Perception of pregnant individuals, health providers and decision makers on interventions to cease substance consumption during pregnancy: a qualitative study.

BACKGROUND: Despite multiple recommendations and strategies implemented at a national and international level, cigarette smoking, alcohol consumption, and cannabis use during pregnancy remains high in most countries. The objective of this study was to examine key stakeholders' perception of the treatment interventions adopted in Spain, to identify political, organizational and personal factors associated with successful implementation, and to propose strategies for improvement. METHODS: A qualitative study with a phenomenological approach was conducted in 2022. The target groups were: (1) clinical decision makers in the field of addiction science, (2) health professionals who carry out treatment interventions, and (3) pregnant individuals who use tobacco, alcohol or cannabis. Two focus groups and eight in-depth interviews were conducted, recorded, and transcribed. Exploratory analysis and inductive open coding was performed, codes were merged into categories, and subcategories were identified. RESULTS: The analysis resulted in 10 subcategories which were further merged into three main categories: (1) Degree of adoption and utility of treatment interventions implemented; (2) Needs and demands with respect to the organization of treatment interventions; and, (3) Personal barriers to and facilitators for treatment. Respondents reported that despite multiple national and regional cessation initiatives, treatment interventions were rarely adopted in clinical practice. Health care administrators demanded reliable records to quantify substance use for better planning of activities. Health care professionals advocated for additional time and training and both echoed the importance of integrating cessation interventions into routine prenatal care and creating in-house specialized units. The difficulty in quitting, lack of awareness of risk for foetus and child and the controversial advice were identified as barriers by pregnant individuals. CONCLUSIONS: Consistent with previous work, this study found that cessation strategies implemented by the health authorities are not effective if they are not accompanied by organizational and behavioral changes. The current study identifies a set of factors that could be pivotal in ensuring the success of treatment interventions targeting tobacco, alcohol and cannabis use among pregnant individuals.

Monitoring Elite Soccer Players Physical Performance Using Real-Time Data Generated by Electronic Performance and Tracking Systems.

ABSTRACT: Oliva-Lozano, JM, Martín-Fuentes, I, Granero-Gil, P, and Muyor, JM. Monitoring elite soccer players physical performance using real-time data generated by electronic performance and tracking systems. J Strength Cond Res 36(11): 3224-3228, 2022-The aims of this technical report were to analyze the validity of real-time data collected by electronic performance and tracking systems (EPTS) and investigate the effect of varying real-time receiver's position on the real-time data collected. Physical performance data were collected from professional soccer players using EPTS. In addition, 3 real-time receivers, which were placed in different positions (i.e., central area of the stadium stands and right and left technical areas), were used to collect real-time data. The real-time data collected by each receiver were visualized on SVivo and compared with the data downloaded directly from the device on SPro. The results showed no statistically significant differences between the data collected by the real-time receivers compared with postsession data in any variable ( p > 0.05), except for total distance and high-speed running distance covered, which showed significant differences but trivial effect size ( p < 0.05; d = 0.01). The coefficient of determination ( R2 ) and intraclass correlation coefficient were greater than 0.97 and 0.99, respectively. Regarding the analysis of varying the receiver's position on the real-time data collected, the results showed that there was no significant effect of the receiver's position on any variable ( p > 0.05). Therefore, valid physical performance data may be obtained by real-time tracking systems such as SVivo, regardless of the position of the real-time receivers and distance to the players. Specifically, high-intensity running actions, distances covered at low and high speed, and accelerometer-derived variables such as player load may be accurately tracked by this real-time tracking software.

Differences in worst-case scenarios calculated by fixed length and rolling average methods in professional soccer match-play.

