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Biomedical subjects

F Taddei

Publications and source records attributed to F Taddei.

At least 19 recordsLinked to original sources

A new software tool for 3D motion analyses of the musculo-skeletal system.

BACKGROUND: Many clinical and biomechanical research studies, particularly in orthopaedics, nowadays involve forms of movement analysis. Gait analysis, video-fluoroscopy of joint replacement, pre-operative planning, surgical navigation, and standard radiostereometry would require tools for easy access to three-dimensional graphical representations of rigid segment motion. Relevant data from this variety of sources need to be organised in structured forms. Registration, integration, and synchronisation of segment position data are additional necessities. With this aim, the present work exploits the features of a software tool recently developed within a EU-funded project ('Multimod') in a series of different research studies. METHODS: Standard and advanced gait analysis on a normal subject, in vivo fluoroscopy-based three-dimensional motion of a replaced knee joint, patellar and ligament tracking on a knee specimen by a surgical navigation system, stem-to-femur migration pattern on a patient operated on total hip replacement, were analysed with standard techniques and all represented by this innovative software tool. Segment pose data were eventually obtained from these different techniques, and were successfully imported and organised in a hierarchical tree within the tool. FINDINGS: Skeletal bony segments, prosthesis component models and ligament links were registered successfully to corresponding marker position data for effective three-dimensional animations. These were shown in various combinations, in different views, from different perspectives, according to possible specific research interests. INTERPRETATION: Bioengineering and medical professionals would be much facilitated in the interpretation of the motion analysis measurements necessary in their research fields, and would benefit therefore from this software tool.

Aged↗

Impact of in utero environment on the offspring of lupus patients.

The number of patients affected by systemic lupus erythematosus (SLE) that decide to have children has greatly increased probably because of recent improvements in the diagnosis and management of the disease. This has stimulated our interest in defining the outcome of children, focusing both on neonatal problems and long term development. SLE patients still carry a risk of pregnancy loss. However, due to careful monitoring and treatment by a multidisciplinary team, the number of losses has dramatically decreased, but an increased number of preterm deliveries is still a problem. Neonatal lupus is linked to the presence of anti-Ro/SS-A and anti-La/SS-B antibodies in the mother, although other factors probably of fetal origin are important. Neonatal lupus is a complex condition whose most serious manifestation is the congenital heart block (CHB). Usually, children with complete CHB need permanent pacing, but apparently do not have neuropsychological problems. Studies focusing on the neuropsychological development of SLE offspring show an increased number of learning disabilities in children with normal intelligence levels. Fetal consequence of maternal treatment need to be considered choosing non teratogenic drugs, but the withdrawal of medications just because the patient is pregnant should be avoided to avoid SLE flares.

Central Nervous System↗

Adiabatic pumping in a superconductor-normal-superconductor weak link.

We present a formalism to study adiabatic pumping through a superconductor-normal-superconductor weak link. At zero temperature, the pumped charge is related to the Berry phase accumulated, in a pumping cycle, by the Andreev bound states. We analyze in detail the case when the normal region is short compared to the superconducting coherence length. The pumped charge turns out to be an even function of the superconducting phase difference. Hence, it can be distinguished from the charge transferred due to the standard Josephson effect.

Journal Article↗

Kinematic study of a reconstructed hip in paediatric oncology.

In 1997, a large portion of the femur of a four-year-old child affected by a Ewing's sarcoma was reconstructed with an innovative technique that used a massive bone allograft, in conjunction with a vascularised fibula autograft that was directly articulated within the acetabulum. The aim of the present study was to assess the kinematic behaviour of the reconstructed hip during flexion, once the acute remodelling process observed after the operation had ceased. A few additional CT slices of the hip joint region, in a flexed position, were taken at month 33 of the follow-up. The helical axes relative to the neutral-flexion motor action were estimated: their relative positions, with respect to the anatomical femoral heads, were compared, and the translation of the anatomical head centres was estimated. The angles spanned by the two femurs were almost equal, as were the translations along the respective helical axis. The main difference between the two femurs was the distance between the estimated femoral head centres and the relative helical axes. This resulted in a non-negligible translation of 2.9 mm of the fibula head inside the acetabulum during flexion, significantly higher than the 0.5 mm found for the intact contralateral femur. The results showed that, although the transplanted fibula grew and remodelled during the follow up, the action of the reconstructed hip joint still cannot be described as a ball-and-socket.

