Rewiring the Sex-Determination Pathway During the Evolution of Self-Fertility.

Although evolution is driven by changes in how regulatory pathways control development, we know little about the molecular details underlying these transitions. The TRA-2 domain that mediates contact with TRA-1 is conserved in Caenorhabditis. By comparing the interaction of these proteins in two species, we identified a striking change in how sexual development is controlled. Identical mutations in this domain promote oogenesis in Caenorhabditis elegans but promote spermatogenesis in Caenorhabditis briggsae. Furthermore, the effects of these mutations involve the male-promoting gene fem-3 in C. elegans but are independent of fem-3 in C. briggsae. Finally, reciprocal mutations in these genes show that C. briggsae TRA-2 binds TRA-1 to prevent expression of spermatogenesis regulators. By contrast, in C. elegans TRA-1 sequesters TRA-2 in the germ line, allowing FEM-3 to initiate spermatogenesis. Thus, we propose that the flow of information within the sex determination pathway has switched directions during evolution. This result has important implications for how evolutionary change can occur.

Nursing harm reduction education and care for people who use drugs or who engage in sex work.

Harm reduction is an evidence-based approach that could promote health equity through the implementation of pragmatic strategies for people who use drugs or who engage in sex work. The purposes of this study were to describe whether nurses received harm reduction education in their nursing programs, whether nurses are practicing harm reduction, and strategies for integrating harm reduction within nursing curriculum. An online survey was delivered to nurses and an interview with a nurse harm reductionist was conducted. Among the 30 survey participants, only 17% (n = 5) stated they were taught about harm reduction in their nursing programs. On average, survey participants practiced harm reduction less than "half of the time" by meeting people where they are in their drug use or sex work. The nurse harm reductionist described how harm reduction should be taught as a skillset for evidence-based nursing practice. By incorporating harm reduction principles into nursing education and nursing practice, nurses can provide competent care for people who use drugs or who engage in sex work.

A small molecule G6PD inhibitor reveals immune dependence on pentose phosphate pathway.

Glucose is catabolized by two fundamental pathways, glycolysis to make ATP and the oxidative pentose phosphate pathway to make reduced nicotinamide adenine dinucleotide phosphate (NADPH). The first step of the oxidative pentose phosphate pathway is catalyzed by the enzyme glucose-6-phosphate dehydrogenase (G6PD). Here we develop metabolite reporter and deuterium tracer assays to monitor cellular G6PD activity. Using these, we show that the most widely cited G6PD antagonist, dehydroepiandosterone, does not robustly inhibit G6PD in cells. We then identify a small molecule (G6PDi-1) that more effectively inhibits G6PD. Across a range of cultured cells, G6PDi-1 depletes NADPH most strongly in lymphocytes. In T cells but not macrophages, G6PDi-1 markedly decreases inflammatory cytokine production. In neutrophils, it suppresses respiratory burst. Thus, we provide a cell-active small molecule tool for oxidative pentose phosphate pathway inhibition, and use it to identify G6PD as a pharmacological target for modulating immune response.

Papua New Guinea agri-food trade and household consumption trends point towards dietary change and increased overweight and obesity prevalence.

BACKGROUND: Papua New Guinea (PNG) experienced positive GDP growth at approximately 4.3% per year during the last decade. With increases in overall wealth within the country, PNG is facing a double burden of malnutrition: comparatively high child stunting rates and a growing overweight and obesity epidemic. We focus on the latter by evaluating trends in agri-food import data from 2001 to 2018 and household consumption data from 2018 and 2009/10. RESULTS: The analysis presented in this paper raises three red flags. First, international food import data suggest that the demand for ultra-processed, sugar-sweetened beverages and food have increased substantially over time in PNG. Sugar-sweetened beverages dominated the largest growth in processed food imports, increasing by 23% per capita per year between 2001 and 2018. Second, households across the country with a greater food expenditure on sugar-sweetened beverages have a higher probability of an overweight child (under 5 years old). Last, the probability of soft-drink consumption in PNG increases with greater income acquisition and improved market access. While the price of a soft drink is negatively correlated with the quantity consumed, analysis suggests that total household income has a quantitatively larger (and positive) association with soft drink consumption. CONCLUSIONS: Taxing (or increasing taxes on) sugar-sweetened beverages may not be a sufficient policy mechanism to curb overconsumption of soft drinks in PNG. Education and advocacy programs should be fostered that integrate improved dietary information on packaging, as well as greater access to and understanding of nutrition and diet information of common household consumption items. While increases in household income and market access are crucial to economic growth and transformation, PNG's economic transition must be dovetailed with programs that expand and enhance health and nutrition information and education to improve household consumption decisions and overall household wellbeing.

