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Finding an easily accessible and reliable tool to diagnose the diseases collectively defined as ‘synucleinopathies’ is an urgent, unmet priority. The synucleinopathies include Parkinson's disease, multiple system atrophy, pure autonomic failure and dementia with Lewy bodies. There are millions of people who have a diagnosis of a synucleinopathy, with more diagnosed every year. With accessibility, ease of implementation, consistently high sensitivity (>80%) and specificity approaching 100%, skin biopsy has great potential as the clinical test of choice for the diagnosis of synucleinopathies. The large, multi-center Synuclein-One study will determine the sensitivity, specificity, accuracy and precision of α-synuclein detection within punch skin biopsies in patients with clinically established synucleinopathies using standardized, robust methods suitable for large-scale analysis. Clinical Trial Registration: NCT04700722 ( ClinicalTrials.gov )

The potential infectivity of SARS-CoV-2 in animals raises a public health and economic concern, particularly the high susceptibility of white-tailed deer (WTD) to SARS-CoV-2. The disparity in the disease outcome between humans and WTD is very intriguing, as the latter are often asymptomatic, subclinical carriers of SARS-CoV-2. To date, no studies have evaluated the innate immune factors responsible for the contrasting SARS-CoV-2-associated disease outcomes in these mammalian species. A comparative transcriptomic analysis in primary respiratory epithelial cells of human (HRECs) and WTD (Deer-RECs) infected with SARS-CoV-2 was assessed throughout 48 hours post inoculation (hpi). Both HRECs and Deer-RECs were susceptible to SARS-COV-2, with significantly (P< 0.001) lower virus replication in Deer-RECs. The number of differentially expressed genes (DEG) gradually increased in Deer-RECs but decreased in HRECs throughout the infection. The ingenuity pathway analysis of DEGs further identified that genes commonly altered during SARS-CoV-2 infection mainly belong to cytokine and chemokine response pathways mediated via IL-17 and NF-κB signaling pathways. Inhibition of the NF-κB signaling in the Deer-RECs pathway was predicted as early as 6 hpi. The findings from this study could explain the lack of clinical signs reported in WTD in response to SARS-CoV-2 infection as opposed to the severe clinical outcomes reported in humans.HIGHLIGHTSWhite-tailed deer primary respiratory epithelial cells are susceptible to SARS- CoV-2 without causing hyper cytokine gene expression.Downregulation of IL-17 and NF-κB signaling pathways after SARS-CoV-2 infection could be key to the regulated cytokine response in deer cells.Deer innate immune system could play a critical role in early antiviral and tissue repair response following SARS-CoV-2 infection.

The American Association of Thoracic Surgery published guidelines in 2018 encouraging regular surveillance rather than surgical intervention for ascending aortic aneurysms under 5.5 cm in both bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) patients. Since then, there have been limited studies reporting outcomes, especially by valve type. We aimed to analyze clinical outcomes including survival and aortic events in a cohort of BAV and TAV patients with ascending aortic aneurisms followed conservatively with routine computerized tomography (CT) surveillance per current guidelines.We followed 188 patients in our clinic between 2016 and 2019; 147 had two or more CT scans which allowed measurement of aortic growth. Echocardiogram data was evaluated for each patient. We identified similar cohorts of BAV (n = 32) and TAV (n = 64) patients matched by age, sex, hypertension, smoking history, family history of aortic disease, coronary artery disease, and hyperlipidemia. Univariate and multivariate analyses of the unmatched cohorts were performed.The mean aneurysm size was 4.3 ± 0.58 cm with 95% confidence interval (3.14, 5.46). This did not differ between BAV and TAV patients, nor did aneurysm growth rates. Overall adverse event rate (dissection, rupture, and death) was low for the entire cohort (BAV group, 3% and TAV group, 3.5%). Survival at 10 years for the entire cohort was 90 ± 32%.Regardless of aortic valve type, there was a similar natural history and low adverse event rate. In the absence of risk factors, conservative management can be accomplished with minimal risk to the patient.

Compatibility between the rubber material of radial shaft seals and the lubricants to be sealed is an important requirement that customers demand of their lubricant suppliers. Among other effects that may result from incompatibility, the penetration of lubricant components into the rubber (swelling) can impair the seal's functionality due to changes in its geometry and mechanical behavior. Typically, the penetration of a lubricant into an elastomer is evaluated after an immersion test using volumetric, gravimetric, and extraction measurements. Due to the small changes that need to be detected, such methods may not be sufficient to obtain meaningful results. In this contribution, we use magnetic resonance imaging (MRI) to investigate swelling on special tribometer samples as well as a radial shaft seal that were previously used in component tests. Several combinations of rubbers and lubricants that have proven to be compatible were tested in addition to combinations with expected incompatibilities in real applications. The results indicate that MRI measurements can be used to quantify the penetration depth and potentially also the velocity with which the lubricant diffuses into the rubber, thereby yielding detailed insights into the swelling process of the seal.

Osteomyelitis of the patella is a rare disease primarily affecting the pediatric population. Because it often presents with nonspecific symptoms, such as fever and pain, the diagnosis and treatment can be delayed. Prepatellar septic bursitis is also rare in the pediatric population; if left untreated it can progress to patella osteomyelitis. We present a case of prepatellar bursitis that progressed to septic knee arthritis and severe patella osteomyelitis in a 5-year-old male patient. This case demonstrates the importance of further evaluation and close follow up of suspected prepatellar bursitis in pediatric patients with consideration of magnetic resonance imaging (MRI) to monitor for early patella osteomyelitis, an uncommon but treatable disease.

