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2.
Open Forum Infect Dis ; 11(9): ofae481, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39286032

RESUMO

Pregnant people face increased risk of severe COVID-19. Current guidelines recommend updated COVID-19 vaccination (2023-2024) for those aged ≥6 months, irrespective of pregnancy status. To refine recommendations for pregnant people, further data are needed. Using a test-negative design, we evaluated COVID-19 vaccine effectiveness against medically attended COVID-19 with COVID-19-like illness among pregnant people aged 18 to 45 years during June 2022 to August 2023. When doses were received during pregnancy, vaccine effectiveness was 52% (95% CI, 29%-67%); when received <6 months prior to pregnancy, 28% (95% CI, 11%-42%); and when received ≥6 months prior to pregnancy, 6% (95% CI, -11% to 21%). Pregnant people should stay up-to-date with recommended COVID-19 vaccination.

3.
Soft Matter ; 20(36): 7227-7236, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39225393

RESUMO

Photoresponsive hydrogels are an emerging class of stimuli-responsive materials that exhibit changes in physical or chemical properties in response to light. Previous investigations have leveraged photothermal mechanisms to achieve reversible changes in hydrogel friction, although few have focused on photochemical means. To date, the tribological properties of photoswitchable hydrogels (e.g., friction and lubrication) have remained underexplored. In this work, we incorporated photoresponsive methoxy-spiropyran-methacrylate monomers (methoxy-SP-MA) into a hydrogel network to form a copolymerized system of poly(N-isopropylacrylamide-co-2-acrylamido-2-methylpropane sulfonic acid-co-methoxy-spiropyran-methacrylate) (p(NIPAAm-co-AMPS-co-SP)). We demonstrated repeatable photoresponsive changes to swelling, friction, and stiffness over three light cycles. Our findings suggest that volume changes driven by the decreased hydrophilicity of the methoxy-SP-MA upon light irradiation are responsible for differences in the mechanical and tribological properties of our photoresponsive hydrogels. Our results could inform future designs of photoswitchable hydrogels for applications ranging from biomedical applications to soft robotics.

4.
NPJ Precis Oncol ; 8(1): 203, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39277699

RESUMO

Recent trials have shown the efficacy of trastuzumab deruxtecan (T-DXd) in HER2-negative patients, but there is not yet a way to identify which patients will best respond, especially with the inability of current HER2 IHC and FISH assays to accurately determine HER2 expression in the unamplified setting. Here, we present a heavily pre-treated patient with triple-negative breast cancer (HER2 IHC 0 who had a complete response to T-DXd. In this case, we used a CLIA-certified reverse-phase protein array-based proteomic assay (RPPA) to determine that the patient had moderate HER2 protein expression (HER2Total 2+, 42%) and activation (HER2Y1248 1+, 23%). Using these results, we determined that the patient may benefit from T-Dxd despite being traditionally qualified as HER2 IHC 0. These findings highlight the potential for proteomics-based assays that may more accurately quantitate HER2 and (its activation) in the HER2 unamplified/IHC 0 setting to better select patients whose tumors are classically molecularly defined as HER2 IHC 0, but still could respond to HER2-directed therapy, and give patients access to therapies which for which they otherwise would not be eligible.

5.
Genetics ; 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39259277

RESUMO

Germ cell development and gamete production in animals require small RNA pathways. While studies indicate that microRNAs (miRNAs) are necessary for normal sperm production and function, the specific roles for individual miRNAs are largely unknown. Here, we use small RNA sequencing of dissected gonads and functional analysis of new loss of function alleles to identify functions for miRNAs in the control of fecundity and sperm production in Caenorhabditis elegans (C. elegans) males and hermaphrodites. We describe a set of 29 male gonad-enriched miRNAs and identify a set of individual miRNAs (mir-58.1 and mir-235) and a miRNA cluster (mir-4807-4810.1) that are required for optimal sperm production at 20°C and a set of miRNAs (mir-49, mir-57, mir-83, mir-261, and mir-357/358) that are required for sperm production at 25°C. We observed defects in meiotic progression in mutants missing mir-58.1, mir-83, mir-235, and mir-4807-4810.1, which may contribute to the observed defects in sperm production. Further, analysis of multiple mutants of these miRNAs suggested genetic interactions between these miRNAs. This study provides insights on the regulatory roles of miRNAs that promote optimal sperm production and fecundity in males and hermaphrodites.