Impacts of COVID-19 induced income and rice price shocks on household welfare in Papua New Guinea: Household model estimates.

Concerns over the potential effects of the COVID-19 pandemic have led to trade restrictions by major rice exporters, contributing to an average 25% increase in Thai and Vietnamese rice export prices between December 2019 and March-September 2020. This article assesses the consequences of these rice price increases in Papua New Guinea (PNG), where 99% of rice is imported. Utilizing data from a PNG 2018 rural household survey along with earlier national household survey data, we examine rice consumption patterns in PNG and estimate demand parameters for urban and rural households. Model simulations indicate that a 25% rise in the world price of rice would reduce total rice consumption in PNG by 14% and reduce rice consumption of the poor (bottom 40% of total household expenditure distribution) by 15%. Including the effects of a possible 12% decrease in household incomes because of the COVID-19 related economic slowdown, rice consumption of the urban and rural poor fall by 20% and 17%, respectively. Maintaining functioning domestic supply chains of key staple goods is critical to mitigating the effects of global rice price increases, allowing urban households to increase their consumption of locally produced staples.

Limits to commercially iodized salt to address dietary iodine deficiency in rural Papua New Guinea.

BACKGROUND AND OBJECTIVES: Fortifying commercial table salt with iodine is the principal strategy used globally to prevent dietary iodine deficiency. However, the costs of providing fortified salt to remote communities may result in it not being locally available or too expensive for many households. This study shows that barriers to consuming adequately iodized salt remain significant for remote rural households in Papua New Guinea (PNG). METHODS AND STUDY DESIGN: Using data from a rural household survey conducted in four areas of PNG in 2018, two issues are examined. First, we contrast the characteristics of households that reported consuming or not consuming iodized table salt, respectively. Second, the adequacy of the iodine content of samples of table salt consumed was assessed in the laboratory. RESULTS: Nine percent of the 1,026 survey households reported not consuming iodized table salt. These households tend to live in remote communities, are among the poorest households, have received no formal education, and have experienced recent food insecurity. Second, 17 percent of the 778 salt samples tested had inadequate iodine. The brand of salt most commonly consumed had the highest share of samples with inadequate iodine levels. CONCLUSIONS: Particularly in remote communities, ensuring that individuals consume sufficient iodine will require going beyond salt iodization to use other approaches to iodine supplementation. To ensure that the iodine intake of those using commercial table salt is adequate, closer monitoring of the iodine content in table salt produced or imported into PNG and enforcement of salt iodization regulations is required.

CTLA-4 controls follicular helper T-cell differentiation by regulating the strength of CD28 engagement.

Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) is an essential regulator of T-cell responses, and its absence precipitates lethal T-cell hyperactivity. However, whether CTLA-4 acts simply to veto the activation of certain clones or plays a more nuanced role in shaping the quality of T-cell responses is not clear. Here we report that T cells in CTLA-4-deficient mice show spontaneous T-follicular helper (T(FH)) differentiation in vivo, and this is accompanied by the appearance of large germinal centers (GCs). Remarkably, short-term blockade with anti-CTLA-4 antibody in wild-type mice is sufficient to elicit T(FH) generation and GC development. The latter occurs in a CD28-dependent manner, consistent with the known role of CTLA-4 in regulating the CD28 pathway. CTLA-4 can act by down-regulating CD80 and CD86 on antigen presenting cells (APCs), thereby altering the level of CD28 engagement. To mimic reduced CD28 ligation, we used mice heterozygous for CD28, revealing that the magnitude of CD28 engagement is tightly linked to the propensity for T(FH) differentiation. In contrast, other parameters of T-cell activation, including CD62L down-regulation and Ki67 expression, were relatively insensitive to altered CD28 level. Altered T(FH) generation as a result of graded reduction in CD28 was associated with decreased numbers of GC B cells and a reduction in overall GC size. These data support a model in which CTLA-4 control of immunity goes beyond vetoing T-cell priming and encompasses the regulation of T(FH) differentiation by graded control of CD28 engagement.

A novel upstream enhancer of FOXP3, sensitive to methylation-induced silencing, exhibits dysregulated methylation in rheumatoid arthritis Treg cells.

