Life Cycle Assessment of a system for the extraction and transformation of Waste Water Treatment Sludge (WWTS)-derived lipids into biodiesel.

In recent years, the demand for biofuels has been growing exponentially, as has the interest in biodiesel produced from organic matrices. Particularly interesting, due to its economic and environmental advantages, is the use of the lipids present in sewage sludge as a raw material for the synthesis of biodiesel. The possible processes of this biodiesel synthesis, starting from lipid matter, are represented by the conventional process with sulfuric acid, by the process with aluminium chloride hexahydrate and by processes that use solid catalysts such as those consisting of mixed metal oxides, functionalized halloysites, mesoporous perovskite and functionalized silicas. In literature there are numerous Life Cycle Assessment (LCA) studies concerning biodiesel production systems, but not many studies consider processes that start from sewage sludge and that use solid catalysts. In addition, no LCA studies were reported on solid acid catalysts nor on those based on mixed metal oxides which present some precious advantages, over the homogeneous analogous ones, such as higher recyclability, prevention of foams and corrosion phenomena, and an easier separation and purification of biodiesel product. This research work reports the results of a comparative LCA study applied to a system that uses a solvent free pilot plant for the extraction and transformation of lipids from sewage sludge via seven different scenarios that differ in the type of catalyst used. The biodiesel synthesis scenario using aluminium chloride hexahydrate as catalyst has the best environmental profile. Biodiesel synthesis scenarios using solid catalysts are worse due to higher methanol consumption which requires higher electricity consumption. The worst scenario is the one using functionalized halloysites. Further future developments of the research require the passage from the pilot scale to the industrial scale in order to obtain environmental results to be used for a more reliable comparison with the literature data.

Stabilometric findings in patients affected by organic dysphonia before and after phonomicrosurgery.

The purpose of this study is to understand if there is any alteration in the posture of patients affected by organic dysphonia and describe possible postural modifications after phonomicrosurgery on the vocal folds. Forty subjects (22 males, 18 females; mean age 32.6 ± 7.5 years) suffering from organic dysphonia (15 cases of polyps, 11 submucosal retention cysts, 10 bilateral fibrous vocal fold nodules and 4 bilateral Reinke's oedema) were examined by open-eye and closed-eye posturography while breathing spontaneously before surgery, 24 hours after surgery and after 6 months. The variables taken into account were: the coordinates of the centre of pressure on both frontal and sagittal planes, length and surface of the track, mean velocity of the oscillations and relative standard deviations, spectral analysis of oscillation frequency, statokinesigram and stabilogram values. No characteristic pathological pattern was seen in basal stabilometry in any of the subgroups (polyps, cysts, Reinke's oedema). Only the subgroup of patients with fibrous vocal fold nodules (8/10; 80%) showed a slight forward shift from the centre of gravity when analysed in both open-eye and closed-eye posturography. A comparison performed within the same subgroup using open-eye and closed-eye posturography before and after surgery revealed no significant difference in any of the parameters being studied. The use of static stabilometry in this study demonstrates the absence of characteristic postural alterations in patients affected by organic dysphonia and also excludes that simple removal of the vocal fold lesion can change posture.

Comparison between videofluoroscopy, fiberoptic endoscopy and scintigraphy for diagnosis of oro-pharyngeal dysphagia.

The purpose of this study was to compare videofluoroscopy (VFS), fiberoptic endoscopic evaluation of swallowing (FEES) and oro-pharyngo- oesophageal scintigraphy (OPES) with regards to premature spillage, post-swallowing residue and aspiration to assess the reliability of these tests for detection of oro-pharyngeal dysphagia. Sixty patients affected with dysphagia of various origin were enrolled in the study and submitted to VFS, FEES and OPES using a liquid and semi-solid bolus. As a reference, we used VFS. Both the FEES and the OPES showed good sensitivity with high overall values (≥ 80% and ≥ 90% respectively). The comparison between FEES vs VFS concerning drop before swallowing showed good specificity (84.4% for semi-solids and 86.7% for liquids). In the case of post-swallowing residue, FEES vs VFS revealed good overall validity (75% for semi-solids) with specificity and sensitivity well balanced for the semi-solids. OPES vs. VFS demonstrated good sensitivity (88.6%) and overall validity (76.7%) for liquids. The analysis of FEES vs. VFS for aspiration showed that the overall validity was low (≤ 65%). On the other hand, OPES demonstrated appreciable overall validity (71.7%). VFS, FEES and OPES are capable of detecting oro-pharyngeal dysphagia. FEES gave significant results in the evaluation of post-swallowing residues.