6.
Physiol Rep ; 12(17): e70040, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39256891

RESUMO

Cardiac metabolism ensures a continuous ATP supply, primarily using fatty acids in a healthy state and favoring glucose in pathological conditions. Pyruvate kinase muscle (PKM) controls the final step of glycolysis, with PKM1 being the main isoform in the heart. PKM2, elevated in various heart diseases, has been suggested to play a protective role in cardiac stress, but its function in basal cardiac metabolism remains unclear. We examined hearts from global PKM2 knockout (PKM2-/-) mice and found reduced intracellular glucose. Isotopic tracing of U-13C glucose revealed a shift to biosynthetic pathways in PKM2-/- cardiomyocytes. Total ATP content was two-thirds lower in PKM2-/- hearts, and functional analysis indicated reduced mitochondrial oxygen consumption. Total reactive oxygen species (ROS) and mitochondrial superoxide were also increased in PKM2-/- cardiomyocytes. Intriguingly, PKM2-/- hearts had preserved ejection fraction compared to controls. Mechanistically, increased calcium/calmodulin-dependent kinase II activity and phospholamban phosphorylation may contribute to higher sarcoendoplasmic reticulum calcium ATPase 2 pump activity in PKM2-/- hearts. Loss of PKM2 led to altered glucose metabolism, diminished mitochondrial function, and increased ROS in cardiomyocytes. These data suggest that cardiac PKM2 acts as an important rheostat to maintain ATP levels while limiting oxidative stress. Although loss of PKM2 did not impair baseline contractility, its absence may make hearts more sensitive to environmental stress or injury.


Assuntos
Miócitos Cardíacos , Estresse Oxidativo , Animais , Miócitos Cardíacos/metabolismo , Camundongos , Camundongos Knockout , Glucose/metabolismo , Masculino , Espécies Reativas de Oxigênio/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/genética , Mitocôndrias Cardíacas/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética , Camundongos Endogâmicos C57BL , Piruvato Quinase/metabolismo , Piruvato Quinase/genética , Trifosfato de Adenosina/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Miocárdio/metabolismo
7.
Vaccine ; 42(24): 126288, 2024 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-39241356

RESUMO

BACKGROUND: There are known disparities in U.S. COVID-19 vaccination but there is limited information on national vaccine uptake in a large, racially diverse, all-age population. Here, we describe COVID-19 vaccination coverage in a large U.S. population accessing care in OCHIN (not an acronym), a national network of community-based healthcare organizations. METHODS: Within OCHIN, we identified patients aged 6 months and older with ≥1 completed clinical encounter since becoming age-eligible for the COVID-19 vaccine between December 13, 2020 and December 31, 2022. Patients' COVID-19 vaccination status was assessed from OCHIN's Epic® electronic health record which includes data from state immunization information systems. Patients were considered vaccinated if they received ≥1 dose of a monovalent vaccine product; coverage was categorized by age groups (6 months-4 years; 5-11 years, 12-15 years, 16+ years). Multivariate analyses assessed factors associated with COVID-19 vaccination across age groups. RESULTS: The cohort included 3.3 million Hispanic (37 %), non-Hispanic (NH) White (31 %), NH Black (15 %), and NH Asian (7 %) patients; 45 % of whom were Medicaid-enrolled, 19 % uninsured, and 53 % with a household income below 100 % of the federal poverty level. The proportion with ≥1 COVID-19 vaccine dose increased with age, from 11.7 % (6 months through 4 years) to 72.3 % (65 years and older). The only factors associated with significantly higher COVID-19 vaccine coverage across age groups were prior receipt of an influenza vaccine and having private insurance. In adjusted modeling, when compared to NH whites, COVID-19 vaccine coverage was significantly higher among Hispanic, NH Asian, and NH multiple-race patients aged ≥5 years and significantly lower among NH Black and NH Native Hawaiian/Other Pacific Islander patients aged 6 months-4 years old. CONCLUSIONS: We identified disparities in primary series COVID-19 vaccine coverage by age, race and ethnicity, household income, insurance status, and prior influenza vaccination within this large, diverse population accessing care in community-based healthcare organizations.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Etnicidade , Disparidades em Assistência à Saúde , Determinantes Sociais da Saúde , Cobertura Vacinal , Humanos , Feminino , Adolescente , Vacinas contra COVID-19/administração & dosagem , COVID-19/prevenção & controle , Masculino , Adulto , Pessoa de Meia-Idade , Criança , Adulto Jovem , Pré-Escolar , Cobertura Vacinal/estatística & dados numéricos , Lactente , Estados Unidos , Idoso , Etnicidade/estatística & dados numéricos , Disparidades em Assistência à Saúde/estatística & dados numéricos , SARS-CoV-2/imunologia , Vacinação/estatística & dados numéricos , Centros Comunitários de Saúde/estatística & dados numéricos , Grupos Raciais/estatística & dados numéricos
8.
Ann Surg ; 280(3): 432-443, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39264354

