Does loneliness contribute to mild cognitive impairment and dementia? A systematic review and meta-analysis of longitudinal studies

There is growing evidence that loneliness is associated with mild cognitive impairment (MCI) and dementia. However, the extent of this association remains unclear. A systematic review and meta-analysis of longitudinal studies examining this association was conducted. Six electronic databases were searched from inception to November 15th 2018. A random-effects meta-analysis was performed to obtain pooled estimates and 95% CIs. Studies were also assessed for heterogeneity, methodological quality and publication bias. A total of 4270 hits were retrieved based on the initial search strategy and ten studies met the eligibility criteria involving 37339 individuals (mean age from 64.9 to 83.1 years). Variation between studies was present for the measurement of loneliness as well as for the case ascertainment of MCI and dementia. Loneliness was positively associated with increased risk of dementia (overall RR = 1.26; 95% CI = 1.14, 1.40; n = 8). Due to lack of sufficient data, we could not explore the association between loneliness and risk of MCI through a meta-analysis, but limited evidence suggests a potential effect of loneliness on MCI. A further understanding of the deleterious effects of loneliness on MCI and dementia may assist the design of environmental and psychological interventions to prevent or delay the onset of these neuropsychiatric condition

Orodispersible tablets: therapeutic and technological advantages of development

Los comprimidos bucodispersables se definen como comprimidos no recubiertos destinados a ser colocados en la boca, donde se dispersan rápidamente antes de ser tragados. Estas formulaciones son conocidas por las siglas FDDT´s (Fast Dissolving Disintegrating Tablets). Son útiles para la administración a pacientes con dificultades en la deglución, presentan una elevada aceptación por parte del paciente, mejoran de la biodisponibilidad del principio activo y suponen una nueva alternativa para la industria farmacéutica. Dentro de sus inconvenientes destacan el poco conocimiento por parte del paciente, la baja resistencia mecánica, su mayor susceptibilidad a la degradación por temperatura y humedad; la falta, a veces, de bioequivalencia con las formulaciones convencionales, y la dificultad de obtener liberaciones prolongadas o retardadas del principio activo.A nivel tecnológico, existen varios procesos que se pueden aplicar en su elaboración. Con los métodos clásicos de elaboración de comprimidos, mediante la correcta selección de los excipientes y de las variables de la etapa de compresión se obtienen unos comprimidos en los que existe un equilibrio entre dureza y disgregación. Han surgido una serie de tecnologías novedosas: Flashtab, Wowtab, Orasolv y Durasolv. Otra opción es el empleo de técnicas de liofilización, aunque presenta como desventaja su alto coste. Algunas tecnologías especiales patentadas como son Lyoc, QuickSolv y Zydis. Por último, estos comprimidos se pueden elaborar por el método de los polímeros entrecruzados, también conocido como FlashDose y se basa en la formación de una matriz de hilos de azúcares entrelazados.The orally disintegrating tablets are defined as non-coated tablets intended to be placed in the mouth where they disperse rapidly before being swallowed. These formulations are known by the acronym FDDT's (Fast Dissolving Disintegrating Tablets). They are useful for administration to patients with swallowing difficulties, have a high acceptance by the patient, improve bioavailability of the active ingredient and represent a new alternative for the pharmaceutical industry. Among its disadvantages include limited knowledge by the patient, low mechanical strength, increased susceptibility to degradation by temperature and humidity; lack sometimes bioequivalence with conventional formulations, and the difficulty of obtaining prolonged release or delayed active ingredient. At the technological level, there are several processes that can be applied in their preparation. With classical methods of tabletting, by proper selection of excipients and the variables of the compression stage a tablet in which there is a balance between hardness and disintegration are obtained. Flashtab, Wowtab, Orasolv and Durasolv: They have a number of new technologies emerged. Another option is the use of freeze drying techniques, but has the disadvantage of its high cost. Some special patented technologies such as Lyoc, QuickSolv and Zydis. Finally, these tablets may be made by the method of Crosslinked polymers, also known as FlashDose and is based on the formation of a matrix of interwoven threads sugars

Congenital long QT syndrome

Artículo especialThe long QT syndrome (LQTS) is an hereditary disease that produces a malfunction on the sodium and potassium channels of the heart and lengthens the duration of the cardiac repolarization stage. It is characterized by the appearance of syncopes, arrhythmias and even sudden death. There are two variants of the congenital LQTS: the autosomal dominant Romano-Ward syndrome and the autosomal recessive Jervell-Lange-Nielsen syndrome, that is associated with sensorineural deafness and is less frequent than the other type. The diagnosis is made from the clinical criteria, the electrocardiogram and the family history. In the last few years, molecular studies have been developed, opening new possibilities not only for its diagnosis but also for the treatment of these patients.N

Shell structures in aluminum nanocontacts at elevated temperatures

Aluminum nanocontact conductance histograms are studied experimentally from room temperature up to near the bulk melting point. The dominant stable configurations for this metal show a very early crossover from shell structures at low wire diameters to ionic subshell structures at larger diameters. At these larger radii, the favorable structures are temperature-independent and consistent with those expected for ionic subshell (faceted) formations in face-centered cubic geometries. When approaching the bulk melting temperature, these local stability structures become less pronounced as shown by the vanishing conductance histogram peak structure

Dynamics of disease characteristics and clinical management of critically ill COVID-19 patients over the time course of the pandemic: an analysis of the prospective, international, multicentre RISC-19-ICU registry.

