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The co-occurrence of Geobacter and Methanosarcinales is often used as a proxy for the manifestation of direct interspecies electron transfer (DIET) in the environment. Here we tested eleven new co-culture combinations between methanogens and electrogens. Previously, only the most electrogenic Geobacter paired by DIET with Methanosarcinales methanogens, namely G . metallireducens and G . hydrogenophilus . Here we provide additional support, and show that five additional Methanosarcinales paired with G . metallireducens , while a strict hydrogenotroph could not. We also show that G . hydrogenophilus , which is incapable to grow with a strict hydrogenotrophic methanogen, could pair with a strict non-hydrogenotrophic Methanosarcinales . Likewise, an electrogen outside the Geobacter cluster ( Rhodoferrax ferrireducens ) paired with Methanosarcinales but not with strict hydrogenotrophic methanogens. The ability to interact with electrogens appears to be conserved among Methanosarcinales , the only methanogens with c -type cytochromes, including multihemes (MHC). Nonetheless, MHC, which are often linked to extracellular electron transfer, were neither unique nor universal to Methanosarcinales and only two of seven Methanosarcinales tested had MHC. Of these two, one strain had an MHC-deletion knockout available, which we hereby show is still capable to retrieve extracellular electrons from G . metallireducens or an electrode suggesting an MHC-independent strategy for extracellular electron uptake.

Microbial exposure during development can elicit long-lasting effects on the health of an individual. However, how microbial exposure in early life leads to permanent changes in the immune system is unknown. Here, we show that the microbial environment alters the set point for immune susceptibility by altering the developmental architecture of the CD8+ T cell compartment. In particular, early microbial exposure results in the preferential expansion of highly responsive fetal-derived CD8+ T cells that persist into adulthood and provide the host with enhanced immune protection against intracellular pathogens. Interestingly, microbial education of fetal-derived CD8+ T cells occurs during thymic development rather than in the periphery and involves the acquisition of a more effector-like epigenetic program. Collectively, our results provide a conceptual framework for understanding how microbial colonization in early life leads to lifelong changes in the immune system.

Cellular programming of naïve T cells can improve the efficacy of adoptive T-cell therapy. However, the current ex vivo engineering of T cells requires the pre-activation of T cells, which causes them to lose their naïve state. In this study, cationic-polymer-functionalized nanowires were used to pre-program the fate of primary naïve CD8 + T cells to achieve a therapeutic response in vivo. This was done by delivering single or multiple microRNAs to primary naïve mouse and human CD8 + T cells without pre-activation. The use of nanowires further allowed for the delivery of large, whole lentiviral particles with potential for long-term integration. The combination of deletion and overexpression of miR-29 and miR-130 impacted the ex vivo T-cell differentiation fate from the naïve state. The programming of CD8 + T cells using nanowire-delivered co-delivery of microRNAs resulted in the modulation of T-cell fitness by altering the T-cell proliferation, phenotypic and transcriptional regulation, and secretion of effector molecules. Moreover, the in vivo adoptive transfer of murine CD8 + T cells programmed through the nanowire-mediated dual delivery of microRNAs provided enhanced immune protection against different types of intracellular pathogen (influenza and Listeria monocytogenes ). In vivo analyses demonstrated that the simultaneous alteration of miR-29 and miR-130 levels in naïve CD8 + T cells reduces the persistence of canonical memory T cells whereas increases the population of short-lived effector T cells. Nanowires could potentially be used to modulate CD8 + T-cell differentiation and achieve a therapeutic response in vivo without the need for pre-activation. Ex vivo engineering of T cells for adoptive T-cell therapy without pre-activation is challenging and hinders therapeutic efficacy. Here, using nanowires, the delivery of microRNAs to primary naïve mouse and human CD8 + T cells without pre-activation for immune protection against pathogens is demonstrated.

