JRK binds satellite III DNA and is necessary for the heat shock response.

JRK is a DNA-binding protein of the pogo superfamily of transposons, which includes the well-known centromere binding protein B (CENP-B). Jrk null mice exhibit epilepsy, and growth and reproductive disorders, consistent with its relatively high expression in the brain and reproductive tissues. Human JRK DNA variants and gene expression levels are implicated in cancers and neuropsychiatric disorders. JRK protein modulates ß-catenin-TCF activity but little is known of its cellular functions. Based on its homology to CENP-B, we determined whether JRK binds centromeric or other satellite DNAs. We show that human JRK binds satellite III DNA, which is abundant at the chromosome 9q12 juxtacentromeric region and on Yq12, both sites of nuclear stress body assembly. Human JRK-GFP overexpressed in HeLa cells strongly localises to 9q12. Using an anti-JRK antiserum we show that endogenous JRK co-localises with a subset of centromeres in non-stressed cells, and with heat shock factor 1 following heat shock. Knockdown of JRK in HeLa cells proportionately reduces heat shock protein gene expression in heat-shocked cells. A role for JRK in regulating the heat shock response is consistent with the mouse Jrk null phenotype and suggests that human JRK may act as a modifier of diseases with a cellular stress component.

Crystal structure of the class A extended-spectrum ß-lactamase CTX-M-96 in complex with relebactam at 1.03 Angstrom resolution.

The use of ß-lactam/ß-lactamase inhibitors constitutes an important strategy to counteract ß-lactamases in multidrug-resistant (MDR) Gram-negative bacteria. Recent reports have described ceftazidime-/avibactam-resistant isolates producing CTX-M variants with different amino acid substitutions (e.g., P167S, L169Q, and S130G). Relebactam (REL) combined with imipenem has proved very effective against Enterobacterales producing ESBLs, serine-carbapenemases, and AmpCs. Herein, we evaluated the inhibitory efficacy of REL against CTX-M-96, a CTX-M-15-type variant. The CTX-M-96 structure was obtained in complex with REL at 1.03 Å resolution (PDB 8EHH). REL was covalently bound to the S70-Oγ atom upon cleavage of the C7-N6 bond. Compared with apo CTX-M-96, binding of REL forces a slight displacement of the deacylating water inwards the active site (0.81 Å), making the E166 and N170 side chains shift to create a proper hydrogen bonding network. Binding of REL also disturbs the hydrophobic patch formed by Y105, P107, and Y129, likely due to the piperidine ring of REL that creates clashes with these residues. Also, a remarkable change in the positioning of the N104 sidechain is also affected by the piperidine ring. Therefore, differences in the kinetic behavior of REL against class A ß-lactamases seem to rely, at least in part, on differences in the residues being involved in the association and stabilization of the inhibitor before hydrolysis. Our data provide the biochemical and structural basis for REL effectiveness against CTX-M-producing Gram-negative pathogens and essential details for further DBO design. Imipenem/REL remains an important choice for dealing with isolates co-producing CTX-M with other ß-lactamases.

Response-Adapted Ultralow-Dose Radiation Therapy for Orbital Indolent B-Cell Lymphoma: A Phase 2 Nonrandomized Controlled Trial.

