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1.
bioRxiv ; 2024 Apr 17.
Article En | MEDLINE | ID: mdl-38798314

Opioid use disorder is heritable, yet its genetic etiology is largely unknown. Analysis of addiction model traits in rodents (e.g., opioid behavioral sensitivity and withdrawal) can facilitate genetic and mechanistic discovery. C57BL/6J and C57BL/6NJ substrains have extremely limited genetic diversity, yet can show reliable phenotypic diversity which together, can facilitate gene discovery. The C57BL/6NJ substrain was less sensitive to oxycodone (OXY)-induced locomotor activity compared to the C57BL/6J substrain. Quantitative trait locus (QTL) mapping in an F2 cross identified a distal chromosome 1 QTL explaining 7-12% of the variance in OXY locomotor sensitivity and anxiety-like withdrawal in the elevated plus maze. We identified a second QTL for withdrawal on chromosome 5 near the candidate gene Gabra2 (alpha-2 subunit of GABA-A receptor) explaining 9% of the variance. Next, we generated recombinant lines from an F2 founder spanning the distal chromosome 1 locus (163-181 Mb), captured the QTL for OXY sensitivity and withdrawal, and fine-mapped a 2.45-Mb region (170.16-172.61 Mb). There were five striatal cis-eQTL transcripts in this region (Pcp4l1, Ncstn, Atp1a2, Kcnj9, Igsf9), two of which were confirmed at the protein level (KCNJ9, ATP1A2). Kcnj9, a.k.a., GIRK3, codes for a potassium channel that is a major effector of mu opioid receptor signaling. Atp1a2 codes for a subunit of a Na+/K+ ATPase enzyme that regulates neuronal excitability and shows adaptations following chronic opioid administration. To summarize, we identified genetic sources of opioid behavioral differences in C57BL/6 substrains, two of the most widely and often interchangeably used substrains in opioid addiction research.

2.
medRxiv ; 2024 May 13.
Article En | MEDLINE | ID: mdl-38798476

Background: Hepatitis C virus (HCV) elimination requires treatment access expansion, especially for underserved populations. Telehealth has the potential to improve HCV treatment access, although data are limited on its incorporation into standard clinical practice. Methods: We conducted a cross-sectional, e-mail survey of 598 US HCV treatment providers who had valid email addresses and 1) were located in urban areas and had written ≥20 prescriptions for HCV treatment to US Medicare beneficiaries in 2019-20 or 2) were located in non-urban areas and wrote any HCV prescriptions in 2019-20. Through email, we notified providers of a self-administered electronic 28-item survey of clinical strategies and attitudes about telemedicine for HCV. Results: We received 86 responses (14% response rate), of which 75 used telemedicine for HCV in 2022. Of those 75, 24% were gastroenterologists/hepatologists, 23% general medicine, 17% infectious diseases, and 32% non-physicians. Most (82%) referred patients to commercial laboratories, and 85% had medications delivered directly to patients. Overwhelmingly, respondents (92%) felt that telehealth increases healthcare access, and 76% reported that it promotes or is neutral for treatment completion. Factors believed to be "extremely" or "very" important for telehealth use included patient access to technology (86%); patients' internet access (74%); laboratory access (76%); reimbursement for video visits (74%) and audio-only visits (66%). Non-physician licensing and liability statutes were rated "extremely" or "very" important by 43% and 44%, respectively. Conclusions: Providers felt that telehealth increases HCV treatment access. Major limitations were technological requirements, reimbursement, and access to ancillary services. These findings support the importance of digital equity and literacy to achieve HCV elimination goals.

3.
Nat Commun ; 15(1): 3738, 2024 May 03.
Article En | MEDLINE | ID: mdl-38702297

Whole virus-based inactivated SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide have been critical to the COVID-19 pandemic response. Although these vaccines are protective against homologous coronavirus infection, the emergence of novel variants and the presence of large zoonotic reservoirs harboring novel heterologous coronaviruses provide significant opportunities for vaccine breakthrough, which raises the risk of adverse outcomes like vaccine-associated enhanced respiratory disease. Here, we use a female mouse model of coronavirus disease to evaluate inactivated vaccine performance against either homologous challenge with SARS-CoV-2 or heterologous challenge with a bat-derived coronavirus that represents a potential emerging disease threat. We show that inactivated SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide can cause enhanced respiratory disease during heterologous infection, while use of an alternative adjuvant does not drive disease and promotes heterologous viral clearance. In this work, we highlight the impact of adjuvant selection on inactivated vaccine safety and efficacy against heterologous coronavirus infection.


