Environmental flow limits to global groundwater pumping.

Groundwater is the world's largest freshwater resource and is critically important for irrigation, and hence for global food security1-3. Already, unsustainable groundwater pumping exceeds recharge from precipitation and rivers4, leading to substantial drops in the levels of groundwater and losses of groundwater from its storage, especially in intensively irrigated regions5-7. When groundwater levels drop, discharges from groundwater to streams decline, reverse in direction or even stop completely, thereby decreasing streamflow, with potentially devastating effects on aquatic ecosystems. Here we link declines in the levels of groundwater that result from groundwater pumping to decreases in streamflow globally, and estimate where and when environmentally critical streamflows-which are required to maintain healthy ecosystems-will no longer be sustained. We estimate that, by 2050, environmental flow limits will be reached for approximately 42 to 79 per cent of the watersheds in which there is groundwater pumping worldwide, and that this will generally occur before substantial losses in groundwater storage are experienced. Only a small decline in groundwater level is needed to affect streamflow, making our estimates uncertain for streams near a transition to reversed groundwater discharge. However, for many areas, groundwater pumping rates are high and environmental flow limits are known to be severely exceeded. Compared to surface-water use, the effects of groundwater pumping are markedly delayed. Our results thus reveal the current and future environmental legacy of groundwater use.

Efficacy of Op Koers Online, an online group intervention for parents of children with cancer: Results of a randomized controlled trial.

OBJECTIVE: Parents of children with cancer are at risk for developing psychosocial problems. The present study aims to evaluate the effect of an online group intervention (Op Koers Online, in English: On Track Online) on psychosocial wellbeing and coping skills. METHODS: Parents of a child with cancer (diagnosis <5 years ago) participated in a randomized controlled trial. In six consecutive (and one booster-) protocolled sessions in an online chatroom, trained psychologists and social workers taught coping skills using cognitive behavioral and acceptance and commitment techniques. Questionnaires assessed anxiety, depression, distress, situation-specific emotional reactions and coping skills (Op Koers Questionnaire/Cognitive Coping Strategies Scale Parent Form) and evaluated the intervention. Linear mixed-model analyses were performed to detect differences between the conditions in changes over time; T0-T1 and T0-T2 (6-week and 6-month follow-up), and to detect changes in scores T2-T3 (12-month follow-up) for the intervention group only. RESULTS: 89 parents were included in analyses (mean age 41.9 years, 86% female, 62%/38% post/during treatment of their child). Beneficial intervention effects (p < 0.05) were found at T1 for anxiety, depression, distress, loneliness and relaxation, and at T2 for anxiety, uncertainty and relaxation. In the intervention condition, scores did not change from T2 to T3, except loneliness that decreased and relaxation that improved. All effect sizes were small to medium (ß = -0.21 to 0.46). Parents were generally positive about the intervention. CONCLUSIONS: Op Koers Online for parents of children with cancer has a positive effect on psychosocial wellbeing and the coping skill relaxation. Implementation is recommended to prevent psychosocial problems. CLINICAL TRIAL REGISTRATION: Dutch Trial Register https://onderzoekmetmensen.nl/en NL73763.041.20.

Lifetime ADHD symptoms highly prevalent in women with cardiovascular complaints. A cross-sectional study.

Patients with Attention Deficit Hyperactivity Disorder (ADHD) are at greater cardiovascular risk. We investigated the association between ADHD symptoms and cardiovascular disease in women at a specialized Dutch cardiological clinic. Lifetime ADHD symptoms were found in 35% of women (n = 300) with cardiac complaints. Women with ADHD symptoms compared to those without were significantly younger but had no different cardiological profile. To protect women's health, further research and multidisciplinary cooperation is required to better understand the relationship between ADHD and cardiovascular disease.

Support needs of Dutch young adult childhood cancer survivors.

