A novel mutation of KIF11 in a child with 22q11.2 deletion syndrome associated with MCLMR

Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation (MCLMR; OMIM 152950) is a rare autosomal dominantly inherited syndrome. Mutations in the kinesin family member 11 (KIF11) gene have been associated with this condition. Here, we report a de novo novel heterozygous missense mutation in exon 12 of the KIF11 gene [c.1402T>G; p.(Leu468Val)] in a boy with 22q11.2 microdeletion syndrome. His major features were microcephaly, ventricular septal defect, congenital lymphedema of the feet, and distinct facial appearance including upslanting palpebral fissures, a broad nose with rounded tip, anteverted nares, long philtrum with a thin upper lip, pointed chin, and prominent ears. His right eye was enucleated due to subretinal hemorrhage and retinal detachment at age 3 months. Lacunae of chorioretinal atrophy and the pale optic disc were present in the left eye. He also had a de novo 1.6-Mb microdeletion in the Di George/VCFS region of chromosome 22q11.2 in SNP array, which was confirmed by FISH analysis. In this study, for the first time, we describe the co-occurrence of a KIF11 mutation and 22q11.2 deletion syndrome in a patient with MCLMR

Guidelines for initiation of anti-tumour necrosis factor therapy in rheumatoid arthritis: similarities and differences across Europe.

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The EULAR-OMERACT rheumatoid arthritis MRI reference image atlas: the wrist joint

This paper presents the wrist joint MR images of the EULAR–OMERACT rheumatoid arthritis MRI reference image atlas. Reference images for scoring synovitis, bone oedema, and bone erosions according to the OMERACT RA MRI scoring (RAMRIS) system are provided. All grades (0–3) of synovitis are illustrated in each of the three wrist joint areas defined in the scoring system—that is, the distal radioulnar joint, the radiocarpal joint, and the intercarpal-carpometacarpal joints. For reasons of feasibility, examples of bone abnormalities are limited to five selected bones: the radius, scaphoid, lunate, capitate, and a metacarpal base. In these bones, grades 0–3 of bone oedema are illustrated, and for bone erosion, grades 0–3 and examples of higher grades are presented. The presented reference images can be used to guide scoring of wrist joints according to the OMERACT RA MRI scoring system

A new low-field extremity magnetic resonance imaging and proposed compact MRI score: evaluation of anti-tumor necrosis factor biologics on rheumatoid arthritis

Magnetic resonance imaging (MRI) is a useful tool for evaluating disease activity and therapeutic efficacy in rheumatoid arthritis (RA). However, conventional whole-body MRI is inconvenient on several levels. We have therefore developed a new low-field extremity MRI (compact MRI, cMRI) and examined its clinical utility. Thirteen RA patients treated with anti-tumor necrosis factor (TNF) biologics were included in the study. The MRI was performed twice using a 0.21-T extremity MRI system. The MRI images were scored using our proposed cMRI scoring system, which we devised with reference to the Outcome Measures in Rheumatology Clinical Trials RA MRI score (OMERACT RAMRIS). In our cMRI scoring system, synovitis, bone edema, and bone erosion are separately graded on a scale from 0 to 3 by imaging over the whole hand, including the proximal interphalangeal joint. The total cMRI score (cMRIS) is then obtained by calculating the total bone erosion score × 1.5 + total bone edema score × 1.25 + total synovitis score. In this study, one patient showed a progression of bone destruction even under low clinical activity, as assessed by the disease activity score on 28 joints (DAS28); however, another patient’s cMRIS decreased concurrently with the decrease in DAS28, with the positive correlation observed between ΔDAS28 and ΔcMRIS (R = 0.055, P < 0.05). We conclude that cMRI and cMRIS are useful for assessing total disease activity and as a method linking MRI image evaluation to clinical evaluation

Magnetic Resonance Lymphangiography: Establishing Normal.