Aluminum Hydroxide , COVID-19 Vaccines , COVID-19 , SARS-CoV-2 , Vaccines, Inactivated , Animals , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Female , COVID-19/prevention & control , COVID-19/immunology , COVID-19/virology , Mice , Vaccines, Inactivated/immunology , SARS-CoV-2/immunology , Aluminum Hydroxide/administration & dosage , Disease Models, Animal , Adjuvants, Immunologic/administration & dosage , Adjuvants, Vaccine , Antibodies, Viral/immunology , Mice, Inbred BALB C , Humans , Severe acute respiratory syndrome-related coronavirus/immunology
4.
J Phys Chem A ; 128(19): 3830-3839, 2024 May 16.
Article En | MEDLINE | ID: mdl-38709806

As important naturally occurring chromophores, photophysical/chemical properties of quinoid flavins have been extensively studied both experimentally and theoretically. However, little is known about the transition dipole moment (TDM) orientation of excited-state absorption transitions of these important compounds. This aspect is of high interest in the fields of photocatalysis and quantum control studies. In this work, we employ polarization-associated spectra (PAS) to study the excited-state absorption transitions and the underlying TDM directions of a standard quinoid flavin compound. As compared to transient absorption anisotropy (TAA), an analysis based on PAS not only avoids diverging signals but also retrieves the relative angle for ESA transitions with respect to known TDM directions. Quantum chemical calculations of excited-state properties lead to good agreement with TA signals measured in magic angle configuration. Only when comparing experiment and theory for TAA spectra and PAS, do we find deviations when and only when the S0 → S1 of flavin is used as a reference. We attribute this to the vibronic coupling of this transition to a dark state. This effect is only observed in the employed polarization-controlled spectroscopy and would have gone unnoticed in conventional TA.

5.
Viruses ; 16(4)2024 04 19.
Article En | MEDLINE | ID: mdl-38675976

RNA viruses quickly evolve subtle genotypic changes that can have major impacts on viral fitness and host range, with potential consequences for human health. It is therefore important to understand the evolutionary fitness of novel viral variants relative to well-studied genotypes of epidemic viruses. Competition assays are an effective and rigorous system with which to assess the relative fitness of viral genotypes. However, it is challenging to quickly and cheaply distinguish and quantify fitness differences between very similar viral genotypes. Here, we describe a protocol for using reverse transcription PCR in combination with commercial nanopore sequencing services to perform competition assays on untagged RNA viruses. Our assay, called the Universal Competition Assay by Nanopore Sequencing (U-CAN-seq), is relatively cheap and highly sensitive. We used a well-studied N24A mutation in the chikungunya virus (CHIKV) nsp3 gene to confirm that we could detect a competitive disadvantage using U-CAN-seq. We also used this approach to show that mutations to the CHIKV 5' conserved sequence element that disrupt sequence but not structure did not affect the fitness of CHIKV. However, similar mutations to an adjacent CHIKV stem loop (SL3) did cause a fitness disadvantage compared to wild-type CHIKV, suggesting that structure-independent, primary sequence determinants in this loop play an important role in CHIKV biology. Our novel findings illustrate the utility of the U-CAN-seq competition assay.


Chikungunya virus , Mutation , Nanopore Sequencing , Nanopore Sequencing/methods , Chikungunya virus/genetics , Chikungunya virus/classification , Humans , Genotype , Genetic Fitness , RNA, Viral/genetics , Animals , RNA Viruses/genetics , RNA Viruses/classification , Chikungunya Fever/virology
6.
Article En | MEDLINE | ID: mdl-38670234