Unilateral coronal craniosynostosis (UCS) is a congenital disorder resulting from the premature suture fusion, leading to complex primary and compensatory morphologic changes in the shape of not only the calvarium and but also into the skull base. This deformity typically requires surgery to correct the shape of the skull and prevent neurologic sequelae, including increased intracranial pressure, sensory deficits, and cognitive impairment.The present multicenter study sought to reverse-engineer the bone dysmorphogenesis seen in non-syndromic UCS using a geometric morphometric approach. Computed tomography scans for 26 non-syndromic UCS patients were converted to three-dimensional mesh models. Two hundred thirty-six unique anatomical landmarks and semi-landmarked curves were then plotted on each model, creating wireframe representations of the Patients' skulls.Generalized Procrustes superimposition, Principal Component Analysis, and heatmaps identified significant superior displacement of the ipsilateral orbit ("harlequin" eye deformity), anterior displacement of the ear ipsilateral to the fused coronal suture, acute deviation of midline skull base structures ipsilateral to the fused coronal suture and flattening of the parietal bone and associated failure to expand superiorly.The described technique illustrates the impact of premature coronal suture fusion on the development of the entire skull and proposes how bone dysmorphology contributes to the Patients' neurologic sequelae. By bridging novel basic science methodologies with clinical research, the present study quantitatively describes craniofacial development and bone dysmorphogenesis.

This case is based on the 2020 merger between Callaway Golf Company, a leader in the golf equipment and apparel industry, and Topgolf Entertainment Group, the top entertainment brand in the golf industry. Mergers have been known to provide greater efficiency and profitability, but they can also initiate a clash of corporate cultures, creating conflict which may result in a loss of employee satisfaction and brand equity. Along with reviewing the industry and potential outcomes, students will analyze the viability of this merger by conducting a value chain analysis of both companies to look for product alignment. This decision-based case asks students to play the role of Callaway Golf board member Sophia Berckman, who is preparing to make a statement on the prospective merger of the two companies at an emergency board meeting. As such, students will be expected to formulate a recommendation to the board of directors on whether this is a wise business decision using the information provided.

Marginalized patients including those with limited English proficiency (LEP) are at risk of seeing graver health outcomes across many specialties. Communication barriers contribute to impaired shared-decision making and missed education opportunities. Tools are available to clinicians to allow for more accurate and effective education and to facilitate shared decision-making. This article reviews existing guidelines for utilization of professional interpreters. A framework is provided for pre-visit planning, facilitating appropriate introductions, and setting up a clinic room to optimize workflow. Suggestions are provided for utilizing professional interpreters efficiently and prioritizing patient autonomy, respect, and mutual understanding. Pediatric orthopaedic surgeons and providers can promote health equity by utilizing professional interpreters and using other strategies to communicate effectively with patients and families from diverse backgrounds and/or those who have LEP.

The objective of this study was to understand the role of Cosmopolites sordidus in the dispersal of Fusarium oxysporum f. sp. cubense race 1 (Foc) and more specifically to determine whether C. sordidus is preferentially attracted to Foc-contaminated banana plant material vs. Foc-free material. The attraction of C. sordidus to healthy and Foc-contaminated Gros Michel banana bulbs and pseudostems, as well as to pure cultures of Foc, was compared using four-choice olfactometers. Males and females were studied separately. After storage in a dark room, weevils were placed in the central chamber of olfactometers. After 15 min, the orientation of each of the weevil was determined according to the food source located in each of the four peripheral chambers of the olfactometer. Overall, 560 olfactometer assays were carried out. Weevils were found to prefer Foc-infected plant tissues. Weevil preference was not significantly affected by weevil sex. The attraction of C. sordidus to Foc-contaminated plant material suggests that this insect could be important for the dissemination of Foc, especially in early stages of epidemics, when Foc-infected plants are scarce.

Les objectifs de réduction des produits phytopharmaceutiques portés par le plan Ecophyto Il+ apportent de nouveaux défis à I' Agriculture. L'enjeu de l'Axe 2 Recherche & Innovation est de mobiliser l'ensemble du système de recherche-innovation afin d'apporter les connaissances nécessaires pour les relever et d'appuyer les politiques publiques dans la transition vers un modèle agroécologique des cultures. Cet axe est piloté et orienté par un Comité Scientifique d'Orientation {CSO R&I). Le document " Héritage CSO R&I " dresse un bilan et une analyse synthétiques des actions conduites par les membres du CSO R&I lors du mandat 2019-2022. Il met en perspective les réflexions scientifiques stratégiques, leurs concrétisations en actions (appels à projets, animation scientifique, valorisation ... ), les freins rencontrés et les perspectives pour le prochain mandat 2023-2026.

