Detailed dynamical features of the slow hydration water in the vicinity of poly(ethylene oxide) chains.

Poly(ethylene oxide) (PEO) is a well-known biocompatible polymer and has widely been used for medical applications. Recently, we have investigated the dynamic behavior of hydration water in the vicinity of PEO chains at physiological temperature and shown the presence of slow water with diffusion coefficient one order of magnitude less than that of bulk water. This could be evidence for the intermediate water that is critical for biocompatibility; however, its detailed dynamical features were not established. In this article, we analyze the quasi-elastic neutron scattering from hydration water through mode distribution analysis and present a microscopic picture of hydration water as well as its relation to cold crystallization.

Cost-effectiveness of posterior versus anterior surgery for cervical radiculopathy: results from a multicentre randomised non-inferiority trial (FACET).

PURPOSE: For cervical nerve root compression, anterior cervical discectomy with fusion (anterior surgery) or posterior foraminotomy (posterior surgery) are safe and effective options. Posterior surgery might have a more beneficial economic profile compared to anterior surgery. The purpose of this study was to analyse if posterior surgery is cost-effective compared to anterior surgery. METHODS: An economic evaluation was performed as part of a multicentre, noninferiority randomised clinical trial (Foraminotomy ACDF Cost-effectiveness Trial) with a follow-up of 2 years. Primary outcomes were cost-effectiveness based on arm pain (Visual Analogue Scale (VAS; 0-100)) and cost-utility (quality adjusted life years (QALYs)). Missing values were estimated with multiple imputations and bootstrap simulations were used to obtain confidence intervals (CIs). RESULTS: In total, 265 patients were randomised and 243 included in the analyses. The pooled mean decrease in VAS arm at 2-year follow-up was 44.2 in the posterior and 40.0 in the anterior group (mean difference, 4.2; 95% CI, - 4.7 to 12.9). Pooled mean QALYs were 1.58 (posterior) and 1.56 (anterior) (mean difference, 0.02; 95% CI, - 0.05 to 0.08). Societal costs were €28,046 for posterior and €30,086 for the anterior group, with lower health care costs for posterior (€12,248) versus anterior (€16,055). Bootstrapped results demonstrated similar effectiveness between groups with in general lower costs associated with posterior surgery. CONCLUSION: In patients with cervical radiculopathy, arm pain and QALYs were similar between posterior and anterior surgery. Posterior surgery was associated with lower costs and is therefore likely to be cost-effective compared with anterior surgery.

Photodynamic therapy for the prevention and treatment of actinic keratosis/squamous cell carcinoma in solid organ transplant recipients: a systematic review and meta-analysis.

Solid organ transplant recipients (sOTR) are at an increased risk of developing cutaneous cancers, especially squamous cell carcinoma (SCC). Photodynamic therapy (PDT) for the prevention and treatment of actinic keratosis (AK)/SCC in sOTR is increasingly prescribed given the increase in solid organ transplantations performed worldwide. PDT has added advantages of superior cosmetic outcomes and good safety profile compared to conventional surgical methods and other topical therapies. We aim to evaluate the role of PDT in the prevention and treatment of AK/SCC in sOTRs. The Cochrane Library, PubMed and EMBASE database were searched. Articles reporting PDT outcomes amongst sOTR with or without AK/SCC at baseline were selected. We classified the studies into two categories: (i) PDT as prevention measure and (ii) treatment of AK/SCC in sOTR. Primary outcome for the prevention category was 3-year incidence of AK/SCC and complete response (CR) of lesions after PDT exposure in the treatment category. Secondary outcomes were cosmesis and adverse reaction in both categories. Pooled results were expressed as risk difference (RD) with corresponding 95% confidence interval (95% CI). Twelve out of 641 articles met our eligibility criteria, out of which four RCTs reported the preventive effect of AK/SCC and another five RCTs reported the treatment effect of PDT in sOTR. One RCT did not report absolute number of lesions at baseline/end of study for results to be pooled in the quantitative analysis. The remaining three studies were cohort studies reporting treatment and preventive effect of PDT in sOTR. PDT group had a lower incidence as a preventive measure with pooled RD of 0.14 (95% CI 0.08-0.19). The CR in PDT was higher in the treatment group with a pooled RD of 0.77 (95% CI 0.6-0.94) and 0.50 (95% CI 0.22-0.79) in predivided lesional areas and number of lesions, respectively. In conclusion, PDT is efficacious for prevention and treatment of AK/SCC in sOTRs.

