Visual stimulus brightness influences the efficiency of attractant-baited traps for catching Drosophila suzukii Matsumura (Diptera: Drosophilidae).

Drosophila suzukii (Matsumura) is an exotic pest of economic importance that affects several soft-skinned fruits in Mexico. Previously, we found that yellow or yellow-green rectangular cards inside a transparent trap baited with attractants improved D. suzukii capture. In this study, we evaluated the influence of rectangular cards with different yellow shades inside a transparent multi-hole trap baited with apple cider vinegar (ACV) on D. suzukii capture in the field. Second, we tested whether ACV-baited traps with cards of other geometric shapes affected D. suzukii catches compared to traps with rectangular cards. Third, we evaluated the effects of commercial lures combined with a more efficient visual stimulus from previous experiments on trapping D. suzukii flies. We found that ACV-baited traps plus a yellow-shaded rectangle card with 67% reflectance at a 549.74 nm dominant wavelength captured more flies than ACV-baited traps with yellow rectangle cards with a higher reflectance. Overall, ACV-baited traps with rectangles and squares caught more flies than did ACV-baited traps without visual stimuli. The traps baited with SuzukiiLURE-Max, ACV and Z-Kinol plus yellow rectangles caught 57, 70 and 101% more flies, respectively, than the traps baited with the lure but without a visual stimulus.

Fixed-bearing versus mobile-bearing total ankle replacement survivorship. A meta-analysis.

BACKGROUND: Main objective of this research is to know if there is a different survival rate between fixed bearing (FB) and mobile bearing (MB) total ankle replacement (TAR). We hypothesized that there are no differences between the survival rates of both implants. METHODS: A systematic search was performed in PubMed, Cochrane, EMBASE and ClinicalTrials.gov databases to identify published studies from August 2018 to September 2022 including results for FB and MB TAR survivorship. Inclusion criteria included 1) primary TAR in one or both feet in which implant could be identified , 2) a minimum of 20 procedures reported, 3) reported implant survivorship or calculable and 4) a minimum of 12 months follow-up for level 1-3 studies or 60 months for level 4 studies. RESULTS: 3902 ankles in 28 studies were included. 719 were FB and 3104 MB with an overall survivorship of 94% (95% CI [0.89; 0.97]) and 89% (95% CI [0.86; 0.92]) respectively. After subgroup analysis, we did not find differences among both groups (p =  0.429 ). Meta-regression analysis showed that longer follow-up was associated with lower survival rates in MB group (p = 0.000) while no other relationships were found with other factors (age, level of evidence or conflict of interests). CONCLUSIONS: No differences in survival rates between both groups were found. Age and other studied confounders were not found to be related with implant survivorship. However, longer follow-up was found to be related with lower survival rates. Studies with longer follow-up and higher level of evidence are needed to confirm results. LEVEL OF EVIDENCE: IV, systematic review of level I to IV studies.

Myeloid Zfhx3 deficiency protects against hypercapnia-induced suppression of host defense against influenza A virus.

Hypercapnia, elevation of the partial pressure of CO2 in blood and tissues, is a risk factor for mortality in patients with severe acute and chronic lung diseases. We previously showed that hypercapnia inhibits multiple macrophage and neutrophil antimicrobial functions and that elevated CO2 increases the mortality of bacterial and viral pneumonia in mice. Here, we show that normoxic hypercapnia downregulates innate immune and antiviral gene programs in alveolar macrophages (AMØs). We also show that zinc finger homeobox 3 (Zfhx3) - a mammalian ortholog of zfh2, which mediates hypercapnic immune suppression in Drosophila - is expressed in mouse and human macrophages. Deletion of Zfhx3 in the myeloid lineage blocked the suppressive effect of hypercapnia on immune gene expression in AMØs and decreased viral replication, inflammatory lung injury, and mortality in hypercapnic mice infected with influenza A virus. To our knowledge, our results establish Zfhx3 as the first known mammalian mediator of CO2 effects on immune gene expression and lay the basis for future studies to identify therapeutic targets to interrupt hypercapnic immunosuppression in patients with advanced lung disease.

