Prostate Magnetic Resonance Imaging Using the Prostate Imaging for Recurrence Reporting (PI-RR) Scoring System to Detect Recurrent Prostate Cancer: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVE: Prostate Imaging for Recurrence Reporting (PI-RR) was introduced in 2021 to standardize the interpretation and reporting of multiparametric magnetic resonance imaging (MRI) for prostate cancer following whole-gland treatment. The system scores image on a scale from 1 to 5 and has shown promising results in single-center studies. The aim of our systematic review and meta-analysis was to assess the diagnostic performance of the PI-RR system in predicting the likelihood of local recurrence after whole-gland treatment. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for diagnostic test accuracy were followed. Relevant databases were searched up to December 2023. Primary studies met the eligibility criteria if they reported MRI diagnostic performance in prostate cancer recurrence using PI-RR. Diagnostic performance for MRI was assessed using two different cutoff points (≥3 or ≥4 for positivity according to the PI-RR system). A meta-analysis with a random-effects model was used to estimate pooled sensitivity and specificity values. KEY FINDINGS AND LIMITATIONS: Sixteen articles were identified for full-text reading, of which six were considered eligible, involving a total of 467 patients. Using a cutoff of PI-RR ≥3 (4 studies) for recurrent disease, the sensitivity was 77.8% (95% confidence interval [CI] 69.9-84.1%) and the specificity was 80.2% (95% CI 58.2-92.2%). Using a cutoff of PI-RR ≥4 (4 studies), the sensitivity was 61.9% (95% CI 35.6-82.7%) and the specificity was 86.6% (95% CI 75.1-93.3%). Overall, the inter-rater agreement varied from fair to excellent. CONCLUSIONS AND CLINICAL IMPLICATIONS: PI-RR is accurate in detecting local recurrence after whole-gland treatment for prostate cancer and shows fair-to-good to excellent inter-reader agreement. Overall, a PI-RR cutoff of ≥3 showed high sensitivity and specificity. PATIENT SUMMARY: We reviewed studies that reported on how good MRI scans using a scoring system called PI-RR were in detecting recurrence of prostate cancer. We found that this system shows good performance, with fair to excellent agreement between different radiologists.

2D model of groundwater flow and total dissolved HCH transport through the Gállego alluvial aquifer downstream the Sardas landfill (Huesca, Spain).

The organic pollutants disposed at the Sardas landfill in Sabiñánigo (Huesca, northeastern Spain) by the INQUINOSA lindane factory have reached the Gállego alluvial aquifer and could affect the Sabiñánigo reservoir. The daily oscillations of the reservoir water level produce a tidal effect on the piezometric heads of the aquifer. These oscillations are transmitted in a damped way with a time lag, thus attesting that the silting sediments of the reservoir and the natural silts of the Gállego alluvial are interposed between the reservoir water and the layer of sands and gravels. A 2D finite element groundwater flow and total dissolved hexachlorocyclohexane (HCH) transport model through the Gállego alluvial aquifer is presented here. The flow model was constructed to: (1) Quantify the tidal effect, produced by the daily fluctuations of the reservoir water level on the aquifer; (2) Estimate the hydrodynamic parameters of the layer of sands and gravels; and 3) Estimate the vertical hydraulic conductivity of the silting sediments and silts; and (4) Quantify aquifer/reservoir interactions. The flow model reproduces the dynamics of the tidal effect and attests that groundwater velocity and flow direction changes daily in response to the oscillations of the reservoir level. Model results reproduce the measured well hydrographs and the Darcy velocity derived from tracer tests and confirm the validity of the conceptual model. The transport model of total dissolved HCH simulates the time evolution of the contaminant plume. The computed concentrations of total dissolved HCH and the contaminant mass outflux are very sensitive to changes in the source terms and the distribution coefficient, Kd of HCH. The best fit to the measured HCH plumes in September 2010 and December 2020 is obtained with a Kd ranging from 1 to 3 L/kg. The computed flux of dissolved HCH leaving the Sardas site in 2020 towards the Sabiñánigo reservoir ranges from 0.6 kg/year for Kd = 3 L/kg to 3.1 kg/year for Kd = 1 L/kg. The findings of this study will be most useful for planning and designing remedial and containment actions at the Sardas site and other similar lindane-affected sites.

