Origins of Acid-Gas Stability Behavior in Zeolitic Imidazolate Frameworks: The Unique High Stability of ZIF-71.

Zeolitic imidazolate frameworks (ZIFs) are promising materials for industrial process separations, but recent literature reports have highlighted their vulnerability to acid gases (e.g., SO2, CO2, NO2, H2S), often present in practical applications. While previous work has documented the widely varying stability behavior of many ZIFs under varying (humid and dry) acid gas environments, efforts to explain or correlate these experimental observations via empirical descriptors have not succeeded. A key observation is that ZIF-71 (RHO topology) is an extraordinarily stable ZIF material, retaining both structure and porosity under prolonged humid SO2 exposure whereas many other well-known ZIFs with different linkers and topologies (such as ZIF-8) were shown to degrade. Through a combination of hybrid quantum mechanics/molecular mechanics (QM/MM) based methods and statistical mechanical models, we successfully explain this important experimental observation via atomistic investigations of the reaction mechanism. Our holistic approach reveals an ∼9 times lower average defect formation rate in ZIF-71 RHO compared to ZIF-8 SOD, leading to the conclusion that the observed experimental stability of this material rises from kinetic effects. Moreover, our analysis reveals that differing stability of the two materials is determined by the distributions of acid gas molecules, which is difficult to capture using empirical descriptors. Our results suggest wider applicability of the present approach, toward identifying tuned functional groups and topologies that move the acid gas distributions away from more reactive sites and thus allow enhanced kinetic stability.

Upregulating excitability of corticospinal pathways in stroke patients using TMS neurofeedback; A pilot study.

Upper limb weakness following a stroke affects 80% of survivors and is a key factor in preventing their return to independence. State-of-the art approaches to rehabilitation often require that the patient can generate some activity in the paretic limb, which is not possible for many patients in the early period following stroke. Approaches that enable more patients to engage with upper limb therapy earlier are urgently needed. Motor imagery has shown promise as a potential means to maintain activity in the brain's motor network, when the patient is incapable of generating functional movement. However, as imagery is a hidden mental process, it is impossible for individuals to gauge what impact this is having upon their neural activity. Here we used a novel brain-computer interface (BCI) approach allowing patients to gain an insight into the effect of motor imagery on their brain-muscle pathways, in real-time. Seven patients 2-26 weeks post stroke were provided with neurofeedback (NF) of their corticospinal excitability measured by the size of motor evoked potentials (MEP) in response to transcranial magnetic stimulation (TMS). The aim was to train patients to use motor imagery to increase the size of MEPs, using the BCI with a computer game displaying neurofeedback. Patients training finger muscles learned to elevate MEP amplitudes above their resting baseline values for the first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles. By day 3 for ADM and day 4 for FDI, MEP amplitudes were sustained above baseline in all three NF blocks. Here we have described the first clinical implementation of TMS NF in a population of sub-acute stroke patients. The results show that in the context of severe upper limb paralysis, patients are capable of using neurofeedback to elevate corticospinal excitability in the affected muscles. This may provide a new training modality for early intervention following stroke.

Stress Response and Virulence Potential Modulating Effect of Peppermint Essential Oil in Campylobacter jejuni.

Campylobacter jejuni is one of the most common food-borne bacteria that causes gastrointestinal symptoms. In the present study we have investigated the molecular basis of the anti-Campylobacter effect of peppermint essential oil (PEO), one of the oldest EO used to treat gastrointestinal diseases. Transcriptomic, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and proteomic, two-dimensional polyacryl amid gel electrophoresis (2D-PAGE) methods have revealed that, in the presence of a sublethal concentration of PEO, the expression of several virulence-associated genes was decreased (cheY 0.84x; flhB 0.79x; flgE 0.205x; cadF 0.08x; wlaB 0.89x; porA 0.25x; cbf2 4.3x) while impaired motility was revealed with a functional analysis. Scanning electron micrographs of the exposed cells showed that, unlike in the presence of other stresses, the originally curved C. jejuni cells straightened upon PEO exposure. Gaining insight into the molecular background of this stress response, we have revealed that in the presence of PEO C. jejuni dominantly exerts a general stress response that elevates the expression of general stress genes like dnaK, groEL, groES (10.41x, 3.63x, and 4.77x). The most important genes dps, sodB, and katA involved in oxidative stress responses showed however moderate transcriptional elevations (1,58x, 1,55x, and 1,85x).