BACKGROUND: The development of peanut allergy is due to a combination of genetic and environmental factors, although specific genes have proven difficult to identify. Previously, we reported that peanut-sensitized Collaborative Cross strain CC027/GeniUnc (CC027) mice develop anaphylaxis upon oral challenge to peanut, in contrast to C3H/HeJ (C3H) mice. OBJECTIVE: This study aimed to determine the genetic basis of orally induced anaphylaxis to peanut in CC027 mice. METHODS: A genetic mapping population between CC027 and C3H mice was designed to identify the genetic factors that drive oral anaphylaxis. A total of 356 CC027xC3H backcrossed mice were generated, sensitized to peanut, then challenged to peanut by oral gavage. Anaphylaxis and peanut-specific IgE were quantified for all mice. T-cell phenotyping was conducted on CC027 mice and 5 additional Collaborative Cross strains. RESULTS: Anaphylaxis to peanut was absent in 77% of backcrossed mice, with 19% showing moderate anaphylaxis and 4% having severe anaphylaxis. There were 8 genetic loci associated with variation in response to peanut challenge-6 associated with anaphylaxis (temperature decrease) and 2 associated with peanut-specific IgE levels. There were 2 major loci that impacted multiple aspects of the severity of acute anaphylaxis, at which the CC027 allele was associated with worse outcome. At one of these loci, CC027 has a private genetic variant in the Themis gene. Consistent with described functions of Themis, we found that CC027 mice have more immature T cells with fewer CD8+, CD4+, and CD4+CD25+CD127- regulatory T cells. CONCLUSIONS: Our results demonstrate a key role for Themis in the orally reactive CC027 mouse model of peanut allergy.

7.
J Cardiothorac Surg ; 19(1): 239, 2024 Apr 17.
Article En | MEDLINE | ID: mdl-38632653

OBJECTIVES: Aortic pathologies often present with elevated inflammatory biomarkers due to the nature of the disease. Open aortic surgery causes significant trauma to the body due to often mandatory ischemic periods, long cardiopulmonary bypass times and polytransfusion. We aim to determine postoperative trends on inflammation biomarkers for different aortic pathologies and type of surgery in different segments of the aorta. METHODS: Retrospective review of prospectively collected data of 193 consecutive patients who underwent aortic surgery in our centre between 2017 and 2021, grouped according to the type of aortic intervention: (1) Type A aortic dissection (AD) repair with ascending aorta/hemiarch replacement, (2) Aortic root replacement (ARR), (3) Aortic arch + Frozen elephant trunk (FET), (4) Descending thoracic aorta (DTA)/Thoraco-Abdominal aortic repair (TAA). Primary outcomes were daily values of white blood cells (WBC) and C-Reactive Protein (CRP) during the first 15 postoperative days. RESULTS: All groups had a similar inflammatory peak in the first 2-4 days (WBC 12-15 × 109 c/L). AD and FET groups show similar trends with WBC and CRP peaks on days 2 and 10. The ARR group didn't experience the 2nd peak as most patients were already discharged. DTA/TAA patients experienced a more prolonged inflammatory response, reaching a plateau by day 5-10. AD group shows the highest WBC levels and the DTA/TAAA group the highest CRP levels. CRP levels remain elevated (100-200 mg/L) in all groups after 15 postoperative days. CONCLUSIONS: Inflammatory biomarkers show different postoperative trends depending on the clinical presentation and complexity of the aortic procedure performed. Further understanding of the inflammatory response to different aortic pathologies and surgical procedures will permit reduction on the liberal use of antibiotics that this cohort of patients are usually exposed to. An earlier version of the data included in this manuscript was presented as Oral Abstract in the UK Society of Cardiothoracic Surgery Annual meeting in 2021.


Aortic Aneurysm, Thoracic , Blood Vessel Prosthesis Implantation , Humans , Blood Vessel Prosthesis Implantation/methods , Aorta/surgery , Aorta, Thoracic/surgery , Retrospective Studies , Inflammation , Biomarkers , Aortic Aneurysm, Thoracic/surgery , Treatment Outcome , Blood Vessel Prosthesis
8.
Support Care Cancer ; 32(5): 319, 2024 Apr 30.
Article En | MEDLINE | ID: mdl-38689167