The aims of this study were to describe the worst-case scenarios (WCS) in professional soccer players calculated by fixed length and rolling average methods with regards to each playing position. This was done, firstly, by comparing total distance (TD covered in the WCS; secondly, by comparing high-speed running distance (HSRD); and thirdly, by comparing sprint distance (SPD). The study was conducted over a three-mesocycle competitive period. The WCS of three distance-related variables (TD, HSRD, SPD) in four time windows (1, 3, 5, 10 minutes) were calculated according to playing position (central defender; full-back; midfielder, wide midfielder, and forward) using fixed length and rolling average methods. A significant effect of the type of method used to calculate the WCS in TD (F(1, 142) = 151.49, p < 0.001, ηp2 = 0.52), HSRD (F(1, 138) = 336.95, p < 0.001, ηp2 = 0.71) and SPD (F(1, 138) = 76.74, p < 0.001, ηp2 = 0.36) was observed. In addition, there was a significant interaction between type of method and WCS duration in TD (F(1.36, 193.53) = 41.95, p < 0.001, ηp2 = 0.23), HSRD (F(2.28, 315.11) = 21.77, p < 0.001, ηp2 = 0.14) and SPD (F(2.59, 358.41) = 6.93, p < 0.001, ηp2 = 0.05). In conclusion, the use of fixed length methods of different durations significantly underestimated the WCS of TD, HSRD and SPD across the most common playing positions in professional soccer players. Therefore, the application of rolling averages is recommended for an appropriate WCS analysis in professional soccer match-play.

Effect of playing position, passage duration and starting status on the most demanding passages of match play in professional football.

The aims of this research were to analyse the effect that different playing positions, passage durations and starting status had on the most demanding passages (MDP) of play in professional football matches. Players were categorized by positions and the MDP of distance (DIS), high-speed running distance (HSRD) and sprinting distance (SPD) were analysed for four passage durations (1, 3, 5 and 10 minutes). The results indicated that DIS (p < 0.001), HSRD (p < 0.001) and SPD (p < 0.001) covered per minute decreased as the passage durations increased for all positions. Regarding the playing position, it had a significant effect on the DIS (p < 0.001), HSRD (p < 0.001) and SPD (p < 0.001) covered. In addition, although the results reported that the starting status had no significant effect on the DIS (p = 0.36) covered, it had a statistically significant effect on the HSRD (p = 0.01) and SPD (p < 0.001) covered. Coaching and medical departments should consider the impact that these variables have on players' performance when designing training drills aimed at preparing the player for the competitive demands.

Validity and Reliability of an Inertial Device for Measuring Dynamic Weight-Bearing Ankle Dorsiflexion.

A decrease in ankle dorsiflexion causes changes in biomechanics, and different instruments have been used for ankle dorsiflexion testing under static conditions. Consequently, the industry of inertial sensors has developed easy-to-use devices, which measure dynamic ankle dorsiflexion and provide additional parameters such as velocity, acceleration, or movement deviation. Therefore, the aims of this study were to analyze the concurrent validity and test-retest reliability of an inertial device for measuring dynamic weight-bearing ankle dorsiflexion. Sixteen participants were tested using an inertial device (WIMU) and a digital inclinometer. Ankle dorsiflexion from left and right ankle repetitions was used for validity analysis, whereas test-retest reliability was analyzed by comparing measurements from the first and second days. The standard error of the measurement (SEM) between the instruments was very low for both ankle measurements (SEM < 0.6°). No significant differences between instruments were found for the left ankle measurement (p > 0.05) even though a significant systematic bias (~1.77°) was found for the right ankle (d = 0.79). R2 was very close to 1 in the left and right ankles (R2 = 0.85-0.89) as well as the intraclass correlation coefficient (ICC > 0.95). Test-retest reliability analysis showed that systematic bias was below 1° for both instruments, even though a systematic bias (~1.50°) with small effect size was found in the right ankle (d = 0.49) with WIMU. The ICC was very close to 1 and the coefficient of variation (CV) was lower than 4% in both instruments. Thus, WIMU is a valid and reliable inertial device for measuring dynamic weight-bearing ankle dorsiflexion.

Absence of Neospora caninum DNA in Human Clinical Samples, Spain.

Low antibody titers to Neospora caninum have been reported in humans, but infection has not been confirmed. We used N. caninum-specific PCR to test 600 clinical samples from patients with toxoplasmosis signs but Toxoplasma gondii-negative PCR results. We did not detect N. caninum DNA, demonstrating it is an unlikely opportunistic zoonotic agent.

Dual Binding Mode of Metallacarborane Produces a Robust Shield on Proteins.

