Microfluidic synthesis of retinoic acid-loaded nanoparticles for neural differentiation of trabecular meshwork mesenchymal stem cell.

OBJECTIVES: This study aimed to fabricate the PCL-nanoparticles (NPs) loaded retinoic acid (RA) using the microfluidic system for successful cellular uptake and induction of neuronal differentiation of trabecular meshwork mesenchymal stem cells (TMMSCs). METHODS: A microfluidic system used to synthesize RA-loaded NPs, DLS, FTIR, TEM, and UV-spectroscopy was recruited to characterize and study the release of RA. Also, the toxicity, cellular uptake, and neuronal differential of TMMSCs have been assessed. RESULTS: According to the obtained results, the spherical NPs (117.6±0.35 nm, ‒19.4±5.3) and RA-loaded NPs (121.6±0.75 nm, ‒23.6±1.3) were synthesized successfully by microfluidic system. 7.8±2.04 % of RA was loaded in NPs, and 25 % was released in the first four hours. Thus, the NPs have been successfully internalized into the stem cells, leading to a significant increase in neural genes and protein (ß Tubulin III and Map-2) expression. CONCLUSION: Our study's harvested results have represented valid data for practical use of microfluidic systems in the term of NPs loaded RA synthesis and its successful function to cellular internalization and euronal differentiation of TMMSCs (Tab. 2, Fig. 10, Ref. 46).

A prospective, observational study of the performance of MEWS, NEWS, SIRS and qSOFA for early risk stratification for adverse outcomes in patients with suspected infections at the emergency department.

BACKGROUND: Many patients with suspected infection are presented to the emergency Department. Several scoring systems have been proposed to identify patients at high risk of adverse outcomes. METHODS: We compared generic early warning scores (MEWS and NEWS) to the (SIRS) criteria and quick Sequential Organ Failure Assessement (qSOFA), for early risk stratification in 1400 patients with suspected infection in the ED. The primary study end point was 30-day mortality. RESULTS: The AUROC of the NEWS score for predicting 30-day mortality was 0.740 (95% Confidence Interval 0.682- 0.798), higher than qSOFA (AUROC of 0.689, 95% CI 0.615- 0.763), MEWS (AUROC 0.643 (95% CI 0.583-0.702) and SIRS (AUROC 0.586, 95%CI 0.521 - 0.651). The sensitivity was also highest for NEWS⋝ 5 (sensitivity 75,8% specificity of 67,4%). CONCLUSION: Among patients presenting to the ED with suspected infection, early risk stratification with NEWS (cut-off of ⋝5) is more sensitive for prediction of mortality than qSOFA, MEWS or SIRS, with adequate specificity.

Brain lesions in a patient with rectal cancer: mind your step.

Cerebral toxoplasmosis is a potentially fatal infection most commonly seen in immunocompromised patients. We present a patient on long-term immunosuppressive therapy after kidney transplantation and a recent history of oligometastatic rectal cancer, with cerebral lesions as a result of toxoplasmosis. Heightened awareness of the occurrence of opportunistic infections in patients with cancer who are taking immunosuppressive drugs is needed among clinicians.

IFI16 is required for DNA sensing in human macrophages by promoting production and function of cGAMP.

Innate immune activation by macrophages is an essential part of host defence against infection. Cytosolic recognition of microbial DNA in macrophages leads to induction of interferons and cytokines through activation of cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING). Other host factors, including interferon-gamma inducible factor 16 (IFI16), have been proposed to contribute to immune activation by DNA. However, their relation to the cGAS-STING pathway is not clear. Here, we show that IFI16 functions in the cGAS-STING pathway on two distinct levels. Depletion of IFI16 in macrophages impairs cGAMP production on DNA stimulation, whereas overexpression of IFI16 amplifies the function of cGAS. Furthermore, IFI16 is vital for the downstream signalling stimulated by cGAMP, facilitating recruitment and activation of TANK-binding kinase 1 in STING complex. Collectively, our results suggest that IFI16 is essential for efficient sensing and signalling upon DNA challenge in macrophages to promote interferons and antiviral responses.

Comparison of aglycon and glycosidic saponin extracts of Cyclamen coum tuber against Candida spp.

