Time Dependence Between Tobacco Consumption and Lung Cancer Mortality in Spain.

OBJECTIVES: Lung cancer is the leading cause of cancer death and the second most common cancer in both sexes worldwide, with tobacco being its main risk factor. The aim of this study is to establish the temporal relationship between smoking prevalence and lung cancer mortality in Spain. METHODS: To model the time dependence between smoking prevalence and lung cancer mortality, a distributed lag non-linear model was applied adjusting for sex, age, year of mortality and population at risk. Smoking prevalence data from 1991-2020 were used. Considering a maximum lag of 25 years, mortality data from 2016-2020 were included. The effect of prevalence on mortality for each lag is presented in terms of relative risk (RR). To identify the lag at which smoking prevalence has the greatest effect on mortality, the RR of the different lags were compared. RESULTS: The optimal lag observed between smoking prevalence and lung cancer mortality in Spain was 15 years. The maximum RR was 2.9 (95%CI: 2.0-4.3) for a prevalence of 71% and a 15-year lag. The RR was 1.8 for a prevalence of 33%, an approximate median value between 1991-2020, and a 15-year lag. CONCLUSIONS: In Spain, lung cancer mortality is affected by smoking prevalence 15 years prior. Knowing the evolution of the smoking prevalence series in a country and establishing a lag time is essential to predict how lung cancer incidence and mortality will evolve.

Assessing the impact of long-term inhaled corticosteroid therapy on patients with COVID-19 and coexisting chronic lung disease: A multicenter retrospective cohort study.

Background: Patients with chronic lung disease (CLD), such as asthma or chronic obstructive pulmonary disease, were expected to have an increased risk of clinical manifestations and severity of COVID-19. However, these comorbidities have been reported less frequently than expected. Chronic treatment with inhaled corticosteroids (ICS) may impact the clinical course of COVID-19. The main objective of this study is to know the influence of chronic treatment with ICS on the prognosis of COVID-19 hospitalized patients with CLD. Methods: A multicenter retrospective cohort study was designed, including patients hospitalized with COVID-19. Epidemiological and clinical data were collected at admission and at seven days, and clinical outcomes were collected. Patients with CLD with and without chronic treatment with ICS were compared. Results: Two thousand five hundred ninety-eight patients were included, of which 1,171 patients had a diagnosis of asthma and 1,427 of COPD (53.37% and 41.41% with ICS, respectively). No differences were found in mortality, transfer to ICU, or development of moderate-severe ARDS. Patients with chronic ICS had a longer hospital stay in both asthma and COPD patients (9 vs. 8 days, p = 0.031 in asthma patients), (11 vs. 9 days, p = 0.018 in COPD patients); although they also had more comorbidity burden. Conclusions: Patients with chronic inhaled corticosteroids had longer hospital stays and more chronic comorbidities, measured by the Charlson comorbidity index, but they did not have more severe disease at admission, evaluated with qSOFA and PSI scores. Chronic treatment with inhaled corticosteroids had no influence on the prognosis of patients with chronic lung disease and COVID-19.

Correlation Between Tacrolimus Levels in Blood Samples Obtained from Central Catheter and Peripheral Venipuncture in Lung Transplant Patients (Ven-Cat Study).

BACKGROUND: Following lung transplantation (LT), receiving immunosuppressive therapy is crucial. Tacrolimus is considered a drug with a narrow therapeutic range and its use requires constant monitoring. This study aimed to evaluate the correlation between tacrolimus levels obtained from central venous catheter and direct venipuncture in adult patients undergoing LT. METHODS: This prospective study included LT patients hospitalized in conventional ward carrying a central catheter through which no intravenous tacrolimus was administered. Trough samples were obtained through direct puncture and from the central catheter. Pearson correlation coefficient was calculated to quantify the mean difference between the 2 measures. RESULTS: A total of 54 sample pairs from 16 LT patients were obtained, mostly male (81.3%) and bilateral transplant recipients (93.8%); the transplant procedure was the primary reason for admission (81.3%). The difference in tacrolimus levels between both samples was 0.3 (0.1-0.6) mcg/L, with the measurement for the samples obtained through venipuncture being mostly higher than that for those obtained from the catheter. A strong correlation was observed between the tacrolimus levels in the samples obtained from the catheter and through venipuncture (Pearson correlation coefficient, 0.991; P < 0.001; R2 = 0.982). CONCLUSIONS: There is an excellent correlation between tacrolimus levels obtained from venipuncture and those obtained from central venous catheter in LT patients undergoing oral tacrolimus therapy.

