Aortic dilation in adults with repaired tetralogy of Fallot: a single-centre study.

BACKGROUND: Tetralogy of Fallot is the most prevalent cyanotic CHD. With the advent of advanced surgical methods, the majority of tetralogy of Fallot patients reach adulthood. However, many need re-intervention for the residual anomalies including residual right ventricular outflow obstruction, pulmonary regurgitation, residual ventricular septal defects, and progressive aortic dilatation. Aortic dilation could lead to aortic regurgitation or dissection requiring surgical correction. In the current study, we aimed to determine the prevalence and outcomes of aortic root dilatation in adults with repaired tetralogy of Fallot in our tertiary care centre. METHODS: In this retrospective study, 730 consecutive patients with history of repaired tetralogy of Fallot were included. Aortic diameter at the level of annulus, the sinus of Valsalva, sinotubular junction, and the ascending aorta as measured by echocardiography were evaluated. Prevalence of outcomes necessitating re-intervention including aortic regurgitation and dissection were recorded. RESULTS: The mean size of annulus, sinus of Valsalva, sinotubular-junction, and ascending aorta in the latest available echocardiography of patients were 2.4+/-0.4 cm, 3.3+/-0.5 cm, 2.9+/-0.5cm, and 3.2+/-0.5cm, respectively. Prevalence of dilatation of sinus of Valsalva, dilation of Ascending aorta, sinotubular-junction, and aortic annulus was 28.7%, 21%, 8.3%, and 1 %, respectively. Five patients had severe aortic regurgitation (0.6%) and underwent surgical repair. One of these patients presented with acute aortic dissection. CONCLUSION: Aortic dilation is common in tetralogy of Fallot but prevalence of redo surgery for aortic dilation, regurgitation, and adverse events including acute dissection is low.

Can allostatic load in pregnancy explain the association between race and subsequent cardiovascular disease risk: A cohort study.

OBJECTIVE: To assess the relationship between allostatic load, a measure of cumulative chronic stress in early pregnancy and cardiovascular disease risk, 2-7 years postpartum, and pathways contributing to racial disparities in cardiovascular disease risk. DESIGN: Secondary analysis of a prospective cohort study. SETTING MULTICENTER POPULATION: Pregnant women. METHODS: Our primary exposure was high allostatic load in the first trimester, defined as at least 4 of 12 biomarkers (systolic blood pressure, diastolic blood pressure, body mass index, cholesterol, low-density lipoprotein, high-density lipoprotein, high-sensitivity C-reactive protein, triglycerides, insulin, glucose, creatinine and albumin) in the unfavourable quartile. Logistic regression was used to test the association between high allostatic load and main outcome adjusted for confounders: time from index pregnancy and follow up, age, education, smoking, gravidity, bleeding in the first trimester, index adverse pregnancy outcomes, and health insurance. Each main outcome component and allostatic load were analysed secondarily. Mediation and moderation analyses assessed the role of high allostatic load in racial disparities of cardiovascular disease risk. MAIN OUTCOME MEASURE: Incident cardiovascular disease risk: hypertension, or metabolic disorders. RESULTS: Cardiovascular disease risk was identified in 1462/4022 individuals (hypertension: 36.6%, metabolic disorder: 15.4%). After adjustment, allostatic load was associated with cardiovascular disease risk (adjusted odds ratio [aOR] 2.0, 95% CI 1.8-2.3), hypertension (aOR 2.1, 95% CI 1.8-2.4) and metabolic disorder (aOR 1.7, 95% CI 1.5-2.1). Allostatic load was a partial mediator between race and cardiovascular disease risk. Race did not significantly moderate this relationship. CONCLUSIONS: High allostatic load during pregnancy is associated with cardiovascular disease risk. The relationships between stress, subsequent cardiovascular risk and race warrant further study.

Physical therapy for facial nerve paralysis (Bell's palsy): An updated and extended systematic review of the evidence for facial exercise therapy.

