Site matters: Image-guided percutaneous sampling of intervertebral disc results in increased positive diagnostic yield in spondylodiscitis.

Spondylodiscitis is a common referral to spinal on call services. Identification of the causative organism is vital in order to dictate the appropriate antibiotic treatment. In this context, the surgical and interventional radiology team is often asked to perform a diagnostic biopsy. The aim of the present study was to assess whether the sampling location affects the diagnostic yield. Our results suggest that the overall positive diagnostic yield was 35%. When disc material was included in the sample the diagnostic yield significantly improved to 47%. Bone sampling alone had a positive yield of 15%. Age, pre-biopsy CRP, pre-biopsy use of antibiotics did not seem to affect the likelihood of obtaining a positive yield. These results suggests that when performing image guided biopsies for suspected cases of spondylodiscitis the inclusion of disc material is important.

Beyond the Hip Labrum: A Pictorial Review.

Magnetic resonance arthrography and 3T magnetic resonance imaging of the hip are a technique commonly performed in young, physically active patients presenting with pain relating to the hip, with the focus on assessing for the presence of labral tears and femoroacetabular impingement. Abnormal signal within the labrum can be misleading, however, as labral tears are a frequent incidental finding and have been identified in a large proportion of the asymptomatic population. A range of extralabral conditions can cause hip-related pain in young patients, including pathology related to the bones, joints, and periarticular soft tissues. It is vital that the radiologist is aware for these pathologies and examines for them even in the presence of a confirmed labral tear. In this article, we review a range of common extralabral pathologies responsible for hip pain and highlight review areas that aid in their diagnosis.

Interventional Radiology Procedures of the Shoulder.

Using imaging guidance to perform procedures around the shoulder girdle has become established practice in musculoskeletal radiology. Whether it be therapeutic injections for intra-articular pathology, rotator cuff or subacromial/subdeltoid bursal pathology, or injections for diagnostic purposes, such as magnetic resonance or computed tomography arthrography, a range of techniques and imaging modalities can be used. This article discusses the techniques for commonly performed procedures.

Acute Hantavirus Infection Presenting With Fever and Altered Mentation in the Absence of Pulmonary or Renal Manifestations.

Illness caused by hantaviruses is often severe and is typically characterized by diffuse pulmonary disease or renal insufficiency depending on the type of hantavirus. Here we report 2 cases of hantavirus infection that resulted in severe cognitive impairment but did not have any pulmonary or renal manifestations. These 2 cases may be indicative of previously underreported symptoms of hantavirus infection and might represent examples of hantavirus-related encephalopathy.

Intellectual Property Rights and Vaccines.

Over the past 20 years, there has been steady, year-on-year growth in the number of granted vaccine-related patents. It is therefore important that those involved in vaccine research should be aware of both the risks and opportunities that patents create. The aim of this chapter is to offer a brief introduction to how, and when, patent rights might become available to vaccine developers and to explain the potential risk of infringement of third-party patent rights and the potential consequences.This chapter begins with a brief introduction to the patent application process and the international patent systems. The advantages and drawbacks of patent protection are discussed, followed by an overview of patent infringement and the various legal safe-harbors that may be available for certain research activities. Other features of the patent system which may be of particular relevance in the vaccines context are also discussed, such as compulsory licensing, sovereign states' rights to use patented inventions and voluntary technology sharing agreements. The chapter concludes with a discussion of the SARS-CoV-2 (COVID-19) pandemic and recent developments in the field of vaccine patents that have arisen as part of the international response.

Atraumatic fractures of the femur.

Atraumatic fractures of femur, although not as common as traumatic fractures, are frequently encountered in the clinical practice. They present with non-specific symptoms and can be occult on initial imaging making their diagnosis difficult, sometimes resulting in complications. Overlapping terminologies used to describe these fractures may hamper effective communication between the radiologist and the clinician. In this article, we review various atraumatic fractures of femur, terminologies used to describe them, their imaging findings and differential diagnosis. The article also describes the aetiology, pathophysiology and relevant biomechanics behind these fractures. An approach to atraumatic femoral fractures has been outlined.

A retrospective analysis of 34 potentially missed cases of female genital mutilation in the emergency department.

