A clinical-in silico study on the effectiveness of multipoint bicathodic and cathodic-anodal pacing in cardiac resynchronization therapy.

Up to one-third of patients undergoing cardiac resynchronization therapy (CRT) are nonresponders. Multipoint bicathodic and cathodic-anodal left ventricle (LV) stimulations could overcome this clinical challenge, but their effectiveness remains controversial. Here we evaluate the performance of such stimulations through both in vivo and in silico experiments, the latter based on computer electromechanical modeling. Seven patients, all candidates for CRT, received a quadripolar LV lead. Four stimulations were tested: right ventricular (RVS); conventional single point biventricular (S-BS); multipoint biventricular bicathodic (CC-BS) and multipoint biventricular cathodic-anodal (CA-BS). The following parameters were processed: QRS duration; maximal time derivative of arterial pressure (dPdtmax); systolic arterial pressure (Psys); and stroke volume (SV). Echocardiographic data of each patient were then obtained to create an LV geometric model. Numerical simulations were based on a strongly coupled Bidomain electromechanical coupling model. Considering the in vivo parameters, when comparing S-BS to RVS, there was no significant decrease in SV (from 45 ± 11 to 44 ± 20 ml) and 6% and 4% increases of dPdtmax and Psys, respectively. Focusing on in silico parameters, with respect to RVS, S-BS exhibited a significant increase of SV, dPdtmax and Psys. Neither the in vivo nor in silico results showed any significant hemodynamic and electrical difference among S-BS, CC-BS and CA-BS configurations. These results show that CC-BS and CA-BS yield a comparable CRT performance, but they do not always yield improvement in terms of hemodynamic parameters with respect to S-BS. The computational results confirmed the in vivo observations, thus providing theoretical support to the clinical experiments.

Protein intakes and their nutritional sources during the first 2 years of life: secondary data evaluation from the European Childhood Obesity Project.

BACKGROUND/OBJECTIVES: High protein intake in infancy affects future obesity risk and other health outcomes. We aim to describe total protein intake and its sources in a birth cohort in five European countries over the first 2 years of life. SUBJECTS/METHODS: A total of 746 formula-fed infants were included. Three-day weighed dietary records at 6, 7, 8, 9, 12, 18 and 24 months of age were used. Kruskal-Wallis, ANOVA and Friedman's tests were used to assess possible differences in nutritional intake among countries and over time. RESULTS: Dairy products were the main components of the infants' diets. Cow's milk was rarely introduced before 12 months of age, whereas infants' formula was the main contributor of protein intake. Food choices and protein intake differed among countries (P<0.001). Protein intake often exceeded European recommendations from 9 months onwards, partly because of the substitution of dairy protein (mainly infant formula) by meat protein. Two nutritional patterns were identified that were characterised by differences in energy, fat, protein and animal protein intake. Finally, food consumption was not always in line with protein intakes, and thus infants from some countries showed high consumption of specific food groups but relatively low protein intakes. CONCLUSIONS: During weaning, over-limited substitution of dairy products with other sources (especially meat) resulted in relatively high protein intakes in formula-fed infants. Differences in preferences of specific protein sources from complementary foods existed among European countries. Great opportunities in improving early nutrition were revealed, although cultural and geographical differences should always be considered.

Breast milk composition and infant nutrient intakes during the first 12 months of life.

BACKGROUND/OBJECTIVES: The objective of this study was to quantify human milk supply and intake of breastfed infants up to age 12 months. In addition, human milk composition was quantified per energetic macronutrient and fatty-acid composition in a subsample of lactating mothers. SUBJECTS/METHODS: One hundred and seventy-four Italian breastfed children were followed using test-weighing and 3-day food protocols from birth to age 12 months. From a subsample of 30 mothers breast milk samples were collected at child ages one (T1), two (T2), three (T3) and six (T6) months, and were analyzed for the amount of protein, digestible carbohydrates, total lipids and fatty-acid composition. RESULTS: One hundred and forty-two (82%) filled in at least one 3-day food protocol within the first 12 months of life and complied with test-weighing of all milk feeds. The number of valid food protocols declined from 126 infants at 1 month to 77 at 12 months of age. Only galactose, non-protein nitrogen and protein decreased significantly from age 1 to age 6 months of lactation. Maternal body mass index and age affected fatty-acid levels in human milk. Median human milk intake decreased from 625 ml at T1, over 724 ml at T3 to 477 ml/day at T6. Average energy and %energy from protein intake per day increased from 419 kcal (s.d. 99) and 8.4% (1.0) at T1, respectively, to 860 kcal (145) and 16.1% (2.6) at T12. CONCLUSIONS: These data provide a reference range of nutrient intakes in breastfed infants and may provide guidance for defining optimal nutrient intakes for infants that cannot be fully breastfed.

