Group Intervention Program to Facilitate Post-Traumatic Growth and Reduce Stigma in HIV.

Background: Research on post-traumatic growth (PTG) and HIV is scarce and the relationship between PTG and stigma is controversial. Group psychotherapeutic interventions to facilitate PTG in clinical samples are effective but none exist to simultaneously decrease stigma in the HIV population. The main objective was to evaluate the effectiveness of an intervention in increasing PTG and decreasing stigma in HIV, as well as to explore relationships between the variables. Methods: Quasi-experimental design with a sample of 42 HIV-positive adults (M = 46.26, SD = 11.90). The experimental group (EG) was subjected to a 9-week group intervention. Instruments: CBI, PTGI-X, PSS-10, HIV stigma, emotional expression, HIV stress indicators, HIV literacy, and skills. Multiple linear regression analysis was performed to assess the relationship between the variables. Results: There was an increase in PTG and a significant decrease in stigma in all domains and subscales in the EG. Compared to the control group, stigma (t(42) = -3.040, p = 0.004) and negative self-image (W = -2.937, p = 0.003) were significant, showing the efficacy of the intervention. Discussion: The intervention demonstrated success in facilitating PTG, attesting that in order to increase PTG, personal strength, and spiritual change, it is necessary to reduce stigma and negative self-image. The research provides more information on group interventions for PTG in HIV, relationships between variables, and population-specific knowledge for professionals.

Oral Contraceptives Interact with Adiposity-Associated Markers in Patients with Multiple Sclerosis.

Growing evidence suggests the involvement of adipose tissue in modulating the clinical course of relapsing-remitting multiple sclerosis (RRMS). This study aimed to investigate whether the intake of combined oral contraceptives (COCs) affects body weight and leptin and adiponectin (APN) blood levels in these patients. Clinical data from 62 women (M = 33.23 year) were recorded prior to the initiation of disease-modifying therapy. Patients who were taking COCs at the time of experiencing the first symptoms of disease (COC user) were compared with those who never used these formulations or stopped taking them before disease onset (COC non-user). Bivariate Pearson's correlations and hierarchical multiple linear regressions analysis were conducted. Normalized APN levels were lower in the COC-using patients (p = 0.013). Negative correlations between waist circumference and normalized APN (p = 0.001) were observed only in the COC non-user patients. A longer duration of COC intake was associated with increased body mass index and waist circumference (p = 0.003). Normalized APN predicted the MS Severity Score (MSSS) (p = 0.020), but this correlation was lost in the COC user patients. After adjusting for confounders, only age (p = 0.027) and, later, disease onset (p = 0.014) were correlated with the MSSS. Larger and prospective studies are needed to investigate the interactions of sex steroids with adipose metabolism in modulating disease progression.

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.

A Case Report of McArdle Disease Diagnosed Following Statin-Induced Myositis.

McArdle disease is a rare condition, characterized by a deficiency of phosphorylase muscle isoform, an enzyme responsible for the breaking down of glycogen, necessary for obtaining energy. Patients typically present with exercise intolerance, myalgias, fatigue, cramps, muscle stiffness, and/or weakness induced by physical activity. The diagnosis is generally established late, with a median delay of about 29 years. We present the case of a female patient with a long history of myalgias, muscle weakness, and exercise intolerance, diagnosed with McArdle disease by the age of 74, after statin-induced myopathy. We aim to review the diagnosis and treatment of this disease, as a way to raise awareness among the medical community.

opp-Dibenzoporphyrin Pyridinium Derivatives as Potential G-Quadruplex DNA Ligands.

Since the occurrence of tumours is closely associated with the telomerase function and oncogene expression, the structure of such enzymes and genes are being recognized as targets for new anticancer drugs. The efficacy of several ligands in telomerase inhibition and in the regulation of genes expression, by an effective stabilisation of G-quadruplexes (G4) DNA structures, is being considered as a promising strategy in cancer therapies. When evaluating the potential of a ligand for telomerase inhibition, the selectivity towards quadruplex versus duplex DNA is a fundamental attribute due to the large amount of double-stranded DNA in the cellular nucleus. This study reports the evaluated efficacy of three tetracationic opp-dibenzoporphyrins, a free base, and the corresponding zinc(II) and nickel(II) complexes, to stabilise G4 structures, namely the telomeric DNA sequence (AG3(T2AG3)3). In order to evaluate the selectivity of these ligands towards G4 structures, their interaction towards DNA calf thymus, as a double-strand DNA sequence, were also studied. The data obtained by using different spectroscopic techniques, such as ultraviolet-visible, fluorescence, and circular dichroism, suggested good affinity of the free-base porphyrin and of its zinc(II) complex for the considered DNA structures, both showing a pattern of selectivity for the telomeric G4 structure. A pattern of aggregation in aqueous solution was detected for both Zn(II) and Ni(II) metallo dibenzoporphyrins and the ability of DNA sequences to induce ligand disaggregation was observed.