Biomechanical Phenomena↗

Tailoring Josephson coupling through superconductivity-induced nonequilibrium.

The distinctive quasiparticle distribution existing under nonequilibrium in a superconductor-insulator-normal metal-insulator-superconductor mesoscopic line is proposed as a novel tool to control the supercurrent intensity in a long Josephson weak link. We present a description of this system in the framework of the diffusive-limit quasiclassical Green-function theory and take into account the effects of inelastic scattering with arbitrary strength. Supercurrent enhancement and suppression, including a marked transition to a pi junction, are striking features leading to a fully tunable structure.

Journal Article↗

Management of patients with syncope referred urgently to general hospitals.

OBJECTIVE: To evaluate the incidence and the strategy of management of syncope admitted urgently to a general hospital. BACKGROUND: The management of patients with syncope is not standardized. METHODS: The study was a prospective observational registry from a sample of 28 general hospitals in Italy and enroled all consecutive patients referred to their emergency rooms from November 5th 2001 to December 7th 2001 who were affected by transient loss of consciousness as the principal symptom. RESULTS: The incidence of syncope was 0.95% (996 of 105,173 patients attending). Forty-six percent were hospitalized, mostly in the Department of Internal Medicine. The mean in-hospital stay was 8.1+/-5.9 days. A mean of 3.48 tests was performed per patient. A definite diagnosis was made in 80% of cases, neurally-mediated syncope being the most frequent. The findings of each of the 28 hospitals participating in the survey were separately evaluated. We observed great inter-hospital and inter-department heterogeneity regarding the incidence of emergency admission, in-hospital pathways, most of the examinations performed and the final assigned diagnosis. For example, the execution of carotid sinus massage ranged from 0% in one hospital to 58% in another (median 12.5%); tilt testing ranged from 0 to 50% (median 5.8%); the final diagnosis of neurally-mediated syncope ranged from 10 to 78.6% (median 43.3%). CONCLUSION: Great inter-hospital and inter-department heterogeneity in the incidence and management of syncope was observed in general hospitals. As a consequence, we were unable to describe a uniform strategy for the management of syncope in everyday practice.

Adult↗

Mechanical strength of a femoral reconstruction in paediatric oncology: a finite element study.

In 1997 the proximal femur of a four-year-old child affected by a Ewing sarcoma was reconstructed using a massive bone allograft in conjunction with a vascularized fibula autograft. During the first three years of follow-up the reconstruction underwent important morphological changes. The aim of the present study was to evaluate the risk of fracture of the reconstructed proximal femur, once the physiological loads are restored, associated with a short, slow but unprotected level walk. Subject-specific finite element models of the operated femur, and of the intact contralateral one, were generated from a computed tomography exam, taken for routine clinical monitoring at month 33 of follow-up. The material properties were mapped on to the mesh and a loading condition comprising the hip joint reaction and the abductor muscle force was simulated. The risk of fracture was locally estimated, for the operated and intact femur, using the ratio between the bone tissue strength and the predicted Von Mises equivalent stress, taking into account the different behaviours of the bone tissue in tension or compression. The results showed that although the fibula grew dramatically during follow-up, the reconstructed femur had not recovered the whole mechanical strength of a normal femur. The reconstructed femoral neck seemed to be weaker than the contralateral one and hence at a higher fracture risk. However, no region reached the failure limit, so the model predicted no fracture of the femur if a short, slow but unprotected walk were allowed. The model predictions found an indirect clinical validation when the child was allowed to perform short unprotected walks and did not experience any fracture.