BACKGROUND: Studies about support needs of young adult childhood cancer survivors (YACCS) previously focused mainly on information needs. This study assessed support needs and associated factors (sociodemographic, medical, and psychosocial functioning) in Dutch YACCS. METHODS: YACCS (aged 18-30, diagnosed ≤ 18 years, time since diagnosis ≥ 5 years) cross-sectionally filled out a questionnaire regarding their need for various types of support (concrete information, personal counseling, and peer contact) in eight domains (physical consequences of childhood cancer, social-emotional consequences, relationships and sexuality, fertility, lifestyle, school and work, future perspective, insurance and mortgage), and questionnaires assessing health-related quality of life (PedsQL-YA), anxiety and depression (HADS), and fatigue (CIS-20R). Descriptive statistics were used to describe support needs. Linear regression was used to identify characteristics associated with support needs. RESULTS: One hundred fifty-one YACCS participated (response = 40%). Most YACCS reported a need for support in one or more domains (88.0%, N = 133). More than half of the participants reported a need for concrete information in the domains lifestyle, fertility, and physical consequences of childhood cancer and 25-50% in the domains insurance and mortgages, future perspective, and social-emotional consequences of childhood cancer. In the domains lifestyle and physical as well as emotional consequences of childhood cancer, 25-50% reported a need for counseling. Overall need for support was positively associated with middle (ß = 0.26, p = 0.024) and high (ß = 0.35, p = 0.014) compared to low educational attainment and (sub)clinical anxiety (ß = 0.22, p = 0.017), and negatively associated with social functioning (ß = - 0.37, p = 0.002) in multivariate analyses. CONCLUSION: YACCS report the strongest need for support, for concrete information, in the domains lifestyle, fertility, and physical consequences of childhood cancer. Associated factors were mostly socioeconomic and psychosocial in nature. Psychosocial care should be an integral part of survivorship care for YACCS, with screening for psychosocial problems, information provision including associated emotional consequences and support if necessary (psycho-education) and tailored interventions, and adequate referrals to more specialized care if necessary.

Hydrological impacts of ethanol-driven sugarcane expansion in Brazil.

Ethanol production in Brazil is projected to double between 2012 and 2030 in order to meet increased global demand, resulting in the expansion of sugarcane cultivation. Sugarcane expansion drives both direct and indirect land-use changes, and subsequent changes in hydrology may exacerbate problems of (local) water scarcity. This study assesses the impacts of projected ethanol-driven sugarcane expansion on agricultural and hydrological drought in Brazil. Drought due to sugarcane expansion is modelled using a spatial terrestrial hydrological model (PCR-GLOBWB) with spatiotemporally variable land-use change and climate change scenarios as input. We compare an ethanol scenario with increased ethanol demand to a reference situation in which ethanol demand does not increase. The results show that, on average, 29% of the Centre West Cerrado region is projected to experience agricultural drought between 2012 and 2030, and the drought deficit in this region is projected to be 7% higher in the ethanol scenario compared to the reference. The differences between the ethanol and the reference scenario are small when averaged over macro-regions, but can be considerable at a local scale. Differences in agricultural and hydrological drought between the ethanol and reference scenario are most notable in the Centre West Cerrado and Southeast regions. Locally, considerable changes may also occur in other regions, including the Northeast Coast and Northern Amazon region. Because the South East and Centre West Cerrado regions are responsible for a large proportion of agricultural production, increased agricultural drought may result in significant economic losses, while increased hydrological drought could exacerbate existing problems of water supply to large metropolitan areas in these regions. The identification of areas at risk of increased droughts can be important information for policy makers to take precautionary measures to avoid negative hydrological impacts of increased ethanol demand.

Diagnostic performance of MRI for assessment of response to neoadjuvant chemoradiotherapy in oesophageal cancer.

