Mobile PEAR transcription factors integrate positional cues to prime cambial growth.

Apical growth in plants initiates upon seed germination, whereas radial growth is primed only during early ontogenesis in procambium cells and activated later by the vascular cambium1. Although it is not known how radial growth is organized and regulated in plants, this system resembles the developmental competence observed in some animal systems, in which pre-existing patterns of developmental potential are established early on2,3. Here we show that in Arabidopsis the initiation of radial growth occurs around early protophloem-sieve-element cell files of the root procambial tissue. In this domain, cytokinin signalling promotes the expression of a pair of mobile transcription factors-PHLOEM EARLY DOF 1 (PEAR1) and PHLOEM EARLY DOF 2 (PEAR2)-and their four homologues (DOF6, TMO6, OBP2 and HCA2), which we collectively name PEAR proteins. The PEAR proteins form a short-range concentration gradient that peaks at protophloem sieve elements, and activates gene expression that promotes radial growth. The expression and function of PEAR proteins are antagonized by the HD-ZIP III proteins, well-known polarity transcription factors4-the expression of which is concentrated in the more-internal domain of radially non-dividing procambial cells by the function of auxin, and mobile miR165 and miR166 microRNAs. The PEAR proteins locally promote transcription of their inhibitory HD-ZIP III genes, and thereby establish a negative-feedback loop that forms a robust boundary that demarks the zone of cell division. Taken together, our data establish that during root procambial development there exists a network in which a module that links PEAR and HD-ZIP III transcription factors integrates spatial information of the hormonal domains and miRNA gradients to provide adjacent zones of dividing and more-quiescent cells, which forms a foundation for further radial growth.

Infection Rates of an Intraoral Versus Extraoral Approach to Mandibular Fracture Repairs are Equal: A Systematic Review and Meta-Analysis.

PURPOSE: This study investigates whether the intraoral approach to mandibular open reduction and internal fixation, through exposure to the oral cavity's microbiome, results in higher infection rates compared to the extraoral approach, thus addressing a critical public health concern, potentially offering an opportunity to reduce health-care costs, and aiming to guide effective clinical practice. METHODS: In this systematic review with meta-analyses, a review of the literature was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. A comprehensive literature search was conducted using Embase and PubMed for articles published between 1989 and 2023. Inclusion criteria targeted studies on open reduction and internal fixation mandibular fractures comparing intraoral and extraoral approaches and reporting infection rates. Exclusion criteria eliminated non-English articles, case reports, and studies with insufficient approach-specific data. The primary outcome was the postoperative infection rate, with surgical approach as the predictor. Covariates such as age, sex, diabetes, and smoking status were included when reported. Data were analyzed using R software, employing random-effects models due to anticipated heterogeneity (I2 statistics). RESULTS: From 61 studies, 11 provided direct comparisons involving 1,317 patients-937 intraoral and 380 extraoral. Infection rates were 5.9% for intraoral and 10% for extraoral approaches. Pooled relative risk was 0.94 [95% confidence interval, 0.63, 1.39], suggesting no significant risk difference. Prevalence of infections was estimated at 9% for intraoral and 6.1% for extraoral procedures, with significant heterogeneity (I2 = 84% for intraoral and 56% for extraoral). CONCLUSION: Our meta-analysis found no significant difference in infection rates between the two approaches. There is opportunity to expand on reporting complication rates comparing the various approaches to mandibular fixation. Until these data are presented, surgeon preference may dictate the operative approach to expose the mandible for reduction and fixation.

The Evolving Plastic Surgery Applicant: How Far Have We Come in 30 Years?

