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1.  Crop changes from the XVI century to the present in a hill/mountain area of eastern Liguria (Italy) 
Background
Chronological information on the composition and structure of agrocenoses and detailed features of land cover referring to specific areas are uncommon in ethnobotanical studies, especially for periods before the XIX century. The aim of this study was to analyse the type of crop or the characteristics of soil cover from the XVI century to the present.
Methods
This diachronic analysis was accomplished through archival research on the inventories of the Parish of St. Mary and those of the Municipality of Pignone and from recent surveys conducted in an area of eastern Liguria (Italy).
Results
Archival data revealed that in study area the primary means of subsistence during the last five centuries, until the first half of the XX century, was chestnuts. In the XVIII and XIX centuries, crop diversification strongly increased in comparison with previous and subsequent periods. In more recent times, the abandonment of agricultural practices has favoured the re-colonisation of mixed woodland or cluster-pine woodland.
Conclusion
Ancient documents in the ecclesiastic or municipal inventories can be a very useful tool for enhancing the knowledge of agricultural practice, as well as of subsistence methods favoured by local populations during a particular time and for reconstructing land use change over time.
doi:10.1186/1746-4269-5-9
PMCID: PMC2679714  PMID: 19361339
2.  A Cell-free Scaffold-based Cartilage Repair Provides Improved Function Hyaline-like Repair at One year 
Background
Bone marrow stimulation techniques in cartilage repair such as drilling are limited by the formation of fibrous to hyaline-like repair tissue. It has been suggested such techniques can be enhanced by covering the defect with scaffolds. We present an innovative approach using a polyglycolic acid (PGA)-hyaluronan scaffold with platelet-rich-plasma (PRP) in drilling.
Questions/purposes
We asked whether (1) PRP immersed in a cell-free PGA-hyaluronan scaffold improves patient-reported 1-year outcomes for the Knee injury and Osteoarthritis Score (KOOS), and (2) implantation of the scaffold in combination with bone marrow stimulation leads to the formation of hyaline-like cartilage repair tissue.
Patients and Methods
We reviewed 52 patients who had arthroscopic implantation of the PGA-hyaluronan scaffold immersed with PRP in articular cartilage defects of the knee pretreated with Pridie drilling. Patients were assessed by KOOS. At 9 months followup, histologic staining was performed in specimens obtained from five patients to assess the repair tissue quality.
Results
The KOOS subscores improved for pain (55 to 91), symptoms (57 to 88), activities of daily living (69 to 86), sports and recreation (36 to 70), and quality of life (38 to 73). The histologic evaluation showed a homogeneous hyaline-like cartilage repair tissue.
Conclusions
The cell-free PGA-hyaluronan scaffold combined with PRP leads to cartilage repair and improved patient-reported outcomes (KOOS) during 12 months of followup. Histologic sections showed morphologic features of hyaline-like repair tissue. Long-term followup is needed to determine if the cartilage repair tissue is durable.
Level of Evidence
Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-011-2107-4
PMCID: PMC3270167  PMID: 21965060
3.  Brain metastasis from medullary thyroid carcinoma 
BMJ Case Reports  2010;2010:bcr0920103301.
The brain is an exceedingly rare site of metastasis in medullary thyroid carcinoma (MTC). A 50-year-old female who had a history of micro-MTC 11 years prior developed a cerebellar metastasis which was incidentally discovered. Imaging revealed a right cerebellar hemispheric mass with contrast enhancement on CT scans. Histopathologic exam demonstrated a metastatic tumour composed of nodules and sheets of large tumour cells with abundant cytoplasm. Immunohistochemistry confirmed the origin from a MTC. This case report highlights the unique features of an unusual metastatic brain tumour, which followed an indolent course for a long time despite multiple distant metastases.
doi:10.1136/bcr.09.2010.3301
PMCID: PMC3029950  PMID: 22802478
4.  Proteins involved in regulating bone invasion in skull base meningiomas 
Acta Neurochirurgica  2012;155(3):421-427.
Background
Bone invasive skull base meningiomas are a subset of meningiomas that present a unique clinical challenge due to brain and neural structure involvement and limitations in complete surgical resection, resulting in higher recurrence and need for repeat surgery. To date, the pathogenesis of meningioma bone invasion has not been investigated. We investigated immunoexpression of proteins implicated in bone invasion in other tumor types to establish their involvement in meningioma bone invasion.
Methods
Retrospective review of our database identified bone invasive meningiomas operated on at our institution over the past 20 years. Using high-throughput tissue microarray (TMA), we established the expression profile of osteopontin (OPN), matrix metalloproteinase-2 (MMP2), and integrin beta-1 (ITGB1). Differential expression in tumor cell and vasculature was evaluated and comparisons were made between meningioma anatomical locations.