An inorganic sandwich molecule, Na[Co(C2 B9 H11 )2 ], able to produce vesicles through self-assembly and known to produce strong dihydrogen-bond interactions with amine groups is capable of interacting with proteins. This dual non-bonding ability of Na[Co(C2 B9 H11 )2 ] is what makes this molecule unique: it can be firmly anchored to a protein surface and is capable of extending over it. To prove this, the widely available bovine serum albumin (BSA), which has many pendant amino groups in its structure, has been taken as the model protein. It has been found that around 100 molecules of Na[Co(C2 B9 H11 )2 ] preserve the native structure of BSA, while endorsing it with a significantly increased stability with respect to chemical- and thermal-induced denaturation due to efficient encapsulation. The advantages of this encapsulation technique are two-fold; the first is its simplicity as it relies on the anchoring capacity of Na[Co(C2 B9 H11 )2 ] to the surface of the protein through the amine-containing residues and the second is its self-assembling capacity allowing it to spread across the surface. The dense shield of protection offered by Na[Co(C2 B9 H11 )2 ] has been demonstrated by the inhibition of BSA pseudo-esterase activity, which indicates that the inorganic corset around BSA protects its reactive surface residues, thereby preventing their acetylation.

Are the Accompanying Cations of Doping Anions Influential in Conducting Organic Polymers? The Case of the Popular PEDOT.

Conducting organic polymers (COPs) are made of a conjugated polymer backbone supporting a certain degree of oxidation. These positive charges are compensated by the doping anions that are introduced into the polymer synthesis along with their accompanying cations. In this work, the influence of these cations on the stoichiometry and physicochemical properties of the resulting COPs have been investigated, something that has previously been overlooked, but, as here proven, is highly relevant. As the doping anion, metallacarborane [Co(C2 B9 H11 )2 ]- was chosen, which acts as a thistle. This anion binds to the accompanying cation with a distinct strength. If the binding strength is weak, the doping anion is more prone to compensate the positive charge of the polymer, and the opposite is also true. Thus, the ability of the doping anion to compensate the positive charges of the polymer can be tuned, and this determines the stoichiometry of the polymer. As the polymer, PEDOT was studied, whereas Cs+ , Na+ , K+ , Li+ , and H+ as cations. Notably, with the [Co(C2 B9 H11 )2 ]- anions, these cations are grouped into two sets, Cs+ and H+ in one and Na+ , K+ , and Li+ in the second, according to the stoichiometry of the COPs: 2:1 EDOT/[Co(C2 B9 H11 )2 ]- for Cs+ and H+ , and 3:1 EDOT/[Co(C2 B9 H11 )2 ]- for Na+ , K+ , and Li+ . The distinct stoichiometries are manifested in the physicochemical properties of the COPs, namely in the electrochemical response, electronic conductivity, ionic conductivity, and capacitance.

Metallacarboranes on the Road to Anticancer Therapies: Cellular Uptake, DNA Interaction, and Biological Evaluation of Cobaltabisdicarbollide [COSAN].

After uptake by U87 MG and A375 cancer cells, cobaltabisdicarbollide [COSAN]- distributes between membrane and nucleus and presents no relevant cytotoxicity against both cell lines even for long incubation times. The cytotoxicity of Na[COSAN] was also tested towards one normal cell line, the V79 fibroblasts, in order to ascertain the noncytotoxic profile of the compound. As the cell's nucleus contains DNA, the interaction between [COSAN]- and double-stranded calf thymus DNA (CT-dsDNA) has been investigated. There is a strong interaction between both molecules forming a nanohybrid CT-dsDNA-[COSAN] biomaterial, which was fully characterized. Moreover, Na[COSAN] shows characteristic redox peaks ascribed to the oxidation/reduction of Co3+/2+ at a formal potential of -1.444 V and it can be accumulated at a surface-immobilized DNA layer of glassy carbon electrodes. The equilibrium surface-binding constants (Kox /Kred ), which confirm that [COSAN]- interacts with DNA by an intercalative or electrostatic mode, depending on the ionic strength of the solution, were estimated. In addition, high binding affinity of Na[COSAN] to proteins was observed by 11 B{1 H} NMR and confirmed in vivo. Finally, biodistribution studies of [COSAN]- in normal mice were run. After administration, Na[COSAN] was distributed into many organs but mainly accumulated in the reticuloendothelial system (RES), including liver and spleen. After 1 h, the formation of aggregates by plasma protein interaction plays a role in the biodistribution profile; the aggregates accumulate mostly in the lungs. Na[COSAN], which displays low toxicity and high uptake by relevant cancer cells accumulating boron within the nucleus, could act as a suitable compound for further developments as boron neutron capture therapy (BNCT) agents.

