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Inhibitors of poly(ADP-ribose) (PAR) polymerase (PARPi) have entered the clinic for the treatment of homologous recombination (HR)-deficient cancers. Despite the success of this approach, preclinical and clinical research with PARPi has revealed multiple resistance mechanisms, highlighting the need for identification of novel functional biomarkers and combination treatment strategies. Functional genetic screens performed in cells and organoids that acquired resistance to PARPi by loss of 53BP1 identified loss of LIG3 as an enhancer of PARPi toxicity in BRCA1-deficient cells. Enhancement of PARPi toxicity by LIG3 depletion is dependent on BRCA1 deficiency but independent of the loss of 53BP1 pathway. Mechanistically, we show that LIG3 loss promotes formation of MRE11-mediated post-replicative ssDNA gaps in BRCA1-deficient and BRCA1/53BP1 double-deficient cells exposed to PARPi, leading to an accumulation of chromosomal abnormalities. LIG3 depletion also enhances efficacy of PARPi against BRCA1-deficient mammary tumors in mice, suggesting LIG3 as a potential therapeutic target.
Subject(s)
BRCA1 Protein/genetics , DNA Ligase ATP/genetics , DNA, Single-Stranded , MRE11 Homologue Protein/genetics , Ovarian Neoplasms/metabolism , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Poly-ADP-Ribose Binding Proteins/genetics , Triple Negative Breast Neoplasms/metabolism , Tumor Suppressor p53-Binding Protein 1/genetics , Animals , Biopsy , CRISPR-Cas Systems , Cell Line , Cell Nucleus/metabolism , Cell Proliferation , Chromosome Aberrations , DNA Damage , DNA Ligase ATP/metabolism , Female , Humans , Lentivirus/genetics , Mammary Neoplasms, Animal , Mice , Mutation , Poly-ADP-Ribose Binding Proteins/metabolism , RNA, Small Interfering/metabolism , TransgenesABSTRACT
Since the pioneering works of Berg and Purcell, discriminating between diffusion followed by binding has played a central role in understanding cell signaling. B cell receptors (BCR) and antibodies (Ab) challenge that simplified view as binding to the antigen follows after a chain of diffusion and rotations, including whole molecule rotation and independent tilts and twists of their Fab arms due to their Y-shaped structure and flexibility. In this paper, we combine analytical calculations with Brownian simulations to derive the first-passage times due to these three rotations positioning the Fab paratopes at a proper distance and orientation required for antigen binding. Our results indicate that when measuring Ab-Ag effective kinetic binding rates, using experimental methods in which the analyte is in solution only gives values proportional to the intrinsic binding rates, [Formula: see text], and [Formula: see text], for values of [Formula: see text] up to [Formula: see text]. Beyond that, a plateau of the effective 3D on rate between [Formula: see text] and [Formula: see text] is attained. Additionally, for BCR-Ag interactions, the effective 2D on and off binding rates can only be inferred from the corresponding effective 3D on and off rates for values of effective 3D on rates lower than [Formula: see text]. This is highly relevant when trying to relate BCR-antigen-binding strength and B cell response, especially during germinal center reactions. Therefore, there is a pressing need to reexamine our current understanding of the BCR-antigen kinetic rates in germinal centers using the latest experimental assays for BCR-Ag interactions.
Subject(s)
Antibodies , Receptors, Antigen, B-Cell , Kinetics , Signal Transduction , B-LymphocytesABSTRACT
Recent years have witnessed the detection of an increasing number of complex organic molecules in interstellar space, some of them being of prebiotic interest. Disentangling the origin of interstellar prebiotic chemistry and its connection to biochemistry and ultimately, to biology is an enormously challenging scientific goal where the application of complexity theory and network science has not been fully exploited. Encouraged by this idea, we present a theoretical and computational framework to model the evolution of simple networked structures toward complexity. In our environment, complex networks represent simplified chemical compounds and interact optimizing the dynamical importance of their nodes. We describe the emergence of a transition from simple networks toward complexity when the parameter representing the environment reaches a critical value. Notably, although our system does not attempt to model the rules of real chemistry nor is dependent on external input data, the results describe the emergence of complexity in the evolution of chemical diversity in the interstellar medium. Furthermore, they reveal an as yet unknown relationship between the abundances of molecules in dark clouds and the potential number of chemical reactions that yield them as products, supporting the ability of the conceptual framework presented here to shed light on real scenarios. Our work reinforces the notion that some of the properties that condition the extremely complex journey from the chemistry in space to prebiotic chemistry and finally, to life could show relatively simple and universal patterns.