OBJECTIVE: To conduct a systematic review of the effectiveness of facial exercise therapy for facial palsy patients, updating an earlier broader Cochrane review; and to provide evidence to inform the development of telerehabilitation for these patients. DATA SOURCES: MEDLINE, EMBASE, CINAHL, Cochrane Library, PEDro and AMED for relevant studies published between 01 January 2011 and 30 September 2020. METHODS: Predetermined inclusion/exclusion criteria were utilised to shortlist abstracts. Two reviewers independently appraised articles, systematically extracted data and assessed the quality of individual studies and reviews (using GRADE and AMSTAR-2, respectively). Thematic analysis used for evidence synthesis; no quantitative meta-analysis conducted. The review was registered with PROSPERO (CRD42017073067). RESULTS: Seven new randomised controlled trials, nine observational studies, and three quasi-experimental or pilot studies were identified (n = 854 participants). 75% utilised validated measures to record changes in facial function and/or patient-rated outcomes. High-quality trials (4/7) all reported positive impacts; as did observational studies rated as high/moderate quality (3/9). The benefit of therapy at different time points post-onset and for cases of varying clinical severity is discussed. Differences in study design prevented data pooling to strengthen estimates of therapy effects. Six new review articles identified were all rated critically low quality. CONCLUSION: The findings of this targeted review reinforce those of the earlier more general Cochrane review. New research studies strengthen previous conclusions about the benefits of facial exercise therapy early in recovery and add to evidence of the value in chronic cases. Further standardisation of study design/outcome measures and evaluation of cost-effectiveness are recommended.

A clinically friendly viscoelastic finite element analysis model of the mandible with Herbst appliance.

INTRODUCTION: As a powerful numerical approximation tool, finite element analysis (FEA) has been widely used to predict stress and strain distributions in facial bones generated by orthodontic appliances. Previous FEA models were constructed on the basis of a linear elastic phase of the bone response (eg, elastic bone strains to loading). However, what is more useful for clinical understanding would be predicting long-term strains and displacements of bone-segments responding to loading, yet tissue responses are (1) not promptly observable and (2) hard to predict in nature. METHODS: Viscoelastic property of the mandibular bone was incorporated into FEA models to visualize long-term, time-dependent stress and strain patterns in the mandible after being exposed to orthopedic stress. A mandible under loading by a Herbst appliance was modeled, and outcomes of the constructed elastic and viscoelastic models were compared. RESULTS: Patterns and magnitudes of the displacement throughout the mandible predicted by the viscoelastic model were exhibited in accordance with previous clinical outcomes of Herbst appliance therapy. The elastic models exhibited similar displacement patterns; however, the magnitude of the displacements in the models was invariably small (approximately 1 per 100) compared with those outputs of corresponding viscoelastic models. The corresponding maximum stress level in our viscoelastic mandible subjected to the Herbst appliance with the same loading was considerably low and relaxed in various regions when compared with the elastic model. CONCLUSIONS: We suggest that a viscoelastic model of the mandible mimics our general prediction of orthopedic treatment outcomes better than those by elastic models.

Pectin Chemistry and Cellulose Crystallinity Govern Pavement Cell Morphogenesis in a Multi-Step Mechanism.

Simple plant cell morphologies, such as cylindrical shoot cells, are determined by the extensibility pattern of the primary cell wall, which is thought to be largely dominated by cellulose microfibrils, but the mechanism leading to more complex shapes, such as the interdigitated patterns in the epidermis of many eudicotyledon leaves, is much less well understood. Details about the manner in which cell wall polymers at the periclinal wall regulate the morphogenetic process in epidermal pavement cells and mechanistic information about the initial steps leading to the characteristic undulations in the cell borders are elusive. Here, we used genetics and recently developed cell mechanical and imaging methods to study the impact of the spatio-temporal dynamics of cellulose and homogalacturonan pectin distribution during lobe formation in the epidermal pavement cells of Arabidopsis (Arabidopsis thaliana) cotyledons. We show that nonuniform distribution of cellulose microfibrils and demethylated pectin coincides with spatial differences in cell wall stiffness but may intervene at different developmental stages. We also show that lobe period can be reduced when demethyl-esterification of pectins increases under conditions of reduced cellulose crystallinity. Our data suggest that lobe initiation involves a modulation of cell wall stiffness through local enrichment in demethylated pectin, whereas subsequent increase in lobe amplitude is mediated by the stress-induced deposition of aligned cellulose microfibrils. Our results reveal a key role of noncellulosic polymers in the biomechanical regulation of cell morphogenesis.

