The initial steps of the folding pathway of the C-terminal domain of the murine prion protein mPrP(90–231) are predicted based on the sequential collapse model (SCM). A non-local dominant contact is ...found to form between the connecting region between helix 1 and β-sheet 1 and the C-terminal region of helix 3. This non-local contact nucleates the most populated molten globule-like intermediate along the folding pathway. A less stable early non-local contact between segments 120–124 and 179–183, located in the middle of helix 2, promotes the formation of a less populated molten globule-like intermediate. The formation of the dominant non-local contact constitutes an example of the postulated Nature’s Shortcut to the prion protein collapse into the native structure. The possible role of the less populated molten globule-like intermediate is explored as the potential initiation point for the folding for three pathogenic mutants (T182A, I214V, and Q211P in mouse prion numbering) of the prion protein.
In the realm of electric motor design, achieving high efficiency at elevated operational speeds is paramount for various applications, ranging from automotive propulsion to industrial machinery. This ...research delves into the significance of high-efficiency interior permanent magnet synchronous motors (IPMSMs), particularly when operating in the flux-weakening (FW) region. The focus is on the pivotal role played by the characteristic current in expanding the high-efficiency region at these demanding operational speeds. By manipulating the characteristic current, this research explores avenues for improvements in efficiency during FW operation. The investigation is substantiated through a comprehensive approach, incorporating both simulation and experimental validation. Through rigorous analysis, the study demonstrates that manipulating characteristic current represents a viable strategy for improving the high-efficiency region of IPMSMs when operating at high speeds in the FW region.
In Cognitive Radio Non-Orthogonal Multiple Access (CR-NOMA), hybrid successive interference cancellation (SIC) was proposed to improve the probability for a secondary user to be served. It shifts the ...traditional focus on channel state information (CSI) to a quality of service (QoS) driven strategy, which matches cognitive radio philosophy. We present an analytical framework to theoretically study Hybrid SIC (HS) and Hybrid SIC with dynamic power control (HS-P) algorithms in terms of their probability of success under Rayleigh channel. Specifically, considering a CR-NOMA uplink system, we analyse the probability to allocate a primary and a secondary user into a radio resource, given their minimum QoS requirement. We obtain closed-form expressions for the mentioned algorithms and investigate the impact that the minimum QoS and the channel conditions have on the performance. Our analysis demonstrates that both algorithms share similarities in the way the primary user behaves, whereas they significantly differ in the secondary user's case. Finally, we validate the correctness of the study by conducting Monte Carlo simulations using various system parameters. Our results show that our theoretical expressions closely match the simulated results in all testing scenarios. They appear promising to design advanced CR-NOMA features to enhance system performance based on success probability such as grouping algorithms.
In this article, we investigate two issues: (a) the initial contact formation events along the folding pathway of the DNA-binding domain of the tumor suppressor protein p53 (core p53); and (b) the ...intermolecular events leading to its conversion into a prion-like form upon incubation with peptide P8(250-257). In the case of (a), the calculations employ the sequential collapse model (SCM) to identify the segments involved in the initial contact formation events that nucleate the folding pathway. The model predicts that there are several possible initial non-local contacts of comparative stability. The most stable of these possible initial contacts involve the protein segments 159AMAIY163 and 251ILTII255, and it is the only native-like contact. Thus, it is predicted to constitute “Nature’s shortcut” to the native structure of the core domain of p53. In the case of issue (b), these findings are then combined with experimental evidence showing that the incubation of the core domain of p53 with peptide P8(250-257), which is equivalent to the native protein segment 250PILTIITL257, leads to an amyloid conformational transition. It is explained how the SCM predicts that P8(250-257) effectively interdicts in the formation of the most stable possible initial contact and, thereby, disrupts the subsequent normal folding. Interdiction by polymeric P8(250-257) seeds is also studied. It is then hypothesized that enhanced folding through one or several of the less stable contacts could play a role in P8(250-257)-promoted core p53 amyloid misfolding. These findings are compared to previous results obtained for the prion protein. Experiments are proposed to test the hypothesis presented regarding core p53 amyloid misfolding.
