Utility of histone H3K27me3 and H4K20me as diagnostic indicators of melanoma.

Histone posttranslational modifications (PTMs) have been shown to be dysregulated in multiple cancers including melanoma, and as they are abundant and easily detectable, they make ideal biomarkers. The aim of this study was to identify histone PTMs that could be potential biomarkers for melanoma diagnosis. Previously, we utilized mass spectrometry to identify histone PTMs that were dysregulated in matched melanoma cell lines and found two modifications, H3 lysine 27 trimethylation (histone H3K27me3) and H4 lysine 20 monomethylation (histone H4K20me), that were differentially expressed in the more aggressive compared to the less aggressive cell line. In this study, we performed immunohistochemistry on tissue microarrays containing 100 patient tissue spots; 18 benign nevi, 62 primary, and 20 metastatic melanoma tissues. We stained for histone H3K27me3 and histone H4K20me to ascertain whether these histone PTMs could be used to distinguish different stages of melanoma. Loss of histone H4K20me was observed in 66% of malignant patient tissues compared to 14% of benign nevi. A majority (79%) of benign nevi had low histone H3K27me3 staining, while 72% of malignant patient tissues showed either a complete loss or had strong histone H3K27me3 staining. When we analyzed the staining for both marks together, we found that we could identify 71% of the benign nevi and 89% of malignant melanomas. Histone H3K27me3 or histone H4K20me display differential expression patterns that can be used to distinguish benign nevi from melanoma; however, when considered together the diagnostic utility of these PTMs increased significantly. The work presented supports the use of combination immunohistochemistry of histone PTMs to increase accuracy and confidence in the diagnosis of melanoma.

Histone Modifications as Biomarkers for Immunotherapy.

Recent advances in immunotherapy have revolutionized the treatment of certain cancers. Some patients show a durable response to these immunotherapies, while others show little benefit or develop resistance. Identification of biomarkers to predict responsiveness will be helpful for informing treatment strategies; and would furthermore lead to the identification of molecular pathways dysregulated in nonresponding patients that could be targeted for therapeutic development. Pathways of epigenetic modification, such as histone posttranslational modifications (PTMs), have been shown to be dysregulated in certain cancer and immune cells. Histones are abundant cellular proteins readily assayed with high-throughput technologies, making them attractive targets as biomarkers. We explore promising advancements for using histone PTMs as immunotherapy responsiveness biomarkers in both cancer and immune cells, and provide a methodological workflow for assaying histone PTMs in relevant samples.

Recent advances in therapies for eating disorders.

Eating disorders are serious psychiatric illnesses with high rates of morbidity and mortality. Effective treatments have traditionally included behaviorally focused therapies as well as several medication strategies. Recent years have seen promising developments in these treatments, including additional support for family-based approaches for children and adolescents, new evidence for "third-wave" behavioral therapies, and new support for the use of lisdexamfetamine for binge eating disorder and olanzapine for anorexia nervosa. Case study and pilot data are beginning to show limited support for neuromodulatory interventions targeting brain regions thought to be involved in eating disorders. This review summarizes treatment developments over the last several years and points towards future directions for the field.

Current state of melanoma diagnosis and treatment.

Melanoma is the deadliest form of skin cancer. In the early stages, melanoma can be treated successfully with surgery alone and survival rates are high, but after metastasis survival rates drop significantly. Therefore, early and correct diagnosis is key for ensuring patients have the best possible prognosis. Melanoma misdiagnosis accounts for more pathology and dermatology malpractice claims than any cancer other than breast cancer, as an early misdiagnosis can significantly reduce a patient's chances of survival. As far as treatment for metastatic melanoma goes, there have been several new drugs developed over the last 10 years that have greatly improved the prognosis of patients with metastatic melanoma, however, a majority of patients do not show a lasting response to these treatments. Thus, new biomarkers and drug targets are needed to improve the accuracy of melanoma diagnosis and treatment. This article will discuss the major advancements of melanoma diagnosis and treatment from antiquity to the present day.

Leg Length Discrepancy: The Natural History (And What Do We Really Know).

BACKGROUND: The long-term effects of small limb length discrepancies have been poorly documented in the literature. References to low back pain, hip pathology, knee pathology, and foot problems abound in the popular literature. Health care providers frequently recommend the use of lifts for structural and functional limb length discrepancies, yet the natural history of limb length inequality as well as the effectiveness of treatments that may be recommended are obscure. The purpose of this paper is to document and evaluate the literature associated with small limb length discrepancies. METHODS: A search of the English literature was carried out using PubMed to identify papers dealing with the effects of limb length discrepancies. Papers reporting only expert opinion or case reports were excluded. RESULTS: Papers dealing with the natural history of limb length discrepancy as well as studies in which gait analysis was performed in patients with limb length discrepancy were identified. Only 10% of the population has exactly equal lower limb lengths. Approximately 90% of the population has a limb length discrepancy <1.0 cm. Hip and knee pathology is present in an increased number of patients with limb length discrepancies over 5 mm. Hip pathology is more often present in the long leg, knee pathology has been reported in various studies to be more common in either the long or short leg. Low back problems seem to be more common on the short side in patients with limb length discrepancies. A number of different compensatory mechanisms for limb length discrepancy have been identified during gait analysis. CONCLUSIONS: There seems to be a consensus that limb length discrepancies >2.0 cm are frequently a problem. There is some evidence that limb length discrepancies as little as 5 mm can lead to long-term pathology.

A Case of Self-Enucleation in an Incarcerated Patient: Case Report and Review of Literature.

Self-enucleation is a severe form of self-injurious behavior which presents as an ophthalmologic and psychiatric emergency. It is usually known to occur with untreated psychosis, however, there have been reports of self-enucleation across various psychopathologies. We review a case documenting self-enucleation in the forensic setting in a patient with an unusual presentation and cluster of psychotic symptoms. Literature was reviewed using PubMed/Medline databases with key terms: "forensic science," "forensic psychiatry," "auto-enucleation," "self-enucleation," "Oedipism," "self-harm." This case is unique as it offers an alternative presentation to those most commonly depicted in current literature, helps highlight the sparsity of literature depicting self-enucleation in the forensic setting, and stimulates discussion around various potential differential diagnoses, management strategies and complications of self-enucleation within the forensic setting. It is prudent to emphasize need for aggressive and collaborative treatment for the forensic population regardless of psychopathology, presentation, or propensity for secondary gain.

Single-pot extraction-analysis of dyed wool fibers with ionic liquids.

Analytical capabilities to identify dyes associated with structurally robust wool fibers would critically assist crime-scene and explosion-scene forensics. Nondestructive separation of dyes from wool, removal of contaminants, and dye analysis by MALDI- or ESI-MS, were achieved in a single-pot, ionic liquid-based method. Ionic liquids (ILs) that readily denature the wool α-keratin structure have been identified and are conducive to small volume, high-throughput analysis for accelerated threat-response times. Wool dyed with commercial or natural, plant-based dyes have unique signatures that allow classification and matching of samples and identification of dyestuffs. Wool released 0.005 mg of dye per mg of dyed wool into the IL, allowing for analysis of single-thread sample sizes. The IL + dye mixture promotes sufficient ionization in MALDI-MS: addition of common MALDI matrices does not improve analysis of anionic wool dyes. An inexpensive, commercially available tetrabutylphosponium chloride IL was discovered to be capable of denaturing wool and was determined to be the most effective for this readily fieldable method.