RESUMO

OBJECTIVE: We aimed to determine the incidence of growth failure in infants with necrotizing enterocolitis (NEC) or spontaneous intestinal perforation (SIP) and whether initial laparotomy versus peritoneal drainage (PD) impacted the likelihood of growth failure. SUMMARY BACKGROUND DATA: Infants with surgical NEC and SIP have high mortality, and most have neurodevelopmental impairment and poor growth. Existing literature on growth outcomes for these infants is limited. METHODS: This is a preplanned secondary study of the Necrotizing Enterocolitis Surgery Trial dataset. The primary outcome was growth failure (Z-score for weight <-2.0) at 18 to 22 months. We used logistic regression, including diagnosis and treatment, as covariates. Secondary outcomes were analyzed using the Fisher exact or Pearson χ2 test for categorical variables and the Wilcoxon rank sum test or one-way ANOVA for continuous variables. RESULTS: Among 217 survivors, 207 infants (95%) had primary outcome data. Growth failure at 18 to 22 months occurred in 24/50 (48%) of NEC infants versus 65/157 (42%) SIP (P=0.4). The mean weight-for-age Z-score at 18 to 22 months in NEC infants was -2.05±0.99 versus -1.84±1.09 SIP (P=0.2), and the predicted mean weight-for-age Z-score SIP (Beta -0.27; 95% CI: -0.53, -0.01; P=0.041). Median declines in weight-for-age Z-score between birth and 18 to 22 months were significant in all infants but most severe (>2) in NEC infants (P=0.2). CONCLUSIONS: This first ever prospective study of growth outcomes in infants with surgical NEC or SIP demonstrates that growth failure is very common, especially in infants with NEC, and persists at 18-22 months.


Assuntos
Enterocolite Necrosante , Perfuração Intestinal , Humanos , Enterocolite Necrosante/cirurgia , Enterocolite Necrosante/complicações , Perfuração Intestinal/cirurgia , Perfuração Intestinal/etiologia , Masculino , Feminino , Lactente , Recém-Nascido , Drenagem/métodos , Laparotomia/métodos , Perfuração Espontânea/cirurgia , Perfuração Espontânea/etiologia , Transtornos do Crescimento/etiologia , Recém-Nascido Prematuro
9.
Phys Rev Lett ; 133(9): 090802, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39270187

RESUMO

We entangle two cotrapped atomic barium ion qubits by collecting single visible photons from each ion through in vacuo 0.8 NA objectives, interfering them through an integrated fiber beam splitter and detecting them in coincidence. This projects the qubits into an entangled Bell state with an observed fidelity lower bound of F>94%. We also introduce an ytterbium ion for sympathetic cooling to remove the need for recooling interruptions and achieve a continuous entanglement rate of 250 s^{-1}.