BACKGROUND It remains elusive how the characteristics, the course of disease, the clinical management and the outcomes of critically ill COVID-19 patients admitted to intensive care units (ICU) worldwide have changed over the course of the pandemic. METHODS Prospective, observational registry constituted by 90 ICUs across 22 countries worldwide including patients with a laboratory-confirmed, critical presentation of COVID-19 requiring advanced organ support. Hierarchical, generalized linear mixed-effect models accounting for hospital and country variability were employed to analyse the continuous evolution of the studied variables over the pandemic. RESULTS Four thousand forty-one patients were included from March 2020 to September 2021. Over this period, the age of the admitted patients (62 [95% CI 60-63] years vs 64 [62-66] years, p < 0.001) and the severity of organ dysfunction at ICU admission decreased (Sequential Organ Failure Assessment 8.2 [7.6-9.0] vs 5.8 [5.3-6.4], p < 0.001) and increased, while more female patients (26 [23-29]% vs 41 [35-48]%, p < 0.001) were admitted. The time span between symptom onset and hospitalization as well as ICU admission became longer later in the pandemic (6.7 [6.2-7.2| days vs 9.7 [8.9-10.5] days, p < 0.001). The PaO2/FiO2 at admission was lower (132 [123-141] mmHg vs 101 [91-113] mmHg, p < 0.001) but showed faster improvements over the initial 5 days of ICU stay in late 2021 compared to early 2020 (34 [20-48] mmHg vs 70 [41-100] mmHg, p = 0.05). The number of patients treated with steroids and tocilizumab increased, while the use of therapeutic anticoagulation presented an inverse U-shaped behaviour over the course of the pandemic. The proportion of patients treated with high-flow oxygen (5 [4-7]% vs 20 [14-29], p < 0.001) and non-invasive mechanical ventilation (14 [11-18]% vs 24 [17-33]%, p < 0.001) throughout the pandemic increased concomitant to a decrease in invasive mechanical ventilation (82 [76-86]% vs 74 [64-82]%, p < 0.001). The ICU mortality (23 [19-26]% vs 17 [12-25]%, p < 0.001) and length of stay (14 [13-16] days vs 11 [10-13] days, p < 0.001) decreased over 19 months of the pandemic. CONCLUSION Characteristics and disease course of critically ill COVID-19 patients have continuously evolved, concomitant to the clinical management, throughout the pandemic leading to a younger, less severely ill ICU population with distinctly different clinical, pulmonary and inflammatory presentations than at the onset of the pandemic

“Tourism, water, and gender”—An international review of an unexplored nexus

This international literature review of the tourism–water nexus identifies a gender gap. Tourism development can affect water supply both quantitatively and qualitatively. Many regions will face considerable problems of water availability and quality, affecting their tourism sector and increasing competition with local residents, and other industries especially agriculture. This international review of literature explores the tourism–water nexus, comparing and contrasting literature published in English, Chinese, and Spanish. Securing access to safe water for continued tourism development is a common theme and the vast majority of work has focused on hotels including water pricing, water-saving practices and innovative management methods. In all continents, struggles are apparent, and the unsustainability of tourism is having impacts on water quantity and quality. This article identifies significant gaps in the literature including climate change, the energy-water nexus, and the links with the Sustainable Development Goals. Furthermore, studies from a gendered perspective are minimal and the potential for areas of further gendered studies within the tourism–water nexus are highlighted including intersectionality, water insecurity and sanitation, tourism and gender based violence, and additional unpaid care work

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Physical conditions and chemical abundances in photoionized nebulae from optical spectra

This chapter presents a review on the latest advances in the computation of physical conditions and chemical abundances of elements present in photoionized gas H II regions and planetary nebulae). The arrival of highly sensitive spectrographs attached to large telescopes and the development of more sophisticated and detailed atomic data calculations and ionization correction factors have helped to raise the number of ionic species studied in photoionized nebulae in the last years, as well as to reduce the uncertainties in the computed abundances. Special attention will be given to the detection of very faint lines such as heavy-element recombination lines of C, N and O in H II regions and planetary nebulae, and collisionally excited lines of neutron-capture elements (Z >30) in planetary nebulae.Comment: Book Chapter. 31 pages. 6 Figures. Accepted for publication in the book "Reviews in Frontiers of Modern Astrophysics: From Space Debris to Cosmology" (eds Kabath, Jones and Skarka; publisher Springer Nature) funded by the European Union Erasmus+ Strategic Partnership grant "Per Aspera Ad Astra Simul" 2017-1-CZ01-KA203-03556

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues