COVID-19 hospitalization rates rise exponentially with age,inversely proportional to thymic T-cell production

Here, we report that COVID-19 hospitalization rates follow an exponential relationship with age, doubling for every 16 years of age or equivalently increasing by 4.5% per year of life (R² = 0.98). This mirrors the well-studied exponential decline of both thymus volume and T-cell production, which halve every 16 years. COVID-19 can therefore be added to the list of other diseases with this property, including those caused by methicillin-resistant Staphylococcus aureus, MERS-CoV, West Nile virus, Streptococcus pneumoniae and certain cancers, such as chronic myeloid leukaemia and brain cancers. In addition, the incidence of severe disease and mortality due to COVID-19 are both higher in men, consistent with the degree to which thymic involution (and the decrease in T-cell production with age) is more severe in men compared to women. Since these properties are shared with some non-contagious diseases, we hypothesized that the age dependence does not come from social-mixing patterns, i.e. that the probability of hospitalization given infection rises exponentially, doubling every 16 years. A Bayesian analysis of daily hospitalizations, incorporating contact matrices, found that this relationship holds for every age group except for the under 20s. While older adults have fewer contacts than young adults, our analysis suggests that there is an approximate cancellation between the effects of fewer contacts for the elderly and higher infectiousness due to a higher probability of developing severe disease. Our model fitting suggests under 20s have 49–75% additional immune protection beyond that predicted by strong thymus function alone, consistent with increased juvenile cross-immunity from other viruses. We found no evidence for differences between age groups in susceptibility to infection or infectiousness to others (given disease state), i.e. the only important factor in the age dependence of hospitalization rates is the probability of hospitalization given infection. These findings suggest the existence of a T-cell exhaustion threshold, proportional to thymic output and that clonal expansion of peripheral T-cells does not affect disease risk. The strikingly simple inverse relationship between risk and thymic T-cell output adds to the evidence that thymic involution is an important factor in the decline of the immune system with age and may also be an important clue in understanding disease progression, not just for COVID-19 but other diseases as well.     

Foetal alcohol syndrome in Saskatchewan: unchanged incidence in a 20-year period

Ethers and thioethers of monosaccharides have been synthesised which show potent toxicity to mouse (LD50 > or = 4 g.kg-1 O.W. and 0.2 to 1.5 g.kg-1 I.P.W.). A study of calcium antagonist activity for the full series of compounds indicated that the activity was similar for both O- and S- ethers and maximum activities were observed for monoacetoneglucose ethers possessing carbon chain close to 8 carbons.     

Event-related desynchronization (ERD) patterns during verbal memory tasks: effect of age

Event-related desynchronization (ERD) was studied in 10 young (mean age = 19.1) and 10 older (mean age = 62.8) subjects during a verbal recognition task. The attention load of the task varied according to the difficulty of discriminating between targets and distractors. EEG recorded from 29 electrodes was used to compute ERD from 14 source derivations in 125 ms intervals. Thereafter, it was displayed as spatiotemporal maps. The results show that attention influences the characteristics of EEG desynchronization. In young subjects, ERD is more pronounced and more widespread when the attentional load is high. In the elderly, differences between the two attention conditions are less marked. ANOVA reveals main effects of attention and time. The significant 'attention x time x age group' interaction confirms the presence of different brain activation patterns in the two age groups in relation to attention load.     

Cardiac tamponade as a presentation of primary hypothyroidism in a young woman

Pericardial effusion (PE) as a hypothyroidism associated sign, is something that can be found with relative frequency; nevertheless, cardiac tamponade (CT) as the first sign of this disease may be considered exceptional especially in young patients. We report a 31 years old woman with clinical symptoms and signs of CT that in the forward workshop was diagnosed of primary hypothyroidism as cause of the CT. We shortly describe the case and review the literature, emphasizing the importance of the knowledge of CT trigger factors in myxedematous PE, as well as its usual benign evolution with hormonal treatment, without recurrences of the CT after pericardiocentesis is performed. This justify a conservative approach, in spite of the slow resolution of the PE what can take as long as 1.5 years.     