Physics-Informed Neural Networks for Quantum Control.

Quantum control is a ubiquitous research field that has enabled physicists to delve into the dynamics and features of quantum systems, delivering powerful applications for various atomic, optical, mechanical, and solid-state systems. In recent years, traditional control techniques based on optimization processes have been translated into efficient artificial intelligence algorithms. Here, we introduce a computational method for optimal quantum control problems via physics-informed neural networks (PINNs). We apply our methodology to open quantum systems by efficiently solving the state-to-state transfer problem with high probabilities, short-time evolution, and using low-energy consumption controls. Furthermore, we illustrate the flexibility of PINNs to solve the same problem under changes in physical parameters and initial conditions, showing advantages in comparison with standard control techniques.

Roadmap on optical sensors.

Optical sensors and sensing technologies are playing a more and more important role in our modern world. From micro-probes to large devices used in such diverse areas like medical diagnosis, defence, monitoring of industrial and environmental conditions, optics can be used in a variety of ways to achieve compact, low cost, stand-off sensing with extreme sensitivity and selectivity. Actually, the challenges to the design and functioning of an optical sensor for a particular application requires intimate knowledge of the optical, material, and environmental properties that can affect its performance. This roadmap on optical sensors addresses different technologies and application areas. It is constituted by twelve contributions authored by world-leading experts, providing insight into the current state-of-the-art and the challenges their respective fields face. Two articles address the area of optical fibre sensors, encompassing both conventional and specialty optical fibres. Several other articles are dedicated to laser-based sensors, micro- and nano-engineered sensors, whispering-gallery mode and plasmonic sensors. The use of optical sensors in chemical, biological and biomedical areas is discussed in some other papers. Different approaches required to satisfy applications at visible, infrared and THz spectral regions are also discussed.

Role of Mitochondria in Inflammatory Bowel Diseases: A Systematic Review.

Mitochondria are key cellular organelles whose main function is maintaining cell bioenergetics by producing ATP through oxidative phosphorylation. However, mitochondria are involved in a much higher number of cellular processes. Mitochondria are the home of key metabolic pathways like the tricarboxylic acid cycle and ß-oxidation of fatty acids, as well as biosynthetic pathways of key products like nucleotides and amino acids, the control of the redox balance of the cell and detoxifying the cell from H2S and NH3. This plethora of critical functions within the cell is the reason mitochondrial function is involved in several complex disorders (apart from pure mitochondrial disorders), among them inflammatory bowel diseases (IBD). IBD are a group of chronic, inflammatory disorders of the gut, mainly composed of ulcerative colitis and Crohn's disease. In this review, we present the current knowledge regarding the impact of mitochondrial dysfunction in the context of IBD. The role of mitochondria in both intestinal mucosa and immune cell populations are discussed, as well as the role of mitochondrial function in mechanisms like mucosal repair, the microbiota- and brain-gut axes and the development of colitis-associated colorectal cancer.

Spanish Translation, Cross-Cultural Adaptation, and Validation of the Olerud-Molander Ankle Score (OMAS) for Ankle Fractures.

Background: The aim of this study was to translate and cross-culturally adapt the Olerud-Molander Ankle Score (OMAS) into Spanish and to assess its reliability and validity. Methods: The translation and adaptation to develop the Spanish version of the OMAS (OMAS-Sp) was performed according to current international guidelines. The OMAS-Sp was administered to 98 patients with a surgically treated ankle fracture, and it was repeated 7-14 days later to assess construct reliability of each question's score and the total score. Test-retest reliability and the internal consistency were calculated, and concurrent validity was assessed by comparing the OMAS-Sp with the Foot and Ankle Outcome Score (FAOS). The presence of floor and ceiling effects was also analyzed. Results: Adequate internal consistency was found with a Cronbach α of 0.821. Excellent test-retest reliability was demonstrated with an interclass correlation coefficient for the total score of 0.970 (95% CI 0.956-0.980; P < .001). Spearman correlation coefficients (r's) between the OMAS-Sp total score and the 5 FAOS subscales ranged from 0.944 to 0.951 (P < .001). No floor or ceiling effects were found. Conclusion: The OMAS-Sp demonstrated adequate psychometric properties and is a valid and reliable tool for assessing outcomes in Spanish-speaking patients with surgically treated ankle fractures. Level of Evidence: Level II, prospective cohort study.