BACKGROUND: Plastic surgery training has undergone tremendous change and transitioned through many models over the years, including independent, combined, and integrated. This study evaluates how these changes and others have affected plastic surgery applicants' demographics and academic qualifications over the last 30 years. METHODS: Data on applicant demographics and academic qualifications were extracted from multiple sources including the National Resident Matching Program, the American Association of Medical Colleges, and cross-sectional surveys of plastic surgery applicants for the years 1992, 2005, 2011, and 2022. Data were compared using pairwise χ2 goodness of fit tests. RESULTS: The sex distribution of plastic surgery applicants changed significantly over the last 30 years: whereas men predominated in 1992 (86% male vs 14% female), by 2011, the distribution was nearly equal (54% male vs 46% female in both 2011 and 2022, P < 0.001).The racial makeup of applicants also changed over time (P < 0.05). White applicants decreased from 73% in 1992 to 55% in 2011, and 53% in 2022. While there was an increase in Asian (7% to > 17% to > 20%) and other (13% to > 14% to > 21%) applicants over time, whereas the proportion of Black applicants remained stagnant (5% to > 6% to > 8%).Applicants with prior general surgery experience declined precipitously over the years: 96% in 1992, 64% in 2005, 37% in 2011, and 26% in 2022 (P < 0.001). When compared with 1992, Alpha Omega Alpha status increased significantly in 2011 (36% vs 12%, P < 0.05) but did not change considerably in 2005 (22%) and 2022 (23%). Research experience increased dramatically over the years, with the proportion of applicants with at least one publication going from 43% in 1992, to 75% in 2005, to 89% in 2011, and to 99% in 2022 (P < 0.001). Applicant interest in academic plastic surgery did not change considerably over the years at roughly ranging from 30% to 50% of applicants (P = ns). CONCLUSIONS: There has been a shift in the demographics and academic qualifications of plastic surgery applicants over the last 3 decades. Understanding this evolution is critical for reviewing and evaluating the makeup of our specialty, and enacting changes to increase representation where necessary.

Minimizing Nipple-Areolar Complex Complications in Prepectoral Breast Reconstruction After Nipple-Sparing Mastectomy.

PURPOSE: Nipple-areolar complex (NAC) viability remains a significant concern following prepectoral tissue expander (TE) reconstruction after nipple-sparing mastectomy (NSM). This study assesses the impact of intraoperative TE fill on NAC necrosis and identifies strategies for mitigating this risk. METHODS: A chart review of all consecutive, prepectoral TEs placed immediately after NSM was performed between March 2017 and December 2022 at a single center. Demographics, mastectomy weight, intraoperative TE fill, and complications were extracted for all patients. Partial NAC necrosis was defined as any thickness of skin loss including part of the NAC, whereas total NAC necrosis was defined as full-thickness skin loss involving the entirety of the NAC. P < 0.05 was considered statistically significant. RESULTS: Forty-six patients (83 breasts) with an average follow-up of 22 months were included. Women were on average 46 years old, nonsmoker (98%), and nondiabetic (100%) and had a body mass index of 23 kg/m2. All reconstructions were performed immediately following prophylactic mastectomies in 49% and therapeutic mastectomies in 51% of cases. Three breasts (4%) were radiated, and 15 patients (33%) received chemotherapy. Mean mastectomy weight was 346 ± 274 g, median intraoperative TE fill was 150 ± 225 mL, and median final TE fill was 350 ± 170 mL. Partial NAC necrosis occurred in 7 breasts (8%), and there were zero instances of complete NAC necrosis. On univariate analysis, partial NAC necrosis was not associated with any patient demographic or operative characteristics, including intraoperative TE fill. In multivariable models controlling for age, body mass index, mastectomy weight, prior breast surgery, and intraoperative TE fill, partial NAC necrosis was associated with lower body mass index (odds ratio, 0.53; confidence interval [CI], 0.29-0.98; P < 0.05) and higher mastectomy weight (odds ratio, 1.1; CI, 1.01-1.20; P < 0.05). Prior breast surgery approached significance, as those breasts had a 19.4 times higher odds of partial NAC necrosis (95% CI, 0.88-427.6; P = 0.06). CONCLUSIONS: Nipple-areolar complex necrosis following prepectoral TE reconstruction is a rare but serious complication. In this study of 83 breasts, 7 (8%) developed partial NAC necrosis, and all but one were able to be salvaged.

Lymph node core biopsies reliably permit diagnosis of lymphoproliferative diseases. Real-World Experience from 554 sequential core biopsies from a single centre.

