Psychosocial effects of appearance changes due to cancer treatment and needs for information and supportive care in Japanese cancer patients.

PURPOSE: Cancer treatment can alter patient appearance, leading to psychological, social, and behavioral issues. This study aimed to investigate distress and difficulties related to appearance concerns in Japanese cancer patients and to identify information and support needs among them. METHODS: We conducted a questionnaire survey using the Derriford Appearance Scale 59 (DAS59) among cancer patients with a prior history of chemotherapy, molecular targeted therapy, or immunotherapy, who were recruited from the Departments of Medical Oncology and Psychosomatic Medicine, Kindai University Hospital. RESULTS: Participants were 114 patients with a mean age of 62.9 years; 70.2% were female, 86.0% had metastatic or locally advanced unresectable cancer, and 78.1% had concerns about some aspect of their appearance. Mean DAS59 full-scale score was 77.7 ± 36.4. Younger and female participants were found to have higher full-scale scores in univariate analysis (P < .05 for both), and younger participants were found to have higher full-scale scores in multivariate analysis (P < .05). CONCLUSIONS: DAS59 scores had a wide distribution, suggesting that psychological distress due to appearance changes showed large individual differences. Young and female patients tended to have high DAS59 full-scale scores, but some older and male patients also had high scores. Basic information regarding appearance changes should be provided to all patients before initiating cancer treatment. Both information provision prior to treatment and care at the time of actual appearance changes are important, and should be handled through a multidisciplinary approach.

Clinical outcomes of transfer of frozen and thawed single blastocysts derived from nonpronuclear and monopronuclear zygotes.

PURPOSE: In assisted reproductive technology, normal zygotes are bipronuclear (2PN) during fertilization confirmation; however, sometimes, nonpronuclear zygotes (0PN) and monopronuclear zygotes (1PN) are found during routine observations. METHODS: To elucidate the clinical usefulness of in vitro-fertilized embryos, we investigated the rates of clinical pregnancy, live birth, miscarriage, and congenital abnormality after transfer of frozen-thawed 1PN- and 0PN-derived single blastocysts at Denentoshi Ladies Clinic, Kanagawa, Japan. RESULTS: The rates of pregnancy and live birth for 1PN-derived blastocysts obtained by conventional in vitro fertilization were 37.5% and 27.1%, respectively, which was not significantly different from those for 2PN-derived blastocysts; however, the rates for 0PN-derived blastocysts were significantly lower. The pregnancy and live birth rates for 0PN-derived embryos obtained by intracytoplasmic sperm injection (ICSI) were 45.7% and 34.8%, respectively, which was not significantly different from those for 2PN-derived blastocysts; however, the rates for 1PN-derived blastocysts were significantly lower (4.0% for both) than those for 2PN- and 0PN-derived blastocysts. No congenital abnormalities were found in infants resulting from transfer of 0PN- or 1PN-derived blastocysts. CONCLUSIONS: Both 1PN- and 0PN-derived blastocysts can be used for embryo transfer; however, care should be taken in making decisions about 1PN-derived blastocysts, especially if they are obtained by ICSI.

Model-Based Estimation of Aortic and Mitral Valves Opening and Closing Timings in Developing Human Fetuses.

Electromechanical coupling of the fetal heart can be evaluated noninvasively using doppler ultrasound (DUS) signal and fetal electrocardiography (fECG). In this study, an efficient model is proposed using K-means clustering and hybrid Support Vector Machine-Hidden Markov Model (SVM-HMM) modeling techniques. Opening and closing of the cardiac valves were detected from peaks in the high frequency component of the DUS signal decomposed by wavelet analysis. It was previously proposed to automatically identify the valve motion by hybrid SVM-HMM based on the amplitude and timing of the peaks. However, in the present study, six patterns were identified for the DUS components which were actually variable on a beat-to-beat basis and found to be different for the early gestation (16-32 weeks), compared to the late gestation fetuses (36-41 weeks). The amplitude of the peaks linked to the valve motion was different across the six patterns and this affected the precision of valve motion identification by the previous hybrid SVM-HMM method. Therefore in the present study, clustering of the DUS components based on K-means was proposed and the hybrid SVM-HMM was trained for each cluster separately. The valve motion events were consequently identified more efficiently by beat-to-beat attribution of the DUS component peaks. Applying this method, more than 98.6% of valve motion events were beat-to-beat identified with average precision and recall of 83.4% and 84.2% respectively. It was an improvement compared to the hybrid method without clustering with average precision and recall of 79.0% and 79.8%. Therefore, this model would be useful for reliable screening of fetal wellbeing.