Results
MMP2, OPN, and ITGB1 immunoreactivity was cytoplasmic in tumor and/or endothelial cells. Noninvasive transbasal meningiomas exhibited higher vascular endothelial cell MMP2 immunoexpression compared to invasive meningiomas. We found higher expression levels of OPN and ITGB1 in bone invasive transbasal compared to noninvasive meningiomas. Strong vascular ITGB1 expression extending from the endothelium through the media and into the adventitia was found in a subset of meningiomas.
Conclusions
We have demonstrated that key proteins are differentially expressed in bone invasive meningiomas and that the anatomical location of bone invasion is a key determinant of expression pattern of MMP1, OPN, and ITGB1. This data provides initial insights into the pathophysiology of bone invasion in meningiomas and identifies factors that can be pursued as potential therapeutic targets.
doi:10.1007/s00701-012-1577-9
PMCID: PMC3569595  PMID: 23238945
Bone invasion; Integrins; Matrix metalloproteinase; Meningioma; Osteopontin; Transbasal meningioma
5.  Is the Time Necessary to Obtain Preoperative Stabilization a Predictive Index of Outcome in Neonatal Congenital Diaphragmatic Hernia? 
Background. The study aims to verify if the time of preoperative stabilization (≤24 or >24 hours) could be predictive for the severity of clinical condition among patients affected by congenital diaphragmatic hernia. Methods. 55 of the 73 patients enrolled in the study achieved presurgical stabilization and underwent surgical correction. Respiratory and hemodynamic indexes, postnatal scores, the need for advanced respiratory support, the length of HFOV, tracheal intubation, PICU, and hospital stay were compared between patients reaching stabilization in ≤24 or >24 hours. Results. Both groups had a 100% survival rate. Neonates stabilized in ≤24 hours are more regular in the postoperative period and had an easier intensive care path; those taking >24 hours showed more complications and their care path was longer and more complex. Conclusions. The length of preoperative stabilization does not affect mortality, but is a valid parameter to identify difficulties in survivors' clinical pathway.
doi:10.1155/2012/402170
PMCID: PMC3259488  PMID: 22262976
6.  Panbacterial real-time PCR to evaluate bacterial burden in chronic wounds treated with Cutimed™ Sorbact™ 
The impact of polymicrobial bacterial infection on chronic wounds has been studied extensively, but standard bacteriological analysis is not always sensitive enough. Molecular approaches represent a promising alternative to the standard bacteriological analysis. This work aimed to assess the usefulness of a panbacterial quantitative real-time PCR reaction to quantitate the total bacterial load in chronic wounds treated with Cutimed™ Sorbact™, a novel therapeutic approach based on hydrophobic binding of bacteria to a membrane. The results obtained by panbacterial real-time PCR on conserved sequences of the bacterial 16S gene show that the bacterial burden significantly decreased in 10 out of 15 healing chronic wounds, and did not change in 5 out of 5 non-healing chronic wounds. On the contrary, classical culture for S. aureus and P. aeruginosa, and real-time PCR for Bacteroides and Fusobacterium did not show any correlation with the clinical outcome. Our study also shows that quantification of chronic wounds by panbacterial real-time PCR is to be performed on biopsies and not on swabs. These results show that panbacterial real-time PCR is a promising and quick method of determining the total bacterial load in chronic wounds, and suggest that it might be an important biomarker for the prognosis of chronic wounds under treatment.
doi:10.1007/s10096-011-1473-x
PMCID: PMC3364422  PMID: 22113306
7.  Anti-inflammatory activity of monogalactosyldiacylglycerol in human articular cartilage in vitro: activation of an anti-inflammatory cyclooxygenase-2 (COX-2) pathway 
Introduction
The mono- and digalactosyldiacylglycerol (MGDG and DGDG) galactolipids have been purified from the thermophilic blue-green alga Phormidium sp. ETS-05 that colonizes the therapeutic thermal mud of Abano Terme and Montegrotto Terme, Italy. Both compounds present a marked composition in polyunsaturated fatty acids, mainly omega-3. The therapeutic thermal mud is applied mainly to osteoarthritic cartilage patients. In the present study the effect of MGDG treatment on proteins and factors expressed by human articular cartilage cells in culture and on pathways activated in inflammatory conditions was studied.
Methods
Primary cultures of human articular chondrocytes were used at cell passage number 1 (P1). Cells were treated in serum-free medium with inflammatory cytokines in the presence and in the absence of MGDG. Western blot was performed on collected medium and on cell layers. At least three different experiments were performed on primary cultures. The quantitation of the MGDG effect was performed by densitometric scanning of Western blots. p38 Mitogen Activated Protein Kinase (p38) activation, Nuclear Factor-kappaB (NF-kB) activation and Prostaglandin E2 (PGE2) quantitation were performed by commercially available assays. Results are given as the mean values ± SD. All statistical analyses were performed using GraphPad software. The two-tailed Student's t -test was performed.
