Neurotrophin-3 (NT-3) as a Potential Biomarker of the Peripheral Nervous System Damage Following Breast Cancer Treatment.

Damage to the peripheral nervous system (PNS) is a common complication of breast cancer (BC) treatment, with 60 to 80% of breast cancer survivors experiencing symptoms of PNS damage. In the current study, the levels of brain-derived neurotrophic factor (BDNF), galectin-3 (Gal-3), and neurotrophin-3 (NT-3) were measured in the blood serum of BC patients by ELISA as potential biomarkers that might indicate the PNS damage. Sixty-seven patients were enrolled in this multi-center trial and compared to the aged-matched healthy female volunteers (control group) (n = 25). Intergroup comparison of biomarker levels (i.e., Gal-3 and BDNF) did not show significant differences in any of the studied subgroups. However, intriguingly, NT-3 levels were significantly higher in BC patients as compared to healthy volunteers, constituting 14.85 [10.3; 18.0] and 5.74 [4.56; 13.7] pg/mL, respectively (p < 0.001). In conclusion, NT-3 might be employed as a potential biomarker in BC patients with clinical manifestations of PNS damage. However, further studies to validate its correlation to the degree of peripheral nervous system lesions are of high value.

Microstructural Properties of Brain White Matter Tracts in Breast Cancer Survivors: A Diffusion Tensor Imaging Study.

Complex breast cancer (BC) treatment can cause various neurological and psychiatric complications, such as postmastectomy pain syndrome, vestibulocerebellar ataxia, and depression, which can lead to microstructural damage of the white matter tracts of the brain. The purpose of the study is to assess microstructural changes in the white matter tracts of the brain in BC survivors using diffusion tensor imaging (DTI). Single DTI scans were performed on patients (n = 84) after complex BC treatment (i.e., surgery, chemotherapy and/or radiation therapy) and on the control group (n = 40). According to the results, a decrease in the quantitative anisotropy (FDR ≤ 0.05) was revealed in the bilateral corticospinal tracts, cerebellar tracts, corpus callosum, fornix, left superior corticostriatal and left corticopontine parietal in patients after BC treatment in comparison to the control group. A decrease in the quantitative anisotropy (FDR ≤ 0.05) was also revealed in the corpus callosum and right cerebellar tracts in patients after BC treatment with the presence of postmastectomy pain syndrome and vestibulocerebellar ataxia. The use of DTI in patients after BC treatment reveals microstructural properties of the white matter tracts in the brain. The results will allow for the improvement of treatment and rehabilitation approaches in patients receiving treatment for breast cancer.

Breast Cancer Treatment Decreases Serum Levels of TGF-ß1, VEGFR2, and TIMP-2 Compared to Healthy Volunteers: Significance for Therapeutic Outcomes?

Various complications from a breast cancer treatment, in the pathogenesis of which excessive tissue fibrosis plays a leading role, are a common pathology. In this study, the levels of TGF-ß1, VEGFR-2, and TIMP-2 were determined by the immuno-enzyme serum analysis for patients during the long-term period after breast cancer treatment as potential markers of fibrosis. The single-center study enrolled 92 participants, which were divided into two age-matched groups: (1) 67 patients following breast cancer treatment, and (2) 25 healthy female volunteers. The intergroup analysis demonstrated that the patients after breast cancer treatment showed a decrease in the serum levels of TGF-ß1 (U = 666, p < 0.001) and TIMP-2 (U = 637, p < 0.001) as compared to the group of healthy volunteers. The levels of VEGFR-2 in these groups were comparable (U = 1345, p = 0.082). It was also found that the type of treatment, the presence of lymphedema, shoulder joint contracture, and changes in lymphoscintigraphy did not affect the levels of TGF-ß1, VEGFR-2, and TIMP-2 within the group of patients after breast cancer treatment. These results may indicate that these biomarkers do not play a leading role in the maintenance and progression of fibrosis in the long-term period after breast cancer treatment. The reduced levels of TGF-ß1 and TIMP-2 may reflect endothelial dysfunction caused by the antitumor therapy.

Adhesion Molecules ICAM-1 and PECAM-1 as Potential Biomarkers of Central Nervous System Damage in Women Breast Cancer Survivors.

Breast cancer (BC) is the most common tumor in women worldwide with high mortality rates. Surgical methods followed by radio-chemotherapy are used to treat these tumors. Such treatment can lead to various side effects, including neurological complications. The development of a reliable biomarker to predict the onset of CNS complications could improve clinical outcomes. In the current study, ICAM-1 and PECAM-1 serum levels were measured as potential biomarkers in 45 female patients in a long-term follow-up period after breast cancer treatment, and compared to 25 age-matched female healthy volunteers. Serum levels of both biomarkers, ICAM-1 and PECAM-1 were significantly higher in patients after breast cancer treatment and could be associated with cognitive dysfunction, depression, and vestibulocerebellar ataxia. In conclusion, our results provide a first hint that elevated serum levels of ICAM-1 and PECAM-1 could serve as early predictive biomarkers in breast cancer survivors that might help to improve the management of these patients.

