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A 54-year-old patient with a medical history of hypertension, dyslipidemia, and diabetes underwent mitral valve replacement surgery with a biologic valve. During a chest computed tomography scan for breast neoplasia staging, a reduced luminal filling in the left atrium (3.6 cm) was unexpectedly found, prompting further cardiac evaluation. The patient was referred to the emergency department experiencing shortness of breath and fatigue, which improved after furosemide administration, and remaining stable throughout hospitalization. A transesophageal echocardiogram was performed the following day and revealed a biologic mitral valve prosthesis slightly displaced toward the left ventricle with an average transprosthetic gradient of 7 mmHg. Notably, a sizable intermediate echogenic mass measuring 3.0 cm × 3.5 cm was detected and attached to the prosthesis ring in a lateral and posterior position, within the left atrium. A mild degree of periprosthetic regurgitation was also noted. Given the substantial suspicion that the observed mass was a thrombus, the patient was commenced on anticoagulation therapy while awaiting cardiac magnetic resonance imaging for better characterization of the mass. Over 4 weeks, the thrombus notably decreased in size, disappearing entirely by the 6th week. This case highlights the significance of employing multiple imaging techniques in managing cardiac masses. The incidental discovery of the mass, its characterization, and subsequent management through anticoagulation, followed by confirmation and monitoring through echocardiogram, underscore the importance of a multimodal approach in diagnosing and treating such conditions.
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BACKGROUND: A single-dose dengue vaccine that protects individuals across a wide age range and regardless of dengue serostatus is an unmet need. We assessed the safety and efficacy of the live, attenuated, tetravalent Butantan-dengue vaccine (Butantan-DV) in adults, adolescents, and children. We previously reported the primary and secondary efficacy and safety endpoints in the initial 2 years of follow-up. Here we report the results through an extended follow-up period, with an average of 3·7 years of follow-up. METHODS: In this double-blind, randomised, placebo-controlled, phase 3, multicentre trial in Brazil, healthy participants (aged 2-59 years) who had not previously received a dengue vaccine were enrolled and randomly assigned 2:1 (stratified by age 18-59 years, 7-17 years, and 2-6 years) using a central electronic randomisation system to receive 0·5 mL of Butantan-DV (containing approximately 103 plaque-forming units of each of the four vaccine virus strains) or placebo, administered subcutaneously. Syringes containing vaccine or placebo were prepared by an unmasked trial pharmacist who was not involved in any subsequent participant assessments; other site staff and the participants remained unaware of the group allocations. Vaccine efficacy was calculated with the accrual of virologically confirmed dengue (VCD) cases (by RT-PCR) at least 28 days after vaccination up until the cutoff (at least 2 years of follow-up from the last participant enrolled). The primary endpoint was vaccine efficacy against VCD after day 28 by any dengue virus (DENV) serotype regardless of dengue serostatus at baseline in the per-protocol population. The primary and secondary safety endpoints up until day 21 were previously reported; secondary safety endpoints include the frequency of unsolicited vaccine-related adverse events after day 22. Safety analyses were done on all participants as treated. This trial is registered with ClinicalTrials.gov (NCT02406729) and is ongoing. FINDINGS: Of 16â363 participants assessed for eligibility, 16â235 were randomly assigned between Feb 22, 2016, and July 5, 2019, and received single-dose Butantan-DV (10â259 participants) or placebo (5976 participants). 16â162 participants (Butantan-DV n=10â215; placebo n=5947) were included in the per-protocol population and 16â235 (Butantan-DV n=10â259; placebo n=5976) in the safety population. At the data cutoff (July 13, 2021), participants had 2-5 years of follow-up (mean 3·7 years [SD 1·0], median 4·0 years [IQR 3·2-4·5]). 356 VCD cases were captured through the follow-up (128 in the vaccine group and 228 in the placebo group). Vaccine efficacy against VCD caused by any DENV serotype was 67·3% (95% CI 59·4-73·9); cases caused by DENV-3 or DENV-4 were not observed. The proportions of participants who had serious adverse events were similar between treatment groups (637 [6·2%] in the vaccine group and 395 [6·6%] in the placebo group) up until the cutoff. INTERPRETATION: A single dose of Butantan-DV was generally well tolerated and efficacious against symptomatic VCD (caused by DENV-1 and DENV-2) for a mean of 3·7 years. These findings support the continued development of Butantan-DV to prevent dengue disease in children, adolescents, and adults regardless of dengue serostatus. FUNDING: Instituto Butantan and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co. TRANSLATIONS: For the Spanish and Portuguese translations of the abstract see Supplementary Materials section.
