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Background: The International Anorectal Physiology Working Group (IAPWG) suggests a standardized protocol to perform high-resolution anorectal manometry. The applicability and possible limitations of the IAPWG protocol in performing three-dimensional high-definition anorectal manometry (3D-ARM) have still to be extensively evaluated. Methods: The IAPWG protocol was applied in performing 3D-ARM. Anorectal manometry (ARM) and a balloon expulsion test (BET) were performed according to IAPGW protocol in 290 patients. Key Results: A total of 84 males and 206 females (mean age 57.1 ± 15.7 years) were enrolled in six Italian centers. The reasons for which the patients were sent to perform 3D-ARM were: constipation (53.1%), fecal incontinence (26.9%), anal pain (3.1%), postsurgical (3.8%) and presurgical evaluation (4.8%), prolapse (3.4%), anal fissure (2.8%), and other (2.1%). Due to organic and functional conditions (low rectal anterior resections, rectal prolapses, and J-pouch after colectomy), we were unable to perform a complete 3D-ARM on six patients. Overall, a complete 3D-ARM and BET following IAPWG protocol was carried out in 284 patients (97.9%). The following were recorded: rest pressure (81.9 ± 32.0 mmHg) and length of the anal sphincter (37.0 ± 6.2 cm), maximum anal squeeze pressure (201.6 ± 81.3 mmHg), squeeze duration (22.0 ± 8.8 s), maximum rectal (48.7 ± 41.0 mmHg) and minimum anal pressure (73.3 ± 36.5 mmHg) during push, presence/absence of a dyssynergic pattern, cough reflex and rectal sensations (first constant sensation 48.4 ± 29.5 mL, desire to defecate 83.7 ± 52.1 mL, and maximum tolerated volume 149.5 ± 72.6 mL), and presence/absence of rectoanal inhibitory reflex. Mean 3D-ARM registration time was 14 min 7 s ± 3 min 12 s. Conclusions: This is the first multicentric study that evaluates the applicability of the IAPWG protocol in 3D-ARM performed in different manometric laboratories (both gastroenterological and surgical). The IAPWG protocol was easy to perform and was not time consuming. A diagnosis according to the London Classification was easily obtained in most patients in which 3D-ARM was carried out. No clear limitations to the applicability of the IAPWG protocol were detected. [ABSTRACT FROM AUTHOR]

Background: Left bundle branch area pacing (LBBAP) is an emerging cardiac pacing modality that preserves fast electrical activation of the ventricles and provides very good electrical measures. Little is known on mechanical ventricular activation during this pacing modality. Methods: We prospectively enrolled patients receiving LBBAP. Electrocardiographic and electrical parameters were evaluated at implantation, < 24 h and 3 months. Transthoracic echocardiography with strain analysis was performed at baseline and after 3 months, when ventricular mechanical activation and synchrony were analyzed by time-to-peak standard deviation (TPSD) of strain curves for both ventricles. Intraventricular left ventricular (LV) dyssynchrony was investigated by LV TPSD and interventricular dyssynchrony by left ventricle–right ventricle TPSD (LV-RV TPSD). Results: We screened 58 patients with permanent pacing indication who attempted LBBAP. Procedural success was obtained in 56 patients (97%). Strain data were available in 50 patients. QRS duration was 124.1 ± 30.7 ms at baseline, while paced QRS duration was 107.7 ± 13.6 ms (p < 0.001). At 3 months after LBBAP, left ventricular ejection fraction (LVEF) increased from 52.9 ± 10.6% at baseline to 56.9 ± 8.4% (p = 0.004) and both intraventricular LV dyssynchrony and interventricular dyssynchrony significantly improved (LV TPSD reduction from 38.2 (13.6–53.9) to 15.1 (8.3–31.5), p < 0.001; LV-RV TPSD from 27.9 (10.2–41.5) to 13.9 (4.3–28.7), p = 0.001). Ameliorations with LBBAP were consistent in all subgroups, irrespective of baseline QRS duration, types of intraventricular conduction abnormalities, and LVEF. Conclusions: Echocardiographic strain analysis shows that LBBAP determines a fast and synchronous biventricular contraction with a stereotype mechanical activation, regardless of baseline QRS duration, pattern, and LV function. [ABSTRACT FROM AUTHOR]