How does radiotherapy impact swallowing function in nasopharynx and oropharynx cancer? Short-term results of a prospective study.

The objective of this study is to report the initial results of a prospective trial assessing instrumental deglutition function in nasopharynx and oropharynx cancers after radio or chemoradiotherapy using intensity-modulated radiotherapy (IMRT). IMRT was delivered aiming to spare the swallowing organ at risk (SWOARs) for Stage II-IV naso- and oropharynx cancer. Objective instrumental assessment included videofluoroscopy (VFS), fiberoptic endoscopic evaluation of swallowing (FEES) and oro-pharyngeal-oesophageal scintigraphy (OPES) at baseline and at 1 month after radiotherapy. Dysphagia parameter scores were calculated at each exam after liquid (L) and semi-liquid (SL) bolus intake: pre-deglutition penetration, aspiration, pharyngeal transit time (PTT) and hypopharyngeal retention index (HPRI). Overall, 20 patients (6 nasophaynx and 14 oropharynx) completed treatment and instrumental assessment after 1 month. Comparison between pre- and post-treatment HPRI score values showed a significant worsening in both FEES-L (p = 0.021) and SL (p = 0.02) and at VFS-L (p = 0.008) and SL (p = 0.005). Moreover, a relationship between HPRI worsening at FEES-L and FEES-SL (p = 0.005) as well as at VFS-L and VFS-SL (p < 0.001) was observed. PTT was not significantly affected by radiotherapy (p > 0.2). Only a few patients experienced pre-deglutition penetration (1 patient with base of tongue cancer at FEES-L and SL) and aspiration (1 patient with nasopharynx cancer at OPES-L and FEES-SL) after radiotherapy. Our early results showed that IMRT-SWOARs sparing caused a significant increase in the post-deglutition HPRI score. Longer follow-up will be necessary to evaluate if the increase of HPRI is related to a high risk of developing late aspiration.

The value of oropharyngoesophageal scintigraphy in the management of aspiration into the tracheobronchial tree in neurological patients / El valor de la gammagrafía orofaringeoesofágica en el manejo de la aspiración en el árbol traqueobronquial en pacientes neurológicos

Aim. Dysphagia and bolus aspiration are two of the most frequent and invalidating symptoms of various neurological diseases. Swallowing disorders often lead to tracheobronchial aspiration with consequent pneumonia episodes. Aspiration pneumonia per se constitutes the most frequent cause of death in these patients, with mortality rate ranging from 20% to 62%. Oropharyngoesophageal scintigraphy (OPES) permits functional quantitative assessment of the different stages of swallowing, together with the detection and quantitative measurement of bolus aspiration. In this work, we analyzed the role of OPES in patients with different neurological conditions to evaluate swallowing and to detect and quantify bolus aspiration. Material and methods. We enrolled 43 neurological patients (25 women and 18 men, mean age 67.3 ± 12.4 yr) complaining of dysphagia with suspected inhalation. All patients underwent OPES with 99mTc-nanocolloid using a liquid bolus first, followed by a semi-solid bolus. We evaluated the following parameters: Oral, Pharyngeal and Esophageal Transit Time, Oro-Pharyngeal Retention Index, Esophageal Emptying Rate, and Aspiration Rate (% AR). Results. OPES detected some airway aspiration in 26/43 patients. 19 patients had tracheal aspiration (with a mean 18.1% AR) and the remaining 7 patients had bilateral broncho-pulmonary aspiration (mean 44.9% AR). Conclusions. OPES is a feasible, repeatable and noninvasive method that allows quantitative assessment of bolus aspiration into the tracheobronchial tract, thus representing a useful and accurate tool to guide the most appropriate treatment and to monitor response to therapy in neurological patients with dysphagia (AU)

