2500 vibronic eigenstates of the NO radical.

The nitrate radical NO plays an important role in atmospheric chemistry, yet many aspects of its coupled and anharmonic vibronic structure remain elusive. Here, using an accurate, coupled full-dimensional diabatic potential that includes five electronic states, we revisit the vibronic spectrum associated with the electronic state. Using recently developed tensor network state methods, we are able to compute more than 2500 vibronic states, thereby increasing the number of computed full-dimensional states by a factor of 50, compared to previous work.

Pharmacokinetic modeling of sulfamethoxazole-trimethoprim and sulfadiazine-trimethoprim combinations in broilers.

Sulfonamides (S) are old bacteriostatic antibiotics which are widely prescribed in combination with trimethoprim (TMP) for the treatment of various diseases in food-producing animals such as poultry. Nowadays, the 1:5 dose ratio of TMP/S used in broilers is a direct transposition of the ratio determined in Human decades ago for TMP/sulfamethoxazole (SMX), aiming to obtain a supposed synergistic plasma concentration ratio of 1:19. However, major pharmacokinetics (PK) differences exist according to the sulfonamide used in the combination.

Hydrogen-iodine scattering. II. Rovibronic analysis and collisional dynamics.

Our recently published [Weike et al., J. Chem.

Male with an apparently normal phenotype carrying a BRCA1 exon 20 duplication in trans to a BRCA1 frameshift variant.

Background: Reports of dual carriers of pathogenic BRCA1 variants in trans are extremely rare, and so far, most individuals have been associated with a Fanconi Anemia-like phenotype.

Methods: We identified two families with a BRCA1 in-frame exon 20 duplication (Ex20dup). In one male individual, the variant was in trans with the BRCA1 frameshift variant c.

Hydrogen-iodine scattering. I. Development of an accurate spin-orbit coupled diabatic potential energy model.

The scattering of H by I is a prototypical model system for light-heavy scattering in which relativistic coupling effects must be taken into account. Scattering calculations depend strongly on the accuracy of the potential energy surface (PES) model. The methodology to obtain such an accurate PES model suitable for scattering calculations is presented, which includes spin-orbit (SO) coupling within the Effective Relativistic Coupling by Asymptotic Representation (ERCAR) approach.

Toxicological Profile and Anti-Inflammatory Effect of Mucoadhesive Gel from Residues of and .

Inflammation is a natural protective reaction of the body against endogenous and exogenous damage, such as tissue injuries, trauma, and infections. Thus, when the response is adequate, inflammation becomes a defense mechanism to repair damaged tissue, whereas when the response is inadequate and persistent, the increase in inflammatory cells, cytosines, and chymosins impair tissue regeneration and promote a response harmful to the organism. One example is chronic tissue inflammation, in which a simple lesion can progress to ulcers and even necrosis.

Selection of antibiotic resistance in pigs after exposure to feed cross-contaminated with oxytetracycline.

Due to possible cross-contamination of animal feedstuff with antibiotics, food-producing animals may be exposed to undesirable low concentrations of antimicrobials. These sub-therapeutic levels of antibiotics can lead to the selection of resistant bacteria in the animal gut. The goal of this study was to assess, through analysis of the faeces of treated and control pigs, the risk of resistant E.

Promoter Methylation Could Be the Second Hit in Lynch Syndrome Carcinogenesis.

(1) Background: hypermethylation is an epigenetic alteration in the tumorigenesis of colorectal cancer (CRC) and endometrial cancer (EC), causing gene silencing, and, as a consequence, microsatellite instability. Commonly, hypermethylation is considered a somatic and sporadic event in cancer, and its detection is recognized as a useful tool to distinguish sporadic from inherited conditions (such as, Lynch syndrome (LS)). However, hypermethylation has been described in rare cases of CRC and EC in LS patients.

Predicting nanocarriers' efficacy in 3D models with Brillouin microscopy.

Thanks to their unique nanoscale properties, nanomedicines can overcome some of the shortcomings of conventional therapies. For better predictive screening, it is important to assess their performance in three-dimensional (3D) multicellular tumour spheroids (MCTS) that can recapitulate the physiological barriers found in real tumours. Today, the evaluation of drug delivery nanosystems in MCTS is mainly explored by means of microscopy techniques that are invasive and require fluorescent labels which modify the composition and fate of the carriers.

Male breast cancer risk associated with pathogenic variants in genes other than BRCA1/2: an Italian case-control study.

Background: Germline pathogenic variants (PVs) in BRCA1/2 genes are associated with breast cancer (BC) risk in both women and men. Multigene panel testing is being increasingly used for BC risk assessment, allowing the identification of PVs in genes other than BRCA1/2. While data on actionable PVs in other cancer susceptibility genes are now available in female BC, reliable data are still lacking in male BC (MBC).

Hereditary Cancer Syndromes: A Comprehensive Review with a Visual Tool.

Hereditary cancer syndromes account for nearly 10% of cancers even though they are often underdiagnosed. Finding a pathogenic gene variant could have dramatic implications in terms of pharmacologic treatments, tailored preventive programs, and familiar cascade testing. However, diagnosing a hereditary cancer syndrome could be challenging because of a lack of validated testing criteria or because of their suboptimal performance.

PBPK Model To Predict Marbofloxacin Distribution in Edible Tissues and Intestinal Exposure in Pigs.

Marbofloxacin (MAR) is a fluoroquinolone antibiotic used in food-producing animals in European Union, especially in pigs. In this study, MAR concentrations in plasma, comestible tissues, and intestinal segments were determined in pigs injected with MAR. Based on these data and the literature, a flow-limited PBPK model was developed to predict the tissue distribution of MAR and estimate the withdrawal period after label-use in Europe.

