Chromosomal aberrations in cord blood are associated with prenatal exposure to carcinogenic polycyclic aromatic hydrocarbons.

Molecular and traditional epidemiology studies have indicated a possible relationship between in utero environmental exposures and increased risk for childhood cancers, especially acute leukemias. Chromosomal aberrations have been associated with environmental exposures and cancer risk in adults. In order to more clearly define the association between prenatal exposures to carcinogenic polycyclic aromatic hydrocarbons (PAH) and chromosomal aberrations, chromosomal aberration frequencies were measured in a subset of 60 newborns from the Columbia Center for Children's Environmental Health (CCCEH) Prospective Cohort Study. The subset was composed of African American and Dominican, nonsmoking mother-newborn pairs residing in low-income neighborhoods of New York City, who were exposed to varying levels of airborne PAHs. Prenatal exposure was assessed by questionnaire, personal air monitoring during the third trimester, and PAH-DNA adducts in umbilical cord blood. Chromosomal aberrations were measured in cord blood lymphocytes by fluorescence in situ hybridization. PAH-DNA adducts were not associated with chromosomal aberrations. However, airborne PAHs were significantly associated with stable aberration frequencies in cord blood (P < 0.01). Moreover, stable aberration frequencies were significantly higher among African American newborns compared with Dominican, despite no significant differences in PAH exposure. These results show for the first time an association between prenatal exposure to airborne carcinogenic PAHs and chromosomal aberrations in cord blood, suggesting that such prenatal exposures have the potential to cause cytogenetic damage that has been related to increased cancer risk in other populations. If confirmed, this finding may open new avenues for prevention.     

Variation of Mean Absolute Relative Differences of Continuous Glucose Monitoring Systems Throughout the Day

Background:There is an increasing use of continuous glucose monitoring (CGM) by people with diabetes. Measurement performance is often characterized by the mean absolute relative difference (MARD). However, MARD is influenced by a number of factors and little is known about whether MARD is stable throughout the day.Material and Methods:A total of 24 participants with type 1 diabetes were enrolled in the study. The study was performed for seven in-patient days. Participants wore two CGM systems in parallel and performed additional frequent blood glucose (BG) measurements. On two days, glucose excursions were induced.MARD was calculated between pairs of CGM and BG values, with BG values serving as reference values. ARD values calculated from CGM-BG pairs were grouped by hour of the day. Results were analyzed separately for glucose excursion days and for regular days.Results:Total MARDs for the complete study duration were 12.5% ± 3.6% and 13.2% ± 2.4% (n = 24). Throughout the day marked variability of MARD was observed (8.0% ± 1.3%-16.3% ± 2.9% (G5); 9.1% ± 1.4%-16.3% ± 5.3% (FL), up to n = 157 each). Low(est) MARD values were observed before breakfast and dinner, when subjects were in or near a fasting state. Especially after breakfast and lunch, MARD values were higher than average.Conclusions:Analytical performance of the two CGM systems, assessed by MARD, was found to vary markedly throughout the day. Activities of daily life likely triggered these variations. An increasing number of CGM users base therapeutic decisions on CGM values, and they should be aware of these variations of performance throughout the day.     

Investigation of Structural,Physical, and Attenuation Parameters of Glass: TeO2-Bi2O3-B2O3-TiO2-RE2O3 (RE: La,Ce, Sm,Er, and Yb), and Applications Thereof

A novel series of glass, consisting of B₂O₃, Bi₂O₃, TeO₂, and TiO₂ (BBTT) containing rare earth oxide RE₂O₃, where RE is La, Ce, Sm, Er, and Yb, was prepared. We investigated the structural, optical, and gamma attenuation properties of the resultant glass. The optical energy bands, the linear refractive indices, the molar refractions, the metallization criteria, and the optical basicity were all determined for the prepared glass. Furthermore, physical parameters such as the density, the molar volume, the oxygen molar volume, and the oxygen packing density of the prepared glass, were computed. Both the values of density and optical energy of the prepared glass increased in the order of La₂O₃, Ce₂O₃, Sm₂O₃, Er₂O₃, and then Yb₂O₃. In addition, the glass doped with Yb₂O₃ had the lowest refractive index, electronic polarizability, and optical basicity values compared with the other prepared glass. The structures of the prepared glass were investigated by the deconvolution of infrared spectroscopy, which determined that TeO₄, TeO₃, BO₄, BO₃, BiO₆, and TiO₄ units had formed. Furthermore, the structural changes in glass are related to the ratio of the intensity of TeO₄/TeO₃, depending on the type of rare earth. It is also clarified that the resultant glass samples are good attenuators against low-energy radiation, especially those that modified by Yb₂O₃, which exhibited superior shielding efficiency at energies of 622, 1170, and 1330 keV. The optical and gamma ray spectroscopy results of the prepared glass show that it is a good candidate for nonlinear optical fibers, laser solid material, and optical shielding protection.     

