P-FLUX: A phosphorus budget dataset spanning diverse agricultural production systems in the United States and Canada.

Quantifying spatial and temporal fluxes of phosphorus (P) within and among agricultural production systems is critical for sustaining agricultural production while minimizing environmental impacts. To better understand P fluxes in agricultural landscapes, P-FLUX, a detailed and harmonized dataset of P inputs, outputs, and budgets, as well as estimated uncertainties for each P flux and budget, was developed. Data were collected from 24 research sites and 61 production systems through the Long-term Agroecosystem Research (LTAR) network and partner organizations spanning 22 U.S. states and 2 Canadian provinces. The objectives of this paper are to (a) present and provide a description of the P-FLUX dataset, (b) provide summary analyses of the agricultural production systems included in the dataset and the variability in P inputs and outputs across systems, and (c) provide details for accessing the dataset, dataset limitations, and an example of future use. P-FLUX includes information on select site characteristics (area, soil series), crop rotation, P inputs (P application rate, source, timing, placement, P in irrigation water, atmospheric deposition), P outputs (crop removal, hydrologic losses), P budgets (agronomic budget, overall budget), uncertainties associated with each flux and budget, and data sources. Phosphorus fluxes and budgets vary across agricultural production systems and are useful resources to improve P use efficiency and develop management strategies to mitigate environmental impacts of agricultural systems. P-FLUX is available for download through the USDA Ag Data Commons (https://doi.org/10.15482/USDA.ADC/1523365).

Dynamic modulation of inflammatory pain-related affective and sensory symptoms by optical control of amygdala metabotropic glutamate receptor 4.

Contrary to acute pain, chronic pain does not serve as a warning signal and must be considered as a disease per se. This pathology presents a sensory and psychological dimension at the origin of affective and cognitive disorders. Being largely refractory to current pharmacotherapies, identification of endogenous systems involved in persistent and chronic pain is crucial. The amygdala is a key brain region linking pain sensation with negative emotions. Here, we show that activation of a specific intrinsic neuromodulatory system within the amygdala associated with type 4 metabotropic glutamate receptors (mGlu4) abolishes sensory and affective symptoms of persistent pain such as hypersensitivity to pain, anxiety- and depression-related behaviors, and fear extinction impairment. Interestingly, neuroanatomical and synaptic analysis of the amygdala circuitry suggests that the effects of mGlu4 activation occur outside the central nucleus via modulation of multisensory thalamic inputs to lateral amygdala principal neurons and dorso-medial intercalated cells. Furthermore, we developed optogluram, a small diffusible photoswitchable positive allosteric modulator of mGlu4. This ligand allows the control of endogenous mGlu4 activity with light. Using this photopharmacological approach, we rapidly and reversibly inhibited behavioral symptoms associated with persistent pain through optical control of optogluram in the amygdala of freely behaving animals. Altogether, our data identify amygdala mGlu4 signaling as a mechanism that bypasses central sensitization processes to dynamically modulate persistent pain symptoms. Our findings help to define novel and more precise therapeutic interventions for chronic pain, and exemplify the potential of optopharmacology to study the dynamic activity of endogenous neuromodulatory mechanisms in vivo.

[Standardization of spirometry: 2015 update. Published by German Atemwegsliga, German Respiratory Society and German Society of Occupational and Environmental Medicine]. / Leitlinie zur Spirometrie. Leitlinie der Deutschen Atemwegsliga, der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin und der Deutschen Gesellschaft für Arbeitsmedizin und Umweltmedizin zur Spirometrie.

Spirometry is a simple test and considered the gold standard in lung function. An obstructive ventilatory defect is a disproportionate reduction of maximal airflow from the lung in relation to the maximal volume that can be displaced from the lung. It implies airway narrowing and is defined by a reduced FEV1/FVC ratio below the 5th percentile of the predicted value (lower limit of normal, LLN). A restrictive disorder may be suspected when vital capacity (FVC) is reduced and FEV1/FVC is normal. It is definitely proven, however, only by a decrease in TLC below the 5th percentile of predicted value (LLN). The measurement of TLC by body plethysmography is necessary to confirm or exclude a restrictive defect or hyperinflation of the lung when FVC is below the LLN. 2012 a task force of the ERS published new reference values based on 74,187 records from healthy non-smoking males and females from 26 countries. The new reference equations for the 3-95 age range are now available that include appropriate age-dependent mean values and lower limits of normal (LLN). This presentation aims at providing the reader with recommendations dealing with standardization and interpretation of spirometry.

