Synthesis of novel pyrrolobenzodiazepine (PBD) C1-substituted monomers and dimers with DNA-binding activity and cytotoxicity.

The pyrrolobenzodiazepines (PBDs) represent a major class of sequence-selective DNA-alkylating molecules, one example of which, in its dimeric DNA-cross-linking form, is employed as the payload in the anticancer Antibody Drug Conjugate (ADC) loncastuximab tesirine-lpyl. To date, PBD analogues have been produced with substituents at every position of the tricyclic skeleton except the C1-position. We report here the first synthesis of a C1-subsitituted PBD monomer and dimer, both of which possess DNA-binding activity and cytotoxicity in a cancer cell line.

Acute maternal hyperoxygenation to predict hypoxia and need for emergency intervention in fetuses with transposition of the great arteries: a pilot study.

Background: Newborns with transposition of the great arteries (TGA) are at risk of severe hypoxia from inadequate atrial mixing, closure of the arterial duct and/or pulmonary hypertension (PPHN). Acute maternal hyperoxygenation (AMH) might assist in identifying at-risk fetuses. We report pulmonary vasoreactivity to AMH in TGA fetuses and its relationship to early postnatal hypoxia and requirement for emergency balloon atrial septostomy (e-BAS).

Bidirectional longitudinal associations between subjective oral health and subjective well-being.

Objective: This study investigated the bidirectional longitudinal association between subjective oral health (SOH) and subjective well-being (SWB) over time.

Methods: This cohort study was based on a four-wave surveys conducted by the English Longitudinal Study of Aging. SOH was measured by oral impacts on daily performance (OIDP), self-rated oral health (SROH), and SWB was measured by the Center for Epidemiologic Studies-Depression (CES-D) scale, Control, Autonomy, Self-Realization, and Pleasure (CASP-19), and satisfaction with life scale (SWLS).

Epilepsy in acute psychiatric inpatient settings: Prevalence, treatment gaps, and mortality.

Background: The underrepresentation of acute psychiatric settings in epilepsy research presents a barrier to delivering equitable healthcare for people with comorbid epilepsy and severe mental illness. We aimed to report the prevalence of epilepsy among people receiving acute psychiatric inpatient care and examine the sociodemographic and clinical characteristics influencing their treatment outcomes.

Methods: We analysed electronic patient records to estimate the lifetime prevalence of epilepsy in a retrospective cohort of 9,237 people admitted to psychiatric inpatient wards in South London between 2015 and 2019.

Current evidence around key underrepresented women's health topics in pregnancy and postpartum nutrition: a narrative review.

Adequate nutrition during pregnancy and postpartum is critical to maternal and child health, but there is often a missing focus around health outcomes specifically for women. Women's health includes sex-specific biological attributes and socially constructed gender roles framing behaviours and practices. This narrative review aims to highlight key areas where women's health has been underrepresented in pregnancy and postpartum nutrition research.

Navigating choices: understanding the decision-making journey of patients with localised kidney cancer.

Objective: To explore patients' experience of decision making regarding treatment of localised kidney cancer.

Methods: A total of 21 patients with localised kidney cancer, across three countries, participated in either four focus groups or seven semi-structured interviews that lasted on average 2 h. Focus groups and interviews were all conducted in the participants' native language, recorded, transcribed and (if applicable) translated into English.

Characteristics of refractory disease and persistent symptoms in inflammatory arthritis: Qualitative framework analysis of interviews with patients and health care professionals.

Objectives: This study aims to explore patients' and clinicians' understanding and experiences of refractory disease (RD) and persistent physical and emotional symptoms (PPES) in patients with inflammatory arthritis (IA), namely rheumatoid arthritis or polyarticular juvenile idiopathic arthritis from their perspectives through interviews and/or focus groups.

Design: A qualitative study was conducted, following a pragmatic epistemology approach with framework analysis employed.

Methods: Semi-structured interviews or focus groups with IA patients (n = 25) and multi-disciplinary rheumatology HCPs (n = 32) were conducted at one time point to obtain participants respective understanding and experiences of managing RD/PPES, and its impact on the patient-professional relationship.

Health-Related Behaviour Clusters and Functional Dentition in Older People.

Objectives: To identify different clusters of health-related behaviours and examine whether these clusters are associated with maintaining 20 or more teeth.

Background: Engaging in risky behaviours impacts tooth loss, particularly among older adults. Maintaining 20 teeth is a challenge for this age group.

Interventions for quitting vaping.

Rationale: There is limited guidance on the best ways to stop using nicotine-containing vapes (otherwise known as e-cigarettes) and ensure long-term abstinence, whilst minimising the risk of tobacco smoking and other unintended consequences. Treatments could include pharmacological interventions, behavioural interventions, or both.

Objectives: To conduct a living systematic review assessing the benefits and harms of interventions to help people stop vaping compared to each other or to placebo or no intervention.

No prediction without prevention: A global qualitative study of attitudes toward using a prediction tool for risk of developing depression during adolescence.

Given the rate of advancement in predictive psychiatry, there is a threat that it outpaces public and professional willingness for use in clinical care and public health. Prediction tools in psychiatry estimate the risk of future development of mental health conditions. Prediction tools used with young populations have the potential to reduce the worldwide burden of depression.

Co-design of "Baatcheet," a peer-supported, web-based storytelling intervention for young people with common mental health problems in India.

Background: Engaging with personal mental health stories has the potential to help people with mental health difficulties by normalizing distressing experiences, imparting coping strategies and building hope. However, evidence-based mental health storytelling platforms are scarce, especially for young people in low-resource settings.