10.
Pharmaceutics ; 16(8)2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39204375

RESUMO

Intravaginal rings (IVRs) represent a well-established, woman-controlled and sustained vaginal drug delivery system suitable for a wide range of applications. Here, we sought to investigate the differences in etonogestrel (ENG) and ethinyl estradiol (EE) release from a 3D-printed IVR utilizing continuous liquid interface production (CLIP™) (referred to as CLIPLOW for low drug loading and CLIPHIGH IVRs for high drug loading) and NuvaRing, a commercially available injection molded IVR. We conducted in vitro release studies in simulated vaginal fluid to compare the release of ENG and EE from CLIPLOW IVRs and NuvaRing. CLIPLOW IVRs had a similar hormone dose to NuvaRing and exhibited slightly slower ENG release and greater EE release in vitro compared to NuvaRing. When administered to female sheep, NuvaRing demonstrated greater ENG/EE levels in plasma, vaginal tissue and vaginal fluids compared to CLIPLOW IVR despite similar drug loadings. Leveraging observed hormones levels in sheep from NuvaRing as an effective contraceptive benchmark, we developed a long-acting CLIPHIGH IVR with increased ENG and EE doses that demonstrated systemic and local hormone levels greater than the NuvaRing for 90 days in sheep. No signs of toxicity were noted regarding general health, colposcopy, or histological analysis in sheep after CLIPHIGH IVR administration. Our results provided (1) a comparison of ENG and EE release between a 3D-printed IVR and NuvaRing in vitro and in vivo, (2) a preclinical pharmacokinetic benchmark for vaginally delivered ENG and EE and (3) the generation of a 90-day CLIP IVR that will be utilized in future work to support the development of a long-acting ENG/EE IVR combined with an antiretroviral for the prevention of HIV and unplanned pregnancy.

11.
bioRxiv ; 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-39149249

RESUMO

We employed laser microdissection to selectively harvest tumor cells and stroma from the microenvironment of formalin-fixed, paraffin-embedded head and neck squamous cell carcinoma (HNSCC) tissues. The captured HNSCC tissue fractions were analyzed by quantitative mass spectrometry-based proteomics using a data independent analysis approach. In paired samples, we achieved excellent proteome coverage having quantified 6,668 proteins with a median quantitative coefficient of variation under 10%. We observed significant differences in relevant functional pathways between the spatially resolved tumor and stroma regions. Our results identified extracellular matrix (ECM) as a major component enriched in the stroma, including many cancer associated fibroblast signature proteins in this compartment. We demonstrate the potential for comparative deep proteome analysis from very low starting input in a scalable format that is useful to decipher the alterations in tumor and the stromal microenvironment. Correlating such results with clinical features or disease progression will likely enable identification of novel targets for disease classification and interventions.

12.
bioRxiv ; 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39149364

RESUMO

Peripheral artery disease (PAD) is the narrowing of the arteries that carry blood to the lower extremities. PAD has been traditionally associated with atherosclerosis. However, recent studies have found that medial arterial calcification (MAC) is the primary cause of chronic limb ischemia below the knee. MAC involves calcification of the elastin fibers surrounding smooth muscle cells (SMCs) in arteries. Matrix GLA Protein (MGP) binds circulating calcium and inhibits vascular calcification. Mgp -/- mice develop severe MAC and die within 8 weeks of birth due to aortic rupture or heart failure. We previously discovered a rare genetic disease Arterial Calcification due to Deficiency in CD73 (ACDC) in which patients present with extensive MAC in their lower extremity arteries. Using a patient-specific induced pluripotent stem cell model we found that rapamycin inhibited calcification. Here we investigated whether rapamycin could reduce MAC in vivo using Mgp -/- mice as a model. Mgp +/+ and Mgp -/- mice received 5mg/kg rapamycin or vehicle. Calcification content was assessed via microCT, and vascular morphology and extracellular matrix content assessed histologically. Immunostaining and western blot analysis were used to examine SMC phenotypes and cellular functions. Rapamycin prolonged Mgp -/- mice lifespan, decreased mineral density in the arteries, and increased smooth muscle actin protein levels, however, calcification volume, vessel morphology, SMC proliferation, and autophagy flux were all unchanged. These findings suggest that rapamycin's effects in the Mgp -/- mouse are independent of the vascular phenotype.

