Search for Dark Matter Axions with CAST-CAPP.

The CAST-CAPP axion haloscope, operating at CERN inside the CAST dipole magnet, has searched for axions in the 19.74 µeV to 22.47 µeV mass range. The detection concept follows the Sikivie haloscope principle, where Dark Matter axions convert into photons within a resonator immersed in a magnetic field. The CAST-CAPP resonator is an array of four individual rectangular cavities inserted in a strong dipole magnet, phase-matched to maximize the detection sensitivity. Here we report on the data acquired for 4124 h from 2019 to 2021. Each cavity is equipped with a fast frequency tuning mechanism of 10 MHz/ min between 4.774 GHz and 5.434 GHz. In the present work, we exclude axion-photon couplings for virialized galactic axions down to gaγγ = 8 × 10-14 GeV-1 at the 90% confidence level. The here implemented phase-matching technique also allows for future large-scale upgrades.

Pulsed blue light, saliva and curcumin significantly inactivate human coronavirus.

In a recent study, we showed that pulsed blue light (PBL) inactivates as much as 52.3% of human beta coronavirus HCoV-OC43, a surrogate of SARS-CoV-2, and one of the major strains of viruses responsible for the annual epidemic of the common cold. Since curcumin and saliva are similarly antiviral and curcumin acts as blue light photosensitizer, we used Qubit fluorometry and WarmStart RT-LAMP assays to study the effect of combining 405 nm, 410 nm, 425 nm or 450 nm wavelengths of PBL with curcumin, saliva or a combination of curcumin and saliva against human beta coronavirus HCoV-OC43. The results showed that PBL, curcumin and saliva independently and collectively inactivate HCoV-OC43. Without saliva or curcumin supplementation 21.6 J/cm2 PBL reduced HCoV-OC43 RNA concentration a maximum of 32.8% (log10 = 2.13). Saliva supplementation alone inactivated the virus, reducing its RNA concentration by 61% (log10 = 2.23); with irradiation the reduction was as much as 79.1%. Curcumin supplementation alone decreased viral RNA 71.1%, and a maximum of 87.8% with irradiation. The combination of saliva and curcumin reduced viral RNA to 83.1% and decreased the RNA up to 90.2% with irradiation. The reduced levels could not be detected with qPCR. These findings show that PBL in the range of 405 nm to 450 nm wavelength is antiviral against human coronavirus HCoV-OC43, a surrogate of the COVID-19 virus. Further, it shows that with curcumin as a photosensitizer, it is possible to photodynamically inactivate the virus beyond qPCR detectable level using PBL. Since HCoV-OC43 is of the same beta coronavirus family as SARS-CoV-2, has the same genomic size, and is often used as its surrogate, these findings heighten the prospect of similarly inactivating novel coronavirus SARS-CoV-2, the virus responsible for COVID-19 pandemic.

A novel, double intra-carotid cannulation technique to study the effect of central nutrient sensing on glucose metabolism in the rat.

BACKGROUND: The hypothalamus plays a key role in central nutrient sensing and glucose homeostasis. Due to its position next to the third ventricle, intracerebroventricular (ICV) injections or osmotic minipumps are widely applied techniques in studying effects of hormones and other molecules on the hypothalamus and glucose metabolism. NEW METHODS: The intracarotid catheter technique in which a catheter is placed in the carotid artery, pointing towards the brain, provides a physiological route to centrally infuse blood-borne molecules in an undisturbed animal. To measure effects of central interventions on peripheral glucose metabolism, endogenous glucose production (EGP) and insulin sensitivity can be measured using a stable isotope technique. To combine both techniques, it is necessary to combine different catheters. We here describe a novel cannulation technique for the carotid artery, enabling stress-free infusions towards the brain and blood sampling from the carotid artery concomitantly, and infuse a stable isotope via the jugular vein. RESULTS: We showed accurate EGP measurements when intracarotically infusing saline towards the brain. The stress-hormone corticosterone, as well as energy expenditure, did not alter upon central infusion. COMPARISON EXISTING METHOD(S): ICV infusions bypass the blood-brain-barrier (BBB) and are thus a less physiological approach when studying central effects of blood-borne factors. Furthermore, ICV injections can elicit a stress response which can interfere with outcomes of glucose metabolism. We described a stress-free, physiological method to study effects of central infusions on peripheral parameters. CONCLUSIONS: This technique provides new opportunities for studying central effects of, for instance, hormones and nutrients, on glucose metabolism.