Purpose: Intestinal ultrasound (IUS) is widely used as the first exam in patients with suspected inflammatory bowel disease (IBD). This study investigated the accuracy of several IUS parameters, including increased bowel wall thickening (BWT), in detecting IBD in a paediatric population. Methods: The study included an unselected series of 113 patients aged 2–18 years (mean age 10.8 years, 65 male), referred for recurrent abdominal pain or altered bowel habits, without known organic diseases, to perform an IUS as first investigation of a diagnostic workup. Patients with full systematic IUS examination, clinical and biochemical exams, and ileocolonoscopy or an uneventful follow-up at least one year follow up were eligible. Results: 23 IBD patients (20.4%; 8 ulcerative colitis, 12 Crohn's disease and 3 indeterminate colitis) were diagnosed. We found that increased BWT > 3 mm (OR 5.4), altered IUS bowel pattern (IUS-BP, OR 9.8) and mesenteric hypertrophy (MH, OR 5.2) accurately identified IBD at the multivariate analysis. IUS-BP, MH and BWT > 3 mm had a sensitivity of 78.3%, 65.2% and 69.6% and a specificity of 93.3%, 92.2% and 96.7%, respectively. The combination of these three alterations increased the specificity up to 100%, whilst decreased sensitivity to 56.5%. Conclusion: Among several US parameters suggestive of IBD, the increased BWT, MH and altered echopattern are independent predictors of IBD. The ultrasonographic diagnosis of IBD could be more accurate if relied on combination of different sonographic parameters, than on the sole BWT evaluation. [ABSTRACT FROM AUTHOR]

This study investigated the performance of a novel integrated bio-electrochemical system for synergistic hydrogen production from a process combining a dark fermentation reactor and a galvanic cell. The operating principle of the system is based on the electrochemical conversion of protons released upon dissociation of the acid metabolites of the biological process and is mediated by the electron flow from the galvanic cell, coupling biochemical and electrochemical hydrogen production. Accordingly, the galvanic compartment also generates electricity. Four different experimental setups were designed to provide a preliminary assessment of the integrated bio-electrochemical process and identify the optimal configuration for further tests. Subsequently, dark fermentation of cheese whey was implemented both in a stand-alone biochemical reactor and in the integrated bio-electrochemical process. The integrated system achieved a hydrogen yield in the range 75.5–78.8 N LH2/kg TOC, showing a 3 times improvement over the biochemical process. [ABSTRACT FROM AUTHOR]

Purpose: Sacubitril/valsartan has been associated with a positive reverse left ventricular remodelling in patients with heart failure with reduced ejection fraction (HFrEF). These patients may also benefit from an ICD implant. We aimed to assess EF improvement after 6 months of treatment with sacubitril/valsartan, evaluating when ICD as primary prevention was no longer indicated. Methods: Multicentre, observational, prospective study enrolling all consecutive patients with HFrEF and EF ≤ 35% with an ICD as primary prevention and starting treatment with sacubitril/valsartan (NCT03935087). Resynchronization therapy and patients experiencing appropriate ICD therapies before sacubitril/valsartan were excluded. Results: Two-hundred-and-thirty patients were enrolled (73.9% males, mean age 64.3 ± 12.1 years) After 6 months of treatment, a reduction in left ventricular end-diastolic and end-systolic volumes was noted and LVEF increased from 28.3 ± 5.6% to 32.2 ± 6.5% (p < 0.001). At 6 months, a non-ischemic aetiology of cardiomyopathy and a final dose of sacubitril/valsartan > 24/26 mg twice daily were associated with a higher probability of an absolute increase of > 5% in LVEF. A total of 5.3% of primary prevention patients still had an arrhythmic event in the first 6 months after treatment with sacubitril/valsartan started. Conclusions: Sacubitril/valsartan improves systolic function in HFrEF, mainly due to reverse left ventricular remodelling. Improvement in EF after 6 months of treatment could help prevent ICD implantation in nearly one out of four patients, with important clinical and economic implications. However, the risk of sudden cardiac death in this recovered HFrEF population has not been thoroughly studied, and the present data should be interpreted only as hypothesis-generating. [ABSTRACT FROM AUTHOR]

Early B-cell factor-1 (EBF1) is a transcription factor with an important role in cell lineage specification and commitment during the early stage of cell maturation. Originally described during B-cell maturation, EBF1 was subsequently identified as a crucial molecule for proper cell fate commitment of mesenchymal stem cells into adipocytes, osteoblasts and muscle cells. In vessels, EBF1 expression and function have never been documented. Our data indicate that EBF1 is highly expressed in peri-endothelial cells in both tumor vessels and in physiological conditions. Immunohistochemistry, quantitative reverse transcription polymerase chain reaction (RT-qPCR) and fluorescence-activated cell sorting (FACS) analysis suggest that EBF1-expressing peri-endothelial cells represent bona fide pericytes and selectively express well-recognized markers employed in the identification of the pericyte phenotype (SMA, PDGFRβ, CD146, NG2). This observation was also confirmed in vitro in human placenta-derived pericytes and in human brain vascular pericytes (HBVP). Of note, in accord with the key role of EBF1 in the cell lineage commitment of mesenchymal stem cells, EBF1-silenced HBVP cells showed a significant reduction in PDGFRβ and CD146, but not CD90, a marker mostly associated with a prominent mesenchymal phenotype. Moreover, the expression levels of VEGF, angiopoietin-1, NG2 and TGF-β, cytokines produced by pericytes during angiogenesis and linked to their differentiation and activation, were also significantly reduced. Overall, the data suggest a functional role of EBF1 in the cell fate commitment toward the pericyte phenotype. [ABSTRACT FROM AUTHOR]

