An isolated pisiform fracture: a case report

With overall prevalence between 2% to 3%, carpal bone fractures are not encountered frequently in clinical practice. Amongst these, pisiform fractures have very low incidence of <0.2%, in which, more than half are associated with other carpal injuries, and sometimes ulnar styloid and ligamentous injuries. Thus, diagnosis of isolated pisiform fracture requires a very high index of suspicion. Hereby, authors report an isolated pisiform fracture in a 27 year old dentist who sustained an injury due to fall on outstretched hand. After radiographic confirmation in multiple views and CT scan, isolated-minimally displaced pisiform fracture was found. A below-elbow cast with slight palmar flexion was given for 4 weeks. He returned to normal pre-injury activities at 12 weeks

Neuroimaging of Vessel Amyloid in Alzheimer's Disease a , b

Despite extensive recent advances in understanding Alzheimer's disease (AD) we are unable to noninvasively establish a definite diagnosis during life and cannot monitor the cerebral deposition of amyloid Β protein (A/Β) in living patients. We evaluated the use of 10H3, a monoclonal antibody Fab targeting AΒ protein 1-28 labeled with Tc-99m. Six subjects with probable AD were studied using single-photon emission computed tomography (SPECT) at times from 0–24 hours following injection. Curves of radioactivity in blood demonstrate a half-life of the injected Fab of 2–3 hours. Images show uptake around the head in the scalp or bone marrow in all subjects. There is no evidence of cerebral uptake of the antibody. Scalp biopsies in all six patients demonstrate diffuse staining with 10H3 of the scalp, a pattern indistinguishable from that found in controls. Evidence of amyloid deposition in the scalp in AD is not seen with other anti-AΒ antibodies, suggesting that 10H3 is cross-reacting with another protein. Further studies with anti-AΒ antibodies will require longer-lived radionuclides to detect cerebral uptake at later tunes after injection to allow for complete clearance from the blood. Afternately, imaging using labeled AΒ itself may provide a means for noninvasive targeting of cerebral amyloid.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73674/1/j.1749-6632.1997.tb48475.x.pd

Alzheimer\u27s disease and vascular dementia in developing countries: prevalence, management, and risk factors

Despite mortality due to communicable diseases, poverty, and human conflicts, dementia incidence is destined to increase in the developing world in tandem with the ageing population. Current data from developing countries suggest that age-adjusted dementia prevalence estimates in 65 year olds are high (≥5%) in certain Asian and Latin American countries, but consistently low (1–3%) in India and sub-Saharan Africa; Alzheimer\u27s disease accounts for 60% whereas vascular dementia accounts for ∼30% of the prevalence. Early-onset familial forms of dementia with single-gene defects occur in Latin America, Asia, and Africa. Illiteracy remains a risk factor for dementia. The APOE ε4 allele does not influence dementia progression in sub-Saharan Africans. Vascular factors, such as hypertension and type 2 diabetes, are likely to increase the burden of dementia. Use of traditional diets and medicinal plant extracts might aid prevention and treatment. Dementia costs in developing countries are estimated to be US$73 billion yearly, but care demands social protection, which seems scarce in these regions

Small vessel disease pathological changes in neurodegenerative and vascular dementias concomitant with autonomic dysfunction

