Relationships between resilience and quality of life in parents of children with cancer.

CLINICALTRIALS.GOV ID: NCT03631485.

In Vivo Image-Based 4D Modeling of Competent and Regurgitant Mitral Valve Dynamics.

BACKGROUND: In vivo characterization of mitral valve dynamics relies on image analysis algorithms that accurately reconstruct valve morphology and motion from clinical images. The goal of such algorithms is to provide patient-specific descriptions of both competent and regurgitant mitral valves, which can be used as input to biomechanical analyses and provide insights into the pathophysiology of diseases like ischemic mitral regurgitation (IMR). OBJECTIVE: The goal is to generate accurate image-based representations of valve dynamics that visually and quantitatively capture normal and pathological valve function. METHODS: We present a novel framework for 4D segmentation and geometric modeling of the mitral valve in real-time 3D echocardiography (rt-3DE), an imaging modality used for pre-operative surgical planning of mitral interventions. The framework integrates groupwise multi-atlas label fusion and template-based medial modeling with Kalman filtering to generate quantitatively descriptive and temporally consistent models of valve dynamics. RESULTS: The algorithm is evaluated on rt-3DE data series from 28 patients: 14 with normal mitral valve morphology and 14 with severe IMR. In these 28 data series that total 613 individual 3DE images, each 3D mitral valve segmentation is validated against manual tracing, and temporal consistency between segmentations is demonstrated. CONCLUSIONS: Automated 4D image analysis allows for reliable non-invasive modeling of the mitral valve over the cardiac cycle for comparison of annular and leaflet dynamics in pathological and normal mitral valves. Future studies can apply this algorithm to cardiovascular mechanics applications, including patient-specific strain estimation, fluid dynamics simulation, inverse finite element analysis, and risk stratification for surgical treatment.

Relationships among hope, psychological well-being and health-related quality of life in childhood cancer survivors.

This cross-sectional study examined the level of hope among Hong Kong childhood cancer survivors and investigated the relationships among hope, depressive symptoms, self-esteem and health-related quality of life. We recruited 176 survivors aged 10-16 years who underwent medical follow-ups at the outpatient clinic. This study revealed that lower levels of hope were associated with an increase in depressive symptoms and reductions in self-esteem and health-related quality of life. Our results contribute to novel findings by demonstrating that hope may be a significant factor associated with health-related quality of life. This understanding could increase healthcare professionals' awareness about the psychological needs of childhood cancer survivors.

Relationships among resilience, self-esteem, and depressive symptoms in Chinese adolescents.

This study explored the relationships among resilience, self-esteem, and depressive symptoms in Hong Kong Chinese adolescents. We selected a stratified random sample of 1816 Form 1 students from all 18 districts of Hong Kong. This study revealed that about 21 percent adolescents are experiencing some depressive symptoms. Our results contribute novel findings to the literature showing that resilience is a strong indicator of adolescents at a higher risk of depression and increasing adolescents' resilience to psychological distress is crucial to enhance their mental well-being. It is crucial to develop interventions that can enhance resilience and promote positive mental well-being among adolescents.

Microvascular complications in orthokeratology (Ortho-K): A real-time study on the microvasculature of the bulbar conjunctiva in Ortho-K treatment.

Orthokeratology (Ortho-K) is an over-night hard contact lens therapy, which physically reshapes the corneal curvature in order to stabilize or temporally eliminate myopia in patients. We hypothesize that the prolonged physical contact and mechanical pressure induced by the Ortho-K lenses may create lasting inadvertent effects and damages (microangiopathy), and may bring about unwanted changes in the microvasculature of the bulbar conjunctiva. Computer-assisted intravital microscopy (CAIM) was used to view, document (via videotaping) and objectively quantify (via computer-assisted image analysis) the real-time dynamic and morphometric characteristics of the conjunctival microcirculation in long-term (at least over one year) Ortho-K patients (n = 11) and matched non-user control subjects (n = 8). Ortho-K patients were instructed to wear their lenses overnight following standard protocol. During the study, the conjunctival microcirculation of the left eye of all Ortho-K lens users was viewed, frequently re-focused and videotaped, without and with the lens in place, as outlined in Methods. The matched control subjects (non-lens wearing) were videotaped and studied in like manner. The dynamic and morphometric characteristics of each user and control subject were analyzed, quantified and summated as a severity index (SI) collectively for comparison. SI of Ortho-K lens users (4.18±1.08) differed significantly from SI of control subjects (1.75±1.39, p≤0.05). In addition, changes in the conjunctival microcirculation (e.g., flow velocity, vessel diameter, shape change, etc) were viewed and videotaped immediately after the myopic patients put on the Ortho-K lenses. Eight of the 11 Ortho-K lens users displayed significant percentage changes (p≤0.05) in flow velocity and 10 of 11 displayed significant percentage changes (p≤0.05) in vessel diameter, without and with the Ortho-K lenses. The results clearly indicated that significant microvascular changes via tissue remodeling occurred, and were caused directly by the physical presence of the Ortho-K lenses.