Methods to quantify primary plant cell wall mechanics.

The primary plant cell wall is a dynamically regulated composite material of multiple biopolymers that forms a scaffold enclosing the plant cells. The mechanochemical make-up of this polymer network regulates growth, morphogenesis, and stability at the cell and tissue scales. To understand the dynamics of cell wall mechanics, and how it correlates with cellular activities, several experimental frameworks have been deployed in recent years to quantify the mechanical properties of plant cells and tissues. Here we critically review the application of biomechanical tool sets pertinent to plant cell mechanics and outline some of their findings, relevance, and limitations. We also discuss methods that are less explored but hold great potential for the field, including multiscale in silico mechanical modeling that will enable a unified understanding of the mechanical behavior across the scales. Our overview reveals significant differences between the results of different mechanical testing techniques on plant material. Specifically, indentation techniques seem to consistently report lower values compared with tensile tests. Such differences may in part be due to inherent differences among the technical approaches and consequently the wall properties that they measure, and partly due to differences between experimental conditions.

Relating the mechanics of the primary plant cell wall to morphogenesis.

Regulation of the mechanical properties of the cell wall is a key parameter used by plants to control the growth behavior of individual cells and tissues. Modulation of the mechanical properties occurs through the control of the biochemical composition and the degree and nature of interlinking between cell wall polysaccharides. Preferentially oriented cellulose microfibrils restrict cellular expansive growth, but recent evidence suggests that this may not be the trigger for anisotropic growth. Instead, non-uniform softening through the modulation of pectin chemistry may be an initial step that precedes stress-induced stiffening of the wall through cellulose. Here we briefly review the major cell wall polysaccharides and their implication for plant cell wall mechanics that need to be considered in order to study the growth behavior of the primary plant cell wall.

Development and validation of a spontaneous preterm delivery predictor in asymptomatic women.

BACKGROUND: Preterm delivery remains the leading cause of perinatal mortality. Risk factors and biomarkers have traditionally failed to identify the majority of preterm deliveries. OBJECTIVE: To develop and validate a mass spectrometry-based serum test to predict spontaneous preterm delivery in asymptomatic pregnant women. STUDY DESIGN: A total of 5501 pregnant women were enrolled between 17(0/7) and 28(6/7) weeks gestational age in the prospective Proteomic Assessment of Preterm Risk study at 11 sites in the United States between 2011 and 2013. Maternal blood was collected at enrollment and outcomes collected following delivery. Maternal serum was processed by a proteomic workflow, and proteins were quantified by multiple reaction monitoring mass spectrometry. The discovery and verification process identified 2 serum proteins, insulin-like growth factor-binding protein 4 (IBP4) and sex hormone-binding globulin (SHBG), as predictors of spontaneous preterm delivery. We evaluated a predictor using the log ratio of the measures of IBP4 and SHBG (IBP4/SHBG) in a clinical validation study to classify spontaneous preterm delivery cases (<37(0/7) weeks gestational age) in a nested case-control cohort different from subjects used in discovery and verification. Strict blinding and independent statistical analyses were employed. RESULTS: The predictor had an area under the receiver operating characteristic curve value of 0.75 and sensitivity and specificity of 0.75 and 0.74, respectively. The IBP4/SHBG predictor at this sensitivity and specificity had an odds ratio of 5.04 for spontaneous preterm delivery. Accuracy of the IBP4/SHBG predictor increased using earlier case-vs-control gestational age cutoffs (eg, <35(0/7) vs ≥35(0/7) weeks gestational age). Importantly, higher-risk subjects defined by the IBP4/SHBG predictor score generally gave birth earlier than lower-risk subjects. CONCLUSION: A serum-based molecular predictor identifies asymptomatic pregnant women at risk of spontaneous preterm delivery, which may provide utility in identifying women at risk at an early stage of pregnancy to allow for clinical intervention. This early detection would guide enhanced levels of care and accelerate development of clinical strategies to prevent preterm delivery.

Children post liver transplantation hospitalized with fever are at a high risk for bacterial infections.

