Skin cancer prevention: a review of current topical options complementary to sunscreens.

The incidence of non-melanoma skin cancer (NMSC) is dramatically increasing worldwide, despite the increased use of improved sunscreens. In 2014, the Surgeon General estimated that 2.2-5.0 million people were treated annually for NMSC. As the number of newly diagnosed skin cancers continues to rise, there is a need for additional preventative measures beyond sunscreens. Several newer topical products that focus on boosting DNA repair, modulating DNA transcription, decreasing inflammation and selectively targeting precancerous cells may play an important role in future skin cancer prevention.

How to capture patients' concerns and related changes: comparing the MYCaW questionnaire, semi-structured interview and a priority list of outcome areas.

OBJECTIVES: To compare the capacity of the MYCaW questionnaire, a priority list of concerns covered by validated questionnaires, and semi-structured interviews to identify patients' personalized concerns and related changes. DESIGN: In a pragmatic trial on the effectiveness of energy healing as rehabilitation after colorectal cancer, a sub-sample of 31 participants completed the MYCaW questionnaire and the priority list and were interviewed before, during and after the treatment period. SETTING: Treatments were provided in healers' clinics in Denmark. MAIN OUTCOME MEASURES: For each participant convergences and divergences of the outcome measures are identified, and strengths and weaknesses of the three methods in regard to capturing personalized concerns and changes are discussed. RESULTS: Three patterns were identified: (1) in the intervention groups concerns stated in MYCaW were adjusted after experience with the treatment, while concerns stated in interviews and the priority list remained stable throughout the study; (2) emotional concerns were reported more often in interviews than in MYCaW, physical concerns were predominant in MYCaW, and quality of life was marked as a primary concern most frequently on the priority list; (3) participants reported greater improvement in interviews than in MYCaW. CONCLUSIONS: Relevant concerns in the MYCaW questionnaire seem to require that participants are well acquainted with the treatment under study. The priority list directs participants to particular areas of concerns and markings are stable. Interviews are well suited to disclose concerns regarding sensitive issues, e.g. anxiety of relapse, and experiences of subtle, non-specific changes.

Clodronate exerts an anabolic effect on articular chondrocytes mediated through the purinergic receptor pathway.

OBJECTIVE: Bisphosphonates are commonly used anti-osteoporotic drugs which have controversial effects on joint diseases including osteoarthritis. Certain bisphosphonates have been shown to have anabolic effects on cartilage which could have important ramifications for their proposed effects in vivo; however, the underlying mechanisms are poorly understood. Thus, the purpose of this study was to characterize the effects of clodronate on primary articular chondrocyte metabolism and to determine the underlying signaling pathways responsible. DESIGN: The effects of clodronate and pamidronate on extracellular matrix (ECM) biosynthesis, accumulation and MMP-13 activity were observed in high density, 3D cultures of bovine articular chondrocytes for up to 4 weeks were evaluated. Mechanisms were delineated by measuring intracellular Ca(2+) signaling and the effects of pharmacologic inhibition of the purinergic receptor pathway. RESULTS: Clodronate (100 µM) induced an anabolic effect (increased biosynthesis by 13-14%) which resulted in an 89-90% increase in ECM accumulation after 4 weeks of culture and without an associated effect on matrix turn-over. Stimulation by clodronate resulted in a 3.3-fold increase in Ca(2+) signaling and pharmacological inhibitor experiments suggested that the anabolic effects exerted by clodronate are transduced through the purinergic receptor pathway. CONCLUSIONS: These findings support the previous notion that certain bisphosphonates may be useful as adjunctive therapies to potentially ameliorate progression of cartilage degeneration and improve arthritis management.

Mutations in a new gene, encoding a zinc-finger protein, cause tricho-rhino-phalangeal syndrome type I.

