Cadmium hijacks the high zinc response by binding and activating the HIZR-1 nuclear receptor.

Cadmium is an environmental pollutant and significant health hazard that is similar to the physiological metal zinc. In Caenorhabditis elegans, high zinc homeostasis is regulated by the high zinc activated nuclear receptor (HIZR-1) transcription factor. To define relationships between the responses to high zinc and cadmium, we analyzed transcription. Many genes were activated by both high zinc and cadmium, and hizr-1 was necessary for activation of a subset of these genes; in addition, many genes activated by cadmium did not require hizr-1, indicating there are at least two mechanisms of cadmium-regulated transcription. Cadmium directly bound HIZR-1, promoted nuclear accumulation of HIZR-1 in intestinal cells, and activated HIZR-1-mediated transcription via the high zinc activation (HZA) enhancer. Thus, cadmium binding promotes HIZR-1 activity, indicating that cadmium acts as a zinc mimetic to hijack the high zinc response. To elucidate the relationships between high zinc and cadmium detoxification, we analyzed genes that function in three pathways: the pcs-1/phytochelatin pathway strongly promoted cadmium resistance but not high zinc resistance, the hizr-1/HZA pathway strongly promoted high zinc resistance but not cadmium resistance, and the mek-1/sek-1/kinase signaling pathway promoted resistance to high zinc and cadmium. These studies identify resistance pathways that are specific for high zinc and cadmium, as well as a shared pathway.

Human milk oligosaccharides reduce necrotizing enterocolitis-induced neuroinflammation and cognitive impairment in mice.

Necrotizing enterocolitis (NEC) is the leading cause of morbidity and mortality in premature infants. One of the most devastating complications of NEC is the development of NEC-induced brain injury, which manifests as impaired cognition that persists beyond infancy and which represents a proinflammatory activation of the gut-brain axis. Given that oral administration of the human milk oligosaccharides (HMOs) 2'-fucosyllactose (2'-FL) and 6'-sialyslactose (6'-SL) significantly reduced intestinal inflammation in mice, we hypothesized that oral administration of these HMOs would reduce NEC-induced brain injury and sought to determine the mechanisms involved. We now show that the administration of either 2'-FL or 6'-SL significantly attenuated NEC-induced brain injury, reversed myelin loss in the corpus callosum and midbrain of newborn mice, and prevented the impaired cognition observed in mice with NEC-induced brain injury. In seeking to define the mechanisms involved, 2'-FL or 6'-SL administration resulted in a restoration of the blood-brain barrier in newborn mice and also had a direct anti-inflammatory effect on the brain as revealed through the study of brain organoids. Metabolites of 2'-FL were detected in the infant mouse brain by nuclear magnetic resonance (NMR), whereas intact 2'-FL was not. Strikingly, the beneficial effects of 2'-FL or 6'-SL against NEC-induced brain injury required the release of the neurotrophic factor brain-derived neurotrophic factor (BDNF), as mice lacking BDNF were not protected by these HMOs from the development of NEC-induced brain injury. Taken in aggregate, these findings reveal that the HMOs 2'-FL and 6'-SL interrupt the gut-brain inflammatory axis and reduce the risk of NEC-induced brain injury.NEW & NOTEWORTHY This study reveals that the administration of human milk oligosaccharides, which are present in human breast milk, can interfere with the proinflammatory gut-brain axis and prevent neuroinflammation in the setting of necrotizing enterocolitis, a major intestinal disorder seen in premature infants.

The administration of amnion-derived multipotent cell secretome ST266 protects against necrotizing enterocolitis in mice and piglets.

