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To Investigate the peripheral inflammatory profile in patients with mild cognitive impairment (MCI) from three subgroups – probable Lewy body disease (probable MCI-LB), possible Lewy body disease, and probable Alzheimer’s disease (probable MCI-AD) – as well as associations with clinical features.
Memory clinics and dementia services.
Patients were classified based on clinical symptoms as probable MCI-LB (n = 38), possible MCI-LB (n = 18), and probable MCI-AD (n = 21). Healthy comparison subjects were recruited (n = 20).
Ten cytokines were analyzed from plasma samples: interferon (IFN)-gamma, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, and tumor necrosis factor (TNF)-alpha. C-reactive protein levels were investigated.
There was a higher level of IL-10, IL-1beta, IL-2, and IL-4 in MCI groups compared to the healthy comparison group (p < 0.0085). In exploratory analyses to understand these findings, the MC-AD group lower IL-1beta (p = 0.04), IL-2 (p = 0.009), and IL-4 (p = 0.012) were associated with increasing duration of memory symptoms, and in the probable MCI-LB group, lower levels of IL-1beta were associated with worsening motor severity (p = 0.002). In the possible MCI-LB, longer duration of memory symptoms was associated with lower levels of IL-1beta (p = 0.003) and IL-4 (p = 0.026).
There is increased peripheral inflammation in patients with MCI compared to healthy comparison subjects regardless of the MCI subtype. These possible associations with clinical features are consistent with other work showing that inflammation is increased in early disease but require replication. Such findings have importance for timing of putative therapeutic strategies aimed at lowering inflammation.
Adding Au to Pd nanoparticles (NPs) can impart high catalytic activity with respect to hydrogenation of a wide range of substances. These materials are often synthesized by reducing metallic precursors; hence, sonochemical and solvothermal processes are commonly used to anchor these bimetals onto thin supports, including graphene. Although similar NPs have been studied reasonably well, a clear understanding of structural characteristics relative to their synthesis parameters is lacking, due to limitations in characterization techniques, which may prevent optimization of this very promising catalyst. In this report, a strategic approach has been used to identify this structural and material synthesis correlation, starting with controlled sample preparation and followed by detailed characterization. This includes advanced scanning transmission electron microscopy and electron energy loss spectroscopy; the latter using a state-of-the-art instrumentation to map the distribution of Pd and Au, and to identify chemical state of the Pd NPs, which has not been previously reported. Results show that catalytic bimetal NP clusters were made of small zero-valent Pd NPs aggregating to form a shell around an Au core. Not only can the described characterization approach be applied to similar material systems, but the results can guide the optimization of the synthesis procedures.
Important Bird and Biodiversity Areas (IBAs) are sites identified as being globally important for the conservation of bird populations on the basis of an internationally agreed set of criteria. We present the first review of the development and spread of the IBA concept since it was launched by BirdLife International (then ICBP) in 1979 and examine some of the characteristics of the resulting inventory. Over 13,000 global and regional IBAs have so far been identified and documented in terrestrial, freshwater and marine ecosystems in almost all of the world’s countries and territories, making this the largest global network of sites of significance for biodiversity. IBAs have been identified using standardised, data-driven criteria that have been developed and applied at global and regional levels. These criteria capture multiple dimensions of a site’s significance for avian biodiversity and relate to populations of globally threatened species (68.6% of the 10,746 IBAs that meet global criteria), restricted-range species (25.4%), biome-restricted species (27.5%) and congregatory species (50.3%); many global IBAs (52.7%) trigger two or more of these criteria. IBAs range in size from < 1 km2 to over 300,000 km2 and have an approximately log-normal size distribution (median = 125.0 km2, mean = 1,202.6 km2). They cover approximately 6.7% of the terrestrial, 1.6% of the marine and 3.1% of the total surface area of the Earth. The launch in 2016 of the KBA Global Standard, which aims to identify, document and conserve sites that contribute to the global persistence of wider biodiversity, and whose criteria for site identification build on those developed for IBAs, is a logical evolution of the IBA concept. The role of IBAs in conservation planning, policy and practice is reviewed elsewhere. Future technical priorities for the IBA initiative include completion of the global inventory, particularly in the marine environment, keeping the dataset up to date, and improving the systematic monitoring of these sites.
