Obstructive sleep apnea in children with Marfan syndrome: Relationships between three-dimensional palatal morphology and apnea-hypopnea index.

OBJECTIVE: To evaluate the relationship between the severity degree of OSA (apnea/hypopnea index AHI>1) and palatal area and volume, measured by 3D analysis of digital casts in Marfan children. METHODS: Twenty children with a clinical diagnosis of MS were recruited from a tertiary medical center. All the subjects underwent standard nocturnal polygraphy testing. Sixteen Marfan patients (7F,9 M; mean age 8.8yy ±â€¯1.5yy) with AHI>1 were enrolled. Marfan Group (MG) was compared with a control group (CG) of 17 children without Marfan syndrome (9F,8 M; mean age 8.5yy ±â€¯1.7yy) presenting with nose-breathing pattern. For each subject maxillary digital casts were taken and palatal area and volume were measured. Unpaired t-test was used to test significant differences between MG and CG for area and volume measurements. Pearson correlation coefficient (PCC) was used to measure the linear correlation between the degree of OSA (AHI index) and palatal volume and palatal area. RESULTS: 80% of Marfan children presented an AHI>1 and a diagnosis of OSA. MG presented statistically significant lower values of palatal surface area (662.68 mm2; P < 0.0001) and palatal volume (2578.1 mm3; P < 0.0001) with respect to CG (923.0 mm2 and 3756.6 mm3, respectively). Correlation analysis showed that AHI index had no linear correlation with palatal area (r = - 0,07) and with palatal volume (r = - 0,11). CONCLUSION: OSA is highly prevalent in children with Marfan's syndrome (80%). Marfan children present a reduction of palatal area and volume when compared to healthy subjects. OSA in Marfan children is not linear correlated to the palatal morphology and it shows a multifactorial aetiology.

Orthopaedic treatment effects of functional therapy on the sagittal pharyngeal dimensions in subjects with sleep-disordered breathing and Class II malocclusion.

The purpose of this cephalometric study was to evaluate the craniofacial changes induced by functional treatment of mandibular advancement with special regard to pharyngeal sagittal airway dimensions, tongue and hyoid bone position in subjects with sleep-disordered breathing (SDB) and dentoskeletal Class II malocclusions compared with an untreated Class II control group. 51 subjects (24 female, 27 male; mean age 9.9 ± 1.3 years) with Class II malocclusion and SDB consecutively treated with a functional appliance (Modify Monobloc, MM) were compared with a control group of 31 subjects (15 males, 16 females; mean age 10.1 ± 1.1) with untreated Class II malocclusion. For the study group, mode of breathing was defined by an otorhinolaryngologist according to complete physical examination. The parents of all participants completed a modified version of the paediatric sleep questionnaire, PSQ-SRBD Scale, by Ronald Chervin (the Italian version in 22 items form) before and after the trial. Lateral cephalograms were available at the start and end of treatment with the MM. Descriptive statistics were used for all cephalometric measurements in the two groups for active treatment changes. Significant, favourable skeletal changes in the mandible were observed in the treated group after T2. Significant short-term changes in sagittal airway dimensions, hyoid position and tongue position were induced by functional therapy of mandibular advancement in subjects with Class II malocclusion and SDB compared with untreated controls. After orthodontic treatment, a significant reduction in diurnal symptoms was observed in 45 of the 51 participants who had received an oral appliance. Orthodontic treatment is considered to be a potential therapeutic approach for SDB in children. Orthodontists are playing an increasingly important role in managing snoring and respiratory problems by oral mandibular advancement devices and rapid maxillary expansion.

Human adipose tissue-derived mesenchymal stem cells abrogate plasmablast formation and induce regulatory B cells independently of T helper cells.

Mesenchymal or stromal stem cells (MSC) interact with cells of the immune system in multiple ways. Modulation of the immune system by MSC is believed to be a therapeutic option for autoimmune disease and transplant rejection. In recent years, B cells have moved into the focus of the attention as targets for the treatment of immune disorders. Current B-cell targeting treatment is based on the indiscriminate depletion of B cells. The aim of this study was to examine whether human adipose tissue-derived MSC (ASC) interact with B cells to affect their proliferation, differentiation, and immune function. ASC supported the survival of quiescent B cells predominantly via contact-dependent mechanisms. Coculture of B cells with activated T helper cells led to proliferation and differentiation of B cells into CD19(+) CD27(high) CD38(high) antibody-producing plasmablasts. ASC inhibited the proliferation of B cells and this effect was dependent on the presence of T cells. In contrast, ASC directly targeted B-cell differentiation, independently of T cells. In the presence of ASC, plasmablast formation was reduced and IL-10-producing CD19(+) CD24(high) CD38(high) B cells, known as regulatory B cells, were induced. These results demonstrate that ASC affect B cell biology in vitro, suggesting that they can be a tool for the modulation of the B-cell response in immune disease.