Properties of the funny current (If) have been studied in several animal and cellular models, but so far little is known concerning its properties in human pacemaker cells. This work provides a detailed characterization of If in human-induced pluripotent stem cell (iPSC)–derived pacemaker cardiomyocytes (pCMs), at different time points. Patch-clamp analysis showed that If density did not change during differentiation; however, after day 30, it activates at more negative potential and with slower time constants. These changes are accompanied by a slowing in beating rate. If displayed the voltage-dependent block by caesium and reversed (Erev) at − 22 mV, compatibly with the 3:1 K+/Na+ permeability ratio. Lowering [Na+]o (30 mM) shifted the Erev to − 39 mV without affecting conductance. Increasing [K+]o (30 mM) shifted the Erev to − 15 mV with a fourfold increase in conductance. pCMs express mainly HCN4 and HCN1 together with the accessory subunits CAV3, KCR1, MiRP1, and SAP97 that contribute to the context-dependence of If. Autonomic agonists modulated the diastolic depolarization, and thus rate, of pCMs. The adrenergic agonist isoproterenol induced rate acceleration and a positive shift of If voltage-dependence (EC50 73.4 nM). The muscarinic agonists had opposite effects (Carbachol EC50, 11,6 nM). Carbachol effect was however small but it could be increased by pre-stimulation with isoproterenol, indicating low cAMP levels in pCMs. In conclusion, we demonstrated that pCMs display an If with the physiological properties expected by pacemaker cells and may thus represent a suitable model for studying human If-related sinus arrhythmias. [ABSTRACT FROM AUTHOR]

Introduction: Lymphangiomas are relatively uncommon head and neck region lymphatic malformations. Although surgery can be still considered the mainstay of treatment, sclerotherapy by OK-432 is becoming a widespread treatment option. The aim of this article is to present and discuss the management and outcomes of a series of cases of lymphangiomas. Methods: All patients with lymphangiomas who were treated from 2010 to 2018 were reviewed. The following data were recorded: age, gender, subtype, staging, type of treatment, outcome, and recurrence. Results: Fifteen patients (9 females, 6 males) were included with 2 microcystic and 13 macrocystic lymphangiomas. Six patients underwent surgery with excision (5 with a complete success, one with a fair success), whereas the remaining 9 subjects underwent sclerotherapy by OK-432 (6 with a complete success, 3 with a fair success). No postoperative complications were observed. Conclusions: All modes of treatment are important in properly selected patients affected by lymphangiomas. OK-432 therapy is a safe and effective option in the treatment of head and neck lymphangiomas. [ABSTRACT FROM AUTHOR]

Purpose: Nasal packing is a common but unpleasant procedure in patients who undergo endoscopic sinus surgery (ESS). The aim of this study was to assess whether a glove-finger pack strategy would reduce pain compared to lidocaine-soaked packs after ESS. Methods: A prospective randomized controlled trial enrolling 120 consecutive patients affected by chronic rhinosinusitis, who underwent bilateral ESS. At the end of surgery 62 subjects received 10 cm non-absorbable pack soaked with 5 mL of 2%-lidocaine solution and 58 received a 10 cm non-absorbable pack coated with a latex free glove finger soaked with saline solution. Data concerning pain were collected using a 0 to 10 visual analogue scale at post-operative hours 1, 4, 8, and 16 and at pack removal (24 h ± 15 min). All post-operative analgesic rescue doses were registered. Also, bleeding was reported. Results: The mean VAS score during pack-removal was significantly lower in glove-finger group than in the lidocaine group (3.22 ± 2.16 vs 4.89 ± 2.90, p = 0.0012). There was no statistically significant difference between re-soaking lidocaine-soaked-packs with saline solution or lidocaine at pack removal time (p = 0.42). Conclusion: Glove-finger nasal pack seems to provide better pain control after ESS, when compared with lidocaine-soaked pack, especially at pack removal time. [ABSTRACT FROM AUTHOR]

Purpose: Endoscopic approach represents a valid alternative to conventional septoplasty. The aim of this study is to analyze the objective and subjective data on 276 patients, who underwent traditional (147) or endoscopic (129) septoplasty. Methods: This is a prospective observational study on 276 consecutive patients affected by deviated nasal septum (DNS), who underwent isolated septoplasty between 2011 and 2018. 147 of them were treated using an "open" approach, while 129 were treated with an endoscopic approach. The two groups were compared 3 months after surgery: the objective results (complications such as bleeding, hematoma, pain, synechiae, septal tears and incomplete correction), objective (rhinomanometric data) and subjective measurements (NOSE questionnaires). Results: Both techniques are effective in decreasing nasal obstruction and discharge. Complications such as pain, synechiae, early postoperative bleeding, septal tears and incomplete correction are less frequent in the endoscopic group (p < 0.05). The rhinomanometric analysis reveal improvement in both groups without statistical differences. Subjective questionnaires show a good symptoms relief with an improved quality of life in all 276 patients without statistical difference between the two gropus. Conclusions: Both techniques are effective in reducing nasal obstruction and related symptoms with fewer overall complications in the endoscopic approach. The endoscope provides improved field of view, less mucosal damages and a more anatomic dissection. Finally, such approach can be a valuable teaching tool for assistants, residents and students. [ABSTRACT FROM AUTHOR]

