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diet rat model, our present study reveals inflammation as the link between a HF diet and dysregulated iron metabolism. Importantly, both inflammation and disrupted iron metabolism have been shown to be pathogenic factors in nonalcoholic fatty liver disease (NAFLD). The iron regulatory hormone, HEPC, is a link between the liver, inflammation, and iron metabolism. As fructose-rich foods become increasingly abundant and people's fructose intake increases, the impact of high fructose on health requires increased attention. Little research has been conducted on the effects of fructose on iron metabolism. Our study provides useful insights into the prevention and treatment of iron metabolism disorders arising from metabolic syndrome.The interaction of nanoparticles (NPs) with proteins and the formation of protein corona in the biological fluids are of great interest and significance for drug delivery. In the past decade, the corona formation in the blood and its impacts on the in vitro and in vivo fate of NPs has been well investigated and reviewed. Recently, more and more attention is paid to the nano-protein interactions taking place in the gastrointestinal tract (GIT) between the orally administered NPs and the digestive enzymes. The enzyme corona formed in the GIT can significantly affect the properties, gastrointestinal transit, and oral absorption of NPs. Since oral delivery is the most preferred delivery route, comprehensively understanding the corona formation in the GIT and its impacts on oral delivery NPs are of great importance. Herein, we aim to summarize the recent updates on the nano-protein interactions between NPs and digestive enzymes, and launch an interesting discussion on the potentials of using the digestive enzyme corona for the colon targeted delivery.Pathogens secrete effector proteins into host cells to suppress host immunity and promote pathogen virulence, although many features at the molecular interface of host-pathogen interactions remain to be characterized. In a yeast two-hybrid assay, we found that the Pseudomonas syringae effector HopZ1a interacts with the Arabidopsis transcriptional regulator Abscisic Acid Repressor 1 (ABR1). Further analysis revealed that ABR1 interacts with multiple P. syringae effectors, suggesting that it may be targeted as a susceptibility hub. Indeed, loss-of-function abr1 mutants exhibit reduced susceptibility to a number of P. syringae strains. The ABR1 protein comprises a conserved APETALA2 (AP2) domain flanked by long regions of predicted structural disorder. We verified the DNA-binding activity of the AP2 domain and demonstrated that the disordered domains act redundantly to enhance DNA binding and to facilitate transcriptional activation by ABR1. Finally, we compared gene expression profiles from wild-type and abr1 plants following inoculation with P. syringae, which suggested that the reduced susceptibility of abr1 mutants is due to the loss of a virulence target rather than an enhanced immune response. These data highlight ABR1 as a functionally important component at the host-pathogen interface.
HBV can evolve under selection pressure exerted by drugs and/or host immunity, resulting in accumulation of escape mutations that can affect the drug or the immune activity. Hepatitis delta virus (HDV) coinfection is also known to exert selection pressure on HBV, which leads to selective amplification of certain mutations, especially in genes that are required for HDV pathogenesis, such as HBsAg. However, little is known about the function of these mutations on HBV or HDV life cycle. The purpose of this study is to determine mutations selectively amplified in the backdrop of HDV, and how these mutations affect processing of CD4- and CD8-T cell epitopes.
HBsAg was successfully amplified from 49/50 HBV mono- and 36/50 coinfected samples. The sequences were used to identify mutations specific to each study group, followed by an in silico analysis to determine the effect of these mutations on (1) proteasomal degradation, (2) MHC-I and MHC-II biding, and (3) processing of T-cell epitopes.
HBV-HDV coinfected sequences exhibited certain unique mutations in HBsAg genes. Some of these mutations affected the generation of proteasomal sites, binding of HBsAg epitopes to MHC-I and -II ligands, and subsequent generation of T- cell epitopes.
These observations suggest that HBV selectively amplifies certain mutations in the backdrop of HDV coinfection. Selective amplification of these mutations at certain strategic locations might not only enable HBV to counteract the inhibitory effects of HDV on HBV replication but also facilitate its survival by escaping the immune response.
These observations suggest that HBV selectively amplifies certain mutations in the backdrop of HDV coinfection. Selective amplification of these mutations at certain strategic locations might not only enable HBV to counteract the inhibitory effects of HDV on HBV replication but also facilitate its survival by escaping the immune response.To develop and validate a nomogram using on admission data to predict in-hospital survival probabilities of coronavirus disease 2019 (COVID-19) patients. We analyzed 855 COVID-19 patients with 52 variables. The least absolute shrinkage and selection operator regression and multivariate Cox analyses were used to screen significant factors associated with in-hospital mortality. A nomogram was established based on the variables identified by Cox regression. The performance of the model was evaluated by C-index and calibration plots. Decision curve analysis was conducted to determine the clinical utility of the nomogram. Six variables, including neutrophil (hazard ratio [HR], 1.088; 95% confidence interval [CI], [1.0004-1.147]; p less then .001), C-reactive protein (HR, 1.007; 95% CI, [1.0026-1.011]; p = .002), IL-6 (HR, 1.001; 95% CI, [1.0003-1.002]; p = .005), d-dimer (HR, 1.034; 95% CI, [1.0111-1.057]; p = .003), prothrombin time (HR 1.086, 95% CI [1.0369-1.139], p less then .001), and myoglobin (HR, 1.001; 95% CI, [1.0007-1.002]; p less then .001), were identified and applied to develop a nomogram. The nomogram predicted 14-day and 28-day survival probabilities with reasonable accuracy, as assessed by the C-index (0.912) and calibration plots. Decision curve analysis showed relatively wide ranges of threshold probability, suggesting a high clinical value of the nomogram. Neutrophil, C-reactive protein, IL-6, d-dimer, prothrombin time, and myoglobin levels were significantly correlated with in-hospital mortality of COVID-19 patients. Demonstrating satisfactory discrimination and calibration, this model could predict patient outcomes as early as on admission and might serve as a useful triage tool for clinical decision making.
