Combined spiroergometry and 31P–MRS of human calf muscle during high‐intensity exercise

Simultaneous measurements of pulmonary oxygen consumption (VO₂), carbon dioxide exhalation (VCO₂) and phosphorus magnetic resonance spectroscopy (³¹P–MRS) are valuable in physiological studies to evaluate muscle metabolism during specific loads. Therefore, the aim of this study was to adapt a commercially available spirometric device to enable measurements of VO₂ and VCO₂ whilst simultaneously performing ³¹P–MRS at 3 T. Volunteers performed intense plantar flexion of their right calf muscle inside the MR scanner against a pneumatic MR‐compatible pedal ergometer. The use of a non‐magnetic pneumotachograph and extension of the sampling line from 3 m to 5 m to place the spirometric device outside the MR scanner room did not affect adversely the measurements of VO₂ and VCO₂. Response and delay times increased, on average, by at most 0.05 s and 0.79 s, respectively. Overall, we were able to demonstrate a feasible ventilation response (VO₂ = 1.05 ± 0.31 L/min; VCO₂ = 1.11 ± 0.33 L/min) during the exercise of a single calf muscle, as well as a good correlation between local energy metabolism and muscular acidification (τ_{PCr fast} and pH; R² = 0.73, p < 0.005) and global respiration (τ_{PCr fast} and VO₂; R² = 0.55, p = 0.01). This provides improved insights into aerobic and anaerobic energy supply during strong muscular performances.     

Self-assembled composite matrix in a hierarchical 3-D scaffold for bone tissue engineering

It is of high clinical relevance in bone tissue engineering that scaffolds promote a high seeding efficiency of cells capable of osteogenic differentiation, such as human bone marrow-derived mesenchymal stem cells (hMSCs). We evaluated the effects of a novel polycaprolactone (PCL) scaffold on hMSC seeding efficiency, proliferation, distribution and differentiation. Porous PCL meshes prepared by fused deposition modeling (FDM) were embedded in matrix of hyaluronic acid, methylated collagen and terpolymer via polyelectrolyte complex coacervation. Scaffolds were cultured statically and dynamically in osteogenic stimulation medium for up to 28 days. Compared to naked PCL scaffolds, embedded scaffolds provided a higher cell seeding efficiency (t-test, P<0.05), a more homogeneous cell distribution and more osteogenically differentiated cells, verified by a more pronounced gene expression of the bone markers alkaline phosphatase, osteocalcin, bone sialoprotein I and bone sialoprotein II. Dynamic culture resulted in higher amounts of DNA (day 14 and day 21) and calcium (day 21 and day 28), compared to static culture. Dynamic culture and the embedding synergistically enhanced the calcium deposition of hMSC on day 21 and day 28. This in vitro study provides evidence that hybrid scaffolds made from natural and synthetic polymers improve cellular seeding efficiency, proliferation, distribution and osteogenic differentiation.     

In vivo infection of ramified microglia from adult cat central nervous system by feline immunodeficiency virus

Infection of microglial cells by the human immunodeficiency virus (HIV) is supposed to play an important role in the pathogenesis of AIDS-related central nervous system (CNS) complications. So far, however, experimental data about interactions between HIV and ramified microglia from the adult CNS were only occasionally reported, making it difficult to understand the exact nature of pathogenic events contributing to HIV-encephalopathy. Therefore, we used the animal model of feline immunodeficiency virus (FIV) infection of domestic cats to establish an experimental system which is suitable for studying the relationships between an immunodeficiency virus and the mature ramified microglia of the central nervous system. By means of density gradient centrifugation approximately 95% pure microglial cells could be isolated from adult feline brain that were characterized by their CD45(low) phenotype. Resident microglia extracted from the CNS of experimentally infected cats harbored FIV-specific DNA and cocultivation with mitogen-activated, but uninfected peripheral blood mononuclear cells (PBMC) resulted in recovery of high-titered infectious virus. Double labeling of brain cell monocultures explanted from persistently infected animals for both microglia and FIV markers disclosed less than 1% of viral antigen expressing microglial cells. This suggests that during the subclinical phase of the infection only a small number of brain-resident macrophages are productively infected. However, interaction of FIV-infected microglia and inflammatory lymphocytes may promote viral replication, thus supporting viral spread in brain tissue.     