Bone Transplantation↗

[Monitoring of pregnancy complicated by maternal-fetal isoimmunization. A comparison between two clinical protocols].

AIM: Invasive techniques such as amniocentesis and cordocentesis are used for the diagnosis and treatment of fetus at risk for anemia due to maternal red-cell alloimmunization. The purpose of this study was to determine the value of non invasive measurements of the peak velocity middle cerebral artery in the fetus (PVMCA) for the diagnosis of fetal anemia. METHODS: From 1996 to September 2002, we studied 23 pregnancies with anti D title >1:32. In the 1(st) group of 11 women (from 1996 to 1999) fetal anemia was detected by invasive techniques (amniocentesis and cordocentesis). In the 2(nd) group of 12 women (from 1999 to 2002) fetal anemia was suspected on the basis of PVMCA. When PVMCA was significantly increased, cordocentesis was performed in order to rule out fetal anemia and to provide in utero transfusions. RESULTS: In the 1(st) period we performed 23 invasive techniques (7 amniocentesis and 16 cordocentesis) in 11 women, but we identified fetal anemia only in 4 cases. In the 2(nd) period we performed only 2 cordocentesis in women in which PVMCA was increased; the blood sampling confirmed fetal anemia in both cases. CONCLUSION: PVMCA and fetal hematocrit are highly significantly correlated: high values of PVMCA are associated with fetal anemia. Doppler velocity of PVMCA is related to fetal anemia with positive predictive value 100% and negative predictive value 100%. The middle cerebral artery blood velocity is a non invasive technique for detecting anemia in pregnancies complicated by alloimmunization.

Adult↗

Prognostic role of umbilical artery Doppler velocimetry in growth-restricted fetuses.

OBJECTIVE: To correlate umbilical artery Doppler velocimetry with perinatal outcome in a group of growth-restricted fetuses. DESIGN: The study was a retrospective analysis of 578 singleton pregnancies with diagnosis of intrauterine growth restriction (IUGR), delivered in a single obstetric unit, at the Spedali Civili, Brescia, Italy, a university and teaching hospital with 3500 deliveries a year and neonatal intensive care unit (NICU). METHODS: During 1991-99 we studied 578 pregnancies with a diagnosis of IUGR referred for Doppler velocimetry. From this population, four subsets were formed: normal umbilical artery pulsatility index (NUAPI; 334 fetuses); increased pulsatility index but with telediastolic flow (abnormal umbilical artery pulsatility index AUAPI; 137 fetuses); absent end-diastolic flow (AEDF; 70 fetuses); reverse telediastolic flow (RF; 37 fetuses). Fetal biometry, amniotic fluid and fetal-maternal Doppler velocimetry were evaluated in all patients, with biophysical profile and routine non-stress test, when indicated. The following outcomes were examined: mean gestational age at delivery, number of preterm deliveries (< 34 weeks), mean neonatal weight, Apgar score at 5 min < 7, prenatal and neonatal deaths (within the first 28 days of life), admission to the NICU and number of days spent after birth in hospital. Neonatal morbidity was analyzed, including respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH, grade 2-3), necrotizing enterocolitis (NEC) and retinopathy of prematurity. Long-term neurological follow-up is still ongoing and will not be presented in this paper. RESULTS: Out of 578 fetuses with IUGR, 547 were born alive. There were 26 neonatal deaths. The mean gestational age at delivery was 35.6 +/- 4 weeks and mean birth weight 1844 +/- 612 g. There were 28 intrauterine deaths and three elective terminations of pregnancy. A total of 60 cases (11%) were complicated by RDS, 13 cases (2.4%) by retinopathy of prematurity, IVH was present in nine cases (1.6%) and NEC in seven cases (1.3%). Total perinatal mortality was 9.8%; in the 26 cases of neonatal death, the mean week at delivery was 29.6 +/- 4 with a mean weight of 840 +/- 425 g. Patients with NUAPI had a mean week at delivery of 37 +/- 3, those with AUAPI delivered at 34 +/- 3.2, those with AEDF delivered at 31 +/- 3 and those with RF delivered at 29 +/- 2 weeks. In progressively worsening umbilical velocimetry, we observed an increase of incidence of low Apgar score. Days of admission to the NICU and incidence of perinatal mortality increased with the worsening of Doppler velocimetry. CONCLUSIONS: Our study underlines the existence of a strict correlation between umbilical Doppler velocimetry and an increased incidence of perinatal complications in IUGR fetuses.