Development of an in-shoe pressure-sensitive device for gait analysis.

In this work, we present the development of an in-shoe device to monitor plantar pressure distribution for gait analysis. The device consists in a matrix of 64 sensitive elements, integrated with in-shoe electronics and battery which provide an high-frequency data acquisition, wireless transmission and an average autonomy of 7 hours in continuous working mode. The device is presented along with its experimental characterization and a preliminary validation on a healthy subject.

Soft artificial tactile sensors for the measurement of human-robot interaction in the rehabilitation of the lower limb.

A new and alternative method to measure the interaction force between the user and a lower-limb gait rehabilitation exoskeleton is presented. Instead of using a load cell to measure the resulting interaction force, we propose a distributed measure of the normal interaction pressure over the whole contact area between the user and the machine. To obtain this measurement, a soft silicone tactile sensor is inserted between the limb and commonly used connection cuffs. The advantage of this approach is that it allows for a distributed measure of the interaction pressure, which could be useful for rehabilitation therapy assessment purposes, or for control. Moreover, the proposed solution does not change the comfort of the interaction; can be applied to connection cuffs of different shapes and sizes; and can be manufactured at a low cost. Preliminary results during gait assistance tasks show that this approach can precisely detect changes in the pressure distribution during a gait cycle.

Sex assessment from the acetabular rim by means of image analysis.

Determining sex from skeletal remains is one of the most important steps in archaeological and forensic anthropology. The present study considers the diagnostic value of the acetabulum based on its planar image and related metric data. For this purpose, 83 adult os coxae of known age were examined. Digital photos of the acetabular area were taken, with each bone in a standardized orientation. Technical drawing software was used to trace the acetabular rim and to measure the related dimensions (area, perimeter, longitudinal and transverse maximum width). The measurements were subjected to SPSS discriminant and classification function analysis. There were significant differences (p

Age of onset of pubertal characteristics in boys aged 6-14 years of the Province of L'Aquila (Abruzzo, Italy).

BACKGROUND: Previous results on growth patterns of children from central-southern Italy (Abruzzo region) showed an increasing tendency to obesity and suggested that the secular trend was still in progress in this region. However, data on pubertal development was lacking. OBJECTIVE: The objective of the study was to provide population data on pubertal development in a sample of 535 boys aged 6-14 years as a contribution to the ongoing debate on earlier onset of pubertal traits and on the slowing down of the secular trend. METHODS: A cross-sectional survey was used. Data for genital and pubic hair development (GD and PHD) were analysed by probit analysis. RESULTS: The boys start developing sexual characteristics at age 9: 13.3% had entered stage 2 of GD and 8.9% showed PHD. At 13 years of age, 5% and 7.4% were still in stage 1 of GD and PHD, respectively, whereas almost one-third had attained stage 5 for both sexual characteristics. The median age for attainment of stage 2 was 11.2 years for GD, 11.5 years for PHD and 11 years for one or both of them. CONCLUSIONS: These results are in line with those for several European and industrialized countries and do not show a significantly earlier onset of sexual maturation.

On the design of an exoskeleton for neurorehabilitation: design rules and preliminary prototype.

The neurorehabilitation robotics is a promising research field that allows improvements of the therapy effects. Some interesting systems for the neurorehabilitation of the upper limb are based on standard robotic arms and their applicability and effectiveness are based on the presence of patient's residual motor control synergy. On the other side, the exoskeletons overcome the single joint control allowing the full control of the arm kinematics. This paper presents the first results obtained at ARTS lab for the development of an exoskeleton for upper limb, starting from one of its building block that is a stand-alone active orthesis for functional assessment of the human wrist. We are addressing the design with a biomechatronic approach, based on an extensive analysis of the state-of-the-art. The design rules of sensorized wrist orthesis for functional assessment of the wrist and its first prototype are presented.

Height and secular trend in conscripts born in the Central Apennines (Italy), 1865-1972.

