Evaluating diagnostic and management agreement between physiotherapists and ear, nose and throat specialist in a primary contact physiotherapy-led vestibular clinic: A prospective blinded inter-rater agreement pilot study.

Background: Dizziness and vertigo are common referrals to Ear Nose Throat (ENT) outpatient services however these services have long waitlists for assessment. Primary contact physiotherapy-led vestibular clinics are recognized as improving access to care. This pilot study investigated agreement between physiotherapists and an ENT medical practitioner for diagnostic and management decisions in patients attending a primary contact physiotherapy-led vestibular clinic.

Comprehensive molecular profiling of UV-induced metastatic melanoma in Nme1/Nme2-deficient mice reveals novel markers of survival in human patients.

Hepatocyte growth factor-overexpressing mice that harbor a deletion of the Ink4a/p16 locus (HP mice) form melanomas with low metastatic potential in response to UV irradiation. Here we report that these tumors become highly metastatic following hemizygous deletion of the Nme1 and Nme2 metastasis suppressor genes (HPN mice). Whole-genome sequencing of melanomas from HPN mice revealed a striking increase in lung metastatic activity that is associated with missense mutations in eight signature genes (Arhgap35, Atp8b4, Brca1, Ift172, Kif21b, Nckap5, Pcdha2, and Zfp869).

Coblation intracapsular tonsillectomy (tonsillotomy) in children: A prospective study of 500 consecutive cases with long-term follow-up.

Objectives: Intracapsular tonsillectomy (tonsillotomy) has been used internationally, mainly in the management of obstructive sleep apnoea, rather than recurrent tonsillitis, with few published data evaluating its use for this latter indication. We present long-term prospective data from 500 paediatric cases undergoing Coblation intracapsular tonsillectomy, for both obstructive and infective indications.

Design: Prospective case series, March 2013-January 2016, all with completed follow-up.

A melanin-independent interaction between Mc1r and Met signaling pathways is required for HGF-dependent melanoma.

Melanocortin 1 receptor (MC1R) signaling stimulates black eumelanin production through a cAMP-dependent pathway. MC1R polymorphisms can impair this process, resulting in a predominance of red phaeomelanin. The red hair, fair skin and UV sensitive phenotype is a well-described melanoma risk factor.

Functional melanocortin 1 receptor Mc1r is not necessary for an inflammatory response to UV radiation in adult mouse skin.

The G-protein-coupled receptor, Mc1r, plays a major role in pigment production and has been reported to be important in the inflammatory response. We have investigated the effect of deficiency in Mc1r on UV-induced inflammation. Mice on the same genetic background were used - C57BL/6-c (albino), C57BL/6 (black), C57BL/6-Mc1r(e/e) deficient (yellow).

Melanoma induction by ultraviolet A but not ultraviolet B radiation requires melanin pigment.

Malignant melanoma of the skin (CMM) is associated with ultraviolet radiation exposure, but the mechanisms and even the wavelengths responsible are unclear. Here we use a mammalian model to investigate melanoma formed in response to precise spectrally defined ultraviolet wavelengths and biologically relevant doses. We show that melanoma induction by ultraviolet A (320-400 nm) requires the presence of melanin pigment and is associated with oxidative DNA damage within melanocytes.

Shedding light on melanocyte pathobiology in vivo.

Cutaneous malignant melanoma is rapidly increasing in the developed world and continues to be a challenge in the clinic. Although extensive epidemiologic evidence points to solar UV as the major risk factor for melanoma, there is a significant gap in our knowledge about how this most ubiquitous environmental carcinogen interacts with the largest organ of the mammalian body (skin) at the microenvironmental and molecular level. We review some recent advances that have started to close this gap.

Interferon-γ links ultraviolet radiation to melanomagenesis in mice.

Cutaneous malignant melanoma is a highly aggressive and frequently chemoresistant cancer, the incidence of which continues to rise. Epidemiological studies show that the major aetiological melanoma risk factor is ultraviolet (UV) solar radiation, with the highest risk associated with intermittent burning doses, especially during childhood. We have experimentally validated these epidemiological findings using the hepatocyte growth factor/scatter factor transgenic mouse model, which develops lesions in stages highly reminiscent of human melanoma with respect to biological, genetic and aetiological criteria, but only when irradiated as neonatal pups with UVB, not UVA.

UVB and UVA initiate different pathways to p53-dependent apoptosis in melanocytes.

The incidence of cutaneous malignant melanoma (CMM) has more than doubled in the past 25 years and continues to increase at over 3% per year across all age groups (Linos et al., this issue), and invasive and disseminated melanoma in young women has increased by almost 10% since 1992 (Purdue et al., 2008).

Deficient inflammatory response to UV radiation in neonatal mice.

