Peri-operative care of elective adult surgical patients with a learning disability.

People with a learning disability can experience significant problems in accessing healthcare and this may be partly reflected in worse health outcomes compared with the general population, including a shorter life expectancy. The Equality Act (2010) requires that organisations and individuals make changes to the way services are provided for all disabled people to mitigate, as far as possible, any disadvantage they may face in accessing these services. These changes are termed 'reasonable adjustments'. This article describes the reasonable adjustments that can be made to facilitate the admission of an adult surgical patient with a learning disability, and therefore reduce health inequality. Each stage of a patient's journey through the hospital needs to be anticipated and planned for. Many of these changes are not only applicable to the wider care of people with a learning disability, but also to any person who lacks capacity and who is struggling to access healthcare. Key recommendations include the development of assessment tools, pathways and policies specific to the learning disabled patient; identification of key personnel including a learning disability lead, an acute liaison learning disability nurse, pre-assessment and operating theatre personnel and ward learning disability champions; regular multidisciplinary team meetings for planning and best interest assessments; and establishing an electronic alert on the patient administration system to identify learning disabled patients. The anaesthetist, operating theatre and learning disability teams play a pivotal role in ensuring individualised admission plans are made for patients with a learning disability to reduce these healthcare inequalities and improve peri-operative care.

RECK controls breast cancer metastasis by modulating a convergent, STAT3-dependent neoangiogenic switch.

Metastasis is the primary cause of cancer-related death in oncology patients. A comprehensive understanding of the molecular mechanisms that cancer cells usurp to promote metastatic dissemination is critical for the development and implementation of novel diagnostic and treatment strategies. Here we show that the membrane protein RECK (Reversion-inducing cysteine-rich protein with kazal motifs) controls breast cancer metastasis by modulating a novel, non-canonical and convergent signal transducer and activator of transcription factor 3 (STAT3)-dependent angiogenic program. Neoangiogenesis and STAT3 hyperactivation are known to be fundamentally important for metastasis, but the root molecular initiators of these phenotypes are poorly understood. Our study identifies loss of RECK as a critical and previously unknown trigger for these hallmarks of metastasis. Using multiple xenograft mouse models, we comprehensively show that RECK inhibits metastasis, concomitant with a suppression of neoangiogenesis at secondary sites, while leaving primary tumor growth unaffected. Further, with functional genomics and biochemical dissection we demonstrate that RECK controls this angiogenic rheostat through a novel complex with cell surface receptors to regulate STAT3 activation, cytokine signaling, and the induction of both vascular endothelial growth factor and urokinase plasminogen activator. In accordance with these findings, inhibition of STAT3 can rescue this phenotype both in vitro and in vivo. Taken together, our study uncovers, for the first time, that RECK is a novel regulator of multiple well-established and robust mediators of metastasis; thus, RECK is a keystone protein that may be exploited in a clinical setting to target metastatic disease from multiple angles.

Long term Gyrodactylus lomi infection on isolated juvenile chub (Leuciscus cephalus).

Previous studies on long term gyrodactylid infections on isolated fish have shown that for the majority of Gyrodactylus-fish interactions, infections peak at a maximum level and then decline as the host mounts an effective immune response. In the current study, juvenile chub collected from the wild still harboured Gyrodactylus lomi infections after 6 - 10 months in the laboratory despite being individually maintained at 12 C.

Vasodilator iontophoresis a possible new therapy for digital ischaemia in systemic sclerosis?

OBJECTIVE: This study investigated whether whole finger vasodilator iontophoresis increases digital blood flow in patients with systemic sclerosis (SSc): If so, this might indicate a novel approach to therapy. METHODS: Eight patients and 8 healthy controls underwent whole finger iontophoresis using a specially designed chamber. Treatment was with 0.5% sodium nitroprusside (NaNP) or 1% acetylcholine chloride (ACh), and the procedure then repeated with the other vasodilator (randomly assigned order). Three treatments were carried out for each chemical; 2 min treatments were carried out bilaterally at 200 microA, a third was then carried out for 5 min on one digit only (randomly assigned to left or right). Blood flow increases were monitored with laser Doppler imaging (LDI). Maximum perfusion increase from baseline (MAX) and the area under the time perfusion curve (AUC), normalized for baseline, were calculated. Data were compared with a three-way analysis of variance test. RESULTS: Perfusion increased in both patients and controls, but significantly more so in controls (P(MAX) = 0.001, P(AUC) = 0.005, respectively). Values were significantly higher for the 5 min treatment compared with the 2 min treatment (P(MAX) = 0.011 and P(AUC) = 0.008 for both groups). No significant differences were found between the use of NaNP and ACh. CONCLUSIONS: The increased perfusion with both ACh and NaNP in the patient group (albeit to a lesser degree than in the control group) indicates that this local approach to vasodilation is effective. Increasing iontophoresis time causes more sustained vasodilation. Further studies are indicated to investigate a possible therapeutic effect in patients with severe digital ischaemia.

