An ultrasonographic monitoring of skin condition in patients receiving radiotherapy for head and neck cancers

Radiodermatitis is one of the commonest side effects of radiotherapy. They are usually assessed by semi‐quantitative clinical scores, which are not validated and may be subject to inter‐observer variability. A few previous studies suggested that high‐frequency ultrasonography (HF‐USG) is useful in the assessment of the acute phase of radiation dermatitis in breast cancer patients. (a) To monitor skin changes by HF‐USG during the course of radiotherapy due to head and neck cancers, and (b) to determine whether there is any connection between skin sonograms and the skin scoring criteria. This prospective, observational study includes patients diagnosed with head and neck cancers, treated with radiotherapy or concomitant chemoradiation. The final analysis includes six patients. In every patient, the HF‐USG as well as dermatological assessment (target lesion score—TLS and CACE v. 4.0) were performed 4×: before, in the middle, day after, and 3 months after radiotherapy. There were significant differences between non‐irradiated skin thickness and thickness of skin with clinically obvious radiodermatitis (TLS grade 1‐4; P < .0001), as well as between irradiated, unchanged skin thickness (TLS grade 0) and thickness of skin with clinically obvious radiodermatitis (TLS grade 1‐4; P = .0002). There was no significant difference between non‐irradiated and irradiated, unchanged skin thickness (TLS grade 0; P = .9318). In four patients, we demonstrated subepidermal low echogenic band (SLEB). HF‐USG can be useful tool to noninvasive and objective assessment of skin changes during radiotherapy.     

The expectations and realities of nutrigenomic testing in australia: A qualitative study

BackgroundConsumer genomic testing for nutrition and wellness, (nutritional genomics), is becoming increasingly popular. Concurrently, health‐care practitioners (HPs) working in private practice (including doctors interested in integrative medicine, private genetic counsellors, pharmacists, dieticians, naturopaths and nutritionists) are involved as test facilitators or interpreters.ObjectiveTo explore Australian consumers’ and HPs’ experiences with nutrigenomic testing.MethodSemi‐structured in‐depth interviews were conducted using predominantly purposive sampling. The two data sets were analysed individually, then combined, using a constant comparative, thematic approach.ResultsOverall, 45 interviews were conducted with consumers (n = 18) and HPs (n = 27). Many of the consumer interviewees experienced chronic ill‐health. Nutrigenomic testing was perceived as empowering and a source of hope for answers. While most made changes to their diet/supplements post‐test, self‐reported health improvements were small. A positive relationship with their HP appeared to minimize disappointment. HPs’ adoption and views of nutrigenomic testing varied. Those enthusiastic about testing saw the possibilities it could offer. However, many felt nutrigenomic testing was not the only ‘tool’ to utilize when offering health care.DiscussionThis research highlights the important role HPs play in consumers’ experiences of nutrigenomics. The varied practice suggests relevant HPs require upskilling in this area to at least support their patients/clients, even if nutrigenomic testing is not part of their practice.Patient or public contributionAdvisory group included patient/public group representatives who informed study design; focus group participants gave feedback on the survey from which consumer interviewees were sourced. This informed the HP data set design. Interviewees from HP data set assisted with snowball sampling.     

Rapid reduction of extremely high kappa free light chains in a patient with myeloma cast nephropathy

This report describes a patient with light chain myeloma and acute renal injury. Serum kappa free light chain (FLC) was extremely elevated, >33,000 mg/dL. Treatment with therapeutic plasma exchange (TPE) started day 2 for biopsy‐confirmed cast nephropathy. Bortezomib‐containing chemotherapy was initiated on day 5, and hemodialysis for tumor lysis syndrome on day 7. TPE alone decreased kappa FLC >70% by day 5, indicating direct FLC removal was successful in this patient. A total of 25 TPE procedures were performed in a 31‐day hospitalization. Hemodialysis was discontinued after 3 months, and the patient's renal function and kappa FLC remain stable. Although the use of TPE for FLC removal is controversial, recent evidence supports its use as adjuvant therapy for acute renal injury secondary to myeloma cast nephropathy. TPE can be effective for rapidly reducing FLC; however, several TPE procedures might be required to reduce the risk of hemodialysis dependency.     

17beta-hydroxysteroid dehydrogenase type 7--an ancient 3-ketosteroid reductase of cholesterogenesis

17beta-hydroxysteroid dehydrogenase type 7 (17beta-HSD7) is a novel estrogenic hydroxysteroid dehydrogenase from mammals. We modeled the three-dimensional structure of human 17beta-HSD7, analyzed the phylogeny of 17beta-HSD7 homologues and determined its expression pattern by in silico Northern blotting. Predominant expression is found not only in reproductive tissues (breast, ovary, placenta) but also in liver and developing brain, principal sites of cholesterol synthesis. The substrate binding pocket is opening towards a conserved membrane-associated helix, which is indicative for a conversion of a membrane component. 17beta-HSD7 shows significant homology to a yeast 3-ketosteroid reductase (ERG27) involved in ergosterol biosynthesis. Our results lead to the conclusion that 17beta-HSD7 is not only involved in estradiol production but plays another (and possibly more important) role as a 3-ketosteroid reductase in cholesterogenesis. This agrees with the striking absence of 17beta-HSD7 homologues in the complete genomes of Drosophila and C. elegans, which are both auxotrophic for cholesterol.     