INTRODUCTION: Whilst excision biopsy is traditionally preferred, advances in radiological and histological techniques warrant a re-look at core biopsy as a viable primary diagnostic method. METHOD: Over a 3-year period, all patients who underwent core biopsy to investigate lymphoma at our centre were included. RESULTS: 554 consecutive patients were included (40.1% prior lymphoma and 59.4% new presentations). Three or more cores were taken in 420 (75.8%) cases. Median time from request to biopsy and biopsy to histology report was 2 (0-40) days and 7 (1-24) days, respectively. 510/544 (93.8%) biopsies were diagnostic. There was no difference in whether the biopsy was diagnostic based on indication (new vs. relapsed lymphoma) (P = .445), whether biopsy was PET-directed (P = .507), for T-cell lymphoma (P = .468) or nodal vs. extra-nodal (P = .693). Thirty-eight patients (6.9%) required a second biopsy due to inadequate tissue. In a patient experience survey, only 13.9% reported any complications (1 self-limiting minor bleeding, 4 bruising) whilst 16.7% reported any discomfort beyond 12 hours. CONCLUSION: Core biopsy performed by experienced radiologists and analysed by expert haemato-pathologists is a reliable, well-tolerated method for diagnosing lymphoma and confirming relapse. Multiple cores can be obtained under local anaesthetic yielding sufficient material in the majority of cases.

Histone H3 Dynamics Reveal Domains with Distinct Proliferation Potential in the Arabidopsis Root.

A coordinated transition from cell proliferation to differentiation is crucial for organogenesis. We found that extensive chromatin reorganization, shown here for histone H3 proteins, characterizes cell population dynamics in the root developmental compartments. The canonical H3.1 protein, incorporated during S-phase, is maintained at high levels in cells dividing at a high rate but is massively evicted in cells undergoing their last cell cycle before exit to differentiation. A similar pattern was observed in the quadruple mutant for the H3.1-encoding genes HTR1, HTR2, HTR3, and HTR9 (htr1,2,3,9), in which H3.1 is expressed only from the HTR13 gene. H3 eviction is a fast process occurring within the G2 phase of the last cell cycle, which is longer than G2 in earlier cell cycles. This longer G2 likely contributes to lower the H3.1/H3.3 ratio in cells leaving the root meristem. The high H3.1/H3.3 ratio and H3.1 eviction process also occurs in endocycling cells before differentiation, revealing a common principle of H3 eviction in the proliferating and endocycling domains of the root apex. Mutants in the H3.1 chaperone CAF-1 (fas1-4) maintain a pattern similar to that of wild-type roots. Our studies reveal that H3 incorporation and eviction dynamics identify cells with different cell division potential during organ patterning.

Exploring titanium(IV) chemical proximity to iron(III) to elucidate a function for Ti(IV) in the human body.

Despite its natural abundance and widespread use as food, paint additive, and in bone implants, no specific biological function of titanium is known in the human body. High concentrations of Ti(IV) could result in cellular toxicity, however, the absence of Ti toxicity in the blood of patients with titanium bone implants indicates the presence of one or more biological mechanisms to mitigate toxicity. Similar to Fe(III), Ti(IV) in blood binds to the iron transport protein serum transferrin (sTf), which gives credence to the possibility of its cellular uptake mechanism by transferrin-directed endocytosis. However, once inside the cell, how sTf bound Ti(IV) is released into the cytoplasm, utilized, or stored remain largely unknown. To explain the molecular mechanisms involved in Ti use in cells we have drawn parallels with those for Fe(III). Based on its chemical similarities with Fe(III), we compare the biological coordination chemistry of Fe(III) and Ti(IV) and hypothesize that Ti(IV) can bind to similar intracellular biomolecules. The comparable ligand affinity profiles suggest that at high Ti(IV) concentrations, Ti(IV) could compete with Fe(III) to bind to biomolecules and would inhibit Fe bioavailability. At the typical Ti concentrations in the body, Ti might exist as a labile pool of Ti(IV) in cells, similar to Fe. Ti could exhibit different types of properties that would determine its cellular functions. We predict some of these functions to mimic those of Fe in the cell and others to be specific to Ti. Bone and cellular speciation and localization studies hint toward various intracellular targets of Ti like phosphoproteins, DNA, ribonucleotide reductase, and ferritin. However, to decipher the exact mechanisms of how Ti might mediate these roles, development of innovative and more sensitive methods are required to track this difficult to trace metal in vivo.

