The importance of lung recruitability: A novel ultrasound pattern to guide lung recruitment in neonates.

BACKGROUND: Lung Ultrasound (LUS)-guided Lung Recruitment Maneuver (LRM) has been shown to possibly reduce ventilator-induced lung injury in preterm infants. However, to avoid potential hemodynamic and pulmonary side effects, the indication to perform the maneuver needs to be supported by early signs of lung recruitability. Recently, a new LUS pattern (S-pattern), obtained during the reopening of collapsed parenchyma, has been described. This study aims to evaluate if this novel LUS pattern is associated with a higher clinical impact of the LUS-guided LRMs. METHODS: All the LUS-guided rescue LRMs performed on infants with oxygen saturation/fraction of inspired oxygen (S/F) ratio below 200, were included in this cohort study. The primary outcome was to determine if the presence of the S-pattern is associated with the success of LUS-guided recruitment, in terms of the difference between the final and initial S/F ratio (Delta S/F). RESULTS: We reported twenty-two LUS-guided recruitments, performed in nine patients with a median gestational age of 34 weeks, interquartile range (IQR) 28-35 weeks. The S-pattern could be obtained in 14 recruitments (64%) and appeared early during the procedure, after a median of 2 cmH2O (IQR 1-3) pressure increase. The presence of the S-pattern was significantly associated with the effectiveness of the maneuver as opposed to the cases in which the S-pattern could not be obtained (Delta S/F 110 +/- 47 vs 44 +/- 39, p = 0.01). CONCLUSIONS: Our results suggest that the presence of the S-pattern may be an early sign of lung recruitability, predicting LUS-guided recruitment appropriateness and efficacy.

Understanding and treating pulmonary hypertension in congenital diaphragmatic hernia.

Lung hypoplasia and pulmonary hypertension are classical features of congenital diaphragmatic hernia (CDH) and represent the main determinants of survival. The mechanisms leading to pulmonary hypertension in this malformation are still poorly understood, but may combine altered vasoreactivity, pulmonary artery remodeling, and a hypoplastic pulmonary vascular bed. Efforts have been directed at correcting the "reversible" component of pulmonary hypertension of CDH. However, pulmonary hypertension in CDH is often refractory to pulmonary vasodilators. A new emerging pattern of late (months after birth) and chronic (months to years after birth) pulmonary hypertension are described in CDH survivors. The true incidence and implications for outcome and management need to be confirmed by follow-up studies from referral centers with high patient output. In order to develop more efficient strategies to treat pulmonary hypertension and improve survival in most severe cases, the ultimate therapeutic goal would be to promote lung and vascular growth.

Circulation of different rhinovirus groups among children with lower respiratory tract infection in Kiremba, Burundi.

The purpose of this investigation was to collect information regarding rhinovirus (RV) circulation in children with lower respiratory tract infections (LRTIs) in Burundi, Central Africa. We enrolled all of the children aged between 1 month and 14 years who were admitted to the hospital of Kiremba, North Burundi, with fever and signs and symptoms of LRTI (i.e., cough, tachypnea, dyspnea or respiratory distress, and breathing with grunting or wheezing sounds with rales) between 1 November 2010 and 31 October 2011, and obtained nasopharyngeal swabs for RV detection by means of polymerase chain reaction (PCR). The VP4/VP2 region of the positive samples was sequenced to determine the species of RV (A, B, or C). Four hundred and sixty-two children were enrolled: 160 (34.6 %) with bronchitis, 35 (7.6 %) with infectious wheezing, and 267 (57.8 %) with community-acquired pneumonia (CAP). RV infection was demonstrated in 186 patients [40.3 %; mean age ± standard deviation (SD) 1.77 ± 2.14 years]. RV infection was detected in 78 patients aged <12 months (40.0 %), 102 aged 12-48 months (44.3 %), and six aged >48 months (16.7 %; p < 0.01 vs. the other age groups). The most frequently identified RV was RV-A (81 cases, 43.5 %), followed by RV-C (47, 25.3 %) and RV-B (18, 9.7 %); subtyping was not possible in 40 cases (21.5 %). RV-A was significantly associated with bronchitis and CAP (p < 0.01) and RV-C with wheezing (p < 0.05). In Burundi, RVs are frequently detected in children with LRTIs. RV-A seems to be the most important species and is identified mainly in patients with bronchitis and CAP.

