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Pertussis is a highly contagious respiratory infection caused by Bordetella pertussis and to minor extent B. parapertussis. Despite high vaccination coverage, epidemics persist worldwide. Laborator...

T1 Figure 1ConclusionsOverall, this largest paediatric single cell COVID-19 study to date showed significant differences in response to SARS-CoV-2 between children and adults, reflecting the changes of the immune landscape over developmental time, which in children are dominated by naive and innate responses.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder that results from repetitive traumatic brain injury (TBI), whether mild or severe. Several popular sports that subject the head to impact have been linked as a primary cause of the disease. Phosphorylated tau and Aβ deposits are the two proteins observed histopathologically in CTE patients. An ischemic environment is created that contributes to the hyperphosphorylation of tau following traumatic brain injury. The use of fluid biomarkers, animal models for TBI, as well as imaging tools are considered valuable in understanding the pathophysiological mechanism of CTE. This review gives particular attention to the characteristics, advantages, and disadvantages of the current fluid biomarkers, use of animal models, and imaging techniques used in CTE diagnosis. Beta-amyloid and phosphorylated tau were suggested as the two main pathological biomarkers for chronic traumatic encephalopathy (CTE) diagnosis, though research into other fluid biomarkers of traumatic brain injury (TBI) such as neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), and C-C motif chemokine 11 (CCL11) has been undertaken but was mostly limited by sample size, and decreased sensitivity in follow-up studies. Animal models and devices that simulate TBI were valuable in exploring injury dynamics and the role it may have on CTE. The use of transgenic animals in CTE research has also uncovered the different risk genes that may enhance CTE pathology. Magnetic resonance imaging (MRI), functional MRI and positron emission tomography (PET) imaging showed enough resolution to accurately diagnose CTE. However, diffusion tensor imaging (DTI) was able to identify microstructural changes in professional boxers that were not apparent in MRI. Currently, a single biomarker or imaging technique is not enough to accurately diagnose CTE and diagnostic accuracy is significantly enhanced when these different parameters are combined.

A detailed live load survey was carried out on floors of the library and newspaper archive at a public library in Mexico City. The study included furniture, racks and shelves, as well as books, journals, papers and other items used in libraries. Considering temporal concentration, an additional survey of people was estimated separately. Those loads were used to estimate distribution functions of the maximum total live loads for different areas. The results were compared with the values specified by the Mexico City Building Code and ASCE 7-16. The paper provides some detailed background behind the normative methodology of the current specialized codes to define the basic value of design live load intensity by considering the maximum load effect as a function of the building uses and the definition of influence area by structural element. The results of the survey corresponding to typical public libraries have shown that the probabilities of occurrence of the design loads recommended in the local code might be a proper representation of the mean values. Based on the results, basic values of design load intensity were proposed.

We studied the effect of different cervicothoracic construct design variables on biomechanical stability in vitro.Six fresh-frozen human cadaveric spines (C5-T4) were used. After intact analysis, each specimen was destabilized and reconstructed, with all groups having 4.0-mm pedicle screws placed at T1-T3. The 2 hook-rod constructs included interlaminar hooks at C6 and C7, with either 3.5-mm or 4.0-mm rods (C6-T3). The 2 screw-rod constructs tested included lateral mass screws at C6 and C7, with either 3.5-mm or 4.0-mm rods (C6-T3). The 2 screw-connector-rod constructs tested included lateral mass screws at C6 and C7, with either 3.5-mm or 4.0-mm rods; 1 rod spanned C6-C7 with a connector to a second rod of the same size spanning T1-T3. Global (C6-T3) and intervertebral (C6-C7, C7-T1, T1-T2, and T2-T3) ranges of motion were compared for each construct.In terms of global (C6-T3) stability, 3.5-mm versus 4.0-mm rod constructs were not significantly different, regardless of whether the construct was hook-rod, screw-rod, or screw-connector-rod. The hook-rod constructs provided less stability compared with the screw-rod and screw-connector-rod constructs in lateral bending (P 0.04) and axial rotation (P0.001). The screw-rod constructs demonstrated a similar range of motion to that of the screw-connector-rod constructs, except for significantly less axial rotation at the C6-C7 level with 3.5-mm rods (P = 0.04).We found that the rod diameter of a construct does not appear to significantly influence the biomechanical stability of subaxial constructs. The screw-rod construct resulted in certain biomechanical advantages compared with the screw-connector-rod construct, and both were significantly superior to the hook-rod construct.

Background: Pertussis is a highly contagious respiratory disease caused by the bacterium Bordetella pertussis (B. pertussis). The infection is difficult to diagnose especially in underserved or resource-limited areas. We developed a low-cost and instrument-free diagnostic method for rapid and accurate detection of B. pertussis on a point-of-care (POC) testing device. Methods: We developed a paper/polymer hybrid microfluidic biochip integrated with loop-mediated isothermal amplification (LAMP) method for the rapid and accurate detection of B. pertussis. This microfluidic approach was validated by testing 100 de-identified remnant clinical nasopharyngeal swabs and aspirates, which were confirmed to be either positive or negative for B. pertussis by a validated real-time PCR assay at the Children's Hospital Los Angeles. Findings: The instrument-free detection results could be successfully read by the naked eye within 45 min with a limit of detection (LOD) of 5 DNA copies per well. Our optimized bacterial lysis protocol allowed the direct testing of clinical samples without any complicated sample processing/preparation (i.e. DNA extraction) or the use of any equipment (e.g. centrifuges). The validation of the microfluidic approach was accomplished by testing 100 clinical samples. High sensitivity (100%) and specificity (96%) with respect to real-time PCR were achieved. Interpretation: This microfluidic biochip shows great potential for point-of-care disease diagnosis in various venues including schools and physician's offices, especially in low-resource settings in developing nations. Funding: NIH/NIAID under award number R21AI107415, NIH RCMI Pilot Grant, the Philadelphia Foundation, the Medical Center of the Americas Foundation. Keywords: Pertussis diagnosis, Point-of-care detection, Microfluidic biochip, Whooping cough, Loop-mediated isothermal amplification (LAMP)