13.
J Food Prot ; 87(10): 100346, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39147098

RESUMO

Dark chocolate produced on equipment used to manufacture milk chocolate can contain milk due to cross-contact. This study evaluated the use of dry cleaning methods for removing milk chocolate residue from a butterfly or ball valve attached to a stainless steel pipe and from pilot-scale equipment used in chocolate manufacture. Milk-free dark chocolate (40 °C) was pumped through a milk chocolate-contaminated valve/pipe assembly after no cleaning, use of a pig purging treatment, or a 40 °C cocoa butter flush. Dark chocolate samples were collected at 7-sec intervals. Treatments investigated for the removal of residual milk chocolate from a conche and a ball mill included no cleaning, a 40 °C cocoa butter rinse, and wet cleaning. After cleaning, three batches of dark chocolate (40 °C) were processed in the ball mill and conche, and each batch was collected. Milk chocolate was processed on a 3-roll refiner, followed by push-through with dark chocolate (∼9 kg) with 0.3 kg samples collected at 5-min intervals. Dark chocolate samples were analyzed for milk concentrations by ELISA. Trials and analyses were completed in triplicate. Dark chocolate push-through alone resulted in milk concentrations ≥4,500 µg/g in samples obtained from the contaminated valve/pipe combinations within the first few seconds of collection, and ≥16.2 kg of dark chocolate was needed to obtain milk concentrations below the ELISA LOQ (2.5 µg/g). A pig purging treatment of the ball valve/pipe assembly resulted in milk concentrations below the ELISA LOQ. A cocoa butter flush of the butterfly valve/pipe decreased initial milk concentrations, but milk was detected until ≥18.7 kg dark chocolate purge. Milk concentrations in first batches of dark chocolate processed in a ball mill and conche without cleaning were ≥17,000 µg/g while the use of a cocoa butter rinse reduced milk levels in dark chocolate by ≥89%. Some dry cleaning treatments were effective at reducing levels of milk in dark chocolate due to cross-contact.

14.
Artigo em Inglês | MEDLINE | ID: mdl-39161931

RESUMO

Background: The current literature shows similar clinical outcomes between first metatarsophalangeal (MTP) joint arthrodesis and synthetic cartilage implant (SCI) hemiarthroplasty in the treatment of hallux rigidus; however, prior studies have not reported validated patient-reported outcome measures (PROMs). To our knowledge, this is the first study to compare PROMs using 6 domains of the validated Patient-Reported Outcomes Measurement Information System (PROMIS) in patients treated for hallux rigidus with MTP joint arthrodesis and with SCI hemiarthroplasty. In addition, this novel study provides comparative data on the complication and revision rates for each procedure. Methods: A single-center, retrospective registry search identified all patients with preoperative PROMIS scores who underwent MTP joint arthrodesis or SCI hemiarthroplasty for hallux rigidus between February 2016 and June 2021. The study aimed to determine if the 2 procedures showed statistically or clinically equivalent PROMIS scores in 6 domains: physical function, pain interference, pain intensity, global physical health, global mental health, and depression. A multivariable linear regression analysis was performed to compare adjusted 1-year postoperative PROMIS scores between the 2 cohorts. Complication and revision rates were also compared. Results: The study included 82 patients who underwent SCI hemiarthroplasty and 101 who underwent MTP joint arthrodesis. Demographic data and preoperative hallux rigidus severity showed no significant differences between the cohorts. PROMIS scores were mostly comparable between the 2 groups, except for the pain intensity domain. The patients who underwent MTP joint arthrodesis exhibited significantly better pain relief at 1 and 2 years postoperatively, which was supported by adjusted postoperative PROMIS scores. At 2 years, the SCI group had worse pain intensity scores and lower global physical health scores. There were no differences between the cohorts in additional PROMIS scores or complication data. Conclusions: While outcomes in most of the domains were similar, MTP joint arthrodesis was more effective at mitigating pain intensity compared with SCI hemiarthroplasty. This information can guide patient counseling and decision-making when considering surgical intervention for hallux rigidus. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