Subject(s)
Extraterrestrial Environment , Origin of LifeABSTRACT
BACKGROUND: Information on infective endocarditis (IE) caused by Cutibacterium spp. is limited and new Duke-ISCVID criteria have not yet been properly assessed. We examined clinical characteristics, outcomes and performance of diagnostic tests for Cutibacterium valvular and cardiac implantable electronic device-related IE (CIED-IE). METHODS: Data corresponding to all episodes of Cutibacterium IE recorded from 2008 to 2023 in a prospective national cohort including 46 Spanish hospitals were examined. Possible IE cases were reassessed using the new criteria. The sensitivity of blood cultures, valvular and CIED cultures, and PCR of the 16SrRNA gene and sequencing (16SPCR) was evaluated. RESULTS: There were 67/6,692 (1%) episodes of IE caused by Cutibacterium spp., 85% affecting men. Of these, 50 were valve-related (45 prosthetic, 5 native) and 17 CIED-related. The new criteria identified 8 additional cases and reclassified 15 as definite IE. Intracardiac complications (abscess, pseudoaneurysm, perforation or intracardiac fistula) occurred in 23/50 (46%) valvular IE episodes, leading to 18% mortality, and up to 40% mortality if surgery was indicated but could not be performed. All CIED-IE cases underwent device removal and no deaths were recorded. Positive diagnosis rates for blood cultures, valve/device cultures and 16SPCR were 52%, 70% and 82%, respectively. CONCLUSION: Cutibacterium IE is a rare yet potentially life-threatening condition that warrants a high index of suspicion in men with endovascular prosthetic material. The new Duke-ISCVID criteria and molecular techniques are useful for its diagnosis. Considering a significant complication rate, cardiac surgery and removal of CIEDs play a key role in reducing mortality.
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Health surveys allow exploring health indicators that are of great value from a public health point of view and that cannot normally be studied from regular health registries. These indicators are usually coded as ordinal variables and may depend on covariates associated with individuals. In this article, we propose a Bayesian individual-level model for small-area estimation of survey-based health indicators. A categorical likelihood is used at the first level of the model hierarchy to describe the ordinal data, and spatial dependence among small areas is taken into account by using a conditional autoregressive distribution. Post-stratification of the results of the proposed individual-level model allows extrapolating the results to any administrative areal division, even for small areas. We apply this methodology to describe the geographical distribution of a self-perceived health indicator from the Health Survey of the Region of Valencia (Spain) for the year 2016.
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Dairy cattle health traits are paramount from a welfare and economic viewpoint; therefore, modern breeding programs prioritize the genetic improvement of these traits. Estimated breeding values for health traits are published as the probability of animals staying healthy. They are obtained using threshold models, which assume that the observed binary phenotype (i.e., healthy or sick) is dictated by an underlying normally distributed liability exceeding or not a threshold. This methodology requires significant computing time and faces convergence challenges as it implies a nonlinear system of equations. Linear models have more straightforward computations and provide a robust approximation to threshold models; thus, they could be used to overcome the mentioned challenges. However, linear models yield estimated breeding values on the observed scale, requiring an approximation to the liability scale analogous to that from threshold models to later obtain the estimated breeding values on the probability scale. In addition, the robustness of the approximation of linear to threshold models depends on the amount of information and the incidence of the trait, with extreme incidence (i.e., ≤ 5%) deviating from optimal approximation. Our objective was to test a transformation from the observed to the liability and then to the probability scale in the genetic evaluation of health traits with moderate and very low (extreme) incidence. Data comprised displaced abomasum (5.1M), ketosis (3.6M), lameness (5M), and mastitis (6.3M) records from a Holstein population with a pedigree of 6M animals, of which 1.7M were genotyped. Univariate threshold and linear models were performed to predict breeding values. The agreement between estimated breeding values on the probability scale derived from threshold and linear models was assessed using Spearman rank correlations and comparison of estimated breeding values distributions. Correlations were at least 0.95, and estimated breeding value distributions almost entirely overlapped for all the traits but displaced abomasum, the trait with the lowest incidence (2%). Computing time was â¼3x longer for threshold than for linear models. In this Holstein population, the approximation was suboptimal for a trait with extreme incidence (2%). However, when the incidence was ≥6%, the approximation was robust, and its use is recommended along with linear models for analyzing categorical traits in large populations to ease the computational burden.