Objective: This paper presents an account of the co-design of 'Baatcheet' ('conversation' in Hindi), a peer-supported, web-based storytelling intervention aimed at 16-24-year-olds with depression and anxiety in New Delhi, India.

Interventions to Reduce Discrimination and Stigma: The State of the Art.

Background: There is a rich literature on the nature of mental health-related stigma and the processes by which it severely affects the life chances of people with mental health problems. However, applying this knowledge to deliver and evaluate interventions to reduce discrimination and stigma in a lasting way is a complex and long-term challenge.

Methods: We conducted a narrative synthesis of systematic reviews published since 2012, and supplemented this with papers published subsequently as examples of more recent work.

Patient-centred outcome measures for oncological surgery: a narrative review.

Introduction: Peri-operative medicine is becoming increasingly relevant in the context of managing frail patients with cancer. This paper outlines how demographic shifts in populations are affecting cancer incidence and frailty rates, the relevance this holds to the management of cancer care, and the outcome measures that should be used to gauge best clinical practice to ensure patient-centred care.

Methods: A targeted literature review was conducted using the search terms 'surgical oncology', 'outcomes', 'frailty', 'quality of life' and 'end of life' from 10 to 17 June 2024.

Reliability and validity of four cognitive interpretation bias measures in the context of social anxiety.

People with social anxiety disorder tend to interpret ambiguous social information in a negative rather than positive manner. Such interpretation biases may cause and maintain anxiety symptoms. However, there is considerable variability in the observed effects across studies, with some not finding a relationship between interpretation biases and social anxiety.

Comparative assessment of chondral defect repair using human bone marrow- and adipose tissue-derived mesenchymal stem cells, adult and foetal articular cartilage-derived chondrocytes, and chondroprogenitors: an ex-vivo model.

Purpose: Cartilage repair necessitates adjunct therapies such as cell-based approaches, which commonly use MSCs and chondrocytes but is limited by the formation of fibro-hyaline cartilage. Articular cartilage-derived chondroprogenitors(CPs) offer promise in overcoming this, as they exhibit higher chondrogenic and lower hypertrophic phenotypes. The study aimed to compare the efficacy of various cell types derived from adult and foetal cartilage suspended in platelet-rich plasma(PRP) in repairing chondral defects in an Ex-vivo Osteochondral Unit(OCU) model.

Change in frailty status in the 12 months following solid organ transplantation: a systematic review and meta-analysis.

Objectives: To investigate if frailty status alters following solid organ transplantation (lung, liver, kidney and heart) without rehabilitation intervention.

Research Design And Methods: Studies published between 1 January 2000 and 30 May 2023 were searched across five databases. Studies measuring frailty, using a validated or established frailty measure, pre- and post-transplant were included.

High Content Image Analysis of Cellular Responses of the Murine J774A.1 Cell Line and Primary Human Cells Alveolar Macrophages to an Extended Panel of Pharmaceutical Agents.

Introduction: In vitro screening of macrophages for drug-induced effects, such as phospholipidosis, is useful for detecting potentially problematic compounds in the preclinical development of oral inhaled products. High-content image analysis (HCIA) is a multi-parameter approach for cytotoxicity screening. This study provides new insights into HCIA-derived response patterns of murine J774A.

Maximum Tumor Diameter is Associated with Relapse Risk in Limited-Stage Hodgkin Lymphoma: An International Study.

Tumour bulk is an established prognostic factor in Hodgkin lymphoma (HL) but most patients with limited-stage (LS) HL do not have 'bulk' by standard binary definitions. In the RAPID trial, maximum tumor diameter (MTD) was associated with risk of relapse for LS-HL patients achieving PET-negativity after ABVD chemotherapy. We aimed to externally validate these findings in the H10 trial.

Patient-Reported Improvements in Patients with PNH Treated with Iptacopan from Two Phase 3 Studies.

Iptacopan, a first-in-class, oral, selective complement factor B inhibitor, demonstrated efficacy and safety as monotherapy in C5 inhibitor (C5i)-experienced (APPLY-PNH [NCT04558918]) and C5i-naive (APPOINT-PNH [NCT04820530]) patients with paroxysmal nocturnal hemoglobinuria (PNH). In APPLY-PNH and APPOINT-PNH, changes in fatigue (FACIT-Fatigue) and health-related quality of life (HRQOL; EORTC QLQ-C30) from baseline to Day 168 were evaluated. The proportion of patients achieving meaningful within-patient change (MWPC) on the FACIT-Fatigue and 4 EORTC QLQ-C30 subscales (physical functioning, role functioning, fatigue, dyspnea) was evaluated using anchor-based thresholds.

A genome-wide scan of non-coding RNAs and enhancers for refractive error and myopia.

Refractive error (RE) and myopia are complex polygenic conditions with the majority of genome-wide associated genetic variants in non-exonic regions. Given this, and the onset during childhood, gene-regulation is expected to play an important role in its pathogenesis. This prompted us to explore beyond traditional gene finding approaches.

Predicting clinical outcomes in a blended care intervention for early psychosis: Acceptance and Commitment Therapy in Daily-Life (ACT-DL).

ACT in Daily Life (ACT-DL) is a blended-care Ecological Momentary Intervention that extends ACT into the daily life of individuals, improving psychotic distress, negative symptoms, and global functioning. However, it remains unclear whether ACT-DL works equally for everyone. We investigated whether moderators (i.