Magnetic-free Extended Kalman Filter for upper limb kinematic assessment in Yoga.

Human motion analysis is gaining increased importance in several fields, from movement assessment in rehabilitation to recreational applications such as virtual coaching. Among all the technologies involved in motion capture, Magneto-Inertial Measurements Units (MIMUs) is one of the most promising due to their small dimensions and low costs. Nevertheless, their usage is strongly limited by different error sources, among which magnetic disturbances, which are particularly problematic in indoor environments. Inertial Measurement Units (IMUs) could, thus, be considered as alternative solution. Indeed, relying exclusively on accelerometers and gyroscopes, they are insensitive to magnetic disturbances. Even if the literature has started to propose few algorithms that do not take into account magnetometer input, their application is limited to robotics and aviation. The aim of the present work is to introduce a magnetic-free quaternion based Extended Kalman filter for upper limb kinematic assessment in human motion (i.e., yoga). The algorithm was tested on five expert yoga trainers during the execution of the sun salutation sequence. Joint angle estimations were compared with the ones obtained from an optoelectronic reference system by evaluating the Mean Absolute Errors (MAEs) and Pearson's correlation coefficients. The achieved worst-case was 6.17°, while the best one was 2.65° for MAEs mean values. The accuracy of the algorithm was further confirmed by the high values of the Pearson's correlation coefficients (lowest mean value of 0.86).Clinical Relevance- The proposed work validated a magnetic free algorithm for kinematic reconstruction with inertial units. It could be used as a wearable solution to track human movements in indoor environments being insensitive to magnetic disturbances, and thus could be potentially used also for rehabilitation purposes.

Carotid Intraplaque-Hemorrhage Volume and Its Association with Cerebrovascular Events.

BACKGROUND AND PURPOSE: Our aim was to assess the relationship between volume and percentage of intraplaque hemorrhage measured using CT and the occurrence of cerebrovascular events at the time of CT. MATERIALS AND METHODS: One-hundred-twenty-three consecutive subjects (246 carotid arteries) with a mean age of 69 years who underwent CTA were included in this retrospective study. Plaque volume of components and subcomponents (including intraplaque hemorrhage volume) was quantified with dedicated software. RESULTS: Forty-six arteries were excluded because no plaque was identified. In the remaining 200 carotid arteries, a statistically significant difference was found between presentation with cerebrovascular events and lipid volume (P = .002), intraplaque hemorrhage volume (P = .002), percentage of lipid (P = .002), percentage of calcium (P = .001), percentage of intraplaque hemorrhage (P = .001), percentage of lipid-intraplaque hemorrhage (P = .001), and intraplaque hemorrhage/lipid ratio (P = .001). The highest receiver operating characteristic area under the curve was obtained with the intraplaque hemorrhage volume with a value of 0.793 (P = .001), percentage of intraplaque hemorrhage with an area under the curve of 0.812 (P = .001), and the intraplaque hemorrhage/lipid ratio with an area under the curve value of 0.811 (P = .001). CONCLUSIONS: Results of our study suggest that Hounsfield unit values <25 have a statistically significant association with the presence of cerebrovascular events and that the ratio intraplaque hemorrhage/lipid volume represents a strong parameter for the association of cerebrovascular events.

Adherence in children with growth hormone deficiency treated with r-hGH and the easypod™ device.

PURPOSE: Poor adherence to recombinant human growth hormone (r-hGH) therapy is associated with reduced growth velocity in children with growth hormone deficiency (GHD). This twelve-month observational study was to assess adherence in r-hGH patients treated with the easypod™, an electronic, fully automated injection device designed to track the time, date and dose administered. METHODS: Ninety-seven prepubertal patients receiving r-hGH therapy were included in the study from ten Italian clinical sites and 88 completed the study. To avoid possible confounding effects, only GHD patients (79/88; 89.7 % of the overall study population) were considered in the final analysis. The primary endpoint-adherence to treatment-was calculated as the proportion of injections correctly administered during the observational period out of the expected total number of injections. The relevant information, tracked by the easypod™, was collected at months 6 (V1) and 12 (V2) after baseline (V0). At study termination, adherence data were partially available from 16 patients and fully available from 53 patients. As secondary endpoints, serum IGF-1 levels, fasting serum glucose and insulin levels and key anthropometric characteristics (height, waist circumference and BMI) were also determined. RESULTS: The easypod™ data showed that 56.7 % of the patients were considered to be fully (≥92 %) adherent to their treatment throughout the period V0-V2. Treatment improved stature, significantly increased IGF-1 and produced a non-significant increase in blood glucose and insulin levels. CONCLUSIONS: The injection-recording system and other characteristics of easypod™ could enhance the ability of physicians to monitor adherence to r-hGH treatment.