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BACKGROUND: The objective of this study was to assess long-term outcome in patients with spontaneous intracerebral hemorrhage admitted to the intensive care unit. METHODS: Mortality and Glasgow Outcome Scale, Barthel Index, and 5-level EQ-5D version (EQ-5D-5L) scores were analyzed in a multicenter cohort study of three Spanish hospitals (336 patients). Mortality was also analyzed in the Medical Information Mart for Intensive Care III (MIMIC-III) database. RESULTS: The median (25th percentile-75th percentile) age was 62 (50-70) years, the median Glasgow Coma Score was 7 (4-11) points, and the median Acute Physiology and Chronic Health disease Classification System II (APACHE-II) score was 21 (15-26) points. Hospital mortality was 54.17%, mortality at 90 days was 56%, mortality at 1 year was 59.2%, and mortality at 5 years was 66.4%. In the Glasgow Outcome Scale, a normal or disabled self-sufficient situation was recorded in 21.5% of patients at 6 months, in 25.5% of patients after 1 year, and in 22.1% of patients after 5 years of follow-up (4.5% missing). The Barthel Index score of survivors improved over time: 50 (25-80) points at 6 months, 70 (35-95) points at 1 year, and 90 (40-100) points at 5 years (p < 0.001). Quality of life evaluated with the EQ-5D-5L at 1 year and 5 years indicated that greater than 50% of patients had no problems or slight problems in all items (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). In the MIMIC-III study (N = 1354), hospital mortality was 31.83% and was 40.5% at 90 days and 56.2% after 5 years. CONCLUSIONS: In patients admitted to the intensive care unit with a diagnosis of nontraumatic intracerebral hemorrhage, hospital mortality up to 90 days after admission is very high. Between 90 days and 5 years after admission, mortality is not high. A large percentage of survivors presented a significant deficit in quality of life and functional status, although with progressive improvement over time. Five years after the hemorrhagic stroke, a survival of 30% was observed, with a good functional status seen in 20% of patients who had been admitted to the hospital.
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BACKGROUND: Recently we reported the design and evaluation of floating semi-implantable devices that receive power from and bidirectionally communicate with an external system using coupling by volume conduction. The approach, of which the semi-implantable devices are proof-of-concept prototypes, may overcome some limitations presented by existing neuroprostheses, especially those related to implant size and deployment, as the implants avoid bulky components and can be developed as threadlike devices. Here, it is reported the first-in-human acute demonstration of these devices for electromyography (EMG) sensing and electrical stimulation. METHODS: A proof-of-concept device, consisting of implantable thin-film electrodes and a nonimplantable miniature electronic circuit connected to them, was deployed in the upper or lower limb of six healthy participants. Two external electrodes were strapped around the limb and were connected to the external system which delivered high frequency current bursts. Within these bursts, 13 commands were modulated to communicate with the implant. RESULTS: Four devices were deployed in the biceps brachii and the gastrocnemius medialis muscles, and the external system was able to power and communicate with them. Limitations regarding insertion and communication speed are reported. Sensing and stimulation parameters were configured from the external system. In one participant, electrical stimulation and EMG acquisition assays were performed, demonstrating the feasibility of the approach to power and communicate with the floating device. CONCLUSIONS: This is the first-in-human demonstration of EMG sensors and electrical stimulators powered and operated by volume conduction. These proof-of-concept devices can be miniaturized using current microelectronic technologies, enabling fully implantable networked neuroprosthetics.
