Exploring barriers and educational needs in implementing dual-task training for Parkinson's disease: insights from professionals.

Introduction: There is growing evidence suggesting that dual-task training benefits people with Parkinson's disease (PD) on both physical and cognitive outcomes. However, there is no known data regarding professionals' educational needs and barriers to its implementation. This study aimed to explore the barriers and educational needs of healthcare and exercise professionals to integrate dual-task training into their practice with people with PD. Methods: We conducted a study based on a web survey. Social media channels were used to recruit a convenience sample of exercise and healthcare professionals working with people with PD. Results: Of the 185 eligible responses, the majority were physiotherapists (68.1%) followed by occupational therapists (10.8%). Most participants attended Parkinson specific training (88.6%) and employed the treatments set up in individual one on-one sessions (58.9%). We identified several barriers to dual-task training implementation, with lack of time (to prepare materials), staying creative and/ or accessing new ideas, unreliable tools for measuring gains, and insufficient expertise as the most referred by participants. The educational needs most referred included accessing examples of interventions in general, knowing what strategies to apply and their application for people with different symptoms. Discussion: Our results highlight that professionals remain challenged to integrate dualtask training into PD clinical care mainly due to knowledge gaps, difficulties in accessing new ideas, and lack of time.

Landing wise program: feasibility study protocol for Parkinson's disease.

Regardless of the benefits of fall prevention programs, people with Parkinson's disease (PD) will still fall. Therefore, it is crucial to explore novel therapeutic approaches that are well-accepted and effective for addressing fall risk and the fear of falls among this population. The present study aims to assess the feasibility of the Landing Wise program as a therapeutic intervention for reducing the fear of falling in people with PD. A mixed-methods study will be conducted using convenience sampling to recruit 20 people with PD with a moderate concern of falling from a Parkinson's Patients Association. In addition to usual care, participants will attend 2 days per week, 90 min group sessions for 8 weeks. The intervention combines group cognitive behavioral intervention with the training of safe landing strategies. Feasibility will be assessed by six key domains (recruitment strategy and rates, enrollment, retention, acceptability, reasons for decline/withdrawal, and adverse events). Quantitative data will be analyzed using descriptive statistics to characterize the sample, followed by inferential statistics to evaluate differences in the Short Falls Efficacy Scale-International Scale, Movement Disorder Society Unified Parkinson's Disease Rating Scale, Timed Up Go, 6-Minutes Walking Distance, and fall frequency and severity scores between baseline and final assessment. Qualitative data will be analyzed using an inductive thematic analysis process. There is a growing interest in developing new effective therapeutic approaches for people with PD. If proven program feasibility, this study precedes a randomized controlled trial to establish the effectiveness of the Landing Wise program.

Adapted Portuguese folk dance intervention for subacute rehabilitation post-stroke: study protocol.

Dance can be an innovative, well-accepted, and effective therapy for stroke survivors. The present protocol aims to assess the feasibility of adapted Portuguese folk dance as a post stroke rehabilitative activity. We will use a mixed-methods pilot study convenience sampling to recruit 16 stroke survivors with mild-moderate lower limb paresis from a rehabilitation center in Lisbon and Tagus Valley. In addition to usual care, participants will attend 3 days per week 1-h dance exercise for 8 weeks. The dance style used for this intervention will be an adaptation of the Portuguese folk dance. Assessment will be conducted before and immediately after the program intervention. Acceptability will be assessed by four key domains (enrollment, retention, satisfaction, and recommendation to others). Safety will be assessed based on the number and type of adverse events. Feasibility will be assessed based on balance performance and functional mobility. Quantitative data will be analyzed through descriptive statistics for sample characterization, followed by inferential statistics to evaluate differences in the balance recovery and functional mobility scores between the initial and final assessment. Qualitative data will be analyzed using an inductive process of content analysis. The Portuguese folk dance program has the potential to improve balance outcomes and functional mobility. Our results will help validate Portuguese folk dance as a tool for rehabilitation settings for stroke survivors. The potential of our program to enhance balance outcomes and functional mobility among stroke survivors bears implications for aging and public health initiatives. Positive results from this study could pave the way for integrating dance-based rehabilitative activities into standard stroke rehabilitation protocols, catering to older stroke survivors' specific needs and preferences.