First-line treatment in lymphomatoid papulosis: a retrospective multicentre study.

BACKGROUND: Data regarding response to treatment in lymphomatoid papulosis (LyP) are scarce. AIM: To assess the daily clinical practice approach to LyP and the response to first-line treatments. METHODS: This was a retrospective study enrolling 252 patients with LyP. RESULTS: Topical steroids, methotrexate and phototherapy were the most common first-line treatments, prescribed for 35%, 20% and 14% of the patients, respectively. Complete response (CR) was achieved in 48% of treated patients. Eczematous lesions significantly increased relative risk (RR) of not achieving CR (RR = 1.76; 95% CI 1.16-2.11). Overall median time to CR was 10 months (95% CI 6-13 months), and 78% of complete responders showed cutaneous relapse; both results were similar for all treatment groups (P > 0.05). Overall estimated median disease-free survival (DFS) was 11 months (95% CI 9-13 months) but DFS for patients treated with phototherapy was 23 months (95% CI 10-36 months; P < 0.03). Having the Type A LyP variant (RR = 2.04; 95% CI 0.96-4.30) and receiving a first-line treatment other than phototherapy (RR = 5.33; 95% CI 0.84-33.89) were significantly associated with cutaneous early relapse. Of the 252 patients, 31 (13%) had associated mycosis fungoides unrelated to therapeutic approach, type of LyP or T-cell receptor clonality. CONCLUSIONS: Current epidemiological, clinical and pathological data support previous results. Topical steroids, phototherapy and methotrexate are the most frequently prescribed first-line treatments. Although CR and cutaneous relapse rates do not differ between them, phototherapy achieves a longer DFS. Presence of Type A LyP and use of topical steroid or methotrexate were associated with an increased risk of early relapse.

Dietas pós-eclosão suplementadas com fontes de gordura e acrescidas de taurina e glicina sobre a morfometria intestinal e o desempenho de frangos de corte de um a 21 dias / Post-hatch diets supplemented with sources of fat and added taurine and glycine on the intestinal morphology and performance of broilers at 1 to 21 days

O objetivo deste estudo foi avaliar o efeito do fornecimento de dietas pós-eclosão suplementadas com diferentes fontes de gordura insaturada e adicionadas ou não de taurina e glicina sobre o desempenho produtivo, a biometria e a morfometria do intestino delgado de pintos de corte de um a 21 dias de idade. Foram utilizados 480 pintos de corte machos de um dia de idade da linhagem Cobb. O delineamento foi inteiramente ao acaso, em esquema fatorial 2 x 4, com e sem suplementação de taurina e glicina e quatro dietas (controle, óleo de peixe, de soja e de girassol), totalizando oito tratamentos com seis repetições de 10 aves cada. As rações experimentais foram fornecidas de zero a quatro dias de idade. O desempenho zootécnico foi avaliado ao alojamento e aos quatro, sete e 21 dias de idade. Nestas mesmas datas, foram sacrificadas duas aves por unidade experimental para biometria do intestino e histomorfometria da mucosa do intestino. A adição de diferentes fontes de gordura e a suplementação de glicina e taurina às dietas de transição não influenciaram o desempenho produtivo de um a 21 dias. A suplementação das dietas com glicina e taurina alterou a morfologia da mucosa intestinal, principalmente do duodeno, resultando em maior comprimento do vilo e relação vilo:cripta. Entretanto, parte dos efeitos positivos depende do tipo de óleo adicionado, mostrando que dietas pós-eclosão acrescidas de fontes de lipídios podem ser benéficas no desenvolvimento da capacidade funcional do intestino de frangos de corte.(AU)

The aim of this study was to assess post-hatch diets supplemented with different sources of unsaturated fat and added or not with taurine and glycine on the productive performance, biometry and morphology of small intestine of chicks from 1 to 21 days of age. Four hundred and eighty (480) one day old male broiler Cobb chicks were used. The experimental design was completely randomized in a factorial 2 x 4, with and without supplemental taurine and glycine and 4 diets (control, fish, soy and sunflower oil), totaling six treatments with six repetitions of 10 birds each. The experimental diets were supplied from 0 to 4 days old. The performance was evaluated in housing and 4, 7 and 21 days of age. On these same dates, 2 birds per experimental unit were sacrificed for gut biometrics and histomorphometry of intestinal mucosa. The addition of different sources of fat, glycine and taurine supplementation on transition diets did not influence productive performance from 1 to 21 days. Supplementation of diets with glycine and taurine altered the morphology of the intestinal mucosa, mainly of the duodenum, resulting in greater length of villi and villi: crypt ratio. However, the positive effects depend on the type of oil added, showing that post-hatch diets increased with lipid sources may be beneficial in the development of the functional capacity of the intestine of broilers.(AU)