Importance: Radiation therapy to doses of 24 to 36 Gy is currently used to treat indolent B-cell lymphoma of the ocular adnexa; however, ocular adverse effects are common. Objective: To determine if a response-adapted radiation therapy strategy will result in excellent disease outcomes while reducing orbital morbidity. Design, Setting, and Participants: This single-institution, phase 2 prospective nonrandomized controlled trial of a response-adapted strategy involved 50 evaluable patients with stage I to IV indolent B-cell lymphoma of the ocular adnexa enrolled between July 2015 and January 2021. This treatment approach was also retrospectively evaluated with a separate 55-patient cohort treated between March 2013 and October 2021. All data were analyzed between November 2021 and December 2023. Interventions: Patients were treated with ultralow-dose radiation therapy to 4 Gy in 2 fractions and assessed for response at 3-month intervals. Patients with persistent orbital lymphoma were offered an additional 20 Gy in 10 fractions to complete the response-adapted treatment. Main Outcome and Measures: The primary end point was 2-year local orbital control within the irradiated field after response-adapted therapy. Secondary end points included overall survival and complete response rate. Results: The 50 prospective patients were a median (range) of 63 (29-88) years old, and 31 (62%) were female. Among the 50 patients, 32 (64%) had mucosa-associated lymphoid tissue lymphoma, 12 (24%) had follicular lymphoma, and 6 (12%) had unclassifiable low-grade B-cell lymphoma. Thirty-one patients (62%) had stage I disease, and 36 (72%) were newly diagnosed. At a median follow-up of 37.4 (95% CI, 33.7-52.5) months, the 2-year local control rate was 89.4% (95% CI, 81.0%-98.7%), and the 2-year overall survival rate was 98.0% (95% CI, 94.1%-100%); 45 patients (90.0%; 95% CI, 78.2%-96.7%) experienced a complete response to response-adapted radiation, including 44 patients with a complete response to ultralow-dose radiation and 1 patient with a complete response after an additional 20 Gy. No local recurrences were observed among patients with a complete response to response-adapted therapy. No grade 3 or higher toxic effects were observed. In a planned subset analysis of 22 patients with newly diagnosed, untreated stage I mucosa-associated lymphoid tissue lymphoma, the 2-year local control rate was 90.7% (95% CI, 79.2%-100%), and the 2-year freedom from distant relapse rate was 95.2% (95% CI, 86.6%-100%). Conclusion and Relevance: In this nonrandomized controlled trial, response-adapted ultralow-dose therapy for indolent orbital B-cell lymphoma resulted in reduced radiation exposure, negligible toxic effects, and excellent disease outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02494700.

Synthesis and Properties of Hydrophilic and Hydrophobic Deep Eutectic Solvents via Heating-Stirring and Ultrasound.

Deep eutectic solvents (DESs) have emerged as a greener alternative to other more polluting traditional solvents and have attracted a lot of interest in the last two decades. The DESs are less toxic dissolvents and have a lower environmental footprint. This paper presents an alternative synthesis method to the classical heating-stirring method. The ultrasound method is one of the most promising synthesis methods for DESs in terms of yield and energy efficiency. Therefore, the ultrasound synthesis method was studied to obtain hydrophobic (Aliquat 336:L-Menthol (3:7); Lidocaine:Decanoic acid (1:2)) and hydrophilic DESs based on choline chloride, urea, ethylene glycol and oxalic acid. The physical characterization of DESs via comparison of Fourier transform infrared (FTIR) spectra showed no difference between the DESs obtained by heating-stirring and ultrasound synthesis methods. The study and comparison of all the prepared DESs were carried out via nuclear magnetic resonance spectroscopy (NMR). The density and viscosity properties of DESs were evaluated. The density values were similar for both synthesis methods. However, differences in viscosity values were detected due to the presence of some water in hygroscopic DESs.

Comorbidities and use of health services in people with diabetes mellitus according to risk levels by adjusted morbidity groups.

BACKGROUND: People with diabetes mellitus frequently have other comorbidities and involve greater use of primary and hospital care services. The aim of this study was to describe the comorbidities and use of primary and hospital care services of people with diabetes according to their risk level by adjusted morbidity groups (AMG) and to analyse the factors associated with the utilisation of these services. METHODS: Cross-sectional study. People with diabetes were identified within the population of patients with chronic conditions of an urban health care centre by the AMG stratification tool integrated into the primary health care electronic clinical record of the Community of Madrid. Sociodemographic, functional, clinical characteristics and annual health care services utilisation variables were collected. Univariate, bivariate and Poisson regression analyses were performed. RESULTS: A total of 1,063 people with diabetes were identified, representing 10.8% of patients with chronic conditions within the health centre. A total of 51.4% were female, the mean age was 70 years, 94.4% had multimorbidity. According to their risk level, 17.8% were high-risk, 40.6% were medium-risk and 41.6% were low-risk. The most prevalent comorbidities were hypertension (70%), dyslipidaemia (67%) and obesity (32.4%). Almost 50% were polymedicated. Regarding health services utilisation, 94% were users of primary care, and 59.3% were users of hospital care. Among the main factors associated with the utilisation of both primary and hospital care services were AMG risk level and complexity index. In primary care, utilisation was also associated with the need for primary caregivers, palliative care and comorbidities such as chronic heart failure and polymedication, while in hospital care, utilisation was also associated with comorbidities such as cancer, chronic obstructive pulmonary disease or depression. CONCLUSIONS: People with diabetes were older, with important needs for care, many associated comorbidities and polypharmacy that increased in parallel with the patient's risk level and complexity. The utilisation of primary and hospital care services was very high, being more frequent in primary care. Health services utilization were principally associated with functional factors related to the need of care and with clinical factors such as AMG medium and high-risk level, more complexity index, some serious comorbidities and polymedication.