BACKGROUND: Although infections post liver transplantation are a main cause of morbidity and mortality, data are limited on transplanted children. The objective of this study was to investigate the incidence, etiology, and predictors of infection in pediatric liver transplant recipients (LTR) in the specific practical clinical setting of hospitalization for fever in order to elucidate the appropriate management of these patients. METHODS: Clinical and laboratory data were retrospectively collected for all febrile pediatric LTR hospitalized from 2004 to 2012. RESULTS: We analyzed 133 hospital admissions for fever among 44 pediatric LTR. Of these, 73 bacterial (54.8%) and 46 viral infections (34.5%) were diagnosed. No cases of protozoa or fungal infections were reported. Bacterial infections were most frequent during the first year post transplantation with ascending cholangitis being the most prevalent. Twenty-six (36%) bacterial infections were microbiologically documented and 47 (64%) were clinically documented. Of the microbiologically confirmed cases, gram-negative bacteria, namely Enterobacteriaceae, were most common (57.7%). Seven cases of bacteremia were observed including 1 case presenting with severe sepsis. Compared with the white blood cell count and absolute neutrophil count, C-reactive protein level was found to be a more sensitive biomarker for bacterial disease. Older age on admission was a significant risk factor for bacterial infection. CONCLUSION: Febrile hospitalized pediatric LTR are immunocompromised hosts at high risk for bacterial infections, and usually warrant prompt evaluation and empirical antibiotic treatment upon admission.

Hepatic involvement in congenital cytomegalovirus infection - infrequent yet significant.

Congenital cytomegalovirus (cCMV) infection can reside in many organ systems; however, the virus has a particular predilection towards inhabiting the reticuloendothelial system, especially the liver. Specific studies focusing only on hepatic involvement in infants with cCMV are lacking. We report our experience with a large cohort of infants treated in our hospital clinic due to cCMV and hepatic involvement. Hepatic involvement was defined either as hepatitis (elevated alanine transaminases (ALT) >80 units/L without cholestatic disease) or cholestatic disease (elevated ALT >80 units/L combined with direct bilirubin >2 mg/dL). During the study period, 198 infants were diagnosed with symptomatic cCMV in our clinic. Hepatic involvement was observed in 13 infants (6.6%); 7 (3.5%) with hepatitis and 6 (3%) with cholestatic disease. Maternal primary infection with cytomegalovirus during pregnancy was diagnosed in 7 (53.8%) of the 13 infants, nonprimary in 3 (23.1%) and unknown in 3 (23.1%). Among these 13 infants, central nervous system (CNS) involvement was observed in 11 (84.6%) and hearing impairment in 7 (53.8%). Treatment with an antiviral agent was initiated in all cases. Gradual improvement of hepatic enzymes and cholestasis was observed over a prolonged period. We found that the incidence of hepatic involvement in infants with cCMV is much less frequent than previously reported. The hepatic involvement in these infants may manifest in two different ways, and thus, a high index of suspicion and a stepwise approach will help in correctly diagnosing these infants. Antiviral treatment due to CNS involvement is warranted and prognosis is excellent.

Vanadium(V) removal from aqueous solution and real wastewater using quaternized pine sawdust.

Cross-linked and quaternized pine sawdust was tested for vanadium removal from a synthetic aqueous solution as well as from real industrial wastewater which had a considerable amount of vanadium and other ions such as sulphate, ammonium and nickel. The maximum vanadium sorption capacity of the modified pine sawdust was found to be 130 mg/g in synthetic solution and 103 mg/g in real wastewater. Modified pine sawdust worked well over a wide range of pH. Column studies with real wastewater proved that vanadium was efficiently desorbed from the material with 2 M NaOH and that the material could be reused.

Combined transaortic/transapical left ventricular septal myectomy for subaortic and midventricular obstruction in a paediatric patient.

The patient is a 15-year-old girl who was diagnosed with hypertrophic cardiomyopathy and has been symptomatic due to severe left ventricular outflow tract obstruction. Combined transaortic and transapical left ventricular septal myectomy was performed to relieve the left ventricular outflow tract obstruction and address both subaortic and midventricular gradients.

Allostatic load in early pregnancy and sleep-disordered breathing.