Ethnobotany, chemical constituents and biological activities of the flowers of Hydnora abyssinica A.Br. (Hydnoraceae).

Hydnora abyssinica A.Br. (Hydnoraceae), a holoparasitic herb, is for the first time recorded for Abyan governorate of South Yemen. Flowers of this species were studied for their ethnobotanical, biological and chemical properties for the first time. In South Yemen, they are traditionally used as wild food and to cure stomach diseases, gastric ulcer and cancer. Phytochemical analysis of the extracts showed the presence of terpenes, tannins, phenols, and flavonoids. The volatile components of the air-dried powdered flowers were identified using a static headspace GC/MS analysis as acetic acid, ethyl acetate, sabinene, α-terpinene, (+)-D-limonene and γ-terpinene. These volatile compounds that characterize the odor and taste of the flowers were detected for the first time in a species of the family Hydnoraceae. The flowers were extracted by n-hexane, dichlormethane, ethyl acetate, ethanol, methanol and water. With exception of the water extract all extracts demonstrated activities against Gram-positive bacteria as well as remarkable radical scavenging activities in DPPH assay. Ethyl acetate, methanol and water extracts exhibited good antifungal activities. The cytotoxic activity of the extracts against FL cells, measured in neutral red assay, was only weak (IC50 > 500 µg/mL). The results justify the traditional use of the flowers of Hydnora abyssinica in South Yemen.

Repellency of the Components of the Essential Oil, Citronella, to Triatoma rubida, Triatoma protracta, and Triatoma recurva (Hemiptera: Reduviidae: Triatominae).

The kissing bugs--Triatoma rubida (Uhler), Triatoma protracta (Uhler), and Triatoma recurva (Stal)--are common hematophagous bugs in southeastern Arizona and responsible for severe allergic reactions in some individuals who are bitten. They also possess the potential to transmit the blood parasite, Trypanosoma cruzi. We previously found the essential oil, citronella, to be an excellent deterrent of feeding of T. rubida on a restrained mouse. In this work, we tested major components--alcohols, aldehydes, and monoterpenes--of citronella oil for repellency against the three common triatome species endemic in southern Arizona. The following citronella oil components--geraniol, citronellol, limonene, and citronellal--in different concentrations and combinations were tested. All components of citronella oil demonstrated some inhibition of feeding, ranging from very weak inhibition (limonene) to significant inhibition (geraniol and citronellol). A mixture of geraniol and citronellol was found to be repellant at concentrations of .165 and .165 vol%, respectively, for all three triatome species. Citronellal and limonene had no significant repellent activity. The repellent activity of citronella oil appears to be acting through direct contact with the bugs rather than diffusion of vapors.

[Retrospective study about 73 consecutive patients treated by direct oral anticoagulant and admitted to an emergency room]. / Étude rétrospective concernant 73 patients traités par un anticoagulant oral direct admis consécutivement dans un service d'urgence.

INTRODUCTION: Direct oral anticoagulants are a recent alternative to vitamin K antagonists but there is a lack of data regarding patients receiving these new types of treatment. The aim of the study was to identify and describe patients receiving direct oral anticoagulants admitted to an emergency unit. METHODS: All the patients taking direct oral anticoagulants, admitted to the emergency room of the Clermont-Ferrand Hospital from January to August 2013, were included in this retrospective and descriptive study. RESULTS: Among the 73 patients included, 47.9% were treated with dabigatran and 52.1% with rivaroxaban. The indication was stroke prevention in 62 patients with atrial fibrillation whose average CHADS2 score was 2.6 [2.3-3](IC95%). The average age was 76.4 years [73.7-79.1](IC95%). Twenty-nine patients (39.7%) had at least one drug association known for increasing the risk of bleeding. Average scores for bleeding risk were: HAS-BLED 3.1 [2.9-3.3](IC95%) and Beyth 1.5 [1.3-1.6](IC95%). Bleeding patients included a higher percentage of men (68.8 vs. 38.2%, P=0.032). Creatinine clearance was lower in patients with major bleeding (45.2% vs. 68.8 mL/min, P=0.002). The Beyth score was highest in both sub-groups. CONCLUSION: In our study, we have found that the bleeding risk factors were: male gender, a high Beyth score, and a lowered creatinine clearance. Overall, patients treated with direct oral anticoagulants admitted to the emergency room were old with many co-morbidities, especially cardiovascular conditions; polymedication was frequent.