Understanding contextual and practical factors to inform WHO recommendations on using chest imaging to monitor COVID-19 pulmonary sequelae: a qualitative study exploring stakeholders' perspective.

BACKGROUND: A recommendation by the World Health Organization (WHO) was issued about the use of chest imaging to monitor pulmonary sequelae following recovery from COVID-19. This qualitative study aimed to explore the perspective of key stakeholders to understand their valuation of the outcome of the proposition, preferences for the modalities of chest imaging, acceptability, feasibility, impact on equity and practical considerations influencing the implementation of using chest imaging. METHODS: A qualitative descriptive design using in-depth interviews approach. Key stakeholders included adult patients who recovered from the acute illness of COVID-19, and providers caring for those patients. The Evidence to Decision (EtD) conceptual framework was used to guide data collection of contextual and practical factors related to monitoring using imaging. Data analysis was based on the framework thematic analysis approach. RESULTS: 33 respondents, including providers and patients, were recruited from 15 different countries. Participants highly valued the ability to monitor progression and resolution of long-term sequelae but recommended the avoidance of overuse of imaging. Their preferences for the imaging modalities were recorded along with pros and cons. Equity concerns were reported across countries (e.g., access to resources) and within countries (e.g., disadvantaged groups lacked access to insurance). Both providers and patients accepted the use of imaging, some patients were concerned about affordability of the test. Facilitators included post- recovery units and protocols. Barriers to feasibility included low number of specialists in some countries, access to imaging tests among elderly living in nursing homes, experience of poor coordination of care, emotional exhaustion, and transportation challenges driving to a monitoring site. CONCLUSION: We were able to demonstrate that there is a high value and acceptability using imaging but there were factors influencing feasibility, equity and some practical considerations associated with implementation. We had a few suggestions to be considered by the expert panel in the formulation of the guideline to facilitate its implementation such as using validated risk score predictive tools for lung complications to recommend the appropriate imaging modality and complementary pulmonary function test.

Nanogel-Mediated antigen delivery: Biocompatibility, immunogenicity, and potential for tailored vaccine design across species.

Nanotechnology has emerged as a promising avenue for enhancing the efficacy of vaccine delivery systems. This study investigates the utilization of nanogels as carriers for the model antigen ovalbumin, with a focus on in vivo assessments in equine and murine models. Nanogels, owing to their biocompatibility and tunable physicochemical properties, offer a versatile platform for efficient antigen encapsulation and controlled release. The encapsulation efficiency and physicochemical characteristics of ovalbumin-loaded nanogels were comprehensively characterized. In vitro biocompatibility was evaluated, finding excellent properties of these nanogels. In vivo evaluations were conducted on both equine and murine subjects, assessing immunogenicity through antibody and splenic cell response. Furthermore, the study propose the potential use of nanogels in tailoring immune responses through the modulation of antigen release kinetics. The results obtained in the in vitro assays showed an increase in the uptake of nanogels by APCs compared to free antigen (OVA). In mice, an absence of inflammatory response in the inoculation site was observed, without systemic damage in the evaluated organs. In addition, non-significant humoral response was found nor cellular proliferation and proinflammatory cytokine production, compared with a traditional adjuvant as aluminum hydroxide, in both animal models. These findings allow further insights into nanogel-based delivery systems and offer valuable insights into their application in various animal models. In conclusion, this research establishes the utility of nanogels as effective carriers for antigens-based vaccines, with interesting biocompatibility properties and highly taken affinity by antigen-presenting cells, without inducing inflammation at the injection site. The study underscores the potential of nanogel technology in revolutionizing vaccine design and highlights the importance of tailored approaches for diverse target species.

Lipid turnover through lipophagy in the newly identified extremophilic green microalga Chlamydomonas urium.