Major abdominal surgery and the clearance of lipid emulsions

Reaction of bacterial adhesins with complementary receptors on the surfaces of mucosal respiratory, gastrointestinal and genitourinary cells leads to bacterial adhesion to the human body. This is the first step in the sequence of events leading to infection. It has been observed that subinhibitory concentrations (sub-MICs) of some antibiotics are able to reduce bacterial adhesion. The pharmacokinetic curves of antibiotics show that these sub-MICs are present in tissues during a typical course of therapy. This study investigated the ability of sub-MICs of seven macrolides and four fluoroquinolones to reduce adhesiveness of Staphylococcus aureus to human buccal cells. The literature generally reports data for only one antibiotic at a time. To obtain an overall view of the findings of eleven antibiotics together, the data have been normalized according to the molecular weight of each antibiotic and the dose-effect curves determined.     

Astrocytes regulate amino acid receptor current densities in embryonic rat hippocampal neurons

Embryonic rat hippocampal neurons were cultured in a serum-free defined medium (MEM/N3) either directly on poly-D-lysine (PDL) or on a confluent monolayer of postnatal cortical astrocytes, C6 glioma cells, or Rat2 fibroblasts. Neurons on PDL were grown in MEM/N3 or in MEM/N3 conditioned for 24 h by astrocytes or C6 cells. Membrane capacitance (Cm) and gamma-aminobutyric acid (GABA)-, glycine-, kainate-, and N-methyl-D-aspartate (NMDA)-induced currents were quantified using whole-cell patch-clamp recordings. Cm as well as the amplitude and the density of these currents in neurons cultured on astrocytes were significantly greater than those in neurons grown on PDL after 24 and 48 h. C6 cells mimicked astrocytes in promoting Cm and GABA-, glycine-, and NMDA-evoked, but not kainate-evoked, currents. Cm and currents in neurons grown on Rat2 cells were comparable to those in neurons on PDL. Astrocytes maintained in culture for 3 months were noticeably less effective than freshly prepared ones just grown to confluence. Suppression of spontaneous cytoplasmic Ca2+ (Ca[c]2+) elevations in astrocytes by 1,2-bis(2-aminophenoxy) ehane-N, N, N, N-tetraacetic acid acetoxymethyl ester (BAPTA-AM) loaded intracellularly blocked the observed modulatory effects. Medium conditioned by either astrocytes or C6 cells mimicked the effects of direct coculture of neurons on these cells in promoting Cm and amino acid-evoked currents. Inclusion of antagonists at GABA and glutamate receptors in coculture experiments blocked the observed effects. Thus, diffusible substances synthesized and/ or secreted by astrocytes in a Ca(c)2+-dependent manner can regulate neuronal growth and aminoacid receptor function, and these effects may involve neuronal GABA and glutamate receptors.     

A linkage map of human chromosome 21:43 PCR markers at average intervals of 2.5 cM

A genetic linkage map of human chromosome 21q (HC21q) containing 43 markers genotyped by the polymerase chain reaction in the CEPH pedigrees is presented. The markers placed on this map are highly polymorphic with an average heterozygosity of 61%. The average interval size of the markers localized at 1000:1 odds is 2.5 cM. The map has a total length of 65.5 cM, with male and female lengths of 47.7 and 83.3 cM, respectively. The genotypes used in the construction of this map were subjected to rigorous error checking, which is reflected in the shorter map length compared to previous maps; the estimated error rate in genotyping is less than 0.04%. As noted in previous linkage maps there is increased recombination in females on proximal HC 21q and in the male in a region near the telomere. This map of HC 21 represents a highly informative and dense meiotic linkage map and will be useful in linking disease phenotypes to loci on this chromosome.