OBJECTIVES: To assess the association between allostatic load in early pregnancy and sleep-disordered breathing (SDB) during pregnancy. METHODS: High allostatic load in the first trimester was defined as ≥ 4 of 12 biomarkers (systolic blood pressure, diastolic blood pressure, body mass index, cholesterol, low-density lipoprotein, high-density lipoprotein, high sensitivity C-reactive protein, triglycerides, insulin, glucose, creatinine, and albumin) in the unfavorable quartile. SDB was objectively measured using the Embletta-Gold device and operationalized as "SDB ever" in early (6-15 weeks) or mid-pregnancy (22-31 weeks); SDB at each time point was analyzed as secondary outcomes. Multivariable logistic regression was used to test the association between high allostatic load and SDB, adjusted for confounders. Moderation and sensitivity analyses were conducted to assess the role of allostatic load in racial disparities of SDB and obesity affected the relationship between allostatic load and SDB. RESULTS: High allostatic load was present in 35.0% of the nuMoM2b cohort. The prevalence of SDB ever occurred among 8.3% during pregnancy. After adjustment, allostatic load remained significantly associated with SDB ever (aOR= 5.3; 3.6-7.9), in early-pregnancy (aOR= 7.0; 3.8-12.8), and in mid-pregnancy (aOR= 5.8; 3.7-9.1). The association between allostatic load and SDB was not significantly different for people with and without obesity. After excluding BMI from the allostatic load score, the association decreased in magnitude (aOR= 2.6; 1.8-3.9). CONCLUSION: The association between allostatic load and SDB was independent of confounders including BMI. The complex and likely bidirectional relationship between chronic stress and SDB deserves further study in reducing SDB.

Plant blindness and diversity in AI language models.

Large language models (LLMs) will benefit science by accelerating task performance. We explored whether answers generated by ChatGPT (generative pretrained transformer) to questions of biology are sufficiently diverse. 'Plant awareness' in ChatGPT answers was found to be highly variable, illustrating the importance of scientists being involved in validating the data and methods used to train artificial intelligence (AI) models.

3D Visualization of Microtubules in Epidermal Pavement Cells.

The plant cytoskeleton is instrumental in cellular processes such as cell growth, differentiation, and immune response. Microtubules, in particular, play a crucial role in morphogenesis by governing the deposition of plant cell wall polysaccharides and, in consequence, the cell wall mechanics and cell shape. Scrutinizing the microtubule dynamics is therefore integral to understanding the spatiotemporal regulation of cellular activities. In this chapter, we outline steps to acquire 3D images of microtubules in epidermal pavement cells of Arabidopsis thaliana cotyledons using a confocal microscope. We introduce the steps to assess the microtubule distribution and organization using image processing software Bitplane Imaris and ImageJ. We also demonstrate how the interpretation of image material can be facilitated by post-processing with general-purpose image enhancement software using methods trained by artificial intelligence-based algorithms.

Cell geometry regulates tissue fracture.

In vascular plants, the epidermal surfaces of leaves and flower petals often display cells with wavy geometries forming intricate jigsaw puzzle patterns. The prevalence and diversity of these complex epidermal patterns, originating from simple polyhedral progenitor cells, suggest adaptive significance. However, despite multiple efforts to explain the evolutionary drivers behind these geometrical features, compelling validation remains elusive. Employing a multidisciplinary approach that integrates microscopic and macroscopic fracture experiments with computational fracture mechanics, we demonstrate that wavy epidermal cells toughen the plants' protective skin. Through a multi-scale framework, we demonstrate that this energy-efficient patterning mechanism is universally applicable for toughening biological and synthetic materials. Our findings reveal a tunable structural-mechanical strategy employed in the microscale design of plants to protect them from deleterious surface fissures while facilitating and strategically directing beneficial ones. These findings hold implications for targeted plant breeding aimed at enhancing resilience in fluctuating environmental conditions. From an engineering perspective, our work highlights the sophisticated design principles the plant kingdom offers to inspire metamaterials.

Abscisic acid regulates inflammation via ligand-binding domain-independent activation of peroxisome proliferator-activated receptor gamma.