In a recent paper, we proposed the folding interdiction target region (FITR) strategy for therapeutic drug design in SARS-CoV-2. This paper expands the application of the FITR strategy by proposing ...therapeutic drug design approaches against Ebola virus disease and influenza A. We predict target regions for folding interdicting drugs on correspondingly relevant structural proteins of both pathogenic viruses: VP40 of Ebola, and matrix protein M1 of influenza A. Identification of the protein targets employs the sequential collapse model (SCM) for protein folding. It is explained that the model predicts natural peptide candidates in each case from which to start the search for therapeutic drugs. The paper also discusses how these predictions could be tested, as well as some challenges likely to be found when designing effective therapeutic drugs from the proposed peptide candidates. The FITR strategy opens a potential new avenue for the design of therapeutic drugs that promises to be effective against infectious diseases.
Cognitive and neuropsychiatric disorders in patients with multiple sclerosis have been extensively documented. The focus of this review will be on cognitive and neuropsychiatric disorders in multiple ...sclerosis patients from Latin America, in the context of international literature. Multicentre studies carried out in Latin America have shown that 43% of the patients have cognitive impairment and 34.5% in early stages of the disease, 29% depression and 20.9% neuropsychiatric disorders. The profile of cognitive impairment corresponds to alterations in visual and verbal memory, in attention, in information processing speed and in verbal fluency. The neuropsychiatric profile showed disorders in anxiety, depression, apathy and irritability domains. In the region, there exist validations of the multiple sclerosis neuropsychological screening questionnaire (MSNQ), the brief repeatable battery of neuropsychological tests (BRB-N) and the brief international cognitive assessment for multiple sclerosis (BICAMS), as well as of the paced auditory serial addition test (PASAT) and the symbol digit modalities test (SDMT). A study showed that 53% of the patients who met the NEDA3 condition had cognitive impairment. This finding highlights the need for taking cognitive assessment into account when determining therapeutic efficacy.
We report the circulating genotypes and the frequency of macrolide-resistance patterns among Treponema pallidum pallidum DNA isolated from syphilitic lesions from patients who attended 2 sexual ...health clinics in Lima, Peru. We implemented and used a molecular typing scheme to describe local T. pallidum pallidum strains. Among 14 specimens, subtype 14d/f was the most prevalent strain in 7 fully typed T. pallidum DNA specimens obtained from men who have sex with men and transgender women presenting with chancre-like lesions. No macrolide-resistance mutations were found in T. pallidum DNA from 10 lesions.
•First Argentinean multicenter study of VRC and TR.•54 PWMS (23 males/31 females) were recruited for VRC.•QOL improved from baseline to the post-intervention assessment at VRC (p=<0.001).•NR ...treatment based on VR in MS in Argentina showed to be an effective tool.
Virtual Reality (VR) has emerged as a new treatment approach in neurorehabilitation (NR). REAVITELEM Study is a specific NR intervention program based on VR at center (VRC) and tele-rehabilitation (TR) in Argentina.
Methods First national multicenter study with a 12-week program intervention of VRC and TR. Participants were assessed at baseline, at 6th and 12th week. Phase I: recruitment and gather of 5 NR Centers from Argentina by the coordinator center (INEBA) to unify evaluation and intervention criteria. Phase II, all centers completed VRC an TR programs. Intervention was 30-minute session, twice a week for 12 weeks. Outcome measures: Expanded Disability Status Scale (EDSS), Fist and Key Pinch Dynamometry, Beck Depression Inventory-Fast Screen, Fatigue Severity Scale, Functional Independence Measure (FIM), International Questionnaire investigating Quality of life in MS (MusiQol) and a Visual Analogue Scale (VAS) of satisfaction after treatment.
Results A total of 54 PWMS (23 males) were recruited for VRC. Afterwards, 14 completed TR. The mean age for VRC was 44.72 (SD ± 13.74) and 41.71 (SD ± 10.5) for TR. The median EDSS was 4, 75 for VR. At VRC, 42 have RRMS, 8 have SPMS and 4 PPMS. At TR, 13 have RRMS and 1 have SPMS. The VAS reported an excellent level of satisfaction after treatment with an average of 9, 02 (SD±1.35) in VRC and 9.42 (SD±0.66) in TR. There were significant differences for MusiQol, which improved from baseline to the post-intervention assessment at VRC (p=<0.001) and at TR (p = 0.004) as well as FIM post-intervention assessment at VCR (p = 0.02) and TR (p = 0.04).
