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Abstract Photoreceptor chromophore, 11-cis retinal (11CR) and the photoproduct, all-trans retinal (ATR), are present in the retina at higher concentrations and interact with the visual cells. Non-visual cells in the body are also exposed to retinal that enters the circulation. Although the cornea and the lens of the eye are transparent to the blue light region where retinal can absorb and undergo excitation, the reported phototoxicity in the eye has been assigned to lipophilic non-degradable materials known as lipofuscins, which also includes retinal condensation products. The possibility of blue light excited retinal interacting with cells; intercepting signaling in the presence or absence of light has not been explored. Using live cell imaging and optogenetic signaling control, we uncovered that blue light-excited ATR and 11CR irreversibly change/distort plasma membrane (PM) bound phospholipid; phosphatidylinositol 4,5 bisphosphate (PIP2) and disrupt its function. This distortion in PIP2 was independent of visual or non-visual G-protein coupled receptor activation. The change in PIP2 was followed by an increase in the cytosolic calcium, excessive cell shape change, and cell death. Blue light alone or retinal alone did not perturb PIP2 or elicit cytosolic calcium increase. Our data also suggest that photoexcited retinal-induced PIP2 distortion and subsequent oxidative damage incur in the core of the PM. These findings suggest that retinal exerts light sensitivity to both photoreceptor and non-photoreceptor cells, and intercepts crucial signaling events, altering the cellular fate.

Circulating tumor cells (CTCs) crosstalk with different blood cells before a few of them settle down as disseminated tumor cells (DTCs). We evaluated the correlation between CTC subtypes, DTCs and the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and monocyte to lymphocyte ratio (MLR) for better prognostication of 171 early staged diagnosed breast cancer (BC) patients. -Clinical data and blood values before treatment were retrospectively recorded, representing the 75% percentile, resulting in 3.13 for NLR, 222.3 for PLR and 0.39 for MLR, respectively. DTCs were analyzed by immunocytochemistry using the pan-cytokeratin antibodyA45-B/B3. CTCs were determined applying the AdnaTests BreastCancerDetect and EMT (Epithelial Mesenchymal Transition) Detect . -Reduced lymphocyte ( p = 0.007) and monocyte counts ( p = 0.012), an elevated NLR ( p = 0.003) and PLR ( p = 0.001) significantly correlated with the presence of epithelial CTCs while a reduced MLR was related to EMT-CTCs ( p = 0.045). PLR ( p = 0.029) and MLR ( p = 0.041) significantly related to lymph node involvement and monocyte counts significantly correlated with OS ( p = 0.034). No correlations were found for NLR, PLR and MLR with DTCs, however, DTC-positive patients, harboring a lower PLR, had a significant shorter OS ( p = 0.043). -Pro-inflammatory markers are closely related to different CTC subsets. This knowledge might improve risk prognostication of these patients.

Background: It is known that suboptimal adherence rates may affect endocrine treatments for breast cancer, but little information has been reported whether any efforts to improve treatment adherence have been successful. We designed a randomized, controlled study to investigate the effect of oral or written patient information program on adherence and persistence when receiving an aromatase inhibitor (AI)., Methods: The study cohort included 181 female patients receiving an adjuvant AI treatment randomly assigned to one of three groups. The first group received reminder letters and information booklets, the second group was reminded and informed through telephone calls and the control group received neither. The primary endpoint was the rate at which patients were classified as adhering to treatment after twelve months., Results: Baseline results showed a well-balanced randomization with no significant differences between groups. After 12 months, 48% (CI 35-62) of the control group, 62.7% (CI 49-75) in the telephone group and 64.7% (CI 51-77) in the letter group were adhering to therapy. A post hoc pooled analysis with a one-way hypothesis for both interventions versus control indicated a significant difference between the groups favouring the intervention (p = 0.039)., Conclusion: The aim of this study was to investigate the efficacy of a simple and practical interventional program in enhancing adherence to breast cancer treatment. Patients receiving additional/supplemental information appeared to have an improved adherence rate even though the differences between groups were not statistically significant for the primary endpoint.

Bone responds to exercise with changes in bone (re-)modelling, which might be monitored non-invasively with biochemical bone markers. The aim of this study was to evaluate the influence of exercise on serum osteocalcin and serum carboxy-terminal cross-linked telopeptide of type I collagen generated by matrix metalloproteinases (CTX-MMP) concentration in young racehorses. Seventy-one 2 to 4-year-old Thoroughbreds were included in this prospective infield study. Blood sampling was performed six times (i.e. six sampling cycles) during a 9-month period. Serum samples were analysed with commercial osteocalcin and CTX-MMP radioimmunoassays. Two-year-old racehorses had higher serum osteocalcin and CTX-MMP values than 3-year-old horses. Gender and training amplitude did not significantly influence serum osteocalcin and CTX-MMP values. Two-year-old horses showed an increase in osteocalcin values between cycles 2 and 3 and an increase in serum CTX-MMP values between cycles 1 and 2. Serum osteocalcin and CTX-MMP concentrations decreased between cycles 4 and 5, and 5 and 6. Three-year-old horses showed an increase in serum osteocalcin levels between cycles 3 and 4 and an increase in serum CTX-MMP concentrations between cycles 1 and 2, and 3 and 4. Serum osteocalcin levels decreased between cycles 5 and 6, whereas serum CTX-MMP levels decreased between cycles 4 and 5, and 5 and 6. Two- and three-year-old horses showed a decreased osteocalcin/CTX-MMP ratio between cycles 1 and 2. Moreover, 2-year-old horses showed an increase in the osteocalcin/CTX-MMP ratio between cycles 2 and 3. Sore shin formation did not significantly influence serum osteocalcin and CTX-MMP values. Serum osteocalcin and CTX-MMP are promising bone markers for monitoring exercise induced changes in equine bone metabolism.

Objective: To evaluate a human assay for quantification of carboxy-terminal cross-linking telopeptide of type I collagen (CTX-I), assess the influence of age on plasma CTX-I concentration, investigate the relationship between plasma CTX-I and serum osteocalcin concentrations, and determine whether concentrations of plasma CTX-I or serum osteocalcin fluctuate in circadian manner in horses. HORSES: 75 clinically normal horses., Procedure: Cross-reactivity between equine serum CTX-I and CTX-I antibodies in an automated electrochemiluminescent sandwich antibody assay (ECLIA) was evaluated via a specificity test (ie, dilution test) and recovery calculation. Serum osteocalcin concentration was measured with an equine-specific osteocalcin radioimmunoassay. To analyze diurnal variations in plasma CTX-I and serum osteocalcin concentrations, blood samples were obtained hourly during a 24-hour period., Results: Results of the dilution test indicated good correlation (r > 0.99) between expected serum CTX-I concentrations and measured serum CTX-I concentrations. The calculated CTX-I recovery was 97.6% to 109.9%. Plasma CTX-I and serum osteocalcin concentrations were correlated. Plasma CTX-I concentration was inversely correlated with age of the horse. No significant circadian variations in plasma CTX-I and serum osteocalcin concentrations were detected., Conclusions and Clinical Relevance: Results suggest that the fully automated CTX-I ECLIA can be used for evaluation of plasma and serum samples from horses and may be a useful tool to monitor bone metabolism changes. Horses in this study did not have notable diurnal fluctuations in serum osteocalcin and plasma CTX-I concentrations.