ABSTRACT
Background: People with pulmonary tuberculosis (PTB) are contagious, particularly to their household contacts. Their infectivity has been associated with the bacterial load in sputum samples. This study investigated if the bacterial load in sputum samples as quantified by Xpert MTB/RIF and Xpert Ultra is correlated with the extent that latent tuberculosis infection (LTBI) occurred in household contacts of people with PTB. Methods: A retrospective study was performed including people with PTB presenting at Vall d'Hebron University Hospital, Barcelona, between 2011 and 2021. Their infection ratio, representing the proportion of household members found with LTBI in contact tracing investigation, was compared with the quantitative results of Xpert MTB/RIF and Xpert Ultra using ordinal regression analysis. Results: A total of 107 people with PTB were included. Among their 398 household contacts, 126 (31.7%) cases of LTBI and 14 cases with active TB disease (3.5%) were reported. Higher bacterial load in Xpert MTB/RIF and Xpert Ultra baseline sputum was significantly associated with increased infection ratios, providing better estimates than conventional acid-fast bacilli (AFB) smear grading. Conclusions: Xpert MTB/RIF and Xpert Ultra could serve as an alternative to AFB sputum-smear grading in determining contact tracing priorities.
ABSTRACT
BACKGROUND: Cardiac rehabilitation is fundamental among patients recovering from a coronary event, and mHealth technology may constitute a useful tool that provides guidelines based on scientific evidence in an entertaining, attractive, and user-friendly format. OBJECTIVE: This study aimed to compare the efficacy of an mHealth intervention involving the eMOTIVA app and that of usual care regarding compliance with cardiac rehabilitation guidelines in terms of lifestyle, cardiovascular risk factors, and satisfaction among patients with acute coronary syndrome. METHODS: A randomized controlled clinical trial with a parallel group design was conducted. It included 300 patients (mHealth group, 150; control group, 150) who underwent percutaneous coronary intervention for acute coronary syndrome. Both groups underwent evaluations initially (during hospitalization) and after 3 and 6 months (face-to-face consultations). The eMOTIVA app incorporates a virtual classroom providing audio and video information about a healthy lifestyle, a section for self-recording cardiovascular risk factors, and a section for feedback messages and gamification. The primary outcome variables were (1) adherence to the Mediterranean diet and the frequency of consumption of food; (2) physical activity level, sedentary time, and exercise capacity; (3) smoking cessation and nicotine dependence; (4) level of knowledge about cardiovascular risk factors; and (5) app satisfaction and usability. RESULTS: The study analyzed 287 patients (mHealth group, 145; control group, 142). Most participants were male (207/300, 69.0%), and the mean age was 62.53 (SD 8.65) years. Significant improvements were observed in the mHealth group compared with the control group at 6 months in terms of (1) adherence to the Mediterranean diet (mean 11.92, SD 1.70 vs 8.92, SD 2.66 points; P<.001) and frequency of eating foods (red meat [≤1/week]: 141/143, 97.9% vs 96/141, 68.1%; industrial pastries [<2/week]: 129/143, 89.6% vs 80/141, 56.8%; oily fish [≥2/week]: 124/143, 86.1% vs 64/141, 41.4%; vegetables [≥2/day]: 130/143, 90.3% vs 78/141, 55.3%; fruit [≥2/day]: 128/143, 88.9% vs 85/141, 60.2%; all P<.001); (2) physical activity (mean 2112.66, SD 1196.67 vs 1372.60, SD 944.62 metabolic equivalents/week; P<.001) and sedentary time (mean 8.38, SD 1.88 vs 9.59, SD 2.09 hours; P<.001); (3) exercise capacity (distance: mean 473.49, SD 102.28 vs 447.25, SD 93.68 meters; P=.04); and (4) level of knowledge (mean 117.85, SD 3.83 vs 111.00, SD 7.11 points; P<.001). App satisfaction was high (mean 42.53, SD 6.38 points), and its usability was excellent (mean 95.60, SD 4.03 points). CONCLUSIONS: With the eMOTIVA app, favorable results were obtained in the intervention group in terms of adherence to the Mediterranean diet, frequency of eating certain foods, physical activity, sedentary time, exercise capacity, knowledge level, systolic blood pressure, heart rate, and blood sugar level. Furthermore, participants reported high app satisfaction and rated its usability as excellent. Thus, this innovative tool is very promising. TRIAL REGISTRATION: ClinicalTrials.gov NCT05247606; https://clinicaltrials.gov/study/NCT05247606.
