Low infection rates after 34,361 intramedullary nail operations in 55 low- and middle-income countries: Validation of the Surgical Implant Generation Network (SIGN) Online Surgical Database

Background: The Surgical Implant Generation Network (SIGN) supplies intramedullary (IM) nails for the treatment of long bone fractures free of charge to hospitals in low- and middle-income countries (LMICs). Most operations are reported to the SIGN Online Surgical Database (SOSD). Follow-up has been reported to be low, however. We wanted to examine the pattern of follow-up and to assess whether infection rates could be trusted. Patients and methods: The SOSD contained 36,454 IM nail surgeries in 55 LMICs. We excluded humerus and hip fractures, and fractures without a registered surgical approach. This left 34,361 IM nails for analysis. A generalized additive regression model (gam) was used to explore the association between follow-up rates and infection rates. Results: The overall follow-up rate in the SOSD was 18.1% (95% CI: 17.7–18.5) and national follow-up rates ranged from 0% to 74.2%. The overall infection rate was 0.7% (CI: 0.6–0.8) for femoral fractures and 1.2% (CI: 1.0–1.4) for tibial fractures. If only nails with a registered follow-up visit were included (n = 6,224), infection rates were 3.5% (CI: 3.0–4.1) for femoral fractures and 7.3% (CI: 6.2–8.4) for tibial fractures. We found an increase in infection rates with increasing follow-up rates up to a level of 5%. Follow-up above 5% did not result in increased infection rates. Interpretation: Reported infection rates after IM nailing in the SOSD appear to be reliable and could be used for further research. The low infection rates suggest that IM nailing is a safe procedure also in low- and middle-income countries.publishedVersio

Tandem quadruplication of HMA4 in the zinc (Zn) and cadmium (Cd) hyperaccumulator noccaea caerulescens

Zinc (Zn) and cadmium (Cd) hyperaccumulation may have evolved twice in the Brassicaceae, in Arabidopsis halleri and in the Noccaea genus. Tandem gene duplication and deregulated expression of the Zn transporter, HMA4, has previously been linked to Zn/Cd hyperaccumulation in A. halleri. Here, we tested the hypothesis that tandem duplication and deregulation of HMA4 expression also occurs in Noccaea. A Noccaea caerulescens genomic library was generated, containing 36,864 fosmid pCC1FOSTM clones with insert sizes ~20–40 kbp, and screened with a PCR-generated HMA4 genomic probe. Gene copy number within the genome was estimated through DNA fingerprinting and pooled fosmid pyrosequencing. Gene copy numbers within individual clones was determined by PCR analyses with novel locus specific primers. Entire fosmids were then sequenced individually and reads equivalent to 20-fold coverage were assembled to generate complete whole contigs. Four tandem HMA4 repeats were identified in a contiguous sequence of 101,480 bp based on sequence overlap identities. These were flanked by regions syntenous with up and downstream regions of AtHMA4 in Arabidopsis thaliana. Promoter-reporter b-glucuronidase (GUS) fusion analysis of a NcHMA4 in A. thaliana revealed deregulated expression in roots and shoots, analogous to AhHMA4 promoters, but distinct from AtHMA4 expression which localised to the root vascular tissue. This remarkable consistency in tandem duplication and deregulated expression of metal transport genes between N. caerulescens and A. halleri, which last shared a common ancestor >40 mya, provides intriguing evidence that parallel evolutionary pathways may underlie Zn/Cd hyperaccumulation in Brassicaceae

Non-host resistance to penetration and hyphal growth of Magnaporthe oryzae in Arabidopsis

Rice blast caused by Magnaporthe oryzae is a devastating disease of rice. Mechanisms of rice resistance to blast have been studied extensively, and the rice–M. oryzae pathosystem has become a model for plant–microbe interaction studies. However, the mechanisms of non-host resistance (NHR) to rice blast in other plants remain poorly understood. We found that penetration resistance to M. oryzae in multiple mutants, including pen2 NahG pmr5 agb1 and pen2 NahG pmr5 mlo2 plants, was severely compromised and that fungal growth was permitted in penetrated epidermal cells. Furthermore, rice Pi21 enhanced movement of infection hyphae from penetrated Arabidopsis epidermal cells to adjacent mesophyll cells. These results indicate that PEN2, PMR5, AGB1, and MLO2 function in both penetration and post-penetration resistance to M. oryzae in Arabidopsis, and suggest that the absence of rice Pi21 contributed to Arabidopsis NHR to M. oryzae