Actinobacillus pleuropneumoniae, surface proteins and virulence: a review.

Actinobacillus pleuropneumoniae (App) is a globally distributed Gram-negative bacterium that produces porcine pleuropneumonia. This highly contagious disease produces high morbidity and mortality in the swine industry. However, no effective vaccine exists to prevent it. The infection caused by App provokes characteristic lesions, such as edema, inflammation, hemorrhage, and necrosis, that involve different virulence factors. The colonization and invasion of host surfaces involved structures and proteins such as outer membrane vesicles (OMVs), pili, flagella, adhesins, outer membrane proteins (OMPs), also participates proteases, autotransporters, and lipoproteins. The recent findings on surface structures and proteins described in this review highlight them as potential immunogens for vaccine development.

Mitochondrial Stress Links Environmental Triggers with Pro-Inflammatory Signaling in Crohn's Disease.

Inflammatory Bowel Diseases (IBD) are a group of chronic, inflammatory disorders of the gut. The incidence and activity of IBD are determined by both genetic and environmental factors. Among these factors, polymorphisms in genes related to autophagy and the consumption of non-steroidal anti-inflammatory drugs (NSAIDs) have been consistently associated with IBD. We show that NSAIDs induce mitochondrial stress and mitophagy in intestinal epithelial cells. In an altered mitophagy context simulating that observed in IBD patients, NSAID-induced mitochondrial stress leads to the release of mitochondrial components, which act as Danger Associated Molecular Patterns with pro-inflammatory potential. Furthermore, colonic organoids from Crohn's disease patients and healthy donors show activation of the mitochondrial Unfolded Protein Response (UPRmt) upon treatment with ibuprofen. Finally, colon biopsies from Crohn's disease patients in remission or with low-to-moderate activity also show expression of genes involved in UPRmt, while patients with severe activity show no increase compared to healthy donors. Our results suggest the involvement of mitochondria in the mechanisms triggering inflammation in IBD after NSAID use. Moreover, our results highlight the clinical relevance of mitochondrial stress and activation of the UPRmt pathway in the pathophysiology of Crohn's disease.

Evaluation of DiaSorin Liaison® calprotectin fecal assay adapted for pleural effusion.

Objectives: Calprotectin (CP) is a calcium and zinc binding protein that is widely measured on faecal samples but its determination in other biological fluids might be of interest. The aim of this work was to validate the measurement of CP in pleural fluid by chemiluminescence. Methods: LIAISON®XL, a fully automated chemiluminescence analyzer, was used for CP quantification on pleural fluid. A validation protocol was designed using both quality control materials provided by the manufacturer and pools of pleural fluid samples. Stability, imprecision, bias, linearity, detection capability and carry over effect were evaluated. Results: CP was stable on pleural fluid at least one week, under refrigerated conditions, and four weeks at -80 °C. The observed intra- and inter-day imprecision was between 2.2 and 6.49 %, with a negative bias under 5.51 %. The linearity of the method was verified up to 2,000 ng/mL. The LoQ for the assay was 48.52 ng/mL. A statistically significant carry-over effect was observed after measuring CP concentrations above the upper limit of linearity, but given the observed magnitude, a clinically relevant impact should not be expected. Conclusions: DiaSorin Liaison® calprotectin assay allows reliable measurement of CP in pleural fluid.