Continuity of midwifery carer improves outcomes, but there is significant variation in how such schemes are implemented and evaluated cross-culturally. The Angus home birth scheme in Scotland incorporates continuity of carer throughout pregnancy, labor, birth, and the postnatal period.
Manual maternity case note review to evaluate the 80% continuity of carer and 3% planned home birth rate targets.
Of 1466 women booking for maternity care, 69 joined the scheme. Forty-four had a planned home birth (3% overall), of whom seven were originally deemed ineligible. Of the 44, eight (18%) also achieved 80% continuity of carer with the primary midwife; by including a home birth team colleague, the continuity rate rose to 73%. Women whose care achieved home birth and continuity targets had lower deprivation scores. Eligibility issues, women's changing circumstances, and data recording lapses were complicating issues.
Targets must be both feasible and meaningful and should be complemented by assessing a broad ranource and political support, and when considered in the round, the scheme's viability within local services was confirmed. Other generalizable learning points included the need to standardize definitions and data recording methods. Comparability across schemes helps grow the evidence base so that the links between processes and outcomes can be identified.An efficient approach to the type III lepadin alkaloids (lepadins F and G) has been developed through a key Diels-Alder reaction, in which a novel ketolactone-type dienophile with chiral diol unit is employed to generate the desirable all-cis-trisubstituted cyclohexene with excellent regio- and stereoselectivity control. The subsequent selective sulfonylation of the diol unit followed by SN 2 cyclization under hydrogenation conditions could construct the substituted piperidine ring. By using this approach, (-)-lepadin F is synthesized from ethyl l-lactate for the first time.Plant reproduction is one key biological process that is very sensitive to heat stress and, as a result, enhanced global warming becomes a serious threat to agriculture. In this work, we have studied the effects of heat on germinated pollen of Arabidopsis thaliana both at the transcriptional and translational level. We have used a high-resolution ribosome profiling technology to provide a comprehensive study of the transcriptome and the translatome of germinated pollen at permissive and restrictive temperatures. We have found significant down-regulation of key membrane transporters required for pollen tube growth by heat, thus uncovering heat-sensitive targets. A subset of the heat-repressed transporters showed coordinated up-regulation with canonical heat-shock genes at permissive conditions. We also found specific regulations at the translational level and we have uncovered the presence of ribosomes on sequences annotated as non-coding. Our results demonstrate that heat impacts mostly on membrane transporters thus explaining the deleterious effects of heat stress on pollen growth. The specific regulations at the translational level and the presence of ribosomes on non-coding RNAs highlights novel regulatory aspects on plant fertilization.Previous research has shown gender-related psychobiological differences in risky and competitive strategies that affect win and loss outcomes. In addition, some studies have found differences in the decision-making process, with women taking longer to reach the same performance as men. However, the underlying neural mechanisms remain unclear. The present study aimed to investigate gender differences in behavioral performance and neural correlates during a decision-making task, the Iowa Gambling Task (IGT). Forty healthy young adults (23 men and 17 women) performed the IGT while the feedback-related negativity (FRN) and P3 were recorded as neural correlates of feedback processing. No gender differences were observed in the behavioral performance on the IGT after 100 and 150 trials, or in the P3 component. In women, but not in men, the FRN component showed a greater amplitude for losses than for wins. There were no significant gender-related differences in behavioral performance, and men and women revealed a similar learning process on the IGT. At the neural level, no direct differences between men and women were observed in the feedback processing stage for the FRN or P3. However, our results indicate that women showed greater sensitivity to losses than to wins during the decision-making task, as reflected in the FRN component.The current study evaluated the effectiveness of a go/no-go successive matching-to-sample procedure (S-MTS) to establish auditory-visual equivalence classes with college students. A sample and a comparison were presented, one at a time, in the same location. During training, after an auditory stimulus was presented, a green box appeared in the center of the screen for participants to touch to produce the comparison. Touching the visual comparison that was related to the auditory sample (e.g., A1B1) produced points, while touching or refraining from touching an unrelated comparison (e.g., A1B2) produced no consequences. Following AB/AC training, participants were tested on untrained relations (i.e., BA/CA and BC/CB), as well as tacting and sorting. During BA/CA relations tests, after touching the visual sample, the auditory stimulus was presented along with a white box for participants to respond. During BC/CB relations tests, after touching the visual sample, a visual comparison appeared. Across 2 experiments, all participants met emergence criterion for untrained relations and for sorting. Additionally, 14 out of 24 participants tacted all visual stimuli correctly. Results suggest the auditory-visual S-MTS procedure is an effective alternative to simultaneous MTS for establishing conditional relations and auditory-visual equivalence classes.In 1969, a few short months after the Warsaw Pact invasion of Czechoslovakia, Sergei I. Prasolov, advisor to the Soviet Ambassador in Prague, informed František Šorm, President of the Czechoslovak Academy of Sciences, at a formal meeting that he welcomed Šorm's suggestion to intensify scientific exchange between Czechoslovakia and the Soviet Union. Šorm politely declined this offer. Behind the veneer of diplomatic courtesy on the part of both actors, a real drama was taking place. Šorm and the Czechoslovak Academy of Sciences had actually never formulated such