OBJECTIVE: The main aim of the research was to evaluate the effects of prolonged isolation on the secular trend of height in an internal zone of the central Apennines (Abruzzo, Province of L'Aquila). METHODS: Personal data for 1006 military conscripts in five sample years from 1865 to 1972 were used. The mean, standard deviation, median, skewness and kurtosis were calculated. Normal distribution of the data was assessed by the Kolmogorov-Smirnov test (Monte Carlo method). Differences between the means were tested by ANOVA and the Tukey test. RESULTS: Mean height increased from 161.3 +/- 5.97 cm in 1865 to 172.6 +/- 6.28 cm in 1972. The increases were slight, but constant, in the first 80 years: between 0.44 and 0.86 cm/decade, but greater thereafter: 2.37 cm/decade between 1945 and 1972. Regarding the frequency distribution, skewness showed negative values only in 1865 (-0.37 +/- 0.21). The Kolmogorov-Smirnov test did not show significance for any period. CONCLUSIONS: The results confirm that the mean heights in south-central Italy, including Abruzzo, were lower than those of the more economically advanced regions of northern Italy in each period. The difference has decreased greatly in the last few generations, but the secular trend is continuing in these communities. This seems to be due to prolonged isolation which has retarded economic development and favoured endogamy and genetic drift. However, it has also prevented the negative effects of wars, since there was no reduction of the secular trend in those periods.

Effects of cyproheptadine clorhydrate, a serotonin receptor antagonist, on endocrine parameters in weight-loss related amenorrhea.

The aim of the study was to evaluate the possible interactions and/or modulations of the serotoninergic system on hormonal parameters and the reproductive axis in amenorrheic subjects. Hypogonadotropic, underweight, amenorrheic patients (n = 8) were studied before and during cyproheptadine clorhydrate administration (4 mg/day for 3 months). A pulsatility study (4 hours, sampling every 10 minutes) and a naloxone test were performed before and after 4 and 12 weeks of treatment. Plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH), estradiol, thryoid-stimulating hormone (TSH), free tri-iodothyronine (fT3), free thyroxine (fT4) and total tri-iodothyonine (total T3), insulin-like growth factor-I (IGF-I) concentrations were determined. Pulse detection analysis was performed using the DETECT program. Serotoninergic receptor blockade affected neither the naloxone-inducted LH response nor the gonadotropin pulsatile parameters. Body mass index (BMI) did not vary; conversely, integrated mean gonadotropins, GH and fT3 concentrations increased during the treatment. In conclusion, cyproheptadine administration affects some of the abnormal endocrine parameters of underweight amenorrheic subjects with no modulation of the opioidergic system. It is likely that the gonadotropin and the fT3 increases take place owing to a change in the metabolic signals modulating hypothalamic function and/or an increased energy availability. Our study suggests a specific central effect of cyproheptadine on the serotonergic pathway controlling food intake at the hypothalamic level.

Seasonality of marriages and ecological contexts in rural communities of central-southern Italy (Abruzzo), 1500-1871.

The seasonality of 27,705 marriages celebrated in a four century span in the Province of Teramo (Abruzzo, Italy) was analyzed to identify the presence of a long-term pattern related to the prevailing subsistence activity and the main factors affecting it. The results show general agreement in all centuries with the agricultural patterns of other lowland or south-central Italian groups (Piedmont, Veneto, Liguria, Emilia Romagna, Tuscany, Latium, Compania, Apulia) and Mediterranean regions (Spain, France), although with some differences. Religious factors strongly affected the timing of marriage only during Lent. Of interest is the progressive increase through the centuries of marriages in the summer-autumn months, associated with a decrease in January and February. This suggests the passage from a summer migration system to a rural sedentary system with occasional seasonal work.

Quality control of 99Mo/99Tcm generators: results of a survey of the Radiopharmacy Working Group of the Italian Association of Nuclear Medicine (AIMN).

A multicentre survey of the quality control of 99Tcm generators has been completed: 245 generators from seven different commercial sources were tested over a period of 2 years. The results indicate that the mean pH of the eluates was 5.8 +/- 0.6; the aluminium contents were typically < 10 ppm; the radiochemical purity was 99.8 +/- 0.4% and the median 99Mo content was 3.8 x 10(-4) percent. The elution profiles gave a volume of 1.9 ml to obtain 50% of the total eluted activity and of 4.9 ml to obtain 95%. Other radionuclide impurities and heavy metal breakthrough were evaluated by graphite furnace absorption spectrometry and inductively coupled plasma mass spectrometry. National guidelines for the standardization of radiopharmacy procedures are currently being compiled.

CEA, MCA, CA 15.3 and CA 549 and their combinations in expressing and monitoring metastatic breast cancer: a prospective comparative study.