Structural and dielectric properties of cobaltacarborane composite polybenzimidazole membranes as solid polymer electrolytes at high temperature.

The conductivity of a series of composite membranes, based on polybenzimidazole (PBI) containing the metallacarborane salt M[Co(C2B9H11)2], M[COSANE] and tetraphenylborate, M[B(C6H5)4], M[TPB] both anions having the same number of atoms and the same negative charge, has been investigated. Different cations (M = H+, Li+ and Na+) have been studied and the composite membranes have been characterized by water uptake, swelling ratios, ATR FT-IR, thermogravimetric analysis and electrochemical impedance spectroscopy to explore the dielectric response and ion dynamics in composite membranes. Our results show that conductivity increases with increasing temperature and it is higher for H+ than for Li+ and Na+ for all temperatures under study. The mobility of Li+ is greater in [COSANE]- than in [TPB]- composite PBI@membranes while for Na+ it is the opposite. The temperature dependence of the conductivity of the composite was followed by a typical Arrhenius behaviour with two different regions: (1) between 20 and 100 °C, and (2) between 100 and 150 °C. Using the analysis of electrode polarization (EP) based on the Thrukhan theory we have calculated the ionic diffusion coefficients and the density of carriers. From the double logarithmic plot of the imaginary part of the conductivity (σ'') versus frequency in the entire range of temperatures studied we have determined for each sample at each temperature, the frequency values of the onset (fON) and full development of electrode polarization (fMAX), respectively, which permit us to calculate static permittivity.

Detection and molecular characterization of Acanthamoeba spp. in stray cats from Madrid, Spain.

Acanthamoeba spp. is a widespread protozoan that has been isolated from air, dust, soil, water and biological samples. An opportunistic pathogen of humans and animals, it may cause ocular keratitis, encephalitis, and even multisystem disease. The frequency of Acanthamoeba in animals is unknown. The aim of present study was determine the presence of Acanthamoeba spp. in immunocompromised stray cats - animals possibly more likely to harbour the infection given their immunocompromised status and frequenting of contaminated environments. Of 307 cats examined, 55 were positive for feline immunodeficiency virus and/or feline leukaemia virus and therefore included in the study. Corneal scrapings were obtained to isolate Acanthamoeba spp. by culture and molecular detection by conventional and real time PCR. None of the samples examined directly by molecular methods were positive for Acanthamoeba spp. However, two (3.6%) cases of the cultured samples provided positive results, which were confirmed by subsequent molecular analysis. Sequencing assigned one isolate to genotype T4 and the other to T2. Since Acanthamoeba spp. may also infect animals and humans, the present findings may raise some public health and veterinary concerns.

Enhanced conductivity of sodium versus lithium salts measured by impedance spectroscopy. Sodium cobaltacarboranes as electrolytes of choice.

The development of new types of ion conducting materials is one of the most important challenges in the field of energy. Lithium salt polymer electrolytes have been the most convenient, and thus the most widely used in the design of the new generation of batteries. However, in this work, we have observed that Na+ ions provide a higher conductivity, or at least a comparable conductivity to that of Li+ ions in the same basic material. This provides an excellent possibility to use Na+ ions in the design of a new generation of batteries, instead of lithium, to enhance conductivity and ensure wide supply. Our results indicate that the dc-conductivity is larger when the anion is [Co(C2B9H11)2]-, [COSANE]-, compared to tetraphenylborate, [TPB]-. Our data also prove that the dc-conductivity behavior of Li+ and Na+ salts is opposite with the two anions. At 40 °C, the conductivity values change from 1.05 × 10-2 S cm-1 (Li[COSANE]) and 1.75 × 10-2 S cm-1 (Na[COSANE]) to 2.8 × 10-3 S cm-1 (Li[TPB]) and 1.5 × 10-3 S cm-1 (Na[TPB]). These findings indicate that metallacarboranes can be useful components of mixed matrix membranes (MMMs), providing excellent conductivity when the medium contains sufficient amounts of ionic components and a certain degree of humidity.