15.
J Physiol ; 602(17): 4309-4326, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39196791

RESUMO

Epithelial Na+ channels (ENaCs) are activated by proteolysis of the α and γ subunits at specific sites flanking embedded inhibitory tracts. To examine the role of α subunit proteolysis in channel activation in vivo, we generated mice lacking the distal furin cleavage site in the α subunit (αF2M mice). On a normal Na+ control diet, no differences in ENaC protein abundance in kidney or distal colon were noted between wild-type (WT) and αF2M mice. Patch-clamp analyses revealed similar levels of ENaC activity in kidney tubules, while no physiologically relevant differences in blood chemistry or aldosterone levels were detected. Male αF2M mice did exhibit diminished ENaC activity in the distal colon, as measured by amiloride-sensitive short-circuit current (ISC). Following dietary Na+ restriction, WT and αF2M mice had similar natriuretic and colonic ISC responses to amiloride. However, single-channel activity was significantly lower in kidney tubules from Na+-restricted αF2M mice compared with WT littermates. ENaC α and γ subunit expression in kidney and distal colon were also enhanced in Na+-restricted αF2M vs. WT mice, in association with higher aldosterone levels. These data provide evidence that disrupting α subunit proteolysis impairs ENaC activity in vivo, requiring compensation in response to Na+ restriction. KEY POINTS: The epithelial Na+ channel (ENaC) is activated by proteolytic cleavage in vitro, but key questions regarding the role of ENaC proteolysis in terms of whole-animal physiology remain to be addressed. We studied the in vivo importance of this mechanism by generating a mouse model with a genetic disruption to a key cleavage site in the ENaC's α subunit (αF2M mice). We found that αF2M mice did not exhibit a physiologically relevant phenotype under normal dietary conditions, but have impaired ENaC activation (channel open probability) in the kidney during salt restriction. ENaC function at the organ level was preserved in salt-restricted αF2M mice, but this was associated with higher aldosterone levels and increased expression of ENaC subunits, suggesting compensation was required to maintain homeostasis. These results provide the first evidence that ENaC α subunit proteolysis is a key regulator of channel activity in vivo.


Assuntos
Canais Epiteliais de Sódio , Furina , Animais , Canais Epiteliais de Sódio/metabolismo , Canais Epiteliais de Sódio/genética , Camundongos , Masculino , Furina/metabolismo , Furina/genética , Sódio/metabolismo , Colo/metabolismo , Camundongos Endogâmicos C57BL , Aldosterona/metabolismo , Dieta Hipossódica
16.
Toxicol Res (Camb) ; 13(4): tfae114, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39086642

RESUMO

Hazard and risk assessment of complex petroleum-derived substances has been in a state of continuous improvement since the 1970s, with the development of approaches that continue to be applied and refined. Alternative feeds are defined here as those coming into a refinery or chemical plant that are not hydrocarbons from oil and gas extraction such as biologically derived oils, pyrolysis oil from biomass or other, and recycled materials. These feeds are increasingly being used for production of liquid hydrocarbon streams, and hence, there is a need to assess these alternatives, subsequent manufacturing and refining processes and end products for potential risk to humans and the environment. Here we propose a tiered, problem formulation-driven framework for assessing the safety of hydrocarbon streams and products derived from alternative feedstocks in use. The scope of this work is only focused on petrochemical safety assessment, though the principles may be applicable to other chemistries. The framework integrates combinations of analytical chemistry, in silico and in vitro tools, and targeted testing together with conservative assumptions/approaches to leverage existing health, environmental, and exposure data, where applicable. The framework enables the identification of scenarios where de novo hazard and/or exposure assessments may be needed and incorporates tiered approaches to do so. It can be applied to enable decisions efficiently and transparently and can encompass a wide range of compositional space in both feedstocks and finished products, with the objective of ensuring safety in manufacturing and use.

18.
Artigo em Inglês | MEDLINE | ID: mdl-39102361

RESUMO

Canine congenital extrahepatic portosystemic shunt (EHPSS) morphologies have not been fully elucidated. The goal of this retrospective, multi-institutional study was to use CT angiography to create an anatomical-based nomenclature system for canine congenital EHPSS. These shunt morphologies were then evaluated to identify any significant association with patient age, sex, breed, weight, or subjective portal perfusion score. Data collected respectively from the SVSTS and VIRIES list-serves included patient DOB, sex, breed, weight, CT date, and reported diagnosis. A single author (C.W.) viewed all CT scans and classified shunts based on the shunt portal vessel(s) of origin, the shunt systemic vessel(s) of insertion, and any substantial portal vessels contributing to the shunt. Additionally, hepatic portal perfusion was subjectively scored between one (poor/none) and five (good/normal) based on the caliber of the intrahepatic portal veins. A total of 1182 CT scans were submitted from 13 different institutions. Due to exclusion criteria, 100 (8.5%) were removed, leaving 1082 CT scans to be included. Forty-five different EHPSS anatomies were identified with five classifications accounting for 85% of all shunts (left gastric-phrenic [27%], left gastric-azygos [19%], left gastric-caval [15%], aberrant left gastric-caval with right gastric vein [12%], and aberrant left gastric-caval with right gastric vein and short gastric vein [11%]). Shunt origin involved the left gastric vein in 95% of the described classifications. Significant differences were identified among the five most common shunt types with respect to age at the time of the CT scan (P < .001), sex (P = .009), breed (P < .001), weight (P < .001), and subjective portal perfusion score (P < .001). An anatomical classification system for canine EHPSS may enable improved understanding, treatment comparisons, and outcome prediction for these patients.