Adventure-based training to promote physical activity and reduce fatigue among childhood cancer survivors: A randomized controlled trial.

BACKGROUND: Cancer-related fatigue is one of the most distressing symptoms reported by childhood cancer survivors. Despite the body of evidence that regular physical activity helps alleviate cancer-related fatigue, insufficient participation in physical activity is frequently observed among childhood cancer survivors. OBJECTIVES: This study examined the effectiveness of an adventure-based training programme in promoting physical activity, reducing fatigue, and enhancing self-efficacy and quality of life among Hong Kong Chinese childhood cancer survivors. DESIGN: A prospective randomised controlled trial. SETTINGS: A paediatric oncology outpatient clinic, a non-governmental organisation, and a non-profit voluntary organisation. PARTICIPANTS: Hong Kong Chinese childhood cancer survivors aged 9-16 years who reported symptoms of fatigue and had not engaged in regular physical exercise in the past 6 months. METHODS: The experimental group underwent a 4-day adventure-based training programme. The control group received a placebo intervention. The primary outcome was fatigue at 12 months. Secondary outcomes were physical activity levels, self-efficacy and quality of life at 12 months. Data collection was conducted at baseline, and 6 and 12 months after the intervention began. We performed intention-to-treat analyses. RESULTS: From 6 January, 2014 to 8 June, 2015, we randomly assigned 222 eligible childhood cancer survivors to either an experimental (n = 117) or a control group (n = 105). The experimental group showed statistically significantly lower levels of cancer-related fatigue (P < 0.001), higher levels of self-efficacy (P < 0.001) and physical activity (P < 0.001), and better quality of life (P < 0.01) than the control group at 12 months. CONCLUSIONS: This study provides evidence that adventure-based training is effective in promoting physical activity, reducing cancer-related fatigue, and enhancing self-efficacy and quality of life among Hong Kong Chinese childhood cancer survivors. These results may help inform parents and healthcare professionals that regular physical activity is crucial for the physical and psychological wellbeing and quality of life of childhood cancer survivors.

Real-time studies of hypertension using non-mydriatic fundus photography and computer-assisted intravital microscopy.

Hypertension is asymptomatic until late stages of pathogenesis, rendering an effective means of detection for early diagnosis essential. The current method of diagnosing hypertension requires two or more sphygmomanometric readings over two or more office visits, which potentially hinders early detection. Though retinopathy is an indicator of vascular damage, it generally presents in later stages of hypertension. Previous and related studies have suggested that the microvasculature in the bulbar conjunctiva may be a sensitive site to assess vasculopathy. Conjunctival microangiopathy was assessed using CAIM and reported on a severity index (SI). Images of the retinal fundus were taken via non-mydriatic fundus photography and graded using the Scheie scale in the same subjects to compare with CAIM. Conjunctival microangiopathy was significantly elevated in hypertensive subjects (SI = 5.35 ± 1.04, n = 20) compared to control subjects (SI = 1.75 ± 1.39, n = 8; p ≤ 0.05), and correlated with time since disease diagnosis (R² = 0.33). Hypertensive subjects with Grade 1 retinopathy displayed increased conjunctival microangiopathy (SI = 5.85 ± 0.90, n = 13) compared to those without retinopathy (SI = 4.43 ± 0.53, n = 7; p ≤ 0.05). These data indicate a possible pre-retinopathy time window during which conjunctival microangiopathy may indicate the risk of organ damage, supporting the hypothesis that the conjunctival microcirculation may serve as a platform for early detection and monitoring disease progression.