Detection and molecular characterisation of Giardia duodenalis, Cryptosporidium spp. and Entamoeba spp. among patients with gastrointestinal symptoms in Gambo Hospital, Oromia Region, southern Ethiopia.

OBJECTIVES: To assess the prevalence and genetic diversity of the enteric protozoa species G. duodenalis, Cryptosporidium spp. and Entamoeba histolytica in individuals with gastrointestinal symptoms compatible with infections by these pathogens seeking medical attention in a rural area in southern Ethiopia. METHODS: A total of 92 stool samples were initially screened by direct microscopy and immunochromatography and further confirmed by molecular methods. G. duodenalis-positive samples were molecularly characterised by multilocus genotyping of the glutamate dehydrogenase and ß-giardin genes of the parasite. PCR and DNA sequence analysis of the gene encoding the 60-kDa glycoprotein was used for the subtyping of Cryptosporidium isolates. Detection and differential diagnosis of E. histolytica/dispar were conducted by real-time PCR. RESULTS: PCR-based prevalences were 10.9% for G. duodenalis, 1.1% for Cryptosporidium spp. and 3.3% for Entamoeba spp. Seven (four novel and three known) subtypes of G. duodenalis assemblage B were identified at the GDH locus and 5 (one novel and four known) at the BG locus. A novel variant of C. hominis subtype IbA9G3 was also identified. Two Entamoeba isolates were assigned to E. dispar and an additional one to E. histolytica. CONCLUSION: Although preliminary, our results strongly suggest that giardiasis, cryptosporidiosis and amoebiasis represent a significant burden in Ethiopian rural population.

Parental Attachment and Psychosocial Adjustment in Adolescents Exposed to Marital Conflict.

(1) Background: Interparental conflict is a phenomenon that poses a serious threat not only to the quality of life of the couple but also to the father-child relationship, mother-child relationship, and well-being of adolescents. This study examined the difference in parental attachment and adjustment in adolescents exposed to marital conflict versus those not exposed to parental conflicts in low-income areas. (2) Methods: 67 adolescents involved in Child Welfare Services (CWS) in disadvantaged neighbourhoods in southern Spain were examined. The sample was split into two groups according to the exposure to marital conflict. Subsequently, differences between groups were analysed on father attachment, mother attachment, aggression, antisocial behaviour, and emotional intelligence. (3) Results: Primarily, the data showed significantly worse attachment with the father among conflict-exposed versus non-conflict-exposed adolescents. These results were not found for the attachment with the mother. Additionally, greater anger and worse stress management were found in conflict-exposed adolescents. (4) Conclusions: The results partially confirmed the spillover and compensatory hypothesis. Practical implications point out that developing preventive interventions that protect the father-adolescent attachment in situations of family conflict is recommended.

Prevalence of Human Toxoplasmosis in Spain Throughout the Three Last Decades (1993-2023): A Systematic Review and Meta-analysis.

Humans are infected by Toxoplasma gondii worldwide and its consequences may seriously affect an immune deprived population such as HIV and transplanted patients or pregnant women and foetuses. A deep knowledge of toxoplasmosis seroprevalence in Spain is needed in order to better shape health policies and educational programs. We present the results of the first systematic review and meta-analysis on the human prevalence for this disease in Spain. Databases (PubMed, Web of Science, SCOPUS and Teseo) were searched for relevant studies that were published between January 1993 and December 2023 and all population-based cross-sectional and longitudinal studies reporting the human seroprevalence in Spain were revised. Within the population analysed, our targeted groups were immunocompetent population, pregnant women and immunocompromised patients. Among 572 studies and 35 doctoral theses retrieved, 15 studies and three doctoral theses were included in the meta-analysis. A random effects model was used for the meta-analyses due to the high heterogeneity found between studies (I2: 99.97), since it is a statistically conservative model, in addition to allowing better external validity. The global pooled seroprevalence was 32.3% (95% CI 28.7-36.2%). Most of the studies carried out were in pregnant women and the meta-analysis reported that the pooled seroprevalence of toxoplasmosis in pregnant women in Spain was 24.4% (24,737/85,703, 95% CI 21.2-28.0%), based on the random effects model. It is recommended to continue monitoring the seroprevalence status of T. gondii in order to obtain essential guidelines for the prevention and control of the infection in the population.

