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Abstract Some patients with autism and severe intellectual disability may experience uncontrolled aggression, causing serious injury or harm to others, and the therapeutic ineffectiveness of traditional pharmacological and behavioral treatment may aggravate symptoms. Deep brain stimulation (DBS) has been tested in patients with little evidence in children and adolescents. Therefore, we analyzed the efficacy and safety of DBS in refractory aggression in pediatric subjects with autism (ASD) and severe intelligence deficit (ID). Methods A meta-analytic review of Web of Science (WOS) and Scopus articles, following Prisma criteria. A total of 555 articles were identified, but after applying the inclusion criteria, only 18 were analyzed. The review of the registries and the extraction of information was performed by 2 independent groups, to reduce the evaluator’s bias. For the description of the results, pediatric patients with ASD or ID present in each registry, with an application of specialized scales (Overt aggression scale, OAS, and THE modified version of the OAS, MOAS) pre and post-DBS, with a clinical follow-up of at least 12 months, were considered valid. Clinical improvement was calculated using tests of aggressiveness. In each registry with available data and then pooling the means of all patients in the OAS and MOAS, the effect size of DBS (overall and per study) was estimated. Finally, the adapted NOS scale was applied to rate the studies’ quality and level of bias. Results In the studies analyzed, 65/100 were pediatric patients, with a mean age of 16.8 years. Most of the studies were conducted in South America and Europe. In all teams, aggressive behavior was intractable, but only 9 groups (53/65) applied specialized scales to measure aggressiveness, and of these, only 51 subjects had a follow-up of at least 12 months. Thus, in 48/51 a clinical improvement of patients was estimated (94.2%), with a considerable overall effect size (OAS: d = 4.32; MOAS: d = 1.46). However, adverse effects and complications were found in 13/65 subjects undergoing DBS. The brain target with the most evidence and the fewest side effects was the posteromedial hypothalamic nuclei (pHypN). Finally, applying the adapted NOS scale, quality, and bias, only 9 studies show the best indicators. Conclusion An optimal level of efficacy was found in only half of the publications. This is mainly due to design errors and irrelevant information in the reports. We believe that DBS in intractable aggressiveness in children and adolescents with ASD and severe ID can be safe and effective if working groups apply rigorous criteria for patient selection, interdisciplinary assessments, objective scales for aggressiveness, and known surgical targets.

The main objective established in this work was to develop a model based on artificial neural networks (ANNs) to predict the corrosion status of stainless steel involved in biogas production, analyzing the influence of the material composition and the breakdown potential value. To achieve this objective, an ANN model capable of predicting the corrosion status of the material without the need to perform microscopic analysis on the material surface was proposed. The applicability of the corrosion models was verified via the experimental data considering different factors such as stainless steel composition, biogas environments simulated by artificial solution, temperature, surface finish, and the breakdown potential of the passive layer of stainless steel obtained from electrochemical tests. The optimal prediction performance shown by the model in terms of specificity and sensitivity values were 0.969 and 0.971, respectively, obtaining an accuracy of 0.966. Furthermore, analyzing the influence of the breakdown potential on corrosion modelling, an alternative model was presented capable of predicting the corrosion status automatically, without the need to resort to electrochemical tests for new conditions. The results demonstrated the utility of this technique to be considered in design and maintenance planning tasks for stainless steel structures subjected to localized corrosion in biogas production.

Abstract The maintained attention is the cause of great functional limitations in CFS/ME, a disease that mainly affects women in the central period of life. Cognitive function is explored using the Montreal Cognitive Assessment, the maintained attention using the Toulouse-Piéron test with which the Global Index of Attention and Perception (GIAP) is obtained, the fatigue using the visual analog scale and the perception of effort using the modified Borg scale. The final sample were 84 patients (66 women/18 men) who met diagnostic criteria (Fukuda-1994, Carruthers-2011) and 22 healthy controls (14 women/8 men). Most of patients maintain normal cognitive function, showing low or very low attention score in the 70% of patients with a marked cognitive fatigue compared to the control group (p

Virtual simulations are a very useful educational resource to improve the teaching of chemistry. Their use makes it possible to facilitate the comprehension of concepts, promotes the development of scientific competences and even improves student attitudes toward chemistry. However, it is important to point out that a simulation by itself is not enough to improve student learning. Methodological design is a crucial aspect in order for its classroom use to be significant. Simulations must form part of an instructional sequence that promotes said learning, and thus the role of the instructor is key. This work conducts a systematic review with the aim of analyzing how to apply the use of simulations in the teaching of chemistry in secondary schools, delving deeper into the way in which simulations are used from a methodological perspective, in order to improve the learning processes and results. In this sense, it was found that there is an improvement in learning on both the level of content comprehension and in scientific competences. Guided research is also identified as the most effective methodology for the application of simulations in the classroom. With a look to the future, it is suggested that there is a need to conduct research on the continued use of simulations in the classroom, as well as their characteristics and the instructional methods used.