Necrotizing enterocolitis (NEC) is the leading cause of death from gastrointestinal disease in premature infants and is steadily rising in frequency. Patients who develop NEC have a very high mortality, illustrating the importance of developing novel prevention or treatment approaches. We and others have shown that NEC arises in part from exaggerated signaling via the bacterial receptor, Toll-like receptor 4 (TLR4) on the intestinal epithelium, leading to widespread intestinal inflammation and intestinal ischemia. Strategies that limit the extent of TLR4 signaling, including the administration of amniotic fluid, can reduce NEC development in mouse and piglet models. We now seek to test the hypothesis that a secretome derived from amnion-derived cells can prevent or treat NEC in preclinical models of this disease via a process involving TLR4 inhibition. In support of this hypothesis, we show that the administration of this secretome, named ST266, to mice or piglets can prevent and treat experimental NEC. The protective effects of ST266 occurred in the presence of marked TLR4 inhibition in the intestinal epithelium of cultured epithelial cells, intestinal organoids, and human intestinal samples ex vivo, independent of epidermal growth factor. Strikingly, RNA-seq analysis of the intestinal epithelium in mice reveals that the ST266 upregulates critical genes associated with gut remodeling, intestinal immunity, gut differentiation. and energy metabolism. These findings show that the amnion-derived secretome ST266 can prevent and treat NEC, suggesting the possibility of novel therapeutic approaches for patients with this devastating disease.NEW & NOTEWORTHY This work provides hope for children who develop NEC, a devastating disease of premature infants that is often fatal, by revealing that the secreted product of amniotic progenitor cells (called ST266) can prevent or treat NEC in mice, piglet, and "NEC-in-a-dish" models of this disease. Mechanistically, ST266 prevented bacterial signaling, and a detailed transcriptomic analysis revealed effects on gut differentiation, immunity, and metabolism. Thus, an amniotic secretome may offer novel approaches for NEC.

Bio-hybrid micro-swimmers propelled by flagella isolated from C. reinhardtii.

Bio-hybrid micro-swimmers, composed of biological entities integrated with synthetic constructs, actively transport cargo by converting chemical energy into mechanical work. Here, using isolated and demembranated flagella from green algae Chlamydomonas reinhardtii (C. reinhardtii), we build efficient axonemally-driven micro-swimmers that consume ATP to propel micron-sized beads. Depending on the calcium concentration, we observed two main classes of motion: whereas beads move along curved trajectories at calcium concentrations below 0.03 mM, they are propelled along straight paths when the calcium concentration increases. In this regime, they reached velocities of approximately 20 µm s-1, comparable to human sperm velocity in vivo. We relate this transition to the properties of beating axonemes, in particular the reduced static curvature with increasing calcium concentration. Our designed system has potential applications in the fabrication of synthetic micro-swimmers, and in particular, bio-actuated medical micro-robots for targeted drug delivery.

Prognostic factors in the decision-making process for sigmoid volvulus: results of a single-centre retrospective cohort study.

BACKGROUND: Sigmoid volvulus is a common cause of emergency surgical admission. Those patients are often treated conservatively with a high rate of recurrence. We wondered if a more aggressive management might be indicated. METHODS: We have reviewed data of patients diagnosed with acute sigmoid volvulus over a 2-year period. The primary endpoint was patient survival. RESULTS: We analysed 332 admissions of 78 patients. 39.7% underwent resection. Survival was 54.9 ± 8.8 months from the first hospitalization, irrespective of the treatment. Long-term survival was positively influenced by being female, having a low "social score", a younger age and surgery. Multivariate analysis showed that only being female and surgery were independently associated with better survival. CONCLUSION: Early surgery may be the best approach in patients with recurrent sigmoid volvulus, as it ensures longer survival with a better quality of life, regardless of the patient's social and functional condition.

Hybrid Surgical Hot Clinic (HSHC): Evaluation of Surgical Hot Clinic Services during COVID-19 Lockdown.

