White Matter Hyperintensities Are Associated with Slower Gait Speed in Older Adults Without Dementia.

BACKGROUND: Slow gait speed is associated with poor health outcomes in aging, but the relationship between cerebral small vessel disease (CSVD) pathologies and gait speed in aging is not well understood. We investigated the relationships between cerebral small vessel disease (CSVD) imaging markers and gait speed during simple (normal pace walking (NPW)) and complex (walking-while talking (WWT)) as both measures are associated with shared health outcomes such as falls, frailty, disability, mortality, and dementia. METHODS: A total of 113 Ashkenazi Jewish adults over 65 (M age=78.6±6.3 years, 45.8% women) and without dementia were examined. Established rating systems were used to quantify white matter hyperintensities (WMH) and lacunes of presumed vascular origin from Fluid Attenuated Inversion Recovery (FLAIR) images. Linear regression models adjusted for age, sex, global health, and total intracranial volume were used to examine associations between CSVD markers and gait speed during NPW and WWT. Student t-tests were used to contrast gait speed in those with "confluent-diffuse" WMH and those with "mild or no" WMH. RESULTS: The number of WMH in the basal ganglia (ß=-3.274 cm/s p=.047) and temporal lobes (ß=-3.113 cm/s p=.048) were associated with slower NPW speed in adjusted models. Participants with higher CSVD burden (confluent-diffuse pattern) in the frontal lobe (94.65 cm/s vs. 105.21 cm/s, p=.018) and globally (98.98 cm/s vs. 107.24 cm/s, p=.028) also had lower NPW speed. WMH were not associated with WWT speeds. Lacunes were not associated with NPW or WWT speed. CONCLUSION: Adjusted models found higher CSVD burden as measured by the presence of WMH in the basal ganglia and temporal lobes were associated with slower normal pace gait speed in older adults, but not with complex walking speeds. Participants with confluent-diffuse WMHs in the frontal lobes were found to have slower average normal gait speed. Further studies are needed to establish the temporality of WMH and gait speed decline as well as mechanistic links between the two. .

Neurological Sequelae of COVID-19.

BACKGROUND: Though primarily a pulmonary disease, Coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus can generate devastating disease states that affect multiple organ systems including the central nervous system (CNS). The various neurological disorders associated with COVID-19 range in severity from mild symptoms such as headache, or myalgias to more severe symptoms such as stroke, psychosis, and anosmia. While some of the COVID-19 associated neurological complications are mild and reversible, a significant number of patients suffer from stroke. Studies have shown that COVID-19 infection triggers a wave of inflammatory cytokines that induce endothelial cell dysfunction and generate coagulopathy that increases the risk of stroke or thromboses. Inflammation of the endothelium following infection may also destabilize atherosclerotic plaque and induce thrombotic stroke. Although uncommon, there have also been reports of hemorrhagic stroke associated with COVID-19. The proposed mechanisms include a blood pressure increase caused by infection leading to a reduction in angiotensin converting enzyme-2 (ACE-2) levels that results in an imbalance of the renin-angiotensin system ultimately manifesting inflammation and vasoconstriction. Coagulopathy, as demonstrated by elevated prothrombin time (PT), has also been posited as a factor contributing to hemorrhagics stroke in patients with COVID-19. Other neurological conditions associated with COVID-19 include encephalopathy, anosmia, encephalitis, psychosis, brain fog, headache, depression, and anxiety. Though there are several hypotheses reported in the literature, a unifying pathophysiological mechanism of many of these disorders remains unclear. Pulmonary dysfunction leading to poor oxygenation of the brain may explain encephalopathy and other disorders in COVID-19 patients. Alternatively, a direct invasion of the CNS by the virus or breach of the blood-brain barrier by the systemic cytokines released during infection may be responsible for these conditions. Notwithstanding, the relationship between the inflammatory cytokine levels and conditions such as depression and anxiety is contradictory and perhaps the social isolation during the pandemic may in part be a contributing factor to some of the reported CNS disorders. OBJECTIVE: In this article, we review the current literature pertaining to some of the most significant and common neurological disorders such as ischemic and hemorrhagic stroke, encephalopathy, encephalitis, brain fog, Long COVID, headache, Guillain-Barre syndrome, depression, anxiety, and sleep disorders in the setting of COVID-19. We summarize some of the most relevant literature to provide a better understanding of the mechanistic details regarding these disorders in order to help physicians monitor and treat patients for significant COVID-19 associated neurologic impairments. METHODS: A literature review was carried out by the authors using PubMed with the search terms "COVID-19" and "Neurology", "Neurological Manifestations", "Neuropsychiatric Manifestations", "Stroke", "Encephalopathy", "Headache", "Guillain-Barre syndrome", "Depression", "Anxiety", "Encephalitis", "Seizure", "Spasm", and "ICUAW". Another search was carried out for "Long-COVID" and "Post-Acute COVID-19" and "Neurological Manifestations" or "Neuropsychiatric Manifestations". Articles such as case reports, case series, and cohort studies were included as references. No language restrictions were enforced. In the case of anxiety and depression, attempts were made to focus mainly on articles describing these conditions in infected patients. RESULTS: A total of 112 articles were reviewed. The incidence, clinical outcomes, and pathophysiology of selected neurological disorders are discussed below. Given the recent advent of this disease, the incidence of certain neurologic sequelae was not always available. Putative mechanisms for each condition in the setting of COVID-19 are outlined.

Fabricating a Portable ECG Device Using AD823X Analog Front-End Microchips and Open-Source Development Validation.