Subject(s)
Cardiac Rehabilitation , Coronary Artery Disease , Mobile Applications , Humans , Male , Female , Middle Aged , Coronary Artery Disease/psychology , Coronary Artery Disease/rehabilitation , Aged , Cardiac Rehabilitation/methods , Cardiac Rehabilitation/standards , Cardiac Rehabilitation/statistics & numerical data , Mobile Applications/standards , Mobile Applications/statistics & numerical data , Patient Compliance/statistics & numerical dataABSTRACT
BACKGROUND: Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1INH) is a genetic rare disease characterized by recurrent, transient and unpredictable episodes of cold, non-pruriginous oedema without associated urticaria. The characteristics of the disease have a considerable impact on the quality of life of patients. The aim of this study was to increase understanding of the patient journey of HAE in Spain. METHODS: A multidisciplinary committee of 16 HAE experts (allergy, immunology, emergency department, hospital pharmacy and nursing) and 3 representatives of the Spanish Hereditary Angioedema Patient Association (AEDAF) who were patients or caregivers participated in the study. A review of the publications on HAE treatment was performed. Semi-structured interviews were performed to HAE experts, patients, or caregivers. Three meetings with the experts, patients and caregivers were held to share, discuss, and validate data obtained from literature and interviews and to build the model. RESULTS: Throughout the project, the patient journey has been drawn up, dividing it into the stages of pre-diagnosis, diagnosis and treatment/follow-up. Some areas for improvement have been identified. Firstly, there is a need to enhance awareness and training on HAE among healthcare professionals, with a particular emphasis on primary care and emergency department personnel. Secondly, efforts should be made to minimize patient referral times to allergy/immunology specialists, ensuring timely access to appropriate care. Thirdly, it is crucial to encourage the study of the relatives of diagnosed patients to early identify potential cases. Fourthly, equitable access to self-administered treatments should be ensured, facilitated by systems that enable medication delivery at home and proper education and training for patients. Equitable access to long-term prophylactic treatment should also be prioritized for all patients in need. To standardize HAE management, the development of consensus guidelines that reduce variability in clinical practice is essential. Lastly, promoting research studies to enhance knowledge of the disease and align its treatment with new developments in the healthcare field should be encouraged. CONCLUSIONS: The knowledge of the patient journey in HAE allowed us to identify improvement areas with the final aim to optimize the disease management.
Subject(s)
Angioedemas, Hereditary , Humans , Angioedemas, Hereditary/diagnosis , Angioedemas, Hereditary/therapy , Spain , Quality of Life , Female , MaleABSTRACT
BACKGROUND: Coronary heart disease is one of the leading causes of mortality worldwide. Secondary prevention is essential, as it reduces the risk of further coronary events. Mobile health (mHealth) technology could become a useful tool to improve lifestyles. OBJECTIVE: This study aimed to evaluate the effect of an mHealth intervention on people with coronary heart disease who received percutaneous coronary intervention. Improvements in lifestyle regarding diet, physical activity, and smoking; level of knowledge of a healthy lifestyle and the control of cardiovascular risk factors (CVRFs); and therapeutic adherence and quality of life were analyzed. METHODS: This was a randomized controlled trial with a parallel group design assigned 1:1 to either an intervention involving a smartphone app (mHealth group) or to standard health care (control group). The app was used for setting aims, the self-monitoring of lifestyle and CVRFs using measurements and records, educating people with access to information on their screens about healthy lifestyles and adhering to treatment, and giving motivation through feedback about achievements and aspects to improve. Both groups were assessed after 9 months. The primary outcome variables were adherence to the Mediterranean diet, frequency of food consumed, patient-reported physical activity, smoking, knowledge of healthy lifestyles and the control of CVRFs, adherence to treatment, quality of life, well-being, and satisfaction. RESULTS: The study analyzed 128 patients, 67 in the mHealth group and 61 in the control group; most were male (92/128, 71.9%), with a mean age of 59.49 (SD 8.97) years. Significant improvements were observed in the mHealth group compared with the control group regarding adherence to the Mediterranean diet (mean 11.83, SD 1.74 points vs mean 10.14, SD 2.02 points; P<.001), frequency of food consumption, patient-reported physical activity (mean 619.14, SD 318.21 min/week vs mean 471.70, SD 261.43 min/week; P=.007), giving up smoking (25/67, 75% vs 11/61, 42%; P=.01), level of knowledge of healthy lifestyles and the control of CVRFs (mean 118.70, SD 2.65 points vs mean 111.25, SD 9.05 points; P<.001), and the physical component of the quality of life 12-item Short Form survey (SF-12; mean 45.80, SD 10.79 points vs mean 41.40, SD 10.78 points; P=.02). Overall satisfaction was higher in the mHealth group (mean 48.22, SD 3.89 vs mean 46.00, SD 4.82 points; P=.002) and app satisfaction and usability were high (mean 44.38, SD 6.18 out of 50 points and mean 95.22, SD 7.37 out of 100). CONCLUSIONS: The EVITE app was effective in improving the lifestyle of patients in terms of adherence to the Mediterranean diet, frequency of healthy food consumption, physical activity, giving up smoking, knowledge of healthy lifestyles and controlling CVRFs, quality of life, and overall satisfaction. The app satisfaction and usability were excellent. TRIAL REGISTRATION: Clinicaltrials.gov NCT04118504; https://clinicaltrials.gov/study/NCT04118504.
