Porphyrins on acid: kinetics of the photoinduced-protonation of tetrakis(4-carboxyphenyl)-porphyrin.

Free-base porphyrins can be protonated, which significantly impacts their electronic and excited state properties. While excited state dynamics are well explored for either neutral or fully protonated porphyrins, the intermediate region has not yet been explored, although their potential implications for photocatalytic reactions are evident. This study explores how partial protonation affects the nature and properties of photoexcited states of tetrakis(4-carboxyphenyl)porphyrin (TCPP) using steady-state and nanosecond transient absorption spectroscopy.

Challenges and Future Perspectives in Photocatalysis: Conclusions from an Interdisciplinary Workshop.

Photocatalysis is a versatile and rapidly developing field with applications spanning artificial photosynthesis, photo-biocatalysis, photoredox catalysis in solution or supramolecular structures, utilization of abundant metals and organocatalysts, sustainable synthesis, and plastic degradation. In this Perspective, we summarize conclusions from an interdisciplinary workshop of young principal investigators held at the Lorentz Center in Leiden in March 2023. We explore how diverse fields within photocatalysis can benefit from one another.

The senescence-associated secretome of Hedgehog-deficient hepatocytes drives MASLD progression.

The burden of senescent hepatocytes correlates with the severity of metabolic dysfunction-associated steatotic liver disease (MASLD), but the mechanisms driving senescence and how it exacerbates MASLD are poorly understood. Hepatocytes experience lipotoxicity and become senescent when Smoothened (Smo) is deleted to disrupt Hedgehog signaling. We aimed to determine whether the secretomes of Smo-deficient hepatocytes perpetuate senescence to drive MASLD progression.

A Qualitative Study Supporting Optimal Nutrition in Advanced Liver Disease-Unlocking the Potential for Improvement.

Malnutrition rates in Advanced Liver Disease (ALD) are significantly higher than those in well-compensated liver disease. In addition to its physiological impact, malnutrition is detrimental for quality of life and social, emotional, and psychological well-being. Studies within oncology and renal supportive care have identified the influence of non-physiological factors on malnutrition risk.

Single-cell multi-omic and spatial profiling of human kidneys implicates the fibrotic microenvironment in kidney disease progression.

Kidneys are intricate three-dimensional structures in the body, yet the spatial and molecular principles of kidney health and disease remain inadequately understood. We generated high-quality datasets for 81 samples, including single-cell, single-nuclear, spot-level (Visium) and single-cell resolution (CosMx) spatial-RNA expression and single-nuclear open chromatin, capturing cells from healthy, diabetic and hypertensive diseased human kidneys. Combining these data, we identify cell types and map them to their locations within the tissue.

Painful to Discuss: The Intersection of Chronic Pain, Mental Health, and Analgesic Use among People with HIV.

Objective: This retrospective chart review study aims to identify patients in an HIV clinical setting in an area of high HIV prevalence in Atlanta, Georgia, USA who have chronic pain, analgesic prescriptions, and/or mental health diagnoses.

Design: People living with HIV (PLWH) are at higher risk for experiencing trauma, mental health conditions, and chronic pain than their HIV-negative counterparts. This study was designed to evaluate the intersection of these factors within an urban HIV clinic.

Performance of ChatGPT and Bard on the official part 1 FRCOphth practice questions.

Background: Chat Generative Pre-trained Transformer (ChatGPT), a large language model by OpenAI, and Bard, Google's artificial intelligence (AI) chatbot, have been evaluated in various contexts. This study aims to assess these models' proficiency in the part 1 Fellowship of the Royal College of Ophthalmologists (FRCOphth) Multiple Choice Question (MCQ) examination, highlighting their potential in medical education.

Methods: Both models were tested on a sample question bank for the part 1 FRCOphth MCQ exam.

Retrospective Comparison of Patients Evaluated for Pediatric Autoimmune Encephalitis with Typical and Atypical Premorbid Neuropsychiatric Development.

Purpose: Patients with neurodevelopmental disorders (NDD) (i.e. autism, developmental delay, early-onset psychiatric or seizure disorders) increasingly seek evaluation of new or exacerbated symptoms concerning for autoimmune encephalitis (AE).