Purpose: Esophageal dysmotility and disorders of the lower esophageal sphincter are well documented in morbidly obese patients. Esophageal achalasia has been reported in up to 1% of obese patients but the development of such esophageal motility disorder after laparoscopic sleeve gastrectomy (LSG) is extremely rare. The purpose of this video was to demonstrate the management of a type II esophageal achalasia diagnosed in a 46-year-old female patient 4-year after LSG. Materials and Methods: An intraoperative video has been anonymized and edited to demonstrate the feasibility of laparoscopic Heller myotomy and anterior Dor fundoplication on the mentioned patient. Results: The operation started with the section of the perigastric adhesions. Proceeding in a clockwise direction, the esophagogastric junction, the anterior esophageal wall, and the His angle were freed. A residual slightly dilated fundus was found and isolated. After mobilization of the distal esophagus and identification of the anterior vagus nerve, a "hockey stick" myotomy was carried out for 6 cm on the esophagus and for 2 cm on the gastric side. An anterior Dor fundoplication was fashioned using the residual gastric fundus. Conclusion: Esophageal achalasia in patients that previously underwent LSG is exceptional but should always be suspected in case of pathognomonic symptoms onset. In tertiary referral centers, laparoscopic Heller myotomy and, if technically feasible, an anterior Dor fundoplication seem safe and effective to relieve gastroesophageal outflow obstruction and prevent gastroesophageal reflux. [ABSTRACT FROM AUTHOR]

In this reply to a letter, the Authors discuss the raised points regarding the nomenclature and management of Lymphatic Malformations / Lymphangiomas. [ABSTRACT FROM AUTHOR]

Behavioural variant frontotemporal dementia (bvFTD) is a form of frontotemporal degeneration characterized by early changes in personality, emotional blunting, and/or loss of empathy. Recent research has highlighted that these features may be at least partially explained by impairments in the theory of mind (ToM; i.e., the ability to understand and predict other people’s behaviour by attributing independent mental states to them). The aim of this randomized, double-blind, placebo-controlled study was to test the hypothesis that transcranial direct current stimulation (tDCS) over the medial frontal cortex (MFC) selectively enhances communicative intention processing, a specific ToM ability. Using a single-session online design, we administered a ToM task that measures the ability to represent other people’s private and communicative intentions during active or sham tDCS to 16 bvFTD patients. To assess the impact of dementia on performance on the ToM task, we included 16 age-matched healthy volunteers who were asked to perform the entire experimental ToM task. BvFTD is characterized by an impairment in the comprehension of both communicative and private intentions relative to a healthy control group and by a disproportional impairment in communicative intention compared with private intention processing. Significant and selective accuracy improvement in the comprehension of communicative intentions after active stimulation was observed in patients with bvFTD. This is the first study that analyses ToM ability in patients with bvFTD using tDCS stimulation. Our findings could potentially contribute to the development of an effective, noninvasive brain stimulation treatment of ToM impairments in patients with bvFTD. [ABSTRACT FROM AUTHOR]

Frontotemporal dementia (FTD) is characterized by behavioural and language impairment, accompanied by atrophic changes in fronto-temporo-insular cortices. In the presymptomatic phases of genetic FTD, subtle or no volumetric changes have been reported. Transcranial magnetic stimulation (TMS) represents an approach to explore cortical connectivity, and some TMS measures have been demonstrated to be impaired in Granulin (GRN) mutation carriers. We aimed at exploring cross-sectional changes in cortical thickness (CT) and surface area (SA) in the presymptomatic phases of GRN-related FTD, and their relationship with TMS parameters. Nineteen presymptomatic GRN mutation carriers and seventeen age and sex-matched non-carriers underwent 3T MRI scanning and a paired-pulse TMS protocol. The surface-based pipeline of FreeSurfer was applied in order to obtain cortical volumes (CVs), CT and SA measures. Then, between groups differences and correlation with TMS parameters were assessed. GRN carriers showed increased CT and decreased SA of the right parietal lobe, without significant volume changes. TMS parameters of intracortical inhibition and facilitation, which were significantly impaired in presymptomatic GRN mutation carriers, correlated with reduced SA and CV of the right insula. Our results suggest that splitting CV into its two main components could improve the sensitivity when exploring structural brain changes in presymptomatic or early phases of neurodegenerative conditions. TMS parameters might reflect damage within cortical regions reported to be affected early in the conversion to the symptomatic phase of the disease. [ABSTRACT FROM AUTHOR]

