Psychological impact of testing for thrombophilic alterations

We investigated the psychological impact of testing for the presence of thrombophilic alterations. The enrolled subjects received counseling from a physician before blood sampling and after receiving results, with a view to provide clear information about the aim of thrombophilia screening (TS). Participants were requested to complete a pre-test questionnaire during this interview and a post-test questionnaire 20 days after receiving the TS results. One hundred ninety-seven subjects completed the pretest questionnaire and 140/197 (71.1%) returned the post-test one. The TS results were altered in 36 (25.7%, R506Q mutation n = 19; G20210A mutation n = 9; antithrombin deficiency n = 1; LAC phenomenon n = 4; hyperhomocysteinemia n = 3) and normal in 104 subjects. We assessed: perceived health status (PHS), state of anxiety, health fears, depressive reactions, moods, perceived well-being, and perceived daily-life stress. For both groups, both at pre- and post-test, none of the psychological variable scores showed significant worsening, regardless of whether TS resulted altered or normal. Anxiety significantly (p < or = 0.05) decreased at post-test in the altered group and a non-significant improvement in PHS after TS result communication was recorded in both groups. Age was an important factor in mediating psychological impact. In conclusion, diagnosis of thrombophilic alterations seems to be well accepted in the short term and TS should not be discouraged for potential adverse psychological effects. However, the psychological impact over a longer period of receiving altered results needs to be further investigated. The relationship between absence of adverse psychological reactions and quality of counseling program provided before and after TS should also be investigated.     

Neurodegeneration induced by complex I inhibition in a cellular model of familial amyotrophic lateral sclerosis

G93A Cu/Zn superoxide dismutase (SOD1), a human mutant SOD1 associated with familial amyotrophic lateral sclerosis, increased the toxicity of the mitochondrial toxin rotenone in the NSC-34 motoneuronal cell line. G93ASOD1 cells died more than untransfected and wild-type SOD1 cells after 6 and 24h exposure to 12.5 microM rotenone. Biparametric flow cytometry showed that rotenone induced rapid hyperpolarization of mitochondrial membrane potential (deltapsi(m)) in all the cell lines, followed by depolarization, and then by cell death. However, G93ASOD1 mitochondria were significantly more likely to shift from a hyperpolarized to a depolarized condition, and within the still viable cell population there was a higher proportion with depolarized mitochondria, a condition that can be envisaged as a commitment to cell death. ATP, which is needed to prevent loss of deltapsi(m), decreased more rapidly and to a greater extent in rotenone-treated G93ASOD1 cells than in the untransfected and wtSOD1cells. In all the cell lines, 1h after rotenone exposure, mitochondrial hyperpolarization was accompanied by the formation of a comparable amount of reactive oxygen species. However, G93ASOD1 cells reached the highest reactive oxygen species level since their basal level was higher than in untransfected and wild-type SOD1 cells. Our findings indicate that the mutant protein G93ASOD1 enhances the vulnerability of motor neurons to rotenone by mechanism(s) involving oxidative stress and perturbed mitochondrial homeostasis. This suggests that motor neurons from individuals carrying the mutant G93ASOD1 are at greater risk of death after inhibition of the electron transport chain.     

Three-Dimensional Co-Culture System of Human Osteoblasts and Osteoclast Precursors from Osteoporotic Patients as an Innovative Model to Study the Role of Nutrients: Focus on Vitamin K2

Several natural compounds, such as vitamin K2, have been highlighted for their positive effects on bone metabolism. It has been proposed that skeletal disorders, such as osteoporosis, may benefit from vitamin K2-based therapies or its regular intake. However, further studies are needed to better clarify the effects of vitamin K2 in bone disorders. To this aim, we developed in vitro a three-dimensional (3D) cell culture system one step closer to the bone microenvironment based on co-culturing osteoblasts and osteoclasts precursors obtained from bone specimens and peripheral blood of the same osteoporotic patient, respectively. Such a 3-D co-culture system was more informative than the traditional 2-D cell cultures when responsiveness to vitamin K2 was analyzed, paving the way for data interpretation on single patients. Following this approach, the anabolic effects of vitamin K2 on the osteoblast counterpart were found to be correlated with bone turnover markers measured in osteoporotic patients’ sera. Overall, our data suggest that co-cultured osteoblasts and osteoclast precursors from the same osteoporotic patient may be suitable to generate an in vitro 3-D experimental model that potentially reflects the individual’s bone metabolism and may be useful to predict personal responsiveness to nutraceutical or drug molecules designed to positively affect bone health.     