Exploring pathways for sustained melanogenesis in facial melasma: an immunofluorescence study.

BACKGROUND: The physiopathology of epidermal hypermelanization in melasma is not completely understood. Several cytokines and growth factors are increased in skin with melasma, nevertheless, nor the pathways involved in the increased αMSH expression have been adequately evaluated, nor a model for sustained focal melanogenesis is available. OBJECTIVE: To explore stimulatory pathways for epidermal pigmentation in facial melasma related to αMSH: those linked to ultraviolet radiation, oxidative stress, inflammation, neural crest pigmentation cell differentiation and antagonism of αMSH. METHODS: Paired skin biopsies (3 mm) from 26 women with facial melasma and from normal adjacent skin (<2 cm far) were processed for immunofluorescence with markers for p53, p38, αMSH, MC1R, Melan-A, IL-1α, COX2, Wnt1, WIF-1 and ASIP. RESULTS: The fluorescence intensity in the skin from melasma was higher for MC1R, αMSH at epidermis as at melanocytes (P < 0.05). There were no differences between the sites in epidermal protein expression of COX2, IL-1α, p53, WIF-1 and ASIP (P > 0.1). P53 was expressed only in epidermis, without difference between sites (P = 0.92). WNT1 was remarkable in the epidermis of melasma (P < 0.01), but not in dermis. Positive p38 cells were prominent in the upper dermis of melasma (P < 0.01), despite no marking in epidermis. CONCLUSION: Melanogenesis in melasma involves epithelial secretion of αMSH and activation of the Wnt pathway; nevertheless, it seems to be independent of the stimulation by ultraviolet radiation/p53, IL-1α, COX2/PgE2 , WIF-1 and ASIP. Damaged cells at upper dermis suggest the role of senescence/autophagy in sustained pigmentation in melasma.

Use of apparent diffusion coefficient as a response biomarker in bone: effect of developing sclerosis on quantified values.

OBJECTIVE: To investigate the effect of sclerosis on apparent diffusion coefficient measurements in bone metastases from prostate cancer undergoing treatment. MATERIALS AND METHODS: Sixteen patients underwent CT scans and MRI at baseline and 12 weeks following commencement of chemotherapy. For each patient, up to five bone metastases were selected. Hounsfield units were measured on CT and apparent diffusion coefficient (ADC) was measured on diffusion weighted MRI at both time points. Correlations between changes in apparent diffusion coefficient and Hounsfield units were investigated. RESULTS: Corresponding pre- and post-treatment apparent diffusion coefficient and Hounsfield units were available on 60 lesions from 16 patients. Overall, there was no significant correlation between changes in apparent diffusion coefficient with Hounsfield units. However, where changes in Hounsfield units increased by more than 50 %, there was a trend for an associated ADC rise. CONCLUSIONS: Increasing sclerosis of bone metastases on treatment does not significantly impede diffusion.

Scalp, skull and brain metastasis of squamous cell carcinoma of the cervix--a rare entity.

Metastasis of squamous cell carcinoma of the uterine cervix on the scalp has been reported only six times in the literature; however, we found no reports of metastasis on the scalp associated with skull and brain invasion. We present an exceptionally rare case with good evolution after neurosurgical resection.

Structure-activity relationship, molecular docking, and molecular dynamic studies of diterpenes from marine natural products with anti-HIV activity.