A fluorescent curcumin-based Zn(II)-complex reactivates mutant (R175H and R273H) p53 in cancer cells

Background

Mutations of the p53 oncosuppressor gene are amongst the most frequent aberration seen in human cancer. Some mutant (mt) p53 proteins are prone to loss of Zn(II) ion that is bound to the wild-type (wt) core, promoting protein aggregation and therefore unfolding. Misfolded p53 protein conformation impairs wtp53-DNA binding and transactivation activities, favouring tumor growth and resistance to antitumor therapies. Screening studies, devoted to identify small molecules that reactivate mtp53, represent therefore an attractive anti-cancer therapeutic strategy. Here we tested a novel fluorescent curcumin-based Zn(II)-complex (Zn-curc) to evaluate its effect on mtp53 reactivation in cancer cells.

Methods

P53 protein conformation was examined after Zn-curc treatment by immunoprecipitation and immunofluorescence assays, using conformation-specific antibodies. The mtp53 reactivation was evaluated by chromatin-immunoprecipitation (ChIP) and semi-quantitative RT-PCR analyses of wild-type p53 target genes. The intratumoral Zn-curc localization was evaluated by immunofluorescence analysis of glioblastoma tissues of an ortothopic mice model.

Results

The Zn-curc complex induced conformational change in p53-R175H and -R273H mutant proteins, two of the most common p53 mutations. Zn-curc treatment restored wtp53-DNA binding and transactivation functions and induced apoptotic cell death. In vivo studies showed that the Zn-curc complex reached glioblastoma tissues of an ortothopic mice model, highlighting its ability to crossed the blood-tumor barrier.

Conclusions

Our results demonstrate that Zn-curc complex may reactivate specific mtp53 proteins and that may cross the blood-tumor barrier, becoming a promising compound for the development of drugs to halt tumor growth.     

Clinical consequences of microdeletions of the Y chromosome: the extended Münster experience

A total of 3179 patients were screened for Y-chromosome microdeletions and 821 patients for partial AZFc deletions. Thirty-nine Y-chromosomal microdeletions were found (2.4% of men with <1 x 10(6)/ml spermatozoa): two AZFa, two AZFb, one AZFbc, one partial AZFb, one partial AZFb+c and 32 AZFc (b2/b4). Partial AZFc deletions were found in 45 patients (5.5%), mostly gr/gr deletions (n = 28). In patients with AZFc deletion, azoospermia was found in 53.1% and sperm concentrations of mostly <0.1 x 10(6)/ml were found in 46.9%. Semen analyses and FSH measurements showed no trend over time. Elongated spermatids were seen in 6/15 AZFc patients and bilateral Sertoli cell-only was found in 4/15. Testicular sperm extraction (TESE) was attempted in 10 patients and spermatozoa were found in six. Compared with infertile men matched by sperm concentration, no differences in hormonal and seminal parameters could be found in patients with AZFc or gr/gr deletions. It is concluded that: (i) frequency of AZF deletions in Germany is much lower than in other countries; (ii) AZFc deletions are associated with severe disturbances of spermatogenesis and TESE is not possible in half of these patients; (iii) AZFc and gr/ gr deletions are not associated with any clinical diagnostic parameter; (iv) and no trend is apparent over time.     

Long-term subcutaneous morphine administration after surgery in newborns

AIM: To analyze the management of newborns after major surgery receiving morphine subcutaneously and to identify possible side effects. METHODS: Morphine was administered via a subcutaneous catheter (Insuflon) in 20 newborns after major surgery. Side effects like hypotension, pain during morphine administration and local infection were noted. Morphine dose was adjusted according to the hospital guidelines with the Neonatal Infant Pain Score (NIPS) and the Finnegan withdrawal score. RESULTS: Surgery was performed at the median age of 38 5/7 weeks (range: 32 1/7-49 5/7 weeks). Before starting subcutaneous morphine administration, patients received intravenous morphine for a median of two weeks (range six days to seven weeks). All patients showed good pain relief with no severe side effects. Three patients reacted with crying to the first dose of subcutaneous morphine. No other side effects occurred. CONCLUSION: Subcutaneous application of morphine with the Insuflon catheter is an alternative to intravenous treatment of postoperative pain in neonates. In this small group pain relief was good and side effects were harmless.     