Quantifying the effect of landscape composition on disease dynamics remains challenging because it depends on many factors. In this study, we used a hybrid process-based/statistical modeling approach to separate the effect of the landscape composition on the epidemiology of banana leaf streak disease (BLSD) from weather and fungicide effects. We parameterized our model with a 5-year dataset, including weekly measures of BLSD on 83 plots in Martinique. After estimating the intrinsic growth parameters of the stage evolution of the disease (SED), we evaluated the dynamic effect of five fungicides. Then, we added the intra- and inter-annual effect on disease dynamics using a generalized linear model. Finally, the whole model was used to assess the annual effect of the landscape on the SED for 11 plots. We evaluated the significance of the landscape composition (proportions of landscape elements in 200-, 500-, 800-, 1,000-m-radius buffer zones) on the landscape effect evaluated with the model. The percentage of hedgerows in a 200-m-radius buffer zone was negatively correlated to the landscape effect, i.e., it acted as a constraint against BLSD spreading and development. The proportion of managed-banana-plants in a 1,000-m-radius buffer zone was negatively correlated to the landscape effect, probably due to a mass effect of fungicide treatments. Inversely, the proportions of forest and the proportion of unmanaged-banana-plants, both in 1,000-m-radius buffer zones, were positively correlated with the landscape effect. Our study provides a holistic approach of the role biotic and abiotic factors play on the dynamics of BLSD.

The ability of SARS-CoV to infect different species, including humans, dogs, cats, minks, ferrets, hamsters, tigers, and deer, pose a continuous threat to human and animal health. Pigs, though closely related to humans, seem to be less susceptible to SARS-CoV-2. Former in vivo studies failed to demonstrate clinical signs and transmission between pigs, while later attempts using a higher infectious dose reported viral shedding and seroconversion. This study investigated species-specific cell susceptibility, virus dose-dependent infectivity, and infection kinetics, using primary human (HRECs) and porcine (PRECs) respiratory epithelial cells. Despite higher ACE2 expression in HRECs compared to PRECs, SARS-CoV-2 infected, and replicated in both PRECs and HRECs in a dose-dependent manner. Cytopathic effect was particularly more evident in PRECs than HRECs, showing the hallmark morphological signs of apoptosis. Further analysis confirmed an early and enhanced apoptotic mechanism driven through caspase 3/7 activation, limiting SARS-CoV-2 propagation in PRECs compared to HRECs. Our findings shed light on a possible mechanism of resistance of pigs to SARS-CoV-2 infection, and it may hold therapeutic value for the treatment of COVID-19.

Introduction: Within the surgical management algorithm for frontal sinus fracture (FSF), the choice of material for nasofrontal duct (NFD) obliteration is controversial, and a multitude of materials have been described in the literature. The present study aims to perform a systematic review to determine postoperative outcomes associated with various NFD obliteration materials. Methods: Two independent reviewers identified studies to be included based on inclusion and exclusion criteria. Odds ratios and Fisher’s Exact Tests were then used to compare outcomes between cohorts based on the material used for NFD obliteration. Complications under review included donor site complications, reoperations, frontal sinus infections, cerebrospinal fluid leaks, cosmetic defects, persistent pain and/or headaches, and mucocele formation. Results: Twenty-nine studies met inclusion criteria. The use of a vascularized flap was associated with a reduced risk of reoperation and postoperative frontal sinus infection compared with non-flap materials (OR = 0.23 (CI: 0.05, 1.04), P = .05. The use of avascular bone graft was associated with an increased risk of reoperation (OR = 8.89 (CI: 2.24, 29.94), P

PURPOSE The purpose of this study is to analyze posts shared on Instagram, Twitter, and Reddit referencing scoliosis surgery to evaluate content, tone, and perspective. METHODS Public posts from Instagram, Twitter, and Reddit were parsed in 2020-2021 and selected based on inclusion of the words 'scoliosis surgery' or '#scoliosissurgery. 100 Reddit posts, 5022 Instagram posts, and 1414 tweets were included in analysis. The Natural Language Toolkit (NLTK) python library was utilized to perform computational text analysis to determine content and sentiment analysis to estimate the tone of posts across each platform. RESULTS 46.4% of Tweets were positive in tone, 39.4% were negative, and 13.8% were neutral. Positive content focused on patients, friends, or hospitals sharing good outcomes after a patient's surgery. Negative content focused on long wait times to receive scoliosis surgery. 64.7% of Instagram posts were positive in tone, 16.3% were negative, and 19.0% were neutral. Positive content centered around post-operative progress reports and educational resources, while negative content focused on long-term back pain. 37% of Reddit posts were positive in tone, 38% were negative, and 25% were neutral. Positive posts were about personal post-operative progress reports, while negative posts were about fears prior to scoliosis surgery and questions about risks of the procedure. CONCLUSION This study highlights scoliosis surgery content in social media formats and stratifies how this content is portrayed based on the platform it is on. Surgeons can use this knowledge to better educate and connect with their own patients, thus harnessing the power and reach of social media. LEVEL OF EVIDENCE IV.

The pathophysiology of Meniere's Disease (MD) involves endolymphatic hydrops (ELH) of the inner ear. Magnetic Resonance Imaging (MRI) has been shown to detect ELH, but changes in ELH have been poorly described using this modality. Our objective was to review MRI-measured changes in ELH over time and after medical and/or surgical intervention in patients with MD. We secondarily aim to associate changes in ELH with changes in MD symptomatology.Medline, Web of Science, and Embase databases.A systematic review of articles was performed to identify studies utilizing MRI to measure ELH changes over time, and after medical or surgical treatment. Articles on non-human subjects and without direct measurement of ELH were excluded.Of 532 studies identified, 12 were included, involving 170 patients (mean age 56.3 years). Ten studies were prospective; two were retrospective. Five studies strictly utilized medical means of intervention, four utilized surgical treatments, one utilized both, and two observed temporal changes without treatment. Across all interventions, 72.1 % of patients exhibited the same or worsening ELH on imaging. In studies reporting vertigo outcomes, 95.9 % of patients exhibited improvement after the treatment period.Medical and surgical interventions often yield symptomatic relief of vertigo in MD patients despite stable or increasing ELH volume. MRI may have greater clinical utility in diagnosing ELH as opposed to assessing treatment response.