Age-related white matter lesion (WML) is considered a manifestation of sporadic cerebral small vessel disease and an important pathological substrate for dementia. Asia is notable for its large population with a looming dementia epidemic. Yet, the burden of WML and its associated risk factors across different Asian societies are unknown. Subjects from 9 Asian cities (Bangkok, Bandung, Beijing, Bengaluru, Hong Kong, Kaohsiung, Manila, Seoul, and Singapore) were recruited (n = 5701) and classified into (i) stroke/transient ischemic attack (TIA), (ii) Alzheimer’s disease (AD)/mild cognitive impairment (MCI), or (iii) control groups. Data on vascular risk factors and cognitive performance were collected. The severity of WML was visually rated on MRI or CT. The prevalence of moderate-to-severe WML was the highest in subjects with stroke/TIA (43.3%). Bandung Indonesia showed the highest prevalence of WML, adjusted for age, sex, education, disease groups, and imaging modality. Hypertension and hyperlipidemia were significant risk factors for WML, and WML was negatively associated with MMSE in all groups. WML is highly prevalent in Asia and is associated with increasing age, hypertension, hyperlipidemia, and worse cognitive performance. Concerted efforts to prevent WML will alleviate the huge dementia burden in the rapidly aging Asian societies.

Background This study investigated the differences in caregiver activity, caregiver burden, and awareness of both caregivers and patients with Alzheimer’s disease (AD) across different Asian locations. Methods This was a secondary analysis of a multi-national cohort study that aimed to assess caregiver activity and caregiver burden using the Caregiver Activity Scale (CAS) and Zarit Burden Interview (ZBI), respectively. Patients’ awareness of their dementia diagnosis was assessed by asking the following yes/no question: “Do you have dementia?” Caregivers’ awareness of the patient’s dementia diagnosis was assessed by asking the following yes/no question: “Does your patient have dementia?” Results In total, 524 caregivers of patients with AD from China, Hong Kong, South Korea, the Philippines, Singapore, Thailand, and Taiwan participated. The CAS and ZBI score were significantly different across most locations (p p = 0.033, respectively). Overall, 56.6% of caregivers and 37.5% of patients had awareness of the dementia diagnosis, and the proportion of patients and caregivers with awareness were also different between each location (all, p Conclusions Caregiving, caregiver burden, and the awareness of caregivers and patients were different across many Asian locations. With understanding of cultural differences, further public education on dementia could help increase the awareness of patients and caregivers and reduce caregiver burden. Trial registration ClinicalTrials.gov, NCT02262975. Registered 13 October 2014

International audience; If the success of agricultural intensification continues to rely on the depletion of aquifers and exploitation of (female) labour, transformations to groundwater sustainability will be impossible to achieve. Hence, the development of new groundwater imaginaries, based on alternative ways of organizing society-water relations is highly important. This paper argues that a comparative documentation of grass-roots initiatives to care for, share or recharge aquifers in places with acute resource pressures provides an important source of inspiration. Using a grounded anti-colonial and feminist approach, we combine an ethnographic documentation of groundwater practices with hydrogeological and engineering insights to enunciate, normatively assess and jointly learn from the knowledges, technologies and institutions that characterize such initiatives. Doing this usefully shifts the focus of planned efforts to regulate and govern groundwater away from government efforts to control individual pumping behaviours, to the identification of possibilities to anchor transformations to sustainability in collective action.

Background Age-related white matter lesion (WML) is considered a manifestation of sporadic cerebral small vessel disease and an important pathological substrate for dementia. Asia is notable for its large population with a looming dementia epidemic. Yet, the burden of WML and its associated risk factors across different Asian societies are unknown. Methods Subjects from 9 Asian cities (Bangkok, Bandung, Beijing, Bengaluru, Hong Kong, Kaohsiung, Manila, Seoul, and Singapore) were recruited (n = 5,701) and classified into i) stroke/transient ischemic attack (TIA), ii) Alzheimer’s disease (AD)/mild cognitive impairment (MCI), or iii) control groups. Data on vascular risk factors and cognitive performance were collected. The severity of WML was visually rated on MRI or CT. ResultsThe prevalence of moderate-to-severe WML was the highest in subjects with stroke/TIA (43.3 %). Bandang Indonesia showed the highest prevalence of WML, adjusted for age, sex, education and disease groups. Hypertension and hyperlipidemia were significant risk factors for WML, and WML was negatively associated with MMSE in all groups. ConclusionsWML is highly prevalent in Asia and is associated with increasing age, hypertension, hyperlipidemia and worse cognitive performance. Concerted efforts to prevent WML will alleviate the huge dementia burden in the rapidly aging Asian societies.