Serum levels of carcinoembryonic antigen (CEA), mucin-like carcinoma-associated antigen (MCA), CA 15.3 and CA 549 were concurrently assayed in patients with metastatic breast cancer. Overall sensitivity in detecting metastatic breast cancer (201 pts) was CEA 45%, MCA 59%, CA 15.3 71% and CA 549 72% (P < 0.01). Sensitivity increased by only 6% to 8% when two or more antigens were simultaneously considered. An overall sensitivity of correlation with objective response (n = 71) was observed in the range of 53-67% (P = n.s.) in patients with abnormal baseline marker values, and in the range of 42-87% (P < 0.05) in patients with normal baseline values. The combination of two or more markers did not improve sensitivity, but decreased specificity of correlation with objective response. In conclusion, CA 15.3 and CA 549 have individually higher sensitivity in detecting metastatic breast cancer. No clinical advantage was observed for using two or more markers concurrently over CA 15.3 or CA 549 alone in the monitoring of metastatic breast cancer.

Thyroid involvement in chronic inflammatory rheumatological disorders.

The association between rheumatological and thyroid disorders has long been known, the most common being the association of rheumatoid arthritis and autoimmune thyroiditis. Little is known as to possible thyroid involvement in other rheumatological disease of possible autoimmune aetiology, such as psoriatic arthritis and ankylosing spondylitis. We measured thyroid volume and function as well as the prevalence of anti-microsome and anti-thyroglobulin antibodies in 107 consecutive patients with rheumatoid arthritis, 42 patients with psoriatic arthritis, and 12 male patients with ankylosing spondylitis. Fifty-two normal subjects were used as controls. The average thyroid volume, measured at ultrasounds, was increased in all groups of patients, and the prevalence of thyroid enlargement (A-P diameter > 20 mm) was 2-3 fold higher in rheumatological disorders in comparison to controls. Both, patients with rheumatoid arthritis and psoriatic arthritis had higher-than-normal fT4 levels and an increased prevalence of anti-microsome antibodies. In the rheumatoid arthritis group alterations in thyroid volume and function were present irrespective of disease activity, whereas in psoriatic arthritis thyroid involvement was confined to patients with active disease. Our data are consistent with a significant thyroid involvement in rheumatological disorders, which is not limited to diseases with a definite autoimmune aetiology.

CA-549 serum levels in breast cancer monitoring.

CA-549 serum levels were assessed in 288 patients, 156 with early breast cancer (after surgery) and 132 with advanced breast cancer. CA-549 was abnormal (> 12 U/ml) in 25/156 patients (16%) without clinical signs of disease after surgery (median 9 U/ml), in 49/60 patients (82%) with disease in progression (P) (median 50 U/ml), in 19/27 patients (70%) with stationary disease (NC) (median 14 U/ml), in 25/33 patients (76%) with partial remission (PR) (median 18 U/ml) and in 4/12 patients (33%) with complete remission (CR) (median 9 U/ml). CA-549 serum levels correlated mainly with the extent of disease and secondarily with the prevalent metastatic site, higher values being observed in patients with visceral involvement (median 32.5 U/ml). CA-549 serum levels were also assessed in 51 patients at the start of treatment and at the time of objective evaluation: the results underline the concordance of CA-549 behavior with the clinical outcome in 71% of the cases. We conclude that CA-549 is a useful marker for monitoring breast cancer patients during the advanced stages of the disease.

Genetic structure of the population of Sicily.

Genetic heterogeneity within Sicily was investigated on the basis of ACP1, ADA, ESD, GLO1, PGD, PGM1, PGM2, SODA, ABO, and MN gene frequencies, and compared to those of other regions of Italy for which these same loci have been examined. Correspondence analysis revealed no differences within the island, at least at the provincial level, but showed genetic differentiation among Italian regions, distinctly clustering northern, central, and southern populations, respectively. These data indicate a close relationship between Sicily and southern Italy. In addition, the contribution of Middle Eastern populations to the gene pool of Sicily was evident.

Thyroid gland size and function in patients with cirrhosis of the liver.