AimsIt is a priority for the NHS to reduce avoidable harm that can lead to full-term babies (babies born after 37 weeks of pregnancy) being admitted to neonatal units. The number of unexpected admissions to neonatal units is seen as a proxy indicator that preventable harm may have been caused at some point along the maternity or neonatal pathwayThe audit aims to study the reasons for term admissions to Special Care baby units (SCBUs) in 2 hospital sites at a DGH in the North East of England.We aim to identify the underlying causes and modifiable factors to reduce avoidable term admissions.We review the impact of the initial phase of Covid-19 pandemic ( from 01/03/2020 to 31/08/2020) on rates and reasons for term admissions to SCBUs.To review if previous action plans from audit of Term admissions to SCBU have improved the rates of term admissions.MethodsThe Neonatal team identified the term babies admitted to SCBU of North Cumbria University Hospitals from the period above at the 2 hospital sites.The Neonatal team designed a list of questions for the audit guided by British Association of Perinatal Medicine (BAPM) which were developed into a survey monkey by the clinical audit team. Total 47 term babies were identified. 46 babies’ notes were reviewed and data collected.Badger Net electronic record and case notes were reviewed and answered the questions on survey monkey.The Clinical Audit department summarised the data and produced the report.31 term babies were admitted to SCBU at 1st hospital site and 16 to SCBU at the 2nd hospital site.ResultsWe found total 79 neonatal admissions to SCBU at 1st hospital site; 31 were term babies. Term admission rate is 39%.There were total 50 neonatal admissions to SCBU at 2nd hospital site; 16 were term babies. Term admission rate is 32%.Compared to the last audit project, a significant improvement in term admission rate is noted. In the year 2018-2019, the term newborn admission rate for 1st hospital site was 56% and was 50% for the 2nd hospital site.Abstract 804 Figure 1Terms admissions in 2020 and 2019 cross site: A (1st site) B ( 2nd Site)Abstract 804 Figure 2Reasons for admissions to SCBU in 2019 audit prior to transitional care provisionConclusionWe have noted an overall improvement in term admissions rates and reasons of admissions to SCBU. Almost all admissions were for primary concerns around the care of the baby.Term admission rate is 39% in 1st hospital site and 32% in 2nd hospital site. (In 2018-2019 audit, rates for sites were 56% and 50% respectively). Term admissions rate was 58% in England In the years 2012–2013.ATAIN (Avoiding Term Admissions Into Neonatal Units) aim is to prevent harm leading to separation of mother and baby.Respiratory concern was noted to be the main reason for term admissions and this is potentially unavoidable in a significant proportion of cases.We conclude that the phased introduction of transitional care service may have made a substantial overall improvement in term admission rates to SCBUs support e.g. by reducing admissions for neonatal jaundice, suspected sepsis, neonatal hypoglycaemia when appropriate and safe to not separate the infant and mother.

The case study discussed patient oriented quality care can enhance patient safety and increase the competency of healthcare professionals, even when they follow standard operating procedures and deal with unforeseen complications in performing LLETZ. This case report aims at validating the qualitative routine procedures against rare and complicated cases of LLETZ. The case concludes that every surgery should be performed carefully and properly to avoid unnecessary aftereffects in order to maintain efficient quality control. Simple and normal procedures were carried out by surgeons performing to the best of their abilities, competently, and with careful attention to patient safety. Though complications arose and were difficult and uncommon, the trained professional successfully navigated the procedure in such circumstantial emergencies.

The rheological properties of drug–polymer mixtures have a significant influence on their processability when using transformative techniques, such as hot-melt-extrusion and material-extrusion 3D printing; however, there has been limited data on printable systems. This study investigated the rheological properties of 17 formulations of successful printed tablets for both immediate and controlled release. Hydroxypropyl cellulose was used in various ratios to obtain printable filaments in combination with various drugs (indomethacin or theophylline), polymers and disintegrants. The complex viscosity, shear thinning behavior and viscoelastic properties were affected by the drug load, polymer composite, disintegrant type, temperature and shear rate applied. Larger windows of processing viscosity were revealed. The viscosity of the printable blends could be as low as the range 10–1000 Pa·s at 100 rad/s angular frequency. All formulations showed shear thinning behavior with a broad slope of complex viscosity from −0.28 to −0.74. The addition of 30–60% drug or disintegrant tended to have greater viscosity values. While microcrystalline cellulose was found to be an alternative additive to lower the storage and loss modulus among disintegrants. This rheological data could be useful for the preformulation and further development of material-extrusion 3D-printing medicines.

