Case report on interstitial pregnancy in a post adenomyomectomy woman

Intramural pregnancy is a rare form of ectopic pregnancy with early diagnosis essential for prevention of severe hemorrhage and uterine rupture. We report a rare case of an interstitial ectopic pregnancy at 09 weeks gestation in a woman 3 year post laparoscopic adenomyomectomy. 3D transvaginal ultrasound was utilized as diagnostic aids in this case. Due to the size and location of the gestational sac, and early diagnosis made this case undergo conservative surgical management saving her uterus for future pregnancy

Contextual Emotion Estimation from Image Captions

Emotion estimation in images is a challenging task, typically using computer vision methods to directly estimate people's emotions using face, body pose and contextual cues. In this paper, we explore whether Large Language Models (LLMs) can support the contextual emotion estimation task, by first captioning images, then using an LLM for inference. First, we must understand: how well do LLMs perceive human emotions? And which parts of the information enable them to determine emotions? One initial challenge is to construct a caption that describes a person within a scene with information relevant for emotion perception. Towards this goal, we propose a set of natural language descriptors for faces, bodies, interactions, and environments. We use them to manually generate captions and emotion annotations for a subset of 331 images from the EMOTIC dataset. These captions offer an interpretable representation for emotion estimation, towards understanding how elements of a scene affect emotion perception in LLMs and beyond. Secondly, we test the capability of a large language model to infer an emotion from the resulting image captions. We find that GPT-3.5, specifically the text-davinci-003 model, provides surprisingly reasonable emotion predictions consistent with human annotations, but accuracy can depend on the emotion concept. Overall, the results suggest promise in the image captioning and LLM approach.Comment: Accepted to ACII 2023. Project page: http://rosielab.github.io/emotion-captions

Novel BCL2 inhibitor, Disarib induces apoptosis by disruption of BCL2-BAK interaction

Apoptosis is a highly regulated pathway of programmed cell death relying on the fine balance between pro and antiapoptotic binding partners. Overexpression of the antiapoptotic protein BCL2 in several cancers makes it an ideal target for chemotherapy, with minimum side effects. In one of our previous studies, we designed, synthesized and characterized Disarib, a BCL2-specific small molecule inhibitor. Interestingly, Disarib showed a novel mode of BCL2 inhibition, by predominantly binding to its BH1 domain, as compared to the BH3-specific action of other known BCL2 inhibitors. Here, we investigate the mechanism by which Disarib induces cell death, upon binding to BCL2. We find that Disarib specifically disrupted the BCL2-BAK interaction, but not that of BCL2-BAX or other members of the proapoptotic family such as PUMA and BIM, in vitro. Biochemical and biophysical studies demonstrate Disarib-induced inhibition of BCL2-BAK interaction with a Ki of 12.76 nM. Genetic knockout cells of BAK/BAX and double knockout (DKO) cells confirmed a BAK-specific action of Disarib, thereby facilitating apoptosis. Importantly, intracellular FRET in BAK/BAX single and double knockout cells demonstrated BCL2-BAK disruption, and activation of intrinsic pathway of apoptosis upon Disarib treatment. Thus, we report a unique mechanism of action of a BCL2 inhibitor, Disarib, by specifically targeting the interaction of BCL2-BAK, while sparing that of other proapoptotic binding partners. (C) 2017 Elsevier Inc. All rights reserved

Distinct roles of the 7-transmembrane receptor protein Rta3 in regulating the asymmetric distribution of phosphatidylcholine across the plasma membrane and biofilm formation in Candida albicans.

Fungal pathogens such as Candida albicans exhibit several survival mechanisms to evade attack by antifungals and colonise host tissues. Rta3, a member of the Rta1-like family of lipid-translocating exporters has a 7-transmembrane domain topology, similar to the G-protein-coupled receptors and is unique to the fungal kingdom. Our findings point towards a role for the plasma membrane localised Rta3 in providing tolerance to miltefosine, an analogue of alkylphosphocholine, by maintaining mitochondrial energetics. Concurrent with miltefosine susceptibility, the rta3Δ/Δ strain displays increased inward translocation (flip) of fluorophore-labelled phosphatidylcholine (PC) across the plasma membrane attributed to enhanced PC-specific flippase activity. We also assign a novel role to Rta3 in the Bcr1-regulated pathway for in vivo biofilm development. Transcriptome analysis reveals that Rta3 regulates expression of Bcr1 target genes involved in cell surface properties, adhesion, and hyphal growth. We show that rta3Δ/Δ mutant is biofilm-defective in a rat venous catheter model of infection and that BCR1 overexpression rescues this defect, indicating that Bcr1 functions downstream of Rta3 to mediate biofilm formation in C. albicans. The identification of this novel Rta3-dependent regulatory network that governs biofilm formation and PC asymmetry across the plasma membrane will provide important insights into C. albicans pathogenesis

Distinct roles of the 7-transmembrane receptor protein Rta3 in regulating the asymmetric distribution of phosphatidylcholine across the plasma membrane and biofilm formation in Candida albicans.

