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.

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.

[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.

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.

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'.

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.

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.

Giant coronary aneurysms: three-dimensional reconstruction.

A 31 year old man was referred for the evaluation of chest pain. Cardiac CT reconstruction revealed multiple calcified giant coronary aneurysms. Most likely this patient suffered from subclinical Kawasaki's disease in his childhood.

Hydrological response to climate change in a glacierized catchment in the Himalayas.

The analysis of climate change impact on the hydrology of high altitude glacierized catchments in the Himalayas is complex due to the high variability in climate, lack of data, large uncertainties in climate change projection and uncertainty about the response of glaciers. Therefore a high resolution combined cryospheric hydrological model was developed and calibrated that explicitly simulates glacier evolution and all major hydrological processes. The model was used to assess the future development of the glaciers and the runoff using an ensemble of downscaled climate model data in the Langtang catchment in Nepal. The analysis shows that both temperature and precipitation are projected to increase which results in a steady decline of the glacier area. The river flow is projected to increase significantly due to the increased precipitation and ice melt and the transition towards a rain river. Rain runoff and base flow will increase at the expense of glacier runoff. However, as the melt water peak coincides with the monsoon peak, no shifts in the hydrograph are expected.

[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.

Topical ophthalmic beta blockers may cause release of histamine through cytotoxic effects on inflammatory cells.

AIM: To evaluate the effects of beta blockers used in ophthalmology on the release of histamine from mixed cell preparations containing human leucocytes and basophils. METHODS: A mixed leucocyte and basophil preparation was obtained from venous blood of healthy non-atopic volunteers. Cell preparations were then incubated with betaxolol, metipranolol, timolol, or carteolol. After incubation for 1 hour the histamine content of the supernatant was analysed by automated fluorometric analysis. Cell viability was tested by measuring lactate dehydrogenase (LDH) concentrations. RESULTS: Betaxolol and metipranolol in concentrations between 10(-2) M and 10(-3) M liberated histamine from human blood cells in a dose dependent manner. Carteolol and timolol had no effect on histamine at these concentrations. At the same concentrations LDH was also detected in the supernatants of cell suspensions incubated with metipranolol or betaxolol. CONCLUSIONS: Betaxolol and metipranolol induce substantial histamine release from human leucocytes, probably as a result of their cytotoxic effect.

Incidence of ocular side effects of topical beta blockers in the Netherlands.

BACKGROUND: Several ocular side effects including uveitis, have been reported following topical beta blocker treatment for glaucoma and ocular hypertension. The incidence of these side effects was investigated in the Netherlands. METHODS: A prospective observational design was used whereby monthly questionnaires were sent to all practising ophthalmologists in the Netherlands during 3 consecutive months. Questionnaires were returned at the end of each month. Any patient whose topical beta blocker therapy was altered because of an ocular reaction was noted on this questionnaire. Ophthalmologists who did not return their questionnaires were interviewed by telephone at the end of the study period. The number of patients using topical beta blockers was derived from drug sales figures. RESULTS: 70% (328/467) of the ophthalmologists in the Netherlands participated in the study. During the 3 month study period 34 cases were reported: 15 patients had periorbital dermatitis, in eight patients eyelids and conjunctiva were affected, in seven patients the conjunctiva was affected, and four patients had punctate keratitis. The calculated incidence of ocular side effects during topical beta blocker therapy was 1.51 cases/1000 patient years. CONCLUSION: Topical beta blocker therapy is associated with few clinically important ocular side effects. No cases of uveitis were reported.

Pharmacological therapy for glaucoma: a review.

For some time the medical treatment of glaucoma has consisted of topical beta-blockers, adrenergic agents, miotics and oral carbonic anhydrase inhibitors (CAIs). However, the therapeutic arsenal available for the medical treatment of glaucoma has recently extended with new classes of ocular hypotensive agents i.e. prostaglandins, local CAIs and alpha2-adrenergic agents. Beta-blockers are still the mainstay in glaucoma treatment and are first line drugs. However, even if they are applied once daily, as with timolol in gel forming solution and levobunolol, the possible cardiopulmonary adverse effects of beta-blockers remain a cause for concern. When monotherapy with beta-blockers is ineffective in reducing intraocular pressure (IOP) or is hampered by adverse effects, a change of monotherapy to prostaglandins, local CAIs, alpha2-adrenergic agonists (brimonidine) or to dipivalyl epinephrine is advised. Prostaglandins, local CAIs and alpha2-adrenergic agonists, such as brimonidine, may in time become first line drugs because they reduce IOP effectively and until now systemic adverse effects have rarely been reported with these agents. The development of a pro-drug of either a local CAI or an alpha2-adrenergic agonist with a sustained and continuous effect on IOP level, which could be applied once a day is suggested. Because of these new developments, miotics, i.e. pilocarpine and carbachol, are recommended as second or third line drugs. The cholinesterase inhibitors are considered third line drugs as better agents with fewer local and systemic adverse effects have become available. Oral CAIs may be used temporarily in patients with elevated IOPs e.g. postsurgery or post-laser, or continuously in patients with glaucoma resistant to other treatment. Combining ocular hypotensive drugs is indicated when the target pressure for an individual patient cannot be reached with monotherapy. Combination therapy of beta-blockers is additive with prostaglandins, topical CAIs and miotics. Prostaglandins such as latanoprost can be combined with beta-blockers, adrenergic agents, local CAIs and miotics. Combinations with brimonidine or local CAIs need further investigation. Treatment of glaucoma with the new ocular hypotensive agents, either in monotherapy or combination therapy, may provide lower IOPs and delay or postpone the need for surgery.