Angular momentum transfer from swift electrons to non-spherical nanoparticles within the dipolar approximation.

In this work, we study the angular momentum transfer from a single swift electron to non-spherical metallic nanoparticles, specifically investigating spheroidal and polyhedral (Platonic Solids) shapes. While previous research has predominantly focused on spherical nanoparticles, our work expands the knowledge by exploring various geometries. Employing classical electrodynamics and the small particle limit, we calculate the angular momentum transfer by integrating the spectral density, ensuring causality through Fourier-transform analysis. Our findings demonstrate that prolate spheroidal nanoparticles exhibit a single blueshifted plasmonic resonance, compared to spherical nanoparticles of equivalent volume, resulting in lower angular momentum transfer. Conversely, oblate nanoparticles display two resonances - one blueshifted and one redshifted - resulting in a higher angular momentum transfer than their spherical counterparts. Additionally, Platonic Solids with fewer faces exhibit significant redshifts in plasmonic resonances, leading to higher angular momentum transfer due to edge effects. We also observe resonances and angular momentum transfers with similar characteristics in specific pairs of Platonic Solids, known as duals. These results highlight promising applications, particularly in electron tweezers technology.

Assessing Endoscopic Response in Locally Advanced Rectal Cancer Treated with Total Neoadjuvant Therapy: Development and Validation of a Highly Accurate Convolutional Neural Network.

BACKGROUND: Rectal tumors display varying degrees of response to total neoadjuvant therapy (TNT). We evaluated the performance of a convolutional neural network (CNN) in interpreting endoscopic images of either a non-complete response to TNT or local regrowth during watch-and-wait surveillance. METHODS: Endoscopic images from stage II/III rectal cancers treated with TNT from 2012 to 2020 at a single institution were retrospectively reviewed. Images were labelled as Tumor or No Tumor based on endoscopy timing (before, during, or after treatment) and the tumor's endoluminal response. A CNN was trained using ResNet-50 architecture. The area under the curve (AUC) was analyzed during training and for two test sets. The main test set included images of tumors treated with TNT. The other contained images of local regrowth. The model's performance was compared to sixteen surgeons and surgical trainees who evaluated 119 images for evidence of tumor. Fleiss' kappa was calculated by respondent experience level. RESULTS: A total of 2717 images from 288 patients were included; 1407 (51.8%) contained tumor. The AUC was 0.99, 0.98, and 0.92 for training, main test, and local regrowth test sets. The model performed on par with surgeons of all experience levels for the main test set. Interobserver agreement was good ( k = 0.71-0.81). All groups outperformed the model in identifying tumor from images of local regrowth. Interobserver agreement was fair to moderate ( k = 0.24-0.52). CONCLUSIONS: A highly accurate CNN matched the performance of colorectal surgeons in identifying a noncomplete response to TNT. However, the model demonstrated suboptimal accuracy when analyzing images of local regrowth.

Health economic evaluation of 2-dose and 3-dose rotavirus vaccines in children below 5 years of age in Morocco.

Following the introduction of rotavirus vaccination into the Moroccan National Immunization Program, the prevalence of the disease has decreased by nearly 50%. However, evidence on the economic value of rotavirus vaccinations in Morocco is limited. This health economic analysis evaluated, from both country payer and societal perspectives, the costs and the cost-effectiveness of three rotavirus vaccines using a static, deterministic, population model in children aged < 5 years in Morocco. Included vaccines were HRV (2-dose schedule), HBRV (3-dose schedule) and BRV-PV 1-dose vial (3-dose schedule). One-way and probabilistic sensitivity analyses were conducted to assess the impact of uncertainty in model inputs. The model predicted that vaccination with HRV was estimated to result in fewer rotavirus gastroenteritis events (-194 homecare events, -57 medical visits, -8 hospitalizations) versus the 3-dose vaccines, translating into 7 discounted quality-adjusted life years gained over the model time horizon. HRV was associated with lower costs versus HBRV from both the country payer (-$1.8 M) and societal (-$4.1 M) perspectives, and versus BRV-PV 1-dose vial from the societal perspective (-$187,000), dominating those options in the cost-effectiveness analysis. However, costs of BRV-PV 1-dose vial were lower than HRV from the payer perspective, resulting in an ICER of approximately $328,376 per QALY, above the assumed cost effectiveness threshold of $3,500. Vaccination with a 2-dose schedule of HRV may be a cost-saving option and could lead to better health outcomes for children in Morocco versus 3-dose schedule rotavirus vaccines.

