Covid-19 in Parkinson's Disease treated by drugs or brain stimulation / COVID-19 en la enfermedad de Parkinson tratada con fármacos o estimulación cerebral

Purpose: Covid-19 has affected all people, especially those with chronic diseases, including Parkinson's Disease (PD). Covid-19 may affect both motor and neuropsychiatric symptoms of PD patients. We intend to evaluate different aspects of Covid-19 impact on PD patients. Methods: 647 PD patients were evaluated in terms of PD-related and Covid-19-related clinical presentations in addition to past medical history during the pandemic through an online questioner. They were compared with an age-matched control group consist of 673 individuals and a sample of the normal population consist of 1215 individuals. Results: The prevalence of Covid-19 in PD patients was 11.28%. The mortality was 1.23% among PD patients. The prevalence of Covid-19 in PD patients who undergone Deep Brain Stimulation (DBS) was 18.18%. No significant association was found between the duration of disease and the prevalence of Covid-19. A statistically significant higher prevalence of Covid-19 in PD patients who had direct contact with SARS-CoV-19 infected individuals was found. No statistically significant association has been found between the worsening of motor symptoms and Covid-19. PD patients and the normal population may differ in the prevalence of some psychological disorders, including anxiety and sleeping disorders, and Covid-19 may affect the psychological status. Conclusion: PD patients possibly follow tighter preventive protocols, which lead to lower prevalence and severity of Covid-19 and its consequences in these patients. Although it seems Covid-19 does not affect motor and psychological aspects of PD as much as it was expected, more accurate evaluations are suggested in order to clarify such effects.(AU)

Objetivo: La COVID-19 ha afectado a toda la población, especialmente a aquellos con enfermedades crónicas, incluyendo a los pacientes con enfermedad de Parkinson (EP). La COVID-19 puede empeorar tanto los signos motores como los síntomas neuropsiquiátricos de los pacientes con EP. El objetivo de este estudio es evaluar diferentes aspectos del impacto de la COVID-19 en los pacientes con EP. Métodos: A través de un cuestionario virtual se evaluó a 647 pacientes con EP de acuerdo con sus presentaciones clínicas relacionadas con la EP y con la COVID-19, además de la historia médica previa durante la pandemia. Se compararon con un grupo de controles sanos de la misma edad que constaba de 673 individuos y una muestra de la población general de 1.215 individuos. Resultados: La prevalencia de la COVID-19 en pacientes con EP fue del 11,28%. La mortalidad fue del 1,23% entre los pacientes con EP. La prevalencia de COVID-19 en pacientes con EP con estimulación cerebral profunda fue del 18,18%. No se encontró una asociación significativa entre la duración de la enfermedad y la prevalencia de COVID-19. Se halló una prevalencia mayor de COVID-19 que fue estadísticamente significativa en pacientes con EP que tuvieron contacto directo con personas infectadas con SARS-CoV-2. No se encontró una asociación estadísticamente significativa entre el empeoramiento de los signos motores y la COVID-19. Los pacientes con EP y la población general podrían diferir en la prevalencia de algunos trastornos psicológicos, incluidos los trastornos de ansiedad y del sueño, y la COVID-19 podría afectar al estado psicológico. Conclusión: Los pacientes con EP posiblemente sigan protocolos preventivos más estrictos, lo que conduce a una menor prevalencia y gravedad de COVID-19 y de sus consecuencias en estos pacientes.(AU)

Covid-19 in Parkinson's Disease treated by drugs or brain stimulation.

