Transcriptional Response to Acute Thermal Exposure in Juvenile Chinook Salmon Determined by RNAseq.

Thermal exposure is a serious and growing challenge facing fish species worldwide. Chinook salmon (Oncorhynchus tshawytscha) living in the southern portion of their native range are particularly likely to encounter warmer water due to a confluence of factors. River alterations have increased the likelihood that juveniles will be exposed to warm water temperatures during their freshwater life stage, which can negatively impact survival, growth, and development and pose a threat to dwindling salmon populations. To better understand how acute thermal exposure affects the biology of salmon, we performed a transcriptional analysis of gill tissue from Chinook salmon juveniles reared at 12° and exposed acutely to water temperatures ranging from ideal to potentially lethal (12° to 25°). Reverse-transcribed RNA libraries were sequenced on the Illumina HiSeq2000 platform and a de novo reference transcriptome was created. Differentially expressed transcripts were annotated using Blast2GO and relevant gene clusters were identified. In addition to a high degree of downregulation of a wide range of genes, we found upregulation of genes involved in protein folding/rescue, protein degradation, cell death, oxidative stress, metabolism, inflammation/immunity, transcription/translation, ion transport, cell cycle/growth, cell signaling, cellular trafficking, and structure/cytoskeleton. These results demonstrate the complex multi-modal cellular response to thermal stress in juvenile salmon

A systematic review of the evidence for single stage and two stage revision of infected knee replacement

BACKGROUND: Periprosthetic infection about the knee is a devastating complication that may affect between 1% and 5% of knee replacement. With over 79 000 knee replacements being implanted each year in the UK, periprosthetic infection (PJI) is set to become an important burden of disease and cost to the healthcare economy. One of the important controversies in treatment of PJI is whether a single stage revision operation is superior to a two-stage procedure. This study sought to systematically evaluate the published evidence to determine which technique had lowest reinfection rates. METHODS: A systematic review of the literature was undertaken using the MEDLINE and EMBASE databases with the aim to identify existing studies that present the outcomes of each surgical technique. Reinfection rate was the primary outcome measure. Studies of specific subsets of patients such as resistant organisms were excluded. RESULTS: 63 studies were identified that met the inclusion criteria. The majority of which (58) were reports of two-stage revision. Reinfection rated varied between 0% and 41% in two-stage studies, and 0% and 11% in single stage studies. No clinical trials were identified and the majority of studies were observational studies. CONCLUSIONS: Evidence for both one-stage and two-stage revision is largely of low quality. The evidence basis for two-stage revision is significantly larger, and further work into direct comparison between the two techniques should be undertaken as a priority

A research agenda for malaria eradication: monitoring, evaluation, and surveillance

Monitoring, evaluation, and surveillance measure how well public health programs operate over time and achieve their goals. As countries approach malaria elimination, these activities will need to shift from measuring reductions in morbidity and mortality, to detecting infections (with or without symptoms) and measuring transmission. Thus, the monitoring and evaluation and surveillance research and development agenda needs to develop the tools and strategies that will replace passive surveillance of morbidity with active and prompt detection of infection, including confirmation of interruption of transmission by detecting present and past infections, particularly in mobile populations. The capacity to assess trends and respond without delay will need to be developed, so that surveillance itself becomes an intervention. Research is also needed to develop sensitive field tests that can detect low levels of parasitaemia, together with strategies for their implementation. Other areas to explore include the rigorous evaluation of the utility of more detailed maps of disease and infection incidence and prevalence, the development of new maps to inform programmatic responses and the use of surveillance technologies based on cell phone or real-time internet Web-based reporting. Because any new strategies for monitoring and evaluation and surveillance for eradication have major implications for program implementation, research is also needed to test systems of delivery for acceptability, feasibility, efficiency, cost-effectiveness, and community engagement. Finally, there is a clear need to systematically review the information from past elimination efforts for malaria and other infectious diseases