Influence of physical activity level and perceived social support on mental health and psychological distress in women with menopause problems.

Perceived Social Support (PSS) and Physical Activity (PA) could have an important role in reducing psychological distress in women with problems in the menopausal period. The aim was to analyze the associations between a) Self-Perceived Health (SPH), prevalence of self-reported depression and anxiety, and mental health and its subscales, through the Goldberg General Health Questionnaire (GHQ-12) with b) the Physical Activity Level (PAL) and c) the PSS, through the Duke-UNC-11 functional social support questionnaire in Spanish women with problems in the menopausal period. This document uses data from the Spanish National Health Survey of 2017, focusing on women between 40 and 69 years of age with problems in the menopausal period. Dependency relationships were found between the prevalence of depression and PAL, anxiety and PAL, and SPH with PAL (p < 0.001). Weak inverse correlations were found between PAL and mental health, Coping Success, Self-confidence, and Stress (rho: - 0.214 to - 0.258; p < 0.001). Also, weak and very weak significant inverse correlations were found between PAL and all items of the GHQ-12. Weak inverse correlations were found between PSS scores and mental health, Coping, and Stress (r: -0.201 to - 0.304; p < 0.001). Likewise, weak and very weak inverse correlations, although statistically significant, were found between the PSS scores and the responses to the GHQ-12 items. Very active women with higher PSS have less psychological distress, higher self-esteem, and better prevalence of positive health.

Identification and expression analysis of two steamer-like retrotransposons in the Chilean blue mussel (Mytilus chilensis).

BACKGROUND: Disseminated neoplasia (DN) is a proliferative cell disorder of the circulatory system of bivalve mollusks. The disease is transmitted between individuals and can also be induced by external chemical agents such as bromodeoxyuridine. In Mya arenaria, we have cloned and characterized an LTR-retrotransposon named Steamer. Steamer mRNA levels and gene copy number correlates with DN and can be used as a marker of the disease. So far, the only mollusk where a retrotransposon expression relates to DN is Mya arenaria. On the other hand, it has been reported that the Chilean blue mussel Mytilus chilensis can also suffers DN. Our aim was to identify retrotransposons in Mytilus chilensis and to study their expression levels in the context of disseminated neoplasia. RESULTS: Here we show that 7.1% of individuals collected in August 2018, from two farming areas, presents morphological characteristics described in DN. Using Steamer sequence to interrogate the transcriptome of M. chilensis we found two putative retrotransposons, named Steamer-like elements (MchSLEs). MchSLEs are present in the genome of M. chilensis and MchSLE1 is indeed an LTR-retrotransposon. Neither expression, nor copy number of the reported MchSLEs correlate with DN status but both are expressed at different levels among individual animals. We also report that in cultured M. chilensis haemocytes MchSLEs1 expression can be induced by bromodeoxyuridine. CONCLUSIONS: We conclude that SLEs present in Mytilus chilensis are differentially expressed among individuals and do not correlate with disseminated neoplasia. Treatment of haemocytes with a stressor like bromodeoxyuridine induces expression of MchSLE1 suggesting that in Mytilus chilensis environmental stressors can induce activation of LTR-retrotransposon.

Spatial and Temporal Dynamics of the Vegetation Cover from the Bijagual Massif, Boyacá, Colombia, during the 1986-2021 Period.