Microvascular abnormalities in the bulbar conjunctiva of contact lens users.

Soft contact lenses are commonly used to improve vision acuity or in cosmetic enhancement. We hypothesize that contact lens use can cause inadvertent damage to either the conjunctival microcirculation via direct vasoocclusion when the lens physically interacts with or damages the underlying vessels, or to the bulbar conjunctiva itself when the lens rests unevenly on the surface of the bulbar conjunctiva. Computer-assisted intravital microscopy was utilized to document (via video recording) and objectively quantify (via image analysis) real-time microvascular abnormalities resulting from changes and vessel remodeling in the conjunctival microcirculation in long-term (>2 yrs) contact lens users (n = 102), with non-users serving as control subjects (n = 29). A severity index (SI)--computed as the arithmetic sum of the abnormalities found in the conjunctival microcirculation in each contact lens user--was established for objective comparison with control subjects and critical interpretation. Contact lens user SI was significantly higher than control SI (user = 6.21 ± 1.26; control = 2.31 ± 1.49; p < 0.05), indicative of severe vasculopathy arising from contact lens use. The users also had significantly wider conjunctival vessel diameter (user = 71.25 ± 12.09 µm; control = 52.20 ± 5.10 µm; p < 0.05). Additional abnormalities, including damaged vessels, hemosiderin deposits (from damaged vessels or injury to the surface of the bulbar conjunctiva), vessel sludging, intermittent blood flow, and vessel tortuosity were commonly found in or adjacent to locations where the contact lens physically rested on the underlying conjunctival vessels. These results strongly suggest that microvascular abnormalities and remodeling changes occurred as a result of the inadvertent physical interaction of the lenses with either the underlying conjunctival vessels or the surface of the bulbar conjunctiva in contact lens users.

Leptin resistance following over-expression of protein tyrosine phosphatase 1B in liver.

Obesity is typically associated with resistance to leptin, yet the mechanism by which leptin signaling becomes impaired is poorly understood. Here we sought to determine if the development of obesity and leptin resistance correlates with increased expression of protein tyrosine phosphatase 1B (PTP1B) in peripheral tissues and whether over-expression of this phosphatase, specifically in liver, could alter the leptin-mediated effects on feeding and glucose metabolism. Obesity was induced in mice through a high-fat diet that resulted in hyperglycemia, hyperinsulinemia and hyperleptinemia. Resistance to leptin was confirmed as exogenous leptin administration reduced food intake in animals on low-fat, but not high-fat diets. Diet-induced resistance to leptin and insulin was associated with increased hepatic levels of PTP1B. Intriguingly, hepatic adenoviral over-expression of PTP1B in ob/ob mice attenuated the ability of exogenous leptin to reduce both plasma glucose levels and food intake. These findings suggest that leptin reduces both plasma glucose and food intake in part through actions on the liver, and hepatic leptin resistance resulting from over-expression of PTP1B may contribute to the development of both diabetes and obesity.

Leptin reduces glucose transport and cellular ATP levels in INS-1 beta-cells.

Leptin suppresses insulin secretion by opening ATP-sensitive K(+) (K(ATP)) channels and hyperpolarizing beta-cells. We measured the intracellular concentration of ATP ([ATP](i)) in tumor-derived beta-cells, INS-1, and found that leptin reduced [ATP](i) by approximately 30%, suggesting that the opening of K(ATP) channels by leptin is mediated by decreased [ATP](i). A reduction in glucose availability for metabolism may explain the decreased [ATP](i), since leptin (30 min) reduced glucose transport into INS-1 cells by approximately 35%, compared to vehicle-treated cells. The twofold induction of GLUT2 phosphorylation by GLP-1, an insulin secretagogue, was abolished by leptin. Therefore, the acute effect of leptin could involve covalent modification of GLUT2. These findings suggest that leptin may inhibit insulin secretion by reducing [ATP](i) as a result of reduced glucose availability for the metabolic pathway. In addition, leptin reduced glucose transport by 35% in isolated rat hepatocytes that also express GLUT2, suggesting that glucose transport may also be altered by leptin in other glucose-responsive tissues such as the liver.