Metabolic engineering of the iodine content in Arabidopsis

Plants are a poor source of iodine, an essential micronutrient for human health. Several attempts of iodine biofortification of crops have been carried out, but the scarce knowledge on the physiology of iodine in plants makes results often contradictory and not generalizable. In this work, we used a molecular approach to investigate how the ability of a plant to accumulate iodine can be influenced by different mechanisms. In particular, we demonstrated that the iodine content in Arabidopsis thaliana can be increased either by facilitating its uptake with the overexpression of the human sodium-iodide symporter (NIS) or through the reduction of its volatilization by knocking-out HOL-1, a halide methyltransferase. Our experiments show that the iodine content in plants results from a balance between intake and retention. A correct manipulation of this mechanism could improve iodine biofortification of crops and prevent the release of the ozone layer-threatening methyl iodide into the atmosphere

Do Students See the “Selection” in Organic Evolution? A Critical Review of the Causal Structure of Student Explanations

This paper critically reviews and characterizes the student's causal-explanatory understanding; this is done as a step toward explicating the problematic of evolution education as it concerns the cognitive difficulties in understanding Darwin's theory of natural selection. The review concludes that the student's understanding is fundamentally different from Darwin's, for the student understands evolutionary change as necessary individual transformation caused by the transformative action of various physical and behavioral factors. This is in complete contrast to Darwin's (and even the Darwinian's, for that matter) understanding of evolutionary change as a change caused by accumulative selection. Hence, to understand natural selection, the student has to learn to “see” how the accumulative selection causes evolutionary change

Long-term results of breast conservation and immediate volume replacement with myocutaneous latissimus dorsi flap

<p>Abstract</p> <p>Background</p> <p>Published long-term outcomes of oncoplastic breast-conserving surgery are scarce and, specifically, aesthetic outcomes assessed with an objective method have not previously been published.</p> <p>Methods</p> <p>A cohort of 41 patients treated with a quadrantectomny and immediate reconstruction using a myocutaneous latissimus dorsi flap were analyzed and their aesthetic outcomes were evaluated objectively by BCCT.core software.</p> <p>Results</p> <p>At the end of a 58-month follow-up from the date of initial diagnosis, one patient (2.4%) developed an ipsilateral recurrence, six patients developed distant metastases and three patients died (7.3%) without ipsilateral recurrence, one of them presenting hepatic metastases at the time of the initial diagnosis. We were able to evaluate aesthetic results in 23 patients, 3 assessed as excellent, 12 good and 8 fair.</p> <p>Conclusion</p> <p>This oncoplastic volume replacement technique obtained a good local control and satisfactory and stable aesthetic results which have maintained unchanged after a long period of time.</p

Divergent Evolution of CHD3 Proteins Resulted in MOM1 Refining Epigenetic Control in Vascular Plants

Arabidopsis MOM1 is required for the heritable maintenance of transcriptional gene silencing (TGS). Unlike many other silencing factors, depletion of MOM1 evokes transcription at selected loci without major changes in DNA methylation or histone modification. These loci retain unusual, bivalent chromatin properties, intermediate to both euchromatin and heterochromatin. The structure of MOM1 previously suggested an integral nuclear membrane protein with chromatin-remodeling and actin-binding activities. Unexpected results presented here challenge these presumed MOM1 activities and demonstrate that less than 13% of MOM1 sequence is necessary and sufficient for TGS maintenance. This active sequence encompasses a novel Conserved MOM1 Motif 2 (CMM2). The high conservation suggests that CMM2 has been the subject of strong evolutionary pressure. The replacement of Arabidopsis CMM2 by a poplar motif reveals its functional conservation. Interspecies comparison suggests that MOM1 proteins emerged at the origin of vascular plants through neo-functionalization of the ubiquitous eukaryotic CHD3 chromatin remodeling factors. Interestingly, despite the divergent evolution of CHD3 and MOM1, we observed functional cooperation in epigenetic control involving unrelated protein motifs and thus probably diverse mechanisms

