Peripheral innervation plays an important role in regulating tissue repair and regeneration. Here we provide evidence that injured peripheral nerves provide a reservoir of mesenchymal precursor cells that can directly contribute to murine digit tip regeneration and skin repair. In particular, using single-cell RNA sequencing and lineage tracing, we identify transcriptionally distinct mesenchymal cell populations within the control and injured adult nerve, including neural crest-derived cells in the endoneurium with characteristics of mesenchymal precursor cells. Culture and transplantation studies show that these nerve-derived mesenchymal cells have the potential to differentiate into non-nerve lineages. Moreover, following digit tip amputation, neural crest-derived nerve mesenchymal cells contribute to the regenerative blastema and, ultimately, to the regenerated bone. Similarly, neural crest-derived nerve mesenchymal cells contribute to the dermis during skin wound healing. These findings support a model where peripheral nerves directly contribute mesenchymal precursor cells to promote repair and regeneration of injured mammalian tissues.

There has been growing concern in the UK over recent years that a perceived mental health crisis is affecting children and adolescents, although published epidemiological evidence is limited.

The COVID-19 pandemic has adversely affected population mental health. We aimed to assess temporal trends in primary care-recorded common mental illness, episodes of self-harm, psychotropic medication prescribing, and general practitioner (GP) referrals to mental health services during the COVID-19 emergency in the UK.

To determine the magnitude of any excess risk of mortality and hospitalisation due to COVID-19 infection in patients with congenital heart disease (CHD) in the UK healthcare system.

To examine the effects of sleep traits on glycated hemoglobin (HbA1c).

Evidence for risk of dying by suicide and other causes following discharge from in-patient psychiatric care throughout adulthood is sparse.

Infection with SARS-CoV-2 is associated with fatigue and sleep problems long after the acute phase of COVID-19. In addition, there are concerns of SARS-CoV-2 infection causing psychiatric illness; however, evidence of a direct effect is inconclusive.

We describe the use of pancreatic retrograde venous infusion in an orthotopic murine model of pancreatic ductal adenocarcinoma and hypothesize that pancreatic retrograde venous infusion delivery of gemcitabine will increase concentrations of gemcitabine in the tumor and the subsequent tumor response to treatment.

To compare rates of performing National Institute for Health and Care Excellence-recommended health checks and prescribing in people with type 2 diabetes (T2D), before and after the first COVID-19 peak in March 2020, and to assess whether trends varied by age, sex, ethnicity and deprivation.

Three leading disease causes of age-related visual loss are cataract, age-related macular degeneration (AMD), and glaucoma. Although all 3 eye diseases have been implicated with falls and fracture risk, evidence is mixed, with the contribution of different eye diseases being uncertain.

Background: People diagnosed with schizophrenia have a much reduced life expectancy compared to the general population, and a more than doubled risk of dying from cardiovascular disease (CVD). Existing CVD risk calculators can be used to detect people with an elevated predicted risk of CVD to inform interventions to reduce risk. Aims: This study aimed to compare four different risk calculators for 10-year predicted CVD risk in a sample of people with schizophrenia. Methods: Thirty participants with a diagnosis of schizophrenia spectrum disorders living within Greater Manchester, United Kingdom took part. Ten-year predicted cardiovascular risk scores were calculated using four different models: QRISK3, Framingham, PRIMROSE BMI, and PRIMROSE lipid. Risk estimates and classified risk categories were compared. Results: QRISK3 identified 11 (39%) as having >10% risk of a CV event within 10 years, 4 (14%) of whom exceeded 20%. The Framingham model identified 4 (14%) as exceeding 10%, none of whom exceeded 20%. PRIMROSE risk calculators identified no participants as having >10% risk of a CV event within 10 years. Pairwise concordance correlation coefficients between types of model ranged 0.22-0.77. Mean (± SD) age was 40 (± 10) years but QRISK3's mean "Heart age" was 58 (± 14) years. Conclusion: Risk calculators generate differing predicted CVD risk scores for patients with schizophrenia. Using one risk calculator might yield different recommended monitoring and treatment plans compared to another. Clinicians should therefore take into account other patient-related factors, such as patients' preferences and other underlying physical conditions when making treatment decisions.

Adult mammals have lost multi-tissue regenerative capacity, except for the distal digit, which is able to regenerate via mechanisms that remain largely unknown. Here, we show that, after adult mouse distal digit removal, nerve-associated Schwann cell precursors (SCPs) dedifferentiate and secrete growth factors that promote expansion of the blastema and digit regeneration. When SCPs were dysregulated or ablated, mesenchymal precursor proliferation in the blastema was decreased and nail and bone regeneration were impaired. Transplantation of exogenous SCPs rescued these regeneration defects. We found that SCPs secrete factors that promote self-renewal of mesenchymal precursors, and we used transcriptomic and proteomic analysis to define candidate factors. Two of these, oncostatin M (OSM) and platelet-derived growth factor AA (PDGF-AA), are made by SCPs in the regenerating digit and rescued the deficits in regeneration caused by loss of SCPs. As all peripheral tissues contain nerves, these results could have broad implications for mammalian tissue repair and regeneration.

Peripheral nerves provide a supportive growth environment for developing and regenerating axons and are essential for maintenance and repair of many non-neural tissues. This capacity has largely been ascribed to paracrine factors secreted by nerve-resident Schwann cells. Here, we used single-cell transcriptional profiling to identify ligands made by different injured rodent nerve cell types and have combined this with cell-surface mass spectrometry to computationally model potential paracrine interactions with peripheral neurons. These analyses show that peripheral nerves make many ligands predicted to act on peripheral and CNS neurons, including known and previously uncharacterized ligands. While Schwann cells are an important ligand source within injured nerves, more than half of the predicted ligands are made by nerve-resident mesenchymal cells, including the endoneurial cells most closely associated with peripheral axons. At least three of these mesenchymal ligands, ANGPT1, CCL11, and VEGFC, promote growth when locally applied on sympathetic axons. These data therefore identify an unexpected paracrine role for nerve mesenchymal cells and suggest that multiple cell types contribute to creating a highly pro-growth environment for peripheral axons.

Surveillance of temporal trends in clinically treated self-harm is an important component of suicide prevention in the dynamic context of COVID-19. There is little evidence beyond the initial months following the onset of the pandemic, despite national and regional restrictions persisting to mid-2021.