Potential Molecular Biomarkers of Central Nervous System Damage in Breast Cancer Survivors.

Damage of the central nervous system (CNS), manifested by cognitive impairment, occurs in 80% of women with breast cancer (BC) as a complication of surgical treatment and radiochemotherapy. In this study, the levels of ICAM-1, PECAM-1, NSE, and anti-NR-2 antibodies which are associated with the damage of the CNS and the endothelium were measured in the blood by ELISA as potential biomarkers that might reflect pathogenetic mechanisms in these patients. A total of 102 patients enrolled in this single-center trial were divided into four groups: (1) 26 patients after breast cancer treatment, (2) 21 patients with chronic brain ischemia (CBI) and asymptomatic carotid stenosis (ICA stenosis) (CBI + ICA stenosis), (3) 35 patients with CBI but without asymptomatic carotid stenosis, and (4) 20 healthy female volunteers (control group). Intergroup analysis demonstrated that in the group of patients following BC treatment there was a significant increase of ICAM-1 (mean difference: −368.56, 95% CI −450.30 to −286.69, p < 0.001) and PECAM-1 (mean difference: −47.75, 95% CI −68.73 to −26.77, p < 0.001) molecules, as compared to the group of healthy volunteers. Additionally, a decrease of anti-NR-2 antibodies (mean difference: 0.89, 95% CI 0.41 to 1.48, p < 0.001) was detected. The intergroup comparison revealed comparable levels of ICAM-1 (mean difference: −33.58, 95% CI −58.10 to 125.26, p = 0.76), PECAM-1 (mean difference: −5.03, 95% CI −29.93 to 19.87, p = 0.95), as well as anti-NR-2 antibodies (mean difference: −0.05, 95% CI −0.26 to 0.16, p = 0.93) in patients after BC treatment and in patients with CBI + ICA stenosis. The NSE level in the group CBI + ICA stenosis was significantly higher than in women following BC treatment (mean difference: −43.64, 95% CI 3.31 to −83.99, p = 0.03). Comparable levels of ICAM-1 were also detected in patients after BC treatment and in the group of CBI (mean difference: −21.28, 95% CI −111.03 to 68.48, p = 0.92). The level of PECAM-1 molecules in patients after BC treatment was also comparable to group of CBI (mean difference: −13.68, 95% CI −35.51 to 8.15, p = 0.35). In conclusion, among other mechanisms, endothelial dysfunction might play a role in the damage of the CNS in breast cancer survivors.

Functional Network Connectivity Reveals the Brain Functional Alterations in Breast Cancer Survivors.

Different neurological and psychiatric disorders such as vertebrobasilar insufficiency, chronic pain syndrome, anxiety, and depression are observed in more than 90% of patients after treatment for breast cancer and may cause alterations in the functional connectivity of the default mode network. The purpose of the present study is to assess changes in the functional connectivity of the default mode network in patients after breast cancer treatment using resting state functional magnetic resonance imaging (rs-fMRI). Rs-fMRI was performed using a 3.0T MR-scanner on patients (N = 46, women) with neurological disorders (chronic pain, dizziness, headaches, and/or tinnitus) in the late postoperative period (>12 months) after Patey radical mastectomy for breast cancer. According to the intergroup statistical analysis, there were differences in the functional connectivity of the default mode network in all 46 patients after breast cancer treatment compared to the control group (p < 0.01). The use of rs-fMRI in in breast cancer survivors allowed us to identify changes in the functional connectivity in the brain caused by neurological disorders, which correlated with a decreased quality of life in these patients. The results indicate the necessity to improve treatment and rehabilitation methods in this group of patients.

How Lasers Ablate Stones: In Vitro Study of Laser Lithotripsy (Ho:YAG and Tm-Fiber Lasers) in Different Environments.