We performed a clinicopathological study to assess the burden of small vessel disease (SVD) type of pathological changes in elderly demented subjects, who had clinical evidence of autonomic dysfunction, either carotid sinus hypersensitivity or orthostatic hypotension or both or had exhibited unexpected repeated falls. Clinical and neuropathological diagnoses in 112 demented subjects comprised dementia with Lewy bodies (DLB), Parkinson's disease with dementia (PDD), Alzheimer's disease (AD), Mixed dementia (mostly AD‐DLB) and vascular dementia (VaD). Of these, 12 DLB subjects had no recorded unexpected falls in life and therefore no evidence of concomitant autonomic dysfunction. A further 17 subjects were assessed as aging controls without significant pathology or signs of autonomic dysfunction. We quantified brain vascular pathological changes and determined severities of neurodegenerative lesions including α‐synuclein pathology. We found moderate‐severe vascular changes and high‐vascular pathology scores (P < 0.01) in all neurodegenerative dementias and as expected in VaD compared to similar age controls. Arteriolosclerosis, perivascular spacing and microinfarcts were frequent in the basal ganglia and frontal white matter (WM) across all dementias, whereas small infarcts (<5 mm) were restricted to VaD. In a sub‐set of demented subjects, we found that vascular pathology scores were correlated with WM hyperintensity volumes determined by MRI in life (P < 0.02). Sclerotic index values were increased by ~50% in both the WM and neocortex in all dementias compared to similar age controls. We found no evidence for increased α‐synuclein deposition in subjects with autonomic dysfunction. Our findings suggest greater SVD pathological changes occur in the elderly diagnosed with neurodegenerative dementias including DLB and who develop autonomic dysfunction. SVD changes may not necessarily manifest in clinically overt symptoms but they likely confound motor or cognitive dysfunction. We propose dysautonomia promotes chronic cerebral hypoperfusion to impact upon aging‐related neurodegenerative disorders and characterize their end‐stage clinical syndromes

Immunotherapy targeting isoDGR-protein damage extends lifespan in a mouse model of protein deamidation

\ua9 2023 The Authors. Published under the terms of the CC BY 4.0 license. Aging results from the accumulation of molecular damage that impairs normal biochemical processes. We previously reported that age-linked damage to amino acid sequence NGR (Asn-Gly-Arg) results in “gain-of-function” conformational switching to isoDGR (isoAsp-Gly-Arg). This integrin-binding motif activates leukocytes and promotes chronic inflammation, which are characteristic features of age-linked cardiovascular disorders. We now report that anti-isoDGR immunotherapy mitigates lifespan reduction of Pcmt1−/− mouse. We observed extensive accumulation of isoDGR and inflammatory cytokine expression in multiple tissues from Pcmt1−/− and naturally aged WT animals, which could also be induced via injection of isoDGR-modified plasma proteins or synthetic peptides into young WT animals. However, weekly injection of anti-isoDGR mAb (1 mg/kg) was sufficient to significantly reduce isoDGR-protein levels in body tissues, decreased pro-inflammatory cytokine concentrations in blood plasma, improved cognition/coordination metrics, and extended the average lifespan of Pcmt1−/− mice. Mechanistically, isoDGR-mAb mediated immune clearance of damaged isoDGR-proteins via antibody-dependent cellular phagocytosis (ADCP). These results indicate that immunotherapy targeting age-linked protein damage may represent an effective intervention strategy in a range of human degenerative disorders

The Vascular Impairment of Cognition Classification Consensus Study

H. Jokinen työryhmän jäsenenä.Introduction: Numerous diagnostic criteria have tried to tackle the variability in clinical manifestations and problematic diagnosis of vascular cognitive impairment (VCI) but none have been universally accepted. These criteria have not been readily comparable, impacting on clinical diagnosis rates and in turn prevalence estimates, research, and treatment. Methods: The Vascular Impairment of Cognition Classification Consensus Study (VICCCS) involved participants (81% academic researchers) from 27 countries in an online Delphi consensus study. Participants reviewed previously proposed concepts to develop new guidelines. Results: VICCCS had a mean of 122 (98-153) respondents across the study and a 67% threshold to represent consensus. VICCCS redefined VCI including classification of mild and major forms of VCI and subtypes. It proposes new standardized VCI-associated terminology and future research priorities to address gaps in current knowledge. Discussion: VICCCS proposes a consensus-based updated conceptualization of VCI intended to facilitate standardization in research. (C) 2016 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.Peer reviewe