BACKGROUND: Patients with a pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) for oesophageal cancer may benefit from non-surgical management. The aim of this study was to determine the diagnostic performance of visual response assessment of the primary tumour after nCRT on T2-weighted (T2W) and diffusion-weighted (DW) MRI. METHODS: Patients with locally advanced oesophageal cancer who underwent T2W- and DW-MRI (1·5 T) before and after nCRT in two hospitals, between July 2013 and September 2017, were included in this prospective study. Three radiologists evaluated T2W images retrospectively using a five-point score for the assessment of residual tumour in a blinded manner and immediately rescored after adding DW-MRI. Histopathology of the resection specimen was used as the reference standard; ypT0 represented a pCR. Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve (AUC) and interobserver agreement were calculated. RESULTS: Twelve of 51 patients (24 per cent) had a pCR. The sensitivity and specificity of T2W-MRI for detection of residual tumour ranged from 90 to 100 and 8 to 25 per cent respectively. Respective values for T2W + DW-MRI were 90-97 and 42-50 per cent. AUCs for the three readers were 0·65, 0·66 and 0·68 on T2W-MRI, and 0·71, 0·70 and 0·70 on T2W + DW-MRI (P = 0·441, P = 0·611 and P = 0·828 for readers 1, 2 and 3 respectively). The κ value for interobserver agreement improved from 0·24-0·55 on T2W-MRI to 0·55-0·71 with DW-MRI. CONCLUSION: Preoperative assessment of residual tumour on MRI after nCRT for oesophageal cancer is feasible with high sensitivity, reflecting a low chance of missing residual tumour. However, the specificity was low; this results in overstaging of complete responders as having residual tumour and, consequently, overtreatment.

IgG is elevated in obese white adipose tissue but does not induce glucose intolerance via Fcγ-receptor or complement.

BACKGROUND/OBJECTIVES: In obesity, B cells accumulate in white adipose tissue (WAT) and produce IgG, which may contribute to the development of glucose intolerance. IgG signals by binding to Fcγ receptors (FcγR) and by activating the complement system. The aim of our study was to investigate whether activation of FcγR and/or complement C3 mediates the development of high-fat diet-induced glucose intolerance. METHODS: We studied mice lacking all four FcγRs (FcγRI/II/III/IV-/-), only the inhibitory FcγRIIb (FcγRIIb-/-), only the central component of the complement system C3 (C3-/-), and mice lacking both FcγRs and C3 (FcγRI/II/III/IV/C3-/-). All mouse models and wild-type controls were fed a high-fat diet (HFD) for 15 weeks to induce obesity. Glucose metabolism was assessed and adipose tissue was characterized for inflammation and adipocyte functionality. RESULTS: In obese WAT of wild-type mice, B cells (+142%, P<0.01) and IgG (+128% P<0.01) were increased compared to lean WAT. Macrophages of FcγRI/II/III/IV-/-mice released lower levels of cytokines compared to wild-type mice upon IgG stimulation. Only C3-/- mice showed reduced HFD-induced weight gain as compared to controls (-18%, P<0.01). Surprisingly, FcγRI/II/III/IV-/- mice had deteriorated glucose tolerance (AUC +125%, P<0.001) despite reduced leukocyte number (-30%, P<0.05) in gonadal WAT (gWAT), whereas glucose tolerance and leukocytes within gWAT in the other models were unaffected compared to controls. Although IgG in gWAT was increased (+44 to +174%, P<0.05) in all mouse models lacking FcγRIIb, only FcγRI/II/III/IV/C3-/- mice exhibited appreciable alterations in immune cells in gWAT, for example, increased macrophages (+36%, P<0.001). CONCLUSIONS: Lack of FcγRs reduces the activity of macrophages upon IgG stimulation, but neither FcγR nor C3 deficiency protects against HFD-induced glucose intolerance or reduces adipose tissue inflammation. This indicates that if obesity-induced IgG contributes to the development of glucose intolerance, this is not mediated by FcγR or complement activation.

Preoperative image-guided identification of response to neoadjuvant chemoradiotherapy in esophageal cancer (PRIDE): a multicenter observational study.