Revision total hip arthroplasty using the Zweymuller femoral stem

Background: A variety of femoral stem designs have been reported to be successful in revision total hip arthroplasty without consensus as to optimal design. We evaluated the clinical and radiographic outcomes in a consecutive series of femoral revisions using a wedge-shape, tapered-stem design at medium and long-term follow-up. Materials and methods: We performed a retrospective review of clinical and radiographic outcomes of twenty-eight consecutive femoral revisions arthroplasties, which were done using the Zweymuller femoral stem. Results: The mean follow-up was 7.4 years (range 2-15 years). No stem re-revision was necessary. All stems were judged to be stable by radiographic criteria at the most recent follow-up. The final mean Harris hip score was 90. There was no difference in Harris hip scores, implant stability, or radiological appearance (distal cortical hypertrophy or proximal stress shielding) of the implants between medium-term (mean 5.7 years) and long-term (mean 12.4 years) follow-up. Conclusions: We found the Zweymuller femoral stem design to be durable for revision hip arthroplasty when there is an intact metaphyseal-diaphyseal junction for adequate press-fit stability at surgery. © Springer-Verlag 2008

Effects of work-related factors on the breastfeeding behavior of working mothers in a Taiwanese semiconductor manufacturer: a cross-sectional survey

BACKGROUND: In recent years, the creation of supportive environments for encouraging mothers to breastfeed their children has emerged as a key health issue for women and children. The provision of lactation rooms and breast pumping breaks have helped mothers to continue breastfeeding after returning to work, but their effectiveness is uncertain. The aim of this study was to assess the effects of worksite breastfeeding-friendly policies and work-related factors on the behaviour of working mothers. METHODS: This study was conducted at a large Taiwanese semiconductor manufacturer in August-September 2003. Questionnaires were used to collect data on female employees' breastfeeding behaviour, child rearing and work status when raising their most recently born child. A total of 998 valid questionnaires were collected, giving a response rate of 75.3%. RESULTS: The results showed that 66.9% of survey respondents breastfed initially during their maternity leave, which averaged 56 days. Despite the provision of lactation rooms and breast pumping breaks, only 10.6% mothers continued to breastfeed after returning to work, primarily office workers and those who were aware of their company's breastfeeding-friendly policies. CONCLUSION: In conclusion, breastfeeding-friendly policies can significantly affect breastfeeding behaviour. However, an unfavourable working environment, especially for fab workers, can make it difficult to implement breastfeeding measures. With health professionals emphasizing that the importance of breastfeeding for infant health, and as only females can perform lactation, it is vital that women's work "productive role" and family "reproductive role" be respected and accommodated by society

Genome-Wide Expression Analysis Identifies a Modulator of Ionizing Radiation-Induced p53-Independent Apoptosis in Drosophila melanogaster

Tumor suppressor p53 plays a key role in DNA damage responses in metazoa, yet more than half of human tumors show p53 deficiencies. Therefore, understanding how therapeutic genotoxins such as ionizing radiation (IR) can elicit DNA damage responses in a p53-independent manner is of clinical importance. Drosophila has been a good model to study the effects of IR because DNA damage responses as well as underlying genes are conserved in this model, and because streamlined gene families make loss-of-function analyses feasible. Indeed, Drosophila is the only genetically tractable model for IR-induced, p53-independent apoptosis and for tissue regeneration and homeostasis after radiation damage. While these phenomenon occur only in the larvae, all genome-wide gene expression analyses after irradiation to date have been in embryos. We report here the first analysis of IR-induced, genome-wide gene expression changes in wild type and p53 mutant Drosophila larvae. Key data from microarrays were confirmed by quantitative RT-PCR. The results solidify the central role of p53 in IR-induced transcriptome changes, but also show that nearly all changes are made of both p53-dependent and p53-independent components. p53 is found to be necessary not just for the induction of but also for the repression of transcript levels for many genes in response to IR. Furthermore, Functional analysis of one of the top-changing genes, EF1a-100E, implicates it in repression of IR-induced p53-independent apoptosis. These and other results support the emerging notion that there is not a single dominant mechanism but that both positive and negative inputs collaborate to induce p53-independent apoptosis in response to IR in Drosophila larvae