Anatomical features and clinical correlations in Caucasian patients with definite arrhythmogenic right ventricular dysplasia/cardiomyopathy.

AIM: Arrhythmogenic right ventrticular dysplasia/cardiomyopathy (ARVD/C) is an inherited cardiomyopathy characterized by fibrofatty replacement and a high risk of ventricular arrhythmias (VA) and sudden cardiac death (SCD). The aim of the present investigation is to examine the pathological profile and the clinical correlations in a group of ARVD/C patients. METHODS: We conducted a multicenter study evaluating 47 patients (31 men; mean age 37±14 years) with definite ARVD/C. Diagnosis was established according to the actual clinicomorphologic criteria at autopsy or clinically. We divided the study population in 2 different groups. First group included 28 alive patients and the second 19 patients dead suddenly. RESULTS: Age at presentation was different in the two groups (P=0.0015). We observed an important association regarding the risk of sudden death and the history of physical exercise (P=0.0017). Moreover patients with negative outcome (i.e., SCD, cardiac transplantation, congestive heart failure) had a significantly association with biventricular form of ARVD/C (P=0.0034) and age presentation (P=0.003). Left ventricular (LV) involvement was frequently observed in the two groups (17% and 32% respectively). Post-mortem examination revealed frequent inflammatory infiltrates (26%) indicating active myocarditis, which probably justify the fatal arrhythmic events occurred in these patients. CONCLUSION: Frequent LV involvement justifies the recent adoption of the broad term Arrhythmogenic Cardiomyopathy. Early age presentation, sport activity and the biventricular form of ARVD/C represent important predictors of adverse outcome that can be useful to early identify patients at high risk.

Effect of haemin on growth, protein content and the antioxidant defence system in Trypanosoma cruzi.

A nutritional characteristic of trypanosomatid protozoa is that in vitro they need a haem-compound as a growth factor, which is supplied as haemoglobin, haematin or haemin. Because haemin and related porphyrins are an important source of oxidative stress in biological systems, the effect of haemin on growth, protein content and the antioxidant defence system in Trypanosoma cruzi was evaluated. We have observed that, in epimastigotes grown under different haemin concentrations in the culture medium (0-30 mg/l), 5 mg/l was the haemin concentration yielding optimum growth. Above 15 mg/l there was a clear decrease in growth rate, producing the epimastigote to amastigote transformation. Such morphological change was observed together with a marked injury of the enzymatic machinery of the parasite, leading to diminished protein synthesis as well as lower activity of the antioxidant enzymes (superoxide dismutase, ascorbate peroxidase and trypanothione reductase), reduced total thiol content and a marked increase in the HaemOx-1 activity and expression. The current work demonstrates that there is a correlation between higher haemin concentrations in the culture medium and oxidative damage in the cells. Under these conditions induction of HaemOx-1 would indicate the important role of this enzyme as an antioxidant defence response in Trypanosoma cruzi.

Recent trends of ophthalmic diseases in Italy: are official data reliable?

PURPOSE: The aim of the study was to investigate the epidemiological trends of ocular diseases using hospital discharge forms as our data source. MATERIALS AND METHODS: We examined official Italian Statistical Institute (ISTAT) data concerning patients discharged from ophthalmologic wards. Our analysis was limited to the years when ISTAT managed health service data (1986, 1990 and 1994); whilst currently this duty has been transferred to the Ministry of Health. RESULTS: The diseases encountered most frequently were cataract, glaucoma and retinal detachment. Patients over 65 years of age represented 54% in 1986 and 67% in 1994. We observed a general trend toward shorter hospital stays (10.5 days in 1986 and 6.4 days in 1994). We applied an indirect analysis that included masculinity and chi 2 homogeneity that were aimed to evaluate results de spite the questionable reliability of ISTAT gross data. CONCLUSIONS: The results of indirect analysis (masculinity and chi 2 homogeneity, of data combined with the significant number of charts presenting incomplete diagnostic information strongly question the reliability of official documentation. The increase of hospitalisation for ophthalmic surgery and a higher average age of affected subjects were confirmed. We observed a reduction of mean hospital stay per admission, indicating a positive achievement in terms of cost reduction.

