Vibrations produced during erbium:yttrium–aluminum–garnet laser irradiation

The purpose of this study was to evaluate vibrations induced by an erbium:yttrium–aluminum–garnet (Er:YAG) laser in the non-contact mode and compare the vibrations with different pulse durations and energy parameters. The experiment was conducted on an extracted tooth built up in silicone impression material. The vibrations were measured by piezoelectric accelerometer for a super-short pulse (SSP), a very short pulse (VSP), and a short pulse (SP) at a frequency of 5 Hz for 1 s. For VSP and SP, the energy parameters tested were 200 mJ, 300 mJ, and 400 mJ. Measurements were performed 15 times for each individual irradiation energy level. The highest values of vibrations were measured for SP (0.160 ± 0.04 m/s²), and the lowest were measured for VSP mode at the energy parameter 200 mJ (0.05 ± 0.02 m/s²). There was a statistically significant (P < 0.01) difference between the various laser pulse modes (SSP, VSP, SP) at different energy parameters. At energy levels of 300 mJ and 400 mJ, the least amount of vibration during cavity preparations with the non-contact Er:YAG laser was produced by SSP mode.     

p21/waf1 and smooth-muscle actin α expression in stromal fibroblasts of oral cancers

Background

Concerted alterations between stromal fibroblasts and neoplastic cells underline the carcinogenic process. Activation of alpha-smooth muscle actin (SMA) expression, a cytoskeleton protein normally expressed only in myoepithelial cells, is considered a landmark for the activation of stromal fibroblasts with little however being known regarding the mechanism governing the expression of SMA in the stroma.

Methods

We have evaluated by immunohistochemistry the expression of SMA in the stroma of oral malignant and pre-malignant lesions, in association with the expression of p53 and p21 tumor suppressors that were shown previously to be deregulated and/or mutated in stromal fibroblasts of various cancers. The effects of p21 knockdown in SMA expression and cell migration and the mRNA levels of endogenous p21 in fibroblasts co-cultured with cancer cells were also assessed.

Results

We found that both p21 and SMA expression was elevated in the stroma, but not the epithelium, of malignant as compared to pre-malignant lesions. We also noted that the expression of both was positively correlated, implying that SMA expression may be regulated by p21. Consistently with this notion we found that siRNA-mediated p21 suppression resulted in the reduction of SMA levels and also inhibited cell migration.

Conclusion

Our results show that p21 deregulation is associated with the activation of stromal fibroblasts of oral cancers by a mechanism that involves the stimulation of SMA expression.     

Tissue-specific therapeutic targeting of p53 in cancer: one size does not fit all

p53, the "guardian of the genome" and the most mutated gene in cancer presents a considerable therapeutic opportunity as well as a challenge. In the past decade, several therapeutic strategies have been developed that aim to take advantage of a wealth of knowledge about p53, including insights into the biology and patho-biology of p53. Nevertheless, considerable challenges remain, not least as a result of tissue- and cancer-specific differences in p53 regulation and/or function. p53 does not act in the same manner in all tissues or in the cancers arising from them. Nor is p53 regulated in the same way in the wide variety of tissues from which cancers develop. Therefore, potential strategies for therapeutic targeting need to be tailored to each tumour/tissue type. This review summarises some of these tissue- and cancer-specific issues to suggest how different strategies are required for cancers arising from different tissues and to illustrate the complexities of therapeutic targeting of p53.     

Humanized SCID mice models of SLE

The pathological DNA-specific B cells in Systemic lupus erythematosus are a logical target for a selected therapeutic intervention. It has been recently shown that complement receptor type 1 on human B and T-lymphocytes has suppressive activity. The co-crosslinking of this receptor with the B-cell receptor (BCR) inhibits B cell activation and proliferation and it could be an attractive new target for negative signal delivery. Experimental therapy in humans is limited by many restrictions. Severe combined immunodeficiency (SCID) mice, which lack both T and B lymphocytes and accept xenogenic cells have been used for human cell transfer for evaluating the pathogenesis of human SLE. We hypothesize that it may be possible to re-establish tolerance to native DNA in humanized SCID mice with cells transferred from SLE patients by administering to them a chimeric molecule, containing a monoclonal antibody against human inhibitory complement receptor type 1 coupled to a decapeptide DWEYSVWLSN that mimics DNA antigenically. These protein-engineered molecules are able to co-crosslink selectively the antigen receptors of B-cells possessing anti-native DNA specificity with the inhibitory surface receptors, thus delivering a strong suppressive signal.     