Tricho-rhino-phalangeal syndrome type I (TRPS I, MIM 190350) is a malformation syndrome characterized by craniofacial and skeletal abnormalities and is inherited in an autosomal dominant manner. TRPS I patients have sparse scalp hair, a bulbous tip of the nose, a long flat philtrum, a thin upper vermilion border and protruding ears. Skeletal abnormalities include cone-shaped epiphyses at the phalanges, hip malformations and short stature. We assigned TRPS1 to human chromosome 8q24. It maps proximal of EXT1, which is affected in a subgroup of patients with multiple cartilaginous exostoses and deleted in all patients with TRPS type II (TRPS II, or Langer-Giedion syndrome, MIM 150230; ref.2-5). We have positionally cloned a gene that spans the chromosomal breakpoint of two patients with TRPS I and is deleted in five patients with TRPS I and an interstitial deletion. Northern-blot analyses revealed transcripts of 7 and 10.5 kb. TRPS1has seven exons and an ORF of 3,843 bp. The predicted protein sequence has two potential nuclear localization signals and an unusual combination of different zinc-finger motifs, including IKAROS-like and GATA-binding sequences. We identified six different nonsense mutations in ten unrelated patients. Our findings suggest that haploinsufficiency for this putative transcription factor causes TRPS I.

Use of a digital hearing aid with directional microphones in school-aged children.

The efficacy of a digital hearing aid with a directional microphone was examined in a school-aged population. Twenty children (9 with a mild-to-moderately-severe hearing loss and 11 with a moderate-to-severe hearing loss) between 7 1/2 and 13 2/3 years of age wore the study hearing aids binaurally for 30 days prior to the evaluation. The testing protocol included speech recognition tests using the CID W-22 word lists presented at 72 dB SPL, 65 dB SPL, and 52 dB SPL (at 0 degrees azimuth) in the presence of a 65 dB SPL party noise (180 degrees azimuth). Subjective rating of hearing aid efficacy in the classroom was examined using the Listening Inventory For Education (LIFE) questionnaire. Parental impression on hearing aid efficacy was also collected at the end of the study. The results showed improved speech recognition in noise with the digital directional hearing aid at all presentation levels. Preference for the digital directional hearing aids over the subjects' own omnidirectional analog hearing aids was also seen on the LIFE questionnaire and parental impression. The degree of hearing loss did not seem to have affected the benefits offered by the digital directional hearing aids. These results were compared to results from other studies on the use of directional microphones in hearing aids.

High-resolution transcriptional analysis of the symbiotic plasmid of Rhizobium sp. NGR234.

Most of the bacterial genes involved in nodulation of legumes (nod, nol and noe ) as well as nitrogen fixation (nif and fix ) are carried on pNGR234a, the 536 kb symbiotic plasmid (pSym) of the broad-host-range Rhizobium sp. NGR234. Putative transcription regulators comprise 24 of the predicted 416 open reading frames (ORFs) contained on this replicon. Computational analyses identified 19 nod boxes and 16 conserved NifA-sigma54 regulatory sequences, which are thought to co-ordinate the expression of nodulation and nitrogen fixation genes respectively. To analyse transcription of all putative ORFs, the nucleotide sequence of pNGR234a was divided into 441 segments designed to represent all coding and intergenic regions. Each of these segments was amplified by polymerase chain reactions, transferred to filters and probed with radioactively labelled RNA. RNA was extracted from bacterial cultures grown under various experimental conditions, as well as from bacteroids of determinate and indeterminate nodules. Generally, genes involved in the synthesis of Nod factors (e.g. the three hsn loci) were induced rapidly after the addition of flavonoids, whereas others thought to act within the plant (e.g. those encoding the type III secretion system) responded more slowly. Many insertion (IS) and transposon (Tn)-like sequences were expressed strongly under all conditions tested, while a number of loci other than those known to encode nod, noe, nol, nif and fix genes were also transcribed in nodules. Many more diverse transcripts were found in bacteroids of determinate as opposed to indeterminate nodules.

Mutations in the zebrafish unmask shared regulatory pathways controlling the development of catecholaminergic neurons.