Fungal pathogens such as Candida albicans exhibit several survival mechanisms to evade attack by antifungals and colonise host tissues. Rta3, a member of the Rta1-like family of lipid-translocating exporters has a 7-transmembrane domain topology, similar to the G-protein-coupled receptors and is unique to the fungal kingdom. Our findings point towards a role for the plasma membrane localised Rta3 in providing tolerance to miltefosine, an analogue of alkylphosphocholine, by maintaining mitochondrial energetics. Concurrent with miltefosine susceptibility, the rta3Δ/Δ strain displays increased inward translocation (flip) of fluorophore-labelled phosphatidylcholine (PC) across the plasma membrane attributed to enhanced PC-specific flippase activity. We also assign a novel role to Rta3 in the Bcr1-regulated pathway for in vivo biofilm development. Transcriptome analysis reveals that Rta3 regulates expression of Bcr1 target genes involved in cell surface properties, adhesion, and hyphal growth. We show that rta3Δ/Δ mutant is biofilm-defective in a rat venous catheter model of infection and that BCR1 overexpression rescues this defect, indicating that Bcr1 functions downstream of Rta3 to mediate biofilm formation in C. albicans. The identification of this novel Rta3-dependent regulatory network that governs biofilm formation and PC asymmetry across the plasma membrane will provide important insights into C. albicans pathogenesis

Dataset for: Distinct roles of the 7-transmembrane receptor protein Rta3 in regulating the asymmetric distribution of phosphatidylcholine across the plasma membrane and biofilm formation in <i>Candida albicans</i>

Fungal pathogens like <i>Candida albicans</i> exhibit several survival mechanisms to evade attack by antifungals and colonize host tissues. Rta3, a member of the Rta1-like family of lipid-translocating exporters has a 7-transmembrane domain (7TMD) topology, similar to the G-protein-coupled receptors (GPCR) and is unique to the fungal kingdom. Our findings point towards a role for plasma membrane localized Rta3 in providing tolerance to miltefosine, an analogue of alkylphosphocholine, by maintaining mitochondrial energetics. Concurrent with miltefosine susceptibility, the <i>rta3Δ/Δ</i> strain displays increased inward translocation (flip) of fluorophore-labelled phosphatidylcholine (PC) across the plasma membrane attributed to enhanced PC-specific flippase activity. We also assign a novel role to Rta3 in the Bcr1- regulated pathway during in vivo biofilm development. Transcriptome analysis reveals that Rta3 regulates expression of Bcr1 target genes involved in cell surface properties, adhesion, and hyphal growth. We show that the <i>rta3Δ/Δ</i> mutant is biofilm-defective in a rat venous catheter model of infection and that <i>BCR1</i> overexpression rescues this defect, indicating that Bcr1 functions downstream of Rta3 to mediate biofilm formation in <i>C. albicans</i>. The identification of this novel Rta3-dependent regulatory network that governs biofilm formation and PC asymmetry across the plasma membrane will provide important insights into <i>C. albicans</i> pathogenesis by providing insight into how <i>C. albicans</i> adapts to the host environment

Systemic treatments for atopic dermatitis (eczema): systematic review and network meta-analysis of randomized trials

BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin condition with multiple systemic treatments and uncertainty regarding their comparative impact on AD outcomes. OBJECTIVE: We systematic synthesized the benefits and harms of AD systemic treatments. METHODS: For the 2023 AAAAI/ACAAI JTFPP AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, Web of Science, and GREAT, from inception to November 29, 2022, for randomized trials addressing systemic treatments and phototherapy for AD. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-quality of life, flares, and harms. The GRADE approach informed certainty of evidence ratings. OSF: https://osf.io/e5sna. RESULTS: 149 included trials (28,686 patients with moderate-to-severe AD) evaluated 75 interventions. With high-certainty, high-dose upadacitinib was among the most effective for five of six patient-important outcomes; high-dose abrocitinib and low-dose upadacitinib were among the most effective for two outcomes. These JAK inhibitors were among the most harmful in increasing adverse events. With high-certainty, dupilumab, lebrikizumab, and tralokinumab were of intermediate effectiveness and among the safest-modestly increasing conjunctivitis. Low-dose baricitinib was among the least effective. The efficacy and safety of azathioprine, oral corticosteroids, cyclosporine, methotrexate, mycophenolate, phototherapy, and many novel agents are less certain. CONCLUSIONS: Among individuals with moderate-to-severe AD, high-certainty evidence demonstrates that high-dose upadacitinib is among the most effective in addressing multiple patient-important outcomes but also among the most harmful. High-dose abrocitinib and low-dose upadacitinib are effective, but also among the most harmful. Dupilumab, lebrikizumab, and tralokinumab are of intermediate effectiveness and favorable safety