Reproductive tract immune cells from pregnant women or those using depot medroxyprogesterone acetate show no excess susceptibility to HIV-1: Results of an ex vivo fusion assay

IntroductionEx vivo fusion assays offer an efficient method for studying HIV-1 entry associated with contraceptive use and pregnancy outside of cohort studies of HIV-1 incidence.MethodsWe measured ex vivo HIV-1 fusion to cervical or endometrial immune cells from three groups of women: pregnant, non-pregnant not using hormonal or intrauterine contraception, and using depot medroxyprogesterone acetate (DMPA).Results and conclusionsThere was no excess susceptibility to HIV-1 fusion of cells from pregnant women or DMPA users compared to controls. Although the number of target cells in endometrium was higher in DMPA users compared to controls, HIV-1 fusion was lower.ImplicationsIn ex vivo assays, HIV-1 showed no enhanced fusion to cervical immune cells from pregnant women or DMPA users compared to controls, and lower fusion to endometrial immune cells from DMPA users. This assay is useful for studying hormonal and contraceptive effects on HIV-1 entry into reproductive tract immune cells.     

Inhibition of cyclooxygenase-2 indirectly potentiates antitumor effects of photodynamic therapy in mice.

PURPOSE: The aim of the present study was to potentiate the antitumor effectiveness of photodynamic therapy (PDT). A cDNA microarray analysis was used to evaluate the gene expression pattern after Photofrin-mediated PDT to find more effective combination treatment with PDT and inhibitor(s) of the identified gene product(s) overexpressed in tumor cells. EXPERIMENTAL DESIGN: Atlas Mouse Stress Array was used to compare the expression profile of control and PDT-treated C-26 cells. The microarray results have been confirmed using Western blotting. Cytostatic/cytotoxic in vitro assay as well as in vivo tumor models were used to investigate the antitumor effectiveness of PDT in combination with cyclooxygenase (COX) 2 inhibitors. RESULTS: PDT induced the expression of 5 of 140 stress-related genes. One of these genes encodes for COX-2, an enzyme important in the tumor progression. Inhibition of COX-2 in vitro with NS-398, rofecoxib, or nimesulide, or before PDT with nimesulide did not influence the therapeutic efficacy of the treatment. Administration of a selective COX-2 inhibitor after PDT produced potentiated antitumor effects leading to complete responses in the majority of treated animals. CONCLUSIONS: COX-2 inhibitors do not sensitize tumor cells to PDT-mediated killing. However, these drugs can be used to potentiate the antitumor effectiveness of this treatment regimen when administered after tumor illumination.     

A New Model Supporting Stability Quality of Materials and Industrial Products

Stabilizing the quality of industrial product materials remains a challenge. This applies mainly to new or significantly modified materials. It also refers to special processes. The tests of product quality can stabilize the quality of industrial product materials. The popular method for this is using the non-destructive testing (NDT). The NDT identifies incompatibility but does not determine the cause of its occurrence. Hence, it was necessary to support the process of identifying causes of incompatibilities in products. The purpose of the article was to develop a model based on a new approach to determine the ranking of actions that are possible as part of the process of stabilizing the quality of industrial products. The model was developed to improve quality through sequential and systematic methods of identification (and reduce) and incompatibility. The quality management techniques and decision method were applied and combined in this model, i.e., SMART(-ER) the method, method of selecting a team of experts, brainstorming (BM), Ishikawa diagram with the 5M rule, Likert scale validation technique, arithmetic average, and Grey Relational Analysis (GRA). The test of this model was carried out to find cracks in the outer hull of 418 alloy four-point bearing (CPW-S 5616), which was identified by NDT (magnetic-powder method). As a result, a ranking of activities was obtained to stabilize the quality of the product and the main cause of incompatibility was indicated, i.e., the cause which can influence to the most degree influence on occurrence the incompatibility. The originality of the proposed model is an application in the right order of specially selected and combined qualitative methods and supporting decision methods. The finding of causes of incompatibility of products is the basis of product improvement in the area of stabilizing the quality of materials, mainly by the occurrence of special processes. The universality of the model refers to the possibility of its application for any material, processes of its formation, and processes of products, and any incompatibilities where the model can be integrated with quality control.     