PURPOSE: Covid-19 has affected all people, especially those with chronic diseases, including Parkinson's Disease (PD). Covid-19 may affect both motor and neuropsychiatric symptoms of PD patients. We intend to evaluate different aspects of Covid-19 impact on PD patients. METHODS: 647 PD patients were evaluated in terms of PD-related and Covid-19-related clinical presentations in addition to past medical history during the pandemic through an online questioner. They were compared with an age-matched control group consist of 673 individuals and a sample of the normal population consist of 1215 individuals. RESULTS: The prevalence of Covid-19 in PD patients was 11.28%. The mortality was 1.23% among PD patients. The prevalence of Covid-19 in PD patients who undergone Deep Brain Stimulation (DBS) was 18.18%. No significant association was found between the duration of disease and the prevalence of Covid-19. A statistically significant higher prevalence of Covid-19 in PD patients who had direct contact with SARS-CoV-19 infected individuals was found. No statistically significant association has been found between the worsening of motor symptoms and Covid-19. PD patients and the normal population may differ in the prevalence of some psychological disorders, including anxiety and sleeping disorders, and Covid-19 may affect the psychological status. CONCLUSION: PD patients possibly follow tighter preventive protocols, which lead to lower prevalence and severity of Covid-19 and its consequences in these patients. Although it seems Covid-19 does not affect motor and psychological aspects of PD as much as it was expected, more accurate evaluations are suggested in order to clarify such effects.

Covid-19 in Parkinson's Disease treated by drugs or brain stimulation.

PURPOSE: Covid-19 has affected all people, especially those with chronic diseases, including Parkinson's Disease (PD). Covid-19 may affect both motor and neuropsychiatric symptoms of PD patients. We intend to evaluate different aspects of Covid-19 impact on PD patients. METHODS: 647 PD patients were evaluated in terms of PD-related and Covid-19-related clinical presentations in addition to past medical history during the pandemic through an online questioner. They were compared with an age-matched control group consist of 673 individuals and a sample of the normal population consist of 1215 individuals. RESULTS: The prevalence of Covid-19 in PD patients was 11.28%. The mortality was 1.23% among PD patients. The prevalence of Covid-19 in PD patients who undergone Deep Brain Stimulation (DBS) was 18.18%. No significant association was found between the duration of disease and the prevalence of Covid-19. A statistically significant higher prevalence of Covid-19 in PD patients who had direct contact with SARS-CoV-19 infected individuals was found. No statistically significant association has been found between the worsening of motor symptoms and Covid-19. PD patients and the normal population may differ in the prevalence of some psychological disorders, including anxiety and sleeping disorders, and Covid-19 may affect the psychological status. CONCLUSION: PD patients possibly follow tighter preventive protocols, which lead to lower prevalence and severity of Covid-19 and its consequences in these patients. Although it seems Covid-19 does not affect motor and psychological aspects of PD as much as it was expected, more accurate evaluations are suggested in order to clarify such effects.

Conformational behavior of polyalanine peptides with and without protecting groups of varying chain lengths: population of PP-II structure!

Oculopharyngeal muscular dystrophy (OPMD), a polyalanine myopathy, occurs due to expansion of homo-polyalanine stretch in normal polyadenylating binding protein nuclear 1 (PABPN1) protein from Ala10 to Ala11-17. Therefore, the conformational behavior of polyalanine peptides with n = 10-17, with and without terminal protecting groups, have been investigated with different starting geometries in water by molecular dynamics simulation studies. Alanine peptides are shown to give rise to unordered structure irrespective of starting geometry and not more than two residues at a stretch have the same/similar set of φ, ψ values. However, the final structure with terminal protecting groups look like ß-strand. Unprotected poly-Ala peptides adopt twisted ß-hairpin/multi hairpin like structure with increasing chain length. The number of residues having φ, ψ values in collagen region is found to be less in peptides with unprotected termini as compared to peptides with protected termini of same chain length. The results have been supported by recent synchrotron radiation circular dichroism spectroscopy of polyproline II and unordered secondary structures. Opening of the helical structure in poly-Ala peptides with protecting groups has been shown to take place from C-terminal and in peptides without protecting groups opening of helix starts from both terminals. Further, opening of helix takes more time in poly-Ala peptides without terminal protecting groups. The deviations in amide bond planarity have been discussed and compared with available experimental and computational results.

Digitally controlled feedback for DC offset cancellation in a wearable multichannel EMG platform.