Growth hormone treatment of adolescents with growth hormone deficiency (GHD) during the transition period: results of a survey among adult and paediatric endocrinologists from Italy. Endorsed by SIEDP/ISPED, AME, SIE, SIMA.

Treatment of adolescents with growth hormone deficiency (GHD) during the transition period is a controversial issue. This paper is a contribution from the Italian community of paediatric and adult endocrinologists surveyed in a Delphi panel. The Delphi method is a structured communication technique, originally developed as a systematic, interactive forecasting method that relies on a panel of experts. The experts answer questionnaires in two or more rounds. There was substantial agreement on the definition of the problems associated with the diagnosis and treatment of adolescents with GHD in the transition period, as well as on the identification of the controversial issues which need further studies. There is general consensus on the need of re-testing all isolated idiopathic GHD after at least 30-day withdrawn from treatment, while in patients with multiple pituitary deficiency and low IGF-I levels there is generally no need to re-test. In patients with permanent or confirmed GHD, a starting low rhGH dose (0.01-0.03 mg per day) to be adjusted according to IGF-I concentrations is also widely accepted. For those continuing treatment, the optimal therapeutic schedule to obtain full somatic maturation, normalization of body composition and bone density, cardiovascular function and Quality of Life, need to be evaluated.

Direct autofluorescence during CO2 laser surgery of the larynx: can it really help the surgeon?

Herein we assessed the impact of direct autofluorescence during intraoperative work-up on obtaining superficial free resection margins, identifying new areas of malignant transformation and altering disease-free survival and local control at 3 years in patients submitted to transoral laser surgery (TLS) for early glottic cancer. Prospective cohort evaluation was carried out on the diagnostic accuracy of the superficial extent and TNM staging in 73 patients with glottic carcinoma undergoing transoral CO2 laser surgery. The use of direct autofluorescence was associated with superficial disease-free margins in 97.2% of cases, and with superficial close margins in 2.8%. The improvement in diagnostic accuracy was 16.4%; in 8.2% of cases, there was upstaging of the TNM classification (in one case, a second neoplastic area in a different laryngeal site was observed and considered to be a second endolaryngeal primary). The sensitivity of direct autofluorescence was 96.5% with a specificity of 98.5%. Overall, 3-year disease-specific survival and local control with laser alone were, respectively: T1a (97.5%, 100%), T1b (86.7%, 86.7%), T2 (88.9%, 88.9%). This study demonstrates that direct autofluorescence can help to identify positive superficial margins, and has a favourable impact on disease-specific survival and local control at 3 years.

How the operated larynx ages.

After open partial laryngectomy (HOPL), many patients experience deterioration of laryngeal function over time. The aim of this study was to evaluate laryngeal functional outcome at least 10 years after surgery in a cohort of 80 elderly patients. The incidence of aspiration pneumonia (AP) and objective/subjective laryngeal functional assessments were carried out. Eight patients experienced AP including four with repeated episodes. A significant association was observed between AP and severity of dysphagia (p < 0.001). Dysphagia was more pronounced than in a normal population of similar age, but less than would be expected. There was a significant association between the type of intervention and grade of dysphagia/dysphonia; a difference in voice handicap was found, depending on the extent of glottic resection. After HOPL, laryngeal function was impaired, but this did not significantly affect the quality of life. AP is more frequent in the initial post-operative period, and decreases in subsequent years.

AME position statement on adrenal incidentaloma.