Results
We report that MGDG: 1) represses the expression of interleukin-6 (IL-6) and interleukin-8 (IL-8) induced by interleukin-1alpha (IL-1α) or IL-1α + tumor necrosis factor α (TNFα) interfering with the p38 and NF-kB pathways; 2) is not toxic for the cells and does not affect the cell phenotype; 3) strongly enhances COX-2 expression induced by IL-1α or IL-1α + TNFα; 4) represses mPGES expression induced by IL-1α and the synthesis of PGE2 and induces the synthesis of 15-deoxy-Δ 12,14-prostaglandin J2 (15ΔPGJ2). In addition, the COX-2 product 15ΔPGJ2 added to the cells: 1) strongly represses IL-6 and IL-8 induced by IL-1α; 2) represses mPGES expression induced by IL-1α and the synthesis of PGE2.
Conclusions
All together these data suggest that MGDG has an anti-inflammatory activity in human articular cartilage and possibly activates an anti-inflammatory loop triggered by COX-2 via 15ΔPGJ2 production, indicating a possible role of COX-2 in resolution of inflammation. The purified compound is a novel anti-inflammatory agent potentially active for human articular cartilage pathologies related to inflammation.
doi:10.1186/ar3367
PMCID: PMC3218907  PMID: 21682897
8.  Upper limb motor function in young adults with spina bifida and hydrocephalus 
Objective
The objective of the study was to measure upper limb motor function in young adults with spina bifida meningomyelocele (SBM) and typically developing age peers.
Method
Participants were 26 young adults with SBM, with a Verbal or Performance IQ score of at least 70 on the Wechsler scales, and 27 age- and gender-matched controls. Four upper limb motor function tasks were performed under four different visual and cognitive challenge conditions. Motor independence was assessed by questionnaire.
Results
Fewer SBM than control participants obtained perfect posture and rebound scores. The SBM group performed less accurately and was more disrupted by cognitive challenge than controls on limb dysmetria tasks. The SBM group was slower than controls on the diadochokinesis task. Adaptive motor independence was related to one upper limb motor task, arm posture, and upper rather than lower spinal lesions were associated with less motor independence.
Conclusions
Young adults with SBM have significant limitations in upper limb function and are more disrupted by some challenges while performing upper limb motor tasks. Within the group of young adults with SBM, upper spinal lesions compromise motor independence more than lower spinal lesions.
doi:10.1007/s00381-009-0948-x
PMCID: PMC3075008  PMID: 19672605
Spina bifida; Upper limb motor function; Quality of life
9.  Altered Effective Connectivity Network of the Amygdala in Social Anxiety Disorder: A Resting-State fMRI Study 
PLoS ONE  2010;5(12):e15238.
The amygdala is often found to be abnormally recruited in social anxiety disorder (SAD) patients. The question whether amygdala activation is primarily abnormal and affects other brain systems or whether it responds “normally” to an abnormal pattern of information conveyed by other brain structures remained unanswered. To address this question, we investigated a network of effective connectivity associated with the amygdala using Granger causality analysis on resting-state functional MRI data of 22 SAD patients and 21 healthy controls (HC). Implications of abnormal effective connectivity and clinical severity were investigated using the Liebowitz Social Anxiety Scale (LSAS). Decreased influence from inferior temporal gyrus (ITG) to amygdala was found in SAD, while bidirectional influences between amygdala and visual cortices were increased compared to HCs. Clinical relevance of decreased effective connectivity from ITG to amygdala was suggested by a negative correlation of LSAS avoidance scores and the value of Granger causality. Our study is the first to reveal a network of abnormal effective connectivity of core structures in SAD. This is in support of a disregulation in predescribed modules involved in affect control. The amygdala is placed in a central position of dysfunction characterized both by decreased regulatory influence of orbitofrontal cortex and increased crosstalk with visual cortex. The model which is proposed based on our results lends neurobiological support towards cognitive models considering disinhibition and an attentional bias towards negative stimuli as a core feature of the disorder.
doi:10.1371/journal.pone.0015238
PMCID: PMC3008679  PMID: 21203551
10.  Affective Response to a Loved One's Pain: Insula Activity as a Function of Individual Differences 
PLoS ONE  2010;5(12):e15268.