ABSTRACT. The COVID-19 pandemic has shown the need for neuropsychological care for older adults with memory complaints in different contexts, including rural areas or areas with difficult access. Objective: This study aimed to analyze the clinical utility of the Phototest, through telemedicine, to identify mild cognitive impairment in rural older adults with memory complaints, during the COVID-19 pandemic. Methods: We performed a cross-sectional, case-control, and clinical utility comparison of brief cognitive tests (BCTs). The sample included 111 rural elderly people with mild cognitive impairment (MCI) and 130 healthy controls from the Los Lagos region, Chile. The instruments adopted were modified Mini-Mental State Examination (MMSEm) and adapted version of the Phototest (PT) for Chile. Results: To identify mild cognitive impairment, using a cutoff score of 27-28 points, the Phototest showed a sensitivity of 96.6% and a specificity of 81.8%; indicators superior to those of the MMSEm. Conclusions: The Phototest is more accurate than the MMSEm in identifying cognitive alterations in rural older adults with cognitive memory complaints through telemedicine. Therefore, its use in primary care is recommended in order to perform early detection of preclinical cognitive alterations in mild cognitive impairment or neurodegenerative diseases.

This research, following a sequential mixed-methods design, delves into metacognitive control in problem solving among 5- to 6-year-olds, using two floor-robot environments. In an initial qualitative phase, 82 pupils participated in tasks in which they directed a floor robot to one of two targets, with the closer target requiring more cognitive effort due to the turns involved. The results of this phase revealed that younger students often rationalised their decisions based on reasons unrelated to the difficulty of the task, highlighting limitations in children's language and abstract thinking skills and leading to the need for a second quantitative study. In this subsequent stage, involving 117 students, a computerised floor-robot simulator was used. The simulator executed the students' planned movements and provided feedback on their validity. Each participant had three attempts per problem, with the option to change their target each time. The simulator stored the information pertaining to the chosen resolution path, design of the plan, and re-evaluation of decision making based on the results and feedback received. This study aims to describe the criteria upon which students base their metacognitive control processes in decision making within problem-solving programming tasks. Additionally, through a comparative analysis focusing on age and gender, this research aims to assess the relationship between metacognitive processes and success in problem-solving programming tasks.

The planned systematized design of the use of serious games in the classroom is presented as a strategy to optimize learning. In this framework, Learning Analytics represents stealth assessment and follow-up method, and a way to personalize such games by simplifying their application for teachers. The aim of this research was to analyze the impact of the use of serious games on improving linguistic competence in socio-educationally disadvantaged students, with a proposal for a planned systematized intervention. We use two specific games to improve linguistic competence and its learning analytics to achieve the proposed goal. This study carried out was pre-experimental, with pretest and posttest, and the sample consisted of 75 students at 4 primary education centers in Spain (36 boys, 39 girls) aged 9-12 (M = 10.6; SD = 0.7) at risk due to socioeconomic conditions in Primary Education. The results show that (a) the serious games integrated into the curriculum and adjusted to the learning objectives can facilitate the development and acquisition of linguistic competence in students with socio-educational disadvantages; (b) these students can match their peers in performance and competencies with appropriate systematic intervention; (c) the level acquired in a key competence can be evaluated and specific needs identified in students with academic difficulties using learning analytics; (d) learning analytics can contribute to predicting student performance in academic subjects through the scores collected in the analysis of learning integrated into serious games. These findings contribute to filling research gaps in these four aspects.

