A Prototype Method for the Detection and Recognition of Pigments in the Environment Based on Optical Property Simulation.

The possibility of pigment detection and recognition in different environments such as solvents or proteins is a challenging, and at the same time demanding, task. It may be needed in very different situations: from the nondestructive in situ identification of pigments in paintings to the early detection of fungal infection in major agro-industrial crops and products. So, we propose a prototype method, the key feature of which is a procedure analyzing the lineshape of a spectrum. The shape of the absorption spectrum corresponding to this transition strongly depends on the immediate environment of a pigment and can serve as a marker to detect the presence of a particular pigment molecule in a sample. Considering carotenoids as an object of study, we demonstrate that the combined operation of the differential evolution algorithm and semiclassical quantum modeling of the optical response based on a generalized spectral density (the number of vibronic modes is arbitrary) allows us to distinguish quantum models of the pigment for different solvents. Moreover, it is determined that to predict the optical properties of monomeric pigments in protein, it is necessary to create a database containing, for each pigment, in addition to the absorption spectra measured in a predefined set of solvents, the parameters of the quantum model found using differential evolution.

Association of NEF2L2 Rs35652124 Polymorphism with Nrf2 Induction and Genotoxic Stress Biomarkers in Autism.

Increased oxidative/genotoxic stress is known to impact the pathophysiology of ASD (autism spectrum disorder). Clinical studies, however, reported limited, heterogeneous but promising responses to treatment with antioxidant remedies. We determined whether the functional polymorphism of the Nrf2 gene, master regulator of anti-oxidant adaptive reactions to genotoxic stress, links to the genotoxic stress responses and to an in vitro effect of a NRF2 inductor in ASD children. Oxidative stress biomarkers, adaptive responses to genotoxic/oxidative stress, levels of master antioxidant regulator Nrf2 and its active form pNrf2 before and after inducing by dimethyl fumarate (DMF), and promotor rs35652124 polymorphism of NFE2L2 gene encoding Nrf2 were studied in children with ASD (n = 179). Controls included healthy adults (n = 101). Adaptive responses to genotoxicity as indicated by H2AX and cytoprotection by NRF2 contents positively correlated in ASD children with a Spearman coefficient of R = 0.479 in T+, but not CC genotypes. ASD children with NRF2 rs35652124 CC genotype demonstrated significantly higher H2AX content (0.652 vs. 0.499 in T+) and pNrf2 induction by DMF, lowered 8-oxo-dG concentration in plasma and higher cfDNA/plasma nuclease activity ratio. Our pilot findings suggest that in ASD children the NEF2L2 rs35652124 polymorphism impacts adaptive responses that may potentially link to ASD severity. Our data warrant further studies to reveal the potential for NEF2L2 genotype-specific and age-dependent repurposing of DMF and/or other NRF2-inducing drugs.

Involvement of Lipids in the Pathogenesis of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive degeneration of upper and lower motor neurons. To study its underlying mechanisms, a variety of models are currently used at the cellular level and in animals with mutations in multiple ALS associated genes, including SOD1, C9ORF72, TDP-43, and FUS. Key mechanisms involved in the disease include excitotoxicity, oxidative stress, mitochondrial dysfunction, neuroinflammatory, and immune reactions. In addition, significant metabolism alterations of various lipids classes, including phospholipids, fatty acids, sphingolipids, and others have been increasingly recognized. Recently, the mechanisms of programmed cell death (apoptosis), which may be responsible for the degeneration of motor neurons observed in the disease, have been intensively studied. In this context, sphingolipids, which are the most important sources of secondary messengers transmitting signals for cell proliferation, differentiation, and apoptosis, are gaining increasing attention in the context of ALS pathogenesis given their role in the development of neuroinflammatory and immune responses. This review describes changes in lipids content and activity of enzymes involved in their metabolism in ALS, both summarizing current evidence from animal models and clinical studies and discussing the potential of new drugs among modulators of lipid metabolism enzymes.

A Comprehensive Approach to Predicting the Outcomes of Transsphenoidal Endoscopic Adenomectomy in Patients with Cushing's Disease.

Persistent and recurrent hypercortisolism after transsphenoidal endoscopic surgery (TSS) is considered to be an urgent issue prompting the search for Cushing's disease (CD) remission predictors. The goal was to find a combination of predictors that can forecast the remission of CD after TSS. A total of 101 patients with CD who had undergone TSS were included. One year after surgery, CD remission status was evaluated. Preoperative pituitary magnetic resonance imaging (MRI) data, preoperative results of a high-dose dexamethasone suppression test (HDDST) and morning serum cortisol level collected 24 h after TSS (24 h MSeC) were compared in patients with and without remission of hypercortisolism. Remission one year after TSS was confirmed in 63 patients. CD remission predictors one year after TSS were: adenoma size ≥ 3 mm in the absence of invasive growth and the suppression of serum cortisol ≥ 74% in the HDDST, 24 h MSeC ≤ 388 nmol/L. A total of 38 patients had three favorable values of detected predictors; all of them had CD remission one year after TSS. With long-term follow-up, 36 of them remained in remission. Patients who had no one favorable predictor had no remission of hypercortisolism one year after TSS. Our data confirmed the prospects of using a combination of selected predictors to forecast CD remission after TSS.