Aging, injuries, and diseases can be considered as the result of malfunctioning or damaged cells. Regenerative medicine aims to restore tissue homeostasis by repairing or replacing cells, tissues, or damaged organs, by linking and combining different disciplines including engineering, technology, biology, and medicine. To pursue these goals, the discipline is taking advantage of pluripotent stem cells (PSCs), a peculiar type of cell possessing the ability to differentiate into every cell type of the body. Human PSCs can be isolated from the blastocysts and maintained in culture indefinitely, giving rise to the so-called embryonic stem cells (ESCs). However, since 2006, it is possible to restore in an adult cell a pluripotent ESC-like condition by forcing the expression of four transcription factors with the rejuvenating reprogramming technology invented by Yamanaka. Then the two types of PSC can be differentiated, using standardized protocols, towards the cell type necessary for the regeneration. Although the use of these derivatives for therapeutic transplantation is still in the preliminary phase of safety and efficacy studies, a lot of efforts are presently taking place to discover the biological mechanisms underlying genetic pathologies, by differentiating induced PSCs derived from patients, and new therapies by challenging PSC-derived cells in drug screening. [ABSTRACT FROM AUTHOR]

Most children with pain are managed by either acetaminophen or ibuprofen. However, no study has so far investigated if children are prescribed adequate doses of acetaminophen or ibuprofen in emergency department. Aim of this retrospective study was to investigate the prevalence of under-dosage of these drugs in children presenting with pain in emergency department. Children initially prescribed with acetaminophen or ibuprofen for pain management were included. The χ 2 automatic interaction detection method was used considering the percentage variation from the minimum of the appropriate dose as dependent variable while prescribed drug, age, gender, body weight, type of hospital (pediatric or general), and availability of internal guidelines on pediatric pain management in the emergency department as independent variables. Data on 1471 children managed for pain were available. Under-dosage was prescribed in 893 subjects (61%), of whom 577 were prescribed acetaminophen and 316 ibuprofen. The use of acetaminophen suppositories, body weight <12 kg or >40 kg, and the use of oral ibuprofen identified clusters of children associated with under-dosage prescription.Conclusion: Prescription of acetaminophen and ibuprofen was frequently under-dosed. The use of suppositories, lower and higher body weight, and the use of ibuprofen were associated with under-dosage. Under-dosing may reflect prescription of anti-pyretic doses.Clinical Trial Registration: Agenzia Italiana del Farmaco-Observational Study Register (RSO). Registration code: PIERRE/1 What is Known: • Pain is frequent in children presented to emergency department. • International recommendations on pain management are often not implemented. What is New: • Acetaminophen and ibuprofen were frequently underdosed in children prescribed for pain in the Italian emergency departments. • Under-dosage may be related to the habit of using acetaminophen and ibuprofen in the recommended range for fever treatment. [ABSTRACT FROM AUTHOR]

In this paper an innovative electrochemical cell equipped with a composite photoanode consisting of an array of highly ordered TiO nanotubes on porous nickel is described. The use of a combined anode makes the system suitable for working both in dark and under solar light exposure. Moreover, the use of a LED lamp as a light source allows to avoid side effects due to the heating of the system, thus giving a more reliable estimation of the produced current. Finally, the photo-electrolyser, due to its innovative design and the optimal management of the gas produced, could reduce of at least 3.5 % its energy consumption. [ABSTRACT FROM AUTHOR]

The study of left atrial (LA) mechanical function during atrial fibrillation (AFib) can provide valuable information, particularly if such profiling is related to the cavity electrical substrate and conveys prognostic information. To assess if there is any relation between LA mechanical and electrical asynchrony and if such evaluation can be of interest in stratifying AFib patients. 50 patients with persistent AFib who underwent electrical cardioversion (CV) were evaluated with pre-CV atrial electrograms (AEGs). Electrical asynchrony was classified according to Wells' patterns of AEGs, ranging from most organized (I) to most dispersed (III) one. LA mechanical asynchrony was addressed by transthoracic 2D-speckle-tracking echo and quantified according to time-to-peak standard deviation (TP-SD) of wall strains and their peak values (PS) before CV, after 24 h, at 1 month. Pre-CV a linear, inverse relation between TP-SD and PS ( p < 0.001) and a direct linear relation between TP-SD and Wells' classes ( p = 0.04) were observed. With sinus rhythm TP-SD decreased ( p = 0.023) and PS increased ( p < 0.001), suggesting improved LA mechanical milieu. A multivariate analysis, testing the effects of baseline variables in predicting post-CV recurrence of AFib, revealed that amount of TP-SD variation pre/24 h post-CV was the only independent predictor at 6 months ( p = 0.046). Speckle tracking-derived LA parameters can describe LA wall forces during AFib, categorizing the asynchronous mechanistic profile of AFib that correlates with the degree of the dispersed LA electrical activity. The amount of changes in LA mechanical asynchrony pre/post-CV seems to have prognostic relevance in predicting SR maintenance. [ABSTRACT FROM AUTHOR]

