Triphenylamine Sensitized 8-Dimethylaminoquinoline: An Efficient Two-Photon Caging Group for Intracellular Delivery.

Triphenylamine-sensitized 8-dimethylaminoquinoline (TAQ) probes showed fair two-photon absorption and fragmentation cross sections in releasing kainate and GABA ligands. The water-soluble PEG and TEG-analogs allowed cell internalization and efficient light-gated liberation of the rhodamine reporter under UV and two-photon (NIR) irradiation conditions.

Value-Based Healthcare: A Primer for the Dermatologist.

Background: Value-based healthcare (VBHC) is an increasingly employed strategy to transform healthcare organizations into economically sustainable systems that deliver high-value care. In dermatology, the need for VBHC is evident as chronic skin diseases require long-term, often expensive treatments. This narrative review aims to introduce dermatologists to the principles and implementation of VBHC.

The purinergic receptor P2X7 and the NLRP3 inflammasome are druggable host factors required for SARS-CoV-2 infection.

Purinergic receptors and NOD-like receptor protein 3 (NLRP3) inflammasome regulate inflammation and viral infection, but their effects on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remain poorly understood. Here, we report that the purinergic receptor P2X7 and NLRP3 inflammasome are cellular host factors required for SARS-CoV-2 infection. Lung autopsies from patients with severe coronavirus disease 2019 (COVID-19) reveal that NLRP3 expression is increased in host cellular targets of SARS-CoV-2 including alveolar macrophages, type II pneumocytes and syncytia arising from the fusion of infected macrophages, thus suggesting a potential role of NLRP3 and associated signaling pathways to both inflammation and viral replication.

Determining patient value profiles in psoriasis.

Background: Healthcare professionals (HCPs) should strive to create the maximum value for their patients in which value is defined as the patient-relevant health outcomes achieved per costs made. However, currently it remains difficult to determine which outcomes matter to an individual psoriasis patient.

Objective: To define outcome profiles, or so called 'patient value profiles', within a cohort of psoriasis patients that can be translated to daily practice to increase value for the individual patient.

Value in psoriasis (IRIS) trial: implementing value-based healthcare in psoriasis management - a 1-year prospective clinical study to evaluate feasibility and value creation.

Introduction: Currently, the healthcare sector is under tremendous financial pressure, and many acknowledge that a dramatic shift is required as the current system is not sustainable. Furthermore, the quality of care that is delivered varies strongly. Several solutions have been proposed of which the conceptual framework known as value-based healthcare (VBHC) is further explored in this study for psoriasis.

A plain language summary of what freedom from disease means to people with psoriasis according to doctors, nurses, and people with psoriasis.

What is this summary about? This summary presents findings from recent research involving people with psoriasis, based on an article originally published in the . Psoriasis is a condition that primarily affects the skin. However, it can also influence people's mental health, social activities, work, and relationships too.

PsoPlus: An Integrated Practice Unit for Psoriasis.

There is a need to revise the current healthcare organization due to the ever-rising costs and variation in quality of delivered care. Over the past decades there have been several strategic frameworks attempting to tackle this problem. Value-based healthcare (VBHC) is one of those frameworks which has gained increasing popularity the last years.

Initiating value-based healthcare in psoriasis: Proposing a value-based outcome set for daily clinical practice.

Background: With the current trend in healthcare moving towards a more value-based approach, it is essential to understand what value encompasses.

Objectives: To develop an actionable value-based outcome set (VOS) for daily practice.

Methods: A mixed method approach was used consisting of four phases.

Mutations in the 3'-PPT Lead to HIV-1 Replication without Integration.

Integration of the reverse-transcribed genome is a critical step of the retroviral life cycle. Strand-transfer inhibitors (INSTIs) used for antiretroviral therapy inhibit integration but can lead to resistance mutations in the integrase gene, the enzyme involved in this reaction. A significant proportion of INSTI treatment failures, particularly those with second-generation INSTIs, show no mutation in the integrase gene.

Patient-Relevant Outcomes in Psoriasis: A Systematic Review.

Importance: There is a need to define which outcomes matter to patients with psoriasis to deliver value for the patient when managing their condition.

Objectives: To generate a comprehensive overview of all outcomes relevant in the management of psoriasis as defined by patients.

Evidence Review: A systematic review was performed by searching 3 databases (MEDLINE, Embase, and Web of Science) from August 1, 2019, until March 27, 2021, using a comprehensive search strategy consisting of 4 concepts including psoriasis, patients, outcomes, and relevance.

Freedom from disease in psoriasis: a Delphi consensus definition by patients, nurses and physicians.

Background: Physician-reported clinical outcome and quality of life (QoL) measures are currently used to assess outcomes and direct treatment of plaque psoriasis. However, people with psoriasis may have different criteria for judging treatment success.

Objectives: To build a unified consensus on the definition of 'freedom from disease' from a European stakeholder group, including people with psoriasis, dermatologists and nurses.

Modulation of Cellular Fate of Vinyl Triarylamines through Structural Fine Tuning: To Stay or Not To Stay in the Mitochondria?

Mitochondria are involved in many cellular pathways and dysfunctional mitochondria are linked to various diseases. Hence efforts have been made to design mitochondria-targeted fluorophores for monitoring the mitochondrial status. However, the factors that govern the mitochondria-targeted potential of dyes are not well-understood.