Subject(s)
Electric Stimulation Therapy , Muscle, Skeletal , Humans , Electromyography , Electrodes, Implanted , Muscle, Skeletal/physiology , Lower Extremity , Wireless TechnologyABSTRACT
Sound classification plays a crucial role in enhancing the interpretation, analysis, and use of acoustic data, leading to a wide range of practical applications, of which environmental sound analysis is one of the most important. In this paper, we explore the representation of audio data as graphs in the context of sound classification. We propose a methodology that leverages pre-trained audio models to extract deep features from audio files, which are then employed as node information to build graphs. Subsequently, we train various graph neural networks (GNNs), specifically graph convolutional networks (GCNs), GraphSAGE, and graph attention networks (GATs), to solve multi-class audio classification problems. Our findings underscore the effectiveness of employing graphs to represent audio data. Moreover, they highlight the competitive performance of GNNs in sound classification endeavors, with the GAT model emerging as the top performer, achieving a mean accuracy of 83% in classifying environmental sounds and 91% in identifying the land cover of a site based on its audio recording. In conclusion, this study provides novel insights into the potential of graph representation learning techniques for analyzing audio data.
ABSTRACT
The protein p32 (C1QBP) is a multifunctional and multicompartmental homotrimer that is overexpressed in many cancer types, including colon cancer. High expression levels of C1QBP are negatively correlated with the survival of patients. Previously, we demonstrated that C1QBP is an essential promoter of migration, chemoresistance, clonogenic, and tumorigenic capacity in colon cancer cells. However, the mechanisms underlying these functions and the effects of specific C1QBP protein inhibitors remain unexplored. Here, we show that the specific pharmacological inhibition of C1QBP with the small molecule M36 significantly decreased the viability rate, clonogenic capacity, and proliferation rate of different colon cancer cell lines in a dose-dependent manner. The effects of the inhibitor of C1QBP were cytostatic and non-cytotoxic, inducing a decreased activation rate of critical pro-malignant and mitogenic cellular pathways such as Akt-mTOR and MAPK in RKO colon cancer cells. Additionally, treatment with M36 significantly affected the mitochondrial integrity and dynamics of malignant cells, indicating that p32/C1QBP plays an essential role in maintaining mitochondrial homeostasis. Altogether, our results reinforce that C1QBP is an important oncogene target and that M36 may be a promising therapeutic drug for the treatment of colon cancer.
Subject(s)
Colonic Neoplasms , Cytostatic Agents , Humans , Cytostatic Agents/pharmacology , Mitogens/pharmacology , Signal Transduction , Mitochondrial Proteins/metabolism , Cell Proliferation , Carrier Proteins/metabolismABSTRACT
BACKGROUND AND AIMS: Large clinical trials and small real-world studies show that a 1L polyethylene glycol and ascorbic acid solution (1L PEG-ASC) is an effective and safe bowel preparation for colonoscopy. Here, the effectiveness and safety of 1L PEG-ASC was evaluated in a large cohort of patients in routine clinical practice in Spain. METHODS: A sub-analysis was performed in an observational, multicenter, retrospective study assessing the effectiveness and safety of 1L PEG-ASC in adult patients undergoing a colonoscopy at 10 centers in Spain. Cleansing quality was assessed with the Boston Bowel Preparation Scale, scores ≥6 with all segmental scores ≥2 was considered adequate colon cleansing, high-quality was considered as cleansing ≥8 or =3 in the right colon. Polyp and adenoma detection rates, and adverse events were also assessed. RESULTS: Data was collected from 7160 patients: 48.3% males; mean age 58.0, 33.6% ≥65 years old. Adequate overall bowel cleansing was achieved in 95.6% of patients (95% CI 95.1%-96.0%), high quality cleansing in 74.4% (95% CI 73.4%-75.4%) and high-quality right colon cleansing in 66.0% (95% CI 64.9-67.1). The adequate overall cleansing rate was 97.0% with a split-dose and 94.0% with same-day regimen (P<0.0001), and high-quality right colon cleansing was 69.0% and 62.5% (P<0.0001), respectively. Colonoscopy was completed in 97.2% of cases. A multivariate regression analysis revealed that an overnight split-dose regimen and age <65 years were independent predictors of adequate bowel cleansing of the overall colon, age <65 years and female gender were independent predictors of HQ cleansing of the overall colon, and the three covariates were independent predictors of HQ cleansing of the right colon. At least one adverse event was experienced by 3.3% of participants, with nausea (1.5%) and vomiting (1.2%) being the most frequent. CONCLUSION: This sub-analysis confirmed 1L PEG-ASC to be an effective and safe bowel cleansing preparation in a real world setting in Spain.