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Introduction: Being one of the "big three" most cultivated cereals in the world, wheat plays a crucial role in ensuring global food/nutrition security, supplying close to 20% of the global needs for calories and proteins. However, the increasingly large fluctuations between years in temperatures and precipitation due to climate change cause important variations in wheat production worldwide. This fact makes wheat breeding programs a tool that, far from going out of fashion, is becoming the most important solution to develop varieties that can provide humanity with the sufficient amount of food it demands without forgetting the objective of quality. Material and methods: The National Institute of Agricultural and Veterinary Research in Portugal has carried out a long-term experiment (9 years) in different locations to test four different bread-making wheat cultivars, each representing important variations in germplasm. Wheat yield and quality traits obtained by official methods were recorded in 18 different environments regarding temperature and precipitation. Results and discussion: According to the ANOVA and PCA, protein content, wet gluten, dough tenacity, and extensibility were found to be highly affected by the environment. Paiva cultivar presented a higher yield in almost all the tested environments, but its quality traits varied enormously. Contrary behavior was recorded for Valbona cultivar. Antequera cultivar, with a production ranging between 4.7 and 9.3 tons/ha and a protein content between 11 and 16.8%, seems to be the most resilient cultivar regarding both productivity and quality of the flour with reference to changes in the main climate traits. The most ancient cultivar, Roxo, released in 1996, showed the worst results in this experiment, supporting the need to continue working in wheat breeding to meet the unavoidable changes in the environment.
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OBJECTIVE: To investigate the relationship between the levels of adipokines and other endocrine biomarkers and patient outcomes in hospitalized patients with COVID-19. METHODS: In a prospective study that included 213 subjects with COVID-19 admitted to the intensive care unit, we measured the levels of cortisol, C-peptide, glucagon-like peptide-1, insulin, peptide YY, ghrelin, leptin, and resistin.; their contributions to patient clustering, disease severity, and predicting in-hospital mortality were analyzed. RESULTS: Cortisol, resistin, leptin, insulin, and ghrelin levels significantly differed between severity groups, as defined by the World Health Organization severity scale. Additionally, lower ghrelin and higher cortisol levels were associated with mortality. Adding biomarkers to the clinical predictors of mortality significantly improved accuracy in determining prognosis. Phenotyping of subjects based on plasma biomarker levels yielded two different phenotypes that were associated with disease severity, but not mortality. CONCLUSION: As a single biomarker, only cortisol was independently associated with mortality; however, metabolic biomarkers could improve mortality prediction when added to clinical parameters. Metabolic biomarker phenotypes were differentially distributed according to COVID-19 severity but were not associated with mortality.