Wearable systems capable to capture vital signs allow the development of advanced medical applications. One notable example is the use of surface electromyography (EMG) to gather muscle activation potentials, in principle an easy input for prosthesis control. However, the acquisition of such signals is affected by high variability and ground loop problems. Moreover, the input impedance influenced in time by motion and perspiration determines an offset, which can be orders of magnitude higher than the signal of interest. We propose a wearable device equipped with a digitally controlled Analog Front End (AFE) for biopotentials acquisition with zero-offset. The proposed AFE solution has an internal Digital to Analog Converter (DAC) used to adjust independently the reference of each channel removing any DC offset. The analog integrated circuit is coupled with a microcontroller, which periodically estimates the offset and implements a closed loop feedback on the analog part. The proposed approach was tested on EMG signals acquired from 4 subjects while performing different activities and shows that the system correctly acquires signals with no DC offset.

Conformational study of N-methylated alanine peptides and design of Abeta inhibitor.

N-Methylation increases the proteolytic stability of peptides and leads to improved pharmacological and increased nematicidal property against plant pathogens. In this study, the quantum mechanical and molecular dynamic simulation approaches were used to investigate conformational behavior of peptides containing only N-methylated alanine (NMeAla) residues and N-methylated alanine and alanine residues at alternate positions. The amide bond geometry was found to be trans and the poly NMeAla peptides were shown to populate in the helical structure without hydrogen bond with phi, psi values of - 0, 90 degrees stabilized by carbonyl-carbonyl interactions. Molecular dynamic simulations in water/methanol revealed the formation of beta-strand structure, irrespective of the starting geometry due to the interaction of solvent molecules with the carbonyl groups of peptide backbone. Analysis of simulation results as a function of time suggested that the opening of helical structure without hydrogen bond started from C-terminal. Conformational behavior of peptides containing N-MeAla and Ala was used to design Abeta peptide inhibitor and the model tetrapeptide Ac-Ala-NMeAla-Ala-NHMe in the beta-strand structure was shown to interact with the hydrophobic stretch of Abeta15-42 peptide.

Conformational behavior of phenylglycines and hydroxyphenylglycines and non-planarity of phenyl rings.

The non-proteinogenic amino acids--phenylglycine (PG) and hydroxyphenylglycine (HPG) are crucial components of certain peptidic natural products and are important for the preparation of various medicines. In this, study, the conformation of model dipeptides Ac-X-NHMe of PG, p-HPG and 3, 5-di-hydroxyphenylglycine (3, 5-DHPG) was studied both in R and S form by quantum mechanical (QM) and molecular dynamics approaches. On the energy scale, the conformational states of these molecules in both the R and S were found to be degenerate by QM studies, stabilized by non-covalent interactions like carbonyl--carbonyl interactions, carbonyl-lp .. π (aromatic ring) interactions etc. These interactions disappeared/weakened due to interaction of water molecules with carbonyl groups of backbone in simulation and water was found to interact with the aromatic ring through O(w)-H .. π or O(w)lp .. π interactions. The degeneracy of conformational states was lifted in favor of R-form of PG and DHPG and water molecules interactions with aromatic ring led to non-planarity of the aromatic ring. In simulation studies, irrespective of the starting geometry, the Φ, ψ values for the R form correspond to inverse ß/inverse collagen region and for the S-form, the Φ, ψ values correspond to ß/collagen region i.e., adopt single conformation. The obtained results were in conformity with the CD spectroscopic data on D-PG and D-p-HPG. The conformational behavior of the unusual amino acids might be of great help in designing of bioactive peptides/peptide based drugs to be realized in single conformation--an essential requirement.

Insights on the structural characteristics of Vim-TBS (58-81) peptide for future applications as a cell penetrating peptide.

