Reviewing fair subject selection considerations for the unique case of post sequelae COVID-19 translational studies.

Fair inclusion of research subjects is necessary to ensure that post-acute sequelae COVID-19 (PASC) research results benefit all members of society. Scientists should conduct research on a broad sample of individuals who represent clinically relevant factors influencing a disease. Without demographic diversity and sociological and environmental variability, research outputs are less likely to apply to different populations and would thus increase health disparities. The goal of this narrative literature review and ethical analysis is to apply fair selection criteria to PASC research studies. We briefly highlight the importance of fair subject selection in translational research and then identify features of PASC, as well as PASC research, that hinder fair inclusion of research participants. We will demonstrate that determining an adequate and representative sample is not simply a matter of ensuring greater diversity; rather, fairness requires a broader evaluation of risks, burdens, and benefits specific to underrepresented populations. We provide recommendations to ensure fair subject selection in PASC research and promote translation toward positive health outcomes for all individuals, including the most vulnerable.

Introducing a gatekeeping system for amyloid status assessment in mild cognitive impairment.

BACKGROUND: In patients with mild cognitive impairment (MCI), enhanced cerebral amyloid-ß plaque burden is a high-risk factor to develop dementia with Alzheimer's disease (AD). Not all patients have immediate access to the assessment of amyloid status (A-status) via gold standard methods. It may therefore be of interest to find suitable biomarkers to preselect patients benefitting most from additional workup of the A-status. In this study, we propose a machine learning-based gatekeeping system for the prediction of A-status on the grounds of pre-existing information on APOE-genotype 18F-FDG PET, age, and sex. METHODS: Three hundred and forty-two MCI patients were used to train different machine learning classifiers to predict A-status majority classes among APOE-ε4 non-carriers (APOE4-nc; majority class: amyloid negative (Aß-)) and carriers (APOE4-c; majority class: amyloid positive (Aß +)) from 18F-FDG-PET, age, and sex. Classifiers were tested on two different datasets. Finally, frequencies of progression to dementia were compared between gold standard and predicted A-status. RESULTS: Aß- in APOE4-nc and Aß + in APOE4-c were predicted with a precision of 87% and a recall of 79% and 51%, respectively. Predicted A-status and gold standard A-status were at least equally indicative of risk of progression to dementia. CONCLUSION: We developed an algorithm allowing approximation of A-status in MCI with good reliability using APOE-genotype, 18F-FDG PET, age, and sex information. The algorithm could enable better estimation of individual risk for developing AD based on existing biomarker information, and support efficient selection of patients who would benefit most from further etiological clarification. Further potential utility in clinical routine and clinical trials is discussed.

Recovery of an urbanised estuary: Clean-up, de-industrialisation and restoration of redundant dock-basins in the Mersey.

For much of the 20th century, the Mersey in North West England was one of the worst polluted estuaries in Europe. Water from a range of polluting industries plus domestic sewage was discharged into the Mersey Catchment and Estuary. Recovery came through a concerted clean-up campaign and tightening environmental regulations, partly driven by European Commission Directives, coupled with de-industrialisation from the 1970s onward. Recovery of oxygen levels in the Estuary led to the return of a productive ecosystem. This led to conservation designations, but also concerns about transfer of pollutants to higher trophic levels in fish, birds and humans. As part of urban renewal, ecosystems in disused dock basins were restored using mussel biofiltration and artificial de-stratification, facilitating commercial redevelopment and creation of a tourist destination. The degradation and recovery of the Mersey from peak-pollution in the mid-20th century is put in the context of wider environmental change and briefly compared to other systems to develop a hysteresis model of degradation and recovery, often to novel ecosystems.

Differential effect of nimodipine in attenuating iron-induced toxicity in brain- and blood-brain barrier-associated cell types.

Metal homeostasis is increasingly being evaluated as a therapeutic target in stroke and neurodegenerative diseases. Metal dysregulation has been shown to lead to protein aggregation, plaque formation and neuronal death. In 2007, we first reported that voltage-gated calcium channels act as a facile conduit for the entry of free ferrous (Fe(2+)) ions into neurons. Herein, we evaluate differential iron toxicity to central nervous system cells and assess the ability of the typical L-type voltage-gated calcium channel blocker nimodipine to attenuate iron-induced toxicity. The data demonstrate that iron sulfate induces a dose-dependent decrease in cell viability in rat brain endothelial cells (RBE4; LC(50) = 150 µM), neuronal cells (Neuro-2α neuroblastoma; LC(50) = 400 µM), and in astrocytes (DI TNC1; LC(50) = 1.1 mM). Pre-treatment with nimodipine prior to iron sulfate exposure provided a significant (P < 0.05) increase in viable cell numbers for RBE4 (2.5-fold), Neuro2-α (~2-fold), and nearly abolished toxicity in primary neurons. Astrocytes were highly resistant to iron toxicity compared to the other cell types tested and nimodipine had no (P > 0.05) protective effect in these cells. The data demonstrate variable susceptibility to iron overload conditions in different cell types of the brain and suggest that typical L-type voltage-gated calcium channel blockers (here represented by nimodipine), may serve as protective agents in conditions involving iron overload, particularly in cell types highly susceptible to iron toxicity.