C terminus of infectious bursal disease virus major capsid protein VP2 is involved in definition of the T number for capsid assembly.

Infectious bursal disease virus (IBDV), a member of the Birnaviridae family, is a double-stranded RNA virus. The IBDV capsid is formed by two major structural proteins, VP2 and VP3, which assemble to form a T=13 markedly nonspherical capsid. During viral infection, VP2 is initially synthesized as a precursor, called VPX, whose C end is proteolytically processed to the mature form during capsid assembly. We have computed three-dimensional maps of IBDV capsid and virus-like particles built up by VP2 alone by using electron cryomicroscopy and image-processing techniques. The IBDV single-shelled capsid is characterized by the presence of 260 protruding trimers on the outer surface. Five classes of trimers can be distinguished according to their different local environments. When VP2 is expressed alone in insect cells, dodecahedral particles form spontaneously; these may be assembled into larger, fragile icosahedral capsids built up by 12 dodecahedral capsids. Each dodecahedral capsid is an empty T=1 shell composed of 20 trimeric clusters of VP2. Structural comparison between IBDV capsids and capsids consisting of VP2 alone allowed the determination of the major capsid protein locations and the interactions between them. Whereas VP2 forms the outer protruding trimers, VP3 is found as trimers on the inner surface and may be responsible for stabilizing functions. Since elimination of the C-terminal region of VPX is correlated with the assembly of T=1 capsids, this domain might be involved (either alone or in cooperation with VP3) in the induction of different conformations of VP2 during capsid morphogenesis.

VP5, the nonstructural polypeptide of infectious bursal disease virus, accumulates within the host plasma membrane and induces cell lysis.

Infectious bursal disease virus (IBDV) encodes a 17-kDa nonstructural polypeptide known as VP5. This polypeptide is not essential for virus replication in vitro but it plays an important role in in vivo dissemination and pathogenesis. We have characterized the expression of VP5 in three eukaryotic systems: (i) IBDV-infected chicken embryo fibroblasts; (ii) BSC-1 cells infected with a recombinant vaccinia virus vector; and (iii) Cos-1 cells transiently transfected with a plasmid vector. Immunofluorescence analyses showed that upon expression VP5 accumulates within the plasma membrane. This finding was consistent with sequence-based topology predictions, indicating that VP5 is a class II membrane protein with a cytoplasmic N-terminus and an extracellular C-terminal domain. Brefeldin A treatment of VP5-expressing cells prevented the accumulation of this polypeptide in the plasma membrane, thus showing the requirement of an active exocytic pathway to reach that compartment. Expression of VP5 was shown to be highly cytotoxic. Induction of VP5 expression resulted in the alteration of cell morphology, the disruption of the plasma membrane, and a drastic reduction of cell viability. VP5-induced cytotoxicity was prevented by blocking its transport to the membrane with Brefeldin A. Our findings suggest that VP5 plays an important role in the release of the IBDV progeny.

A beta-stranded motif drives capsid protein oligomers of the parvovirus minute virus of mice into the nucleus for viral assembly.

The determinants of nuclear import in the VP-1 and VP-2 capsid proteins of the parvovirus minute virus of mice strain i (MVMi) synthesized in human fibroblasts were sought by genetic analysis in an infectious plasmid. Immunofluorescence of transfected cells revealed that the two proteins were involved in cooperative cytoplasmic interactions for nuclear cotransport. However, while VP-1 translocated regardless of extension of deletions and did not form capsid epitopes by itself, VP-2 seemed to require cytoplasmic folding and the overall conformation for nuclear transport. The sequence (528)KGKLTMRAKLR(538) was found necessary for nuclear uptake of VP-2, even though it was not sufficient to confer a nuclear localization capacity on a heterologous protein. In the icosahaedral MVMi capsid, this sequence forms the carboxy end of the amphipathic beta-strand I (betaI), and all its basic residues are contiguously positioned at the face that in the unassembled subunit would be exposed to solvent. Mutations in singly expressed VP-2 that either decrease the net basic charge of the exposed face (K530N-R534T), perturb the hydrophobicity of the opposite face (L531E), or distort the betaI conformation (G529P) produced cytoplasmic subviral oligomers. Particle formation by betaI mutants indicated that the basic residues clustered at one face of betaI drive VP oligomers into the nucleus preceding and uncoupled to assembly and that the nuclear environment is required for MVMi capsid formation in the infected cell. The degree of VP-1/VP-2 transport cooperativity suggests that VP trimers are the morphogenetic intermediates translocating through the nuclear pore. The results support a model in which nuclear transport signaling preserves the VP-1/VP-2 stoichiometry necessary for efficient intranuclear assembly and in which the beta-stranded VP-2 nuclear localization motif contributes to the quality control of viral morphogenesis.

