Mental health in people with Parkinson's disease during the COVID-19 pandemic: potential for targeted interventions?

The COVID-19 pandemic has introduced a myriad of challenges to the social life and care of people with Parkinson's disease (PD), which could potentially worsen mental health problems. We used baseline data of the PRIME-NL study (N = 844) to examine whether the association between COVID-19 stressors and mental health is disproportionately large in specific subgroups of people with PD and to explore effects of hypothetical reductions in COVID-19 stressors on mental health and quality of life. The mean (SD) age of the study population was 70.3 (7.8) years and 321 (38.0%) were women. The linear regression effect estimate of the association of COVID-19 stressors with mental health was most pronounced in women, highly educated people, people with advanced PD and people prone to distancing or seeking social support. Smaller effect estimates were found in people scoring high on confrontive coping or planful problem solving. The parametric G-formula method was used to calculate the effects of hypothetical interventions on COVID-19 stressors. An intervention reducing stressors with 50% in people with above median MDS-UPDRS-II decreased the Beck Depression Inventory in this group from 14.7 to 10.6, the State-Trait Anxiety Inventory from 81.6 to 73.1 and the Parkinson's Disease Quality of Life Questionnaire from 35.0 to 24.3. Insights from this cross-sectional study help to inform tailored care interventions to subgroups of people with PD most vulnerable to the impact of COVID-19 on mental health and quality of life.

Encapsulation of guest molecules into a dendritic box.

Dendrimers are well-defined, highly branched macromolecules that emanate from a central core and are synthesized through a stepwise, repetitive reaction sequence. The synthesis and characterization of dendritic boxes, based on the construction of a chiral shell of protected amino acids onto poly(propyleneimine) dendrimers with 64 amine end groups, is reported here. Nuclear magnetic resonance-relaxation and optical data show that a dense shell with solid-phase character is formed. Guest molecules were captured within the internal cavities of the boxes when these boxes were constructed in the presence of guest molecules. The diffusion of guest molecules out of the boxes into solution was unmeasurably slow because of the close packing of the shell. These monomolecular dendritic containers of 5-nanometer dimensions with physically locked-in guest molecules were characterized spectroscopically.

Predictability and prognosis of PTCA-induced coronary artery aneurysms.

The natural history of coronary aneurysms, defined as local dilatations exceeding the diameter of the normal adjacent vessel segments by at least 1.5 times, is not significantly different from the natural history of nonaneurysmal coronary disease. However, little is known about the prognosis of percutaneous transluminal coronary angioplasty (PCTA)-induced coronary aneurysms. Therefore, we investigated the occurrence and the medium long-term prognosis of such aneurysms in 728 patients who, after successful PTCA, underwent repeat coronary angiography at mean 4.5 months post-PTCA. A coronary aneurysm at the site of PTCA ws noted in 3.9% of patients (n = 28). Of the potentially predictive factors analyzed, only a coronary dissection at the time of PTCA had statistically significant influence. The long-term prognosis of PTCA-induced coronary aneurysms was excellent. One patient underwent (unrelated) cardiac surgery, all other 27 patients remained eventfree. We conclude that the same benign nature of coronary aneurysmal disease holds true for those aneurysms that develop after PTCA.

Bacteriorhodopsin's M412 intermediate contains a 13-cis, 14-s-trans, 15-anti-retinal Schiff base chromophore.

The structure of the retinal chromophore about the C = N and C14-C15 bonds in bacteriorhodopsin's M412 intermediate has been determined by analyzing resonance Raman spectra of 2H and 13C isotopic derivatives. Normal mode calculations on 13-cis-retinal Schiff bases demonstrate that the C15-D rock and N-CLys stretch are strongly coupled for C = N-syn chromophores and weakly coupled for C = N-anti chromophores. When the Schiff base geometry is anti, the C15-D rock appears as a localized resonance Raman active mode at approximately 980 cm-1, which is moderately sensitive to 13C substitution at positions 14 and 15 (approximately 7 cm-1) and insensitive to 13C substitution at the epsilon position of lysine. When the Schiff base geometry is syn, in-phase and out-of-phase combinations of the C15-D rock and N-CLys stretch are predicted at approximately 1060 and approximately 910 cm-1, respectively. The in-phase mode is more sensitive to 13C substitution at positions 14 and 15 (approximately 15 cm-1) and at the epsilon position of lysine (approximately 4 cm-1). Calculations and comparison with experimental data on dark-adapted bacteriorhodopsin indicate that the in-phase mode at approximately 1060 cm-1 carries the majority of the resonance Raman intensity. M412 exhibits a C15-D rock at 968 cm-1 that shifts 8 cm-1 when 13C is added at positions 14 and 15 and is insensitive to 13C substitution at the epsilon-position of lysine. This demonstrates that M412 contains a C = N-anti Schiff base.(ABSTRACT TRUNCATED AT 250 WORDS)

Complete assignment of the hydrogen out-of-plane wagging vibrations of bathorhodopsin: chromophore structure and energy storage in the primary photoproduct of vision.