Effect of summer forage species grazed during finishing on animal performance, carcass quality, and meat quality.

Angus-cross steers (n = 60) were used to assess the effect of forage species [alfalfa (AL; Medicago sativa L.), bermudagrass (BG; Cynodon dactylon), chicory (CH; Cichorium intybus L.), cowpea (CO; Vigna unguiculata L.), and pearl millet (PM; Pennisetum glaucum (L. R Br.)] in replicated 2-ha paddocks for finishing on cattle performance, carcass quality, and meat quality in a 2-yr study. Steers were blocked by BW and assigned randomly to finishing-forage treatments before the start of the experiment. Steers grazing AL and CH had greater (P < 0.05) ADG than those grazing for BG, CO, and PM, whereas AL produced more (P < 0.05) gain/ha than CH, CO, and PM. Days steers spent grazing were longest (P < 0.05) for PM and shortest (P < 0.05) for CO. Steers grazing BG and CO produced heavier (P < 0.05) HCW than steers grazing BG and PM. Dressing percentage was greatest (P < 0.05) in steers grazing CO, and grazing AL resulted in greater (P < 0.05) dressing percentages than grazing BG, CH, and PM. Grazing AL and CH produced carcasses with more (P < 0.05) fat at the 12th rib than steers grazing warm-season grasses (BG and PM). Marbling scores tended to be greater (P = 0.06) for CO, but carcasses from steers grazing CO received greater (P < 0.05) quality grades than AL and CH. Trans-11 vaccenic (C18:1 trans-11; TVA) acid concentration in the LM was greater (P < 0.05) for BG than CH, CO, and AL. Conjugated linoleic acid, cis-9 trans-11 isomer, concentration was greatest (P < 0.05) for BG and PM than AL, CH, and CO. Grazing CH and PM increased (P < 0.05) the ratio of omega-6 to omega-3 fatty acids in the LM compared with AL, BG, and CO. Grazing legumes (AL and CO) resulted in lower (P < 0.05) Warner-Bratzler shear force values than other forage species. Consumers rated steaks from steers finished on AL and CO pastures greatest (P < 0.05) and steaks from steers finished on BG and CH least (P < 0.05) for overall palatability. Consumer preference was greatest (P < 0.05) for steaks from steers finished on AL and least (P < 0.05) for steaks from steers finished on BG and CH. Finishing steers on AL and CH during summer increased steer performance (> 1 kg/d). Finishing on legumes (AL and CO) increased dressing percentage, reduced Warner-Bratzler shear force values, and increased consumers preference, whereas finishing on grasses (BG and PM) enhanced anticarcinogenic fatty acid concentrations.

Repellency of DEET, picaridin, and three essential oils to Triatoma rubida (Hemiptera: Reduviidae: Triatominae).

The kissing bug, Triatoma rubida (Uhler) is a common hematophagous bug in Tucson, AZ, and is responsible for causing severe allergic reactions in some bitten individuals. DEET, picaridin, tea tree oil, peppermint oil, and citronella oil were tested for repellency to T. rubida and its ability to probe and feed on a small restrained rat. No long range repellency was observed with any of the test materials. The lowest repellent concentrations observed were: 10% DEET, 7% picaridin; 30% tea tree oil, 3.3% peppermint oil, and 0.165% citronella oil. Only citronella oil was able to stop all probing and feeding by T. rubida. Citronella oil appears to be a promising potential repellent to prevent sleeping people from being bitten by kissing bugs.

The Yin and Yang of pain: variability in formalin test nociception and morphine analgesia produced by the Yin Yang 1 transcription factor gene.