Vaginal LPS changed gene transcriptional regulation response to ischemic reperfusion and increased vulnerability of fetal brain hemorrhage.

During pregnancy, both ischemic reperfusion and bacterial agent LPS are known risk factors for fetal brain damage. However, there is a lack of evidence to explain whether vaginal LPS affects the fetus response to ischemic reperfusion. Here we reported that there was more than 2 folds higher vulnerability of fetal brain hemorrhage response to ischemic reperfusion when mother mouse was treated with vaginal LPS. As our previously reported, ischemic reperfusion induces P53-dependent fetal brain damage was based on a molecular mechanism: the transcriptional pattern was changed from HIF-1alpha-dependent to P53-dependent immediately. In the present work, only with vaginal LPS precondition, phosphorylation of activated transcriptional factor (ATF) 2 at Thr71 appeared in response to ischemic reperfusion. Moreover, this phosphorylation was completely blocked by pre-treatment with a P53 inhibitor, pifithrin-α. We concluded that vaginal LPS precondition trigged the p53-dependent phosphorylation of ATF2 in response to ischemic reperfusion, which played an important role of increasing vulnerability to hemorrhage in fetus.

Transfer entropy analysis of maternal and fetal heart rate coupling.

Although evidence of the short term relationship between maternal and fetal heart rates has been found in previous model-based studies, knowledge about the mechanism and patterns of the coupling during gestation is still limited. In this study, a model-free method based on Transfer Entropy (TE) was applied to quantify the maternal-fetal heart rate couplings in both directions. Furthermore, analysis of the lag at which TE was maximum and its changes throughout gestation, provided more information about the mechanism of coupling and its latency. Experimental results based on fetal electrocardiograms (fECGs) and maternal ECG showed the evidence of coupling for 62 out of 65 healthy mothers and fetuses in each direction, by statistically validating against the surrogate pairs. The fetuses were divided into three gestational age groups: early (16-25 weeks), mid (26-31 weeks) and late (32-41 weeks) gestation. The maximum TE from maternal to fetal heart rate significantly increased from early to mid gestation, while the coupling delay on both directions decreased significantly from mid to late gestation. These changes occur concomitant with the maturation of the fetal sensory and autonomic nervous systems with advancing gestational age. In conclusion, the application of TE with delays revealed detailed information about the changes in fetal-maternal heart rate coupling strength and latency throughout gestation, which could provide novel clinical markers of fetal development and well-being.

Intrauterine ischemic reperfusion switches the fetal transcriptional pattern from HIF-1α- to P53-dependent regulation in the murine brain.

Ischemic reperfusion (IR) during the perinatal period is a known causative factor of fetal brain damage. So far, both morphologic and histologic evidence has shown that fetal brain damage can be observed only several hours to days after an IR insult has occurred. Therefore, to prevent fetal brain damage under these circumstances, a more detailed understanding of the underlying molecular mechanisms involved during an acute response to IR is necessary. In the present work, pregnant mice were exposed to IR on day 18 of gestation by clipping one side of the maternal uterine horn. Simultaneous fetal electrocardiography was performed during the procedure to verify that conditions resulting in fetal brain damage were met. Fetal brain sampling within 30 minutes after IR insult revealed molecular evidence that a fetal response was indeed triggered in the form of inhibition of the Akt-mTOR-S6 synthesis pathway. Interestingly, significant changes in mRNA levels for both HIF-1α and p53 were apparent and gene regulation patterns were observed to switch from a HIF-1α-dependent to a p53-dependent process. Moreover, pre-treatment with pifithrin-α, a p53 inhibitor, inhibited protein synthesis almost completely, revealing the possibility of preventing fetal brain damage by prophylactic pifithrin-α treatment.

Molecular patterns of neurodevelopmental preconditioning: a study of the effects of antenatal steroid therapy in a protein-restriction mouse model.

