SPLENIC REPLENISHMENT OF SYNERGISTIC ABILITY TO BONE MARROW AND THYMIC CELLS OF NEONATALLY SPLENECTOMIZED CBA MICE

Bone marrow (B) and thymic (T) cells taken from adult mice that had been splenectomized within 24 hr of birth showed an inability to cooperate in the IgM response to sheep red blood cells. The defect in collaborative capacity was apparent in both sets of cells, but appeared to be more pronounced in the T cell population. Splenectomy performed at various neonatal intervals indicated that if removal of the spleen were delayed until 6 days after birth, B and T cells of the adult showed a 60% restoration in cooperation. Replenishment of the synergistic ability after neonatal splenectomy could be achieved by injecting spleen cells immediately after spleen removal or 2 months postsplenectomy

Experimental procedure for the characterization of radiation damage in macromolecular crystals

A novel automatic procedure to determine the sensitivity of macromolecular crystals to radiation damage is presented. The information extracted from this procedure can be directly used for optimal planning of data collection or/and beamline calibration

Identification of circulating microRNAs as diagnostic biomarkers for use in multiple myeloma

BACKGROUND: Multiple myeloma is a plasma cell disorder that is characterised by clonal proliferation of malignant plasma cells in the bone marrow, monoclonal paraprotein in the blood or urine and associated organ dysfunction. It accounts for approximately 1% of cancers and 13% of haematological cancers. Myeloma arises from an asymptomatic proliferation of monoclonal plasma cells termed monoclonal gammopathy of undetermined significance (MGUS). METHODS: MicroRNA expression profiling of serum samples was performed on three patient groups as well as normal controls. Validation of the nine microRNAs detected as promising biomarkers was carried out using TaqMan quantitative RT-PCR. MicroRNA levels in serum were normalised using standard curves to determine the numbers of microRNAs per μl of serum. RESULTS: Three serum microRNAs, miR-720, miR-1308 and miRNA-1246, were found to have potential as diagnostic biomarkers in myeloma. Use of miR-720 and miR-1308 together provides a powerful diagnostic tool for distinguishing normal healthy controls, as well as patients with unrelated illnesses, from precancerous myeloma and myeloma patients. In addition, the combination of miR-1246 and miR-1308 can distinguish MGUS from myeloma patients. CONCLUSION: We have developed a biomarker signature using microRNAs extracted from serum which has potential as a diagnostic and prognostic tool for multiple myeloma

Identifying change processes in group-based health behaviour-change interventions: development of the mechanisms of action in group-based interventions (MAGI) framework

Group-based interventions are widely used to promote health-related behaviour change. While processes operating in groups have been extensively described, it remains unclear how behaviour change is generated in group-based health-related behaviour-change interventions. Understanding how such interventions facilitate change is important to guide intervention design and process evaluations. We employed a mixed-methods approach to identify, map and define change processes operating in group-based behaviour-change interventions. We reviewed multidisciplinary literature on group dynamics, taxonomies of change technique categories, and measures of group processes. Using weight-loss groups as an exemplar, we also reviewed qualitative studies of participants' experiences and coded transcripts of 38 group sessions from three weight-loss interventions. Finally, we consulted group participants, facilitators and researchers about our developing synthesis of findings. The resulting 'Mechanisms of Action in Group-based Interventions' (MAGI) framework comprises six overarching categories: (1) group intervention design features, (2) facilitation techniques, (3) group dynamic and development processes, (4) inter-personal change processes, (5) selective intra-personal change processes operating in groups, and (6) contextual influences. The framework provides theoretical explanations of how change occurs in group-based behaviour-change interventions and can be applied to optimise their design and delivery, and to guide evaluation, facilitator training and further research

Aged garlic has more potent antiglycation and antioxidant properties compared to fresh garlic extract in vitro