OBJECTIVE: To assess currently available evidence on adrenal incidentaloma and provide recommendations for clinical practice. DESIGN: A panel of experts (appointed by the Italian Association of Clinical Endocrinologists (AME)) appraised the methodological quality of the relevant studies, summarized their results, and discussed the evidence reports to find consensus. RADIOLOGICAL ASSESSMENT: Unenhanced computed tomography (CT) is recommended as the initial test with the use of an attenuation value of ≤10 Hounsfield units (HU) to differentiate between adenomas and non-adenomas. For tumors with a higher baseline attenuation value, we suggest considering delayed contrast-enhanced CT studies. Positron emission tomography (PET) or PET/CT should be considered when CT is inconclusive, whereas fine needle aspiration biopsy may be used only in selected cases suspicious of metastases (after biochemical exclusion of pheochromocytoma). HORMONAL ASSESSMENT: Pheochromocytoma and excessive overt cortisol should be ruled out in all patients, whereas primary aldosteronism has to be considered in hypertensive and/or hypokalemic patients. The 1 mg overnight dexamethasone suppression test is the test recommended for screening of subclinical Cushing's syndrome (SCS) with a threshold at 138 nmol/l for considering this condition. A value of 50 nmol/l virtually excludes SCS with an area of uncertainty between 50 and 138 nmol/l. MANAGEMENT: Surgery is recommended for masses with suspicious radiological aspects and masses causing overt catecholamine or steroid excess. Data are insufficient to make firm recommendations for or against surgery in patients with SCS. However, adrenalectomy may be considered when an adequate medical therapy does not reach the treatment goals of associated diseases potentially linked to hypercortisolism.

A large view of CYP21 locus among Sicilians and other populations: identification of a novel CYP21A2 variant in Sicily.

BACKGROUND: Several mutations in CYP21 locus cause 21-hydroxylase deficiency (21-OHD). The most common mutations are widespread among different geographic areas and their frequencies have been also reported to differ among certain populations. AIM: To obtain a large view on the frequencies of the most common mutations in the CYP21 locus, in Sicily, in the Mediterranean and other major geographic areas worldwide. SUBJECTS AND METHODS: Three hundred and eight unrelated CYP21A2 alleles leading 21-OHD in Sicily were genetically typed and compared with other series previously reported in Sicily and in surrounding regions. An analysis of the frequencies of the different geographic areas was also carried out. CYP21A2 typing was carried out using PCR-restriction fragment length polymorphism (RFLP), for the detection of the CYP21A2 deletion, while sequencing analysis was performed to evaluate all the missense/non-sense mutations. RESULTS: Our study revealed that p.V281L (44.4%), I2splice (21.6%) and p.P30L (11.2%) were very frequent alleles, del8bp (0.4%) was found very rarely in Sicily and a novel mutation leading to non-classical phenotype, p.L198F, was also discovered in this population. Allele frequencies were found to be significantly different from previously observed frequencies in Sicily. In addition, here we present the most significant frequency modifications among different geographic areas worldwide. CONCLUSIONS: As the distribution of the disease CYP21A2 alleles is heterogeneous around the world, the knowledge of the relative distributions allows a better management of 21-OHD for fetuses and newborns in different geographic areas.

Elevated plasma homocysteine in acute stroke was not associated with severity and outcome: stronger association with small artery disease.