Endoplasmic reticulum exit sites are segregated for secretion based on cargo size.

TANGO1, TANGO1-Short, and cTAGE5 form stable complexes at the endoplasmic reticulum exit sites (ERES) to preferably export bulky cargoes. Their C-terminal proline-rich domain (PRD) binds Sec23A and affects COPII assembly. The PRD in TANGO1-Short was replaced with light-responsive domains to control its binding to Sec23A in U2OS cells (human osteosarcoma). TANGO1-ShortΔPRD was dispersed in the ER membrane but relocated rapidly, reversibly, to pre-existing ERES by binding to Sec23A upon light activation. Prolonged binding between the two, concentrated ERES in the juxtanuclear region, blocked cargo export and relocated ERGIC53 into the ER, minimally impacting the Golgi complex organization. Bulky collagen VII and endogenous collagen I were collected at less than 47% of the stalled ERES, whereas small cargo molecules were retained uniformly at almost all the ERES. We suggest that ERES are segregated to handle cargoes based on their size, permitting cells to traffic them simultaneously for optimal secretion.

Implications of sedation during the use of noninvasive ventilation in children with acute respiratory failure (SEDANIV Study).

BACKGROUND: The objective of this study was to analyze the effects of sedation administration on clinical parameters, comfort status, intubation requirements, and the pediatric intensive care unit (PICU) length of stay (LOS) in children with acute respiratory failure (ARF) receiving noninvasive ventilation (NIV). METHODS: Thirteen PICUs in Spain participated in a prospective, multicenter, observational trial from January to December 2021. Children with ARF under the age of five who were receiving NIV were included. Clinical information and comfort levels were documented at the time of NIV initiation, as well as at 3, 6, 12, 24, and 48 h. The COMFORT-behavior (COMFORT-B) scale was used to assess the patients' level of comfort. NIV failure was considered to be a requirement for endotracheal intubation. RESULTS: A total of 457 patients were included, with a median age of 3.3 months (IQR 1.3-16.1). Two hundred and thirteen children (46.6%) received sedation (sedation group); these patients had a higher heart rate, higher COMFORT-B score, and lower SpO2/FiO2 ratio than did those who did not receive sedation (non-sedation group). A significantly greater improvement in the COMFORT-B score at 3, 6, 12, and 24 h, heart rate at 6 and 12 h, and SpO2/FiO2 ratio at 6 h was observed in the sedation group. Overall, the NIV success rate was 95.6%-intubation was required in 6.1% of the sedation group and in 2.9% of the other group (p = 0.092). Multivariate analysis revealed that the PRISM III score at NIV initiation (OR 1.408; 95% CI 1.230-1.611) and respiratory rate at 3 h (OR 1.043; 95% CI 1.009-1.079) were found to be independent predictors of NIV failure. The PICU LOS was correlated with weight, PRISM III score, respiratory rate at 12 h, SpO2 at 3 h, FiO2 at 12 h, NIV failure and NIV duration. Sedation use was not found to be independently related to NIV failure or to the PICU LOS. CONCLUSIONS: Sedation use may be useful in children with ARF treated with NIV, as it seems to improve clinical parameters and comfort status but may not increase the NIV failure rate or PICU LOS, even though sedated children were more severe at technique initiation in the present sample.

