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.

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.

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.

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.

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.

[How to anticipate the knowledge of a conjectural index of fertility (author's transl)]. / Come anticipare la conoscenza di un indicatore congiuntural della fecondita.

PIP: A calculation method for the total fertility rate is proposed. It is based on partial knowledge of demographic data and anticipates the exact evaluation of this conjectural measure of about 2 years. Such index is very interesting and its timely evaluation is of notable interest. (author's)^ieng

[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

[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

[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)

[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

[Some questions concerning the demography of Somalia]. / Alcune questioni sulla demografia della Somalia

PIP: The available demographic data for Somalia are reviewed, and summary life tables by sex are constructed. Consideration is given to mortality, age distribution, and fertility. The lack of adequate demographic data is noted. (summary in ENG, FRE)^ieng

[Arithmetic average or harmonic average in the measurement of infant mortality?]. / Media aritmetica o media armonica nella stima della mortalita infantile?

The author examines whether an arithmetic average or harmonic average should be used in infant mortality measures. "The correction of the measure of infant mortality is proposed as [a] harmonic average of live births in two contiguous years." (summary in ENG, FRE)

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.

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.

[Effects of prolonged fasting and vagotomy on the ultrastructure of contractile myocardium in pigeons]. / Effetti del digiuno prolungato e della vagotomia sull'ultra struttura del miocardio contrattile degli uccelli.

Ultrastructural changes in pigeon heart following long fasting and vagotomy are reported. In the fasting pigeons several fat droplets surrounding the adjacent nearest mitochondria represent the most important finding. Conversely, in the fasting and vagotomized pigeons the mean finding is a large decrease of fat droplets. Ultrastructural findings appear related with biochemical changes by different experimental conditions.

[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.