Homocysteine increases in the acute phase of ischaemic stroke and from the acute to the convalescent phase, suggesting that hyper-homocysteinaemia may be a consequence rather than a causal factor. Therefore we measured homocysteine plasma levels in stroke patients in order to investigate possible correlations of homocysteine with stroke severity and clinical outcome. Further we looked for eventual differences in stroke subtypes. We prospectively studied plasma homocysteine levels in acute stroke patients admitted to the stroke unit of our department. Seven hundred and seventy-five ischaemic stroke patients, 39 cerebral haemorrhages and 421 healthy control subjects have been enrolled. Stroke severity and clinical outcome were measured with the Scandinavian Stroke Scale, the Rankin Scale and the Barthel Index. Stroke severity by linear stepwise regression analysis was not an independent determinant of plasma homocysteine levels. Homocysteine was not correlated with outcome measured by the Barthel Index. Mean plasma homocysteine of both ischaemic and haemorrhagic stroke was significantly higher than controls (p<0.05). Homocysteine had an adjusted odds ratios (OR) of 4.2 (95% CI 2.77-6.54) for ischaemic stroke and of 3.69 (95% CI 1.90-7.17) for haemorrhagic stroke. Compared with the lowest quartile, the upper quartile was associated with an adjusted OR of ischaemic stroke due to small artery disease of 17.4 (95% CI 6.8-44.3). Homocysteine in the acute phase of stroke was not associated with stroke severity or outcome. Elevated plasma homocysteine in the acute phase of stroke was associated with both ischaemic and haemorrhagic stroke. Higher levels are associated with higher risk of small artery disease subtype of stroke.

Mutations and polymorphisms of the CLCN2 gene in idiopathic epilepsy.

The authors analyzed the CLCN2 chloride channel gene in 112 probands with familial epilepsy, detecting 18 common polymorphisms. Two brothers with generalized epilepsy and their asymptomatic father, and a father and son with focal epilepsy carried variants of possible functional significance that were not found in 192 controls. The authors conclude that CLCN2 mutations may be a rare cause of familial epilepsy. Further studies are needed to test if polymorphisms in this gene are associated with epilepsy.

[Hyperprolactinemia: from diagnosis to treatment]. / Le iperprolattinemie: dalla diagnosi al trattamento.

Hyperprolactinemia means the presence of abnormally high values of prolactin. It's the most common clinical hypothalamic-hypophysis disorder. Amenorrhea and anovulation are the most usual clinical findings but we can find milder alterations of gonadal function as oligomenorrhea or luteal phase alterations. Galattorrhea appears in approx 30% of patients, but its presence in women with ovulation disorders is highly suggestive of hyperprolactinemia. Subjects with primary amenorrhea and delayed puberty can present hyperprolactinemia. Male hyperprolactinemia can cause hypogonadism (decreased testosterone levels), libido decrease, infertility due oligospermia and gynecomastia while galactorrhea rarely occurs. Accurate anamnesis is very important for a correct diagnosis. It's necessary to exclude pregnancy and primary hypothyroidism. The use of many drugs can be associated with hyperprolactinemia but the most common causes are idiopathic hyperprolactinemia and hypophysis secreting adenoma. Diagnostic examinations are: PRL, FT3, FT4, TSH in case of hypothyroidism, testosterone in men, eventually sampling GH, IGF, ACTH, cortisol, free urinary cortisol. Dynamic tests are used just for idiopathic hyperprolactinemia, but today their meaning is widely discussed. CAT and MNR are necessary to observe hypotalamus, hypophysis and optic chiasm. Twenty years ago the sole option for prolactinoma patients was adenomectomy, today idiopathic hyperprolactinemia can be treated with drugs, while prolactinoma can be treated with a pharmacological, surgical or radiological therapy.

Memory for/and execution of future intentions: evidence from patients with Herpes Simplex Encephalitis.

Prospective remembering was studied in a group of patients who suffered from Herpes Simplex Encephalitis (HSE). All patients showed a marked deficit in executing intentions for future actions under all the given constraints. The deficit extended to both time- and event-based intentions. The analysis of errors showed somewhat different patterns and some dissociations with evidence for selective preservation or damage to specific components involved in prospective remembering. These patients, in fact, may fail because of a difficulty in taking into account all given constraints or in activating stored intentions and in forming intentions or in remembering the content of the actions. Time- and event-based tasks seem to show different sources of errors also in the same patient.

CR 2945: a novel CCKB receptor antagonist with anxiolytic-like activity.