Subject(s)
Mobile Applications , Humans , Male , Female , Middle Aged , Mobile Applications/standards , Mobile Applications/statistics & numerical data , Aged , Quality of Life/psychology , Coronary Disease/psychology , Coronary Disease/prevention & control , Life Style , Telemedicine/methods , Telemedicine/standards , Telemedicine/statistics & numerical dataABSTRACT
Dysregulation of Fibroblast Growth Factor Receptors (FGFRs) signaling has been associated with breast cancer, yet employing FGFR-targeted delivery systems to improve the efficacy of cytotoxic agents is still sparsely exploited. Herein, we report four new bi-functional ruthenium-peptide conjugates (RuPCs) with FGFR-targeting and pH-dependent releasing abilities, envisioning the selective delivery of cytotoxic Ru complexes to FGFR(+)-breast cancer cells, and controlled activation at the acidic tumoral microenvironment. The antiproliferative potential of the RuPCs and free Ru complexes was evaluated in four breast cancer cell lines with different FGFR expression levels (SKBR-3, MDA-MB-134-VI, MCF-7, and MDA-MB-231) and in human dermal fibroblasts (HDF), at pH 6.8 and pH 7.4 aimed at mimicking the tumor microenvironment and normal tissues/bloodstream pHs, respectively. The RuPCs showed higher cytotoxicity in cells with higher level of FGFR expression at acidic pH. Additionally, RuPCs showed up to 6-fold higher activity in the FGFR(+) breast cancer lines compared to the normal cell line. The release profile of Ru complexes from RuPCs corroborates the antiproliferative effects observed. Remarkably, the cytotoxicity and releasing ability of RuPCs were shown to be strongly dependent on the conjugation of the peptide position in the Ru complex. Complementary molecular dynamic simulations and computational calculations were performed to help interpret these findings at the molecular level. In summary, we identified a lead bi-functional RuPC that holds strong potential as a FGFR-targeted chemotherapeutic agent.
Subject(s)
Antineoplastic Agents , Breast Neoplasms , Peptides , Receptors, Fibroblast Growth Factor , Ruthenium , Female , Humans , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Coordination Complexes/chemistry , Coordination Complexes/pharmacology , Coordination Complexes/chemical synthesis , Drug Screening Assays, Antitumor , Hydrogen-Ion Concentration , Peptides/chemistry , Peptides/pharmacology , Peptides/therapeutic use , Receptors, Fibroblast Growth Factor/metabolism , Receptors, Fibroblast Growth Factor/antagonists & inhibitors , Ruthenium/chemistry , Ruthenium/pharmacology , Ruthenium/therapeutic useABSTRACT
Background: Coronary disease is the main cause of death around the world. mHealth technology is considered attractive and promising to promote behavioural changes aimed at healthy lifestyle habits among coronary patients. The purpose of this study is to evaluate the efficacy of an mHealth intervention regarding improved results in secondary prevention in patients after an acute myocardial infarction (AMI) or angina in terms of lifestyle, clinical variables and therapeutic compliance. Methods: Randomised clinical trial with 300 patients who underwent a percutaneous coronary intervention (PCI) with stent implant. They will be assigned to either the mHealth group, subject to a self-monitored educational intervention involving an internet application installed on their mobile phone or tablet, or to a control group receiving standard healthcare (150 patients in each arm). The primary outcome variables will be adherence to the Mediterranean diet, physical activity, smoking, therapeutic compliance, knowledge acquired, user-friendliness and satisfaction with the application. Measurements of blood pressure, heart rate, body weight, waist circumference (WC) and the 6-min walk test will be taken. Furthermore, the blood lipid profile, glucose and HbA1c will be evaluated. Clinical interview will be conducted, and validated questionnaires completed. The primary quantitative results will be compared using an analysis of covariance adjusted for age and sex. A multivariate analysis will be performed to examine the association of the intervention with lifestyle habits, the control of cardiovascular risk factors (CDRFs) and the results after the hospital discharge (major adverse events, treatment compliance and lifestyle). Conclusions: The study will provide evidence about the effectiveness of an mHealth intervention at improving the lifestyle of the participants and could be offered to patients with coronary disease to complement existing services. Trial registration: NCT05247606. [https://ClinicalTrials.gov]. 21/02/2022.