Blood Flow Velocity↗

Growth and remodelling of the autologous bone transplant used in a pediatric femoral reconstruction.

The aim of the present work was to assess how growth and remodelling changed the morphology of the transplanted fibula used to reconstruct the proximal femur of a 5 year old child affected by a Ewing's sarcoma during the first 3 years of follow-up. The morphological evolution of the transplant was quantitatively assessed on diagnostic images. Special software was developed to perform three-dimensional measurements on computed tomography (CT) datasets, while state-of-the-art image processing software was used for conventional radiography. The measurements were then correlated with the loads expected to act on the hip during the various stages of the rehabilitation protocol. A simple cantilever beam model was used for a gross estimate of the risk of fracture of the transplant. The results of the analysis showed that there is no clear correlation between the morphological changes of the autograft and the hip loading conditions experienced. Apart from a drastic increase in the periosteal radius in the frontal plane, occurring in the first 10 months after the operation, the growth of the transplanted fibula seems well within the ranges of the normal fibular growth. The cantilever beam model suggested that, although the autograft is currently subjected to subcritical stresses. morphological evolution could increase the risk of fracture in the next few years if a normal level of loading were allowed.

Bone Remodeling↗

Translational misreading: a tRNA modification counteracts a +2 ribosomal frameshift.

Errors during gene expression from DNA to proteins via transcription and translation may be deleterious for the functional maintenance of cells. In this paper, extensive genetic studies of the misreading of a GA repeat introduced into the lacZ gene of Escherichia coli indicate that in this bacteria, errors occur predominantly by a +2 translational frameshift, which is controlled by a tRNA modification involving the MnmE and GidA proteins. This ribosomal frameshift results from the coincidence of three events: (1) decreased codon-anticodon affinity at the P-site, which is caused by tRNA hypomodification in mnmE(-) and gidA(-) strains; (2) a repetitive mRNA sequence predisposing to slippage; and (3) increased translational pausing attributable to the presence of a rare codon at the A-site. Based on genetic analysis, we propose that GidA and MnmE act in the same pathway of tRNA modification, the absence of which is responsible for the +2 translational frameshift. The difference in the impact of the mutant gene on cell growth, however, indicates that GidA has at least one other function.

Algal Proteins↗

Costs and benefits of high mutation rates: adaptive evolution of bacteria in the mouse gut.

We have shown that bacterial mutation rates change during the experimental colonization of the mouse gut. A high mutation rate was initially beneficial because it allowed faster adaptation, but this benefit disappeared once adaptation was achieved. Mutator bacteria accumulated mutations that, although neutral in the mouse gut, are often deleterious in secondary environments. Consistently, the competitiveness of mutator bacteria is reduced during transmission to and re-colonization of similar hosts. The short-term advantages and long-term disadvantages of mutator bacteria could account for their frequency in nature.

Adaptation, Physiological↗

Genotoxic hazard of pollutants in cetaceans: DNA damage and repair evaluated in the bottlenose dolphin (Tursiops truncatus) by the Comet Assay.

Single cell gel electrophoresis (or Comet Assay) was used for evaluation of the in vitro genotoxicity of hydrogen peroxide (used as a positive control), polychlorinated biphenyls (PCBs) (Aroclor 1254) and methyl mercury chloride, in isolated bottlenose dolphin leukocytes. Results showed that hydrogen peroxide and methyl mercury induced DNA strand breakage in a dose-dependent manner, while PCBs did not induce a clear dose-effect response at the low doses investigated. Efficiency in repairing DNA breakage induced by methyl mercury was also evaluated. Findings demonstrated that dolphin cells are characterized by higher efficiency in DNA repair when compared to human leukocytes. The observed resistance to methyl mercury toxicity in dolphins was hypothesized to be a defence strategy developed to combat high dietary exposure and compensate for limited capacity to excrete persistent pollutants.