Identificación de Rickettsias sp. y hemoparásitos en garrapatas de la especie Rhipicephalus sanguineus en perros de la ciudad de San Juan Bautista, departamento de Misiones, Paraguay / Identification of Rickettsias sp.and hemoparasites in ticks of the genus Rhipicephalus sanguineusin dogs from the city of San Juan Bautista, department of Misiones, Paraguay

El objetivo principal de esta investigación fue identificar la presencia de Rickettsias sp. y hemoparásitos en garrapatas de la especie Rhipicephalus sanguineus en perros. Se analizaron un total de 62 garrapatas adultas cargadas recolectadas de 62 perros del barrio Concepción, zona urbana de la ciudad de San Juan Bautista, en el departamento de Misiones, Paraguay, durante el año 2017. La muestra incluyó perros de diversas edades, razas y sexos. Para el análisis, se realizó un frotis directo de la hemolinfa de las garrapatas extraídas de los caninos, y posterior tinción Wright. Los resultados revelaron que el 13% de las garrapatas resultaron positivas para Rickettsias sp. y hemoparásitos. En detalle, el 6,5% mostró la presencia de cuerpos elementales de Ehrlichia spp., mientras que otro 6,5% presentó cuerpos vermiformes de Babesia spp. El 87% restante de las muestras resultaron negativas para Rickettsias sp. y hemoparásitos. En cuanto a los perros cuyas garrapatas dieron positivo para Rickettsias sp. y hemoparásitos, el 50% eran machos, y el otro 50% eran hembras. En cuanto a la edad de los perros muestreados, el 25% tenían menos de 1 año, el 50% tenían entre 1 y 5 años, y el 25% restante tenían más de 5 años. Con relación a la raza de los perros cuyas garrapatas resultaron positivas para Rickettsias sp. y hemoparásitos, el 37,5% eran de raza pura y el 62,5% eran de raza mestiza.

Systematic Review on the Impact of Mobile Applications with Augmented Reality to Improve Health.

Physical inactivity represents a significant public health challenge globally. Mobile applications, particularly those utilizing augmented reality (AR), have emerged as innovative tools for promoting physical activity. However, a systematic evaluation of their efficacy is essential. This systematic review aims to evaluate and synthesize the evidence regarding the effectiveness and benefits of mobile applications with augmented reality in enhancing physical activity and improving health outcomes. A comprehensive search was conducted in Scopus, PubMed, WOS, and the Cochrane Library databases following PRISMA guidelines. Observational and interventional studies evaluating AR mobile applications for physical exercise were included, without restrictions on publication date or language. The search terms included "Mobile Applications", "Augmented Reality", "Physical Fitness", "Exercise Therapy", and "Health Behavior". The methodological quality was assessed using the ROBINS tool. The review identified twelve eligible studies encompassing 5,534,661 participants. The findings indicated significant increases in physical activity and improvements in mental health associated with the use of AR applications, such as Pokémon GO. However, potential risk behaviors were also noted. The evidence suggests that AR interventions can effectively promote physical activity and enhance health. Nonetheless, further research is needed to address limitations and optimize their efficacy. Future interventions should be tailored to diverse cultural contexts to maximize benefits and mitigate risks. AR mobile applications hold promise for promoting physical activity and improving health outcomes. Strategies to optimize their effectiveness and address identified risks should be explored to fully realize their potential.

A comprehensive, predictive mortality score for patients with bloodstream infections (PROBAC): a prospective, multicentre cohort study.