ABSTRACT
OBJECTIVES: Although hemispheric surgeries are among the most effective procedures for drug-resistant epilepsy (DRE) in the pediatric population, there is a large variability in seizure outcomes at the group level. A recently developed HOPS score provides individualized estimation of likelihood of seizure freedom to complement clinical judgement. The objective of this study was to develop a freely accessible online calculator that accurately predicts the probability of seizure freedom for any patient at 1-, 2-, and 5-years post-hemispherectomy. METHODS: Retrospective data of all pediatric patients with DRE and seizure outcome data from the original Hemispherectomy Outcome Prediction Scale (HOPS) study were included. The primary outcome of interest was time-to-seizure recurrence. A multivariate Cox proportional-hazards regression model was developed to predict the likelihood of post-hemispheric surgery seizure freedom at three time points (1-, 2- and 5- years) based on a combination of variables identified by clinical judgment and inferential statistics predictive of the primary outcome. The final model from this study was encoded in a publicly accessible online calculator on the International Network for Epilepsy Surgery and Treatment (iNEST) website (https://hops-calculator.com/). RESULTS: The selected variables for inclusion in the final model included the five original HOPS variables (age at seizure onset, etiologic substrate, seizure semiology, prior non-hemispheric resective surgery, and contralateral fluorodeoxyglucose-positron emission tomography [FDG-PET] hypometabolism) and three additional variables (age at surgery, history of infantile spasms, and magnetic resonance imaging [MRI] lesion). Predictors of shorter time-to-seizure recurrence included younger age at seizure onset, prior resective surgery, generalized seizure semiology, FDG-PET hypometabolism contralateral to the side of surgery, contralateral MRI lesion, non-lesional MRI, non-stroke etiologies, and a history of infantile spasms. The area under the curve (AUC) of the final model was 73.0%. SIGNIFICANCE: Online calculators are useful, cost-free tools that can assist physicians in risk estimation and inform joint decision-making processes with patients and families, potentially leading to greater satisfaction. Although the HOPS data was validated in the original analysis, the authors encourage external validation of this new calculator.
Subject(s)
Drug Resistant Epilepsy , Epilepsy , Hemispherectomy , Spasms, Infantile , Child , Humans , Hemispherectomy/methods , Spasms, Infantile/surgery , Retrospective Studies , Fluorodeoxyglucose F18 , Treatment Outcome , Epilepsy/diagnostic imaging , Epilepsy/surgery , Seizures/diagnosis , Seizures/etiology , Seizures/surgery , Drug Resistant Epilepsy/diagnostic imaging , Drug Resistant Epilepsy/surgery , Magnetic Resonance Imaging , ElectroencephalographyABSTRACT
OBJECTIVE: Lennox-Gastaut syndrome (LGS) is a severe form of epileptic encephalopathy, presenting during the first years of life, and is very resistant to treatment. Once medical therapy has failed, palliative surgeries such as vagus nerve stimulation (VNS) or corpus callosotomy (CC) are considered. Although CC is more effective than VNS as the primary neurosurgical treatment for LGS-associated drop attacks, there are limited data regarding the added value of CC following VNS. This study aimed to assess the effectiveness of CC preceded by VNS. METHODS: This multinational, multicenter retrospective study focuses on LGS children who underwent CC before the age of 18 years, following prior VNS, which failed to achieve satisfactory seizure control. Collected data included epilepsy characteristics, surgical details, epilepsy outcomes, and complications. The primary outcome of this study was a 50% reduction in drop attacks. RESULTS: A total of 127 cases were reviewed (80 males). The median age at epilepsy onset was 6 months (interquartile range [IQR] = 3.12-22.75). The median age at VNS surgery was 7 years (IQR = 4-10), and CC was performed at a median age of 11 years (IQR = 8.76-15). The dominant seizure type was drop attacks (tonic or atonic) in 102 patients. Eighty-six patients underwent a single-stage complete CC, and 41 an anterior callosotomy. Ten patients who did not initially have a complete CC underwent a second surgery for completion of CC due to seizure persistence. Overall, there was at least a 50% reduction in drop attacks and other seizures in 83% and 60%, respectively. Permanent morbidity occurred in 1.5%, with no mortality. SIGNIFICANCE: CC is vital in seizure control in children with LGS in whom VNS has failed. Surgical risks are low. A complete CC has a tendency toward better effectiveness than anterior CC for some seizure types.