Effectiveness of palbociclib with aromatase inhibitors for the treatment of advanced breast cancer in an exposure retrospective cohort study: implications for clinical practice.

BACKGROUND: New drugs for locally advanced or metastatic breast cancer have led to clinical benefits, aside with increasing costs to healthcare systems. The current financing model for health technology assessment (HTA) privileges real-world data. As part of the ongoing HTA, this study aimed to evaluate the effectiveness of palbociclib with aromatase inhibitors (AI) and compare it with the efficacy reported in PALOMA-2. METHODS: A population-based retrospective exposure cohort study was conducted including all patients initiating treatment in Portugal with palbociclib under early access use and registered in the National Oncology Registry. The primary outcome was progression free survival (PFS). Secondary outcomes considered included time to palbociclib failure (TPF), overall survival (OS), time to next treatment (TTNT), and proportion of patients discontinuing treatment due to  adverse events (AEs). The Kaplan-Meier method was used and median, 1- and 2-year survival rates were computed, with two-sided 95% confidence intervals (95%CI). STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines for reporting observational studies were used. RESULTS: There were 131 patients included. Median follow-up was 28.3 months (IQR: 22.7-35.2) and median duration of treatment was 17.5 months (IQR: 7.8-29.1). Median PFS was 19.5 months (95%CI 14.2-24.2), corresponding to a 1-year PFS rate of 67.9% (95%CI 59.2-75.2) and a 2-year PFS rate of 42.0% (95%CI 33.5-50.3). Sensitivity analysis showed median PFS would increase slightly when excluding those not initiating treatment with the recommended dose, raising to 19.8 months (95%CI 14.4-28.9). By considering only patients meeting PALOMA-2 criteria, we could observe a major difference in treatment outcomes, with a mean PFS of 28.8 months (95%CI 19.4-36.0). TPF was 19.8 months (95%CI 14.2-24.9). Median OS was not reached. Median TTNT was 22.5 months (95%CI 18.0-29.8). A total of 14 patients discontinued palbociclib because of AEs (10.7%). CONCLUSIONS: Data suggest palbociclib with AI to have an effectiveness of 28.8 months, when used in patients with overlapping characteristics to those used in PALOMA-2. However, when used outside of these eligibility criteria, namely in patients with less favorable prognosis (e.g., presence of visceral disease), the benefits are inferior, even though still favorable.

Lisbon Intensive Falls Trampoline Training (LIFTT) Program for people with Parkinson's for balance, gait, and falls: study protocol for a randomized controlled trial.

BACKGROUND: Falling and gait difficulties in people with Parkinson's disease (PD) are associated with impaired reactive postural adjustments and impairments in attentional resources. Combined intensive balance motor and cognitive exercise can be beneficial. However, uncertainties persist regarding the true effects and safety when applying such training. Using trampoline beds may be a favorable safe environment for a highly intensive, cognitive, and balancing training approach. The primary goal of this randomized controlled trial is to assess the effects of an intensive cognitive-motor training program in a safe trampoline environment in addition to usual care on balance impairment, gait, physical capacity, fear of falling, falls frequency and severity, cognition, and clinical impairments in people with mild or moderate PD. METHODS: Sixty participants diagnosed with idiopathic PD, in stage 2-4 Hoehn and Yahr, with a clinical history of gait deficits and a fall history (at least one fall in the last 6 months) will be recruited and randomly allocated to an intervention group receiving cognitive-motor trampoline training or a control group undergoing their usual care. The intervention will consist of 8-week individual training sessions (1-h training, 3 days per week) led by specialized physiotherapists that will provide progressive, challenging training, and guarantee safety. Assessment will be conducted prior to and immediately after the 8-week intervention and at 3 months follow-up after participating in the study. Primary outcome measures will be balance performance (assessed using the Mini-BEST Test and nonlinear analysis) and change in gait parameters (Motor and Cognitive Timed-Up-Go and nonlinear analysis). Secondary outcomes will be change in clinical improvement (Movement Disorder Society Unified Parkinson's Disease Rating Scale), falls (falls weekly registry), fear of falling (assessed using the Falls Efficacy Scale), physical capacity (6-min walk test), and cognition (Montreal Cognitive Assessment). DISCUSSION: This study will provide new evidence on the benefits of intensive cognitive-motor balance training on a trampoline for people living with PD. Better guidance on how professionals can apply safer dual-task balance and gait training in rehabilitation is needed. TRIAL REGISTRATION: ISRCTN Registry ISRCTN13160409 . Retrospectively registered on February 23, 2022.

