Hospitalisation without delirium is not associated with cognitive decline in a population-based sample of older people-results from a nested, longitudinal cohort study

Background: Acute hospitalisation and delirium have individually been shown to adversely affect trajectories of cognitive decline but have not previously been considered together. This work aimed to explore the impact on cognition of hospital admission with and without delirium, compared to a control group with no hospital admissions. // Methods: The Delirium and Cognitive Impact in Dementia (DECIDE) study was nested within the Cognitive Function and Ageing Study II (CFAS II)–Newcastle cohort. CFAS II participants completed two baseline interviews, including the Mini-Mental State Examination (MMSE). During 2016, surviving participants from CFAS II–Newcastle were recruited to DECIDE on admission to hospital. Participants were reviewed daily to determine delirium status. During 2017, all DECIDE participants and age, sex and years of education matched controls without hospital admissions during 2016 were invited to repeat the CFAS II interview. Delirium was excluded in the control group using the Informant Assessment of Geriatric Delirium Scale (i-AGeD). Linear mixed effects modelling determined predictors of cognitive decline. // Results: During 2016, 82 of 205 (40%) DECIDE participants had at least one episode of delirium. At 1 year, 135 of 205 hospitalised participants completed an interview along with 100 controls. No controls experienced delirium (i-AGeD>4). Delirium was associated with a faster rate of cognitive decline compared to those without delirium (β = −2.2, P < 0.001), but number of hospital admissions was not (P = 0.447). // Conclusions: These results suggest that delirium during hospitalisation rather than hospitalisation per se is a risk factor for future cognitive decline, emphasising the need for dementia prevention studies that focus on delirium intervention

Micro-scale environment and mental health in later life: Results from the Cognitive Function and Ageing Study II (CFAS II)

$\textit{Background:}$ Poor micro-scale environmental features, such as graffiti and broken windows, have been associated with crime and signs of social disorder with a potential impact on mental health. The aim of this study is to investigate the association between micro-scale environment and mental health problems in later life, including cognitive (cognitive impairment and dementia) and common mental disorders (depressive and anxiety symptoms). $\textit{Methods:}$ The method of visual image audits was used to collect micro-scale environmental data for 3590 participants in the Cognitive Function and Ageing Study II, a population-based multicentre cohort of people aged 65 or above in England. Multilevel logistic regression was used to examine the associations between the quality of micro-scale environment and mental health problems taking into account urban/rural difference. $\textit{Results:}$ Poor quality of micro-scale environment was associated with nearly 20% increased odds of depressive (OR: 1.19; 95% CI: 0.99, 1.44) and anxiety symptoms (OR: 1.17; 95% CI: 0.99, 1.38) while the direction of association for cognitive disorders differed across urban and rural settings. Although higher odds of cognitive disorders were found in rural settings, living in a poor quality environment was associated with nearly twice higher odds of cognitive impairment (OR: 1.88; 95% CI: 1.18, 2.97) in urban conurbations but 20% lower odds in rural areas (OR: 0.80; 95% CI: 0.57, 1.11). $\textit{Limitations:}$ The causal direction could not be fully determined due to the cross-sectional nature of the data. The visual nature of the environmental assessment tool means it likely does not fully capture features related to the availability of local support services, or opportunities for social participation and interaction. $\textit{Conclusions:}$ The quality of micro-scale environment appears to be important to mental health in older people. Interventions may incorporate the environmental aspect to reduce cognitive and common mental disorders.Medical Research Counci

The role of anti-malarial drugs in eliminating malaria

Effective anti-malarial drug treatment reduces malaria transmission. This alone can reduce the incidence and prevalence of malaria, although the effects are greater in areas of low transmission where a greater proportion of the infectious reservoir is symptomatic and receives anti-malarial treatment. Effective treatment has greater effects on the transmission of falciparum malaria, where gametocytogenesis is delayed, compared with the other human malarias in which peak gametocytaemia and transmissibility coincides with peak asexual parasite densities. Mature Plasmodium falciparum gametocytes are more drug resistant and affected only by artemisinins and 8-aminoquinolines. The key operational question now is whether primaquine should be added to artemisinin combination treatments for the treatment of falciparum malaria to reduce further the transmissibility of the treated infection. Radical treatment with primaquine plays a key role in the eradication of vivax and ovale malaria. More evidence is needed on the safety of primaquine when administered without screening for G6PD deficiency to inform individual and mass treatment approaches in the context of malaria elimination programmes

Hospitalisation without delirium is not associated with cognitive decline in a population-based sample of older people – results from a nested, longitudinal cohort study

