Impact of Two-Body Currents on Magnetic Dipole Moments of Nuclei.

We investigate the effects of two-body currents on magnetic dipole moments of medium-mass and heavy nuclei using the valence-space in-medium similarity renormalization group with chiral effective field theory interactions and currents. Focusing on near doubly magic nuclei from oxygen to bismuth, we have found that the leading two-body currents globally improve the agreement with experimental magnetic moments. Moreover, our results show the importance of multishell effects for ^{41}Ca, which suggest that the Z=N=20 gap in ^{40}Ca is not as robust as in ^{48}Ca. The increasing contribution of two-body currents in heavier systems is explained by the operator structure of the center-of-mass dependent Sachs term.

Nuclear Charge Radii of Silicon Isotopes.

The nuclear charge radius of ^{32}Si was determined using collinear laser spectroscopy. The experimental result was confronted with ab initio nuclear lattice effective field theory, valence-space in-medium similarity renormalization group, and mean field calculations, highlighting important achievements and challenges of modern many-body methods. The charge radius of ^{32}Si completes the radii of the mirror pair ^{32}Ar-^{32}Si, whose difference was correlated to the slope L of the symmetry energy in the nuclear equation of state. Our result suggests L≤60 MeV, which agrees with complementary observables.

Validation of a rapid molecular detection test for gram-negative multidrug-resistant bacteria in rectal swabs upon admission of patients to the intensive care unit.

In ICU settings, screening patients upon admission for potential multiresistant bacteria (BMR) carriers is crucial. Traditionally, clinical decisions relied on delayed culture results, but a rapid PCR molecular test called RealCycler-Rezero-U/G (Progenie-molecular©), emerged as an alternative. This study aimed to validate its effectiveness in detecting gram-negative BMR in rectal swabs at ICU admission. Over 24 months, an observational study was conducted on 1,234 admitted patients, with 217 meeting isolation criteria and undergoing both PCR and culture tests. Results showed a 17.5 % positive rate for screening. The PCR test exhibited impressive accuracy at 98.6 % and a strong negative predictive value of 99.4 %. The area under the ROC curve (AUC) was 0.98, indicating high reliability. Notably, PCR results were available 44.5 h earlier than culture. In conclusion, PCR-based molecular testing for gram-negative BMR offers excellent diagnostic performance and a valuable negative predictive value, making it a suitable screening tool for ICU admissions.

Adjuvants influence the immune cell populations present at the injection site granuloma induced by whole-cell inactivated paratuberculosis vaccines in sheep.

Vaccination is the most effective tool for paratuberculosis control. Currently, available vaccines prevent the progression of clinical disease in most animals but do not fully protect them against infection and induce the formation of an injection site granuloma. The precise mechanisms that operate in response to vaccination and granuloma development, as well as the effect that adjuvants could trigger, have not been fully investigated. Therefore, this study aimed to investigate the injection site granulomas induced by two inactivated paratuberculosis vaccines, which differ in the adjuvant employed. Two groups of 45-day-old lambs were immunized with two commercially available vaccines-one (n = 4) with Gudair® and the other (n = 4) with Silirum®. A third group (n = 4) was not vaccinated and served as control. The peripheral humoral response was assessed throughout the study by a commercial anti-Mycobacterium avium subspecies paratuberculosis (Map) antibody indirect ELISA, and the cellular immune response was assessed similarly by the IFN-γ release and comparative intradermal tests. The injection site granulomas were measured during the experiment and sampled at 75 days post-vaccination (dpv) when the animals were euthanized. The tissue damage, antigen and adjuvant distribution, and the presence and amount of immune cells were then determined and assessed by immunohistochemical methods. Antibodies against Map antigens; a general macrophage marker (Iba1), M1 (iNOS), and M2 (CD204) macrophages; T (CD3), B (CD20), and γδ T lymphocytes, proteins MHC-II and NRAMP1, and cytokines IL-4, IL-10, TNF, and IFN-γ were employed. Silirum® elicited a stronger peripheral cellular immune response than Gudair®, while the latter induced larger granulomas and more tissue damage at the site of injection. Additionally, adjuvant and Map antigen distribution throughout the granulomatous inflammatory infiltrate, as well as the NRAMP1 cell expression, which is linked to antigen phagocytosis, were highly irregular. In Silirum® induced granulomas, a higher number of MHC-II and TNF-expressing cells and a lower number of M2 macrophages suggested an improved antigen presentation, which could be due to the better antigen distribution and reduced tissue damage induced by this vaccine.