Individual variability in emotion processing may be associated with genetic variation as well as with psychological predispositions such as dispositional affect styles. Our previous fMRI study demonstrated that amygdala reactivity was independently predicted by affective-cognitive styles (phobic prone or eating disorders prone) and genotype of the serotonin transporter in a discrimination task of fearful facial expressions. Since the insula is associated with the subjective evaluation of bodily states and is involved in human feelings, we explored whether its activity could also vary in function of individual differences. In the present fMRI study, the association between dispositional affects and insula reactivity has been examined in two groups of healthy participants categorized according to affective-cognitive styles (phobic prone or eating disorders prone). Images of the faces of partners and strangers, in both painful and neutral situations, were used as visual stimuli. Interaction analyses indicate significantly different activations in the two groups in reaction to a loved one's pain: the phobic prone group exhibited greater activation in the left posterior insula. These results demonstrate that affective-cognitive style is associated with insula activity in pain empathy processing, suggesting a greater involvement of the insula in feelings for a certain cohort of people. In the mapping of individual differences, these results shed new light on variability in neural networks of emotion.
doi:10.1371/journal.pone.0015268
PMCID: PMC3002948  PMID: 21179564
11.  Diaphragmatic rupture with right colon and small intestine herniation after blunt trauma: a case report 
Introduction
Traumatic diaphragmatic hernias are an unusual presentation of trauma, and are observed in about 10% of diaphragmatic injuries. The diagnosis is often missed because of non-specific clinical signs, and the absence of additional intra-abdominal and thoracic injuries.
Case presentation
We report a case of a 59-year-old Italian man hospitalized for abdominal pain and vomiting. His medical history included a blunt trauma seven years previously. A chest X-ray showed right diaphragm elevation, and computed tomography revealed that the greater omentum, a portion of the colon and the small intestine had been transposed in the hemithorax through a diaphragm rupture. The patient underwent laparotomy, at which time the colon and small intestine were reduced back into the abdomen and the diaphragm was repaired.
Conclusions
This was a unusual case of traumatic right-sided diaphragmatic hernia. Diaphragmatic ruptures may be revealed many years after the initial trauma. The suspicion of diaphragmatic rupture in a patient with multiple traumas contributes to early diagnosis. Surgical repair remains the only curative treatment for diaphragmatic hernias. Prosthetic patches may be a good solution when the diaphragmatic defect is severe and too large for primary closure, whereas primary repair remains the gold standard for the closure of small to moderate sized diaphragmatic defects.
doi:10.1186/1752-1947-4-289
PMCID: PMC2936927  PMID: 20735836
12.  Intrauterine Growth Restriction and Differential Patterns of Hepatic Growth and Expression of IGF1, PCK2, and HSDL1 mRNA in the Sheep Fetus in Late Gestation1 
Biology of Reproduction  2009;80(6):1121-1127.
Fetal adaptations to periods of substrate deprivation can result in the programming of glucose intolerance, insulin resistance, and metabolic dysfunction in later life. Placental insufficiency can be associated with either sparing or sacrifice of fetal liver growth, and these different responses may have different metabolic consequences. It is unclear what intrahepatic mechanisms determine the differential responses of the fetal liver to substrate restriction. We investigated the effects of placental restriction (PR) on liver growth and the hepatic expression of SLC2A1, IGF1, IGF2, IGF1R, IGF2R, PPARGC1A, PPARA, PRKAA1, PRKAA2, PCK2, and HSDL1 mRNA in fetal sheep at 140–145 days of gestation. A mean gestational arterial partial pressure of oxygen less than 17 mmHg was defined as hypoxic, and a relative liver of weight more than 2 SD below the mean liver weight of controls was defined as reduced liver growth. Fetuses therefore were defined as control-normoxic (C-N; n = 9), PR-normoxic (PR-N; n = 7), PR-hypoxic (PR-H; n = 8), or PR-hypoxic reduced liver growth (PR-H RLG; n = 4). Hepatic SLC2A1 mRNA expression was highest (P < 0.05) in the PR-H fetuses, in which liver growth was maintained. Expression of IGF1 mRNA was decreased (P < 0.05) only in the PR-H RLG group. Hepatic expression of HSDL1, PPARGC1A, and PCK2 mRNA also were increased (P < 0.05) in the PR-H RLG fetuses. The present study highlights that intrahepatic responses to fetal substrate restriction may exist that protect the liver from decreased growth and, potentially, from a decreased responsiveness to the actions of insulin in postnatal life.
Intrauterine growth restriction results in differential growth of the fetal liver that is associated with changes in metabolic gene expression, including PCK2, and glucose transporters.
doi:10.1095/biolreprod.108.073569
PMCID: PMC2849808  PMID: 19208549
developmental biology; fetus; insulin-like growth factor receptor; liver; placenta
14.  Quantification of Hepatitis C Virus (HCV) RNA in a Multicenter Study: Implications for Management of HCV Genotype 1-Infected Patients▿  
Journal of Clinical Microbiology  2009;47(9):2931-2936.