Prognostic value of the PIK3CA,AKT, and PTEN mutations in oral squamous cell carcinoma: literature review

Over 260,000 (2013) new oral squamous cell carcinoma (OSCC) cases are reported annually worldwide. Despite development in OSCC management, the outcome is still unsatisfactory. Identification of new molecular markers may be of use in prevention, prognosis, and choice of an appropriate therapy. The intracellular molecular signalling pathway of phosphatidyl-inositol-3-kinase is involved in the process of cell growth, differentiation, migration, and survival. The main components of this pathway: PIK3CA (phosphatidylinositol-4,5-bisphosphate-3-kinase catalytic subunit α), PTEN (phosphatase and tensin homologue deleted on chromosome 10), and AKT (serine-threonine kinase) are potential objects of research when introducing new therapeutic agents. The aim of this paper is to evaluate the PIK3CA, PTEN, and AKT gene mutations as prognostic factors in OSCC and to describe their role in aggressive disease progression. This is crucial for oral cancer biology understanding and for indicating which direction new clinical treatments should take.     

The oxytocin/vasopressin receptor family has at least five members in the gnathostome lineage, inclucing two distinct V2 subtypes

The vertebrate oxytocin and vasopressin receptors form a family of G-protein-coupled receptors (GPCRs) that mediate a large variety of functions, including social behavior and the regulation of blood pressure, water balance and reproduction. In mammals four family members have been identified, three of which respond to vasopressin (VP) named V1A, V1B and V2, and one of which is activated by oxytocin (OT), called the OT receptor. Four receptors have been identified in chicken as well, but these have received different names. Until recently only V1-type receptors have been described in several species of teleost fishes. We have identified family members in several gnathostome genomes and performed phylogenetic analyses to classify OT/VP-receptors across species and determine orthology relationships. Our phylogenetic tree identifies five distinct ancestral gnathostome receptor subtypes in the OT/VP receptor family: V1A, V1B, V2A, V2B and OT receptors. The existence of distinct V2A and V2B receptors has not been previously recognized. We have found these two subtypes in all examined teleost genomes as well as in available frog and lizard genomes and conclude that the V2A-type is orthologous to mammalian V2 receptors whereas the V2B-type is orthologous to avian V2 receptors. Some teleost fishes have acquired additional and more recent gene duplicates with up to eight receptor family members. Thus, this analysis reveals an unprecedented complexity in the gnathostome repertoire of OT/VP receptors, opening interesting research avenues regarding functions such as regulation of water balance, reproduction and behavior, particularly in reptiles, amphibians, teleost fishes and cartilaginous fishes.     

Alcohol-induced metabolomic differences in humans

Alcohol consumption is one of the world''s major risk factors for disease development. But underlying mechanisms by which moderate-to-heavy alcohol intake causes damage are poorly understood and biomarkers are sub-optimal. Here, we investigated metabolite concentration differences in relation to alcohol intake in 2090 individuals of the KORA F4 and replicated results in 261 KORA F3 and up to 629 females of the TwinsUK adult bioresource. Using logistic regression analysis adjusted for age, body mass index, smoking, high-density lipoproteins and triglycerides, we identified 40/18 significant metabolites in males/females with P-values <3.8E−04 (Bonferroni corrected) that differed in concentrations between moderate-to-heavy drinkers (MHD) and light drinkers (LD) in the KORA F4 study. We further identified specific profiles of the 10/5 metabolites in males/females that clearly separated LD from MHD in the KORA F4 cohort. For those metabolites, the respective area under the receiver operating characteristic curves were 0.812/0.679, respectively, thus providing moderate-to-high sensitivity and specificity for the discrimination of LD to MHD. A number of alcohol-related metabolites could be replicated in the KORA F3 and TwinsUK studies. Our data suggests that metabolomic profiles based on diacylphosphatidylcholines, lysophosphatidylcholines, ether lipids and sphingolipids form a new class of biomarkers for excess alcohol intake and have potential for future epidemiological and clinical studies.     

Efficient migration of dendritic cells toward lymph node chemokines and induction of T(H)1 responses require maturation stimulus and apoptotic cell interaction

Dendritic cells (DCs) have the unique ability to initiate primary immune responses, and they can be conditioned for vaccinal purposes to present antigens after the engulfment of apoptotic cells. To recruit the rare antigen-specific naive T cells, DCs require a maturation step and subsequent transport toward lymph node (LN). To date, prostaglandin E2 (PGE2) is the best-characterized compound inducing this LN-directed migration in vitro, but PGE2 may skew the immune responses in a T(H)2 direction. We demonstrate here that on incubation with apoptotic tumor cells and tumor necrosis factor-alpha (TNF-alpha) or lipopolysaccharide (LPS), human monocyte-derived DCs become fully mature and acquire high migratory capacities toward LN-directing chemokines. The migration of TNF-alpha-treated DCs occurs only after cotreatment with apoptotic cells but not with necrotic cells. DC migration requires CD36 expression and incubation with apoptotic cells in the presence of heat-labile serum components. Moreover, on treatment with apoptotic cells and LPS, the migrating DCs are able to recruit naive T cells to generate T(H)1 immune responses. Our results show that the cotreatment of DCs with apoptotic tumor cells and inflammatory signals is promising for the design of an antitumoral DC-based vaccine.