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Background and Objectives: Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. Accumulating evidence in animal models suggests that loss of interleukin-10 (IL-10) anti-inflammatory actions might contribute to lobular inflammation, considered one of the first steps toward NASH development. However, the role of IL-10 in lobular inflammation remains poorly explored in humans. We examined mRNA and protein levels of IL-10 in liver biopsies and serum samples from morbidly obese patients, investigating the relationship between IL-10 and lobular inflammation degree. Materials and Methods: We prospectively enrolled morbidly obese patients of both sexes, assessing the lobular inflammation grade by the Brunt scoring system to categorize participants into mild (n = 7), moderate (n = 19), or severe (n = 13) lobular inflammation groups. We quantified the hepatic mRNA expression of IL-10 by quantitative polymerase chain reaction and protein IL-10 levels in liver and serum samples by Luminex Assay. We estimated statistical differences by one-way analysis of variance (ANOVA) and Tukey's multiple comparison test. Results: The hepatic expression of IL-10 significantly diminished in patients with severe lobular inflammation compared with the moderate lobular inflammation group (p = 0.01). The hepatic IL-10 protein levels decreased in patients with moderate or severe lobular inflammation compared with the mild lobular inflammation group (p = 0.008 and p = 0.0008, respectively). In circulation, IL-10 also significantly decreased in subjects with moderate or severe lobular inflammation compared with the mild lobular inflammation group (p = 0.005 and p < 0.0001, respectively). Conclusions: In liver biopsies and serum samples of morbidly obese patients, the protein levels of IL-10 progressively decrease as lobular inflammation increases, supporting the hypothesis that lobular inflammation develops because of the loss of the IL-10-mediated anti-inflammatory counterbalance.
Subject(s)
Inflammation , Interleukin-10 , Liver , Obesity, Morbid , Humans , Interleukin-10/blood , Interleukin-10/analysis , Obesity, Morbid/complications , Obesity, Morbid/blood , Female , Male , Adult , Middle Aged , Liver/metabolism , Liver/pathology , Prospective Studies , Inflammation/blood , Non-alcoholic Fatty Liver Disease/blood , Non-alcoholic Fatty Liver Disease/complicationsABSTRACT
The chromosomal region 17q21.31 harbors a 900 kb inversion polymorphism named after the microtubule-associated protein tau (MAPT) gene. Since no recombination occurs, two haplotypes are recognized: a directly oriented variant (H1) and an inverted variant (H2). The H2 haplotype features a distribution pattern with high frequencies in the Near East and Europe, medium levels in South Asia and North Africa, and low levels elsewhere. Studies of this genomic region are relevant owing to its likely association with numerous neurodegenerative diseases. However, the causes underlying the geographic distribution of the haplotype frequencies remain a bone of contention among researchers. With this work, we have intended to outline a plausible hypothesis on the origin of the high European H2 frequencies. To that end, we have analyzed an extensive population database (including three new Iberian populations) to explore potential clinal variations of H2 frequencies. We found a sigmoidal frequency cline with an upward trend from South Asia to Europe. The maximum value was detected in the Basques from Gipuzkoa province (0.494) with the curve's inflection point in the Near East. From our results, we suggest that the most likely scenario for high H2 frequencies in Europe would be a founding event in the Near East during the late Paleolithic or early Neolithic. Subsequently, such H2 overrepresentation would have reached Europe with the arrival of the first Neolithic farmers. The current frequencies and geographic distribution of the 17q21.31 inversion suggest that the founding events mainly affected the H2D subhaplotype.
