Creatine kinase B controls futile creatine cycling in thermogenic fat.

Obesity increases the risk of mortality because of metabolic sequelae such as type 2 diabetes and cardiovascular disease1. Thermogenesis by adipocytes can counteract obesity and metabolic diseases2,3. In thermogenic fat, creatine liberates a molar excess of mitochondrial ADP-purportedly via a phosphorylation cycle4-to drive thermogenic respiration. However, the proteins that control this futile creatine cycle are unknown. Here we show that creatine kinase B (CKB) is indispensable for thermogenesis resulting from the futile creatine cycle, during which it traffics to mitochondria using an internal mitochondrial targeting sequence. CKB is powerfully induced by thermogenic stimuli in both mouse and human adipocytes. Adipocyte-selective inactivation of Ckb in mice diminishes thermogenic capacity, increases predisposition to obesity, and disrupts glucose homeostasis. CKB is therefore a key effector of the futile creatine cycle.

Multicenter Comparison of the Safety and Efficacy of Clopidogrel Versus Ticagrelor for Neuroendovascular Stents.

BACKGROUND: Dual antiplatelet therapy (DAPT) is commonly employed for neuroendovascular stenting due to the significant risk of thromboembolism. Clopidogrel and aspirin are most often selected as initial DAPTs; however, there is limited literature available to support guidance of DAPT in this setting. The objective of this study was to evaluate safety and efficacy in patients whose final regimen included either DAPT with aspirin and clopidogrel (DAPT-C) or DAPT with aspirin and ticagrelor (DAPT-T). METHODS: This was a multicenter, retrospective cohort of patients who underwent neuroendovascular stenting and received DAPT between July 1, 2017, and October 31, 2020. Study participants were allocated into groups based on discharge DAPT regimen. The primary outcome was incidence of stent thrombosis at 3-6 months on DAPT-C versus DAPT-T, as defined by the presence of thrombus on imaging or new onset stroke. Secondary outcomes included major and minor bleeding and death within 3-6 months after the procedure. RESULTS: Five hundred and seventy patients were screened across 12 sites. Of those, 486 were included (DAPT-C n = 360, DAPT-T n = 126). There was no difference in the primary outcome of stent thrombosis between the DAPT-C and DAPT-T groups (8% vs. 8%, p = 0.97) and no difference in any of the secondary safety outcomes. CONCLUSIONS: Using DAPT-C or DAPT-T regimens in a broad population of neuroendovascular stenting procedures appears to have similar safety and efficacy profiles. Further prospective evaluation is warranted to streamline the practice of DAPT selection and monitoring to determine the impact on clinical outcomes.

Locating the ventral intermediate thalamic nucleus for deep brain stimulation surgery: analysis of a case series comparing CT and MR targeting.

BACKGROUND: Deep brain stimulation (DBS) surgery targeting the ventral intermediate thalamic nucleus (Vim) has proven efficacy in the treatment of tremor. AIMS: The primary aim is to investigate whether there is a statistically significant difference in patient outcomes when CT-guided targeting of the Vim is compared with MRI-guided targeting. METHODS: This is a retrospective study concerning patients undergoing Vim-targeted DBS at the Department of Neurosurgery, Royal Victoria Infirmary in Newcastle (9th August 2012 to 4th January 2019). Fahn-Tolosa-Marin Tremor Scale (FTM TS) and EQ-5D scores were collected from patient notes. Statistical analysis was performed using IBM® SPSS® Statistics Version 24. Independent samples t-tests were used to compare means. RESULTS: Independent samples t-test did not reveal a statistically significant difference between CT (n = 10; FTM TS mean = 65.40, SD = 11.40; EQ-5D mean = 39.50, SD = 17.87) and MR (n = 7; FTM TS mean = 60.57, SD = 7.50; EQ-5D mean = 32.14, SD = 9.94) groups in pre-surgery FTM TS (t(15) = 0.977, p = 0.344) and EQ-5D (t(15) = 0.982, p = 0.342) scores. No statistically significant difference between the CT (FTM TS mean = 24.12, SD = 20.47; EQ-5D mean = 75.56, SD = 15.63) and MR (FTM TS mean = 22.86, SD = 6.72; EQ-5D mean = 70.43, SD = 15.48) groups was revealed at 1 year assessment of FTM TS (t(14) = 0.155, p = 0.879) and EQ-5D (t(14) = 0.654, p = 0.524). The median difference between pre- and post-surgery FTM TS and EQ-5D scores in the CT group at 1 year was 43.00 and 35.00, respectively. The MR patient group median difference in pre- and post-surgery at 1 year was 35.00 and 35.00 respectively. CONCLUSION: No statistically significant difference between CT and MR image-guided targeting patient groups was detected.