Cholinergic mechanism underlying prepulse inhibition of the startle response in rats.

Startle responses are attenuated by prepulse inhibition (PPI), which is considered to reflect a sensorimotor gating mechanism and is impaired in patients suffering from schizophrenia. A midbrain circuit that mediates PPI in rats has been proposed and behavioral experiments have indicated an important role of acetylcholine and GABA in inhibiting startle. We here test the hypothesis that activation of the midbrain neurons can inhibit startle signaling through a cholinergic mechanism. We have developed a brain slice that comprises startle mediating giant pontine neurons as well as midbrain mesopontine neurons required for PPI. Patch clamp recordings of startle mediating brainstem neurons combined with stimulation of sensory afferents within the startle pathway and activation of mesopontine neurons revealed a delayed inhibition of synaptic transmission 300 ms and 1 s after midbrain activation. The latter was reversed by the muscarinic antagonist scopolamine. Further, there was a shift in the paired pulse ratio 1 s but not 300 ms after midbrain stimulation. Our results show that there is a direct cholinergic projection from the proposed PPI midbrain circuit to startle mediating neurons in the brainstem and that this projection inhibits synaptic transmission in the startle pathway in a distinct time window through the activation of presynaptic muscarinic receptors. Moreover, there is indication for a different receptor that mediates inhibition through this projection in a shorter time window and is located postsynaptically. Our results contribute to the understanding of mechanisms underlying PPI, which is important for developing new targets in the treatment of disorders accompanied with pre-attentive cognitive deficits.

Long-term follow-up of thalamic stimulation versus thalamotomy for tremor suppression.

Thalamic stimulation and thalamotomy for treatment of tremor due to Parkinson's disease, essential tremor, and multiple sclerosis were compared in a randomized trial. The symptomatic and functional outcome was studied after 5 years of follow-up. Sixty-eight patients were treated (45 Parkinson's disease, 13 essential tremor, 10 multiple sclerosis) by thalamotomy (n = 34) or thalamic stimulation (n = 34). After 5 years, 48 patients were available for follow-up. The primary outcome measure was change in functional status measured by the Frenchay Activities Index (FAI), scores ranging from 0 to 60. Secondary outcome measures were tremor severity, frequency of complications, and patients' assessment of the outcome. The mean difference in FAI scores between thalamic stimulation and thalamotomy was 4.4 (95% CI: 1.1-7.7) after 6 months, 3.3 (95% CI: -0.03-6.6) after 2 years and 4.0 (95% CI: 0.3-7.7) after 5 years in favor of stimulation. Tremor suppression was equally effective after both procedures, and stable in Parkinson patients. In ET and multiple sclerosis, a diminished effect of stimulation was observed in half of the patients. There were six stimulation equipment-related complications, but neurological side effects of surgery were higher after thalamotomy. Subjective outcome-assessment by the patients was more favorable in the stimulation group.

What is the value of emission tomography studies in patients with a primary glioblastoma multiforme treated by 192Ir brachytherapy?

BACKGROUND: We studied the use of (201)Thallium SPECT and L-[1-(11)C]-tyrosine PET in patients with a primary glioblastoma multiforme treated with (192)Ir brachytherapy after surgery and external beam radiation therapy. We hypothesised that the patients most likely to benefit from further surgery after deterioration would be those with radiation necrosis and would be recognised by a negative emission tomography scan. METHODS: Twenty-one patients underwent (201)Thallium SPECT performed before brachytherapy, and this was repeated in 19 patients when recurrence was suspected. Nine patients also underwent a PET scan at the same time. Nine patients underwent a second operation. FINDINGS: SPECT and PET were highly concordant concerning the prediction of radionecrosis and/or tumour recurrence. Repeat surgery did not lead to a significant increase in survival. There was no significant association between the duration of survival and tumour-to-background ratio but the number studied was small. Both SPECT and PET showed highly active lesions, which were proved to be recurrent tumour by clinical and histological follow-up. CONCLUSION: Although PET and SPECT are both highly sensitive in detecting active tumour tissue, emission tomography was not clinically valuable in the investigation of patients with a primary glioblastoma treated with brachytherapy.

[COPD outpatient education programme (ATEM) and BODE index]. / Ambulante COPD-Patientenschulung (ATEM) und BODE-Index.