Subject(s)
Biomarkers , COVID-19 , Phenotype , Humans , COVID-19/blood , COVID-19/mortality , COVID-19/diagnosis , Biomarkers/blood , Male , Female , Prospective Studies , Prognosis , Middle Aged , Aged , Severity of Illness Index , Intensive Care Units , Hydrocortisone/blood , Hospital Mortality , SARS-CoV-2ABSTRACT
In this paper we examine several definitions of vaccine efficacy (VE) that we found in the literature, for diseases that express themselves in outbreaks, that is, when the force of infection grows in time, reaches a maximum and then vanishes. The fact that the disease occurs in outbreaks results in several problems that we analyse. We propose a mathematical model that allows the calculation of VE for several scenarios. Vaccine trials usually needs a large number of volunteers that must be enrolled. Ideally, all volunteers should be enrolled in approximately the same time, but this is generally impossible for logistic reasons and they are enrolled in a fashion that can be replaced by a continuous density function (for example, a Gaussian function). The outbreak can also be replaced by a continuous density function, and the use of these density functions simplifies the calculations. Assuming, for example Gaussian functions, one of the problems one can immediately notice is that the peak of the two curves do not occur at the same time. The model allows us to conclude: First, the calculated vaccine efficacy decreases when the force of infection increases; Second, the calculated vaccine efficacy decreases when the gap between the peak in the force of infection and the peak in the enrollment rate increases; Third, different trial protocols can be simulated with this model; different vaccine efficacy definitions can be calculated and in our simulations, all result are approximately the same. The final, and perhaps most important conclusion of our model, is that vaccine efficacy calculated during outbreaks must be carefully examined and the best way we can suggest to overcome this problem is to stratify the enrolled volunteer's in a cohort-by-cohort basis and do the survival analysis for each cohort, or apply the Cox proportional hazards model for each cohort.
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Background: Microglia and inflammation play a significant role in Alzheimer's disease (AD). Physical exercise and peripheral signals can influence microglial activity in the brain. Modulating the inflammatory response in the brain may provide therapeutic approaches for AD. Objective: To assess the effects of intravenously administered blood plasma from exercise-trained donor rats on cognitive function, microglia, and cytokine levels in an AD rat model at two different pathological stages; an early pre-plaque stage and a later stage closer to the emergence of extracellular plaques. Methods: Male transgenic McGill-R-Thy1-APP rats aged 2 and 5 months received 14 injections over 6 weeks: 1) plasma from exercise-trained rats (ExPlas), 2) plasma from sedentary rats (SedPlas), or 3) saline. Cognitive function was evaluated in a novel object recognition task. Microglia count and morphology were analyzed in cornu ammonis, dentate gyrus, entorhinal cortex, and subiculum. Amyloid plaque number and size were assessed in the rats with the later treatment start. A multiplex assay was used to measure 23 cytokines in cornu ammonis. Results: In rats treated from 2 months of age, ExPlas and SedPlas increased number and length of microglial branches in cornu ammonis and dentate gyrus compared to saline. Only ExPlas-treated rats exhibited similar changes in subiculum, while entorhinal cortex showed no differences across treatments. Microglia count remained unaffected. In rats treated from 5 months of age, there were no significant differences in microglia count or morphology or the number or size of amyloid plaques in any brain region. Compared to both other treatments in early pre-plaque stage rats, SedPlas increased TNF-α levels. ExPlas upregulated GM-CSF, IL-18, and VEGF, while SedPlas increased IL-10 compared to saline. In later-stage rats, ExPlas upregulated IL-17, and SedPlas upregulated TNF-α compared to saline. There were no effects of treatments on recognition memory. Conclusions: Intravenous injections of blood plasma from exercise-trained and sedentary donors differentially modulated microglial morphology and cytokine levels in the AD rat model at an early pre-plaque stage of pathology. Exercised plasma may reduce proinflammatory TNF-α signaling and promote microglial responses to early Aß accumulation but the lack of treatment effects in the later-stage rats emphasizes the potential importance of treatment timing.