Background Dementia shows sex difference in its epidemiology. Childbirth, a distinctive experience of women, is associated with the risk for various diseases. However, its association with the risk of dementia in women has rarely been studied. Methods We harmonized and pooled baseline data from 11 population-based cohorts from 11 countries over 3 continents, including 14,792 women aged 60 years or older. We investigated the association between parity and the risk of dementia using logistic regression models that adjusted for age, educational level, hypertension, diabetes mellitus, and cohort, with additional analyses by region and dementia subtype. Results Across all cohorts, grand multiparous (5 or more childbirths) women had a 47% greater risk of dementia than primiparous (1 childbirth) women (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.10–1.94), while nulliparous (no childbirth) women and women with 2 to 4 childbirths showed a comparable dementia risk to primiparous women. However, there were differences associated with region and dementia subtype. Compared to women with 1 to 4 childbirths, grand multiparous women showed a higher risk of dementia in Europe (OR = 2.99, 95% CI = 1.38–6.47) and Latin America (OR = 1.49, 95% CI = 1.04–2.12), while nulliparous women showed a higher dementia risk in Asia (OR = 2.15, 95% CI = 1.33–3.47). Grand multiparity was associated with 6.9-fold higher risk of vascular dementia in Europe (OR = 6.86, 95% CI = 1.81–26.08), whereas nulliparity was associated with a higher risk of Alzheimer disease (OR = 1.91, 95% CI 1.07–3.39) and non-Alzheimer non-vascular dementia (OR = 3.47, 95% CI = 1.44–8.35) in Asia. Conclusion Parity is associated with women’s risk of dementia, though this is not uniform across regions and dementia subtypes.

Agricultural workers are at risk for the development of acute and chronic lung diseases due to their exposure to organic agricultural dusts. A diet intervention using the omega-3 fatty acid docosahexaenoic acid (DHA) has been shown to be an effective therapeutic approach for alleviating a dust-induced inflammatory response. We thus hypothesized a high-DHA diet would alter the dust-induced inflammatory response through the increased production of specialized pro-resolving mediators (SPMs). Mice were pre-treated with a DHA-rich diet 4 weeks before being intranasally challenged with a single dose of an extract made from dust collected from a concentrated swine feeding operation (HDE). This omega-3-fatty-acid-rich diet led to reduced arachidonic acid levels in the blood, enhanced macrophage recruitment, and increased the production of the DHA-derived SPM Resolvin D1 (RvD1) in the lung following HDE exposure. An assessment of transcript-level changes in the immune response demonstrated significant differences in immune pathway activation and alterations of numerous macrophage-associated genes among HDE-challenged mice fed a high DHA diet. Our data indicate that consuming a DHA-rich diet leads to the enhanced production of SPMs during an acute inflammatory challenge to dust, supporting a role for dietary DHA supplementation as a potential therapeutic strategy for reducing dust-induced lung inflammation.

Concussion is a transitory brain injury resulting from a blow to the head. Concussion is considered a mild traumatic brain injury (mTBI), which is self-limited. Repetitive mTBI has been associated with chronic, progressive neurological damage. Extreme biochemical changes occur in neuron cells as a result of mTBI. These metabolic disturbances may reflect the symptoms observed in patients who had suffered concussions. However, it has been difficult to correlate clinical signs and symptoms. Currently, there are no laboratory tests to diagnose concussion, though several biomarkers are being investigated. Further studies are needed to elucidate the biochemical details of the metabolic cascade and the associated time frame, which will help determine when an athlete can safely return to the game.

Background The Ginkgo biloba special extract, EGb 761® has been widely used in the treatment of neuropsychiatric disorders, including Alzheimer’s disease (AD). Methods To guide clinical practice in the Asian region, the Asian Clinical Expert Group on Neurocognitive Disorders compiled evidence‐based consensus recommendations regarding the use of EGb 761® in neurocognitive disorders with/without cerebrovascular disease. Results Key randomized trials and robust meta‐analyses have demonstrated significant improvement in cognitive function, neuropsychiatric symptoms, activities of daily living (ADL) and quality of life with EGb 761®versus placebo in patients with mild‐to‐moderate dementia. In those with mild cognitive impairment (MCI), EGb 761® has also demonstrated significant symptomatic improvement versus placebo. World Federation of Societies of Biological Psychiatry guidelines list EGb 761® with the same strength of evidence as acetylcholinesterase inhibitors and N‐methyl‐D‐aspartate (NMDA) antagonists e.g. memantine (Grade 3 recommendation; Level B evidence). Only EGb 761® had Level B evidence in improving cognition, behaviour, and ADL in both AD and vascular dementia patients. Safety analyses show EGb 761® to have a positive risk‐benefit profile. While concerns have been raised regarding a possible increased bleeding risk, several randomized trials and two meta‐analyses have not supported this association. Conclusions The Expert Group foresee an important role for EGb 761®, used alone or as an add‐on therapy, in the treatment of MCI and dementias, particularly when patients do not derive benefit from acetylcholinesterase inhibitors or NMDA antagonists. EGb 761® should be used in alignment with local clinical practice guidelines.

We have deposited Pt(50 nm)/BTO(54 nm)/LCMO(44 nm) and LCMO(55 nm)/BTO(48 nm)/LCMO(54 nm) multilayers on (001)STO substrates to study the top electrode influence in the electrical conduction mechanisms. In this case, LCMO layer was used as bottom electrode in contact with BTO, while Pt and LCMO layers were the top electrodes. From XRD we found that the LCMO and BTO layers grew textured aligned with substrate,obtaining values ofcLCMO =3.805 A and cBTO = 4.125 A. Magnetization measurements reveal a TC∼150 K and Ms∼ 600 emu/cm3 at 10 K. Additionally, for the electrical measurements the samples were pattered using photolithography technique obtaining square capacitive structures to allow the electrical measurementsat low temperatures and the study of the manganite metal-insulator transition implications on the electrical transport.