Companion cells: a diamond in the rough.

Vascular plants have developed highly specialized cells to transport nutrients and developmental signals. The differentiation process includes the degradation of multiple organelles of the sieve element cells (SEs) to facilitate transport and, as a consequence, SEs become dependent on neighboring companion cells (CCs). Despite its importance for phloem function and flowering time control, CCs are still a mysterious cell type. In this review, we gather all the genes known to be expressed in CCs, in different organs and organisms, with the objective of better understanding CC identity and function.

Anticonvulsant effect of sodium cyclamate and propylparaben on pentylenetetrazol-induced seizures in zebrafish.

Screening for novel anticonvulsant drugs requires appropriate animal seizure models. Zebrafish provide small, accessible, and cost-efficient preclinical models applicable to high-throughput small molecule screening. Based on previous results in rodents, we have here examined the effects of artificial sweetener sodium cyclamate and antimicrobial agent sodium propylparaben on a model of pentylenetetrazole (PTZ)-induced seizures in zebrafish. Sodium cyclamate reduced the bursts of hyperactivity, the spasms, increased the latency to spasms, and the latency to seizure, while propylparaben increased the latency to spasms. The results show the potential of zebrafish to detect novel anticonvulsant compounds while they also demonstrate the ability of two commonly ingested chemical compounds to modify the seizure threshold when were administrated at low concentration.

Genome-wide analysis of histone H3.1 and H3.3 variants in Arabidopsis thaliana.

Nucleosomes package eukaryotic DNA and are composed of four different histone proteins, designated H3, H4, H2A, and H2B. Histone H3 has two main variants, H3.1 and H3.3, which show different genomic localization patterns in animals. We profiled H3.1 and H3.3 variants in the genome of the plant Arabidopsis thaliana and found that the localization of these variants shows broad similarity in plants and animals, along with some unique features. H3.1 was enriched in silent areas of the genome, including regions containing the repressive chromatin modifications H3 lysine 27 methylation, H3 lysine 9 methylation, and DNA methylation. In contrast, H3.3 was enriched in actively transcribed genes, especially peaking at the 3' end of genes, and correlated with histone modifications associated with gene activation, such as histone H3 lysine 4 methylation and H2B ubiquitylation, as well as RNA Pol II occupancy. Surprisingly, both H3.1 and H3.3 were enriched on defined origins of replication, as was overall nucleosome density, suggesting a novel characteristic of plant origins. Our results are broadly consistent with the hypothesis that H3.1 acts as the canonical histone that is incorporated during DNA replication, whereas H3.3 acts as the replacement histone that can be incorporated outside of S-phase during chromatin-disrupting processes like transcription.

Histone H3 dynamics in plant cell cycle and development.

Chromatin is a macromolecular complex where DNA associates with histone proteins and a variety of non-histone proteins. Among the 4 histone types present in nucleosomes, histone H3 is encoded by a large number of genes in most eukaryotic species and is the histone that contains the largest variety of potential post-translational modifications in the N-terminal amino acid residues. In addition to centromeric histone H3, 2 major types of histone H3 exist, namely the canonical H3.1 and the variant H3.3. In this article, we review the most recent observations on the distinctive features of plant H3 proteins in terms of their expression and dynamics during the cell cycle and at various developmental stages. We also include a discussion on the histone H3 chaperones that actively participate in H3 deposition, in particular CAF-1, HIRA and ASF1, and on the putative plant homologs of human ATRX and DEK chaperones. Accumulating evidence confirms that the balanced deposition of H3.1 and H3.3 is of primary relevance for cell differentiation during plant organogenesis.

Resistance in cholinesterase activity after an acute and subchronic exposure to azinphos-methyl in the freshwater gastropod Biomphalaria straminea.