Prevalence of hepatic steatosis and fibrosis in apparently healthy airline pilots: A transient elastography study.

Background and Aim: Airline pilots (APs) are often characterized by a sedentary lifestyle, predisposing them to adverse cardiometabolic consequences. In this cross-sectional study, we used transient elastography (TE) to investigate the prevalence of hepatic steatosis and fibrosis among apparently healthy APs. Materials and Methods: The study cohort consisted of 137 male APs of Caucasian descent who voluntarily underwent TE. To evaluate the extent and severity of hepatic steatosis and fibrosis, we employed established cutoff values for the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). Results: Of the APs, 34 (24.8%) were diagnosed with TE-defined steatosis. Specifically, 25 APs (18.2%) exhibited mild steatosis, 6 (4.4%) moderate steatosis, and 3 (2.2%) severe steatosis. The majority of participants (80 APs or 58.4%) showed no signs of liver fibrosis based on LSM values. However, 49 APs (35.8%) were diagnosed with mild fibrosis (F1), 7 (5.1%) with significant fibrosis (F2), and one (0.7%) with advanced fibrosis (F3). None of the pilots had F4 (cirrhosis). In multivariable linear regression analysis, BMI was the sole independent predictor of both CAP (ß=0.34, p<0.001) and LSM (ß=0.41, p<0.001) values in our sample of male APs. Conclusion: TE is a straightforward and convenient non-invasive method for detecting hepatic steatosis and fibrosis in high-risk occupational groups such as APs.

The Role of the Redox Enzyme p66Shc in Biological Aging of the Lung.

The mitochondrial adaptor protein p66Shc has been suggested to control life span in mice via the release of hydrogen peroxide. However, the role of p66Shc in lung aging remains unsolved. Thus, we investigated the effects of p66Shc-/- on the aging of the lung and pulmonary circulation. In vivo lung and cardiac characteristics were investigated in p66Shc-/- and wild type (WT) mice at 3, 12, and 24 months of age by lung function measurements, micro-computed tomography (µCT), and echocardiography. Alveolar number and muscularization of small pulmonary arteries were measured by stereology and vascular morphometry, respectively. Protein and mRNA levels of senescent markers were measured by western blot and PCR, respectively. Lung function declined similarly in WT and p66Shc-/- mice during aging. However, µCT analyses and stereology showed slightly enhanced signs of aging-related parameters in p66Shc-/- mice, such as a decline of alveolar density. Accordingly, p66Shc-/- mice showed higher protein expression of the senescence marker p21 in lung homogenate compared to WT mice of the corresponding age. Pulmonary vascular remodeling was increased during aging, but aged p66Shc-/- mice showed similar muscularization of pulmonary vessels and hemodynamics like WT mice. In the heart, p66Shc-/- prevented the deterioration of right ventricular (RV) function but promoted the decline of left ventricular (LV) function during aging. p66Shc-/- affects the aging process of the lung and the heart differently. While p66Shc-/- slightly accelerates lung aging and deteriorates LV function in aged mice, it seems to exert protective effects on RV function during aging.

The etiology of congenital diaphragmatic hernia: the retinoid hypothesis 20 years later.

Congenital diaphragmatic hernia (CDH) is a severe birth defect and a major cause of neonatal respiratory distress. Impacting ~2-3 in 10,000 births, CDH is associated with a high mortality rate, and long-term morbidity in survivors. Despite the significant impact of CDH, its etiology remains incompletely understood. In 2003, Greer et al. proposed the Retinoid Hypothesis, stating that the underlying cause of abnormal diaphragm development in CDH was related to altered retinoid signaling. In this review, we provide a comprehensive update to the Retinoid Hypothesis, discussing work published in support of this hypothesis from the past 20 years. This includes reviewing teratogenic and genetic models of CDH, lessons from the human genetics of CDH and epidemiological studies, as well as current gaps in the literature and important areas for future research. The Retinoid Hypothesis is one of the leading hypotheses to explain the etiology of CDH, as we continue to better understand the role of retinoid signaling in diaphragm development, we hope that this information can be used to improve CDH outcomes. IMPACT: This review provides a comprehensive update on the Retinoid Hypothesis, which links abnormal retinoic acid signaling to the etiology of congenital diaphragmatic hernia. The Retinoid Hypothesis was formulated in 2003. Twenty years later, we extensively review the literature in support of this hypothesis from both animal models and humans.