Experimental infections of the monogenean Gyrodactylus turnbulli indicate that it is not a strict specialist.

Parasites represent a threat to endangered fish species, particularly when the parasite can host switch and the new host is vulnerable. If the parasite is highly host specific then successful host switching should be a rare occurrence; however, the host range of many parasites which are assumed to be specialists has never been tested. This includes the monogenean Gyrodactylus turnbulli, a well-studied ectoparasite found caudally on its known host, the guppy, Poecilia reticulata. In this study, we monitored parasite establishment and reproduction on a range of poeciliids and more distantly related fish. Individually maintained fish were experimentally infected with a single parasite and monitored daily to establish whether G. turnbulli could survive and reproduce on other fish species. Gyrodactylus turnbulli can infect a wider range of hosts than previously considered, highlighting the fact that host specificity can never be assumed unless experimentally tested. Our findings also have significant implications for parasite transmission to novel hosts and provide further insight into the evolutionary origins of this ubiquitous group of fish pathogens. Previous molecular evidence indicates that host switching is the key mechanism for speciation within the genus Gyrodactylus. Until recently, most Gyrodactylus spp. were assumed to be narrowly host specific. However, our findings suggest that even so-called specialist species, such as G. turnbulli, may represent a threat to vulnerable fish stocks. In view of the potential importance of host switching under artificial conditions, we propose to describe this as 'artificial ecological transfer' as opposed to 'natural ecological transfer', host switching under natural conditions.

Abnormal microvascular response is localized to the digits in patients with systemic sclerosis.

OBJECTIVE: To investigate the hypothesis that cutaneous microvascular perfusion of the dorsum of the hand (in response to local heating) and distal phalanx (in response to occlusion) is impaired in patients with systemic sclerosis (SSc) compared with healthy controls. METHODS: Twenty-nine patients with SSc and 29 control subjects were recruited. Perfusion was monitored using novel dual-wavelength laser Doppler imaging, allowing measurement of both smaller (capillaries) and larger (thermoregulatory) vessels. Postacclimatization, a baseline dorsum scan (red or green wavelength) was performed. A heating pad was placed on the dorsum (total stimulus time 6 minutes at 34-40 degrees C), and following removal of the pad, baseline wavelength scans were performed until perfusion returned to baseline values. This was then repeated for the second wavelength. The maximum perfusion increase due to heating (PEAK1) and area under the perfusion-time curve (AUC) were determined. In addition, scans (both wavelengths) of the index finger were performed prior to and during 2 minutes of suprasystolic occlusion, and the response upon occlusion release was monitored with single-point laser Doppler. The decrease in perfusion due to occlusion (from preocclusion baseline values) (%DECREASE) and the maximum increase (from baseline perfusion values under occlusion) in hyperemic perfusion upon removal of occlusion (PEAK/OCC) were calculated. RESULTS: PEAK1 and AUC values were not significantly different between patients and controls, as assessed with either wavelength. A significant difference between groups was found in the %DECREASE values with the green, but not the red, wavelength. A significant between-group difference was also found in PEAK/OCC values, using both wavelengths. CONCLUSION: This study suggests that SSc has no effect on microvascular perfusion in the dorsum of the hand, and that the abnormal microvascular response is localized to the digits, affecting both smaller and larger vessels.

Dual wavelength (532 and 633 nm) laser Doppler imaging of plaque psoriasis.

BACKGROUND: Increased blood flow occurs in plaques of psoriasis, and an increase in blood flow has been shown to occur in uninvolved skin adjacent to the active edge. OBJECTIVES: In order to gain more insight into the pathophysiology of the active edges of plaques of psoriasis, we investigated different components of the microcirculation in the lesional and nonlesional skin of patients with psoriasis, using dual wavelength laser Doppler imaging (LDI). METHODS: The cutaneous blood flow in 23 plaques on the forearms of 20 patients with chronic plaque psoriasis was recorded using dual wavelength LDI. Perfusion was determined within the plaque (P), in uninvolved skin adjacent to the plaque (A) and in nonadjacent skin (U). RESULTS: Perfusion in plaques was increased as imaged by either 633 nm (red wavelength) or 532 nm (green wavelength) compared with both adjacent and nonadjacent uninvolved skin: median (interquartile range) P/A(RED) = 3.7 (2.5-4.9), P/A(GREEN) = 1.3 (1.2-1.6), P/U(RED) = 4.2 (2.7-6.1), P/U(GREEN) = 1.5 (1.3-1.9). CONCLUSIONS: Vascular perfusion is increased within plaques of psoriasis compared with adjacent and nonadjacent uninvolved skin. The results suggest an area of increased perfusion in skin adjacent to plaques, when compared with nonadjacent skin, for both deeper (large) and superficial (small) vessels (imaged by 633 and 532 nm, respectively). We believe that this dual wavelength tool may be a suitable and useful way of assessing pathophysiology and treatment response in psoriasis.