Treg-cell function is compromised in rheumatoid arthritis (RA). As the master regulator of Treg cells, FOXP3 controls development and suppressive function. Stable Treg-cell FOXP3 expression is epigenetically regulated; constitutive expression requires a demethylated Treg-specific demethylated region. Here, we hypothesised that methylation of the FOXP3 locus is altered in Treg cells of established RA patients. Methylation analysis of key regulatory regions in the FOXP3 locus was performed on Treg cells from RA patients and healthy controls. The FOXP3 Treg-specific demethylated region and proximal promoter displayed comparable methylation profiles in RA and healthy-donor Treg cells. We identified a novel differentially methylated region (DMR) upstream of the FOXP3 promoter, with enhancer activity sensitive to methylation-induced silencing. In RA Treg cells we observed significantly reduced DMR methylation and lower DNA methyltransferase (DNMT1/3A) expression compared with healthy Treg cells. Furthermore, DMR methylation negatively correlated with FOXP3 mRNA expression, and Treg cells isolated from rheumatoid factor negative RA patients were found to express significantly higher levels of FOXP3 than Treg cells from RhF-positive patients, with an associated decrease in DMR methylation. In conclusion, the novel DMR is involved in the regulation of Treg-cell FOXP3 expression, but this regulation is lost post-transcriptionally in RA Treg cells.

Selective blockade of tumor necrosis factor receptor I inhibits proinflammatory cytokine and chemokine production in human rheumatoid arthritis synovial membrane cell cultures.

OBJECTIVE: To determine whether selective blockade of tumor necrosis factor receptor I (TNFRI) affects spontaneous proinflammatory cytokine and chemokine production in ex vivo-cultured human rheumatoid arthritis synovial membrane mononuclear cells (MNCs) and to compare this response to that of TNF ligand blockade using etanercept. METHODS: A bispecific, single variable-domain antibody (anti-TNFRI moiety plus an albumin binding moiety [TNFRI-AlbudAb]) was used to selectively block TNFRI. Inhibition of TNFα-mediated responses in cell lines expressing TNFRI/II confirmed TNFRI-AlbudAb potency, human rhabdomyosarcoma cell line KYM-1D4 cytotoxicity, and human umbilical vein endothelial cell (HUVEC) vascular cell adhesion molecule 1 (VCAM-1) upregulation. Eighteen RA synovial membrane MNC suspensions were cultured for 2 days or 5 days, either alone or in the presence of TNFRI-AlbudAb, control-AlbudAb, or etanercept. Proinflammatory cytokines and chemokines in culture supernatants were measured by enzyme-linked immunosorbent assays. A mixed-effects statistical analysis model was used to assess the extent of TNFRI selective blockade, where the results were expressed as the percentage change with 95% confidence intervals (95% CIs). RESULTS: TNFRI-AlbudAb inhibited TNFα-induced KYM-1D4 cell cytotoxicity (50% inhibition concentration [IC50 ] 4 nM) and HUVEC VCAM-1 up-regulation (IC50 12 nM) in a dose-dependent manner. In ex vivo-cultured RA synovial membrane MNCs, selective blockade of TNFRI inhibited the production of proinflammatory cytokines and chemokines to levels similar to those obtained with TNF ligand blockade, without inducing cellular toxicity. Changes in cytokine levels were as follows: -23.5% (95% CI -12.4, -33.2 [P = 0.004]) for granulocyte-macrophage colony-stimulating factor, -33.4% (95% CI -20.6, -44.2 [P ≤ 0.0001]) for interleukin-10 (IL-10), -17.6% (95% CI 3.2, -34.2 [P = 0.0880]) for IL-1ß, and -19.0% (95% CI -3.4, -32.1 [P = 0.0207]) for IL-6. Changes in chemokine levels were as follows: -34.2% (-14.4, -49.4 [P = 0.0030]) for IL-8, -56.6% (-30.7, -72.9 [P = 0.0011]) for RANTES, and -24.9% (2, -44.8 [P = 0.0656]) for monocyte chemotactic protein 1. CONCLUSION: In ex vivo-cultured RA synovial membrane MNCs, although a limited role of TNFRII cannot be ruled out, TNFRI signaling was found to be the dominant pathway leading to proinflammatory cytokine and chemokine production. Thus, selective blockade of TNFRI could potentially be therapeutically beneficial over TNF ligand blockade by retaining the beneficial TNFRII signaling.

Cutting edge: cell-extrinsic immune regulation by CTLA-4 expressed on conventional T cells.