a request. To the contrary, since the late 1950s the academy had repeatedly pointed out that the Soviets were incapable of coordinating scientific activities in the Eastern Bloc. The Soviet system of academic cooperation within the Eastern Bloc had already begun to collapse after the Geneva Summit of 1955, where the Soviets opened the door to international collaboration across the Iron Curtain. Yet it was only in the late 1960s that the Soviets realized that while they dominated large-scale international collaboration, they had lost control of internal developments within the Eastern Bloc.D-limonene or 4-isopropenyl-1-methylcyclohexene (C10 H16 ) is a monocyclic monoterpene abundant in citrus plants like lemon, orange, and grape. The application of D-limonene in the form of flavor and fragrance additive in perfumes, soaps, foods, and beverages is consistently increased due to its high-quality fragrance property. This review is intended to analyze and delineate every possible available evidence and details about D-limonene with the special focus on its therapeutic efficacy. Many studies have reported that D-limonene effectively plays a valuable role in the prevention of several chronic and degenerative diseases. This review provides worthy information about the beneficial effects of D-limonene such as antioxidant, antidiabetic, anticancer, anti-inflammatory, cardioprotective, gastroprotective, hepatoprotective, immune modulatory, anti-fibrotic, anti-genotoxic etc. This could in turn help in the application of D-limonene for clinical studies. PRACTICAL IMPLICATIONS Various plant families contain Terpenes as their secondary metabolites. Monoterpenes constitute an important part of these secondary metabolites. D-limonene is a well-identified monoterpene that is commonly applied as a fragrance ingredient in essential oils. D-limonene is known to possess remarkable biological activities. It can be effectively used for treating various ailments and diseases. Due to its diverse functions, it can be efficiently utilized for human health.
To assess the characteristics of adipose-derived regenerative cells, and provide supportive data explaining the mechanism of efficacy observed for the use of these cells in the treatment of stress urinary incontinence.
Adipose tissues were harvested by abdominal liposuction from healthy donors and patients with stress urinary incontinence. Adipose-derived regenerative cells were isolated from tissues using the Celution system, and assessed for their characteristics and ability to differentiate into smooth muscle cells.
Adipose-derived regenerative cells isolated by the Celution system developed into fibroblastic colonies. Flow cytometric analysis of adipose-derived stem cell markers showed that adipose-derived regenerative cells were positive for CD34 and CD44, and negative for CD31. Immunofluorescence staining after differentiation showed that colony-forming cells were positive for alpha-smooth muscle actin, calponin and desmin, which are smooth muscle cell markers. A cytokine release assay showed that adherent cells secreted cytokines associated with angiogenesis, including vascular endothelial growth factor-A, angiopoietin-2 and placental growth factor.
Adipose-derived regenerative cells collected by the Celution system might have clonogenic capacity and an angiogenetic function. These properties might contribute to the mechanisms through which regenerative cell therapy by periurethral injection of autologous adipose-derived regenerative cells ameliorates stress urinary incontinence.
Adipose-derived regenerative cells collected by the Celution system might have clonogenic capacity and an angiogenetic function. These properties might contribute to the mechanisms through which regenerative cell therapy by periurethral injection of autologous adipose-derived regenerative cells ameliorates stress urinary incontinence.Human activities have caused toxic metal pollution and ecological risks to agricultural soil. In this study, 291 topsoil samples, collected in the agricultural soil system of Yuzhong, China, were selected to study the toxic metals and metalloids contamination characteristics, source and ecological risk based on geostatistics, pollution index, and ecological risk index. The main distribution of As is adjacent to pasture land and mainly comes from animal husbandry; Pb was observed near a coal mining factory and the Yellow River and was derived from industry and transportation; Cd was similar to Pb and was mainly derived from industry, transportation, and agriculture; Cr was found near a cement plant and was derived from industry and transportation; and Hg was found near an urban area and was mainly from industry and domestic garbage. The ratio of these elements exceeding the soil background value reached 99.9%. Except for the excess amounts of Cd and Hg in some samples, Cr, Hg, and As were mostly below permissible limits. Moreover, the comprehensive potential ecological risk of toxic metals is mainly at medium level and below, whereas the risks of Cd and Hg are higher. Control of Cd and Hg is important to prevent soil pollution. This study explains the current contamination situation, the predominant contaminants and their sources, and provides emphasis and direction for agricultural soil remediation.
Carbon dots (C-dots) with antimicrobial activity were synthesized from the white mulberry extract in order to fabricate anti-listeria nanopaper using bacterial nanocellulose (BNC). A highly dispersed synthesized C-dots with a size smaller than 10 nm (~4.9 nm) was impregnated into BNC by an ex-situ coating method and mechanical, morphological, UV-protectant, and antibacterial activity were assessed. Randomized response surface (RSM) methodology using central composite design was applied to investigate the optimized concentration of C-dots in the BNC membrane.
An optimized nanopaper with C-dots at 530 g L
concentration and impregnation time of 14 hr at 30 °C with significant antimicrobial activity on Listeria monocytogenes was designed. The addition of C-dots into BNC significantly increased ultimate tensile strength and decreased strain to break of BNC. A BNC sheet with high-efficient UV-blocking property was prepared by C-dots.
Based on the results, the designed nanopaper has an important capability for fabrication of antimicrobial/ UV-blocking sheets for food active packaging. This article is protected by copyright. All rights reserved.