This year is the 80th anniversary of the Women's Army Auxiliary Corps. The passage of this seminal legislation - sponsored by Edith Nourse Rogers - formalized the role of women in the US military and compensated them for their service and in the event of injury or illness. Rogers was a pioneer in her own right. A trailblazer for women and a staunch advocate for military veterans' healthcare, Rogers was forged by her wartime experiences. The authors describe Rogers' contributions as a congresswoman during World War II and during her 35 years of public service in the House of Representatives. Congresswoman Rogers was foundational to the modern US healthcare system.

Surgical coaching is a form of mentoring that can improve surgical performance. While professional athletes have coaching their entire career, other professions, such as medicine, law, and education, are expected to manage their own improvement in performance over their careers. Methods of surgical coaching and the pros and cons of coaching to improve surgical performance and improve patient safety will be presented.

While the risks and benefits of smooth versus textured implants for breast reconstruction and primary breast augmentation are thoroughly supported in the literature, few studies have examined the relationship between implant shell texture and complications following direct-to-implant (DTI) breast reconstruction. The present study examines the relationship between implant shell texture and complications in patients receiving DTI breast reconstruction. Retrospective chart review of patients undergoing DTI breast reconstruction between 2011 and 2018 by a single surgeon was performed. A propensity score matching algorithm was used to eliminate unwanted bias stemming from clinical covariates. Chi-squared and Fisher’s exact tests were used to examine the association between implant shell texture and the following major postoperative complications: capsular contracture, hematoma, seroma, necrosis, infection, and implant loss. A total of 402 unique patients (751 breasts) were included. The majority received smooth implants compared with textured implants (80.3% vs. 19.7%, respectively); 444 breasts were included for comparative analysis after 2:1 propensity score matching (296 smooth implants, 148 textured implants). The only statistically significant difference in outcomes between the two groups was a higher incidence of hematoma in the textured group (2.0% vs 0.0%), Fisher’s Exact Test p = 0.04. Additionally, the matched cohort revealed a very low overall rate of capsular contracture (1.0%) for smooth implants. Our data demonstrated non-significant differences for most major complication rates or revision surgery rates for smooth versus textured implants after matching. DTI breast reconstruction with smooth implants remains a safe and effective reconstructive option for select patients. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine Ratings, please refer to Table of Contents or online Instructions to Authors www.springer.com/00266 .

Bacillus anthracis, the causative agent of anthrax, continues to be a prominent biological warfare and bioterrorism threat. Vaccination is likely to remain the most effective and user-friendly public health measure to counter this threat in the foreseeable future. The commercially available AVA BioThrax vaccine has a number of shortcomings where improvement would lead to a more practical and effective vaccine for use in the case of an exposure event. Identification of more effective adjuvants and novel delivery platforms is necessary to improve not only the effectiveness of the anthrax vaccine, but also enhance its shelf stability and ease-of-use. Polyanhydride particles have proven to be an effective platform at adjuvanting the vaccine-associated adaptive immune response as well as enhancing stability of encapsulated antigens. Another class of adjuvants, the STING pathway-targeting cyclic dinucleotides, have proven to be uniquely effective at inducing a beneficial inflammatory response that leads to the rapid induction of high titer antibodies post-vaccination capable of providing protection against bacterial pathogens. In this work, we evaluate the individual contributions of cyclic di-GMP (CDG), polyanhydride nanoparticles, and a combination thereof towards inducing neutralizing antibody (nAb) against the secreted protective antigen (PA) from B. anthracis. Our results show that the combination nanovaccine elicited rapid, high titer, and neutralizing IgG anti-PA antibody following single dose immunization that persisted for at least 108 DPI.

Background Peripheral nerve injuries (PNIs) are most commonly treated with direct nerve repair procedures or nerve autografts. However, recent advancements in synthetic and vein conduits have led to their increased utilization. The present study quantifies the incidence of these procedures over time and geography and identifies differences in complication rates, illustrating the current epidemiologic climate regarding conduit use for PNI repair. Methods A query was conducted using the State Ambulatory Surgery and Services Databases data from 2006 to 2011 in both Florida and California for patients undergoing nerve repair, nerve grafting, synthetic conduits, and vein conduits. Patient zip code data were analyzed to determine the geographic distribution of various types of repair. In addition, text-mining algorithms were used to identify trends in PNI-related publications. Results In the 6-year period investigated, direct nerve repair was the most frequently used procedure for PNIs. However, the utilization of direct repairs declined significantly from 2006 to 2011. Synthetic and vein conduits demonstrated a significant increase over the same period. There were significantly higher rates of complications for autologous grafts (3.3%), vein conduits (3.5%), and synthetic conduits (2.4%), as compared with direct nerve repairs (1.4%). There was a nonsignificant difference in infection rates between these types of nerve repair. Conclusions From an epidemiologic perspective, both graft and synthetic conduit-based PNI repairs are increasing in prevalence both in clinical practice and in the academic literature. This will likely continue in the future with the development of advancements in biologic and synthetic nerve conduit PNI repair options.