Autophagy is a central degradative pathway highly conserved among eukaryotes, including microalgae, which remains unexplored in extremophilic organisms. In this study, we described and characterized autophagy in the newly identified extremophilic green microalga Chlamydomonas urium, which was isolated from an acidic environment. The nuclear genome of C. urium was sequenced, assembled and annotated in order to identify autophagy-related genes. Transmission electron microscopy, immunoblotting, metabolomic and photosynthetic analyses were performed to investigate autophagy in this extremophilic microalga. The analysis of the C. urium genome revealed the conservation of core autophagy-related genes. We investigated the role of autophagy in C. urium by blocking autophagic flux with the vacuolar ATPase inhibitor concanamycin A. Our results indicated that inhibition of autophagic flux in this microalga resulted in a pronounced accumulation of triacylglycerols and lipid droplets (LDs). Metabolomic and photosynthetic analyses indicated that C. urium cells with impaired vacuolar function maintained an active metabolism. Such effects were not observed in the neutrophilic microalga Chlamydomonas reinhardtii. Inhibition of autophagic flux in C. urium uncovered an active recycling of LDs through lipophagy, a selective autophagy pathway for lipid turnover. This study provided the metabolic basis by which extremophilic algae are able to catabolize lipids in the vacuole.

Assessment of effectiveness and impact of universal prophylaxis with nirsevimab for prevention of hospitalizations due to respiratory syncytial virus in infants. The NIRSE-GAL study protocol.

Nirsevimab has been recently licensed for universal RSV prophylaxis in infants. NIRSE-GAL is a three-year population-based study initiated in Galicia in September 2023. It aims to evaluate nirsevimab effectiveness against RSV-related hospitalizations lower respiratory tract infections (LRTI), severe RSV, all-cause LRTI, and all-cause hospitalization. NIRSE-GAL also aims to estimate nirsevimab impact on primary healthcare use in the short and mid-term, children's wheezing and asthma, and medical prescriptions for RSV. The immunization campaigns will be scheduled based on the expected start week for the RSV season and will last the whole season. Immunization will be offered to: i) infants born during the campaign (seasonal), ii) infants < 6 months at the start of the campaign (catch-up), and iii) infants with high-risk factors, aged 6-24 months at the start of the campaign (high-risk). The follow-up period will start: i) the immunization date for all immunized infants, ii) the start of the campaign, for the non-immunized catch-up or high-risk groups, or iii) the birthdate for the non-immunized seasonal group. Infants will be followed up until outcome occurrence, death, or end of study. Nirsevimab effectiveness will be estimated using Poisson and Cox regression models. Sensitivity and stratified analyses will be undertaken. The number of averted cases and the number needed to immunize will be estimated. Immunization failure and nirsevimab safety will be monitored. NIRSE-GAL was approved by the ethics committee of Galicia (CEIC 2023-377) and registered in ClinicalTrials.gov (ID: NCT06180993). Findings will be mainly shared via peer-reviewed publications and scientific conferences.

Pegvisomant and pasireotide in PRL and GH co-secreting vs GH-secreting Pit-NETs.

The objective of the study was to evaluate the efficacy of second-line therapies in patients with acromegaly caused by a growth hormone (GH) and prolactin (PRL) co-secreting pituitary neuroendocrine tumor (GH&PRL-Pit-NET) compared to their efficacy in patients with acromegaly caused by a GH-secreting pituitary neuroendocrine tumor (GH-Pit-NET). This is a multicenter retrospective study of patients with acromegaly on treatment with pasireotide and/or pegvisomant. Patients were classified in two groups: GH&PRL-Pit-NETs when evidence of hyperprolactinemia and immunohistochemistry (IHC) for GH and PRL was positive or if PRL were >200 ng/dL regardless of the PRL-IHC and GH-Pit-NETs when the previously mentioned criteria were not met. A total of 28 cases with GH&PRL-Pit-NETs and 122 with GH-Pit-NETs met the inclusion criteria. GH&PRL-Pit-NETs presented at a younger age, caused hypopituitarism, and were invasive more frequently than GH-Pit-NETs. There were 124 patients treated with pegvisomant and 49 with pasireotide at any time. The efficacy of pegvisomant for IGF-1 normalization was of 81.5% and of pasireotide of 71.4%. No differences in IGF-1 control with pasireotide and with pegvisomant were observed between GH&PRL-Pit-NETs and GH-Pit-NETs. All GH&PRL-Pit-NET cases treated with pasireotide (n = 6) and 82.6% (n = 19/23) of the cases treated with pegvisomant normalized PRL levels. No differences in the rate of IGF-1 control between pegvisomant and pasireotide were detected in patients with GH&PRL-Pit-NETs (84.9% vs 66.7%, P = 0.178). We conclude that despite the more aggressive behavior of GH&PRL-Pit-NETs than GH-Pit-NETs, no differences in the rate of IGF-1 control with pegvisomant and pasireotide were observed between both groups, and both drugs have shown to be effective treatments to control IGF-1 and PRL hypersecretion in these tumors.

