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Supplemental Digital Content is available in the text.Therapeutic activation of macrophage phagocytosis has the ability to restrain tumour growth through phagocytic clearance of tumour cells and activation of the adaptive immune response. Our objective for this study was to evaluate the effects of modulating pro- and anti-phagocytic pathways in malignant melanoma. In order to identify evolutionarily conserved mechanisms of resistance that may be important for melanoma cell survival, we utilized a multi-species approach and examined the phagocytosis of human, mouse, and dog melanoma cells. We observed that melanoma cells from all three species displayed unexpected resistance to phagocytosis that could not be fully mitigated by blockade of the ‘don’t eat me’ signal CD47 or by chemotherapeutic enhancement of known ‘eat me’ signals. Additionally, CD47 blockade failed to promote anti-melanoma immune responses or tumour regression in vivo. This melanoma resistance to phagocytosis was not mediated by soluble factors, and it was unaffected by siRNA-mediated knockdown of 47 prospective ‘don’t eat me’ signals or by CRISPR-Cas-mediated CD47 knockout. Unexpectedly, CD47 knockout also did not enhance phagocytosis of lymphoma cells, but it eliminated the pro-phagocytic effect of CD47 blockade, suggesting that the pro-phagocytic effects of CD47 blockade are due in part to Fc receptor engagement. From this study, we conclude that melanoma cells possess an evolutionarily conserved resistance to macrophage phagocytosis. Further investigation will be needed to overcome the mechanisms that mediate melanoma cell resistance to innate immunity.

AimsCubitus varus is the most common late complication of a supracondylar fracture of the humerus in children. Correction can be performed using one of a number of techniques of osteotomy but each has disadvantages. We describe a new technique for correcting post-traumatic cubitus varus using a lateral closing wedge isosceles triangular osteotomy.Patients and MethodsA lateral closing wedge isosceles triangular osteotomy was performed in 25 patients (15 male and ten female with a mean age of 9.5 years (6 to 12)) between May 2010 and April 2013. All patients had cubitus varus secondary to malunion of a supracondylar fracture, with good function of the elbow and a full range of movement. The osteotomy lines were marked on the bone with an isosceles triangular template made before surgery, after which the osteotomy was performed leaving the medial cortex intact. Fixation was performed using two lateral 2 mm Kirschner (K)-wires and patients were immobilised in an above-elbow plaster. By six to eight weeks callus was present and the wires and cast were removed. Patients were reviewed at four and six weeks, three, six and 12 months and then every two years until skeletal maturity. Clinical and radiographic outcomes were categorised as excellent, good or poor.ResultsA total of 23 patients had an excellent and two had a good outcome at a mean final follow-up of 3.4 years (two to four). The mean post-operative carrying angle in the corrected elbow was 11.7° (7° to 18°). One patient fell, displacing the osteotomy, and needed revision of the fixation. No patient had a nerve injury.ConclusionA lateral isosceles triangular osteotomy and with K-wire fixation is a practical, effective, reliable, safe and simple method of correcting post-traumatic cubitus varus in children. It has inherent stability and excellent cosmesis without prominence of the lateral condyle. Cite this article: Bone Joint J2016;98-B:1521–5.

Background/Objectives:: Coffee is one of the most popularly consumed beverages worldwide. Many epidemiological studies have investigated the association between coffee consumption and lung cancer risk, but the results are inconsistent. Hence, we conducted a systematic analysis of relevant population-based studies to examine this association and derive a more precise estimation. Subjects/Methods:: The Cochrane library, PubMed and Embase databases were searched to identify studies published through Mar 2015 that met the predetermined inclusion criterion. Seventeen studies (5 cohort and 12 case–control studies) involving 12 276 cases and 102 516 controls were included. Results:: The summary odds ratio (OR) of lung cancer was 1.17 (95% confidence interval (CI): 1.03–1.33) for coffee drinkers compared with nondrinkers and 1.31 (95% CI: 1.11–1.55) for the highest category of coffee consumption compared with the lowest category. Compared with nondrinkers, the pooled ORs for lung cancer were 1.10 (95% CI: 0.92–1.31) for ⩽1 cup per day, 1.10 (95% CI: 0.93–1.30) for 2–3 cups per day and 1.20 (95% CI: 1.02–1.39) for ⩾3 cups per day. Further analysis showed that the ORs for hospital-based case–control studies, population-based case–control studies and prospective cohort studies were 1.36 (95% CI: 1.10–1.69), 0.99 (95% CI: 0.77–1.28) and 1.59 (95% CI: 1.26–2.00), respectively. Significant associations for high coffee intake with increased risk of lung cancer were observed in men (OR=1.41 95% CI: 1.21–1.63), but not in women (OR=1.16, 95% CI: 0.86–1.56), in American (OR=1.34 95% CI: 1.08–1.65) and Asian populations (OR=1.49 95% CI: 1.28–1.74), but not in European populations (OR=1.12, 95% CI: 0.74–1.67), and in smokers (OR=1.24, 95% CI: 1.00–1.54), but not in nonsmokers (OR=0.85, 95% CI: 0.64–1.11). Particularly over the last 5 years, studies have consistently indicated that lung cancer risk is significantly increased by 47% in the population with the highest category intake of coffee compared with that with the lowest category intake (OR=1.47, 95% CI: 1.21–1.79). Conclusion:: The present study suggested that coffee intake was associated with an increased risk of lung cancer.

SuccessfulAgrobacterium-mediated transformation of monocots such as orchids hinges on the induction of virulence(vir)genes in the bacterium, an event that is required for the activation of the T-DNA processing and transfer pathway. In dicots, several plant phenolic compounds, for example acetosyringone, coumaryl alcohol and sinapyl alcohol, are knownvirgene inducers, but in monocots their presence and characteristics are not well established. We report herein the presence and identification of coniferyl alcohol as thevirgene inducer in the monocotDendrobium.At an early stage of development as protocorm-like bodies (PLBs), this orchid contains an aryl β-glycoside, similar to coniferin, whose aglycone moiety is coniferyl alcohol. Coniferyl alcohol is elaborated in high amounts from PLBs and its production or stability is enhanced almost six-fold higher when the PLBs were exposed to light than when maintained in the dark. PLBs produced 11-fold more inducer than leaves. These studies show for the first time that orchids, i.e.Dendrobium,exude coniferyl alcohol as avirgene inducer.

The title complex (I) crystallizes in C2/c with Z=4 as its MeCN solvate and in P1 with Z=2 as its DMSO solvate.