Organophosphorous and carbamates insecticides are ones of the most popular classes of pesticides used in agriculture. Its success relies on their high acute toxicity and rapid environmental degradation. These insecticides inhibit cholinesterase and cause severe effects on aquatic non-target species, particularly in invertebrates. Since the properties of cholinesterases may differ between species, it is necessary to characterize them before their use as biomarkers. Also organophosphorous and carbamates inhibit carboxylesterases and the use of both enzymes for biomonitoring is suggested. Azinphos-methyl is an organophosphorous insecticide used in several parts of the word. In Argentina, it is the most applied insecticide in fruit production in the north Patagonian region. It was detected with the highest frequency in superficial and groundwater of the region. This work aims to evaluate the sensitivity of B. straminea cholinesterases and carboxylesterases to the OP azinphos-methyl including estimations of 48 h NOEC and IC50 of the pesticide and subchronic effects at environmentally relevant concentrations. These will allow us to evaluate the possibility of using cholinesterase and carboxylesterase of B. straminea as sensitive biomarkers. Previously a partial characterization of these enzymes will be performed. As in most invertebrates, acetylthiocholine was the preferred hydrolyzed substrate of B. straminea ChE, followed by propionylthiocholine and being butyrylthiocholine hydrolysis very low. Cholinesterase activity of B. straminea was significantly inhibited by the selective cholinesterases inhibitor (eserine) and by the selective inhibitor of mammalian acethylcholinesterase (BW284c51). In contrast, iso-OMPA, a specific inhibitor of butyrylcholinesterase, did not inhibit cholinesterase activity. These results suggest that cholinesterase activity in total soft tissue of B. straminea corresponds to acethylcholinesterase. Carboxylesterases activity was one order of magnitude higher than cholinesterase. A greater efficiency (Vmax/Km) was obtained using acetylthiocholine and p-nitrophenyl butyrate. Acute exposure to azinphos-methyl did not cause inhibition of cholinesterase activity until 10 mg L(-1) used. Carboxylesterases towards p-nitrophenyl butyrate was inhibited by azinphos-methyl being the IC502.20±0.75 mg L(-1) of azinphos-methyl. Subchronic exposure to environmental concentrations of azinphos-methyl (0.02 and 0.2 mg L(-1)) produced a decrease in survival, protein content and carboxylesterases activity despite no inhibition of cholinesterase activity was observed. B. straminea cholinesterase is not a sensible biomarker. On the contrary, carboxylesterases activity was inhibited by azinphos-methyl. Carboxylesterases could be protecting cholinesterase activity and therefore, protecting the organism from neurotoxicity. This work confirms the advantages of measuring cholinesterases and carboxylesterases jointly in aquatic biomonitoring of pesticide contamination. This becomes relevant in order to find more sensitive biomarkers and new strategies to protect non-target aquatic organisms from pesticide contamination.

Merit-Based Incentive Payment System: How Are Plastic Surgeons Performing?

PURPOSE: Merit-based incentive payment system (MIPS) is a payment model implemented to promote high-value care through performance-based adjustments of Medicare reimbursements. Higher scores indicate superior performance in healthcare quality, efficiency, and interoperability, which can result in financial advantages. Given the paucity of literature, we aimed to characterize plastic surgery performance in MIPS. METHOD: The Centers for Medicare and Medicaid Services (CMS) online data repository was queried for data on MIPS performance of plastic surgeons from 2019-2021. Descriptive analyses and multivariable logistic regression were conducted to identify predictors of receiving bonus payment for exceptional performance. RESULTS: Approximately 1400 surgeons were sampled in each year. The median number of Medicare beneficiaries and percent of dually eligible beneficiaries-eligible for Medicare and Medicaid-were higher in 2019 (p<0.001). Beneficiary median HCC risk score, which measures expected healthcare costs and needs based on health status, was lower in 2021 (p<0.001). The most common reporting schema was reporting as a group. Total MIPS score increased from 2019 to 2020 to 2021 (90.2 vs 96.4 vs 98.3, p<0.001), but quality score progressively decreased (98.8 vs 95.5 vs 89.90, p<0.001). Fewer physicians received positive adjustment and bonus payments in 2020 and 2021. Predictors of receiving bonus payments were reporting as an alternative payment model, practice size >24, and having 10-49% of dually eligible beneficiaries (p<0.05). CONCLUSION: Understanding performance of plastic surgeons in MIPS can guide future policy direction and ensure that high-quality care translates into improved patient outcomes across all fields and levels of social vulnerability.

Auxin and epigenetic regulation of SKP2B, an F-box that represses lateral root formation.