The CTLA-4 pathway is a key regulator of T cell activation and a critical failsafe against autoimmunity. Although early models postulated that CTLA-4 transduced a negative signal, in vivo evidence suggests that CTLA-4 functions in a cell-extrinsic manner. That multiple cell-intrinsic mechanisms have been attributed to CTLA-4, yet its function in vivo appears to be cell-extrinsic, has been an ongoing paradox in the field. Although CTLA-4 expressed on conventional T cells (Tconv) can mediate inhibitory function, it is unclear why this fails to manifest as an intrinsic effect. In this study, we show that Tconv-expressed CTLA-4 can function in a cell-extrinsic manner in vivo. CTLA-4(+/+) T cells, from DO11/rag(-/-) mice that lack regulatory T cells, were able to regulate the response of CTLA-4(-/-) T cells in cotransfer experiments. This observation provides a potential resolution to the above paradox and suggests CTLA-4 function on both Tconv and regulatory T cells can be achieved through cell-extrinsic mechanisms.

Texturized pinto bean protein fortification in straight dough bread formulation.

Pinto beans were milled and then air-classified to obtain a raw high protein fraction (RHPF) followed by extrusion to texturize the protein fraction. The texturized high protein fraction (THPF) was then milled to obtain flour, and combined with wheat flour at 5, 10, and 15% levels to make bread. The air-classification process produced flour with high concentration of lipids and phytic acid in the protein-rich fraction. However, extrusion significantly reduced hexane extractable lipid and phytic acid. However, the reduction observed may simply indicate a reduction in recovery due to bind with other components. Total protein and lysine contents in composite flours increased significantly as THPF levels increased in composite flour. Bread made with 5% THPF had 48% more lysine than the 100 % wheat flour (control). The THPF helped to maintain dough strength by reducing mixing tolerance index (MTI), maintaining dough stability and increasing departure time on Farinograph. Bread loaf volume was significantly reduced above 5% THPF addition. THPF increased water absorption causing an increase in bread weights by up to 6%. Overall, loaf quality deteriorated at 10 and 15% THPF levels while bread with 5% THPF was not significantly different from the control. These results support the addition of 5% THPF as a means to enhance lysine content of white pan bread.

CBrowse: a SAM/BAM-based contig browser for transcriptome assembly visualization and analysis.

SUMMARY: To address the impending need for exploring rapidly increased transcriptomics data generated for non-model organisms, we developed CBrowse, an AJAX-based web browser for visualizing and analyzing transcriptome assemblies and contigs. Designed in a standard three-tier architecture with a data pre-processing pipeline, CBrowse is essentially a Rich Internet Application that offers many seamlessly integrated web interfaces and allows users to navigate, sort, filter, search and visualize data smoothly. The pre-processing pipeline takes the contig sequence file in FASTA format and its relevant SAM/BAM file as the input; detects putative polymorphisms, simple sequence repeats and sequencing errors in contigs and generates image, JSON and database-compatible CSV text files that are directly utilized by different web interfaces. CBowse is a generic visualization and analysis tool that facilitates close examination of assembly quality, genetic polymorphisms, sequence repeats and/or sequencing errors in transcriptome sequencing projects. AVAILABILITY: CBrowse is distributed under the GNU General Public License, available at http://bioinfolab.muohio.edu/CBrowse/ CONTACT: liangc@muohio.edu or liangc.mu@gmail.com; glji@xmu.edu.cn SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Overview of stab injuries in Far North Queensland: A new insight into the demographics, injury patterns and management.

BACKGROUND: Cairns Hospital is the northernmost tertiary referral hospital in Far North Queensland (FNQ) and manages trauma from a large catchment area. A large burden of stab injuries occurs in at-risk patient groups, such as Indigenous and mental health patients, in this region. This research aims to present an overview of the demographics, injury patterns, management and outcomes for stabbings injuries in FNQ. METHODS: A five-year retrospective single-centre study of all patients treated for neck, torso or junctional stab wounds in Far North Queensland was performed searching for all patients with a coded diagnosis of stabbing or knife injury from 1 March 2016 to 31 March 2021. RESULTS: 214 knife injuries were identified and 50.5% of those injured identified as Aboriginal and/or Torres Strait Islander. Stabbing injury locations were most commonly the abdomen/flank/pelvis (n = 81) and the chest/thorax (n = 77). Two-thirds of injuries that breached abdominal fascia had concurrent intra-abdominal injury. Hollow viscus injury commonly involved the small bowel (n = 8), colon (n = 5) and stomach (n = 2), whilst the liver was the most frequently injured solid organ (n = 6). There were 19 vascular injuries, excluding the extremities. 89.2% received diagnostic imaging in the emergency department. FAST scan had 76% sensitivity and 100% specificity for intra-abdominal injury at operation. Overall, 35% of patients required an operation. There were only two in-hospital deaths. CONCLUSION: Stab injuries annually in FNQ are comparable to other centres in Australia. Overall injury severity was low, with excellent survival rates and outcomes for patients who reached hospital. Operative intervention rates for abdominal stab wounds were low in FNQ compared to available data and imaging again appears protective against negative laparotomy rate.