Based on the results, the designed nanopaper has an important capability for fabrication of antimicrobial/ UV-blocking sheets for food active packaging. This article is protected by copyright. All rights reserved.
This retrospective study aims to determine whether the maxilla-mandible-nasion (MMN) angle can be reliably measured in the first trimester, to describe normal ranges, and to determine if significant changes occur in foetuses with aneuploidies.
The MMN angle was measured in stored 2D-ultrasound images of 200 normal fetal profiles between 11
and 13
weeks of gestation. Each image was analyzed by two observers at two independent time points. Bland-Altmann analysis was performed to evaluate the reliability of the measurements. Additionally, the MMN angle was measured on sonograms from 140 aneuploid foetuses.
The mean MMN angle in normal foetuses from 11 to 14 weeks of gestation was 15.4°. Reliability of the measurement was high when repeatedly measured by the same observer (ICC = 0.92 and 0.82) and between two observers (ICC = 0.77 and 0.63). Average MMN values in foetuses with trisomy 21, 13, and Turner syndrome were significantly higher than those measured in normal foetuses. The highest differences were observed in foetuses with trisomy 13. Among those, 62% had an MMN angle above the 95th percentile and 92% above the normal mean.
The MMN angle can be reliably measured in early pregnancy and is abnormal in about 60% of foetuses with trisomy 13.
The MMN angle can be reliably measured in early pregnancy and is abnormal in about 60% of foetuses with trisomy 13.Extracellular α-amylase and protease were coproduced from halotolerant Virgibacillus dokdonensis VITP14 with banana peels (2% w/v) as substrate. The pH optima for α-amylase and protease were 6.5 and 7.0 respectively. The temperature optima of α-amylase and protease were 30°C and 50°C respectively. Both the enzymes were active in the presence of various metal ions (1 mM of Ni2+, Ca2+, Ba2+, Sr2+ and Mg2+), detergents (Tween 20, Tween 80, Triton X-100) and other additives (2-mercaptoethanol and urea). Both the enzymes followed Michaelis-Menten type enzyme kinetics with Vmax of 121.40 μmol min-1 ml-1 and 4.17 μmol min-1 ml-1 and Km of 0.59 mg ml-1 and 0.28 mg ml-1 for amylase and protease respectively. Amylase showed higher activation energy for inactivation (75.55 kJ mol-1 compared to 59.70 kJ mol-1 for protease) and higher thermal stability (reflected by longer half-life 53.23 min compared to 0.11 min for protease) at 60°C. The coexistence of amylase and protease could be attributed to the difference in the optimum temperatures of activity and thermal stability of the two enzymes. This article is protected by copyright. All rights reserved.
Completion lymph node dissection (CLND) did not improve melanoma-specific survival for patients with sentinel lymph node (SLN)-positive melanoma in the second Multicenter Selective Lymphadenectomy Trial (MSLT-II). We assessed surgeons' awareness of MSLT-II and its impact on CLND recommendations.
An anonymous online cross-sectional survey of the Society of Surgical Oncology membership evaluated surgeon thresholds in offering CLND using patient scenarios and clinicopathologic characteristics ranking.
Of the 2881 e-mails delivered, 146 surgeons (5.1%) completed all seven scenarios. Most (129 of 131, 98%) were aware of MSLT-II and 125 (95%) found it practice-changing. Specifically, 52% (65 of 125) always, 40% usually, 6% rarely, and 3% never offered CLND before MSLT-II. Meanwhile, 4% always, 9% usually, 78% rarely, and 8% never offer CLND now, after MSLT-II (p < .0001). The most important clinicopathologic factors in determining CLND recommendations were extracapsular extension, number of positive SLN, and SLN tumor deposit size, while primary tumor mitotic index and nodal basin location were the least important. Surgical oncology fellowship training, melanoma patient volume, and academic center practice also influenced CLND recommendations.
Most surgeon respondents are aware of MSLT-II, but its application in practice varies according to several clinicopathologic and surgeon factors.
Most surgeon respondents are aware of MSLT-II, but its application in practice varies according to several clinicopathologic and surgeon factors.
We investigated the clinical significance of indeterminate pulmonary nodules (IPNs) in patients diagnosed with nonmetastatic, high-grade localized osteosarcoma.
We retrospectively analyzed the clinical data of 364 patients with nonmetastatic, high-grade localized osteosarcoma. Based on pulmonary computed tomography findings at presentation, the patients were categorized into the no-nodules and the IPNs group and were further categorized into subgroups based on age (<18and ≥18 years). We performed an intergroup comparison of event-free survival (EFS) and overall survival (OS).
At presentation, 276 (75.8%) patients showed no nodules, and 88 (24.2%) patients showed IPNs. The EFS and OS were similar between adults with IPNs (n = 54 [30.5%]) and without nodules (n = 123 [69.5%]) (p = .200 and p = .609, respectively). No significant intergroup difference in OS was observed in pediatric patients (p = .093). However, pediatric patients with IPNs (n = 34 [18.2%]) had poorer EFS than those without nodules (n = 153 [81.8%]) (p = .016). Multivariate analyses confirmed that IPNs were independently associated with poorer EFS in pediatric patients (hazard ratio 1.788, 95% confidence interval 1.092-2.926, p = .021).
This study showed that IPNs at presentation did not affect the survival of adults with nonmetastatic, high-grade localized osteosarcoma but were associated with poorer EFS in pediatric patients.