Orthopaedic Surgery Attrition Before Board Certification: A National-Cohort Study of US MD Graduates in Orthopaedic Surgery Residency Programs.

Introduction: Little is known about attrition before American Board of Orthopaedic Surgery (ABOS) board certification for orthopaedic residents training in Accreditation Council for Graduate Medical Education (ACGME)-accredited orthopaedics programs. This national-cohort study examined orthopaedic surgery attrition, associated risk factors, and specialties pursued by residents who left orthopaedics. Methods: From August 2022 through July 2023, we analyzed deidentified, individual-level data from the Association of American Medical Colleges for 129,860 US MD-granting medical-school matriculants in academic years 1993 to 1994 through 2000 to 2001. Graduates with records of training ≥1 year in orthopaedic surgery during GME and of board certification as of May 2020 were included. Retention was defined as being ABOS-certified; attrition was defined as being certified by another specialty board and not ABOS. We identified variables independently associated with attrition from orthopaedics using multivariable logistic regression analysis and reported adjusted odds ratios (OR) and 95% confidence intervals (CI). Results: Of 4,319 US medical-school graduates from 1997 to 2009 with ≥1 year of orthopaedic surgery GME, 4,085 (94.6%) obtained ABOS board certification (retention) and 234 did not (attrition). Women (OR 2.8, 95% CI 2.0-3.9), first-generation college graduates (OR 1.6, 95% CI 1.1-2.2), Asians (OR 1.9, 95% CI 1.4-2.7), and residents who placed greater importance on innovation/research in choosing medicine as a career (OR 1.4, 95% CI 1.1-1.7) and completed ≥1 year of research during GME (OR 2.4, 95% CI 1.7-3.5) were more likely to leave orthopaedics. Overall, 121 trainees who left orthopaedics selected surgical specialties for board certification, most commonly plastic surgery (n = 66) and general surgery (n = 45). Conclusions: The increased risk of attrition among women, Asians, first-generation college graduates, and trainees endorsing higher importance of innovation/research in choosing medicine and participating in research during GME raises concerns about the potential loss of underrepresented groups among orthopaedic surgeons and surgeon-scientists. Efforts to mitigate attrition among residents in high-risk groups are warranted.

Teaching Literacy to Filipino Deaf Students in Multilingual Classrooms Amid a Pandemic.

This article describes the current landscape of teaching literacy to Filipino Deaf students in a multilingual, multi-cultural classroom amid the pandemic. The article highlights the uniqueness of Filipino Deaf students as multilingual learners in a multi-cultural classroom and the lack of literature and research on Deaf multilingualism both locally and globally. Moreover, the article focuses on the role of Deaf teachers in teaching Filipino Deaf students, especially in their literacy development. The steps being done to ensure that the curriculum is inclusive of Deaf learners who use Filipino Sign Language (FSL), teacher preparation and materials development, and the challenges in the shift to distance learning amid the COVID-19 pandemic are also discussed. Future directions and recommendations include review of curriculum and adaptation, enhancement of teacher preparation, promotion of collaborative teaching and research efforts, and the production of more appropriate and accessible instructional materials for Deaf students.

Late metastases: a rare cause of diarrhea.

We present the case of a 64-year-old female with personal history of breast carcinoma diagnosed in 2011, treated and discharged from the Oncology service after 10 years disease-free who, 21 years after the diagnosis, undergoes a colonoscopy with biopsy sampling due to a 2-year period of diarrhea and weight loss, which histological study show infiltration of the large intestine's by breast carcinoma. Due to the usual lymphatic widespread, metastases of breast cancer in the gastrointestinal tract are extremely rare with nonspecific symptoms, long latency periods and poor prognosis.

Time series analysis of a 22-year record of 7Be, 210Pb and gross alpha activities in the Canary Islands (Spain) using Principal Component and Multifractal Detrended Fluctuation Analyses.