The plasma membrane presents a remarkable barrier for the delivery of peptide and nucleic acid based drugs to the inside of cells. This restraint in the path of their development as therapeutic agents can be offset by their conjugation to cell penetrating peptides (CPPs) that can lead to an improved pharmacological profile. In this context, conformational behavior of Vimentin Tubulin Binding Site (TBS) peptide, Vim-TBS (58-81), was investigated for its acknowledged cell penetrating properties along with Trans-activating Tat (48-60) peptide and a pro-apoptogenic peptide of p21/WAFI protein (p10). Also, the fusion peptides Vim- TBS (58-81)-p10 & Tat (48-60)-p10 were studied using molecular mechanics (MM) and molecular dynamics (MD) based strategies. MM results revealed formation of stable α-helix like secondary structures in Vim-TBS (58-81), Tat (48-60) and p10 peptides. In water, three peptides adopted either a helical structure or a random conformation; the stability of either of the two states being governed by the formation of polar contacts with the solvent. The fusion peptides formed helical structures after MD simulations but the structure obtained for the fusion peptide, Vim-TBS-p10 is relatively better characterized in terms of its amphipathic nature with a hydrophilic face formed by the positively charged residues facilitating a better interaction of this fusion peptide with the membrane as compared to that of Tat-p10 peptide. This is the first report on the conformational characteristics of the Vim-TBS (58-81) peptide and the fusion peptide, Vim-TBS (58-81)-p10. The results presented here are significant for their potential role in guiding and facilitating the future efforts of designing peptide based cell penetrating drugs.

Efficacy and safety of mycophenolate mofetil vs. methotrexate for the treatment of chronic plaque psoriasis.

BACKGROUND: Methotrexate (MTX) is a well-known systemic drug for moderate to severe chronic plaque psoriasis. Recently, mycophenolate mofetil (MMF) has been recommended for psoriasis. OBJECTIVE: To compare the efficacy and safety of MMF vs. MTX for the treatment of chronic plaque psoriasis. METHODS: Thirty-eight consecutive patients with Psoriasis Area and Severity Index (PASI)>10 were randomly assigned for 12 weeks of treatment with either MTX (18 patients; initial dose, 7.5 mg/week) or MMF (20 patients; dose; 2 g/day) and were followed for 12 weeks after discontinuing the treatment. The differences between the two groups were analysed at the end of treatment and follow-up comparing with baseline values. RESULTS: After 12 weeks of treatment, the mean ± SD score for the PASI decreased from 16.46 ± 5.29 at baseline to 3.17 ± 2.35 among 15 patients treated with MTX, whereas the score decreased from 17.43 ± 7.42 to 3.97 ± 5.95 among 17 patients treated with MMF (P>0.05). Twelve weeks after discontinuing the treatment, the scores were 4.77 ± 3.52 and 5.94 ± 4.27, respectively (P>0.05). PASI -75 were achieved in 58.8% of patients in MMF group and 73.3% in MTX group (P > 0.05). Three months after discontinuing the treatment, PASI-75 remained in 33.3% of patients in MMF and 53.3% of MTX group (P > 0.05). Both drugs were well tolerated and side-effects were minor and transient. CONCLUSIONS: No significant differences in efficacy were found between MTX and MMF groups. MMF may represent a good alternative for the treatment of psoriasis in patients who are unable to take MTX or other available drugs due to contraindication or toxicity.

Effects of oral clonidine premedication on haemodynamic response to laryngoscopy and tracheal intubation: a clinical trial.

The objective of this study was to evaluate the efficacy of pre-anesthetic orally administration of clonidine on pulse rate and blood stress response to laryngoscopy and tracheal intubation. In a double-blinded, randomized study, 274 ASA I and II subjects with age of 18 to 45 years scheduled for elective surgery under general anesthesia were enrolled. They were randomly allocated to receive oral clonidine (0.2 mg) or placebo as premedication 90-120 min before surgery. All the patients received Succinylcholine (1.5 mg kg(-1)) after induction of anesthesia with Fentanyl (50 microg) and Thiopentone (5 mg kg(-1)). The anesthesia was maintained with halothane (1.5 Mac) in 50% mixture of N2O/O2. Heart rate and systolic blood pressure were recorded before, immediately after and then every 5 min after intubation until 20 min. The Clonidine group showed a significant superiority over placebo in the prevention of increase in systolic blood pressure as well as heart rate over the intubation. A significant difference was observed in both heart rate and systolic blood pressures were significantly higher in Control group at three subsequent measurements following intubation. The results of this study suggest that orally administered clonidine in preanesthetic period, provides more haemodynamic stability and attenuates the stress response to laryngoscopy and intubation.