Current heart failure disease management and treatment in accredited units from cardiology and internal medicine in Spain.

BACKGROUND AND OBJECTIVES: Heart failure (HF) is a complex disease with high prevalence, incidence and mortality rates leading to high healthcare burden. In Spain, there are multidisciplinary HF units coordinated by cardiology and internal medicine. Our objective is to describe its current organizational model and their adherence to the latest scientific recommendations. MATERIALS AND METHODS: In late 2021, a scientific committee (with cardiology and internal medicine specialists) developed a questionnaire that was sent as an online survey to 110 HF units. 73 from cardiology (accredited by SEC-Excelente) and 37 from internal medicine, (integrated in UMIPIC program). RESULTS: We received 83 answers (75.5% total: 49 from cardiology and 34 from internal medicine). The results showed that HF units are mostly integrated by specialists from cardiology, internal medicine and specialized nurse practitioners (34.9%). Patient characteristics from HF units are widely different when comparing those in cardiology to UMIPIC, being the latter older, more frequently with preserved ejection fraction and higher comorbidity burden. Most HF units (73.5%) currently use a hybrid face-to-face/virtual model to perform patient follow-up. Natriuretic peptides are the biomarkers most commonly used (90%). All four disease-modifying drug classes are mainly implemented at the same time (85%). Only 24% of HF units hold fluent communication with primary care. CONCLUSIONS: Both models from cardiology and internal medicine HF units are complementary, they include specialized nursing, they use hybrid approach for patient follow-up and they display a high adherence to the latest guideline recommendations. Coordination with primary care remains as the major improvement area.

Effect of the Mode of Fermentation on the Behavior of Penicillium bilaiae in Conditions of Abiotic Stress.

The ability of a Penicillium bilaiae strain to support acid production and simultaneously solubilize inorganic sources of phosphate in conditions of submerged, solid-state fermentation (SSF) and immobilized cell system was examined in this study. Abiotic stress factors such as NaCl and different values of pH were introduced into the different fermentation process schemes to measure the fungal response. The results showed a higher tolerance of P. bilaiae when the fermentation process was carried out in solid-state and immobilized-cell conditions, which mimics the natural state of the soil microorganisms. The acidic culture conditions were not found to be suitable for fungal growth, which increased at a higher pH, with values of 4.0 and 6.0 being optimal for all types of fermentation. The presence of increasing amounts of NaCl provoked low biomass growth, titratable acidity, and simultaneous phosphate (P) solubilization. These results were, however, less pronounced at pH 4.0 and 6.0, particularly in conditions of SSF. Studying stress-tolerant microbial characteristics, particularly in different conditions and combinations of stress factors, is of great importance for further managing the overall microbial inoculants' production and formulation process as well as their applications in specific soil-plant systems.

Skin biophysical parameters and serum dermokine levels in airline pilots: a comparative study with office workers.

Introduction: Concerns are growing in the aviation industry about occupational skin diseases like malignant melanoma (MM) among airline pilots (APs), due to the unique working environment that exposes them to various skin stressors. Aim: To compare five skin biophysical parameters in a group of 40 male APs, each matched in terms of age and service tenure (minimum of 5 years) with a control group of 40 male office workers (OWs). Considering the potential role of dermokine (DMKN) in skin barrier dysfunction and the pathogenesis of MM, we further analyzed the serum levels of this molecule and correlated them with the measured skin parameters. Material and methods: Stratum corneum skin hydration, transepidermal water loss (TEWL), sebum content, erythema index (EI), and melanin index (MI) were quantified by non-invasive instruments in the cheek region. Serum DMKN levels were measured using a commercially available enzyme-linked immunosorbent assay kit. Results: Compared with OWs, the skin of APs exhibited a decrease in hydration levels in the stratum corneum, coinciding with a higher TEWL. However, there was no significant variance in sebum content between the groups. MI was notably higher in APs than in OWs, as was EI. In APs, serum DMKN levels were independently associated with MI (ß = 0.56, p < 0.05). Conclusions: We found a significant link between the profession of an airline pilot and changes in skin biophysical parameters. Further research into the interplay between serum DMKN levels and the risk of MM in APs is warranted.

