Prevalence and course of pregnancy symptoms using self-reported pregnancy app symptom tracker data.

During pregnancy, almost all women experience pregnancy-related symptoms. The relationship between symptoms and their association with pregnancy outcomes is not well understood. Many pregnancy apps allow pregnant women to track their symptoms. To date, the resulting data are primarily used from a commercial rather than a scientific perspective. In this work, we aim to examine symptom occurrence, course, and their correlation throughout pregnancy. Self-reported app data of a pregnancy symptom tracker is used. In this context, we present methods to handle noisy real-world app data from commercial applications to understand the trajectory of user and patient-reported data. We report real-world evidence from patient-reported outcomes that exceeds previous works: 1,549,186 tracked symptoms from 183,732 users of a smartphone pregnancy app symptom tracker are analyzed. The majority of users track symptoms on a single day. These data are generalizable to those users who use the tracker for at least 5 months. Week-by-week symptom report data are presented for each symptom. There are few or conflicting reports in the literature on the course of diarrhea, fatigue, headache, heartburn, and sleep problems. A peak in fatigue in the first trimester, a peak in headache reports around gestation week 15, and a steady increase in the reports of sleeping difficulty throughout pregnancy are found. Our work highlights the potential of secondary use of industry data. It reveals and clarifies several previously unknown or disputed symptom trajectories and relationships. Collaboration between academia and industry can help generate new scientific knowledge.

Lipophilic rather than hydrophilic photosensitizers show strong adherence to standard cell culture microplates under cell-free conditions.

Analysis of photosensitizer (PS) uptake kinetics into tumor cells is a standard cell culture experiment in photodynamic therapy (PDT) - usually performed in plastic microplates or petri dishes. Organic substances such as PS can potentially interact with the plastic surfaces. In this study, we provide a qualitative comparison of three lipophilic PS (hypericin, Foscan® and Photofrin®) and two rather hydrophilic PS formulations (PVP-hypericin and aluminum (III) phthalocyanine tetrasulfonate chloride) regarding their adherence to the surfaces of 96-well microplates obtained from four different manufacturers. For estimation of the relevance of PS adherence for cellular uptake studies we compared the fluorescence signal of the respective PS in microplates containing A431 human epithelial carcinoma cells with microplates incubated with the respective PS under cell-free conditions. We demonstrate that lipophilic PS substances show a strong adherence to microplates - in case of direct lysis and fluorescence measurement resulting in 50% up to 90% of the overall signal to be caused by adherence of the substances to the plastic materials in a cellular uptake experiment. For the hydrophilic compounds, adherence is negligible. Interestingly, adherence of PS agents to microplates takes place in a time-dependent and thus kinetic-like manner, requiring up to several hours to reach a plateau of the fluorescence signal. Furthermore, PS adherence is a function of the PS concentration applied and no saturation effect was observed for the concentrations used in this study. Taken together, this study provides a systematic analysis under which conditions PS adherence to cell culture plates may contribute to the overall fluorescence signal in - for example - PS uptake experiments.

Comparative in vitro study on the characteristics of different photosensitizers employed in PDT.

At present a wide range of photosensitizers are employed in photodynamic therapy (PDT) that have very different characteristics. Although, countless in vitro studies on the attributes of photosensitizers do exist, a direct comparison of these substances on one cell line are rare and may contribute to the choice of the optimal photoactive substance for a specific application. We therefore evaluated the properties of six widespread photosensitizers, namely Foscan, Fospeg, hypericin, aluminum (III) phthalocyanine tetrasulfonate chloride (AlPcS(4)), 5-aminolevulinic acid (ALA), and Photofrin in terms of: (i) cytotoxicity without illumination, (ii) phototoxicity, (iii) cellular uptake and release, and (iv) apoptosis induction in A431 human epidermoid carcinoma cells using comparable illumination regimens. We clearly show that meso-tetrahydroxyphenylchlorin (mTHPC, Foscan) is a very effective photosensitizer inducing high phototoxicity at very low concentrations. Similar in vitro characteristics and phototoxicity were observed for Fospeg, the water-soluble formulation of mTHPC. Hypericin, a photosensitizer extracted from plants of the Hypericum genus, is very effective in inducing apoptosis over a wide range of light fluences. AlPcS(4) absorbs light of 674 nm wavelength providing a higher penetration depth in tissue. Its hydrophilic character allows for application as aqueous solution. ALA can be administered at very high concentrations without producing cytotoxic effects in the dark. The intracellular concentration of protoporphyrin IX rapidly decreases after withdrawal of ALA, thus minimizing the period of light sensitivity post PDT. Among all photosensitizers Photofrin has most clinical approvals and serves as standard.

Antibacterial photodynamic therapy using water-soluble formulations of hypericin or mTHPC is effective in inactivation of Staphylococcus aureus.

Antibacterial photodynamic treatment (APDT) might prove valuable as an alternative to the application of chemoantibiotics for the treatment of staphylococcal infections. The rapid uptake of the photosensitizing agent into bacteria allows for selective killing of microorganisms whilst sparing the eukaryotic host tissue, but also requires removal of excessive dye after the incubation period. We tested water-soluble formulations of hypericin (PVP-hypericin) and m-tetrahydroxyphenylchlorin (Fospeg), which could be applied as aqueous sprays and removed easily by flushing with buffers, for their efficiency in killing Staphylococcus aureus. For both sensitizers, 100 nM of the photoactive substance incubated for 5 min and illuminated for 30 min at 75 mW cm(-2) lead to a 4-5 log unit reduction in bacterial count. At a concentration of 300 nM (incubation time 5 min), 30 min illumination at 25 mW cm(-2) is more effective than 10 min illumination at 75 mW cm(-2) (both resulting in the same fluence). We suggest both substances as promising candidates for treatment of staphylococcal infections in wounds with APDT.

Revised morphology and hemodynamics of the anorectal vascular plexus: impact on the course of hemorrhoidal disease.

PURPOSE: The pathogenesis of hemorrhoidal disease is based mainly on the vascular hyperplasia theory. The aim of this study was to reassess the morphology and the functional mechanisms of the anorectal vascular plexus with regard to hemorrhoidal disease. MATERIALS AND METHODS: The anorectal vascular plexus was investigated in 17 anorectal and five hemorrhoidectomy specimens by means of conventional histology and immunohistochemistry. Vascular corrosion casts from two fresh rectal specimens were used for scanning electron microscopy. Transperineal color Doppler ultrasound (CDUS) with spectral wave analysis (SWA) was performed in 38 patients with hemorrhoidal disease and 20 healthy volunteers. RESULTS: The anorectal vascular plexus was characterized by a network of submucosal vessels exhibiting multiple thickened venous vessels separated by distinct sphincter-like constrictions. CDUS and SWA showed significant flow differences in peak velocities (6.8 +/- 1.3 cm/s vs. 10.7 +/- 1.5 cm/s; P = 0.026) and acceleration velocities (51 +/- 4 ms vs. 94 +/- 11 ms; P = 0.001) of afferent vessels between the control group and patients with hemorrhoidal disease. CONCLUSIONS: Coordinated filling and drainage of the anorectal vascular plexus is regulated by intrinsic vascular sphincter mechanisms. Both morphological and functional failure of this vascular system may contribute to the development of hemorrhoidal disease.