Subject(s)
Polymorphism, Genetic , tau Proteins , Haplotypes/genetics , tau Proteins/genetics , Europe , Middle EastABSTRACT
Bacterial keratitis is a vision-threatening infection of the cornea that is typically treated with antibiotics. However, antibiotics sometimes fail to eradicate the infection and do not prevent or repair the damage caused directly by the bacteria or the host immune response to the infection. Our group previously demonstrated that treatment of Pseudomonas aeruginosa keratitis in rabbits with innovative cold atmospheric plasma (iCAP) resulted in reduced edema, ulcer formation, and bacterial load. In this study, we investigated the efficacy of iCAP treatment in methicillin-resistant Staphylococcus aureus (MRSA). New Zealand white rabbits were infected intrastromally with MRSA then treated with iCAP, moxifloxacin, vancomycin, or combination of iCAP with each antibiotic to assess the safety and efficacy of iCAP treatment compared to untreated controls and antibiotics. iCAP treatment significantly reduced bacterial loads and inflammation, improved anterior chamber clarity, and prevented corneal ulceration compared to untreated controls and antibiotic treatment. Safety assessments of grimace test scores and tear production showed that iCAP was not significantly different from either antibiotic treatment in terms of distress or tear production. Combination iCAP/antibiotic treatment did not appear to provide significant added benefit over iCAP alone. Our findings suggest that the addition of iCAP may be a viable tool in reducing damage to the cornea and anterior chamber of the eye following S. aureus keratitis.
Subject(s)
Corneal Ulcer , Eye Infections, Bacterial , Keratitis , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Rabbits , Animals , Corneal Ulcer/drug therapy , Corneal Ulcer/microbiology , Bacterial Load , Staphylococcus aureus , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Keratitis/drug therapy , Keratitis/prevention & control , Keratitis/microbiology , Anti-Bacterial Agents/therapeutic use , Eye Infections, Bacterial/drug therapy , Eye Infections, Bacterial/prevention & control , Eye Infections, Bacterial/microbiologyABSTRACT
Metabarcoding is a powerful tool to characterize biodiversity in biological samples. The interpretation of taxonomic profiles from metabarcoding data has been hindered by their compositional nature. Several strategies have been proposed to transform compositional data into quantitative data, but they have intrinsic limitations. Here, I propose a workflow based on bacterial and fungal cellular internal standards (spike-ins) for absolute quantification of the microbiota in soil samples. These standards were added to the samples before DNA extraction in amounts estimated after qPCRs, to target around 1-2% coverage in the sequencing run. In bacteria, proportions of spike-in reads in the sequencing run were very similar (< 2-fold change) to those predicted by the qPCR assessment, and for fungi they differed up to 40-fold. The low variation among replicates highlights the reproducibility of the method. Estimates based on multiple bacterial spike-ins were highly correlated (r = 0.99). Procrustes analysis evidenced significant biological effects on the community composition when normalizing compositional data. A protocol based on qPCR estimation of input amounts of cellular spikes is proposed as a cheap and reliable strategy for quantitative metabarcoding of biological samples.
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This research describes the functionalization of polymer-matrix-trapping porphyrins, considering that the transcendental properties of meso-substituted porphyrins, such as optical and chemical stability, combined with the strength of the polymers, can produce photoactive advanced polymeric networks. Polystyrene (PS) and O,O´-bis-(2-aminopropyl)-polyethyleneglycol-300 (2NH2peg300, APEG), or their combination, were used to confine the meso-substituted porphyrin species 5,10,15,20-tetrakis(4'-carboxy-1,1'-biphenyl-4-yl)porphyrin and 5,10,15,20-tetrakis((pyridin-4-yl)phenyl)porphyrin. The samples were characterized by Fourier-transform infrared (FTIR), X-ray diffraction (XRD), ultraviolet-visible (UV-Vis) and fluorescence spectroscopies. The absorption and emission properties of the materials were compared to those of their respective porphyrin solutions. The fluorescence was preserved in the obtained composite through a mixture of polymers, PS, and APEG, yielding translucent polymeric networks. Moreover, analysis of individual polymeric assemblies by molecular docking was performed to support the understanding of the experimental findings. This analysis corroborates that the stronger the estimated binding energies, the stronger the interactions that occur between porphyrin and the polymer via non-polar covalent bonds.