BACKGROUND: Nearly one third of patients undergoing neoadjuvant chemoradiotherapy (nCRT) for locally advanced esophageal cancer have a pathologic complete response (pCR) of the primary tumor upon histopathological evaluation of the resection specimen. The primary aim of this study is to develop a model that predicts the probability of pCR to nCRT in esophageal cancer, based on diffusion-weighted magnetic resonance imaging (DW-MRI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and 18F-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG PET-CT). Accurate response prediction could lead to a patient-tailored approach with omission of surgery in the future in case of predicted pCR or additional neoadjuvant treatment in case of non-pCR. METHODS: The PRIDE study is a prospective, single arm, observational multicenter study designed to develop a multimodal prediction model for histopathological response to nCRT for esophageal cancer. A total of 200 patients with locally advanced esophageal cancer - of which at least 130 patients with adenocarcinoma and at least 61 patients with squamous cell carcinoma - scheduled to receive nCRT followed by esophagectomy will be included. The primary modalities to be incorporated in the prediction model are quantitative parameters derived from MRI and 18F-FDG PET-CT scans, which will be acquired at fixed intervals before, during and after nCRT. Secondary modalities include blood samples for analysis of the presence of circulating tumor DNA (ctDNA) at 3 time-points (before, during and after nCRT), and an endoscopy with (random) bite-on-bite biopsies of the primary tumor site and other suspected lesions in the esophagus as well as an endoscopic ultrasonography (EUS) with fine needle aspiration of suspected lymph nodes after finishing nCRT. The main study endpoint is the performance of the model for pCR prediction. Secondary endpoints include progression-free and overall survival. DISCUSSION: If the multimodal PRIDE concept provides high predictive performance for pCR, the results of this study will play an important role in accurate identification of esophageal cancer patients with a pCR to nCRT. These patients might benefit from a patient-tailored approach with omission of surgery in the future. Vice versa, patients with non-pCR might benefit from additional neoadjuvant treatment, or ineffective therapy could be stopped. TRIAL REGISTRATION: The article reports on a health care intervention on human participants and was prospectively registered on March 22, 2018 under ClinicalTrials.gov Identifier: NCT03474341 .

Intranasal vaccination with protein bodies elicit strong protection against Streptococcus pneumoniae colonization.

Protein bodies (PBs) are particles consisting of insoluble, aggregated proteins with potential as a vaccine formulation. PBs can contain high concentrations of antigen, are stable and relatively resistant to proteases, release antigen slowly and are cost-effective to manufacture. Yet, the capacity of PBs to provoke immune responses and protection in the upper respiratory tract, a major entry route of respiratory pathogens, is largely unknown. In this study, we vaccinated mice intranasally with PBs comprising antigens from Streptococcus pneumoniae and evaluated the level of protection against nasopharyngeal colonization. PBs composed of the α-helical domain of pneumococcal surface protein A (PspAα) provided superior protection against colonization with S. pneumoniae compared to soluble PspAα. Immunization with soluble protein or PBs induced differences in antibody binding to pneumococci as well as a highly distinct antigen-specific nasal cytokine profile upon in vivo stimulation with inactivated S. pneumoniae. Moreover, immunization with PBs composed of conserved putative pneumococcal antigens reduced colonization by S. pneumoniae in mice, both as a single- and as a multi-antigen formulation. In conclusion, PBs represent a vaccine formulation that elicits strong mucosal immune responses and protection. The versatility of this platform offers opportunities for development of next-generation vaccine formulations.

[Lithium levels need to be monitored: discrepancies between guidelines and practice]. / Controles bij de behandeling met lithium: de richtlijn en de klinische praktijk.