Effects of adenovirus-mediated liver-selective overexpression of protein tyrosine phosphatase-1b on insulin sensitivity in vivo.

AIM: Protein tyrosine phosphatase-1B (PTP-1B) is an intracellular PTP known to dephosphorylate and inactivate upstream tyrosine phosphoproteins in the insulin signalling cascade. We and others reported increased abundance of catalytically impaired PTP-1B in tissue lysates from obese human subjects with and without type 2 diabetes, while genetic knockout of PTP-1B improves insulin sensitivity and prevents nutritionally mediated insulin resistance and obesity. The aim of the present work was to further elucidate the role of PTP-1B in glucose metabolism in vivo. METHODS: We used adenoviral constructs incorporating cDNAs for either wild-type (W/T) or a catalytically inactive C(215)S (C/S) mutant PTP-1B to achieve liver-selective PTP-1B overexpression in young Sprague-Dawley rats using tail vein injection, based on the high degree of hepatotropism of adenovirus 5 (Ad5). An Ad5-lacZ construct encoding beta-galactosidase was used as a control for viral effects alone. A hyperinsulinaemic euglycaemic clamp was used to study whole body glucose disposal and endogenous glucose production rates. RESULTS: Control studies in HIRcB cells confirmed catalytic activity and inactivity of W/T and C/S respectively. Mean PTP-1B abundance was 2.24 +/- 0.02- and 2.33 +/- 0.04-fold of saline-treated control in liver lysates of W/T and C/S rats respectively. Liver selective overexpression was confirmed by analysis of tissue lysates from liver, fat and muscle tissues. Ad5 treatment did not result in a statistically or clinically significant liver injury, as determined by serum alanine aminotransferase and histological examination. Seven days post injection, no significant difference in rate of weight gain, fasting blood glucose or insulin levels were seen in any group. Similarly, under steady-state glucose clamp conditions, glucose disposal rate (R(d)), endogenous glucose production rate (EGP) and serum insulin levels were similar in all groups. CONCLUSION: We conclude that moderate medium-term overabundance, to a degree resembling that seen in insulin-resistant states, of PTP-1B in liver tissue does not alter insulin action on glucose metabolism and that the major site of action of PTP-1B is presumably at insulin-responsive target tissue or tissues other than the liver.

Microvascular abnormalities in the bulbar conjunctiva of patients with type 2 diabetes mellitus.

OBJECTIVE: To study and quantify microvascular abnormalities objectively in vivo in patients with type 2 diabetes mellitus (T2DM). METHODS: The conjunctival microcirculation in 14 patients with T2DM and in age-matched healthy control subjects without diabetes was videotaped and objectively studied by using computer-assisted intravital microscopy (CAIM), a novel and quantitative real-time technology. RESULTS: Patients with T2DM (N = 14) had significantly (P<0.01) wider conjunctival vessel diameters (71.9 +/- 5.2 mm) than did healthy nondiabetic control subjects (54.0 +/- 4.4 mm). In the study patients, microvascular distribution was significantly (P<0.01) abnormal (36.7 +/- 18.2 versus 45.3 +/- 9.6 cm per unit area, patients versus control subjects), and vessel distribution was uneven on the surface of the bulbar conjunctiva. The arteriole:venule (A:V) ratio in patients with T2DM was extremely variable and differed significantly (P<0.01) from that in the nondiabetic control subjects (A:V approximately 1:2). In addition, a unique sinusoidal (hypertensive) vascular pattern frequently existed in some of the large veins of all study patients with T2DM but in none of the nondiabetic control subjects. CONCLUSION: We identified the presence of microvascular changes (abnormalities) in the conjunctival microcirculation of patients with T2DM. Although all these abnormalities did not appear in the same patient at the same time, the sum total of their presence in each patient correlated significantly with disease severity, as noted in the medical records. The severity of microvascular abnormalities, however, did not correlate with the duration of the disease since diagnosis. CAIM may be a useful objective and quantitative technique for assessing microangiopathy in patients with T2DM. The easy noninvasive accessibility of the conjunctival vessels and the ability to identify and locate the same vessels repeatedly for longitudinal evaluations further emphasize the usefulness of this real-time technology.