Presence and Depletion of Sulfadiazine, Trimethoprim, and Oxytetracycline into Feathers of Treated Broiler Chickens and Impact on Antibiotic-Resistant Bacteria.

The valorization of poultry byproducts, like feathers (processed to feather meal), in animal feed could contribute to the presence of veterinary drugs, including antibiotics. An animal study was carried out to study the fate of sulfadiazine, trimethoprim, and oxytetracycline in feathers, plasma, and droppings of broiler chickens. Cage and floor housing, different from current farm practices, were studied.

Ionophore coccidiostats - disposition kinetics in laying hens and residues transfer to eggs.

Poultry production is linked with the use of veterinary medicinal products to manage diseases. Ionophore coccidiostats have been permitted for use as feed additives within the European Union (EU) for the prevention of coccidiosis in various species of poultry with except of laying hens. The presence of chemical residues in eggs is a matter of major concern for consumers' health.

Biallelic Mutations in a Family with Uncommon Clinical and Molecular Features.

We describe a patient with constitutional mismatch repair-deficiency (CMMR-D) in whom the syndrome started at age 10 with the development of multiple adenomas in the large bowel. In the successive 25 years, four malignancies developed in different organs (rectum, ileum, duodenum, and lymphoid tissue). The patient had biallelic constitutional pathogenic variants in the gene.

Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers.

The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation.

Validation of a LC-MS/MS method for the quantitative analysis of four antibiotics in pig tissues and plasma to assess the risk of transfer of residues to edible matrices after exposure to cross-contaminated feed.

Cross-contamination between medicated and non-medicated feed can occur during production, processing, transport or storage of animal feed. This may lead to the presence of low concentrations of antibiotics in supposedly drug-free feed for food production animals, which potentially could also harm consumers due to residues. In addition, consumption of sub-therapeutic concentrations of antibiotics may increase the risk of emergence of resistant bacteria.

Clinical, splicing, and functional analysis to classify BRCA2 exon 3 variants: Application of a points-based ACMG/AMP approach.

Skipping of BRCA2 exon 3 (∆E3) is a naturally occurring splicing event, complicating clinical classification of variants that may alter ∆E3 expression. This study used multiple evidence types to assess pathogenicity of 85 variants in/near BRCA2 exon 3. Bioinformatically predicted spliceogenic variants underwent mRNA splicing analysis using minigenes and/or patient samples.

Antiglycation, antioxidant and cytotoxicity activities of crude extract of Turnera ulmifolia L. before and after microencapsulation process.

Turnera ulmifolia L. is used in folk medicine and it is known to have anti-hyperglycemic effect on the organism in order to reduce complications in diabetic patients. Glycation process is directly related to oxidative stress, acting as an important endogenous source, inducing the production of free radicals, and thus increasing the production of reactive oxygen species.

Simulation of the photodetachment spectra of the nitrate anion (NO) in the B̃ E' energy range and non-adiabatic electronic population dynamics of NO.

The photodetachment spectrum of the nitrate anion (NO) in the energy range of the NO second excited state is simulated from first principles using quantum wave packet dynamics. The prediction at 10 K and 435 K relies on the use of an accurate full-dimensional fully coupled five state diabatic potential model utilizing an artificial neural network. The ability of this model to reproduce experimental spectra was demonstrated recently for the lower energy range [A.

An Exceptional Response to Dostarlimab in Mismatch Repair Deficient, Microsatellite Instability-High and Platinum Refractory Endometrial Cancer.

Until recently, effective therapies for advanced endometrial cancer progressing to a platinum-based combination were lacking. In this setting, immunotherapy with anti PD-1/PDL-1 monoclonal antibodies is rising as a new paradigm in particular for patients with microsatellites instability/mismatch repair deficiency. In this case report, we describe an exceptional and rapid response to dostarlimab in a platinum refractory endometrial cancer patient with high disease burden harboring a mismatch repair deficiency.

A physiologically based pharmacokinetic (PBPK) model exploring the blood-milk barrier in lactating species - A case study with oxytetracycline administered to dairy cows and goats.

Antibiotic excretion into milk depends on several factors such as the compound's physicochemical properties, the animal physiology, and the milk composition. The objective of this study was to develop a physiologically based pharmacokinetic (PBPK) model describing the passage of drugs into the milk of lactating species. The udder is described as a permeability limited compartment, divided into vascular, extracellular water (EW), intracellular water (IW) and milk, which was stored in alveolar and cistern compartments.

A liquid chromatography coupled to tandem mass spectrometry method for the quantification of spiramycin and its active metabolite neospiramycin in milk of major and minor species: Validation using the accuracy profile.

A liquid chromatography with tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous quantification of residues of spiramycin, a macrolide antibiotic, and its active metabolite neospiramycin in cow's milk as well as in minor species 'milk, goat and ewe. Spiramycin-d3 was used as internal standard for quantification of both analytes. This analytical method was validated using a global accuracy profile as a graphical decision tool built according to the trueness and the precision of the method.

Filling the gap: A thorough investigation for the genetic diagnosis of unsolved polyposis patients with monoallelic MUTYH pathogenic variants.

Backgrounds: MUTYH-associated polyposis (MAP) is an autosomal recessive disease caused by biallelic pathogenic variants (PV) of the MUTYH gene. The aim of this study was to investigate the genetic causes of unexplained polyposis patients with monoallelic MUTYH PV. The analysis focused on 26 patients with suspected MAP, belonging to 23 families.