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PLoS Biology Jun 2024In the highly regulative embryo of the sea urchin Paracentrotus lividus, establishment of the dorsal-ventral (D/V) axis critically depends on the zygotic expression of...
In the highly regulative embryo of the sea urchin Paracentrotus lividus, establishment of the dorsal-ventral (D/V) axis critically depends on the zygotic expression of the TGF-β nodal in the ventral ectoderm. nodal expression is first induced ubiquitously in the 32-cell embryo and becomes progressively restricted to the presumptive ventral ectoderm by the early blastula stage. This early spatial restriction of nodal expression is independent of Lefty, and instead relies on the activity of Panda, a maternally expressed TGF-β ligand related to Lefty and Inhibins, which is required maternally for D/V axis specification. However, the mechanism by which Panda restricts the early nodal expression has remained enigmatic and it is not known if Panda works like a BMP ligand by opposing Nodal and antagonizing Smad2/3 signaling, or if it works like Lefty by sequestering an essential component of the Nodal signaling pathway. In this study, we report that Panda functions as an antagonist of the TGF-β type II receptor ACVRII (Activin receptor type II), which is the only type II receptor for Nodal signaling in the sea urchin and is also a type II receptor for BMP ligands. Inhibiting translation of acvrII mRNA disrupted D/V patterning across all 3 germ layers and caused acvrII morphants to develop with a typical Nodal loss-of-function phenotype. In contrast, embryos overexpressing acvrII displayed strong ectopic Smad1/5/8 signaling at blastula stages and developed as dorsalized larvae, a phenotype very similar to that caused by over activation of BMP signaling. Remarkably, embryos co-injected with acvrII mRNA and panda mRNA did not show ectopic Smad1/5/8 signaling and developed with a largely normal dorsal-ventral polarity. Furthermore, using an axis induction assay, we found that Panda blocks the ability of ACVRII to orient the D/V axis when overexpressed locally. Using co-immunoprecipitation, we showed that Panda physically interacts with ACVRII, as well as with the Nodal co-receptor Cripto, and with TBR3 (Betaglycan), which is a non-signaling receptor for Inhibins in mammals. At the molecular level, we have traced back the antagonistic activity of Panda to the presence of a single proline residue, conserved with all the Lefty factors, in the ACVRII binding motif of Panda, instead of a serine as in most of TGF-β ligands. Conversion of this proline to a serine converted Panda from an antagonist that opposed Nodal signaling and promoted dorsalization to an agonist that promoted Nodal signaling and triggered ventralization when overexpressed. Finally, using phylogenomics, we analyzed the emergence of the agonist and antagonist form of Panda in the course of evolution. Our data are consistent with the idea that the presence of a serine at that position, like in most TGF-β, was the ancestral condition and that the initial function of Panda was possibly in promoting and not in antagonizing Nodal signaling. These results highlight the existence of key functional and structural elements conserved between Panda and Lefty, allow to draw an intriguing parallel between sea urchin Panda and mammalian Inhibin α and raise the unexpected possibility that the original function of Panda may have been in activation of the Nodal pathway rather than in its inhibition.
PubMed: 38913712
DOI: 10.1371/journal.pbio.3002701 -
PloS One 2024There is limited understanding of how social determinants of health (SDOH) impact family decision-making when seeking surgical care for children. Our objectives of this...
BACKGROUND
There is limited understanding of how social determinants of health (SDOH) impact family decision-making when seeking surgical care for children. Our objectives of this study are to identify key family experiences that contribute to decision-making when accessing surgical care for children, to confirm if family experiences impact delays in care, and to describe differences in family experiences across populations (race, ethnicity, socioeconomic status, rurality).