BACKGROUND Pseudocercospora fijiensis is the causal agent of the black leaf streak disease (BLSD) of banana. Bananas are important global export commodities and a major staple food. Their susceptibility to BLSD pushes disease management towards excessive fungicide use, largely relying on multisite inhibitors and sterol demethylation inhibitors (DMIs). These fungicides are ubiquitous in plant disease control, targeting the CYP51 enzyme. We examined sensitivity to DMIs in P. fijiensis field isolates collected from various major banana production zones in Colombia, Costa Rica, Dominican Republic, Ecuador, the Philippines, Guadalupe, Martinique and Cameroon and determined the underlying genetic reasons for the observed phenotypes. RESULTS We observed a continuous range of sensitivity towards the DMI fungicides difenoconazole, epoxiconazole and propiconazole with clear cross‐sensitivity. Sequence analyses of PfCYP51 in 266 isolates showed 28 independent amino acid substitutions, nine of which correlated with reduced sensitivity to DMIs. In addition to the mutations, we observed up to six insertions in the Pfcyp51 promoter. Such promoter insertions contain repeated elements with a palindromic core and correlate with the enhanced expression of Pfcyp51 and hence with reduced DMI sensitivity. Wild‐type isolates from unsprayed bananas fields did not contain any promoter insertions. CONCLUSION The presented data significantly contribute to understanding of the evolution and global distribution of DMI resistance mechanisms in P. fijiensis field populations and facilitate the prediction of different DMI efficacy. The overall reduced DMI sensitivity calls for the deployment of a wider range of solutions for sustainable control of this major banana disease. © 2021 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., Studies on Pseudocercospora fijiensis demethylation inhibitor (DMI) sensitivity shows that Pfcyp51 modulations correlated with fungicide resistance. The importance of amino acid substitutions at positions 137, 311, 378, 379 and 458–461 is strengthened by mathematical modelling. Changes in these positions compromise the three‐dimensional structure of the protein resulting in an affinity change. The presence of repeated elements and insertions in the promotor region of Pfcyp51 was also positively correlated with resistance to DMIs. © 2021 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Background With the undergoing world outbreak of Fusarium wilt of bananas, it is essential to unravel all the possible process of dissemination of this disease. The host-pest interactions of the banana weevil with banana plants make this insect an important potential vector. This study, carried out in controlled conditions, explores the interaction between the banana weevil and Fusarium oxysporum f.sp. cubense race 1 (Foc), with a focus on the external and internal transport of viable fungal propagules. Results Viable inoculum of Foc was detected very rapidly on external teguments and in the digestive tract of the insect, i.e. at the lowest time studied of 5 min after contact with infected pseudostems. Maximal inoculum acquisition occurred after 1 h contact with an inoculum source. External inoculum was higher than the inoculum present in the digestive tract, but external and internal inoculum had the same dynamics. After a contact of an infected source, external and internal inoculum decreased exponentially within 50 h, but weevils remained infested for a long time, as long as 2 or 3 days that would be enough for inoculum dispersal. Viable inoculum was also detected in feces. Foc strains isolated were pathogenic when inoculated to banana plants of the Gros Michel variety but did not provoke any symptom on Cavendish banana plants. Conclusion These results demonstrate that the infective structures of Foc remain externally viable in the digestive system and the excreta of the banana weevil. Such excreta are capable of making healthy banana plants of the Gros Michel variety. © 2021 Society of Chemical Industry.

OBJECTIVEEndoscopic surgery is an effective treatment strategy for pituitary adenomas; however, intrinsic tumor properties such as tumor consistency can challenge or preclude gross-total resection. Preoperative characterization of tumor consistency may help to guide the surgical approach and to predict the extent of resection that is possible. Advanced radiological modalities such as 7T diffusion-weighted imaging (DWI) may be useful in probing biological tissue properties of pituitary adenomas. The objective of the present study was to examine 7T DWI as a novel method of measuring the consistency of pituitary adenomas.METHODSThirteen patients with pituitary macroadenomas underwent 7T MRI, including a DWI image acquisition. Tumor apparent diffusion coefficient (ADC) was normalized to the adjacent temporal gray matter ADC. All patients underwent resection, and a single neurosurgeon blinded to ADC values rated tumor firmness from 1 (least firm) to 5 (most firm) using objective criteria. The tumor specimens were evaluated histopathologically for cellularity, collagen content, and vascularity by a neuropathologist who was also blinded to ADC values. The tumor ADC was correlated with intraoperative consistency rating, histopathology, and extent of resection. Receiver operating characteristic (ROC) curve analyses were performed to identify thresholds to predict tumor consistency.RESULTSCorrected ADC values were significantly correlated with both tumor firmness (r = −0.60, p = 0.029) and the extent of trichrome staining (r = −0.72, p = 0.009) such that greater ADC values were associated with both decreased tumor firmness and decreased collagen staining. Correlations between ADC values and tumor vascularity were not significant (r = −0.09, p = 0.78). Corrected ADC values in totally resected tumors (1.54) were greater than those in subtotally resected tumors (0.85) (p = 0.02), and ADC values were greater with moderate tumor cellularity (1.51) than with high tumor cellularity (0.8) (p = 0.035). There was a trend-level association for partial resections to exhibit greater tumor firmness rating (3 vs 1.7; p = 0.051). Finally, the degree of trichrome staining positively correlated with tumor firmness (r = 0.60, p = 0.04). The optimal threshold for predicting intraoperative consistency rating was an ADC ratio of 0.87 (sensitivity 80%, specificity 100%, area under the curve [AUC] 0.90; p = 0.043). The optimal cutoff for distinguishing the extent of resection was 1.19 (sensitivity 85.7%, specificity 83.3% AUC 0.833; p = 0.046).CONCLUSIONSThe authors’ results suggest that a high-resolution ADC of pituitary adenomas is a sensitive measure of tumor consistency. 7T DWI may hold clinical value in the preoperative workup and surgical management of patients with pituitary macroadenomas.