HIV-1 infection is a global epidemic whose treatment is limited majorly by viral resistance and adverse effects. Natural products from algae have been studied for many years, including antiviral, being an alternative to anti-HIV drug design. Since the isolation of natural products can be a hurdle, molecular modeling is an important tool to study these compounds. Herein, structure-activity relationship, molecular docking, and molecular dynamic studies were performed to direct the studies of ten marine natural products with anti-HIV activity. In the structure-activity relationship, descriptors were identified associating the anti-HIV activity of five diterpenes with possible action on the reverse transcriptase allosteric site. These diterpenes were evaluated by molecular docking, and it was identified that only dolabelladienetriol interacted in the allosteric site. Molecular dynamics suggested that the dolabelladienetriol might interfere with the viral RNA binding to HIV-1 RT by inducing a conformational change of the enzyme. Also, in silico ADMET simulations predicts that the dolabelladienetriol present a high potential to be successfully developed as a drug. Thus, applying in silico approaches was possible to suggest potential anti-HIV compounds derived from marine natural products.Communicated by Ramaswamy H. Sarma.

Assessing response in bone metastases in prostate cancer with diffusion weighted MRI.

OBJECTIVES: To determine whether changes in ADC of bone metastases secondary to prostate carcinoma are significantly different in responders compared with progressors on chemotherapy. METHODS: Twenty-six patients with known bone metastases secondary to prostate carcinoma underwent diffusion-weighted MRI of the lumbar spine and pelvis at baseline and 12 weeks following chemotherapy. RECIST assessment of staging CT and PSA taken at the same time points were used to classify patients as responders, progressors or stable. ADC (from b = 0,50,100,250,500,750 smm⁻²) and ADC(slow) (from b = 100,250,500,750 smm⁻²) were calculated for up to 5 lesions per patient. RESULTS: Mean ADC/ADC(slow) in lesions from responders and progressors showed a significant increase. Although the majority of lesions demonstrated an ADC/ADC(slow) rise, some lesions in both responders and progressors demonstrated a fall in ADC beyond the limits of reproducibility. CONCLUSIONS: Mean ADC is not an appropriate measure of response in bone metastases. The heterogeneity of changes in ADC is likely to be related to the composition of bone marrow with changes that have opposing effects on ADC.

Sterols: isolation from a blue-green alga.

A crystalline mixture of sterols was isolated from the filamentous blue-green alga Phormidium luridum. The mixture consisted of unsaturated 24-ethylcholesterols possessing Delta(7)-, Delta(5,7)-, and Delta(5)-bonds together with their Delta(22)-derivatives and a small amount of cholesterol. The major component was 24-ethyl-Delta(7)-cholestenol. Squalene and phytol were also evident.

Fas/CD95 promoter polymorphism gene and its relationship with cervical carcinoma.

OBJECTIVE: Apoptosis is an important fail-safe control in human papillomavirus (HPV)-associated carcinogenesis. We tested the hypothesis that the A/G polymorphism at -670 of Fas promoter is associated with an increased risk for cervical cancer, using a matched case-control setting. METHODS: The material in this case-control study consisted of 91 patients with cervical carcinoma and 176 population-based control subjects, recruited between 2002 and 2004; all the ethnic Brazilian women had histologically confirmed cervical carcinoma. Control subjects were age-matched; healthy women who were selected following a negative cervical cytology and normal colposcopy. Fas genotyping was performed using a PCR-RFLP technique. RESULTS: No significant difference existed in the distribution of the Fas polymorphisms (wild, heterozygous, mutant) between the cases and controls. The heterozygous (OR: 4.85, 95% CI: 1.1-22.6) genotypes among the younger (< 48 yrs) cancer patients were almost 5-fold increased, as compared with the wild type. No such increase was observed among the patients older than 48 years. CONCLUSIONS: Our data suggest that 670A/G polymorphism in the promoter region of the death receptor Fas is associated with an increased risk of cervical cancer among Brazilian women under 48 years. The mechanisms would be the inhibition of apoptosis by Fas -670G allele-mediated down-regulation of Fas transcription.

Experimental cryptorchidism enhances testicular susceptibility to dibutyl phthalate or acrylamide in Sprague-Dawley rats.