Difficulties in Emotion Regulation and Problematic Pornography Use: The Mediating Role of Loneliness.

Objectives: To analyze the association between difficulties in emotion regulation and problematic pornography use (PPU) and test the mediating effect of loneliness. Methods: All 339 participants (M = 28.53 years, SD = 10.32) completed online self-report scales assessing difficulties in emotion regulation, PPU, and loneliness. Results: Difficulties in emotion regulation are positively correlated with PPU. Loneliness partially mediates the relationship between difficulties in emotion regulation and PPU. Gender and intimate relationship status had moderating effects on the tested mediation model. Conclusions: Greater difficulties in emotion regulation have a significant indirect effect on PPU through loneliness.

Meaning in life, meaning-making and posttraumatic growth in cancer patients: Systematic review and meta-analysis.

Introduction: The purpose of this systematic review and meta-analysis is to assess the association between meaning in life (MiL), meaning-making and posttraumatic growth (PTG) in the context of cancer. Methods: A systematic search was conducted in eighteen electronic databases. The screening and selection process followed the PRISMA guidelines. For the purpose of the meta-analysis, the correlation coefficients between meaning in life and posttraumatic growth were extracted from the included studies. The effect size (r) was calculated using the restricted maximum-likelihood estimator, a random-effects model. Heterogeneity was assessed through the Q statistic, I2 index and forest plot, while publication bias was analyzed with the use of the funnel plot and Egger's test. Results: 889 records were considered according to the inclusion criteria. A total of nine articles, published between 2006 and 2021, were included in the systematic review. More than half were published in the last five years. The sample was mostly diagnosed with breast cancer. The meta-analysis included five articles (N = 844) and the results indicate a significant moderate correlation between meaning in life and posttraumatic growth (r = 0.43, 95% IC [0.36, 0.50]). Discussion: In conclusion, there is a clear association between meaning in life and posttraumatic growth in cancer patients. Future research should explore this relationship further, in order to better assist and guide meaning centered interventions that can potentiate a positive adjustment and possibly growth from the cancer experience.

Spatial and seasonal variation in macrozoobenthic density, biomass and community composition in a major tropical intertidal area, the Bijagós Archipelago, West-Africa.

The coastal intertidal ecosystem of the Bijagós Archipelago, Guinea-Bissau, one of the largest and most important in West Africa, sustains a considerable proportion of the migratory shorebird populations of the East Atlantic Flyway and operates as a nursery area for benthic fish in the region. The macrozoobenthos in these mudflats constitute the main food source for both groups so that spatial and temporal variation in their abundance and community composition is likely to influence the abundance and distribution of fish and birds. In this study we described the spatial and temporal dynamics in the density, biomass, and community composition of macrozoobenthos across six intertidal flats in three islands of the Bijagós Archipelago. Overall, the Bijagós Archipelago was characterised by a highly species-rich macrozoobenthic community, with ca. 88 taxa identified across all sites, reaching a mean density of 1871 ± 58.3 ind.m-2 (mean ± SE) and mean biomass of 5.65 ± 0.41 g of AFDM.m-2 (ash-free dry mass per m2), values much lower than what was described for nearby intertidal areas, namely the Band d'Arguin, Mauritania. Density and biomass of major macrozoobenthos classes (Bivalvia, Polychaeta, Malacostraca and Gastropoda) differed across sites and months, displaying an overall increase in density towards the final months of the dry season (March and April). Similarly, community composition also differed significantly between sites and throughout the season. The site with most distinct community composition (Adonga) supported low diversity and high abundance of a few bivalve species, whilst other two sites that hosted the most diverse communities, were also the most similar between them (Anrumai and Abu). These spatial and temporal patterns constitute an important baseline to improve knowledge of this intertidal ecosystem and will contribute towards a better understanding of the spatial and temporal distribution patterns of their consumers.