Subject(s)
Epilepsy , Lennox Gastaut Syndrome , Vagus Nerve Stimulation , Child , Male , Humans , Infant , Child, Preschool , Adolescent , Lennox Gastaut Syndrome/surgery , Retrospective Studies , Corpus Callosum/surgery , Seizures/therapy , Syncope , Treatment Outcome , Vagus NerveABSTRACT
BACKGROUND: Coronary artery disease is the main cause of death and loss of disability-adjusted life years worldwide. Information and communication technology has become an important part of health care systems, including the innovative cardiac rehabilitation services through mobile phone and mobile health (mHealth) interventions. OBJECTIVE: In this study, we aimed to determine the effectiveness of different kinds of mHealth programs in changing lifestyle behavior, promoting adherence to treatment, and controlling modifiable cardiovascular risk factors and psychosocial outcomes in patients who have experienced a coronary event. METHODS: A systematic review of the literature was performed following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A thorough search of the following biomedical databases was conducted: PubMed, Embase, Web of Science, SciELO, CINAHL, Scopus, The Clinical Trial, and Cochrane. Articles that were randomized clinical trials that involved an intervention consisting of an mHealth program using a mobile app in patients after a coronary event were included. The articles analyzed some of the following variables as outcome variables: changes in lifestyle behavior, cardiovascular risk factors, and anthropometric and psychosocial variables. A meta-analysis of the variables studied was performed with the Cochrane tool. The risk of bias was assessed using the Cochrane Collaboration tool; the quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation tool; and heterogeneity was measured using the I2 test. RESULTS: A total of 23 articles were included in the review, and 20 (87%) were included in the meta-analysis, with a total sample size of 4535 patients. Exercise capacity measured using the 6-minute walk test (mean difference=21.64, 95% CI 12.72-30.55; P<.001), physical activity (standardized mean difference [SMD]=0.42, 95% CI 0.04-0.81; P=.03), and adherence to treatment (risk difference=0.19, 95% CI 0.11-0.28; P<.001) were significantly superior in the mHealth group. Furthermore, both the physical and mental dimensions of quality of life were better in the mHealth group (SMD=0.26, 95% CI 0.09-0.44; P=.004 and SMD=0.27, 95% CI 0.06-0.47; P=.01, respectively). In addition, hospital readmissions for all causes and cardiovascular causes were statistically higher in the control group than in the mHealth group (SMD=-0.03, 95% CI -0.05 to -0.00; P=.04 vs SMD=-0.04, 95% CI -0.07 to -0.00; P=.05). CONCLUSIONS: mHealth technology has a positive effect on patients who have experienced a coronary event in terms of their exercise capacity, physical activity, adherence to medication, and physical and mental quality of life, as well as readmissions for all causes and cardiovascular causes. TRIAL REGISTRATION: PROSPERO (International Prospective Register of Systematic Reviews) CRD42022299931; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=299931.
Subject(s)
Cardiovascular Diseases , Telemedicine , Humans , Quality of Life , Cardiovascular Diseases/prevention & control , Risk Factors , Heart Disease Risk Factors , Life Style , Randomized Controlled Trials as TopicABSTRACT
The General and Sport Nutrition Knowledge Questionnaire (GeSNK) is an instrument that has been developed and validated to assess the level of nutrition knowledge in adolescents and young adults. The aim of the present study was to validate the GeSNK questionnaire in a group of Spanish adolescents in the framework of a Nutrition Education Programme in Secondary Schools in Andalusia, Spain. This cross-sectional questionnaire validation study was developed in two phases: translation-cultural adaptation and validation. A total of 305 adolescents aged 11 to 17 years, studying from the first to the third year of compulsory secondary education, participated on a voluntary basis. The GeSNK questionnaire consists of 62 items: 29 items for the General Nutrition section and 33 items for the Sports Nutrition section. Cronbach's alpha coefficient for the complete questionnaire (GeSNK Total) was: 0.934; for the GeSNK General Nutrition section it was 0.918; and for the GeSNK Sports Nutrition section it was 0.856. The stability measured by the correlation coefficient for the General Nutrition section was 0.406 (p = 0.000); for the Sports Nutrition section it was 0.198 (p = 0.017); and for GeSNK Total the stability was 0.545 (p = 0.000). The questionnaire also demonstrated adequate construct validity. We therefore conclude that the Spanish version of the GeSNK questionnaire is a valid instrument to measure the level of knowledge in general nutrition and sports nutrition in adolescents.
