A graphical classification of European countries according to physical activity Level of its citizens

Data on self-reported frequency of exercising or playing sport of adults aged 15 and above in 27 EU countries were collected, from the European Commission's Special Eurobarometer. A graphical output was obtained using classical a statistical methodology known as metric Multidimensional Scaling method to better define the interrelationships between a large set of variables for the data from the 27 European countries and "average" country included in the study. People in Sweden, Denmark and Finland had the highest level of exercise and playing sport level. High level of exercise and play sport level were detected in Slovenia, the Netherlands, Belgium, Germany, Luxembourg, the United Kingdom and France while low level of exercise and play sport level were found in Romania, Hungary, Italy, Poland and Portugal. The lowest level of exercise and play sport was observed in Bulgaria and Greece. The groups of countries that result from this classification also are characterized by the extent of the difference between the lowest levels of activity (never practising) and the highest (regularly practising); Austria, Czech Republic and Slovakia, have the highest proportion of people who seldom practising. In 4 countries, Ireland, Malta, Republic of Cyprus and Portugal, the proportion of citizens who practice exercise or play sport regularly or never (extreme behaviour) is high. This study shows what a high level and regularly of exercise and playing sport are associated with adults participating in education and training, satisfaction with household financial situation and kind of work activity

Decreased CX3CL1 Levels in the Cerebrospinal Fluid of Patients With Alzheimer’s Disease

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by the presence of neurofibrillary tangles, constituted by tau protein, and plaques formed by amyloid-beta protein. The disease courses with high neural damage, which leads to memory loss and death. Here we analyzed the presence of CX3CL1, a chemokine expressed by neurons, in cerebrospinal fluid (CSF) samples from control subjects and patients with mild cognitive impairment and AD dementia. CX3CL1 was decreased in the CSF of AD dementia patients compared to control subjects. However, there was not difference in plasma samples from the same subjects

Dense core vesicle markers in CSF and cortical tissues of patients with Alzheimer’s disease

Background: New fluid biomarkers for Alzheimer's disease (AD) that reveal synaptic and neural network dysfunctions are needed for clinical practice and therapeutic trial design. Dense core vesicle (DCV) cargos are promising cerebrospinal fluid (CSF) indicators of synaptic failure in AD patients. However, their value as biomarkers has not yet been determined. Methods: Immunoassays were performed to analyze the secretory proteins prohormone convertases PC1/3 and PC2, carboxypeptidase E (CPE), secretogranins SgIII and SgII, and Cystatin C in the cerebral cortex (n = 45, provided by Bellvitge University Hospital) and CSF samples (n = 66, provided by The Sant Pau Initiative on Neurodegeneration cohort) from AD patients (n = 56) and age-matched controls (n = 55). Results: In AD tissues, most DCV proteins were aberrantly accumulated in dystrophic neurites and activated astrocytes, whereas PC1/3, PC2 and CPE were also specifically accumulated in hippocampal granulovacuolar degeneration bodies. AD individuals displayed an overall decline of secretory proteins in the CSF. Interestingly, in AD patients, the CSF levels of prohormone convertases strongly correlated inversely with those of neurodegeneration markers and directly with cognitive impairment status. Conclusions: These results demonstrate marked alterations of neuronal-specific prohormone convertases in CSF and cortical tissues of AD patients. The neuronal DCV cargos are biomarker candidates for synaptic dysfunction and neurodegeneration in AD

El discurso subversivo de Bernard Rudofsky a través de la fotografía: estrategias visuales contra la modernidad.