CdS-Decorated Porous Anodic SnOx Photoanodes with Enhanced Performance under Visible Light

Electrochemically generated nanoporous tin oxide films have already been studied as photoanodes in photoelectrochemical water splitting systems. However, up to now, the most significant drawback of such materials was their relatively wide band gap (ca. 3.0 eV), which limits their effective performance in the UV light range. Therefore, here, we present for the first time an effective strategy for sensitization of porous anodic SnO_x films with another narrow band gap semiconductor. Nanoporous tin oxide layers were obtained by simple one-step anodic oxidation of metallic Sn in 1 M NaOH followed by further surface decoration with CdS by the successive ionic layer adsorption and reaction (SILAR) method. It was found that the nanoporous morphology of as-anodized SnO_x is still preserved after CdS deposition. Such SnO_x/CdS photoanodes exhibited enhanced photoelectrochemical activity in the visible range compared to unmodified SnO_x. However, the thermal treatment at 200 °C before the SILAR process was found to be a key factor responsible for the optimal photoresponse of the material.     

Postpartum depression: Identifying associations with bipolarity and personality traits. Preliminary results from a cross-sectional study in Poland

The goals of this study have been to determine the prevalence of the bipolar spectrum features in the population of women with postpartum depression (PPD) symptoms, as well as to analyze the personality differences between putative ‘unipolar’ and ‘bipolar’ PPD subjects. The sample enrolled into the cross-sectional study consisted of 344 women at 6–12 weeks postpartum. The authors used the Edinburgh Postnatal Depression Scale (EPDS; cut-off score: 13 pts.) for the assessment of the PPD symptoms, the Mood Disorder Questionnaire (MDQ; cut-off scores: 7 or 8 pts.) for diagnosing the bipolar features, and the NEO-Five Factor Inventory (NEO-FFI) for the assessment of personality traits. The EPDS-positive subjects were more likely to score positively on the MDQ, as compared to the EPDS-negative ones. The EPDS-positive subjects who also scored ≥8 pts. on the MDQ were characterized by higher index of neuroticism, as compared to those who scored positively on the EPDS only. The results suggest that the presence of PPD symptoms is related to significantly higher scores of bipolarity and neuroticism. The more robust trait of neuroticism might be a marker of the ‘bipolar’ PPD, as compared to the ‘unipolar’ form of the disorder.     

Significantly elevated Helicobacter pylori density and different genotype distribution in erosions as compared with normal gastric biopsy specimen detected by quantitative real-time PCR

BACKGROUND AND AIM: Determination of the local densities of Helicobacter pylori and its genotypic variations in gastric biopsy specimens by using novel real-time PCR-based methods could support the precise diagnosis and understanding of H. pylori infections. METHODS: Serial dilutions of H. pylori (0.016-16 microg/microl), control, bacterial, and human DNA samples were prepared. Fresh-frozen gastric biopsy specimens were taken from 103 patients, and the DNA was isolated. Quantitative determination of the ureaseA gene using hybridization probes with parallel evaluation of an internal human control gene (beta-globin) was performed by real-time PCR. CagA and VacA s1 genotypic characterizations were also performed. The data were compared with urea breath test (UBT), histology, and serological testing. RESULTS: The presence of H. pylori could be detected by ureaseA-fluorescence energy transfer (53%), UBT (51%), serological testing (48%), and histology (52%) when compared with the gold standard (54%). A significant correlation was found between the quantitative real-time ureaseA/beta-globin ratio-based H. pylori frequency and the UBT results (P<0.01). Significantly increased bacterial density was found in the erosions when compared with the healthy part of the antrum and corpus (P<0.01). Real-time PCR VacA s1 results were in significant correlation (P<0.01) with those of serological tests, but CagA results were not. The genomic profiles (VAC/GAC) were different in 13.7% of the cases, which involved three different locations in the stomach. CONCLUSION: Real-time PCR was the most reliable method for H. pylori diagnosis. Furthermore, quantification and genotyping could also be performed using this technique. The density of H. pylori was significantly increased in macroscopic erosions.     

