The Clinical and Molecular Response of Pyoderma Gangrenosum to IL-23 Blockade: Result from a Proof-of-Concept Open-Label Clinical Trial.

Pyoderma gangrenosum is a severe ulcerative disease with a great need for novel therapies. A major barrier to the development of novel therapies is a lack of understanding of disease pathogenesis. We present the results of a proof-of-concept open-label clinical trial of IL-23p19 antagonism with tildrakizumab in pyoderma gangrenosum.

Educator perceptions of the complex needs of young people in Pupil Referral Units: An exploratory qualitative analysis.

Background: Alternative education provision such as Pupil Referral Units support young people who have been excluded from mainstream school settings and often from disadvantaged backgrounds. However, there is limited research to date exploring educators' perceptions of the complex needs of young people in PRUs, and the extent to which PRUs as currently configured can meet such needs.

Methods: Between March 2019 and October 2020 twenty-two participants holding various educational roles from five different Pupil Referral Units across London and Southeast England were interviewed.

Aperiodic and Hurst EEG exponents across early human brain development: A systematic review.

In electroencephalographic (EEG) data, power-frequency slope exponents (1/f) can provide non-invasive markers of in vivo neural activity excitation-inhibition (E:I) balance. E:I balance may be altered in neurodevelopmental conditions; hence, understanding how 1/f evolves across infancy/childhood has implications for developing early assessments/interventions. This systematic review (PROSPERO-ID: CRD42023363294) explored the early maturation (0-26 yrs) of resting-state EEG 1/f measures (aperiodic [AE], power law [PLE] and Hurst [HE] exponents), including studies containing ≥1 1/f measures and ≥10 typically developing participants.

Metatranscriptome sequencing identifies are major contributors to pathogenic functions and biofilm formation in diabetes related foot osteomyelitis.

Osteomyelitis in the feet of persons with diabetes is clinically challenging and is associated with high rates of amputation. In this study RNA-sequencing was employed to explore microbial metatranscriptomes with a view to understand the relative activity and functions of the pathogen/s responsible for diabetes foot osteomyelitis (DFO). We obtained 25 intraoperative bone specimens from persons with confirmed DFO, observing that spp.

Meta-analysis of longitudinal neurocognitive performance in people at clinical high-risk for psychosis.

Persons at clinical high-risk for psychosis (CHR) are characterised by specific neurocognitive deficits. However, the course of neurocognitive performance during the prodromal period and over the onset of psychosis remains unclear. The aim of this meta-analysis was to synthesise results from follow-up studies of CHR individuals to examine longitudinal changes in neurocognitive performance.

A metatranscriptomic approach to explore longitudinal tissue specimens from non-healing diabetes related foot ulcers.

Cellular mechanisms and/or microbiological interactions which contribute to chronic diabetes related foot ulcers (DRFUs) were explored using serially collected tissue specimens from chronic DRFUs and control healthy foot skin. Total RNA was isolated for next-generation sequencing. We found differentially expressed genes (DEGs) and enriched hallmark gene ontology biological processes upregulated in chronic DRFUs which primarily functioned in the host immune response including: (i) Inflammatory response; (ii) TNF signalling via NFKB; (iii) IL6 JAK-STAT3 signalling; (iv) IL2 STAT5 signalling and (v) Reactive oxygen species.

Dissociable impairments of verbal learning differentiate childhood risk profiles for schizophrenia.

Poor verbal learning and memory function is well-documented among individuals with schizophrenia and those at clinical high-risk for psychosis. This study aimed to identify these impairments among children aged 9-12 years with different schizophrenia risk profiles (family history or antecedents of schizophrenia, each of higher or lower risk load) relative to typically developing peers. These three groups were recruited via community-screening, and differentiated for analysis into: typically developing children (TD = 45); children who had 1 first- or ≥2 second-degree affected relatives (FHx = 16) or one second-degree relative (FHx = 15); and children presenting multiple replicated antecedents of schizophrenia whose clinical symptoms persisted at 2- and/or 4-year follow-up (ASz = 16) or remitted during follow-up (ASz = 16).