Thyroid dysfunction has long been reported in patients with liver disease, but limited information is available on thyroid gland size in cirrhosis. Most studies were carried out on small, selected series of patients, and no study has measured thyroid volume in relation to the etiology of liver disease. Thyroid volume was measured at ultrasound in 118 consecutive patients with cirrhosis of different etiology and 48 healthy subjects matched for age and sex. No subjects had evidence of overt thyroid disease. The mean volume was increased by 17% (from 16.0 [SD 5.2] ml in controls to 18.8 [7.6] in cirrhosis; P less than 0.025), and thyroid enlargement (antero-posterior diameter greater than 20 mm) was present in 38% of cases, in the presence of hormone values indicative of low-T3 syndrome. No significant differences in thyroid gland size were observed in relation to the extent of liver dysfunction or to the etiology of liver disease. The prevalence of thyroid nodules was similar in controls and in patients with cirrhosis. In only 8% of cases were laboratory values indicative of hypothyroidism, with low free triiodothyronine and raised thyroid-stimulating hormone levels; in these patients thyroid volume was decreased on average by 26%. This was mainly the case with patients with primary biliary and alcoholic cirrhosis. The largest mean thyroid volume was observed in patients with HBsAg + ve postnecrotic cirrhosis, whose thyroid volume was increased on average by 37%, and 53% of subjects had thyroid enlargement. This finding raises the question of a possible direct involvement of the thyroid in hepatitis B virus infection.

Correlation between prostate-specific antigen and prostate volume, evaluated by transrectal ultrasonography: usefulness in diagnosis of prostate cancer.

The authors calculated the volume of the prostate by transrectal ultrasonography and evaluated prostate-specific antigen (PSA) in 108 patients with benign prostatic disease or with clinically suspected carcinoma and in 35 normal subjects. In each case the PSA value was related to the corresponding gland volume (V), which gives a PSA/V index. 32 patients underwent transurethral resection, 23 underwent open prostatectomy and biopsy was performed in 53. Histological examination revealed benign prostatic hyperplasia in 63, prostatitis in 12 and carcinoma in 33. In normal subjects and in those with benign prostatic diseases, the mean PSA/V index was 0.090 and 0.099, respectively. In patients with prostatic carcinoma the ratio was 1.73. The authors propose that this ratio be used, as an alternative to the absolute value of PSA, to differentiate patients with benign and malignant diseases of the prostate.

"Low T3 syndrome" in cirrhosis: effect of beta-blockade.

The so-called "low T3 syndrome" has frequently been reported in patients with cirrhosis. In this study, we aimed to determine whether administration of propranolol to such patients leads to further changes in plasma thyroid hormones, since it can affect their peripheral metabolism. Twenty cirrhotics (11 with ascites) whom we investigated showed no clinical evidence of thyroid dysfunction. The free fractions of plasma T3 and T4 (FT3, FT4) were determined by radioimmunoassay before and after the achievement of an effective beta-blockade by propranolol. The activity of the sympathetic nervous system also was evaluated by measuring plasma norepinephrine concentration. Under basal conditions, cirrhotics showed a reduced FT3 (2.45 +/- 0.11 SEM vs 3.55 +/- 0.16 pg/ml; p less than 0.001) and comparable FT4 (7.62 +/- 0.79 vs 9.2 +/- 0.42 pg/ml) and FT3/FT4 ratio (0.38 +/- 0.04 vs 0.42 +/- 0.013) with respect to healthy controls. When patients with ascites were considered apart, a reduction of FT4 was also found (6.78 +/- 0.74 pg/ml; p less than 0.01). In these patients, many of whom showed an increased plasma norepinephrine concentration, an inverse correlation between log FT3/FT4 and log plasma norepinephrine concentration was found (r = -0.79; p less than 0.01). The effective beta-blockade did not lead to significant changes in either FT3 or FT4 or FT3/FT4, whether the patients were considered as a whole (2.52 +/- 0.19 pg/ml, 9.3 +/- 1.41 pg/ml, and 0.36 +/- 0.04, respectively), or were split into groups according to the presence of ascites. When administered to cirrhotics, propranolol did not worsen thyroid hormone abnormalities, thus appearing to be safe in this respect. This may result from an impaired influence of the sympathoadrenergic system on thyroid hormone metabolism.

Spontaneous circadian fluctuations of prostate specific antigen and prostatic acid phosphatase serum activities in patients with prostatic cancer.

Spontaneous circadian variations of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP), determined simultaneously by radioimmunoassay (RIA), were investigated by multiple sampling, over a 24-hour period, in 32 patients with prostatic cancer. In 29/32 patients (91%), the coefficient of variation of 24-hour values, for either marker, was greater than that of the RIA method at the same range of values; stage D patients showed the greatest spontaneous variability. Fluctuations around the mean of 24-hour values ranged from -65% to +85% for PAP, from -72% to +190% for PSA, occurring random and independently for each marker. Variability was about 20% greater for PSA than for PAP. The existence of spontaneous fluctuations should be considered in multiple marker evaluation of prostatic cancer patients.