This study showed that IPNs at presentation did not affect the survival of adults with nonmetastatic, high-grade localized osteosarcoma but were associated with poorer EFS in pediatric patients.There is limited investigation of neonatal foal pharmacokinetic parameters for the antimicrobial combination of sulfadiazine (SDZ) and trimethoprim (TMP). Neonatal pharmacokinetic investigation of the sulfadiazine-trimethoprim combination is required to ensure safe and effective utilization in this population. The purpose of this study was to determine the pharmacokinetics of sulfadiazine-trimethoprim in five healthy neonatal foals with oral administration at 24 mg/kg every 12 hr (hrs) for 10 days. Blood samples were collected at serial time points at approximately 72 hr of age (steady-state) and at days 5 and 10 to monitor the influence of age within the neonatal period. Pharmacokinetic parameters were determined using a one-compartment model analysis, and mean ± SD was calculated. Cmax was 37.8 ± 13.4 μg/ml (SDZ) and 1.92 ± 0.25 μg/ml (TMP). Tmax was 1.4 ± 0.6 hr (SDZ) and 1.4 ± 0.4 hr (TMP). Cmin for SDZ and TMP was 16.84 ± 8.46 μg/ml and 0.46 ± 0.24 μg/ml, respectively. Elimination half-life was 10.8 ± 6.1 hr (SDZ) and 6.5 ± 2 hr (TMP). AUC0 → ∞ was 667 ± 424 μg × hr/ml (SDZ) and 21.1 ± 5.3 μg × hr/ml (TMP). Foals remained healthy, and the plasma concentration of sulfadiazine-trimethoprim reached levels above MIC(90) for Streptococcus equi ssp. (SDZ/TMP) 9.5/0.5 μg/ml).To investigate the relationship between Bacille Calmette-Guérin (BCG) vaccination and SARS-CoV-2 by a bioinformatics approach, two datasets for the SARS-CoV-2 infection group and BCG-vaccinated group were downloaded. Differentially Expressed Genes were identified. Gene ontology and pathways were functionally enriched, and networking was constructed in NetworkAnalyst. Lastly, the correlation between post-BCG vaccination and COVID-19 transcriptome signatures was established. A total of 161 DEGs (113 upregulated DEGs and 48 downregulated genes) were identified in the SARS-CoV-2 group. In the pathway enrichment analysis, a cross-reference of upregulated Kyoto Encyclopedia of Genes and Genomes pathways in SARS-CoV-2 with downregulated counterparts in the BCG-vaccinated group, resulted in the intersection of 45 common pathways, accounting for 86.5% of SARS-CoV-2 upregulated pathways. Of these intersecting pathways, a vast majority were immune and inflammatory pathways with top significance in interleukin-17, tumor necrosis factor, NOD-like receptors, and nuclear factor-κB signaling pathways. Given the inverse relationship of the specific differentially expressed gene pathways highlighted in our results, the BCG-vaccine may play a protective role against COVID-19 by mounting a nonspecific immunological response and further investigation of this relationship is warranted.Glucocorticoids are highly effective medicines in the treatment of inflammatory disorders. However they cause severe adverse reactions, particularly where taken at high doses systemically for prolonged periods. Systemic glucocorticoids are therefore given at dosage sufficient to control the disease, then withdrawn as fast as is possible to minimise dose- and time-related adverse drug reactions without losing disease control. Adverse withdrawal reactions present a major challenge in the withdrawal of long term glucocorticoids. Suppression of the hypothalamic-pituitary-adrenal (HPA) axis causes adrenal insufficiency, which is potentially life threatening and can become symptomatic as treatment is withdrawn. Adrenal insufficiency can be extremely difficult to differentiate from 'glucocorticoid withdrawal syndrome', where patients experience symptoms despite adequate adrenal function, and from psychological dependence. Long term systemic glucocorticoids should therefore be withdrawn slowly. The rate at which the dose is tapered should initially be determined by treatment requirements of the underlying disease. Once 'physiological' doses are reached, the rate of reduction is determined by rate of HPA recovery and need for exogenous glucocorticoid cover while endogenous secretion recovers. If symptoms prevent treatment withdrawal, HPA testing should be used to look for adrenal insufficiency. Patients with adrenal insufficiency require 'physiological' doses of glucocorticoids for adrenal replacement, which may be lifelong if the HPA axis fails to recover.Driven exercise (i.e., feeling compelled to exercise to control one's weight or shape, to obtain other positive consequences of exercising, or to avoid other negative consequences of not exercising) is a common phenomenon in individuals with eating disorders (EDs), typically associated with negative clinical outcomes. Current theoretical models of driven exercise highlight the short-term affect-regulating outcome of acute driven exercise, which is implicated to maintain this symptom either by positive or negative reinforcement. However, few studies have actually investigated cognitive, affective, and psychobiological mechanisms related to acute driven exercise. In particular, experimental studies that directly test mechanisms leading to the short-term affective improvement after acute driven exercise are scarce. In this article, we therefore propose potential cognitive, affective, and psychobiological mechanisms that could explain the affect-regulating function of driven exercise in individuals with EDs. In addition, we suggest examples of experimental studies that could directly test these mechanisms in individuals with EDs, as recent studies have demonstrated the safety of supervised exercise in EDs research. Our aim of stimulating research on the underlying causes and maintenance factors of driven exercise in EDs has the potential to critically inform treatment development for this high-risk population.
Childhood obesity is a public health concern that disproportionately affects populations from low socioeconomic status (SES) and minority groups. Evaluation of social and health risk factors of preschool children living along the Texas-Mexico border provides feedback to design health interventions.