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Contact tracing is a non-pharmaceutical intervention (NPI) widely used in the control of the COVID-19 pandemic. Its effectiveness may depend on a number of factors including the proportion of contacts traced, delays in tracing, the mode of contact tracing (e.g. forward, backward or bidirectional contact training), the types of contacts who are traced (e.g. contacts of index cases or contacts of contacts of index cases), or the setting where contacts are traced (e.g. the household or the workplace). We performed a systematic review of the evidence regarding the comparative effectiveness of contact tracing interventions. 78 studies were included in the review, 12 observational (ten ecological studies, one retrospective cohort study and one pre-post study with two patient cohorts) and 66 mathematical modelling studies. Based on the results from six of the 12 observational studies, contact tracing can be effective at controlling COVID-19. Two high quality ecological studies showed the incremental effectiveness of adding digital contact tracing to manual contact tracing. One ecological study of intermediate quality showed that increases in contact tracing were associated with a drop in COVID-19 mortality, and a pre-post study of acceptable quality showed that prompt contact tracing of contacts of COVID-19 case clusters / symptomatic individuals led to a reduction in the reproduction number R. Within the seven observational studies exploring the effectiveness of contact tracing in the context of the implementation of other non-pharmaceutical interventions, contact tracing was found to have an effect on COVID-19 epidemic control in two studies and not in the remaining five studies. However, a limitation in many of these studies is the lack of description of the extent of implementation of contact tracing interventions. Based on the results from the mathematical modelling studies, we identified the following highly effective policies: (1) manual contact tracing with high tracing coverage and either medium-term immunity, highly efficacious isolation/quarantine and/ or physical distancing (2) hybrid manual and digital contact tracing with high app adoption with highly effective isolation/ quarantine and social distancing, (3) secondary contact tracing, (4) eliminating contact tracing delays, (5) bidirectional contact tracing, (6) contact tracing with high coverage in reopening educational institutions. We also highlighted the role of social distancing to enhance the effectiveness of some of these interventions in the context of 2020 lockdown reopening. While limited, the evidence from observational studies shows a role for manual and digital contact tracing in controlling the COVID-19 epidemic. More empirical studies accounting for the extent of contact tracing implementation are required.
Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , COVID-19/prevention & control , Contact Tracing/methods , Pandemics/prevention & control , Retrospective Studies , Communicable Disease Control/methods , SARS-CoV-2ABSTRACT
BACKGROUND: Physical inactivity, excessive sedentary time, and lack of sleep time have been independently associated with lower health-related physical fitness. However, little is known about the combined association between 24-h movement guidelines (i.e., physical activity, recreational screen time, and sleep duration) and components of physical fitness. OBJECTIVE: The main aim was to examine the likelihood of having high/very high levels on different components of physical fitness based on meeting with 24-h movement guidelines. METHODS: In this cross-sectional study, 1276 Spanish youths (13.07 ± 0.86; 55.88% boys), aged 11-16 years, completed self-reported questionnaires on physical activity, recreational screen time, and sleep duration. Physical fitness components were assessed by 20-m shuttle-run test, standing long jump test, handgrip strength test, and 4 × 10-m shuttle-run test. Meeting 24-h movement guidelines was defined as: 9-11 h/day (children aged 5-13) or 8-10 h/day (adolescents aged 14-17) of sleep, ≤2 h/day of recreational screen time and at least 60 min/day of moderate-to-vigorous physical activity. The probability of having a high/very high score for each physical fitness components (i.e., ≥60th centile according to the normative cut-off points for European adolescents) in relation to adherence to 24-h movement guidelines was analyzed using a series of binary logistic regressions. RESULTS: Participants who met the three 24-h movement guidelines were more likely to have high/very high for cardiorespiratory fitness (OR = 3.31; 95% CI: 1.79, 6.14; p < 0.001), standing long jump (OR = 1.91; 95% CI: 1.06, 3.45; p = 0.031), muscular fitness (OR = 2.05; 95% CI: 1.09, 3.86; p = 0.048) and physical fitness (OR = 1.99; 95% CI: 1.08, 3.66; p = 0.012), but not for handgrip strength (OR = 1.15; 95% CI: 0.64, 2.01; p = 0.636) and speed/agility (OR = 1.65; 95% CI: 0.92, 2.96; p = 0.093), compared to those who did not meet all three recommendations. CONCLUSION: Since meeting the three 24-h movement guidelines increased the likelihood of having higher levels in most physical fitness components, it seems necessary to promote these movement behaviors early in life, as they could serve as a gateway for improving health-related fitness in future generations.