OBJECTIVES: Bloodstream infections (BSI) are an important cause of mortality, although they show heterogeneity depending on patients and aetiological factors. Comprehensive and specific mortality scores for BSI are scarce. The objective of this study was to develop a mortality predictive score in BSI based on a multicentre prospective cohort. METHODS: A prospective cohort including consecutive adults with bacteraemia recruited between October 2016 and March 2017 in 26 Spanish hospitals was randomly divided into a derivation cohort (DC) and a validation cohort (VC). The outcome was all-cause 30-day mortality. Predictors were assessed the day of blood culture growth. A logistic regression model and score were developed in the DC for mortality predictors; the model was applied to the VC. RESULTS: Overall, 4102 patients formed the DC and 2009 the VC. Mortality was 11.8% in the DC and 12.34% in the CV; the patients and aetiological features were similar for both cohorts. The mortality predictors selected in the final multivariate model in the DC were age, cancer, liver cirrhosis, fatal McCabe underlying condition, polymicrobial bacteraemia, high-risk aetiologies, high-risk source of infection, recent use of broad-spectrum antibiotics, stupor or coma, mean blood pressure <70 mmHg and PaO2/FiO2 ≤ 300 or equivalent. Mortality in the DC was <2% for ≤2 points, 6%-14% for 3-7 points, 26%-45% for 8-12 points and ≥60% for ≥13 points. The predictive score had areas under the receiving operating curves of 0.81 (95% CI 0.79-0.83) in the DC and 0.80 (0.78-0.83) in the VC. CONCLUSIONS: A 30 day mortality predictive score in BSI with good discrimination ability was developed and internally validated.

Medicaid Policy Change and Immediate Postpartum Long-Acting Reversible Contraception.

Importance: Improving access to the choice of postpartum contraceptive methods is a national public health priority, and the need is particularly acute within the Medicaid population. One strategy to ensure individuals have access to the full range of contraceptive methods is the provision of a method prior to hospital discharge following a birth episode. Beginning in 2016, some states changed their Medicaid billing policy, allowing separate reimbursement for intrauterine devices and contraceptive implants to increase the provision of long-acting reversible contraceptive (LARC) methods immediately postpartum (IPP). Objective: To assess the association of a change in Medicaid billing policy with use of IPP LARC. Design, Setting, and Participants: The cohort study of postpartum Medicaid recipients in 9 treatment and 6 comparison states was conducted from January 2016 to October 2019. Data were analyzed from August 2023 to January 2024. Main Outcomes and Measures: The primary outcome was use of IPP LARC. Results: The final sample included 1 378 885 delivery encounters for 1 197 287 Medicaid enrollees occurring in 15 states. Mean age of beneficiaries at delivery was 27 years. The IPP LARC billing policy was associated with a mean increase of 0.74 percentage points (95% CI, 0.30-1.18 percentage points) in the immediate receipt of IPP LARC, with a prepolicy baseline rate of 0.54%. The IPP LARC billing policy was also associated with an overall increase of 1.48 percentage points (95% CI, 0.43-2.73 percentage points) in LARC use by 60 days post partum. Conclusions and Relevance: In this cohort study, changing Medicaid billing policy to allow for separate reimbursement of LARC devices from the global fee was associated with increased use of IPP LARC, suggesting that this may be a strategy to improve access to the full range of postpartum contraceptive methods.

Workplace health promotion programs: The role of compliance with workers' expectations, the reputation and the productivity of the company.

INTRODUCTION: Addressing the health and safety of workers is key to achieving Sustainable Development Goals 3 and 8. The European Union urges companies in its member countries to promote measures in this regard. However, this type of program is not a general approach in European companies. This study aims to identify whether the implementation of Workplace Health Promotion measures is influenced by the company's desire to meet its employees' expectations in this area; and if this relationship involves the company's reputation and productivity. METHODS: A multi-step methodology is used (descriptive sample portrait, analysis of influences by linear regression, and double-intermediation model analysis) to find out if reputation and productivity mediate the relationship between the satisfaction of employee health expectations and the number of Workplace Health Promotion measures applied. RESULTS: The more weight the company gives to this compliance, the more motivated it is to implement a more significant number of Workplace Health Promotion measures. The increase in productivity does not seem to weigh in this relationship, but the improvement of the company's reputation does. CONCLUSIONS: The more the employees' expectations of working in a healthy company are desired to be met, the more measures the company will put in place. PRACTICAL APPLICATIONS: The findings have theoretical implications, by increasing knowledge about the factors that influence a company's decision to activate Workplace Health Promotion policies. They can also serve as guidance for implementing policies that encourage health promotion in companies and contribute to the achievement of Sustainable Development Goals 3 and 8: for workers' representatives, by better understanding how these factors influence the fulfillment of their constituents' expectations; for company managers, by better knowing the variables involved in this relationship; and for researchers of this topic.

Human cerebral organoids: cellular composition and subcellular morphological features.