High fat induces acute and chronic inflammation in the hypothalamus: effect of high-fat diet, palmitate and TNF-α on appetite-regulating NPY neurons.

BACKGROUND: Consumption of dietary fat is one of the key factors leading to obesity. High-fat diet (HFD)-induced obesity is characterized by induction of inflammation in the hypothalamus; however, the temporal regulation of proinflammatory markers and their impact on hypothalamic appetite-regulating neuropeptide Y/agouti-related peptide (NPY/AgRP) neurons remains undefined. METHODS: Mice were injected with an acute lipid infusion for 24 h or fed a HFD over 8-20 weeks. Characterized mouse NPY/AgRP hypothalamic cell lines were used for in vitro experimentation. Immunohistochemistry in brain slices or quantitative real-time PCR in cell lines, was performed to determine changes in the expression of key inflammatory markers and neuropeptides. RESULTS: Hypothalamic inflammation, indicated by tumor necrosis factor (TNF)-α expression and astrocytosis in the arcuate nucleus, was evident following acute lipid infusion. HFD for 8 weeks suppressed TNF-α, while significantly increasing heat-shock protein 70 and ciliary neurotrophic factor, both neuroprotective components. HFD for 20 weeks induced TNF-α expression in NPY/AgRP neurons, suggesting a detrimental temporal regulatory mechanism. Using NPY/AgRP hypothalamic cell lines, we found that palmitate provoked a mixed inflammatory response on a panel of inflammatory and endoplasmic reticulum (ER) stress genes, whereas TNF-α significantly upregulated IκBα, nuclear factor (NF)-κB and interleukin-6 mRNA levels. Palmitate and TNF-α exposure predominantly induced NPY mRNA levels. Utilizing an I kappa B kinase ß (IKKß) inhibitor, we demonstrated that these effects potentially occur via the inflammatory IKKß/NF-κB pathway. CONCLUSIONS: These findings indicate that acute lipid and chronic HFD feeding in vivo, as well as acute palmitate and TNF-α exposure in vitro, induce markers of inflammation or ER stress in the hypothalamic appetite-stimulating NPY/AgRP neurons over time, which may contribute to a dramatic alteration in NPY/AgRP content or expression. Acute and chronic HFD feeding in vivo temporally regulates arcuate TNF-α expression with reactive astrocytosis, which suggests a time-dependent neurotrophic or neurotoxic role of lipids.

Characterization and typification of small ruminant farms providing fuelbreak grazing services for wildfire prevention in Andalusia (Spain).

Several wildfire prevention programs in Spain are using grazing livestock to maintain fuelbreaks with low levels of biomass. Even though shepherds are remunerated for these services, many of their farms are hardly viable in the current socio-economic context. By analyzing 54 small ruminant farms participating in the Grazed Fuelbreak Network in Andalusia (southern Spain), this research aimed to identify the main types and characteristics of such farms and, considering the challenges they are facing, propose strategies to improve both their economic viability and their effectiveness in fuelbreak grazing. Based on data collected through a survey on key farm management aspects, a multivariate analysis was performed and four main types of farm were identified: two clusters of dairy goat farms and two composed mostly of meat-purpose sheep farms. Farms in all clusters could benefit from improvements in the feeding and reproductive management of livestock, either to enhance their productivity or to make better use of the pasture resources available. Dairy goat farms remain more dependent on external animal feed to ensure a better lactation, therefore they should either diminish their workforce costs per animal or sell transformed products directly to consumers to improve their economic viability. Best fuelbreak grazing results were related to larger flocks combining sheep and goats, lower ratios of fuelbreak surface area per animal, and longer (year-long) grazing periods on fuelbreaks. Therefore, such farm features and adjusted fuelbreak assignments should be favored in wildfire prevention programs using grazing services.