Animals↗

The rise and fall of mutator bacteria.

Bacteria with elevated mutation rates are frequently found among natural isolates. This is probably because of their ability to generate genetic variability, the substrate for natural selection. However, such high mutation rates can lead to the loss of vital functions. The evolution of bacterial populations may happen through alternating periods of high and low mutation rates. The cost and benefits of high mutation rates in the course of bacterial adaptive evolution are reviewed.

Adaptation, Physiological↗

Genes and olympic performance: a co-twin study.

An Olympic gold medalist in a 20 km competitive walking race and his identical twin brother, also an Olympic athlete in the same event but with inferior performance, were tested in order to obtain some further insight into the relative importance of genetic factors in modulating athletic excellence. Both twins had undergone the same strenuous, long-term training for 19 years since the age of 15 under the guidance of the same coach. An assessment of their bio-behavioural profiles at 40 years of age, i. e. 7 years after they ceased training, revealed that intrapair differences were negligible in physiological attributes but divergent in personality traits measured. Respective values for the Olympic winner and his identical counterpart were as follows: Body mass index 23.2 and 22.7, cardiac mass index 85.4 and 84.4 g x m2, squatjumping 25.3 and 27.3 cm, VO2 at running speed 9 km x h(-1) 33.1 and 33.6 ml x kg(-1) x min(-1), VO2 max 57.1 and 58.6 ml x kg(-1) x min(-1) (72.5ml x kg(-1) x min(-1) for the Olympic winner at age 22 yrs), reaction to anger 97 and 9 and anger expression 2 and 76 in percentile of the State-Trait Anger Expression Inventory. Findings suggest that although genetic constitution and years of physical training are prerequisites for making an Olympic athlete, success may be largely influenced by personality traits.

Adult↗

Mutator natural Escherichia coli isolates have an unusual virulence phenotype.

A small percentage of natural Escherichia coli isolates (both commensal and pathogenic) have a mutator phenotype related to defects in methyl-directed mismatch repair (MR) genes. We investigated whether there was a direct link between the mutator phenotype and virulence by (i) studying the relationships between mutation rate and virulence in a mouse model of extraintestinal virulence for 88 commensal and extraintestinal pathogenic E. coli isolates and (ii) comparing the virulence in mice of MR-deficient and MR-proficient strains that were otherwise isogenic. The results provide no support for the hypothesis that the mutator phenotype has a direct role in virulence or is associated with increased virulence. Most of the natural mutator strains studied displayed an unusual virulence phenotype with (i) a lack of correspondence between the number of virulence determinants and pathogenicity in mice and (ii) an intermediate level of virulence. On a large evolutionary scale, the mutator phenotype may help parasites to achieve an intermediate rate of virulence which mathematical models predict to be selected for during long-term parasite-host interactions.

Animals↗

Evolutionary implications of the frequent horizontal transfer of mismatch repair genes.

Mutation and subsequent recombination events create genetic diversity, which is subjected to natural selection. Bacterial mismatch repair (MMR) deficient mutants, exhibiting high mutation and homologous recombination rates, are frequently found in natural populations. Therefore, we have explored the possibility that MMR deficiency emerging in nature has left some "imprint" in the sequence of bacterial genomes. Comparative molecular phylogeny of MMR genes from natural Escherichia coli isolates shows that, compared to housekeeping genes, individual functional MMR genes exhibit high sequence mosaicism derived from diverse phylogenetic lineages. This apparent horizontal gene transfer correlates with hyperrecombination phenotype of MMR-deficient mutators. The sequence mosaicism of MMR genes may be a hallmark of a mechanism of adaptive evolution that involves modulation of mutation and recombination rates by recurrent losses and reacquisitions of MMR gene functions.

Adenosine Triphosphatases↗