Combination of one-view digital breast tomosynthesis with one-view digital mammography versus standard two-view digital mammography: per lesion analysis

Objective

To evaluate the clinical value of combining one-view mammography (cranio-caudal, CC) with the complementary view tomosynthesis (mediolateral-oblique, MLO) in comparison to standard two-view mammography (MX) in terms of both lesion detection and characterization.

Methods

A free-response receiver operating characteristic (FROC) experiment was conducted independently by six breast radiologists, obtaining data from 463 breasts of 250 patients. Differences in mean lesion detection fraction (LDF) and mean lesion characterization fraction (LCF) were analysed by analysis of variance (ANOVA) to compare clinical performance of the combination of techniques to standard two-view digital mammography.

Results

The 463 cases (breasts) reviewed included 258 with one to three lesions each, and 205 with no lesions. The 258 cases with lesions included 77 cancers in 68 breasts and 271 benign lesions to give a total of 348 proven lesions. The combination, DBT_(MLO)+MX_(CC), was superior to MX (CC+MLO) in both lesion detection (LDF) and lesion characterization (LCF) overall and for benign lesions. DBT_(MLO)+MX_(CC) was non-inferior to two-view MX for malignant lesions.

Conclusions

This study shows that readers’ capabilities in detecting and characterizing breast lesions are improved by combining single-view digital breast tomosynthesis and single-view mammography compared to two-view digital mammography.

Key Points

? Digital breast tomosynthesis is becoming adopted as an adjunct to mammography (MX) ? DBT _(MLO) +MX _(CC) is superior to MX _(CC+MLO) in lesion detection (overall and benign lesions) ? DBT _(MLO) +MX _(CC) is non-inferior to MX _(CC+MLO) in cancer detection ? DBT _(MLO) +MX _(CC) is superior to MX _(CC+MLO) in lesion characterization (overall and benign lesions) ? DBT _(MLO) +MX _(CC) is non-inferior to MX _(CC+MLO) in characterization of malignant lesions     

Public awareness of ear and hearing management as measured using a specific questionnaire

Public awareness of audiological issues has never been measured in the general public even if the World Health Organization (WHO) has detected a common urgent need for action to prevent and manage ear diseases and hearing loss. The aim of this study was to measure urban community citizens’ awareness of managing and preventing ear disease and hearing loss using a specific questionnaire. A questionnaire was formulated on the basis of WHO material concerning the major specific audiological issues and attitudes, focusing in particular on four domains: (1) knowledge of infant hearing loss, (2) correct management of the ears including cleaning and treating, (3) focus on the effect of overexposure to loud sounds and noise, (4) underestimated ear symptoms leading to diagnostic delay. 254 volunteers were enrolled in this cross-sectional study by a team of medical doctors and audiologists stationed in a mobile unit that visited different areas of Milan, Italy. More than 80% of correct responses were given to almost all of the statements by the interviewees, although certain important knowledge was found to be lacking. The proposed audiological questionnaire seems to be a suitable tool to evaluate the public awareness of ear and hearing management. The results showed a need for continued development of comprehensive hearing conservation programs, focused on hearing aid management and early infant hearing loss identification as well as noise exposure.     

Exploring Validity,Reliability, and Factor Analysis of the Quebec User Evaluation of Satisfaction with Assistive Technology in an Italian Population: A Cross-Sectional Study

Abstract

This study explores validity, reliability, and factor analysis of the Quebec User Evaluation of Satisfaction with Assistive Technology (IT-QUEST) for users of assistive technology devices in an Italian population. It was administered to 75 people to determine which of the 24 original items were relevant to the Italian context using exploratory and confirmatory factor analyses (EFAs and CFAs) were conducted with internal consistency and test-retest reproducibility also evaluated. The EFA and CFA showed that the 24-item survey may have limited relevance to the Italian context. We individuated 12 significative items, divided into two subscales, as well as the original validation. The test-retest showed high values of the Intraclass Correlation Coefficient (ICC) (0.7–0.9), with a 0.812 ICC for the total scale providing support and evidence for Italian professionals to evaluate user satisfaction with assistive technology devices. This research also lays the foundation for developing a validation study of the IT-QUEST 2.0 that is relevant to the Italian culture. Further research may investigate psychometric properties involving more participants and different users of assistive technology devices.     

