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Aims: Incorrectly fitting footwear (IFF) poses a risk of trauma to at‐risk feet with diabetes. The aim of this systematic review was to summarise and assess the evidence that IFF is a statistically significant cause of ulceration. Methods: We searched PubMed, Scopus, Web of Science and Google Scholar for English‐language peer‐reviewed studies reporting the number or percentage of people with diabetes‐related foot ulceration (DFU) attributed to wearing IFF and included a physical examination of the footwear worn. Two independent reviewers assessed the risk of bias using the Newcastle–Ottawa scale. Results: 4318 results were retrieved excluding duplicates with 45 studies shortlisted. Ten studies met the inclusion criteria with most rated as fair (n = 6) or good (n = 3). There is some evidence that DFU is significantly associated with IFF, but this is limited: only 3 of 10 included studies found a statistically significant percentage of those with DFU were wearing IFF or inappropriate footwear which included fastening, material, type or fit (15.0%–93.3%). Risk of bias in these three studies ranged from 'fair' to 'poor'. IFF definitions were often unreported or heterogeneous. Only one study reported IFF‐related ulcer sites: 70% were at plantar hallux/toes and 10% at plantar metatarsal heads. Conclusions: There is some evidence that IFF is a cause of DFU, but further research is needed, which defines IFF, and methodically records footwear assessment, ulcer location and physical activity. Researchers need to uncover why IFF is worn and if this is due to economic factors, a need for footwear education or other reasons. [ABSTRACT FROM AUTHOR]

Background: Home foot temperature monitoring (HFTM) is recommended for those at moderate to high ulcer risk. Where a > 2.2°C difference in temperature between feet (hotspot) is detected, it is suggested that individuals (1) notify a healthcare professional (HCP); (2) reduce daily steps by 50%. We assess adherence to this and HFTM upon detecting a recurrent hotspot. Methods: PubMed and Google Scholar were searched until 9 June 2023 for English‐language peer‐reviewed HFTM studies which reported adherence to HFTM, daily step reduction or HCP hotspot notification. The search returned 1030 results excluding duplicates of which 28 were shortlisted and 11 included. Results: Typical adherence among HFTM study participants for >3 days per week was 61%–93% or >80% of study duration was 55.6%–83.1%. Monitoring foot temperatures >50% of the study duration was associated with decreased ulcer risk (Odds Ratio: 0.50, p < 0.001) in one study (n = 173), but no additional risk reduction was found for >80% adherence. Voluntary dropout was 5.2% (Smart mats); 8.1% (sock sensor) and 4.8%–35.8% (infrared thermometers). Only 16.9%–52.5% of participants notified an HCP upon hotspot detection. Objective evidence of adherence to 50% reduction in daily steps upon hotspot detection was limited to one study where the average step reduction was a pedometer‐measured 51.2%. Conclusions: Ulcer risk reduction through HFTM is poorly understood given only half of the participants notify HCPs of recurrent hotspots and the number of reducing daily steps is largely unknown. HFTM adherence and dropout are variable and more research is needed to determine factors affecting adherence and those likely to adhere. [ABSTRACT FROM AUTHOR]

Background: Identifying clusters of physical activity (PA) from accelerometer data is important to identify levels of sedentary behaviour and physical activity associated with risks of serious health conditions and time spent engaging in healthy PA. Unsupervised machine learning models can capture PA in everyday free-living activity without the need for labelled data. However, there is scant research addressing the selection of features from accelerometer data. The aim of this systematic review is to summarise feature selection techniques applied in studies concerned with unsupervised machine learning of accelerometer-based device obtained physical activity, and to identify commonly used features identified through these techniques. Feature selection methods can reduce the complexity and computational burden of these models by removing less important features and assist in understanding the relative importance of feature sets and individual features in clustering.Method: We conducted a systematic search of Pubmed, Medline, Google Scholar, Scopus, Arxiv and Web of Science databases to identify studies published before January 2021 which used feature selection methods to derive PA clusters using unsupervised machine learning models.Results: A total of 13 studies were eligible for inclusion within the review. The most popular feature selection techniques were Principal Component Analysis (PCA) and correlation-based methods, with k-means frequently used in clustering accelerometer data. Cluster quality evaluation methods were diverse, including both external (e.g. cluster purity) or internal evaluation measures (silhouette score most frequently). Only four of the 13 studies had more than 25 participants and only four studies included two or more datasets.Conclusion: There is a need to assess multiple feature selection methods upon large cohort data consisting of multiple (3 or more) PA datasets. The cut-off criteria e.g. number of components, pairwise correlation value, explained variance ratio for PCA, etc. should be expressly stated along with any hyperparameters used in clustering. [ABSTRACT FROM AUTHOR]