Architecture without Architects (AWA) se proyectó como una exposición menor en el MoMA (Nueva York, 1964). Ampliamente citada, AWA acuñó incluso un neologismo para designar la arquitectura tradicional. Comisario, arquitecto, diseñador, crítico y fotógrafo, Bernard Rudofsky (1905-1988) evitó categorizaciones históricas o geográficas construyendo una experiencia en la que lugares muy distantes quedan conectados visualmente a través de sus paisajes vernaculares, siendo la fotografía la base principal de su mensaje. Cuestiona la hegemonía occidental de la historiografía arquitectónica y denuncia el paralelismo entre tradicional y subdesarrollado. Su crítica a la Modernidad provocó la reacción y censura del American Institute of Architects, aunque no evitó su itinerancia durante 11 años a más de 80 lugares del mundo. Esta investigación muestra las metodologías y estrategias visuales que caracterizan su discurso controvertido y desobediente hacia la Modernidad. El viaje es un componente esencial de su trayectoria; él documentó su experiencia peripatética especialmente con fotografías. Comenzando con un análisis de las metodologías rudofskianas en AWA y publicaciones, la investigación revela su aproximación naturalista, sin pretensiones antológicas, donde la imágenes no ilustran un texto sino que construyen un discurso visual paralelo. Su mirada creativa de arquitecto presenta la arquitectura tradicional como material para la construcción del presente. Con su vivienda en Frigiliana (Málaga, 1969-1971), el caso de Andalucía constituye objeto de estudio destacado hasta su muerte. Usando la metodología visual del autor y centrándonos en su fase madura, se presentan las fotografías de Rudofsky en tres escalas temáticas: la calle, la ciudad y el territorio. La investigación reflexiona sobre la naturaleza de su producción gráfica, transita entre la fotografía de paisaje y documental, y excepcionalmente de arquitectura. Se constata una aproximación fenomenológica, multisensorial, que la fotografía recoge parcialmente desde su componente plástico. La experiencia prevalece sobre el medio y la fotografía no puede ni pretende sustituirla.Architecture without Architects (AWA) was expected to be a minor exhibition at the MoMA (New York, 1964). Widely quoted, AWA even brought about a neologism used to refer to traditional architecture. Curator, architect, designer, subversive critic and photographer Bernard Rudofsky (1905-1988) avoided historical or geographical categorization, creating an experience in which very distant geographies are connected through their vernacular architectures, with photographs as the core of his message. He challenged western hegemony in architectural history and denounced the presumed parallelism between traditional architecture and the under-developed world. His critique of Modern architecture provoked the reaction and censure of the American Institute of Architects, although this did not prevent it from travelling to over 80 locations worldwide over an eleven-year period. This research shows the characteristic visual methodologies and strategies of his controversial discourse, which rebelled against Modernity. Travel is essential in Rudofsky’s trajectory; he documented his peripatetic experience especially in photographs. Using an analysis of Rudofsky’s methodologies in AWA and publications as a starting point, this research reveals his naturalist approach, with no anthological aspiration, where images build a parallel visual discourse instead of merely illustrating a text. His creative architect’s gaze presents traditional architecture as a material for the construction of the present. The case of Andalusia became a major object of study from the time his residence in Frigiliana (Malaga, 1969-1971) was built, until his death. Using Rudofsky’s visual methodology and focusing on his later period, his photographs are presented at three thematic levels: street, city and territory. The paper reflects on the nature of his graphic production, which ranges from documentary, landscape and exceptionally architectural photography. A phenomenological multi-sensory approach is observed, and partly reproduced by photography through its visual aspect. The experience prevails over the medium, and photography cannot replace it, nor does it aim to

Feasibility of lumbar puncture in the study of cerebrospinal fluid biomarkers for Alzheimer disease in subjects with Down syndrome

Background: Alzheimer's disease (AD) is the main medical problem in older adults with Down syndrome (DS). Studies of cerebrospinal fluid (CSF) AD biomarkers are limited and the feasibility of lumbar puncture (LP) is controversial in this population. Objective: to analyze the frequency of complications after a LP in DS. Methods: we collected data from 80 adults with DS that underwent a LP within the Down Alzheimer Barcelona Neuroimaging Initiative. Demographics, cognitive status, headache history, and presence of complications after the LP were recorded in every subject. In 53 of them (active group), this information was collected following a semi-structured and validated protocol that actively looks for complications. Other variables related to the LP procedure were also recorded. A telephone interview to the caregiver was performed 5-7 days after the procedure to ask about complications. Data from 27 subjects (clinical practice group), from whom the presence of complications was obtained in a medical follow-up visit within the three months after the LP, were also included. Results: there were no adverse events in 90% of our participants. The most frequent complication was headache (6.25%); only one subject reported a typical post-lumbar puncture headache with moderate severity that required analgesic treatment. Dizziness (3.75%) and back pain (1.25%) were also reported. All the participants that reported complications belonged to the active group. Conclusion: LP can be safely performed to study CSF biomarkers in DS. The reported complications are qualitatively similar to the general population, but are less frequently reported, even when actively searched for

GVPC Medium Manufactured without Oxygen Improves the Growth of Legionella spp. and Exhibits Enhanced Selectivity Properties