Toxoplasma gondii exposure in wildlife in Spain: Is there any predictable threat for humans and domestic animals?

Toxoplasmosis is a parasitic zoonosis of key importance in veterinary and public health. This article summarizes the available data (from 2000 to 2023) of exposition to Toxoplasma gondii in wildlife species in Spain based on a systematic bibliographic search, as well as further analysis of its potential relationship with environmental variables, biodiversity, anthropogenic impact on the habitat, and the reported human cases of toxoplasmosis. The overall seroprevalence of T. gondii in carnivorous mammals, birds, ungulate and lagomorph species in Spain was estimated at 69.3 %, 36.4 %, 18.4 %, and 16.2 %, respectively. Among the studies considered, great heterogeneity was observed both between and within taxonomic groups [Cohen's d > 0.8; X2 = 1039.10, df = 4 (p < 0.01) I2 = 97 %, r2 = 1.88, (p < 0.001)] and between and within bioregions [Cohen's d > 0.5; X2 = 368.59, df = 4 (p < 0.01)]. The results of a generalized linear model explaining T. gondii seroprevalence in wild animals suggest the influence of abiotic variables [wetland (p < 0.001), unvegetated (p < 0.001), isothermality (p < 0.001), and mean temperature during wettest quarter (p < 0.05)] and number of intermediate host species as positively associated with increased exposure of wildlife to T. gondii (p < 0.01). Toxoplasma gondii DNA was detected in both wild birds and wild mammals (range: 0.0-51.2 %) mainly from north-centre, northeast, and central-west of Spain. Regarding hospitalisation rates due to toxoplasmosis in humans, some abiotic variables [permanent crops (p < 0.05) and mean temperature during wettest quarter (p < 0.05)] showed a positive association. Despite certain limitations, this research evidences a substantial gap of knowledge on the implication of wildlife in the life cycle of T. gondii in Spain. This lack of knowledge is particularly evident in areas where the human-livestock-wildlife interface overlaps, preventing us from accurately determining its true distribution in different habitats, as well as its potential direct or indirect implications on public and veterinary health.

Associations between muscular strength and mental health in cognitively normal older adults: a cross-sectional study from the AGUEDA trial.

Objective: To examine the associations between muscular strength and mental health. Design: We used baseline data of 91 cognitively healthy older adults (71.69 ± 3.91 years old, 57 % women) participating in the AGUEDA randomized controlled trial. Methods: Muscular strength was assessed using both objective (i.e., handgrip strength, biceps curl, squats, and isokinetic test) and perceived (i.e., International Fitness Scale) indicators. Psychological ill-being indicators: anxiety, depression, stress, and loneliness; and psychological well-being indicators: satisfaction with life, self-esteem, and emotional well-being) were assessed using a set of valid and reliable self-reported questionnaires. Linear regression analyses were performed adjusting for sex, age, years of education, body mass index , alcohol, diet, and smoking (model 1), and additionally by cardiorespiratory fitness (model 2). Results: Elbow extension was positively associated with stress in model 1 (ß = 0.252, 95 % Confidence Interval [95 % CI] = 0.007 to 0.497, p = 0.044), and even after further adjustment for cardiorespiratory fitness (ß = 0.282, 95 % CI = 0.032 to 0.532, p = 0.028). Perceived strength was negatively associated with depressive symptoms in model 1 (ß = -0.271, 95 % CI = -0.491 to -0.049, p = 0.017) and model 2 reported associations tending towards significant (ß = -0.220, 95 % CI = -0.445 to 0.005, p = 0.055). Handgrip strength was positively associated with self-esteem in model 1 (ß = 0.558, 95 % CI = 0.168 to 0.949, p = 0.006) and model 2 (ß = 0.546, 95 % CI = 0.135 to 0.956, p = 0.010). No further associations were found among other muscular strength and mental health variables. Conclusion: Handgrip had a moderate association with self-esteem and there was a small association between perceived strength with depressive symptoms and elbow extension with stress. No other associations were observed between muscular strength and mental health outcomes in cognitively normal older adults.

Inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and application of statins as a novel effective therapeutic approach against Acanthamoeba infections.