Reaction of Corroles with Sarcosine and Paraformaldehyde: A New Facet of Corrole Chemistry.

Details on the unexpected formation of two new (dimethylamino)methyl corrole isomers from the reaction of 5,10,15-tris(pentafluorophenyl)corrolatogallium(III) with sarcosine and paraformaldehyde are presented. Semi-empirical calculations on possible mechanism pathways seem to indicate that the new compounds are probably formed through a Mannich-type reaction. The extension of the protocol to the free-base 5,10,15-tris(pentafluorophenyl)corrole afforded an unexpected new seven-membered ring corrole derivative, confirming the peculiar behavior of corroles towards known reactions when compared to the well-behaved porphyrin counterparts.

Posttraumatic growth among childhood cancer survivors and their care-givers: associations with rumination and beliefs challenge / Crecimiento postraumático entre sobrevivientes de cáncer infantil y sus cuidadores: asociaciones con rumiación y desafío de creencias

Abstract. The main purpose of the study was to assess the relationship between PTG, challenge to core beliefs, intrusive and deliberate rumination in a sample of 43 dyads of childhood cancer survivors and their caregivers. Methods: Survivors (mean age = 17.04; SD=3.67) and caregivers (mean age = 46.84; SD = 8.32) completed the Posttraumatic Growth Inventory (PTGI), the Core Beliefs Inventory (CBI) and the Event-related Rumination Inventory (ERRI). Results: Results showed a positive and high correlation among PTG, CBI, and ERRI in both groups, separately. CBI was the main predictor of PTG both among survivors (β=0.826; t=9.393; R²=0.683; p≤0.001) and caregivers (β=0.552; t=4.235; R²=0.304; p≤0.001). Caregivers reported higher scores than survivors in PTG (t=-2.999 p≤0.01) and its dimensions Relationship with others (t=2.498; p≤0.05), Spiritual change (t=-15.823; p≤0.001), Life appreciation (t=-3.129;

Resumen. El objetivo principal del estudio fue evaluar la relación entre el CPT, el desafío a las creencias, la rumiación intrusiva y deliberada en una muestra de 43 díadas de sobrevivientes de cáncer infantil y sus cuidadores. Métodos: Los sobrevivientes (edad media = 17,04; SD = 3,67) y los cuidadores (edad media = 46,84; SD = 8,32) completaron el Inventario de Crecimiento Postraumático (PTGI), el Inventario de Creencias Básicas (CBI) y el Inventario de Rumiación Relacionada con Eventos (ERRI). Resultados: Los resultados mostraron una correlación positiva y alta entre PTG, CBI y ERRI en ambos grupos, por separado. El CBI fue el principal predictor de CPT tanto entre los sobrevivientes (β=0,826; t=9,393; R²=0,683; p≤0,001) como entre los cuidadores (β=0,552; t=4,235; R²=0,304; p≤0,001). Los cuidadores reportaron puntajes más altos que los sobrevivientes en CPT (t=-2,999 p≤0,01) y sus dimensiones Relación con los demás (t=2,498; p≤0,05), Cambio espiritual (t=-15,823; p≤0,001), Valoración de la vida (t =-3,129;

Prevalence and Factors Associated with Poor Respiratory Function among Firefighters Exposed to Wildfire Smoke.

One of the world's biggest disasters are wildfires. The firefighting environment involves physical and respiratory risks, due the inhalation of fire smoke. This study aims to determine the respiratory function of firefighters exposed to wildfire smoke and explore the potential risk factors associated with poor respiratory function. The sample involved 53 firefighters, aged between 23 and 60 years (39.28 ± 8.71), 41 (77.40%) male and 12 (22.60%) female, who fought in wildfires. The measurement instruments used were as follows: a scale, a stadiometer, a questionnaire, a Fagerstrom test and a spirometer. Thirty-six (67.9%) firefighters showed a restrictive pattern. Firefighters fought between 1 and 9 (3.64 ± 1.97) fires and in total between 5 and 212 (62.34 ± 46.89) h. Nineteen (52.8%) firefighters, who showed a restrictive pattern, did not perform any physical exercise (p = 0.045). Twelve (70.6%) firefighters who practiced exercise and revealed a restrictive pattern trained at least 3 or less hours weekly, whilst five (29.4%) practiced more than 3 h (p = 0.030) of weekly exercise. Twenty (55.6%) firefighters with a restrictive pattern spent more than 48 h in combat (p = 0.029) and twenty-two (61.1%) did not use any respiratory protection (p = 0.011). The study data showed that occupational exposure to wildfire smoke was associated with the development of a restrictive pattern and associated factors included a sedentary lifestyle, limited duration of physical exercise, longer exposure to fire smoke and non-use of respiratory protection.