Introduction: The World Health Organization Safe Childbirth Checklist is a supporting tool for safe delivery that is essential for maternal and perinatal care practices. It has to be well mentored with its accurate implications to the health care providers who attend the deliveries so that they can protect delivering mothers from major causes of maternal death such as haemorrhage, infection, obstructed labour, hypertensive disorders, intrapartum-related stillbirths, and neonatal deaths. Purpose: The purpose of the study is to determine the level of awareness about the Safe Childbirth Checklist and its accurate application among the health care providers who attend the childbirth delivery procedures. Methodology: This study is a qualitative study on knowledge and practises regarding the World Health Organization Safe Childbirth Checklist among obstetrics and gynaecology professionals. The secondary data is collected from the literature search from various electronic databases such as PubMed, Google scholar, and PubMed Central. Results: the study intellectualizes and advances the knowledge concerning the use of world health organization safe child birth checklist among nurses and other health care providers who are the attenders of child delivery procedures. Conclusion: The study brings out better awareness concerning knowledge and practise concerning the World Health Organization safe childbirth checklist that indicates safe practise concerning maternal and child safety. This suggests training programmes to enhance the quality of practise among staff nurses and other health providers among child birth professionals.

IntroductionThe challenges of IBD patients on biologics include complex decision making, securing funding and logistics of administration. Aim: To assess the impact of a Virtual Biologics Clinic (VBC) on clinical decision making and patient outcome.MethodsElectronic records of IBD patients at Barnet Hospital were retrospectively reviewed. Patients discussed at VBCs conducted by IBD consultant gastroenterologists, nurses and pharmacists from 09/2019 to 01/2022 were included.Results66 patients were reviewed, 2 excluded due to misdiagnosis and death. 24 patients had UC and 40 Crohn’s disease; 48% were female and median age was 43.Of those with UC, 58% had left sided disease only, 42% had pancolitis. Clinically, 55% had mild to moderate disease and 45% moderate to severe.Of those with Crohn’s, 80% had terminal ileal disease, 63% colonic disease and 30% perianal disease. 43% had stricturing disease and 38% fistulating disease. Clinically, 30% had mild disease, 50% moderate and 20% severe.80% of all patients used biologics previously with infliximab (63%), adalimumab (49%), vedolizumab (20%) or ustekinimab (12%). Previous treatments also included azathioprine in 67% of patients, mesalazine 25%, 6-mercaptopurine 16%, methotrexate 8%, sulfasalazine 2%, and tofacitinib 2%.At VBC, 67% patients were on biologics: infliximab (20%), adalimumab (19%), vedolizumab (14%), or ustekinimab (14%). 92% of patients on infliximab had drug levels and/or antibodies measured. of those tested, none had positive antibodies. 81% had faecal calprotectin available and 50% of those had results >1000µg/g; 28% had endoscopies of which there was quiescent disease in 6%, mild 22%, moderate 33%, severe 22%, stricturing 11% and suboptimal views 6%. 44% of endoscopies had histology confirming active disease.Reasons for VBC discussion were inadequate disease control (64%), funding review (9%), remission (2%), reactions to biologics (3%), or other (22%).Outcomes from VBC were to switch biologics (23%), continue current treatment (22%), escalate frequency or dose (14%), stop biologics (13%), rediscuss after further investigations (8%), start biologics (6%), re-initiate biologics (5%) or other (9%).60 VBC outcomes were confirmed as actioned. 1 was not actioned due to patient choice, 2 are pending and 1 patient was uncontactable.At latest follow up 52% showed clinical response or were in remission and 34% were clinically symptomatic. 14% of patients are awaiting follow up.ConclusionsVBC is an effective resource for clinical decision making in IBD patients requiring biologics.Over half the patients reviewed following VBC showed at least clinical improvement.VBC is a robust approach of ensuring multifaceted management plans are actioned.

