Therapeutic ultrasound: Recent trends and future perspectives

AbstractBefore ultrasound-imaging systems became widely available, ultrasound therapy devices showed great promise for general use in medicine. However, it is only in the last decade that ultrasound therapy has begun to obtain clinical acceptance. Recently, a variety of novel applications of therapeutic ultrasound have been developed that include sonothrombolysis, site-specific and ultrasound-mediated drug delivery, shock wave therapy, lithotripsy, tumor ablation, acoustic hemostasis and several others. This paper reviews a few selected applications of therapeutic ultrasound. It will address some of the basic scientific questions and future challenges in developing these methods and technologies for general use in our society. As a plenary presentation, its audience is intended for the ultrasound scientist or engineer, and thus is not presented at the level of the experienced medical ultrasound professional

Predicting the onset of major depression in subjects with subthreshold depression in primary care: A prospective study.

Objective: That subjects with subthreshold depression have an increased probability of developing major depression has been confirmed by many studies. However, the factors which may predict the onset of major depression have yet to be fully examined. Method: We examined the control group of a randomized trial in primary care patients with subthreshold depression (N ¼ 109), of whom 20 had developed major depression 1 year later. Using the vulnerability-stress theory, we examined which factors predicted the onset of major depression. Results: In both univariate and multivariate analyses, family history and chronic illnesses predicted the onset of major depression. Conclusion: It is possible to predict to a certain degree whether a subject with subthreshold depression will develop major depression within a year

The relationship between parental socio-economic status and episodes of drunkenness among adolescents: findings from a cross-national survey

BACKGROUND: Behavioral factors such as (excessive) alcohol consumption play a major role in the explanation of social inequalities in health. The unequal distribution of health risk behaviors among socio-economic groups has important consequences for both the current and future health status of the younger generation. However, little is known about socio-economic differences in unhealthy lifestyles during adolescence. The purpose of the present study is to investigate socio-economic differences in adolescent drinking behaviour among 11–15 year old adolescents in Europe and North America. METHODS: Data was obtained from the Health Behaviour in School-aged Children (HBSC) study 2001/02, a cross-national survey conducted in collaboration with the World Health Organization. The present analysis is based on 69249 male and 73619 female students from 28 countries. The effect of parental occupation and family affluence on episodes of drunkenness was assessed using separate logistic regression models controlling for age. RESULTS: Socio-economic circumstances of the family had only a limited effect on repeated drunkenness in adolescence. For girls only in one out of 28 countries a significant association between family affluence and repeated drunkenness was observed, while boys from low and/or medium affluent families in nine countries faced a lower risk of drunkenness than boys from more affluent families. Regarding parental occupation, significant differences in episodes of drunkenness were found in nine countries for boys and in six countries for girls. Compared to family affluence, which was positively related to risk of drunkenness, a decreasing occupational status predicted an increasing risk of drunkenness. This pattern was identified within a number of countries, most noticeably for boys. CONCLUSION: Parental socio-economic status is only of limited importance for episodes of drunkenness in early adolescence, and this very limited role seems to apply for girls more than for boys and for parental occupation more than family affluence. For future studies it might be important to look at the effects of socio-economic status within the context of other peer, family and school related factors in order to assess to what extent those factors might mediate the effects of social class background

Host Immune Transcriptional Profiles Reflect the Variability in Clinical Disease Manifestations in Patients with Staphylococcus aureus Infections

Staphylococcus aureus infections are associated with diverse clinical manifestations leading to significant morbidity and mortality. To define the role of the host response in the clinical manifestations of the disease, we characterized whole blood transcriptional profiles of children hospitalized with community-acquired S. aureus infection and phenotyped the bacterial strains isolated. The overall transcriptional response to S. aureus infection was characterized by over-expression of innate immunity and hematopoiesis related genes and under-expression of genes related to adaptive immunity. We assessed individual profiles using modular fingerprints combined with the molecular distance to health (MDTH), a numerical score of transcriptional perturbation as compared to healthy controls. We observed significant heterogeneity in the host signatures and MDTH, as they were influenced by the type of clinical presentation, the extent of bacterial dissemination, and time of blood sampling in the course of the infection, but not by the bacterial isolate. System analysis approaches provide a new understanding of disease pathogenesis and the relation/interaction between host response and clinical disease manifestations

Change of Positive Selection Pressure on HIV-1 Envelope Gene Inferred by Early and Recent Samples

HIV-1 infection has been on the rise in Japan recently, and the main transmission route has changed from blood transmission in the 1980s to homo- and/or hetero-sexual transmission in the 2000s. The lack of early viral samples with clinical information made it difficult to investigate the possible virological changes over time. In this study, we sequenced 142 full-length env genes collected from 16 Japanese subjects infected with HIV-1 in the 1980s and in the 2000s. We examined the diversity change in sequences and potential adaptive evolution of the virus to the host population. We used a codon-based likelihood method under the branch-site and clade models to detect positive selection operating on the virus. The clade model was extended to account for different positive selection pressures in different viral populations. The result showed that the selection pressure was weaker in the 2000s than in the 1980s, indicating that it might have become easier for the HIV to infect a new host and to develop into AIDS now than 20 years ago and that the HIV may be becoming more virulent in the Japanese population. The study provides useful information on the surveillance of HIV infection and highlights the utility of the extended clade models in analysis of virus populations which may be under different selection pressures