Reliability of nurses' neurological assessments in the cardiothoracic surgical intensive care unit.

BACKGROUND: Alterations in mental status are common among patients in the cardiothoracic surgical intensive care unit. Changes in mental status can be caused by metabolic factors, medications, or brain injury. In this setting, reliable, serial neurological evaluations are critical for assessing the effectiveness of treatment and the need for additional studies. OBJECTIVES: To estimate the reliability of the Rancho Los Amigos Cognitive Scale and the newly developed Neurologic Intensive Care Evaluation as measures of cognitive function in the cardiothoracic surgical intensive care unit. METHODS: Nurses used 1 of the 2 scales as part of routine neurological assessments of patients in the cardiothoracic surgical intensive care unit. For each test, scores of different observers were correlated and a reliability estimate formed. RESULTS: Interrater reliability was high for both evaluations (Rancho scale, 0.91; Neurologic Intensive Care Evaluation, 0.94). Correlations between the scores of different pairs of observers were also high (mean rho values, 0.84 for the Rancho scale and 0.77 for the Neurologic Intensive Care Evaluation). CONCLUSIONS: Both scales are reliable indicators of the neurological state of patients in the cardiothoracic surgical intensive care unit. These scales measure different, although limited, aspects of cognitive function. Each test was simple to administer and did not take more time than the standard nursing neurological examination. Most of the variability in scoring was related to the different degrees of stimulation used by examiners when assessing patients, not to differences in the interpretation of patients' responses.

The effects of hemoglobin glutamer-200 (bovine) on the microcirculation in a canine hypovolemia model: a noninvasive computer-assisted intravital microscopy study.

UNLABELLED: We sought to correlate in vivo microvascular, systemic function, hemodynamic, and oxygenation changes in autologous shed blood (n = 4) and hemoglobin glutamer-200 (Hb-200) (n = 4) resuscitations in hypovolemic dogs. Hemorrhage (approximately 40% blood loss) reduced mean arterial pressure to approximately 50 mm Hg and caused significant (P < 0.01) decreases in hematocrit, total hemoglobin, mean pulmonary arterial pressure, cardiac output, and oxygen delivery and significant (P < 0.01) increases in heart rate, systemic vascular resistance, and lactic acidosis. Significant (P < 0.01) changes in conjunctival microvascular variables also occurred, including a 19% decrease in venular diameter and 79% increase in average blood flow velocity. Shed blood resuscitation returned microvascular, systemic function, hemodynamic, and oxygenation variables to prehemorrhagic baseline values. In contrast, Hb-200 failed to restore hematocrit, total hemoglobin, cardiac output, oxygen delivery index, and systemic venous resistance to baseline, but it restored other systemic functions and all hemodynamic and microvascular changes. In addition, Hb-200 resuscitation in hypovolemic dogs (approximately 40% blood loss) did not cause extreme hemodilution or fatal outcome. This study confirms that real-time (in vivo) microvascular studies, which were conducted only in small rodent models in the past, can be performed simultaneously with systemic function, hemodynamic, and oxygenation studies in a large animal model for relevant data correlation. IMPLICATIONS: This is the first time that changes in the blood circulation have been studied, quantified, and correlated with systemic function, hemodynamic, and oxygenation changes in shock and during shock treatment in a large animal model. This study was performed by a new technology developed in-house to noninvasively and quantitatively study blood vessels in real time.

Correlation of abnormal intracranial vessel velocity, measured by transcranial Doppler ultrasonography, with abnormal conjunctival vessel velocity, measured by computer-assisted intravital microscopy, in sickle cell disease.