PURPOSE: Cancer-related fatigue (CRF) is a common side effect of cancer and cancer treatment that significantly impairs the quality of life and can persist for years after treatment completion. Although fatigue is often associated with cancer treatment, it is also a result of the disease itself, even before intervention. CRF at the time of diagnosis may affect treatment timing or completion and is a consistent predictor of post-treatment fatigue at any time. The mechanisms underlying CRF are multidimensional and not well understood, particularly at the time of diagnosis. METHODS: Sixty-five breast cancer patients at the time of diagnosis were included. The participants completed self-assessment questionnaires about CRF, sleep disturbances, and emotional symptoms and wore an accelerometer to assess levels of spontaneous physical activity and sleep quality. During the experimental session, the participants underwent cognitive, neuromuscular, and exercise metabolism evaluations. RESULTS: Using augmented backward elimination regression, this study found that emotional symptoms and perceived sleep disturbances were the strongest predictors of CRF (adjusted r2 = 0.51). Neuromuscular fatigability and sleep disturbance were also associated with physical dimensions, whereas cognitive performance was associated with cognitive dimensions. CONCLUSION: At the time of diagnosis, emotional and cognitive dimensions are over-represented compared to the general population, and specific subdimensions have specific predictors that support the idea of distinct mechanisms. Evaluating CRF subdimensions and their potential mechanisms at the time of diagnosis would be particularly relevant for identifying high-risk patients and offering them appropriate interventions. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov (NCT04391543) in May, 2020.


Breast Neoplasms , Fatigue , Sleep Wake Disorders , Humans , Fatigue/etiology , Fatigue/diagnosis , Female , Middle Aged , Surveys and Questionnaires , Breast Neoplasms/complications , Adult , Sleep Wake Disorders/etiology , Aged , Cohort Studies , Quality of Life , Exercise/physiology , Sleep Quality
9.
Theranostics ; 14(6): 2560-2572, 2024.
Article En | MEDLINE | ID: mdl-38646643

Management of prostate cancer (PC) might be improved by combining external beam radiotherapy (EBRT) and prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) with lutetium-177 (177Lu)-labeled PSMA inhibitors. We hypothesized a higher efficacy of the combination due to augmentation of the radiation dose to the tumor and interactions of EBRT with PSMA expression potentially increasing radiopharmaceutical uptake. Therefore, this study analyzed the influence of radiation on PSMA expression levels in vitro. The results were translated to evaluate the efficacy of the combination of photon EBRT and [177Lu]Lu-PSMA-617 in a murine PC xenograft model. Finally, a clinical case report on a combined elective field EBRT with RLT dose escalation illustrates a proof-of-concept. Methods: PSMA gene and protein expression were assessed in human PSMA-overexpressing LNCaP cells after irradiation using reverse transcription quantitative polymerase chain reaction (RT-qPCR), flow cytometry and On-Cell Western assays. In the in vivo therapy study, LNCaP tumor-bearing BALB/c nu/nu mice were irradiated once with 2 Gy X-ray EBRT and injected with 40 MBq [177Lu]Lu-PSMA-617 after 4 h or received single or no treatment (n = 10 each). Tumor-absorbed doses by [177Lu]Lu-PSMA-617 were calculated according to the Medical Internal Radiation Dosimetry (MIRD) formalism after deriving time-activity curves using a gamma probe. An exemplified patient case is demonstrated where fractionated EBRT (54 Gy to prostate; 45 Gy to pelvic lymphatics) and three cycles of [177Lu]Lu-PSMA-617 (3.4-6.0 GBq per cycle) were sequentially combined under concurrent androgen deprivation for treating locally advanced PC. Results: At 4 h following irradiation with 2-8 Gy, LNCaP cells displayed a PSMA protein upregulation by around 18% relative to non-irradiated cells, and a stronger upregulation on mRNA level (up to 2.6-fold). This effect was reversed by 24 h when PSMA protein levels were downregulated by up to 22%. Mice treated with the combination therapy showed significantly improved outcomes regarding tumor control and median survival (p < 0.0001) as compared to single or no treatment. Relative to monotherapy with PSMA-RLT or EBRT, the tumor doubling time was prolonged 1.7- or 2.7-fold and the median survival was extended by 24% or 60% with the combination, respectively. Additionally, tumors treated with EBRT exhibited a 14% higher uptake of the radiopharmaceutical as evident from the calculated tumor-absorbed dose, albeit with high variability in the data. Concerning the patient case, the tri-modality treatment was well tolerated and the patient responded with a long-lasting complete biochemical remission for five years following end of PSMA-RLT. The patient then developed a biochemical relapse with oligo-recurrent disease on follow-up imaging. Conclusion: The present preclinical and clinical data demonstrate that the combination of EBRT with dose escalation by PSMA-RLT improves tumor control and potentially prolongs survival. This may pave the way for further clinical investigations of this approach to explore the curative potential of the combination therapy.