Conclusion this study suggest that the NR treatment based on VR in MS in Argentina, is an additional effective tool, which favors improvements in the level of functioning in activities of daily living, quality of life, mood, and satisfaction with the treatment.
According to previous studies, therapeutic inertia (TI) may affect 7 out of 10 physicians who care for MS patients, particularly in countries where clinical guidelines are not widely used. Limited ...information is available on the prevalence of TI and its associated factors across Canada.
(i) To evaluate factors associated with TI amongst neurologists caring for MS patients across Canada; (ii) to compare the prevalence of TI observed in Canadian neurologists to the prevalence of TI observed in Argentinean, Chilean, and Spanish neurologists (historical controls from prior studies).
One hundred and eight neurologists with expertise in MS were invited to participate in an online study in Canada. Participants answered questions regarding their clinical practice, risk preferences, management of 10 simulated case-scenarios. The design of that study was similar to that of the prior studies completed in Argentina and Chile (
= 115). TI was defined as lack of treatment initiation or escalation when there was clear evidence of clinical and radiological disease activity (8 case-scenarios, 440 individual responses). A TI score was created & defined as the number of case-scenarios that fit the TI criteria over the total number of presented cases (score range from 0 to 8), with a higher score corresponding to a higher TI. TI scores observed in the Canadian study were compared with those observed in Argentina and Chile, as both studies followed the same design, case-scenarios and methodologies. Predictors of TI included demographic data, MS specialist vs. general neurologist, practice setting, years of practice, volume of MS patients and risk preferences.
Fifty-five Canadian neurologists completed the study (completion rate: 50.9%). The mean age (±SD) was 38.3 (±15) years; 47.3% of the participants were female and 56.4% self-identified as MS specialists. Overall, 54 of 440 (12.3%) individual responses were classified as TI. 60% of participants displayed TI in at least one case-scenario. The mean TI score across Canada 0.98 (SD = 1.15) was significantly lower than the TI score observed in the Argentinean-Chilean 1.82 (SD = 1.47);
< 0.001 study. The multivariable analysis revealed that older age (
= 0.018), years of experience (
= 0.04) and willingness to risk further disease progression by avoiding treatment initiation or treatment change (
= 0.043) were independent predictors of TI.
TI in Canada was observed in 6 out of 10 neurologists, affecting on average 1 in 8 therapeutic decisions in MS care. TI in Canada is significantly lower than in the other studied countries. Factors associated with TI include older age, lower years of experience, and willingness to risk disease progression by avoiding treatment initiation or treatment change. Differences in clinical practice patterns and adherence/access to accepted MS guidelines may explain how TI in Canada differs significantly from TI in Argentina-Chile.
The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) was developed to provide valid assessment of cognitive impairment in multiple sclerosis (MS). The relationship between ...clinical and social variables and cognitive disorders has been extensively studied, but primarily in developed countries with a focus on other cognitive measures or batteries. The objectives of this study were to analyze the relationship between the BICAMS data and key clinical and sociodemographic variables in the Argentine MS population. A total of 50 MS patients were administered the Argentinean BICAMS Battery, comprised of the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test I (CVLT I), and the Brief Visuospatial Memory Test Revised (BVMTR). Disease progression, fatigue, depression, self-reported and informant report cognitive status, and employment status were assessed. Disease progression and employment status were most strongly associated with overall BICAMS performance (η
2
effect size values ranging from .302 to .624, all comparisons statistically significant). Informant rating of patient cognition, age, depression, disease duration, fatigue, and work hours were significantly associated as well. Gender, years of education, and patient-reported cognitive status were nonpredictive. A similar pattern was seen at the individual test level, with more variables related to the SDMT and CVLT I than BVMTR. BICAMS is strongly associated with overall disease progression and employment status.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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