Adoption in England: past and present challenges.

Over the last century, changes in legislation, social constructs and the perceptions of what family life 'should' look like have significantly transformed the process of adoption in England. The role of adoption has shifted from providing orphaned children a stable new home to today's regulated process mainly supporting children who have suffered early physical or social adversity. This provides significant challenges to adopters, paediatricians, child psychiatrists and teachers who can only support adopted children by understanding their needs.

Empowering healthcare professionals with health promotion information for transgender adolescents.

While the majority of lesbian, gay, bisexual and transgender (LGBT) adolescents, much like their cis-gendered heterosexual peers, will be confident and healthy young individuals, there are well-known health disparities, particularly within the transgendered community, which may lead to inferior health outcomes. To improve these outcomes, we must empower professionals to feel confident in their interactions with transgender adolescents so they can recognise, discuss and address these disparities. For many healthcare professionals, this may be a novel experience, but following the announcement in 2022 that the Gender Identity Development Service (GIDS) will move towards a regional model, these discussions increasingly frequently be encountered in a general paediatric setting. In this article, we discuss some of the topics which may be relevant to transgender young people during a general paediatric consultation.

Management of Enteritis Associated With Tricohepatoenteric Syndrome due to SKIV2L Mutation Using the Combination of JAK1/2 Inhibition and Azathioprine.

Tricohepatoenteric syndrome is a rare genetic disorder caused by mutations in SKIV2L or TTC37. An upregulation of type 1 interferon signaling is associated with the SKIV2L variation. Introduction of Baricitinib as a JAK1/ 2 kinase inhibitor alongside traditional immunosuppressive agents successfully reduced the symptoms of enteritis by blocking the inflammogenic effects of type 1 interferonopathy in a case of tricohepatoenteric syndrome diagnosed in a 5-year-old boy.

A Systematic Review of the Clinical Efficacy of Treatments in Relapsed or Refractory Diffuse Large B Cell Lymphoma.

INTRODUCTION: Novel treatment options are needed to improve outcomes in transplant-ineligible relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). This systematic literature review evaluated clinical evidence on treatments for patients with R/R DLBCL ineligible for, or relapsed following, stem cell transplantation. METHODS: We assessed the feasibility of conducting an indirect treatment comparison (ITC) or network meta-analysis (NMA) to evaluate the relative efficacy and safety of polatuzumab vedotin in combination with bendamustine + rituximab versus other relevant treatments. RESULTS: Thirty-seven studies were identified, of which 20 were eligible [seven randomized, controlled trials (RCTs); 13 observational/single-arm trials]. Due to a lack of RCTs, an ITC/NMA summary of the relative efficacy and safety of the treatment options was not possible. Only two of the seven RCTs had positive outcomes. CONCLUSIONS: These findings highlight the paucity of published RCTs to establish the comparative efficacy of treatments for transplant-ineligible R/R DLBCL and lack of standard of care in this setting.

Impact of primary tumour location on efficacy of bevacizumab plus chemotherapy in metastatic colorectal cancer.

BACKGROUND: Two first-line (1L) bevacizumab trials showed the prognostic value of primary tumour location in metastatic colorectal cancer (mCRC). In this retrospective subgroup analysis, further analysis of the predictive effect of bevacizumab is presented. METHODS: Patients with sidedness information from two randomised phase III studies of bevacizumab + chemotherapy (CT) vs CT as 1L mCRC treatment were analysed retrospectively. RESULTS: Sidedness was determined in 1590 (27% right and 73% left) of 2214 patients. Progression-free survival was improved with bevacizumab + CT vs CT in right-sided (HR = 0.75; 95% CI 0.61, 0.93; p = 0.008) and left-sided (HR = 0.76; 95% CI 0.67, 0.86; p < 0.001) mCRC (pooled analysis). Similarly, overall survival was numerically improved with bevacizumab + CT vs CT in right-sided mCRC (HR = 0.82; 95% CI 0.65, 1.03; p = 0.085), and significantly improved in left-sided mCRC (HR = 0.85; 95% CI 0.74, 0.98; p = 0.028). CONCLUSIONS: This analysis indicates that the effect of bevacizumab is independent of tumour location in mCRC.

Interaction of cationic lipoplexes with floating bilayers at the solid-liquid interface.

Neutron reflection has been used to study the interaction of cationic lipoplexes with different model membrane systems. The model membranes used are prepared as "floating" phospholipid bilayers deposited at a silicon/water interface and separated from the solid substrate either by an adsorbed phospholipid bilayer, polymer cushions composed of polyethylene glycol lipids, or a lipid monolayer adsorbed onto a chemically grafted hydrocarbon layer. The cationic lipoplexes studied are those formed by the complexation of calf thymus DNA with dimethyl-dioctadecylammonium bromide (DDAB), with either cholesterol or dioleoyl-L-alpha-phosphatidylethanolamine (DOPE) incorporated as "helper" lipid. The cationic lipoplexes are found to destroy three of the four types of (negatively charged) floating bilayers, with the rate of destruction dependent on the nature of the layer separating the floating bilayer from the silicon substrate. The only bilayers to remain intact after exposure to the lipoplexes were those fabricated above the chemically grafted (octadecyl) hydrocarbon layer. This supports the hypothesis that the high negative charge density of the SiO2 layer on the silicon surface may influence, by way of electrostatic interaction with the cationic lipid, the interaction of the lipoplexes with the model bilayer. It is concluded that the floating bilayer supported on a chemically grafted hydrocarbon layer lends itself perfectly to the study of lipoplex-membrane interactions and, with sufficient exposure time, would allow a detailed characterization of the structures formed at the membrane interface during the interaction.

Ice recrystallization inhibition proteins (IRIPs) and freeze tolerance in the cryophilic Antarctic hair grass Deschampsia antarctica E. Desv.

Antarctic hair grass (Deschampsia antarctica E. Desv.), the only grass indigenous to Antarctica, has well-developed freezing tolerance, strongly induced by cold acclimation. Here, we show that in response to low temperatures, D. antarctica expresses potent recrystallization inhibition (RI) activity that, inhibits the growth of small ice crystals into potentially damaging large ones, is proteinaceous and localized to the apoplasm. A gene family from D. antarctica encoding putative homologs of an ice recrystallization inhibition protein (IRIP) has been isolated and characterized. IRIPs are apoplastically targeted proteins with two potential ice-binding motifs: 1-9 leucine-rich repeats (LRRs) and c. 16 'IRIP' repeats. IRIP genes appear to be confined to the grass subfamily Pooideae and their products, exhibit sequence similarity to phytosulphokine receptors and are predicted to adopt conformations with two ice-binding surfaces. D. antarctica IRIP (DaIRIP) transcript levels are greatly enhanced in leaf tissue following cold acclimation. Transgenic Arabidopsis thaliana expressing a DaIRIP has novel RI activity, and purified DaIRIP, when added back to extracts of leaves from non-acclimated D. antarctica, can reconstitute the activity found in acclimated plants. We propose that IRIP-mediated RI activity may contribute to the cryotolerance of D. antarctica, and thus to its unique ability to have colonized Antarctica.