This is the final version. Available on open access from Oxford University Press via the DOI in this recordBackground Acute hospitalisation and delirium have individually been shown to adversely affect trajectories of cognitive decline but have not previously been considered together. This work aimed to explore the impact on cognition of hospital admission with and without delirium, compared to a control group with no hospital admissions. Methods The Delirium and Cognitive Impact in Dementia (DECIDE) study was nested within the Cognitive Function and Ageing Study II (CFAS II)–Newcastle cohort. CFAS II participants completed two baseline interviews, including the MiniMental State Examination (MMSE). During 2016, surviving participants from CFAS II–Newcastle were recruited to DECIDE on admission to hospital. Participants were reviewed daily to determine delirium status. During 2017, all DECIDE participants and age, sex and years of education matched controls without hospital admissions during 2016 were invited to repeat the CFAS II interview. Delirium was excluded in the control group using the Informant Assessment of Geriatric Delirium Scale (i-AGeD). Linear mixed effects modelling determined predictors of cognitive decline. Results During 2016, 82 of 205 (40%) DECIDE participants had at least one episode of delirium. At one-year, 135 of 205 hospitalised participants completed an interview along with 100 controls. No controls experienced delirium (iAGeD>4). Delirium was associated with a faster rate of cognitive decline compared to those without delirium (β=-2.2, p<0.001), but number of hospital admissions was not (p=0.447). Conclusions These results suggest that delirium during hospitalisation rather than hospitalisation per se is a risk factor for future cognitive decline, emphasising the need for dementia prevention studies that focus on delirium intervention.Alzheimer’s SocietyMedical Research Council (MRC

Inhibition of Hippocampal Synaptic Activity by ATP, Hypoxia or Oxygen-Glucose Deprivation Does Not Require CD73

Adenosine, through activation of its A1 receptors, has neuroprotective effects during hypoxia and ischemia. Recently, using transgenic mice with neuronal expression of human equilibrative nucleoside transporter 1 (hENT1), we reported that nucleoside transporter-mediated release of adenosine from neurons was not a key mechanism facilitating the actions of adenosine at A1 receptors during hypoxia/ischemia. The present study was performed to test the importance of CD73 (ecto-5′-nucleotidase) for basal and hypoxic/ischemic adenosine production. Hippocampal slice electrophysiology was performed with CD73+/+ and CD73−/− mice. Adenosine and ATP had similar inhibitory effects in both genotypes, with IC50 values of approximately 25 µM. In contrast, ATP was a less potent inhibitor (IC50 = 100 µM) in slices from mice expressing hENT1 in neurons. The inhibitory effects of ATP in CD73+/+ and CD73−/− slices were blocked by the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) and were enhanced by the nucleoside transport inhibitor S-(4-nitrobenzyl)-6-thioinosine (NBTI), consistent with effects that are mediated by adenosine after metabolism of ATP. AMP showed a similar inhibitory effect to ATP and adenosine, indicating that the response to ATP was not mediated by P2 receptors. In comparing CD73−/− and CD73+/+ slices, hypoxia and oxygen-glucose deprivation produced similar depression of synaptic transmission in both genotypes. An inhibitor of tissue non-specific alkaline phosphatase (TNAP) was found to attenuate the inhibitory effects of AMP and ATP, increase basal synaptic activity and reduce responses to oxygen-glucose deprivation selectively in slices from CD73−/− mice. These results do not support an important role for CD73 in the formation of adenosine in the CA1 area of the hippocampus during basal, hypoxic or ischemic conditions, but instead point to TNAP as a potential source of extracellular adenosine when CD73 is absent

Developing and testing a nurse-led intervention to support bereavement in relatives in the intensive care (BRIC study): a protocol of a pre-post intervention study

BACKGROUND: When a patient is approaching death in the intensive care unit (ICU), patients' relatives must make a rapid transition from focusing on their beloved one's recovery to preparation for their unavoidable death. Bereaved relatives may develop complicated grief as a consequence of this burdensome situation; however, little is known about appropriate options in quality care supporting bereaved relatives and the prevalence and predictors of complicated grief in bereaved relatives of deceased ICU patients in the Net

Telomeric expression sites are highly conserved in trypanosoma brucei

Subtelomeric regions are often under-represented in genome sequences of eukaryotes. One of the best known examples of the use of telomere proximity for adaptive purposes are the bloodstream expression sites (BESs) of the African trypanosome Trypanosoma brucei. To enhance our understanding of BES structure and function in host adaptation and immune evasion, the BES repertoire from the Lister 427 strain of T. brucei were independently tagged and sequenced. BESs are polymorphic in size and structure but reveal a surprisingly conserved architecture in the context of extensive recombination. Very small BESs do exist and many functioning BESs do not contain the full complement of expression site associated genes (ESAGs). The consequences of duplicated or missing ESAGs, including ESAG9, a newly named ESAG12, and additional variant surface glycoprotein genes (VSGs) were evaluated by functional assays after BESs were tagged with a drug-resistance gene. Phylogenetic analysis of constituent ESAG families suggests that BESs are sequence mosaics and that extensive recombination has shaped the evolution of the BES repertoire. This work opens important perspectives in understanding the molecular mechanisms of antigenic variation, a widely used strategy for immune evasion in pathogens, and telomere biology

Structure of bryozoan communities in an Antarctic glacial fjord (Admiralty Bay, South Shetlands)