Relevant to mobile health, the design of a portable electrocardiograph (ECG) device using AD823X microchips as the analog front-end is presented. Starting with the evaluation board of the chip, open-source hardware and software components were integrated into a breadboard prototype. This required modifying the microchip with the breadboard-friendly Arduino Nano board in addition to a data logger and a Bluetooth breakout board. The digitized ECG signal can be transmitted by serial cable, via Bluetooth to a PC, or to an Android smartphone system for visualization. The data logging shield provides gigabytes of storage, as the signal is recorded to a microSD card adapter. A menu incorporates the device's several operating modes. Simulation and testing assessed the system stability and performance parameters in terms of not losing any sample data throughout the length of the recording and finding the maximum sampling frequency; and validation determined and resolved problems that arose in open-source development. Ultimately, a custom printed circuit board was produced requiring advanced manufacturing options of 2.5 mils trace widths for the small package components. The fabricated device did not degrade the AD823X noise performance, and an ECG waveform with negligible distortion was obtained. The maximum number of samples/second was 2380 Hz in serial cable transmission, whereas in microSD recording mode, a continuous ECG signal for up to 36 h at 500 Hz was verified. A low-cost, high-quality portable ECG for long-term monitoring prototype that reasonably complies with electrical safety regulations and medical equipment design was realized.

Alda-1 modulates the kinetic properties of mitochondrial aldehyde dehydrogenase (ALDH2).

Mitochondrial aldehyde dehydrogenase (ALDH2) has been proposed as a key enzyme in cardioprotection during ischemia-reperfusion processes. This proposal led to the search for activators of ALDH2 with the aim to develop cardioprotective drugs. Alda-1 was the first activator of ALDH2 identified and its cardioprotective effect has been extensively proven in vivo; however, the mechanism of activation is not fully understood. A crystallographic study showed that Alda-1 binds to the entrance of the aldehyde-binding site; therefore, Alda-1 should in essence be an inhibitor. In the present study, kinetic experiments were performed to characterize the effect of Alda-1 on the properties of ALDH2 (kinetic parameters, determination of the rate-limiting step, reactivity of the catalytic cysteine) and on the kinetic mechanism (type of kinetics, sequence of substrates entering, and products release). The results showed that Alda-1 dramatically modifies the properties of ALDH2, the Km for NAD+ decreased by 2.4-fold, and the catalytic efficiency increased 4.4-fold; however, the Km for the aldehyde increased 8.6-fold, thus, diminishing the catalytic efficiency. The alterations in these parameters resulted in a complex behavior, where Alda-1 acts as inhibitor at low concentrations of aldehyde and as an activator at high concentrations. Additionally, the binding of Alda-1 to ALDH2 made the deacylation less limiting and diminished the pKa of the catalytic cysteine. Finally, NADH inhibition patterns indicated that Alda-1 induced a change in the sequence of substrates entry and products release, in agreement with the proposal of both substrates entering ALDH2 by the NAD+ entrance site.

The magic of dioxygen.

Oxygen has to be considered one of the most important elements on Earth. Earlier, some dispute arose as to which of the three scientists, Carl Wilhelm Scheele (Sweden), Joseph Priestley (United Kingdom) or Antoine Lavoisier (France), should get credit for the air of life.Today it is agreed that the Swede discovered it first, the fire air in 1772. The British chemist published it first, the dephlogisticated air in 1775, and the Frenchman understood it first, the oxygen in 1775-1778. Surely, there is credit enough for all three to split the "Nobel Prize" awarded by Carl Djerassi and Roald Hoffmann in their play Oxygen. Molecular oxygen means life. So-called aerobes - these include humans, animals, and plants - need O2 to conserve the energy they have to gain from their environment. Eliminate O2 and these organisms cannot support an active lifestyle. What makes dioxygen that special? It is a non-metal and oxidizing agent that readily reacts with most elements to form compounds, notably oxides. From a biological point of view, the most important compound of course is water, H2O, which provides an excellent solvent for biomolecules. It influences the climate of the Earth, and it is the source of almost all of the molecular oxygen in the atmosphere.

Magnetic and high-frequency EPR studies of an octahedral Fe(III) compound with unusual zero-field splitting parameters.

Temperature-dependent magnetic susceptibility and multi-frequency EPR (9.4, 34.5, 94 and 188 GHz) spectroscopic measurements have been carried out together with an X-ray study at 100 K to study [Fe(DMSO)(6)](NO(3))(3). The iron(III) ion remains high-spin (S = 5/2) in the temperature range studied, therefore, the EPR data were interpreted using the conventional S = 5/2 spin Hamiltonian. A full analysis of EPR spectra at 95 GHz of a powdered sample at 290 K revealed that they are extremely sensitive to D and E values. The zfs parameters were precisely determined: D = + 0.1730 cm(-1), E = 0.00 cm(-1) and lambda = |E/D| = 0.00. A sequence of the spectra neatly shows that the compound has a clear magnetic dependence on temperature. The study at 5 K, showed that the zfs parameters increase: D = + 0.1970 cm(-1), E = 0.017 cm(-1) and lambda = |E/D| = 0.086. These data indicate that as the temperature decreases the D tensor increases slightly showing an increase in the rhombicity. These results confirm that |2D| is congruent to h nu at X-band in this case. Additionally, it has been shown by X-ray crystal analysis of [Fe(DMSO)(6)](NO(3))(3) at 100 K that this is involved in a hydrogen bonding network, consisting of C-H...O interactions between the nitrate anions and the methyl groups of the coordinated DMSO molecules, thus suggesting that the differences found in the spectroscopic parameters D and E at different temperatures must be due to these supramolecular interactions.