Antimicrobial resistance among uropathogens responsible for community-acquired urinary tract infections in an Italian community.

This study aimed to establish the pattern of the antimicrobial resistance among the leading uropathogens causing community-acquired UTIs in an area of the region of Apulia, Southern Italy. Twenty-one thousand and two hundred outpatients, 6,893 males and 14,307 females, were enrolled. Urinary isolates were identified by conventional methods and the susceptibility to 18 antimicrobials determined. Recognized uropathogens Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were isolated from 3175 positive samples, E. coli accounting for 68.04% of positive cultures. Most overall resistance was to ampicillin, while the resistance rate to cephalothin was higher than that of third generation cephalosporins. Although to a different degree, all the bacteria had an overall good susceptibility rate to quinolones as well as to fosfomycin but increased resistance to sulfamethoxazole/trimethoprim. Our results confirm that E. coli is the leading uropathogen and provide information about the antimicrobial susceptibility patterns of the main pathogens causing community-acquired UTIs. These findings should be taken into account to help maintain the safety and efficacy of treatment for community-acquired UTIs.

Pediatric spinal cord injury: approach for urological rehabilitation and treatment.

PURPOSE: As proposed in this report, early urological rehabilitative management of patients with spinal cord injuries (SCIs) is mandatory, in order to prevent a poorly compliant bladder with related upper urinary tract complications and secondary renal failure. Moreover, the approach to treating this traumatic condition in children must be as much rapid as appropriate. MATERIALS AND METHODS: We evaluated our experience of the last 5 years with 17 patients (12 males and five females), with a mean age of 9.6 years at injury (range 6 months-18 years), all affected by an SCI and with direct trauma involved in more than 50%. Mechanism of injury, lesional level, the mean interval between injury and bladder management onset, and the mean interval between bladder management onset and our last control were evaluated. A standardized diagnostic approach was instituted, and all patients received at least a video-urodynamic evaluation before and after the start of urological management. A continence score was established and evaluated before and at least 6 months after the application of rehabilitation treatments (catheterization, medication). Follow-up ranged from 12 to 60 months (average 29.6 months). RESULTS: Sixteen of the 17 patients showed, at first urodynamic evaluation, a neurogenic overactive bladder. Mean bladder maximum capacity was 287.7 ml+/-146.4 SD. Mean reflex volume and end filling pressure were 119.7 ml+/-76.4 SD and 44.6 cmH(2)O+/-25 SD, respectively. Detrusor sphincter dyssynergia was present in 16 out of 17 of the cases. All patients but one began self-catheterization and medication (anticholinergics). Urinary continence improved in all patients but one. An adjunctive endoscopic procedure for continence was carried out in five out of 17 cases. The upper urinary tract was involved in two out of 17 cases. CONCLUSIONS: A prompt and standardized urological approach to pediatric SCIs is mandatory. The aims of this initial management are the prevention of further secondary damage to the upper tract and the achievement of a socially acceptable degree of urinary continence as soon as possible after the traumatic event.

Anoxic brain injury following near-drowning in children. Rehabilitation outcome: three case reports.

PRIMARY OBJECTIVE: To describe the outcome of near-drowning and rehabilitation contexts for recovery. METHODS AND PROCEDURES: Standardized measures were used to emphasize the functional impact of deficits over the first year post-injury in three children <2 years. Multimodal contexts for meaningful interplay were early adapted to the three cases. MAIN OUTCOMES AND RESULTS: The clinical pathways of recovery are identified. Initially all three cases manifested a generalized dystonia. Case 1 exhibited a good outcome with transient dyskinetic-dystonic syndrome; subsequently Bálint's syndrome emerged. In this case, the rehabilitation approach was organized on the pickup of direct perception of task-specific affordances. Cases 2 and 3 had poor outcomes presenting the worsening of torsion dystonia (status dystonicus) that hindered rehabilitation intervention. CONCLUSIONS: The dynamic reaggregation of spatial organization through meaningful interaction in specific ecological contexts is the principal goal of rehabilitation intervention. Status dystonicus represents the worst feature for recovery.