Chemical Analysis of Gunpowder and Gunshot Residues.

The identification of firearms is of paramount importance for investigating crimes involving firearms, as it establishes the link between a particular firearm and firearm-related elements found at a crime scene, such as projectiles and cartridge cases. This identification relies on the visual comparison of such elements against reference samples from suspect firearms or those existing in databases. Whenever this approach is not possible, the chemical analysis of the gunpowder and gunshot residue can provide additional information that may assist in establishing a link between samples retrieved at a crime scene and those from a suspect or in the identification of the corresponding model and manufacturer of the ammunition used. The most commonly used method for the chemical analysis of gunshot residue is scanning electron microscopy with energy dispersive X-ray, which focuses on the inorganic elements present in ammunition formulation, particularly heavy metals. However, a change in the legal paradigm is pushing changes in these formulations to remove heavy metals due to their potential for environmental contamination and the health hazards they represent. For this reason, the importance of the analysis of organic compounds is leading to the adoption of a different set of analytical methodologies, mostly based on spectroscopy and chromatography. This manuscript reviews the constitution of primer and gunpowder formulations and the analytical methods currently used for detecting, characterising, and identifying their compounds. In addition, this contribution also explores how the information provided by these methodologies can be used in ammunition identification and how it is driving the development of novel applications within forensic ballistics.

Cortisol dynamics in undergraduate nursing students during clinical practice: protocol for an exploratory cross-sectional study.

INTRODUCTION: This paper presents a protocol for the Investigation of Cortisol Dynamics in Undergraduate Nursing Students, a funded project aiming to understand the fluctuations in anxiety and salivary cortisol levels due to clinical setting changes and the anxiety associated with clinical practice. METHODS AND ANALYSIS: This study is an exploratory, cross-sectional, observational study that will be conducted at a health and science school in Portugal. Data collection will involve phycological assessment instruments for personality, anxiety, stress, depression and saliva cortisol levels. The target population consists of undergraduate nursing students enrolled in our institution for the academic year of 2022/2023 (N=272), of whom we aim to recruit 35% (N=96) to the study. ETHICS AND DISSEMINATION: The project obtained approval from the Institutional Review Board of the Egas Moniz-Cooperativa de Ensino Superior, CRL, on 5 July 2022 (ID: 116/21.22) and ethical approval from the Egas Moniz Ethics Committee on 28 July 2022 (ID:1110.22). Informed consent will be obtained from those who wish to participate, ensuring students' voluntary participation in the project. The results of this study will be disseminated through open-access peer-reviewed publications and presented at scientific events.

Perspectives on the Person-Centered Practice of Healthcare Professionals at an Inpatient Hospital Department: A Descriptive Study.

The characteristics of health professionals and their understanding of person-centeredness may have important implications for the development of person-centered practice in specific care settings. In this study, we characterized the perceptions of the person-centered practice of a multidisciplinary team of health professionals working in the internal medicine inpatient unit of a Portuguese hospital. Data were collected using a brief sociodemographic and professional questionnaire and the person-centered practice inventory-staff (PCPI-S), and the effect of different sociodemographic and professional variables on each PCPI-S domain was determined using an analysis of variance (ANOVA). The results showed that a person-centered practice was positively perceived in the major constructs of prerequisites (M = 4.12; SD = 0.36), the practice environment (M = 3.50; SD = 0.48), and person-centered process (M = 4.08; SD = 0.62) domains. The highest scored construct was developed interpersonal skills (M = 4.35; SD = 0.47), and the lowest was supportive organization systems (M = 3.08; SD = 0.80). Gender was found to influence the perceptions of knowing self (F(2,75) = 3.67, p = 0.03, partial η2 = 0.089) and the physical environment (F(2,75) = 3.63, p = 0.03, partial η2 = 0.088), as was profession on shared decision-making systems (F(2,75) = 5.38, p < 0.01, partial η2 = 0.125) and commitment to the job (F(2,75) = 5.27, p < 0.01, partial η2 = 0.123), and the educational level on being professionally competent (F(1,75) = 4.99, p = 0.03, partial η2 = 0.062) and having commitment to the job (F(2,75) = 4.49, p = 0.04, partial η2 = 0.056). In addition, the PCPI-S proved to be a reliable instrument for characterizing healthcare professionals' perceptions of the person-centeredness of care in this context. Identifying personal and professional variables that influence these perceptions could provide a starting point for defining strategies to move practice toward person-centeredness and for monitoring changes in healthcare practice.