Objetivo. La disfagia y la broncoaspiración de comida son 2 de los síntomas más frecuentes e invalidantes de diversas enfermedades neurológicas. Los trastornos de deglución producen una aspiración traqueobronquial y episodios de neumonía. La neumonía por aspiración constituye en sí misma la causa más frecuente de muerte en estos pacientes, con tasas de mortalidad entre 20–62%. La gammagrafía orofaringeoesofágica (OPES) permite la evaluación funcional cuantitativa de los diferentes estadios de la deglución, junto con la detección y la cuantificación de la broncoaspiración. En este trabajo analizamos el papel de la OPES para evaluar la deglución y para detectar y cuantificar la broncoaspiración de comida en pacientes con variadas situaciones neurológicas. Material y métodos. Se estudiaron 43 pacientes neurológicos (25 mujeres y 18 hombres, edad media 67,3 + 12,4 años) que presentaban disfagia y sospecha de inhalación. A todos los pacientes se les realizó OPES con 99mTc-nanocoloide usando primero un bolo líquido y después un bolo semisólido. Se evaluaron los siguientes parámetros: tiempos de tránsito oral, faríngeo y esofágico, índice de retención orofaríngea, tasa de vaciamiento esofágico, índice de retención orofaríngea, tasa de vaciamiento esofágico y tasa de aspiración (%AR). Resultados. La OPES detectó broncoaspiración en 26/43 pacientes. Diecinueve pacientes tuvieron aspiración traqueal (media AR 18,1%) y los restantes 7 pacientes aspiración broncopulmonar bilateral (media AR 44,9%). Conclusiones. La OPES es un método no invasivo, factible y repetible que permite la evaluación cuantitativa de la aspiración de comida en el tracto traqueobronquial. Por ello, representa un procedimiento útil y exacto para guiar el tratamiento más apropiado y para monitorizar la respuesta terapéutica en pacientes neurológicos con disfagia (AU)

The value of oropharyngoesophageal scintigraphy in the management of aspiration into the tracheobronchial tree in neurological patients.

AIM: Dysphagia and bolus aspiration are two of the most frequent and invalidating symptoms of various neurological diseases. Swallowing disorders often lead to tracheobronchial aspiration with consequent pneumonia episodes. Aspiration pneumonia per se constitutes the most frequent cause of death in these patients, with mortality rate ranging from 20% to 62%. Oropharyngoesophageal scintigraphy (OPES) permits functional quantitative assessment of the different stages of swallowing, together with the detection and quantitative measurement of bolus aspiration. In this work, we analyzed the role of OPES in patients with different neurological conditions to evaluate swallowing and to detect and quantify bolus aspiration. MATERIAL AND METHODS: We enrolled 43 neurological patients (25 women and 18 men, mean age 67.3±12.4 yr) complaining of dysphagia with suspected inhalation. All patients underwent OPES with (99m)Tc-nanocolloid using a liquid bolus first, followed by a semi-solid bolus. We evaluated the following parameters: Oral, Pharyngeal and Esophageal Transit Time, Oro-Pharyngeal Retention Index, Esophageal Emptying Rate, and Aspiration Rate (% AR). RESULTS: OPES detected some airway aspiration in 26/43 patients. 19 patients had tracheal aspiration (with a mean 18.1% AR) and the remaining 7 patients had bilateral broncho-pulmonary aspiration (mean 44.9% AR). CONCLUSIONS: OPES is a feasible, repeatable and noninvasive method that allows quantitative assessment of bolus aspiration into the tracheobronchial tract, thus representing a useful and accurate tool to guide the most appropriate treatment and to monitor response to therapy in neurological patients with dysphagia.

A biorobotic model of the human larynx.

This work focuses on a physical model of the human larynx that replicates its main components and functions. The prototype reproduces the multilayer vocal folds and the ab/adduction movements. In particular, the vocal folds prototype is made with soft materials whose mechanical properties have been obtained to be similar to the natural tissue in terms of viscoelasticity. A computational model was used to study fluid-structure interaction between vocal folds and the airflow. This tool allowed us to make a comparison between theoretical and experimental results. Measurements were performed with this prototype in an experimental platform comprising a controlled air flow, pressure sensors and a high-speed camera for measuring vocal fold vibrations. Data included oscillation frequency at the onset pressure and glottal width. Results show that the combination between vocal fold geometry, mechanical properties and dimensions exhibits an oscillation frequency close to that of the human vocal fold. Moreover, computational results show a high correlation with the experimental one.