Charmed-meson decay constants in three-flavor lattice QCD.

We present the first lattice QCD calculation with realistic sea quark content of the D+-meson decay constant f(D+). We use the MILC Collaboration's publicly available ensembles of lattice gauge fields, which have a quark sea with two flavors (up and down) much lighter than a third (strange). We obtain f(D+)=201+/-3+/-17 MeV, where the errors are statistical and a combination of systematic errors. We also obtain f(Ds)=249+/-3+/-16 MeV for the Ds meson.

Follow-up of neuropsychological function recovery in a 9-year-old girl with anoxic encephalopathy: a window on the brain re-organization processes.

OBJECTIVE: To investigate comprehensive neuropsychological outcome, disabilities in daily life and individual recovery processes in a case of anoxic encephalopathy. DESIGN: A 9-year-old child's functional outcome after anoxic coma was evaluated in a follow-up study with assessments at 5, 9 and 12 months post-injury. A comprehensive neuropsychological protocol was administered. Qualitative methods of analysis and ecological observation were associated with standard and non-standard quantitative measures. RESULTS: The child presented pervasive functional deficits with prevalence of gnosic, praxic and self-regulatory dysfunction. Dissociated functional recovery was documented in 12 months time. Improvement of self-regulatory abilities was likely a 'propeller' of global system re-organization. CONCLUSION: A descriptive longitudinal study of functional and ecological behavioural changes after anoxic coma provides insight into the re-adaptation processes in the brain connected to post-lesion ecological and training experiences. Contextual factors and their relations to functional improvements deserve further study.

High-precision lattice QCD confronts experiment.

The recently developed Symanzik-improved staggered-quark discretization allows unquenched lattice-QCD simulations with much smaller (and more realistic) quark masses than previously possible. To test this formalism, we compare experiment with a variety of nonperturbative calculations in QCD drawn from a restricted set of "gold-plated" quantities. We find agreement to within statistical and systematic errors of 3% or less. We discuss the implications for phenomenology and, in particular, for heavy-quark physics.

[Celiac disease; a world in exploration]. / La celiachia: un mondo in esplorazione.

Celiac disease (CD) or gluten-sensitive enteropathy is an autoimmune disorder triggered by gluten ingestion in genetically predisposed subjects. The presence of gluten in these patients leads to a self-perpetuating mucosal damage, while the elimination of gluten results in a full mucosal recovery. The prevalence of CD in the general population is between 0.3% and 1%. The clinical manifestation of CD is variable; in addition to the classical gastrointestinal form a variety of other clinical manifestation of the disease have been described, including atypical and asymptomatic form. The diagnosis of CD is still based on the small intestinal biopsy findings, but can be suspected using serological testing, e.g. the antigliadin antibody (AGA), the antiendomysial antibody (EMA) and the anti-tissue transglutaminase antibody (tTG). The keystone treatment of CD patients is a life-long gluten-free diet.

Early effects of gliadin on enterocyte intracellular signalling involved in intestinal barrier function.

BACKGROUND AND AIMS: Despite the progress made in understanding the immunological aspects of the pathogenesis of coeliac disease (CD), the early steps that allow gliadin to cross the intestinal barrier are still largely unknown. The aim of this study was to establish whether gliadin activates a zonulin dependent enterocyte intracellular signalling pathway(s) leading to increased intestinal permeability. METHODS: The effect of gliadin on the enterocyte actin cytoskeleton was studied on rat intestinal epithelial (IEC-6) cell cultures by fluorescence microscopy and spectrofluorimetry. Zonulin concentration was measured on cell culture supernatants by enzyme linked immunosorbent assay. Transepithelial intestinal resistance (Rt) was measured on ex vivo intestinal tissues mounted in Ussing chambers. RESULTS: Incubation of cells with gliadin led to a reversible protein kinase C (PKC) mediated actin polymerisation temporarily coincident with zonulin release. A significant reduction in Rt was observed after gliadin addition on rabbit intestinal mucosa mounted in Ussing chambers. Pretreatment with the zonulin inhibitor FZI/0 abolished the gliadin induced actin polymerisation and Rt reduction but not zonulin release. CONCLUSIONS: Gliadin induces zonulin release in intestinal epithelial cells in vitro. Activation of the zonulin pathway by PKC mediated cytoskeleton reorganisation and tight junction opening leads to a rapid increase in intestinal permeability.