Cryptorchidism (CPT), the most common male congenital abnormality, is variably associated with other male reproductive tract problems. We evaluated if cryptorchid rats develop enhanced testicular susceptibility to dibutyl phthalate (DBP) or acrylamide (AA) after extended exposure. Three studies with rats were performed: (1) in utero and postnatal exposure to DBP or AA; (2) establishment of CPT and orchiopexy; and (3) in utero and postnatal exposures to DBP or AA associated with CPT/orchiopexy. Seminiferous tubules were histologically scored according to the severity of lesions: (1) Rats exposed to DBP (score 1.5) or AA (score 1.1) presented mostly preserved spermatogenesis. Some seminiferous tubules showed vacuolated germinative epithelium, germ cell apoptosis, and a Sertoli cell-only (SCO) pattern. (2) CPT (score 3.3) resulted in decreased absolute testes weights, degenerated and SCO tubules, and spermatogenesis arrest that were reversed by orchiopexy (score 1.1). (3) Exposure to DBP or AA with CPT/orchiopexy led to atrophic testes, spermatogenesis arrest, germ cell exfoliation/multinucleation, and SCO tubules (both chemicals score 2.5). Exposure to chemicals such as DBP or AA prevented the recovery of cryptorchid testes by orchiopexy. The possible role of environmental contaminants should be considered when looking for factors that modulate human testicular disorders associated with CPT.

CYP17 polymorphism and hot flushes in postmenopausal women.

OBJECTIVE: To investigate the association between the CYP17alpha gene polymorphism and hot flushes in postmenopausal women. METHODS: Ninety-three non-hysterectomized, postmenopausal women were enrolled in this study. Vasomotor symptoms were assessed at the baseline visit and based on information provided by each participant. The genotypic polymorphism of CYP17alpha gene was analyzed by PCR-RFLP assay using genomic DNA isolated from peripheral blood lymphocytes. RESULTS: Thirty-six women reported hot flushes of mild intensity, 25 reported hot flushes of moderate intensity and 32 of severe intensity. There was no significant difference between the severity of hot flushes and the CYP17 genotype or allele frequencies, 0.58 and 0.67 respectively. No association was found between hot flush severity and the CYP17 allele (odds ratio = 1.17, p = 0.61). CONCLUSION: The results of this study suggest that the CYP17 MspAI polymorphism was not significantly associated with an increased risk of reporting hot flushes.

Study of p53 codon 72 polymorphism in patients with breast cancer.

Breast cancer is a common disease in Western societies, with an incidence of 46.31/100,000 women/year in Brazil. The tumor suppressor gene TP53 is one of the most studied genes regarding the presence of mutations. Indeed, 50% of all tumors are known to exhibit changes in the TP53 nucleotide sequence due to carcinogenic processes. As to the presence of polymorphism, the TP53 gene is polymorphic at the nucleotide residue 347 (codon 72). In the current study, we examine if this polymorphism is associated with the clinicopathological parameters of breast cancer patients in a Brazilian population. One hundred and thirteen patients with breast cancer were included. The polymorphic region of the TP53 gene was PCR-amplified from genomic DNA obtained from buccal cells. Specific primers for the Pro and Arg allele were used. Correlations of polymorphism with age, staging, nuclear grade, lymph node status, estrogen receptor status and lymphatic and/or blood vessel invasion were evaluated. Statistical analysis was performed using the Fisher's exact test. The frequency of p53 Arg/Arg was 57% and of the heterozygous allele Arg/Pro it was 39%. There was no correlation between polymorphism and clinicopathological parameters. According to our results, the TP53 polymorphism, at the 347 residue, is not associated with any clinicopathological findings of patients with breast cancer.

Polymorphisms of p53, GSTM1 and GSTT1, and HPV in uterine cervix adenocarcinoma.

OBJECTIVE: To analyze the participation of glutathione-S-transferase (GST) M1 and T1 polymorphisms associated or not with protein p53 polymorphism at codon 72 and in the presence of HPV in the carcinogenesis of uterine cervix adenocarcinoma. METHODS: Forty-three samples of uterine cervix adenocarcinoma were studied and 86 samples of endocervical cells of women without tumors formed the control group. The presence of HPV was determined in order to genotype the isoforms of p53 at codon 72, GSTM1, GSTM1*0, GSTT1 and GSTT1*0 which were evaluated by the PCR method. RESULTS: HPV was present in 97.67% of the adenocarcinoma cases and in 31.40% of the control group. Statistical analysis showed differences (p = 0.001) and an OR of 113.3 (CI 95%: 13.67-947.14). GSTT1 and GSTT1*0 analysis showed a significant difference between the groups (p = 0.001) with an OR of 4.58 (CI 95%: 2.041-10.28) (p < 0.001) for the presence of GSTT1*0. When it was associated with HPV OR was 6.6 (CI 95%: 0.04-0.50). Analyses of p53 and GSTM1 and GSTM1*0 either alone or associated with HPV were not significant. CONCLUSION: The presence of GSTT1*0 increased the risk for uterine cervix adenocarcinoma development while the allele GSTT1 had a protective action. The other isoforms did not appear to participate in the carcinogenesis of uterine cervix adenocarcinoma.