Long-term follow up of sudden sensorineural hearing loss patients treated with intratympanic steroids: audiological and quality of life evaluation.

OBJECTIVE: To evaluate the long-term stability of intratympanic steroids and investigate the 'real' impact of sudden sensorineural hearing loss on patients. METHOD: A total of 14 patients treated with intratympanic steroids were evaluated by audiometric and vestibular examinations. The modified Glasgow Benefit Inventory was used to evaluate quality of life changes after intratympanic steroid treatment. RESULTS: There was no significant difference between pure tone average post-intratympanic steroids and at follow up. The general Glasgow Benefit Inventory score was not significantly associated with the presence of tinnitus or dizziness, or with patient age. The change in pure tone average after intratympanic steroid treatment did not correlate with social or physical scores, but correlated strongly with the general Glasgow Benefit Inventory score (p = 0.0023). Intratympanic steroid administration led to a stable improvement in hearing. Quality of life assessment showed that patients can feel satisfaction regardless of the hearing outcome. Patients who regained a social hearing level expressed greater satisfaction than patients without serviceable hearing. Overall, quality of life improvement was not related to hearing improvement. CONCLUSION: Sudden sensorineural hearing loss is devastating. Considering the audiological effects alone ignores the 'human' perspective. Audiological success can correlate with poor quality of life outcome.

The Pooling-score (P-score): inter- and intra-rater reliability in endoscopic assessment of the severity of dysphagia.

This study evaluated the intra- and inter-rater reliability of the Pooling score (P-score) in clinical endoscopic evaluation of severity of swallowing disorder, considering excess residue in the pharynx and larynx. The score (minimum 4 - maximum 11) is obtained by the sum of the scores given to the site of the bolus, the amount and ability to control residue/bolus pooling, the latter assessed on the basis of cough, raclage, number of dry voluntary or reflex swallowing acts (< 2, 2-5, > 5). Four judges evaluated 30 short films of pharyngeal transit of 10 solid (1/4 of a cracker), 11 creamy (1 tablespoon of jam) and 9 liquid (1 tablespoon of 5 cc of water coloured with methlyene blue, 1 ml in 100 ml) boluses in 23 subjects (10 M/13 F, age from 31 to 76 yrs, mean age 58.56±11.76 years) with different pathologies. The films were randomly distributed on two CDs, which differed in terms of the sequence of the films, and were given to judges (after an explanatory session) at time 0, 24 hours later (time 1) and after 7 days (time 2). The inter- and intra-rater reliability of the P-score was calculated using the intra-class correlation coefficient (ICC; 3,k). The possibility that consistency of boluses could affect the scoring of the films was considered. The ICC for site, amount, management and the P-score total was found to be, respectively, 0.999, 0.997, 1.00 and 0.999. Clinical evaluation of a criterion of severity of a swallowing disorder remains a crucial point in the management of patients with pathologies that predispose to complications. The P-score, derived from static and dynamic parameters, yielded a very high correlation among the scores attributed by the four judges during observations carried out at different times. Bolus consistencies did not affect the outcome of the test: the analysis of variance, performed to verify if the scores attributed by the four judges to the parameters selected, might be influenced by the different consistencies of the boluses, was not significant. These initial data validate the clinical use of the P-score in the management of patients with deglutition disorders by a multidisciplinary team.

Boronic acid chemistry in MALDI MS: a step forward in designing a reactive matrix with molecular recognition capabilities.

A boronic analogue of the archetype matrix α-cyano-4-hydroxycinnamic acid (CHCA) has been synthesised providing a new "reactive matrix" that possesses molecular recognition properties. This matrix selectively recognizes vic-diols, α-hydroxyacids, aminols and first allowed the detection of anions as fluoride (unaffordable by usual matrices).

The use and role of the Ambulatory Phonation Monitor (APM) in voice assessment.