Pulmonary embolism is rare in children aged less than 15 years in whom its estimated annual incidence is 0.2 cases per 100,000, against the approximately 700 cases per 100,000 in patients aged more than 85 years. We describe the case of a 15-year-old girl who had a history of thrombocytopenia with anti-platelet and anti-nuclear antibodies. Misdiagnosed chest pain and dyspnea were treated for 6 weeks as community-acquired pneumonia, but proved to be the onset of pulmonary thromboembolism. Although this life-threatening event is rare in paediatrics, the presence of lupus anticoagulant combined with previously asymptomatic thrombocytopenia allowed a diagnosis of systemic lupus erythematosus (SLE). The combination of a history of thrombocytopenia and the presence of antinuclear antibodies, even in the absence of any other diagnostic criteria, should always suggest considering SLE as a differential diagnosis, particularly when the course of a clinical manifestation is atypical. [ABSTRACT FROM AUTHOR]

Traditional indexes of LV dyssynchrony (DYS) in pts to be resynchronized are sensitive to noise, while the concordance between LV lead position and site of latest mechanical activation is suggested to be, in these patients, clinically relevant. Both aspects, asynchrony and lead position have been addressed separately but unclear is their potential synergistic role in the clinical evolution of CRT patients. We assessed clinical and echocardiographic outcome, as well as mid-term prognosis, in a population of CHF patients submitted to CRT, stratified according to a novel asynchrony quantitation (temporal uniformity of strain: TUS) method and concordance or not between presumed LV lead position and site of latest mechanical activation. TUS was computed in 85 pts (QRS > 120 ms, EF < 0.35) in whom we measured circumferential and longitudinal strains using speckle-tracking 2D-echocardiography before and 3-6 months after CRT, together with triplane apical LV volumes. Optimal LV lead position in short axis view was defined as concordance of the segment with latest systolic circumferential strain prior-CRT and segment with assumed LV lead position. Assumed LV lead position was defined from a chest X-ray obtained 1 day after implantation and scored as anterior, lateral, posterior or inferior using 2 orthogonal views (antero-posterior and lateral). Following CRT, LV volume decreased (diastolic −8 ± 20%) and EF improved (+6 ± 9%, P < 0.001 for both). Two-way ANOVA revealed TUS improvement post-CRT (+22 ± 68%, P = 0.025), with a clear evidence for more marked asynchrony detectable at circumferential (from 0.53 ± 0.20 to 0.55 ± 0.19) as compared with longitudinal level (from 0.56 ± 0.14 to 0.62 ± 0.14) ( P = 0.017). Multivariate analysis revealed that greater baseline asynchrony, as assessed circumferentially ( P = 0.079), together with concordance between LV lead position and site of activation ( P = 0.012), besides younger age ( P = 0.051), longer QRS duration ( P = 0.021) and higher baseline EF ( P = 0.04),), but not longitudinal TUS ( P = 0.231) did predict death from any cause or new episodes of pulmonary or systemic congestion requiring i.v. diuretics during a 529 ± 357 days clinical follow-up. We conclude that DYS indexed by circumferential TUS yields CRT benefits, supporting the idea of targeting TUS-measured DYS as the informative asynchrony quantitative measurement in CRT pts. Significant predictability in medium-term clinical follow-up of patients to be resynchronized is also associated with concordance between site of latest mechanical activation and presumed LV lead position in the present study. [ABSTRACT FROM AUTHOR]

Cirrhosis is characterized by a complex coagulation defect leading to the prolongation of the prothrombin and activated partial thromboplastin times (PT and APTT). Arbitrary PT cut-off values are still used as a yardstick to guide treatment with fresh-frozen plasma (FFP) or other pro-coagulant agents in patients undergoing invasive procedures. No randomized studies on the FFP efficacy are available, and are unlikely to be carried out because of their complex organization. An interim solution could be to evaluate the in vitro thrombin generation in plasmas from patients with cirrhosis when mixed with appropriate amounts of pooled normal plasma (PNP). The PT, APTT and thrombin generations in the presence of thrombomodulin were examined in 58 patients with cirrhosis and 24 healthy subjects both before and after mixing their plasmas with PNP at a proportion of 4 + 1 (patient + PNP), chosen to mimic in vivo conditions when patients are treated with 10 ml/kg of FFP. The PT and APTT, which were abnormal in the majority of unmixed patient plasmas were shortened considerably, but did not normalize completely when mixed with PNP. Thrombin generation, which was already within normal limits in all unmixed patient plasmas, remained essentially unchanged after mixing with PNP. In conclusion, thrombin generation in patients with cirrhosis does not appreciably change after in vitro addition of PNP despite PT and APTT shortening would suggest otherwise. These results question the validity of the PT as a stand-alone test to guide transfusion ofFFP in the setting of chronic liver disease. [ABSTRACT FROM AUTHOR]