ß1-Integrin-Mediated Uptake of Chondrocyte Extracellular Vesicles Regulates Chondrocyte Homeostasis.

Osteoarthritis (OA) is the most prevalent age-related degenerative disorder, which severely reduces the quality of life of those affected. Whilst management strategies exist, no cures are currently available. Virtually all joint resident cells generate extracellular vesicles (EVs), and alterations in chondrocyte EVs during OA have previously been reported. Herein, we investigated factors influencing chondrocyte EV release and the functional role that these EVs exhibit. Both 2D and 3D models of culturing C28I/2 chondrocytes were used for generating chondrocyte EVs. We assessed the effect of these EVs on chondrogenic gene expression as well as their uptake by chondrocytes. Collectively, the data demonstrated that chondrocyte EVs are sequestered within the cartilage ECM and that a bi-directional relationship exists between chondrocyte EV release and changes in chondrogenic differentiation. Finally, we demonstrated that the uptake of chondrocyte EVs is at least partially dependent on ß1-integrin. These results indicate that chondrocyte EVs have an autocrine homeostatic role that maintains chondrocyte phenotype. How this role is perturbed under OA conditions remains the subject of future work.

In-House Intraoperative Monitoring in Neurosurgery in England - Benefits and Challenges.

BACKGROUND: Intraoperative neurophysiological monitoring (IOM) is a valuable adjunct for neurosurgical operative techniques, and has been shown to improve clinical outcomes in cranial and spinal surgery. It is not necessarily provided by NHS hospitals so may be outsourced to private companies, which are expensive and at cost to the NHS trusts. We discuss the benefits and challenges of developing an in-house service. METHODS: We surveyed NHS neurosurgical departments across England regarding their expenditure on IOM over the period January 2018 - December 2022 on cranial neurosurgery and spinal surgery. Out of 24 units, all responded to our Freedom of Information requests and 21 provided data. The standard NHS England salary of NHS staff who would normally be involved in IOM, including physiologists and doctors, was also compiled for comparison. RESULTS: The total spend on outsourced IOM, across the units who responded, was over £8 million in total for the four years. The annual total increased, between 2018 and 2022, from £1.1 to £3.5 million. The highest single unit yearly spend was £568,462. This is in addition to salaries for staff in neurophysiology departments. The mean NHS salaries for staff is also presented. CONCLUSION: IOM is valuable in surgical decision-making, planning, and technique, having been shown to lead to fewer patient complications and shorter length of stay. Current demand for IOM outstrips the internal NHS provision in many trusts across England, leading to outsourcing to private companies. This is at significant cost to the NHS. Although there is a learning curve, there are many benefits to in-house provision, such as stable working relationships, consistent methods, training of the future IOM workforce, and reduced long-term costs, which planned expansion of NHS services may provide.

Galectin-9 mediates neutrophil capture and adhesion in a CD44 and ß2 integrin-dependent manner.