Variability of immediate-early gene 62 in german varicella-zoster virus wild-type strains.

Varicella-zoster virus strains of European genotypes have developed a high variability of open reading frame (ORF) 62 during their occurrence over many years in Germany. M1 strains in Germany display a uniform ORF 62 pattern, suggesting that these strains were introduced from Africa and/or Asia via few sources during the last years.

Free-flight encounters between praying mantids (Parasphendale agrionina) and bats (Eptesicus fuscus).

Through staged free-flight encounters between echolocating bats and praying mantids, we examined the effectiveness of two potential predator-evasion behaviors mediated by different sensory modalities: (1) power dive responses triggered by bat echolocation detected by the mantis ultrasound-sensitive auditory system, and (2) ;last-ditch' maneuvers triggered by bat-generated wind detected by the mantis cercal system. Hearing mantids escaped more often than deafened mantids (76% vs 34%, respectively; hearing conveyed 42% advantage). Hearing mantis escape rates decreased when bat attack sequences contained very rapid increases in pulse repetition rates (escape rates <40% for transition slopes >16 p.p.s. 10 ms(-1); escape rates >60% for transition slopes <16 p.p.s. 10 ms(-1)). This suggests that echolocation attack sequences containing very rapid transitions (>16 p.p.s. 10 ms(-1)) could circumvent mantis/insect auditory defenses. However, echolocation attack sequences containing such transitions occurred in only 15% of the trials. Since mantis ultrasound-mediated responses are not 100% effective, cercal-mediated evasive behaviors triggered by bat-generated wind could be beneficial as a backup/secondary system. Although deafened mantids with functioning cerci did not escape more often than deafened mantids with deactivated cerci (35% vs 32%, respectively), bats dropped mantids with functioning cerci twice as frequently as mantids with deactivated cerci. This latter result was not statistically reliable due to small sample sizes, since this study was not designed to fully evaluate this result. It is an interesting observation that warrants further investigation, however, especially since these dropped mantids always survived the encounter.

Auditory sensitivity and frequency selectivity in greater spear-nosed bats suggest specializations for acoustic communication.

We investigated the relationship between auditory sensitivity, frequency selectivity, and the vocal repertoire of greater spear-nosed bats ( Phyllostomus hastatus). P. hastatus commonly emit three types of vocalizations: group-specific foraging calls that range from 6 to 11 kHz, low amplitude echolocation calls that sweep from 80 to 40 kHz, and infant isolation calls from 15 to 100 kHz. To determine if hearing in P. hastatus is differentially sensitive or selective to frequencies in these calls, we determined absolute thresholds and masked thresholds using an operant conditioning procedure. Both absolute and masked thresholds were lowest at 15 kHz, which corresponds with the peak energy of isolation calls. Auditory and masked thresholds were higher at sound frequencies used for group-specific foraging calls and echolocation calls. Isolation calls meet the requirements of individual signatures and facilitate parent-offspring recognition. Many bat species produce isolation calls with peak energy between 10 and 25 kHz, which corresponds with the frequency region of highest sensitivity in those species for which audiogram data are available. These findings suggest that selection for accurate offspring recognition exerts a strong influence on the sensory system of P. hastatus and likely on other species of group-living bats.

[Effect on the lipid profile of diet supplemented with fish oil concentrate]. / Effekt på lipidprofil av kosttilskudd med fiskeoljekonsentrat.

Effects on serum lipids were examined in a double blind placebo controlled trial including 111 male and females with cholesterol values higher than 7.0 mmol/l. The patients were treated with 6 g Almarin capsules consisting of the highly concentrated fish-oil EPAX 6000 EE in a daily dose corresponding to 2.1 g eicosapentaenoic acid and 1.5 g docosahexaenoic acid, or olive oil control for 12 weeks. We registered the effects on serum triglycerides, total cholesterol and HDL cholesterol. Compared with baseline values a 19.5% median reduction in serum triglycerides could be observed in the n-3 treated group. This reduction was significantly different from control and baseline values. We also observed a favourable trend towards lower total serum cholesterol and higher serum HDL cholesterol.

[Laboratory procedures with adenoviruses. IX. Hexon antibody determination by countercurrent immunoelectrophoresis]. / Laboratoriumspraxis bei Adenoviren. IX. Hexon-Antikörpernachweis mit Gegenstrom-Immunelektrophorese.

101 paired sera from patients with proved adenovirus infections (mostly conjunctivitis) were tested quantitatively by counter immunoelectrophoresis, with hexon of adenovirus 5 as a genus-specific antigen, in comparison with complement-fixation. Both methods were equally sensitive to demonstrate antibodies; also the titers showed a marked correlation. The number of titer rises, however, was higher in counter immunoelectrophoresis; the titer rises mostly occurred around the 10th day after onset of disease. No differences between patients infected with different adenovirus types were found.