Prognostic markers of low-grade squamous intraepithelial lesions: the role of topoisomerase IIalpha and active caspase-3.

PURPOSE: To study the relationship between topoisomerase IIalpha, active caspase-3 expressions and HPV DNA in uterine cervices with low-grade squamous intraepithelial lesions (LSIL). METHODS: Forty women with LSIL and 32 without cervical neoplasia diagnosed through cytologic and histopathologic examination were evaluated regarding topoisomerase IIalpha and active caspase-3 expressions and HPV DNA detection using PCR (GP5/GP6) in cervicovaginal smears. RESULTS: The mean percentage of cells immunomarked by topoisomerase in the group with LSIL was 11.62% while in the control it was 4.13% (p < 0.0001). In the presence of HPV DNA, topoisomerase expression was higher in the group with productive viral infection than in nonneoplastic tissue (p = 0.004). Caspase-3 expression was observed in 17 patients with LSIL (42.5%) and in five without cervical neoplasia (15.63%). CONCLUSION: The use of topoisomerase IIalpha and active caspase-3 in cervical biopsies may help to define the prognosis of HPV cervical infection.

Cassava starch fermentation wastewater: characterization and preliminary toxicological studies.

Cassava starch fermentation wastewater is an industrial residue composed mainly of lactic acid bacteria with predominance of the genera Lactobacillus, and organic acids. To evaluate the safety of this residue for possible production of probiotic beverages, acute in mice and sub-chronic (28-day repeated dose) toxicity studies in rats were carried. The administration of a single dose of 5 g/kg/body weight did not produce mortality in mice. Rats treated with water containing 0 (control), 25%, 50%, and 100% of the residue for 28 days, did not present alterations in behaviour or in food and water consumption. There were no treatment-related changes of toxicological significance in the relative weight of the organs neither in the haematological nor in the biochemical parameters. Histopathologic alterations observed in the small intestine did not seem to be associated with the treatment.

Comparative study of the degradation of real textile effluents by photocatalytic reactions involving UV/TiO2/H2O2 and UV/Fe2+/H2O2 systems.

This work investigated the treatability of real textile effluents using several systems involving advanced oxidation processes (AOPs) such as UV/H2O2, UV/TiO2, UV/TiO2/H2O2, and UV/Fe2+/H2O2. The efficiency of each technique was evaluated according to the reduction levels observed in the UV absorbance of the effluents, COD, and organic nitrogen reduction, as well as mineralization as indicated by the formation of ammonium, nitrate, and sulfate ions. The results indicate the association of TiO2 and H2O2 as the most efficient treatment for removing organic pollutants from textile effluents. In spite of their efficiency, Fenton reactions based treatment proved to be slower and exhibited more complicated kinetics than the ones using TiO2, which are pseudo-first-order reactions. Decolorization was fast and effective in all the experiments despite the fact that only H2O2 was used.

Irisin Levels Are not Associated to Resistance Training-Induced Alterations in Body Mass Composition in Older Untrained Women with and without Obesity.