BACKGROUND: Surgical Hot Clinic (SHC) is an acute, ambulatory service for management provided on an outpatient basis. Following the start of global Novel Coronavirus (COVID-19) pandemic and as per the statement released by the Association of Surgeons of Great Britain and Ireland (ASGBI), we also modified our services to hybrid SHC (HSHC) by mainly providing telephonic follow-up with an occasional face-to-face (F2F) service. We conducted a service evaluation to assess the effectiveness and serviceability of HSHC during a pandemic. METHODS: This service evaluation was conducted from 30th March till 26th May 2020. The pathway was developed to mostly telephonic consultation with selective face-to-face consultation at a designated area in the medical ambulatory unit. The analysis then performed using SPSS version 21. RESULTS: As the overall attendance fell in hospital, 149 patients, including 54(36.2%) male, and 95(63.8%) females, attended SHC during COVID-19 lockdown. Out of these 149, 87(58.3%) were referred from Accident & Emergency (A&E), 2(1.3%) from GP, 9(6.04%) after scan through radiology department, while 51(34.2%) after discharge from hospital. Out of those who have telephonic consultation (n = 98), 12 patients were called in for review with either blood tests or further clinical examination. In total, only 10 out of 149 patients required admission to the hospital, for either intervention or symptomatic treatment. CONCLUSION: Hybrid Surgical Hot Clinic (HSHC) with both telephonic & face-to-face consultation, as per requirement, is flexible, effective and safe patient-focused acute surgical service during COVID-19 like crisis.

Synthetic applications and methodology development of Chan-Lam coupling: a review.

Chan-Lam coupling is one of the most popular and easy methods to perform arylation of amines (N-arylations). This cross-coupling is generally performed by reacting aryl boronate derivatives with a variety of substrates involving nitrogen containing functional groups such as amines, amides, ureas, hydrazine, carbamates. This article summarizes the synthetic applications of this reaction and the efforts of scientists to develop novel and efficient methodologies for this reaction.

Barcode DNA-Mediated Signal Amplifying Strategy for Ultrasensitive Biomolecular Detection on Matrix-Assisted Laser Desorption Ionization Time of Flight (MALDI-TOF) Mass Spectrometry.

We have devised a barcode DNA-mediated signal amplifying strategy for ultrasensitive biomolecular detection by utilizing matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). As a model target, thrombin was first captured by specific aptamer15 functionalized on magnetic beads (MBs-apt15) and sandwiched through the simultaneous interaction with gold nanoparticles modified with another specific aptamer29 and barcode DNA molecules (apt29-AuNPs-bcDNAs). The sandwiched complex was collected by convenient magnetic separation and then treated with potassium cyanide (KCN) to dissolve the gold nanoparticles (AuNPs) and consequently release the barcode DNA molecules (bcDNAs), which were then again magnetically separated and analyzed by using MALDI-TOF MS. Under optimized conditions, this strategy revealed an excellent sensitivity with a limit of detection of 0.89 aM in a wide linear detection range from 0 aM to 0.1 nM and exhibited an acceptable recovery for thrombin detection in complex biological matrices. This signal amplifying strategy based on MALDI-TOF MS could greatly enable the ultrasensitive detection of various low abundant biomolecules.

A Pumpless Acoustofluidic Platform for Size-Selective Concentration and Separation of Microparticles.

We have designed a pumpless acoustofluidic device for the concentration and separation of different sized particles inside a single-layered straight polydimethylsiloxane (PDMS) microfluidic channel. The proposed device comprises two parallel interdigitated transducers (IDTs) positioned underneath the PDMS microchannel. The IDTs produce high-frequency surface acoustic waves that generate semipermeable virtual acoustic radiation force field walls that selectively trap and concentrate larger particles at different locations inside the microchannel and allow the smaller particles to pass through the acoustic filter. The performance of the acoustofluidic device was first characterized by injecting into the microchannel a uniform flow of suspended 9.9 µm diameter particles with various initial concentrations (as low as 10 particles/mL) using a syringe pump. The particles were trapped with ∼100% efficiency by a single IDT actuated at 73 MHz. The acoustofluidic platform was used to demonstrate the pumpless separation of 12.0, 4.8, and 2.1 µm microparticles by trapping the 12 and 4.8 µm particles using the two IDTs actuated at 73 and 140 MHz, respectively. However, most of the 2.1 µm particles flowed over the IDTs unaffected. The acoustofluidic device was capable of rapidly processing a large volume of sample fluid pumped through the microchannel using an external syringe pump. A small volume of the sample fluid was processed through the device using a capillary flow and a hydrodynamic pressure difference that did not require an external pumping device.