Chronic presentation of Boerhaave's syndrome

Background  

Spontaneous rupture of the esophagus (Boerhaave's syndrome) is a rare, well-defined clinical syndrome caused by a longitudinal perforation of the esophagus. It is a life-threatening condition that necessitates rapid diagnosis and treatment. Patients typically present acutely with a history of vomiting followed by chest or abdominal pain. However, the diagnosis may be difficult or missed when patients present with chronic symptoms that mimic other conditions.     

Acute stress modulates genotype effects on amygdala processing in humans

Probing gene–environment interactions that affect neural processing is crucial for understanding individual differences in behavior and disease vulnerability. Here, we tested whether the current environmental context, which affects the acute brain state, modulates genotype effects on brain function in humans. We manipulated the context by inducing acute psychological stress, which increases noradrenergic activity, and probed its effect on tonic activity and phasic responses in the amygdala using two MRI techniques: conventional blood oxygen level–dependent functional MRI and arterial spin labeling. We showed that only carriers of a common functional deletion in ADRA2B, the gene coding for the α2b-adrenoreceptor, displayed increased phasic amygdala responses under stress. Tonic activity, reflecting the perfusion of the amygdala, increased independently of genotype after stress induction. Thus, when tonic activity was heightened by stress, only deletion carriers showed increased amygdala responses. Our results demonstrate that genetic effects on brain operations can be state dependent, such that they only become apparent under specific, often environmentally controlled, conditions.     

Poor Health‐related Quality of Life After Severe Preeclampsia

Abstract: Background: Preeclampsia is a major complication of pregnancy associated with increased maternal morbidity and mortality, and adverse birth outcomes. The objective of this study was to describe changes in all domains of health‐related quality of life between 6 and 12 weeks postpartum after mild and severe preeclampsia; to assess the extent to which it differs after mild and severe preeclampsia; and to assess which factors contribute to such differences. Methods: We conducted a prospective multicenter cohort study of 174 postpartum women who experienced preeclampsia, and who gave birth between February 2007 and June 2009. Health‐related quality of life was measured at 6 and 12 weeks postpartum by the RAND 36‐item Short‐Form Health Survey (SF‐36). The population for analysis comprised women (74%) who obtained scores on the questionnaire at both time points. Results: Women who experienced severe preeclampsia had a lower postpartum health‐related quality of life than those who had mild preeclampsia (all p < 0.05 at 6 wk postpartum). Quality of life improved on almost all SF‐36 scales from 6 to 12 weeks postpartum (p < 0.05). Compared with women who had mild preeclampsia, those who experienced severe preeclampsia had a poorer mental quality of life at 12 weeks postpartum (p < 0.05). Neonatal intensive care unit admission and perinatal death were contributing factors to this poorer mental quality of life. Conclusions: Obstetric caregivers should be aware of poor health‐related quality of life, particularly mental health quality of life in women who have experienced severe preeclampsia (especially those confronted with perinatal death or their child’s admission to a neonatal intensive care unit), and should consider referral for postpartum psychological care. (BIRTH 38:3 September 2011)     

Circadian and age-related modulation of thermoreception and temperature regulation: mechanisms and functional implications

