State-of-the-Art Management of Complications of Myeloma and Its Treatment

Multiple myeloma is an incurable disease, although patient survival has increased with the availability of novel agents. Both multiple myeloma and its therapies often affect the renal, immune, skeletal, hematologic, and nervous systems. The resulting organ dysfunctions often impair the quality of life of affected patients, complicate and limit subsequent therapies, and may result in significant mortality. Research on the treatment of complications of multiple myeloma has been limited; hence, preventative and management strategies for patients with these complications are heterogeneous and often based on anecdotal experience. In this paper, we review the effects of myeloma and the novel therapies on organ systems and suggest management strategies

Transcriptional regulation of topoisomerase II at confluence and pharmacological modulation of expression by bis-benzimidazole drugs

ABSTRACT Topoisomerase II␣ is a critical gene involved in DNA replication and maintenance of genomic stability. Several chemotherapeutic agents target topoisomerase II and levels of expression are an important factor in chemosensitivity. Transcriptional regulation has been demonstrated to regulate topoisomerase II␣ levels under several circumstances, including cellular confluence, heat shock, and expression of oncogenes including ras and myb. Expression of topoisomerase II␣ is regulated by cellular proliferation; transcriptional down-regulation in confluent cells is modulated through sequences within the promoter. In this study, we examined DNA-protein interactions within the topoisomerase II␣ promoter in exponential and confluent phase NIH3T3 cells. Using electrophoretic mobility shift assay and in vitro DNase I footprint experiments, the involvement of NF-Y in transcriptional regulation was established. Incubation of the DNA minor groove-binding agents Hoechst 33342 and Hoechst 33258 with nuclear extracts revealed drug binding to regions surrounding the inverted CCAAT boxes within the topoisomerase II␣ promoter and displacement of proteins binding to these elements. Addition of both Hoechst 33342 and Hoechst 33258 to NIH3T3 cells at confluence resulted in increased expression of topoisomerase II␣. In addition, MTT cytotoxicity assays in confluent cells showed an additive effect of incubation with Hoechst 33342 and the topoisomerase II␣ poison etoposide. Therefore, DNA binding drugs which block transcription factor activation of the promoter may deregulate topoisomerase II␣ and this strategy may be of value in modifying gene expression and modulating chemosensitivity

Resonance line-profile calculations based on hydrodynamical models of cataclysmic variable winds

We present synthetic line profiles as predicted by the models of 2-D line- driven disk winds due to Proga, Stone & Drew. We compare the model line profiles with HST observations of the cataclysmic variable IX Vel. The model wind consists of a slow outflow that is bounded on the polar side by a fast stream. We find that these two components of the wind produce distinct spectral features. The fast stream produces profiles which show features consistent with observations. These include the appearance of the P-Cygni shape for a range of inclinations, the location of the maximum depth of the absorption component at velocities less than the terminal velocity, and the transition from absorption to emission with increasing inclination. However the model profiles have too little absorption or emission equivalent width. This quantitative difference between our models and observations is not a surprise because the line-driven wind models predict a mass loss rate that is lower than the rate required by the observations. We note that the model profiles exhibit a double-humped structure near the line center which is not echoed in observations. We identify this structure with a non-negligible redshifted absorption which is formed in the slow component of the wind where the rotational velocity dominates over expansion velocity. We conclude that the next generation of disk wind models, developed for application to CVs, needs to yield stronger wind driving out to larger disk radii than do the present models.Comment: LaTeX, 19 pages, to appear in Ap

NF-Y activates genes of metabolic pathways altered in cancer cells

The trimeric transcription factor NF-Y binds to the CCAAT box, an element enriched in promoters of genes overexpressed in tumors. Previous studies on the NF-Y regulome identified the general term metabolism as significantly enriched. We dissect here in detail the targeting of metabolic genes by integrating analysis of NF-Y genomic binding and profilings after inactivation of NF-Y subunits in different cell types. NF-Y controls de novo biosynthetic pathways of lipids, teaming up with the master SREBPs regulators. It activates glycolytic genes, but, surprisingly, is neutral or represses mitochondrial respiratory genes. NF-Y targets the SOCG (Serine, One Carbon, Glycine) and Glutamine pathways, as well as genes involved in the biosynthesis of polyamines and purines. Specific cancer-driving nodes are generally under NF-Y control. Altogether, these data delineate a coherent strategy to promote expression of metabolic genes fuelling anaerobic energy production and other anabolic pathways commonly altered in cancer cells

A meta‐analysis of fish behavioural reaction to underwater human presence

WOS:000483722600001In an increasingly anthropic world, humans have profound impacts on the distribution and behaviour of marine fishes. The increased human presence has modified fishes' antipredator behavioural responses, and consequently flight decisions, as a function of their changed perceptions of risk. Understanding how fish react to human presence can help identify the most vulnerable functional groups/species and estimate impacts caused by human disturbance. Shoal and body size are known to influence fish flight initiation distance (FID; the distance between the predator and prey when the prey begins to escape); however, few studies attempt to test the moderators of these relationships. Here, we present a comprehensive meta-analysis evaluating FID of fish in response to human presence. Specifically, we investigated six candidate moderators that could influence the relationship between FID with shoal and body size. Our results showed that individual fish size was strongly and positively correlated with FID and the most important moderator that explained the variance in individual body size-FID relationship was shoaling behaviour. However, and somehow surprisingly, we detected no significant relationship between shoal size and FID. We discuss how these results can inform the development of fish conservation strategies and ultimately assist in the management of marine protected areas