Introduction: Human cerebral organoids (hCOs) derived from pluripotent stem cells are very promising for the study of neurodevelopment and the investigation of the healthy or diseased brain. To help establish hCOs as a powerful research model, it is essential to perform the morphological characterization of their cellular components in depth. Methods: In this study, we analyzed the cell types consisting of hCOs after culturing for 45 days using immunofluorescence and reverse transcriptase qualitative polymerase chain reaction (RT-qPCR) assays. We also analyzed their subcellular morphological characteristics by transmission electron microscopy (TEM). Results: Our results show the development of proliferative zones to be remarkably similar to those found in human brain development with cells having a polarized structure surrounding a central cavity with tight junctions and cilia. In addition, we describe the presence of immature and mature migrating neurons, astrocytes, oligodendrocyte precursor cells, and microglia-like cells. Discussion: The ultrastructural characterization presented in this study provides valuable information on the structural development and morphology of the hCO, and this information is of general interest for future research on the mechanisms that alter the cell structure or function of hCOs.

Response-adapted ultra-low-dose 4 Gy radiation as definitive therapy of gastric MALT lymphoma: a single-centre, pilot trial.

BACKGROUND: Given the favourable prognosis of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma, treatment-related toxicity should be minimised. We aimed to evaluate the efficacy of 4 Gy radiotherapy given in a response-adapted approach. METHODS: We conducted a single-centre, single-arm, prospective trial at MD Anderson Cancer Center (Houston, TX, USA) of response-adapted ultra-low-dose radiotherapy. Eligible patients were 18 years or older and had newly diagnosed or relapsed Helicobacter pylori-negative gastric MALT lymphoma, with stage I-IV disease. Given the expected low toxicity profile of treatment, performance status was not an exclusion criterion. Patients received external beam photon-based radiotherapy for a total dose of 4 Gy in two fractions. Patients with a complete response to 4 Gy via endoscopy and imaging at 3-4 months were observed; patients with a partial response were re-evaluated in 6-9 months. Residual disease at 9-13 months or stable or progressive disease at any time required additional treatment with 20 Gy. The primary endpoint was gastric complete response at 1 year (second evaluation timepoint) after 4 Gy treatment. All analyses were performed as intention to treat. This trial is registered at ClinicalTrials.gov (NCT03680586) and is complete and closed to enrolment. FINDINGS: Between March 27, 2019, and Oct 12, 2021, we enrolled 24 eligible patients. The median age of participants was 67 years (IQR 58-74; range 40-85); 15 (63%) were female and nine (37%) male; 18 (75%) were White, four (17%) Asian, and two (8%) Hispanic; 20 (83%) had stage I disease, one (4%) stage II, and three (13%) stage IV. Median follow-up time was 36 months (IQR 26-42). 20 patients (83%) had a complete response to 4 Gy (16 at 3-4 months, four at 9-13 months); two patients received 20 Gy for symptomatic stable disease at 3-4 months and two for residual disease at 9-13 months; all had a complete response. The 3-year local control rate was 96% (95% CI 88-100), with one local relapse at 14 months after 4 Gy radiotherapy salvaged successfully with 20 Gy. One patient with stage IV disease had a distant relapse. The most common adverse events were grade 1 nausea (nine [38%] of 24 patients who received 4 Gy and two [50%] of four patients who received 20 Gy) and grade 1 abdominal pain (five [21%] of 24 and zero of four, respectively). No grade 3 or worse adverse events were noted, including no treatment-related deaths. INTERPRETATION: Most patients had a complete response after 4 Gy radiotherapy; all who required an additional 20 Gy had a complete response within 12 months. This response-adapted strategy could be used to select patients who would benefit from additional radiotherapy and spare others potential associated toxicity. FUNDING: National Cancer Institute.

Cancer is not a risk factor for severe COVID-19 in children, except in patients with recent allogeneic hematopoietic stem cell transplantation or comorbidities.