Introduction: There are two main mechanisms of stone ablation with long-pulsed infrared lasers: photothermal and photomechanical. Which of them is primary in stone destruction is still a matter of discussion. Water holds importance in both mechanisms but plays a major role in the latter. We sought to identify the prevailing mechanism of stone ablation by evaluating the stone mass loss after lithotripsy in different media. Materials and Methods: We tested a holmium:yttrium-aluminum-garnet (Ho:YAG) laser (100 W; Lumenis), a thulium-fiber laser U1 (TFL U1) (120 W; NTO IRE-Polus, Russia), and a SuperPulse thulium-fiber laser U2 (TFL U2) (500 W; NTO IRE-Polus). A single set of laser parameters (15 W = 0.5 J × 30 Hz) was used. Contact lithotripsy was performed in phantoms (BegoStones) in different settings: (a) hydrated phantoms in water, (b) hydrated phantoms in air, (c) dehydrated phantoms in water, and (d) dehydrated phantoms in air. Laser ablation was performed with total energy of 0.3 kJ. Phantom mass loss was defined as the difference between the initial phantom mass and the final phantom mass of the ablated phantoms. Results: All lasers demonstrated effective ablation in hydrated phantoms ablated in water; no visual differences between the lasers were detected. The ablation of dehydrated phantoms in air was also effective with visible vapor during ablation and condensation on the cuvette wall. Dehydrated phantoms in water and in air show minimal to no ablation accompanied with formation of white crust on phantom surface. Among laser types, TFL U2 had the highest phantom mass loss in all groups except for dehydrated phantoms ablated in air. Conclusions: Our results suggest that both photothermal and thermomechanical ablation mechanisms (explosive vaporization) occur in parallel during laser lithotripsy. In Ho:YAG and TFL U2 stone ablation explosive vaporization prevails, whereas in TFL U1 ablation photothermal mechanism appears to predominate.

Chicken embryos can maintain heart rate during hypoxia on day 4 of incubation.

Acute exposure to hypoxic conditions is a frequent natural event during the development of bird eggs. However, little is known about the effect of such exposure on the ability of young embryos in which cardiovascular regulation is not yet developed to maintain a normal heart rate (HR). To address this question, we studied the effect of 10-20 min of exposure to moderate or severe acute hypoxia (10% or 5% O2, respectively) on the HR of day 4 (D4) chicken embryos. In ovo, video recording of the beating embryo heart inside the egg revealed that severe, but not moderate, hypoxia resulted in significant HR changes. The HR response to severe hypoxia consisted of two phases: the first phase, consisting of an initial decrease in HR, was followed by a phase of partial HR recovery. Upon the restoration of normoxia, after an overshoot period of a few minutes, the HR completely recovered to its basal level. In vitro (isolated heart preparation), the first phase of the HR response to severe hypoxia was strengthened (nearly complete heart silencing) compared to that in ovo, and the HR recovery phase was greatly attenuated. Furthermore, neither an overshoot period nor complete HR recovery after hypoxia was observed. Thus, the D4 chicken embryo heart can partially maintain its rhythm during hypoxia in ovo, but not in vitro. Some factors from the egg, such as catecholamines, are likely to be critical for avian embryo responding to hypoxic condition and survival.

Temperature changes during laser lithotripsy with Ho:YAG laser and novel Tm-fiber laser: a comparative in-vitro study.

AIM: The aim of this study was to compare the thermal effects of Ho:YAG and Tm-fiber lasers during lithotripsy in an in-vitro model via real-time temperature measurement. METHODS: We compared a Ho:YAG laser (pav up to 100 W, Lumenis, Yokneam, Israel) and a superpulse Tm-fiber laser (SP TFL, pav up to 40 W, NTO IRE-Polus, Fryazino, Russia), both equipped with 200 µm bare-ended fibers. The following settings were used: 0.2 J, 40 Hz (nominal pav 8 W). Power meter FieldMaxII-TO (Coherent, Santa Clara, CA, USA) was used to verify output laser power (pav). Each laser was fired for 60 s in two setups: (1) thermos-insulated (quasi-adiabatic) cuvette; (2) actively irrigated setup with precise flow control (irrigation rates 0, 10, 35 mL/min). RESULTS: Power measurements performed before the test revealed a 10% power drop in Ho:YAG (up to 7.2 ± 0.1 W) and 6.25% power drop in SP TFL (up to 7.5 ± 0.1). At the second step of our experiment, irrigation reduced the respective temperatures in the same manner for both lasers (e.g., at 35 mL/s SP TFL - 1.9 °C; for Ho:YAG laser - 2.8 °C at 60 s). CONCLUSION: SP TFL and Ho:YAG lasers are not different in terms of volume-averaged temperature increase when the same settings are used in both lasers. Local temperature rises may fluctuate to some degree and differ for the two lasers due to varying jet streaming caused by non-uniform heating of the aqueous medium by laser light.

Novel thulium fiber laser for endoscopic enucleation of the prostate: A prospective comparison with conventional transurethral resection of the prostate.