At older ages, the circadian rhythm of body temperature shows a decreased amplitude, an advanced phase, and decreased stability. The present review evaluates to what extent these changes may result from age-related deficiencies at several levels of the thermoregulatory system, including thermoreception, thermogenesis and conservation, heat loss, and central regulation. Whereas some changes are related to the aging process per se, others appear to be secondary to other factors, for which the risk increases with aging, notably a decreased level of fitness and physical activity. Moreover, functional implications of the body temperature rhythm are discussed. For example, the relation between circadian rhythm and thermoregulation has hardly been investigated, while evidence showed that sleep quality is dependent on both aspects. It is proposed that the circadian rhythm in temperature in homeotherms should not be regarded as a leftover of ectothermy in early evolution, but appears to be of functional significance for physiology from the level of molecules to cognition. A new view on the functional significance of the circadian rhythm in peripheral vasodilation and the consequent out-of-phase rhythms in skin and core temperature is presented. It is unlikely that the strong, daily occurring, peripheral vasodilation primarily represents heat loss in response to a lowering of set point, since behavioral measures are simultaneously taken in order to prevent heat loss. Several indications rather point towards a supportive role in immunological host defense mechanisms. Given the functional significance of the temperature rhythm, research should focus on the feasibility and effectiveness of methods that can in principle be applied in order to enhance the weakened circadian temperature rhythm in the elderly.     

CRIPTO promotes an aggressive tumour phenotype and resistance to treatment in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the third leading cause of cancer‐related death worldwide. Despite increasing treatment options for this disease, prognosis remains poor. CRIPTO (TDGF1) protein is expressed at high levels in several human tumours and promotes oncogenic phenotype. Its expression has been correlated to poor prognosis in HCC. In this study, we aimed to elucidate the basis for the effects of CRIPTO in HCC. We investigated CRIPTO expression levels in three cohorts of clinical cirrhotic and HCC specimens. We addressed the role of CRIPTO in hepatic tumourigenesis using Cre‐loxP‐controlled lentiviral vectors expressing CRIPTO in cell line‐derived xenografts. Responses to standard treatments (sorafenib, doxorubicin) were assessed directly on xenograft‐derived ex vivo tumour slices. CRIPTO‐overexpressing patient‐derived xenografts were established and used for ex vivo drug response assays. The effects of sorafenib and doxorubicin treatment in combination with a CRIPTO pathway inhibitor were tested in ex vivo cultures of xenograft models and 3D cultures. CRIPTO protein was found highly expressed in human cirrhosis and hepatocellular carcinoma specimens but not in those of healthy participants. Stable overexpression of CRIPTO in human HepG2 cells caused epithelial‐to‐mesenchymal transition, increased expression of cancer stem cell markers, and enhanced cell proliferation and migration. HepG2‐CRIPTO cells formed tumours when injected into immune‐compromised mice, whereas HepG2 cells lacking stable CRIPTO overexpression did not. High‐level CRIPTO expression in xenograft models was associated with resistance to sorafenib, which could be modulated using a CRIPTO pathway inhibitor in ex vivo tumour slices. Our data suggest that a subgroup of CRIPTO‐expressing HCC patients may benefit from a combinatorial treatment scheme and that sorafenib resistance may be circumvented by inhibition of the CRIPTO pathway. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Reducing Alcohol Use During Pregnancy Via Health Counseling by Midwives and Internet-Based Computer-Tailored Feedback: A Cluster Randomized Trial