We recently observed a reliable phenotypic difference in the inflammatory pain sensitivity of a congenic mouse strain compared to its background strain. By constructing and testing subcongenic strains combined with gene-expression assays, we provide evidence for the candidacy of the Yy1 gene - encoding the ubiquitously expressed and multifunctional Yin Yang 1 transcription factor - as responsible. To confirm this hypothesis, we used a Cre/lox strategy to produce mutant mice in which Yy1 expression was ablated in Nav 1.8-positive neurons of the dorsal root ganglion. These mutants also displayed reduced inflammatory pain sensitivity on the formalin test. Further testing of pain-related phenotypes in these mutants revealed robustly increased sensitivity to systemic and spinal (but not supraspinal) morphine analgesia, and greatly increased endogenous (swim stress-induced) opioid analgesia. None of the known biological roles of Yin Yang 1 were suggestive of such a phenotype, and thus a novel player in pain modulatory systems has been identified.

Development of a subcutaneous formulation for trastuzumab - nonclinical and clinical bridging approach to the approved intravenous dosing regimen.

A subcutaneous (SC) formulation has been developed for the humanized monoclonal antibody (mAb) trastuzumab as an alternative to established intravenous (IV) infusion. The ready-to-use liquid SC formulation is injected as a fixed dose in approximately 5 min, which is expected to increase patient's convenience, reduce pharmacy preparation time, and administration costs overall.The trastuzumab dose as well as the dose of recombinant human hyaluronidase (rHuPH20), an enzyme that enables SC administration of volumes larger than 2 mL, was selected based on nonclinical xenograft, pharmacology, and pharmacokinetics mouse and minipig studies.The basic assumption for bridging from the IV to the SC regimen was that comparable trastuzumab serum trough concentrations would result in comparable efficacy. This hypothesis is confirmed by the results from the Phase 3 study in the neo-adjuvant/adjuvant setting. The safety profiles of the trastuzumab SC and IV formulations are comparable and consistent with the known safety profile of trastuzumab.

Safety and tolerance of Bacteroides xylanisolvens DSM 23964 in healthy adults.

We recently presented the strain Bacteroides xylanisolvens DSM 23964 to be safe for use in food. In order to confirm the tolerance of healthy humans to a regular oral intake of the strain B. xylanisolvens DSM 23964, we here report on the safety data of two successive human studies: a randomised and double-blind parallel group-controlled pilot study with 41 volunteers receiving a daily dose of a pasteurised fermented milk product containing up to 8.5×1011B. xylanisolvens DSM 23964 cells for 3 weeks, and a randomised and placebo-controlled double-blind major study with 140 volunteers receiving the same product but spray-dried and containing up to 1012 cells for 6 weeks. In both studies no persistent side effects of any kind were reported. The measured haematological parameters, and the serum concentrations of immunoglobulin and of inflammatory markers (IL-6, CRP, IFN-γ) were unaffected by the supplementation in both studies. A small decrease in the phagocytic activity of granulocytes and a small increase of TNF-α detected in the pilot study were both invalidated by the major study. This study further revealed that the supplementation induced no modification in natural killer cell activity and in liver enzyme values (gamma-glutamyl-transferase, glutamate-oxalacetate transaminase, glutamate-pyruvate transaminase). Our results definitively demonstrate that the pasteurised B. xylanisolvens DSM 23964 strain is safe and well tolerated by healthy human individuals.

Free Fatty acids and delayed cerebral ischemia after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The purpose of this study was to understand factors related to increases in serum free fatty acid (FFA) levels and association with delayed cerebral ischemia (DCI) after subarachnoid hemorrhage. METHODS: We performed serial measurement of systemic oxygen consumption by indirect calorimetry and FFA levels by liquid chromatography/mass spectrometry in the first 14 days after ictus in 50 consecutive patients with subarachnoid hemorrhage. Multivariable generalized estimating equation models identified associations with FFA levels in the first 14 days after SAH and Cox proportional hazards model used to identified associations with time to DCI. RESULTS: There were 187 measurements in 50 patients with subarachnoid hemorrhage (mean age, 56±14 years old; 66% women) with a median Hunt-Hess score of 3. Adjusting for Hunt-Hess grade and daily caloric intake, n-6 and n-3 FFA levels were both associated with oxygen consumption and the modified Fisher score. Fourteen (28%) patients developed DCI on median postbleed Day 7. The modified Fisher score (P=0.01), mean n-6:n-3 FFA ratio (P=0.02), and mean oxygen consumption level (P=0.04) were higher in patients who developed DCI. In a Cox proportional hazards model, the mean n-6:n-3 FFA ratio (P<0.001), younger age (P=0.05), and modified Fisher scale (P=0.004) were associated with time to DCI. CONCLUSIONS: Injury severity and oxygen consumption hypermetabolism are associated with higher n-FFA levels and an increased n-6:n-3 FFA ratio is associated with DCI. This may indicate a role for interventions that modulate both oxygen consumption and FFA levels to reduce the occurrence of DCI.