Bryozoans are among the most important groups of the Southern Ocean benthic macrofauna, both in terms of species richness and abundance. However, there is a considerable lack of ecological research focused on their distribution patterns and species richness on smaller scale, especially in the soft bottom habitats of Antarctic glacial fjords. The aim of this study was to describe those patterns in the Admiralty Bay. Forty-nine Van Veen grab samples were collected at the depth range from 15 to 265 m, in the summer season of 1979/1980, at three sites distributed along the main axis of the fjord. Among 53 identified species of bryozoans, 32 were recorded in the Admiralty Bay for the first time. The most common and abundant species were Himantozoum antarcticum, Inversiula nutrix and Nematoflustra flagellata. Genera such as Arachnopusia, Cellarinella and Osthimosia were the most speciose taxa. It was demonstrated that depth was important for the distribution of the bryozoans. More than half of the recorded species were found only below 70 m. An influence of glacial disturbance was reflected in the dominance structure of colony growth-forms. The inner region of the fjord was dominated almost entirely by encrusting species, while the diversity of bryozoan growth-forms in less disturbed areas was much higher. In those sites the highest percentage of branched, tuft like species represented by buguliform and flustriform zoaria was observed.The study was supported by a grant of Polish Ministry of Science and Higher Education No. 51/N-IPY/2007/0 as well as Census of Antarctic Marine Life Project. Krzysztof Pabis was also partially supported by University of Lodz internal funds. This research was also supported by the Polish Geological Institute-National Research Institute during the realization of the project numbered 40.2900.0903.18.0 titled “Bryozoan assemblage of Admiralty Bay—richness, diversity and abundance.” Urszula Hara is deeply grateful to Leszek Giro (Micro-area Analyses Laboratory at the Polish Geological Institute-National Research Institute, Warsaw), for providing SEM assistance during the project. We also want to thank two anonymous reviewers for their suggestions that helped us improve this article. Thanks are also due to Magdalena Błażewicz-Paszkowycz for language correction and polishing the final version of the manuscript

Optimally timing primaquine treatment to reduce Plasmodium falciparum transmission in low endemicity Thai-Myanmar border populations

<p>Abstract</p> <p>Background</p> <p>Effective malaria control has successfully reduced the malaria burden in many countries, but to eliminate malaria, these countries will need to further improve their control efforts. Here, a malaria control programme was critically evaluated in a very low-endemicity Thai-Myanmar border population, where early detection and prompt treatment have substantially reduced, though not ended, <it>Plasmodium falciparum </it>transmission, in part due to carriage of late-maturing gametocytes that remain post-treatment. To counter this effect, the WHO recommends the use of a single oral dose of primaquine along with an effective blood schizonticide. However, while the effectiveness of primaquine as a gametocidal agent is widely documented, the mismatch between primaquine's short half-life, the long-delay for gametocyte maturation and the proper timing of primaquine administration have not been studied.</p> <p>Methods</p> <p>Mathematical models were constructed to simulate 8-year surveillance data, between 1999 and 2006, of seven villages along the Thai-Myanmar border. A simple model was developed to consider primaquine pharmacokinetics and pharmacodynamics, gametocyte carriage, and infectivity.</p> <p>Results</p> <p>In these populations, transmission intensity is very low, so the <it>P. falciparum </it>parasite rate is strongly linked to imported malaria and to the fraction of cases not treated. Given a 3.6-day half-life of gametocyte, the estimated duration of infectiousness would be reduced by 10 days for every 10-fold reduction in initial gametocyte densities. Infectiousness from mature gametocytes would last two to four weeks and sustain some transmission, depending on the initial parasite densities, but the residual mature gametocytes could be eliminated by primaquine. Because of the short half-life of primaquine (approximately eight hours), it was immediately obvious that with early administration (within three days after an acute attack), primaquine would not be present when mature gametocytes emerged eight days after the appearance of asexual blood-stage parasites. A model of optimal timing suggests that primaquine follow-up approximately eight days after a clinical episode could further reduce the duration of infectiousness from two to four weeks down to a few days. The prospects of malaria elimination would be substantially improved by changing the timing of primaquine administration and combining this with effective detection and management of imported malaria cases. The value of using primaquine to reduce residual gametocyte densities and to reduce malaria transmission was considered in the context of a malaria transmission model; the added benefit of the primaquine follow-up treatment would be relatively large only if a high fraction of patients (>95%) are initially treated with schizonticidal agents.</p> <p>Conclusion</p> <p>Mathematical models have previously identified the long duration of <it>P. falciparum </it>asexual blood-stage infections as a critical point in maintaining malaria transmission, but infectiousness can persist for two to four weeks because of residual populations of mature gametocytes. Simulations from new models suggest that, in areas where a large fraction of malaria cases are treated, curing the asexual parasitaemia in a primary infection, and curing mature gametocyte infections with an eight-day follow-up treatment with primaquine have approximately the same proportional effects on reducing the infectious period. Changing the timing of primaquine administration would, in all likelihood, interrupt transmission in this area with very good health systems and with very low endemicity.</p