The EPICO (Spanish general registry of COVID-19 in children)-SEHOP (Spanish Society of Pediatric Hematology and Oncology) platform gathers data from children with SARS-CoV-2 in Spain, allowing comparison between children with cancer or allogeneic hematopoietic stem cell transplantation (alloHSCT) and those without. The infection is milder in the cancer/alloHSCT group than in children without comorbidities (7.1% vs. 14.7%), except in children with recent alloHSCT (less than 300 days), of which 35.7% experienced severe COVID-19. These data have been shared with the SEHOP members to support treatment and isolation policies akin to those for children without cancer, except for those with recent alloHSCT or additional comorbidities. This highlights the collaborative registries potential in managing pandemic emergencies.

Development of a biotechnology process for the production of a novel hyperglycosylated long-acting recombinant bovine follicle-stimulating hormone.

Follicle-stimulating hormone (FSH) is an important protein used for bovine ovarian hyperstimulation in multiple ovulation and embryo transfer technology (MOET). Several attempts to produce bovine FSH (bFSH) in recombinant systems have been reported, nonetheless, up to date, the most commonly used products are partially purified preparations derived from porcine or ovine (pFSH or oFSH) pituitaries. Here we describe the development of a biotechnology process to produce a novel, hyperglycosylated, long-acting recombinant bFSH (LA-rbFSH) by fusing copies of a highly O-glycosylated peptide. LA-rbFSH and a nonmodified version (rbFSH) were produced in suspension CHO cell cultures and purified by IMAC with high purity levels (>99%). LA-rbFSH presented a higher glycosylation degree and sialic acid content than rbFSH. It also demonstrated a notable improvement in pharmacokinetic properties after administration to rats, including a higher concentration in plasma and a significant (seven-fold) reduction in apparent clearance (CLapp). In addition, the in vivo specific bioactivity of LA-rbFSH in rats was 2.4-fold higher compared to rbFSH. These results postulate this new molecule as an attractive substitute for commercially available porcine pituitary-derived products.

Reference values and associated factors of controlled attenuation parameter and liver stiffness in adults: A cross-sectional study.

BACKGROUND & AIMS: The utilization of non-invasive techniques for liver fibrosis and steatosis assessment has gained acceptance as a viable substitute for liver biopsy in clinical practice. This study aimed to establish normative data for the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) by age and gender, as well as to explore the relationship between anthropometric measures, clinical status, and biochemical profile according to the 90th percentile cut-off values for CAP/LSM in a U.S. adult population. METHODS AND RESULTS: In this cross-sectional analysis, 7.522 US adults aged 20-80 years from the National Health and Nutrition Examination Survey (NHANES 2017-2020) were included. CAP and LSM were quantified using the FibroScan® 502-v2 device. A comprehensive range of data was collected, including sociodemographic, anthropometric, biochemical, lifestyle, and clinical conditions. Participants were segmented by sex and age. The median ± standard deviation (SD) for CAP was significantly lower in women (258.27 ± 61.02 dB/m) than in men (273.43 ± 63.56 dB/m), as was the median ± SD for LSM (women: 5.50 ± 4.12 kPa, men: 6.36 ± 5.63 kPa). Although median CAP and LSM values displayed an upward trend with age, statistical significance was not achieved. Notably, higher liver CAP values (above the 90th percentile) correlated with more pronounced clinical and biochemical profile differences compared to lower CAP values (below the 90th percentile) (p < 0.001). CONCLUSIONS: Our study provides age- and sex-stratified standard values for CAP and LSM in a sizeable, nationally representative cohort of adults. The evidence of sex-specific variations in TE test results from our study sets the stage for future research to further corroborate these findings.

Trends in interstate abortion travel to Oregon following the Dobbs court decision.

OBJECTIVES: This study describes how interstate travel for abortion to the state of Oregon changed following the Dobbs decision. STUDY DESIGN: We conducted a retrospective cohort study using vital statistics data from the Oregon Health Authority of all medical and surgical abortions between 2015 and 2023. RESULTS: Following the Dobbs decision, 14.3% of abortions in Oregon were out-of-state residents, compared to 9.6% pre-Dobbs. Out-of-state individuals had significantly higher odds of having abortions in the second or third trimester and having a procedural abortion compared to their in-state counterparts. CONCLUSIONS: Following the Dobbs decision, interstate travel to Oregon increased significantly and represents a distinct population.