Background: Adequate footwear fit is critical in preventing diabetes-related foot ulcers. One important element is the toe gap, the difference between foot length and internal footwear length available to the foot. We summarised the literature on toe gaps in studies assessing footwear worn by people with diabetes, the methods used to measure both foot length and internal footwear length and identify ambiguities which may impact on toe gap assessment in clinical practice, and suggest pragmatic solutions. Methods: The Google Scholar database was searched to April 2020 for peer-reviewed studies using keywords related to incorrectly fitting or ill-fitting and diabetes, foot and ulcer which returned 979 results. Included studies within this narrative review encompassed toe gap measurement to assess footwear worn by people with diabetes. Results: A total of eight studies were included after full paper review. Toe gap ranges as used in assessments of footwear worn by people with diabetes vary, with a minimum of 1.0–1.6 cm and a maximum of 1.5–2.0 cm, as do methods of measuring internal footwear length. Only three published studies suggested possible measuring devices. Conclusions: Toe gap ranged as used when assessing footwear fit in people with diabetes vary and a gold standard device for internal footwear length measurement has yet to emerge. International guidelines provide welcome standardisation, but further research is needed to evaluate both the effect of toe gap ranges upon pressure, plantar stress response and ulceration and available measuring devices to facilitate development of toe gap measurement protocols that may further enhance consistency in practical assessments. [ABSTRACT FROM AUTHOR]

Aims: Incorrectly fitting shoes are implicated in callus formation and a significant proportion of diabetic foot ulcers, yet remain surprisingly prevalent. We review the current shoe fit guidelines for consistency and discuss ways in which technology may assist us in standardising methods of footwear assessment.Methods: Narrative review.Results: Incorrectly fitted shoes are implicated in the development of some diabetic foot ulcers yet surprisingly there's no consensus on shoe fit, despite substantial spending on prescription footwear. Suggested toe gaps vary from 6 to 20 mm and measurement methods also vary from Brannock Devices and callipers to manual measurement.Conclusions: To prevent fit-related foot ulceration, we need to standardise our biomechanical definition of fit. Future research should (1) evaluate the potential use of 3D scanning technology to provide a standardised means of capturing foot morphology; (2) develop a working biomechanical definition of fit, including toe gap through the identification of key physiological markers that capture and predict dynamic foot shape changes during different physical activities and body weight loading conditions; and (3) determine whether changes in dynamic foot shape of those with diabetes differs from those without, impacting on their shoe fitting needs, potentially necessitating specialist footwear at an earlier stage to avoid ulceration. [ABSTRACT FROM AUTHOR]

Background: Evidence from epidemiological studies investigating associations between adherence to the Mediterranean diet and colorectal cancer is inconsistent. The aim of this study is to assess in the UK Women's Cohort Study whether adherence to the Mediterranean dietary pattern is associated with reduced incidence of cancers of the colon and rectum.Method: A total of 35 372 women were followed for a median of 17.4 years. A 10-component score indicating adherence to the Mediterranean diet was generated for each cohort participant, using a 217-item food frequency questionnaire. The Mediterranean diet score ranged from 0 for minimal adherence to 10 for maximal adherence. Cox proportional hazards regression was used to provide adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for colon and rectal cancer risk.Results: A total of 465 incident colorectal cancer cases were documented. In the multivariable adjusted model, the test for trend was positive (HR = 0.88, 95% CI: 0.78 to 0.99; Ptrend = 0.03) for a 2-point increment in the Mediterranean diet score. For rectal cancer, a 2-point increment in the Mediterranean diet score resulted in an HR (95% CI) of 0.69 (0.56 to 0.86), whereas a 62% linear reduced risk (HR 0.38; 95% CI: 0.20 to 0.74; Ptrend < 0.001) was observed for women within the highest vs the lowest category of the MD score. Estimates for an association with colon cancer were weak (Ptrend = 0.41).Conclusions: Findings suggest that women adhering to a Mediterranean dietary pattern may have a lower risk of colorectal cancer, especially rectal cancer. [ABSTRACT FROM AUTHOR]