El presente trabajo de investigación hace énfasis a la adaptación y aplicación de las tecnologías educativas en el entorno del Covid-19, el coronavirus, no solo ha afectado la resistencia de la urbe universal, sino al sistema pedagógico, uno de los retos más relevantes ha sido la resiliencia del medio formativo para adaptarse al mundo digital; Está indagación tiene como objeto de estudio las tecnologías en la nueva normalidad enmarcada en la aplicación de la metodología Presencia, Alcance, Capacitación, Interacción y E-learning (PACIE) y modelos instruccionales, en cuanto al desarrollo de este trabajo de investigación se manifestará las medidas adoptadas por el sistema educativo para mantener la relación educando - educador, así como implantar una singularidad de instrucción remota que se equilibra al contar con medios de primera y segunda generación; Para ello se utilizaron métodos de la investigación científica, desde una perspectiva adjetiva de tipo documental, con una trascendencia deductiva, experimenta la poyada en fuentes elementales, artículos e informes de investigación. Los resultados muestran que, para el desarrollo de la educación virtual, los estudiantes utilizan el teléfono móvil como recurso técnico y aprecian que sus métodos de aprendizaje presencial no son los mismos, por lo que señalan que en el entorno virtual el método de enseñanza, excluye la metodología PACIE.

La presente investigación brindó un aporte significativo, dando a conocer el impacto que han tenido las ciudades inteligentes en el Ecuador, el objetivo fue analizar el desarrollo en los últimos años de los servicios e infraestructura de telecomunicaciones y de las Ciudades Inteligentes.En el Ecuador se han desarrollado cambios en el área de las telecomunicaciones, existen avances significativos como utilización de las TIC, desarrollo de conceptos de ciudades inteligentes y sostenibles, Internet de las Cosas, entre otros. Las Ciudades Inteligentes innovan y aprovechan las TIC para mejorar la calidad de vida de los ciudadanos; así como, la eficiencia de los servicios urbanos y la competitividad.Los métodos científicos utilizados en el estudio fueron del nivel teórico y empírico.Los principales resultados en el país en telecomunicaciones son: 60 mil km de fibra óptica; reducción de 17 puntos porcentuales en la brecha digital; cobertura de red 4G en el 49% del territorio nacional.Los resultados evidenciaron los avances por años y la situación actual de las TIC’S en el Ecuador. Se concluye que el acceso a las Tic’s constituyen un derecho de todos los ciudadanos, pues promueve el desarrollo de la sociedad ecuatoriana.

El uso apropiado de los recursos informáticos se comprobará que es la herramienta que facilita al maestro lograr que los estudiantes desarrollen sus destrezas y criterios que les dará la posibilidad de un óptimo desenvolvimiento en el campo laboral y en sus actividades diarias. Encaminar en forma correcta la utilización de estas tecnologías modernas constituye una responsabilidad muy grande, razón por la cual, el docente que se encuentre encargado de capacitar a los educandos, deberá también poseer la capacidad y dominio con el fin de que ponga en práctica lo que enseña y para mejorar el proceso de enseñanza aprendizaje ya que, con la globalización, la información viaja con mayor rapidez y el conocimiento de cosas nuevas se encuentra al alcance de quien lo necesita. Se requiere, además, una apropiada preparación de los docentes para guiar a los jóvenes en mejorar y renovar los conocimientos de forma continua, al ritmo de los cambios tecnológicos que se producen constantemente. La propuesta sugiere dar el uso apropiado a los recursos informáticos existentes en las instituciones educativas, con el fin de optimizar la calidad de la educación tecnológica que se brinda a los estudiantes y de igual forma estimular a los docentes.

El objetivo del trabajo es analizar las representaciones sociales de conservación de la naturaleza por la población rural de la zona de amortiguamiento en la Reserva Nacional del Titicaca; bajo el supuesto de que las reflexiones y acciones de cuidado ambiental se sustentan en los beneficios de conservar la naturaleza canalizadas desde la cosmovisión andina. El enfoque es mixto, por lo que se recurrió a las técnicas de encuesta y entrevista. Se concluye que las concepciones, prácticas culturales y organización social tienen como fin la interacción armónica entre el hombre y la naturaleza.

