Prolonged oral cannabinoid administration prevents neuroinflammation, lowers β-amyloid levels and improves cognitive performance in Tg APP 2576 mice

This is an Open Access article distributed under the terms of the Creative Commons Attribution License.-- et al.[Background]: Alzheimer's disease (AD) brain shows an ongoing inflammatory condition and non-steroidal anti-inflammatories diminish the risk of suffering the neurologic disease. Cannabinoids are neuroprotective and anti-inflammatory agents with therapeutic potential. [Methods]: We have studied the effects of prolonged oral administration of transgenic amyloid precursor protein (APP) mice with two pharmacologically different cannabinoids (WIN 55,212-2 and JWH-133, 0.2 mg/kg/day in the drinking water during 4 months) on inflammatory and cognitive parameters, and on 18F-fluoro-deoxyglucose (18FDG) uptake by positron emission tomography (PET). [Results]: Novel object recognition was significantly reduced in 11 month old Tg APP mice and 4 month administration of JWH was able to normalize this cognitive deficit, although WIN was ineffective. Wild type mice cognitive performance was unaltered by cannabinoid administration. Tg APP mice showed decreased 18FDG uptake in hippocampus and cortical regions, which was counteracted by oral JWH treatment. Hippocampal GFAP immunoreactivity and cortical protein expression was unaffected by genotype or treatment. In contrast, the density of Iba1 positive microglia was increased in Tg APP mice, and normalized following JWH chronic treatment. Both cannabinoids were effective at reducing the enhancement of COX-2 protein levels and TNF-α mRNA expression found in the AD model. Increased cortical β-amyloid (Aβ) levels were significantly reduced in the mouse model by both cannabinoids. Noteworthy both cannabinoids enhanced Aβ transport across choroid plexus cells in vitro. [Conclusions]: In summary we have shown that chronically administered cannabinoid showed marked beneficial effects concomitant with inflammation reduction and increased Aβ clearance.This work was supported by the Spanish Ministry of Science and Technology (SAF 2005-02845 to M.L.C). A.M.M-M. was recipient a fellowship from the Ministry of Education and Science.Peer Reviewe

X-ray emission from a liquid curtain jet when irradiated by femtosecond laser pulses

Laser-based sources of ionizing radiation have attracted considerable attention in the last years for their broad potential applications. However, the stability and robustness of such sources are still issues that need to be addressed. Aiming to solve such problems, we propose a source that uses a liquid jet—rather than a solid—as a target for the production of X-rays. Liquid jets offer always a clean surface for every laser shot which represent a clear advantage over solids. In this work, we present an experimental characterization of the X-ray emission of such targets, and study the efficiency of the process when two temporally delayed pulses are used. According to the obtained results, the X-ray yield is comparable with commonly used targets.Ministerio de Economía y Competitividad FIS2016- 81056-

Spatial Distribution of Temporalis Pressure Pain Sensitivity in Men with Episodic Cluster Headache

Background: Spatial changes in pressure sensitivity have been described in migraine and tension-type headaches. Our aim was to determine differences in the spatial distribution of pressure pain sensitivity of the temporalis muscle between cluster headache (CH) patients and headache-free controls. Methods: Pressure pain thresholds (PPTs) were determined over nine points covering the temporalis muscle in 40 men with episodic CH and 40 matched headache-free controls in a blinded fashion. Topographical pressure pain sensitivity maps were constructed based on interpolation of the PPTs. Patients were evaluated in a pain-free period (remission phase), at least 3 months from the last attack and without medication. Results: The analysis of covariance (ANCOVA) found significant difference between points (F = 21.887; P 0.8). Conclusions: Bilateral pressure pain hypersensitivity to pressure pain in the temporalis muscle and an anterior-to-posterior gradient to pressure pain was observed in men with episodic CH.s

Two new records of sponges from NW Atlantic: Iotroata acanthostylifera (Stephens, 1916) and Janulum spinispiculum (Carter, 1876).