The long-term variability of a 22-year dataset of 7Be, 210Pb and gross alpha concentrations in surface aerosols collected in the Canary Islands has been analysed in this study. These "time series" were collected on a weekly basis. Various analytical techniques, including Principal Component Analysis (PCA), K-means clustering, correlation analyses, and back-trajectory were used to determine the variability of the data and assess the statistical importance of the source of the air masses reaching the study area. Monthly and annual variations for the time series were also studied. As expected, 7Be, 210Pb time series showed common variability, while gross alpha concentrations were strongly correlated with average PM10 concentration in air. The fractal properties of the time series were studied to gain a deeper understanding of the underlying structure and dynamics of the data. Multifractal Detrended Fluctuation Analysis (MF-DFA) and Multifractal Detrended Cross-Correlation Analysis (MF-DCCA) techniques were also used to detect and analyse the multifractal characteristics of the 7Be, 210Pb, and gross alpha time series. Multifractality was observed, with values of 0.28, 0.67, and 0.61 for 7Be, 210Pb, and gross alpha, respectively. Long-range correlation was found to be the source of the observed multifractality in the three parameters. Multifractal detrended cross-correlation analysis supports the correlation between 7Be - Alpha, 210Pb - Alpha, and 7Be - 210Pb pairs. The results from this study will help model the transport and destiny of natural radionuclides in the atmosphere at this site. The evolution and interactions between 7Be, 210Pb, and gross alpha, reported herein occurred not just locally but also across extensive temporal domains, leading to the emergence of multifractal behaviour in their concentrations. These long-range behaviours/correlations might result from various factors such as atmospheric circulation patterns, global transport mechanisms, or large-scale environmental processes.

Intracranial thrombus composition is associated with occlusion location and endovascular treatment outcomes: results from ITACAT multicenter study.

BACKGROUND: The impact of thrombolytics directed towards different thrombus components regarding site of occlusion in combination with mechanical thrombectomy (MT) to achieve endovascular complete recanalization is unclear. METHODS: Retrospective analysis of a prospective database in two stroke centers. Intracranial thrombi retrieved by MT were analyzed using hematoxylin-eosin staining for fibrin and red blood cell proportions, and CD61 immunostaining for platelets proportion in thrombus (PLTPT) assessment. Thrombi composition, baseline variables, etiology, treatment features and occlusion location were analyzed. RESULTS: Overall, 221 patients completed the per protocol analysis and 110 cases achieved a final expanded Thrombolysis in Cerebral Infarction (eTICI) 3 (49%) of which 70 were MT (32%) by first pass effect (FPE). Thrombi from medium distal vessel occlusions had higher PLTPT compared with thrombi from proximal large vessel occlusions (68% vs 61%, P=0.026). In particular, middle cerebral artery M2-M3 segment thrombi had the highest PLTPT (70%), and basilar artery thrombi the lowest PLTPT (41%). After logistic regression analysis adjusted for occlusion location and intravenous fibrinolysis, lower baseline National Institutes of Health Stroke Scale score (adjusted OR (aOR) 0.95, 95% CI 0.913 to 0.998) and PLTPT (aOR 0.97, 95% CI 0.963 to 0.993) were independently associated with FPE. Fewer MT passes (aOR 0.67, 95% CI 0.538 to 0.842) and platelet poor thrombus (<62% PLTPT; aOR 2.39, 95% CI 1.288 to 4.440) were independently associated with final eTICI 3. CONCLUSIONS: Occlusion location might be a surrogate parameter for thrombus composition. Platelet poor clots and fewer MT passes were independently associated with complete endovascular recanalization. Clinical trials testing the benefits of combining selective intra-arterial platelet antagonists with MT to improve endovascular outcomes are warranted.

A comparison of the upper anterior teeth movements with optimized and conventional attachment.