Dragon 1 Protocol Manuscript: Training, Accreditation, Implementation and Safety Evaluation of Portal and Hepatic Vein Embolization (PVE/HVE) to Accelerate Future Liver Remnant (FLR) Hypertrophy.

STUDY PURPOSE: The DRAGON 1 trial aims to assess training, implementation, safety and feasibility of combined portal- and hepatic-vein embolization (PVE/HVE) to accelerate future liver remnant (FLR) hypertrophy in patients with borderline resectable colorectal cancer liver metastases. METHODS: The DRAGON 1 trial is a worldwide multicenter prospective single arm trial. The primary endpoint is a composite of the safety of PVE/HVE, 90-day mortality, and one year accrual monitoring of each participating center. Secondary endpoints include: feasibility of resection, the used PVE and HVE techniques, FLR-hypertrophy, liver function (subset of centers), overall survival, and disease-free survival. All complications after the PVE/HVE procedure are documented. Liver volumes will be measured at week 1 and if applicable at week 3 and 6 after PVE/HVE and follow-up visits will be held at 1, 3, 6, and 12 months after the resection. RESULTS: Not applicable. CONCLUSION: DRAGON 1 is a prospective trial to assess the safety and feasibility of PVE/HVE. Participating study centers will be trained, and procedures standardized using Work Instructions (WI) to prepare for the DRAGON 2 randomized controlled trial. Outcomes should reveal the accrual potential of centers, safety profile of combined PVE/HVE and the effect of FLR-hypertrophy induction by PVE/HVE in patients with CRLM and a small FLR. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04272931 (February 17, 2020). Toestingonline.nl: NL71535.068.19 (September 20, 2019).

[Diagnostic and treatment protocol for vascular complications of COVID-19]. / Protocolo diagnóstico y terapéutico de las complicaciones vasculares de la COVID-19.

The clinical spectrum of the disease caused by SARS-CoV-2 (COVID-19) is highly variable. It commonly has a mild or asymptomatic course. Around 15% to 20% of patients have lung involvement, which can progress to acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome, with marked alteration of the inflammatory and immune response. In these severe forms, there is an increased prevalence of vascular thrombotic complications which manifest as venous thromboembolism, acute arterial ischemia in the limbs, and, less frequently, myocardial involvement or cerebrovascular accident. The proposed pathogenic mechanisms include diffuse endothelial damage or endotheliitis, microvascular inflammation, cytokine release, hypercoagulability, and hypoxia. Early recognition of these complications is vital for improving the prognosis and survival of these patients.

[Diagnostic protocol for febrile lung infiltrates during the COVID-19 pandemic]. / Protocolo diagnóstico de los infiltrados pulmonares febriles durante la pandemia de la COVID-19.

Chest x-ray and computed tomography (CT) scans are important pillars for the diagnosis of lung involvement in COVID-19. The radiological image is typically characterized by peripheral, bilateral ground glass opacities (GGO), mainly located in the lower lobes. The limited sensitivity and specificity of these imaging techniques and possible atypical morphological or topographical presentations make it necessary to always rule out other infectious and non-infectious diseases. Therefore, it is fundamental to consider the patient's clinical and analytical data and the epidemiological circumstances.

[Treatment protocol for COVID-19 in patients with and without an indication for hospital admission]. / Protocolo de tratamiento de la COVID-19 en pacientes con y sin indicación de ingreso hospitalario.