Probing the influence of substrate binding on photocatalytic dehalogenation with a heteroleptic supramolecular [MLL] square containing PDI photosensitizers as ligands.

Photoredox catalysis is a valuable tool in a large variety of chemical reactions. Main challenges still to be overcome are photodegradation of photocatalysts and substrates, short lifetimes of reactive intermediates, and selectivity issues due to unwanted side reactions. A potential solution to these challenges is the pre-organization of the photosensitizer, substrate and (co)-catalyst in supramolecular self-assembled structures.

Co-designing an Integrated Health and Social Care Hub With and for Families Experiencing Adversity.

Introduction: Integrated care research often fails to adequately describe co-design methods. This article outlines the process, principles and tools to co-design an integrated health and social care Hub for families experiencing adversity.

Research Methods: The Child and Family Hub was co-designed in four stages: (1) partnership building and stakeholder engagement, (2) formative research, (3) persona development and (4) co-design workshops and consultations.

Spatz: the time-of-flight neutron reflectometer with vertical sample geometry at the OPAL research reactor.

The Spatz neutron beam instrument is the second time-of-flight neutron reflectometer to be installed at the OPAL research reactor. The instrument was formerly the V18 BioRef reflectometer at the BER-II reactor in Berlin and was transferred to Australia in 2016. Subsequently the instrument was re-installed in the neutron guide hall of the OPAL reactor at the end position of the CG2B cold-neutron guide and recommissioned.

Supramolecular Coordination Cages for Artificial Photosynthesis and Synthetic Photocatalysis.

Because sunlight is the most abundant energy source on earth, it has huge potential for practical applications ranging from sustainable energy supply to light driven chemistry. From a chemical perspective, excited states generated by light make thermodynamically uphill reactions possible, which forms the basis for energy storage into fuels. In addition, with light, open-shell species can be generated which open up new reaction pathways in organic synthesis.

Hepatocyte Smoothened Activity Controls Susceptibility to Insulin Resistance and Nonalcoholic Fatty Liver Disease.

Background & Aims: Nonalcoholic steatohepatitis (NASH), a leading cause of cirrhosis, strongly associates with the metabolic syndrome, an insulin-resistant proinflammatory state that disrupts energy balance and promotes progressive liver degeneration. We aimed to define the role of Smoothened (Smo), an obligatory component of the Hedgehog signaling pathway, in controlling hepatocyte metabolic homeostasis and, thereby, susceptibility to NASH.

Methods: We conditionally deleted Smo in hepatocytes of healthy chow-fed mice and performed metabolic phenotyping, coupled with single-cell RNA sequencing (RNA-seq), to characterize the role of hepatocyte Smo in regulating basal hepatic and systemic metabolic homeostasis.

The Novel, Clinical-Stage Soluble Guanylate Cyclase Activator BI 685509 Protects from Disease Progression in Models of Renal Injury and Disease.

Activation of soluble guanylate cyclase (sGC) to restore cyclic guanosine monophosphate (cGMP) and improve functionality of nitric oxide (NO) pathways impaired by oxidative stress is a potential treatment of diabetic and chronic kidney disease. We report the pharmacology of BI 685509, a novel, orally active small molecule sGC activator with disease-modifying potential. BI 685509 and human sGC 1/1 heterodimer containing a reduced heme group produced concentration-dependent increases in cGMP that were elevated modestly by NO, whereas heme-free sGC and BI 685509 greatly enhanced cGMP with no effect of NO.

Deep learning-based quantification of NAFLD/NASH progression in human liver biopsies.

Non-alcoholic fatty liver disease (NAFLD) affects about 24% of the world's population. Progression of early stages of NAFLD can lead to the more advanced form non-alcoholic steatohepatitis (NASH), and ultimately to cirrhosis or liver cancer. The current gold standard for diagnosis and assessment of NAFLD/NASH is liver biopsy followed by microscopic analysis by a pathologist.

Pharmacological TRPC6 inhibition improves survival and muscle function in mice with Duchenne muscular dystrophy.