Interfacial assembly of zinc(II) phthalocyanines on graphene oxide (GO): Stable "turn-off-on" nanoplatforms to detect G-quadruplexes (G4).

HYPOTHESIS: The aggregation of phthalocyanines (Pcs) enfeebles their suitability as G-quadruplex (G4) ligands over time. It is hypothesized that the interfacial assembly of Pcs on graphene oxide (GO) influences intermolecular interactions, thereby affecting their physicochemical properties and inducing stabilization of Pcs in solution. Hence, the stacking of Pcs on GO could be tuned to create nanosystems with the ability to detect G4 for longer periods through a slow release of Pcs. EXPERIMENTS: Four cationic structurally-related zinc(II) phthalocyanines (ZnPc) were non-covalently assembled on GO by ultrasonic exfoliation. A comprehensive characterization of ZnPcs@GO was carried out by spectroscopic techniques and electron microscopy to understand the organization of ZnPcs on GO. The fluorescence of ZnPcs@GO was studied in the presence of G4 (T2G5T)4 and duplex ds26 through spectrofluorimetric titrations and monitored along time. FINDINGS: GO induced a re-organization of the ZnPcs mostly to J-aggregates and quenched their original fluorescence up to 98 % ("turn-off"). In general, ZnPcs@GO recovered their fluorescence ("turn-on") after the titrations and showed affinity to G4 (KD up to 1.92 µM). This is the first report that highlights the contribution of GO interfaces to assemble ZnPcs and allow their slow and controlled release to detect G4 over longer periods.

Exercise Dependence and Anxiety in Cross-Trainers, Bodybuilders and Gym Exercisers During COVID19.

The World Health Organization declared the COVID-19 pandemic an international public health emergency in January 2020, and, soon thereafter, a worldwide adoption of quarantine and physical isolation measures restricted regular practitioners of indoor group physical exercise from many of their usual practices. Some, with exercise dependence (ED), may have experienced exercise withdrawal symptoms that triggered unhealthy anxiety levels. In February 2021, during Portugal's second COVID-19 lockdown, we characterized and compared ED and anxiety levels among different groups of indoor exercise practitioners (cross trainers [CG], bodybuilders [BG] and gym practitioners [GG]). In this cross-sectional study, we recruited 234 adult participants through the internet. To assess participants' ED and anxiety levels, we used Portuguese versions of the ED Scale-21 (EDS-21) and the State-Trait Anxiety Inventory (STAI-State; STAI-Trait). ED symptoms were evident in all participant subgroups, and we found no gender differences in ED. Anxiety was higher among women than men in CG and GG groups, and there were significant differences in ED between groups such that BG practitioners showed higher ED than GG and CG practitioners (small effect size). Bodybuilders reported most ED behavior, followed by CG and regular gym exercisers, but on some criteria BG and CG groups had similar ED levels. Our results are in line with prior ED prevalence reports conducted before COVID-19 restrictions among regular GG, but these are the first data to report a higher ED prevalence among BG and CG, relative to GG.

The Difficulties in Emotion Regulation Scale - Short Form (DERS-SF): psychometric properties and invariance between genders.

BACKGROUND: The understanding of how individuals manage their emotional experiences has flourished dramatically over the last decades, including assessing of emotion (dys)regulation. The Difficulties in Emotion Regulation Scale (DERS) is a well-validated and extensively used self-report instrument for emotion regulation problems. Despite the wide use of DERS in both clinical and research settings, its length potentially increases fatigue and frustration in respondents and limits its inclusion in brief research protocols. Consequently, a short-form version of the DERS (DERS-SF) was developed, which requires cross-cultural adaptations and the study of its reliability and validity. OBJECTIVES: In order to address this issue, this study aimed to analyze the factorial structure and psychometric properties of the Portuguese version of DERS-SF and examine the DERS-SF factor structure invariance between men and women. METHODS: The sample comprised 646 participants aged between 18 and 66 years (M = 29.93, SD = 11.71). RESULTS: The correlated six-factor structure of the original version has an acceptable fit, good reliability, and convergent validity. Our results also suggested the invariance of the factor structure of the DERS-SF across genders. CONCLUSION: The DERS-SF has good psychometric properties, and it may be useful for future research and clinical work to use this six-factor brief version and improve emotion regulation assessment.