Abscisic acid (ABA) has shown efficacy in the treatment of diabetes and inflammation; however, its molecular targets and the mechanisms of action underlying its immunomodulatory effects remain unclear. This study investigates the role of peroxisome proliferator-activated receptor γ (PPAR γ) and lanthionine synthetase C-like 2 (LANCL2) as molecular targets for ABA. We demonstrate that ABA increases PPAR γ reporter activity in RAW 264.7 macrophages and increases ppar γ expression in vivo, although it does not bind to the ligand-binding domain of PPAR γ. LANCL2 knockdown studies provide evidence that ABA-mediated activation of macrophage PPAR γ is dependent on lancl2 expression. Consistent with the association of LANCL2 with G proteins, we provide evidence that ABA increases cAMP accumulation in immune cells. ABA suppresses LPS-induced prostaglandin E(2) and MCP-1 production via a PPAR γ-dependent mechanism possibly involving activation of PPAR γ and suppression of NF-κB and nuclear factor of activated T cells. LPS challenge studies in PPAR γ-expressing and immune cell-specific PPAR γ null mice demonstrate that ABA down-regulates toll-like receptor 4 expression in macrophages and T cells in vivo through a PPAR γ-dependent mechanism. Global transcriptomic profiling and confirmatory quantitative RT-PCR suggest novel candidate targets and demonstrate that ABA treatment mitigates the effect of LPS on the expression of genes involved in inflammation, metabolism, and cell signaling, in part, through PPAR γ. In conclusion, ABA decreases LPS-mediated inflammation and regulates innate immune responses through a bifurcating pathway involving LANCL2 and an alternative, ligand-binding domain-independent mechanism of PPAR γ activation.

Characteristics of non-typhi Salmonella gastroenteritis associated with bacteremia in infants and young children.

PURPOSE: To characterize the clinical and laboratory manifestations of non-typhi Salmonella gastroenteritis associated with bacteremia in children less than 36 months old. METHODS: The study group included 17 patients, aged 2-34 months, with non-typhi Salmonella gastroenteritis and bacteremia, hospitalized in a tertiary pediatric medical center during the period 1995-2010. Clinical data were collected by medical chart review. Culture-related data were taken from the microbiology laboratory files. The results were compared with an assigned, age-matched, control group of 17 infants hospitalized with non-typhi Salmonella gastroenteritis without bacteremia. RESULTS: Eleven cases (65%) occurred during the summer season. All patients presented with diarrhea, usually mixed with blood or mucus (clinical dysentery 65%). All but one had a high-grade fever (average 39.5°C). Three patients (19%) experienced convulsions during the acute episode of gastroenteritis. None of the patients had been previously treated with antibiotics. The most prevalent Salmonella serotype identified in the stool and blood was group C. Toxic appearance and convulsions on admission were more common among children with non-typhi Salmonella bacteremia, as opposed to those with non-typhi Salmonella gastroenteritis alone. No other epidemiological or laboratory differences were found. CONCLUSIONS: Non-typhi Salmonella gastroenteritis poses a risk of bacteremia not only in infants younger than 3 months of age, but also in children younger than 36 months of age.

Uplink OFDM detection with random multiple access.

Orthogonal Frequency-Division Multiplexing with Random multiple access (OFDRMA) is discussed for uplink communications, whereby several active users send information towards a single base-station (BS), while all other users are dormant. Originally, uplink communication methods included sharing the frequency resources among the active users in an orthogonal fashion, i.e., a central unit is required to dynamically allocate the resources. More recently, non-orthogonal methods have arisen, meaning that several active users share the same frequency bins, but they still do require a central unit to dynamically allocate the resources in a uniform (as possible) manner over the available bandwidth. The task and overhead required for managing the frequency allocations among the users can be quite cumbersome. In OFDRMA, the frequency allocations for any user are independent of the frequency allocations for the other users, and independent of which of the other users are currently active. Rather, OFDRMA relies on random, yet predetermined, allocation of frequency bins for each user, known only to that user and the BS. A multi-user detection approach is presented based on a graphical representation of the system. It is shown to provide robustness against the forced randomness of the scheme. Capacity of OFDRMA and its optimization are analyzed and provided in detail. Simulation results are provided for demonstrating the performance attainable with OFDRMA and the proposed detection scheme. Both the capacity and the simulations are compared with modern multi-user multiple-input multiple-output (MU-MIMO) schemes.