Transplanted human cones incorporate into the retina and function in a murine cone degeneration model

Once human photoreceptors die, they do not regenerate, thus, photoreceptor transplantation has emerged as a potential treatment approach for blinding diseases. Improvements in transplant organization, donor cell maturation, and synaptic connectivity to the host will be critical in advancing this technology for use in clinical practice. Unlike the unstructured grafts of prior cell-suspension transplantations into end-stage degeneration models, we describe the extensive incorporation of induced pluripotent stem cell (iPSC) retinal organoid–derived human photoreceptors into mice with cone dysfunction. This incorporative phenotype was validated in both cone-only as well as pan-photoreceptor transplantations. Rather than forming a glial barrier, Müller cells extended throughout the graft, even forming a series of adherens junctions between mouse and human cells, reminiscent of an outer limiting membrane. Donor-host interaction appeared to promote polarization as well as the development of morphological features critical for light detection, namely the formation of inner and well-stacked outer segments oriented toward the retinal pigment epithelium. Putative synapse formation and graft function were evident at both structural and electrophysiological levels. Overall, these results show that human photoreceptors interacted readily with a partially degenerated retina. Moreover, incorporation into the host retina appeared to be beneficial to graft maturation, polarization, and function.     

Magnesium—A Potential Key Player in Inflammatory Bowel Diseases?

The altered magnesium status in inflammatory bowel disease (IBD) patients may have a significant clinical imprint considering its role in cell signaling and genomic stability, as well as its involvement in IBD patients’ fatigue. Our study pioneers the investigation of magnesium hair concentration patterns in an adult population of IBD patients. The hair magnesium concentration in IBD patients is compared to healthy controls in order to identify correlations between the magnesium status and relevant parameters related to disease activity, psychological status, and sleep quality. We report a significantly lower hair magnesium concentration within the IBD group compared to healthy controls (95%CI: 0.006–0.062; p = 0.017) and lower levels in CD compared to UC (95%CI: −0.061–−0.002; p = 0.038). We identified a borderline statistical significance between the hair magnesium concentration and UC disease activity (95%CI; −0.679–0.008; p = 0.055) and a significantly lower magnesium concentration in patients who reported increased sleep latency (95%CI −0.65–−0.102; p = 0.011) or decreased sleep duration (95%CI −0.613–−0.041; p = 0.028). Our results advance several hypotheses with substantial clinical impact to be confirmed in future studies. Magnesium levels appear to be modified in IBD patients, which suggests it either plays a primary role in disease pathophysiology or a is result of the disease’s evolution. Magnesium could be used in predictive models for clinical/subclinical disease activity. Moreover, magnesium supplementation may improve IBD evolution and sleep quality for patients with a deficit of this mineral. However, confirmatory evidence-based studies are needed to generate specific dosing, time of supplementation, and optimum monitoring of magnesium status in IBD patients.     

Comparison of Melting Processes for WPC and the Resulting Differences in Thermal Damage,Emissions and Mechanics

The necessity for resource-efficient manufacturing technologies requires new developments within the field of plastic processing. Lightweight design using wood fibers as sustainable reinforcement for thermoplastics might be one solution. The processing of wood fibers requires special attention to the applied thermal load. Even at low processing temperatures, the influence of the dwell time, temperature and shear force is critical to ensure the structural integrity of fibers. Therefore, this article compares different compounding rates for polypropylene with wood fibers and highlights their effects on the olfactory, visual and mechanical properties of the injection-molded part. The study compares one-step processing, using an injection-molding compounder (IMC), with two-step processing, using a twin-scew-extruder (TSE), a heating/cooling mixer (HCM) and an internal mixer (IM) with subsequent injection molding. Although the highest fiber length was achieved by using the IMC, the best mechanical properties were achieved by the HCM and IM. The measured oxidation induction time and volatile organic compound content indicate that the lowest amount of thermal damage occurred when using the HCM and IM. The advantage of one-time melting was evened out by the dwell time. The reinforcement of thermoplastics by wood fibers depends more strongly on the structural integrity of the fibers compared to their length and homogeneity.