Neutrophil trafficking is a key component of the inflammatory response. Here, we have investigated the role of the immunomodulatory lectin Galectin-9 (Gal-9) on neutrophil recruitment. Our data indicate that Gal-9 is upregulated in the inflamed vasculature of RA synovial biopsies and report the release of Gal-9 into the extracellular environment following endothelial cell activation. siRNA knockdown of endothelial Gal-9 resulted in reduced neutrophil adhesion and neutrophil recruitment was significantly reduced in Gal-9 knockout mice in a model of zymosan-induced peritonitis. We also provide evidence for Gal-9 binding sites on human neutrophils; Gal-9 binding induced neutrophil activation (increased expression of ß2 integrins and reduced expression of CD62L). Intra-vital microscopy confirmed a pro-recruitment role for Gal-9, with increased numbers of transmigrated neutrophils following Gal-9 administration. We studied the role of both soluble and immobilized Gal-9 on human neutrophil recruitment. Soluble Gal-9 significantly strengthened the interaction between neutrophils and the endothelium and inhibited neutrophil crawling on ICAM-1. When immobilized, Gal-9 functioned as an adhesion molecule and captured neutrophils from the flow. Neutrophils adherent to Gal-9 exhibited a spread/activated phenotype that was inhibited by CD18 and CD44 neutralizing antibodies, suggesting a role for these molecules in the pro-adhesive effects of Gal-9. Our data indicate that Gal-9 is expressed and released by the activated endothelium and functions both in soluble form and when immobilized as a neutrophil adhesion molecule. This study paves the way for further investigation of the role of Gal-9 in leukocyte recruitment in different inflammatory settings.

A systematic review and meta-analysis of hernia sac management in laparoscopic groin hernia mesh repair: reduction or transection?

BACKGROUND: There is no consensus regarding hernia sac management during laparoscopic hernia repair, and this systematic review and meta-analysis aimed to compare the postoperative outcomes of sac reduction (RS) and sac transection (TS) during laparoscopic mesh hernia repair. METHODS: We conducted a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) 2020 and AMSTAR 2 (Assessing the Methodological Quality of Systematic Reviews) guidelines. We used the RevMan 5.4 statistical package from the Cochrane collaboration for meta-analysis. A random effects model was used. RESULTS: The literature search yielded six eligible studies including 2941 patients: 821 patients in the TS group and 2120 patients in the RS group. In the pooled analysis, the TS group was associated with a lower incidence of seroma (OR = 1.71; 95% CI [1.22, 2.39], p = 0.002) and shorter hospital stay (MD = -0.07; 95% CI [-0.12, -0.02], p = 0.008). There was no significant difference between the two groups in terms of morbidity (OR = 0.87; 95% CI [0.34, 2.19], p = 0.76), operative time (MD = -4.39; 95% CI [-13.62, 4.84], p = 0.35), recurrence (OR = 2.70; 95% CI [0.50, 14.50], p = 0.25), and Postoperative pain. CONCLUSIONS: This meta-analysis showed that hernia sac transection is associated with a lower seroma rate and shorter hospital stay with similar morbidity, operative time, recurrence, and postoperative pain compared to the reduction of the hernia sac. PROTOCOL: The protocol was registered in PROSPERO with ID CRD42023391730.

Patient selection and outcome of deep brain stimulation for multiple sclerosis-associated tremor.

INTRODUCTION: Tremor is a disabling symptom of multiple sclerosis (MS), with limited treatment modalities. Thalamic ventral-intermediate-nucleus (VIM) deep brain stimulation (DBS) is a method of neuromodulation. We describe the long-term outcomes of our carefully selected patients who underwent VIM DBS for their MS-associated tremor. METHODS: Patients were referred from the regional neurology units. Pre-operative assessments included suitability for anesthesia, tremor quantification by the Fahn-Tolosa-Marin scores, and quality-of-life (EQ5D) measures. Exclusion criteria included prominent cerebellar symptoms such as ataxia and dysmetria, intracranial pathology such as ventriculomegaly, cerebellar plaques and thalamic abnormality, and comorbid psychiatric symptoms. Seven patients (3M:4F) underwent DBS for MS-associated tremor between September 2013 and February 2019. Mean age was 42 years (±SD 8 years). DBS was performed at a mean of 13 years (±SD 9 years) after diagnosis of MS. RESULTS: There were no postoperative surgical complications. All patients showed improvement in FTM tremor scores, by up to 61% at 6 months postoperatively. There was an improvement of 30-175% in quality-of-life scores at 6 months. Improvement of tremor and quality of life, over baseline, was sustained over a long period of follow-up (mean 26.6 months ± SD 20.7 months), including our longest duration at 72 months. CONCLUSION: With careful selection, DBS is a safe, efficacious intervention for MS-tremor and can positively impact on tremor and quality of life, with effects over a long period. As patients live longer with MS and the advent of new therapies, DBS should be considered for selected patients.