A novel device to evaluate the stiffness of ankle-foot orthosis devices.

The evaluation of mechanical behavior of plastic Ankle-Foot Orthosis (AFO) is important since AFO can provide an efficient support to patients with disabilities in locomotion. This paper reports on a novel testing apparatus that allows: (a) the evaluation of AFO stiffness in sagittal and frontal planes; (b) the conduction of semi-automatic trials; and, finally, (c) a global accuracy associated to the AFO stiffness values always less than 4%. The stiffness values are determined by the measurements of the imposed relative displacements between the foot and the shank of the orthosis and the induced reaction forces. The data collected together in an exact 2-D approach, together with those provided by gait analysis systems, allows to better understand gait alteration induced by ankle orthosis, and to improve clinical management of patients.

Evaluation of communicative and functional abilities in Wolf-Hirshhorn syndrome.

BACKGROUND: Wolf-Hirschhorn syndrome (WHS) is a genetic condition characterized by many clinical disorders, learning difficulties, dysphagia, neuromotor deficits and communicative deficits. Up until now, no studies in the literature have described the development of communicative and functional abilities in subjects with WHS. METHOD: In the present study of 11 patients with WHS, a descriptive analysis was made of several abilities and three groups of patients were identified on the basis of the severity of their functional deficit. RESULTS: A non-homogeneous picture of impairment emerged in various areas of development. Overall, the neuromotor abilities of these patients were more adequate than their abilities related to autonomy in personal life, alimentary function, and cognitive and communicative-linguistic aspects. CONCLUSION: Based on the identification of specific patterns of communicative and functional impairment in subjects with WHS, rehabilitative intervention strategies can be planned to increase their communicative opportunities, and possibilities for active and autonomous participation in various life contexts (e.g. home, school and the social environment).

[Steinert disease: abnormal onset or "casual" diagnosis?]. / Malattia di Steinert: esordio anomalo o diagnosi "casuale"?

The most frequent myopathy is "Steinert's disease" (also called myotonic dystrophy). We present a case of particular interest due to the way diagnosis was made. A 20-year-old male was transferred to our Department from another Hospital with a diagnosis of "acute liver disease". He presented with fever (39 degrees C), tetrahyposthenia, dehydration and spatial-temporal disorientation. The most apparent laboratory data was a significant increase in serum levels of creatine phosphokinase (196,260 IU/L; normal values < 50 IU/L). After therapy based on parenteral nutrition and steroids, our patient improved progressively, with normalization of laboratory values. Muscle biopsy and electromyography yielded a diagnosis of Steinert's disease, and the patient's mother was found to be the carrier of a myotonine-kinase gene mutation. In this case, the onset of what appeared to be an influenza-A virus infection (the only positive data observed in the serological analysis) permitted the diagnosis of a hereditary myopathy that had remained asymptomatic up to that time.

[Zonula occludens toxin: an innovative method of oral drugs delivery]. / Zanula occlidens toxin: un nuovo sistema per somministrare l'insulina per via orale.

Conventional forms of administration of nonabsorbable drugs and peptides often rely on parenteral injection, because the intestinal epithelium represents a major barrier to the oral absorption of these therapeutical agents into the systemic circulation. Recently, a number of innovative drug-delivery approaches have been developed, including drug entrapment within small vesicles or the passage of the therapeutic molecules through the space between adjacent intestinal cells. This article reviews some of the most promising techniques currently available for oral delivery and their possible practical applications for the delivery of vaccines and drugs for the treatment of clinical conditions that require frequent, chronic parenteral administration.

