uire them for safe chemotherapy administration. Further study of a possible leukemogenic association with HRD and the various forms of colony-stimulating factors is badly needed. © AlphaMed Press 2020.Immune checkpoint blockade (ICB) is highly effective for the treatment of metastatic cancers, but its side effects are incompletely understood. The objective of this article is to highlight hypertrophic lichen planus (HLP) with histological features diagnosed as squamous cell carcinoma (SCC), which is a potential cutaneous reaction to ICB. Two patients (75 and 69 years) presented with lesions diagnosed as SCC on biopsy, which developed after 3-9 months on ICB therapy. Biopsies demonstrated endophytic, atypical, or cystic squamous proliferations consistent with cutaneous SCC. However, the clinical presentation including monomorphic nature of the lesions and lichenoid inflammation in the background were consistent with HLP. Patients initially received topical 5-fluorouracil (5-FU) to reduce the hyperkeratotic lesions followed by topical steroids. The eruptions readily responded to this treatment regimen. Dermatologic immune-related adverse events (irAEs) are the most common irAEs associated with ICB therapy. Our findings indicate that HLP resembling SCC on biopsy is a potential side effect of ICB that can be correctly diagnosed on careful clinical exam and is responsive to ICB cessation and topical steroid with or without 5-FU treatment. KEY POINTS Immune checkpoint blockade is associated with cutaneous immune-related adverse events including lichen planus. Hypertrophic lichen planus can appear as squamous cell carcinoma histologically and clinical context is key for the proper diagnosis. Hypertrophic lichen planus can be safely treated with topical steroids with or without topical 5-fluorouracil in cases with severe hyperkeratotic lesions. Immune checkpoint blockade may be safely continued if clinical presentation is consistent with hypertrophic lichen planus. © AlphaMed Press 2020.BACKGROUND Familial hypercholesterolemia (FH) is a lipid disorder caused by pathogenic mutations in LDLRAP1 gene. The present study has aimed to deepen our understanding about the pathogenicity predictions of FH causative genetic mutations, as well as their relationship to phenotype changes in LDLRAP1 protein, by utilizing multidirectional computational analysis. METHODS FH linked LDLRAP1 mutations were mined from databases, and the prediction ability of several pathogenicity classifiers against these clinical variants, was assessed through different statistical measures. Furthermore, these mutations were 3D modelled in protein structures to assess their impact on protein phenotype changes. RESULTS Our findings suggest that Polyphen-2, when compared with SIFT, M-CAP and CADD tools, can make better pathogenicity predictions for FH causative LDLRAP1 mutations. Through, 3D simulation and superimposition analysis of LDLRAP1 protein structures, it was found that missense mutations do not create any gross changes in the protein structure, although they could induce subtle structural changes at the level of amino acid residues. Near native molecular dynamic analysis revealed that missense mutations could induce variable degrees of fluctuation differences guiding the protein flexibility. Stability analysis showed that most missense mutations shifts the free energy equilibrium and hence they destabilize the protein. Molecular docking analysis demonstrates the molecular shifts in hydrogen and ionic bonds and Van der waals bonding properties, which further cause differences in the binding energy of LDLR-LDLRAP1 proteins. CONCLUSIONS The diverse computational approaches used in the present study may provide a new dimension for exploring the structure-function relationship of the novel and deleterious LDLRAP1 mutations linked to FH. © 2020 John Wiley & Sons, Ltd.AIMS Parents' Evaluation of Developmental Status (PEDS) is a validated tool used to assess child development that has not previously been tested in Australian general practice. We examined the effect of a Quality-Improvement intervention in a single general practice in Melbourne, Australia, that aimed to use this tool to improve the documented assessment of child developmental surveillance during vaccination visits. METHODS Mixed methods incorporated audits of clinical records of children aged 1-5 years, before and after intervention, written questionnaires and a focus group (informed by the theoretical domains framework and Capability, Opportunity, Motivation-Behaviour (COM-B model)) with clinical and non-clinical staff. RESULTS After 6 months, developmental surveillance more than doubled and was documented in more than one in three visits (34.1%). Almost one in five (18.6%) vaccination visits included the PEDS tool.  https://www.selleckchem.com/products/semaxanib-su5416.html  Overall, the tool was positively received with staff expressing high levels of comfort asking parents to complete it (92.8%), increasing development of professional skills (71.4% staff) and confidence (55% clinicians) detecting developmental delays. Thematic analysis of the focus group transcript revealed underlying barriers arising from the practice environment, staff capabilities and motivation. CONCLUSIONS In a whole of practice Quality-Improvement intervention that applied PEDS training and implementation, including the receptionist in the medical team more than doubled documented rates of child developmental surveillance during vaccination visits. Solutions to underlying barriers could be incorporated into a revised training module. Future studies need to test the tool in more methodologically robust studies that include analysis of the outcomes of developmental surveillance. © 2020 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).We report herein a synthesis of aza-BODIPY substituted with strongly electron-donating p -(diphenylamino)phenyl substituents ( p -Ph 2 N-) at 3,5-positions. The presence of p -Ph 2 N- groups lowered the energy of the singlet excited state ( E s ) to 1.48 eV and induced NIR absorption with λ abs at 789 nm in THF. The compound studied was weakly emissive with the emission band ( λ f ) at 837 nm and with the singlet lifetime ( τ S ) equal 100 ps. Nanosecond laser photolysis experiments of aza-BODIPY in question revealed T 1 →T n absorption spanning from ca. 350 nm to ca. 550 nm with the triplet lifetime ( τ T ) equal 21 μs. By introducing a heavy atom (Br) into the structure of the aza-BODIPY we managed to turn it into a NIR operating photosensitizer. The photosensitized oxygenation of the model compound - diphenylisobenzofuran (DPBF) - proceeded via Type I and/or Type III mechanism without formation of singlet oxygen ( 1 O 2 ). As estimated by CV/DPV measurements, the p -Ph 2 N- substituted aza-BODIPYs studied exhibited oxidation processes at a relatively low oxidation potentials ( E ox 1 ), pointing to the very good electron-donating properties of these molecules.