Landscape changes based on spectral responses allow showing plant cover changes through diversity, composition, and ecological connectivity. The spatial and temporal vegetation dynamics of the Bijagual Massif from 1986 to 2021 were analyzed as a measure of ecological integrity, conservation, and territory. The covers identified were high open forest (Hof), dense grassland of non-wooded mainland (Dgnm), a mosaic of pastures and crops (Mpc), lagoons (Lag), and bare and degraded lands (Bdl). The Bijagual Massif has 8574.1 ha. In 1986, Dgnm occupied 42.6% of the total area, followed by Mpc (32.8%) and Hof (24.5%); by 2000, Mpc and Hof increased (43.7 and 28.1%, respectively), while Dgnm decreased (28%); by 2021, Dgnm was restricted to the northeastern zone and continued to decrease (25.2%), Mpc occupied 52.9%, Hof 21.7% and Bdl 0.1%. Of the three fractions of the connectivity probability index, only dPCintra and dPCflux contribute to ecological connectivity. Hof and Dgnm show patches with biota habitat quality and availability. Between 1986 and 2021, Dgnm lost 1489 ha (41%) and Hof 239.5 ha (11%). Mpc replaced various covers (1722.2 ha; 38%) in 2021. Bijagual has a valuable biodiversity potential limited by Mpc. Territorial planning and sustainable agroecological and ecotourism proposals are required due to the context of the ecosystems.

Modelling the Public Health Burden of Herpes Zoster and the Impact of Adjuvanted Recombinant Zoster Vaccine in Five Selected Countries in Southeast Asia.

INTRODUCTION: Herpes zoster (HZ) can cause substantial patient morbidity and lead to large healthcare costs. However, the disease burden of HZ in Southeast Asia may be underestimated. This study aimed to estimate the public health burden of HZ and the impact of vaccinating adults aged ≥ 50 years old in five Southeast Asian countries (Indonesia, Malaysia, Philippines, Thailand, and Vietnam), with adjuvanted recombinant zoster vaccine (RZV) compared with no vaccination. METHODS: For each country, we adapted a static multicohort Markov model developed with a 1-year cycle length and lifetime horizon. Demographics were obtained from the World Health Organization, HZ incidence from a worldwide meta-regression reporting Asian-specific values, proportions of postherpetic neuralgia (PHN) and non-PHN complications from local/regional studies, and vaccine efficacy from a long-term follow-up trial. First-dose coverage and second-dose compliance were assumed to be 30% and 70%, respectively. A one-way deterministic sensitivity analysis (OWSA) and probabilistic sensitivity analysis (PSA) were performed to assess the robustness and uncertainty of inputs for each country. RESULTS: Without RZV, it was estimated that there would be a total of approximately 10 million HZ cases, 2.1 million PHN cases, and 1.4 million non-PHN complications in individuals aged ≥ 50 years included in the model. Introducing RZV under 30% coverage could avoid approximately 2.2 million (22%) HZ cases, almost 500,000 (21%) PHN cases, and around 300,000 (22%) non-PHN complications. OWSA showed that first-dose coverage and initial HZ incidence had the largest impact on the estimated number of HZ cases avoided. The number needed to vaccinate ranged from 15 to 21 to prevent one case of HZ and from 68 to 104 to prevent one case of PHN across each country. CONCLUSIONS: This study demonstrated that there is substantial HZ disease burden in older adults for the five selected countries in Southeast Asia, negatively impacting national healthcare systems. Introducing RZV could potentially reduce this burden. A graphical abstract is available with this article.

Movement Disorder Perspectives on Monocarboxylate 8 Deficiency: A Case Series of 3 Colombian Patients with Allan-Herndon-Dudley Syndrome.

BACKGROUND: Deficiencies in the thyroid hormone transporter monocarboxylate 8 (MCT8) due to pathogenic variants in the SLC16A2 gene (OMIM 300095) result in a complex phenotype with main endocrine and neurologic symptoms. This rare disorder, named Allan-Herndon-Dudley syndrome (AHDS) (OMIM 300523), is inherited in an X-linked trait. One of the prominent features of AHDS is the presence of movement disorders (MD), which are complex and carry a significant burden of the disease. CASES: Patient 1: male with hypotonia since birth, developmental delay, dystonic posturing at 4 months and at 15 months, and startle reaction developed with sensory stimuli. Patient 2: male, at 2 months, shows hypotonia and developmental delay, paroxysmal episodes triggered by a stimulus with sudden blush, tonic asymmetric posture, and no epileptiform activity. At 10 months, generalized dystonic posturing. Patient 3: typical neurodevelopmental milestones until 6 months; at 24 months, dystonia, startle reaction, and upper motoneuron signs. CONCLUSIONS: We aim to describe our patients diagnosed with AHDS, focusing on MD phenomenology and strengthening the phenotype-genotype correlations for this rare condition.