OBJECTIVES: To discover if healthcare professionals working within an ED are able to make a diagnosis of female genital mutilation (FGM) in those patients who have previously undergone the procedure and report it as per UK law. DESIGN: A retrospective analysis of patients' notes who were assigned an FGM code during the period of May 2015 to August 2016. SETTING: Single-centre, large UK major trauma centre offering a tertiary FGM clinic. PARTICIPANTS: Any woman coded during the study period as having undergone FGM. PRIMARY OUTCOME: Number of FGM cases identified by the ED. SECONDARY OUTCOMES: Mean age, presenting complaint, discharge diagnosis, genitourinary exam and defibulation status. RESULTS: 34 patients were identified as having undergone FGM, 19 had previously attended ED and none had their FGM identified during their ED attendance. The age range of those identified was 23 to 40 years. None had undergone defibulation. CONCLUSION: This study demonstrates that the identification of FGM victims by an ED is very poor, and more work needs to be done to increase awareness of the subject by front-line staff.

Artemisinin resistance in rodent malaria--mutation in the AP2 adaptor µ-chain suggests involvement of endocytosis and membrane protein trafficking.

BACKGROUND: The control of malaria, caused by Plasmodium falciparum, is hampered by the relentless evolution of drug resistance. Because artemisinin derivatives are now used in the most effective anti-malarial therapy, resistance to artemisinin would be catastrophic. Indeed, studies suggest that artemisinin resistance has already appeared in natural infections. Understanding the mechanisms of resistance would help to prolong the effective lifetime of these drugs. Genetic markers of resistance are therefore required urgently. Previously, a mutation in a de-ubiquitinating enzyme was shown to confer artemisinin resistance in the rodent malaria parasite Plasmodium chabaudi. METHODS: Here, for a mutant P. chabaudi malaria parasite and its immediate progenitor, the in vivo artemisinin resistance phenotypes and the mutations arising using Illumina whole-genome re-sequencing were compared. RESULTS: An increased artemisinin resistance phenotype is accompanied by one non-synonymous substitution. The mutated gene encodes the µ-chain of the AP2 adaptor complex, a component of the endocytic machinery. Homology models indicate that the mutated residue interacts with a cargo recognition sequence. In natural infections of the human malaria parasite P. falciparum, 12 polymorphisms (nine SNPs and three indels) were identified in the orthologous gene. CONCLUSION: An increased artemisinin-resistant phenotype occurs along with a mutation in a functional element of the AP2 adaptor protein complex. This suggests that endocytosis and trafficking of membrane proteins may be involved, generating new insights into possible mechanisms of resistance. The genotypes of this adaptor protein can be evaluated for its role in artemisinin responses in human infections of P. falciparum.

The use of recombinant activated factor VII in a patient with penetrating chest trauma and ongoing pulmonary hemorrhage.

A case is described where recombinant activated factor VII was used to control pulmonary hemorrhage in a patient who had sustained a high-velocity gunshot wound to the chest, in the deployed medical setting, allowing onward transfer of the patient to the United Kingdom for further management.

Genomewide scan reveals amplification of mdr1 as a common denominator of resistance to mefloquine, lumefantrine, and artemisinin in Plasmodium chabaudi malaria parasites.

Multidrug-resistant Plasmodium falciparum malaria parasites pose a threat to effective drug control, even to artemisinin-based combination therapies (ACTs). Here we used linkage group selection and Solexa whole-genome resequencing to investigate the genetic basis of resistance to component drugs of ACTs. Using the rodent malaria parasite P. chabaudi, we analyzed the uncloned progeny of a genetic backcross between the mefloquine-, lumefantrine-, and artemisinin-resistant mutant AS-15MF and a genetically distinct sensitive clone, AJ, following drug treatment. Genomewide scans of selection showed that parasites surviving each drug treatment bore a duplication of a segment of chromosome 12 (translocated to chromosome 04) present in AS-15MF. Whole-genome resequencing identified the size of the duplicated segment and its position on chromosome 4. The duplicated fragment extends for ∼393 kbp and contains over 100 genes, including mdr1, encoding the multidrug resistance P-glycoprotein homologue 1. We therefore show that resistance to chemically distinct components of ACTs is mediated by the same genetic mutation, highlighting a possible limitation of these therapies.

Experimental evolution, genetic analysis and genome re-sequencing reveal the mutation conferring artemisinin resistance in an isogenic lineage of malaria parasites.