Patterns of care and survival for adolescents and young adults with acute leukaemia – a population-based study

We report a population-based study of patterns of care and survival for people with acute leukaemia diagnosed at age 15–29 years during 1984–94 in regions of England and Wales covered by specialist leukaemia registries. There were 879 patients: 417 with acute lymphoblastic leukaemia (ALL) and 462 with acute myeloid leukaemia (AML). For ALL, actuarial survival rates were 43% at 5 years after diagnosis and 37% at 10 years. Survival improved significantly between 1984–88 and 1989–94 for those aged 15–19 at diagnosis. Patients entered in national clinical trials and those not entered had similar survival rates. Survival rates were similar at teaching and non-teaching hospitals and at hospitals treating different numbers of study patients per year. For AML, survival rates were 42% at 5 years after diagnosis and 39% at 10 years. Survival improved significantly between 1984–88 and 1989–94. Patients entered in the Medical Research Council AML10 trial had a higher survival rate than those who were in the earlier AML9 trial. Survival did not vary with category of hospital. We conclude that survival has improved for adolescents and young adults with acute leukaemia but that there is at present no evidence that centralized treatment results in a survival benefit for patients in this age group. © 1999 Cancer Research Campaig

Regulation of Gene Expression in Plants through miRNA Inactivation

Eukaryotic organisms possess a complex RNA-directed gene expression regulatory network allowing the production of unique gene expression patterns. A recent addition to the repertoire of RNA-based gene regulation is miRNA target decoys, endogenous RNA that can negatively regulate miRNA activity. miRNA decoys have been shown to be a valuable tool for understanding the function of several miRNA families in plants and invertebrates. Engineering and precise manipulation of an endogenous RNA regulatory network through modification of miRNA activity also affords a significant opportunity to achieve a desired outcome of enhanced plant development or response to environmental stresses. Here we report that expression of miRNA decoys as single or heteromeric non-cleavable microRNA (miRNA) sites embedded in either non-protein-coding or within the 3′ untranslated region of protein-coding transcripts can regulate the expression of one or more miRNA targets. By altering the sequence of the miRNA decoy sites, we were able to attenuate miRNA inactivation, which allowed for fine regulation of native miRNA targets and the production of a desirable range of plant phenotypes. Thus, our results demonstrate miRNA decoys are a flexible and robust tool, not only for studying miRNA function, but also for targeted engineering of gene expression in plants. Computational analysis of the Arabidopsis transcriptome revealed a number of potential miRNA decoys, suggesting that endogenous decoys may have an important role in natural modulation of expression in plants

Regulation of seed germination and seedling growth by an Arabidopsis phytocystatin isoform, AtCYS6

Phytocystatins are cysteine proteinase inhibitors in plants that are implicated in the endogenous regulation of protein turnover and defense mechanisms against insects and pathogens. A cDNA encoding a phytocystatin called AtCYS6 (Arabidopsis thaliana phytocystatin6) has been isolated. We show that AtCYS6 is highly expressed in dry seeds and seedlings and that it also accumulates in flowers. The persistence of AtCYS6 protein expression in seedlings was promoted by abscisic acid (ABA), a seed germination and post-germination inhibitory phytohormone. This finding was made in transgenic plants bearing an AtCYS6 promoter–β-glucuronidase (GUS) reporter construct, where we found that expression from the AtCYS6 promoter persisted after ABA treatment but was reduced under control conditions and by gibberellin4+7 (GA4+7) treatment during the germination and post-germinative periods. In addition, constitutive over-expression of AtCYS6 retarded germination and seedling growth, whereas these were enhanced in an AtCYS6 knock-out mutant (cys6-2). Additionally, cysteine proteinase activities stored in seeds were inhibited by AtCYS6 in transgenic Arabidopsis. From these data, we propose that AtCYS6 expression is enhanced by the germination inhibitory phytohormone ABA and that it participates in the control of germination rate and seedling growth by inhibiting the activity of stored cysteine proteinases