Clinical diagnosis of Alzheimer's disease (AD) is based on symptoms; however, the challenge is to diagnose AD at the preclinical stage with the application of biomarkers and initiate early treatment (still not widely available). Currently, cerebrospinal fluid (CSF) amyloid-β 42 (Aβ42) and tau are used in the clinical diagnosis of AD; nevertheless, blood biomarkers (Aβ42 and tau) are less predictive. Amyloid-positron emission tomography (PET) imaging is an advancement in technology that uses approved radioactive diagnostic agents (florbetapir, flutemetamol, or florbetaben) to estimate Aβ neuritic plaque density in adults with cognitive impairment evaluated for AD and other causes of cognitive decline. There is no cure for AD to date-the disease progression cannot be stopped or reversed; approved pharmacological agents (donepezil, galantamine, and rivastigmine; memantine) provide symptomatic treatment. However, the disease-modifying therapies are promising; aducanumab and CAD106 are in phase III trials for the early stages of AD. In conclusion, core CSF biomarkers reflect pathophysiology of AD in the early and late stages; the application of approved radiotracers have potential in amyloid-PET brain imaging to detect early AD.

Background The Philippines is experiencing rapid demographic aging and with it, the dementia epidemic. Prevalence of dementia and associated risk factors have not been studied in the Philippines. Objectives The study aimed to provide a reliable estimate of dementia prevalence and identify associated risk factors in the Filipino population. Methods 1460 participants 60 years and older were randomly selected from the Marikina City's senior registry. A multidisciplinary team (nurse, psychologist, and neurologist) administered a comprehensive assessment to the study population: health history, neurological examination, Geriatric Depression Scale, Neuropsychiatric Inventory, Disability Assessment for Dementia, Alzheimer's Disease 8, and Clinical Dementia Rating Scale. The neurologist analyzed all clinical data to diagnose dementia based on the DSM-IV criteria, Alzheimer's Disease (AD) on the NINCDS-ADRDA criteria, vascular dementia (VaD) on the Hachinski Ischemic Scale, cognitive impairment no dementia (CIND) on a CDR score of 0.5 and not fulfilling DSM-IV criteria for dementia. Risk factors were correlated with dementia prevalence using multivariate binary logistic regression. Results 1460 persons were randomly selected. 1367 agreed to participate and underwent all assessments. The response rate was 93.6%. Dementia prevalence was found to be 10.6% (95% CI 9.0 to 12.4) with the breakdown 85.5% AD, 11.7% VaD, and 2.7% other dementias. In this population, 82.0% of men and 70.4% of women had at least one cardiovascular risk factor (hypertension, diabetes, dyslipidemia, smoking), which was associated with VaD prevalence but not AD. Conclusion The prevalence of dementia, CIND, and cardiovascular risk factors are high in the Philippines.

Background:TNF inhibitors (TNFi) represent an extraordinary advance in the management of Rheumatoid Arthritis (RA). Despite their benefits, there is a percentage of patients (20–40%) that do not achieve clinical improvement. Therefore, it is necessary to search for new and easily accessible biomarkers predictive of therapeutic response that might guide precision medicine.Objectives:1. To explore changes in the molecular profile of RA patients following TNFi therapy in serum samples. 2. To search for new and reliable biomarkers predictive of TNFi response, based on clinical and molecular profiles of RA patients, by using machine learning algorithms.Methods:In a prospective multicenter study, 79 RA patients undergoing TNFi and 29 healthy donors (HD) were enrolled. Twenty-two RA patients were further included as a validation cohort. Serum samples were obtained before and after 6 months of treatment, and therapeutic efficacy was evaluated. Patients’ response was determined following EULAR response criteria. Serum inflammatory profile was analyzed by a multiplex immunoassay, along with oxidative and NETotic profiles, evaluated by commercial kits. A circulating miRNA array was also performed by next-generation sequencing. Clustering analysis was carried out to identify groups of patients with distinctive molecular signatures. Then, clinical and molecular changes induced by TNFi were delineated after 6 months of therapy. Finally, integrative clinical and molecular signatures as predictors of response were assessed at baseline by supervised machine learning methods, using regularized logistic regressions.Results:Inflammatory, oxidative stress and NETosis-derived biomolecules were found altered in RA patients versus HD, closely interconnected and associated with several deregulated miRNAs. This altered molecular profile at baseline allowed the unsupervised division of three clusters of RA patients with distinctive clinical phenotypes, further linked to TNFi effectiveness. Cluster 1 included RA patients with low levels of pro-inflammatory cytokines, associated with a medium-low disease activity score and good clinical response. Clusters 2-3 comprised patients with high levels of pro-inflammatory cytokines, associated with a high disease activity and a non-response rate of 30%.After 6 months of therapy the molecular profile found altered in RA patients was reversed in responder patients, who achieved a molecular phenotype similar to HDs. However, non-responder patients’ molecular profile remained significantly deregulated, including alterations in inflammatory mediators (IL-6, L-8, TNFα, VEGF, IL-1RA, IL-5, IL-15, GMCSF, GCSF, FGFb), oxidative stress markers (LPO) and NETosis-derived products (Elastase), along with specific miRNAs (miR-199a-5p). These molecular changes further correlated with changes in disease activity score. Machine-learning algorithms identified clinical (Creatinine, IgM, Vitamin D, Swollen Joints, C4, Disease Duration and Tryglicerides) and molecular (Nucleosomes, IL-10, miR-106a-5p, IL-13, IL-12p70, IL-15 and LPO) signatures as potential predictors of response to TNFi treatment with high accuracy. Furthermore, the integration of both features in a combined model increased the predictive value of these signatures (AUC: 0.91). These results were further confirmed in an independent validation cohort.Conclusion:1. RA patients display distinctive altered molecular profiles directly linked to their clinical status and associated with TNFi effectiveness. 2. Clinical response was associated with a specific modulation of the inflammatory profile, the reestablishment of the altered oxidative status, the reduction of NETosis and the reversion of related altered miRNAs. 3. The integrative analysis of the clinical and molecular profiles using machine learning allows the identification of novel signatures as potential predictors of therapeutic response to TNFi therapy.Disclosure of Interests:None declared

In the paper by Mok et al. (“Tackling challenges in care of Alzheimer's disease and other dementias amid the COVID-19 pandemic, now and in the future.”Alzheimer's Dement. 2020; 16: 1571-1581. https://doi.org/10.1002/alz.12143), an error occurred in the preparation of the paper for publication, requiring the following correction. In the initial publication of this article, Vorapun Senanarong, BSc, MD, was inadvertently omitted from the author group. The corrected author group and affiliations list appear above. We regret the error.