Resonance Raman vibrational spectra of the retinal chromophore in bathorhodopsin have been obtained after regenerating bovine visual pigments with an extensive series of 13C- and deuterium-labeled retinals. A low-temperature spinning cell technique was used to produce high-quality bathorhodopsin spectra exhibiting resolved hydrogen out-of-plane wagging vibrations at 838, 850, 858, 875, and 921 cm-1. The isotopic shifts and a normal coordinate analysis permit the assignment of these lines to the HC7 = C8H Bg, C14H, C12H, C10H, and C11H hydrogen out-of-plane wagging modes, respectively. The coupling constant between the C11H and C12H wags as well as the C12H wag force constant are unusually low compared to those of retinal model compounds. This quantitatively confirms the lack of coupling between the C11H and C12H wags and the low C12H wag vibrational frequency noted earlier by Eyring et al. [(1982) Biochemistry 21, 384]. The force constants for the C10H and C14H wags are also significantly below the values observed in model compounds. We suggest that the perturbed hydrogen out-of-plane wagging and C-C stretching force constants for the C10-C11 = C12-C13 region of the chromophore in bathorhodopsin result from electrostatic interactions with a charged protein residue. This interaction may also contribute to the 33 kcal/mol energy storage in bathorhodopsin.

Chromophore structure in bacteriorhodopsin's N intermediate: implications for the proton-pumping mechanism.

By elevating the pH to 9.5 in 3 M KCl, the concentration of the N intermediate in the bacteriorhodopsin photocycle has been enhanced, and time-resolved resonance Raman spectra of this intermediate have been obtained. Kinetic Raman measurements show that N appears with a half-time of 4 +/- 2 ms, which agrees satisfactorily with our measured decay time of the M412 intermediate (2 +/- 1 ms). This argues that M412 decays directly to N in the light-adapted photocycle. The configuration of the chromophore about the C13 = C14 bond was examined by regenerating the protein with [12,14-2H]retinal. The coupled C12-2H + C14-2H rock at 946 cm-1 demonstrates that the chromophore in N is 13-cis. The shift of the 1642-cm-1 Schiff base stretching mode to 1618 cm-1 in D2O indicates that the Schiff base linkage to the protein is protonated. The insensitivity of the 1168-cm-1 C14-C15 stretching mode to N-deuteriation establishes a C = N anti (trans) Schiff base configuration. The high frequency of the C14-C15 stretching mode as well as the frequency of the 966-cm-1 C14-2H-C15-2H rocking mode shows that the chromophore is 14-s-trans. Thus, N contains a 13-cis, 14-s-trans, 15-anti protonated retinal Schiff base.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteriorhodopsin's L550 intermediate contains a C14-C15 s-trans-retinal chromophore.

Conformational changes of the retinal chromophore about the C14-C15 bond in bacteriorhodopsin (BR) have been proposed in models for the mechanism of light-driven proton transport. To determine the C14-C15 conformation in BR's L550 intermediate, we have examined the resonance Raman spectra of BR derivatives regenerated with retinal deuterated at the 14 and 15 positions. Vibrational calculations show that the C14-2H and C15-2H rocking modes form symmetric (A) and antisymmetric (B) combinations in [14,15-2H]retinal chromophores. When there is a trans conformation about the single bond between C14 and C15 (14-s-trans), a small frequency separation or splitting is observed between the A and B modes, which are found at approximately equal to 970 cm-1. In 14-s-cis molecules, the splitting is large, and the Raman-active symmetric A mode is predicted at approximately equal to 850 cm-1. In addition, the monodeuterium rock should appear at an unusually low frequency (920-930 cm-1) in the 14-2H-labeled 14-s-cis molecules. These patterns are insensitive to computational details: similar results are predicted by a modified Urey-Bradley force field and by MNDO (modified neglect of differential overlap) calculations for twisted chromophores and for highly delocalized protonated Schiff base cations. Time-resolved resonance Raman spectra were obtained of BR's L550 intermediate regenerated with [14-2H]-, [15-2H]- and [14,15-2H]retinal. The symmetric A rock in L550 is found at 968 cm-1, within 4 cm-1 of the frequencies for the monodeuterio derivatives, and no scattering is observed between 800 and 940 cm-1. The rocking frequencies of deuterated L550 are within 5 cm-1 of those observed in BR568, which contains a 14-s-trans chromophore. These results show that L550 contains a 14-s-trans chromophore and suggest that only 14-s-trans structures are involved in the proton pumping photocycle of BR.

Vibrational analysis of the all-trans retinal protonated Schiff base.

We have obtained Raman spectra of a series of all-trans retinal protonated Schiff-base isotopic derivatives. 13C-substitutions were made at the 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, and 15 positions while deuteration was performed at position 15. Based on the isotopic shifts, the observed C--C stretching vibrations in the 1,100-1,400 cm-1 fingerprint region are assigned. Normal mode calculations using a modified Urey-Bradley force field have been refined to reproduce the observed frequencies and isotopic shifts. Comparison with fingerprint assignments of all-trans retinal and its unprotonated Schiff base shows that the major effect of Schiff-base formation is a shift of the C14--C15 stretch from 1,111 cm-1 in the aldehyde to approximately 1,163 cm-1 in the Shiff base. This shift is attributed to the increased C14--C15 bond order that results from the reduced electronegativity of the Schiff-base nitrogen compared with the aldehyde oxygen. Protonation of the Schiff base increases pi-electron delocalization, causing a 6 to 16 cm-1 frequency increase of the normal modes involving the C8--C9, C10--C11, C12--C13, and C14--C15 stretches. Comparison of the protonated Schiff base Raman spectrum with that of light-adapted bacteriorhodopsin (BR568) shows that incorporation of the all-trans protonated Schiff base into bacterio-opsin produces an additional approximately 10 cm-1 increase of each C--C stretching frequency as a result of protein-induced pi-electron delocalization. Importantly, the frequency ordering and spacing of the C--C stretches in BR568 is the same as that found in the protonated Schiff base.