When What's Left Is Right: Visuomotor Transformations in an Aged Population

Background: There has been little consensus as to whether age-related visuomotor adaptation effects are readily observable. Some studies have found slower adaptation, and/or reduced overall levels. In contrast, other methodologically similar studies have found no such evidence of aging effects on visuomotor adaptation. A crucial early step in successful adaptation is the ability to perform the necessary transformation to complete the task at hand. The present study describes the use of a viewing window paradigm to examine the effects of aging in a visuomotor transformation task. Methods: Two groups of participants, a young adult control group (age range 18–33 years old, mean age = 22) and an older adult group (age range 62–74, mean age = 68) completed a viewing window task that was controlled by the user via a computer touchscreen. Four visuomotor ‘‘flip’ ’ conditions were created by varying the relationship between the participant’s movement, and the resultant on-screen movement of the viewing window: 1) No flip 2) X-Axis and Y-axis body movements resulted in the opposite direction of movement of the viewing window. In each of the 3) Flip-X and 4) Flip-Y conditions, the solitary X- or Y-axes were reversed. Response times and movement of the window were recorded. Conclusions: Older participants demonstrated impairments in performing a required visuomotor transformation, as evidenced by more complex scanning patterns and longer scanning times when compared to younger control participants. These results provide additional evidence that the mechanisms involved in visuomotor transformation are negatively affected by age

Regulation of ABCC6 trafficking and stability by a conserved C-terminal PDZ-like sequence

Mutations in the ABCC6 ABC-transporter are causative of pseudoxanthoma elasticum (PXE). The loss of functional ABCC6 protein in the basolateral membrane of the kidney and liver is putatively associated with altered secretion of a circulatory factor. As a result, systemic changes in elastic tissues are caused by progressive mineralization and degradation of elastic fibers. Premature arteriosclerosis, loss of skin and vascular tone, and a progressive loss of vision result from this ectopic mineralization. However, the identity of the circulatory factor and the specific role of ABCC6 in disease pathophysiology are not known. Though recessive loss-of-function alleles are associated with alterations in ABCC6 expression and function, the molecular pathologies associated with the majority of PXE-causing mutations are also not known. Sequence analysis of orthologous ABCC6 proteins indicates the C-terminal sequences are highly conserved and share high similarity to the PDZ sequences found in other ABCC subfamily members. Genetic testing of PXE patients suggests that at least one disease-causing mutation is located in a PDZ-like sequence at the extreme C-terminus of the ABCC6 protein. To evaluate the role of this C-terminal sequence in the biosynthesis and trafficking of ABCC6, a series of mutations were utilized to probe changes in ABCC6 biosynthesis, membrane stability and turnover. Removal of this PDZ-like sequence resulted in decreased steady-state ABCC6 levels, decreased cell surface expression and stability, and mislocalization of the ABCC6 protein in polarized cells. These data suggest that the conserved, PDZ-like sequence promotes the proper biosynthesis and trafficking of the ABCC6 protein. © 2014 Xue et al

Mechanobiological Modulation of Cytoskeleton and Calcium Influx in Osteoblastic Cells by Short-Term Focused Acoustic Radiation Force

Mechanotransduction has demonstrated potential for regulating tissue adaptation in vivo and cellular activities in vitro. It is well documented that ultrasound can produce a wide variety of biological effects in biological systems. For example, pulsed ultrasound can be used to noninvasively accelerate the rate of bone fracture healing. Although a wide range of studies has been performed, mechanism for this therapeutic effect on bone healing is currently unknown. To elucidate the mechanism of cellular response to mechanical stimuli induced by pulsed ultrasound radiation, we developed a method to apply focused acoustic radiation force (ARF) (duration, one minute) on osteoblastic MC3T3-E1 cells and observed cellular responses to ARF using a spinning disk confocal microscope. This study demonstrates that the focused ARF induced F-actin cytoskeletal rearrangement in MC3T3-E1 cells. In addition, these cells showed an increase in intracellular calcium concentration following the application of focused ARF. Furthermore, passive bending movement was noted in primary cilium that were treated with focused ARF. Cell viability was not affected. Application of pulsed ultrasound radiation generated only a minimal temperature rise of 0.1°C, and induced a streaming resulting fluid shear stress of 0.186 dyne/cm2, suggesting that hyperthermia and acoustic streaming might not be the main causes of the observed cell responses. In conclusion, these data provide more insight in the interactions between acoustic mechanical stress and osteoblastic cells. This experimental system could serve as basis for further exploration of the mechanosensing mechanism of osteoblasts triggered by ultrasound