Hepatitis B specific T cell immunity induced by primary vaccination persists independently of the protective serum antibody level

In 2005, in accordance with recommendations made by the European Medicines Agency, the Italian Drug Agency ordered withdrawal of the hexavalent Hexavac^® vaccine (Sanofi Pasteur MSD) from the market. Concerns had been raised about the low immunogenicity of the hepatitis B virus component of the vaccine, assessed by measurement of serum antibody levels, and its potential consequences on long-term protection against hepatitis B infection. We evaluated memory T cell response to establish whether there are differences in the protective mechanisms among children who had received either Hexavac^® or Infanrix-hexa^® (GlaxoSmithKline) as their primary vaccination. Immunological memory was determined by measuring the ability of T cells to proliferate and secrete IFNγ by ELISA and intracellular cytokines (IFNγ and IL-2) when cultured with hepatitis B surface antigen (HBsAg). The different memory subsets of T cells were also measured.     

Efficacy of specific bioelectrical impedance vector analysis (BIVA) for assessing body composition in the elderly

Objectives

This study aimed to ascertain the efficacy of bioelectrical impedance vector analysis (BIVA) in assessing body composition in the elderly by comparing findings with the results of dual-energy X-ray absorptiometry (DXA), and to test an analytical variant of the method (specific BIVA).

Design

Cross-sectional study.

Participants

The sample comprised 207 free-living elderly individuals (75 men and 132 women) aged 65 to 93 years.

Measurements

Anthropometric and bioelectrical measurements were taken according to standard criteria. BIVA was applied using the ‘classic’ procedure and correcting bioelectrical values for body geometry to obtain an estimate of the whole-body impedivity. DXA was used as a reference body composition assessment method. BIVA (classic and specific values) and DXA findings were compared using Student’s t and Hotelling’s T2 tests, and Pearson’s correlation coefficient.

Results

In both sexes, BIVA distinguished between individuals with different amounts of fat and fat-free mass (lean mass including bone mineral content), according to DXA, but not between those with different proportions of fat mass (FM%). Specific bioelectrical values detected changes in body composition.

Conclusion

BIVA should be used with caution for evaluating body composition in the elderly. Specific bioelectrical values proved effective, showing promise as a methodological variant of BIVA, suitable for identifying age-related changes in body fatness.     

Outcome of a phase II prospective study on partial breast irradiation with interstitial multi-catheter high-dose-rate brachytherapy

Background and purpose

Partial breast irradiation (PBI) is an alternative to whole-breast irradiation after breast-conserving surgery in selected patients. Until the results of randomized phase III studies are available, phase II studies inform about PBI. We report the 5 year results of a phase II prospective study with PBI using interstitial multi-catheter high-dose-rate brachytherapy (ClinicalTrials.gov Identifier: NCT00499057).

Methods

Hundred patients received PBI (4 Gy, twice a day for 4 days, until 32 Gy). Inclusion criteria were: age ?40 years, infiltrating carcinoma without lobular histology, ductal in situ carcinoma, tumor size ?2.5 cm, negative surgical margins and axillary lymph nodes.

Results

At a median follow-up of 60 months late toxicity occurred in 25 patients; the 5-year probability of freedom from late toxicity was 72.6% (95% CI: 63.7–81.7). Tamoxifen was the only significant risk factor for late toxicity. Cosmetic results, judged by physicians and patients, were good/excellent in 98 patients. Three local relapses (1 true, 2 elsewhere) and 1 regional relapse occurred. The 5-year probability of local or regional relapse-free survival was 97.7% (95% CI: 91.1–99.4) and 99.0% (95% CI: 92.9–99.8), respectively.

Conclusion

PBI with interstitial multi-catheter brachytherapy is associated with low relapse and late toxicity rates.