Protein glycation involves formation of early (Amadori) and late advanced glycation endproducts (AGEs) together with free radicals via autoxidation of glucose and Amadori products. Glycation and increased free radical activity underlie the pathogenesis of diabetic complications. This study investigated whether aged garlic has more potent antiglycation and antioxidant properties compared to fresh garlic extract in vitro in a cell-free system. Proteins were glycated by incubation with sugars (glucose, methylglyoxal or ribose) ±5–15 mg/mL of aged and fresh garlic extracts. Advanced glycation endproducts were measured using SDS-PAGE gels and by ELISA whereas Amadori products were assessed by the fructosamine method. Colorimetric methods were used to assess antioxidant activity, free radical scavenging capacity, protein-bound carbonyl groups, thiol groups and metal chelation activities in addition to phenolic, total flavonoid and flavonol content of aged and fresh garlic extracts. Aged garlic inhibited AGEs by 56.4% compared to 33.5% for an equivalent concentration of fresh garlic extract. Similarly, aged garlic had a higher total phenolic content (129 ± 1.8 mg/g) compared to fresh garlic extract (56 ± 1.2 mg/g). Aged garlic has more potent antiglycation and antioxidant properties compared to fresh garlic extract and is more suitable for use in future in vivo studies

A persistent neutrophil-associated immune signature characterizes post-COVID-19 pulmonary sequelae.

Interstitial lung disease and associated fibrosis occur in a proportion of individuals who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through unknown mechanisms. We studied individuals with severe coronavirus disease 2019 (COVID-19) after recovery from acute illness. Individuals with evidence of interstitial lung changes at 3 to 6 months after recovery had an up-regulated neutrophil-associated immune signature including increased chemokines, proteases, and markers of neutrophil extracellular traps that were detectable in the blood. Similar pathways were enriched in the upper airway with a concomitant increase in antiviral type I interferon signaling. Interaction analysis of the peripheral phosphoproteome identified enriched kinases critical for neutrophil inflammatory pathways. Evaluation of these individuals at 12 months after recovery indicated that a subset of the individuals had not yet achieved full normalization of radiological and functional changes. These data provide insight into mechanisms driving development of pulmonary sequelae during and after COVID-19 and provide a rational basis for development of targeted approaches to prevent long-term complications

Healthy Parent Carers: Acceptability and practicability of online delivery and learning through implementation by delivery partner organisations

This is the final version. Available on open access from Wiley via the DOI in this recordData availability statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.BACKGROUND: Parent carers of disabled children are at increased risk of physical and mental health problems. The Healthy Parent Carers (HPC) programme is a manualised peer-led group-based programme that aims to promote parent carer health and wellbeing. Previously, the programme had been delivered in person, with recruitment and delivery managed in a research context. This study explored implementation by two delivery partner organisations in the United Kingdom. Facilitator Training and Delivery Manuals were modified for online delivery using Zoom due to COVID-19. METHODS: The study methodology utilised the Replicating Effective Programs framework. A series of stakeholder workshops informed the development of the Implementation Logic Model and an Implementation Package. After delivering the programme, delivery partner organisations and facilitators participated in a workshop to discuss experiences of implementing the programme. A wider group of stakeholders, including commissioners, Parent Carer Forums and charity organisations representatives and researchers subsequently met to consider the sustainability and potential barriers to delivering the programme outside the research context. RESULTS: This study explored implementation by two delivery partner organisations in the United Kingdom that were able to recruit facilitators, who we trained, and they recruited participants and delivered the programme to parent carers in different localities using Zoom. The co-created Implementation Logic Model and Implementation Package were subsequently refined to enable the further roll-out of the programme with other delivery partner organisations. CONCLUSIONS: This study provides insight and understanding of how the HPC programme can be implemented sustainably outside of the research context. Further research will evaluate the effectiveness of the programme and refine the implementation processes. PATIENT AND PUBLIC CONTRIBUTION: Parent carers, delivery partner organisation staff and service commissioners were consulted on the design, delivery and reporting of the research.Economic and Social Research Council (ESRC)National Lottery Community Fund Coronavirus Support GrantNational Institute for Health and Care Research (NIHR