Acoustic Wave-Driven Functionalized Particles for Aptamer-Based Target Biomolecule Separation.

We developed a hybrid microfluidic device that utilized acoustic waves to drive functionalized microparticles inside a continuous flow microchannel and to separate particle-conjugated target proteins from a complex fluid. The acoustofluidic device is composed of an interdigitated transducer that produces high-frequency surface acoustic waves (SAW) and a polydimethylsiloxane (PDMS) microfluidic channel. The SAW interacted with the sample fluid inside the microchannel and deflected particles from their original streamlines to achieve separation. Streptavidin-functionalized polystyrene (PS) microparticles were used to capture aptamer (single-stranded DNA) labeled at one end with a biotin molecule. The free end of the customized aptamer15 (apt15), which was attached to the microparticles via streptavidin-biotin linkage to form the PS-apt15 conjugate, was used to capture the model target protein, thrombin (th), by binding at exosite I to form the PS-apt15-th complex. We demonstrated that the PS-apt15 conjugate selectively captured thrombin molecules in a complex fluid. After the PS-apt15-th complex was formed, the sample fluid was pumped through a PDMS microchannel along with two buffer sheath flows that hydrodynamically focused the sample flow prior to SAW exposure for PS-apt15-th separation from the non-target proteins. We successfully separated thrombin from mCardinal2 and human serum using the proposed acoustofluidic device.

Isolated Duodenal Injuries After Blunt Abdominal Trauma.

Isolated duodenal injury after blunt abdominal trauma is a very rare entity. In contrast to penetrating injuries, duodenal injuries after blunt trauma are difficult to diagnose. Early diagnosis and management is required to prevent high morbidity and mortality associated with these injuries. We present three young patients of blunt abdominal trauma with an isolated injury to duodenum in which primary repair of perforations were done with good outcomes.

Characteristics and trends of pediatric firepit burns: insights for prevention and safety.

Introduction: As fire pits grow in popularity, so do the associated burn injuries. Our study examines pediatric fire pit burns characteristics to raise awareness and promote safety precautions. Methods: We conducted a retrospective review of pediatric patients (≤21 years) with firepit burns at a tertiary care hospital from 2016 to 2021. Results: Eighty-four patients were identified, of whom 70.2% were male, with a median age of 62 months. The median percent total body surface area burned was 2% (interquartile range (IQR)=1-4). Thirty-five (41.7%) patients were admitted and 7 (8.3%) underwent grafting. Neck and trunk burns had the highest grafting rates (66% and 33%, respectively). The hands (41.7%) and the lower extremities (27.4%) were the most frequently burned body areas. The leading causes of burns were ashes/hot coals (34.5%), flames (31.0%), and direct contact (25.0%), often resulting from falling into the fire (59.5%) or running or playing in activities near it (26.2%). Thirty-five (41.7%) were admitted for inpatient management, while 49 (58.3%) were treated as outpatient. Eleven (13.2%) underwent at least one reconstructive surgery, 7 (8.4%) had at least one rehabilitation visit, and 65 (77.4%) had follow-up clinic visits. The median length of stay was 2 days (IQR=1.0-3.5). The peak months for burns were from August through October (n=40, 46.0%), with an increase observed from 10 cases in 2016 to 20 cases in 2020. Conclusions: Given the significant proportion of firepit burns resulting from unsafe fire behaviors, it is crucial that caretakers are aware of proper firepit safety precautions. Level of evidence: III.

A microfluidic double emulsion platform for spatiotemporal control of pH and particle synthesis.

