Molecular Recognition of Insulin by a Synthetic Receptor

The discovery of molecules that bind tightly and selectively to desired proteins continues to drive innovation at the interface of chemistry and biology. This paper describes the binding of human insulin by the synthetic receptor cucurbit[7]uril (Q7) in vitro. Isothermal titration calorimetry and fluorescence spectroscopy experiments show that Q7 binds to insulin with an equilibrium association constant of 1.5 × 106 M−1 and with 50−100-fold selectivity versus proteins that are much larger but lack an N-terminal aromatic residue, and with \u3e1000-fold selectivity versus an insulin variant lacking the N-terminal phenylalanine (Phe) residue. The crystal structure of the Q7·insulin complex shows that binding occurs at the N-terminal Phe residue and that the N-terminus unfolds to enable binding. These findings suggest that site-selective recognition is based on the properties inherent to a protein terminus, including the unique chemical epitope presented by the terminal residue and the greater freedom of the terminus to unfold, like the end of a ball of string, to accommodate binding. Insulin recognition was predicted accurately from studies on short peptides and exemplifies an approach to protein recognition by targeting the terminus

Do Multidisciplinary Team (MDT) processes influence survival in patients with colorectal cancer? A population-based experience

BACKGROUND: MDT (multidisciplinary team) meetings are considered an essential component of care for patients with cancer. However there is remarkably little direct evidence that such meetings improve outcomes. We assessed whether or not MDT (multidisciplinary team) processes influenced survival in a cohort of patients with colorectal cancer. METHODS: Observational study of a population-based cohort of 586 consecutive patients with colorectal cancer diagnosed in Tayside (Scotland) during 2006 and 2007. RESULTS: Recommendations from MDT meetings were implemented in 411/586 (70.1 %) of patients, the MDT+ group. The remaining175/586 (29.9 %) were either never discussed at an MDT, or recommendations were not implemented, MDT- group. The 5-year cause-specific survival (CSS) rates were 63.1 % (MDT+) and 48.2 % (MDT-), p < 0.0001. In analysis confined to patients who survived >6 weeks after diagnosis, the rates were 63.2 % (MDT+) and 57.7 % (MDT-), p = 0.064. The adjusted hazard rate (HR) for death from colorectal cancer was 0.73 (0.53 to 1.00, p = 0.047) in the MDT+ group compared to the MDT- group, in patients surviving >6 weeks the adjusted HR was 1.00 (0.70 to 1.42, p = 0.987). Any benefit from the MDT process was largely confined to patients with advanced disease: adjusted HR ((early)) 1.32 (0.69 to 2.49, p = 0.401); adjusted HR((advanced)) 0.65 (0.45 to 0.96, p = 0.031). CONCLUSIONS: Adequate MDT processes are associated with improved survival for patients with colorectal cancer. However, some of this effect may be more apparent than real – simply reflecting selection bias. The MDT process predominantly benefits the 40 % of patients who present with advanced disease and conveys little demonstrable advantage to patients with early tumours. These results call into question the current belief that all new patients with colorectal cancer should be discussed at an MDT meeting

Sex Selective Abortion, Neoliberal Patriarchy and Structural Violence in India

This article explores sex selective abortion (SSA) as a form of structural violence within the broader notion of women’s ‘protection’ in contemporary India. While SSA tends to be framed more generally within ethical and choice-based frameworks around abortion access and reproductive ‘rights’, and specifically in India around preference for sons as a discriminatory, cultural, technological misogyny, this article argues that sex selective abortion in India needs to be understood as an outcome of broader systemic economic, political and social processes. The deepening of neoliberal values through state policies has impacted significantly on social relations, shaping SSA as a manifestation of structural violence. State-driven policies in India reflect a neoliberal governmentality through state patriarchy that is implicit within the neoliberal developmental, governmental and capitalist paradigm of contemporary India. This article argues that SSA is structurally produced and therefore cannot be remedied through awareness-raising strategies such as beti bachao or financial inclusion as a means to ‘protect’ or ‘save the girl child’. Indeed, it is neoliberal economic forces that actively, though seemingly inadvertently, promote anti-women, sex selective abortion as a reproductive strategy, which is then disciplined through neoliberal governmentality. This highlights SSA as a form of gendered and structural, rather than discriminatory, violence

What is known about the patient's experience of medical tourism? A scoping review