NEREIDA, a Spanish-led multidisciplinary and international project with contribution from various NAFO contracting parties such as Canada, the UK, and Russia, was initiated in response to the UNGA Resolution 61/105. The main objective of the NEREIDA project is to gather information for the identification and delineation of VMEs in the NAFO Regulatory Area with special focus on those dominated by deep-water corals and sponges. This demarcation is a necessary step in the decision making process for the protection of these areas. The NEREIDA data collection programme comprised six research cruises conducted between May and July of 2009 and June and August 2010, aboard the Spanish R/V Miguel Oliver. In 2009, surveys were conducted to the east, north and west of the Flemish Cap and Flemish Pass, whereas in 2010, surveys covered the area south of the Flemish Cap and along the slope of the Tail of the Grand Bank of Newfoundland. In this work we present some results from the analysis of sponges samples collected by rock dredge during the NEREIDA survey programme (2009-2010). There are two new records in the NW Atlantic region: Janulum spinispiculum (Carter, 1876) with distribution in the Northeast Atlantic region: southern Portugal, Azores, Rockall Bank; Mediterranean Sea: Alboran and Ionian Seas, Canyon de la Cassidaigne; North Atlantic: Iceland; Arctic Ocean: Barents Sea, northern Norway and Spitzbergenand (Kelly et al., 2015) and Iotroata acanthostylifera (Stephens, 1916) cited only of Celtics Seas (van Soest, 2007)

Wallenberg’s syndrome and symptomatic trigeminal neuralgia

Symptomatic trigeminal neuralgia due to a brainstem infarction is said to be rare. However, facial pain is not uncommon in Wallenberg’s syndrome. Facial pain related to a Wallenberg’s syndrome may be either persistent of intermittent, and occasionally occurs in brief attacks. Here, we report a patient with a right lateral medullary infarction who started having first division trigeminal neuralgia 1 month after the stroke. The pain paroxysms were suppressed with gabapentin

The Val158Met polymorphism of the catechol-O-methyltransference gene is not associated with long-term treatment outcomes in carpal tunnel syndrome: A randomized clinical trial

DESIGN: Randomized clinical trial. OBJECTIVE: To investigate the association of the Val158Met polymorphism with pain and function outcomes in women with carpal tunnel syndrome (CTS) who received surgery or manual therapy including desensitization manoeuvres of the central nervous system. METHODS: A pre-planned secondary analysis of a randomized controlled trial investigating the efficacy of manual therapy including desensitization manoeuvres of the central nervous system vs. surgery in 120 women with CTS was conducted. Women were randomized to receive 3 sessions of manual therapy (n = 60) or decompression of the carpal tunnel (n = 60). The primary outcome was intensity of pain (mean pain and the worst pain), and secondary outcomes included function and symptoms severity subscales of the Boston Carpal Tunnel Questionnaire. Outcomes were assessed at baseline, and 1, 3, 6, and 12 months after the intervention. Rs4680 genotypes were determined after amplifying the Val158Met polymorphism by polymerase chain reactions. We classified subjects according to their Val158Met polymorphism: Val/Val, Val/Met, or Met/Met. The primary aim (treatment group*Val158Met*time) was examined with repeated measures ANCOVA with intention-to-treat analysis. RESULTS: At 12 months, 111 (92%) women completed the follow-up. No interaction was observed between the Val158Met genotype and any outcome: mean pain intensity (F = 0.60; P = 0.69), worst pain intensity (F = 0.49; P = 0.61), function (F = 0.12; P = 0.88) or symptom severity (F = 0.01; P = 0.98). CONCLUSION: The current clinical trial did not show an association between the Val158Met polymorphism and changes in pain and function outcomes after either surgery or physical therapy in women with CTS.Funding: The study was funded by a research project grant (FIS PI11/01223) from the Health Institute Carlos III and PN I+D+I 2012-2014, Spanish Government