Chronic immune mediated inflammation is characterized by continuous chemokine mediated recruitment and activation of pro-inflammatory cells, monocytes in particular. We believe that an evaluation of the recruitment profile of monocytes during healthy condition is essential for the understanding of cellular response in disease. For this, we have established normal reference values and 95% confidence intervals for receptor expression of 20 chemokine receptors on monocyte subsets; classical (CD14 + CD16 − ), non-classical (CD14 + CD16 + ) and HLA-DR hi monocytes from 20 healthy controls using flow cytometry. We demonstrate significant differences in the chemokine receptor expression profiles and high correlation between fraction of cells and level of expression. This is the first global approach to provide a platform for comparable evaluation of cell recruitment during normal and under inflammatory conditions. This will be useful when exploring chemokine–chemokine receptor interactions, inhibition of chemokine signaling and selective removal of migrating cells, which are new treatment strategies in immune mediated diseases. [ABSTRACT FROM AUTHOR]

Abstract: Cytokine profile assessment is important to characterize immune responses to pathogens. To identify optimal time points for determination of cytokine profiles, we diluted whole blood 1:10, to enable daily cytokine measurements during one week. Cultures for 10 blood donors were set up in the presence of phytohemagglutinin (PHA), cytomegalovirus (CMV) or Candida. Supernatant levels of interleukin-2 (IL-2), IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, interferon-γ (IFN-γ), granulocyte/macrophage colony-stimulating factor, and tumor necrosis factor-α (TNF-α), were determined by multiplex technique, and intracellular cytokine staining (ICS) was employed to detect IFN-γ, IL-2, IL-4 and IL-13 in CD3+ cells. The multiplex analysis detected representative cytokine profiles for the majority of the cytokines on day 7 by identifying peak levels or good correlation with peak levels, with the exception of IL-2 and TNF-α in PHA and CMV cultures and IL-10 in PHA cultures. For these cytokines an extracellular measurement on day 2–3 would be appropriate. The intracellular cytokines showed distinct kinetics for IFN-γ and IL-2, while IL-4 and IL-13 were not detected at all with ICS. In conclusion, the combination of whole blood cultures with multiplex analysis is a simple and powerful tool that can be used to identify detailed cytokine profiles of specific cell-mediated immune responses. [Copyright &y& Elsevier]

Introduction: In-shoe pressure thresholds play an increasingly important role in the prevention of diabetes-related foot ulceration (DFU). The evidence of their effectiveness, methodological consistency and scope for refinement are the subject of this review.Methods: 1107 records were identified (after duplicate removal) based on a search of five databases for studies which applied a specific in-shoe pressure threshold to reduce the risk of ulceration. 37 full text studies were assessed for eligibility of which 21 were included.Results: Five in-shoe pressure thresholds were identified, which are employed to reduce the risk of diabetes-related foot ulceration: a mean peak pressure threshold of 200 kPa used in conjunction with a 25% baseline reduction target; a sustained pressure threshold of 35 mm Hg, a threshold matrix based on risk, shoe size and foot region, and a 40-80% baseline pressure reduction target. The effectiveness of the latter two thresholds have not been assessed yet and the evidence for the effectiveness of the other in-shoe pressure thresholds is limited, based only on two RCTs and two cohort studies.Conclusions: The heterogeneity of current measures precludes meta-analysis and further research and methodological standardisation is required to facilitate ready comparison and the further development of these pressure thresholds. [ABSTRACT FROM AUTHOR]