Vocal load plays a significant role in the aetiology of voice disorders and influences the response to treatment. For this reason, many researchers have focused their attention on how a voice is used, especially when vocal load is increased, during working hours for instance. The majority of studies in this regard have been performed by recording vocal parameters for brief periods with the aid of microphones. The first devices produced recorded only a few parameters and for relatively short periods of time, and since microphones were used there was a problem with both privacy and background noise such as the inclusion of voices from nearby people. Recently, microprocessors that can monitor a voice for an entire day have been developed; these use miniaturised accelerometers as vocal sensors. The latest commerciallyavailable version is the Ambulatory Phonation Monitor (APM) (KayPENTAX, Lincoln Park, NJ, USA) which can record several vocal parameters for over 18 hours and supply a series of graphic representations of the variations in these parameters during the recording period. In particular, the APM permits recording vocal load by measuring the cycle dose and distance dose, and evaluates vocal intensity (dB sound pressure level [SPL]), fundamental frequency and total phonation time. This report describes the APM, the use of an accelerometer as a vocal sensor, the importance of its calibration and the parameters it records. In particular, details are given on phonation time, variations in frequency, vocal intensity, phonation density and vocal dose. The role of the APM in voice studies is also described, in addition to its potential clinical applications as demonstrated by the few reports available in the literature. We also discuss our experience with the device in groups of euphonic and dysphonic elementary school teachers.

When less is better: the safety and efficacy of reduced intensity gemcitabine in a difficult patient population with advanced non-small-cell lung cancer.

Treatment of elderly or poor performance status (PS) patients with advanced non-small-cell lung cancer (NSCLC) is a debated topic. To evaluate the efficacy of a modified schedule of gemcitabine, 59 patients unfit for platinum were enrolled. Mean age was 75.8 years and 41 % of patients had an ECOG PS 2. Gemcitabine was given at 1000 mg/m(2) on days 1, 8 each 28. Most of patients received gemcitabine as first-line chemotherapy, which was continued as maintenance over 6 cycles in responding and stable patients. Median overall survival (OS) and progression-free survival (PFS) were 7.2 and 5 months. In those 45 evaluable patients, treatment resulted in 1 complete remission (CR), 9 partial remissions (PR), and 20 stable diseases (SDs) with a response rate (CR + PR) of 22 % and a clinical benefit (CR + PR + SD) of 68 %. Gemcitabine was continued over 6 cycles in 16 patients (27 %). These patients were treated until progression with a mean of further 8.6 cycles. Median OS and PFS in these selected patients were 19 and 16 months. The toxicity profile was excellent with only 8 % of overall G3-G4 adverse events. None of the 16 patients under the maintenance phase reported significant toxicity. Gemcitabine given at a lower dose intensity than standard should be considered as valuable therapeutic option in elderly or poor PS patients with advanced NSCLC unfit for platinum. Extending the treatment beyond 6 cycles in responding patients is feasible and may prolong survival.

Posturographic analysis in patients with dysfunctional dysphonia before and after speech therapy/rehabilitation treatment.

The relationship between voice and posture has been previously investigated. The aim of this study was to evaluate postural alterations in subjects with dysfunctional dysphonia and to analyse their variations after rehabilitation. Forty subjects with hypokinetic dysfunctional dysphonia were submitted to posturographic analysis with alternatively open and closed eyes; subjects were invited to stand upright and breath normally so that the vestibular-spinal reflex could be assessed. The following variables were considered: pressure centre coordinates on frontal and sagittal planes and standard deviations (SD), length and surface of the tract, mean velocity of the oscillations and SD, spectral frequency analysis of oscillations, statokinesigram and stabilogram. At baseline, the parameters showing the highest alterations were surface and velocity SD. All parameters improved after rehabilitation, particularly SD(X) and SD(Y), surface, velocity and relative SD; the centre of pressure shifted backwards in all patients. These results confirm that in subjects with dysfunctional dysphonia, the greater proprioceptive awareness acquired through speech therapy permits improvement in postural performance. Static stabilometry is a fundamental test for demonstrating basal postural alterations and for evaluating improvement after rehabilitation.

Efficacy and safety of low-dose metronomic chemotherapy with capecitabine in heavily pretreated patients with metastatic breast cancer.