BACKGROUND AND OBJECTIVES: TMEM106B has been proposed as a modifier of disease risk in FTLD-TDP, particularly in GRN pathogenic variant carriers. Furthermore, TMEM106B has been investigated as a disease modifier in the context of healthy aging and across multiple neurodegenerative diseases. The objective of this study was to evaluate and compare the effect of TMEM106B on gray matter volume and cognition in each of the common genetic FTD groups and in patients with sporadic FTD. METHODS: Participants were enrolled through the ARTFL/LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study, which includes symptomatic and presymptomatic individuals with a pathogenic variant in C9orf72, GRN, MAPT, VCP, TBK1, TARDBP, symptomatic nonpathogenic variant carriers, and noncarrier family controls. All participants were genotyped for the TMEM106B rs1990622 SNP. Cross-sectionally, linear mixed-effects models were fitted to assess an association between TMEM106B and genetic group interaction with each outcome measure (gray matter volume and UDS3-EF for cognition), adjusting for education, age, sex, and CDR+NACC-FTLD sum of boxes. Subsequently, associations between TMEM106B and each outcome measure were investigated within the genetic group. For longitudinal modeling, linear mixed-effects models with time by TMEM106B predictor interactions were fitted. RESULTS: The minor allele of TMEM106B rs1990622, linked to a decreased risk of FTD, associated with greater gray matter volume in GRN pathogenic variant carriers under the recessive dosage model (N = 82, beta = 3.25, 95% CI [0.37-6.19], p = 0.034). This was most pronounced in the thalamus in the left hemisphere (beta = 0.03, 95% CI [0.01-0.06], p = 0.006), with a retained association when considering presymptomatic GRN pathogenic variant carriers only (N = 42, beta = 0.03, 95% CI [0.01-0.05], p = 0.003). The minor allele of TMEM106B rs1990622 also associated with greater cognitive scores among all C9orf72 pathogenic variant carriers (N = 229, beta = 0.36, 95% CI [0.05-0.066], p = 0.021) and in presymptomatic C9orf72 pathogenic variant carriers (N = 106, beta = 0.33, 95% CI [0.03-0.63], p = 0.036), under the recessive dosage model. DISCUSSION: We identified associations of TMEM106B with gray matter volume and cognition in the presence of GRN and C9orf72 pathogenic variants. The association of TMEM106B with outcomes of interest in presymptomatic GRN and C9orf72 pathogenic variant carriers could additionally reflect TMEM106Bs effect on divergent pathophysiologic changes before the appearance of clinical symptoms.

Glycosylphosphatidylinositols (GPIs) are highly conserved anchors for eukaryotic cell surface proteins. The apicomplexan parasite, Toxoplasma gondii, is a widespread intracellular parasite of warm-blooded animals whose plasma membrane is covered with GPI-anchored proteins, and free GPIs called GIPLs. While the glycan portion is conserved, species differ in sidechains added to the triple mannose core. The functional significance of the Glcα1,4GalNAcβ1- sidechain reported in Toxoplasma gondii has remained largely unknown without understanding its biosynthesis. Here we identify and disrupt two glycosyltransferase genes and confirm their respective roles by serology and mass spectrometry. Parasites lacking the sidechain on account of deletion of the first glycosyltransferase, PIGJ, exhibit increased virulence during primary and secondary infections, suggesting it is an important pathogenesis factor. Cytokine responses, antibody recognition of GPI-anchored SAGs, and complement binding to PIGJ mutants are intact. By contrast, the scavenger receptor CD36 shows enhanced binding to PIGJ mutants, potentially explaining a subtle tropism for macrophages detected early in infection. Galectin-3, which binds GIPLs, exhibits an enhancement of binding to PIGJ mutants, and the protection of galectin-3 knockout mice from lethality suggests that Δpigj parasite virulence in this context is sidechain dependent. Parasite numbers are not affected by Δpigj early in the infection in wild-type mice, suggesting a breakdown of tolerance. However, increased tissue cysts in the brains of mice infected with Δpigj parasites indicate an advantage over wild-type strains. Thus, the GPI sidechain of T. gondii plays a crucial and diverse role in regulating disease outcomes in the infected host.IMPORTANCEThe functional significance of sidechain modifications to the glycosylphosphatidylinositol (GPI) anchor in parasites has yet to be determined because the glycosyltransferases responsible for these modifications have not been identified. Here we present identification and characterization of both Toxoplasmsa gondii GPI sidechain-modifying glycosyltransferases. Removal of the glycosyltransferase that adds the first GalNAc to the sidechain results in parasites without a sidechain on the GPI, and increased host susceptibility to infection. Loss of the second glycosyltransferase results in a sidechain with GalNAc alone, and no glucose added, and has negligible effect on disease outcomes. This indicates GPI sidechains are fundamental to host-parasite interactions.

