Accelerated forgetting in healthy older samples: Implications for methodology, future ageing studies, and early identification of risk of dementia

Accelerated long-term forgetting (ALF) has been reported in healthy older individuals, and is a possible early marker for risk of developing Alzheimer’s disease (AD). The Verbal Associative Learning & Memory Test (VALMT; McGibbon & Jansari, 2013) addresses methodological weaknesses in existing clinical tests and has detected ALF in epilepsy within an hour. We used VALMT to investigate learning and forgetting in healthy older participants. Older (60-69yrs) and Younger (19-31yrs) participants were compared. Using VALMT, unrelated word-pairs were learnt to criterion, then cued-recall tested at delays of 5, 30 and 55 minutes. Unique pairs were tested at each delay. Subjective memory complaints data was gathered, and the Wechsler Memory Scale Logical Memory test (WMS-LM; a standard clinical measure) was administered. VALMT identified a significant difference in delayed recall between Younger and Older groups by 55 minutes (d = 1.32). While ‘fast-learning’ Older participants scored similarly to Younger participants, ‘slow-learning’ Older participants were impaired at all delays. Forgetting rates suggested degradation of memory starts during early synaptic consolidation rather than later system-level consolidation. Increased subjective memory complaints were associated with reduced VALMT scores. By contrast, WMS-LM failed to identify significant differences between any groups, and did not correlate with memory complaints. We conclude VALMT may be better able than WMS-LM to identify subtle impairments in healthy older adults within a single clinical visit, and VALMT results better reflect subjective experience. Older slow-learners forget faster and report more subjective memory complaints, which may indicate a group at risk of developing AD

Locally Preferred Structure and Frustration in Glassforming Liquids: A Clue to Polyamorphism?

We propose that the concept of liquids characterized by a given locally preferred structure (LPS) could help in understanding the observed phenomenon of polyamorphism. ``True polyamorphism'' would involve the competition between two (or more) distinct LPS, one favored at low pressure because of its low energy and one favored at high pressure because of its small specific volume, as in tetrahedrally coordinated systems. ``Apparent polyamorphism'' could be associated with the existence of a poorly crystallized defect-ordered phase with a large unit cell and small crystallites, which may be illustrated by the metastable glacial phase of the fragile glassformer triphenylphosphite; the apparent polyamorphism might result from structural frustration, i. e., a competition between the tendency to extend the LPS and a global constraint that prevents tiling of the whole space by the LPS.Comment: 11, 6 figures, Proceedings of the Conference "Horizons in Complex Systems", Messina; in honor of the 60th birthday of H.E. Stanle

Whole-genome sequencing reveals widespread presence of Staphylococcus capitis NRCS-A clone in neonatal units across the United Kingdom

OBJECTIVE: Increased incidence of neonatal Staphylococcus capitis bacteraemia in summer 2020, London, raised suspicion of widespread multidrug-resistant clone NRCS-A. We set out to investigate the molecular epidemiology of this clone in neonatal units (NNUs) across the UK. METHODS: We conducted whole-genome sequencing (WGS) on presumptive S. capitis NRCS-A isolates collected from infants admitted to NNUs and from environmental sampling in two distinct NNUs in 2021. Previously published S. capitis genomes were added for comparison. Genetic clusters of NRCS-A isolates were defined based on core-genome single-nucleotide polymorphisms. RESULTS: We analysed WGS data of 838S. capitis isolates and identified 750 NRCS-A isolates. We discovered a possible UK-specific NRCS-A lineage consisting of 611 isolates collected between 2005-2021. We determined 28 genetic clusters of NRCS-A isolates, which covered all geographical regions in the UK, and isolates of 19 genetic clusters were found in ≥2 regions, suggesting inter-regional spread. Within the NRCS-A clone, strong genetic relatedness was identified between contemporary clinical and incubator-associated fomite isolates and between clinical isolates associated with inter-hospital infant transfer. CONCLUSIONS: This WGS-based study confirms the dispersion of S. capitis NRCS-A clone amongst NNUs across the UK and urges research on improving clinical management of neonatal S. capitis infection

Malnutrition Has No Effect on the Timing of Human Tooth Formation

The effect of nutrition on the timing of human tooth formation is poorly understood. Delays and advancements in dental maturation have all been reported as well as no effect. We investigated the effect of severe malnutrition on the timing of human tooth formation in a large representative sample of North Sudanese children. The sample (1102 males, 1013 females) consisted of stratified randomly selected healthy individuals in Khartoum, Sudan, aged 2-22 years using a cross-sectional design following the STROBE statement. Nutritional status was defined using WHO criteria of height and weight. Body mass index Z-scores and height for age Z-scores of ≤-2 (cut-off) were used to identify the malnourished group (N = 474) while the normal was defined by Z-scores of ≥0 (N = 799). Clinical and radiographic examination of individuals, with known ages of birth was performed including height and weight measurements. Mandibular left permanent teeth were assessed using eight crown and seven root established tooth formation stages. Mean age at entry and mean age within tooth stages were calculated for each available tooth stage in each group and compared using a t-test. Results show the mean age at entry and mean age within tooth stages were not significantly different between groups affected by severe malnutrition and normal children (p>0.05). This remarkable finding was evident across the span of dental development. We demonstrate that there is little measurable effect of sustained malnutrition on the average timing of tooth formation. This noteworthy finding supports the notion that teeth have substantial biological stability and are insulated from extreme nutritional conditions compared to other maturing body systems