BackgroundEffective interventions are needed to reduce neurobehavioral impairments in children due to maternal alcohol use during pregnancy. Currently, health-counseling interventions have shown inconsistent results to reduce prenatal alcohol use. Thus, more research using health counseling is needed to gain more knowledge about the effectiveness of this type of intervention on reducing alcohol use during pregnancy. An alternative and promising strategy is computer tailoring. However, to date, no study has shown the effectiveness of this intervention mode.ObjectiveThe aim was to test the effectiveness of health counseling and computer tailoring on stopping and reducing maternal alcohol use during pregnancy in a Dutch sample of pregnant women using alcohol.MethodsA total of 60 Dutch midwifery practices, randomly assigned to 1 of 3 conditions, recruited 135 health counseling, 116 computer tailoring, and 142 usual care respondents from February to September 2011. Health-counseling respondents received counseling from their midwife according to a health-counseling protocol, which consisted of 7 steps addressed in 3 feedback sessions. Computer-tailoring respondents received usual care from their midwife and 3 computer-tailored feedback letters via the Internet. Usual care respondents received routine alcohol care from their midwife. After 3 and 6 months, we assessed the effect of the interventions on alcohol use.ResultsMultilevel multiple logistic regression analyses showed that computer-tailoring respondents stopped using alcohol more often compared to usual care respondents 6 months after baseline (53/68, 78% vs 51/93, 55%; P=.04). Multilevel multiple linear regression analyses showed that computer-tailoring respondents (mean 0.35, SD 0.31 units per week) with average (P=.007) or lower (P<.001) alcohol use before pregnancy or with average (P=.03) or lower (P=.002) social support more strongly reduced their alcohol use 6 months after baseline compared to usual care respondents (mean 0.48, SD 0.54 units per week). Six months after baseline, 72% (62/86) of the health-counseling respondents had stopped using alcohol. This 17% difference with the usual care group was not significant.ConclusionsThis is the first study showing that computer tailoring can be effective to reduce alcohol use during pregnancy; health counseling did not effectively reduce alcohol use. Future researchers developing a health-counseling intervention to reduce alcohol use during pregnancy are recommended to invest more in recruitment of pregnant women and implementation by health care providers. Because pregnant women are reluctant to disclose their alcohol use to health professionals and computer tailoring preserves a person’s anonymity, this effective computer-tailoring intervention is recommended as an attractive intervention for pregnant women using alcohol.

Trial Registration

Dutch Trial Register NTR 2058; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2058 (Archived by WebCite at http://www.webcitation.org/6NpT1oHol)     

Efficacy of a Web-Based Computer-Tailored Smoking Prevention Intervention for Dutch Adolescents: Randomized Controlled Trial

Background

Preventing smoking initiation among adolescents is crucial to reducing tobacco-caused death and disease. This study focuses on the effectiveness of a Web-based computer-tailored smoking prevention intervention aimed at adolescents.

Objective

The intent of the study was to describe the intervention characteristics and to show the effectiveness and results of a randomized controlled trial. We hypothesized that the intervention would prevent smoking initiation among Dutch secondary school students aged 10-20 years and would have the largest smoking prevention effect among the age cohort of 14-16 years, as smoking uptake in that period is highest.

Methods

The intervention consisted of a questionnaire and fully automated computer-tailored feedback on intention to start smoking and motivational determinants. A total of 89 secondary schools were recruited via postal mail and randomized into either the computer-tailored intervention condition or the control condition. Participants had to complete a Web-based questionnaire at baseline and at 6-month follow-up. Data on smoking initiation were collected from 897 students from these schools. To identify intervention effects, multilevel logistic regression analyses were conducted using multiple imputation.

Results

Smoking initiation among students aged 10-20 years was borderline significantly lower in the experimental condition as compared to the control condition 6 months after baseline (OR 0.25, 95% CI 0.05-1.21, P=.09). Additional analyses of the data for the 14-16 year age group showed a significant effect, with 11.5% (24/209) of the students in the control condition reporting initiation compared to 5.7% (10/176) in the experimental condition (OR 0.22, 95% CI 0.05-1.02, P=.05). No moderation effects were found regarding gender and educational level.

Conclusions

The findings of this study suggest that computer-tailored smoking prevention programs are a promising way of preventing smoking initiation among adolescents for at least 6 months, in particular among the age cohort of 14-16 years. Further research is needed to focus on long-term effects.

Trial Registration

International Standard Randomized Controlled Trial Number (ISRCTN): 77864351; http://www.controlled-trials.com/ISRCTN77864351 (Archived by WebCite at http://www.webcitation.org/6BSLKSTm5).