Person-Centered Practice in Hospitalized Older Adults with Chronic Illness: Clinical Study Protocol.

The aging trend in the population, the high rate of hospitalization, the affliction by multiple chronic illnesses, and the increased vulnerability of older people when hospitalized undoubtedly require a person-centered approach to healthcare-an approach that values a person's participation in the healthcare relationship, supports shared decision making and mutual understanding, and respects a person's values, preferences, and beliefs. However, despite widespread recognition that the adoption of such a clinical practice paradigm is paramount, its implementation and development are still challenging for various health systems and professionals worldwide. The implementation strategy for such a healthcare paradigm must be based on each country's health system organization and practice contexts, as well as the professionals involved. The present work aims to provide guidelines for the understanding of the state of development of person-centered practice in the daily care of hospitalized older adults with chronic illnesses within the internal medicine department of a secondary hospital in an urban area of Portugal. We focus on the characterization of (i) the perceptions of a multidisciplinary team working at an inpatient hospital department of person-centered practice, (ii) the perceptions of hospitalized older adults with chronic illnesses about person-centered practice, (iii) the work culture of an inpatient hospital department with a high prevalence of older adults with chronic illnesses, (iv) the Person-Centred Practice Framework at the organizational and structural levels of the healthcare system, and (v) the elements that influence the implementation of person-centered practice at the individual, organizational, and structural levels in this specific hospital context. To this end, a mixed-methods analysis with a convergent design was planned to use questionnaire instruments to collect data in parallel and independently from distinct samples of health professionals and older inpatient adults within this department. Furthermore, health policies and strategic plans will be analyzed to identify and evaluate references and guidelines for the practice of person-centered care. Studying the dimensions of clinical practice in this specific healthcare context following the Person-Centred Practice Framework can allow us to understand the extent of its development in terms of prerequisites, care environment, care processes, and the macro-context of the healthcare system. Therefore, it is possible to identify and characterize the dimensions achieved and those that need to be improved and, thus, establish a starting point for the definition of new strategies to advance practice towards person-centeredness and monitor changes in healthcare practice.

Stigma towards People with Mental Illness among Portuguese Nursing Students.

Stigma is a substantial obstacle when caring for people with mental illness. Nursing students' negative attitudes towards people with mental illness may impact the quality of care delivered and consequentially patient outcomes. In this study, we assessed the stigmatising attitudes and beliefs of nursing students towards people with mental illness and examined its relationship with several psycho-socio-demographic variables. This was a quantitative, cross-sectional descriptive correlational study, which was developed with a non-probabilistic convenience sample of 110 nursing students. Stigmatising attitudes and beliefs were assessed using the Portuguese version of the Attribution Questionnaire AQ-27. Results show that the dimensions of stigma with higher scores were help, pity, coercion and avoidance. However, significant differences were only observed depending on the year of study (fourth-year students, who already had clinical placements in this area, are less likely to show stigma), the relationship (family is less prone to show coercion), the history of mental health treatment (students with a history of mental health treatment have more tendency to help) and whether they considered working in the mental health field (students who have considered working in this field are less prone to show anger, avoidance and think of patients as dangerous). Therefore, we conclude that education in a classroom setting alone is not enough to reduce stigma in nursing students, clinical placement in the area is required to achieve such results. It is thus essential to improve nursing curricula worldwide so that students are exposed to both psychiatric nursing theory and clinical practice in the first years of the nursing degree.

Is Being Physically Active Enough or Do People with Parkinson's Disease Need Structured Supervised Exercise? Lessons Learned from COVID-19.