METHODS
We will use a prospective, cross-sectional, mixed methods design to examine family experiences during access to care for children with appendicitis. Participants will include 242 parents of consecutive children (0-17 years) with acute appendicitis over a 15-month period at two academic health systems in North Carolina and Virginia. We will collect demographic and clinical data. Parents will be administered the Adult Responses to Children's Symptoms survey (ARCS), the child and parental forms of the Adverse Childhood Experiences (ACE) survey, the Accountable Health Communities Health-Related Social Needs Screening Tool, and Single Item Literacy Screener. Parallel ARCS data will be collected from child participants (8-17 years). We will use nested concurrent, purposive sampling to select a subset of families for semi-structured interviews. Qualitative data will be analyzed using thematic analysis and integrated with quantitative data to identify emerging themes that inform a conceptual model of family-level decision-making during access to surgical care. Multivariate linear regression will be used to determine association between the appendicitis perforation rate and ARCS responses (primary outcome). Secondary outcomes include comparison of health literacy, ACEs, and SDOH, clinical outcomes, and family experiences across populations.
DISCUSSION
We expect to identify key family experiences when accessing care for appendicitis which may impact outcomes and differ across populations. Increased understanding of how SDOH and family experiences influence family decision-making may inform novel strategies to mitigate surgical disparities in children.
Topics: Humans; Child; Cross-Sectional Studies; Adolescent; Decision Making; Child, Preschool; Male; Female; Appendicitis; Infant; Health Services Accessibility; Prospective Studies; Parents; Infant, Newborn; Family; North Carolina; Virginia
PubMed: 38913675
DOI: 10.1371/journal.pone.0304165 -
Microbiology Spectrum Jun 2024Amplicon sequencing stands as a cornerstone in microbiome profiling, yet concerns persist regarding its resolution and accuracy. The enhancement of reference databases...
Amplicon sequencing stands as a cornerstone in microbiome profiling, yet concerns persist regarding its resolution and accuracy. The enhancement of reference databases and annotations marks a new era for 16S rRNA-based profiling. Capitalizing on this potential, we introduce PM-profiler, a novel tool for profiling amplicon short reads. PM-profiler is implemented by C++-based advanced algorithms, such as pre-allocated hash for reference construction, hybrid and dynamic short-read matching, big-data-guided dual-mode hierarchical taxonomy annotation strategy, and full-procedure parallel computing. This tool delivers species-level resolution and ultrafast speed for large-scale microbiomes, surpassing alignment-based approaches and the Naïve-Bayesian model. Furthermore, recognizing the global uneven distribution of microbes, we delineate optimal annotation strategies for each sampling habitat based on microbial patterns over 270,000 microbiomes. Integrated with the established workflow of Parallel-Meta Suite and the latest curated reference databases, this endeavor offers a swift and dependable solution for high-precision microbiome surveys.IMPORTANCEOur study introduces PM-profiler, a new tool that deciphers the complexity of microbial communities. With advanced algorithms, flexible annotation strategies, and well-organized big-data, PM-profiler provides a faster and more accurate way to study on microbiomes, paving the way for discoveries that could improve our understanding of microbiomes and their impact on the world.
PubMed: 38912828
DOI: 10.1128/spectrum.00695-24 -
Heliyon Jun 2024Alveolar epithelial barrier integrity is essential for lung homeostasis. Na, K-ATPase β1 subunit (ATP1B1) involves alveolar edema fluid clearance and alveolar...
AIMS
Alveolar epithelial barrier integrity is essential for lung homeostasis. Na, K-ATPase β1 subunit (ATP1B1) involves alveolar edema fluid clearance and alveolar epithelial barrier stability. However, the underlying molecular mechanism of ATP1B1 in alveolar epithelial cells still needs to be understood.
MAIN METHODS
We utilized Co-Immunoprecipitation mass spectrometry proteomic analysis, protein-protein interaction (PPI) analysis, enrichment analysis, and parallel reaction monitoring (PRM) analysis to investigate proteins interacting with ATP1B1 in A549 cells.
KEY FINDINGS
A total of 159 proteins were identified as significant proteins interacting with ATP1B1 in A549 cells. Ribosomal and heat shock proteins were major constituents of the two main functional modules based on the PPI network. Enrichment analysis showed that significant proteins were involved in protein translation, posttranslational processing, and function regulation. Moreover, 10 proteins of interest were verified by PRM, and fold changes in 6 proteins were consistent with proteomics results. Finally, HSP90AB1, EIF4A1, TUBB4B, HSPA8, STAT1, and PLEC were considered candidates for binding to ATP1B1 to function in alveolar epithelial cells.