Factors associated with general and health-related quality of life in menopausal transition among women from Serbia

ABSTRACT

This study assessed factors associated with quality of life (QOL) among Serbian peri- and postmenopausal women using two menopause-specific scales. This cross-sectional study included 500 women aged 40–65 years who had a gynecologic check-up in one of two Community Health Centers in Belgrade during February 2014 to January 2015. Women completed: a questionnaire about socio-demographics, habits, and health status; a menopause-specific questionnaire, Utian’s Quality of Life Scale (UQOL); and a Women’s Health Questionnaire (WHQ) and Beck’s Depression Inventory (BDI). Higher education was associated with better occupational UQOL and memory/concentration, but with lower emotional UQOL and more anxiety/fears. City center residency was associated with better occupational and sexual UQOL. Being employed was associated with better occupational UQOL and lower anxiety/fears. Higher income was associated with better emotional UQOL. Not having uterine prolapse, insomnia, or tachycardia was associated with better occupational UQOL and fewer sleep problems. Higher parity was associated with better sexual UQOL. Having regular recreation was associated with better health and sexual UQOL but with more frequent vasomotor symptoms. Leaner women felt more attractive. QOL during the menopausal transition does not entail only somatic symptoms and therefore requires a more comprehensive approach that includes psychosocial underpinnings.     

Random-coil behavior and the dimensions of chemically unfolded proteins

Spectroscopic studies have identified a number of proteins that appear to retain significant residual structure under even strongly denaturing conditions. Intrinsic viscosity, hydrodynamic radii, and small-angle x-ray scattering studies, in contrast, indicate that the dimensions of most chemically denatured proteins scale with polypeptide length by means of the power-law relationship expected for random-coil behavior. Here we further explore this discrepancy by expanding the length range of characterized denatured-state radii of gyration (R(G)) and by reexamining proteins that reportedly do not fit the expected dimensional scaling. We find that only 2 of 28 crosslink-free, prosthetic-group-free, chemically denatured polypeptides deviate significantly from a power-law relationship with polymer length. The R(G) of the remaining 26 polypeptides, which range from 16 to 549 residues, are well fitted (r(2) = 0.988) by a power-law relationship with a best-fit exponent, 0.598 +/- 0.028, coinciding closely with the 0.588 predicted for an excluded volume random coil. Therefore, it appears that the mean dimensions of the large majority of chemically denatured proteins are effectively indistinguishable from the mean dimensions of a random-coil ensemble.     

The influence of cytokine gene polymorphisms on the risk of developing gastric cancer in patients with Helicobacter pylori infection

Background

Helicobacter pylori infection is the main cause of gastric cancer. The disease progression is influenced by the host inflammatory responses, and cytokine single nucleotide polymorphisms (SNPs) may have a role in the course of the disease. The aim of our study was to investigate proinflammatory cytokine polymorphisms, previously associated with the development of gastric cancer, in a Slovenian population.

Patients and methods.

In total 318 patients and controls were selected for the study and divided into three groups: (i) patients with gastric cancer (n = 58), (ii) patients with chronic gastritis (n = 60) and (iii) healthy control group (n = 200). H. pylori infection in patient groups was determined by serology, histology and culture. Four proinflammatory gene polymorphisms were determined (IL-1β, IL-1ra, TNF-α, TLR-4) in all subjects.

Results

We found a statistically significant difference between males and females for the groups (p = 0.025). Odds ratio (OR) for gastric cancer risk for females was 0.557 (95% confidence interval [CI]: 0.233–1.329) and for chronic gastritis 2.073 (95% CI: 1.005–4.277). IL-1B-511*T/T homozygous allele for cancer group had OR = 2.349 (95% CI: 0.583–9.462), heterozygous IL-1B-511*T had OR = 1.470 (95% CI: 0.583–3.709) and heterozygotes in TNF-A-308 genotype for chronic gastritis had OR = 1.402 (95% CI: 0.626–3.139). Other alleles had OR less than 1.

Conclusions

We could not prove association between gastric cancer and chronic gastritis due to H. pylori in any cytokine SNPs studied in Slovenian population. Other SNPs might be responsible besides infection with H. pylori for the progression from atrophy to neoplastic transformation.     

Perceptibility and acceptability thresholds of simulated facial skin color differences

Purpose

This study investigates the perceptibility and acceptability thresholds (PT, AT) of observers for L*, a* and b* facial skin differences, very important for the fabrication of a maxillofacial prosthesis.