The mechanism by which pluripotent progenitors give rise to distinct classes of mature neurons in vertebrates is not well understood. To address this issue we undertook a genetic screen for mutations which affect the commitment and differentiation of catecholaminergic (CA) [dopaminergic (DA), noradrenergic (NA), and adrenergic] neurons in the zebrafish, Danio rerio. The identified mutations constitute five complementation groups. motionless and foggy affect the number and differentiation state of hypothalamic DA, telencephalic DA, retinal DA, locus coeruleus (LC) NA, and sympathetic NA neurons. The too few mutation leads to a specific reduction in the number of hypothalamic DA neurons. no soul lacks arch-associated NA cells and has defects in pharyngeal arches, and soulless lacks both arch-associated and LC cell groups. Our analyses suggest that the genes defined by these mutations regulate different steps in the differentiation of multipotent CA progenitors. They further reveal an underlying universal mechanism for the control of CA cell fates, which involve combinatorial usage of regulatory genes.

An L-type calcium-channel gene mutated in incomplete X-linked congenital stationary night blindness.

The locus for the incomplete form of X-linked congenital stationary night blindness (CSNB2) maps to a 1.1-Mb region in Xp11.23 between markers DXS722 and DXS255. We identified a retina-specific calcium channel alpha1-subunit gene (CACNA1F) in this region, consisting of 48 exons encoding 1966 amino acids and showing high homology to L-type calcium channel alpha1-subunits. Mutation analysis in 13 families with CSNB2 revealed nine different mutations in 10 families, including three nonsense and one frameshift mutation. These data indicate that aberrations in a voltage-gated calcium channel, presumably causing a decrease in neurotransmitter release from photoreceptor presynaptic terminals, are a frequent cause of CSNB2.

Effect of moderate bone hyperthermia on cell viability and mechanical function.

Extracorporeal hyperthermia treatment of bone followed by its reimplantation may be an optional treatment of bone tumors. In this study, the authors examined the minimal hyperthermic condition in which complete eradication of all viable cells in rat bone can be achieved and the mechanical effect of this treatment on the tested bone. When the results were evaluated histologically by special lactate dehydrogenase activity staining, it was found that complete bone cell death occurred after 30 minutes of heating at 60 degrees C. Cartilage cells, including those of the epiphysis, were more resistant to thermal damage. When the ability of the specimens to proliferate in cell cultures was tested, no growth was observed after heating at temperatures of 50 degrees C or greater. The mechanical stiffness tested in the Instron machine showed decreased bone stiffness at 70 degrees C but no change in the breaking load of the bones. Controlled hyperthermia's ability to eradicate viable cells without significant damage to the mechanical properties may have clinical relevance in limb salvage tumor surgery.

Molecular basis of symbiosis between Rhizobium and legumes.

Access to mineral nitrogen often limits plant growth, and so symbiotic relationships have evolved between plants and a variety of nitrogen-fixing organisms. These associations are responsible for reducing 120 million tonnes of atmospheric nitrogen to ammonia each year. In agriculture, independence from nitrogenous fertilizers expands crop production and minimizes pollution of water tables, lakes and rivers. Here we present the complete nucleotide sequence and gene complement of the plasmid from Rhizobium sp. NGR234 that endows the bacterium with the ability to associate symbiotically with leguminous plants. In conjunction with transcriptional analyses, these data demonstrate the presence of new symbiotic loci and signalling mechanisms. The sequence and organization of genes involved in replication and conjugal transfer are similar to those of Agrobacterium, suggesting a recent lateral transfer of genetic information.

Urinary incontinence in the elderly. Often simple to treat when properly evaluated.

Urinary incontinence is a prevalent problem in the elderly, and its medical, social, and economic costs are significant. Incontinence may be transient or long-standing; reversible causes must be ruled out. Thorough history taking, a targeted physical examination, and simple office tests usually lead to a diagnosis. When the type of incontinence is known, appropriate treatment may bring improvement in symptoms or a return to continence. Clinicians and patients alike benefit from the realization that urinary incontinence is a treatable problem.

Extension of incomplete cDNAs (ESTs) by biotin/streptavidin-mediated walking using the polymerase chain reaction.

In the last 2 years thousands of new partial cDNAs or expressed sequence tags (ESTs) have been identified by single pass sequencing methods. It is expected that this number will further increase in order to help to isolate all human genes. However, the scientific value of partial cDNA fragments is limited unless they are used as tools for isolating and sequencing their full length parent molecules. Conventional library screening methods are tedious and not very effective in achieving this goal. We present a modified PCR technique which allows rapid isolation of the ends of partial cDNA fragments in vitro using a biotin/streptavidin capture procedure. Our method has several advantages over the RACE technique, is very specific, and allows to frequently sequence the final product directly without subcloning. We also show that cDNA walks can be obtained from partial sequences as short as 26 bp.