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BACKGROUND: Genetic disease has recently emerged as a cause of cardiac conduction disorders (CCDs), but the diagnostic yield of genetic testing and the contribution of the different genes to CCD is still unsettled. OBJECTIVES: This study sought to determine the diagnostic yield of genetic testing in young adults with CCD of unknown etiology requiring pacemaker implantation. We also studied the prevalence of rare protein-altering variants across individual genes and functional gene groups. METHODS: We performed whole exome sequencing in 150 patients with CCD of unknown etiology who had permanent pacemaker implanted at age ≤60 years at 14 Spanish hospitals. Prevalence of rare protein-altering variants in patients with CCD was compared with a reference population of 115,522 individuals from gnomAD database (control subjects). RESULTS: Among 39 prioritized genes, patients with CCD had more rare protein-altering variants than control subjects (OR: 2.39; 95% CI: 1.75-3.33). Significant enrichment of rare variants in patients with CCD was observed in all functional gene groups except in the desmosomal genes group. Rare variants in the nuclear envelope genes group exhibited the strongest association with CCD (OR: 6.77; 95% CI: 3.71-13.87). Of note, rare variants in sarcomeric genes were also enriched (OR: 1.73; 95% CI: 1.05-3.10). An actionable genetic variant was detected in 21 patients (14%), with LMNA being the most frequently involved gene (4.6%). CONCLUSIONS: Unrecognized rare genetic variants increase the risk of CCD in young adults with CCD of unknown etiology. Genetic testing should be performed in patients age ≤60 years with CCD of unknown etiology. The role of genetic variants in sarcomeric genes as a cause of CCD should be further investigated.
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The issue of MeHg contamination is a significant concern due to its detrimental impact on the environment. This study aimed to thoroughly investigate the effects of MeHg on neurodevelopmental biomarkers, as there is a lack of systematic reviews in this area. We conducted a comprehensive search of three databases (PubMed, Scopus, and Web of Science) and found 522 records, which were then meticulously reviewed by two independent reviewers. A total of 66 studies were included, with biomarkers related to oxidative stress, neurotransmission, inflammation, epigenetics, and apoptosis being the most prominent. The results of both in vitro and in vivo models indicate that antioxidant enzymes and other oxidative stress-related markers are indeed, altered following MeHg exposure. Moreover, MeHg exposure causes significant disruptions to neurotransmitter levels, activities of neurotransmitter synthesis enzymes, receptor densities, and proteins involved in synaptic function. Proinflammatory biomarkers are consistently overexpressed in both MeHg-treated cells and the brains of exposed rats. Furthermore, studies on DNA methylation and biomarker activity suggest that MeHg exposure may lead to neurotoxicity and neurodevelopmental issues via perturbations to epigenetic markers and the apoptosis pathway.
Subject(s)
Biomarkers , Methylmercury Compounds , Oxidative Stress , Methylmercury Compounds/toxicity , Biomarkers/metabolism , Animals , Humans , Oxidative Stress/drug effects , Neurotoxicity Syndromes/metabolism , Neurotoxicity Syndromes/etiology , Apoptosis/drug effects , Rats , Epigenesis, Genetic/drug effects , DNA Methylation/drug effects , Neurodevelopmental Disorders/chemically induced , Neurodevelopmental Disorders/metabolismABSTRACT
This meta-analysis aims to investigate the effects of residual feed intake (RFI) phenotype on performance, nutrient utilization and meat quality traits in Zebu (Bos indicus) cattle. Twenty-three peer-reviewed publications with 37 treatment means were included in the dataset. Weighted mean difference analysis compared animals categorized into low RFI (more efficient) versus medium or high RFI (less efficient) groups. Data heterogeneity via meta-regression and subgroup analysis, considering variables such as animal age, sex class, experimental duration, RFI group, dietary concentrate, and estimated metabolizable energy intake were also explored. The predominant genetic group of cattle in the dataset was Nellore (89.18%), followed by Brahman (10.81%). More efficient animals (low RFI phenotype) exhibited less dry matter intake (DMI; P < 0.010) than medium or high RFI animals (-0.95 kg vs. -0.42 kg/d). Cattle dietary crude protein and fiber digestibility were consistent across RFI groups (P > 0.05), while dietary ether extract digestibility tended to decrease (P = 0.050) in low RFI animals (-13.20 g/kg DM). Low RFI animals tended to increased (P = 0.065) ribeye area (REA) compared to the high/medium RFI groups, while carcass backfat thickness (BFT) decreased (P = 0.042) compared to high/medium RFI groups. Moreover, there was an increase (P < 0.001) of 0.22 kg in Warner-Bratzler shear force (WBSF) and a reduction (P < 0.001) in the myofibrillar fragmentation index (MFI) in low RFI animals. Meat color parameters (lightness [L*] and yellowness [b*]) and visual marbling scores were consistent (P > 0.05) across RFI groups. In conclusion, Zebu cattle classified as efficient (low RFI) exhibited reduced DMI, which improves their feed efficiency. However, BFT and meat quality parameters such as tenderness (WBSF and MFI) and redness [a*] were compromised by low RFI phenotype, highlighting the challenge of enhancing feed efficiency and meat quality traits in Zebu cattle.