The temporal control of pH in microreactors such as emulsion droplets plays a vital role in applications including biomineralisation and microparticle synthesis. Typically, pH changes are achieved either by passive diffusion of species into a droplet or by acid/base producing reactions. Here, we exploit an enzyme reaction combined with the properties of a water-oil-water (W/O/W) double emulsion to control the pH-time profile in the droplets. A microfluidic platform was used for production of ∼100-200 µm urease-encapsulated double emulsions with a tuneable mineral oil shell thickness of 10-40 µm. The reaction was initiated on-demand by addition of urea and a pulse in base (ammonia) up to pH 8 was observed in the droplets after a time lag of the order of minutes. The pH-time profile can be manipulated by the diffusion timescale of urea and ammonia through the oil layer, resulting in a steady state pH not observed in bulk reactive solutions. This approach may be used to regulate the formation of pH sensitive materials under mild conditions and, as a proof of concept, the reaction was coupled to calcium phosphate precipitation in the droplets. The oil shell thickness was varied to select for either brushite microplatelets or hydroxyapatite particles, compared to the mixture of different precipitates obtained in bulk.

Flagellum-driven cargoes: Influence of cargo size and the flagellum-cargo attachment geometry.

The beating of cilia and flagella, which relies on an efficient conversion of energy from ATP-hydrolysis into mechanical work, offers a promising way to propel synthetic cargoes. Recent experimental realizations of such micro-swimmers, in which micron-sized beads are propelled by isolated and demembranated flagella from the green algae Chlamydomonas reinhardtii (C. reinhardtii), revealed a variety of propulsion modes, depending in particular on the calcium concentration. Here, we investigate theoretically and numerically the propulsion of a bead as a function of the flagellar waveform and the attachment geometries between the bead and the flagellum. To this end, we take advantage of the low Reynolds number of the fluid flows generated by the micro-swimmer, which allows us to neglect fluid inertia. By describing the flagellar waveform as a superposition of a static component and a propagating wave, and using resistive-force theory, we show that the asymmetric sideways attachment of the flagellum to the bead makes a contribution to the rotational velocity of the micro-swimmer that is comparable to the contribution caused by the static component of the flagellar waveform. Remarkably, our analysis reveals the existence of a counter-intuitive propulsion regime in which an increase in the size of the cargo, and hence its drag, leads to an increase in some components of the velocity of the bead. Finally, we discuss the relevance of the uncovered mechanisms for the fabrication of synthetic, bio-actuated medical micro-robots for targeted drug delivery.

Models of necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is the leading cause of death and disability from gastrointestinal disease in premature infants. The mortality of patients with NEC is approximately 30%, a figure that has not changed in many decades, reflecting the need for a greater understanding of its pathogenesis. Progress towards understanding the cellular and molecular mechanisms underlying NEC requires the study of highly translational animal models. Such animal models must mimic the biology and physiology of premature infants, while still allowing for safe experimental manipulation of environmental and microbial factors thought to be associated with the risk and severity of NEC. Findings from animal models have yielded insights into the interactions between the host, the colonizing microbes, and the innate immune receptor Toll-like Receptor 4 (TLR4) in driving disease development. This review discusses the relative strengths and weaknesses of available in vivo, in vitro, and NEC-in-a-dish models of this disease. We also highlight the unique contributions that each model has made to our understanding of the complex interactions between enterocytes, microbiota, and immune cells in the pathogenesis of NEC. The overall purpose of this review is to provide a menu of options regarding currently available animal models of NEC, while in parallel hopefully reducing the potential uncertainty and confusion regarding NEC models to assist those who wish to enter this field from other disciplines.

The Role of Transthoracic Echocardiography for Assessment of Mortality in Patients with Carcinoid Heart Disease Undergoing Valve Replacement.