The presence of headache at onset in SARS-CoV-2 infection is associated with long-term post-COVID headache and fatigue:A case-control study

OBJECTIVE: To investigate the association of headache during the acute phase of SARS-CoV-2 infection with long-term post-COVID headache and other post-COVID symptoms in hospitalised survivors. METHODS: A case-control study including patients hospitalised during the first wave of the pandemic in Spain was conducted. Patients reporting headache as a symptom during the acute phase and age- and sex-matched patients without headache during the acute phase participated. Hospitalisation and clinical data were collected from medical records. Patients were scheduled for a telephone interview 7 months after hospital discharge. Participants were asked about a list of post-COVID symptoms and were also invited to report any additional symptom they might have. Anxiety/depressive symptoms and sleep quality were assessed with the Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index. RESULTS: Overall, 205 patients reporting headache and 410 patients without headache at hospitalisation were assessed 7.3 months (Standard Deviation 0.6) after hospital discharge. Patients with headache at onset presented a higher number of post-COVID symptoms (Incident Rate Ratio: 1.16, 95% CI: 1.03–1.30). Headache at onset was associated with a previous history of migraine (Odd Ratio: 2.90, 95% Confidence Interval: 1.41–5.98) and with the development of persistent tension-type like headache as a new post-COVID symptom (Odd Ratio: 2.65, 95% CI: 1.66–4.24). Fatigue as a long-term symptom was also more prevalent in patients with headache at onset (Odd Ratio: 1.55, 95% CI: 1.07–2.24). No between-group differences in the prevalence of anxiety/depressive symptoms or sleep quality were seen. CONCLUSION: Headache in the acute phase of SARS-CoV-2 infection was associated with higher prevalence of headache and fatigue as long-term post-COVID symptoms. Monitoring headache during the acute phase could help to identify patients at risk of developing long-term post-COVID symptoms, including post-COVID headache

Genome comparison of erythromycin resistant campylobacter from Turkeys identifies hosts and pathways for horizontal spread of erm(B) genes

Los patógenos en el género Campylobacter son la causa más común de gastroenteritis bacteriana transmitida por los alimentos. La campilobacteriosis, causada principalmente por Campylobacter jejuni y Campylobacter coli, se transmite a los humanos mediante alimentos de origen animal, especialmente aves de corral. En cuanto a muchos patógenos, la resistencia antimicrobiana en Campylobacter está aumentando a un ritmo alarmante. La prescripción de eritromicina es el tratamiento de elección para los casos clínicos que requieren terapia antimicrobiana, pero esto se ve comprometido por la movilidad del gen de resistencia a la eritromicina erm (B) entre las cepas. Aquí, evaluamos la resistencia a seis antimicrobianos en 170 aislados de Campylobacter (133 C. coli y 37 C. jejuni) de pavos. Los aislados resistentes a la eritromicina (n = 85; 81 C. coli y 4 C. jejuni) se examinaron en busca de la presencia del gen erm (B), que no se ha identificado previamente en aislamientos de pavos. Se secuenciaron los genomas de dos aislamientos positivos de C. coli y en ambos aislamientos el gen erm (B) se agrupó con determinantes de resistencia contra aminoglucósidos más tetraciclina, incluidos aad9, aadE, aph (2 ") - IIIa, aph (3 ') - IIIa , y genes tet (O). El análisis genómico comparativo identificó secuencias erm (B) idénticas entre Campylobacter de pavos, Streptococcus suis de cerdos y Enterococcus faecium y Clostridium difficile de humanos. Esto es consistente con múltiples eventos de transferencia horizontal entre diferentes especies de bacterias que colonizan pavos. Este ejemplo destaca el potencial de diseminación de la resistencia antimicrobiana a través de los límites de las especies bacterianas que pueden comprometer su efectividad en la terapia antimicrobiana.Pathogens in the genus Campylobacter are the most common cause of food-borne bacterial gastro-enteritis. Campylobacteriosis, caused principally by Campylobacter jejuni and Campylobacter coli, is transmitted to humans by food of animal origin, especially poultry. As for many pathogens, antimicrobial resistance in Campylobacter is increasing at an alarming rate. Erythromycin prescription is the treatment of choice for clinical cases requiring antimicrobial therapy but this is compromised by mobility of the erythromycin resistance gene erm(B) between strains. Here, we evaluate resistance to six antimicrobials in 170 Campylobacter isolates (133 C. coli and 37 C. jejuni) from turkeys. Erythromycin resistant isolates (n = 85; 81 C. coli and 4 C. jejuni) were screened for the presence of the erm(B) gene, that has not previously been identified in isolates from turkeys. The genomes of two positive C. coli isolates were sequenced and in both isolates the erm(B) gene clustered with resistance determinants against aminoglycosides plus tetracycline, including aad9, aadE, aph(2″)-IIIa, aph(3′)-IIIa, and tet(O) genes. Comparative genomic analysis identified identical erm(B) sequences among Campylobacter from turkeys, Streptococcus suis from pigs and Enterococcus faecium and Clostridium difficile from humans. This is consistent with multiple horizontal transfer events among different bacterial species colonizing turkeys. This example highlights the potential for dissemination of antimicrobial resistance across bacterial species boundaries which may compromise their effectiveness in antimicrobial therapy.• Ministerio de Ciencia e Innovación. Ayudas AGL2009-07550, AGL2012-39028 • Ministerio de Agricultura, Alimentación y Medio Ambiente. Ayuda 2014/000223 • Comunidad Autónoma de Madrid. Ayudas S2009 / AGR-1489; S2013 / ABI-2747 • Ministerio de Economía y Competitividad de España. Ayuda AGL2012-39028 • Ministerio de Economía y Competitividad. Beca BES-2013-065003, para Diego Flórez Cuadrado • Consejo de Investigación Médica. Ayuda MR / L015080 / 1, para Samuel K. SheppardpeerReviewe