Metabolic benefits of surface counter warming during therapeutic temperature modulation.

OBJECTIVE: To determine the impact of counter warming (CW) with an air circulating blanket on shivering and metabolic profile during therapeutic temperature modulation (TTM). DESIGN: A prospective observational study. SETTING: An 18-bed neurologic intensive care unit. PATIENTS: Fifty mechanically ventilated patients with brain injury undergoing TTM with automated surface and intravascular devices. INTERVENTIONS: Fifty indirect calorimetry (IDC) measurements with and without CW during TTM. MEASUREMENTS AND MAIN RESULTS: IDC was continuously performed for 10-15 minutes at baseline with CW (phase I), off CW (phase II), and again after the return of CW (phase III). Shivering severity during each phase was scored on a scale of 0-3 using the Bedside Shivering Assessment Scale (BSAS). Resting energy expenditure (REE), oxygen consumption, and carbon dioxide production were determined by IDC; 56% were women, with mean age 61 +/- 15 years. At the time of IDC, 72% of patients had signs of shivering (BSAS >0). All measures of basal metabolism increased after removal of the air warming blanket (from phases I and II); REE increased by 27% and oxygen consumption by 29% (both p < 0.002). A one-point increase in baseline BSAS was noted in 55% (n = 23/42) of patients from phase I to phase II. In a multivariate analysis, sedative use (p = 0.03), baseline moderate to severe shivering (p = 0.04), and lower serum magnesium levels (p = 0.01) were associated with greater increases in REE between phase I and phase II of CW. Phase III of CW was associated with a reversal in the increases in all metabolic variables. CONCLUSIONS: Surface CW provides beneficial control of shivering and improves the metabolic profile during TTM.

Prospective, randomized, double-blind, multi-center, Phase III clinical study on transarterial chemoembolization (TACE) combined with Sorafenib versus TACE plus placebo in patients with hepatocellular cancer before liver transplantation - HeiLivCa [ISRCTN24081794].

BACKGROUND: Disease progression of hepatocellular cancer (HCC) in patients eligible for liver transplantation (LTx) occurs in up to 50% of patients, resulting in withdrawal from the LTx waiting list. Transarterial chemoembolization (TACE) is used as bridging therapy with highly variable response rates. The oral multikinase inhibitor sorafenib significantly increases overall survival and time-to-progression in patients with advanced hepatocellular cancer. DESIGN: The HeiLivCa study is a double-blinded, controlled, prospective, randomized multi-centre phase III trial. Patients in study arm A will be treated with transarterial chemoembolization plus sorafenib 400 mg bid. Patients in study arm B will be treated with transarterial chemoembolization plus placebo. A total of 208 patients with histologically confirmed hepatocellular carcinoma or HCC diagnosed according to EASL criteria will be enrolled. An interim patients' analysis will be performed after 60 events. Evaluation of time-to-progression as primary endpoint (TTP) will be performed at 120 events. Secondary endpoints are number of patients reaching LTx, disease control rates, OS, progression free survival, quality of live, toxicity and safety. DISCUSSION: As TACE is the most widely used primary treatment of HCC before LTx and sorafenib is the only proven effective systemic treatment for advanced HCC there is a strong rational to combine both treatment modalities. This study is designed to reveal potential superiority of the combined TACE plus sorafenib treatment over TACE alone and explore a new neo-adjuvant treatment concept in HCC before LTx.

Innovative process scheme for removal of organic matter, phosphorus and nitrogen from pig manure.