Femtosecond laser oocyte enucleation as a low-invasive and effective method of recipient cytoplast preparation.

Recipient cytoplast preparation, commonly performed by DNA aspiration with a needle, inevitably leads to the loss of reprogramming factors. As an alternative to the traditional enucleation technique, femtosecond laser enucleation can eliminate DNA effectively without loss of reprogramming factors and without oocyte puncturing. In this work we have performed oocyte enucleation by destructing the metaphase plate using a 795 nm femtosecond laser. The disability of the enucleated oocytes to develop after the parthenogenetic activation, as well as the lack of DNA staining luminescence, strongly confirms the efficiency of the femtosecond laser enucleation. The parthenogenetic development of oocytes after the cytoplasm treatment suggests a low-invasive effect of the laser enucleation technique.

Implantable and transcutaneous continuous glucose monitoring system: a randomized cross over trial comparing accuracy, efficacy and acceptance.

AIM: To compare accuracy, efficacy and acceptance of implantable and transcutaneous continuous glucose monitoring (CGM) systems. METHODS: In a randomized crossover trial we compared 12 weeks with Eversense implantable sensor (EVS) and 12 weeks with Dexcom G5 transcutaneous sensor (DG5) in terms of accuracy, evaluated as Mean Absolute Relative Difference (MARD) vs capillary glucose (SMBG), time of CGM use, adverse events, efficacy (as HbA1c, time in range, time above and below range) and psychological outcomes evaluated with Diabetes Treatment Satisfaction Questionnaire (DTSQ), Glucose Monitoring Satisfaction Survey (GMSS), Hypoglycemia Fear Survey (HFS2), Diabetes Distress Scale (DDS). RESULTS: 16 subjects (13 males, 48.8 ± 10.1 years, HbA1c 55.8 ± 7.9 mmol/mol, mean ± SD) completed the study. DG5 was used more than EVS [percentage of use 95.7 ± 3.6% vs 93.5 ± 4.3% (p = 0.02)]. MARD was better with EVS (12.2 ± 11.5% vs. 13.1 ± 14.7%, p< 0.001). No differences were found in HbA1c. While using EVS time spent in range increased and time spent in hyperglycemia decreased, but these data were not confirmed by analysis of retrofitted data based on SMBG values. EVS reduced perceived distress, without significant changes in other psychological outcomes. CONCLUSIONS: CGM features may affect glycemic control and device acceptance.

Optical Monitoring of the Biodegradation of Porous and Solid Silicon Nanoparticles.

Silicon nanoparticles (SiNP) are currently of great interest, especially in biomedicine, because of their unique physicochemical properties combined with biodegradability. SiNPs can be obtained in various ways and can have either a non-porous solid (sol-) or porous (por-) structure. In this work, we carry out detailed optical monitoring of sol- and por-SiNP biodegradation using Raman and photoluminescence (PL) micro-spectroscopy. SiNPs were obtained by ultrasound grinding of sol- or por-silicon nanowires, created by silver-assisted chemical etching of crystalline Si with different doping levels. In this case, sol-SiNPs consist of nanocrystals 30 nm in size, while por-SiNPs consist of small 3 nm nanocrystals and 16 nm pores. Both SiNPs show low in vitro cytotoxicity towards MCF-7 and HEK293T cells up to 800 µg/mL. The appearance of the F-band (blue-yellow) PL, as well as a decrease in the intensity of the Raman signal, indicate the gradual dissolution of the sol-SiNPs during 20 days of incubation. At the same time, the rapid dissolution of por-SiNP within 24 h is identified by the quenching of their S-band (red) PL and the disappearance of the Raman signal. The obtained results are important for development of intelligent biodegradable drug delivery systems based on SiNPs.

The effects of drying technique and surface pre-treatment on the cytotoxicity and dissolution rate of luminescent porous silicon quantum dots in model fluids and living cells.