TREX-DM: a low-background Micromegas-based TPC for low-mass WIMP detection.

If Dark Matter is made of Weakly Interacting Massive Particles (WIMPs) with masses below [Formula: see text] GeV, the corresponding nuclear recoils in mainstream WIMP experiments are of energies too close, or below, the experimental threshold. Gas Time Projection Chambers (TPCs) can be operated with a variety of target elements, offer good tracking capabilities and, on account of the amplification in gas, very low thresholds are achievable. Recent advances in electronics and in novel radiopure TPC readouts, especially micro-mesh gas structure (Micromegas), are improving the scalability and low-background prospects of gaseous TPCs. Here we present TREX-DM, a prototype to test the concept of a Micromegas-based TPC to search for low-mass WIMPs. The detector is designed to host an active mass of [Formula: see text] kg of Ar at 10 bar, or alternatively [Formula: see text] kg of Ne at 10 bar, with an energy threshold below 0.4 keVee, and is fully built with radiopure materials. We will describe the detector in detail, the results from the commissioning phase on surface, as well as a preliminary background model. The anticipated sensitivity of this technique may go beyond current experimental limits for WIMPs of masses of 2-8 GeV.

Dietary triglycerides act on mesolimbic structures to regulate the rewarding and motivational aspects of feeding.

Circulating triglycerides (TGs) normally increase after a meal but are altered in pathophysiological conditions, such as obesity. Although TG metabolism in the brain remains poorly understood, several brain structures express enzymes that process TG-enriched particles, including mesolimbic structures. For this reason, and because consumption of high-fat diet alters dopamine signaling, we tested the hypothesis that TG might directly target mesolimbic reward circuits to control reward-seeking behaviors. We found that the delivery of small amounts of TG to the brain through the carotid artery rapidly reduced both spontaneous and amphetamine-induced locomotion, abolished preference for palatable food and reduced the motivation to engage in food-seeking behavior. Conversely, targeted disruption of the TG-hydrolyzing enzyme lipoprotein lipase specifically in the nucleus accumbens increased palatable food preference and food-seeking behavior. Finally, prolonged TG perfusion resulted in a return to normal palatable food preference despite continued locomotor suppression, suggesting that adaptive mechanisms occur. These findings reveal new mechanisms by which dietary fat may alter mesolimbic circuit function and reward seeking.

Central orchestration of peripheral nutrient partitioning and substrate utilization: implications for the metabolic syndrome.

Energy homoeostasis is maintained through a complex interplay of nutrient intake and energy expenditure. The central nervous system is an essential component of this regulation, as it integrates circulating signals of hunger and satiety to develop adaptive responses at the behavioural and metabolic levels, while the hypothalamus is regarded as a particularly crucial structure in the brain in terms of energy homoeostasis. The arcuate nucleus (ARC) of the hypothalamus contains at least two intermingled neuronal populations: the neurons that produce neuropeptide Y (NPY); and the Agouti-related protein (AgRP) produced by AgRP/NPY neurons situated below the third ventricle in close proximity to proopiomelanocortin (POMC)-producing neurons. POMC neurons exert their catabolic and anorectic actions by releasing α-melanocyte-stimulating hormone (α-MSH), while AgRP neurons oppose this action by exerting tonic GABAergic inhibition of POMC neurons and releasing the melanocortin receptor inverse agonist AgRP. The release of neurotransmitters and neuropeptides by second-order AgRP neurons appears to take place on a multiple time scale, thereby allowing neuromodulation of preganglionic neuronal activity and subsequent control of nutrient partitioning - in other words, the coordinated regulation of conversion, storage and utilization of carbohydrates vs. lipids. This suggests that the function of AgRP neurons extends beyond the strict regulation of feeding to the regulation of efferent organ activity, such that AgRP neurons may now be viewed as an important bridge between central detection of nutrient availability and peripheral nutrient partitioning, thus providing a mechanistic link between obesity and obesity-related disorders.