Acanthamoeba is an opportunistic pathogen in humans, whose infections most commonly manifest as Acanthamoeba keratitis or, more rarely, granulomatous amoebic encephalitis. Although there are many therapeutic options for the treatment of Acanthamoeba, they are generally lengthy and/or have limited efficacy. Therefore, there is a requirement for the identification, validation, and development of novel therapeutic targets against these pathogens. Recently, RNA interference (RNAi) has been widely used for these validation purposes and has proven to be a powerful tool for Acanthamoeba therapeutics. Ergosterol is one of the major sterols in the membrane of Acanthamoeba. 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase is an enzyme that catalyzes the conversion of HMG-CoA to mevalonate, one of the precursors for the production of cholesterol in humans and ergosterol in plants, fungi, and protozoa. Statins are compounds which inhibit this enzyme and so are promising as chemotherapeutics. In order to validate whether this enzyme could be an interesting therapeutic target in Acanthamoeba, small interfering RNAs (siRNAs) against HMG-CoA were developed and used to evaluate the effects induced by the inhibition of Acanthamoeba HMG-CoA. It was found that HMG-CoA is a potential drug target in these pathogenic free-living amoebae, and various statins were evaluated in vitro against three clinical strains of Acanthamoeba by using a colorimetric assay, showing important activities against the tested strains. We conclude that the targeting of HMG-CoA and Acanthamoeba treatment using statins is a novel powerful treatment option against Acanthamoeba species in human disease.

Single stop analysis of a protein surface using molecular probe electrochemistry.

Visualization of a protein in its native form and environment without any interference has always been a challenging task. Contrary to the assumption that protein surfaces are smooth, they are in fact highly irregular with undulating surfaces. Hence, in this study, we have tackled this ambiguous nature of the 'surface' of a protein by considering the 'effective' protein surface (EPS) with respect to its interaction with the geometrically well-defined and structurally inert anionic molecule [3,3'-Co(1,2-C2B9H11)2]-, abbreviated as [o-COSAN]-, whose stability, propensity for amine residues, and self-assembling abilities are well reported. This study demonstrates the intricacies of protein surfaces exploiting simple electrochemical measurements using a 'small molecule' redox-active probe. This technique offers the advantage of not utilizing any harsh experimental conditions that could alter the native structure of the protein and hence the protein integrity is retained. Identification of the amino acid residues which are most involved in the interactions with [3,3'-Co(1,2-C2B9H11)2]- and how a protein's environment affects these interactions can help in gaining insights into how to modify proteins to optimize their interactions particularly in the fields of drug design and biotechnology. In this research, we have demonstrated that [3,3'-Co(1,2-C2B9H11)2]- anionic small molecules are excellent candidates for studying and visualizing protein surfaces in their natural environment and allow proteins to be classified according to the surface composition, which imparts their properties. [3,3'-Co(1,2-C2B9H11)2]- 'viewed' each protein surface differently and hence has the potential to act as a simple and easy to handle cantilever for measuring and picturing protein surfaces.

Active Gains in brain Using Exercise During Aging (AGUEDA): protocol for a randomized controlled trial.

Alzheimer's disease is currently the leading cause of dementia and one of the most expensive, lethal and severe diseases worldwide. Age-related decline in executive function is widespread and plays a key role in subsequent dementia risk. Physical exercise has been proposed as one of the leading non-pharmaceutical approaches to improve executive function and ameliorate cognitive decline. This single-site, two-arm, single-blinded, randomized controlled trial (RCT) will include 90 cognitively normal older adults, aged 65-80 years old. Participants will be randomized to a 24-week resistance exercise program (3 sessions/week, 60 min/session, n = 45), or a wait-list control group (n = 45) which will be asked to maintain their usual lifestyle. All study outcomes will be assessed at baseline and at 24-weeks after the exercise program, with a subset of selected outcomes assessed at 12-weeks. The primary outcome will be indicated by the change in an executive function composite score assessed with a comprehensive neuropsychological battery and the National Institutes of Health Toolbox Cognition Battery. Secondary outcomes will include changes in brain structure and function and amyloid deposition, other cognitive outcomes, and changes in molecular biomarkers assessed in blood, saliva, and fecal samples, physical function, muscular strength, body composition, mental health, and psychosocial parameters. We expect that the resistance exercise program will have positive effects on executive function and related brain structure and function, and will help to understand the molecular, structural, functional, and psychosocial mechanisms involved.