Subject(s)
Sports Nutritional Sciences , Sports , Young Adult , Humans , Adolescent , Cross-Sectional Studies , Surveys and Questionnaires , Translations , Reproducibility of ResultsABSTRACT
Antibodies against the carboxy-terminal section of the membrane-proximal external region (C-MPER) of the HIV-1 envelope glycoprotein (Env) are considered as nearly pan-neutralizing. Development of vaccines capable of producing analogous broadly neutralizing antibodies requires deep understanding of the mechanism that underlies C-MPER recognition in membranes. Here, we use the archetypic 10E8 antibody and a variety of biophysical techniques including single-molecule approaches to study the molecular recognition of C-MPER in membrane mimetics. In contrast to the assumption that an interfacial MPER helix embodies the entire C-MPER epitope recognized by 10E8, our data indicate that transmembrane domain (TMD) residues contribute to binding affinity and specificity. Moreover, anchoring to membrane the helical C-MPER epitope through the TMD augments antibody binding affinity and relieves the effects exerted by the interfacial MPER helix on the mechanical stability of the lipid bilayer. These observations support that addition of TMD residues may result in more efficient and stable anti-MPER vaccines.
Subject(s)
HIV-1 , HIV-1/chemistry , HIV Envelope Protein gp41/chemistry , HIV Envelope Protein gp41/metabolism , HIV Antibodies/chemistry , Epitopes , Lipid Bilayers/chemistryABSTRACT
Ctn[15-34], the C-terminal section of crotalicidin (Ctn), a cathelicidin from a South American pit viper, is an antimicrobial and antitumoral peptide with remarkably longer stability in human serum than the parent Ctn. In this work, a set of topoisomers of both Ctn and Ctn[15-34], including the retro, enantio, and retroenantio versions, were synthesized and tested to investigate the structural requirements for activity. All topoisomers were as active as the cognate sequences against Gram-negative bacteria and tumor cells while slightly more toxic towards normal cells. More importantly, the enhanced serum stability of the D-amino-acid-containing versions suggests that such topoisomers must be preferentially considered as future antimicrobial and anticancer peptide leads.
ABSTRACT
BACKGROUND: It is important for health professionals to have tools available to assess patients' knowledge of lifestyle and cardiovascular risk factors after they have suffered a coronary event and determine whether educational interventions are effective. This study aims to design and validate a scale to evaluate this knowledge. METHODS: Four-phase instrument design: (A) Conceptual review. (B) Review by experts. (C) Pilot test-retest. (D) Psychometric validation of the final version of the questionnaire with 24 items. A panel of experts performed the content validity. The reliability of the scale was measured using Cronbach's alpha score and criterion validity was evaluated by comparing the total scores for knowledge obtained by the participants among the three education level groups. The construct and dimensional structure validity were assessed using exploratory factor analysis. RESULTS: A total of 143 people participated, 30 in the pilot study and 113 (68% male, 60.2 ± 9 years) in the psychometric validation of version 3 of the scale. A Cronbach's alpha score of 0.887 was reached for this version. The factor analysis showed that the items were distributed into five factors that explained 57% of the variance. Significant differences were observed in the level of knowledge among the patients of the three levels of education (low, moderate and high) (99.20 ± 11.93, 105.92 ± 7.85, 109.78 ± 8.76 points, p = 0.003), as there was a negative correlation between age and knowledge level (r = -0.213, p = 0.024). CONCLUSIONS: The scale presents psychometric properties that are evidence of its reliability and validity. The relationship demonstrated between the level of knowledge and age, sex and level of education shows the importance of emphasizing educational interventions for elderly people and those with a lower level of education.
ABSTRACT
Heterodimerization of RNA binding proteins Nrd1 and Nab3 is essential to communicate the RNA recognition in the nascent transcript with the Nrd1 recognition of the Ser5-phosphorylated Rbp1 C-terminal domain in RNA polymerase II. The structure of a Nrd1-Nab3 chimera reveals the basis of heterodimerization, filling a missing gap in knowledge of this system. The free form of the Nrd1 interaction domain of Nab3 (NRID) forms a multi-state three-helix bundle that is clamped in a single conformation upon complex formation with the Nab3 interaction domain of Nrd1 (NAID). The latter domain forms two long helices that wrap around NRID, resulting in an extensive protein-protein interface that would explain the highly favorable free energy of heterodimerization. Mutagenesis of some conserved hydrophobic residues involved in the heterodimerization leads to temperature-sensitive phenotypes, revealing the importance of this interaction in yeast cell fitness. The Nrd1-Nab3 structure resembles the previously reported Rna14/Rna15 heterodimer structure, which is part of the poly(A)-dependent termination pathway, suggesting that both machineries use similar structural solutions despite they share little sequence homology and are potentially evolutionary divergent.