Formulation, nutritive value and sensory evaluation of a new weaning food based on sweet corn (Nutrimaiz) dehydrated pulp.

The objective of the present work was to develop a formulation for complementary infant and child feeding employing linear programing as a mathematical model for optimization. High lysine/high tryptophan sweet corn pulp in the dehydrated form was used as the main ingredient. The restrictions imposed on the model were nutrient requirements, adequate protein/energy ratio and minimum cost. The formula derived by the computer (FC) matched the amino acid requirements, the protein/energy ratio (NDPCal%) and was rated high in laboratory tests in terms of sensory qualities. The cost determined for this formula was competitive in relation to commercial products used for the same purpose. Formula A, which contained 5% more sweet corn pulp and 10% less whole powdered milk, did not differ in nutritional, sensorial and functional properties from the formula FC and was chosen for the field acceptability trial because of its lower cost. Formula A had protein efficiency ratio and Biological Value similar to casein for the rat but protein digestibility and net protein utilization were statistically lower (p less than 0.05) for formula A than for casein. Acceptability tested on children who were 8-18 months of age ranged from 80-90%, average value 87%.

Arthritis associated with calcium oxalate crystals in an anephric patient treated with peritoneal dialysis.

We report a case of calcium oxalate arthropathy in a woman undergoing intermittent peritoneal dialysis who was not receiving pharmacologic doses of ascorbic acid. She developed acute arthritis, with calcium oxalate crystals in Heberden's and Bouchard's nodes, a phenomenon previously described in gout. Intermittent peritoneal dialysis may be less efficient than hemodialysis in clearing oxalate, and physicians should now consider calcium oxalate-associated arthritis in patients undergoing peritoneal dialysis who are not receiving large doses of ascorbic acid.

Fluorometholone acetate: clinical evaluation in the treatment of external ocular inflammation.

Separate, randomized, double-masked clinical studies were conducted to determine the therapeutic efficacy of fluorometholone acetate, a new ophthalmic corticosteroid formulation, in suppressing external ocular inflammation (conjunctivitis, episcleritis, scleritis). Fluorometholone acetate 0.1% was compared to fluorometholone 0.1%, and the acetate formulation was found to be significantly (p = 0.03) more effective. Fluorometholone acetate 0.1% also was compared to prednisolone acetate 1.0%; there was no significant difference (p = 0.49) between these two corticosteroids in their ability to suppress external ocular inflammation. It appears that alteration of fluorometholone from its alcohol base to its acetate derivative changes the drug from a moderately effective to a highly effective anti-inflammatory agent.

Moderate grade astrocytoma presenting in a 4-month-old child with a family history of von Recklinghausen's neurofibromatosis spanning four generations: a case report.

Intracranial gliomas are found in association with von Recklinghausen's neurofibromatosis. However, few truly neonatal lesions have been identified and studied. This case report concerns a 4-month-old child who was found to have a massive thalamic glioma of moderate grade. Four paternal generations had suffered from different manifestations of this transmissible autosomal-dominant (Ad) phakomatosis.

[Polyacrylic bone cement with added erythromycin and colistin. In vitro studies on bacteriologic activity and diffusion properties]. / Polyacryl-Knochenzement angereichert mit Erythromycin und Colistin

Erythromycin and colistin are not antagonists and have the property of inhibiting the growth of a large number of aerobic and anaerobic organisms. When they were worked into Chirurgischen Knochenzement Simplex P Radiopaque, the growth of 98% of all anaerobic and aerobic test organisms was inhibited. Separately conducted investigations have shown that each antibiotic can diffuse out of polymerized cement and that the concentration of each antibiotic is far above the minimal inhibitory concentration (MIC) of 96% of the organisms. Consequently, in our opinion it would be of benefit to test the Chirurgische Knochenzement Simplex P Radiopaque with erythromycin and colistin clinically.