Effect of body temperature on retinal damage by 488 nm light in rat.

Retinal light damage is influenced by the body temperature during exposure, but previous studies do not agree on the magnitude of the effect. A study in rats with broadband green light reported a much larger effect than a study with 380 nm light. The present study set out to clarify whether the spectral composition of the damaging light is responsible for this discrepancy by using 488 nm instead of 380 nm light. Wavelengths in the range of 470-550 nm are known to produce a different damage type than 380 nm. Small patches of retina of anesthetized rats were exposed to 488 nm radiation of an argon ion laser. Body temperature was varied between 30 and 40.5 degrees C. Three days after irradiation, the retina was inspected by funduscopy and prepared for light microscopy. The dose of radiation needed for a just visible change in fundo decreased by 6% per degree increase in body temperature. Damage was mainly found in the retinal pigment epithelium. Temperature had no effect on damage morphology. The temperature effect at 488 nm is much smaller than reported for broadband green light. We conclude that the spectral composition of the damaging light is not responsible for the discrepancy on the magnitude of the temperature effect. Other differences between the studies must be responsible, such as difference in retinal irradiance levels.

Short-term (6-week) oral toxicity study of selenium in Syrian hamsters.

The subacute toxicity of selenium was tested by feeding sodium selenite to Syrian hamsters at dietary levels of 0.1, 1, 5, 10 and 20 ppm selenium for 42 days. General health, survival and organ weights were not adversely affected at any of the dose levels. Weight gain and food intake were relatively low in males fed the highest dose level. The differences from the control values were not statistically significant and there was no similar effect in females. Hamsters fed 10 or 20 ppm retained considerably higher levels of selenium in the liver than did the controls. Microscopic examination of the liver revealed degenerative changes in males and females in the 20-ppm group. The no-toxic-effect level of selenium fed in the diet for 42 days to Syrian hamsters was found to be 10 ppm, equivalent to an intake of about 0.7 mg selenium/kg body weight/day.

Modifying effect of dietary fat on benzo[a]pyrene-induced respiratory tract tumours in hamsters.

Groups of 40 Syrian golden hamsters of both sexes were fed diets containing either 5% fat (control), 20% saturated fat (beef tallow) or 20% unsaturated fat (sunflower seed oil) from weaning and during the whole experimental period (up to 656 days). Respiratory tract tumours were induced by intratracheal instillation of benzo[a]pyrene attached to ferric oxide and suspended in saline. Mortality was slightly, but not statistically significantly higher in the high fat groups than in the low fat control group. Microscopic examination of the respiratory tract revealed an increased number of tumour bearing animals, an increased multiplicity of respiratory tract tumours and an increased total number of respiratory tract tumours in animals fed high fat diets. The tumour enhancing effect of fat was most pronounced in the high unsaturated fat group. Especially epidermoid papillomas, epidermoid carcinomas and combined epidermoid and adenocarcinomas contributed to the observed differences in tumour response amongst groups. It was concluded that dietary fat enhances benzo[a]pyrene-induced respiratory tract carcinogenesis in hamsters.

Effects of alkali-treated proteins: feeding studies with free and protein-bound lysinoalanine in rats and other animals.

To find out whether alkali-treated proteins posses nephrotoxic properties, feeding studies were conducted with drastically treated soybean protein and casein, and also with lysinoalanine (LAL), the amino acid known to be formed in protein subjected to high pH at elevated temperature. The feeding of synthesized LAL to rats at dietary levels of 100 ppm and above induced typical renal changes, called nephrocytomegalia. No such changes or any other indications of toxicity were observed, however, upon feeding much higher levels of LAL (up to 6,000 ppm) when provided as the protein-bound compound in alkali-treated casein or soybean protein. When set free by complete acid hydrolysis, LAL induced considerable renal activity, comparable to that of the synthetic compound. These results indicate that alkali treatment of proteins does not induce nephrotoxic properties provided that the compound remains protein-bound. Some nephrotoxic activity was observed, however, with peptide-boound LAL in break-down products (molecular weight less than 5,000) of alkali-treated casein, but considerably less than that of the free compound. LAL-analyses in blood, urine, and feces of rats fed free or protein-bound LAL indicated a positive correlation between intestinal absorption and nephrotoxic potential. No renal changes were encountered upon feeding diets with 1,000 ppm synthetic LAL to mice, hamsters, rabbits, quail, dogs or monkeys, which suggest a species specificity of LAL-induced renal changes in rats.