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A large body of evidence suggests that dietary supplementation with omega-3 fatty acids may ameliorate depressed mood. The magnitude of the effect varies between studies, however, ranging from none at all to being of clinical significance. Given that substantial comorbidity occurs between mood and anxiety disorders, suggesting that they have one or more pathophysiological mechanisms in common, we hypothesized that omega-3 fatty acids may be acting primarily to reduce anxiety rather than depression per se, a possibility which could underlie their variable effects on mood. To test this hypothesis rats were fed for 8 weeks with diets containing one of three types of omega-3 fatty acids, alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid, as well as a low omega-3 fatty acid control diet. Although brain omega-3 fatty acid concentrations were altered by dietary supplementation with eicospentaenoic acid and docosahexaenoic acid, no significant change in anxiety related behaviors were observed compared to the control group as assessed by the elevated-plus maze test. Our data therefore do not support an anxiolytic effect of omega-3 fatty acids and suggest that any effect of these lipids on mood likely occurs by a mechanism unrelated to reducing anxiety., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Reactive oxygen species react with unsaturated fatty acids to form a variety of metabolites including aldehydes. Many aldehydes are volatile enough to be detected in headspace gases of blood or cultured cells and in exhaled breath, in particular propanal and hexanal which are derived from omega-3 and omega-6 polyunsaturated fatty acids, respectively. Aldehydes are therefore potential non-invasive biomarkers of oxidative stress and of various diseases in which oxidative stress is thought to play a role including cancer, cardiovascular disease and diabetes. It is unclear, however, how changes in the abundance of the fatty acid precursors, for example by altered dietary intake, affect aldehyde concentrations. We therefore fed male Wistar rats diets supplemented with either palm oil or a combination of palm oil plus an n-3 fatty acid (alpha-linolenic, eicosapentaenoic, or docosahexaenoic acids) for 4 weeks. Fatty acid analysis revealed large changes in the abundance of both n-3 and n-6 fatty acids in the liver with smaller changes observed in the brain. Despite the altered fatty acid abundance, headspace concentrations of C1-C8 aldehydes, and tissue concentrations of thiobarbituric acid reactive substances, did not differ between the 4 dietary groups. Our data suggest that tissue aldehyde concentrations are independent of fatty acid abundance, and further support their use as volatile biomarkers of oxidative stress.

Background: Mutations in various desmosomal proteins were shown to cause inherited forms of cardiomyopathy. Carvajal syndrome (Online Mendelian Inheritance in Man [OMIM] 605676) is characterized by the association of dilated cardiomyopathy, striate palmoplantar keratoderma, and woolly hair. It is caused by homozygous as well as heterozygous mutations in DSP, which encodes the desmosomal plaque protein desmoplakin. An overlapping cardiocutaneous phenotype was also described with homozygous mutations in genes encoding two other desmosomal proteins; plakoglobin (Naxos disease; OMIM 601214) and desmocollin-2 (OMIM 610476)., Methods: We performed clinical and molecular workups in two consanguineous Arab Palestinian families manifesting an autosomal recessive pattern of inheritance of the above mentioned clinical findings. Whole exome sequencing was employed in the search for the causing mutation., Results: Affected family members suffered from biventricular involvement and arrhythmogenic right ventricular dysplasia based on echocardiography and magnetic resonance imaging. One patient who underwent implantation of an implantable cardioverter-defibrillator (ICD) is still alive at the age of 59 years. Whole exome sequencing revealed two novel homozygous mutations in DSP, each affecting one family., Conclusions: The association of woolly hair with palmoplantar keratoderma in a child should lead to a cardiac workup in the search for those at increased risk for sudden cardiac death. Early diagnosis and ICD implantation may be lifesaving. Whole exome sequencing should be utilized for rapid genetic analysis since the cardiocutaneous phenotype may result from mutations in one of several genes., (© 2015 Wiley Periodicals, Inc.)

Monophasic Co-Al-CO3-like layered double hydroxides has been prepared by the coprecipitation method. It has been characterised by Rietveld refinement of the X-ray powder diffraction pattern, DTA-TGA, infrared and Raman spectroscopies. Its structure is trigonal, R3̅m with cell parameters a=0.3061(4) nm and c=2.252 (3) nm. The decomposition of this hydrotalcite-like structure on heating up to 800 °C yields to a single phase spinel oxide. Besides, infrared and Raman spectroscopies showed the presence of spinel-like domains. The results of Rietveld refinement have revealed that this compound has the Fd3̅m space group (a=0.8088(4) nm), with crystallographic formula [Co(II)0.75Al0.25](8a)[Co(II)0.252Co(III)0.77Al0.98](16d)O4, which is of the general formula Co1.77Al1.23O4. This structure is also validated by the charge distribution (CD) analysis., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: H syndrome is an autosomal recessive histiocytosis with multisystemic involvement caused by mutations in the SLC29A3 gene. The term H syndrome was coined to denote the major clinical findings which include hyperpigmentation, hypertrichosis, hearing loss, hepatosplenomegaly, hypogonadism, hyperglycemia/diabetes mellitus and hallux valgus/flexion contractures. Almost 100 individuals affected with this disorder have been reported, however, a thorough evaluation of the ophthalmologic features of H syndrome has not yet been performed., Materials and Methods: Ophthalmic examination of a 50-year-old male with H syndrome. Mutation analysis of SLC29A3 was also performed in this patient., Results: Ophthalmic findings included; shallow orbits with exorbitism, bilateral pterygium, limbal thickening, corneal arcus and cortical cataract. We also review ophthalmologic findings in previously reported H syndrome patients., Conclusions: The presence of dilated lateral scleral vessels, corneal arcus and shallow orbits should raise the suspicion of H syndrome, especially when seen in young age.