The role of the nurse in the care and management of patients with atopic dermatitis.

Background: The purpose of this paper is to provide an overview of key aspects of specialised dermatology nursing practice in the management of patients with moderate to severe atopic dermatitis. The role of dermatology nurse specialists in supporting patients and promoting disease understanding, education and treatment adherence continues to evolve. As features of specialised nursing care can also inform other nursing staff in a wide range of care settings, an overview of key components is examined.

Interplay between Cellular Uptake, Intracellular Localization and the Cell Death Mechanism in Triphenylamine-Mediated Photoinduced Cell Death.

Triphenylamines (TPAs) were previously shown to trigger cell death under prolonged one- or two-photon illumination. Their initial subcellular localization, before prolonged illumination, is exclusively cytoplasmic and they translocate to the nucleus upon photoactivation. However, depending on their structure, they display significant differences in terms of precise initial localization and subsequent photoinduced cell death mechanism.

The implementation of a structured specialized consultation for psoriasis management.

: Psoriasis is a chronic skin disease requiring a multidimensional approach, given its varying appearance, presence of comorbidities and complex treatment regimens. Psoriasis care is however often performed fragmented and, in case of flares, reactive with little integrated information on and for the patient. Literature suggests a multileveled approach of psoriasis, but the effects of its implementation have not yet been validated.

Design of Light-Sensitive Triggers for Endothelial NO-Synthase Activation.

A specific light trigger for activating endothelial Nitric Oxide-Synthase (eNOS) in real time would be of unique value to decipher cellular events associated with eNOS activation or to generate on demand cytotoxic levels of NO at specific sites for cancer research. We previously developed novel tools called nanotriggers (NT), which recognized constitutive NO-synthase, eNOS or neuronal NOS (nNOS), mainly via their 2' phosphate group which is also present in NADPH in its binding site. Laser excitation of NT1 bound to eNOS triggered recombinant NOS activity and released NO.

Interplay between Intrinsic and Innate Immunity during HIV Infection.

Restriction factors are antiviral components of intrinsic immunity which constitute a first line of defense by blocking different steps of the human immunodeficiency virus (HIV) replication cycle. In immune cells, HIV infection is also sensed by several pattern recognition receptors (PRRs), leading to type I interferon (IFN-I) and inflammatory cytokines production that upregulate antiviral interferon-stimulated genes (ISGs). Several studies suggest a link between these two types of immunity.

Light-induced formation of NO in endothelial cells by photoactivatable NADPH analogues targeting nitric-oxide synthase.

Background: Nitric-oxide synthases (NOS) catalyze the formation of NO using NADPH as electron donor. We have recently designed and synthesized a new series of two-photon absorbing and photoactivatable NADPH analogues (NT). These compounds bear one or two carboxymethyl group(s) on the 2'- or/and 3'-position(s) of the ribose in the adenosine moiety, instead of a 2'-phosphate group, and differ by the nature of the electron donor in their photoactivatable chromophore (replacing the nicotinamide moiety).

Two-long terminal repeat (LTR) DNA circles are a substrate for HIV-1 integrase.

Integration of the HIV-1 DNA into the host genome is essential for viral replication and is catalyzed by the retroviral integrase. To date, the only substrate described to be involved in this critical reaction is the linear viral DNA produced in reverse transcription. However, during HIV-1 infection, two-long terminal repeat DNA circles (2-LTRcs) are also generated through the ligation of the viral DNA ends by the host cell's nonhomologous DNA end-joining pathway.

High uptake of pre-exposure prophylaxis (PrEP) during early roll-out in Belgium: results from surveillance reports.

Unlabelled: Background Since 1 June 2017, oral pre-exposure prophylaxis (PrEP) could be prescribed and reimbursed in Belgium as prophylactic medication for people who are at increased risk of HIV acquisition. The aim of this study was to determine the uptake of daily and event-driven PrEP in Belgium during the first 9 months of roll-out.

Methods: Routine aggregated data on the number of reimbursement requests and the number of boxes of Truvada (Gilead Sciences, Cambridge, UK) delivered for PrEP through the Belgian pharmacies were obtained from the National Institute for Health and Disability Insurance.

Pathway involving the N155H mutation in HIV-1 integrase leads to dolutegravir resistance.

Background: Dolutegravir, an integrase strand-transfer inhibitor (STI), shows a high genetic barrier to resistance. Dolutegravir is reported to be effective against viruses resistant to raltegravir and elvitegravir. In this study, we report the case of a patient treated with dolutegravir monotherapy.

Probing Resistance Mutations in Retroviral Integrases by Direct Measurement of Dolutegravir Fluorescence.

FDA-approved integrase strand transfer inhibitors (raltegravir, elvitegravir and dolutegravir) efficiently inhibit HIV-1 replication. Here, we present fluorescence properties of these inhibitors. Dolutegravir displays an excitation mode particularly dependent on Mg chelation, allowing to directly probe its Mg-dependent binding to the prototype foamy virus (PFV) integrase.

Triphenylamines Induce Cell Death Upon 2-Photon Excitation.

Photodynamic therapy (PDT) is a promising therapeutic method for several diseases, in particular for cancer. This approach uses a photosensitizer, oxygen, and an external light source to produce reactive oxygen species (ROS) at lethal doses to induce cell death. One drawback of current PDT is the use of visible light which has poor penetration in tissues.