Rapid identification of esophageal intubations is critical to avoid patient morbidity and mortality. Continuous waveform capnography remains the gold standard for endotracheal tube (ETT) confirmation, but it has limitations. Point-of-care ultrasound (POCUS) may be a useful alternative for confirming ETT placement. The objective of this study was to determine the accuracy of paramedic-performed POCUS identification of esophageal intubations with and without ETT manipulation.
A prospective, observational study using a cadaver model was conducted. Local paramedics were recruited as subjects and each completed a survey of their demographics, employment history, intubation experience, and prior POCUS training. Subjects participated in a didactic session in which they learned POCUS identification of ETT location. During each study session, investigators randomly placed an ETT in either the trachea or esophagus of four cadavers, confirmed with direct laryngoscopy. Subjects then attempted to determine position using POCUS both without and with manipulation of the ETT. Manipulation of the tube was performed by twisting the tube. Descriptive statistics and logistic regression were used to assess the results and the effects of previous paramedic experience.
During 12 study sessions, from March 2014 through December 2015, 57 subjects participated, evaluating a total of 228 intubations: 113 tracheal and 115 esophageal. Subjects were 84.0% male, mean age of 39 years (range: 22 - 62 years), with median experience of seven years (range: 0.6 - 39 years). Paramedics correctly identified ETT location in 158 (69.3%) cases without and 194 (85.1%) with ETT manipulation. The sensitivity and specificity of identifying esophageal location without ETT manipulation increased from 52.2% (95% confidence interval [CI], 43.0-61.0) and 86.7% (95% CI, 81.0-93.0) to 87.0% (95% CI, 81.0-93.0) and 83.2% (95% CI, 0.76-0.90) after manipulation (P<.0001), without affecting specificity (P=.45). Subjects correctly identified 41 previously incorrectly identified esophageal intubations. Paramedic experience, previous intubations, and POCUS experience did not correlate with ability to identify tube location.
Paramedics can accurately identify esophageal intubations with POCUS, and manipulation improves identification. Further studies of paramedic use of dynamic POCUS to identify inadvertent esophageal intubations are needed.
LemaPC, O’BrienM, WilsonJ, St. JamesE, LindstromH, DeAngelisJ, CaldwellJ, MayP, ClemencyB.Avoid the Goose! Paramedic Identification of Esophageal Intubation by Ultrasound. Prehosp Disaster Med.2018;33(4):406–410
Palladium (Pd) and gold (Au) nanoparticles (NPs) hybridized on two types of carbon supports, graphene and granular activated carbon (GAC), were shown to be promising catalysts for the sustainable hydrodehalogenation of aqueous trichloroethylene (TCE). These catalysts are capable of degrading TCE more rapidly than commercial Pd-on-GAC catalysts. The catalysts were synthesized at room temperature without the use of any environmentally unfriendly chemicals. Pd was chosen for its catalytic potency to break down TCE, while Au acts as a strong promoter of the catalytic activity of Pd. The results indicate that both graphene and GAC are favorable supports for the NPs due to high surface-to-volume ratios, unique surface properties, and the prevention of NP aggregation. The properties of NP catalysts were characterized using electron microscopy and spectroscopy techniques. The TCE degradation results indicate that the GAC-supported catalysts have a higher rate of TCE removal than the commercial Pd-on-GAC catalyst, and the degradation rate is greatly increased when using graphene-supported samples.
Dopaminergic imaging has high diagnostic accuracy for dementia with Lewy bodies (DLB) at the dementia stage. We report the first investigation of dopaminergic imaging at the prodromal stage.