Human coronavirus (HCoV)-NL63 is an important contributor to upper and lower respiratory tract infections, mainly in children, while severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, can cause lower respiratory tract infections, and more severe, respiratory and systemic disease, which leads to fatal consequences in many cases. Using microscopy, immunohistochemistry (IHC), virus-binding assay, reverse transcriptase qPCR (RT-qPCR) assay, and flow cytometry, we compared the characteristics of the susceptibility, replication dynamics, and morphogenesis of HCoV-NL63 and SARS-CoV-2 in monolayer cultures of primary human respiratory epithelial cells (HRECs). Less than 10% HRECs expressed ACE2, and SARS-CoV-2 seemed much more efficient than HCoV-NL63 at infecting the very small proportion of HRECs expressing the ACE2 receptors. Furthermore, SARS-CoV-2 replicated more efficiently than HCoV-NL63 in HREC, which correlates with the cumulative evidence of the differences in their transmissibility.

Introduction Geometric morphometrics (GM) is an advanced landmark-based quantitative method used to study biological shape and form. Historically, GM has been limited to non-biomedical fields such as comparative biology; however, this technique confers advantages over traditional cephalometric methods, warranting a review of current applications of GM to human craniofacial disorders. Methods The RISmed package was used to extract metadata associated with PubMed publications referencing GM analysis techniques in craniofacial and reconstructive surgery. PubMed search terms included "geometric AND morphometric AND craniofacial;" and "geometric AND morphometric AND reconstructive surgery." Duplicate search results were eliminated. Results Search yielded 139 studies between 2005 and 2020, of which 27 met inclusion criteria. Human craniofacial studies constituted 2% of all queried GM studies. Among these, cleft lip and palate were the most commonly studied craniofacial conditions (7 studies, 26%), followed by sagittal craniosynostosis (4 studies, 15%). Seventeen studies (63%) used GM to assess skeletal structures, seven studies (26%) examined both skeletal and soft tissues, and three studies (11%) analyzed soft tissues only. Eleven studies (40.1%) employed a GM approach to evaluate postoperative changes in craniofacial morphology. Two studies (7%) systematically compared GM analysis with conventional shape measurements. Conclusion The ability to study shape while controlling for variability in structure size and imaging technique make GM a promising tool for understanding growth patterns in complex craniofacial diseases. Furthermore, GM overcomes many limitations of traditional cephalometric techniques, and hence may claim an expanded role in the study of human craniofacial disorders in clinical and research settings.

As the leading global search engine with billions of daily queries, Google and its open-source Google Trends (Google, Mountain View, CA) represent an emerging and powerful tool for epidemiological and medical research. Within the field of plastic surgery, Google Trends has yielded insights into online interest for facial feminization surgery, gender-affirmation surgery, cosmetic body procedures, and breast reconstruction, among other common procedures. The existing literature of Google Trends in plastic surgery was systematically reviewed following established Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Google Trends’ 4 input variables—keyword, region, period, and category—were assessed. Seventeen plastic surgery studies employing Google Trends were reviewed. There was strong inter-rater reliability (Cohen’s kappa = 0.68). Analyzing keyword syntax, only 3 of 17 studies (17.6%) used the “+” function to combine terms, which can significantly improve sensitivity. For the region variable, 12 of 16 studies (75%) conducted worldwide searches; yet, none of the studies used any non-English keywords, introducing significant bias. For the period, 88.2% of studies utilized a timespan of greater than 5 years, resulting in monthly intervals between data points in Google Trends. For the “category” variable, none of the studies appear to have employed the “surgery,” “cosmetic surgery” or “health” categories to improve specificity. Google Trends is presented as an emerging methodology in plastic surgery research. The strengths and limitations of Google Trends as a resource for plastic surgeons and medical professionals are discussed, and a recommended step-by-step guide for conducting and interpreting Google Trends research is outlined.

Antimicrobial resistance is a serious challenge facing human and veterinary health. Current methods of detecting resistance are limited in turn-around time or universal detection. In this work, a new antimicrobial susceptibility test is developed and validated, which utilizes deuterium labeling of membrane lipids to track the growth of bacterial cells. We hypothesize that deuterium uptake and subsequent labeling of lipids can be detected using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). Additionally, bacteria growth is performed on the MALDI target, minimizing sample preparation materials and time. When two

In the present work, we use nuclear magnetic resonance imaging (MRI) to measurethe mutual diffusion coefficient of methane in toluene at 298 K. The concentrationfield obtained upon dissolving gaseous methane in liquid toluene wasmonitored with two-dimensional MRI. To cope with the low concentration ofmethane, a chemical shift-selective pulse sequence was employed. The diffusioncoefficient was determined from the resulting temporally and spatially resolvedconcentration data based on Fick’s second law. The resulting diffusion coefficientis in good agreement with reference data. We conclude that MRI experimentsare well-suited for quantitative studies of mutual diffusion in liquidmixtures, also in challenging applications as the one studied here.