Evaluating mountain goat dairy systems for conversion to the organic model, using a multicriteria method.

Organic farming conserves natural resources, promotes biodiversity, guarantees animal welfare and obtains healthy products from raw materials through natural processes. In order to evaluate possibilities of increasing organic animal production, this study proposes a farm-scale multicriteria method for assessing the conversion of dairy goat systems to the organic model. In addition, a case study in the Northern Sierra of Seville, southern Spain, is analysed. A consensus of expert opinions and a field survey are used to validate a list of potential indicators and issues for assessing the conversion, which consider not only the European Community regulations for organic livestock farming, but also agroecological principles. As a result, the method includes 56 variables integrated in nine indicators: Nutritional management, Sustainable pasture management, Soil fertility and contamination, Weed and pest control, Disease prevention, Breeds and reproduction, Animal welfare, Food safety and Marketing and management. The nine indicators are finally integrated in a global index named OLPI (Organic Livestock Proximity Index). Application of the method to a case study with 24 goat farms reveals an OLPI value of 46.5% for dairy goat farms located in mountain areas of southern Spain. The aspects that differ most from the agroecological model include soil management, animal nutrition and product marketing. Results of the case study indicate that the proposed method is easy to implement and is useful for quantifying the approximation of conventional farms to an organic model.

Use of intraoperative monitoring of somatosensory evoked potentials to prevent ischaemic stroke after surgical exclusion of middle cerebral artery aneurysms.

OBJECTIVE: The aim of this study was to assess the value of monitoring somatosensory evoked potentials (SEP) in the prevention of ischaemic stroke occurring during surgical exclusion of middle cerebral artery aneurysms. METHODS: SEP monitoring was performed during the surgical exclusion of 131 aneurysms in 122 patients. All SEP variations over 30% were notified to the surgeon and those over 50% were considered as highly significant. If this happened, and in concert with the conduct of the operation, a return to the basal level was systematically sought. RESULTS: Post-operative ischemic stroke was observed after 15 (11.4%) operations, leading to a permanent neurological deficit in 12 (9.2%). During nine (6.9%) operations there was a highly significant SEP change that persisted, or was only partially reversed, after corrective procedure. Nine of these patients had a post-operative ischaemic stroke. In 25 (19%), operations there was a highly significant SEP change followed by complete recovery. Of these 25 patients, 2 suffered a post-operative ischemic stroke. Following 49 operations (37.4%) with less significant SEP modifications, 4 patients suffered a post-operative stroke (8%). A stroke did not occur in the 48 (36.6%) operations during which there was not a variation in SEP. The strokes were related to temporary clipping in 9 patients to definitive clipping in 3 to sylvian fissure opening in 1 to brain retraction in and to dissection of the aneurysm in 1 (1 case). CONCLUSION: Changes in the SEP correlated well with the occurrence of post-operative stroke. This early detection of ischemia directs attention to the need for measures such as withdrawal of temporary clipping or identification of another factor (e.g. release of brain retraction or repositioning of an occlusive clip) so that the risk of post-operative is reduced.

Crop load affects maximum daily trunk shrinkage of plum trees.

We studied the effects of low fruit load (3-4 fruits cm(-2) of trunk cross-sectional area (TCSA), and high fruit load (6-7 fruits cm(-2) TCSA) on maximum daily trunk shrinkage (MDS) and trunk growth rates (TGR) over two seasons in plum (Prunus salicina Lindell) trees receiving full irrigation or deficit irrigation. Seasonal changes in MDS and TGR were compared with those in midday stem water potential (Psi(s)) and leaf stomatal conductance (g (s)). Crop load increased g (s) in fully irrigated trees approaching harvest. Although crop load did not affect plant water status in either watering regime, there were considerable differences in both MDS and TGR as a function of crop load. Compared with low-cropping [corrected] trees, MDS was 34% higher and TGR was 48% lower in high-cropping [corrected] trees. The differential responses of MDS and Psi(s) to crop load were a consequence of a higher MDS for a given Psi(s) in the high-cropping trees compared with the low-cropping trees. There was a linear increase in MDS with crop load, with a slope of 15.2 microm MPa(-1) per unit increment of crop load. In the fully irrigated trees, day-to-day variations in MDS were related to evaporative demand; however, the slope of the relationship between MDS and evaporative demand increased with crop load, indicating that different reference equations must be used to adjust for tree crop load when using MDS to determine plant water status and irrigation requirements.