Inercia clínica o terapéutica en neumología: una reflexión sobre su definición y actores principales / Clinical or therapeutic inertia in pneumology: critical reflection on its definition and main actors

La inercia clínica se define como los fallos del médico en el inicio o la intensificación del tratamiento cuando están indicados. Nuestro objetivo es reflexionar sobre este concepto aplicado en enfermedad pulmonar obstructiva crónica y asma, y el papel del profesional sanitario y del sistema de salud como actores implicados. Dejamos aparte la inercia del paciente para otro ámbito de estudio e intervención. Proponemos definir la inercia clínica para procesos durante el diagnóstico y el tratamiento cuando no se inicia o modifica (intensifica o disminuye) una terapia. También se identifican los factores que contribuyen a la inercia clínica o terapéutica y se plantean estrategias de mejora. (AU)

Clinical inertia is defined as the physician’s failure to initiate or intensify treatment when it is indicated. Our objective is to reflect on this concept applied to chronic obstructive pulmonary disease and asthma, and the role of health professional and health system as stakeholders. We leave patient inertia aside for another area of study and intervention. We propose to define clinical inertia for diagnosis and therapeutic processes when a treatment is not started or modified (intensifies or decreases). Factors that contribute to clinical and/or therapeutic inertia are also identified and improvement strategies are proposed. (AU)

Bougainvillea glabra Choisy (Nyctinaginacea): review of phytochemistry and antimicrobial potential.

The Bougainvillea glabra or bougainvillea is a climbing plant native from South America belonging to the Nyctaginaceae family. The bougainvillea is recognized worldwide for its horticultural importance, due to the color of its bracts, commonly known as "flowers," made up of bracts, which are the striking parts, and the true flowers, which are white and small. Bougainvillea is widely known in traditional medicine to treat respiratory diseases such as cough, asthma, and bronchitis, gastrointestinal diseases, also for its antibacterial and insecticidal capacity. The antimicrobial potential of the involucre of this plant has not been studied, despite research showing a high phytochemical presence of secondary metabolites such as alkanes, phenols, terpenes, and betalains. This review compiles information about the traditional uses of B. glabra, its botanical description, ecological relevance, phytochemistry, antimicrobial and antibiofilm activity, such as the toxicology of bracts and flowers.

PPP1R12C Promotes Atrial Hypocontractility in Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF)-the most common sustained cardiac arrhythmia-increases thromboembolic stroke risk 5-fold. Although atrial hypocontractility contributes to stroke risk in AF, the molecular mechanisms reducing myofilament contractile function remain unknown. We tested the hypothesis that increased expression of PPP1R12C (protein phosphatase 1 regulatory subunit 12C)-the PP1 (protein phosphatase 1) regulatory subunit targeting MLC2a (atrial myosin light chain 2)-causes hypophosphorylation of MLC2a and results in atrial hypocontractility. METHODS: Right atrial appendage tissues were isolated from human patients with AF versus sinus rhythm controls. Western blots, coimmunoprecipitation, and phosphorylation studies were performed to examine how the PP1c (PP1 catalytic subunit)-PPP1R12C interaction causes MLC2a dephosphorylation. In vitro studies of pharmacological MRCK (myotonic dystrophy kinase-related Cdc42-binding kinase) inhibitor (BDP5290) in atrial HL-1 cells were performed to evaluate PP1 holoenzyme activity on MLC2a. Cardiac-specific lentiviral PPP1R12C overexpression was performed in mice to evaluate atrial remodeling with atrial cell shortening assays, echocardiography, and AF inducibility with electrophysiology studies. RESULTS: In human patients with AF, PPP1R12C expression was increased 2-fold versus sinus rhythm controls (P=2.0×10-2; n=12 and 12 in each group) with >40% reduction in MLC2a phosphorylation (P=1.4×10-6; n=12 and 12 in each group). PPP1R12C-PP1c binding and PPP1R12C-MLC2a binding were significantly increased in AF (P=2.9×10-2 and 6.7×10-3, respectively; n=8 and 8 in each group). In vitro studies utilizing drug BDP5290, which inhibits T560-PPP1R12C phosphorylation, demonstrated increased PPP1R12C binding with both PP1c and MLC2a and dephosphorylation of MLC2a. Mice treated with lentiviral PPP1R12C vector demonstrated a 150% increase in left atrial size versus controls (P=5.0×10-6; n=12, 8, and 12), with reduced atrial strain and atrial ejection fraction. Pacing-induced AF in mice treated with lentiviral PPP1R12C vector was significantly higher than in controls (P=1.8×10-2 and 4.1×10-2, respectively; n=6, 6, and 5). CONCLUSIONS: Patients with AF exhibit increased levels of PPP1R12C protein compared with controls. PPP1R12C overexpression in mice increases PP1c targeting to MLC2a and causes MLC2a dephosphorylation, which reduces atrial contractility and increases AF inducibility. These findings suggest that PP1 regulation of sarcomere function at MLC2a is a key determinant of atrial contractility in AF.

