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It has been recognised that throughout the UK, rural economies have a significant potential for growth but despite the potential for growth, many rural businesses face barriers that prohibit their expansion. In this study, we focus on one particular group of rural small- to medium-sized enterprises (SMEs): food and drink producers. Through user engagement activities, we identify the issues and needs associated with distributing products to the market, in order to understand the main issues which prevent rural food and drink SMEs from expansion, and to establish the requirements for a digital solution to this challenge.

OBJECTIVES: This paper aims to evaluate if any ultrasonographic aspect of metacarpo-phalangeal (MCP) joint can be predictors for the development of new joint damage, at single joint level, in rheumatoid arthritis (RA) patients. METHODS: Two hundred and forty MCP joints of 24 patients with RA were prospectively evaluated both clinically and by ultrasound (US) at time 0, at six months and 12 months, in order to collect the following variables: presence of synovial hypertrophy and power-Doppler (PD) vascularisation both graded on a semiquantitative (0-3) scale, and the number and dimension of bone erosions. X-ray examinations were carried out at time 0 and at 12 months and lesions were graded using the Sharp/van der Heijde (S/vdH) method at single joint level. Potential prognostic determinants for joint damage obtained at the first examination and during follow-up were entered in a conditional logistic regression analysis. RESULTS: Fifteen out of seventeen (88%) of the new eroded joints on x-rays examination had persistent PD vascularity and 14/17 (82%) had persistent synovial thickening (p=0.001 and p=0.02, vs. non-eroded joints, respectively). In multiple conditional logistic regression analysis, the most important factor associated with the development of radiological joint damage was the presence of a synovial PD score ≥2 on two or more US evaluations (OR 8.51 [95%CI 1.84-39.48] for Rx new erosions and OR 8.30 [95%CI 1.97-38.9] for increased S/vdH local joint score). Both baseline synovial score ≥2 and presence of Rx erosions were also significantly associated with the development of radiological joint damage. Two predictive models for x-ray erosions and total single joint level S/vdH damage score were constructed consisting of 2 baseline plus one longitudinal variable with a ROC AUC of 0.916 (95%CI 0.867-0.965) and 0.886 (95%CI 0.814-0.957). CONCLUSIONS: At the single joint level, the presence of US determined synovial thickness and PD signal at baseline and the persistent PD signal over time have relevant prognostic value for the development of articular damage in the same MCP joints of RA patients.

AIM: The aim of the study was to determine the doses of ropivacaine combined with mepivacaine for sciatic nerve blockade to enable the extension of analgesia without prolonged motor blockade, for the management of very painful operations in one-day surgery. METHODS: After obtaining approval by the ethics committee and written informed consent, we recruited 30 ASA I-III patients undergoing corrective orthopedic surgery of the forefoot in one-day surgery with sciatic nerve blockade. The patients were randomly divided into 3 groups: one control group, treated by 1.5% mepivacaine (300 mg), and two groups differentiated by the dose of 0.5% ropivacaine (25 and 40 mg) used in combination with 1.5% mepivacaine (225 mg). The offset data of the blockade were obtained by a self-assessment form filled in by the patients, and a direct check on discharge by a blinded observer. RESULTS: There was no significant difference in the duration of the blockade among the 3 groups; the extension of analgesia was significant (P

In recent years, classification of soft-tissue sarcomas (STS) has improved with cytogenetic analyses, but their clinical behavior is still not easily predictable. The aim of this study was to detect alterations in the urokinase-type plasminogen system, involved in tumor growth and invasion, by comparing mRNA levels of its components with those of paired normal tissues, and relating them with patient clinical course. Real-time PCR was performed on human STS cell lines and tissues from highly malignant STS, including leiomyosarcomas and malignant fibrous histiocytomas, to evaluate the expression of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1). Immunohistochemistry of gene products was also performed. Median mRNA values of all genes studied were higher in tumors than in paired normal tissues. In agreement with data on STS cell lines, significant upregulation for uPA and PAI-1 genes compared to reference values was seen. Moreover, different levels of expression were related to histotype and metastatic phenotype. There was accordance between uPA mRNA and protein expression, while immunodetection of PAI-1 product was weak and scattered. In recent years, classification of soft-tissue sarcomas (STS) has improved with cytogenetic analyses, but their clinical behavior is still not easily predictable. The aim of this study was to detect alterations in the urokinase-type plasminogen system, involved in tumor growth and invasion, by comparing mRNA levels of its components with those of paired normal tissues, and relating them with patient clinical course. Real-time PCR was performed on human STS cell lines and tissues from highly malignant STS, including leiomyosarcomas and malignant fibrous histiocytomas, to evaluate the expression of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1). Immunohistochemistry of gene products was also performed. Median mRNA values of all genes studied were higher in tumors than in paired normal tissues. In agreement with data on STS cell lines, significant upregulation for uPA and PAI-1 genes compared to reference values was seen. Moreover, different levels of expression were related to histotype and metastatic phenotype. There was accordance between uPA mRNA and protein expression, while immunodetection of PAI-1 product was weak and scattered.