SIGNIFICANCE
Our study provides new insights into the role of ATP1B1 in alveolar epithelial cells and indicates that six proteins, in particular HSP90AB1, may be key proteins interacting with and regulating ATP1B1, which might be potential targets for the treatment of acute respiratory distress syndrome.
PubMed: 38912441
DOI: 10.1016/j.heliyon.2024.e32579 -
Frontiers in Microbiology 2024Mastitis is commonly recognized as a localized inflammatory udder disease induced by the infiltration of exogenous pathogens. In the present study, our objective was to...
Mastitis is commonly recognized as a localized inflammatory udder disease induced by the infiltration of exogenous pathogens. In the present study, our objective was to discern fecal and milk variations in both microbiota composition and metabolite profiles among three distinct groups of cows: healthy cows, cows with subclinical mastitis and cows with clinical mastitis. The fecal microbial community of cows with clinical mastitis was significantly less rich and diverse than the one harbored by healthy cows. In parallel, mastitis caused a strong disturbance in milk microbiota. Metabolomic profiles showed that eleven and twenty-eight molecules exhibited significant differences among the three groups in feces and milk, respectively. Similarly, to microbiota profile, milk metabolome was affected by mastitis more extensively than fecal metabolome, with particular reference to amino acids and sugars. Pathway analysis revealed that amino acids metabolism and energy metabolism could be considered as the main pathways altered by mastitis. These findings underscore the notable distinctions of fecal and milk samples among groups, from microbiome and metabolomic points of view. This observation stands to enhance our comprehension of mastitis in dairy cows.
PubMed: 38912351
DOI: 10.3389/fmicb.2024.1374911 -
Frontiers in Public Health 2024Pre-frailty represents an ideal window of opportunity to potentially prevent frailty and disability. Early and effective interventions to delay or reverse pre-frailty... (Randomized Controlled Trial)
Randomized Controlled Trial
Effectiveness of a mHealth platform-based lifestyle integrated multicomponent exercise () program to reverse pre-frailty in community-dwelling older adults: a randomized controlled trial study protocol.
BACKGROUND
Pre-frailty represents an ideal window of opportunity to potentially prevent frailty and disability. Early and effective interventions to delay or reverse pre-frailty are public health imperative. The present trial aims to evaluate the effectiveness and underlying mechanisms of mobile health (mHealth) platform-supported lifestyle-integrated multicomponent exercise () to reverse pre-frailty in community-dwelling older adults.
METHODS
This is an open-label, prospective, two-arm parallel randomized controlled trial with allocation concealment and outcome assessment blinding. We aim to recruit 140 pre-frail community-dwelling older adults who will be randomized into two groups. The control group will receive a health education program, while the intervention group will receive training as planned for 1 year. The proportion of pre-frailty, functional performance (muscular strength, aerobic capacity, flexibility, and balance), body composition, and physical activity will be measured at pre-intervention, post-intervention, and 12-month follow-up. Inflammatory biomarkers will also be collected to explore the underlying mechanisms.
DISCUSSION
This is the first study to evaluate the effects of a novel digital lifestyle-integrated multicomponent exercise for pre-frail older people. The results of this trial will provide much-needed information on the short-and long-term effects of based on functional performance and body composition. Meanwhile, inflammatory biomarkers and physical activity levels will be used to elucidate the underlying mechanisms of . The findings from this trial will provide evidence for the effectiveness of lifestyle multicomponent exercise intervention supported by the mHealth platform that may reverse or even halt the onset of frailty.
CLINICAL TRIAL REGISTRATION
https://www.chictr.org.cn/showproj.html?proj=176477, identifier ChiCTR2200063431.
Topics: Humans; Aged; Independent Living; Male; Female; Telemedicine; Prospective Studies; Exercise; Frailty; Frail Elderly; Life Style; Exercise Therapy; Aged, 80 and over
PubMed: 38912262
DOI: 10.3389/fpubh.2024.1389297 -
BMJ Open Sport & Exercise Medicine 2024Muscle function and size decline with age, but long-term effects of resistance training in older adults are largely unknown. Here, we explored the long-lasting (3 years)...