ATP1A2-related epileptic encephalopathy and movement disorder: Clinical features of three novel patients.

OBJECTIVE: Variants in the ATP1A2 gene exhibit a wide clinical spectrum, ranging from familial hemiplegic migraine to childhood epilepsies and early infantile developmental epileptic encephalopathy (EIDEE) with movement disorders. This study aims to describe the epileptology of three unpublished cases and summarize epilepsy features of the other 17 published cases with ATP1A2 variants and EIDEE. METHODS: Medical records of three novel patients with pathogenic ATP1A2 variants were retrospectively reviewed. Additionally, the PUBMED, EMBASE, and Cochrane databases were searched until December 2023 for articles on EIDEE with ATP1A2 variants, without language or publication year restrictions. RESULTS: Three female patients, aged 6 months-10 years, were investigated. Epilepsy onset occurred between 5 days and 2 years, accompanied by severe developmental delay, intellectual disability, drug-resistant epilepsy, severe movement disorder, and recurrent status epilepticus. All individuals had pathogenic variants of the ATP1A2 gene (ATP1A2 c.720_721del (p.Ile240MetfsTer9), ATP1A2c.3022C > T (p.Arg1008Trp), ATP1A2 c.1096G > T (p.Gly366Cys), according to ACMG criteria. Memantine was p) rescribed to three patients, one with a reduction in ictal frequency, one with improvement in gait pattern, coordination, and attention span, and another one in alertness without significant side effects. SIGNIFICANCE: This study reinforces the association between ATP1A2 variants and a severe phenotype. All patients had de novo variants, focal motor seizures with impaired awareness as the primary type of seizure; of the 11 EEGs recorded, 10 presented a slow background rhythm, 7 multifocal interictal epileptiform discharges (IED), predominantly temporal IEDs, followed by frontal IED, as well as ten ictal recordings, which showed ictal onset from the same regions mentioned above. Treatment with antiseizure medication was generally ineffective, but memantine showed moderate improvement. Prospective studies are needed to enlarge the phenotype and assess the efficacy of NMDA receptor antagonist therapies in reducing seizure frequency and improving quality of life.

Immediate Impact on Tear Osmolarity Following the Application of Different Ocular Lubricants in Patients Experiencing Moderate Dry Eye Symptoms.

PURPOSE: This study addresses the growing concern of Dry Eye Disease (DED), which has become increasingly prevalent due to modern lifestyles characterized by prolonged screen usage, global warming, polypharmacy, and extended life expectancy. METHODS: Grounded in the Dry Eye Workshop II (DEWSII) diagnosis framework, the study focuses on DED as a multifactorial condition affecting the ocular surface's tear film homeostasis. The study evaluates the short-term impact of 5 commercially available ocular lubricants on disrupting the hyperosmolar environment and determine whether these lubricants can offer potential treatment benefits for DED. RESULTS: Conducted on 300 eyes (from 150 patients) with 5 preservative-free lubricants compared to a control group, the study reveals that all lubricants effectively reduced tear film osmolarity within 15 minutes of application. Notably, the control group exhibited an increase in average osmolarity (+0.98 mOsm/L) without lubricant use. Siccafluid demonstrated the most substantial osmolarity reduction after 15 minutes, with an average decrease of 11.54 mOsm/L. Statistical significance was observed for Siccafluid, Optive Fusion unique dose (UD), and Systane Ultra UD, while Hyabak and Freegen preservative free (PF) showed lower significance. CONCLUSIONS: Emphasizing the importance of disrupting the hyperosmolar environment to break the cycle of inflammation, the study concludes that ocular lubricants, at least as an immediate post-application effect, can interrupt this cycle and improve the hyperosmolar environment of the ocular surface.