Assessment of the viral load in hepatitis C virus (HCV) genotype 1-infected patients is critical before, during, and after antiviral therapy. In patients achieving a rapid virological response at week 4 of treatment, the viral load at the baseline is considered a predictive criterion of a sustained virological response 24 weeks after the discontinuation of treatment. A ≥2-log10 drop in the viral load at week 12 of treatment (early virological response) triggers the continuation of therapy. We organized a multicenter study (MS) for diagnostic laboratories involved in the quantification of HCV RNA. Commercial assays, including two based on real-time reverse transcription-PCR (TaqMan system), and in-house methods, were used by the 61 participants. The overall reproducibility of the commercial quantitative nucleic acid amplification techniques (qNAT) was acceptable. As the intermethod variability among commercial qNAT for HCV RNA was still present, the manufacturers of these test kits should join efforts to harmonize the means of quantification of HCV RNA. This study also shows that caution should be exercised when the baseline viral load is evaluated and when the 2-log10 reduction after 12 weeks of therapy is interpreted. Finally, this MS confirms the higher sensitivity of the commercial qNAT based on the TaqMan system, making them the elective assays for the monitoring of therapy.
doi:10.1128/JCM.00532-09
PMCID: PMC2738106  PMID: 19605574
15.  Serological levels of mutated p53 protein are highly detected at early stages in breast cancer patients 
The aim of this study was to compare the sensitivity of the serological level of anti-p53 antibodies in breast cancer patients and to correlate its expression level with patient age, histological stage and grade of tumor differentiation. Total p53 protein expression (mutant and wild-type) was also determined in the breast cancer tissues using immunohistochemistry (IHC). The serological levels of mutant p53 expression were found to be age-dependent, reaching the highest level at 50 years of age. Faint or low detection was observed in patients ≤30 years of age. Anti-p53-antibodies were detected in patients ≤40 and ≥61 years of age. The serological levels of mutant p53 protein were highly detected in all stages of breast cancer, including the early stages. However, anti-p53 antibodies reached a high level of detection only in stage III breast carcinomas. No expression was found in patients with benign breast disease. The detection of p53 mutations was dependent on the grade of tumor differentiation, achieving the highest level in the poorly differentiated breast carcinomas. Results from IHC were highly correlated with serological p53 mutational analysis. Our findings indicate that mutant p53 in serum is a promising novel parameter for the evaluation of cellular biology and the prognosis of breast cancer from its early stages using blood samples. Anti-p53 antibodies were demonstrated to be less sensitive in this study. It is also possible to use the expression of mutant p53 protein as a molecular marker to differentiate benign breast disease from breast carcinoma prior to surgery.
doi:10.3892/etm_00000056
PMCID: PMC3445953  PMID: 22993549
breast cancer; p53 mutational analysis; serological detection of p53 mutations
16.  Is Social Phobia a “Mis-Communication” Disorder? Brain Functional Connectivity during Face Perception Differs between Patients with Social Phobia and Healthy Control Subjects 
Recently, a differential recruitment of brain areas throughout the distributed neural system for face perception has been found in social phobic patients as compared to healthy control subjects. These functional abnormalities in social phobic patients extend beyond emotion-related brain areas, such as the amygdala, to include cortical networks that modulate attention and process other facial features, and they are also associated with an alteration of the task-related activation/deactivation trade-off. Functional connectivity is becoming a powerful tool to examine how components of large-scale distributed neural systems are coupled together while performing a specific function. This study was designed to determine whether functional connectivity networks among brain regions within the distributed system for face perception also would differ between social phobic patients and healthy controls. Data were obtained from eight social phobic patients and seven healthy controls by using functional magnetic resonance imaging. Our findings indicated that social phobic patients and healthy controls have different patterns of functional connectivity across brain regions within both the core and the extended systems for face perception and the default mode network. To our knowledge, this is the first study that shows that functional connectivity during brain response to socially relevant stimuli differs between social phobic patients and healthy controls. These results expand our previous findings and indicate that brain functional changes in social phobic patients are not restricted to a single specific brain structure, but rather involve a mis-communication among different sensory and emotional processing brain areas.
doi:10.3389/fnsys.2010.00152
PMCID: PMC2996271  PMID: 21152341
social phobia; functional connectivity; face perception; fMRI
17.  Effects of Visual Experience on the Human MT+ Functional Connectivity Networks: An fMRI Study of Motion Perception in Sighted and Congenitally Blind Individuals 
Human middle temporal complex (hMT+) responds also to the perception of non-visual motion in both sighted and early blind individuals, indicating a supramodal organization. Visual experience, however, leads to a segregation of hMT+ into a more anterior subregion, involved in the supramodal representation of motion, and a posterior subregion that processes visual motion only. In contrast, in congenitally blind subjects tactile motion activates the full extent of hMT+. Here, we used fMRI to investigate brain areas functionally connected with the two hMT+ subregions (seeds) during visual and tactile motion in sighted and blind individuals. A common functional connectivity network for motion processing, including bilateral ventral and dorsal extrastriate, inferior frontal, middle and inferior temporal areas, correlated with the two hMT+ seeds both in sighted and blind individuals during either visual or tactile motion, independently from the sensory modality through which the information was acquired. Moreover, ventral premotor, somatosensory, and posterior parietal areas correlated only with the anterior but not with the posterior portion of hMT+ in sighted subjects, and with both hMT+ seeds in blind subjects. Furthermore, a correlation between middle temporal and occipital areas with primary somatosensory seeds was demonstrated across conditions in both sighted and blind individuals, suggesting a cortico-cortical pathway that conveys non-visual information from somatosensory cortex, through posterior parietal regions, to ventral extrastriate cortex. These findings expand our knowledge about the development of the functional organization within hMT+ by showing that distinct patterns of brain functional correlations originate from the anterior and posterior hMT+ subregions as a result of visual experience.