Subject(s)
Animal Feed , Animal Nutritional Physiological Phenomena , Diet , Animals , Cattle/physiology , Female , Male , Animal Feed/analysis , Diet/veterinary , Phenotype , Red Meat/analysisABSTRACT
BACKGROUND: Addressing informal caregivers' needs is essential for ensuring quality healthcare and promoting citizen-centred care. This systematic review assessed current knowledge about programmes aimed at meeting the needs of informal caregivers of adults who are dependent on others for daily life activities. METHODS: Following the PRISMA guidelines, the electronic databases EBSCOhost Research Platform, MEDLINE, CINAHL, Scopus, Web of Science and The Virtual Health Library were searched for randomized experimental studies published between 2012 and 2022 that implemented programmes addressing informal caregivers' needs to improve their experiences, health, and well-being. Quality was assessed using the standardized critical evaluation tools from the Joanna Briggs Institute. Two independent investigators performed the eligibility assessment and data extraction. Quantitative data on the effectiveness of interventions were collected, and the content of each intervention was synthesized and aggregated into categories, through narrative synthesis. RESULTS: The majority of the included studies (n = 16) were conducted in European countries and implemented a structured intervention programme compared to the provision of usual care. The studies were of fair to high methodological quality, with a higher risk of bias related to blinding. The results supported the achievement of favourable health outcomes among informal caregivers, namely improvements in mental health (n = 3) and quality of life (n = 3) and a decrease in psychological symptomatology (n = 5) and burden (n = 3). None of the interventions reported adverse outcomes; however, five studies did not describe significant differences in the outcomes assessed after the implementation of the programmes. Interventions focusing on training and educating caregivers (n = 14) and cognitive-behavioural strategies (n = 7) were the most common, while programmes focusing on emotional and psychological support as a resource to improve caregivers' psychological outcomes were scarce. CONCLUSIONS: This systematic review adds to the growing body of evidence and insight showing that programmes that address informal caregivers' needs seem to contribute to better physical and psychological health outcomes through the promotion of caregivers' educational support and the implementation of cognitive-behavioural strategies. Future research should implement methodologically robust cross-country programmes tailored to informal caregivers' physical, emotional, psychosocial, societal, and educational needs throughout the care trajectory.
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Myocarditis is defined as myocardial inflammation and its etiology is highly diverse, including infectious agents, drugs, and autoimmune diseases. The clinical presentation also varies widely, extending beyond the classic clinical picture of acute chest pain, and includes cases of cardiomyopathy of unknown cause whose etiology may be inflammatory. Because certain patients may benefit from targeted treatments, the search for the etiology should begin when myocarditis is first suspected. There remain several areas of uncertainty in the diagnosis and treatment of this disease. Consequently, this consensus document aims to provide clear recommendations for its diagnosis and treatment. Hence, a diagnostic algorithm is proposed, specifying when non-invasive diagnosis with cardiac MR is appropriate vs a noninvasive approach with endomyocardial biopsy. In addition, more novel aspects are discussed, such as when to suspect an underlying genetic etiology. The recommendations cover the management of myocarditis and inflammatory cardiomyopathy, both for general complications and specific clinical entities.