In plants, lateral roots originate from pericycle founder cells that are specified at regular intervals along the main root. Here, we show that Arabidopsis (Arabidopsis thaliana) SKP2B (for S-Phase Kinase-Associated Protein2B), an F-box protein, negatively regulates cell cycle and lateral root formation as it represses meristematic and founder cell divisions. According to its function, SKP2B is expressed in founder cells, lateral root primordia and the root apical meristem. We identified a novel motif in the SKP2B promoter that is required for its specific root expression and auxin-dependent induction in the pericycle cells. Next to a transcriptional control by auxin, SKP2B expression is regulated by histone H3.1/H3.3 deposition in a CAF-dependent manner. The SKP2B promoter and the 5' end of the transcribed region are enriched in H3.3, which is associated with active chromatin states, over H3.1. Furthermore, the SKP2B promoter is also regulated by H3 acetylation in an auxin- and IAA14-dependent manner, reinforcing the idea that epigenetics represents an important regulatory mechanism during lateral root formation.

Different effects of subchronic exposure to low concentrations of the organophosphate insecticide chlorpyrifos in a freshwater gastropod.

Chlorpyrifos is an organophosphate insecticide used for pest control on a number of food crops in many parts of the world. In recent years, there has been an important decrease in the number of organisms of Planorbarius corneus. Since the presence of pesticides in the water can be one of the reasons for this decrease, it is very important to study the effect of subchronic exposure to environmental concentrations of pesticides on these organisms. The aim of the present work was to investigate different effects of the subchronic exposure to low concentrations of the organophosphate chlorpyrifos in P. corneus and the possibility to use these as biomarkers. To this end, we have exposed the organisms to 0.4 and 5 µg L(-1) of chlorpyrifos for 14 days and recorded the number of egg masses, the number of eggs per mass, the number of eggs without embryo, the time for hatching, and the % of hatching and survival. We have also determined the activities of cholinesterases, carboxylesterases and glutathione S-transferase in whole organism soft tissue and in the gonads. A 14 days exposure to 0.4 µg L(-1) caused an increase in the number of egg masses without eggs and a decrease in carboxylesterases measured with p-nitrophenyl butyrate. However the exposure to 5 µg L(-1) also caused an increase in the time for hatching, a decrease in the % of hatching and survival and also inhibition of cholinesterases and carboxylesterases with p-nitrophenyl acetate and butyrate. In contrast, the glutathione S-transferase has not been modified with the tested concentrations. We concluded that when P. corneus exposed to chlorpyrifos for 14 days, the CES determined with p-nitrophenyl butyrate proved to be the most sensitive biomarker. However, exposure to environmental concentrations showed a decrease in the reproduction ability which could cause a decrease in the number of organisms of this species.

Putative pectate lyase PLL12 and callose deposition through polar CALS7 are necessary for long-distance phloem transport in Arabidopsis.

In plants, the phloem distributes photosynthetic products for metabolism and storage over long distances. It relies on specialized cells, the sieve elements, which are enucleated and interconnected through large so-called sieve pores in their adjoining cell walls. Reverse genetics identified PECTATE LYASE-LIKE 12 (PLL12) as critical for plant growth and development. Using genetic complementations, we established that PLL12 is required exclusively late during sieve element differentiation. Structural homology modeling, enzyme inactivation, and overexpression suggest a vital role for PLL12 in sieve-element-specific pectin remodeling. While short distance symplastic diffusion is unaffected, the pll12 mutant is unable to accommodate sustained plant development due to an incapacity to accommodate increasing hydraulic demands on phloem long-distance transport as the plant grows-a defect that is aggravated when combined with another sieve-element-specific mutant callose synthase 7 (cals7). Establishing CALS7 as a specific sieve pore marker, we investigated the subcellular dynamics of callose deposition in the developing sieve plate. Using fluorescent CALS7 then allowed identifying structural defects in pll12 sieve pores that are moderate at the cellular level but become physiologically relevant due to the serial arrangement of sieve elements in the sieve tube. Overall, pectin degradation through PLL12 appears subtle in quantitative terms. We therefore speculate that PLL12 may act as a regulator to locally remove homogalacturonan, thus potentially enabling further extracellular enzymes to access and modify the cell wall during sieve pore maturation.