Gene mutations causing loss of dystrophin result in the severe muscle disease known as Duchenne muscular dystrophy (DMD). Despite efforts at genetic repair, DMD therapy remains largely palliative. Loss of dystrophin destabilizes the sarcolemmal membrane, inducing mechanosensitive cation channels to increase calcium entry and promote cell damage and, eventually, muscle dysfunction.

Use of North Carolina Medicaid Collaborative Care Billing Codes After Statewide Approval for Reimbursement.

Effective October 2018, North Carolina Medicaid approved reimbursement for collaborative care model (CoCM) billing codes. From October 2018 through December 2019, only 915 of the estimated two million eligible Medicaid beneficiaries had at least one CoCM claim, and the median number of claims per patient was two. Availability of reimbursement for CoCM Medicaid billing codes in North Carolina did not immediately result in robust utilization of CoCM.

Transition Metal Catalysis Controlled by Hydrogen Bonding in the Second Coordination Sphere.

Transition metal catalysis is of utmost importance for the development of sustainable processes in academia and industry. The activity and selectivity of metal complexes are typically the result of the interplay between ligand and metal properties. As the ligand can be chemically altered, a large research focus has been on ligand development.

Towards a better understanding of attitudes and beliefs held by traditional healers and recipients of traditional medicine concerning mental health conditions in post-conflict Liberia: a qualitative investigation.

Background: A better understanding of attitudes and beliefs held by traditional healers and utilizers of traditional medicine concerning mental health conditions in Liberia is important as Liberia seeks to improve its delivery of mental healthcare in the context of scarce resources and recovery from civil war.

Methods: A qualitative research design was used to collect data from 24 Liberian traditional healers, and 11 utilizers of Liberian traditional medicine. Participants were queried about mental health problems in Liberia, treatments, and attitudes towards modern healthcare.

The key role of NLRP3 and STING in APOL1-associated podocytopathy.

Coding variants in apolipoprotein L1 (APOL1), termed G1 and G2, can explain most excess kidney disease risk in African Americans; however, the molecular pathways of APOL1-induced kidney dysfunction remain poorly understood. Here, we report that expression of G2 APOL1 in the podocytes of Nphs1rtTA/TRE-G2APOL1 (G2APOL1) mice leads to early activation of the cytosolic nucleotide sensor, stimulator of interferon genes (STING), and the NLR family pyrin domain-containing 3 (NLRP3) inflammasome. STING and NLRP3 expression was increased in podocytes from patients with high-risk APOL1 genotypes, and expression of APOL1 correlated with caspase-1 and gasdermin D (GSDMD) levels.

Mapping the genetic architecture of human traits to cell types in the kidney identifies mechanisms of disease and potential treatments.

The functional interpretation of genome-wide association studies (GWAS) is challenging due to the cell-type-dependent influences of genetic variants. Here, we generated comprehensive maps of expression quantitative trait loci (eQTLs) for 659 microdissected human kidney samples and identified cell-type-eQTLs by mapping interactions between cell type abundances and genotypes. By partitioning heritability using stratified linkage disequilibrium score regression to integrate GWAS with single-cell RNA sequencing and single-nucleus assay for transposase-accessible chromatin with high-throughput sequencing data, we prioritized proximal tubules for kidney function and endothelial cells and distal tubule segments for blood pressure pathogenesis.

From Silos to Solidarity: Case Study of a Patient-Centered, Integrative Approach to Opioid Tapering and Chronic Pain Mitigation in a Multidisciplinary AIDS Clinic.

Background: People with HIV (PWH) are at a disproportionate risk for experiencing both chronic pain and opioid use disorder (OUD). Prescription opioid tapering is typically addressed within the "silo model" of medical care, whereby attention is focused solely on opioid addiction rather than also addressing chronic pain management, and limited communication occurs between patient and providers.

Objective: This descriptive case study examined an integrative, collaborative care model consisting of Provider, Physical Therapist (PT), and Patient aimed at decreasing chronic pain and opioid use within a multidisciplinary HIV/AIDS clinic.