Subject(s)
Cardiomyopathies , Consensus , Myocarditis , Humans , Myocarditis/diagnosis , Myocarditis/therapy , Myocarditis/etiology , Cardiomyopathies/diagnosis , Cardiomyopathies/therapy , Cardiomyopathies/etiology , Biopsy , Algorithms , Myocardium/pathologyABSTRACT
Isoquinolinequinones represent an important family of natural alkaloids with profound biological activities. Heterologous expression of a rare bifunctional indole prenyltransferase/tryptophan indole-lyase enzyme from Streptomyces mirabilis P8-A2 in S. albidoflavus J1074 led to the activation of a putative isoquinolinequinone biosynthetic gene cluster and production of a novel isoquinolinequinone alkaloid, named maramycin (1). The structure of maramycin was determined by analysis of spectroscopic (1D/2D NMR) and MS spectrometric data. The prevalence of this bifunctional biosynthetic enzyme was explored and found to be a recent evolutionary event with only a few representatives in nature. Maramycin exhibited moderate cytotoxicity against human prostate cancer cell lines, LNCaP and C4-2B. The discovery of maramycin (1) enriched the chemical diversity of natural isoquinolinequinones and also provided new insights into crosstalk between the host biosynthetic genes and the heterologous biosynthetic genes in generating new chemical scaffolds.
Subject(s)
Dimethylallyltranstransferase , Isoquinolines , Streptomyces , Streptomyces/genetics , Streptomyces/metabolism , Streptomyces/enzymology , Humans , Dimethylallyltranstransferase/metabolism , Dimethylallyltranstransferase/genetics , Cell Line, Tumor , Isoquinolines/chemistry , Isoquinolines/metabolism , Isoquinolines/pharmacology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/metabolism , Terpenes/metabolism , Terpenes/chemistry , Multigene FamilyABSTRACT
Major depressive disorder (MDD) is a global health concern, affecting over 250 million individuals worldwide. In recent years, the gut-brain axis has emerged as a promising field for understanding the pathophysiology of MDD. Microbial metabolites, such as short-chain fatty acids (SCFAs)-acetate, butyrate, and propionate-, have gained attention for their potential to influence epigenetic modifications within the host brain. However, the precise mechanisms through which these metabolites participate in MDD pathophysiology remain elusive. This study was designed to investigate the effects of oral SCFA supplementation in adult male Wistar rats subjected to chronic unpredictable mild stress (CUMS). A subset of control and CUMS-exposed rats received different supplementations: sodium acetate (NaOAc) at a concentration of 60 mM, sodium butyrate (NaB) at 40 mM, sodium propionate (NaP) at 50 mM, or a mixture of these SCFAs. The gut microbiome was assessed through 16S rRNA sequencing, and epigenetic profiling was performed using Western blot analysis. Results demonstrated that NaP supplementation significantly alleviated anhedonia in stressed animals, as evidenced by improved performance in the sucrose consumption test. This ameliorative effect was potentially associated with the modulation of gut bacterial communities, accompanied by the attenuation of the region-specific epigenetic dysregulation in the brain of the animals exposed to chronic stress. These findings suggest a potential association between gut dysbiosis and stress response, and NaP could be a promising target for future MDD interventions. However, further studies are needed to fully elucidate the underlying mechanisms of these effects.
Subject(s)
Dietary Supplements , Epigenesis, Genetic , Gastrointestinal Microbiome , Propionates , Rats, Wistar , Animals , Gastrointestinal Microbiome/drug effects , Male , Epigenesis, Genetic/drug effects , Propionates/metabolism , Histones/metabolism , Stress, Psychological , Rats , Depression/drug therapy , Fatty Acids, Volatile/metabolism , Behavior, Animal/drug effects , Administration, Oral , Depressive Disorder, Major/metabolism , Butyric Acid/pharmacologyABSTRACT
Cinnamoyl moiety containing nonribosomal peptides represented by pepticinnamin E are a growing family of natural products isolated from different Streptomyces species and possess diverse bioactivities. The soil bacterium Streptomyces mirabilis P8-A2 harbors a cryptic pepticinnamin biosynthetic gene cluster, producing azodyrecins as major products. Inactivation of the azodyrecin biosynthetic gene cluster by CRISPR-BEST base editing led to the activation and production of pepticinnamin E (1) and its analogues, pepticinnamins N, O, and P (2-4), the structures of which were determined by detailed NMR spectroscopy, HRMS data, and Marfey's reactions. These new compounds did not show a growth inhibitory effect against the LNCaP and C4-2B prostate cancer lines, respectively.