doi:10.3389/fnsys.2010.00159
PMCID: PMC3010764  PMID: 21191477
human middle temporal complex; supramodality; visual motion; tactile motion; blindness; functional connectivity; fMRI
18.  Antiinflammatory effect of peripheral nerve blocks after knee surgery: clinical and biologic evaluation 
Anesthesiology  2008;109(3):484-490.
Background
Nerve blocks provide analgesia after surgery. We tested whether they have anti-inflammatory effects.
Methods
Patient had combined sciatic (single shot) and continuous femoral block (48 hours) (block group) or morphine patient-controlled analgesia (PCA group) after total knee arthroplasty. Pain at rest and upon movement was monitored at one (D1), four (D4) and seven days (D7) and one (M1) and three months (M3) after surgery. Knee inflammation was evaluated (skin temperature, knee circumference) before surgery and at D1, D4, D7, M1 and M3. Plasma cytokine concentrations (IL6, IL1β, TNF, IL10, sTNF-R1) were measured before surgery, then at four hours, D1, D4 and D7 after surgery. Capsule and synovial membrane cytokines were measured (IL6, TNF, IL1, IL10). Knee flexion was evaluated before surgery and at D1, D4, D7, M1 and M3. We monitored morphine use and recovery time to autonomy.
Results
Pain at rest and upon movement was lower in the block group than in PCA patients between D1 and D7 (Anova; P<0.005). Knee flexion was improved in the block group for D1 to M1 (Anova; p<0.0001). Block group patients recovered non-assisted mobilization (t test; p=0.04) and toilet use (t test; p=0.03) more rapidly. Knee circumference and skin temperature were lower in the block group between D1 and D7 (Anova; p<0.05). Synovial membrane IL1 (p<0.05) and IL10 (p<0.01) increased and plasma IL6 and sTNF-R1 peaked at 24 hours, with no difference between groups.
Conclusion
Nerve blocks inhibited clinical inflammation after total knee arthroplasty with no change in tissue and plasma cytokine concentrations.
doi:10.1097/ALN.0b013e318182c2a1
PMCID: PMC2758602  PMID: 18719447
Aged; Amides; administration & dosage; therapeutic use; Analgesia, Patient-Controlled; Analgesics, Opioid; administration & dosage; Anesthetics, Local; administration & dosage; therapeutic use; Anti-Inflammatory Agents; administration & dosage; therapeutic use; Arthroplasty, Replacement, Knee; adverse effects; Cytokines; blood; metabolism; Female; Femoral Nerve; drug effects; Follow-Up Studies; Humans; Knee Joint; surgery; Male; Morphine; administration & dosage; Nerve Block; methods; Pain Measurement; statistics & numerical data; Pain, Postoperative; drug therapy; Peripheral Nerves; drug effects; immunology; Range of Motion, Articular; drug effects; Sciatic Nerve; drug effects
19.  Lack of impact of intravenous lidocaine on analgesia, functional recovery, and nociceptive pain threshold after total hip arthroplasty 
Anesthesiology  2008;109(1):118-123.
Background
The analgesic effect of perioperative low doses intravenous lidocaine has been demonstrated after abdominal surgery. This study aimed to evaluate whether a continuous intravenous (IV) low-dose lidocaine infusion reduced postoperative pain and modified nociceptive pain threshold after total hip arthroplasty.
Methods
Sixty patients participated in this randomised double-blinded study. Thirty patients received lidocaine 1% (lido group) with a 1.5 mg.kg−1 IV bolus in 10 min followed by a 1.5 mg.kg−1.h−1 IV infusion and other patients received saline (control group). These regimens were started 30 min before surgical incision and stopped one hour after skin closure. Lidocaine blood concentrations were measured at the end of administration. In both groups, postoperative analgesia was provided exclusively by patient-controlled IV morphine. Pain scores, morphine consumption, operative hip flexion were recorded over 48 h. In addition, pressure pain thresholds and the extent of hyperalgesia around surgical incision were systematically measured at 24 and 48h.
Results
In comparison with the placebo, lidocaine did not induce any opioid-sparing effect during the first 24 hours (− 2 mg with 95 CI [−5; 9]; p = 0.55). There was no significant difference regarding the effects of lidocaine and placebo on pain score, pressure pain thresholds, extent in the area of hyperalgesia, and maximal degree of active hip flexion tolerated. Mean plasma lidocaine concentration was 2,1 ± 0,4 μg/ml.
