings indicated that in general TTV does not permeate effectively an intact blood-brain barrier. Furthermore, the CNS does not represent a common site of TTV replication and persistence. However, at least one exception was observed: the third TTV positive CSF sample (obtained from a patient with subacute dementia of unknown origin) showed no markers suggestive of disrupted blood-brain barrier or blood contamination and had a TTV DNA concentration similar to that found in the patient's serum. In addition, the TTV isolates detected in the two body fluids were distinct genetically. The detection of TTV DNA in CSF is of considerable interest but the clinical significance remains unknown.

Rapid changes in hepatitis C virus quasispecies produced by a single dose of IFN-alpha in chronically infected patients.

The effects of a single dose of 3 international megaunits of interferon-alpha2b (IFN-alpha2b) on hepatitis C virus (HCV) load and quasispecies were examined 24 h after administration in 12 previously untreated, chronically infected patients. All patients had viremia loads appreciably reduced relative to baseline values, thus confirming that the viral load is rapidly affected by IFN-alpha2b. Five patients also exhibited changes in plasma HCV quasispecies composition that were clearly evident by single-strand conformation polymorphism, analysis, thus indicating that one dose of IFN-alpha2b may suffice to produce rapid perturbations in the genetic heterogeneity of circulating HCV. Prior to IFN-alpha2b administration, 3 patients exhibited viral quasispecies differences between plasma and peripheral blood mononuclear cells (PBMC). Interestingly, in 2 such patients, the viral quasispecies found in the 24-h plasma resembled that in the pre-IFN PBMC. The latter finding raises the possibility that in these patients, the differences in quasispecies composition between pre-IFN and post-IFN plasma resulted from increased representation of lymphoid tissue-originated variants in the latter sample, possibly because of poor sensitivity to IFN-alpha2b of HCV replication in the lymphoid compartment.

TT virus (TTV) loads associated with different peripheral blood cell types and evidence for TTV replication in activated mononuclear cells.

TT virus (TTV) loads associated with the peripheral blood cells of seven patients known to carry the virus in plasma were investigated by real-time PCR. Whereas red cells/platelets were uniformly negative, six and four patients yielded positive peripheral blood mononuclear cells (PBMCs) and polymorphonuclear leukocytes, respectively, but viral titres were generally low. Fractionation of PBMCs into monocyte- and B, T4, and T8 lymphocyte-enriched subpopulations showed no pattern in the viral loads that might suggest the preferential association of TTV to one or more specific cell types. TTV-negative PBMCs absorbed measurable amounts of virus when incubated with infected plasma at 4 degrees C. Furthermore, cultures of TTV-negative phytohaemagglutinin-stimulated PBMCs exposed in vitro to virus-positive plasma and faecal extracts released considerable levels of infectious TTV into the supernatant fluid and the same was true for TTV-positive stimulated PBMCs. These results indicate that, whereas freshly harvested resting PBMCs seem to produce little, if any TTV, stimulated PBMCs actively replicate the virus.

High prevalence of TT virus (TTV) and TTV-like minivirus in cervical swabs.

Genomes of TT virus (TTV) and TTV-like minivirus DNA were detected in 80% and 61% of cervical swabs from healthy women, respectively, regardless of concurrent human papillomavirus infection. These results show that the potential exists for sexual transmission of TTV and related viruses.

TT virus levels in the plasma of infected individuals with different hepatic and extrahepatic pathology.

TT virus (TTV) infection is extremely widespread in the general population. A sensitive real-time PCR assay was developed that quantitated accurately the most prevalent TTV genotypes in Italy. When used to test 217 individuals for TTV viraemia, the overall prevalence was 94%. Viraemia levels varied widely amongst individual subjects, with no major differences related to gender or age. The highest TTV titres were in haemophiliacs and in patients with non-A-E hepatitis, but they did not differ from the group with miscellaneous diseases. HIV- and HCV-infected subjects and patients with primary liver diseases had TTV loads similar to those of healthy individuals.

Molecular properties, biology, and clinical implications of TT virus, a recently identified widespread infectious agent of humans.

TT virus (TTV) was first described in 1997 by representational difference analysis of sera from non-A to non-G posttransfusion hepatitis patients and hence intensively investigated as a possible addition to the list of hepatitis-inducing viruses. The TTV genome is a covalently closed single-stranded DNA of approximately 3.8 kb with a number of characteristics typical of animal circoviruses, especially the chicken anemia virus. TTV is genetically highly heterogeneous, which has led investigators to group isolates into numerous genotypes and subtypes and has limited the sensitivity of many PCR assays used for virus detection. The most remarkable feature of TTV is the extraordinarily high prevalence of chronic viremia in apparently healthy people, up to nearly 100% in some countries. The original hypothesis that it might be an important cause of cryptogenic hepatitis has not been borne out, although the possibility that it may produce liver damage under specific circumstances has not been excluded. The virus has not yet been etiologically linked to any other human disease. Thus, TTV should be considered an orphan virus.

High prevalence of TT virus viremia in italian patients, regardless of age, clinical diagnosis, and previous interferon treatment.

The pathogenic potential of the newly discovered TT virus (TTV) is currently a matter of conjecture. Its presence was investigated in the serum of 660 patients, by polymerase chain reaction. TTV was detected in 50% of 221 patients with unselected pathologies, and no significant differences related to age, sex, or organ disease were noted. TTV was present at a significantly higher rate in hemophiliacs (73%) and at lower rates in patients with cirrhosis (30%) and rheumatoid arthritis (28%). Patients with other liver diseases, systemic lupus erythematosus, or psoriasis or receiving hemodialysis had rates of infection similar to those in unselected patients. TTV-positive patients treated with interferon-alpha for underlying type C hepatitis showed no appreciable changes of TTV viremia levels. Type 1b was by far the most frequent viral genotype (92%), followed by types 2c (5%) and 1a (3%).

Detection and quasispecies analysis of hepatitis C virus in the cerebrospinal fluid of infected patients.

Hepatitis C virus (HCV) is a leading cause of liver damage and has also been implicated in extrahepatic pathologies. We examined for HCV RNA paired CSF and plasma samples from 12 viremia positive patients using PCR. The CSF from 5/5 HIV-infected patients and 5/7 HIV-negative patients were HCV RNA positive. Branched DNA analysis showed that HCV loads in CSF were much lower than in plasma. Several HCV-positive CSF showed no evidence of blood contamination, impaired blood-brain barrier, or intrathecal IgG production. Comparison of HCV quasispecies in three sets of samples suggested that the virus in CSF was of plasma origin.

Susceptibility of human and non-human cell lines to HCV infection as determined by the centrifugation-facilitated method.

The centrifugation-facilitated inoculation method was used to test 51 human and non-human cell lines for ability to support HCV replication. As determined by nested RT-PCR, one fifth of the cell lines tested were virus positive 15 days post inoculation suggesting that the centrifugation-facilitated inoculation is an efficient method for cell infection with HCV. However, virus production by infected cultures remained of low grade, thus showing that the unknown factors which limit HCV replication in vitro are not overcome by the procedure.