Subject(s)
Soil Microbiology , Streptomyces , Streptomyces/chemistry , Molecular Structure , Humans , Multigene Family , Peptides/chemistry , Peptides/pharmacology , Peptides/isolation & purification , Cell Line, TumorSubject(s)
Humans , Male , Female , Aged , Cardiology , Amyloidosis , Prealbumin , Cardiomyopathies , Heart Diseases , Inpatients , Physical Examination , Coronary Disease , HypertensionABSTRACT
BACKGROUND: Disease penetrance in genotype-positive (G+) relatives of families with dilated cardiomyopathy (DCM) and the characteristics associated with DCM onset in these individuals are unknown. OBJECTIVES: This study sought to determine the penetrance of new DCM diagnosis in G+ relatives and to identify factors associated with DCM development. METHODS: The authors evaluated 779 G+ patients (age 35.8 ± 17.3 years; 459 [59%] females; 367 [47%] with variants in TTN) without DCM followed at 25 Spanish centers. RESULTS: After a median follow-up of 37.1 months (Q1-Q3: 16.3-63.8 months), 85 individuals (10.9%) developed DCM (incidence rate of 2.9 per 100 person-years; 95% CI: 2.3-3.5 per 100 person-years). DCM penetrance and age at DCM onset was different according to underlying gene group (log-rank P = 0.015 and P <0.01, respectively). In a multivariable model excluding CMR parameters, independent predictors of DCM development were: older age (HR per 1-year increase: 1.02; 95% CI: 1.0-1.04), an abnormal electrocardiogram (HR: 2.13; 95% CI: 1.38-3.29); presence of variants in motor sarcomeric genes (HR: 1.92; 95% CI: 1.05-3.50); lower left ventricular ejection fraction (HR per 1% increase: 0.86; 95% CI: 0.82-0.90) and larger left ventricular end-diastolic diameter (HR per 1-mm increase: 1.10; 95% CI: 1.06-1.13). Multivariable analysis in individuals with cardiac magnetic resonance and late gadolinium enhancement assessment (n = 360, 45%) identified late gadolinium enhancement as an additional independent predictor of DCM development (HR: 2.52; 95% CI: 1.43-4.45). CONCLUSIONS: Following a first negative screening, approximately 11% of G+ relatives developed DCM during a median follow-up of 3 years. Older age, an abnormal electrocardiogram, lower left ventricular ejection fraction, increased left ventricular end-diastolic diameter, motor sarcomeric genetic variants, and late gadolinium enhancement are associated with a higher risk of developing DCM.
Subject(s)
Cardiomyopathy, Dilated , Genotype , Penetrance , Adult , Female , Humans , Male , Middle Aged , Young Adult , Cardiomyopathy, Dilated/genetics , Cardiomyopathy, Dilated/physiopathology , Connectin/genetics , Electrocardiography , Follow-Up Studies , Spain/epidemiology , Retrospective StudiesABSTRACT
Different musculoskeletal conditions affect people all over the world and were considered by the WHO to be the main cause of disability in 4 of 6 regions in 2017, with an increase in the associated burden and the impact they have on today's society. One of these conditions is related to the knee, which is associated with complex and vulnerable injuries associated with ligaments, menisci, and cartilage. After surgery, there is a reflex inhibition of motor neurons and immobilization, there is rapid atrophy and weakness in the different associated muscles, affecting proprioception, strength and muscle function, compromising quality of life. The aim of this article is to describe a protocol for a rehabilitation program after surgery for people with knee injuries. An experimental study will be carried out with 75 patients, with control and experimental groups. In both groups, initial measurements will be compared with measurements after the program, at different times. It is hoped that this study will generate significant information on rehabilitation intervention for people with knee injuries.