How old are you now? A new ageing method for nonadults based on dental wear

The main aim of this study is to present a novel method of nonadult (ca. 1–19 years) age‐at‐death estimation using the dental wear of deciduous, mixed deciduous‐permanent, and permanent dentitions, including the incisors, canines, premolars, and first and second molars. The stage‐based method is derived from degrees of dental wear in known‐age (n = 39) and estimated‐age (n = 11) nonadults containing 951 teeth from the predominately 19th century cemetery of Middenbeemster, The Netherlands. The need for such a method is warranted in cases where dental development and/or eruption cannot be assessed for age‐at‐death estimation. As well, by establishing a baseline for normal age‐related nonadult tooth wear, users may better document wear that could be due to extramasticatory behaviours. The regression analysis reveals a strong quadratic correlation—F(2, 47) = 555.1, p R2 = .95, standard error of the estimate = 1.14, residual sum of squares (RSS) = 68.89, predicted residual error sum of squares (PRESS) = 77.67—between age and wear and multivariate adaptive regression splines (R2 = .95, generalised cross validation = 1.67, RSS = 67.68, PRESS = 89.34), which are used to develop an R‐package that users may employ to estimate age‐at‐death from dental wear. The accuracy of this method (78–98%) is evaluated using leave‐one‐out cross‐validation. Analyses of males versus females, deciduous versus permanent, upper versus lower, and anterior versus posterior teeth revealed no apparent reason to warrant separate methods for these groups of separated dentitions. This method fills a disciplinary gap in the understudied area of deciduous and nonadult dental wear and hopes to stimulate much future research. With the R‐package, we also provide the foundation and framework for the development of additional reference populations across different spatiotemporal contexts, to make the method more widely applicable. Bioarchaeolog

Continuous venovenous hemodiafiltration with a low citrate dose regional anticoagulation protocol and a phosphate-containing solution: effects on acid–base status and phosphate supplementation needs

BACKGROUND: Recent guidelines suggest the adoption of regional citrate anticoagulation (RCA) as first choice CRRT anticoagulation modality in patients without contraindications for citrate. Regardless of the anticoagulation protocol, hypophosphatemia represents a potential drawback of CRRT which could be prevented by the adoption of phosphate-containing CRRT solutions. The aim was to evaluate the effects on acid--base status and phosphate supplementation needs of a new RCA protocol for Continuous Venovenous Hemodiafiltration (CVVHDF) combining the use of citrate with a phosphate-containing CRRT solution. METHODS: To refine our routine RCA-CVVH protocol (12 mmol/l citrate, HCO3- 32 mmol/l replacement fluid) (protocol A) and to prevent CRRT-related hypophosphatemia, we introduced a new RCA-CVVHDF protocol (protocol B) combining an 18 mmol/l citrate solution with a phosphate-containing dialysate/replacement fluid (HCO3- 30 mmol/l, Phosphate 1.2). A low citrate dose (2.5--3 mmol/l) and a higher than usual target circuit-Ca2+ (<=0.5 mmol/l) have been adopted. RESULTS: Two historical groups of heart surgery patients (n = 40) underwent RCA-CRRT with protocol A (n = 20, 102 circuits, total running time 5283 hours) or protocol B (n = 20, 138 circuits, total running time 7308 hours). Despite higher circuit-Ca2+ in protocol B (0.37 vs 0.42 mmol/l, p < 0.001), circuit life was comparable (51.8 +/- 36.5 vs 53 +/- 32.6 hours). Protocol A required additional bicarbonate supplementation (6 +/- 6.4 mmol/h) in 90% of patients while protocol B ensured appropriate acid--base balance without additional interventions: pH 7.43 (7.40--7.46), Bicarbonate 25.3 (23.8--26.6) mmol/l, BE 0.9 (-0.8 to +2.4); median (IQR). No episodes of clinically relevant metabolic alkalosis, requiring modifications of RCA-CRRT settings, were observed. Phosphate supplementation was needed in all group A patients (3.4 +/- 2.4 g/day) and in only 30% of group B patients (0.5 +/- 1.5 g/day). Hypophosphatemia developed in 75% and 30% of group A and group B patients, respectively. Serum phosphate was significantly higher in protocol B patients (P < 0.001) and, differently to protocol A, appeared to be steadily maintained in near normal range (0.97--1.45 mmol/l, IQR)

Histopathological findings from the investigation of paediatric acute hepatitis of unknown aetiology, United Kingdom 2022

In 2022, there were global reports of increased numbers of acute hepatitis not explained by hepatitis A–E virus infection in children. This manuscript summarises histopathology results from 20 patients in the United Kingdom who underwent liver transplant or had a liver biopsy as part of aetiological investigations. All available histopathological samples were reviewed centrally as part of the outbreak investigation. A working group comprised of infection specialists, hepatologists and histopathologists met virtually to review the cases, presentation, investigations and histopathology. All 20 liver samples had evidence of inflammation without significant interface activity, and submassive confluent pan-lobular or multilobular hepatocellular necrosis. Overall, the predominant histopathological findings were of acute nonspecific hepatitis with submassive hepatic necrosis and central vein perivenulitis and endothelitis. Histopathological findings were a poor indicator of aetiology