G-quadruplex is critical to epigenetic activation of the lncRNA HOTAIR in cancer cells.

The cancer-promoting lncRNA HOTAIR has multiple isoforms. Which isoform of HOTAIR accounts for its expression and functions in cancer is unknown. Unlike HOTAIR's canonical intergenic isoform NR_003716 (HOTAIR-C), the novel isoform NR_047517 (HOTAIR-N) forms an overlapping antisense transcription locus with HOXC11. We identified HOTAIR-N as the dominant isoform that regulates the gene expression programs and networks for cell proliferation, survival, and death in cancer cells. The CpG island in the HOTAIR-N promoter was marked with epigenetic markers for active transcription. We identified a G-quadruplex (G4) motif rich region in the HOTAIR-N CpG island. Our findings indicate that G4s in HOTAIR-N CpG island is critical for expression of HOTAIR-N in cancer cells. Disruption of G4 may represent a novel therapeutic approach for cancer. The transcriptomes regulated by HOTAIR-N and Bloom in cancer cells as provided herein are important resources for the exploration of lncRNA, DNA helicases, and G4 in cancer.

PeanutDB: an integrated bioinformatics web portal for Arachis hypogaea transcriptomics.

BACKGROUND: The peanut (Arachis hypogaea) is an important crop cultivated worldwide for oil production and food sources. Its complex genetic architecture (e.g., the large and tetraploid genome possibly due to unique cross of wild diploid relatives and subsequent chromosome duplication: 2n = 4x = 40, AABB, 2800 Mb) presents a major challenge for its genome sequencing and makes it a less-studied crop. Without a doubt, transcriptome sequencing is the most effective way to harness the genome structure and gene expression dynamics of this non-model species that has a limited genomic resource. DESCRIPTION: With the development of next generation sequencing technologies such as 454 pyro-sequencing and Illumina sequencing by synthesis, the transcriptomics data of peanut is rapidly accumulated in both the public databases and private sectors. Integrating 187,636 Sanger reads (103,685,419 bases), 1,165,168 Roche 454 reads (333,862,593 bases) and 57,135,995 Illumina reads (4,073,740,115 bases), we generated the first release of our peanut transcriptome assembly that contains 32,619 contigs. We provided EC, KEGG and GO functional annotations to these contigs and detected SSRs, SNPs and other genetic polymorphisms for each contig. Based on both open-source and our in-house tools, PeanutDB presents many seamlessly integrated web interfaces that allow users to search, filter, navigate and visualize easily the whole transcript assembly, its annotations and detected polymorphisms and simple sequence repeats. For each contig, sequence alignment is presented in both bird's-eye view and nucleotide level resolution, with colorfully highlighted regions of mismatches, indels and repeats that facilitate close examination of assembly quality, genetic polymorphisms, sequence repeats and/or sequencing errors. CONCLUSION: As a public genomic database that integrates peanut transcriptome data from different sources, PeanutDB (http://bioinfolab.muohio.edu/txid3818v1) provides the Peanut research community with an easy-to-use web portal that will definitely facilitate genomics research and molecular breeding in this less-studied crop.

B1 cells promote pancreas infiltration by autoreactive T cells.

The entry of autoreactive T cells into the pancreas is a critical checkpoint in the development of autoimmune diabetes. In this study, we identify a role for B1 cells in this process using the DO11 x RIP-mOVA mouse model. In transgenic mice with islet-specific T cells, but no B cells, T cells are primed in the pancreatic lymph node but fail to enter the pancreas. Reconstitution of the B1 cell population by adoptive transfer permits extensive T cell pancreas infiltration. Reconstituted B1 cells traffic to the pancreas and modify expression of adhesion molecules on pancreatic vasculature, notably VCAM-1. Despite substantial pancreas infiltration, islet destruction is minimal unless regulatory T cells are depleted. These data identify a role for B1 cells in permitting circulating islet-specific T cells to access their Ag-bearing tissue and emphasize the existence of multiple checkpoints to regulate autoimmune disease.