Deficiency of interleukin-36 (IL-36) receptor antagonist (DITRA; OMIM 614204) is a rare autoinflammatory disorder characterized by periodic fever associated with a generalized erythematous and pustular skin rash. A 6-year-old Arab-Palestinian boy presented with a history of periodic fever and unremitting, erythematous, scaly skin rash accompanied by widespread pustules that had been present since the age of one month. The patient's skin lesions were compatible with generalized pustular psoriasis. Sequence analysis revealed a homozygous nonsense mutation, c.28C>T (p.Arg10X) in the IL36RN gene. The patient improved with oral methotrexate in combination with oral and topical corticosteroids. The molecular basis for DITRA has only recently been identified, and the mutation spectrum for this disorder in many populations is still obscure. This paper reports the presence of the c.28C>T mutation in an Arab-Palestinian patient and thus represents the first description of this mutation in a non-Japanese subject., (© 2014 The International Society of Dermatology.)

Background: The combination of palmoplantar keratoderma and woolly hair is uncommon and reported as part of Naxos and Carvajal syndromes, both caused by mutations in desmosomal proteins and associated with cardiomyopathy. We describe two large consanguineous families with autosomal-recessive palmoplantar keratoderma and woolly hair, without cardiomyopathy and with no mutations in any known culprit gene. The aim of this study was to find the mutated gene in these families., Methods and Results: Using whole-exome sequencing, we identified a homozygous missense c.2009C>T mutation in KANK2 in the patients (p.Ala670Val). KANK2 encodes the steroid receptor coactivator (SRC)-interacting protein (SIP), an ankyrin repeat containing protein, which sequesters SRCs in the cytoplasm and controls transcription activation of steroid receptors, among others, also of the vitamin D receptor (VDR). The mutation in KANK2 is predicted to abolish the sequestering abilities of SIP. Indeed, vitamin D-induced transactivation was increased in patient's keratinocytes. Furthermore, SRC-2 and SRC-3, coactivators of VDR and important components of epidermal differentiation, are localised to the nucleus of epidermal basal cells in patients, in contrast to the cytoplasmic distribution in the heterozygous control., Conclusions: These findings provide evidence that keratoderma and woolly hair can be caused by a non-desmosomal mechanism and further underline the importance of VDR for normal hair and skin phenotypes., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: H syndrome is an autosomal recessive genodermatosis with multisystem involvement caused by mutations in SLC29A3., Objective: We sought to investigate the clinical and molecular findings in 79 patients with this disorder., Methods: A total of 79 patients were included, of which 13 are newly reported cases. Because of the phenotypic similarity and molecular overlap with H syndrome, we included 18 patients with allelic disorders. For 31 patients described by others, data were gathered from the medical literature., Results: The most common clinical features (>45% of patients) were hyperpigmentation, phalangeal flexion contractures, hearing loss, and short stature. Insulin-dependent diabetes mellitus and lymphadenopathy mimicking Rosai-Dorfman disease were each found in approximately 20%. Additional systemic features were described in less than 15% of cases. Marked interfamilial and intrafamilial clinical variability exists. Twenty mutations have been identified in SLC29A3, with no genotype-phenotype correlation., Limitations: In the 31 patients described by others, data were collected from the medical literature., Conclusions: H syndrome is a multisystemic disease with clinical variability. Consequently, all SLC29A3-related diseases should be considered a single entity. Recognition of the pleomorphic nature of H syndrome is important for diagnosis of additional patients., (Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Objective: Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE syndrome) is an autoinflammatory syndrome recently described in children. We undertook this study to investigate the clinical phenotype, genetic cause, and immune dysregulation in 9 CANDLE syndrome patients., Methods: Genomic DNA from all patients was screened for mutations in PSMB8 (proteasome subunit β type 8). Cytokine levels were measured in sera from 3 patients. Skin biopsy samples were evaluated by immunohistochemistry, and blood microarray profile and STAT-1 phosphorylation were assessed in 4 patients and 3 patients, respectively., Results: One patient was homozygous for a novel nonsense mutation in PSMB8 (c.405C>A), suggesting a protein truncation; 4 patients were homozygous and 2 were heterozygous for a previously reported missense mutation (c.224C>T); and 1 patient showed no mutation. None of these sequence changes was observed in chromosomes from 750 healthy controls. Of the 4 patients with the same mutation, only 2 shared the same haplotype, indicating a mutational hot spot. PSMB8 mutation-positive and -negative patients expressed high levels of interferon-γ (IFNγ)-inducible protein 10. Levels of monocyte chemotactic protein 1, interleukin-6 (IL-6), and IL-1 receptor antagonist were moderately elevated. Microarray profiles and monocyte STAT-1 activation suggested a unique IFN signaling signature, unlike in other autoinflammatory disorders., Conclusion: CANDLE syndrome is caused by mutations in PSMB8, a gene recently reported to cause "JMP" syndrome (joint contractures, muscle atrophy, microcytic anemia, and panniculitis-induced childhood-onset lipodystrophy) in adults. We extend the clinical and pathogenic description of this novel autoinflammatory syndrome, thereby expanding the clinical and genetic disease spectrum of PSMB8-associated disorders. IFN may be a key mediator of the inflammatory response and may present a therapeutic target., (Copyright © 2012 by the American College of Rheumatology.)