ABSTRACTGlycine-vancomycin-polymyxin-cycloheximide agar (GVPC) is a recommended medium for the detection of Legionella spp. in water samples. However, its quality could be improved in terms of recovery of Legionella spp. and selectivity properties. Modifications were introduced in GVPC manufacture: autoclaving conditions (115°C, 15 min) and atmosphere during component-stirring (removal of oxygen and N2 injection). The use of softer autoclaving conditions (115°C, 15 min) improved the growth of Legionella anisa by the spiral method and Legionella pneumophila after membrane filtration. The medium manufactured with O2 removal and autoclaving for 15 min at 115°C allowed a faster growth of L. pneumophila (colonies visible at day 2) and a notable increase of L. anisa growth (colonies appearing at day 3, and statistically significant numbers of CFU at day 5). After 3 to 5 days of incubation, the improved media showed higher selectivity properties, particularly for Enterococcus faecalis ATCC 29212 and Pseudomonas aeruginosa ATCC 9027. A further improvement was achieved by the addition of N2 during ingredient stirring, leading to a statistically significant faster growth of L. pneumophila at days 2 and 3 and L. anisa at day 3. Selectivity properties were also enhanced, resulting in the complete inhibition of both E. faecalis strains and Escherichia coli and complete-partial inhibition of P. aeruginosa. Oxygen removal during GVPC manufacture using a vacuum pump system promotes the growth of L. pneumophila and L. anisa, and markedly inhibits the growth of E. coli, P. aeruginosa, and E. faecalis. IMPORTANCE Currently, GVPC is a recommended medium for the detection of Legionella spp. in water samples. However, recovery of Legionella spp. and selectivity properties can be improved. GVPC medium manufactured without oxygen improved the growth of Legionella pneumophila and Legionella anisa. Oxygen removal during GVPC manufacture also improved selectivity properties. A further improvement was achieved by the addition of N2 during ingredient stirring, leading to a faster growth of L. pneumophila at days 2 and 3 and L. anisa at day 3 and enhancement of selectivity properties. The introduction of the modified GVPC medium in routine practice can allow a better detection of Legionella spp. in water samples

Increased plasma neurofilament light chain levels in patients with type-1 diabetes with impaired awareness of hypoglycemia

Altres ajuts: This work was financially supported by a grant from the SPANISH DIABETES SOCIETY.Impaired awareness of hypoglycemia (IAH) is a common complication in patients with type-1 diabetes (T1D). IAH is a major risk factor for severe hypoglycemic events, leading to adverse clinical consequences and cerebral damage. Non-invasive, cost-effective, and logistically efficient biomarkers for this condition have not been validated. Here, we propose plasma neurofilament light chain (NfL) levels as a biomarker of neuroaxonal damage in patients with T1D-IAH. 54 patients were included into the study (18 T1D-IAH, 18 T1D with normal awareness of hypoglycemia (NAH) and 18 healthy controls). We measured plasma NfL levels and studied cerebral gray matter alterations on MRI. We found that NfL levels were increased in patients with T1D-IAH compared with patients with T1D-NAH and healthy controls. Importantly, increased NfL levels correlated with reduced cerebral gray matter volume and increased IAH severity in patients with T1D-IAH. Overall, our findings identify plasma NfL levels as a potential biomarker of cerebral damage in this population, motivating further confirmatory studies with potential implications in clinical trials

Blood amyloid and tau biomarkers as predictors of cerebrospinal fluid profiles

Blood biomarkers represent a major advance for improving the management, diagnosis, and monitoring of Alzheimer's disease (AD). However, their context of use in relation to routine cerebrospinal fluid (CSF) analysis for the quantification of amyloid peptides and tau proteins remains to be determined. We studied in two independent cohorts, the performance of blood biomarkers in detecting "nonpathological" (A−/T−/N−), amyloid (A+) or neurodegenerative (T+ /N+) CSF profiles. Plasma Aβ/Aβ ratio and phosphorylated tau (p-tau(181)) were independent and complementary predictors of the different CSF profile and in particular of the nonpathological (A−/T−/N−) profile with a sensitivity and specificity close to 85%. These performances and the corresponding biomarker thresholds were significantly different from those related to AD detection. The use of blood biomarkers to identify patients who may benefit from secondary CSF testing represents an attractive stratification strategy in the clinical management of patients visiting memory clinics. This could reduce the need for lumbar puncture and foreshadow the use of blood testing on larger populations. The online version contains supplementary material available at 10.1007/s00702-022-02474-9

Apolipoprotein E imbalance in the cerebrospinal fluid of Alzheimer's disease patients.

Objective: The purpose of this study was to examine the levels of cerebrospinal fluid (CSF) apolipoprotein E (apoE) species in Alzheimer's disease (AD) patients. Methods: We analyzed two CSF cohorts of AD and control individuals expressing different APOE genotypes. Moreover, CSF samples from the TgF344-AD rat model were included. Samples were run in native- and SDS-PAGE under reducing or non-reducing conditions (with or without β-mercaptoethanol). Immunoprecipitation combined with mass spectrometry or western blotting analyses served to assess the identity of apoE complexes. Results: In TgF344-AD rats expressing a unique apoE variant resembling human apoE4, a ~35-kDa apoE monomer was identified, increasing at 16.5 months compared with wild-types. In humans, apoE isoforms form disulfide-linked dimers in CSF, except apoE4, which lacks a cysteine residue. Thus, controls showed a decrease in the apoE dimer/monomer quotient in the APOE ε3/ε4 group compared with ε3/ε3 by native electrophoresis. A major contribution of dimers was found in APOE ε3/ε4 AD cases, and, unexpectedly, dimers were also found in ε4/ε4 AD cases. Under reducing conditions, two apoE monomeric glycoforms at 36 kDa and at 34 kDa were found in all human samples. In AD patients, the amount of the 34-kDa species increased, while the 36-kDa/34-kDa quotient was lower compared with controls. Interestingly, under reducing conditions, a ~100-kDa apoE complex, the identity of which was confirmed by mass spectrometry, also appeared in human AD individuals across all APOE genotypes, suggesting the occurrence of aberrantly resistant apoE aggregates. A second independent cohort of CSF samples validated these results. Conclusion: These results indicate that despite the increase in total apoE content the apoE protein is altered in AD CSF, suggesting that function may be compromised