Subject(s)
Cardiorespiratory Fitness , Hand Strength , Male , Child , Humans , Adolescent , Female , Cross-Sectional Studies , Physical Fitness , Exercise , SleepABSTRACT
OBJECTIVE: This systematic review and meta-analysis aimed to examine the effects of out-of-school physical activity (PA) interventions, based on Self-Determination Theory (SDT), on basic psychological needs (BPN), motivation toward PA, and PA levels in youths. DESIGN: Systematic review and meta-analyses. METHOD: We searched for intervention studies examining the effects of PA interventions based on SDT implemented outside the school published in English and Spanish in six electronic databases up to January 2022. RESULTS: Outcomes of interest were BPN, motivation, and PA levels. In total, nine studies were included in this review. Seven individual meta-analyses were conducted for each variable, revealing nonsignificant clustered effects for the outcomes autonomy satisfaction (g = 0.12, 95% CI [-0.31, 0.55]), competence satisfaction (g = 0.02, 95% CI [-0.28, 0.32]), relatedness satisfaction (g = 0.13, 95% CI [-0.43, 0.68]), autonomous motivation (g = 0.15, 95% CI [-0.38, 0.67]), controlled motivation (g = 0.12, 95% CI [-0.32, 0.55]), amotivation (g = -0.36, 95% CI [-0.88, 0.16]), and PA behavior (g = 0.02, 95% CI [-0.08, 0.12]). CONCLUSION: Meta-analyses suggest that out-of-school PA interventions based on SDT are not effective in increasing levels of needs satisfaction, types of motivation, and PA levels.
Subject(s)
Exercise , Motivation , Humans , Adolescent , Child , Personal Autonomy , Personal Satisfaction , SchoolsABSTRACT
The endoscopic transventricular transchoroidal approach facilitates entry into the posterior part of the third ventricle, allowing a visualization field from the foramen of Monro to the pineal region through this anatomical corridor. Combined surgery to treat the target lesion and possible endoscopic third ventriculostomy (ETV) can be performed through a single burr hole. A detailed description of this surgical technique is given, and a series of cases from our center is presented. This retrospective study included patients with lesions in the pineal region or posterior zone of the third ventricle who underwent surgery between 2004 and 2022 in our center for tumor biopsy or endoscopic cyst fenestration. In nine cases, the transchoroidal approach was performed. Demographic and clinical variables were collected: sex, age at diagnosis, clinical presentation, characteristics of the lesion, pathological diagnosis, characteristics of the procedure, complications, subsequent treatments, evolution, follow-up time, and degree of success of the endoscopic procedure. The mean and range of the quantitative variables and frequency of the qualitative variables were analyzed, together with the statistical significance (p < 0.05). Surgical planning was carried out by performing a preoperative MRI, calculating the ideal entry point and trajectory for each case. The preoperative planning of the surgical technique is described in detail. Of our sample, 55.6% were women, with a mean age of 35 years (7-78). The most common clinical presentation was intracranial hypertension (55.6%), with or without a focus. Eight patients presented hydrocephalus at diagnosis. The most frequent procedure was endoscopic biopsy with ETV (66.7%). The pathological diagnosis varied widely. Procedure-related complications included one case of self-limited bleeding of the choroidal fissure at its opening and one intraventricular hemorrhage due to tumor bleeding in the postoperative period. Non-procedure-related complications comprised two ETV failures and one case of systemic infection, while late complications included one case of disease progression and one case of radionecrosis. Four patients died, one due to poor neurological evolution after post-surgical tumor bleeding and three due to causes unrelated to the procedure. The rest of the patients had a favorable evolution and were asymptomatic or stable. The transchoroidal approach through a single burr hole is a feasible and safe option for access to the posterior part of the third ventricle. Proper planning of each case is necessary to avoid complications.