AIM: Registered dose capecitabine monotherapy is active against metastatic breast cancer (MBC), but retrospective analyses indicate that lower doses may be as effective and better tolerated. This study was conducted to assess the safety and efficacy of metronomic capecitabine in heavily pretreated patients with MBC. PATIENTS AND METHODS: In this phase II study 60 MBC patients received continuous metronomic capecitabine monotherapy (1500 mg once a day). Primary endpoint was clinical benefit rate, secondary end points were clinical benefit rates (CBRs), tumour response rates (RRs), overall survival (OS), time to progression (TTP), duration of response (DOR) and toxicity. RESULTS: Fifty eight assessable patients received two or more 28-day cycles of metronomic capecitabine. The CBR was 62%. Median DOR was 7 months. Median TTP and OS were 7 and 17 months, respectively. Two partial responses and 7 cases of stable disease were recorded in 13 patients who had previously received capecitabine intermittently (2000 mg/m(2)/day on days 1-14 every 21 days) as first- or subsequent-line treatment for MBC. Grade 3-4 adverse events were uncommon; haematologic toxicity was infrequent (5%) and consistently mild. CONCLUSION: This regimen of metronomic capecitabine displayed good activity and excellent tolerability in MBC patients, including those who had previously received the drug at standard doses.

Modifications of muscle synergies and spinal maps due to absence of visual feedback in patients with unilateral vestibular disease.

The present study aimed at describing the modifications of muscle synergies and spinal activity due to the absence of visual feedback, in patients affected by unilateral vestibular disease. Patients were tested both during unperturbed quite stance and walking while the activity of 7 bilateral muscles, from the leg to the trunk, were recorded for the estimation of muscle synergies and spinal activity. Results showed that during locomotion the absence of visual feedback did not significantly modify either the principal roles underlying muscle activity (i.e., synergies) or the spinal bursts. Conversely, during the upright stance, the absence of visual feedback involved a significant coupling of ankle dorsi- and plantar-flexor muscle groups with a consequent shift of the motoneuronal (MN) activity toward most caudal segments. Results revealed that the muscle synergies are able to document an increased activity of sensory-motor afferences leading a more intense role of the forward based mechanism underlying balance control in vestibular patients.

Intratympanic methylprednisolone as first-line therapy in sudden sensorineural hearing loss: preliminary results from a case-control series.

BACKGROUND: Sudden sensorineural hearing loss is a true audiological emergency, and its management is much discussed. Currently, no single therapy has been proven effective according to evidence criteria. Recently, intratympanic application of steroids has been increasingly used in refractory cases; however, it has only rarely been reported as first-line therapy. MATERIALS AND METHODS: Twenty consecutive patients with sudden sensorineural hearing loss treated between July 2008 and January 2010 were enrolled in this prospective, case-control study. Ten patients were treated with intratympanic steroids and 10 with systemic 'shotgun' therapy (including steroids, pentoxifylline, low molecular weight heparin and vitamin E). The two groups were homogeneous in all respects. Pure tone averages were assessed before and after treatment for both groups. RESULTS: There were no statistically significant differences between the two groups. CONCLUSION: Intratympanic steroids seem to offer a valid alternative to systemic therapy, with few risks, in sudden sensorineural hearing loss patients, and we recommend their use as first-line therapy.

Vestibular and stabilometric findings in whiplash injury and minor head trauma.