Zonula occludens toxin structure-function analysis. Identification of the fragment biologically active on tight junctions and of the zonulin receptor binding domain.

Zonula occludens toxin (Zot) is an enterotoxin elaborated by Vibrio cholerae that increases intestinal permeability by interacting with a mammalian cell receptor with subsequent activation of intracellular signaling leading to the disassembly of the intercellular tight junctions. Zot localizes in the bacterial outer membrane of V. cholerae with subsequent cleavage and secretion of a carboxyl-terminal fragment in the host intestinal milieu. To identify the Zot domain(s) directly involved in the protein permeating effect, several zot gene deletion mutants were constructed and tested for their biological activity in the Ussing chamber assay and their ability to bind to the target receptor on intestinal epithelial cell cultures. The Zot biologically active domain was localized toward the carboxyl terminus of the protein and coincided with the predicted cleavage product generated by V. cholerae. This domain shared a putative receptor-binding motif with zonulin, the Zot mammalian analogue involved in tight junction modulation. Amino acid comparison between the Zot active fragment and zonulin, combined with site-directed mutagenesis experiments, confirmed the presence of an octapeptide receptor-binding domain toward the amino terminus of the processed Zot.

Reduced quality of life in patients with chronic hepatitis C: effects of interferon treatment.

BACKGROUND: Quality of life is an area of increasing interest in hepatology. Studies, so far, have assessed quality of life in patients with chronic virus C-related hepatitis in relation to antiviral therapy by means of generic questionnaires. AIM: To measure quality of life in chronic hepatitis patients without cirrhosis by means of the Nottingham Health Profile questionnaire, a measure of "distress" in comparison with the Medical Outcome Survey SF-36, an index of well-being. PATIENTS: A series of 126 outpatients with chronic hepatitis; 37 on and 89 not on active interferon treatment. METHODS: The two questionnaires were used in random order. Clinical and laboratory data were also collected. The final score of any domain of the two questionnaires, for any individual patient, was compared to age-adjusted normal values obtained in 2 random samples of Italian population. RESULTS: Patients showed a significant modification of 3 domains of Nottingham Health Profile (Energy, Social Isolation and Physical Mobility) and 6 domains of SF-36. In relation to interferon treatment, the Nottingham Health Profile questionnaire was able to detect differences in Energy, Physical Mobility and Pain, which were modified only in treated patients. SF-36 did not show any differences in relation to treatment. In addition, the Nottingham Health Profile demonstrated that treated patients had a lower prevalence of concern for family life, possibly due to expectations of treatment itself. CONCLUSIONS: Active interferon treatment causes considerable distress in chronic hepatitis C patients, adding to the perceived change in health status caused by liver disease.

Drinking habits of subjects with hepatitis C virus-related chronic liver disease: prevalence and effect on clinical, virological and pathological aspects.

Alcohol changes the progression of hepatitis C virus (HCV)-related chronic liver disease and may affect the outcome of interferon therapy. The ethanol intake of 245 patients with biopsy-proven chronic hepatitis C with or without cirrhosis, its interaction with laboratory and histological parameters common to alcohol and HCV-mediated liver damage, and its effects on therapy were evaluated. The results show that 60-70% of subjects regularly consumed alcohol (median intake >40 g/day in about 30%). Less than 50% stopped drinking after being diagnosed as having liver disease. Ethanol intake affected: fibrosis, especially in women, HCV RNA levels, which were significantly lower in abstainers than in drinkers (0.6 +/- 0.3 vs 6.9 +/- 5.9 Eq/ml x10(6); P < 0.01), and response to interferon therapy. The number of responders decreased as ethanol intake increased. There were less abstainers than drinkers among non-responders (10.7% vs 63.1% respectively; P < 0.001). Data indicate that alcohol will induce and worsen liver damage and, in subjects with chronic liver disease who continue to drink, adversely affect their response to treatment.