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INTRODUCTION: Suicide is a worldwide health concern and up to date there is no good predictor of it except a previous suicide attempt. Therefore, there are increasing efforts in the understanding of which factors, genetic or environmental, are associated with suicide behaviour. OBJECTIVE: To review evidence of the effect of childhood trauma and impulsivity on suicidal behavior through a systematic review and meta-analysis. METHODS: Searches were conducted on the 12th of June 2021 in the PubMed, Scopus, and Web of Science databases. Two reviewers evaluated each record for eligibility and discussed upon disagreement, when no consensus was reached, a third reviewer was involved to make a decision. RESULTS: A total of 11,530 records were identified through the searches. After duplicates were removed, 6,595 records remained to be screened. The full text was sought for 1,561 records. Our qualitative synthesis included 22 studies, from which 9 were included in the meta-analyses. We found a significant effect of sexual abuse, physical abuse, emotional abuse and physical neglect on suicide attempts in the prisoners, and Substance Use Diorder (SUD) subgroups. Moreover, there was a significant effect of Childhood Trauma Questionnaire (CTQ) total score and emotional neglect dimension for all the subgroups. CONCLUSION: The present study has provided an overview of the state-of-the-art research on childhood trauma and impulsivity and their association with suicidal behavior and quantified their effects on suicide attempts. Hopefully this evidence will be considered in future research and harnessed for clinical gain in detection and treatment of suicide behaviour.
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BACKGROUND: Several risk factors have been involved in the poor clinical progression of coronavirus disease-19 (COVID-19), including ageing, and obesity. SARS-CoV-2 may compromise lung function through cell damage and paracrine inflammation; and obesity has been associated with premature immunosenescence, microbial translocation, and dysfunctional innate immune responses leading to poor immune response against a range of viruses and bacterial infections. Here, we have comprehensively characterized the immunosenescence, microbial translocation, and immune dysregulation established in hospitalized COVID-19 patients with different degrees of body weight. RESULTS: Hospitalised COVID-19 patients with overweight and obesity had similarly higher plasma LPS and sCD14 levels than controls (all p < 0.01). Patients with obesity had higher leptin levels than controls. Obesity and overweight patients had similarly higher expansions of classical monocytes and immature natural killer (NK) cells (CD56+CD16-) than controls. In contrast, reduced proportions of intermediate monocytes, mature NK cells (CD56+CD16+), and NKT were found in both groups of patients than controls. As expected, COVID-19 patients had a robust expansion of plasmablasts, contrasting to lower proportions of major T-cell subsets (CD4 + and CD8+) than controls. Concerning T-cell activation, overweight and obese patients had lower proportions of CD4+CD38+ cells than controls. Contrasting changes were reported in CD25+CD127low/neg regulatory T cells, with increased and decreased proportions found in CD4+ and CD8+ T cells, respectively. There were similar proportions of T cells expressing checkpoint inhibitors across all groups. We also investigated distinct stages of T-cell differentiation (early, intermediate, and late-differentiated - TEMRA). The intermediate-differentiated CD4 + T cells and TEMRA cells (CD4+ and CD8+) were expanded in patients compared to controls. Senescent T cells can also express NK receptors (NKG2A/D), and patients had a robust expansion of CD8+CD57+NKG2A+ cells than controls. Unbiased immune profiling further confirmed the expansions of senescent T cells in COVID-19. CONCLUSIONS: These findings suggest that dysregulated immune cells, microbial translocation, and T-cell senescence may partially explain the increased vulnerability to COVID-19 in subjects with excess of body weight.