Usefulness of diurnal trunk shrinkage as a water stress indicator in plum trees.

We compared seasonal changes in maximum diurnal trunk shrinkage (MDS) with seasonal changes in midday stem water potential (Psi(s)) over three years in plum trees grown in differing drip-irrigated regimes. In well-irrigated trees, day-to-day variations in Psi(s) and MDS were related to evaporative demand. Reference equations were obtained to predict MDS and Psi(s) values for well-irrigated trees as functions of environmental conditions. A decrease in plant water status toward the end of the growing season occurred even in the well-irrigated trees, probably reflecting a reduced volume of soil wetted by the drip irrigation system. Thus, for the prediction of Psi(s), different reference equations are required for the fruit-growth and after-harvest phenological periods. A seasonal change in the relationship between MDS and Psi(s) was observed, which compensated for the decrease in plant water status such that well-irrigated trees had similar MDS values during both the fruit-growth and after-harvest periods. The influence of tree size on the relationship between MDS and Psi(s) was also investigated. For tree trunk diameters ranging between 8 and 13 cm, MDS increased 13% for each cm of increase in trunk diameter, as a result of the thicker phloem tissues of the larger trees. This finding may allow extrapolation of Psi(s) predictions based on empirical relationships with MDS to plum trees of different sizes.

[Origin and consequences of the hypodensity surrounding spontaneous intracerebral hemorrhage in the acute phase]. / Origine et conséquences de l'hypodensité entourant une hémorragie cérébrale spontanée à la phase aiguë

In the acute phase, spontaneous intracerebral hemorrhage is surrounded by hypodensity, the origin of which is controversial. Its clinical consequences are still under evaluation. Surrounding cerebral ischemia was suggested as its main etiology, but no experimental or clinical data currently supports this etiology. The hypodensity reflects the presence of cytotoxic and vasogenic edema secondary to prolonged contact between hemorrhage and adjacent brain tissue. This would mainly be due to local release of activated thrombin. However, other metabolites released from blood degradation products would also be involved. This edematous process is unique due to its early occurrence (as early as 2 hours), early maximum peak (24 hours), and regression over the next few days. In humans, no definitive proof exists that this edematous process of variable intensity is pathological. No specific treatment is currently available.

[The evolution of use of anti-Parkinson drugs in Spain]. / Evolución del consumo de fármacos antiparkinsonianos en España.

INTRODUCTION: In recent years new anti Parkinson drugs have been marketed and there has been controversy over the safety of some drugs. OBJECTIVE: To analyze the evolution of the consumption of anti Parkinson drugs and the effect of the newer drugs. PATIENTS AND METHODS: A study of the consumption of anti Parkinson drugs (1989 1998). Data were obtained from the ECOM database of the Ministry of Health and TEMPUS of the National Statistics Institute. The drugs were classified using the Anatomo Therapeutic Clinical Classification (ATC). Consumption was expressed in defined daily dosage (DDD) and the costs in euros. The drugs marketed since 1990 were classified as new drugs and the others as classical drugs. RESULTS: The total consumption of drugs increased from 1.92 DDD/1,000 inhabitants/day in 1989 to 3.64 DDD/1,000 inhabitants/day in 1998. The drugs showing the greatest increase were selegiline, pergolide and levodopa. The total pharmaceutical expenses tripled. There was a smaller increase in the consumption of new drugs (1.2% of the total in 1991 and 6.6% in 1998) than in their costs (6.7% of the total in 1991 and 38.8% in 1998). The cost per DDD of the new drugs increased five times (1989: 2.55 euros and 1998: 13.59 euros) and that of the classical drugs was similar (1989: 0.54 euros and 1998: 0.62 euros). CONCLUSIONS: The total consumption of anti Parkinson drugs has progressively increased. The consumption of selegiline has also increased in spite of controversy over its safety. The new drugs have a major economic effect.