Introduction. Prenatal programming secondary to maternal protein restriction renders an inherent susceptibility to neural compromise in neonates and any addition of glucocorticosteroids results in further damage. This is an investigation of consequent global gene activity due to effects of antenatal steroid therapy on a protein restriction mouse model. Methods. C57BL/6N pregnant mice were administered control or protein restricted diets and subjected to either 100 µ g/Kg of dexamethasone sodium phosphate with normosaline or normosaline alone during late gestation (E10-E17). Nontreatment groups were also included. Brain samples were collected on embryonic day 17 and analyzed by mRNA microarray analysis. Results. Microarray analyses presented 332 significantly regulated genes. Overall, neurodevelopmental genes were overrepresented and a subset of 8 genes allowed treatment segregation through the hierarchical clustering method. The addition of stress or steroids greatly affected gene regulation through glucocorticoid receptor and stress signaling pathways. Furthermore, differences between dexamethasone-administered treatments implied a harmful effect during conditions of high stress. Microarray analysis was validated using qPCR. Conclusion. The effects of antenatal steroid therapy vary in fetuses according to maternal-fetal factors and environmental stimuli. Defining the key regulatory networks that signal either beneficial or damaging corticosteroid action would result in valuable adjustments to current treatment protocols.

Automated estimation of fetal cardiac timing events from Doppler ultrasound signal using hybrid models.

In this paper, a new noninvasive method is proposed for automated estimation of fetal cardiac intervals from Doppler Ultrasound (DUS) signal. This method is based on a novel combination of empirical mode decomposition (EMD) and hybrid support vector machines-hidden Markov models (SVM/HMM). EMD was used for feature extraction by decomposing the DUS signal into different components (IMFs), one of which is linked to the cardiac valve motions, i.e. opening (o) and closing (c) of the Aortic (A) and Mitral (M) valves. The noninvasive fetal electrocardiogram (fECG) was used as a reference for the segmentation of the IMF into cardiac cycles. The hybrid SVM/HMM was then applied to identify the cardiac events, based on the amplitude and timing of the IMF peaks as well as the sequence of the events. The estimated timings were verified using pulsed doppler images. Results show that this automated method can continuously evaluate beat-to-beat valve motion timings and identify more than 91% of total events which is higher than previous methods. Moreover, the changes of the cardiac intervals were analyzed for three fetal age groups: 16-29, 30-35, and 36-41 weeks. The time intervals from Q-wave of fECG to Ac (Systolic Time Interval, STI), Ac to Mo (Isovolumic Relaxation Time, IRT), Q-wave to Ao (Preejection Period, PEP) and Ao to Ac (Ventricular Ejection Time, VET) were found to change significantly ( ) across these age groups. In particular, STI, IRT, and PEP of the fetuses with 36-41 week were significantly ( ) different from other age groups. These findings can be used as sensitive markers for evaluating the fetal cardiac performance.

A multi-dimensional Hidden Markov Model approach to automated identification of fetal cardiac valve motion.

Fetal cardiac assessment techniques are aimed to identify fetuses at risk of intrauterine compromise or death. Evaluation of the electromechanical coupling as a fundamental part of the fetal heart physiology, provides valuable information about the fetal wellbeing during pregnancy. It is based on the opening and closing time of the cardiac valves and the onset of the QRS complex of the fetal electrocardiogram (fECG). The focus of this paper is on the automated identification of the fetal cardiac valve opening and closing from Doppler Ultrasound signal and fECG as a reference. To this aim a novel combination of Emprical Mode Decomposition (EMD) and multi-dimensional Hidden Markov Models (MD-HMM) was employed which provided beat-to-beat estimation of cardiac valve event timings with improved precision (82.9%) compared to the one dimensional HMM (77.4%) and hybrid HMM-Support Vector Machine (SVM) (79.8%) approaches.

Investigating the beat by beat phase synchronization between maternal and fetal heart rates.

The development of the fetal cardiovascular system plays a crucial role in fetal health. The evolution of the relationship between fetal and maternal cardiac systems during fetal maturation is a characterizing feature for fetal cardiac development. This paper aims to evaluate this relationship by investigating the beat-to-beat synchronization between fetal and maternal heart rates and its variation at different stages of pregnancy. Synchronization epochs and phase locking patterns are analyzed at certain synchronization ratios (SRs) for three gestational age groups (16-26 weeks, 27-33 weeks, 34-40 weeks). Results show that the normalized synchronization epoch is significantly different for three age groups with the p-value of 6.72*10(-6) and 2.89*10(-4) at SR of 1:2 and 4:5 respectively. The variance of phase locking also shows significant difference for three groups with the p-value less than 10(-7) at four SRs. Results also suggest that synchronization may be the force behind the increase in the maternal heart rate to maintain the fetal development and provide supplies for the fetus. Overall, the findings propose new clinical markers for evaluating the antenatal development.