Background: Invisalign® attachments are divided into two main groups: the conventional group and the optimized group, which is also known as the SmartForce™. The aim of this study is to compare the movements produced by an optimized crescent-shaped attachment in superior incisor teeth with the movements produced by a conventional rectangular attachment (vertical and horizontal) in the same teeth. Material and Methods: This retrospective study examined the movement table of the initial ClinCheck® and the first refinement of 95 patients (mean age 44.18 ± 4.125, 40 males and 55 females). It represented 147 upper incisors divided into two groups: 87 with rectangular attachment and 60 with optimized attachment. Applying Kravitz's accuracy formula for each movement and each tooth of interest (with attachments of interest), we underlined the effectiveness of each attachment. Mann-Whitney U test, Kruskal-Wallis test, and Pearson and Spearman correlation coefficients were used for statistical analysis. Results: The accuracies of rotation, mesio-distal angulation and vestibulo-lingual inclination are highly significantly related to the type of attachment used on the upper lateral incisor. The optimized attachment presented greater accuracy in the rotation of the lateral incisors than the conventional attachment. However, conventional vertical attachment showed a higher accuracy (p<.01) in the mesio-distal angulation and horizontal attachments showed a higher accuracy (p<.01) in the vestibulo-lingual inclination in the same group of teeth. Conclusions: Optimized attachments rotate better lateral incisors; conventional vertical attachments are more efficient to improve mesio-distal angulation; and horizontal attachments serve best for torque movements. Key words:Orthodontics, clear aligners, orthodontic tooth movements, attachments.

Femtosecond-Assisted Mushroom Deep Anterior Lamellar Keratoplasty.

PURPOSE: The aim of this study was to describe our technique for performing femtosecond laser (FSL)-assisted mushroom configuration in deep anterior lamellar keratoplasty (DALK). METHODS: We describe our surgical technique for a mushroom-configuration DALK using a femtosecond laser (FSL) both to prepare the graft and to perform a precut of the recipient cornea, as well as the steps for the dissection of the recipient cornea and for donor cornea implantation. Moreover, we show the parameters of energy and spot separation and the external and internal diameters as well as the thickness of the external and internal keratotomy. RESULTS: We performed a retrospective case series study of 20 patients with a mean follow-up of 4.36 ± 2.54 years. The indication for surgery was leukoma in 15 cases (75%), keratoconus in 4 cases (20%), and stromal corneal dystrophy in 1 case (5%). Four cases had to be converted to penetrating keratoplasty. The overall results were as follows: The mean preoperative corrected distance visual acuity increased from 0.11 ± 0.09 (0.01-0.30) to 0.78 ± 0.22 (0.30-1.0) with spectacles and to 0.92 ± 0.13 (0.5-1.0) with a gas permeable contact lens. The mean final cylinder was 3.90 ± 1.86 (1.25-7.0). The mean endothelial cell count at 6 months was 2033.83 ± 570.53 cells/mm2 (930-3207), and the mean final spherical equivalent was -4.67 ± 2.91 (-0.25 to -9.00). CONCLUSIONS: FSL-assisted technology is useful to achieve a predictable and safe procedure when using mushroom configuration to perform DALK. Our conversion rate from DALK to penetrating keratoplasty was similar to or even lower than that reported in the literature. In the successful DALK cases, the visual and refractive results were similar to those reported in other studies using FSL-assisted DALK (with a standard or mushroom configuration).

Effectiveness and impact of universal prophylaxis with nirsevimab in infants against hospitalisation for respiratory syncytial virus in Galicia, Spain: initial results of a population-based longitudinal study.