Background Amyotrophic lateral sclerosis (ALS) is a devastating disease which leads to loss of muscle function and paralysis. Historically, clinical drug development has been unsuccessful, but promising disease-modifying therapies (DMTs) may be on the horizon. Objectives The aims of this study were to estimate survival, quality-adjusted life-years (QALYs) and costs under current care, and to explore the conditions under which new therapies might be considered cost effective. Methods We developed a health economic model to evaluate the cost effectiveness of future ALS treatments from a UK National Health Service and Personal Social Services perspective over a lifetime horizon using data from the ALS-CarE study. Costs were valued at 2021/22 prices. Two hypothetical interventions were evaluated: a DMT which delays progression and mortality, and a symptomatic therapy which improves utility only. Sensitivity analysis was conducted to identify key drivers of cost effectiveness. Results Starting from King’s stage 2, patients receiving current care accrue an estimated 2.27 life-years, 0.75 QALYs and lifetime costs of £68,047. Assuming a 50% reduction in progression rates and a UK-converted estimate of the price of edaravone, the incremental cost-effectiveness ratio for a new DMT versus current care is likely to exceed £735,000 per QALY gained. Symptomatic therapies may be more likely to achieve acceptable levels of cost effectiveness. Conclusions Regardless of efficacy, DMTs may struggle to demonstrate cost effectiveness, even at a low price. The cost effectiveness of DMTs is likely to be strongly influenced by drug price, the magnitude and durability of relative treatment effects, treatment starting/stopping rules and any additional utility benefits over current care.

Haemoperitoneum secondary to a rupture of tortuous vessels from the serosal surface of the right uterine fundal region after coitus is a rare but life-threatening condition. This case demonstrates that even a very rare diagnosis should be considered, especially when dealing with patients with atypical presentations. This case report evidences a 31-year-old woman in her first pregnancy, presenting to our hospital triage at night for abdominal pain after sexual intercourse at a gestational age of 33 weeks and 4 days, and there was no history suggestive of endometriosis or fibroids. Apart from mild pain and slight pallor, she was stable. Her initial CTG was normal, but we noted two unprovoked decelerations about 8 and 10 hours after admission. During the morning rounds review, intra-abdominal bleeding was highly suspected and an emergency caesarean section was arranged. The on-call surgeon was also alerted, and a class I caesarean section was performed through the midline sub-umbilical incision. About 800 ml of intraoperative hemoperitoneum was noted upon opening the peritoneum. A male infant weighing 2.3 kg was delivered. Clear liquor was noted. Meanwhile, a small defect of about 1 cm in diameter with active bleeding from the underlying tortuous vessel was noted over the right posterior wall of the fundus. The underlying myometrium was intact and there was neither through nor through tear nor perforation. Discussion: The precise mechanism for postcoital haemoperitoneum due to rupture of uterine subserosal vessels is not known, but it is hypothesized that: pregnancy-with the increased friability of the tissues and fixation of the genital tract coincident with gestation; vigorous intercourse; coital positions; vaginismus and genital disproportion are the possible explanations. A complete gynaecological history, including endometriosis, fibroids, pelvic inflammatory disease, and any recent surgical procedures, is required to make a diagnosis. Ruptured ectopic pregnancy and ruptured corpus luteal cyst are on the top of the list of diagnoses in the early stage of pregnancy. The majority of such cases do not voluntarily admit the preceding act of coitus during initial presentation, and care must be taken to elicit a detailed sexual history. Interestingly, spontaneous haemoperitoneum in pregnancy complicated by endometriosis may occur during pregnancy. Conclusion: The study concludes that pregnant women with a history of the recent coitus present with acute abdominal pain, even in the absence of vaginal bleeding, haemoperitoneum has to be considered. On the other hand, idiopathic or spontaneous bleeding should be kept in mind even if there is no possible explanation.