Verbal memory performance predicts remission and functional outcome in people at clinical high-risk for psychosis.

Robust deficits in cognitive functioning are present in people with psychosis and are evident in the early stages of the disorder. Impairments in verbal memory and verbal fluency are reliably seen in individuals at clinical high-risk for psychosis (CHR) compared to healthy populations. As previous studies have shown a relationship between cognition and longer-term outcomes in schizophrenia, the aim of this paper was to explore whether verbal memory and verbal fluency performance predicted outcomes in a large CHR sample recruited as part of the EU-GEI High Risk Study.

Host-microbe metatranscriptome reveals differences between acute and chronic infections in diabetes-related foot ulcers.

Virtually all diabetes-related foot ulcers (DRFUs) will become colonized by microorganisms that may increase the risk of developing an infection. The reasons why some ulcerations develop acute clinical infections (AI-DRFUs) whilst others develop chronic infection (CI-DRFUs) and the preceding host-microbe interactions in vivo remain largely unknown. Establishing that acute and chronic infections are distinct processes requires demonstrating that these are two different strategies employed by microbes when interacting with a host.

Reliability of structural MRI measurements: The effects of scan session, head tilt, inter-scan interval, acquisition sequence, FreeSurfer version and processing stream.

Background: Large-scale longitudinal and multi-centre studies are used to explore neuroimaging markers of normal ageing, and neurodegenerative and mental health disorders. Longitudinal changes in brain structure are typically small, therefore the reliability of automated techniques is crucial. Determining the effects of different factors on reliability allows investigators to control those adversely affecting reliability, calculate statistical power, or even avoid particular brain measures with low reliability.

Comparative analysis between self-collected and clinician-collected samples for HPV testing in public health facilities in Zimbabwe.

Background: Cervical cancer screening programs that use visual inspection with acetic acid to identify women with pre-cancerous lesions in Zimbabwe have had limited success due to challenges with human resource constraints and patient acceptability. Nucleic acid amplification tests for human papillomavirus (HPV) have been endorsed by the World Health Organization for cervical cancer screening, along with self-collection of samples. As evidence shows self-collected sampling to be acceptable and preferable, Zimbabwe's Ministry of Health and Child Care (MOHCC) required a comparative analysis on the agreement between self- and clinician-collected samples for testing with Hologic Aptima HPV mRNA assay, to determine if self-collected samples could be used as another method to increase coverage of cervical cancer screening programs.

The Effectiveness of Trauma-Focused Interventions in Prison Settings: A Systematic Review and Meta-Analysis.

Background: Posttraumatic stress disorder (PTSD) is overrepresented in prison relative to community populations and can be difficult to manage in an environment which can inherently exacerbate trauma-related symptomology. Little is known about the effectiveness of trauma-focused interventions in prison and less is known about factors that moderate the effectiveness of these interventions.

Aim/methods: We examined the effectiveness of trauma-focused interventions in prison relative to prison controls using meta-analytic techniques.

Identification and characterization of CYPs induced in the Drosophila antenna by exposure to a plant odorant.

Members of the cytochrome p450 (CYP) enzyme family are abundantly expressed in insect olfactory tissues, where they are thought to act as Odorant Degrading Enzymes (ODEs). However, their contribution to olfactory signaling in vivo is poorly understood. This is due in part to the challenge of identifying which of the dozens of antennal-expressed CYPs might inactivate a given odorant.

A multiomics approach to identify host-microbe alterations associated with infection severity in diabetic foot infections: a pilot study.

Diabetic foot infections (DFIs) are a major cause of hospitalization and can lead to lower extremity amputation. In this pilot study, we used a multiomics approach to explore the host-microbe complex within DFIs. We observed minimal differences in the overall microbial composition between PEDIS infection severities, however Staphylococcus aureus and Streptococcus genera were abundant and highly active in most mild to moderate DFIs.

Utilisation of the 2019 IWGDF diabetic foot infection guidelines to benchmark practice and improve the delivery of care in persons with diabetic foot infections.