OBJECTIVE: To compare the efficacy and safety of a novel thulium fiber laser for endoscopic enucleation of the prostate with monopolar transurethral resection of the prostate in patients with smaller glands (<80 cc). METHODS: A total of 51 patients underwent thulium fiber laser enucleation of the prostate, and 52 patients underwent monopolar transurethral resection of the prostate. All patients were assessed preoperatively, and at 3, 6, and 12 months postoperatively (International Prostate Symptom Score, maximum urine flow rate, International Prostate Symptom Score-quality of life). Preoperative prostate volumes and prostate-specific antigen levels were comparable (P = 0.543 and P = 0.078, respectively). The complications were graded according to the Clavien classification. RESULTS: Mean surgery time was longer in the thulium fiber laser enucleation of the prostate group (46.6 ± 10.2 vs 39.9 ± 8.6 min, P < 0.001), while catheterization and hospital stay were greater in the transurethral resection of the prostate group (P < 0.001). At 12 months, there were no differences in functional outcomes (International Prostate Symptom Score, maximum urine flow rate). Despite comparable prostate volumes at 12 months (P = 0.864), the prostate-specific antigen level in the thulium fiber laser enucleation of the prostate group (0.5 ± 0.5 ng/mL) was lower than in the transurethral resection of the prostate group (1.1 ± 1.0 ng/mL; P < 0.001). Hemoglobin and serum sodium decrease was lower in the thulium fiber laser enucleation of the prostate group (1.01 ± 0.4 g/dL and 1.1 ± 1.1 mmol/L) than in the transurethral resection of the prostate group (1.8 ± 0.8 g/dL and 4.1 ± 1.1 mmol/L; P < 0.001). Urinary incontinence rates at 12 months were comparable (P = 0.316). CONCLUSIONS: Thulium fiber laser enucleation of the prostate with novel thulium fiber laser in patients with smaller prostate glands (<80 cc) is comparable to transurethral resection of the prostate in voiding parameters improvement and complication rates. At the same time, the technique allows for a more substantial prostate-specific antigen decrease, indicating more complete removal of adenoma.

En bloc and two-lobe techniques for laser endoscopic enucleation of the prostate: retrospective comparative analysis of peri- and postoperative outcomes.

OBJECTIVES: Various techniques can be used for endoscopic enucleation of the prostate (EEP): removal of all nodes as a single unit (en bloc) or a step-by-step removal of adenomatous nodes (two- and three-lobe techniques). The objective of this study was to perform a comparative analysis of en bloc and two-lobe techniques for holmium laser enucleation of the prostate (HoLEP) and thulium fiber laser enucleation of the prostate (ThuFLEP). METHODS: Retrospective assessment included patients with bladder outlet obstruction (IPSS > 20, Qmax < 10) secondary to BPH treated from January 2013 to December 2018. All the patients were assessed prior to surgery, as well as at 1, 3 and 6 months after surgery. RESULTS: The data of 1115 patients who underwent HoLEP or ThuFLEP were analyzed. Two techniques were used: en bloc (406 patients) and two-lobe (709 patients). Mean prostate volumes were comparable between groups. Mean surgery times (68.8 ± 30.6 min vs 67.4 ± 30.1 min; p = 0.604) and enucleation rates (1.9 ± 0.74 g/min vs 1.9 ± 0.69 g/min; p = 0.217) were also comparable. Morcellation rate was lower in en bloc patients with prostate > 150 cc (2.8 ± 1.1 g/min vs 3.7 ± 2.3 g/min; p < 0.001). At 6 months, no differences in functional outcomes (IPSS, PVR, Qmax and QoL) were found. CONCLUSIONS: Outcomes and complication rates of en bloc and two-lobe EEP techniques were comparable. En bloc technique was found to have less favorable outcomes in morcellation rate for prostates > 150 cc. The choice of the technique should depend on surgeon's preferences.

Oxygen consumption as related to the development of the extraembryonic membranes and cardiovascular system in the European pond turtle (Emys orbicularis) embryogenesis.

The rate of oxygen consumption (V(O2)), embryo mass, distribution and mass of the chorioallantoic membrane (CAM), heart rate (HR), heart mass, and amnion rhythmic contractions (ARC) were studied in eggs of the European pond turtle (Emys orbicularis) incubated at 28 degrees C for 62.5+/-0.3 days. The V(O2) rapidly increased beginning from incubation day 19 (D19) to a maximum on D50 and then decreased until pipping. The rapid V(O2) rise was correlated with an increase in the CAM surface and mass, heart mass, and ARC amplitude, whereas the functional parameters such as HR and ARC frequency remained unchanged. The drop in V(O2) before pipping was accompanied by a decrease in HR, while the heart and CAM masses were almost constant. In the cases of short-term temperature deviations of +/-3 degrees C from 28 degrees C, changes in (O2) were significant until D50 and nonsignificant after that, the changes in ARC frequency and HR being significant at all stages studied. Thus, the developmental V(O2) changes were contributed mainly by the slow morphogenetic processes during D19-D50, whereas changes in functional parameters began to play a role at later stages. The response to temperature fluctuations was mediated by a rapid change in functional parameters at all these stages.