The Stroke Prevention Trial has confirmed that utilization of transcranial Doppler ultrasonography (TCD), which examines blood flow in large intracranial vessels, can identify children with sickle cell disease (SCD) who are at high risk of developing a premature stroke. It is not known to what extent the vasculopathy in SCD involves small vessels and whether the abnormalities, if present, correlate with large-vessel vasculopathy. Eighteen children with SCD were examined with TCD to determine middle cerebral artery (MCA) velocity and computer-assisted intravital microscopy (CAIM) to determine bulbar conjunctival vessel velocity during the same visit for vasculopathy correlation. High MCA velocity (> or = 200 cm/sec) was found by TCD in 4 patients who also showed abnormal conjunctival velocity (< 0.2 mm/sec or intermittent trickle flow) by CAIM. Three patients had conditional (> or = 170 cm/sec and < 200 cm/sec) MCA velocity: 2 showed abnormal (trickle) and 1 showed normal conjunctival velocity (1.9 mm/sec). One patient with unmeasurable MCA velocity had abnormal (trickle) conjunctival velocity. Of the remaining 10 patients who had normal MCA velocity, 2 showed abnormal (0.05 mm/sec and 0.1 mm/sec) and 8 showed normal conjunctival velocities (1.1-2.4 mm/sec). The MCA velocities correlated significantly with bulbar conjunctival flow velocities (P < or =.008, Fisher exact test). A correlation exists between MCA (large-vessel) and conjunctival (small-vessel) flow velocities. CAIM is a noninvasive quantitative technique that might contribute to the identification of SCD patients at high risk of stroke. Small-vessel vasculopathy might be an important pathological indicator and should be further explored in a large-scale study. (Blood. 2001;97:3401-3404)

Deep hypothermic circulatory arrest: I. Effects of cooling on electroencephalogram and evoked potentials.

BACKGROUND: Deep hypothermia is an important cerebral protectant and is critical in procedures requiring circulatory arrest. The purpose of this study was to determine the factors that influence the neurophysiologic changes during cooling before circulatory arrest, in particular the occurrence of electrocerebral silence. METHODS: In 109 patients undergoing hypothermic circulatory arrest with neurophysiologic monitoring, five electrophysiologic events were selected for detailed study. RESULTS: The mean nasopharyngeal temperature when periodic complexes appeared in the electroencephalogram after cooling was 29.6 degrees C +/- 3 degrees C, electroencephalogram burst-suppression appeared at 24.4 degrees C +/- 4 degrees C, and electrocerebral silence appeared at 17.8 degrees C +/- 4 degrees C. The N20-P22 complex of the somatosensory evoked response disappeared at 21.4 degrees C +/- 4 degrees C, and the somatosensory evoked response N13 wave disappeared at 17.3 degrees C +/- 4 degrees C. The temperatures of these various events were not significantly affected by any patient-specific or surgical variables, although the time to cool to electrocerebral silence was prolonged by high hemoglobin concentrations, low arterial partial pressure of carbon dioxide, and by slow cooling rates. Only 60% of patients demonstrated electrocerebral silence by either a nasopharyngeal temperature of 18 degrees C or a cooling time of 30 minutes. CONCLUSIONS: With the high degree of interpatient variability in these neurophysiologic measures, the only absolute predictors of electrocerebral silence were nasopharyngeal temperature below 12.5 degrees C and cooling longer than 50 minutes.

Deep hypothermic circulatory arrest: II. Changes in electroencephalogram and evoked potentials during rewarming.

BACKGROUND: Electrophysiologic studies during rewarming after deep hypothermic circulatory arrest probe the state of the brain during this critical period and may provide insight into the neurological effects of circulatory arrest and the neurologic outcome. METHODS: Electroencephalogram (EEG) and evoked potentials were monitored during rewarming in 109 patients undergoing aortic surgery with hypothermic circulatory arrest. RESULTS: The sequence of neurophysiologic events during rewarming did not mirror the events during cooling. The evoked potentials recovered first followed by EEG burst-suppression and then continuous EEG. The time to recovery of the evoked potentials N20-P22 complex was significantly correlated with the time of circulatory arrest even in patients without postoperative neurologic deficits (r = 0.37, (p = 0.002). The nasopharyngeal temperatures at which continuous EEG activity and the N20-P22 complex returned were strongly correlated (r = 0.44, p = 0.0002; r = 0.41, p = 0.00003) with postoperative neurologic impairment. Specifically, the relative risk for postoperative neurologic impairment increased by a factor of 1.56 (95% CI 1.1 to 2.2) for every degree increase in temperature at which the EEG first became continuous. CONCLUSIONS: No trend toward shortened recovery times or improved neurologic outcome was noted with lower temperatures at circulatory arrest, indicating that the process of cooling to electrocerebral silence produced a relatively uniform degree of cerebral protection, independent of the actual nasopharyngeal temperature.