Addressing Ageism-Be Active in Aging: Study Protocol.

Ageism refers to stereotyping (how we think), prejudice (how we feel), and discrimination (how we act) against people based on their age. It is a serious public health issue that can negatively impact older people's health and quality of life. The present protocol has several goals: (1) adapt the Ambivalent Ageism Scale for the general Portuguese population and healthcare professionals; (2) assess the factorial invariance of the questionnaire between general population vs. healthcare professionals; (3) evaluate the level of ageism and its predictors in the general population and evaluate the level of ageism and its predictors in healthcare professionals; (4) compare the levels of ageism between groups and the invariance between groups regarding the explanatory model of predictors of ageism. This quantitative, cross-sectional, descriptive, observational study will be developed in partnership with several Healthcare Professional Boards/Associations, National Geriatrics and Gerontology Associations, and the Universities of the Third Age Network Association. The web-based survey will be conducted on a convenience sample recruited via various social media and institutional channels. The survey consists of three questionnaires: (1) Demographic data; (2) Ambivalent Ageism Scale; (3) Palmore-Neri and Cachioni questionnaire. The methodology of this study will include translation, pilot testing, semantic adjustment, exploratory and confirmatory factor analysis, and multigroup analysis of the Ambivalent Ageism Scale. Data will be treated using International Business Machines Corporation (IBM®) Statistical Package for the Social Sciences (SPSS) software and Analysis of Moment Structures (AMOS). Descriptive analysis will be conducted to assess the level of ageism in the study sample. The ageism levels between the two groups will be compared using the t-student test, and two Structural Equation Modeling will be developed to evaluate the predictors of ageism. Assessing ageism is necessary to allow healthcare professionals and policymakers to design and implement strategies to solve or reduce this issue. Findings from this study will generate knowledge relevant to healthcare and medical courses along with anti-ageism education for the Portuguese population.

Systematic Review of the Effects of Exercise and Physical Activity on the Gut Microbiome of Older Adults.

Recent evidence suggests that exercise/physical activity (PA) can beneficially alter the gut microbiome composition of young people, but little is known about its effects in older adults. The aim of this systematic review was to summarize results of human studies that have assessed the effects/associations of PA/exercise on the gut microbiome of older adults and to better understand whether this can help promote healthy ageing. Seven studies were included in the review and overall, exercise and increased amounts of PA were associated with decreases in the abundance of several well-known harmful taxa and increases in the abundance of health-promoting taxa. Altogether, the findings from the included studies suggest that exercise/PA have a beneficial impact on the gut health of older adults by improving the gut microbiome composition. However, due to methodological and sampling disparities, it was not possible to reach a consensus on which taxa were most affected by exercise or PA.

Diketopyrrolo[3,4-c]pyrrole derivative as a promising ligand for the stabilization of G-quadruplex DNA structures.

Telomerase, oncogenes and tumor suppressors are closely associated with tumour occurrence, therefore these structures are being recognized as targets for the development of new anticancer drugs. The efficacy of several molecules in telomerase inhibition and regulation of genes expression, by adduct formation with G-quadruplexes (G4), has been studied by biophysical and biochemical methods with promising results. We report here the synthesis and structural characterization of a small positively charged diketopyrrolo[3,4-c]pyrrole derivative, identified as DPP(PyMe)2, that showed very promising results as G4 stabilizing ligand. The data obtained from UV-Vis and fluorescence experiments suggest that DPP(PyMe)2 presents high affinity to G4 structures. Docking studies and molecular dynamics simulations unraveled the binding modes of the ligand with four G4 structures. The obtained results also allowed us to conclude that the DPP(PyMe)2 ligand binds into the top G-tetrad or in a mixed binding mode depending on the GQ structure. A remarkable selectivity of DPP(PyMe)2 for c-MYC and KRAS 32R in the presence of ds26 was observed by circular dichroism (CD) and fluorescence resonance energy transfer (FRET) melting experiments. CD titrations revealed a stabilization higher than 30 °C in the case of c-MYC G4 structure and, for the same sequence, DPP(PyMe)2 showed the ability to block the activity of Taq polymerase in a dose-dependent manner. The subcellular localization obtained with confocal microscopy corroborates the results obtained by the other techniques and the obtained data suggest that DPP(PyMe)2 is an attractive ligand for the development of G4 labelling probes.