<p>Abstract</p> <p>Background</p> <p>Medical tourism is understood as travel abroad with the intention of obtaining non-emergency medical services. This practice is the subject of increasing interest, but little is known about its scope.</p> <p>Methods</p> <p>A comprehensive scoping review of published academic articles, media sources, and grey literature reports was performed to answer the question: what is known about the patient's experience of medical tourism? The review was accomplished in three steps: (1) identifying the question and relevant literature; (2) selecting the literature; (3) charting, collating, and summarizing the information. Overall themes were identified from this process.</p> <p>Results</p> <p>291 sources were identified for review from the databases searched, the majority of which were media pieces (<it>n </it>= 176). A further 57 sources were included for review after hand searching reference lists. Of the 348 sources that were gathered, 216 were ultimately included in this scoping review. Only a small minority of sources reported on empirical studies that involved the collection of primary data (<it>n </it>= 5). The four themes identified via the review were: (1) decision-making (e.g., push and pull factors that operate to shape patients' decisions); (2) motivations (e.g., procedure-, cost-, and travel-based factors motivating patients to seek care abroad); (3) risks (e.g., health and travel risks); and (4) first-hand accounts (e.g., patients' experiential accounts of having gone abroad for medical care). These themes represent the most discussed issues about the patient's experience of medical tourism in the English-language academic, media, and grey literatures.</p> <p>Conclusions</p> <p>This review demonstrates the need for additional research on numerous issues, including: (1) understanding how multiple information sources are consulted and evaluated by patients before deciding upon medical tourism; (2) examining how patients understand the risks of care abroad; (3) gathering patients' prospective and retrospective accounts; and (4) the push and pull factors, as well as the motives of patients to participate in medical tourism. The findings from this scoping review and the knowledge gaps it uncovered also demonstrate that there is great potential for new contributions to our understanding of the patient's experience of medical tourism.</p

Groin wound infection after vascular exposure ( GIVE ) multicentre cohort study

Surgical site infections (SSIs) of groin wounds are a common and potentially preventable cause of morbidity, mortality, and healthcare costs in vascular surgery. Our aim was to define the contemporaneous rate of groin SSIs, determine clinical sequelae, and identify risk factors for SSI. An international multicentre prospective observational cohort study of consecutive patients undergoing groin incision for femoral vessel access in vascular surgery was undertaken over 3 months, follow‐up was 90 days. The primary outcome was the incidence of groin wound SSI. 1337 groin incisions (1039 patients) from 37 centres were included. 115 groin incisions (8.6%) developed SSI, of which 62 (4.6%) were superficial. Patients who developed an SSI had a significantly longer length of hospital stay (6 versus 5 days, P = .005), a significantly higher rate of post‐operative acute kidney injury (19.6% versus 11.7%, P = .018), with no significant difference in 90‐day mortality. Female sex, Body mass index≥30 kg/m2, ischaemic heart disease, aqueous betadine skin preparation, bypass/patch use (vein, xenograft, or prosthetic), and increased operative time were independent predictors of SSI. Groin infections, which are clinically apparent to the treating vascular unit, are frequent and their development carries significant clinical sequelae. Risk factors include modifiable and non‐modifiable variables

Factors influencing the choice of treatment modality for individual patients with varicose veins.

INTRODUCTION There is evidence of effectiveness for a range of different treatment modalities for varicose veins but limited information about factors that influence treatment choice for individual patients. METHODS A postal survey was sent to 438 UK members of the Vascular Society of Great Britain and Ireland. RESULTS Overall, 251 responses were received (response rate 57%). A total of 222 respondents treated varicose veins using conventional surgery (84%), endothermal ablation (82%) and foam sclerotherapy (68%). The clinical pattern of veins appeared to have the greatest influence on treatment choice. This was followed by guidance from the National Institute for Health and Care Excellence, patient expectations, facilities, cost and whether treatment was carried out in the public or private sector. Respondents were asked to indicate whether each of 13 clinical 'scenarios' (eg very extensive varicose veins in both legs) would influence them towards or against using specified treatment modalities. 'Consensus' was defined as ≥80% of responses either towards or against any treatment modality; and disagreement as 41-59% both towards and against any modality (i.e. ∼50:50 split). There was consensus towards using endothermal ablation for truncal reflux, towards UGFS for localised varicose veins and towards conventional surgery for large, extensive, bilateral veins. There was consensus against UGFS for large truncal veins, and against surgery for obese patients and those with a history of venous thromboembolism. There were important disagreements about the influence of large or extensive veins, about whether patients were obese or slim and about a prior history of venous thromboembolism. CONCLUSIONS Conventional surgery is still widely available in the UK. Disagreements about treatment choice in different clinical scenarios suggest substantial variation in the treatments patients are offered. Attention to identifying subgroups in trials would help to guide treatment choice for individual patients