Altogether, our data suggest that TET enzymes may play a dynamic role in the regulation of transcriptional activity of trophoblast progenitors and differentiated cell subtypes in mouse and human placentas.
Fetal growth restriction (FGR) causes a wide variety of defects in the neonate which can lead to increased risk of heart disease, diabetes, anxiety and other disorders later in life. However, the effect of FGR on the immune system, is poorly understood. We used a well-characterized mouse model of FGR in which placental Igf-2 production is lost due to deletion of the placental specific Igf-2 P0 promotor. The thymi in such animals were reduced in mass with a ~70% reduction in cellularity. We used single cell RNA sequencing (Drop-Seq) to analyze 7,264 thymus cells collected at postnatal day 6. We identified considerable heterogeneity among the Cd8/Cd4 double positive cells with one subcluster showing marked upregulation of transcripts encoding a sub-set of proteins that contribute to the surface of the ribosome. The cells from the FGR animals were underrepresented in this cluster. Furthermore, the distribution of cells from the FGR animals was skewed with a higher proportion of immature double negative cells and fewer mature T-cells. Cell cycle regulator transcripts also varied across clusters. The T-cell deficit in FGR mice persisted into adulthood, even when body and organ weights approached normal levels due to catch-up growth. This finding complements the altered immunity found in growth restricted human infants. This reduction in T-cellularity may have implications for adult immunity, adding to the list of adult conditions in which the in utero environment is a contributory factor.
Provision of extracorporeal membrane oxygenation as part of support escalation in severe refractory acute respiratory failure in England is provided by five specialist centres that operate within a well-defined quality and safety framework. We conducted a qualitative study of the extracorporeal membrane oxygenation retrieval service provided by one of the five centres. We analysed 176 consecutive debrief reports written between October 2013 and April 2018 by the consultant. Main identified issues were short delays in retrieval predominantly due to insufficient communication or equipment failure. All issues were addressed in subsequent practice. Our results suggest a need for improved communication between the referring intensive care unit and retrieving team. Our findings highlight the value of regular reflection-based evaluation to ensure continued provision of safe and efficient service.
Acute diverticulitis is associated with a range of complications including fistula formation. Colovenous fistula formation, where there is a fistula between the inferior mesenteric vein and colon, is an extremely rare and serious complication of diverticulitis. Pylephlebitis, which is defined as infective suppurative thrombosis of the portal vein, is another uncommon complication of any intra-abdominal source of infection, including diverticulitis. Both complications are independently associated with significant morbidity and mortality. We report a case of a patient with acute diverticulitis who subsequently developed both colo-venous fistula and pylephlebitis and was successfully managed conservatively.
Introduction: Segmental long bone defects are some of the most challenging to surgically reconstruct; however, there is no clear guidance on which of the myriad of techniques is superior in a given clinical context. We describe three cases of segmental bone loss presenting to a major trauma center and have use these to develop a treatment algorithm for the sub-acute management of such fractures. Case Report: Case 1 – Acute shortening and delayed lengthening using lengthening intramedullary (IM) nail to treat diaphyseal non-union of the femur with associated 3 cm shortening. Case 2 – 15 cm traumatic bone loss of femur, failed Masquelet, treated with IM nail, monolateral external-fixation and cable with a mean lengthening rate of 46 days/cm. Case 3 – 12 cm tibial traumatic bone loss, failed Masquelet, treated with fine wire frame with a mean lengthening rate of 49 days/cm. Conclusion: As our cases illustrate; attempting complicated, definitive management in the acute phase generates complications and necessitates re-intervention. As such, we have developed a treatment algorithm for traumatic segmental bone loss. We recommend waiting 6 weeks and reimaging to check for evidence of spontaneous bone formation before deciding on definitive treatment. First-line treatment for femoral defects <4 cm is acute limb shortening with delayed lengthening using lengthening IM nail. First-line treatment for femoral defects >4 cm is lengthening over nail with monolateral external fixator. First-line treatment of tibial segmental bone defects in our hands is fine wire circular frames which provide excellent scope for soft tissue coverage and deformity correction. Treatment times of over 2 years in a frame are not uncommon and patients must diligently comply with pin sites management and lengthening protocols. This is the first paper providing an algorithm to guide surgeons in choosing the best lower limb reconstruction options in the sub-acute setting; considering the skill s
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