SARS-CoV-2 infection causes a wide spectrum of symptoms with varying degrees of severity, from asymptomatic cases or cases in the form of self-limiting influenza-like illness to cases of rapidly progressing respiratory distress syndrome due to an anomalous immune system response in the form of a cytokine storm. Thrombotic complications are also common. Multiple antiviral treatments have been tested in COVID-19 without favorable outcomes. Only remdesivir may be useful, but not in all cases, and its use is controversial. On the contrary, immunomodulating treatments have the most solid evidence, particularly glucocorticoids. Other more specific immunosuppressors, such as interleukin-6 inhibitors, have also shown favorable results and many others are currently being studied. Thromboprophylaxis is the other pillar of COVID-19 treatment, although the anticoagulant dose to be used is still being discussed.

Inhibition of major histocompatibility complex-I antigen presentation by sarbecovirus ORF7a proteins

Viruses employ a variety of strategies to escape or counteract immune responses, including depletion of cell surface major histocompatibility complex class I (MHC-I), that would ordinarily present viral peptides to CD8+ cytotoxic T cells. As part of a screen to elucidate biological activities associated with individual SARS-CoV-2 viral proteins, we found that ORF7a reduced cell surface MHC-I levels by approximately 5-fold. Nevertheless, in cells infected with SARS-CoV-2, surface MHC-I levels were reduced even in the absence of ORF7a, suggesting additional mechanisms of MHC-I downregulation. ORF7a proteins from a sample of sarbecoviruses varied in their ability to induce MHC-I downregulation and, unlike SARS-CoV-2, the ORF7a protein from SARS-CoV lacked MHC-I downregulating activity. A single-amino acid at position 59 (T/F) that is variable among sarbecovirus ORF7a proteins governed the difference in MHC-I downregulating activity. SARS-CoV-2 ORF7a physically associated with the MHC-I heavy chain and inhibited the presentation of expressed antigen to CD8+ T-cells. Speficially, ORF7a prevented the assembly of the MHC-I peptide loading complex and causing retention of MHC-I in the endoplasmic reticulum. The differential ability of ORF7a proteins to function in this way might affect sarbecovirus dissemination and persistence in human populations, particularly those with infection- or vaccine-elicited immunity.

Early genomic, epidemiological, and clinical description of the SARS-CoV-2 Omicron variant in Mexico City

BackgroundOmicron is the most mutated SARS-CoV-2 variant that has emerged, resulting in viral phenotype alterations, which can affect transmissibility, disease severity, and immune evasiveness. Genomic surveillance of a highly transmissible variant is important in cities with millions of inhabitants and an economic center such as Mexico City. In this work, we describe the early effects of the Omicron variant in Mexico City, exploring its genomic profile and clinical description. MethodologyWe sequenced SARS-CoV-2-positive samples in November and December 2021 and we using the public database GISAID. Haplotype and phylogenetic analyses were performed to genomically characterize Omicron. We used the Mexican federal database toexplore the association with clinical information such as symptoms and vaccination status. FindingsThe first case of Omicron was detected on November 16, 2022, and until December 31, 2021, we observed an increase from 88% in sequenced samples. Nineteen nonsynonymous mutations were found in the Omicron RBD, and we further explored the R346K substitution, which was prevalent in 42% of the samples and associated with immune escape by monoclonal antibodies. In the phylogenetic analysis, we found that there were several independent exchanges between Mexico and the world, and there was an event followed by local transmission that gave rise to most of the Omicron diversity in Mexico City. The haplotype analysis allowed us to observe that there was no association between haplotype and vaccination status. Of the patients with clinical data, 66% were vaccinated, none of the reported comorbidities were associated with Omicron, the presence of odynophagia and absence of dysgeusia were significant predictor symptoms for Omicron, and the Ct value on RT-qPCR was lower in Omicron. ConclusionsGenomic surveillance in highly populated and fast-moving urban regions such as Mexico City is key to detecting the emergence and spread of SARS-CoV-2 variants in a timely manner, even weeks before the onset of an infection wave, to detect patterns that can inform public health decisions. It is also necessary to continue sequencing to detect the spread of any mutation that may affect the therapeutic efficacy or guide it.