Conclusion
Low dose perioperative IV lidocaine after total hip arthroplasty offers no beneficial effect on postoperative analgesia and does not modify pressure and tactile pain thresholds.
doi:10.1097/ALN.0b013e31817b5a9b
PMCID: PMC2728117  PMID: 18580181
Aged; Anesthetics, Local; administration & dosage; Arthroplasty, Replacement, Hip; adverse effects; Double-Blind Method; Female; Humans; Infusions, Intravenous; Lidocaine; administration & dosage; Male; Middle Aged; Pain Measurement; drug effects; methods; Pain Threshold; drug effects; physiology; Pain, Postoperative; etiology; pathology; prevention & control; Recovery of Function; drug effects; physiology
20.  Information gaps for patients requiring craniotomy for benign brain lesion: a qualitative study 
Journal of Neuro-Oncology  2009;96(2):241-247.
Doctor–patient communication in the setting of a life-threatening illness poses considerable challenges. This study aimed to determine the information needs of a subset of neurosurgical patients. Qualitative case study methodology was used. Twenty-five semi-structured interviews were conducted with ambulatory adult patients who had undergone surgery for a benign brain tumor, arteriovenous malformation, or unruptured aneurysm. Interviews were digitally audio recorded and transcribed, and the data subjected to thematic analysis. Six overarching themes emerged from the data: (1) the amount of information patients want varies; (2) the type of information needed is not limited to information about treatment options and risks; (3) patients engage in independent information seeking for a variety of reasons; (4) patients consider compassion from their surgeon as important; (5) direct communication with the surgeon post-operatively is very important; and (6) patients’ information needs are greatest post-operatively. Many patients felt that the amount and quality of information they received was not sufficient, particularly regarding post-operative recovery and long-term life issues, leading many to do their own research. The findings from this study emphasize the need for improved communication with patients so they can participate meaningfully in choices about their treatment, give a truly informed consent, and effectively participate in their own recovery.
doi:10.1007/s11060-009-9955-8
PMCID: PMC2808535  PMID: 19575147
Information needs; Neurosurgery; Qualitative research
21.  Integration of Gravitational Torques in Cerebellar Pathways Allows for the Dynamic Inverse Computation of Vertical Pointing Movements of a Robot Arm 
PLoS ONE  2009;4(4):e5176.
Background
Several authors suggested that gravitational forces are centrally represented in the brain for planning, control and sensorimotor predictions of movements. Furthermore, some studies proposed that the cerebellum computes the inverse dynamics (internal inverse model) whereas others suggested that it computes sensorimotor predictions (internal forward model).
Methodology/Principal Findings
This study proposes a model of cerebellar pathways deduced from both biological and physical constraints. The model learns the dynamic inverse computation of the effect of gravitational torques from its sensorimotor predictions without calculating an explicit inverse computation. By using supervised learning, this model learns to control an anthropomorphic robot arm actuated by two antagonists McKibben artificial muscles. This was achieved by using internal parallel feedback loops containing neural networks which anticipate the sensorimotor consequences of the neural commands. The artificial neural networks architecture was similar to the large-scale connectivity of the cerebellar cortex. Movements in the sagittal plane were performed during three sessions combining different initial positions, amplitudes and directions of movements to vary the effects of the gravitational torques applied to the robotic arm. The results show that this model acquired an internal representation of the gravitational effects during vertical arm pointing movements.
Conclusions/Significance
This is consistent with the proposal that the cerebellar cortex contains an internal representation of gravitational torques which is encoded through a learning process. Furthermore, this model suggests that the cerebellum performs the inverse dynamics computation based on sensorimotor predictions. This highlights the importance of sensorimotor predictions of gravitational torques acting on upper limb movements performed in the gravitational field.
doi:10.1371/journal.pone.0005176
PMCID: PMC2668755  PMID: 19384420
22.  The validation of the Italian Perceived Disability Scale (IPDS) in chronic daily headache sufferers 
The goals of this study were to assess the validity and usefulness of a new scale and to assess disability in a sample of patients with chronic daily headache. Participants were a convenience sample of 61 adult outpatients admitted to the Department of Medical Sciences of the Sant’Andrea Hospital in Rome, between September 2007 and May 2008. Inclusion criteria were, a diagnosis of chronic daily headache (illness duration >5 years). Patients were administered the Beck Hopelessness Scale (BHS), a specific section of the Mini-International Neuropsychiatric Interview (MINI) assessing suicidal intent, the Gotland Male Depression Scale (GMDS), and a scale devised to measure the degree of disability caused by the headache [Italian Perceived Disability Scale (IPDS)]. Analyses indicated that the IPDS had good internal consistency (Cronbach alpha = 0.93; average inter-item correlation = 0.40), and good convergent validity, with moderate to strong associations with measures assessing emotional distress (BHS, r = 0.47; P < 0.0001; GMDS, r = 0.72; P < 0.001). A single-item, logistic regression analysis indicated that the IPDS is able to predict suicide intent (Wald χ2 = 5.04; P < 0.05) in chronic daily headache patients. The IPDS is a brief instrument that is useful for comparisons with other chronic illnesses, and it may be used both for basic research and clinical applications when screening for comorbidity with emotional distress and disorders.