The effects of CR 2945, an antranilic acid derivative member of a novel family of non-peptide CCKB receptor antagonists, have been compared with those of CAM-1028, an analogue of the CCKB receptor antagonist CI-988, L-365,260 a benzodiazepine derivative CCKB antagonist, CR 1795, an analogue of the CCKA receptor antagonist lorglumide and diazepam, a benzodiazepine receptor agonist, in several rodent screens sensitive to conventional anxiolytics. CR 2945 displayed nanomolar affinity for rat CCKB receptors and showed a selectivity ratio of about 9000 for the CCKB over the CCKA receptor. In ex-vivo binding studies, CR 2945, after i.v. and s.c. administration, inhibited the binding of [125I] (BH)-CCK8 in rat cortex homogenate with ID50s of 10.9 mg/kg and 13.5 mg/kg, respectively. In four rodent tests of anxiety (mouse black/white box, rat elevated plus-maze, rat elevated zero-maze and punished licking test in the rat) CR 2945 (0.1-10 mg/kg s.c. or orally) showed significant dose-dependent anxiolytic-like effects. The reference CCKB antagonist compounds CAM-1028 and L-365,260 showed an anxiolytic-like activity less robust than that of CR 2945 in the elevated zero-maze after s.c. administration, and these compounds were inactive in the elevated plus-maze after oral administration. The magnitude of the activity of CR 2945 was comparable to that of diazepam, but without signs of sedation and ataxia. Furthermore, a 7-day repeated treatment with CR 2945 at 10 mg/kg/day s.c. did not induce tolerance or withdrawal anxiety in rats. CR 1795 showed anxiolytic-like activity with a bell-shaped dose-response curve in the elevated zero-maze model in rats (0.1-10 mg/kg, orally and s.c.), whereas in the mouse black/white box test and in the rat elevated plus-maze test it was less effective. The results suggest that CR 2945 might be a promising alternative to the existing therapy of anxiety-related disorders.

Unusual EEG pattern linked to chromosome 3p in a family with idiopathic generalized epilepsy.

OBJECTIVE: To map the gene causing an unusual EEG pattern of delta bursts that appears to segregate as an autosomal dominant trait in an Italian family. The EEG pattern was observed in four family members affected by idiopathic generalized epilepsy (IGE) and in six other clinically unaffected members. METHODS: All available family members underwent clinical and EEG examination. DNA samples were obtained and used to perform a whole-genome scan with 270 microsatellite markers. After the first linked marker was identified, 12 additional markers in the same chromosomal region were tested to confirm linkage and define a candidate interval. RESULTS: The gene responsible for the EEG trait was mapped to an 11-cM interval on the proximal short arm of chromosome 3 (3p14.2-p12.1). CONCLUSION: In this family, a characteristic EEG activity is due to the effect of a single gene on chromosome 3p. A gene encoding a Ca2+ channel subunit maps in the interval and is a potential candidate for the trait. The clinical expression of epilepsy in four family members may reflect the interaction of additional genes, though environmental or other factors cannot be excluded.

CR 2249: a new putative memory enhancer. Behavioural studies on learning and memory in rats and mice.

The effects of S-4-amino-5-[4,4-dimethylcyclohexyl)amino]-5-oxopentanoic acid (CR 2249), a new entity selected from a new series of glutamic acid derivatives, has been investigated in different paradigms for screening nootropics. CR 2249 ameliorated the memory retention deficit produced by scopolamine in step-through-type passive avoidance in rats and by electroconvulsive shock in step-down-type passive avoidance in mice. CR 2249 was also capable of improving performance in behavioural tests of learning and memory in the absence of cholinergic hypofunction or cognitive deficit. The activity was determined using different passive and active avoidance behavioural test procedures on rats. CR 2249 was active only when given 45 min before training and did not show any effect when administered immediately after the learning training or before the retention trial. No changes in the general behaviour or motor activity of the animals were observed, indicating that CR 2249 effects cannot be attributed to sensory-motor deficit. Microdialysis experiments have shown that CR 2249 significantly increased noradrenaline release in the hippocampus of freely moving rats and reduced 3,4-dihydroxyphenylglycol efflux. These effects have led us to hypothesize that CR 2249 memory effect might be mediated by a direct or indirect action on noradrenergic transmission. These behavioural results suggest that this new agent has clinical application in memory disorders.

8-OH-DPAT impairs spatial but not visual learning in a water maze by stimulating 5-HT1A receptors in the hippocampus.