Subject(s)
Nuclear Proteins , RNA-Binding Proteins , Saccharomyces cerevisiae Proteins , Amino Acid Sequence , Calorimetry , Circular Dichroism , Nuclear Magnetic Resonance, Biomolecular , Nuclear Proteins/chemistry , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Protein Conformation , Protein Multimerization/genetics , RNA-Binding Proteins/chemistry , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Saccharomyces cerevisiae Proteins/chemistry , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae Proteins/metabolism , mRNA Cleavage and Polyadenylation Factors/chemistry , mRNA Cleavage and Polyadenylation Factors/genetics , mRNA Cleavage and Polyadenylation Factors/metabolismABSTRACT
OBJECTIVE: This study was undertaken to determine whether the vertical parasagittal approach or the lateral peri-insular/peri-Sylvian approach to hemispheric surgery is the superior technique in achieving long-term seizure freedom. METHODS: We conducted a post hoc subgroup analysis of the HOPS (Hemispheric Surgery Outcome Prediction Scale) study, an international, multicenter, retrospective cohort study that identified predictors of seizure freedom through logistic regression modeling. Only patients undergoing vertical parasagittal, lateral peri-insular/peri-Sylvian, or lateral trans-Sylvian hemispherotomy were included in this post hoc analysis. Differences in seizure freedom rates were assessed using a time-to-event method and calculated using the Kaplan-Meier survival method. RESULTS: Data for 672 participants across 23 centers were collected on the specific hemispherotomy approach. Of these, 72 (10.7%) underwent vertical parasagittal hemispherotomy and 600 (89.3%) underwent lateral peri-insular/peri-Sylvian or trans-Sylvian hemispherotomy. Seizure freedom was obtained in 62.4% (95% confidence interval [CI] = 53.5%-70.2%) of the entire cohort at 10-year follow-up. Seizure freedom was 88.8% (95% CI = 78.9%-94.3%) at 1-year follow-up and persisted at 85.5% (95% CI = 74.7%-92.0%) across 5- and 10-year follow-up in the vertical subgroup. In contrast, seizure freedom decreased from 89.2% (95% CI = 86.3%-91.5%) at 1-year to 72.1% (95% CI = 66.9%-76.7%) at 5-year to 57.2% (95% CI = 46.6%-66.4%) at 10-year follow-up for the lateral subgroup. Log-rank test found that vertical hemispherotomy was associated with durable seizure-free progression compared to the lateral approach (p = .01). Patients undergoing the lateral hemispherotomy technique had a shorter time-to-seizure recurrence (hazard ratio = 2.56, 95% CI = 1.08-6.04, p = .03) and increased seizure recurrence odds (odds ratio = 3.67, 95% CI = 1.05-12.86, p = .04) compared to those undergoing the vertical hemispherotomy technique. SIGNIFICANCE: This pilot study demonstrated more durable seizure freedom of the vertical technique compared to lateral hemispherotomy techniques. Further studies, such as prospective expertise-based observational studies or a randomized clinical trial, are required to determine whether a vertical approach to hemispheric surgery provides superior long-term seizure outcomes.
Subject(s)
Drug Resistant Epilepsy , Epilepsy , Hemispherectomy , Child , Drug Resistant Epilepsy/surgery , Epilepsy/surgery , Hemispherectomy/methods , Humans , Pilot Projects , Prospective Studies , Retrospective Studies , Seizures/surgery , Treatment OutcomeABSTRACT
Multidrug resistance against conventional antibiotics poses an important threat to human health. In this context, antimicrobial peptides (AMPs) have been extensively studied for their antibacterial activity and promising results have been shown so far. However, AMPs tend to be rather vulnerable to protease degradation, which offsets their therapeutic appeal. Here, we demonstrate how replacing functional residues in the antimicrobial region of human RNase 3-also named eosinophil cationic protein-by non-natural amino acids increases stability in human serum. These changes were also shown to reduce the hemolytic effect of the peptides in general terms, whereas the antimicrobial activity was reasonably preserved. Digestion profiles enabled us to design new peptides with superior stability and lower toxicity that could become relevant candidates to reach clinical stages.
Subject(s)
Anti-Bacterial Agents/pharmacology , Antimicrobial Cationic Peptides/pharmacology , Eosinophil Cationic Protein/chemistry , Gram-Negative Bacteria/drug effects , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Antimicrobial Cationic Peptides/chemical synthesis , Antimicrobial Cationic Peptides/chemistry , Dose-Response Relationship, Drug , Humans , Microbial Sensitivity Tests , Molecular Structure , Structure-Activity RelationshipABSTRACT
Coronary heart disease is one of the main causes of morbimortality around the world. Patients that survive a coronary event suffer a high risk of readmission, relapse and mortality, attributed to the sub-optimal control of cardiovascular risk factors (CVRF), which highlights the need to improve secondary prevention strategies aimed at improving their lifestyle and adherence to treatment. Through a randomized controlled clinical trial, this study aims to evaluate the effect of an intervention involving an online health application supported by a mobile telephone or tablet (mHealth) on lifestyle (diet, physical activity, and tobacco consumption) and treatment adherence among people with coronary heart disease after percutaneous coronary intervention. The sample will comprise 240 subjects (120 in each arm: intervention and usual care). They are assessed immediately and nine months after their hospital discharge about sociodemographic, clinical, CVRF, lifestyle, and treatment adherence characteristics. The educative intervention, involving a follow-up and self-monitoring, will be performed using an online mHealth tool consisting of an application for mobile phones and tablets. The quantitative primary outcomes from the two groups will be compared using an analysis of covariance (ANCOVA) adjusted for age and gender. A multivariate analysis will be performed to examine the association of the intervention with lifestyle habits, the control of CVRFs, and outcomes after discharge in terms of the use of health services, emergency visits, cardiovascular events and readmissions.