BACKGROUND: Despite an increased interest in visualising the lymphatic vessels (lymphatics) with Magnetic Resonance Lymphangiography (MRL), there remains little literature describing their appearance in non-lymphoedematous individuals. To determine lymphatic abnormalities, an understanding of how healthy lymphatics appear and behave needs to be established. In this study, MRL of individuals without a history of lymphatic disease was therefore performed. METHODS: A total of 25 individuals (15 female) underwent MRL of their lower limbs using a 3.0T Philips MRI scanner. The first 9 cases were recruited to establish the concentration of Gadolinium-based contrast agent (GBCA) to administer, with the remainder imaged pre- and post-inter-digital forefoot GBCA injections at the optimised dose. Outcomes including lymphatic vessel diameter, tortuosity and the frequency of drainage via particular drainage routes were recorded. RESULTS: Healthy lymphatics following the anteromedial pathway were routinely observed in post-contrast T1 weighted images (average tortuosity = 1.09 ±0.03), with an average of 2.16 ± 0.93 lymphatic vessels, of diameter 2.47 ± 0.50 mm, crossing the anterior ankle. In six limbs, vessels following the anterolateral pathways were observed. No vessels traversing the posterior of the legs were seen. In a subset of ten vessels lymphatic signal, measured at the ankle, peaked 29:50 ± 09:29 mm:ss after GBCA administration. No lymphatic vessels were observed in T2 weighted images. CONCLUSIONS: Contrast-enhanced MRL reliably depicts the lymphatics in the legs of healthy controls. Following inter-digital contrast injection, anteromedial drainage appears dominant. Quantitative measures related to lymphatic vessel size, tortuosity and drainage rate are readily obtainable, and could be beneficial for detecting even subtle lymphatic impairment

Combinations of β-lactam or aminoglycoside antibiotics with plectasin are synergistic against methicillin-sensitive and methicillin-resistant Staphylococcus aureus.

Bacterial infections remain the leading killer worldwide which is worsened by the continuous emergence of antibiotic resistance. In particular, methicillin-sensitive (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) are prevalent and the latter can be difficult to treat. The traditional strategy of novel therapeutic drug development inevitably leads to emergence of resistant strains, rendering the new drugs ineffective. Therefore, rejuvenating the therapeutic potentials of existing antibiotics offers an attractive novel strategy. Plectasin, a defensin antimicrobial peptide, potentiates the activities of other antibiotics such as β-lactams, aminoglycosides and glycopeptides against MSSA and MRSA. We performed in vitro and in vivo investigations to test against genetically diverse clinical isolates of MSSA (n = 101) and MRSA (n = 115). Minimum inhibitory concentrations (MIC) were determined by the broth microdilution method. The effects of combining plectasin with β-lactams, aminoglycosides and glycopeptides were examined using the chequerboard method and time kill curves. A murine neutropenic thigh model and a murine peritoneal infection model were used to test the effect of combination in vivo. Determined by factional inhibitory concentration index (FICI), plectasin in combination with aminoglycosides (gentamicin, neomycin or amikacin) displayed synergistic effects in 76-78% of MSSA and MRSA. A similar synergistic response was observed when plectasin was combined with β-lactams (penicillin, amoxicillin or flucloxacillin) in 87-89% of MSSA and MRSA. Interestingly, no such interaction was observed when plectasin was paired with vancomycin. Time kill analysis also demonstrated significant synergistic activities when plectasin was combined with amoxicillin, gentamicin or neomycin. In the murine models, plectasin at doses as low as 8 mg/kg augmented the activities of amoxicillin and gentamicin in successful treatment of MSSA and MRSA infections. We demonstrated that plectasin strongly rejuvenates the therapeutic potencies of existing antibiotics in vitro and in vivo. This is a novel strategy that can have major clinical implications in our fight against bacterial infections

Performing the high-school prom in the UK: Locating authenticity through practice

The purpose of this study was threefold: to develop an understanding of the appropriation of the US High School Prom in the UK and more importantly to generate an insight into the producers and consumers of such an event; to establish if the performance of the prom is hyper-real or if there is an awareness of the authentic or inauthentic elements of this ritual and finally to ascertain local interpretation of authenticity and glocal practice. The method used here was a qualitative approach employing 24 in-depth interviews with young adults (18-20 years) who had attended a prom in the UK in the last three years. The findings illustrated that the role and the social network of the individual was key to engagement with the High School Prom and also indicated a possible symbiosis of the strands of theory associated with authenticity. Diverse localised meanings of the prom performance were also identified. As the school prom is a growth market in the UK businesses should be aware of adolescents&rsquo; desire for ownership of this event and should tailor their marketing accordingly

How do general practitioners experience providing care to refugees with mental health problems? A qualitative study from Denmark

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited