Leukocyte Counts During Digestion in Bottle-Fed Infants

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How to study basement membrane stiffness as a biophysical trigger in prostate cancer and other age-related pathologies or metabolic diseases

Here we describe a protocol that can be used to study the biophysical microenvironment related to increased thickness and stiffness of the basement membrane (BM) during age-related pathologies and metabolic disorders (e.g. cancer, diabetes, microvascular disease, retinopathy, nephropathy and neuropathy). The premise of the model is non-enzymatic crosslinking of reconstituted BM (rBM) matrix by treatment with glycolaldehyde (GLA) to promote advanced glycation endproduct (AGE) generation via the Maillard reaction. Examples of laboratory techniques that can be used to confirm AGE generation, non-enzymatic crosslinking and increased stiffness in GLA treated rBM are outlined. These include preparation of native rBM (treated with phosphate-buffered saline, PBS) and stiff rBM (treated with GLA) for determination of: its AGE content by photometric analysis and immunofluorescent microscopy, its non-enzymatic crosslinking by ((sodium dodecyl sulfate polyacrylamide gel electrophoresis)) (SDS PAGE) as well as confocal microscopy, and its increased stiffness using rheometry. The procedure described here can be used to increase the rigidity (elastic moduli, E) of rBM up to 3.2-fold, consistent with measurements made in healthy versus diseased human prostate tissue. To recreate the biophysical microenvironment associated with the aging and diseased prostate gland three prostate cell types were introduced on to native rBM and stiff rBM: RWPE-1, prostate epithelial cells (PECs) derived from a normal prostate gland; BPH-1, PECs derived from a prostate gland affected by benign prostatic hyperplasia (BPH); and PC3, metastatic cells derived from a secondary bone tumor originating from prostate cancer. Multiple parameters can be measured, including the size, shape and invasive characteristics of the 3D glandular acini formed by RWPE-1 and BPH-1 on native versus stiff rBM, and average cell length, migratory velocity and persistence of cell movement of 3D spheroids formed by PC3 cells under the same conditions. Cell signaling pathways and the subcellular localization of proteins can also be assessed

An Online Survey of the Dietary Practices of Saudi Students in the UK: A Quantitative Study

There has been an abundance of research on the dietary practices of international university students in the United Kingdom (UK), as they comprise a significant proportion of the country’s undergraduate population. However, there is a paucity in the literature with regard to the dietary practices, or other health behaviours, of Saudi students studying in the UK. Therefore, this empirical study sought to provide new insights to address this gap. This study contribution to investigate the dietary practices of Saudi students in the UK. The data was collected from a sample of 212 university students and encompassed an age range from 18 to 31+ years. A quantitative methodology was adopted in the form of an exploratory survey questionnaire. The sample was recruited through voluntary and snowball sampling techniques. Questionnaire data was analysed using Microsoft Excel and SPSS for Windows, version 26. The results demonstrated that various intrapersonal, interpersonal, and environmental factors play a significant role in developing eating behaviours and dietary choices. Some favourable changes in dietary practices were observed among Saudi students in the UK as opposed to Saudi Arabia, including a higher intake of fruit and vegetables, along with a lower intake of soft drinks, sugary and fatty foods. However, there was a notable reduction in consumption of all types of meat and fish as well as the total number of daily meals. Additionally, around a third of participants regularly consumed ready-to-eat food and takeaways 2-6 times a week. Interventions should therefore consider individual, societal and environmental factors

The COVID-19 pandemic and environmental health: Lessons learned

Environmental health is historically an overlooked and underrated discipline. The COVID-19 pandemic highlighted the value of environmental health and environmental health professionals (EHPs). EHPs have a unique set of skills and knowledge that were, or could have been, signifi cant in controlling the pandemic. This skill set includes a thorough understanding of legislation and regulations; the ability to conduct human health risk assessment and implement effective risk-control measures; enforcement, communication, and education skills; and a signifi cant understanding of their own local communities. The opportunities for applying the skills of EHPs vary across the world depending on several factors, including legislative and regulatory frameworks in each jurisdiction. Here we present our early evaluation of the unique skills and knowledge base of EHPs and lessons that can be learned from EHP engagement in public health protection. We also argue that local knowledge and engagement need to be recognized as valuable tools in emergency preparedness. In our increasingly globalized world, mechanisms to maintain and value local knowledge are needed, which could be achieved by embedding the “value of local” into policy to ensure that the importance and value of local knowledge are captured. We also advocate for raising awareness of the value of public health, and specifi cally, environmental health.info:eu-repo/semantics/publishedVersio