OBJECTIVES
Muscle function and size decline with age, but long-term effects of resistance training in older adults are largely unknown. Here, we explored the long-lasting (3 years) effects of 1 year of supervised resistance training with heavy loads.
METHODS
The LIve active Successful Ageing (LISA) study was a parallel group randomised controlled trial at a university hospital in Denmark. Older adults (n=451) at retirement age were randomised to 1 year of heavy resistance training (HRT), moderate-intensity training (MIT) or a non-exercising control group (CON). Primary outcome measure was leg extensor power. Secondary outcomes included maximal isometric quadriceps torque (isometric leg strength) and body composition (dual-energy X-ray absorptiometry (DXA)). Participants completed test procedures at baseline, following the 1-year intervention, and 2 and 4 years post study start.
RESULTS
At the 4-year assessment, 369 participants attended (mean age=71 years, 61% women). The main finding was that across all four time points, there was a significant group×time interaction in isometric leg strength (F=8.607, p<0.001, =0.05). Individuals in HRT maintained baseline performance in isometric leg strength (Baseline: 149.7±51.5 Nm, 4 years: 151.5±51.1 Nm, t(1050)=1.005, p=1.00) while participants in CON and MIT decreased.
CONCLUSION
In well-functioning older adults at retirement age, 1 year of HRT may induce long-lasting beneficial effects by preserving muscle function.
TRIAL REGISTRATION NUMBER
NCT02123641.
PubMed: 38911477
DOI: 10.1136/bmjsem-2024-001899 -
Lancet Regional Health. Americas Jul 2024Reducing cigarette addictiveness has the potential to avert millions of yearly tobacco-related deaths worldwide. Substantially reducing nicotine in cigarettes decreases...
BACKGROUND
Reducing cigarette addictiveness has the potential to avert millions of yearly tobacco-related deaths worldwide. Substantially reducing nicotine in cigarettes decreases cigarette consumption, but no large clinical trial has determined the effects of reduced-nicotine cigarettes when other nicotine-containing products are available. The aim of this study was to examine the effects of reduced-nicotine cigarettes in the context of the availability of alternative nicotine delivery systems.
METHODS
In a U.S. six-site, open-label, parallel-arm study, smokers were randomized for twelve weeks to an experimental marketplace containing cigarettes with either 0.4 mg or 15.8 mg nicotine per gram of tobacco; all had access to non-combusted alternative nicotine delivery systems (e.g., e-cigarettes; medicinal nicotine). Group differences in the primary outcomes (cigarettes per day, number of smoke-free days) were examined using linear and negative binomial regression, respectively (Trial Registration: NCT03272685).
FINDINGS
Among 438 randomized participants (mean [standard deviation (SD), range] age, 44.5 [11.9, 20-73] years, 225 [51.4%] women, 282 [64.4%] White and 339 [77.4%] trial completers), those in the 0.4 mg vs. 15.8 mg nicotine cigarette condition experienced significantly lower cigarettes per day at the end of intervention (mean [SD], 7.05 [7.88] vs. 12.95 [9.07], adjusted mean difference, -6.21 [95% CI, -7.66 to -4.75], P < 0.0001) and greater smoke-free days during intervention (mean [SD], 18.59 [27.97] vs. 5.06 [13.77], adjusted rate ratio, 4.25 [95% CI, 2.58-6.98], P < 0.0001).
INTERPRETATION
A reduced-nicotine cigarette standard in the context of access to other non-combusted nicotine products has the potential to benefit public health.
FUNDING
U.S. NIH/FDA U54DA03165.
PubMed: 38911348
DOI: 10.1016/j.lana.2024.100796 -
Diabetes, Metabolic Syndrome and... 2024Autonomic nervous system dysfunction (ANSD), for which presently no treatment exists, has a negative impact on prognosis in people with type 2 diabetes (T2D). Periosteal... (Clinical Trial)
Clinical Trial
New Diabetic Treatment by Alleviation of Autonomic Nervous System Dysfunction Measured as Periosteal Pressure Sensitivity at Sternum Improves Empowerment, Treatment Satisfaction, and Self-Reported Health of People with Type 2 Diabetes: A Randomized Trial.