Effect of adding ketamine to pethidine on postoperative pain in patients undergoing major abdominal operations: a double blind randomized controlled trial.

To determine the effect of adding ketamine to pethidine in reducing post-operative pain in patients undergoing major abdominal operations, in a double blind randomized controlled trial, 100 patients aged 15-60 years who were candidate for elective major abdominal surgery allocated into two groups of pethidine + ketamine group (5 mg pethidine and 0.25 mg kg(-1) ketamine) or pethidine and placebo group (10 mg pethidine and NS) according to the regimen prescribed in postanesthesia care unit. Severity of pain (using visual analogue scale), prescribed dose of pethidine and side effects were recorded until 24 h after operation. Regarding post-operative pain, pethidine + ketamine group showed significant lower scores in all the times except 0 min, 2, 6 and 16 h. Nausea was significantly less frequent amongst pethidine + placebo group at times of 0, 15, 30 and 45 min (p < 0.05). Comparison of two groups did not show significant differences in prescribed pethedine dose in 0, 9, 12, 16, 20 and 24 h (p > 0.05). Yet, the mean dose of administered pethidine as rescue analgesic was significant lower in pethidine + ketamine group compared to pethidine + placebo group (112 +/- 31.5 mg vs. 133.5 +/- 24.5 mg, p < 0.001). In conclusion, our results showed that co-administration of ketamine and pethidine in postanesthesia care unit will improve postoperative pain and reduce narcotic consumption. It may, however, increase rate of postoperative nausea in the first hour after operation.

Conformational study of poly-DeltaAbu peptides and construction of amphipathic nanostructure.

Generally, it is believed that alpha,beta-dehydroamino acid residues are most stable in the Z- form rather than in the E- form. In this study, it has been shown that poly-DeltaAbu exists in alternate Delta(E)Abu and Delta(Z)Abu form, with phi, psi values of approximately 0 degrees , 80 degrees and 35 degrees , 27 degrees for the E- and Z- forms, respectively, rather than the all Z- form. The conformational results for the peptides Ac-DeltaAbu(2)-NHMe and Ac-L/D-Ile-Delta(Z)Abu/Delta(E)Abu-NHMe suggest the incorporation of DeltaAbu in both the Z- and E- forms, which is consistent with the available observations in natural systems. Because of adoption of phi, psi values corresponding to the collagen type structure ( approximately -30 degrees , 120 degrees ) by Ile residue and with phi, psi values in the left-handed helical region for Delta(Z)Abu residue, the peptide Ac-(L-Ile-Delta(Z)Abu)(3)-NHMe adopts an amphipathic left-handed helical beta-sheet type structure. This structure is stabilized by network of hydrogen bonding, carbonyl-carbonyl, and CH-O interactions and can be exploited for the construction of antimicrobial peptides and nanomaterials.

The Alzheimer beta-amyloid (Abeta(1-39)) dimer in an implicit solvent.

Oligomers of Abeta peptides are suspected as the underlying cause of Alzheimer disease. Knowledge of their structural properties could therefore lead to a deeper understanding of the mechanism behind the outbreak of this disease. As a step in this direction we have studied Abeta dimers by all-atom molecular dynamics simulations. Equilibrated structures at 300 K were clustered into different families with similar structural features. The dominant cluster has parallel N-terminals and a well defined segment Leu17-Ala21 that are stabilized by salt bridges between Lys28 of one chain and either Glu22 or Asp23 of the other chain. The formation of these salt bridges may be the limiting step in oligomerization and fibrillogenesis.