Identifying Best Practices to Improve Evaluation and Management of In-Hospital Stroke: A Scientific Statement From the American Heart Association.

This scientific statement describes a path to optimizing care for patients who experience an in-hospital stroke. Although these patients are in a monitored environment, their evaluation and treatment are often delayed compared with patients presenting to the emergency department, contributing to higher rates of morbidity and mortality. Reducing delays and optimizing treatment for patients with in-hospital stroke could improve outcomes. This scientific statement calls for the development of hospital systems of care and targeted quality improvement for in-hospital stroke. We propose 5 core elements to optimize in-hospital stroke care: 1. Deliver stroke training to all hospital staff, including how to activate in-hospital stroke alerts. 2. Create rapid response teams with dedicated stroke training and immediate access to neurological expertise. 3. Standardize the evaluation of patients with potential in-hospital stroke with physical assessment and imaging. 4. Address barriers to treatment potentially, including interfacility transfer to advanced stroke treatment. 5. Establish an in-hospital stroke quality oversight program delivering data-driven performance feedback and driving targeted quality improvement efforts. Additional research is needed to better understand how to reduce the incidence, morbidity, and mortality of in-hospital stroke.

Incidence of synchronous contralateral tonsillar malignancy in a known case of unilateral tonsillar carcinoma.

OBJECTIVE: The literature is divided with regards to contralateral tonsillectomy in a known/suspected case of ipsilateral tonsillar malignancy. In this study, we evaluate the incidence of indolent synchronous contralateral tonsillar malignancy (SCTC) in patients with known ipsilateral tonsillar malignancy. METHODS: All patients diagnosed with ipsilateral tonsillar carcinoma (TC) at a tertiary teaching center between January 2016 and December 2019 were screened. None of the patients were suspected to have bilateral TC. All patients underwent appropriate imaging in the form of Magnetic resonance imaging and computed tomography of head and neck region and then underwent bilateral tonsillectomy. The prevalence of bilateral tonsillar malignancy and the factors predicting them were analyzed. RESULTS: In all 59 patients were included in the study. The mean and median age of the patient population was 60.8 and 59 years, respectively, with a male to female ratio of 3.2:1. The incidence of bilateral tonsillar malignancy in carcinoma of unknown primary (CUP) was 3/10 (33.3%). Among the remaining 49 patients, incidence of synchronous contralateral tonsillar carcinoma (SCTC) was 2/49 (4.08%). Overall, 5/59 (8.5%) patients had synchronous bilateral tonsillar malignancy. Furthermore, dysplasia was found in the contralateral tonsil in 4/10 (40%) CUP patients. Among the remaining 49 patients, dysplasia was seen in the contralateral tonsil in 20/49 (40.8%) patients. The absence of p16 expression predicted higher probability of SCTC. Factors like gender, T stage, nodal status or smoking did not predict SCTC. CONCLUSION: We recommend bilateral tonsillectomy in all patients with suspected or proven TC (unilateral or bilateral) and CUP as it helps identify indolent SCTC and it does not add any significant morbidity to the patients. LEVEL OF EVIDENCE: III.

Delays in surgery for cholesteatoma due to COVID-19: is there an impact on rates of recidivism and major complications?

PURPOSE: To evaluate the relationship between the waiting time for surgery, and cholesteatoma recidivism rates and major complications. The secondary aims were to identify any other prognostic factors for cholesteatoma recidivism. METHODS: A retrospective single-centre study of 312 patients who underwent cholesteatoma surgery under the care of a single-surgeon, between 2004 and 2018, was performed. Waiting times for surgery were categorised into ≤ 90 days, 91-180 days, 181-270 days and > 271 days. The outcome measures were cholesteatoma recidivism and major complications (facial nerve palsy or intracranial complications). RESULTS: The mean age was 36.1 years ± 21.5 with 242 adults (77.6%) and 70 children (22.4%). The mean waiting time for surgery was 126.2 days (4.1 months) ± 96.0 days and the overall rate of recidivism was 11.2% (35/312 patients). No instances of facial nerve palsy or intracranial complications were identified. Rates of recidivism by waiting time for surgery were: 15.3% for 118 patients who waited ≤ 90 days, 9.7% for 134 patients who waited 91-180 days, 6.7% for 30 patients who waited 181-270 days and 4.3% for 23 patients who waited > 271 days. There was no significant difference amongst the different waiting time groups for rates of recidivism (p = 0.266). CONCLUSION: Increased waiting times for cholesteatoma surgery do not appear to be associated with increased rates of recidivism or major complications. Clinical judgement will always be required for complicated disease or patients with additional risk factors. The other prognostic factors for recidivism identified in this study were age (< 15 years) and congenital cholesteatoma.