OBJECTIVES: To investigate serum levels of IL- 6 and soluble IL-6 receptor (sIL-6R) in patients with large-vessel vasculitis and their relationship with disease activity. METHODS: Sera were obtained from 33 Takayasu's arteritis (TAK) patients and 14 giant cell arteritis (GCA) patients, and from 60 age-matched normal controls (NCs). Disease activity was assessed using 18F-FDG PET/CT and clinical indices including NIH/Kerr criteria and ITAS. Among TAK patients with active disease at baseline, clinical records and serum samples from 11 TAK patients were available for the longitudinal study. IL-6 and sIL-6R serum levels were evaluated using commercial ELISA kits. RESULTS: IL-6 and sIL-6R serum levels were significantly higher in both GCA and TAK patients compared to NCs. IL-6 levels in TAK patients were significantly increased irrespective of disease phase, while a significant increase in sIL-6R concentrations was only found in TAK patients with active disease. Conversely, in GCA, IL-6 levels were significantly raised only in patients with active diseases, whereas sIL-6R levels appeared to be significantly higher irrespective of disease activity. Longitudinal analysis showed that levels of sIL-6R in TAK patients were significantly higher only at baseline, compared to NCs, whereas IL-6 levels were found to be significantly increased at each follow-up time point. CONCLUSIONS: These overall results might suggest a role for sIL-6R as a potential biomarker for disease activity in TAK patients, whereas in GCA, modifications of IL-6 might better identify patients with active disease.

Objective. To investigate serum levels of a panel of angiogenic inducers (VEGF, FGF-2, Angiopoietin 1, -2, soluble VCAM-1) and inhibitors (angiostatin, endostatin, pentraxin-3) in patients with giant cell arteritis (GCA) and Takayasu’s arteritis (TAK), in order to gain further insights into the molecular mechanisms driving angiogenesis dysregulation in large-vessel vasculitis (LVV). Methods. Sera were obtained from 33 TAK patients and 14 GCA patients and from two groups of age-matched normal controls (NC). Disease activity was assessed using 18F-FDG PET/CT and clinical indices including NIH/ Kerr criteria and ITAS. Angiogenic and anti-angiogenic factor serum levels were evaluated using commercial ELISA kits. Pentraxin 3 (PTX3) serum levels were evaluated by non-commercial ELISA, as already described. Results. Among the angiogenic factors, only VEGF serum levels were significantly higher in TAK patients compared to NC. No difference was found between angiogenic factor levels in GCA patients compared to those detected in NC. Anti-angiogenic factor (Angiostatin, Endostatin, PTX3) serum levels were significantly higher in both GCA and TAK patients compared to NC. Significant associations were observed between VEGF and PTX3 levels and disease activity evaluated using PET scan and clinical indices. Cluster analysis based on PET scan scores in TAK patients showed significant ordered differences in VEGF and angiostatin serum levels. Indeed, we noted a progressive increase of VEGF and angiostatin from NC to the cluster including patients with the highest and more diffuse scan positivity. Conclusion. Our overall results demonstrate a circulating molecular profile characterised by a prevailing expression of anti-angiogenic soluble factors.

Purpose: To evaluate serum levels of visfatin, resistin and adiponectin in patients with erosive (E) and non-erosive (NE) osteoarthritis (OA) of the hand (HOA) compared to normal controls (NC). Methods: 94 outpatients with E HOA and NE HOA and 21 NC were enrolled. The radiological assessment of both hands was performed according to the Kellgren–Lawrence and Kallman score. Patients were divided into two subsets (lone HOA or generalized OA) based on clinically OA involvement of knee and hip. Serum visfatin, resistin and adiponectin levels were determined by ELISA assay. Results: Visfatin was significantly higher in E HOA patients in comparison to NC and NE HOA group. Resistin showed a significant increase in both E HOA and NE HOA groups versus NC, in particular in generalized OA. No significant differences among groups were found in adiponectin. The Kallman score was more severe in the two subsets of E HOA patients compared to NE HOA. Conclusions: This study showed increased levels of resistin in erosive and non-erosive HOA, and higher visfatin levels in E HOA in comparison to NE HOA. These data suggest the adipokines possible role in the pathogenesis of HOA and their potential usefulness as biomarkers of the disease.