Resumen Objetivos Determinar el porcentaje de perdida de masa osea y el riesgo de fractura inducido por la terapia de deprivacion androgenica en pacientes con cancer de prostata. Material y metodos Estudio prospectivo en 2 fases. En la primera se recogieron variables demograficas, FRAX ® , densidad mineral osea y fracturas clinicas antes de iniciar la terapia y hasta un ano despues de finalizada. En la segunda se realizo una entrevista telefonica una media de 8,5 anos despues del inicio del estudio para evaluar nuevas fracturas. Resultados Se incluyeron 150 pacientes con una edad media de 67 anos y duracion media de la terapia de 24 meses. Antes del inicio del tratamiento 62 pacientes (41%) presentaban osteoporosis o baja masa osea en la densitometria. Despues del primer ano de tratamiento la densidad mineral osea descendio una media de 3,7% y 2,1% en la columna lumbar y el cuello femoral, respectivamente. Al final del segundo y tercer ano el porcentaje de perdida fue menor. Durante la primera fase del estudio 4 pacientes (2,7%) sufrieron una fractura. En la entrevista telefonica a 80 pacientes (53%) solo uno habia sufrido una fractura. Conclusiones En los pacientes con cancer de prostata y terapia de deprivacion androgenica la mayor perdida osea se produce durante el primer ano. Cuando el tratamiento no supera los 2 anos el riesgo absoluto de fractura es bajo, y la fractura clinica infrecuente a corto y a largo plazo.

The COVID‐19 pandemic has caused tremendous suffering for patients with dementia and their caregivers. We conducted a survey to study the impact of the pandemic on patients with mild frontotemporal dementia (FTD). Our preliminary findings demonstrate that patients with FTD have significant worsening in behavior and social cognition, as well as suffer greater negative consequences from disruption to health‐care services compared to patients with AD. The reduced ability to cope with sudden changes to social environments places patients with FTD at increased vulnerability to COVID‐19 infection as well as to poorer clinical and social outcomes. Caregivers of FTD patients also demonstrate high burden during crisis situations. A proportion of patients with FTD benefitted from use of web‐based interactive platforms. In this article, we outline the priority areas for research as well as a roadmap for future collaborative research to ensure greatest benefit for patients with FTD and their caregivers.

The University of Leicester, UK has been supporting the Catholic University of Cuenca (UCACUE) in Ecuador to deliver its vision of ensuring that every student on every course is exposed to an authentic problem-based learning (PBL) experience. By doing so, it is hoped that students gain a deeper understanding of their subject while also developing and using high level research, professional, and 21st Century skills to solve real community, regional, or national health, environmental, societal, business, or economic problems.The project’s primary object was the training of 70 core academic staff, composed of teams representing departments from all 8 faculties of UCACUE . The resulting capacity building programme has required the participants to participate in a series of 5-day workshops designed to develop their expertise in the application of two structured models of PBL. Based on a four-stage model and a 5E learning cycle model, the training programme has provided the academic staff with high-level skills to develop their own problem-based learning units (PBLs), perform action research to evaluate the outcomes of using PBL with their own students, capacity build other academics within their subject teams, and carry out and publish research on the implementation of the programme at UCACUE.After completion of the second year of a 3-year project (2015 – 2018), this team of 70 core academic staff have capacity built a further 103 academics, overseen development of 53 new PBLs, helped engage 2,561 students in problem-based learning activities, and published 5 academic papers.This paper will provide an introduction to the two PBL models adopted by the project and approaches used to capacity build the core team of 70 academics. It will also introduce case studies detailing how students from different faculties have utilised PBL to address real community problems, the solutions they have developed, and the outcomes of extensive research carried out on the professional development of academic staff. Also presented will be descriptions of how these forms of PBL have impacted the student learning experiences in terms of their ownership of individual projects, motivation, knowledge retention, overall understanding, achievement, team working skills, communication skills, problem solving capabilities, collaboration outside the classroom, engagement in the learning process, and their development of critical and creative thinking skills.UCACUE places a high level of importance on community outreach and this paper will also explore the ways in which their adoption of PBL has allowed its academics to engage with external bodies in ways that have raised the institution’s profile in ways that were not originally envisaged at the project outset.

Introducción: El paciente en diálisis va a sufrir una desnutrición proteico-calórica, con diferentes factores implicados en su aparición, lo cual se asocia con una elevadísima morbilidad cardiovascular y mortalidad. Se ha estimado una prevalencia de desnutrición en la población en hemodiálisis del 18-75%, siendo por tanto, un problema de especial relevancia en este tipo de pacientes. Objetivo: Realizar una revisión bibliográfica de los artículos científicos existentes sobre las variables que intervienen en la desnutrición del paciente en diálisis. Metodología: Se ha realizado una revisión bibliográfica mediante las bases de datos PubMed, Scielo, Pro- Quest. La búsqueda se ha realizado con términos Mesh, con una antigüedad no mayor de 5 años y con distintas palabras clave. Resultados: Se han revisado 19 artículos. La mayoría de los artículos fueron estudios observacionales y de revisión. Los factores que se asocian con desnutrición son la edad, pérdida de masa muscular, baja actividad física y dieta pobre en micronutrientes. Otro factor muy importante, es la inflamación. En cuanto a los métodos diagnósticos, son variados y diferentes, debido a la gran cantidad de variables que influyen en la desnutrición. Conclusiones: La desnutrición en pacientes en diálisis depende de distintas variables y no solamente de la dieta. Los factores que se asocian con desnutrición son mayor edad, pérdida de masa muscular, baja actividad física y dieta pobre en micronutrientes. Además, habría que añadir el doble papel que juega la inflamación en este proceso, pues puede ser tanto consecuencia como factor predisponente a la desnutrición.