Few methods for classifying physical activity from accelerometer data have been tested using an independent dataset for cross-validation, and even fewer using multiple independent datasets. The aim of this study was to evaluate whether unsupervised machine learning was a viable approach for the development of a reusable clustering model that was generalisable to independent datasets. We used two labelled adult laboratory datasets to generate a k-means clustering model. To assess its generalised application, we applied the stored clustering model to three independent labelled datasets: two laboratory and one free-living. Based on the development labelled data, the ten clusters were collapsed into four activity categories: sedentary, standing/mixed/slow ambulatory, brisk ambulatory, and running. The percentages of each activity type contained in these categories were 89%, 83%, 78%, and 96%, respectively. In the laboratory independent datasets, the consistency of activity types within the clusters dropped, but remained above 70% for the sedentary clusters, and 85% for the running and ambulatory clusters. Acceleration features were similar within each cluster across samples. The clusters created reflected activity types known to be associated with health and were reasonably robust when applied to diverse independent datasets. This suggests that an unsupervised approach is potentially useful for analysing free-living accelerometer data. [ABSTRACT FROM AUTHOR]

Abstract: Patients with the monogenic disease autoimmune polyendocrine syndrome type I (APSI) develop autoimmunity against multiple endocrine organs and suffer from chronic mucocutaneous candidiasis (CMC), a paradoxical complication with an unknown mechanism. We report here that saliva from APSI patients with CMC is defective in inhibiting growth of Candida albicans in vitro and show reduced levels of a salivary protein identified as cystatin SA1. In contrast, APSI patients without CMC express salivary cystatin SA1 and can inhibit C. albicans to the same extent as healthy controls. We evaluated the anti-fungal activity of cystatin SA1 and found that synthesized full length cystatin SA1 efficiently inhibits growth of C. albicans in vitro. Moreover, APSI patients exhibit salivary IgA autoantibodies recognizing myosin-9, a protein expressed in the salivary glands, thus linking autoimmunity to cystatin SA1 deficiency and CMC. This data suggests an autoimmune mechanism behind CMC in APSI and provides rationale for evaluating cystatin SA1 in antifungal therapy. [Copyright &y& Elsevier]

Background: Acute respiratory distress syndrome (ARDS) is a devastating disorder. Despite enormous efforts in clinical research, effective treatment options are lacking, and mortality rates remain unacceptably high. Objectives: A male patient with severe ARDS showed no clinical improvement with conventional therapies. Hence, an emergent experimental intervention was performed. Methods: We performed intratracheal administration of autologous peripheral blood-derived mononuclear cells (PBMCs) and erythropoietin (EPO). Results: We found that after 2 days of initial PBMC/EPO application, lung function improved and extracorporeal membrane oxygenation (ECMO) support was reduced. Bronchoscopy and serum inflammatory markers revealed reduced inflammation. Additionally, serum concentration of miR-449a, b, c and miR-34a, a transient upregulation of E-cadherin and associated chromatin marks in PBMCs indicated airway epithelial differentiation. Extracellular vesicles from PBMCs demonstrated anti-inflammatory capacity in a TNF-α-mediated nuclear factor-κB in vitro assay. Despite improving respiratory function, the patient died of multisystem organ failure on day 38 of ECMO treatment. Conclusions: This case report provides initial encouraging evidence to use locally instilled PBMC/EPO for treatment of severe refractory ARDS. The observed clinical improvement may partially be due to the anti-inflammatory effects of PBMC/EPO to promote tissue regeneration. Further studies are needed for more in-depth understanding of the underlying mechanisms of in vivo regeneration. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Leukapheresis removes circulating leukocytes en route to the target organ. Hitherto unspecific matrixes have been used to remove leukocytes in inflammatory bowel disease (IBD). This report describes a novel selective leukapheresis column based on chemokine–chemokine receptor interaction. We found an increased expression of the gut homing chemokine receptor CCR9 on CD14+ monocytes and on CD3+ T lymphocytes from IBD patients. Biologically active CCL25 was coupled to a Sepharose matrix and demonstrated to selectively remove CCR9-expressing cells leaving other cell populations largely unaffected. A patient with active ulcerative colitis, was subjected to CCL25-column leukapheresis. Four days after treatment, he experienced clinical improvement and stable disease improvement ensued. The study illustrates that specific cells can be targeted using high affinity interactions, i.e., CCL25–CCR9 interactions to remove pathogenic gut-homing cells. Leukapheresis using the bCCL25 column should be investigated in a clinical phase I trial of patients with inflammatory bowel disease. [Copyright &y& Elsevier]

An abstract of the article "Autoimmunity and cystatin SA 1 deficiency behind chronic mucocutaneous candidiasis in autoimmune polyendocrine syndrome," by Emma Lindh and colleagues is presented.