Shunt disconnection is less likely using a surgeon's knot compared with a surgical constrictor knot.

INTRODUCTION: Ventriculo-peritoneal shunt malfunction is a common neurosurgical presentation, which may occur as a result of shunt disconnection at the level of the valve. Previous studies assessing ligatures have suggested that the constrictor knot is stronger in securing a ligature compared to the surgeon's knot. Our study compared the ability of each knot to secure shunt tubing to the valve. METHODS: A medtronic shunt valve was secured to a peritoneal catheter using the surgeon's knot versus constrictor's knot. The weight and subsequent force (N) required to pull off the shunt tubing at the knot site were recorded. RESULTS: The mean pull-off force was 11.7 N for the surgeon knot, and 8.9 N for the constrictor knot. There was significant difference in favour for the surgeon's knot compared to the constrictor knot. CONCLUSIONS: The surgeon's knot is significantly stronger than the constrictor knot for securing a peritoneal catheter to a CSF shunt valve.

Pemphigus Vulgaris and Bullous Pemphigoid of the Upper Aerodigestive Tract: A Review Article and Novel Approaches to Management.

BACKGROUND: Autoimmune bullous diseases are rare conditions characterized by blistering of the skin and mucous membranes. The 2 commonest forms are pemphigus vulgaris and bullous pemphigoid. The oral cavity or oropharynx may be the initial site of presentation or often the only site involved. SUMMARY: These conditions are often misdiagnosed or overlooked leading to poorer patient outcomes. Due to the chronic nature of these conditions and the systemic effects of treatment, there is a significant associated morbidity and mortality. As such, an understanding of the fundamentals of autoimmune bullous diseases is vital to those working in otolaryngology. The mainstay of management in both conditions is topical and systemic corticosteroids. There is also a role for immunomodulating and non-steroidal anti-inflammatory drugs as adjunct or alternative therapies. Surgical intervention may be required to protect the airway. Often multimodality treatment is required involving multidisciplinary input from otolaryngologists, oral surgeons, dermatologists, and rheumatologists. This review article will highlight the aetiology, pathology, clinical features, investigations, and management of both pemphigus vulgaris and bullous pemphigoid including recent advances in management.

A Case of Large Calcifying Fibroma of Tendo-achilles Managed by En-block Resection and Tendon Reconstruction.

Calcifying aponeurotic fibroma is a rare benign fibrous tumor with typical radiological and histopathological features seen in young children and adolescents. It commonly involves the extremities and is characterized by a very high chance of local recurrence. A complete excision of the tumor is considered to be the treatment of choice. We report a case of the tumor involving the substance of achilles tendon and extending up till its insertion in the calcaneum. To the best of our knowledge, this is the largest reported case of calcifying fibroma, with the tumor measuring 10 cm in its largest diameter. The tumor was excised in toto followed by reconstruction of the tendon defect with V-Y plasty of the native tendon and supplemented with semitendinosus and gracilis graft. There was no evidence of recurrence during the follow up period of 1 year.

Recombinant Human Adenovirus-p53 Therapy for the Treatment of Oral Leukoplakia and Oral Squamous Cell Carcinoma: A Systematic Review.