BACKGROUND: Since lithium can affect the thyroid gland and the kidneys, it is important to perform regular checks on levels of lithium, creatinine and thyroid-stimulating hormone (TSH). AIM: To investigate whether psychiatrists and general practitioners (GPs) perform the required checks twice a year on the levels of lithium, creatinine and tsh in accordance with the Dutch guidelines on bipolar disorder as laid down in 2001. METHOD: The study was based on data that the clinical-chemical laboratory had regarding the lithium checks performed in 2004 in GPs' practices or by the mental health authority in Apeldoorn and the surrounding area. About 250,000 people live in this region. RESULTS: Some of the psychiatrists (11%) and GPs (about 25%) did not check lithium levels as frequently as recommended in the guidelines of 2001. The GPs checked significantly less frequently that the psychiatrists. Both the GPs and the psychiatrists monitored creatinine and TSH less frequently than recommended in the guidelines, creatinine was monitored in 65.8 and 61.2% and TSH in 68.3 and 58% respectively. CONCLUSION We recommend that a warning system be installed in the laboratory which will alert the doctor when a patient has missed a check. Another suggestion is that lithium should be prescribed only by psychiatrists, and not by GPs.

[Patients with intellectual disabilities]. / Patiënten met een verstandelijke beperking: 10 tips.

Almost all physicians see patients with intellectual disabilities in their practices. There are still health disparities between people with intellectual disability and the general population. Consultations with this group of patients can be challenging, but there are ways to improve on them. Take your time when it comes to communicating with patients with intellectual disabilities, adapt language use and make use of visual aids. People with intellectual disabilities and complex care needs can be referred to intellectual disability physicians (AVG in Dutch) or syndrome-specific outpatient clinics.

Coexistence of malnutrition, frailty, physical frailty and disability in patients with COPD starting a pulmonary rehabilitation program.

BACKGROUND & AIMS: Malnutrition, frailty, physical frailty, and disability are common conditions in patients with chronic obstructive pulmonary disease (COPD). Insight in the coexistence and relations between these conditions may provide information on the nature of the relationship between malnutrition and frailty. Such information may help to identify required interventions to improve the patient's health status. We therefore aimed to explore whether malnutrition, frailty, physical frailty, and disability coexist in patients with COPD at the start of pulmonary rehabilitation. METHODS: For this cross-sectional study, from March 2015 to May 2017, patients with COPD were assessed at the start of a pulmonary rehabilitation program. Nutritional status was assessed with the Scored Patient-Generated Subjective Global Assessment (PG-SGA) based Pt-Global app. Frailty was assessed by the Evaluative Frailty Index for Physical activity (EFIP), physical frailty by Fried's criteria, and disability by the Dutch version of World Health Organization Disability Assessment Schedule 2.0 (WHODAS). These variables were dichotomized to determine coexistence of malnutrition, frailty, physical frailty, and disability. Associations between PG-SGA score and respectively EFIP score, Fried's criteria, and WHODAS score were analyzed by Pearson's correlation coefficient. Two tailed P-values were used, and significance was set at P < 0.05. RESULTS: Of the 57 participants included (age 61.2 ± 8.7 years), malnutrition and frailty coexisted in 40%. Malnutrition and physical frailty coexisted in 18%, and malnutrition and disability in 21%. EFIP score and PG-SGA score were significantly correlated (r = 0.43, P = 0.001), as well as Fried's criteria and PG-SGA score (r = 0.37, P = 0.005). CONCLUSIONS: In this population, malnutrition substantially (40%) coexists with frailty. Although the prevalence of each of the four conditions is quite high, the coexistence of all four conditions is limited (11%). The results of our study indicate that nutritional interventions should be delivered by health care professionals across multiple disciplines.

[Increase in extrapulmonary tuberculosis in The Netherlands associated with an increase in the number of residents with non-Dutch nationality; observational study of data from 1993-2001]. / Toename van extrapulmonale tuberculose in Nederland door toename van het aantal inwoners met een niet-Nederlandse nationaliteit; observationeel onderzoek over 1993-2001.