Methanol intoxication can cause irreversible neurologic sequelae if unrecognized and untreated. Ingestion is the most common form of toxicity; however, dermal and inhalational exposures likewise occur but are documented rarely. While acute intoxication is commonly encountered, chronic exposure to methanol should also be highlighted. We report a case of a 57-year old female presenting in the emergency room with progressive dyspnea, metabolic acidosis with high anion gap, and metabolic encephalopathy. After emergency hemodialysis, the patient complained of vision loss on both eyes. Initial non-contrast cranial magnetic resonance imaging (MRI) revealed restricted diffusion of the intraorbital segment of both optic nerves. A thorough history revealed that she was applying a clear colorless liquid bought online all over her body for alleged pruritus for more than a year. The syndrome of metabolic acidosis with high anion gap, metabolic encephalopathy, vision loss, and laboratory findings led us to suspect a diagnosis of chronic methanol poisoning with an acute component. The liquid in question was sent for chemical analysis and result showed that it consisted of 95.5% Methanol. This case highlights the need for high index of clinical suspicion for methanol toxicity in the absence of oral consumption, the complications of chronic form of methanol intoxication, and the uncommon radiologic finding seen in diffusion-weighted imaging (DWI)., Highlights • Topical and inhalational exposures are less common but equally significant routes of methanol toxicity. • Chronic methanol intoxication can present with acute vision loss. • Restricted diffusion of the optic nerves on MRI is an uncommon finding in methanol intoxication.

Objectives:To evaluate the changes promoted in levels of circulating inflammatory mediators in RA patients in response to TNF-α inhibitors (TNFi) and anti-CD20 therapies, in order to identify biomarkers of clinical efficacy and potential predictors of therapeutic response to these drugs.Methods:In a prospective RA cohort multicenter study, we collected serum from RA patients with moderate or high disease activity prior and after 6 months of treatment with TNFi or rituximab (RTX), and analyzed levels of 27 proteins that constitute a multi-biomarker test of the inflammatory profile of these samples, using a multiplex immunoassay. Patients’ response was determined according to the EULAR response criteria (good/moderate/no). We compared basal levels of inflammatory molecules between the differential response patient groups and analyzed their discriminative ability. Logistic prediction models were created to assess the added value of potential inflammatory predictors.Results:Among 111 total RA patients, 50 of 85 (59%) patients in the TNFi group and 18 of 26 patients in the RTX group (69%) responded to the biologic treatment. High DAS28 or SDAI scores, or titers of auto-antibodies (RF or ACPA) at baseline were not predictive of response to any treatment. Instead, smoking habit and hyperlipidemia at baseline were predictors of a worse response to any of these bDMARDs.Of the molecules analyzed by the multiplex assay, 14 inflammatory mediators showed a significant downregulation on patients’ responders to TNFi therapy. Moreover, the decline on 7 biomolecules was related to reduced DAS28. After RTX treatment, 15 inflammatory mediators were reduced in patients with good clinical response; downregulation in 4 of those biomolecules correlated with reduced DAS28.In the search for predictors of response to each bDMARD, by using the MetaboAnalyst software, we could classify patients with distinctive therapeutic response based on the baseline levels of the inflammatory molecules analyzed. Receiver operating characteristic (ROC) analyses for those multiple biomarkers allowed us to further identify specific signatures of inflammatory biomolecules that may serve as predictors of response to each bDMARD therapy with high sensitivity and specificity. Thus, a signature of five molecules was identified as potential predictor of TNFi response [Vascular endothelial growth factor (VEGF), Eotaxin, RANTES, IL7 and IL-17]. Indeed, a signature including three highly expressed cytokines/chemokines in RA serum were identified as predictors of RTX response [interferon-inducible protein 10 (IP10), Eotaxin and monocyte chemotactic protein 1 (MCP-1)].Conclusion:The extensive analysis of serum inflammatory profile allowed to identify specific and distinctive signatures of biomolecules that, in coordination with known clinical and serological profiles, might predict the response of RA patients to TNFi or RTX treatments.Acknowledgments :Funded by Junta de Andalucía (PI-0285-2017), ISCIII, (PI18/00837 and RIER RD16/0012/0015) co-funded with FEDERDisclosure of Interests:María Luque-Tévar: None declared, Carlos Perez-Sanchez: None declared, Font Ugalde Pilar: None declared, Montserrat Romero-Gómez: None declared, Alejandra M. Patiño-Trives: None declared, Desiree Ruiz: None declared, Iván Arias de la Rosa: None declared, Maria del Carmen Abalos-Aguilera: None declared, Rafaela Ortega Castro: None declared, Alejandro Escudero Contreras: None declared, Carlos Rodríguez-Escalera Speakers bureau: Lilly, GSK, Novartis and Sanofi, José Javier Pérez Venegas: None declared, María Dolores Ruiz Montesinos: None declared, Carmen Dominguez: None declared, Carmen Romero Barco: None declared, Antonio Fernandez-Nebro: None declared, Natalia Mena-Vázquez: None declared, Jose Luis Marenco Speakers bureau: ABbvie, Pfzer, lilly, Julia Uceda: None declared, Mª Dolores Toledo-Coello: None declared, Nuria Barbarroja Puerto Grant/research support from: ROCHE and Pfizer., Speakers bureau: ROCHE and Celgene., Maria A Aguirre: None declared, Chary Lopez-Pedrera Grant/research support from: ROCHE and Pfizer., Eduardo Collantes-Estévez Grant/research support from: ROCHE and Pfizer., Speakers bureau: ROCHE, Lilly, Bristol and Celgene.