Objectives Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.Setting Prospective, international, multicentre, observational cohort study.Participants Patients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome 30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.Results This study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).Conclusions Patients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration number NCT04323644

The aim of present paper is to identify clinical phenotypes in a cohort of patients affected of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Ninety-one patients and 22 healthy controls were studied with the following questionnaires, in addition to medical history: visual analogical scale for fatigue and pain, DePaul questionnaire (post-exertional malaise, immune, neuroendocrine), Pittsburgh sleep quality index, COMPASS-31 (dysautonomia), Montreal cognitive assessment, Toulouse-Piéron test (attention), Hospital Anxiety and Depression test and Karnofsky scale. Co-morbidities and drugs-intake were also recorded. A hierarchical clustering with clinical results was performed. Final study group was made up of 84 patients, mean age 44.41 ± 9.37 years (66 female/18 male) and 22 controls, mean age 45 ± 13.15 years (14 female/8 male). Patients meet diagnostic criteria of Fukuda-1994 and Carruthers-2011. Clustering analysis identify five phenotypes. Two groups without fibromyalgia were differentiated by various levels of anxiety and depression (13 and 20 patients). The other three groups present fibromyalgia plus a patient without it, but with high scores in pain scale, they were segregated by prevalence of dysautonomia (17), neuroendocrine (15), and immunological affectation (19). Regarding gender, women showed higher scores than men in cognition, pain level and depressive syndrome. Mathematical tools are a suitable approach to objectify some elusive features in order to understand the syndrome. Clustering unveils phenotypes combining fibromyalgia with varying degrees of dysautonomia, neuroendocrine or immune features and absence of fibromyalgia with high or low levels of anxiety-depression. There is no a specific phenotype for women or men.