OBJECTIVE: To describe the epidemiology of extrapulmonary and pulmonary tuberculosis (TB) in The Netherlands between 1993 and 2001, with special attention given to the relationship between disease site and patient nationality. DESIGN: Retrospective descriptive and comparative study. METHOD: Data were collected from all patients diagnosed with TB and entered in The Netherlands Tuberculosis Register between 1 January 1993 and 31 December 2001. Information on age, sex, nationality, year of diagnosis, culture result, disease site and HIV status was retrieved and compared. RESULTS: Of the total 13,258 TB patients, 8,216 (62%) had pulmonary TB and 5,042 (38%) had extrapulmonary TB. The proportion of extrapulmonary TB cases increased during the study period. The most common types of extrapulmonary TB were lymphatic TB, pleural TB and TB of the bones and/or joints. Patients with a non-Dutch nationality were diagnosed with extrapulmonary TB more often than Dutch patients. CONCLUSION: The proportional increase in extrapulmonary TB was explained by an increase in the number of inhabitants with non-Western ethnic backgrounds in The Netherlands. Physicians must be aware of the changing clinical picture of TB.

Test data from pullout experiments on vetiver grass (Vetiveria zizanioides) grown in semi-arid climate.

The data set presented in this article includes the results of pullout tests carried out on vetiver grass (Vetiveria zizanioides) growing on an abandoned terrace slopes in Spain. The results comprise tables showing the resistance of each tested vetiver plant to pullout forces applied to it at various angles. The dataset also contains the measurements of the displacement at each pullout force increment. The dataset also includes the plots of the pullout resistance of each vetiver plant against the measured displacement.

Changes in surface hydrology, soil moisture and gross primary production in the Amazon during the 2015/2016 El Niño.

The 2015/2016 El Niño event caused severe changes in precipitation across the tropics. This impacted surface hydrology, such as river run-off and soil moisture availability, thereby triggering reductions in gross primary production (GPP). Many biosphere models lack the detailed hydrological component required to accurately quantify anomalies in surface hydrology and GPP during droughts in tropical regions. Here, we take the novel approach of coupling the biosphere model SiBCASA with the advanced hydrological model PCR-GLOBWB to attempt such a quantification across the Amazon basin during the drought in 2015/2016. We calculate 30-40% reduced river discharge in the Amazon starting in October 2015, lagging behind the precipitation anomaly by approximately one month and in good agreement with river gauge observations. Soil moisture shows distinctly asymmetrical spatial anomalies with large reductions across the north-eastern part of the basin, which persisted into the following dry season. This added to drought stress in vegetation, already present owing to vapour pressure deficits at the leaf, resulting in a loss of GPP of 0.95 (0.69 to 1.20) PgC between October 2015 and March 2016 compared with the 2007-2014 average. Only 11% (10-12%) of the reduction in GPP was found in the (wetter) north-western part of the basin, whereas the north-eastern and southern regions were affected more strongly, with 56% (54-56%) and 33% (31-33%) of the total, respectively. Uncertainty on this anomaly mostly reflects the unknown rooting depths of vegetation.This article is part of a discussion meeting issue 'The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications'.

High rates of suicide and attempted suicide using pesticides in Nickerie, Suriname, South America.

Suicide and attempted suicide are identified as a serious mental health problem in Suriname, especially in the district of Nickerie. An epidemiological study in the Nickerie catchment area revealed high rates of suicide (48 per 100,000) and attempted suicide (207 per 100,000) on average in the years 2000-2004. Particularly remarkable is the high number of attempted suicides among males (49%), and the use of pesticides in both fatal (55%) and nonfatal suicidal behavior (44%). Probably this high incidence of suicidal behavior reflects the very poor economic situation of the district, poverty of most of the population, high levels of alcohol misuse, domestic violence, the rigidity of Hindustani culture regarding family traditions, the accessibility of pesticides, and the lack of future perspectives. Health care alone will not be sufficient to tackle this problem. One of the most urgent measures to prevent suicides is to stow away pesticides in locked cabinets with the key held by the proprietor.