South Texas Early Prevention Study-PreK (STEPS-PreK) is a cluster randomized trial designed to assess the effect of the Bienestar coordinated school health program on children's health outcomes. Family characteristics, dietary intake, fitness, and anthropometric data were collected from 1277 preschool students enrolled in 28 preschools.
The response rate was 67%. Overall, 57% of families lived in poverty. The mean age of students was 4.7 years, 95% were Hispanic, and 51% were male. The average serving of fruits and vegetables per day were 1 and 1/3, respectively. Of these, students consumed 39.7% of fruits and 18.9% of vegetables. Obesity prevalence for boys was 19.2% and for girls 16.8%. Nearly one-half reported some form of food insecurity.
Children living in low-income areas are affected by high levels of social and health risk factors. It is these families who should be targeted with early-age and culturally appropriate health programs.
Children living in low-income areas are affected by high levels of social and health risk factors. It is these families who should be targeted with early-age and culturally appropriate health programs.Signal transducer and activator of transcription 3 (STAT3) is one of the crucial transcription factors, responsible for regulating cellular proliferation, cellular differentiation, migration, programmed cell death, inflammatory response, angiogenesis, and immune activation. In this review, we have discussed the classical regulation of STAT3 via diverse growth factors, cytokines, G-protein-coupled receptors, as well as toll-like receptors. We have also highlighted the potential role of noncoding RNAs in regulating STAT3 signaling. However, the deregulation of STAT3 signaling has been found to be associated with the initiation and progression of both solid and hematological malignancies. Additionally, hyperactivation of STAT3 signaling can maintain the cancer stem cell phenotype by modulating the tumor microenvironment, cellular metabolism, and immune responses to favor drug resistance and metastasis. Finally, we have also discussed several plausible ways to target oncogenic STAT3 signaling using various small molecules derived from natural products.During the coronavirus disease 2019 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), reliable diagnostics are absolutely indispensable. Molecular SARS-CoV-2 diagnostics based on nucleic acids (NA) derived from oro- or nasopharyngeal swabs constitute the current gold standard. Given the importance of test results, it is crucial to assess the quality of the underlying swab samples and NA extraction procedures. We determined NA concentrations in clinical samples used for SARS-CoV-2 testing applying an NA-specific dye. In comparison to cut-offs defined by SARS-CoV-2-positive samples, internal positive controls, and references from a federal laboratory, 90.85% (923 of 1016) of swabs contained NA concentrations enabling SARS-CoV-2 recognition. Swabs collected by local health authorities and the central emergency department either had significantly higher NA concentrations or were less likely to exhibit insufficient quality, arguing in favor of sampling centers with routined personnel. Interestingly, samples taken from females had significantly higher NA concentrations than those from males. Among eight longitudinal patient sample sets with intermitting negative quantitative reverse transcription polymerase chain reaction results, two showed reduced NA concentrations in negative specimens. The herein described fluorescence-based NA quantification approach is immediately applicable to evaluate swab qualities, optimize sampling strategies, identify patient-specific differences, and explain some peculiar test results including intermittent negative samples with low NA concentrations.
Growth of capillaries is an essential process after a dermal injury. An immature scar with robust growth of capillaries tends to be hypertrophic. Pulsed dye laser (PDL) causes damage to microvascular structures and is increasingly used for early erythematous scars to limit scar growth. To have a better understanding of the impact of PDL on scar vascularity and to optimize the clinical use of PDL for managing hypertrophic scars, this study aimed to explore changes in scar erythema, blood perfusion, and thickness of immature hypertrophic scars in Asian patients who received PDL treatments at an early stage.
Thiswas a 3-month, assessor-blinded, clinical study. There were two groups of patients, the PDL group and the control group, who had hypertrophic scars less than 1-year post-injury. Patients in the PDL group received three PDL sessions at 4-week intervals. A total of three assessments were performed, at baseline, 1 and 3 months, consisting of the Patient and Observer Scar Assessment Scale (POSAS) and objscar maturation. Lasers Surg. Med. 0000-00, 2020. © 2020 Wiley Periodicals LLC.
Use of PDL at an early stage controls vascularity of immature hypertrophic scar by improving its poor blood perfusion that further limits scar thickness growth and promotes scar maturation. Lasers Surg. Med. 0000-00, 2020. © 2020 Wiley Periodicals LLC.
Fruit and vegetable consumption has increased due to their tremendous health benefits. However, recent studies have shown that contaminated products may serve as vehicles for foodborne pathogens and harmful chemicals. Therefore, fresh vegetables must be decontaminated before consumption to ensure food safety.
In this study, the combined decontamination treatment of lactic acid (2.5 mL L
) and ozone (9 mg L
) for 10 min showed better efficacy in the removal of contaminants from fresh vegetables as compared to individual treatments. The combined treatment resulted in a reduction of 1.5-3.5 log CFU of native mesophilic bacteria per gram and 1.6-2.9 log CFU of artificially inoculated Escherichia coli per gram from tomato, cucumber, carrot and lettuce. The combined treatment also removed spiked pesticides, which represent artificial chemical contamination (28-97% chlorpyrifos and 62-100% λ-cyhalothrin residues), from fresh vegetables. No significant difference (P > 0.05) in various sensory attributes of vegetables was observed between untreated and treated (lactic acid and ozone) vegetables.
The combination treatment provides a novel approach to target two groups of contaminants using a single procedure. The combination treatment can be used as an alternative to currently used decontamination techniques for the supply of safe vegetables to consumers. © 2020 Society of Chemical Industry.