Mechanisms of juvenile susceptibility to cancer are not well understood. The immune response in neonates favors nonresponsiveness or T(H)2-dominant responses, raising the question of a role for neonatal immunity in this susceptibility. We have investigated the postulate that the inflammatory response differs in neonatal and adult skin.

The effects on human health from stratospheric ozone depletion and its interactions with climate change.

Ozone depletion leads to an increase in the ultraviolet-B (UV-B) component (280-315 nm) of solar ultraviolet radiation (UVR) reaching the surface of the Earth with important consequences for human health. Solar UVR has many harmful and some beneficial effects on individuals and, in this review, information mainly published since the previous report in 2003 (F. R.

Neonatal susceptibility to UV induced cutaneous malignant melanoma in a mouse model.

UV irradiation has multiple effects on skin including erythema, immunosuppression and the induction of keratinocyte-derived skin cancers and cutaneous malignant melanoma (CMM). CMM which arises from damage to the melanocyte, the pigment cell of the skin, is associated in epidemiologic studies with sun-exposure of susceptible populations, especially children. Our experimental studies have supported the concept that the epidemiologically observed susceptibility in children has a biologic basis.

Ultraviolet B but not ultraviolet A radiation initiates melanoma.

Cutaneous malignant melanoma is one of the fastest increasing cancers with an incidence that has more than doubled in the last 25 years. Sunlight exposure is strongly implicated in the etiology of cutaneous malignant melanoma and the UV portion of the sunlight spectrum is considered responsible. Data are, however, conflicting on the roles of ultraviolet B [UVB; 280-320 nanometers (nm)] and ultraviolet A (UVA; 320-400 nm), which differ in their ability to initiate DNA damage, cell signaling pathways and immune alterations.

Mice with genetically determined high susceptibility to ultraviolet (UV)-induced immunosuppression show enhanced UV carcinogenesis.

To assess the premise that genetically determined differences in susceptibility to UV-induced immunosuppression are reflected in UV carcinogenesis, we investigated UV skin cancer induction in two strains of reciprocal F1 hybrid mice CB6F1 males with high susceptibility to UV immunosuppression and a BALB/c X-chromosome and B6CF1 males with low susceptibility to UV immunosuppression and a C57BL/6 X-chromosome. Four experimental groups comprising both strains treated three times weekly with two UV regimens (daily doses incremented from 2.25 to 6 or 4.

Ultraviolet radiation and cutaneous malignant melanoma.

Recent years have seen a steady rise in the incidence of cutaneous malignant melanoma worldwide. Although it is now appreciated that the key to understanding the process by which melanocytes are transformed into malignant melanoma lies in the interplay between genetic factors and the ultraviolet (UV) spectrum of sunlight, the nature of this relation has remained obscure. Recently, prospects for elucidating the molecular mechanisms underlying such gene-environment interactions have brightened considerably through the development of UV-responsive experimental animal models of melanoma.

Modeling gene-environment interactions in malignant melanoma.

Many cancers are the pathological consequence of environmentally initiated disruptions to cellular genetic control mechanisms. For most cancers the relevant environmental carcinogens have not been identified, but one major exception is cutaneous malignant melanoma, for which the primary environmental agent is solar ultraviolet (UV) radiation. Hence, melanomagenesis represents a potential model of detrimental gene-environment interaction.

Antisense transcripts at the EMX2 locus in human and mouse.

The homeodomain transcription factor EMX2 is critical for central nervous system and urogenital development. In addition, EMX2 maps to a region of allelic deletion corresponding to a putative endometrial tumor suppressor at 10q26. We now report another polyadenylated transcript that is transcribed on the strand opposite to EMX2 and overlaps with the EMX2 transcript.

Animal models of melanoma: an HGF/SF transgenic mouse model may facilitate experimental access to UV initiating events.

Cutaneous malignant melanoma, the most lethal of the skin cancers, known for its intractability to current therapies, continues to increase in incidence, providing a significant public health challenge. There is a consensus that skin cancer is initiated by sunlight exposure. For non-melanoma skin cancer there is substantial evidence that chronic exposure to the ultraviolet B radiation (UVB) (280-320 nm) portion of the sunlight spectrum is responsible.

Ink4a/arf deficiency promotes ultraviolet radiation-induced melanomagenesis.

Cutaneous malignant melanoma (CMM), already known for its highly aggressive behavior and resistance to conventional therapy, has evolved into a health crisis by virtue of a dramatic elevation in incidence. The underlying genetic basis for CMM, as well as the fundamental role for UV radiation in its etiology, is now widely accepted. However, the only bona fide genetic locus to emerge from extensive analysis of CMM suppressor candidates is INK4a/ARF at 9p21, which is lost frequently in familial and occasionally in somatic CMM.