While pulmonary rehabilitation is well established in the therapy for COPD (chronic obstructive pulmonary disease), the effectiveness of isolated patient education programmes still remains unclear. The aim of this study was to evaluate the effectiveness of a COPD outpatient education programme (ATEM). In a prospective randomised design, 50 patients (38 intervention, 12 control) with mild to very severe COPD have been examined with respect to a variety of follow-up parameters. At the end of the follow-up period of 12 months, the data of 11 patients of the control group (standard therapy) and 30 patients of the intervention group (additional participation in the education programme) were analysed. At entry, the two groups showed a good comparability. Over the follow-up period only the education group showed a favourable course. The BODE index (BMI, Obstruction, Dyspnea, Exercise capacity) showed a significant improvement of 17% for the education group, while the score for the patients of the control group was seen to deteriorate by about 39%. The advantages of the intervention group were also apparent for the markers of morbidity, namely hospitalisation and the need for antibiotics. In conclusion, participation in the education programme ATEM seems to be able to improve exercise capacity and well being, as measured with the BODE index, as well as important markers of morbidity in patients with mild to very severe COPD.

Nitrogen and phosphorus runoff losses from variable and constant intensity rainfall simulations on loamy sand under conventional and strip tillage systems.

Further studies on the quality of runoff from tillage and cropping systems in the southeastern USA are needed to refine current risk assessment tools for nutrient contamination. Our objective was to quantify and compare effects of constant (Ic) and variable (Iv) rainfall intensity patterns on inorganic nitrogen (N) and phosphorus (P) losses from a Tifton loamy sand (Plinthic Kandiudult) cropped to cotton (Gossypium hirsutum L.) and managed under conventional (CT) or strip-till (ST) systems. We simulated rainfall at a constant intensity and a variable intensity pattern (57 mm h(-1)) and collected runoff continuously at 5-min intervals for 70 min. For cumulative runoff at 50 min, the Iv pattern lost significantly greater amounts (p < 0.05) of total Kjeldahl N (TKN) and P (TKP) (849 g N ha(-1) and 266 g P ha(-1) for Iv; 623 g N ha(-1) and 192 g P ha(-1) for Ic) than did the Ic pattern. However, at 70 min, no significant differences in total losses were evident for TKN or TKP from either rainfall intensity pattern. In contrast, total cumulative losses of dissolved reactive P (DRP) and NO3-N were greatest for ST-Ic, followed by ST-Iv, CT-Ic, and CT-Iv in diminishing order (69 g DRP ha(-1) and 361 g NO3-N ha(-1); 37 g DRP ha(-1) and 133 g NO3-N ha(-1); 3 g DRP ha(-1) and 58 g NO3-N ha(-1); 1 g DRP ha(-1) and 49 g NO3-N ha(-1)). Results indicate that constant-rate rainfall simulations may overestimate the amount of dissolved nutrients lost to the environment in overland flow from cropping systems in loamy sand soils. We also found that CT treatments lost significantly greater amounts of TKN and TKP than ST treatments and in contrast, ST treatments lost significantly greater amounts of DRP and NO3-N than CT treatments. These results indicate that ST systems may be losing more soluble fractions than CT systems, but only a fraction the total N (33%) and total P (11%) lost through overland flow from CT systems.

Unilateral pallidotomy versus bilateral subthalamic nucleus stimulation in Parkinson's disease: one year follow-up of a randomised observer-blind multi centre trial.

BACKGROUND: To investigate whether STN stimulation is more efficacious than unilateral pallidotomy in advanced Parkinson's disease (PD) one year after surgery. METHOD: Thirty-four patients with advanced PD were randomly assigned to unilateral pallidotomy or bilateral STN stimulation. Outcome measures were parkinsonian symptoms in off and on phases (UPDRS 3), dyskinesias, functional status, Parkinson's disease quality of life questionnaire, the effects on separate symptoms, timed tests, patient diaries, dopaminergic drugs changes, adverse effects, and global outcome scale. Patients were assessed before surgery, six months and one year after surgery. The primary outcome measure was the off phase UPDRS 3 at six months follow-up. FINDINGS: The off phase UPDRS 3 score improved from 46.5 to 32 points in the pallidotomy patients and from 51.5 to 24 in the STN stimulation patients (p = 0.002). On phase UPDRS 3 and off phase Schwab and England functional scale improved significantly in favour of the STN stimulation patients. Dopaminergic drugs reduction was larger in the STN group although the difference between the treatment groups was not significant. One patient in each group had a major adverse effect. CONCLUSIONS: Bilateral STN stimulation is more efficacious than unilateral pallidotomy in advanced PD up to one year after surgery.

Development of a cost-effective oral vaccination method against viral disease in fish.