We recruited 75 patients over 60 with mild cognitive impairment (MCI), 33 with probable MCI with Lewy body disease (MCI-LB), 15 with possible MCI-LB and 27 with MCI with Alzheimer's disease. All underwent detailed clinical, neurological and neuropsychological assessments and FP-CIT [123I-N-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)] dopaminergic imaging. FP-CIT scans were blindly rated by a consensus panel and classified as normal or abnormal.
The sensitivity of visually rated FP-CIT imaging to detect combined possible or probable MCI-LB was 54.2% [95% confidence interval (CI) 39.2–68.6], with a specificity of 89.0% (95% CI 70.8–97.6) and a likelihood ratio for MCI-LB of 4.9, indicating that FP-CIT may be a clinically important test in MCI where any characteristic symptoms of Lewy body (LB) disease are present. The sensitivity in probable MCI-LB was 61.0% (95% CI 42.5–77.4) and in possible MCI-LB was 40.0% (95% CI 16.4–67.7).
Dopaminergic imaging had high specificity at the pre-dementia stage and gave a clinically important increase in diagnostic confidence and so should be considered in all patients with MCI who have any of the diagnostic symptoms of DLB. As expected, the sensitivity was lower in MCI-LB than in established DLB, although over 50% still had an abnormal scan. Accurate diagnosis of LB disease is important to enable early optimal treatment for LB symptoms.
The accurate clinical characterisation of mild cognitive impairment (MCI) is becoming increasingly important. The aim of this study was to compare the neuropsychiatric symptoms and cognitive profile of MCI with Lewy bodies (MCI-LB) with Alzheimer's disease MCI (MCI-AD).
Participants were ⩾60 years old with MCI. Each had a thorough clinical and neuropsychological assessment and 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane single photon emission computed tomography FP-CIT SPECT). MCI-LB was diagnosed if two or more diagnostic features of dementia with Lewy bodies were present (visual hallucinations, cognitive fluctuations, motor parkinsonism, rapid eye movement sleep behaviour disorder or positive FP-CIT SPECT). A Lewy body Neuropsychiatric Supportive Symptom Count (LBNSSC) was calculated based on the presence or absence of the supportive neuropsychiatric symptoms defined by the 2017 DLB diagnostic criteria: non-visual hallucinations, delusions, anxiety, depression and apathy.
MCI-LB (n = 41) had a higher LBNSSC than MCI-AD (n = 24; 1.8 ± 1.1 v. 0.7 ± 0.9, p = 0.001). 67% of MCI-LB had two or more of those symptoms, compared with 16% of MCI-AD (Likelihood ratio = 4.2, p < 0.001). MCI-LB subjects scored lower on tests of attention, visuospatial function and verbal fluency. However, cognitive test scores alone did not accurately differentiate MCI-LB from MCI-AD.
MCI-LB is associated with neuropsychiatric symptoms and a cognitive profile similar to established DLB. This supports the concept of identifying MCI-LB based on the presence of core diagnostic features of DLB and abnormal FP-CIT SPECT imaging. The presence of supportive neuropsychiatric clinical features identified in the 2017 DLB diagnostic criteria was helpful in differentiating between MCI-LB and MCI-AD.
Lewy body dementia (consisting of dementia with Lewy bodies and Parkinson's disease dementia) is a common neurodegenerative disease characterised by visual hallucinations, fluctuating attention, motor disturbances, falls, and sensitivity to antipsychotics. This combination of features presents challenges for pharmacological management. Given this, we sought to review evidence for non-pharmacological interventions with patients with Lewy body dementia and their carers. Bibliographic databases were searched using a wide range of search terms and no restrictions were placed on study design, language, or clinical setting. Two reviewers independently assessed papers for inclusion, rated study quality, and extracted data. The search identified 21 studies including two randomised controlled trials with available subgroup data, seven case series, and 12 case studies. Most studies reported beneficial effects of the interventions used, though the only sizeable study was on dysphagia, showing a benefit of honey-thickened liquids. Given the heterogeneity of interventions and poor quality of the studies overall, no quantitative synthesis was possible. Overall, identified studies suggested possible benefits of non-pharmacological interventions in Lewy body dementia, but the small sample sizes and low quality of studies mean no definite recommendations can be offered. Our findings underscore the clear and urgent need for future research on this topic.