BACKGROUND: Galicia (Spain) was one of the first regions worldwide to incorporate nirsevimab for universal respiratory syncytial virus (RSV) prophylaxis in infants into its immunisation programme. The NIRSE-GAL longitudinal population-based study aimed to assess nirsevimab effectiveness in preventing hospitalisations (ie, admittance to hospital). METHODS: The 2023-24 immunisation campaign with nirsevimab in Galicia began on Sept 25, 2023, and concluded on March 31, 2024. The campaign targeted three groups: infants born during the campaign (seasonal group), infants younger than 6 months at the start of the campaign (catch-up group), and infants aged 6-24 months with high-risk factors at the start of the campaign (high-risk group). Infants in the seasonal group were offered immunisation on the first day of life before discharge from hospital. Infants in the catch-up and high-risk groups received electronic appointments to attend a public hospital or health-care centre for nirsevimab administration. For this interim analysis, we used data collected from Sept 25 to Dec 31, 2023, from children born up to Dec 15, 2023. Data were retrieved from public health registries. Nirsevimab effectiveness in preventing RSV-associated lower respiratory tract infection (LRTI) hospitalisations; severe RSV-related LRTI requiring intensive care unit admission, mechanical ventilation, or oxygen support; all-cause LRTI hospitalisations; and all-cause hospitalisations was estimated using adjusted Poisson regression models. Data from five past RSV seasons (2016-17, 2017-18, 2018-19, 2019-20, and 2022-23), excluding the COVID-19 pandemic period, were used to estimate the number of RSV-related LRTI hospitalisations averted along with its IQR. The number needed to immunise to avoid one case in the 2023-24 season was then estimated from the averted cases. Nirsevimab safety was routinely monitored. The NIRSE-GAL study protocol was registered on ClinicalTrials.gov (NCT06180993), and follow-up of participants is ongoing. FINDINGS: 9408 (91·7%) of 10 259 eligible infants in the seasonal and catch-up groups received nirsevimab, including 6220 (89·9%) of 6919 in the seasonal group and 3188 (95·4%) of 3340 in the catch-up group. 360 in the high-risk group were offered nirsevimab, 348 (97%) of whom received it. Only infants in the seasonal and catch-up groups were included in analyses to estimate nirsevimab effectiveness and impact because there were too few events in the high-risk group. In the catch-up and seasonal groups combined, 30 (0·3%) of 9408 infants who received nirsevimab and 16 (1·9%) of 851 who did not receive nirsevimab were hospitalised for RSV-related LRTI, corresponding to an effectiveness of 82·0% (95% CI 65·6-90·2). Effectiveness was 86·9% (69·1-94·2) against severe RSV-related LRTI requiring oxygen support, 69·2% (55·9-78·0) against all-cause LRTI hospitalisations, and 66·2% (56·0-73·7) against all-cause hospitalisations. Nirsevimab effectiveness against other endpoints of severe RSV-related LRTI could not be estimated because of too few events. RSV-related LRTI hospitalisations were reduced by 89·8% (IQR 87·5-90·3), and the number needed to immunise to avoid one RSV-related LRTI hospitalisation was 25 (IQR 24-32). No severe adverse events related to nirsevimab were registered. INTERPRETATION: Nirsevimab substantially reduced infant hospitalisations for RSV-associated LRTI, severe RSV-associated LRTI requiring oxygen, and all-cause LRTI when given in real-world conditions. These findings offer policy makers and health authorities robust, real-world, population-based evidence to guide the development of strategies for RSV prevention. FUNDING: Sanofi and AstraZeneca. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Protein Citrullination by Peptidyl Arginine Deiminase/Arginine Deiminase Homologs in Members of the Human Microbiota and Its Recognition by Anti-Citrullinated Protein Antibodies.

The human microbiome exists throughout the body, and it is essential for maintaining various physiological processes, including immunity, and dysbiotic events, which are associated with autoimmunity. Peptidylarginine deiminase (PAD) enzymes can citrullinate self-proteins related to rheumatoid arthritis (RA) that induce the production of anti-citrullinated protein antibodies (ACPAs) and lead to inflammation and joint damage. The present investigation was carried out to demonstrate the expression of homologs of PADs or arginine deiminases (ADs) and citrullinated proteins in members of the human microbiota. To achieve the objective, we used 17 microbial strains and specific polyclonal antibodies (pAbs) of the synthetic peptide derived from residues 100-200 of human PAD2 (anti-PAD2 pAb), and the recombinant fragment of amino acids 326 and 611 of human PAD4 (anti-PAD4 pAb), a human anti-citrulline pAb, and affinity ACPAs of an RA patient. Western blot (WB), enzyme-linked immunosorbent assay (ELISA), elution, and a test with Griess reagent were used. This is a cross-sectional case-control study on patients diagnosed with RA and control subjects. Inferential statistics were applied using the non-parametric Kruskal-Wallis test and Mann-Whitney U test generated in the SPSS program. Some members of phyla Firmicutes and Proteobacteria harbor homologs of PADs/ADs and citrullinated antigens that are reactive to the ACPAs of RA patients. Microbial citrullinome and homolog enzymes of PADs/ADs are extensive in the human microbiome and are involved in the production of ACPAs. Our findings suggest a molecular link between microorganisms of a dysbiotic microbiota and RA pathogenesis.

Biodegradable Biocomposite of Starch Films Cross-Linked with Polyethylene Glycol Diglycidyl Ether and Reinforced by Microfibrillated Cellulose.