Patients with carcinoid heart disease (CHD) are referred for valve replacement if they have severe symptomatic disease or evidence of right ventricular (RV) failure and an anticipated survival of at least 12 months. Data are lacking, however, on the role of transthoracic echocardiography in predicting outcomes. We carried out a retrospective, single-centre cohort study of patients with a biopsy-confirmed neuroendocrine tumour (NET) and CHD undergoing valve replacement for severe valve disease and symptoms of right heart failure. The aim was to identify factors associated with postoperative mortality, both within one year of surgery and during long-term follow-up. Of 88 patients with NET, 49 were treated surgically (mean age: 64.4 ± 7.6 years; 55% male), of whom 48 had a bioprosthetic tricuspid valve replacement for severe tricuspid regurgitation; 39 patients had a pulmonary valve replacement. Over a median potential follow-up of 96 months (interquartile range: 56-125), there were 37 deaths, with 30-day and one-year mortality of 14% (n = 7) and 39% (n = 19), respectively. A significant relationship between RV size and one-year mortality was observed, with 57% of those with severe RV dilatation dying within a year of surgery, compared to 33% in those with normal RV size (p = 0.039). This difference remained significant in the time-to-event analysis of long-term survival (p = 0.008). RV size was found to reduce significantly with surgery (p < 0.001). Those with persisting RV dilatation (p = 0.007) or worse RV function (p = 0.001) on postoperative echocardiography had significantly shorter long-term survival. In this single-centre retrospective study of patients undergoing surgery for CHD, increasingly severe RV dilatation on preoperative echocardiography predicted adverse outcomes, yielding a doubling of the one-year mortality rate relative to normal RV size. These data support the possibility that early surgery might deliver greater long-term benefits in this patient cohort.

A Bis(imidazole)-based cysteine labeling tool for metalloprotein assembly.

Precise metal-protein coordination by design remains a considerable challenge. Polydentate, high-metal-affinity protein modifications, both chemical and recombinant, can enable metal localization. However, these constructs are often bulky, conformationally and stereochemically ill-defined, or coordinately saturated. Here, we expand the biomolecular metal-coordination toolbox with the irreversible attachment to cysteine of bis(1-methylimidazol-2-yl)ethene ("BMIE"), which generates a compact imidazole-based metal-coordinating ligand. Conjugate additions of small-molecule thiols (thiocresol and N-Boc-Cys) with BMIE confirm general thiol reactivity. The BMIE adducts are shown to complex the divalent metal ions Cu++ and Zn++ in bidentate (N2) and tridentate (N2S*) coordination geometries. Cysteine-targeted BMIE modification (>90% yield at pH 8.0) of a model protein, the S203C variant of carboxypeptidase G2 (CPG2), measured with ESI-MS, confirms its utility as a site-selective bioconjugation method. ICP-MS analysis confirms mono-metallation of the BMIE-modified CPG2 protein with Zn++, Cu++, and Co++. EPR characterization of the BMIE-modified CPG2 protein reveals the structural details of the site selective 1:1 BMIE-Cu++ coordination and symmetric tetragonal geometry under physiological conditions and in the presence of various competing and exchangeable ligands (H2O/HO-, tris, and phenanthroline). An X-ray protein crystal structure of BMIE-modified CPG2-S203C demonstrates that the BMIE modification is minimally disruptive to the overall protein structure, including the carboxypeptidase active sites, although Zn++ metalation could not be conclusively discerned at the resolution obtained. The carboxypeptidase catalytic activity of BMIE-modified CPG2-S203C was also assayed and found to be minimally affected. These features, combined with ease of attachment, define the new BMIE-based ligation as a versatile metalloprotein design tool, and enable future catalytic and structural applications.

Effect of glutamate side chain length on intrahelical glutamate-lysine ion pairing interactions.