Síndrome de robo de la subclavia tras tratamiento endovascular de aorta torácica / Subclavian steal syndrome after endovascular treatment of the thoracic aorta

Introducción: el síndrome de robo de la subclavia es una entidad poco habitual que se presenta en pacientes con estenosis u oclusión de la arteria subclavia, habitualmente la izquierda, y secundario a ateroesclerosis. Los síntomas derivados de esta entidad son: la isquemia del miembro superior y los síntomas neurológicos. Caso clínico: se presenta un caso de un varón que, tras cinco meses de tratamiento endovascular de úlcera de aorta torácica penetrante, presenta síntomas neurológicos. Se realizó diagnóstico del síndrome a través de eco Doppler y se confirmó con angio RM. Finalmente, y debido a la incapacidad que producían los síntomas, se decidió tratamiento quirúrgico mediante cirugía de bypass carótido subclavio izquierdo. Discusión: el síndrome del robo de la subclavia es una entidad que raramente se presenta asociada a síntomas. Debe tenerse una alta sospecha para diagnosticarlo y tratarlo si es necesario. Aunque la tendencia actual es el tratamiento endovascular, en ocasiones la cirugía de derivación tradicional es la única opción. Siempre que sea posible, debe estudiarse la dominancia de las arterias vertebrales antes de ocluir la arteria subclavia en los procedimientos. (AU)

Introduction: subclavian steal syndrome is a rare entity, occurring in patients with stenosis or occlusion of the subclavian artery, usually the left subclavian artery and secondary to atherosclerosis. The symptoms derived from this entity are: ischemia of the upper limb and neurological symptoms. Case report: we present a case of a man who, after five months of endovascular treatment of penetrating thoracic aortic ulcer, presented neurological symptoms. The syndrome was diagnosed by echo-Doppler and confirmed by MRI angiography. Finally, due to the incapacity caused by the symptoms, surgical treatment was decided by left carotid-subclavian bypass. Discussion: subclavian steal syndrome is an entity rarely presents with symptoms, it must be highly suspected in order to diagnose it and, if necessary, treat it. Although, the current trend is endovascular treatment, sometimes traditional bypass surgery is the only option. Whenever possible, the dominance of the vertebral arteries should be studied before occluding the subclavian artery in the procedures. (AU)

Effects of a multicomponent training followed by a detraining period on metabolic syndrome profile of older adults.

AIMS: The present study sought to analyze the effects of 6-month multicomponent training (MCT) combined with a 4-month detraining on metabolic syndrome (MetS) profile among older adults with decreased functional capacity. METHODS: This quasi-experimental study included a total of 104 older adults (80.5 ± 6.0 years) and the sample was divided into a training (TRAIN, n = 55) or control group (CON). Harmonized definition was used to diagnose the MetS. Functional capacity, blood biochemical parameters, blood pressure, body composition and anthropometric measurements were assessed 3 times. Analysis of variance for repeated measures and Wilcoxon signed-rank test were used to check the differences within groups. RESULTS: TRAIN decreased diastolic blood pressure (DBP), high-density lipoprotein cholesterol (HDLC) and total fat mass during training period, whereas CON did not show any significant changes. During detraining, TRAIN increased HDLC, systolic blood pressure (SBP), waist circumference (WC) and total fat mass; and decreased glucose and fat free mass, whereas CON increased the concentration of glucose and HDLC. From baseline to post-detraining assessment, CON increased the concentration of triglycerides and the WC, while TRAIN only increased the WC (all p < 0.05). CONCLUSIONS: Exercise can be a key component in the treatment of the MetS, since MCT seems to be effective to decrease DBP and total fat mass. Nevertheless, 4-months of detraining could cause a drop of total fat mass, but no in DBP. To avoid reversibility of the benefits obtained, it could be beneficial to promote continuing exercise programs. TRIAL REGISTRATION: ClinicalTrial.gov identifier: NCT03831841.

Prospective Teachers' Knowledge of Physical Activity in Children and Adolescents.

Over the past few years, organizations around the world have tried to reach different populations with recommendations about physical activity (PA), due to this subject playing an important role in the phases of intention development and in preparation for it. Thus, the knowledge of future educators in the fields of health and PA is of vital importance when improving the levels of the latter in students. The objective of this research is to determine what knowledge future teachers have about health and PA, examining possible disparities according to the gender, age, and level of physical exercise of the participants. In addition, the psychometric properties of the instrument used were explored. A total of 321 Colombian university students from the Faculty of Education between the ages of sixteen and thirty-five participated in this study, providing sociodemographic information by filling out the CUAFYS-A questionnaire. Significant differences were found in the scale items according to sex and self-perception of being physically active. Also, the findings revealed a single-factor structure with nine items that had satisfactory reliability (α = 0.71; CR = 0.72) and excellent goodness-of-fit indices (RMSEA = 0.055 (90% CI (0.3, 0.8), RMSR = 0.02, CFI = 0.935, NNFI = 0.912, CMIN/DF = 1.97). Therefore, strategies and campaigns to promote PA knowledge in prospective teachers should be tailored according to gender and PA levels. Similarly, the CUAFYS-A questionnaire can be considered a valid and reliable instrument to identify the PA knowledge of future educators.