Hypothalamic pregnenolone mediates recognition memory in the context of metabolic disorders

Obesity and type 2 diabetes are associated with cognitive dysfunction. Because the hypothalamus is implicated in energy balance control and memory disorders, we hypothesized that specific neurons in this brain region are at the interface of metabolism and cognition. Acute obesogenic diet administration in mice impaired recognition memory due to defective production of the neurosteroid precursor pregnenolone in the hypothalamus. Genetic interference with pregnenolone synthesis by Star deletion in hypothalamic POMC, but not AgRP neurons, deteriorated recognition memory independently of metabolic disturbances. Our data suggest that pregnenolone’s effects on cognitive function were mediated via an autocrine mechanism on POMC neurons, influencing hippocampal long-term potentiation. The relevance of central pregnenolone on cognition was also confirmed in metabolically unhealthy patients with obesity. Our data reveal an unsuspected role for POMC neuron-derived neurosteroids in cognition. These results provide the basis for a framework to investigate new facets of POMC neuron biology with implications for cognitive disorders.This work was supported by the Swiss National Science Foundation (no.176206; NCCR Synapsy grant no.185897) to C.S.; the European Research Council (ERC) advanced grant SYNEME to J.C.B.; Instituto de Salud Carlos III (ISCIII)—Fondo Europeo de Desarrollo Regional (FEDER) (PI17/00296), RETICs Oftared (RD16/0008/0014), and Generalitat de Catalunya (2017SGR737) to X.G.; Ministerio de Ciencia e Innovación (BFU2017-83317-P) to D.S.; Ministerio de Economia, Industria y Competitividad, Maria de Maeztu (MDM-2017-0729) to Institut de Neurociencies, Universitat de Barcelona; ISCIII-FEDER (PI14/01126, PI17/01019), the National Institutes of Health (NIA grants 1R01AG056850-01A1, R21AG056974, and R01AG061566), Fundació La Marató de TV3 (20141210), and Generalitat de Catalunya (SLT006/17/00119) to J.F.; ISCIII-FEDER (PI17/00279 and PI20/0042), Fundació La Marató de TV3 (201614.31), and Generalitat de Catalunya (SLT008/18/00127) to A.J.; Plan Nacional de I+D funded by the Agencia Estatal de Investigación (AEI) and FEDER (PID2019-111669RB-I00 and PID2020-115055RB-I00), CIBEREHD, the center grant P50AA011999 Southern California Research Center for ALPD and Cirrhosis funded by NIAAA/NIH, Generalitat de Catalunya (SGR-2017-1112), the European Cooperation in Science & Technology (COST) ACTION CA17112, FUNDACIÓN BBVA (“ER stress-mitochondrial cholesterol axis in obesity-associated insulin resistance and comorbidities”), and Red Nacional 2018-102799-T de Enfermedades Metabólicas y Cáncer and Fundació La Marató de TV3 (201916/31) to J.C.F.-C.; and ERC consolidator grant MITOSENSING (725004), ISCIII-FEDER (PI16/00963), “la Caixa” Foundation (ID100010434) under agreement LCF/PR/HR19/52160016, and CERCA Programme/Generalitat de Catalunya to M.C. D.A. is supported by ISCIII (INT19/00016) and Generalitat de Catalunya PERIS program (SLT006/17/125), A.P. is supported by Hospital Clínic de Barcelona (“Ajut Josep Font”), A.O. is supported by a Miguel Servet contract (CP19/00083) from ISCIII-FEDER, and R.H.-T. is supported by a Marie Skłodowska-Curie Action fellowship (H2020-MSCA-IF) and NEUROPREG (891247). S.R. is a recipient of Juan de la Cierva Formación (FJCI-2016-28911) and Incorporación (IJC2018-037341-I) programs from the Spanish Ministry of Science and Innovation. This work was carried out in part at Esther Koplowitz Centre.Peer reviewe