The UBA-UIM Domains of the USP25 Regulate the Enzyme Ubiquitination State and Modulate Substrate Recognition

USP25m is the muscle isoform of the deubiquitinating (DUB) enzyme USP25. Similarly to most DUBs, data on USP25 regulation and substrate recognition is scarce. In silico analysis predicted three ubiquitin binding domains (UBDs) at the N-terminus: one ubiquitin-associated domain (UBA) and two ubiquitin-interacting motifs (UIMs), whereas no clear structural homology at the extended C-terminal region outside the catalytic domains were detected. In order to asses the contribution of the UBDs and the C-terminus to the regulation of USP25m catalytic activity, ubiquitination state and substrate interaction, serial and combinatorial deletions were generated. Our results showed that USP25m catalytic activity did not strictly depend on the UBDs, but required a coiled-coil stretch between amino acids 679 to 769. USP25 oligomerized but this interaction did not require either the UBDs or the C-terminus. Besides, USP25 was monoubiquitinated and able to autodeubiquitinate in a possible loop of autoregulation. UBDs favored the monoubiquitination of USP25m at the preferential site lysine 99 (K99). This residue had been previously shown to be a target for SUMO and this modification inhibited USP25 activity. We showed that mutation of K99 clearly diminished USP25-dependent rescue of the specific substrate MyBPC1 from proteasome degradation, thereby supporting a new mechanistic model, in which USP25m is regulated through alternative conjugation of ubiquitin (activating) or SUMO (inhibiting) to the same lysine residue (K99), which may promote the interaction with distinct intramolecular regulatory domains

Outcome of prosthesis exchange for infected knee arthroplasty: the effect of treatment approach: A systematic review of the literature

Background and purpose Two-stage revision remains the gold standard in the treatment of infected knee arthroplasty. Lately, good long-term results of direct exchange arthroplasty have been reported. The purpose of this literature review is to compare the clinical outcome achieved with one-stage revision and two-stage revision with different types of spacers

Deficient maternal care resulting from immunological stress during pregnancy is associated with a sex-dependent enhancement of conditioned fear in the offspring

Activation of maternal stress response systems during pregnancy has been associated with altered postpartum maternal care and subsequent abnormalities in the offspring’s brain and behavioral development. It remains unknown, however, whether similar effects may be induced by exposure to immunological stress during pregnancy. The present study was designed to address this issue in a mouse model of prenatal immune activation by the viral mimic polyriboinosinic–polyribocytidilic acid (PolyI:C). Pregnant mice were exposed to PolyI:C-induced immune challenge or sham treatment, and offspring born to PolyI:C- and sham-treated dams were simultaneously cross-fostered to surrogate rearing mothers, which had either experienced inflammatory or vehicle treatment during pregnancy. We evaluated the effects of the maternal immunological manipulation on postpartum maternal behavior, and we assessed the prenatal and postnatal maternal influences on anxiety- and fear-related behavior in the offspring at the peri-adolescent and adult stage of development. We found that PolyI:C treatment during pregnancy led to changes in postpartum maternal behavior in the form of reduced pup licking/grooming and increased nest building activity. Furthermore, the adoption of neonates by surrogate rearing mothers, which had experienced PolyI:C-induced immunological stress during pregnancy, led to enhanced conditioned fear in the peri-adolescent and adult offspring, an effect that was exclusively seen in female but not male subjects. Unconditioned (innate) anxiety-related behavior as assessed in the elevated plus maze and open field explorations tests were not affected by the prenatal and postnatal manipulations. Our results thus highlight that being raised by gestationally immune-challenged surrogate mothers increases the vulnerability for specific forms of fear-related behavioral pathology in later life, and that this association may be mediated by deficits in postpartum maternal care. This may have important implications for the identification and characterization of early-life risk factors involved in the developmental etiology of fear-related neuropsychiatric disorders