19.
J Chem Phys ; 161(6)2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39120036

RESUMO

The interactions of electrons with molecular systems under various conditions are essential to interdisciplinary research fields extending over the fundamental and applied sciences. In particular, investigating electron-induced ionization and dissociation of molecules may shed light on the radiation damage to living cells, the physicochemical processes in interstellar environments, and reaction mechanisms occurring in combustion or plasma. We have, therefore, studied electron-induced ionization and dissociation of the gas phase 3,4-dihydro-2H-pyran (DHP), a cyclic ether appearing to be a viable moiety for developing efficient clinical pharmacokinetics and revealing the mechanisms of biofuel combustion. The mass spectra in the m/z = 10-90 mass range were measured at several different energies of the ionizing electron beam using mass spectrometry. The mass spectra of DHP at the same energies were simulated using on-the-fly semi-classical molecular dynamics (MD) within the framework of the QCxMS formalism. The MD settings were suitably adjusted until a good agreement with the experimental mass spectra intensities was achieved, thus enabling a reliable assignment of cations and unraveling the plausible fragmentation channels. Based on the measurement of the absolute total ionization cross section of DHP (18.1 ± 0.9) × 10-16 cm2 at 100 eV energy, the absolute total and partial ionization cross sections of DHP were determined in the 5-140 eV electron energy. Moreover, a machine learning algorithm that was trained with measured cross sections from 25 different molecules was used to predict the total ionization cross section for DHP. Comparison of the machine learning simulation with the measured data showed acceptable agreement, similar to that achieved in past predictions of the algorithm.

20.
Front Nutr ; 11: 1386257, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39135556

RESUMO

Reducing dairy fat intake is a common dietary guideline to limit energy and saturated fatty acid intake for the promotion of cardiometabolic health. However, research utilizing a holistic, food-based approach to assess the consumption of the fat found in dairy, a broad and diverse food group, may provide new insight into these guidelines. Dairy fat is comprised of a diverse assembly of fatty acids, triacylglycerols, sterols, and phospholipids, all uniquely packaged in a milk fat globule. The physical structure of this milk fat globule and its membrane is modified through different processing methods, resulting in distinctive dairy-fat matrices across each dairy product. The objectives of this narrative review were to first define and compare the dairy-fat matrix in terms of its unique composition, physical structure, and fat content across common dairy products (cow's milk, yogurt, cheese, and butter). With this information, we examined observational studies and randomized controlled trials published within the last 10 years (2013-2023) to assess the individual effects of the dairy-fat matrix in milk, yogurt, cheese, and butter on cardiometabolic health and evaluate the implications for nutrition guidance. Searches conducted on Ovid MEDLINE and PubMed® utilizing search terms for cardiometabolic health, both broadly and regarding specific disease outcomes and risk factors, yielded 59 studies that were analyzed and included in this review. Importantly, this review stratifies by both dairy product and fat content. Though the results were heterogeneous, most studies reported no association between intake of these individual regular-fat dairy products and cardiometabolic outcome measures, thus, the current body of evidence suggests that regular-fat dairy product consumption may be incorporated within overall healthy eating patterns. Research suggests that there may be a beneficial effect of regular-fat milk and yogurt intake on outcome measures related to body weight and composition, and an effect of regular-fat cheese intake on outcome measures related to blood lipids, but more research is necessary to define the directionality of this relationship. Lastly, we identify methodological research gaps and propose future research directions to bolster the current evidence base available for ascertaining the role of dairy fat in a healthy diet.

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