Dipeptides , Heterocyclic Compounds, 1-Ring , Lutetium , Prostate-Specific Antigen , Prostatic Neoplasms , Radioisotopes , Radiopharmaceuticals , Animals , Male , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/metabolism , Humans , Lutetium/therapeutic use , Lutetium/pharmacology , Heterocyclic Compounds, 1-Ring/therapeutic use , Heterocyclic Compounds, 1-Ring/pharmacology , Dipeptides/pharmacology , Dipeptides/therapeutic use , Cell Line, Tumor , Mice , Radiopharmaceuticals/therapeutic use , Radiopharmaceuticals/pharmacology , Radiopharmaceuticals/pharmacokinetics , Radioisotopes/therapeutic use , Radioisotopes/pharmacology , Mice, Inbred BALB C , Mice, Nude , Glutamate Carboxypeptidase II/metabolism , Glutamate Carboxypeptidase II/genetics , Xenograft Model Antitumor Assays , Antigens, Surface/metabolism , Antigens, Surface/genetics
10.
HCA Healthc J Med ; 5(1): 39-43, 2024.
Article En | MEDLINE | ID: mdl-38560396

Introduction: Primary mucinous carcinoma of the thyroid is an exceedingly rare malignancy that is histologically similar to mucinous carcinoma of other sites. Accurate diagnosis is a challenging yet crucial component of clinical management for both patients and our understanding of this rare disease. Case Presentation: We report the case of a 69-year-old male patient with primary mucinous carcinoma of the thyroid. Microscopic examination of a biopsy specimen showed fibrous tissue, which was extensively and irregularly infiltrated by a cytologically malignant epithelial neoplasm showing glandular differentiation with mucin production. Immunohistochemistry demonstrated that tumor cells were positive for TTF1, thyroglobulin, CK7, and PAX8. Co-expression of TTF1 and PAX8 is most commonly seen in thyroid tumors. These findings support our diagnosis of mucinous carcinoma of thyroid origin, which is rare and highly aggressive. Conclusion: In this report, we present the only documented case of primary mucinous carcinoma of the thyroid reported in the United States in the last decade. The diagnosis of primary mucinous carcinoma of the thyroid can be challenging. Therefore, we discuss and detail the clinicopathologic tumor profile and provide more current, detailed histological criteria to assist in the diagnosis of this rare disease.

11.
Cell Rep ; 43(5): 114127, 2024 Apr 21.
Article En | MEDLINE | ID: mdl-38652660

Ebola virus (EBOV), a major global health concern, causes severe, often fatal EBOV disease (EVD) in humans. Host genetic variation plays a critical role, yet the identity of host susceptibility loci in mammals remains unknown. Using genetic reference populations, we generate an F2 mapping cohort to identify host susceptibility loci that regulate EVD. While disease-resistant mice display minimal pathogenesis, susceptible mice display severe liver pathology consistent with EVD-like disease and transcriptional signatures associated with inflammatory and liver metabolic processes. A significant quantitative trait locus (QTL) for virus RNA load in blood is identified in chromosome (chr)8, and a severe clinical disease and mortality QTL is mapped to chr7, which includes the Trim5 locus. Using knockout mice, we validate the Trim5 locus as one potential driver of liver failure and mortality after infection. The identification of susceptibility loci provides insight into molecular genetic mechanisms regulating EVD progression and severity, potentially informing therapeutics and vaccination strategies.

