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Weight-loss after bariatric surgery improves insulin sensitivity, but the underlying molecular mechanism is not clear. To ascertain the effect of bariatric surgery on insulin signalling, we examined glucose disposal and Akt activation in morbidly obese volunteers before and after Roux-en-Y gastric bypass surgery (RYGB), and compared this to lean volunteers. The hyperinsulinaemic euglycaemic clamp, at five infusion rates, was used to determine glucose disposal rates (GDR) in eight morbidly obese (body mass index, BMI=47.3 ± 2.2 kg/m(2)) patients, before and after RYGB, and in eight lean volunteers (BMI=20.7 ± 0.7 kg/m2). Biopsies of brachioradialis muscle, taken at fasting and insulin concentrations that induced half-maximal (GDR50) and maximal (GDR100) GDR in each subject, were used to examine the phosphorylation of Akt-Thr308, Akt-473, and pras40, in vivo biomarkers for Akt activity. Pre-operatively, insulin-stimulated GDR was lower in the obese compared to the lean individuals (P<0.001). Weight-loss of 29.9 ± 4 kg after surgery significantly improved GDR50 (P=0.004) but not GDR100 (P=0.3). These subjects still remained significantly more insulin resistant than the lean individuals (p<0.001). Weight loss increased insulin-stimulated skeletal muscle Akt-Thr308 and Akt-Ser473 phosphorylation, P=0.02 and P=0.03 respectively (MANCOVA), and Akt activity towards the substrate PRAS40 (P=0.003, MANCOVA), and in contrast to GDR, were fully normalised after the surgery (obese vs lean, P=0.6, P=0.35, P=0.46, respectively). Our data show that although Akt activity substantially improved after surgery, it did not lead to a full restoration of insulin-stimulated glucose disposal. This suggests that a major defect downstream of, or parallel to, Akt signalling remains after significant weight-loss.

Recurrence of leg cellulitis is common. In this pragmatic community study involving 274 patients in the United Kingdom and Ireland, daily low-dose penicillin prophylaxis decreased recurrent cellulitis during the active-treatment stage but not subsequently. Cellulitis of the leg is a common infection of the skin and subcutaneous tissue. 1 , 2 Most infections that affect intact skin are thought to be due to streptococci, 3 , 4 although other organisms may be responsible if the integrity of the skin is compromised. Each recurrent episode of cellulitis results in further damage to the lymphatic system 5 , 6 and is associated with additional morbidity and health care costs. 7 Current guidelines for the prevention of cellulitis are consensus-based and recommend prophylactic antibiotic therapy for recurrent disease. 8 , 9 Three small, randomized, controlled trials have suggested a possible benefit of prophylactic antibiotics in patients . . .

Malignant melanoma is a life threatening skin tumour which may arise on the foot. The prognosis for the condition is good when lesions are diagnosed and treated early. However, lesions arising on the soles and within the nail unit can be difficult to recognise leading to delays in diagnosis. These guidelines have been drafted to alert health care practitioners to the early signs of the disease so an early diagnosis can be sought.

Background Malignant melanoma is a rare but potentially lethal form of cancer which may arise on the foot. Evidence suggests that due to misdiagnosis and later recognition, foot melanoma has a poorer prognosis than cutaneous melanoma elsewhere. Methods A panel of experts representing podiatry and dermatologists with a special interest in skin oncology was assembled to review the literature and clinical evidence to develop a clinical guide for the early recognition of plantar and nail unit melanoma. Results A systematic review of the literature revealed little high quality data to inform the guide. However a significant number of case reports and series were available for analysis. From these, the salient features were collated and summarised into the guide. Based on these features a new acronym \"CUBED\" for foot melanoma was drafted and incorporated in the guide. Conclusions The use of this guide may help clinicians in their assessment of suspicious lesions on the foot (including the nail unit). Earlier detection of suspicious pedal lesions may facilitate earlier referral for expert assessment and definitive diagnosis. The guide is currently being field tested amongst practitioners.