ICTV Virus Taxonomy Profile: Herpesviridae 2021

Members of the family Herpesviridae have enveloped, spherical virions with characteristic complex structures consisting of symmetrical and non-symmetrical components. The linear, double-stranded DNA genomes of 125–241 kbp contain 70–170 genes, of which 43 have been inherited from an ancestral herpesvirus. In general, herpesviruses have coevolved with and are highly adapted to their hosts, which comprise many mammalian, avian and reptilian species. Following primary infection, they are able to establish lifelong latent infection, during which there is limited viral gene expression. Severe disease is usually observed only in the foetus, the very young, the immunocompromised or following infection of an alternative host. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Herpesviridae, which is available at ictv.global/report/herpesviridae

Measurement in Economics and Social Science

The paper discusses measurement, primarily in economics, from both analytical and historical perspectives. The historical section traces the commitment to ordinalism on the part of economic theorists from the doctrinal disputes between classical economics and marginalism, through the struggle of orthodox economics against socialism down to the cold-war alliance between mathematical social science and anti-communist ideology. In economics the commitment to ordinalism led to the separation of theory from the quantitative measures that are computed in practice: price and quantity indexes, consumer surplus and real national product. The commitment to ordinality entered political science, via Arrow’s ‘impossibility theorem’, effectively merging it with economics, and ensuring its sterility. How can a field that has as its central result the impossibility of democracy contribute to the design of democratic institutions? The analytical part of the paper deals with the quantitative measures mentioned above. I begin with the conceptual clarification that what these measures try to achieve is a restoration of the money metric that is lost when prices are variable. I conclude that there is only one measure that can be embedded in a satisfactory economic theory, free from unreasonable restrictions. It is the Törnqvist index as an approximation to its theoretical counterpart the Divisia index. The statistical agencies have at various times produced different measures for real national product and its components, as well as related concepts. I argue that all of these are flawed and that a single deflator should be used for the aggregate and the components. Ideally this should be a chained Törnqvist price index defined on aggregate consumption. The social sciences are split. The economic approach is abstract, focused on the assumption of rational and informed behavior, and tends to the political right. The sociological approach is empirical, stresses the non-rational aspects of human behavior and tends to the political left. I argue that the split is due to the fact that the empirical and theoretical traditions were never joined in the social sciences as they were in the natural sciences. I also argue that measurement can potentially help in healing this split

Sibling relationships and family functioning in siblings of early adolescents, adolescents and young adults with autism spectrum disorder

The purpose of the study was to investigate how family functioning (defined as the ability that family members hold to manage stressful events, and intimate and social relationships), the degree to which family members feel happy and fulfilled with each other (called family satisfaction), and the demographical characteristics of siblings (age and gender) impacted on sibling relationships. The Circumplex Model of Marital and Family Systems and Behavioral Systems constituted the theoretical frameworks that guided our study. Eighty-six typically developing adolescents and young adults having a sister or a brother with autism spectrum disorder were enrolled. Results indicated that the youngest age group (early adolescents) reported to engage more frequently in negative behaviors with their siblings with ASD than the two older age groups (middle adolescents and young adults). No significant differences were found among the three age groups regarding behaviors derived from attachment, caregiving and affiliative systems. Family satisfaction and age significantly predicted behaviors during sibling interactions. Suggestions on prevention and intervention programs were discussed in order to prevent parentification among typically developing siblings and decrease episodes of quarrels and overt conflicts between brothers and sisters with and without AS

Are sexual health survey items understood as intended by African and Asian migrants to Australia? Methods, results and recommendations for qualitative pretesting

Introduction: More research and policy action are needed to improve migrant health in areas such as sexual health and blood-borne viruses (SHBBV). While Knowledge, Attitudes and Practice Surveys (KAPS) can inform planning, there are no SHBBV KAPS suitable for use across culturally and linguistically diverse contexts. This study pretests one instrument among people born in Sub-Saharan Africa, South-East and North-East Asia living in Australia. Methods: Employees of multicultural organisations were trained to collect data over three rounds using a hybrid qualitative pretesting method. Two researchers independently coded data. Researchers made revisions to survey items after each round. Responses to feedback questions in the final survey were analysed. Results: Sixty-two participants pretested the survey. Issues were identified in all three rounds of pretesting. Of the 77 final survey respondents who responded to a survey experience question, 21% agreed and 3% strongly agreed with the statement ‘I found it hard to understand some questions/words’. Conclusion: It is essential to pretest SHBBV surveys in migrant contexts. We offer the following pretesting guidance: (1) large samples are needed in heterogeneous populations; (2) intersectionality must be considered; (3) it may be necessary to pretest English language surveys in the participants’ first language; (4) bilingual/bicultural workers must be adequately trained to collect data; (5) results need to be interpreted in the context of other factors, including ethics and research aims; and (6) pretesting should occur over multiple rounds