Social isolation imposed by the COVID-19 pandemic negatively impacted people's lifestyles and daily activities. In this work we compared pre- and post-pandemic clinical outcomes in people with Parkinson's disease, to assess differences according to the type of behaviour and exercise habits adopted by participants. After two months of COVID-19 lockdown, we assessed: changes in exercise behaviour; motor and non-motor aspects of daily life experiences (MDS-UPDRS I & II); activities of daily living (The Schwab & England scale); quality of life (Parkinson Disease Questionnaire); sleep (Parkinson Disease Sleep Scale); falls; and Clinical Global Impression Change. Twenty-seven individuals aged between 57 and 92 years old participated; from these, ten individuals (37%) completely interrupted physical activities, while seventeen (63%) maintained some level of active lifestyle. Regardless of whether they remained active or not, all participants perceived a significant worsening of their clinical condition, reporting an increase in difficulties completing daily activities or chores (37%) and worsening of their health condition (51.8%). The quantifiable influence of exercise habits was borderline for the group who kept active. The active group seem to have a better self-perception of their health condition, although it was not enough to show a clear benefit. People with Parkinson's disease should be informed that being physically active may not be enough and more structured exercise could be needed.

The synthetic cannabinoid JWH-018 modulates Saccharomyces cerevisiae energetic metabolism.

Synthetic cannabinoids are a group of novel psychoactive substances with similar properties to Δ9-THC. Among the vast number of synthetic cannabinoids, designed to be tested in clinical trials, JWH-018 was the first novel psychoactive substance found in the recreational drug marketplace. The consumption of JWH-018 shows typical effects of CB1 agonists including sedation, cognitive dysfunction, tachycardia, postural hypotension, dry mouth, ataxia and psychotropic effects, but appeared to be more potent than Δ9-THC. However, studies on human cells have shown that JWH-018 toxicity depends on the cellular line used. Despite these studies, the underlying molecular mechanisms to JWH-018 action has not been clarified yet. To understand the impact of JWH-018 at molecular and cellular level, we used Saccharomyces cerevisiae as a model. The results showed an increase in yeast growth rate in the presence of this synthetic cannabinoid due to an enhancement in the glycolytic flux at expense of a decrease in pentose phosphate pathway, judging by 2D-Gel proteomic analysis, qRT-PCR experiments and ATP measurements. Overall, our results provide insights into molecular mechanisms of JWH-018 action, also indicating that Saccharomyces cerevisiae is a good model to study synthetic cannabinoids.

Prediction of Peptide and Protein Propensity for Amyloid Formation.

Understanding which peptides and proteins have the potential to undergo amyloid formation and what driving forces are responsible for amyloid-like fiber formation and stabilization remains limited. This is mainly because proteins that can undergo structural changes, which lead to amyloid formation, are quite diverse and share no obvious sequence or structural homology, despite the structural similarity found in the fibrils. To address these issues, a novel approach based on recursive feature selection and feed-forward neural networks was undertaken to identify key features highly correlated with the self-assembly problem. This approach allowed the identification of seven physicochemical and biochemical properties of the amino acids highly associated with the self-assembly of peptides and proteins into amyloid-like fibrils (normalized frequency of ß-sheet, normalized frequency of ß-sheet from LG, weights for ß-sheet at the window position of 1, isoelectric point, atom-based hydrophobic moment, helix termination parameter at position j+1 and ΔG° values for peptides extrapolated in 0 M urea). Moreover, these features enabled the development of a new predictor (available at http://cran.r-project.org/web/packages/appnn/index.html) capable of accurately and reliably predicting the amyloidogenic propensity from the polypeptide sequence alone with a prediction accuracy of 84.9 % against an external validation dataset of sequences with experimental in vitro, evidence of amyloid formation.

Evolution of the human immunodeficiency virus type 2 envelope in the first years of infection is associated with the dynamics of the neutralizing antibody response.