Wegener's granulomatosis (WG) is an idiopathic systemic disease that usually onsets in adolescence and is rare in young children. Its diagnosis is usually based on the presence of fever with arthralgia and weight loss, associated with symptoms of upper and/or lower respiratory tract involvement and renal disorders. We describe the appearance of a life-threatening lung hemorrhage in the absence of hemoptysis in a 7-year-old girl with a completely negative previous clinical history, who was subsequently diagnosed as having WG. The teaching message is that immediate bronchoscopy with bronchoalveolar lavage seems to be advisable in the presence of severe respiratory distress and bilateral lung as well as renal involvement. When a diffuse alveolar hemorrhage syndrome is demonstrated, WG should be considered among the main etiologies even in a relatively young child without a clinically suggestive history. [ABSTRACT FROM AUTHOR]

Abstract  The following document covers the determination of the diffusion coefficient of two powder materials: LiFePO4 and LiMn2O4 by using potentiostatic intermittent titration technique (PITT) and impedance spectroscopy methodology and compares relevant results with the following relation: $$D = \frac{{R^2 I_0 }}{{3\alpha Q}}$$, which is obtained by solving Fick’s spherical coordinate equation (where I 0 is the initial step current in the PITT experiment, R is the particle radius, Q is the charge that intercalated during the step, and α is the percentage of the theoretical intercalated charge). This procedure allowed the verification of the validity of the spherical model for the powder materials, the accuracy of the expression proposed for the diffusion coefficient determination, and the correctness of the measures that had been taken. [ABSTRACT FROM AUTHOR]

OBJECTIVES: A reduction in hepatic venous pressure gradient (HVPG) of ≥20% of baseline or to ≤12 mmHg (responders) is associated with a reduced risk of first variceal bleeding. The aim of this study was to evaluate whether this protective effect is maintained in the long term and if it extends to other portal hypertension complications. METHODS: Seventy-one cirrhotic patients with esophageal varices and without previous variceal bleeding who entered into a program of prophylactic pharmacological therapy and were followed for up to 8 yr were evaluated. All had two separate HVPG measurements, at baseline and after pharmacological therapy with propranolol ± isosorbide mononitrate. RESULTS: Forty-six patients were nonresponders and 25 were responders. Eight-year cumulative probability of being free of first variceal bleeding was higher in responders than in nonresponders (90% vs 45%, p= 0.026). The lack of hemodynamic response and low platelet count were the only independent predictors of first variceal bleeding. Additionally, reduction of HVPG was independently associated with a decreased risk of spontaneous bacterial peritonitis (SBP) or bacteremia. No significant differences in the development of ascites, hepatic encephalopathy, or survival were observed. CONCLUSIONS: The hemodynamic response in cirrhotic patients is associated with a sustained reduction in the risk of first variceal bleeding over a long-term follow-up. Reduction of HVPG also correlate with a reduced risk of SBP or bacteremia. [ABSTRACT FROM AUTHOR]

p12 represents the smallest, so far poorly characterized subunit of the mammalian DNA polymerased(pold) heterotetramer. Previously, to gain a molecular understanding of endothelial cell activation by fibroblast growth factor-2 (FGF2), we identified an upregulated transcript in FGF2-overexpressing murine aortic endothelial cells (FGF2-T-MAE cells) showing 89%identity with human p12. Here, we cloned the open reading frame of the murine p12 cDNA and confirmed the capacity of overexpressed or exogenously added FGF2 to upregulate p12 mRNA and protein in endothelial and NIH3T3 cells with no effect on the other poldsubunits. p12 expression was instead unaffected by serum and different mitogens. Also, anti-p12 antibodies decorated FGF2-T-MAE cell nuclei and their chromosome outline during metaphase. Small interfering RNA-mediated knockdown of p12 caused a significant decrease in FGF2-driven proliferation rate of FGF2-T-MAE cells, in keeping with a modulatory role of p12 in poldactivity. Immunoistochemistry of FGF2-embedded Matrigel plugs and FGF2-overexpressing tumor xenografts demonstrated a nuclear p12 staining of angiogenic CD31+ endothelium. p12 immunoreactivity was also observed in the CD45+/CD11b+ inflammatory infiltrate. Thus, FGF2 upregulates p12 expression in endothelial cells in vitro and in vivo. p12 expression in infiltrating inflammatory cells may suggest additional, cell proliferation-unrelated functions for this poldsubunit.Oncogene (2005) 24, 1117-1121. doi:10.1038/sj.onc.1208359 Published online 20 December 2004 [ABSTRACT FROM AUTHOR]

Presents a study that investigated the molecular mechanisms mediating the mitogenic activity of substrate-bound fibroblast growth factor (FGF2) in endothelial cells. Analysis of the role of angiogenesis in different physiological and pathological conditions; Examination of the significance of integrins to cell adhesion and the regulation of the response of endothelial cells to soluble growth factors; Discussion on the extracellular matrix as a physical reservoir for FGF2.