VP1, the putative RNA-dependent RNA polymerase of infectious bursal disease virus, forms complexes with the capsid protein VP3, leading to efficient encapsidation into virus-like particles.

A cDNA corresponding to the coding region of VP1, the putative RNA-dependent RNA polymerase, of infectious bursal disease virus (IBDV) was cloned and inserted into the genome of a vaccinia virus inducible expression vector. The molecular mass and antigenic reactivity of VP1 expressed in mammalian cells are identical to those of its counterpart expressed in IBDV-infected cells. The results presented here demonstrate that VP1 is efficiently incorporated into IBDV virus-like particles (VLPs) produced in mammalian cells coexpressing the IBDV polyprotein and VP1. Incorporation of VP1 into VLPs requires neither the presence of IBDV RNAs nor that of the nonstructural polypeptide VP5. Immunofluorescence, confocal laser scanning microscopy, and immunoprecipitation analyses conclusively showed that VP1 forms complexes with the structural polypeptide VP3. Formation of VP1-VP3 complexes is likely to be a key step for the morphogenesis of IBDV particles.

[In vivo dosimetry and radiographic confirmation in radiotherapy of Hodgkin's lymphoma]. / Dosimetria in vivo e verifica radiografica nella radioterapia del linfoma di Hodgkin.

In September 1991 a protocol for quality control of large shaped irradiation fields was started in our department. In vivo dosimetry with semiconductor detectors was used to measure the absorbed dose and patient positioning was checked with portal films weekly. First, we set a computed dosimetric system yielding dosimetric values in real time and allowing their easy storage. Then, we calibrated the diodes and determined the correction factors for each of them outside standard conditions. Entrance dose, exit dose and midline dose were measured in 62 patients undergoing supradiaphragmatic radiation therapy for Hodgkin's lymphoma. The exist dose was measured weekly to assess treatment repeatability. High agreement was observed between measured and calculated doses; repeatability was also high, since only 6% of exit dose measurements exceeded 5% of the first determination. In 33 patients portal films were obtained in the first treatment session, and thereafter weekly, to assess mispositioning relative to simulation (reproducibility) and from one session to another (repeatability). A small systematic error was detected in both longitudinal (x = -3 mm; SD = 3.7 mm) and transverse (x = -2 mm; SD = 3.4 mm) directions. Statistically significant errors (> 6 mm) were observed in 14% of patients. Reproducibility was excellent. The protocol reported on in this paper not only helps avoid systematic dosimetric and/or positioning errors in the patients, but also helps identify the main causes of uncertainty and thus remove them.

Attitudes of elementary, middle and high school teachers toward mainstreaming: implications for job satisfaction.

Little attention has been paid to the job satisfaction experienced by human services personnel, including classroom teachers. This study examines teacher's response to postal questionnaires seeking information about job satisfaction and attitudes to the mainstreaming of children with special needs. Results suggest that teachers at secondary or high school level experience lower job satisfaction than those working in middle or elementary schools. Comparison between teachers with or without experiences of mainstreaming reveals further differences between these groups with regard to their attitude toward the value of special educator involvement in the classroom; the importance of special assessments; discipline; the role of mainstreaming in enhancing peer relationships; and appreciation of school administrators' awareness of the implications of mainstreaming.

[Mortality at the end of the sixteenth century according to the data of Jean Hudde]. / La mortalita alla fine del XVI secolo secondo i dati di Jean Hudde.

PIP: The author presents survival probability and mortality information for Holland in the late sixteenth century based on life annuity data for the years 1586-1590, examined by Jean Hudde and discussed in a letter he wrote in 1671 to Christiaan Huygens.^ieng

[Life expectancy and median life in life tables: the historical emergence of these measures]. / Speranza di vita e vita mediana nelle tavole di mortalita: la traccia storica del sorgere di queste misure

PIP: The author describes the development of two measures used in life tables, life expectancy and median length of life. These measures were developed during the course of correspondence between the Dutch brothers Christiaan and Lodewijk Huygens in 1669. (summary in ENG, FRE)^ieng

[Prognostic value of echocardiographic finding of valvular vegetations in patients with infectious endocarditis]. / II valore prognostico del rilievo ecocardiografico di vegetazioni valvolari in pazienti con endocardite infettiva.