Tailoring of the biodegradation of photoluminescent silicon quantum dots (Si QDs) is important for their future applications in diagnostics and therapy. Here, the effect of drying and surface pretreatment on the dissolution rate of Si QDs in model liquids and living cells was studied in vitro using a combination of photoluminescence and Raman micro-spectroscopy. Porous silicon particles were obtained by mechanical milling of electrochemically etched mesoporous silicon films, and consist of interlinked silicon nanocrystals (QDs) and pores. The samples were subjected to super-critical drying with CO2 solvent (SCD) or air drying (AD) and then annealed at 600 °C for 16 hours in 1% oxygen to obtain nano-sized Si QDs. The obtained samples were characterized by a core-shell structure with a crystalline silicon core and a SiO2 layer on the surface. The sizes of the crystalline silicon cores, calculated from Raman scattering spectra, were about 4.5 nm for the initial AD-SiQDs, and about 2 nm for the initial SCD-SiQDs. Both the AD-Si QDs and the SCD-Si QDs exhibited visible photoluminescence (PL) properties due to quantum confinement effects. The dissolution of the nanocrystals was evaluated through their PL quenching, as well as by the presence of a low-frequency shift, broadening, and a decrease in the intensity of the Raman signal. The stability of the AD-Si QDs and the complete dissolution of the SCD-Si QDs during 24 hours of incubation with cells have been demonstrated. This might explain the apparent lower cytotoxicity observed for SCD-Si QDs.

Sexual reproduction of the placental brooder Celleporella hyalina (Bryozoa, Cheilostomata) in the White Sea.

The evolution of parental care is a central field in many ecological and evolutionary studies, but integral approaches encompassing various life-history traits are not common. Else, the structure, development and functioning of the placental analogues in invertebrates are poorly understood. Here, we describe the life-history, sexual colony dynamics, oogenesis, fertilization and brooding in the boreal-Arctic cheilostome bryozoan Celleporella hyalina. This placental brooder incubates its progeny in calcified protective chambers (ovicells) formed by polymorphic sexual zooids. We conducted a detailed ultrastructural study of the ovary and oogenesis, and provide evidence of both auto- and heterosynthetic mechanisms of vitellogenesis. We detected sperm inside the early oocyte and within funicular strands, and discuss possible variants of fertilization. We also detail the development and functioning of the placental analogue (embryophore) in the various stages of embryonic incubation as well as embryonic histotrophic nourishment. In contrast to all known cheilostome placentas, the main part of embryophore of C. hyalina is not a single cell layer. Rather, it is a massive "nutritive tissue" whose basal part is associated with funicular strands presumably providing transport function. C. hyalina shows a mixture of reproductive traits with macrolecithal oogenesis and well-developed placenta. These features give it an intermediate position in the continuum of variation of matrotrophic provisioning between lecithotrophic and placentotrophic cheilostome brooders. The structural and developmental differences revealed in the placental analogue of C. hyalina, together with its position on the bryozoan molecular tree, point to the independent origin of placentation in the family Hippothoidae.

What is to blame for postnatal pelvic floor dysfunction in primiparous women-Pre-pregnancy or intrapartum risk factors?

BACKGROUND: The aetiology of pelvic floor dysfunction (PFD) is still poorly understood. However childbearing is recognized as a major risk factor. OBJECTIVES: To elucidate the natural history of PFD by investigating the impact of the mode of delivery on postnatal pelvic floor dysfunction in primiparas, when PFD existing before the first pregnancy is taken into consideration. STUDY DESIGN: 4P-study (Prevalence and Predictors of Pelvic floor dysfunction in Primips) is a prospective cohort study, nested within the Screening for Pregnancy Endpoints (SCOPE) study set in a tertiary referral teaching hospital with 9000 deliveries annually. Established and proposed risk factors for urinary, fecal, prolapse and sexual dysfunction and the severity of symptoms for each of these outcomes were assessed using the Australian Pelvic Floor Questionnaire in 1482 nulliparous women, who each completed the questionnaire in early pregnancy. Of these, 1060 (72%) repeated the questionnaire 12 months postpartum.Outcomes were analyzed using multivariate ordinal logistic regression. RESULTS: Significant (p<0.05) risk factors for postpartum PFD were pre-pregnancy presence of similar symptoms Odds Ratio (OR) (5.0-30.0), smoking (OR 2.2-4.6), recurrent UTI (OR 2.2-17.3), high hip circumference (OR1.4-1.6), vigorous exercising (OR 3.1-17.9), induction of labor (OR 1.5-2.3), forceps delivery (OR 1.8-8.8), and 3rd degree perineal tear (OR 2.4-2.7). Cesarean section was associated with a lower risk of stress urinary incontinence (OR 0.3-0.5). Other common pre-pregnancy significant (p<0.05) risk factors for various PFD types prior to the first pregnancy were: diagnosed depression - (OR 1.6-2.1), high BMI (OR 3.1), strenuous exercising (OR 1.3-2.2), recurrent UTI (OR 1.5-2.5) and lower educational achievement (OR 1.5-1.6). CONCLUSIONS: Pre-pregnancy PFD was mainly associated with modifiable risk factors such as smoking and exercising. The main risk factor for postpartum PFD was the presence of similar symptoms prior to pregnancy, followed by anthropometric and intrapartum factors. Hip circumference seems to be a better predictor of PFD compared to BMI. When pre-pregnancy PFD was included in the analysis, Cesarean section was protective only for stress urinary incontinence, while delivery by forceps increased the risk of prolapse.