Banana susceptibility to crown rot is influenced by many biotic and abiotic preharvest factors, which include source‐sink (So‐Si) ratio modifications through trimming of leaves and fruit. Banana plant's resistance to biotic stress has been previously correlated to its phenolic content; it is hypothesized that the crown's phenolic content may influence the fruit's susceptibility. The aim of this work was to investigate the influence of severe So‐Si ratio modifications, via the removal of leaves and fruit, and the involvement of phenolics in the fruit's susceptibility to crown rot. Fruit susceptibility was evaluated 13 days postinoculation (13 dpi) with Colletotrichum musae. Banana crowns obtained on the day of harvest before inoculation (dhbi) and 13 dpi were analysed for changes in phenolics using GC‐MS, HPLC, and LC‐MS devices. Severe So‐Si ratio modifications had a significant effect (p

BACKGROUND Geometric morphometric analysis with Procrustes superimposition is an advanced computational tool that can be used to quantify dynamic changes in complex three-dimensional structures. The present study couples high resolution CT imaging with a Geometric Morphometric approach in order to further understand the complex dysmorphology that occurs in unilateral coronal synostosis (UCS). METHODS Forty-one UCS patients and 41 age- and sex-matched controls received high-resolution CT imaging. Thirty-one anatomical landmarks were identified on each imaging set. A geometric morphometric workflow was used to perform a Procrustes superimposition to register landmarks into a common space. Procrustes-aligned landmarks were used to derive angle calculations, lengths, and other anatomical measurements. Three-dimensional coordinates were also used to perform a principal components analysis (PCA). RESULTS Unilateral coronal synostosis patients exhibited significant angular deviation at the levels of the inferior skull base, mid-posterior fossa, and vertex. Both left- and right-sided UCS patients showed increased lengthening in the transverse (left-right) dimension, exhibiting increased length between the left and right EAC (P = 0.047). Conversely, UCS patients revealed shortening in the midline AP dimension as evidenced by the decreased Nasal root-Lambda (P

Summary Genotyping‐by‐sequencing has enabled approaches for genomic selection to improve yield, stress resistance and nutritional value. More and more resource studies are emerging providing 1000 and more genotypes and millions of SNPs for one species covering a hitherto inaccessible intraspecific genetic variation. The larger the databases are growing, the better statistical approaches for genomic selection will be available. However, there are clear limitations on the statistical but also on the biological part. Intraspecific genetic variation is able to explain a high proportion of the phenotypes, but a large part of phenotypic plasticity also stems from environmentally driven transcriptional, post‐transcriptional, translational, post‐translational, epigenetic and metabolic regulation. Moreover, regulation of the same gene can have different phenotypic outputs in different environments. Consequently, to explain and understand environment‐dependent phenotypic plasticity based on the available genotype variation we have to integrate the analysis of further molecular levels reflecting the complete information flow from the gene to metabolism to phenotype. Interestingly, metabolomics platforms are already more cost‐effective than NGS platforms and are decisive for the prediction of nutritional value or stress resistance. Here, we propose three fundamental pillars for future breeding strategies in the framework of Green Systems Biology: (i) combining genome selection with environment‐dependent PANOMICS analysis and deep learning to improve prediction accuracy for marker‐dependent trait performance; (ii) PANOMICS resolution at subtissue, cellular and subcellular level provides information about fundamental functions of selected markers; (iii) combining PANOMICS with genome editing and speed breeding tools to accelerate and enhance large‐scale functional validation of trait‐specific precision breeding.

Background Triple combinations of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators demonstrate enhanced clinical efficacy in CF patients with F508del mutation, compared with modest effects of dual combinations. GLPG2737 was developed as a novel corrector for triple combination therapy. Methods This multicenter, randomized, double-blind, placebo-controlled, phase 2a study evaluated GLPG2737 in F508del homozygous subjects who had been receiving lumacaftor 400 mg/ivacaftor 250 mg for ≥12 weeks. The primary outcome was change from baseline in sweat chloride concentration. Other outcomes included assessment of pulmonary function, respiratory symptoms, safety, tolerability, and pharmacokinetics. Results Between November 2017 and April 2018, 22 subjects were enrolled and randomized to oral GLPG2737 (75 mg; n = 14) or placebo (n = 8) capsules twice daily for 28 days. A significant decrease from baseline in mean sweat chloride concentration occurred at day 28 for GLPG2737 versus placebo (least-squares-mean difference − 19.6 mmol/L [95% confidence interval (CI) –36.0, −3.2], p = .0210). The absolute improvement, as assessed by least-squares-mean difference in change from baseline, in forced expiratory volume in 1 s (percent predicted) at day 28 for GLPG2737 versus placebo was 3.4% (95% CI –0.5, 7.3). Respiratory symptoms in both groups remained stable. Mild/moderate adverse events occurred in 10 (71.4%) and 8 (100%) subjects receiving GLPG2737 and placebo, respectively. Lower exposures of GLPG2737 (and active metabolite M4) were observed than would be expected if administered alone (as lumacaftor induces CYP3A4). Lumacaftor and ivacaftor exposures were as expected. Conclusions GLPG2737 was well tolerated and yielded significant decreases in sweat chloride concentration versus placebo in subjects homozygous for F508del receiving lumacaftor/ivacaftor, demonstrating evidence of increased CFTR activity when added to a potentiator–corrector combination. Funding Galapagos NV. Clinical trial registration: ClinicalTrials.gov identifier, NCT03474042