An overview of carbapenem-resistant organisms from food-producing animals, seafood, aquaculture, companion animals, and wildlife.

Carbapenem resistance (CR) is a major global health concern. CR is a growing challenge in clinical settings due to its rapid dissemination and low treatment options. The characterization of its molecular mechanisms and epidemiology are highly studied. Nevertheless, little is known about the spread of CR in food-producing animals, seafood, aquaculture, wildlife, their environment, or the health risks associated with CR in humans. In this review, we discuss the detection of carbapenem-resistant organisms and their mechanisms of action in pigs, cattle, poultry, seafood products, companion animals, and wildlife. We also pointed out the One Health approach as a strategy to attempt the emergency and dispersion of carbapenem-resistance in this sector and to determine the role of carbapenem-producing bacteria in animals among human public health risk. A higher occurrence of carbapenem enzymes in poultry and swine has been previously reported. Studies related to poultry have highlighted P. mirabilis, E. coli, and K. pneumoniae as NDM-5- and NDM-1-producing bacteria, which lead to carbapenem resistance. OXA-181, IMP-27, and VIM-1 have also been detected in pigs. Carbapenem resistance is rare in cattle. However, OXA- and NDM-producing bacteria, mainly E. coli and A. baumannii, are cattle's leading causes of carbapenem resistance. A high prevalence of carbapenem enzymes has been reported in wildlife and companion animals, suggesting their role in the cross-species transmission of carbapenem-resistant genes. Antibiotic-resistant organisms in aquatic environments should be considered because they may act as reservoirs for carbapenem-resistant genes. It is urgent to implement the One Health approach worldwide to make an effort to contain the dissemination of carbapenem resistance.

Discriminant canonical tool for inferring the effect of αS1, αS2, ß, and κ casein haplotypes and haplogroups on zoometric/linear appraisal breeding values in Murciano-Granadina goats.

Genomic tools have shown promising results in maximizing breeding outcomes, but their impact has not yet been explored. This study aimed to outline the effect of the individual haplotypes of each component of the casein complex (αS1, ß, αS2, and κ-casein) on zoometric/linear appraisal breeding values. A discriminant canonical analysis was performed to study the relationship between the predicted breeding value for 17 zoometric/linear appraisal traits and the aforementioned casein gene haplotypic sequences. The analysis considered a total of 41,323 zoometric/linear appraisal records from 22,727 primiparous does, 17,111 multiparous does, and 1,485 bucks registered in the Murciano-Grandina goat breed herdbook. Results suggest that, although a lack of significant differences (p > 0.05) was reported across the predictive breeding values of zoometric/linear appraisal traits for αS1, αS2, and κ casein, significant differences were found for ß casein (p < 0.05). The presence of ß casein haplotypic sequences GAGACCCC, GGAACCCC, GGAACCTC, GGAATCTC, GGGACCCC, GGGATCTC, and GGGGCCCC, linked to differential combinations of increased quantities of higher quality milk in terms of its composition, may also be connected to increased zoometric/linear appraisal predicted breeding values. Selection must be performed carefully, given the fact that the consideration of apparently desirable animals that present the haplotypic sequence GGGATCCC in the ß casein gene, due to their positive predicted breeding values for certain zoometric/linear appraisal traits such as rear insertion height, bone quality, anterior insertion, udder depth, rear legs side view, and rear legs rear view, may lead to an indirect selection against the other zoometric/linear appraisal traits and in turn lead to an inefficient selection toward an optimal dairy morphological type in Murciano-Granadina goats. Contrastingly, the consideration of animals presenting the GGAACCCC haplotypic sequence involves also considering animals that increase the genetic potential for all zoometric/linear appraisal traits, thus making them recommendable as breeding animals. The relevance of this study relies on the fact that the information derived from these analyses will enhance the selection of breeding individuals, in which a desirable dairy type is indirectly sought, through the haplotypic sequences in the ß casein locus, which is not currently routinely considered in the Murciano-Granadina goat breeding program.