This work builds on a survey first done in 1999 to understand how old age psychiatry teaching is embedded in undergraduate medical schools in the UK and Ireland and the influence of academic old age psychiatrists on teaching processes. We invited deans of 31 medical schools in the UK and Ireland in 2015 to complete an online survey to reassess the situation 16 years later.
Response rate was 74%. As found in the original survey, there was variation across medical schools in how old age psychiatry is taught. Half of schools stated there was not enough space in the curriculum dedicated to old age psychiatry, and not all medical school curricula offered a clinical attachment. Medical schools that involved academic old age psychiatrists in teaching (59%) showed a greater diversity of teaching methods.
There is a need to recognise the importance of old age psychiatry teaching, with the consensus of opinion continuing to be that more curriculum space needs to be given to old age psychiatry. To achieve this we advocate increasing the number of old age psychiatrists with teaching roles, as relying on academics to teach and lead on curriculum development is challenging given their greater research pressures.
Synthesis of Ni and Zn substituted nano-greigite,
Fe3S4, is achieved from single source
diethyldithiocarbamato precursor compounds, producing particles typically
50–100 nm in diameter with plate-like pseudohexagonal morphologies. Up to 12
wt.% Ni is incorporated into the greigite structure, and there is evidence
that Zn is also incorporated but Co is not substituted into the lattice. The
Fe L3 X-ray absorption spectra for these materials have a narrow
single peak at 707.7 eV and the resulting main X-ray magnetic circular
dichroism (XMCD) has the same sign at 708.75 eV. All XMCD spectra also have
a broad positive feature at 711 eV, a characteristic of covalent mixing. The
greigite XMCD spectra contrast with the three clearly defined XMCD site
specific peaks found in the ferrite spinel, magnetite. The Fe
L2,3X-ray absorption spectra and XMCD spectra of the
greigite reflect and reveal the high conductivity of greigite and the very
strong covalency of the Fe–S bonding. The electron hopping between
Fe3+ and Fe2+ on octahedral sites results in an
intermediate oxidation state of the Fe in the Oh site of
Fe2.5+ producing an effective formula of [Fe3+
↑]A-site[2Fe2.5+ ↓]B-siteS42–]. The Ni L2,3 X-ray absorption spectra and XMCD reveal substitution on the
Oh site with a strongly covalent character and an
oxidation state <Ni1.5+ in a representative formula
[Fe3+ ↑]A[[(2 – x)Fe2.5+
Alterations in the visual system may underlie visual hallucinations in
dementia with Lewy bodies (DLB). However, cortical excitability as measured
by transcranial magnetic stimulation (TMS) and functional magnetic resonance
imaging (fMRI) activation of lower visual areas (V1–3) to visual stimuli
appear normal in DLB. We explored the relationship between TMS-determined
phosphene threshold and fMRI-related visual activation and found a positive
relationship between the two in controls but a negative one in DLB. This
double dissociation suggests a loss of inhibition in the visual system in
DLB, which may predispose individuals to visual dysfunction and visual
Dementia with Lewy bodies (DLB) is a common cause of dementia in the elderly population after Alzheimer's disease (AD), and at early stages differential diagnosis between DLB and AD might be difficult due to their symptomatic overlap, e.g. cognitive and memory impairments. We aimed to investigate functional brain differences between both diseases in patients recently diagnosed.