Background:Objectives:To analyse the effect of a teaching intervention for the technical performance of a reduced index of ultrasound synovitis by nurses without previous experience in musculoskeletal ultrasound (MSUS).Methods:Design: Quasi-experimental study of the before-after type. Protocol: The nurses received a theoretical-practical, face-to-face and intensive training of 8 hours, by an expert rheumatologist in musculoskeletal ultrasound (MSUS), to perform the Perricone index, which assesses the presence of grey-scale synovitis (GS) and quantifies the presence of a power-doppler (PD) signal semiquantitatively (0-3), in 6 joints (Wrists, 2nd Metacarpophalangeal (MCP) joints and knees). The theoretical knowledge acquired was assessed by an exam test type at the end of the training, and the technical skills were assessed by an ultrasound examination in patients with rheumatoid arthritis, immediately after the teaching session and at 18 months later. Variables: Illumination of the consultation, protection of privacy and unequivocal identification of the patient, technique (explorer ergonomics, bilateral comparison, use of both hands, measurement, marking and saving data), GS (probe position, centred image, cortical-cartilage-tendon display, depth, focus, frequency, gain), PD (probe pressure, PRF, position-width-depth of the box, focus, frequency, gain), synovial recesses (dorsal and palmar examination of the wrist, 2nd Metacarpophalangeal (MCP) joints and supra and parapatellar medial and lateral examination of the knees) and semi-quantitative gradation of synovitis in GS and PD. Statistical analysis: descriptive analysis, and in relation to the statistical significance tests for paired variables (pre and post teaching intervention) the McNemar test was used for dichotomous qualitative variables and McNemar-Bowker test for those of more than two categories.Results:5 nurses, 80% women, aged between 36 and 54 years participated. They adequately answered 100% of the 4-student test questions, and the remaining one matched 80% of them. The average time of baseline exploration was 45,2 ±3,8 minutes and the final time was 32,6 ± 3,5, improving the 5 students in an average of 12,6± 4,4 minutes. The technical aspects not performed correctly in the baseline ultrasound examination were the bilateral comparative, centred image, grey scale gain, measuring, correct anatomical image of the synovial recess of the wrist and position-width-depth of the Doppler box. An improvement was observed at 18 months in the unequivocal identification of the patient, adequate illumination of the consultation, bilateral comparison, correct anatomical acquisition of synovial recesses and the quantification of GS synovitis, but no statistically significant differences were observed, before and after the teaching intervention, in possible relation with the difficulty to use the ultrasound in their respective Rheumatology Units in clinical practice, but mainly because the aspects correctly performed in the baseline exploration were numerous.Conclusion:A formal training of rheumatology nurses in musculoskeletal ultrasound (MSUS) could be very useful, and cost-efficient, in the health care of patients with rheumatoid arthritis.Disclosure of Interests:None declared

Introduction Oligomeric amyloid-ß is a major toxic species associated with Alzheimer’s disease pathogenesis. Methods used to measure oligomeric amyloid-β in the blood have increased in number in recent years. The Multimer Detection System-Oligomeric Amyloid-β (MDS-OAβ) is a specific method to measure oligomerization tendencies in the blood. The objective of this study was to determine the association between amyloid-ß oligomerization in the plasma and structural changes of the brain. Methods We studied 162 subjects composed of 92 community-based normal healthy subjects, 17 with subjective cognitive decline, 14 with mild cognitive impairment and 39 with Alzheimer’s disease dementia. All subjects underwent MDS-OAβ and three-dimensional T1 magnetic resonance imaging. To determine the structural changes of the brain that are statistically correlated with MDS-OAβ level, we used voxel-based morphometry with corrections for age and total intracranial volume covariates. Results We found brain volume reduction in the bilateral temporal, amygdala, parahippocampal and lower parietal lobe and left cingulate and precuneus regions (family-wise error, p

The discovery of antibiotics has been one of the foremost medical advances of the 20th century. Antibiotics are essential components of medical practice used to treat, prevent, and control bacterial pathogens. Unfortunately the misuse and abuse of these “wonder” drugs has led to the development of multidrug-resistant organisms, which are very difficult to treat. Coincident with the increasing development of resistance is the decline in the development of new antibiotics by the pharmaceutical industry. The possibility of a “postantibiotic era” where bacterial infections will be untreatable may become real if international efforts do not come together to combat this complex problem. The present chapter will provide a general overview of antimicrobial resistance including a brief history of antibiotics, main mechanisms of resistance, “superbugs,” the spread of resistant genes in humans and nature, and antibiotics in the environment. New therapeutic approaches and alternatives to antibiotics will also be reviewed briefly.