The combination treatment provides a novel approach to target two groups of contaminants using a single procedure. The combination treatment can be used as an alternative to currently used decontamination techniques for the supply of safe vegetables to consumers. © 2020 Society of Chemical Industry.Recent studies and guidelines have indicated that lipoprotein(a) [Lp(a)]was an independent risk factor of arteriosclerotic cardiovascular disease (ASCVD). This study aimed to determine the relationship between serum Lp(a) levels and the risk of periprocedural myocardial injury following percutaneous coronary intervention (PCI) in coronary heartdisease (CHD) patients. This study enrolled 528 nonacute myocardial infarction (AMI) coronary heart disease (CHD) patients who successfully underwent PCI. Fasting serum lipids including Lp(a) were tested before PCI. High-sensitivity cardiac troponin I (hs-cTnI) was tested before PCI and 24 h after PCI. Univariate and multivariate logistic regression analyses were used to determine the relationship between preprocedural Lp(a) levels and postprocedural cTnI elevation from 1 × upper limit of normal (ULN) to 70 × ULN. As a continuous variable, multivariate analyses adjusting for conventional covariates and other serum lipids revealed that increased Lp(a) levels were independently associated with the risk of elevated postprocedural cTnI values above 1 × ULN (odds ratio [OR] per log-unit higher 1.31, 95% confidence interval [CI] 1.02-1.68, P = 0.033], 5 × ULN (OR 1.25, 95%CI 1.02-1.53, P = 0.032), 10 × ULN (OR 1.48, 95%CI 1.18-1.86, P = 0.001) and 15 × ULN (OR 1.28, 95%CI 1.01-1.61, P = 0.038). As a categorical variable, Lp(a) > 300 mg/L was an independent risk factor of postproceduralc TnI≥1 × ULN (OR 2.17, 95%CI 1.12-4.21, P = 0.022), ≥5 × ULN (OR 1.82, 95%CI 1.12-2.97, P = 0.017) and ≥10 × ULN (OR 2.17, 95%CI 1.33-3.54, P = 0.002). Therefore, it could be concluded that elevated preprocedural Lp(a) levels were associated with the risk of PCI-related myocardial injury in non-AMI CHD patients.Paleopathology, or the study of ancient injuries and diseases, can enable the ecology and life history of extinct taxa to be deciphered. Large-bodied ornithopods are the dinosaurs with the highest frequencies of paleopathology reported to-date. Among these, the crested hadrosaurid Parasaurolophus walkeri is one of the most famous, largely due to its dramatic elongated and tubular nasal crest. The holotype of Parasaurolophus walkeri at the Royal Ontario Museum, Canada, displays several paleopathologies that have not been discussed in detail previously a dental lesion in the left maxilla, perhaps related to periodontal disease; callus formation associated with fractures in three dorsal ribs; a discoidal overgrowth above dorsal neural spines six and seven; a cranially oriented spine in dorsal seven, that merges distally with spine six; a V-shaped gap between dorsal spines seven and eight; and a ventral projection of the pubic process of the ilium which covers, and is fused with, the lateral side of the iliac pro mississippiensis, Iguana iguana), but its presence, structure, and origin-attachment sites are still debated. The V-shaped gap is hypothesized as representing the point between the stresses of the nuchal ligament, pulling the anterior neural spines forward, and the ossified tendons pulling the posterior neural spines backward. Different reconstructions of the morphology of the structure based on the pathological conditions affecting the neural spines of ROM 768 are proposed. Finally, we review the history of reconstructions for Parasaurolophus walkeri showing how erroneous misconceptions have been perpetuated over time or have led to the development of new hypotheses, including the wide neck model supported in the current research.Flowering time is a key adaptive and agronomic trait. In Arabidopsis, natural variation in expression levels of the floral repressor FLOWERING LOCUS C (FLC) leads to differences in vernalization. In Brassica napus there are nine copies of FLC. Here, we study how these multiple FLC paralogues determine vernalization requirement as a system. We collected transcriptome time series for Brassica napus spring, winter, semi-winter, and Siberian kale crop types. Modelling was used to link FLC expression dynamics to floral response following vernalization. We show that relaxed selection pressure has allowed expression of FLC paralogues to diverge, resulting in variation of FLC expression during cold treatment between paralogues and accessions. We find that total FLC expression dynamics best explains differences in cold requirement between cultivars, rather than expression of specific FLC paralogues. The combination of multiple FLC paralogues with different expression dynamics leads to rich behaviour in response to cold and a wide range of vernalization requirements in B. napus. We find evidence for different strategies to determine the response to cold in existing winter rapeseed accessions.The experiment determined whether equivalence class formation required overlap of comparison stimuli and responding. Each trial contained a sample first, a single, nonoverlapping comparison second, and a nonoverlapping response-window (RW) third, during which the participant made one of two responses (2R). All 11 participants formed two 3-member ABC equivalence classes using these "trace-stimulus-pairing two-response with response window" (TSP-2R-RW) trials. After adding a fourth stimulus (D) by CD training, ABCD tests showed immediate expansion to 4-member ABCD classes. When 4-member probes (AD, DA, BD, DB, CD, DC) were administered without 3-member probes, many participants showed decrements in class-indicative responding that then resurged to mastery with test repetition. Thus, 3-member probes enhanced class expansion. Class formation occurred for all participants when responding was temporally dissociated from the comparisons. In a matched, contemporaneously published experiment, where responding occurred during comparisons, only 54% of participants formed the classes. Thus, the comparison-response-separation nearly doubled class formation. Additionally, a special post-class-formation sorting test documented the emergence of two explicit equivalence classes. Finally, we noted a 11 correspondence for TSP-2R-RW and priming trials. Since priming measures neural substrates of equivalence classes, TSP-2R-RW trials should do the same.Aicardi-Goutières syndrome type 6 (AGS6) and dyschromatosis symmetrica hereditaria (DSH) are allelic disorders caused respectively by biallelic and heterozygous pathogenic variants in ADAR1. We report three unrelated children presenting with features of both AGS6 and DSH, two of whom had compound heterozygous pathogenic variants in ADAR1. We also describe the novel genetic variants in our cases and review the literature on association of ADAR1-related AGS6 and DSH with these phenotypes.