Inteligencia artificial en la colonoscopia de tamizaje y la disminución del error.

Artificial Intelligence (AI) has the potential to change many aspects of healthcare practice. Image discrimination and classification has many applications within medicine. Machine learning algorithms and complicated neural networks have been developed to train a computer to differentiate between normal and abnormal areas. Machine learning is a form of AI that allows the platform to improve without being programmed. Computer Assisted Diagnosis (CAD) is based on latency, which is the time between the captured image and when it is displayed on the screen. AI-assisted endoscopy can increase the detection rate by identifying missed lesions. An AI CAD system must be responsive, specific, with easy-to-use interfaces, and provide fast results without substantially prolonging procedures. AI has the potential to help both, trained and trainee endoscopists. Rather than being a substitute for high-quality technique, it should serve as a complement to good practice. AI has been evaluated in three clinical scenarios in colonic neoplasms: the detection of polyps, their characterization (adenomatous vs. non-adenomatous) and the prediction of invasive cancer within a polypoid lesion.

La inteligencia artificial (IA) tiene el potencial de cambiar muchos aspectos de la práctica sanitaria. La discriminación y la clasificación de imágenes tiene muchas aplicaciones dentro de la medicina. Se han desarrollado algoritmos de aprendizaje automático y redes neuronales complicadas para entrenar a una computadora a diferenciar las áreas normales de las anormales. El aprendizaje automático es una forma de IA que permite que la plataforma mejore sin ser programada. El diagnóstico asistido por computadora (CAD) se basa en latencia, que es el tiempo entre la imagen capturada y cuando es mostrada en la pantalla. La endoscopia asistida por IA puede incrementar la tasa de detección al identificar lesiones obviadas. Un sistema CAD de IA debe ser sensible, específico, con interfaces fáciles de usar, y proporcionar resultados rápidos sin prolongar sustancialmente los procedimientos. La IA tiene el potencial de ayudar tanto a endoscopistas entrenados como a los que están en entrenamiento. En vez de ser un sustituto para una técnica de alta calidad, deberá servir como un complemento de las buenas prácticas. La IA ha sido evaluada en tres escenarios clínicos en las neoplasias colónicas: la detección de pólipos, su caracterización (adenomatosos vs. no adenomatosos) y la predicción de cáncer invasor dentro de una lesión polipoide.

Real-world safety and effectiveness of cenobamate in patients with focal onset seizures: Outcomes from an Expanded Access Program.