The effect of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, on spatial and non-spatial learning in a water maze was studied using two tasks of equal difficulty, with the same motor, motivational and reinforcement demands. Rats were examined for choice accuracy in a two-platform spatial discrimination task. Rats treated subcutaneously with 100 micrograms/kg 8-OH-DPAT were impaired in choice accuracy with no effect on latency. Treated rats made more errors of omission than controls only on days 1 and 2 of training. Infusion of 1 microgram/microliter spiroxatrine (SPX) or 5 micrograms/microliters of (+)WAY100135, two potent 5-HT1A receptor antagonists, in the CA1 region of the dorsal hippocampus antagonized the impairment in choice accuracy caused by 8-OH-DPAT. The effect on errors of omission on days 1 and 2 of training were not significantly modified by spiroxatrine or (+)WAY100135. Rats treated with 8-OH-DPAT were not impaired in their ability to learn a visual discrimination in a water maze. The results suggest that stimulation of 5-HT1A receptors in the CA1 region of the dorsal hippocampus impairs spatial but not visual discrimination in rats.

Thrombosis of parietal, but not striate, cortex impairs acquisition of a 14-unit T-maze in the rat.

We evaluated parietal cortex (PCTX) involvement in learning a shock-motivated, 14-unit T-maize in young F344 rats. In Experiment 1, each rat was placed into a stereotaxic instrument, and the scalp was retracted before either the photosensitive dye, rose bengal, or saline (CON) was provided via a jugular catheter. After 60 s, halogen lamps were used to illuminate the cranium bilaterally over PCTX for 40 min to activate the dye and generate a thrombus in dye-injected rats. Active avoidance pretraining in a straight runway occurred 12 days after surgery. Each rat was provided acquisition (ACQ) trials in the 14-unit T-maze 24-h later. The PCTX rats were impaired relative to CON in errors, run time, alternation errors, and shock frequency measures in the 14-unit T-maze, but not in shock duration. The thrombosis extended to areas comprising anteromedial and posterior PCTX, and also into the striate cortex (SCTX). In Experiment 2, rats were divided into four groups: a PCTX group that received bilateral illumination; PCTX+SCTX and SCTX groups that were illuminated at midline; and a CON group that received the surgery and either dye or illumination. Only PCTX differed from CON, with maze performance similar to Experiment 1. The thrombosis for the PCTX group in Experiment 2 was confined to anteromedial and posterior PCTX. Thus, PCTX, but not SCTX, was implicated in ACQ of this maze task, suggesting that PCTX might be involved in the robust age-related impairments in ACQ previously observed.

Erythrocyte-depleted allogeneic human umbilical cord blood transplantation.

Cord blood is a recently recognized source of hematopoietic stem cells. It can be employed successfully to reconstitute hematopoiesis following allogeneic transplantation. One current drawback of cord blood as a treatment has been a risk of transfusion reactions attributable to ABO blood group mismatch. Removal of red cells from the cord blood has led to reduction of the stem cells by 30-50%. In this paper we report red cell depletion by a method that employs 3% gelatin to effectively sediment the erythrocytes and selectively deplete red cells but permits 94% recovery of nucleated cells and enrichment of colony-forming cells by granulocyte-macrophage colony-forming units, erythrocyte burst-forming units, and granulocyte-macrophage-megakaryocyte colony-forming units in the cord blood preparation. This technique has been employed in our study to remove red cells from the cord blood of a male infant delivered by cesarean section, which has permitted treatment of a female sibling suffering from leukemia. The recipient was 8 years old and weighted 36.7/kg. Complete HLA identity between the two siblings was established. A cord blood cell transplant of cryopreserved and later thawed cells (4 x 10(7) nucleated cells per kilogram) was administered to the patient after intensive myeloablative chemotherapy. The patient exhibited a prompt hematologic recovery (absolute neutrophil count > 500 by day 31, 100% male cells in bone marrow and peripheral blood by day 25) and has experienced a 13-month disease-free survival to date.(ABSTRACT TRUNCATED AT 250 WORDS)