Different vaccination methods have been applied to protect fish against the detrimental effects of various pathogens. Several studies have shown the potentials of oral vaccination. In theory oral vaccination is an effortless and stress-free method which can be applied at almost any age. In general, however, the vaccine has to be protected to avoid digestion, which results in high costs for application in aquaculture. In this paper we introduce a cost-effective oral vaccination strategy for viral diseases of fish. The vaccines discussed here include fusion proteins consisting of a gut adhesion molecule and a viral peptide expressed in plants. The adhesion molecule mediates binding to and uptake from the gut, whereas the viral peptide functions as vaccine antigen mediating the induction of a humoral immune response. The first pilot studies using a fusion of the gut adhesion molecule and well-characterised heterologous linear B- and T-cell viral epitopes, produced in potato tubers, showed a promising binding and subsequent uptake in the end gut of carp. The results further indicated that a specific humoral immune response was evoked.

A comparison of neuropsychological effects of thalamotomy and thalamic stimulation.

OBJECTIVE: The neuropsychological effects of thalamotomy and thalamic stimulation in patients with severe drug-resistant tremor due to PD, essential tremor (ET), or MS were compared in a randomized trial. METHODS: Complete neuropsychological evaluations at baseline and 6 months after surgery were obtained in 62 patients who underwent thalamotomy (n = 32: 21 PD, 6 ET, 5 MS) or thalamic stimulation (n = 30: 19 PD, 7 ET, 4 MS). RESULTS: Six months after thalamotomy, a decline was seen in the scores of the Stroop Color-Word Test, with the exception of the interference score. In the thalamic stimulation group, no significant changes were found on any of the cognitive tests. Age, diagnosis, disease severity, and baseline cognitive status were not correlated to cognitive changes. A difference in score changes between right- and left-sided surgery was found in verbal fluency and Stroop Test scores after both thalamotomy and thalamic stimulation. CONCLUSIONS: Both thalamotomy and thalamic stimulation are associated with a minimal overall risk of cognitive deterioration. Verbal fluency decreased after both left-sided thalamotomy and thalamic stimulation.

Stereotactic neurosurgery for tremor.

The role of the motor thalamus as surgical target in stereotactic neurosurgery for different kinds of tremor is discussed. For tremor in Parkinson's disease, the subthalamic nucleus becomes more and more often the surgical target, because this target also gives relief of other and more incapacitating symptoms (hypokinesia, rigidity). Stimulation is as effective in tremor suppression as coagulation but has less adverse events and permits bilateral surgery. In selected cases, thalamotomy can still be indicated.

Plant members of the alpha1-->3/4-fucosyltransferase gene family encode an alpha1-->4-fucosyltransferase, potentially involved in Lewis(a) biosynthesis, and two core alpha1-->3-fucosyltransferases.

Three putative alpha1-->3/4-fucosyltransferase (alpha1-->3/4-FucT) genes have been detected in the Arabidopsis thaliana genome. The products of two of these genes have been identified in vivo as core alpha1-->3-FucTs involved in N-glycosylation. An orthologue of the third gene was isolated from a Beta vulgaris cDNA library. The encoded enzyme efficiently fucosylates Galbeta1-->3GlcNAcbeta1-->3Galbeta1-->4Glc. Analysis of the product by 400 MHz (1)H-nuclear magnetic resonance spectroscopy showed that the product is alpha1-->4-fucosylated at the N-acetylglucosamine residue. In vitro, the recombinant B. vulgaris alpha1-->4-FucT acts efficiently only on neutral type 1 chain-based glycan structures. In plants the enzyme is expected to be involved in Lewis(a) formation on N-linked glycans.

[Stereotaxic neurosurgery for treatment of Parkinson disease]. / Stereotactische neurochirurgie bij de behandeling van de ziekte van Parkinson.

Three target structures are available in stereotactic surgery for Parkinson's disease: the thalamus, the globus pallidus and the subthalamic nucleus. The subthalamic nucleus appears to be the most promising structure. However, the thalamus can be considered in the case of an incapacitating tremor presenting as a primary symptom. Surgery in the globus pallidus may be as effective as in the subthalamic nucleus, but in the latter it is often accompanied by a reduction in dopaminergic medication. The surgical technique of electrical stimulation causes fewer adverse effects than that of coagulation and can therefore be applied bilaterally, but does require more intense postoperative care. In the selection of patients for surgery, levodopa responsiveness plays an important role in predicting effectiveness, except in the case of tremor.

Oral immunisation of naive and primed animals with transgenic potato tubers expressing LT-B.