Transcription factor NFE2L2/NRF2 is a regulator of macroautophagy genes

Autophagy is a highly coordinated process that is controlled at several levels including transcriptional regulation. Here, we identify the transcription factor NFE2L2/NRF2 (nuclear factor, erythroid 2 like 2) as a regulator of autophagy gene expression and its relevance in a mouse model of Alzheimer disease (AD) that reproduces impaired APP (amyloid β precursor protein) and human (Hs)MAPT/TAU processing, clearance and aggregation. We screened the chromatin immunoprecipitation database ENCODE for 2 proteins, MAFK and BACH1, that bind the NFE2L2-regulated enhancer antioxidant response element (ARE). Using a script generated from the JASPAR's consensus ARE sequence, we identified 27 putative AREs in 16 autophagy-related genes. Twelve of these sequences were validated as NFE2L2 regulated AREs in 9 autophagy genes by additional ChIP assays and quantitative RT-PCR on human and mouse cells after NFE2L2 activation with sulforaphane. Mouse embryo fibroblasts of nfe2l2-knockout mice exhibited reduced expression of autophagy genes, which was rescued by an NFE2L2 expressing lentivirus, and impaired autophagy flux when exposed to hydrogen peroxide. NFE2L2-deficient mice co-expressing HsAPP(V717I) and HsMAPT(P301L), exhibited more intracellular aggregates of these proteins and reduced neuronal levels of SQSTM1/p62, CALCOCO2/NDP52, ULK1, ATG5 and GABARAPL1. Also, colocalization of HsAPP(V717I) and HsMAPT(P301L) with the NFE2L2-regulated autophagy marker SQSTM1/p62 was reduced in the absence of NFE2L2. In AD patients, neurons expressing high levels of APP or MAPT also expressed SQSTM1/p62 and nuclear NFE2L2, suggesting their attempt to degrade intraneuronal aggregates through autophagy. This study shows that NFE2L2 modulates autophagy gene expression and suggests a new strategy to combat proteinopathies