New type of helix and 2(7) ribbon structure formation in poly DeltaLeu peptides: construction of a single-handed template.

alpha,beta-Dehydroamino acid residues due to the presence of Calpha = Cbeta double bond influences the main chain and the side chain conformations. These residues have interesting chemical features including the increased resistance to enzymatic degradation. The chain length dependent conformational behavior of poly alpha,beta-dehydroleucine (DeltaLeu) peptides in both the pure forms Z and E and their various combinations like alternate ZE/EZ etc. have been investigated by using quantum mechanical method PCILO (perturbative configuration interaction of localized orbitals). The conformational states in alternate Z and E forms, with Phi, Psi values of -10 degrees , 105 degrees /1 degrees , -88 degrees for Z form and 35 degrees , 22 degrees /-34 degrees , -27 degrees for the E form are found to be the most stable and degenerate than the states in pure Z and E forms and the EZ form etc. The repeated Phi, Psi values give rise to altogether new types of left and right handed helices, and their stability increases with increasing chain length. These structures are stabilized by intramolecular hydrogen bonding, carbonyl-carbonyl interactions and hydrophobic interactions between the side chains of DeltaZLeu and DeltaELeu residues. The 2(7) ribbon structure (seven-membered hydrogen-bonded ring involving two consecutive amino acid residues) is found to be most stable and degenerate in the pentapeptide Ac-DeltaELeu5-NHMe, due to the formation of maximum hydrogen bonds. A right-handed template from achiral DeltaLeu peptides has been achieved by incorporating L-Leu at the C-terminal or D-Leu at the N-terminal.

Effect of terminal achiral and chiral residues on the conformational behaviour of poly Δ(z)Phe and analysis of various interactions.

Conformational properties of the peptides containing (Δ(Z)Phe)6 with achiral (ΔAla, Gly) and chiral (Ala, Leu) residues at both the N- and C-terminal positions have been studied with a view to design a peptide with desired helical screw sense. In all the peptides, the lowest energy conformational state corresponds to Φ = 0° and Ψ = + 90° or - 90° or both +/- 90°. These structures are characterized by rise per residue of 1.94 Å; rotation per residue of 114° and 3.12 residues per turn and are stabilized by: (i) carbonyl-carbonyl interactions with the carbonyl oxygen of ith residue and carbonyl carbon atom of the carbonyl group of ith+1 residue; and (ii) N-H....π interactions between the amino group of Δ(Z)Phe and its own aromatic moiety. The Ala/Leu residues at the N-terminus further stabilized the structure, through C-H....π interactions with the farthest edge of the aromatic ring of ith+3 Δ(Z)Phe residue. For peptides Ac-L-Ala/L-Leu-(Δ(Z)Phe)6-NHMe, the low energy left handed helical structure (approximately 2.5 Kcalmol⁻¹ higher in energy) state corresponds to Φ = -30°, Ψ = 120° for L-residue and Φ = Ψ = 30° for Δ(Z)Phe residues and is in good agreement with the X-ray crystallography results for the peptide Boc-L-Ala-(Δ(Z)Phe)4-NHMe crystals grown from acetonitrile/ethanol mixture. Computational results suggest that the peptides Ac-DAla/D-Leu-(Δ(Z)Phe)6-NHMe adopt a right handed helical structure in polar solvents with Φ = 30°, Ψ = -120° for D-residues and Φ = Ψ = -30° for Δ(Z)Phe residues. Both in the left handed and right handed structures, the carbonyl oxygen of acetyl group is involved in 10-membered hydrogen bonded ring formation with NH of 3rd Δ(z)Phe residue whereas Δ(Z)Phe residues backbone adopts a 310 helix structure. Computational results also suggest that the conformational state with Φ = 0° and Ψ = 90° can be realized by keeping D-Ala or D-Leu at the C-terminal. There is hardly any effect of achiral residues Gly/ΔAla on the conformational behaviour of poly-Δ(Z)Phe.