Objectives To investigate the prevalence of REM sleep behavior disorder (RBD) in patients with inflammatory arthritis (IA) to ascertain if RBD could be an internal red flag signaling a fluctuating state of inflammation based on the theory of “protoconsciousness”. Materials & Methods One hundred and three patients with a confirmed diagnosis of IA were consecutively recruited. The patients underwent general (IA activity, functional status, laboratory tests) and neurological evaluations. A neurologist investigated RBD and REM sleep parasomnias in a semi‐structured interview. Sleep quality was assessed with the Pittsburgh Sleep Quality Index, while the risk of obstructive sleep apnea syndrome (OSAS) was evaluated with the Berlin questionnaire. Beck Depression Inventory II and State‐Trait Anxiety Inventory investigated depression and anxiety. Results Patients had a mean age of 53.7 ± 14.6 years, 65% were women; 57.3% were in a clinically active phase of IA. Two women fulfilled ICSD‐3 criteria for RBD appearing 11 years after and 20 years before IA onset respectively. 31 patients scored positive for nightmare disorder (ND), 8 for recurrent isolated sleep paralysis. 65 (63.1%) patients reported poor sleep quality and 25 (24.3%) resulted at high risk for OSAS. 32 (31.0%) patients scored positively for depression or anxiety. Conclusions The prevalence of RBD in patients with IA did not differ from that in the general population, whereas ND presented a 2‐fold increased prevalence. Whether RBD can be considered a red flag signaling an internal danger remains an open question, while ND may be a new player in this intriguing relation.

The correlation between solar radiation and sea surface temperature (SST) and growth was assessed along a latitudinal gradient. Extension rate and skeletal density were both correlated with calcification rate, indicating that calcium carbonate deposition was allocated evenly between skeletal density and linear extension. Unlike most studies on other tropical and temperate corals, in which calcification was positively correlated with solar radiation and SST, in the present study calcification was not correlated with solar radiation, whereas it was negatively correlated with SST. We hypothesize that photosynthesis of the symbiotic algae of Balanophyllia europaea is inhibited at high temperatures, consequently causing an inhibition of calcification. The regressions between calcification and SST predicted that the calcification of B. europaea would be depressed at 20.5–21.0uC mean annual SST. The scenarios of the Intergovernmental Panel on Climate Change conclude that by 2100, SST will exceed this physiological threshold for most of the populations considered in this study. This study comprises the first field investigation of the relationships between environmental parameters and calcification of a Mediterranean coral and highlights the risks of losing Mediterranean marine biodiversity over the course of future decades.

Objective To investigate the modulation of systemic levels of soluble interleukin-6 receptor (sIL-6R) and soluble gp130 (sgp130) in untreated and treated polymyalgia rheumatica (PMR) patients during a followup period of at least 24 months in order to evaluate the relationship of these molecules with clinical outcome and their feasibility to provide a prognostic tool in clinical practice. Methods We analyzed sIL-6R and sgp130 serum levels in 93 PMR patients, and 46 age-matched normal controls, at disease onset and at 1, 3, 6, 12, and 24 months of followup during corticosteroid therapy by enzyme-linked immunosorbent assay. Results No difference in sIL-6R and sgp130 levels was observed between PMR patients and normal controls at disease onset or during followup. A significant correlation was found between the number of relapses and sIL-6R concentrations at baseline and after 1, 3, and 12 months of therapy. No correlation was found between sgp130 levels and the number of relapses. Cox multivariate analysis indicated that the best model for predicting relapses was identified by sIL-6R levels and the hemoglobin value at baseline. We found that high sIL-6R levels combined with low hemoglobin values resulted in a 10.1-fold increased risk of relapse. Conclusion Our data support the identification of a potential prognostic marker of PMR outcome that might have important implications in clinical practice. Because targeting sIL-6R with blocking antibodies has proven useful in other rheumatic disorders, our results could suggest the opportunity to evaluate sIL-6R–blocking treatment in patients with PMR and elevated levels of sIL-6R at disease onset.