BACKGROUND: Classical and quantitative linkage analyses of genetic crosses have traditionally been used to map genes of interest, such as those conferring chloroquine or quinine resistance in malaria parasites. Next-generation sequencing technologies now present the possibility of determining genome-wide genetic variation at single base-pair resolution. Here, we combine in vivo experimental evolution, a rapid genetic strategy and whole genome re-sequencing to identify the precise genetic basis of artemisinin resistance in a lineage of the rodent malaria parasite, Plasmodium chabaudi. Such genetic markers will further the investigation of resistance and its control in natural infections of the human malaria, P. falciparum. RESULTS: A lineage of isogenic in vivo drug-selected mutant P. chabaudi parasites was investigated. By measuring the artemisinin responses of these clones, the appearance of an in vivo artemisinin resistance phenotype within the lineage was defined. The underlying genetic locus was mapped to a region of chromosome 2 by Linkage Group Selection in two different genetic crosses. Whole-genome deep coverage short-read re-sequencing (Illumina Solexa) defined the point mutations, insertions, deletions and copy-number variations arising in the lineage. Eight point mutations arise within the mutant lineage, only one of which appears on chromosome 2. This missense mutation arises contemporaneously with artemisinin resistance and maps to a gene encoding a de-ubiquitinating enzyme. CONCLUSIONS: This integrated approach facilitates the rapid identification of mutations conferring selectable phenotypes, without prior knowledge of biological and molecular mechanisms. For malaria, this model can identify candidate genes before resistant parasites are commonly observed in natural human malaria populations.

Estimating SNP proportions in populations of malaria parasites by sequencing: validation and applications.

We have developed a rapid and simple method for determining accurately the proportions of alleles or individual malaria clones in a mixed infection. The technique uses a nested PCR reaction to amplify, from parasite mixtures, alleles of genes differing by single nucleotide polymorphisms, simultaneously, using common primers to non-polymorphic sequences. The mixed products are sequenced, and the heights of fluorescence peaks associated with different nucleotides at the polymorphic site used to quantitate the proportions of each allele in the mixture. We have confirmed the accuracy and precision of the method using a set of well-validated mixtures of genetically different malaria parasites. This technique can be used in the mapping of genetic loci underlying phenotypic traits and in the evaluation of the effects of different alleles upon the reproductive success (fitness) of parasites.

An AFLP-based genetic linkage map of Plasmodium chabaudi chabaudi.

BACKGROUND: Plasmodium chabaudi chabaudi can be considered as a rodent model of human malaria parasites in the genetic analysis of important characters such as drug resistance and immunity. Despite the availability of some genome sequence data, an extensive genetic linkage map is needed for mapping the genes involved in certain traits. METHODS: The inheritance of 672 Amplified Fragment Length Polymorphism (AFLP) markers from two parental clones (AS and AJ) of P. c. chabaudi was determined in 28 independent recombinant progeny clones. These, AFLP markers and 42 previously mapped Restriction Fragment Length Polymorphism (RFLP) markers (used as chromosomal anchors) were organized into linkage groups using Map Manager software. RESULTS: 614 AFLP markers formed linkage groups assigned to 10 of 14 chromosomes, and 12 other linkage groups not assigned to known chromosomes. The genetic length of the genome was estimated to be about 1676 centiMorgans (cM). The mean map unit size was estimated to be 13.7 kb/cM. This was slightly less then previous estimates for the human malaria parasite, Plasmodium falciparum CONCLUSION: The P. c. chabaudi genetic linkage map presented here is the most extensive and highly resolved so far available for this species. It can be used in conjunction with the genome databases of P. c chabaudi, P. falciparum and Plasmodium yoelii to identify genes underlying important phenotypes such as drug resistance and strain-specific immunity.

Gene synteny and chloroquine resistance in Plasmodium chabaudi.

Chloroquine resistance in the rodent malaria parasite Plasmodium chabaudi has been shown to be caused by a gene on chromosome 11, and is not linked to orthologues of the Plasmodium falciparum chloroquine resistance transporter (pfcrt) or Pgh-1 (pfmdr1) genes. In the current work, the progeny of crosses between chloroquine-resistant and sensitive clones of P. chabaudi have been analysed for the inheritance of 658 AFLP markers. Markers linked to the chloroquine responses of the progeny, including two which are completely linked, have been genetically mapped, sequenced and their homologues, or closely linked loci, identified in P. falciparum. The chromosome 11 markers most closely linked to chloroquine resistance in P. chabaudi map to loci which are also closely linked in P. falciparum, although in two linkage groups on chromosomes 6 and 13 of this species. The P. falciparum orthologue of the gene conferring chloroquine resistance in P. chabaudi is predicted to lie within a 250 kb region of P. falciparum chromosome 6, containing approximately 50 genes. The genetic order of the markers in P. chabaudi is co-linear with the physical linkage represented in the P. falciparum genome database. The findings provide evidence for extensive conservation of synteny between the two species.