The Growing Block’s past problems

The Growing-Block view of time has some problems with the past. It is committed to the existence of the past, but needs to say something about the difference between the past and present. I argue that we should resist Correia and Rosenkranz’ (Oxford studies in metaphysics, vol 8, pp 333–350, 2013) response to Braddon-Mitchell’s (Analysis 64:199–203, 2004) argument that the Growing-Block leads to scepticism about whether we are present. I consider an approach, similar to Peter Forrest (Analysis 64:358–362, 2004), and show it is not so counter-intuitive as Braddon-Mitchell suggests and further show that it requires no ‘semantic and metaphysical gymnastics’, as Chris Heathwood (Analysis 65:249–251, 2005) has suggested. In doing these things I make the problem of the past on the Growing-Block view a problem in its history, not its present

EBV T-cell immunotherapy generated by peptide selection has enhanced effector functionality compared to LCL stimulation

Adoptive immunotherapy with Epstein–Barr virus (EBV)-specific T cells is an effective treatment for relapsed or refractory EBV-induced post-transplant lymphoproliferative disorders (PTLD) with overall survival rates of up to 69%. EBV-specific T cells have been conventionally made by repeated stimulation with EBV-transformed lymphoblastoid cell lines (LCL), which act as antigen-presenting cells. However, this process is expensive, takes many months, and has practical risks associated with live virus. We have developed a peptide-based, virus-free, serum-free closed system to manufacture a bank of virus-specific T cells (VST) for clinical use. We compared these with standard LCL-derived VST using comprehensive characterization and potency assays to determine differences that might influence clinical benefits. Multi-parameter flow cytometry revealed that peptide-derived VST had an expanded central memory population and less exhaustion marker expression than LCL-derived VST. A quantitative HLA-matched allogeneic cytotoxicity assay demonstrated similar specific killing of EBV-infected targets, though peptide-derived EBV T cells had a significantly higher expression of antiviral cytokines and degranulation markers after antigen recall. High-throughput T cell receptor-beta (TCRβ) sequencing demonstrated oligoclonal repertoires, with more matches to known EBV-binding complementary determining region 3 (CDR3) sequences in peptide-derived EBV T cells. Peptide-derived products showed broader and enhanced specificities to EBV nuclear antigens (EBNAs) in both CD8 and CD4 compartments, which may improve the targeting of highly expressed latency antigens in PTLD. Importantly, peptide-based isolation and expansion allows rapid manufacture and significantly increased product yield over conventional LCL-based approaches.</p

Multicentric Carpotarsal Osteolysis Is Caused by Mutations Clustering in the Amino-Terminal Transcriptional Activation Domain of MAFB

(The American Journal of Human Genetics, 90, 494–501; March 9, 2012)\ud In the published version of this article, the amino acid alteration caused by c.161C>T should have been notated as\ud p.Ser54Leu and not p.Pro54Leu. The wild-type amino acid is incorrectly notated in the main text, in Table 2, and in\ud Figure 4. The authors regret this error. Additionally, The Journal regrets that this erratum, originally requested in 2012,\ud was not published in a timely fashion

Significance testing testate amoeba water table reconstructions

Transfer functions are valuable tools in palaeoecology, but their output may not always be meaningful. A recently-developed statistical test ('randomTF') offers the potential to distinguish among reconstructions which are more likely to be useful, and those less so. We applied this test to a large number of reconstructions of peatland water table depth based on testate amoebae. Contrary to our expectations, a substantial majority (25 of 30) of these reconstructions gave non-significant results (P > 0.05). The underlying reasons for this outcome are unclear. We found no significant correlation between randomTF P-value and transfer function performance, the properties of the training set and reconstruction, or measures of transfer function fit. These results give cause for concern but we believe it would be extremely premature to discount the results of non-significant reconstructions. We stress the need for more critical assessment of transfer function output, replication of results and ecologically-informed interpretation of palaeoecological data

Improving the Quality of Dentistry (IQuaD):a cluster factorial randomised controlled trial comparing the effectiveness and cost-benefit of oral hygiene advice and/or periodontal instrumentation with routine care for the prevention and management of periodontal disease in dentate adults attending dental primary care

Acknowledgements The authors wish to thank Mark Forrest and the programming team at CHaRT; Cynthia Fraser, our information specialist, for assistance with referencing; Moira Swan, who was the dental research nurse and part of the OA team in Newcastle upon Tyne; Louise Campbell for secretarial support and data management; our original statistician in the group, Andy Elders; senior IT manager Gladys Macpherson; senior trial administrator at the TCOD Marilyn Laird; Luke Vale for his involvement with the design of the health economic analysis at the inception of the trial; Maria Dimitrova, who assisted the health economists in the collection of unit costs; staff of the Scottish Primary Care Research Network, who assisted with screening eligible patients at dental practices; staff of the North East Commissioning Support Unit who assisted with research payments to dental practices in the north-east; members of the TMC and Periodontal Advisory Group for their ongoing advice and support of the trial; the independent members of the TSC and DMC; and the staff at recruitment sites who facilitated recruitment, treatment and follow-up of trial participants. The Health Services Research Unit and the Health Economics Research Unit is core funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorate.Peer reviewedPublisher PD