Background and Objectives: Oral cancer is the 6th most common cancer in the world and oral leukoplakia is an oral potentially malignant disorder that could develop into oral cancer. This systematic review focusses on randomized clinical trials for recombinant adenovirus p-53 (rAD-p53) therapy for the treatment of oral leukoplakia and cancer. Materials and Methods: We searched for research articles on various databases such as Pubmed/Medline, Embase, CNKI (China National Knowledge Infra-structure), Springerlink, cochrane and Web of sciences from 2003 to 2020. MeSH (Medical Subject Headings) terms were used for the search. Inclusion criteria included original research, randomized clinical trials and articles only in English language. Exclusion criteria were any articles that were not research articles, not randomized trials, non-human studies, etc. The articles were further graded on the Jadad scale. Results: 578 articles were assessed from various databases; only 3 articles were found to be appropriate for this review. Thus, meta-analysis was not performed because of heterogeneity and lack of data. In the three studies, whether rAD-p53 was used as a standalone therapy or with other therapies, there was a beneficial effect of the therapy. Furthermore, there were no serious adverse events and the only adverse events reported were fever, pain at the local injection site, flu-like symptoms and lowered WBC count. Conclusions: Thus, we can conclude that this therapy has a potential for beneficial therapeutic effects and further clinical trials with more patients need to be performed to get better understanding of the effect of rAD-p53 therapy, which probably will pave the way to its approval in other parts of the world.

Cannabinoid receptor 2 deficiency exacerbates inflammation and neutrophil recruitment.

Cannabinoid receptor (CB)2 is an immune cell-localized GPCR that has been hypothesized to regulate the magnitude of inflammatory responses. However, there is currently no consensus as to the mechanism by which CB2 mediates its anti-inflammatory effects in vivo. To address this question, we employed a murine dorsal air pouch model with wild-type and CB2-/- 8-12-wk-old female and male C57BL/6 mice and found that acute neutrophil and lymphocyte antigen 6 complex, locus Chi monocyte recruitment in response to Zymosan was significantly enhanced in CB2-/- mice. Additionally, levels of matrix metalloproteinase 9 and the chemokines C-C motif chemokine ligand (CCL)2, CCL4, and C-X-C motif chemokine ligand 10 in CB2-/- pouch exudates were elevated at earlier time points. Importantly, using mixed bone marrow chimeras, we revealed that the proinflammatory phenotype in CB2-/- mice is neutrophil-intrinsic rather than stromal cell-dependent. Indeed, neutrophils isolated from CB2-/- mice exhibited an enhanced migration-related transcriptional profile and increased adhesive phenotype, and treatment of human neutrophils with a CB2 agonist blocked their endothelial transmigration. Overall, we have demonstrated that CB2 plays a nonredundant role during acute neutrophil mobilization to sites of inflammation and, as such, it could represent a therapeutic target for the development of novel anti-inflammatory compounds to treat inflammatory human diseases.-Kapellos, T. S., Taylor, L., Feuerborn, A., Valaris, S., Hussain, M. T., Rainger, G. E., Greaves, D. R., Iqbal, A. J. Cannabinoid receptor 2 deficiency exacerbates inflammation and neutrophil recruitment.

A novel technique for complete laparoscopic excision of a transobturator sling with lower urinary tract mesh erosion.

INTRODUCTION AND HYPOTHESIS: To demonstrate a novel technique for complete laparoscopic removal of a transobturator sling for mesh erosion involving a large area of the urethra and bladder neck, without the need for concomitant vaginal dissection. METHOD: A 56-year-old woman had a transobturator sling inserted for stress urinary incontinence (SUI) in 2009. In 2017, 8 years following surgery, she experienced groin pain, exacerbated by exercise, and developed recurrent urinary tract infections with dysuria and urethral pain. A cystoscopy demonstrated mesh erosion from the midurethra to bladder neck with a 2-cm calculus formed around the mesh. After careful counselling and discussion at a multi-disciplinary meeting, a decision was made to proceed with laparoscopy with a view to remove the mesh completely. The mesh was removed from the points of erosion into the urethra through a total laparoscopic procedure. The patient made a good recovery with no ongoing pain or voiding difficulties. CONCLUSION: Combined approaches for complete excision of transobturator slings, including bilateral inguinal dissection, are relatively morbid with prolonged recovery time and in most centres will require involvement of plastic surgeons. The laparoscopic approach not only allows for the mesh to be removed in total (including the intramural portion of the mesh), but also provides magnified views compared with open surgery and thus allows for better identification of planes and dissection. It also has the added benefit of avoiding vaginal incisions and therefore reducing the risk of fistula formation between the urethra/bladder and vagina.