Electronic supplementary material
The online version of this article (doi:10.1007/s10194-008-0076-0) contains supplementary material, which is available to authorized users.
doi:10.1007/s10194-008-0076-0
PMCID: PMC3451762  PMID: 18854920
Chronic daily headache; Self-injurious behavior; Disability; Depression; Hopelessness
23.  Performance of a Protected Wireless Sensor Network in a Fire. Analysis of Fire Spread and Data Transmission 
Sensors (Basel, Switzerland)  2009;9(8):5878-5893.
The paper deals with a Wireless Sensor Network (WSN) as a reliable solution for capturing the kinematics of a fire front spreading over a fuel bed. To provide reliable information in fire studies and support fire fighting strategies, a Wireless Sensor Network must be able to perform three sequential actions: 1) sensing thermal data in the open as the gas temperature; 2) detecting a fire i.e., the spatial position of a flame; 3) tracking the fire spread during its spatial and temporal evolution. One of the great challenges in performing fire front tracking with a WSN is to avoid the destruction of motes by the fire. This paper therefore shows the performance of Wireless Sensor Network when the motes are protected with a thermal insulation dedicated to track a fire spreading across vegetative fuels on a field scale. The resulting experimental WSN is then used in series of wildfire experiments performed in the open in vegetation areas ranging in size from 50 to 1,000 m2.
doi:10.3390/s90805878
PMCID: PMC3312421  PMID: 22454563
wireless sensor network; thermal insulation; natural fire; fire spread
24.  Mental turmoil, suicide risk, illness perception, and temperament, and their impact on quality of life in chronic daily headache 
The Journal of Headache and Pain  2008;9(6):349-357.
To evaluate the relationship among quality of life, temperament, illness perception, and mental turmoil in patients affected by chronic daily headache with concomitant medication overuse headache. Participants were 116 consecutive adult outpatients admitted to the Department of General Medicine of the Sant’Andrea Hospital in Rome, between January 2007 and December 2007 with a diagnosis of chronic daily headache (illness duration >5 years). Patients were administered the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-autoquestionnaire version (TEMPS-A), the Beck Hopelessness Scale (BHS), the Hamilton Rating Scale for Depression (HAM-D), the Mini-International Neuropsychiatric Interview (MINI), the Revised Illness Perception Questionnaire (IPQ), the Suicide Score Scale (SSS), and the Quality of Life Index (QL-Index). Twenty-eight percent of the patients evidenced moderate to severe depression, and 35% evidenced severe hopelessness. Analyses also indicated that quality of life, temperament, illness perception, and psychological turmoil are associated. However, a hierarchical multivariate regression analysis with quality of life as dependent variable indicated that only a model with mental turmoil variables may fit data; further, only the MINI suicidal intent resulted associated with quality of life (standardized regression coefficient = −0.55; t = −3.06; P < 0.01). Suicide risk may play a central role in affecting the quality of life of patients with chronic headache. The investigation of the interplay of factors that precipitate suicide risk should include assessment of chronic headache and its effects on wellbeing.
doi:10.1007/s10194-008-0072-4
PMCID: PMC3452079  PMID: 18953488
Chronic daily headache; Medication overuse headache; Self-injurious behaviour; Suicide; Depression; Hopelessness; Quality of life
25.  Noncontiguous Bilateral Esthesioneuroblastoma: A Case Report 
Skull Base  2007;17(6):405-407.
ABSTRACT
Esthesioneuroblastoma is a rare malignant neoplasm arising from the olfactory epithelium. This tumor has a tendency to originate from one side of the nasal cavity or paranasal sinuses with frequent extension into the contralateral nasal cavity through direct invasion. A review of the literature reveals numerous case reports describing esthesioneuroblastoma with unilateral or bilateral involvement; however, there have been no known reports of bilateral noncontiguous (multifocal) esthesioneuroblastoma. We present a unique case of a patient diagnosed with two separate primary esthesioneuroblastomas who was managed with preoperative radiation followed by surgical resection of the tumor. This case illustrates that esthesioneuroblastoma must remain as part of the differential diagnosis for a multifocal, noncontiguous intranasal and paranasal sinus mass.
doi:10.1055/s-2007-986459
PMCID: PMC2111137  PMID: 18449333
Esthesioneuroblastoma; noncontiguous sinus mass; olfactory neuroblastoma

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