Apocrine hidrocystoma is a benign cystic tumour. The head and neck region is the site of predilection; occurrence in the scalp is extremely rare. We report a rare case of giant apocrine hidrocystoma with an unusual presentation as scalp haematoma.

Polyamines are a class of aliphatic compounds which include putrescine, cadaverine, spermine and spermidine. They are involved in a variety of cellular processes and have been implicated in a number of different pathophysiological mechanisms. Polyamines are volatile compounds having a distinctive odour normally perceived as being unpleasant. The measurement of their abundance has, however, been restricted to compounds present in the aqueous phase. Using selected ion flow tube mass spectrometry (SIFT-MS) we have shown that the polyamines react with the ions H3O+, NO+ and O2+ to form distinctive product ions allowing their levels to be quantified in the vapour phase. The low volatility of spermine did not allow extensive analysis of this compound by SIFT-MS while the adherent properties of cadaverine and putrescine required the use of PTFE transfer lines and couplers. Our data suggested the presence of cadaverine and putrescine in both oral air and the headspace of putrefying bovine muscle, while product ions corresponding to putrescine and spermidine were found in the headspace of human semen. SIFT-MS therefore appears to be a practical means of measuring vapour-phase polyamine levels, having applications in biology, medicine and dentistry, and food science., (Copyright 2009 John Wiley & Sons, Ltd.)

Diagnosis of papillary thyroid carcinoma (PTC), in many but not all cases, is an easily achievable diagnosis with almost minimal interobservable variability between pathologists. However, some cases of PTC, particularly the follicular variant, are quite challenging and show wide interobservable variability even among expert thyroid pathologists. Since proper diagnosis of PTC is crucial as it affects patients' clinical management and prognosis, indications of PTC must be clearly apparent to be an objective rather than a subjective diagnosis. Unfortunately, to date, immunohistochemistry and molecular studies have failed to fully solve this problem. In this study, we assessed the protein expression and loss using antibodies against CD56 in normal follicular thyroid epithelium, follicular thyroid lesions, and follicular thyroid neoplasms in an attempt to evaluate its diagnostic value. A total of 185 cases were studied with tissues from 75 carcinomas (72 papillary, 2 follicular, 1 Hürthle cell) and 35 adenomas (32 follicular and 3 Hürthle cell) evaluated by immunohistochemistry for the expression of this marker. Non-neoplastic thyroids included 65 cases: nodular hyperplasia (n=25), thyrotoxic hyperplasia (Grave's disease) (n=5), lymphocytic thyroiditis (n=19), and Hashimoto's thyroiditis (n=6). Ten cases of normal thyroids from radical laryngectomies for laryngeal squamous cell carcinomas were also studied. The marker pattern and intensity of staining were scored. Positive expression of the markers in 10% or more of follicular epithelium within the tumor or lesional cells was considered positive. An expression of <10% was considered to be negative. Diffuse CD56 expression was consistently present in normal, lesional, and neoplastic follicular epithelium, except for PTC, including the follicular variant. We concluded that CD56 is of value to distinguish PTC from other thyroid follicular pathology/histology with a sensitivity of 100% and a specificity of 100%. We suggest that CD56 is extremely useful in the diagnosis of PTC, including the follicular variant, and to distinguish it from other follicular cell-derived thyroid tumors/lesions. Application of CD56 by a group of expert pathologists on a larger series of follicular thyroid neoplasms of uncertain malignant potentials may potentially provide an objective diagnostic tool.