Nuclear Charge Radii of the Nickel Isotopes

Collinear laser spectroscopy is performed on the nickel isotopes ^{58-68,70}Ni, using a time-resolved photon counting system. From the measured isotope shifts, nuclear charge radii R_{c} are extracted and compared to theoretical results. Three ab initio approaches all employ, among others, the chiral interaction NNLO_{sat}, which allows an assessment of their accuracy. We find agreement with experiment in differential radii δ⟨r_{c}^{2}⟩ for all employed ab initio methods and interactions, while the absolute radii are consistent with data only for NNLO_{sat}. Within nuclear density functional theory, the Skyrme functional SV-min matches experiment more closely than the Fayans functional Fy(Δr,HFB).

T cell reactivity to the SARS-CoV-2 Omicron variant is preserved in most but not all prior infected and vaccinated individuals

The SARS-CoV-2 Omicron variant (B.1.1.529) contains mutations that mediate escape from infection and vaccine-induced antibody responses, although the extent to which these substitutions in spike and non-spike proteins affect T cell recognition is unknown. Here we show that T cell responses in individuals with prior infection, vaccination, both prior infection and vaccination, and boosted vaccination are largely preserved to Omicron spike and non-spike proteins. However, we also identify a subset of individuals ([~]21%) with a >50% reduction in T cell reactivity to the Omicron spike. Evaluation of functional CD4+ and CD8+ memory T cell responses confirmed these findings and reveal that reduced recognition to Omicron spike is primarily observed within the CD8+ T cell compartment. Booster vaccination substantially enhanced T cell responses to Omicron spike. In contrast to neutralizing immunity, these findings suggest preservation of T cell responses to the Omicron variant, although with reduced reactivity in some individuals.

Low maternal vitamin A intake increases the incidence of teratogen induced congenital diaphragmatic hernia in mice.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a severe birth defect associated with high perinatal mortality and long-term morbidity. The etiology of CDH is poorly understood although abnormal retinoid signaling has been proposed to contribute to abnormal diaphragm development. Existing epidemiological data suggest that inadequate dietary vitamin A intake is a risk factor for developing CDH. METHODS: Using a mouse model of teratogen-induced CDH, the objective of this study was to test the hypothesis that low maternal vitamin A intake contributes to abnormal diaphragm development. To test this hypothesis, we optimized a model of altered maternal dietary vitamin A intake and a teratogenic model of CDH in mice that recapitulates the hallmark features of posterolateral diaphragmatic hernia in humans. RESULTS: Our data uniquely show that low maternal dietary vitamin A intake and marginal vitamin A status increases the incidence of teratogen-induced CDH in mice. CONCLUSION: Low dietary vitamin A intake and marginal vitamin A status lead to an increased incidence of teratogen-induced CDH in mice, highlighting the importance of adequate dietary vitamin A intake and CDH risk. IMPACT: This study describes and validates a mouse model of altered maternal and fetal vitamin A status. This study links existing epidemiological data with a mouse model of teratogen-induced congenital diaphragmatic hernia, highlighting the importance of low maternal vitamin A intake as a risk factor for the development of congenital diaphragmatic hernia. This study supports the Retinoid Hypothesis, which posits that the etiology of congenital diaphragmatic hernia is linked to abnormal retinoid signaling in the developing diaphragm.

mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant

Recent surveillance has revealed the emergence of the SARS-CoV-2 Omicron variant (BA.1/B.1.1.529) harboring up to 36 mutations in spike protein, the target of vaccine-induced neutralizing antibodies. Given its potential to escape vaccine-induced humoral immunity, we measured neutralization potency of sera from 88 mRNA-1273, 111 BNT162b, and 40 Ad26.COV2.S vaccine recipients against wild type, Delta, and Omicron SARS-CoV-2 pseudoviruses. We included individuals that were vaccinated recently (<3 months), distantly (6-12 months), or recently boosted, and accounted for prior SARS-CoV-2 infection. Remarkably, neutralization of Omicron was undetectable in most vaccinated individuals. However, individuals boosted with mRNA vaccines exhibited potent neutralization of Omicron only 4-6-fold lower than wild type, suggesting that boosters enhance the cross-reactivity of neutralizing antibody responses. In addition, we find Omicron pseudovirus is more infectious than any other variant tested. Overall, this study highlights the importance of boosters to broaden neutralizing antibody responses against highly divergent SARS-CoV-2 variants.