42 consecutive patients with infective endocarditis on native valves, according to Pelletier and Petersdorf's criteria of definite (13 pts), probable (12 pts.) and possible (17 pts) endocarditis, were identified and prospectively followed-up with M-mode and two-dimensional echocardiography, since 1980. We compared: 1) these three groups; 2) survivors not referred for surgery versus surgical patients plus nonsurvivors; 3) patients who suffered embolic events versus those who did not; 4) patients with severe-moderate heart failure versus those with no failure or mild failure; 5) patients with aortic valve echocardiographic vegetations versus those with mitral valve vegetations. Furthermore 11 of these patients who did not undergo surgery (9 with mitral and 2 with mitro-aortic vegetations on echo) were serially followed-up with echocardiography for 6-42 months (average: 32 months). The presence of ultrasound detectable vegetations itself and their size, without considering their site, did not identify a major risk of embolization, heart failure, death or need of surgery. The site of vegetations was the only significant feature in our series. It identified a high-risk group and a relatively low-risk group. Aortic valve involvement, with echocardiographic vegetations, was related to severe or moderate heart failure (P less than 0.01), death or need of surgery (P less than 0.05). Mitral valve involvement carried on a relatively low risk. The 9 patients with mitral valve vegetations only, not referred for surgery and followed-up, did well on medical treatment and returned to work. They did not have relapses or embolization. On serial echocardiographic examinations, mitral vegetations become smaller in the long run. Two years after the acute episode, usually echocardiography did not allow identification of vegetations.

[New data on Albanian demography]. / Nuovi dati sulla demografia albanese

PIP: An introduction to the demography of Albania is presented using data from a recent study by V. Misja and Y. Vejsiu. These data indicate that the demographic transition has begun and that infant mortality is about 50 per 1,000. (summary in FRE, ENG)^ieng

[Diagnostic value of echocardiographic examinations in the evaluation of patients with infectious endocarditis of aortic and/or mitral valve localization]. / Utilità diagnostica dell'esame ecocardiografico nella valutazione dei pazienti con endocardite infettiva a localizzazione valvolare aortica e/o mitralica.

We estimated sensitivity, specificity, predictive value and efficiency of echocardiography in detecting vegetations and ruptured valves in patients with aortic and/or mitral valves infective endocarditis. We studied two groups of patients, in whom both high quality echocardiography examination and surgical inspection of heart valves were available. Group I: 16 patients (32 valves) with aortic and/or mitral valves endocarditis and surgical demonstration of vegetations and/or ruptured valves. In this group the prevalence of vegetations was 65.6%, the prevalence of ruptured valves was 43.7%. Group II was composed of the 16 patients of group I with endocarditis and of 93 other patients without endocarditis. In this group (139 valves) the prevalence of vegetations was 15%, the prevalence of ruptured valves was 13.6%. Echocardiographic detection of valve vegetations. Sensitivity (71.4%) was the same in group I and II. Specificity was 91% in group I and 91.5% in group II. The positive predictive value was 93.7% in group I and 60% in group II. The negative predictive value was 62.5% and 94.7% respectively. Echocardiographic detection of ruptured valves: sensitivity was 50% in I and 42% in group II. Specificity was 94.4% in group I and 99% in group II. The positive predictive value was 87.5% in group I and 89% in group II. The negative predictive value was 70.8% in group I and 91.5% in group II. The echocardiographic efficiency was higher in group II: 88.4% for vegetations and 91.3% for ruptured valves. This reflects the high specificity and the high definition of normal valves in this unselected low-risk group. The efficiency was lower in group I: 78% for vegetations and 75% for ruptured valves. This reflects the poor sensitivity and the failure of the test to identify all the vegetations or the ruptured valves in this selected high-risk group.

[The estimation of the expectation of life in the case of truncation of the survivorship function at older ages: some considerations]. / La stima della vita media nel caso di troncamento della funzione di sopravvivenza alle eta elevate: alcune osservazioni

"A tentative approximation of the expectation of life at 60-65 years, for populations with defective demographic statistics, is explored and expounded on the basis of a recent Horiuchi and [Coale] paper." The method is applied to data for El Salvador, Mexico, Puerto Rico, and Peninsular Malaysia, and it is shown that the method can be used on actual data, although it requires some drastic rounding off. (summary in ENG, FRE)