Immune regulation by CTLA-4--relevance to autoimmune diabetes in a transgenic mouse model.

BACKGROUND: The importance of cytotoxic T lymphocyte antigen-4 (CTLA-4) in immune regulation is unquestioned, yet a precise understanding of which cells express it, and how it mediates immune inhibitory function, is lacking. Regulatory T cells are known to constitutively express CTLA-4 intracellularly, whereas conventional T cells require activation to trigger CTLA-4 expression. However comparative analysis of CTLA-4 trafficking in regulatory and conventional subsets has not been performed. METHODS: Here we assess CTLA-4 expression in antigen-specific conventional and regulatory cells responding to immunizing antigen in vivo and analyse the membrane trafficking of CTLA-4 using an in vitro recycling assay. We assess the expression of CTLA-4 on Treg infiltrating the pancreas in the DO11×RIP-mOVA diabetes model and the role of CTLA-4 in Treg function. RESULTS: Regulatory T cells show an enhanced capacity to traffic CTLA-4 following stimulation compared with conventional T cells. Treg infiltrating the pancreas in DO11×RIP-mOVA mice show high expression of CTLA-4. Furthermore CTLA-4-deficient Treg fail to control diabetes in an adoptive transfer model of diabetes, even in situations where they outnumber the disease-inducing conventional T cells. CONCLUSIONS: These data show that not only do regulatory T cells express higher levels of intracellular CTLA-4 than conventional T cells, but they also show an increased capacity to traffic CTLA-4 to the cell surface following stimulation. CTLA-4 is strongly upregulated in regulatory T cells infiltrating the target tissue in a mouse model of type 1 diabetes and expression of this protein is critical for effective regulation.

Ctla-4 controls regulatory T cell peripheral homeostasis and is required for suppression of pancreatic islet autoimmunity.

The CTLA-4 pathway is recognized as a major immune inhibitory axis and is a key therapeutic target for augmenting antitumor immunity or curbing autoimmunity. CTLA-4-deficient mice provide the archetypal example of dysregulated immune homeostasis, developing lethal lymphoproliferation with multiorgan inflammation. In this study, we show that surprisingly these mice have an enlarged population of Foxp3(+) regulatory T cells (Treg). The increase in Treg is associated with normal thymic output but enhanced proliferation of Foxp3(+) cells in the periphery. We confirmed the effect of CTLA-4 deficiency on the Treg population using OVA-specific Treg which develop normally in the absence of CTLA-4, but show increased proliferation in response to peripheral self-Ag. Functional analysis revealed that Ag-specific Treg lacking CTLA-4 were unable to regulate disease in an adoptive transfer model of diabetes. Collectively, these data suggest that the proliferation of Treg in the periphery is tuned by CTLA-4 signals and that Treg expression of CTLA-4 is required for regulation of pancreas autoimmunity.

Fistulating diverticular disease masquerading as a peri-anal abscess: a laparoscopic approach to management.

We present a rare case of complicated sigmoid diverticulitis presenting as a peri-anal abscess from an extra-sphincteric fistulous tract. This presentation of a colocutaneous peri-anal abscess is extremely rare, with only a handful of cases described in the literature. Most are managed with an open sigmoid colectomy, however, this case was successfully managed laparoscopically. It highlights the need to consider extra-levator causes of peri-anal abscess, such as pelvic sepsis causing fistulating disease, and to consider early magnetic resonance imaging if there is clinical suspicion of underlying pathology. It also demonstrates that a safe and potentially less morbid outcome is possible via laparoscopic approach when compared to traditional open surgical approach.

Unusual source of fever: the curious case of an infected arterial stent graft presenting as a ruptured popliteal artery aneurysm.

A 71-year-old man presented to the emergency department with a 1-week history of lethargy, general malaise and intermittent high fever. He had presented 18 months ago, and again 12 months earlier with similar symptoms. On this third presentation, the fever was accompanied by right thigh swelling and pain. The patient was referred to the vascular surgeons with concern regarding an infected vascular stent graft from previous treatment of popliteal artery aneurysms (PAA) 8 years earlier. CT angiogram demonstrated a collapsed right PAA sac with a large collection, consistent with ruptured PAA, and a single gas bubble around the indwelling stent graft. The patient recovered well after a course of antibiotics and surgical explantation of the graft. Infection is a potential complication of any implanted arterial advice, and needs to be considered even years after initial intervention and with no localising symptoms.