Nail involvement in psoriasis is common and can have a significant impact on quality of life. Manifestations of nail dystrophy in psoriasis include pitting, onycholysis, subungual hyperkeratosis and splinter haemorrhages. Clear evidence regarding the range of treatment options for nail psoriasis is lacking. Topical therapies, including corticosteroids and vitamin D 3 analogues, are simple to administer and readily available, but are not effective in treating all types of psoriatic nail dystrophy. Other topical agents have been tried, but may be less readily available. Intralesional corticosteroid injections can be helpful, but may be painful and time consuming. Psoralen plus ultraviolet A treatment has been shown to improve subungual hyperkeratosis, onycholysis, discolouration and nail crumbling, but not pitting. The possibility of future harm with other types of radiation treatment, including superficial radiotherapy and Grenz rays, limits their use. The use of systemic therapies, including the recent introduction of biological agents, is largely restricted to those with concomitant widespread cutaneous or joint involvement because of cost implications and potential toxicity. Further studies regarding the treatment of nail psoriasis are required in order to ascertain the best regimen of therapy for each patient.

Anonychia and hyponychia congenita (OMIM 206800) are rare autosomal recessive conditions in which the only presenting phenotype is the absence or severe hypoplasia of all fingernails and toenails. After determining linkage to chromosome 20p13, we identified homozygous or compound heterozygous mutations in the gene encoding R-spondin 4 ( RSPO4 ), a secreted protein implicated in Wnt signaling, in eight affected families. Rspo4 expression was specifically localized to developing mouse nail mesenchyme at embryonic day 15.5, suggesting a crucial role in nail morphogenesis. NOTE: In the version of this article initially published, the national origin of the three consanguineous families (P2–P4) was incorrectly described as Indian. The national origin of all three families (P2–P4) is Pakistani. This error has been corrected in the HTML and PDF versions of the article.

Pili annulati, a rare hair shaft abnormality with a characteristic shiny appearance due to alternating light and dark bands of the hair, is assumed to be inherited in an autosomal dominant mode with high penetrance. A locus for pili annulati has not been found yet. We identified one large and four small European kindreds with pili annulati and conducted a genomewide linkage analysis using 382 microsatellite markers. A multipoint logarithm of the odds (LOD) score of 3.19 was demonstrated between D12S1659 and D12S1723 on the telomeric part of the long arm of chromosome 12. Subsequent finemapping in a region of 20 cM gave a maximum multipoint LOD score of 3.24 at D12S1723 under the assumption of homogeneity and a LOD score of 3.57 around D12S343 under the assumption of heterogeneity, both exceed the statistical thresholds necessary to conclude linkage. Most of this LOD score came from the largest family, which reached a maximum LOD score of 3.81. The maximum two-point LOD score for all families was 3.97 at D12S1609. Definite recombination events narrowed the region of shared haplotype in the affected individuals to an 8 Mb region between the marker D12S324 and the telomeric end of the long arm of chromosome 12.

A 68-year-old man reports changes in his left big toenail. It has been discolored distally for the past 2 years. It has become thickened and difficult to cut and is painful when the man is walking in certain shoes. He is otherwise well. On physical examination, the nail appears thickened, has crumbling yellow material beneath, and is more discolored distally than proximally. The nearby skin is normal, although the interdigital space of the little toe is macerated. How should his case be managed? A 68-year-old man reports changes in his left big toenail. It has been discolored for the past 2 years and now is difficult to cut and painful. The nail appears thickened, has crumbling yellow material beneath, and is more discolored distally than proximally. How should his case be managed? Foreword This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author's clinical recommendations. Stage A 68-year-old man reports changes in his left big toenail. It has been discolored distally for the past 2 years. It has become thickened and difficult to cut and is painful when the man is walking in certain shoes. He is otherwise well. On physical examination, the nail appears thickened, has crumbling yellow material beneath, and is more discolored distally than proximally. The nearby skin is normal, although the interdigital space of the little toe is macerated. How should his case be managed? The Clinical Problem The reported prevalence of toenail onychomycosis in Western adult populations is 2 to . . .

A change in colour, size, shape or texture of finger- and toenails can be an indicator of underlying systemic disease. An appreciation of these nail signs, and an ability to interpret them when found, can help guide diagnosis and management of a general medical patient. This article discusses some common, and some more rare, nail changes associated with systemic disease.

Results Following a systematic review of published evidence and existing guidelines it was concluded there was insufficient research to fully inform such a guide. [...] using the available literature and case reports a paper was drafted using expert opinion and clinical experience.