Aims: To utilise the 2019 International Working Group on the Diabetic Foot (IWGDF) - diabetic foot infection (DFI) guidelines as an audit tool for clinical practice in patients with diabetes attending a High-Risk Foot Service.

Methods: Data from 93 consecutive patients were collected over a 19-month period in patients attending a High-Risk Foot Service. The diagnosis and management of each patient in the sample were compared against the 2019 IWGDF DFI guidelines, grouped into four categories: Diagnosis, Microbiology, Treatment of soft tissue infection, and Surgical treatment and osteomyelitis.

Educational attainment trajectories among children and adolescents with depression, and the role of sociodemographic characteristics: longitudinal data-linkage study.

Background: Depression is associated with lower educational attainment, but there has been little investigation of long-term educational trajectories in large cohorts with diagnosed depression.

Aims: To describe the educational attainment trajectories of children with a depression diagnosis in secondary care, and to investigate whether these trajectories vary by sociodemographic characteristics.

Method: We identified new referrals to South London and Maudsley's NHS Foundation Trust between 2007 and 2013 who received a depression diagnosis at under 18 years old.

Trajectories of Mismatch Negativity and P3a Amplitude Development From Ages 9 to 16 Years in Children With Risk Factors for Schizophrenia.

Background: Mismatch negativity (MMN) and P3a amplitude reductions are robust abnormalities of sensory information processing in schizophrenia, but they are variably present in different profiles of risk (family history vs. clinical high risk) for the disorder. This study aimed to determine whether these abnormalities characterize children presenting replicated risk factors for schizophrenia, using longitudinal assessment over the ages of 9-16 years in children with multiple replicated antecedents of schizophrenia (ASz) and with family history of schizophrenia (FHx), relative to typically developing (TD) peers.

Academic achievement and schizophrenia: a systematic meta-analysis.

Background: Cognitive impairments in childhood are associated with increased risk of schizophrenia in later life, but the extent to which poor academic achievement is associated with the disorder is unclear.

Methods: Major databases were searched for articles published in English up to 31 December 2019. We conducted random-effects meta-analyses to: (1) compare general academic and mathematics achievement in youth who later developed schizophrenia and those who did not; (2) to examine the association between education level achieved and adult-onset schizophrenia; and, (3) compare general academic achievement in youth at-risk for schizophrenia and typically developing peers.

Monitoring wound progression to healing in diabetic foot ulcers using three-dimensional wound imaging.

Aim: 3D wound imaging has provided clinicians with even greater wound measurement options. No data is available to guide clinicians as to which 3D measurements may yield the most reflective marker of wound progression to healing.

Method: A prospective pilot study was undertaken to assess the accuracy of five 3D wound measurements that best reflect metrics of interest to clinicians.

Risk and protective factors for offending among UK Armed Forces personnel after they leave service: a data linkage study.

Background: A proportion of ex-military personnel who develop mental health and social problems end up in the Criminal Justice System. A government review called for better understanding of pathways to offending among ex-military personnel to improve services and reduce reoffending. We utilised data linkage with criminal records to examine the patterns of offending among military personnel after they leave service and the associated risk (including mental health and alcohol problems) and socio-economic protective factors.

Adolescent trajectories of fine motor and coordination skills and risk for schizophrenia.

Premorbid motor dysfunction is one of the earliest of developmental antecedents identified among individuals who develop schizophrenia in adulthood. However, among individuals with schizophrenia, premorbid motor dysfunction is not apparent at all stages of childhood development and may reduce with increasing age. Currently, little is known about the trajectories of motor development during adolescence among youth at-risk for the disorder.

Impaired processing of threat in psychopathy: A systematic review and meta-analysis of factorial data in male offender populations.

Background: Psychopathy is a personality disorder characterised by two underlying factors. Factor 1 (affective and interpersonal deficits) captures affective deficits, whilst Factor 2 (antisocial and impulsive/disorganised behaviours) captures life course persistent antisocial behaviours. Impaired processing of threat has been proposed as an aetiologically salient factor in the development of psychopathy, but the relationship of this impairment to the factorial structure of the disorder in adult male offenders is unclear.