A portable multiplexed bar-chart SpinChip (MB-SpinChip) integrated with nanoparticle-mediated magnetic aptasensors was developed for visual quantitative instrument-free detection of multiple pathogens. This versatile multiplexed SpinChip combines aptamer-specific recognition and nanoparticle-catalyzed pressure amplification to achieve a sample-to-answer output for sensitive point-of-care testing (POCT). This is the first report of pathogen detection using a volumetric bar-chart chip, and it is also the first bar-chart chip using a "spinning" mechanism to achieve multiplexed bar-chart detection. Additionally, the introduction of the spin unit not only enabled convenient sample introduction from one inlet to multiple separate channels in the multiplexed detection, but also elegantly solved the pressure cross-interference problem in the multiplexed volumetric bar-chart chip. This user-friendly MB-SpinChip allows visual quantitative detection of multiple pathogens simultaneously with high sensitivity but without utilizing any specialized instruments. Using this MB-SpinChip, three major foodborne pathogens including Salmonella enterica, Escherichia coli, and Listeria monocytogenes were specifically quantified in apple juice with limits of detection of about 10 CFU/mL. This MB-SpinChip with a bar-chart-based visual quantitative readout has great potential for the rapid simultaneous detection of various pathogens at the point of care and wide applications in food safety, environmental surveillance, and infectious disease diagnosis.

Background in March 2012 was implemented a FLS Unit coordinated by Rheumatology Objectives communicate the results of the unit in the 2012–2017 period. Methods Patients>50 years with fragility fracture. The program consists of: 1) training of primary care doctors (GP), 2) recruitment from the emergency room or admitted with hip fracture; 3) Bone densitometry; 4) patient education by a nurse; 6) report to GP with recommendations of managing; and 7) follow-up of persistence of treatment (telephonic survey plus prescription in the electronic records) at 3, 6, 12 and 24 months. Results The FLS has attended 1739 patients: mean age 73 y, 81% women. The location of fractures was forearm (32%), hip (24%), humerus (21%), vertebra (10%) and other locations (12%). Previous treatment with bisphosphonate 17%, 10% of them at baseline. After the baseline visit, 75% of patients were sent to GP and 25% to rheumatology. Treatment with bisphosphonate or equivalent was recommended to 1264 patients (72%). Persistence of treatment (analysed at 3, 6, 12 and 24 months in 1,051, 823, 622 and 351 patients, respectively) was 74%, 72%, 75% and 69%, respectively. Conclusions Our FLS is effective in terms of beginning and persistence of antifracture treatment in the medium term. Disclosure of Interest None declared

Background: People with mild cognitive impairment (MCI) are considered a high-risk population for developing dementia and therefore potential targets for preventive interventions. So far, no pharmacological interventions have proven to be effective. Latest evidence has laid the groundwork for the hypothesis that dancing can have beneficial effect on cognition by improving neuroplasticity. Objective: This study aimed to examine whether a structured modular ballroom dance intervention (INDAK) could improve cognition among Filipino older persons with MCI. Methods: A two-armed, single-blinded, quasi-experimental study was conducted in a community-based population at Marikina City, Philippines. Two hundred and seven participants older than 60 years old with MCI participated through self-assigned allocation to dance (N=101) and control (N=106) groups. The intervention group received INDAK consisting eight types of ballroom dances with increasing complexity lasting one hour, twice a week for 48 weeks. Neurologists and psychologists blinded to the group allocation administered baseline and post intervention assessments using Alzheimer’s Disease Assessment Scale – Cognitive (ADAS-Cog), Filipino version of the Montreal Cognitive Assessment (MoCA-P), Boston Naming Test (BNT), Geriatric Depression Scale (GDS), Instrumental Activities of Daily Living (IADL) and Disability Assessment for Dementia (DAD). Results: Baseline sociodemographic and clinical characteristics did not differ between groups. The mean differences between baseline and 48-week assessments were compared between dancers and controls, showing that the intervention group improved in ADAS-Cog, MoCA-P, BNT and GDS. Conclusion: INDAK is potentially a novel, ecological and inexpensive non-pharmacological intervention that can improve cognition among older Filipinos with MCI.

In this paper, we develop a local method to obtain depths from the 4D light field. In contrast to previous local depth from light field methods based on EPIs, e.g., 2D slices of the light field, the proposed method takes into account the 4D nature of the light field and uses its four dimensions. Furthermore, our technique adapts well to parallel hardware. The performance of the method is tested against a publicly available benchmark dataset and compared with other algorithms that previously have been tested with the same benchmark. Results show that the proposed method can achieve competitive results in reasonable time.

Crumpled metal foils are a new type of lightweight cellular materials. The engineering applications of crumpled foils require a deep understanding of their response to mechanical loads. In order to establish a comprehensive understanding of the mechanical behavior of crumpled foils, in the present study, the uniaxial compression experiments were performed on cylindrical samples of different packing densities manufactured by die compaction of randomly crumpled aluminum foils. This has allowed us to deduce the constitutive stress–strain relationship and quantify the relaxation behavior of crumpled foils. Consequently, we determine the mechanical properties (apparent Young modulus, yield stress, and longitudinal stiffness modulus) that govern the deformation behavior of crumpled samples in the whole range of relative deformation. The power-law dependence of mechanical properties on the initial packing density is revealed. The stress and strain relaxation behavior of crumpled foils is also elucidated. These findings provide further insight into the deformation behavior and relaxation mechanisms of crumpled aluminum foils. The knowledge of the mechanical and relaxation characteristics of crumpled aluminum foils is useful for their engineering application.

Most patients undergoing limb amputations suffer significant emotional changes. The aim of this study was to estimate the prevalence of suicide attempts and depression in a sample of Mexican patients with limb amputations and, second, to determine whether the patients' functionality correlates with the presence of depression. We studied 40 patients who had undergone a limb amputation. The suicide attempt was evaluated using the Suicide Intent Scale. The depression was assessed using the Hamilton Depression Rating Scale, whereas the functionality of the patients was measured using the Functional Independence Measure. In this sample, 90% were men, whereas only 10% were women. In terms of the suicide behavior, we identified suicide attempts in 27.5% of the patients. The rate of depression was 92.5%. In the Functional Independence Measure, we observed that 57.5% of the patients showed complete dependence. Finally, a significant correlation was found between depression and functionality (r=-0.75, P