Clinical Relevance and Mechanisms of Antagonism Between the BMP and Activin/TGF-β Signaling Pathways.

The transforming growth factor β (TGF-β) superfamily is a large group of signaling molecules that participate in embryogenesis, organogenesis, and tissue homeostasis. These molecules are present in all animal genomes. Dysfunction in the regulation or activity of this superfamily\u27s components underlies numerous human diseases and developmental defects. There are 2 distinct arms downstream of the TGF-β superfamily ligands-the bone morphogenetic protein (BMP) and activin/TGF-β signaling pathways-and these 2 responses can oppose one another\u27s effects, most notably in disease states. However, studies have commonly focused on a single arm of the TGF-β superfamily, and the antagonism between these pathways is unknown in most physiologic and pathologic contexts. In this review, the authors summarize the clinically relevant scenarios in which the BMP and activin/TGF-β pathways reportedly oppose one another and identify several molecular mechanisms proposed to mediate this interaction. Particular attention is paid to experimental findings that may be informative to human pathology to highlight potential therapeutic approaches for future investigation

Determining Factors for Parents to Choose a School: Empirical Analysis of Religious Based Private Schools

This study explores the factors influencing parental decision-making in choosing a school in the context of private, faith-based education. Using a quantitative descriptive and exploratory approach, this research investigates various factors shaping parents' interest in choosing a school. The population examined were parents of students attending private Christian schools, resulting in a purposive sample of 235 respondents. The sampling technique targets parents actively involved in the school community and has varying levels of involvement and perspectives on the school selection process. Data was collected through an online survey conducted between June and September 2023. Next, Confirmatory Factor Analysis (CFA) using SmartPLS was used for data analysis. This study identified eight factors influencing parental decision-making: teacher ability, school location, religious values, school facilities, school image, perceived costs, school environment, and school safety. The implications of these findings highlight the school's strategy to increase its attractiveness, thereby increasing school enrollment rates

Calculating Milnor Numbers and Versal Component Dimensions from P-Resolution Fans

We use Altmann's toric fan description of P-resolutions to formulate a new description of deformation theory invariants for two-dimensional cyclic quotient singularities. In particular, we show how to calculate the dimensions of the (reduced) versal base space components as well as Milnor numbers of smoothings over them.Comment: 8 pages; 2 figures; v2 added section on Milnor numbers, reworked proof of dimension formula, new example, and new titl

SARS-CoV-2 Nasopharyngeal Swab Testing—False-Negative Results From a Pervasive Anatomical Misconception

This article is made available for unrestricted research re-use and secondary analysis in any form or be any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Given our subspecialty focus on nasal anatomy, we have been involved in training personnel at our respective institutions on the proper techniques for NPS collection for SARS-CoV-2 testing, and we have noticed pervasive misperception about the location of the nasopharynx. Although many sites around the world are likely providing proper training, we are concerned that inadequate NPS collection may continue to lead to false-negative results. The rate of false-negative results in reverse transcriptase polymerase chain reaction testing is a great concern because it underestimates the prevalence of SARS-CoV-2 infection, gives a false sense of security to patients and the health care workers caring for them, and limits public health efforts in identifying and tracing the spread of the virus. We hope highlighting that the nasopharynx is back, not up, can help limit false-negative results in testing for SARS-CoV-2 and other respiratory viruses.Dr Higgins reported being a paid research investigator for Optinose and Gossamer and receiving personal fees from Sanofi-Regeneron and Genentech outside the submitted work. Dr Wu reported receiving payment for positions as a speaker for Sanofi-Regeneron and Optinose, a member of a medical advisory board for Optinose and Gossamer, and an investigator for Gossamer outside the submitted work. No other disclosures were reported

Development of the corpus callosum and cognition after neonatal encephalopathy

Objective: Neonatal imaging studies report corpus callosum abnormalities after neonatal hypoxic–ischaemic encephalopathy (HIE), but corpus callosum development and relation to cognition in childhood are unknown. Using magnetic resonance imaging (MRI), we examined the relationship between corpus callosum size, microstructure and cognitive and motor outcomes at early school-age children cooled for HIE (cases) without cerebral palsy compared to healthy, matched controls. A secondary aim was to examine the impact of HIE-related neonatal brain injury on corpus callosum size, microstructure and growth. Methods: Participants aged 6–8 years underwent MRI, the Movement Assessment Battery for Children Second Edition and Wechsler Intelligence Scale for Children Fourth Edition. Cross-sectional area, volume, fractional anisotropy and radial diffusivity of the corpus callosum and five subdivisions were measured. Multivariable regression was used to assess associations between total motor score, full-scale IQ (FSIQ) and imaging metrics. Results: Adjusting for age, sex and intracranial volume, cases (N = 40) compared to controls (N = 39) demonstrated reduced whole corpus callosum area (β = −26.9, 95% confidence interval [CI] = −53.17, −0.58), volume (β = −138.5, 95% CI = −267.54, −9.56), fractional anisotropy and increased radial diffusivity (P < 0.05) within segments II–V. In cases, segment V area (β = 0.18, 95% CI = 0.004, 0.35), volume (β = 0.04, 95% CI = 0.001, 0.079), whole corpus callosum fractional anisotropy (β = 13.8 95% CI = 0.6, 27.1) and radial diffusivity (β = −11.3, 95% CI = −22.22, −0.42) were associated with FSIQ. Growth of the corpus callosum was restricted in cases with a FSIQ ≤85, and volume was reduced in cases with mild neonatal multifocal injury compared to white matter injury alone. Interpretation: Following neonatal HIE, morphological and microstructural changes in the corpus callosum are associated with reduced cognitive function at early school age