Ion pairing interactions between oppositely charged amino acids are important for protein structure stability. Despite the apparent electrostatic nature of these interactions, the charged amino acids Lys, Arg, Glu, and Asp have a different number of hydrophobic methylenes linking the charged functionality to the backbone. To investigate the effect of Glu (and Asp) side chain length on ion pairing interactions, a series of 36 monomeric α-helical peptides containing Zbb-Xaa (i, i+3), (i, i+4), and (i, i+5) (Zbb = Aad, Glu, Asp; Xaa = Lys, Orn, Dab, Dap) sequence patterns were studied by circular dichroism (CD) spectroscopy at pH 7 and 2. Peptides with Glu and Aad exhibited similar helicity and pH dependence, whereas peptides with Asp behaved distinctly different. The side chain interaction energetics were derived from the CD data using the nesting block method coupled with modified Lifson-Roig theory. At pH 7, no Zbb-Xaa (i, i+5) interaction was observed, regardless of side chain length (consistent with the helix geometry). Interestingly, only Lys was capable of supporting Zbb-Xaa (i, i+3) interactions, whereas any Xaa side chain length supported Zbb-Xaa (i, i+4) interactions. In particular, the magnitude of both Zbb(-)-Lys (i, i+4) and Zbb(-)-Orn (i, i+4) interaction energies followed the trend Asp > Glu > Aad. Side chain conformational analysis by molecular mechanics calculations showed that the Zbb-Xaa (i, i+3) interactions involved the χ(1) dihedral combination (g+, g+) for the i and i+3 residues, whereas the Zbb-Xaa (i, i+4) interactions were supported by the χ(1) dihedral combination (t, g+) for the i and i+4 residues. These calculated low energy conformers were consistent with conformations of intrahelical Asp-Lys and Glu-Lys salt bridges in a nonredundant protein structure database. These results suggest that Asp and Glu provide natural variation, and lengthening the Glu side chain further to Aad does not furnish additional characteristics that Glu cannot supply.

Emergency multivisceral resection for spontaneous haemorrhage rupture of huge solid pseudopapillary neoplasm of the pancreas during pregnancy†.

Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare malignancy with a low malignant potential and strong female preponderance. Diagnosis during pregnancy is extraordinary, and management must consider the risks to the mother and foetus of tumour growth and rupture. A large 35-cm SPN was identified on magnetic resonance imaging (MRI) in a 24-year-old woman at 6 weeks of gestation following presentation with an abdominal mass. Surgery was delayed to allow the foetus to reach as close to term as possible because surveillance MRIs showed incremental mass growth. Emergency c-section was undertaken at 35 weeks of gestation due to persistent tachycardia and suspected haemorrhage into the tumour. A Hb of 70 g/l post-delivery despite four units of RBCs and an albumin of 11 g/l necessitated urgent multivisceral surgery. Surgical resection is the mainstay of treatment for SPN. However, the strategy of choice during pregnancy remains undetermined, with more recent reports delaying surgery until post-partum.

Lysine methyltransferase Kmt2d regulates naive CD8+ T cell activation-induced survival.

Lysine specific methyltransferase 2D (Kmt2d) catalyzes the mono-methylation of histone 3 lysine 4 (H3K4me1) and plays a critical role in regulatory T cell generation via modulating Foxp3 gene expression. Here we report a role of Kmt2d in naïve CD8+ T cell generation and survival. In the absence of Kmt2d, the number of CD8+ T cells, particularly naïve CD8+ T cells (CD62Lhi/CD44lo), in spleen was greatly decreased and in vitro activation-related death significantly increased from Kmt2d fl/flCD4cre+ (KO) compared to Kmt2d fl/flCD4cre- (WT) mice. Furthermore, analyses by ChIPseq, RNAseq, and scRNAseq showed reduced H3K4me1 levels in enhancers and reduced expression of apoptosis-related genes in activated naïve CD8+ T cells in the absence of Kmt2d. Finally, we confirmed the activation-induced death of antigen-specific naïve CD8+ T cells in vivo in Kmt2d KO mice upon challenge with Listeria monocytogenes infection. These findings reveal that Kmt2d regulates activation-induced naïve CD8+ T cell survival via modulating H3K4me1 levels in enhancer regions of apoptosis and immune function-related genes.