12.
Pediatr Radiol ; 2024 Apr 26.
Article En | MEDLINE | ID: mdl-38671145

Bone marrow metastases-noted in 6% of patients with rhabdomyosarcoma-have been linked to very poor outcomes. Bilateral bone marrow sampling from iliac crests has been the gold standard for bone marrow examination in rhabdomyosarcoma, but sampling errors due to patchy bone marrow involvement may limit its sensitivity. Here, we report the case of a 6-year-old boy with embryonal rhabdomyosarcoma of the skull base and multiple 2-[18F]fluoro-2-deoxy-D-glucose (2-[18F]FDG)-avid bone marrow metastases visualized by positron emission tomography and computed tomography (2-[18F]FDG PET/CT). His bone marrow aspirates were tumor-free. This case illustrates the diagnostic value of 2-[18F]FDG PET/CT in the detection of bone marrow metastases in rhabdomyosarcoma patients, which may re-shape the definition of bone marrow disease and, ultimately, alter disease staging and risk stratification.

13.
Chaos ; 34(4)2024 Apr 01.
Article En | MEDLINE | ID: mdl-38668587

In this short review (written to celebrate David Campbell's 80th birthday), we provide a theoretical description of quantum transport in nanoscale systems in the presence of single-electron excitations generated by Lorentzian voltage drives, termed Levitons. These excitations allow us to realize the analog of quantum optics experiments using electrons instead of photons. Importantly, electrons in condensed matter systems are strongly affected by the presence of different types of non-trivial correlations, with no counterpart in the domain of photonic quantum optics. After providing a short introduction about Levitons in non-interacting systems, we focus on how they operate in the presence of two types of strong electronic correlations in nanoscale systems, such as those arising in the fractional quantum Hall effect or in superconducting systems. Specifically, we consider Levitons in a quantum Hall bar of the fractional quantum Hall effect, pinched by a quantum point contact, where anyons with fractional charge and statistics tunnel between opposite edges. In this case, a Leviton-Leviton interaction can be induced by the strongly correlated background. Concerning the effect of superconducting correlations on Levitons, we show that, in a normal metal system coupled to BCS superconductors, half-integer Levitons minimize the excess noise in the Andreev regime. Interestingly, energy-entangled electron states can be realized on-demand in this type of hybrid setup by exploiting crossed Andreev reflection. The results exposed in this review have potential applications in the context of quantum information and computation with single-electron flying qubits.

14.
bioRxiv ; 2024 Mar 25.
Article En | MEDLINE | ID: mdl-38562845

The obligate intracellular parasite Toxoplasma gondii can infect and replicate in any warm-blooded cell tested to date, but much of our knowledge about T. gondii cell biology comes from just one host cell type: human foreskin fibroblasts (HFFs). To expand our knowledge of host-parasite lipid interactions, we studied T. gondii in intestinal epithelial cells, the first site of host-parasite contact following oral infection and the exclusive site of parasite sexual development in feline hosts. We found that highly metabolic Caco-2 cells are permissive to T. gondii growth even when treated with high levels of linoleic acid (LA), a polyunsaturated fatty acid (PUFA) that kills parasites in HFFs. Caco-2 cells appear to sequester LA away from the parasite, preventing membrane disruptions and lipotoxicity that characterize LA-induced parasite death in HFFs. Our work is an important step toward understanding host-parasite interactions in feline intestinal epithelial cells, an understudied but important cell type in the T. gondii life cycle.

15.
J Pediatr Surg ; 2024 Feb 26.
Article En | MEDLINE | ID: mdl-38485535

BACKGROUND: Is vascular training in paediatric surgical oncology considered desirable ? METHODS: A voluntary survey of work practice was undertaken with the surgeon membership of The International Society Of Paediatric Surgical Oncology (IPSO) using a structured designed questionnaire. RESULTS: A total of 149 IPSO surgeon members completed the survey. 57% (N = 84) of surgeons surveyed had no specific training in vascular surgery. 43% surgeons (N = 63) stated they had acquired some skills in residency training and/or with transplantation surgery. 65% (N = 96) of respondent surgeons stated that vascular surgical training must be incorporated into pediatric surgical oncology training and 27% (N = 40) agreed that it was considered desirable. 89% (N = 133) of surgeon respondents had encountered major vascular injury during work practice while operating on pediatric solid tumors. Vascular injury repairs were undertaken and attempted by pediatric surgeons though expert assistance of vascular surgeons proved crucially essential in many instances. Emergent operations included patch repairs, vessel ligation techniques and insertion of vascular graft prostheses. Interventional radiology services to arrest life-threatening hemorrhage were also reportedly utilized by respondents. CONCLUSION: Vascular injuries have significant potential for devastating patient outcomes including never event 'mortality'. The IPSO surgeon survey highlights that there are visible 'gaps' in skills training. Training to be a pediatric oncology surgeon must incorporate acquisition of skill sets proficiency in vascular surgery.