We investigated regional functional synchronizations using regional homogeneity (ReHo) in patients clinically diagnosed with DLB (n = 19) and AD (n = 18), and for comparisons we also included healthy controls (HC, n = 16). Patient groups were matched by age, education, and by the level of cognitive impairment (MMSE p-value = 0.36). Additionally, correlations between ReHo values and clinical scores were investigated.
The DLB group showed lower ReHo in sensory-motor cortices and higher ReHo in left middle temporal gyrus when compared with HCs (p-value < 0.001 uncorrected). The AD group demonstrated lower ReHo in the cerebellum and higher ReHo in the left/right lingual gyri, precuneus cortex, and other occipital and parietal regions (p-value < 0.001 uncorrected).
Our results agree with previous ReHo investigations in Parkinson's disease (PD), suggesting that functional alterations in motor-related regions might be a characteristic of the Lewy body disease spectrum. However, our results in AD contradict previously reported findings for this disease and ReHo, which we speculate are a reflection of compensatory brain responses at early disease stages. ReHo differences between patient groups were at regions related to the default mode and sensory-motor resting state networks which might reflect the aetiological divergences in the underlying disease processes between AD and DLB.
Gregory O'Brien, (deceased) formerly Professor of Developmental Psychiatry, Northumbria University and the University of Queensland,
Paul White, Dual Diagnosis (Intellectual Disability) Service, Park Centre for Mental Health, Wacol, Queensland, Australia
Until very recently the notion that there might be a population of older adults with serious intellectual and developmental disabilities was not widely considered. Most efforts in care, treatment, service development and planning were focused on children and ‘early intervention’. Now there is a growing population of elderly adults with developmental disabilities because of innovations in health and social care. This chapter focuses on health and general care needs of those with disorders of intellectual development (DID), with a particular focus on comorbid dementia.
People are living longer. The life expectancy of ‘three score years and ten’ has not only been replaced by a much older age but has also been steadily increasing. Recent figures for England and Wales quote a life expectancy for boys born in England and Wales in 2009–11 of 78.7 years and 82.6 years for girls. This rising life expectancy is largely due to advances in nutrition and in medical services.
The overall severity of intellectual disability is a strong determinant of life expectancy among people with DID. Recent estimates are framed for high-income countries, given that life expectancy is so inextricably linked to the availability of healthcare. It is estimated that in the year 2000, life expectancy for adults with mild intellectual disability was 70 years, while life expectancy for adults with severe intellectual disability was 60 years (Bittles & Glasson, 2004). In the UK, Valuing People, the official government policy document, estimated that there were over 200 000 people over the age of 60 years with DID in 2000 (Department of Health, 2001). It was further estimated therein that this will increase by 1% per year for at least the next 15 years, due to further increased longevity. In the USA, the American Association for Intellectual Disability estimated that at the turn of the century there were between 600 000 and 1.6 million adults over the age of 60 years with intellectual disabilities and other similarly disabling developmental disabilities (Braddock et al, 2008). The most recent US estimate for the average life expectancy of adults with DID is 66 years and rising (Fisher & Ketti, 2005).
There is a lack of knowledge regarding the information and support needs of people with dementia with Lewy bodies (DLB) and their families around the time of diagnosis.
A volunteer sample of patients with DLB and their family members completed a web survey hosted by the UK based Lewy Body Society in May 2014. This focused on past experiences of information and support received and what information and support needs would have been beneficial at the time of diagnosis.
One hundred and twenty five adults responded to the survey. The majority were first degree relatives or spouses of people with DLB (n = 107, 86%). Approximately 50% (n = 61) reported they had not received any tangible support at diagnosis. Thirteen categories of information needs were identified.
People with DLB and their family members are currently inadequately supported at diagnosis. There is a need to address information needs related to symptomology, medication and prognosis, including provision of emotional and instrumental social support. Seeking the views of recipients of information and support is important in ensuring relevance and appropriateness prior to the development of interventions to improve the knowledge and coping skills of people with DLB and caregivers.