Towards potent but less toxic nanopharmaceuticals – lipoic acid bioconjugates of ultrasmall gold nanoparticles with an anticancer drug and addressing unit

Modification of ultrasmall gold nanoparticles (AuNPs) with the lipoic acid derivative of folic acid was found to enhance their accumulation in the cancer cell, as compared to AuNPs without addressing units. The application of lipoic acid enabled the control of the gold nanoparticle functionalities leading to enhanced solubility and allowing for attachment of both the folic acid and the cytotoxic drug, doxorubicin. More robust attachment of doxorubicin to the nanoparticle through the amide bond resulted in toxicity comparable with that of the drug alone, opening a new perspective for designing more potent, but less toxic nanopharmaceuticals. The increased uptake was accompanied by pronounced nuclear accumulation and observable cytotoxicity. Doxorubicin binding via covalent amide bonds enhanced stability of the whole drug vehicle and provided much better control over doxorubicin release in the cell environment, as compared to physical adsorption or pH sensitive bonding commonly used for anthracycline carriers. Confocal microscopy revealed that the bond was stable in the cytoplasm for 22 h. The ability to slow down the rate of drug release may be crucial for the application in sustained anticancer drug delivery. Biological analyses performed using MTT assay and confocal microscopy confirmed that the ultrasmall AuNPs with the lipoic acid derivative of folic acid exhibit relatively low cytotoxicity, however when loaded with a chemotherapeutic, they cause a significant reduction in the cell viability.

Modification of ultrasmall gold nanoparticles (AuNPs) with the lipoic acid derivative of folic acid was found to enhance their accumulation in the cancer cell, as compared to AuNPs without addressing units.     

Acute morphine affects the rat circadian clock via rhythms of phosphorylated ERK1/2 and GSK3β kinases and Per1 expression in the rat suprachiasmatic nucleus

Background and Purpose

Opioids affect the circadian clock and may change the timing of many physiological processes. This study was undertaken to investigate the daily changes in sensitivity of the circadian pacemaker to an analgesic dose of morphine, and to uncover a possible interplay between circadian and opioid signalling.

Experimental Approach

A time-dependent effect of morphine (1 mg·kg⁻¹, i.p.) applied either during the day or during the early night was followed, and the levels of phosphorylated ERK1/2, GSK3β, c-Fos and Per genes were assessed by immunohistochemistry and in situ hybridization. The effect of morphine pretreatment on light-induced pERK and c-Fos was examined, and day/night difference in activity of opioid receptors was evaluated by [³⁵S]-GTPγS binding assay.

Key Results

Morphine stimulated a rise in pERK1/2 and pGSK3β levels in the suprachiasmatic nucleus (SCN) when applied during the day but significantly reduced both kinases when applied during the night. Morphine at night transiently induced Period1 but not Period2 in the SCN and did not attenuate the light-induced level of pERK1/2 and c-Fos in the SCN. The activity of all three principal opioid receptors was high during the day but decreased significantly at night, except for the δ receptor. Finally, we demonstrated daily profiles of pERK1/2 and pGSK3β levels in the rat ventrolateral and dorsomedial SCN.

Conclusions and Implications

Our data suggest that the phase-shifting effect of opioids may be mediated via post-translational modification of clock proteins by means of activated ERK1/2 and GSK3β.Tables of Links

The H2020 “NoHoW Project”: A Position Statement on Behavioural Approaches to Longer-Term Weight Management

There is substantial evidence documenting the effects of behavioural interventions on weight loss (WL). However, behavioural approaches to initial WL are followed by some degree of longer-term weight regain, and large trials focusing on evidence-based approaches to weight loss maintenance (WLM) have generally only demonstrated small beneficial effects. The current state-of-the-art in behavioural interventions for WL and WLM raises questions of (i) how we define the relationship between WL and WLM, (ii) how energy balance (EB) systems respond to WL and influence behaviours that primarily drive weight regain, (iii) how intervention content, mode of delivery and intensity should be targeted to keep weight off, (iv) which mechanisms of action in complex interventions may prevent weight regain and (v) how to design studies and interventions to maximise effective longer-term weight management. In considering these issues a writing team within the NoHoW Consortium was convened to elaborate a position statement, and behaviour change and obesity experts were invited to discuss these positions and to refine them. At present the evidence suggests that developing the skills to self-manage EB behaviours leads to more effective WLM. However, the effects of behaviour change interventions for WL and WLM are still relatively modest and our understanding of the factors that disrupt and undermine self-management of eating and physical activity is limited. These factors include physiological resistance to weight loss, gradual compensatory changes in eating and physical activity and reactive processes related to stress, emotions, rewards and desires that meet psychological needs. Better matching of evidence-based intervention content to quantitatively tracked EB behaviours and the specific needs of individuals may improve outcomes. Improving objective longitudinal tracking of energy intake and energy expenditure over time would provide a quantitative framework in which to understand the dynamics of behaviour change, mechanisms of action of behaviour change interventions and user engagement with intervention components to potentially improve weight management intervention design and evaluation.