BACKGROUND: Differently from HIV-1, HIV-2 disease progression usually takes decades without antiretroviral therapy and the majority of HIV-2 infected individuals survive as elite controllers with normal CD4⁺ T cell counts and low or undetectable plasma viral load. Neutralizing antibodies (Nabs) are thought to play a central role in HIV-2 evolution and pathogenesis. However, the dynamic of the Nab response and resulting HIV-2 escape during acute infection and their impact in HIV-2 evolution and disease progression remain largely unknown. Our objective was to characterize the Nab response and the molecular and phenotypic evolution of HIV-2 in association with Nab escape in the first years of infection in two children infected at birth. RESULTS: CD4⁺ T cells decreased from about 50% to below 30% in both children in the first five years of infection and the infecting R5 viruses were replaced by X4 viruses within the same period. With antiretroviral therapy, viral load in child 1 decreased to undetectable levels and CD4+ T cells recovered to normal levels, which have been sustained at least until the age of 12. In contrast, viral load increased in child 2 and she progressed to AIDS and death at age 9. Beginning in the first year of life, child 1 raised high titers of antibodies that neutralized primary R5 isolates more effectively than X4 isolates, both autologous and heterologous. Child 2 raised a weak X4-specific Nab response that decreased sharply as disease progressed. Rate of evolution, nucleotide and amino acid diversity, and positive selection, were significantly higher in the envelope of child 1 compared to child 2. Rates of R5-to-X4 tropism switch, of V1 and V3 sequence diversification, and of convergence of V3 to a ß-hairpin structure were related with rate of escape from the neutralizing antibodies. CONCLUSION: Our data suggests that the molecular and phenotypic evolution of the human immunodeficiency virus type 2 envelope are related with the dynamics of the neutralizing antibody response providing further support for a model in which Nabs play an important role in HIV-2 pathogenesis.

Insights into the molecular mechanism of protein native-like aggregation upon glycation.

Several human neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and Familial Amyloidotic Polyneuropathy, have long been associated with, structural and functional changes in disease related proteins leading to aggregation into amyloid fibrils. Such changes can be triggered by post-translational modifications. Methylglyoxal modifications have been shown to induce the formation of small and stable native-like aggregates in the case of the amyloidogenic proteins insulin and α-synuclein. However, the fundamental biophysical mechanism underlying such methylglyoxal-induced protein aggregation is not yet fully understood. In this work cytochrome c (Cyt c) was used as a model protein for the characterization of specific glycation targets and to study their impact on protein structure, stability, and ability to form native-like aggregates. Our results show that methylglyoxal covalently modifies Cyt c at a single residue and induces early conformational changes that lead to the formation of native-like aggregates. Furthermore, partially unfolded species are formed, but do not seem to be implicated in the aggregation process. This shows a clear difference from the amyloid fibril mechanisms which involve partially or totally unfolded intermediates. Equilibrium-unfolding experiments show that glycation strongly decreases Cyt c conformational stability, which is balanced with an increase of conformational stability upon aggregation. Data collected from analytical and spectroscopic techniques, along with kinetic analysis based on least-squares parameter fitting and statistical model discrimination are used to help to understand the driving force underlying glycation-induced native-like aggregation, and enable the proposal of a comprehensive thermodynamic and kinetic model for native-like aggregation of methylglyoxal glycated Cyt c.

Resistance to antibody neutralization in HIV-2 infection occurs in late stage disease and is associated with X4 tropism.

OBJECTIVES: To characterize the nature and dynamics of the neutralizing antibody (NAb) response and escape in chronically HIV-2 infected patients. METHODS: Twenty-eight chronically infected adults were studied over a period of 1-4 years. The neutralizing activity of plasma immunoglobulin G (IgG) antibodies against autologous and heterologous primary isolates was analyzed using a standard assay in TZM-bl cells. Coreceptor usage was determined in ghost cells. The sequence and predicted three-dimensional structure of the C2V3C3 Env region were determined for all isolates. RESULTS: Only 50% of the patients consistently produced IgG NAbs to autologous and contemporaneous virus isolates. In contrast, 96% of the patients produced IgG antibodies that neutralized at least two isolates of a panel of six heterologous R5 isolates. Breadth and potency of the neutralizing antibodies were positively associated with the number of CD4(+) T cells and with the titer and avidity of C2V3C3-specific binding IgG antibodies. X4 isolates were obtained only from late stage disease patients and were fully resistant to neutralization. The V3 loop of X4 viruses was longer, had a higher net charge, and differed markedly in secondary structure compared to R5 viruses. CONCLUSION: Most HIV-2 patients infected with R5 isolates produce C2V3C3-specific neutralizing antibodies whose potency and breadth decreases as the disease progresses. Resistance to antibody neutralization occurs in late stage disease and is usually associated with X4 viral tropism and major changes in V3 sequence and conformation. Our studies support a model of HIV-2 pathogenesis in which the neutralizing antibodies play a central role and have clear implications for the vaccine field.