OBJECTIVE: This study investigated early, real-world outcomes with cenobamate (CNB) in a large series of patients with highly drug-resistant epilepsy within a Spanish Expanded Access Program (EAP). METHOD: This was a multicenter, retrospective, observational study in 14 hospitals. Inclusion criteria were age ≥18 years, focal seizures, and EAP authorization. Data were sourced from patient clinical records. Primary effectiveness endpoints included reductions (100%, ≥90%, ≥75%, and ≥50%) or worsening in seizure frequency at 3-, 6-, and 12-month visits and at the last visit. Safety endpoints included rates of adverse events (AEs) and AEs leading to discontinuation. RESULTS: The study included 170 patients. At baseline, median epilepsy duration was 26 years and median number of seizures/month was 11.3. The median number of prior antiseizure medications (ASMs) and concomitant ASMs were 12 and 3, respectively. Mean CNB dosages/day were 176 mg, 200 mg, and 250 mg at 3, 6, and 12 months. Retention rates were 98.2%, 94.5%, and 87% at 3, 6, and 12 months. At last available visit, the rate of seizure freedom was 13.3%; ≥90%, ≥75%, and ≥50% responder rates were 27.9%, 45.5%, and 63%, respectively. There was a significant reduction in the number of seizures per month (mean: 44.6%; median: 66.7%) between baseline and the last visit (P < 0.001). Responses were maintained regardless of the number of prior or concomitant ASMs. The number of concomitant ASMs was reduced in 44.7% of patients. The cumulative percentage of patients with AEs and AEs leading to discontinuation were 68.2% and 3.5% at 3 months, 74.1% and 4.1% at 6 months, and 74.1% and 4.1% at 12 months. The most frequent AEs were somnolence and dizziness. SIGNIFICANCE: In this highly refractory population, CNB showed a high response regardless of prior and concomitant ASMs. AEs were frequent but mostly mild-to-moderate, and few led to discontinuation.

Myosin Light Chain Dephosphorylation by PPP1R12C Promotes Atrial Hypocontractility in Atrial Fibrillation.

Background: Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, increases thromboembolic stroke risk five-fold. Although atrial hypocontractility contributes to stroke risk in AF, the molecular mechanisms reducing myofilament contractile function remain unknown. We tested the hypothesis that increased expression of PPP1R12C, the PP1 regulatory subunit targeting atrial myosin light chain 2 (MLC2a), causes hypophosphorylation of MLC2a and results in atrial hypocontractility. Methods: Right atrial appendage tissues were isolated from human AF patients versus sinus rhythm (SR) controls. Western blots, co-immunoprecipitation, and phosphorylation studies were performed to examine how the PP1c-PPP1R12C interaction causes MLC2a de-phosphorylation. In vitro studies of pharmacologic MRCK inhibitor (BDP5290) in atrial HL-1 cells were performed to evaluate PP1 holoenzyme activity on MLC2a. Cardiac-specific lentiviral PPP1R12C overexpression was performed in mice to evaluate atrial remodeling with atrial cell shortening assays, echocardiography, and AF inducibility with EP studies. Results: In human patients with AF, PPP1R12C expression was increased two-fold versus SR controls ( P =2.0×10 -2 , n=12,12 in each group) with > 40% reduction in MLC2a phosphorylation ( P =1.4×10 -6 , n=12,12 in each group). PPP1R12C-PP1c binding and PPP1R12C-MLC2a binding were significantly increased in AF ( P =2.9×10 -2 and 6.7×10 -3 respectively, n=8,8 in each group). In vitro studies utilizing drug BDP5290, which inhibits T560-PPP1R12C phosphorylation, demonstrated increased PPP1R12C binding with both PP1c and MLC2a, and dephosphorylation of MLC2a. Lenti-12C mice demonstrated a 150% increase in LA size versus controls ( P =5.0×10 -6 , n=12,8,12), with reduced atrial strain and atrial ejection fraction. Pacing-induced AF in Lenti-12C mice was significantly higher than controls ( P =1.8×10 -2 and 4.1×10 -2 respectively, n= 6,6,5). Conclusions: AF patients exhibit increased levels of PPP1R12C protein compared to controls. PPP1R12C overexpression in mice increases PP1c targeting to MLC2a and causes MLC2a dephosphorylation, which reduces atrial contractility and increases AF inducibility. These findings suggest that PP1 regulation of sarcomere function at MLC2a is a key determinant of atrial contractility in AF.