Biopolymers are biodegradable and renewable and can significantly reduce environmental impacts. For this reason, biocomposites based on a plasticized starch and cross-linker matrix and with a microfibrillated OCC cardboard cellulose reinforcement were developed. Biocomposites were prepared by suspension casting with varied amounts of microfibrillated cellulose: 0, 4, 8, and 12 wt%. Polyethylene glycol diglycidyl ether (PEGDE) was used as a cross-linking, water-soluble, and non-toxic agent. Microfibrillated cellulose (MFC) from OCC cardboard showed appropriate properties and potential for good performance as a reinforcement. In general, microfiber incorporation and matrix cross-linking increased crystallization, reduced water adsorption, and improved the physical and tensile properties of the plasticized starch. Biocomposites cross-linked with PEGDE and reinforced with 12 wt% MFC showed the best properties. The chemical and structural changes induced by the cross-linking of starch chains and MFC reinforcement were confirmed by FTIR, NMR, and XRD. Biodegradation higher than 80% was achieved for most biocomposites in 15 days of laboratory compost.

Taxonomic inflation as a conservation trap for inbred populations.

Conservation is prioritized based on accepted taxa. As a consequence, a conservation incentive exists to emphasize inter-population differences to define taxa, potentially leading to taxonomic inflation. But stressing the uniqueness of threatened populations has the side effect of hindering conservation actions that promote inter-population gene flow, such as genetic rescue. These actions may be of critical importance for severely inbred populations involved in extinction vortices, for which an inflated taxonomy can become a conservation trap. Here, we exemplify this scenario with the western capercaillie (Tetrao urogallus, Phasianidae) population in the Cantabrian Mountains, described and legally listed as a subspecies not supported by recent molecular data. The Cantabrian capercaillie population is Critically Endangered after a long-lasting decline and a recent demographic collapse. It shows clear signs of inbreeding depression, including striking clutch size decreases as well as reduced hatchability and chick survival. This critical situation could be alleviated through a genetic rescue, but this possibility is hindered by inertias rooted in the putative uniqueness of the Cantabrian capercaillie. It had been previously argued that poor taxonomy could hamper conservation, through the oblivion of populations deserving, but not having, a taxonomic status. We show that taxonomic inflation can also become an obstacle for effective conservation.

Risk and resilience in eating disorders: differentiating pathways among psychosocial predictors.

OBJECTIVE: Eating disorders (EDs) represent a rising global health concern. The current study takes a multivariate approach to examine psychological (i.e., perfectionism, anxiety sensitivity [AS], emotion dysregulation) and sociocultural factors (i.e., body dissatisfaction) that may relate to risk and resilience in EDs. METHODS: Participants were 698 undergraduate students (Mage = 21, SDage = 4.02), mainly female (71%) and Hispanic (61.6%), who participated in an online survey assessing perfectionism, emotion dysregulation, AS, body dissatisfaction, and eating behaviors. RESULTS: The results from structural equation model analyses revealed differential associations with disordered eating (DE) outcomes. Self-oriented perfectionism and dysmorphic appearance concerns were associated with increased dieting/carb restriction, desire for thinness, and binging tendencies. Specifically, emotional nonacceptance and lack of emotional awareness showed associations with elevated risk for dieting/carb restriction and purging tendencies, respectively. Conversely, lack of emotional clarity showed a protective pathway to these risk behaviors. Anxiety sensitivity cognitive concerns related to higher purging tendencies, while AS social concerns related to lower purging and binging tendencies. DISCUSSION: Findings highlight the differential pathways of psychosocial risk and resilience for EDs. Subscales of emotional dysregulation and AS showed risk as well as resilience associations with DE outcomes. This information is key for advancing transdiagnostic prevention and intervention to reduce the rising rates of EDs.

Eating disorders are rising worldwide at alarming rates. We know their development is complex involving multiple factors, but the specific contributions of different factors are not well understood. This study demonstrates differential pathways of risk and resilience among psychosocial factors (i.e., perfectionism, emotion dysregulation, anxiety sensitivity, and body dissatisfaction) and eating behaviors and cognitions. Facets of perfectionism and body dissatisfaction were associated with unhealthy eating behaviors like dieting and bingeing. However, different aspects of emotional dysregulation and anxiety sensitivity were linked to maladaptive eating behaviors, but others seemed to protect against risky eating behaviors. This information is crucial for creating more effective prevention and treatment strategies for eating disorders.