Dysautonomia syndrome in the acute recovery phase after traumatic brain injury: relief with intrathecal Baclofen therapy.

In the initial phase of severe head injury, dysautonomic abnormalities are frequent. Within the framework of a prospective study, evaluating the efficacy of continuous intrathecal Baclofen therapy (CIBT) on hypertonia during the initial recovery phase of severe head injury, the authors report on the preliminary results of this treatment on paroxysmal dysautonomia about four patients. Continuous intrathecal Baclofen infusion was first delivered, for a test period, continuously for 6 days. If a relapse of dysautonomia occurred at the end of the test period, an implantation of a continuous intrathecal infusion pump delivering Baclofen was performed. Results were assessed with four continuous variables; duration (days), dose of Baclofen per day (microg/d), number of dysautonomic paroxysmal episodes per day, and initial recovery evaluated by a scale of the first initial stages of head injury coma recovery. For three patients: (1) the number of dysautonomic paroxysmal episodes per day and the doses of Baclofen during the follow-up period were correlated (p = 0.02, p < 0.001, p = 0.008, respectively, distribution-free test of Spearman), (2) during the test period and the relapse after the test period, the number of paroxysmal episodes and the Baclofen dose are correlated to p < 0.05, p = 0.03, p = 0.04, respectively (distribution-free test of Spearman). The second statistical test was used to prove that Baclofen doses and number of paroxysmal dysautonomic episodes are correlated independently of the duration of follow-up. The fourth patient improved with CIBT without any recurrence at the end of the treatment test period. For the four patients, recovery score increased during the overall follow-up. In the authors' experience CIBT is very efficient to control paroxysmal dysautonomia during the initial recovery phase in severe head injury, and seems to facilitate recovery.

[Postoperative morbidity and mortality after microsurgical exclusion of cerebral arteriovenous malformations. Current data and analysis of recent literature]. / Morbidité et mortalité du traitement chirurgical des malformations artério-veineuses cérébrales. Données actuelles et analyse de la littérature récente.

BACKGROUND AND PURPOSE: Microsurgical exclusion of a cerebral arteriovenous malformation (AVM) can compare favorably with radiosurgery. We sought to assess its rate of morbidity-mortality as it is presently reported in the literature, and to discuss some of its current and worthwhile indications. METHODS: Through Medline and additional searches by hand, we retrieved studies reporting the clinical and angiographic results after microsurgical excision of an AVM published between january 1990 and december 2000. RESULTS: a) Postoperative mortality was 3.3% (68/2 452 patients from 25 studies). Permanent postoperative morbidity was 8.6%. Morbidity was never absent varying from 1.5% to 18,7%. The morbidity-mortality rate increased with an increasing Spetzler-Martin's grade, and was related to the location of the AVM. A 4.6% morbidity (from 1.5% to 9.7%) and a zero mortality were reported after microsurgical removal of small lesions of less than 3 cm in diameter. b) Postoperative angiography confirmed a total excision of the AVM in 97% of the cases (1 050/1 076 patients over 11 series), varying from 91% to 100%. c) Permanent morbidity related to pre-surgical embolization varied from 4% to 8.9%. Results from multiple or combined treatment including microsurgery could not be summed up. CONCLUSIONS: A complete and definitive microsurgical excision of an AVM can be achieved with a high success rate and a low morbidity-mortality rate, according to sound indications and to the neurosurgeon's personal experience. The choice for a best treatment of an AVM is no longer limited to microsurgery; it is a team decision where the neurosurgeon plays a determining role.