16.
Nat Commun ; 15(1): 2040, 2024 Mar 06.
Article En | MEDLINE | ID: mdl-38448429

Metal-organic framework (MOF) glasses are an emerging class of glasses which complement traditional inorganic, organic and metallic counterparts due to their hybrid nature. Although a few zeolitic imidazolate frameworks have been made into glasses, how to melt and quench the largest subclass of MOFs, metal carboxylate frameworks, into glasses remains challenging. Here, we develop a strategy by grafting the zwitterions on the carboxylate ligands and incorporating organic acids in the framework channels to enable the glass formation. The charge delocalization of zwitterion-acid subsystem and the densely filled channels facilitate the coordination bonding mismatch and thus reduce the melting temperature. Following melt-quenching realizes the glass formation of a family of carboxylate MOFs (UiO-67, UiO-68 and DUT-5), which are usually believed to be un-meltable. Our work opens up an avenue for melt-quenching porous molecular solids into glasses.

17.
Front Bioeng Biotechnol ; 12: 1363126, 2024.
Article En | MEDLINE | ID: mdl-38532882

Background: Seroma formation is a common postoperative complication. Fibrin-based glues are typically employed in an attempt to seal the cavity. Recently, the first nanoparticle (NP)-based treatment approaches have emerged. Nanoparticle dispersions can be used as tissue glues, capitalizing on a phenomenon known as 'nanobridging'. In this process, macromolecules such as proteins physically adsorb onto the NP surface, leading to macroscopic adhesion. Although significant early seroma reduction has been shown, little is known about long-term efficacy of NPs. The aim of this study was to assess the long-term effects of NPs in reducing seroma formation, and to understand their underlying mechanism. Methods: Seroma was surgically induced bilaterally in 20 Lewis rats. On postoperative day (POD) 7, seromas were aspirated on both sides. In 10 rats, one side was treated with NPs, while the contralateral side received only NP carrier solution. In the other 10 rats, one side was treated with fibrin glue, while the other was left untreated. Seroma fluid, blood and tissue samples were obtained at defined time points. Biochemical, histopathological and immunohistochemical assessments were made. Results: NP-treated sides showed no macroscopically visible seroma formation after application on POD 7, in stark contrast to the fibrin-treated sides, where 60% of the rats had seromas on POD 14, and 50% on POD 21. At the endpoint (POD 42), sides treated with nanoparticles (NPs) exhibited significant macroscopic differences compared to other groups, including the absence of a cavity, and increased fibrous adhesions. Histologically, there were more macrophage groupings and collagen type 1 (COL1) deposits in the superficial capsule on NP-treated sides. Conclusion: NPs not only significantly reduced early manifestations of seroma and demonstrated an anti-inflammatory response, but they also led to increased adhesion formation over the long term, suggesting a decreased risk of seroma recurrence. These findings highlight both the adhesive properties of NPs and their potential for clinical therapy.

18.
Small ; : e2311115, 2024 Mar 31.
Article En | MEDLINE | ID: mdl-38556634

Engineering of catalytically active inorganic nanomaterials holds promising prospects for biomedicine. Catalytically active metal oxides show applications in enhancing wound healing but have also been employed to induce cell death in photodynamic or radiation therapy. Upon introduction into a biological system, nanomaterials are exposed to complex fluids, causing interaction and adsorption of ions and proteins. While protein corona formation on nanomaterials is acknowledged, its modulation of nanomaterial catalytic efficacy is less understood. In this study, proteomic analyses and nano-analytic methodologies quantify and characterize adsorbed proteins, correlating this protein layer with metal oxide catalytic activity in vitro and in vivo. The protein corona comprises up to 280 different proteins, constituting up to 38% by weight. Enhanced complement factors and other opsonins on nanocatalyst surfaces lead to their uptake into macrophages when applied topically, localizing >99% of the nanomaterials in tissue-resident macrophages. Initially, the formation of the protein corona significantly reduces the nanocatalysts' activity, but this activity can be partially recovered in endosomal conditions due to the proteolytic degradation of the corona. Overall, the research reveals the complex relationship between physisorbed proteins and the catalytic characteristics of specific metal oxide nanoparticles, providing design parameters for optimizing nanocatalysts in complex biological environments.