Longitudinal Changes in the Body Composition of Non-Institutionalized Spanish Older Adults after 8 Years of Follow-Up: The Effects of Sex, Age, and Organized Physical Activity.

Aging leads to physiological changes affecting body composition, mediated by lifestyle. However, the effectiveness of organized physical activities (OPAs) in attenuating or delaying these age-related transformations remains an area of limited understanding. The primary objectives of this study were threefold: (I) to comprehensively assess the evolution of body composition in a cohort of Spanish older adults over an 8-year period; (II) to compare this evolution in the different age groups; and (III) to investigate the influence of active engagement in OPAs on these age-related changes. From a sample of 3136 Spanish older adults recruited in 2008, 651 agreed to participate in the 8-year follow-up. Anthropometric and bioelectrical impedance data were included for 507 females (70.3 ± 4.4 years) and 144 males (77.8 ± 4.5 years). Age groups were categorized as follows: youngest (65-69 years), mid (70-74 years), and oldest (≥75 years). The engagement in OPA was recorded before and after the follow-up. A repeated measures ANOVA was performed to evaluate the 8-year changes. Males increased in hip (98.1 ± 9.3 vs. 101.5 ± 10.2 cm) and waist circumferences (101.2 ± 6.6 vs. 103.2 ± 6.1 cm), specifically in the youngest group (p < 0.05). Females decreased in weight (67.6 ± 10.0 vs. 66.6 ± 10.5 kg) and fat mass percentage (39.3 ± 5 vs. 38.8 ± 5.4%) and increased in hip circumference (104.4 ± 9.0 vs. 106.5 ± 9.7 cm); these effects were the most remarkable in the oldest group (all p < 0.05). OPA engagement seemed to slow down fat-free mass loses in males, but not in females (grouped by time, p < 0.05). Body composition changes caused by aging seem to happen earlier in males than in females. Moreover, participating in OPAs does not prevent fat-free mass due to aging.

An IL-4 signalling axis in bone marrow drives pro-tumorigenic myelopoiesis.

Myeloid cells are known to suppress antitumour immunity1. However, the molecular drivers of immunosuppressive myeloid cell states are not well defined. Here we used single-cell RNA sequencing of human and mouse non-small cell lung cancer (NSCLC) lesions, and found that in both species the type 2 cytokine interleukin-4 (IL-4) was predicted to be the primary driver of the tumour-infiltrating monocyte-derived macrophage phenotype. Using a panel of conditional knockout mice, we found that only deletion of the IL-4 receptor IL-4Rα in early myeloid progenitors in bone marrow reduced tumour burden, whereas deletion of IL-4Rα in downstream mature myeloid cells had no effect. Mechanistically, IL-4 derived from bone marrow basophils and eosinophils acted on granulocyte-monocyte progenitors to transcriptionally programme the development of immunosuppressive tumour-promoting myeloid cells. Consequentially, depletion of basophils profoundly reduced tumour burden and normalized myelopoiesis. We subsequently initiated a clinical trial of the IL-4Rα blocking antibody dupilumab2-5 given in conjunction with PD-1/PD-L1 checkpoint blockade in patients with relapsed or refractory NSCLC who had progressed on PD-1/PD-L1 blockade alone (ClinicalTrials.gov identifier NCT05013450 ). Dupilumab supplementation reduced circulating monocytes, expanded tumour-infiltrating CD8 T cells, and in one out of six patients, drove a near-complete clinical response two months after treatment. Our study defines a central role for IL-4 in controlling immunosuppressive myelopoiesis in cancer, identifies a novel combination therapy for immune checkpoint blockade in humans, and highlights cancer as a systemic malady that requires therapeutic strategies beyond the primary disease site.