The efficacy of edible vaccines produced in potato tubers was examined in mice. Transgenic plants were developed by Agrobacterium tumefaciens-mediated transformation. The antigen selected was the non-toxic B subunit of the Escherichia coli enterotoxin (recLT-B). A synthetic gene coding for recLT-B was made and optimised for expression in potato tubers and accumulation in the endoplasmic reticulum. Introduction of this gene under control of the tuber-specific patatin promoter in potato plants resulted in the production of functional, i.e. Gm1-binding, recLT-B pentamers in tubers. Selected tubers containing about 13 microg of recLT-B per gram fresh weight were used for immunisation. Subcutaneous immunisation with an extract of recLT-B tubers yielded high antibody titres in serum that were similar to those obtained with bacterial recLT-B. The efficacy of oral administration of recLT-B tubers was determined by measuring mucosal and systemic immune responses in naive and primed mice. Animals were primed by subcutaneous injection of an extract of recLT-B tuber plus adjuvant. Naive and primed mice were fed 5 g of tubers ( approximately 65 microg of recLT-B) or were intubated intragastrically with 0.4 ml of tuber extract ( approximately 2 microg of recLT-B). In naive mice, feeding recLT-B tubers or intubation of tuber extract did not induce detectable anti-LT antibody titres. In primed animals, however, oral immunisation resulted in significant anti-LT IgA antibody responses in serum and faeces. Intragastric intubation of tuber extract revealed higher responses than feeding of tubers. These results indicate clearly that functional recLT-B can be produced in potato tubers, that this recombinant protein is immunogenic and that oral administration thereof elicits both systemic and local IgA responses in parentally primed, but not naive, animals.

Characterization of potato proteinase inhibitor II reactive site mutants.

Potato proteinase inhibitor II (PI-2) is composed of two sequence repeats. It contains two reactive site domains. We developed an improved protocol for the production of PI-2 using the yeast Pichia pastoris as the expression host. We then assessed the role of its two reactive sites in the inhibition of trypsin and chymotrypsin by mutating each of the two reactive sites in various ways. From these studies it appears that the second reactive site strongly inhibits both trypsin (Ki = 0.4 nM) and chymotrypsin (Ki = 0.9 nM), and is quite robust towards mutations at positions P2 or P1'. In contrast, the first reactive site inhibits only chymotrypsin (Ki = 2 nM), and this activity is very sensitive to mutations. Remarkably, replacing the reactive site amino acids of domain I with those of domain II did not result in inhibitory activities similar to domain II. The fitness for protein engineering of each domain is discussed.

A comparison of continuous thalamic stimulation and thalamotomy for suppression of severe tremor.

BACKGROUND: Deep-brain stimulation through an electrode implanted in the thalamus was developed as an alternative to thalamotomy for the treatment of drug-resistant tremor. Stimulation is thought to be as effective as thalamotomy but to have fewer complications. We examined the effects of these two procedures on the functional abilities of patients with drug-resistant tremor due to Parkinson's disease, essential tremor, or multiple sclerosis. METHODS: Sixty-eight patients (45 with Parkinson's disease, 13 with essential tremor, and 10 with multiple sclerosis) were randomly assigned to undergo thalamotomy or thalamic stimulation. The primary outcome measure was the change in functional abilities six months after surgery, as measured by the Frenchay Activities Index. Scores for this index can range from 0 to 60, with higher scores indicating better function. Secondary outcome measures were the severity of tremor, the number of adverse effects, and patients' assessment of the outcome. RESULTS: Functional status improved more in the thalamic-stimulation group than in the thalamotomy group, as indicated by increases in the score for the Frenchay Activities Index (from 31.4 to 36.3 and from 32.0 to 32.5, respectively; difference between groups, 4.4 points; 95 percent confidence interval, 2.0 to 6.9). After adjustment for base-line characteristics, multivariate analysis also showed that the thalamic-stimulation group had greater improvement (difference between groups, 5.1 points; 95 percent confidence interval, 2.3 to 7.9). Tremor was suppressed completely or almost completely in 27 of 34 patients in the thalamotomy group and in 30 of 33 patients in the thalamic-stimulation group. One patient in the thalamic-stimulation group died perioperatively after an intracerebral hemorrhage. With the exception of this incident, thalamic stimulation was associated with significantly fewer adverse effects than thalamotomy. Functional status was reported as improved by 8 patients in the thalamotomy group, as compared with 18 patients in the thalamic-stimulation group (P=0.01). CONCLUSIONS: Thalamic stimulation and thalamotomy are equally effective for the suppression of drug-resistant tremor, but thalamic stimulation has fewer adverse effects and results in a greater improvement in function.