[A man with Candida pyopneumopericarditis and cardiac tamponade in conjunction with gastric tube infection]. / Een man met candida-pyopneumopericarditis en harttamponnade bij een buismaaginfectie.

A 55-year-old man who had undergone oesophagectomy with retrosternal gastric tube reconstruction for oesophageal carcinoma several years before, presented with retrosternal pain, fever and chills. He appeared to have Candida glabratarelated pyopneumopericarditis and a fungal infection in the gastric tube. Because of cardiac tamponade, the pericardium was surgically drained. The patient was given antibiotics and fluconazole. He left the hospital after one month in relatively good condition. Two months later, he was readmitted for haematemesis. During an emergency surgical procedure a fistula was found between the gastric tube and the left atrium. For these patients is early treatment of the underlying cause lifesaving. Monthly check-ups in an outpatient clinic are needed due to the risk of constrictive pericarditis and recurrent cardiac tamponade.

MRI for diagnosing aortic valve stenosis: a comparison study of MRI and ultrasound.

BACKGROUND: In cases when Doppler ultrasound examinations are not reliable for determining the severity of aortic valve stenosis, patients undergo a catheterisation. Cardiac magnetic resonance imaging (MRI) is a promising tool for the determination of this disease. AIM: We investigated the value of MRI as a substitute for catheterisation in such circumstances, by comparing MRI measurements with Doppler ultrasound measurements. METHODS: Five volunteers and ten patients entered this study, which was approved by the Institutional Ethics Committee. A 1.0T MRI scanner was used for cardiac MRI. On the same day, a Doppler ultrasound examination was performed. The maximum velocity and the orifice area of the aortic valve (called orifice) were compared. RESULTS: A good correlation was observed between the maximum velocity measured with MRI and that measured with ultrasound (r2=0.95) and between the orifice determined by MRI and by ultrasound (r2=0.94); however, the orifice determined by MRI is consistently larger than the orifice determined by ultrasound. CONCLUSION: MRI measurements of velocity and orifice of the aortic valve correlate well with Doppler ultrasound measurement. MRI is a useful diagnostic tool and can be a good substitute for catheterisation, in particular because it allows simultaneous acquisition of anatomical and functional information.

Prostanoid receptor gene expression profile in human trabecular meshwork: a quantitative real-time PCR approach.

PURPOSE: To assess the expression pattern of prostanoid receptor-encoding genes in trabecular meshwork (TM) of human donor eyes. METHODS: Disposed human donor eyes (n = 10) were obtained from the Cornea Bank, Amsterdam. The TM was dissected from the scleral tissue and homogenized in lysis buffer, and total RNA was isolated. The RNA was converted into cDNA and used as a template for noncompetitive quantitative real-time polymerase chain reaction (PCR) using green fluorescent dye to quantify the accumulation of double-stranded PCR product. Specific primers for four housekeeping genes and DP, EP(1), EP(2), EP(3,) EP(4), FP, IP, and TP receptor-encoding transcripts were developed and tested for their efficiency. RESULTS: The characterized expression profile was highly reproducible in all samples, with the EP(2) receptor-encoding transcript in the highest abundance, followed by FP, TP, IP, and EP(4) at levels that were approximately 10 to 15 times lower than that of the EP(2) subtype. DP and EP(3) were at the lowest levels, which were, on average, 45 times and 228 times lower than EP(2), respectively. CONCLUSIONS: These data show that all prostanoid receptors are expressed at different levels in human TM tissue. Because the gene expression of the EP(2) receptor is, on average, 15 times more abundant than that of the EP(4) receptor, it may be expected that the increase in flow and cAMP levels in response to the activation of the EP receptors by application of prostaglandin E(1) (PGE(1)), is primarily mediated by the EP(2) receptor. These data should be considered when designing prostanoid receptor mimetics intended to enhance the aqueous humor outflow through the TM and Schlemm's canal.