OBJECTIVE: The present study aimed to determine whether Irisin levels are correlated with body composition changes following 16 weeks of resistance training (RT) in older women with and without obesity. Design, Setting, Participants, Intervention: We recruited 49 inactive women (n = 23, non-obese: < 41.0% and n = 26, obese: ≥ 41.0% of body fat) aged 61-68 years to perform 16-week of RT consisting of 10 exercises (three sets of 10 exercises, 6-12 repetitions maximum and 1-min and 30-s rest intervals between sets and exercises, respectively) with two sessions per week. MEASUREMENTS: Before and after the intervention period, blood samples were collected to determine Irisin levels and body composition (percentage body fat and fat-free mass) was measured by dual energy x-ray absorptiometry. RESULTS: Circulating Irisin displayed a decrease for the non-obese group as compared with pre-intervention and obese group (p = 0.01 and p = 0.04, respectively), with no change for the obese group (p = 0.79). In addition, fat mass displayed a significant reduction (p < 0.05) following the training period only for the obese group. Furthermore, there was no association between changes in circulating Irisin with body mass index, body fat, fat-free mass and muscle strength. There was an increase in muscle strength (p < 0.05), regardless of obesity status. CONCLUSION: The modulation of body composition and muscle strength induced by 16-week of resistance training in older women with and without obesity is not associated with changes in circulating Irisin levels.

Relined Fiberglass Post: Effect of Luting Length, Resin Cement, and Cyclic Loading on the Bond to Weakened Root Dentin.

This study evaluated the effects of luting length of the post, the resin cement, and cyclic loading on pull-out bond strength of fiberglass posts relined with composite resin in weakened roots. The canals of 80 bovine incisors were endodontically treated and weakened with diamond burs. The teeth were randomly divided into eight groups (n=10) according to the luting procedures of the relined fiberglass post (RFP): In groups 1, 2, 3, and 4, the RFPs were luted with RelyX ARC, and in groups 5, 6, 7, and 8 they were luted with RelyX U200. In groups 1, 3, 5, and 7, the RFPs were luted at a length of 5 mm, and in groups 2, 4, 6, and 8 they were luted at a length of 10 mm. Specimens from groups 3, 4, 7, and 8 were submitted to cyclic loading. Specimens were subjected to a pull-out bond strength test in a universal testing machine. The results (MPa) were analyzed by three-way analysis of variance and the Tukey post hoc test (α=0.05). Six human upper anterior teeth were used to analyze the bond interface by confocal laser scanning microscopy (CLSM). The pull-out bond strength of RFPs luted with RelyX U200 was statistically higher than that of RelyX ARC. Cyclic loading influenced the bond strength only for the luting length of 5 mm. CLSM analysis revealed the formation of resin cement tags for both materials. Luting length is an important factor in retaining RFPs in weakened roots when they are subjected to cyclic loading, and RelyX U200 resulted in greater bond strengths to the root canal in comparison with RelyX ARC.

Activity of the new quinolone WCK 771 against pneumococci.

The activity of WCK 771, a new experimental quinolone being developed to overcome quinolone resistance in staphylococci, against quinolone-susceptible and -resistant pneumococci was determined. Comparative activities of ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, clinafloxacin, vancomycin, linezolid, amoxycillin, cefuroxime, azithromycin and clarithromycin were determined with MIC and time-kill experiments. Animal experiments were also performed to test the in-vivo anti-pneumococcal activity of WCK 771 compared to levofloxacin. WCK 771 MIC50/90 values for 300 quinolone-susceptible Streptococcus pneumoniae isolates (108 penicillin-susceptible, 92 penicillin-intermediate and 100 penicillin-resistant) were 0.5/0.5 mg/L; the MICs of beta-lactams and macrolides rose with those of penicillin G, and all isolates were susceptible to vancomycin and linezolid. WCK 771 MIC50/90 values for 25 quinolone-resistant pneumococcal isolates were 4/8 mg/L, compared to 0.5/1 mg/L for clinafloxacin, 2/4 mg/L for gatifloxacin and moxifloxacin, 8/16 mg/L for levofloxacin, and 16/>32 mg/L for ciprofloxacin. Time-kill studies showed that WCK 771 was bactericidal against pneumococci after 24 h at 4 x MIC, as were the other quinolones tested. Animal model studies showed that WCK 771 had efficacy comparable to that of levofloxacin, by both the oral and subcutaneous routes, for systemic infection caused by three quinolone-susceptible isolates of pneumococci. Overall, WCK 771 was potent both in vivo and in vitro against quinolone-susceptible, but not quinolone-resistant, S. pneumoniae, regardless of penicillin susceptibility.