PURPOSE
Autonomic nervous system dysfunction (ANSD), for which presently no treatment exists, has a negative impact on prognosis in people with type 2 diabetes (T2D). Periosteal pressure sensitivity (PPS) on sternum may be a measure of autonomic nervous system dysfunction (ANSD). We tested if a non-pharmacological PPS-feedback-guided treatment program based on non-noxious sensory nerve stimulation, known to reduce PPS, changed empowerment, treatment satisfaction, and quality of life in people with T2D, compared to usual treatment.
PATIENTS AND METHODS
Analysis of secondary endpoints in a single center, two-armed, parallel-group, observer-blinded, randomized controlled trial of individuals with T2D. Participants were randomized to non-pharmacological intervention as an add-on to treatment as usual. Endpoints were evaluated by five validated questionnaires: Diabetes specific Empowerment (DES-SF), Diabetes Treatment Satisfaction (DTSQ), quality of life (QOL) (WHO-5), clinical stress signs (CSS), and self-reported health (SF-36). Sample size calculation was based on the primary endpoint HbA1c.
RESULTS
We included 144 participants, 71 allocated to active intervention and 73 to the control group. Active intervention compared to control revealed improved diabetes-specific empowerment (p = 0.004), DTSQ (p = 0.001), and SF-36 self-reported health (p=0.003) and tended to improve quality of life (WHO-5) (p = 0.056). The findings were clinically relevant with a Cohen's effect size of 0.5 to 0.7.
CONCLUSION
This non-pharmacological intervention, aiming to reduce PPS, and thus ANSD, improved diabetes-specific empowerment, treatment satisfaction, and self-reported health when compared to usual treatment. The proposed intervention may be a supplement to conventional treatment for T2D.
PubMed: 38910915
DOI: 10.2147/DMSO.S455216 -
BMC Oral Health Jun 2024One of the main goals for pediatric dentists is to offer a painless anesthesia experience. Laser photobiomodulation is among the suggested strategies to decrease... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
One of the main goals for pediatric dentists is to offer a painless anesthesia experience. Laser photobiomodulation is among the suggested strategies to decrease injection pain. So, this study aimed to assess the impact of laser photobiomodulation on local anesthesia (LA) injection pain in children and its effect on the efficacy of LA during pulpotomy and SSC procedures.
METHODS
The research was carried out as a randomized controlled clinical trial with two parallel group design. It involved 64 cooperative healthy children, age range from 5 to 7 years, each having at least one maxillary molar indicated for pulpotomy. Children were randomly allocated to one of the two groups based on the pre-anesthetic tissue management technique used: test group received laser photobiomodulation, while control group received topical anesthetic gel. Pain during injection, pulpotomy, and SSC procedures was assessed using physiological measures (Heart Rate (HR)), subjective evaluation (modified Face-Pain-Scale (FPS), and objective analysis (Sound-Eye-Motor scale (SEM)).
RESULTS
A total of 64 children with mean age 6.23 ± 0.78 participated in this research. The mean HR scores were significantly lower in the laser PBM group during buccal and palatal infiltration injections. The SEM mean scores were significantly lower in the laser PBM group during both injections. For the FPS scale, the number of children who recorded satisfaction during injection was significantly higher in laser PBM group. There was no statistically significant difference in mean HR as well as in SEM and FPS scores between the two groups during pulpotomy and SSC procedures. Comparisons between the two study groups were performed using independent samples t- and Mann-Whitney U tests. Significance was set at p value < 0.05.
CONCLUSION
Laser photobiomodulation is a promising non-pharmacological pre-anesthetic tissue management technique in children that offered less painful injection compared to topical anesthetic gel without compromising the effectiveness of LA.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT05861154. Registered on 16/5/2023.
Topics: Humans; Child; Low-Level Light Therapy; Female; Child, Preschool; Male; Pain Measurement; Pulpotomy; Anesthetics, Local; Injections; Anesthesia, Dental; Anesthesia, Local; Pain Management; Heart Rate
PubMed: 38909229
DOI: 10.1186/s12903-024-04430-3