Vertigo and postural instability following whiplash and/or minor head injuries is very frequent. According to some authors, post-whiplash vertigo cannot be caused by real injury to vestibular structures; other authors maintain that vestibular damage is possible even in the case of isolated whiplash, with vascular or post-traumatic involvement. Furthermore, many of the balance disorders reported after trauma can be justified by post-traumatic modification to the cervical proprioceptive input, with consequent damage to the vestibular spinal reflex. The aim of this study was to evaluate the vestibular condition and postural status in a group of patients (Group A, n = 90) affected with balance disorders following whiplash, and in a second group (Group B, n = 20) with balance disorders after minor head injury associated with whiplash. Both groups were submitted to videonystagmography (VNG) and stabilometric investigation (open eyes - O E, closed eyes - CE, closed eyes with head retroflexed - CER) within 15 days of their injuries and repeated within 10 days after conclusion of cervical physiotherapy treatment. The VNG tests revealed vestibulopathy in 19% of cases in Group A (11% peripheral, 5% central, 3% in an undefined site) and in 60% of subjects in Group B (50% peripheral, 10% central). At the follow-up examination, all cases of non-compensated labyrinth deficit showed signs of compensation, while there were two cases (2%) in Group A and one case (5%) in Group B of PPV. As far as the altered posturographic recordings are concerned, while there was no specific pattern in the two groups, they were clearly pathologic, especially during CER. Both in OE and in CE there was an increase in the surface values and in those pertaining to shifting of the gravity centre on the sagittal plane, which was even more evident during CER. In Group A, the pre-post-physiotherapy comparison of CER results showed that there was a statistically significant improvement in the majority of the parameters after treatment. Moreover, in Group B there was frequent lateral shifting of the centre of gravity that was probably linked with the high percentage of labyrinth deficits. The comparison between the first and second stabilometric examinations was statistically significant only in those parameters referring to gravity centre shifting on the frontal plane, which was probably due to the progressive improvement in the associated vestibulopathy rather than to the physiotherapy treatment performed for the cervical damage. Hence, our study confirms that only in a minority of cases can whiplash cause central or peripheral vestibulopathy, and that this is more probable after minor head injury associated with whiplash. In addition, our data confirm that static stabilometry is fundamental for assessing postural deficits following a cervical proprioceptive disorder. In these cases, in fact, analysis of the different parameters and the indices referring to cervical interference not only permits evaluation of altered postural performance, but also detects and quantifies destabilisation activity within the cervical proprioceptive component.

Molecularly targeted endocrine therapies for breast cancer.

The identification of the estrogen receptor (ER) provided the first target for antiestrogenic therapeutic agents. Endocrine therapies, either by blocking or downregulating the receptor or by suppressing the estrogen production, inhibit the proliferative effect of estradiol on ER. While the activity on ER is considered a real target-mediated therapy, the effect on enzymatic activity involved in estrogen production (mainly inhibition of aromatase by aromatase inhibitors, AIs, and ovarian ablation) could be considered an "indirect" targeted strategy. In addiction to the direct ligand-ER signal, the complexity of endocrine and non endocrine pathways has led to combination therapies against different targets. Tamoxifen is the widely investigated, most used and representative of drugs blocking the ER and has been introduced in the advanced disease, in neoadjuvant and adjuvant setting and for chemo-prevention of high risk women. Its role has been challenged in the last years by the introduction of third generation aromatase inhibitors that have proven a higher activity than tamoxifen and different toxicity. Several other SERMs (selective estrogen receptor modulators) have been investigated, but none of them was clearly superior to tamoxifen. SERDs (selective estrogen receptor downregulators) act as pure estrogen antagonist. They are used in the treatment of advanced breast cancers and their role in other settings still needs further investigation. Here we discuss the well established data with SERMs, SERDs and AIs, mechanisms underlying resistance and rationale for recycling endocrine compounds and for simultaneously targeting different pathways.

Analysis of voice in patients with untreated active acromegaly.

BACKGROUND: Voice changes are common clinical findings of acromegaly, although scanty data are available so far. OBJECTIVE: To analyze features and quantify changes of voice in patients with untreated active acromegaly. DESIGN AND METHODS: This was a pilot case-control study. Voice was analyzed using the Multi Dimensional Voice Program software, which generates 33 parameters related to fundamental frequency (F0), micro-perturbation of F0 and amplitude, noise, tremor, voice breaks and irregularities, and diplophony. PATIENTS: Thirteen consecutive patients (8 women, 5 men, mean age 48+/-9 yr) with active acromegaly, at first diagnosis, and 13 sex- and age-matched normal subjects (controls). RESULTS: Patients with untreated active acromegaly had mean values of parameters related to F0 significantly lower than those of controls, although mostly remaining in the normal range. Most acromegalic patients had micro-perturbation of F0, as indicated by higher mean of absolute or percentage jitter values than those of controls; micro-perturbation of amplitude was a common feature of voice in most acromegalic men. Noise-related parameters were also affected by acromegaly, being higher in male acromegalic patients than in controls and acromegalic women. On the contrary, parameters related to tremors, voice breaks, voice irregularities and diplophony did not differ in acromegalic patients and controls. CONCLUSIONS: Patients with untreated active acromegaly had low-pitched voice characterized by lowering F0 and increased values related to noise, micro perturbation of frequency, and amplitude.