Automated Identification of fetal cardiac valve timings.

In this paper a new noninvasive method is proposed for automated estimation of opening and closure timings of fetal cardiac valves. These timings are obtained from Doppler Ultrasound (DUS) signal and fetal electrocardiogram (fECG) as a reference. Empirical Mode Decomposition (EMD) is first applied to the DUS signal to decompose it into different components called Intrinsic Mode Functions (IMFs). The envelope of the first IMF is then taken and its peaks are identified. The opening and closure of the valves are then automatically assigned to the IMF peaks by using Hidden Markov Model (HMM). It is shown that this new method can continuously evaluate fetal cardiac valves' (aortic and mitral) motion timings for 82.5~99.7% of cardiac cycles. The estimated timings are verified using the Pulsed Doppler images. These findings can be used as sensitive markers for evaluating the fetal cardiac performance.

Use of ultrasonic cleansing in managing the couplers of dialyzer systems.

Dialysis-related complications have become a major concern as the number of patients receiving long-term maintenance dialysis increases. One cause of complications is contamination of the dialysis fluid. When dialysis fluid contaminated by bacteria or endotoxin (ET) or both has been used for a long time, cytokine production in vivo is enhanced and can lead to such complications as dialysis amyloidosis. The rate of dialysis-related complications might be reduced with a hemopurification method that uses a large amount of dialysis fluid as a substitution fluid (on-line hemodiafiltration) or an efficient dialyzer with enhanced internal filtration in which the dialysis fluid returns to the body as a replacement fluid; however, at the same time, there is an increased risk of ET entering the body because the dialysis fluid might be contaminated. Therefore, the dialysis fluid must be made aseptic, and the dialysis fluid line must be properly managed to prevent contamination of the dialysis fluid. A half-opened line is at great risk of contamination by living microbes, which can grow in dead spaces and where the flow of dialysis fluid is interrupted. The management of couplers is an important measure for maintaining cleanliness at the end of the dialysis fluid flow. We attempted to separate and regularly clean the main body of the coupler with ultrasonic equipment as a method of managing the conventional coupler. Using improved types of coupler, the water quality of the postcoupler flow was maintained at a level as high as that of the precoupler flow for the duration of the evaluation period without separate cleansing being done. Although separate once-a-week cleansing of the conventional coupler was able to keep ET values less than the detection limit, viable cell counts were unstable. On the other hand, twice-a-week ultrasonic cleansing eliminated almost all viable cells. No definite difference in ET values or viable cell counts was found between the cleansing groups, and ultrasonic cleansing was able, by itself, to provide a sufficient cleansing effect. We conclude that ultrasonic cleansing of conventional couplers is a useful method for maintaining the water quality of the postcoupler flow because the cleansing of the coupler twice or more a week is sufficient to keep the water quality of the postcoupler flow as high as that of the precoupler flow.

Inhibitory effect of lysophosphatidylcholine on pancreatic lipase-mediated hydrolysis in lipid emulsion.

In the lipid metabolism pathway, dietary lipid emulsified with bile salts and phospholipids is mainly digested by pancreatic lipase into free fatty acids and monoacylglycerols. In order to study substrate recognition mechanism of a pancreatic lipase, we investigated its catalytic property toward the lipid emulsion prepared with long- or intermediate-chain acylglycerols and several physiological surfactants. When lysophosphatidylcholine (LysoPC), rather than bile salts or phospholipid, was incorporated into the lipid emulsion, it caused an increase in the Km(app) and a decrease in the Vmax(app) values in the interactions between the lipase and triacylglycerol (triolein or tricaprin). This indicated that LysoPC inhibited hydrolysis by decreasing both the substrate affinities and the catalytic activity of this lipase. Interestingly, further addition of taurodeoxycholic acid sodium salts or phospholipid completely restored the inhibitory effect of LysoPC on hydrolysis by lipase. On the other hand, the change in these kinetic values between the lipase and two 1-monoacylglycerols (1-monocaprin and 1-monoolein) were not particularly large when LysoPC was added. Particle size analysis of the lipid emulsion composed of LysoPC and triacylglycerols showed that most of the particles were less than 200 nm in size, which was smaller than the particle size in the triacylglycerol emulsions containing bile salts or phospholipid. The composition of the emulsion would affect its surface characteristics and thus contribute to changing lipase activity.