Insulin glycation by methylglyoxal results in native-like aggregation and inhibition of fibril formation.

BACKGROUND: Insulin is a hormone that regulates blood glucose homeostasis and is a central protein in a medical condition termed insulin injection amyloidosis. It is intimately associated with glycaemia and is vulnerable to glycation by glucose and other highly reactive carbonyls like methylglyoxal, especially in diabetic conditions. Protein glycation is involved in structure and stability changes that impair protein functionality, and is associated with several human diseases, such as diabetes and neurodegenerative diseases like Alzheimer's disease, Parkinson's disease and Familiar Amyloidotic Polyneuropathy. In the present work, methylglyoxal was investigated for their effects on the structure, stability and fibril formation of insulin. RESULTS: Methylglyoxal was found to induce the formation of insulin native-like aggregates and reduce protein fibrillation by blocking the formation of the seeding nuclei. Equilibrium-unfolding experiments using chaotropic agents showed that glycated insulin has a small conformational stability and a weaker dependence on denaturant concentration (smaller m-value). Our observations suggest that methylglyoxal modification of insulin leads to a less compact and less stable structure that may be associated to an increased protein dynamics. CONCLUSIONS: We propose that higher dynamics in glycated insulin could prevent the formation of the rigid cross-ß core structure found in amyloid fibrils, thereby contributing to the reduction in the ability to form fibrils and to the population of different aggregation pathways like the formation of native-like aggregates.

Evolutionary and structural features of the C2, V3 and C3 envelope regions underlying the differences in HIV-1 and HIV-2 biology and infection.

BACKGROUND: Unlike in HIV-1 infection, the majority of HIV-2 patients produce broadly reactive neutralizing antibodies, control viral replication and survive as elite controllers. The identification of the molecular, structural and evolutionary footprints underlying these very distinct immunological and clinical outcomes may lead to the development of new strategies for the prevention and treatment of HIV infection. METHODOLOGY/PRINCIPAL FINDINGS: We performed a side-by-side molecular, evolutionary and structural comparison of the C2, V3 and C3 envelope regions from HIV-1 and HIV-2. These regions contain major antigenic targets and are important for receptor binding. In HIV-2, these regions also have immune modulatory properties. We found that these regions are significantly more variable in HIV-1 than in HIV-2. Within each virus, C3 is the most entropic region followed by either C2 (HIV-2) or V3 (HIV-1). The C3 region is well exposed in the HIV-2 envelope and is under strong diversifying selection suggesting that, like in HIV-1, it may harbour neutralizing epitopes. Notably, however, extreme diversification of C2 and C3 seems to be deleterious for HIV-2 and prevent its transmission. Computer modelling simulations showed that in HIV-2 the V3 loop is much less exposed than C2 and C3 and has a retractile conformation due to a physical interaction with both C2 and C3. The concealed and conserved nature of V3 in the HIV-2 is consistent with its lack of immunodominancy in vivo and with its role in preventing immune activation. In contrast, HIV-1 had an extended and accessible V3 loop that is consistent with its immunodominant and neutralizing nature. CONCLUSIONS/SIGNIFICANCE: We identify significant structural and functional constrains to the diversification and evolution of C2, V3 and C3 in the HIV-2 envelope but not in HIV-1. These studies highlight fundamental differences in the biology and infection of HIV-1 and HIV-2 and in their mode of interaction with the human immune system and may inform new vaccine and therapeutic interventions against these viruses.