Presents a study which examined the gene expression profile in fibroblast growth factor 2 (FGF2)-transformed endothelial cells. Characteristics of angiogenesis; Function of FGF2 endothelial cells; Factors which affect the angiogenesis process.

The t(4;14)(p16.3;q32) chromosomal translocation occurs in approximately 20% of multiple myelomas (MM) and leads to the apparent deregulation of two genes located on 4p16.3: the fibroblast growth factor receptor 3 (FGFR3) and the putative transcription factor WHSC1/MMSET. Interestingly, FGFR3 mutations known to be associated with autosomal dominant human skeletal disorders have also been found in some MM cell lines with t(4;14) but their pathogenetic role in MM is still controversial. Since cell lines may represent useful models for investigating the effects of deregulated FGFR3 mutants in MM, we analysed the expression, activation, signaling pathways and oncogenic potential of three mutants identified so far: the Y373C and K650E in the KMS-11 and OPM-2 cell lines respectively, and the novel G384D mutation here identified in the KMS-18 cell line. All of the cell lines present a heterozygous FGFR3 gene mutation and transcribe the mutated allele; unlike KMS-11 and OPM-2 (which express the IIIc isoform), the KMS-18 cell line expresses prevalently the isoform IIIb. We demonstrated that, under serum-starved conditions, KMS-11 and OPM-2 cells express appreciable levels of phosphorylated FGFR3 mutants indicating a constitutive activation of the Y373C and K650E receptors; the addition of the aFGF ligand further increased the level of receptor phosphorylation. Conversely, the FGFR3 mutant in KMS-18 does not seem to be constitutively activated since it was phosphorylated only in the presence of the ligand. In all three MM cell lines, ligand-stimulated FGFR3 mutants activated the MAP kinase signaling pathway but did not apparently involve either the STAT1 or STAT3 cascades. However, when transfected in 293T cells, G384D, like Y373C and K650E, was capable of activating MAPK, STAT1 and STAT3 under serum-starved condition. Finally, a focus formation assay of NIH3T3 cells transfected with FGFR3-expressing plasmid vectors showed that Y373C and K650E (albeit at different... [ABSTRACT FROM AUTHOR]

Recombinant Fibroblast Growth Factor-4 (FGF4) and FGF2 induce extracellular signal-regulated kinase-1/2 activation and DNA synthesis in murine aortic endothelial (MAE) cells. These cells co-express the IIIc/Ig-3 loops and the novel glycosaminoglycan-modified IIIc/Ig-2 loops isoforms of FGF receptor-2 (FGFR2). The affinity of FGF4/FGFR2 interaction is 20–30 times lower than that of FGF2 and is enhanced by heparin. Overexpression of FGF2 or FGF4 cDNA in MAE cells results in a transformed phenotype and increased proliferative capacity, more evident for FGF2 than FGF4 transfectants. Both transfectants induce angiogenesis when applied on the top of the chick embryo chorioallantoic membrane. However, in contrast with FGF2-transfected cells, FGF4 transfectants show a limited capacity to growth under anchorage-independent conditions and lack the ability to invade 3D fibrin gel and to undergo morphogenesis in vitro. Also, they fail to induce hemangiomas when injected into the allantoic sac of the chick embryo. In conclusion, although exogenous FGF2 and FGF4 exert a similar response in MAE cells, significant differences are observed in the biological behavior of FGF4 versus FGF2 transfectants, indicating that the expression of the various members of the FGF family can differently affect the behavior of endothelial cells and, possibly, of other cell types, including tumor cells. Oncogene (2001) 20, 2655–2663. [ABSTRACT FROM AUTHOR]

Small synovial cysts are a common manifestation of juvenile idiopathic arthritis; large brachial cysts, however, are a rare sign of the disease and they must be differentiated from other soft tissue swelling which are not related to articular involvement. We describe the case of three children with juvenile idiopathic arthritis who came to our attention with large synovial cysts. Ultrasonographic examination and MRI were performed in all cases, showing the real nature of the swelling and the connection to the joint. In all cases, swelling reduced and then disappeared with control of disease activity; in two cases, they reappeared in coincidence with a severe relapse of juvenile idiopathic arthritis. Brachial swellings represent a diagnostic challenge because they can be the clinical expression of a variety of diseases. In children with juvenile idiopathic arthritis who present with a sudden swelling of the upper arm, synovial cysts must be considered in the diagnostic workout, because they are a possible rare manifestation of juvenile idiopathic arthritis. [ABSTRACT FROM AUTHOR]