Survey of endoscopic skull base surgery practice patterns among otolaryngologists

Background Endoscopic skull base surgery (ESBS) is a rapidly expanding field. Despite divergent reported preferences for reconstructive techniques and perioperative management, limited data exist regarding contemporary practice patterns among otolaryngologists performing ESBS. This study aims to elucidate current practice patterns, primarily the volumes of cases performed and secondarily a variety of other perioperative preferences. Methods An anonymous 32-item electronic survey examining perioperative ESBS preferences was distributed to the American Rhinologic Society membership. Statistical significance between variables was determined utilizing Student t, chi-square, and Fisher exact tests. Results Seventy otolaryngologists completed the survey. The effective response rate was approximately 22.5%. Sixty percent of respondents were in full-time academic practice and 70% had completed rhinology/skull base fellowships. Annually, 43.3 mean ESBS cases were performed (29.1 private practice vs. 52.9 academic practice, P = .009). Academic practice averaged 24.1 expanded cases versus only 11 in private practice (P = .01). Of respondents, 55.7% stood on the same side as the neurosurgeon and 72.9% remained present for the entire case. Current procedural terminology coding and antibiotic regimens were widely divergent; 31.4% never placed lumbar drains preoperatively, while 41.4% did so for anticipated high-flow cerebrospinal fluid leaks. While considerable variation in reconstructive techniques were noted, intradural defect repairs utilized vascularized flaps 86.3% of the time versus only 51.3% for extradural repairs (P < 0.001). Major complications were rare. Postoperative restrictions varied considerably, with most activity limitations between 2–8 weeks and positive airway pressure use for 2–6 weeks. Most respondents started saline irrigations 0–2 weeks postoperatively. Conclusions Based on responses from fellowship- and non-fellowship-trained otolaryngologists in various practice settings, there remains considerable variation in the perioperative management of patients undergoing ESBS. Level of Evidence

Antagonism Between Bone Morphogenetic Protein and Activin Signaling Pathways in Osteoprogenitor Cells

Osteoporosis is a disease characterized by low bone mineral density due to the rate of bone resorption exceeding that of bone formation. Evidence indicates the Bone Morphogenetic Protein (BMP) pathway promotes bone formation through action of effectors SMAD1/5/8 while the Activin pathway negatively influences bone mass through effectors SMAD2/3. Studies suggest that BMPs and Activins regulate bone mass in a see-saw-like mechanism. We seek to test this hypothesis in vitro via signaling responsiveness assays using pathway-specific western blot analyses in the osteogenic murine bone marrow stromal cell line W-20-17. We first confirmed that W-20-17 cells exhibit basal activation of SMAD1/5/8 and SMAD2/3 under serum-restricted conditions. Treatment with Follistatin, which sequesters Activin ligands in the extracellular environment, leads to an increase in BMP pathway activation. To determine the mechanism allowing for this, we treated W-20-17 cells with SB431542, an intracellular inhibitor of Activin signaling that functions downstream of receptor engagement, and found no effect on BMP pathway activation. In contrast, treatment with BMP pathway inhibitor Noggin had no effect on Activin pathway activation despite robust inhibition of BMP signaling. Our results suggest Activin-mediated repression of BMP signaling in these cells is ligand-dependent but occurs upstream of SMAD2/3 activation. Gene expression analyses indicate that W-20-17 cells express Activin A and its receptors ALK4, ACVR2A, and ACVR2B. Given that ACVR2A and ACVR2B also have high affinity for BMP ligands, this raises the possibility that Activin-mediated repression of BMP signaling may occur via competition for a shared pool of receptors. Over-expression studies and osteoblast activity assays are underway to examine this hypothesis. Our work seeks to elucidate the mechanism(s) that regulate antagonism of BMP and Activin signaling pathways to identify novel opportunities for treating low bone mass in humans