Participatory implementation research in the field of migrant health: Sustainable changes and ripple effects over time.

OBJECTIVE: This study aimed to explore whether positive impacts were sustained and unanticipated ripple effects had occurred four years after the implementation of interventions to improve cross-cultural communication in primary care. BACKGROUND: Sustaining the implementation of change using complex interventions is challenging. The EU-funded "RESTORE" study implemented guidelines and training on cross-cultural communication in five Primary Care sites in Europe, combining implementation theory (Normalisation Process Theory) with participatory methodology (participatory learning and action-PLA). There were positive impacts on knowledge, skills and clinical routines. DESIGN, SETTING AND PARTICIPANTS: Four of the five original sites (England, Ireland, Greece, The Netherlands) were available for this qualitative follow-up study. The study population (N = 44) was primary healthcare staff and migrants, most of whom had participated in RESTORE. INTERVENTION; MAIN OUTCOME MEASURES: PLA-style focus groups and interviews explored routine practice during consultations with migrants. Etic cards based on the effects of RESTORE stimulated the discussion. Deductive framework analysis was performed in each country followed by comparative data analysis and synthesis. RESULTS: Changes in knowledge, attitudes and behaviour with regard to consultations with migrants were sustained and migrants felt empowered by their participation in RESTORE. There were ongoing concerns about macro level factors, like the political climate and financial policies, negatively affecting migrant healthcare. CONCLUSION: There were sustained effects in clinical settings, and additional unanticipated positive ripple effects, due in part, from the participatory approach employed.

Trace metals in different socioeconomic indoor residential settings, implications for human health via dust exposure.

In this study a number of heavy metals namely chromium (Cr), cadmium (Cd), zinc (Zn), barium (Ba), copper (Cu), manganese (Mn), cobalt (Co), rubidium (Rb), selenium (Se) are studied in the floor and air condition (AC) filter dust collected from urban and rural households of Saudi Arabia. To the best of our knowledge, many of these heavy metals are reported for the very first time in the indoor dust of Saudi Arabia. Studied metals were higher in urban dust than rural except Mn and Rb which were significantly higher (P < 0.05) in rural dust. All metals, except Cd, Zn, and Ba in urban settings, were detected at higher (P < 0.05) levels in AC filter dust than household floor dust from both rural and urban residential settings. Levels of the two dominant metals i.e., Zn and Mn were up to 1600 and 700 µg/g, respectively in studied dust samples. Also associations between heavy metals and a number of different socio-economic parameters were studied which was significant for some trace metals. In literature exposure to many of trace metals are associated with various health problems, therefore health risk assessment for the Saudi population was calculated by incremental lifetime cancer risk (ILCR) and hazardous index (HI) via dust ingestion, inhalation, and dermal contact. The ILCR for all metals was within the tolerable range of reference values of USEPA (1 × 10- 11 to 1 × 10- 4). However, calculated HI for Mn, Cu, Ni, and Zn was more than 1 via dust exposure, which signifies the non-carcinogenic risk. The study highlights the occurrence of toxic metals in the indoor environments of Saudi Arabia and provides baseline data for future studies on these toxic metals in the region.

The Role and Impact of Extracellular Vesicles in the Modulation and Delivery of Cytokines during Autoimmunity.

Cytokines and extracellular vesicles are two methods of initiating and maintaining cellular crosstalk. The role of cytokines in the initiation, progression, and resolution of inflammation has been well studied and more so, their pathophysiological role in the development of autoimmune disease. In recent years, the impact of extracellular vesicles on the progression of autoimmunity has become more widely appreciated. In this review, we discuss the mechanisms that allow extracellular vesicles of various sources to modulate cytokine production, and release, and how extracellular vesicles might be involved in the direct delivery and modulation of cytokine levels. Moreover, we explore what challenges are faced by current therapies and the promising future for extracellular vesicles as therapeutic agents in conditions driven by immune dysregulation.