Subject(s)
Coronary Disease , Mobile Applications , Secondary Prevention/methods , Telemedicine/methods , Cell Phone , Coronary Disease/prevention & control , Coronary Disease/therapy , Humans , Internet , Life Style , Text Messaging , Treatment Adherence and ComplianceABSTRACT
Passing through the blood-brain barrier (BBB) to treat neurological conditions is one of the main hurdles in modern medicine. Many drugs with promising in vitro profiles become ineffective in vivo due to BBB restrictive permeability. In particular, this includes drugs such as antiviral porphyrins, with the ability to fight brain-resident viruses causing diseases such as HIV-associated neurocognitive disorders (HAND). In the last two decades, BBB shuttles, particularly peptide-based ones, have shown promise in carrying various payloads across the BBB. Thus, peptide-drug conjugates (PDCs) formed by covalent attachment of a BBB peptide shuttle and an antiviral drug may become key therapeutic tools in treating neurological disorders of viral origin. In this study, we have used various approaches (guanidinium, phosphonium, and carbodiimide-based couplings) for on-resin synthesis of new peptide-porphyrin conjugates (PPCs) with BBB-crossing and potential antiviral activity. After careful fine-tuning of the synthetic chemistry, DIC/oxyma has emerged as a preferred method, by which 14 different PPCs have been made and satisfactorily characterized. The PPCs are prepared by coupling a porphyrin carboxyl group to an amino group (either N-terminal or a Lys side chain) of the peptide shuttle and show effective in vitro BBB translocation ability, low cytotoxicity toward mouse brain endothelial cells, and low hemolytic activity. Three of the PPCs, MP-P5, P4-MP, and P4-L-MP, effectively inhibiting HIV infectivity in vitro, stand out as most promising. Their efficacy against other brain-targeting viruses (Dengue, Zika, and SARS-CoV-2) is currently under evaluation, with preliminary results confirming that PPCs are a promising strategy to treat viral brain infections.
Subject(s)
Anti-HIV Agents/pharmacokinetics , Blood-Brain Barrier/metabolism , Peptides/pharmacokinetics , Porphyrins/pharmacokinetics , Animals , Anti-HIV Agents/chemistry , Anti-HIV Agents/pharmacology , Biological Transport , Cell Line , Drug Discovery , HEK293 Cells , HIV/drug effects , HIV Infections/drug therapy , Humans , Mice , Peptides/chemistry , Peptides/pharmacology , Porphyrins/chemistry , Porphyrins/pharmacologyABSTRACT
OBJECTIVE: To develop and validate a model to predict seizure freedom in children undergoing cerebral hemispheric surgery for the treatment of drug-resistant epilepsy. METHODS: We analyzed 1267 hemispheric surgeries performed in pediatric participants across 32 centers and 12 countries to identify predictors of seizure freedom at 3 months after surgery. A multivariate logistic regression model was developed based on 70% of the dataset (training set) and validated on 30% of the dataset (validation set). Missing data were handled using multiple imputation techniques. RESULTS: Overall, 817 of 1237 (66%) hemispheric surgeries led to seizure freedom (median follow-up = 24 months), and 1050 of 1237 (85%) were seizure-free at 12 months after surgery. A simple regression model containing age at seizure onset, presence of generalized seizure semiology, presence of contralateral 18-fluoro-2-deoxyglucose-positron emission tomography hypometabolism, etiologic substrate, and previous nonhemispheric resective surgery is predictive of seizure freedom (area under the curve = .72). A Hemispheric Surgery Outcome Prediction Scale (HOPS) score was devised that can be used to predict seizure freedom. SIGNIFICANCE: Children most likely to benefit from hemispheric surgery can be selected and counseled through the implementation of a scale derived from a multiple regression model. Importantly, children who are unlikely to experience seizure control can be spared from the complications and deficits associated with this surgery. The HOPS score is likely to help physicians in clinical decision-making.