Hypertension is associated with left ventricular (LV) hypertrophy, impaired LV relaxation, and left atrial (LA) enlargement. Cardiac rehabilitation (CR) improves clinical outcomes in a broad spectrum of cardiac disease. The aim of our study was to determine the effect of CR on blood pressure (BP), and on LA and LV functions in hypertensive patients.
Thirty consecutive hypertensive patients who would undergo CR program, and 38 hypertensive patients who refused to undergo CR program were included. All patients underwent ambulatory BP monitoring and transthoracic echocardiography, which were repeated after completion of the CR program, or 12 weeks later in the control group. LA and LV functions were assessed by both speckle tracking and 3-dimensional echocardiography. N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were assessed before and after CR.
Although initial ambulatory BP values and NT-proBNP levels were similar between the groups, daily, day-time, and night-time BP and NT-proBNP were significantly lower in the CR group after rehabilitation. LA reservoir strain and LV global longitudinal strain of the CR group significantly increased after CR while no significant increase was observed in controls.
CR improves LA and LV strain while lowering BP and should be encouraged in routine management of hypertensive patients.
CR improves LA and LV strain while lowering BP and should be encouraged in routine management of hypertensive patients.Dendritic cells (DCs) are key immune modulators and are able to mount immune responses or tolerance. DC differentiation and activation imply a plethora of molecular and cellular responses, including transcriptional changes. PU.1 is a highly expressed transcription factor in DCs and coordinates relevant aspects of DC biology. Due to their role as immune regulators, DCs pose as a promising immunotherapy tool. However, some of their functional features, such as survival, activation, or migration, are compromised due to the limitations to simulate in vitro the physiologic DC differentiation process. A better knowledge of transcriptional programs would allow the identification of potential targets for manipulation with the aim of obtaining "qualified" DCs for immunotherapy purposes. Most of the current knowledge regarding DC biology derives from studies using mouse models, which not always find a parallel in human. In the present study, we dissect the PU.1 transcriptional regulome and interactome in mouse and human DCs, in the steady state or LPS activated. The PU.1 transcriptional regulome was identified by performing PU.1 chromatin immunoprecipitation followed by high-throughput sequencing and pairing these data with RNAsequencing data. The PU.1 interactome was identified by performing PU.1 immunoprecipitation followed by mass spectrometry analysis. Our results portray PU.1 as a pivotal factor that plays an important role in the regulation of genes required for proper DC activation and function, and assures the repression of nonlineage genes. The interspecies differences between human and mouse DCs are surprisingly substantial, highlighting the need to study the biology of human DCs.The recent release of the 11th version of The International Classification of Diseases (ICD-11 WHO, 2018) marked a significant departure from the previous similarities between it and the Diagnostic and Statistical Manual of Mental Disorders (DSM-5; APA, 2013) in terms of their conceptualization of posttraumatic stress disorder (PTSD). The ICD-11 proposed a reduced symptom set for PTSD and a sibling disorder called Complex PTSD. There have been numerous studies that have provided support for the integrity of, and distinction between, PTSD and CPTSD diagnoses in adult samples. Elliot and colleagues (2020) have added to the research literature by providing a valuable examination of the differences between ICD and DSM PTSD/CPTSD in a sample of youth aged 8 to 17 years. This commentary reviews this study and reflects on the need for greater understanding of developmental changes in the presentation of PTSD and Complex PTSD.In this study, for the first time, Porphyromonas gingivalis, an anaerobic bacterium, was selected to synthesize carbon dots. The achieved P.gingivalis-carbon dots (Pg-CDs) exhibited strong fluorescence and high stability with capacity for dual function as Fe3+ sensor and intracellular imaging agent. The detection limit for Fe3+ was as low as 1.85µM. On the other hand, the prepared Pg-CDs were an excellent candidate for biosensor with high biocompatibility.Since their discovery in the 60s´, B cells have been extensively studied because of their unique and critical role in immunoglobulin (Ig) production. In addition, B cells contribute to other aspects of the immune response via antigen presentation to T cells and cytokine production. Despite the intensive study of B cells, its classification in different subsets based on surface markers remained controversial. Historically, B cells in the periphery (i.e., blood, secondary lymphoid organs) were classified according to their maturation stage and the Ig isotype expressed in 5 populations transitional, naive, non-switched memory, switched memory and plasma cells. Importantly, this classification does not reflect precisely functional aspects (i.e., metabolism, cell signaling, tissue of origin), and in some cases the markers used to identify B-cell subsets were faulty. For example, CD27 was long considered a classical marker of memory B cells and associated with somatic hypermutation (SHM), however some memory B cells lack CD27 expression.1 In this context, B-cell biologists were demanding to update the criteria used to classify B cells and the inclusion of novel functionality markers, which has been possible with the advent of single cell multi-omics.