Stroke in Africa: Profile, progress, prospects and priorities

Funding text 1 R.O.A. is supported by the UK Royal Society/African Academy of Sciences FLAIR Grants FLR/R1/191813 and FCG/R1/ 201034, and a GCRF Networking Grant from the UK Academy of Medical Sciences. R.O.A., M.O.O., B.O. and F.S.S. are also supported by grants U54HG007479 and U01HG010273 from the US National Institutes of Health (NIH) as part of the H3Africa Consortium. M.O.O., B.O., R.O.A. and F.S.S. are further supported by NIH grant R01NS107900. R.N.K.’s research on elderly survivors of stroke has been supported by the Medical Research Council, RCUK Newcastle Centre for Brain Ageing and Vitality (MRC G0500247), Alzheimer’s Research UK, the Dunhill Medical Trust, UK, and the Newcastle National Institute for Health Research Biomedical Research Centre in Ageing and Age-Related Diseases, Newcastle upon Tyne Hospitals National Health Service Foundation Trust. Funding text 2 funds provided by the Wellcome Trust and the NIH. The NIH-funded SIREN study is exploring the genetic architecture of stroke among Indigenous Africans. More than 4,000 case–control pairs have already been recruited to the study and several publications on stroke phenom-ics and preliminary candidate gene analyses have been generated. The SIREN study has also undertaken the first-ever GWAS to unravel the genetic architecture of stroke in Indigenous Africans and the results are eagerly awaited. Stroke neurobanking resources consisting of blood fractions, extracted DNA, neuroimages and databases of clinical information are also being built in Africa and could facilitate data science-driven trans-omics research (including epigenomics, tran-scriptomics, proteomics and metabolomics) as well as the development of precision medicine products such as Afrocentric risk calculators, polygenic risk scores, biomarkers and drug targets23–25,227,307,308. The SIREN neurobiobank comprises a group of constantly monitored ultra-low-temperature (–86 °C) freezers located in Ibadan, Nigeria, constantly powered –20 °C chest freezers located in Ibadan and other recruitment sites, barcode scanners and printers, a laboratory information management system, a secure multi-terabyte server,Stroke is a leading cause of disability, dementia, and death worldwide. Approximately 70% of deaths from stroke and 87% of stroke-related disabilities occur in low-income and middle-income countries. At the turn of the century, the most common diseases in Africa were communicable diseases, whereas non-communicable diseases, including stroke, were considered rare, particularly in sub-Saharan Africa. However, evidence indicates that today, Africa could have up to 2–3-fold greater rates of stroke incidence and higher stroke prevalence than western Europe and the USA. In Africa, data published within the past decade show that stroke has an annual incidence rate of up to 316 per 100,000, a prevalence of up to 1,460 per 100,000, and a 3-year fatality rate greater than 80%. Moreover, many Africans have a stroke within the fourth to sixth decades of life, with serious implications for the individual, their family, and society. This age profile is particularly important as strokes in younger people tend to result in a greater loss of self-worth and socioeconomic productivity than in older individuals. Emerging insights from research into stroke epidemiology, genetics, prevention, care, and outcomes offer great prospects for tackling the growing burden of stroke on the continent. In this article, we review the unique profile of stroke in Africa and summarize current knowledge on stroke epidemiology, genetics, prevention, acute care, rehabilitation, outcomes, cost of care, and awareness. We also discuss knowledge gaps, emerging priorities, and future directions of stroke medicine for the more than 1 billion people who live in Africa. © 2021, Springer Nature Limited.Newcastle National Institute for Health Research Biomedical Research Centre in Ageing and Age-Related Diseases Newcastle upon Tyne Hospitals National Health Service Foundation Trust RCUK Newcastle Centre for Brain Ageing and Vitality Royal Society/African Academy of Sciences: FCG/R1/ 201034,FLR/R1/191813 National Institutes of Health (NIH): R01NS107900 Wellcome Trust (WT) Medical Research Council (MRC): G0500247 Dunhill Medical Trust (DMT) Academy of Medical Sciences: U01HG010273,U54HG007479 Alzheimer’s Research UK (ARUK