19.
J Anim Sci ; 1022024 Jan 03.
Article En | MEDLINE | ID: mdl-38517473

The aim of the present study was to determine the optimal concentration of dietary protein required in transition diets for multiparous sows that enhance the farrowing process, colostrum production, and subsequent lactation performance. Forty-eight multiparous sows were allotted to one of six dietary treatments according to body weight (290 ±â€…3 kg) and parity (3.8 ±â€…0.2) from day 108 of gestation until 24 h after the onset of farrowing. The diets were isoenergetic and contained increasing concentrations of dietary protein (expressed as standardized ileal digestible [SID] Lys) and were supplied at a daily feed supply of 3.8 kg. On day 108 of gestation and days 2, 7, 14, 21, and 28 of lactation, body weight, and back fat thickness were recorded, and blood was sampled on day 108 of gestation, at the onset of farrowing, and days 3, 10, 17, and 24 of lactation from the sows for analysis of plasma metabolites. On day 115 of gestation, urine, and feces were collected for nitrogen (N) balance. The number of liveborn and stillborn piglets and time of birth were recorded and blood from every fourth piglet was sampled at birth for blood gas analysis. Piglets were weighed individually from birth until weaning, to estimate the colostrum and milk yield of the sows. Colostrum and milk samples were collected, and their compositions were determined. On days 3 and 28 of lactation, sows were injected with deuterium oxide to estimate body composition. The N utilization was maximized when the concentration of SID Lys in the transition diet was 6.06 g/kg (P < 0.01). When urinary concentrations of urea were expressed relative to creatinine, the relative concentration of urea remained low until a dietary concentration of 6.08 g SID Lys/kg, above which the relative concentration of urea increased (P < 0.01). Stillbirth rate increased linearly with increasing SID Lys concentration in the transition diet (P < 0.001), thus the concentration of SID Lys should be kept as low as possible without impairing sow performance excessively. A carry-over effect on milk yield was observed, showing that a dietary SID Lys concentration of 5.79 g/kg during transition optimized milk production at an average yield of 13.5 kg/d (P = 0.04). Increasing loss of body fat in lactation was observed with increasing SID Lys concentration in the transition diet (P = 0.03). In conclusion, the transition diet of multiparous sows should contain 5.79 g SID Lys/kg when fed 3.8 kg/d (13.0 MJ ME/kg), for a total SID Lys intake of 22 g/d.


In late gestation, the protein requirement of sows increases rapidly due to growth of the fetuses and mammary glands, whereas their energy requirement only is slightly increasing. Recent studies show that a feed supply of 4.1 kg/d in the last week of gestation is beneficial for the farrowing process and subsequent lactation performance. However, studies on feed supply cannot separate the effects of dietary fractions, so the sows' requirement for protein in the transition period remain unclear. The aim of the present study was to determine the dietary protein requirement of multiparous sows using a dose­response design with six diets containing increasing dietary protein (expressed as standardized ileal digestible [SID] Lys) from 3.99 to 8.57 g SID Lys/kg at a feeding level of 3.8 kg/d. Results indicate that the utilization of nitrogen (protein) during the transition period was maximized when the diet contained 6.06 g SID Lys/kg. Colostrum yield was unaffected by dietary treatment while dietary SID Lys in transition diet was found to have a carry-over effect on milk yield in the subsequent lactation period that was optimized at 5.79 g SID Lys/kg. As the concentration of SID Lys in the transition diet increased, stillbirth rate also increased, therefore, the concentration of SID Lys should be kept as low as possible without impairing sow performance excessively. In conclusion, the transition diet of multiparous sows should contain 5.79 g SID Lys/kg when fed 3.8 kg/d (13.0 MJ ME/kg), for a total SID Lys intake of 22 g/d.


Diet , Lactation , Pregnancy , Animals , Swine , Female , Diet/veterinary , Body Weight , Dietary Proteins , Urea , Animal Feed/analysis
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