BACKGROUND AND PURPOSE: Candidiasis, an important fungal infection, is considered the fourth most common nosocomial blood stream infection. Nowadays, because of increased fungal resistance to antibiotics, the use of herbal medicine has gained particular attention. Cyclamen species are medicinal plants containing triterpenoid saponins, which are shown to have antimicrobial properties. MATERIALS AND METHODS: Three species of Candida including C.albicans, 10231 C.tropicalis 0750 ,and C.krusei and nine clinical samples were cultured on Sabouraud dextrose agar. Active substances of the tubers were extracted by fractionation method. Susceptibility of Candida to Cyclamencoum tuber extracts was evaluated via minimum inhibitory concentration) MIC( and minimum fungicidal concentration (MFC.(. RESULTS: Our results demonstrated that ethyl acetate extract had no inhibitory effect on Candida strains, whereas the aqueous and n-butanolic extracts showed considerable activity. MIC and MFC of these extracts varied within the range of 2-32 µg/mL of saponin for different Candida samples. Aglyconic aqueous phase of the extract had the most effective anticandida activity. Glycosidic and aglyconic aqueous extracts were less active on C. albicans strains and C. Tropicalis, respectively. CONCLUSION: Tuber extract of Cyclamen was rich in triterpenoid saponins and had antifungal effect. Sugar chain structure, as well as type and concentration of the aglycones were effective in this activity.

The evaluation of Candida albicans biofilms formation on silicone catheter, PVC and glass coated with titanium dioxide nanoparticles by XTT method and ATPase assay.

Lots of Candida albicans infections involve in biofilm formation on medical devices. This kind of biofilm can impede antifungal therapy and complicates the treatment of infectious diseases particularly in field of chronic diseases associated with implanted devices. This study has investigated the influence of treating silicone catheter, PVC and glass coated with Titanium dioxide (TiO2) nanoparticles on attachment of C. albicans. In this study TiO2 nanoparticles were synthesized from precursor TiCl4 and characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD) which showed TiO2 nanoparticles are 70-100 nm in size. In the simplest model of biofilms formation, C. albicans isolates (ATCC10231) and (ATCC 76615) were grown on the surface of small disks of catheter, PVC and glass in a flat-bottomed 12-well plates and evaluated biofilm formation using ATP bioluminescence and tetrazolium salt (XTT) reduction assays. In addition, morphology of C. albicans biofilms after 48 h incubation was observed by SEM. Results indicated that there is a statistical difference between mean of coated samples especially catheter and glass before and after TiO2 nanoparticles coating (p<0.05). In SEM analysis, C. albicans biofilm was more aggregated on the surface of glass and catheter than PVC and control groups and after treatment by these nanoparticles, catheter and glass both showed most significant decrease of C. albicans attachment in comparison to the control groups (Fig. 4, Ref. 23).

Reproducibility of postural changes in intraocular pressure with the Tono-Pen and Pulsair tonometers.

Reproducibility of measurements of postural changes in intraocular pressure was determined by using the Tono-Pen (Mentor O & O, Inc., Norwell, Massachusetts) and Pulsair (Keeler Instruments, Inc., Broomhall, Pennsylvania) tonometers. Thirty subjects had three repeated sitting and reclining measurements performed on three separate visit days. Reproducibility coefficients of 3.3% for the Tono-Pen and 6.3% for the Pulsair were obtained for the within-visit postural change measurements. Across-visit reproducibility coefficients were 7.9% and 26.2% for the Tono-Pen and Pulsair, respectively. The estimated standard deviations for both the within-visit and across-visit postural change measurements were high for both instruments. These results indicate poor reproducibility of measurements of postural changes in intraocular pressure.

[Consequences of a delayed start of therapy in primary irradiated gynecologic malignomas on five-year healing and mortality. A clinical epidemiological study]. / Die Auswirkungen eines verschleppten Behandlungsbeginns primär bestrahlter gynäkologischer Malignome auf die Fünfjahresheilung und Mortalität. Eine klinisch-epidemiologische Studie

The cases of 627 women with gynaecological malignomas, who were primarily irradiated in 1967 to 1969, were interpreted, questioning the temporary difference between clinical and histological diagnosis and beginning of treatment with regard to five-years' healing-results and mortality. The study has demonstrated, that - a delay of only four weeks considered - the part of living patients waas 11,28% of the total number of living patients, the part of dead patients however was 21,62% of the total number of dead patients. We emphasize therefore the urgency of an immediate beginning of therapy following a reliable diagnosis.