Disposal of pig manure often requires treatment with respect to environmental legislations. In this study different processes for reduction of the organic matter (anaerobic digestion, effluent separation by decanter centrifugation, membrane microfiltration, post-digestion in upflow anaerobic sludge blanket (UASB) reactor, partial oxidation), nitrogen (oxygen-limited autotrophic nitrification-denitrification, OLAND) and phosphorus (phosphorus removal by precipitation as struvite, PRS) from pig manure were tested. Results obtained showed that microfiltration was unsuitable for pig manure treatment. PRS treated effluent was negatively affecting the further processing of the pig manure in UASB, and was therefore not included in the final process flow scheme. In a final scheme (PIGMAN concept) combination of the following successive process steps was used: thermophilic anaerobic digestion with sequential separation by decanter centrifuge, post-digestion in UASB reactor, partial oxidation and finally OLAND process. This combination resulted in reduction of the total organic, nitrogen and phosphorus contents by 96%, 88%, and 81%, respectively.

Believing in order to understand: Hahnemann's hierarchisation of values.

During the last 200 years, the social, scientific, and religious framework in which homeopathy is taught and practiced has changed tremendously. Various different forms of homeopathy have been advocated. To avoid being misled by the prevailing pluralism as a standard of reference for assessing new concepts, Hahnemann's original ideas and attitude toward medicine, philosophy, and ethics are discussed. Hahnemann's hierarchisation of values appears to consist primarily in striving for a world view in which he could conceive of himself as a spiritual and moral being, secondly in a yearning for scientific advancement, and thirdly in his need to earn a living. Homeopaths are challenged to match this hierarchisation and be aware that homeopathy comprises dimensions other than just science and economics.

Creatine improves health and survival of mice.

The supplementation of creatine (Cr) has a marked neuroprotective effect in mouse models of neurodegenerative diseases. This has been assigned to the known bioenergetic, anti-apoptotic, anti-excitotoxic, and anti-oxidant properties of Cr. As aging and neurodegeneration share pathophysiological pathways, we investigated the effect of oral Cr supplementation on aging in 162 aged C57Bl/6J mice. Outcome variables included "healthy" life span, neurobehavioral phenotyping, as well as morphology, biochemistry, and expression profiling from brain. The median healthy life span of Cr-fed mice was 9% higher than in control mice, and they performed significantly better in neurobehavioral tests. In brains of Cr-treated mice, there was a trend towards a reduction of reactive oxygen species and significantly lower accumulation of the "aging pigment" lipofuscin. Expression profiling showed an upregulation of genes implicated in neuronal growth, neuroprotection, and learning. These data show that Cr improves health and longevity in mice. Cr may be a promising food supplement to promote healthy human aging.

Arachidonic acid as a retrograde signal controlling growth and dynamics of retinotectal arbors.

In the developing visual system, correlated presynaptic activity between neighboring retinal ganglion cells (RGC) stabilizes retinotopic synapses via a postsynaptic NMDAR (N-methyl-D-aspartate receptor)-dependent mechanism. Blocking NMDARs makes individual axonal arbors larger, which underlies an unsharpened map, and also increases branch turnover, as if a stabilizing factor from the postsynaptic partner is no longer released. Arachidonic acid (AA), a candidate retrograde stabilizing factor, is released by cytoplasmic phospholipase A2 (cPLA2) after Ca(2+) entry through activated NMDARs, and can activate presynaptic protein kinase C to phosphorylate various substrates such as GAP43 to regulate cytoskeletal dynamics. To test the role of cPLA2 in the retinotectal system of developing zebrafish, we first used PED6, a fluorescent reporter of cPLA2 activity, to show that 1-3 min of strobe flashes activated tectal cPLA2 by an NMDAR-dependent mechanism. Second, we imaged the dynamic growth of retinal arbors during both local inhibition of tectal cPLA2 by a pharmacological inhibitor, arachidonic tri-fluoromethylketone, and its suppression by antisense oligonucleotides (both injected intraventricularly). Both methods produced larger arbors and faster branch dynamics as occurs with blocking NMDARs. In contrast, intraocular suppression of retinal cPLA2 with large doses of antisense oligos produced none of the effects of tectal cPLA2 inhibition. Finally, if AA is the retrograde messenger, the application of exogenous AA to the tectum should reverse the increased branch turnover caused by blocking either NMDARs or cPLA2. In both cases, intraventricular injection of AA stabilized the overall branch dynamics, bringing rates down below the normal values. The results suggest that AA generated postsynaptically by cPLA2 downstream of Ca(2+) entry through NMDARs acts as a retrograde signal to regulate the dynamic growth of retinal arbors.