Patients with neuromuscular scoliosis (NMS) who undergo posterior spinal fusion (PSF) often have long, protracted hospital stays because of numerous comorbidities. Coordinated perioperative pathways can reduce length of hospitalization (LOH) without increasing complications; however, a subset of patients may not be suited to rapid mobilization and early discharge.197 patients with NMS underwent PSF at a single hospital by two surgeons with a post-operative care pathway emphasizing early mobilization, rapid transition to enteral feeds, and discharge prior to first bowel movement. Average LOH was 4.9 days for all patients. Patients were divided into quartiles ( 3 days, 3-5 days, 5-7 days, 7 days) based on their LOH, and their charts were retrospectively reviewed for preoperative, intraoperative, and postoperative factors associated with their LOH.Age at surgery, gender, the need for tube feeds, and specific underlying neuromuscular disorder were not significant predictors of LOH; however, severely involved cerebral palsy (CP) patients (GMFCS 4/5) were more likely to have extended stays than GMFCS 1-3 patients (p = 0.02). Radiographic predictors of LOH included major coronal Cobb angle (p = 0.002) and pelvic obliquity (p = 0.02). Intraoperative predictors included longer surgical times, greater numbers of levels fused and need for intraoperative or postoperative blood transfusion (p 0.05). The need for ICU admission and development of a pulmonary complication were significantly more likely to fall into the extended LOH group (p 0.05).Several variables have been identified as significant predictors of LOH after PSF for NMS in the setting of a standardized discharge pathway. Patients with smaller curves and less complex surgeries were more amenable to accelerated discharge. Conversely, patients with severe CP with large curves and pelvic obliquity requiring longer surgeries with more blood loss may not be ideal candidates. These data can be used to inform providers' and families' post-operative expectations.Therapeutic Level III.

Antisense peptide nucleic acids (PNAs) have yet to translate to the clinic because of poor cellular uptake, limited solubility, and rapid elimination. Cell-penetrating peptides (CPPs) covalently attached to PNAs may facilitate clinical development by improving uptake into cells. We report an efficient technology that utilizes a fully automated fast-flow instrument to manufacture CPP-conjugated PNAs (PPNAs) in a single shot. The machine is rapid, with each amide bond being formed in 10 s. Anti-IVS2-654 PPNA synthesized with this instrument presented threefold activity compared to transfected PNA in a splice-correction assay. We demonstrated the utility of this approach by chemically synthesizing eight anti-SARS-CoV-2 PPNAs in 1 day. A PPNA targeting the 5' untranslated region of SARS-CoV-2 genomic RNA reduced the viral titer by over 95% in a live virus infection assay (IC

Common ragweed (Ambrosia artemisiifolia) is an invasive plant with allergenic pollen. Due to environmental changes, ragweed pollen (RWP) airborne concentrations are predicted to quadruple in Europe by 2050 and more than double allergic sensitization of Europeans by 2060. We developed an experimental RWP model of allergy in BALB/c mice to evaluate how the number of RWP and how RWP collected from different geographical environments influence disease. We administered RWP six times over 3 weeks intranasally to the mice and then evaluated disease parameters 72 h later or allowed the mice to recover for at least 90 days before rechallenging them with RWP to elicit a disease relapse. Doses over 300 pollen grains induced lung eosinophilia. Higher doses of 3,000 and 30,000 pollen grains increased both eosinophils and neutrophils and induced disease relapses. RWP harvested from diverse geographical regions induced a spectrum of allergic lung disease from mild inflammation to moderate eosinophilic and severe mixed eosinophilic-neutrophilic lung infiltrates. After a recovery period, mice rechallenged with pollen developed a robust disease relapse. We found no correlation between Amb a 1 content, the major immunodominant allergen, endotoxin content, or RWP structure with disease severity. These results demonstrate that there is an environmental impact on RWP with clinical consequences that may underlie the increasing sensitization rates and the severity of pollen-induced disease exacerbation in patients. The multitude of diverse environmental factors governing distinctive patterns of disease induced by RWP remains unclear. Further studies are necessary to elucidate how the environment influences the complex interaction between RWP and human health.

With the dramatic increase of organic banana production worldwide, it is essential to be able to monitor compliance with organic specifications. While the detection of pesticide fraud is routinely controlled by detecting pesticide residues in organic bananas, the detection of fertilizer fraud is much more complex. We compared the δ13C and δ15N isotopic values of green bananas from organic and conventional farms at seven sites around the world. In our whole dataset, the δ15N values of banana fruits ranged between −1.25 and + 8.91‰. In all sites, δ15N values of organic banana were significantly higher than conventional fruits (mean value of + 5.24‰ and + 2.342‰, respectively). Conversely, the type of fertilization did not significantly alter δ13C values. Our results suggest that it is possible, upon arrival in importing countries, to differentiate bananas grown with synthetic fertilizer from those grown with organic fertilizer.