Abstract: —J. Blunden and T. Boyer In 2023, La Niña conditions that generally prevailed in the eastern Pacific Ocean from mid-2020 into early 2023 gave way to a strong El Niño by October. Atmospheric concentrations of Earth’s major greenhouse gases—carbon dioxide, methane, and nitrous oxide—all increased to record-high levels. The annual global average carbon dioxide concentration in the atmosphere rose to 419.3±0.1 ppm, which is 50% greater than the pre-industrial level. The growth from 2022 to 2023 was 2.8 ppm, the fourth highest in the record since the 1960s. The combined short-term effects of El Niño and the long-term effects of increasing levels of heat-trapping gases in the atmosphere contributed to new records for many essential climate variables reported here. The annual global temperature across land and oceans was the highest in records dating as far back as 1850, with the last seven months (June–December) having each been record warm. Over land, the globally averaged temperature was also record high. Dozens of countries reported record or near-record warmth for the year, including China and continental Europe as a whole (warmest on record), India and Russia (second warmest), and Canada (third warmest). Intense and widespread heatwaves were reported around the world. In Vietnam, an all-time national maximum temperature record of 44.2°C was observed at Tuong Duong on 7 May, surpassing the previous record of 43.4°C at Huong Khe on 20 April 2019. In Brazil, the air temperature reached 44.8°C in Araçuaí in Minas Gerais on 20 November, potentially a new national record and 12.8°C above normal. The effect of rising temperatures was apparent in the cryosphere, where snow cover extent by June 2023 was the smallest in the 56-year record for North America and seventh smallest for the Northern Hemisphere overall. Heatwaves contributed to the greatest average mass balance loss for Alpine glaciers around the world since the start of the record in 1970. Due to rapid volume loss beginning in 2021, St. Anna Glacier in Switzerland and Ice Worm Glacier in the United States disappeared completely. In August, as a direct result of glacial thinning over the past 20 years, a glacial lake on a tributary of the Mendenhall Glacier in Alaska burst through its ice dam and caused unprecedented flooding on Mendenhall River near Juneau. Across the Arctic, the annual surface air temperature was the fourth highest in the 124-year record, and summer (July–September) was record warm. Smaller-than-normal snow cover extent in May and June contributed to the third-highest average peak tundra greenness in the 24-year record. In September, Arctic minimum sea ice extent was the fifth smallest in the 45-year satellite record. The 17 lowest September extents have all occurred in the last 17 years. In Antarctica, temperatures for much of the year were up to 6°C above average over the Weddell Sea and along coastal Dronning Maud Land. The Antarctic Peninsula also experienced well-above-average temperatures during the 2022/23 melt season, which contributed to its fourth consecutive summer of above-average surface melt. On 21 February, Antarctic sea ice extent and sea ice area both reached all-time lows, surpassing records set just a year earlier. Over the course of the year, new daily record-low sea ice extents were set on 278 days. In some instances, these daily records were set by a large margin, for example, the extent on 6 July was 1.8 million km2 lower than the previous record low for that day. Across the global oceans, the annual sea surface temperature was the highest in the 170-year record, far surpassing the previous record of 2016 by 0.13°C. Daily and monthly records were set from March onward, including an historic-high daily global mean sea surface temperature of 18.99°C recorded on 22 August. Approximately 94% of the ocean surface experienced at least one marine heatwave in 2023, while 27% experienced at least one cold spell. Globally averaged ocean heat content from the surface to 2000-m depth was record high in 2023, increasing at a rate equivalent to ∼0.7 Watts per square meter of energy applied over Earth’s surface. Global mean sea level was also record high for the 12th consecutive year, reaching 101.4 mm above the 1993 average when satellite measurements began, an increase of 8.1±1.5 mm over 2022 and the third highest year-over-year increase in the record. A total of 82 named tropical storms were observed during the Northern and Southern Hemispheres’ storm seasons, below the 1991–2020 average of 87. Hurricane Otis became the strongest landfalling hurricane on record for the west coast of Mexico at 140 kt (72 m s−1), causing at least 52 fatalities and $12–16 billion U.S. dollars in damage. Freddy became the world’s longest-lived tropical cyclones on record, developing into a tropical cyclone on 6 February and finally dissipating on 12 March. Freddy crossed the full width of the Indian Ocean and made one landfall in Madagascar and two in Mozambique. In the Mediterranean Sea—outside of traditional tropical cyclone basins—heavy rains and flooding from Storm Daniel killed more than 4300 people and left more than 8000 missing in Libya. The record-warm temperatures in 2023 created conditions that helped intensify the hydrological cycle. Measurements of total-column water vapor in the atmosphere were the highest on record, while the fraction of cloud area in the sky was the lowest since records began in 1980. The annual global mean precipitation total over land surfaces for 2023 was among the lowest since 1979, but global one-day maximum totals were close to average, indicating an increase in rainfall intensity. In July, record-high areas of land across the globe (7.9%) experienced extreme drought, breaking the previous record of 6.2% in July 2022. Overall, 29.7% of land experienced moderate or worse categories of drought during the year, also a record. Mexico reported its driest (and hottest) year since the start of its record in 1950. In alignment with hot and prolonged dry conditions, Canada experienced its worst national wildfire season on record. Approximately 15 million hectares burned across the country, which was more than double the previous record from 1989. Smoke from the fires were transported far into the United States and even to western European countries. August to October 2023 was the driest three-month period in Australia in the 104-year record. Millions of hectares of bushfires burned for weeks in the Northern Territory. In South America, extreme drought developed in the latter half of the year through the Amazon basin. By the end of October, the Rio Negro at Manaus, a major tributary of the Amazon River, fell to its lowest water level since records began in 1902. The transition from La Niña to El Niño helped bring relief to the prolonged drought conditions in equatorial eastern Africa. However, El Niño along with positive Indian Ocean dipole conditions also contributed to excessive rainfall that resulted in devastating floods over southeastern Ethiopia, Somalia, and Kenya during October to December that displaced around 1.5 million people. On 5 September, the town of Zagora, Greece, broke a national record for highest daily rainfall (754 mm in 21 hours, after which the station ceased reporting) due to Storm Daniel; this one-day accumulation was close to Zagora’s normal annual total.

OBJECTIVES: Chronic inflammation promotes cardiovascular risk in rheumatoid arthritis (RA). Biological disease-modifying antirheumatic drugs (bDMARDs) improve disease activity and cardiovascular disease outcomes. We explored whether bDMARDs influence the impact of disease activity and inflammatory markers on long-term cardiovascular risk in RA. METHODS: We studied 4370 participants without cardiovascular disease in a 10-country observational cohort of patients with RA. Endpoints were (1) major adverse cardiovascular events (MACE) encompassing myocardial infarction, stroke and cardiovascular death; and (2) any ischaemic cardiovascular events (iCVE) including MACE plus revascularisation, angina, transient ischaemic attack and peripheral arterial disease. RESULTS: Over 26 534 patient-years, 239 MACE and 362 iCVE occurred. The interaction between 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) and bDMARD use was significant for MACE (p=0.017), suggesting the effect of DAS28-CRP on MACE risk differed among bDMARD users (n=515) and non-users (n=3855). DAS28-CRP (per unit increase) is associated with MACE risk in bDMARD non-users (HR 1.21 (95% CI 1.07 to 1.37)) but not users (HR 0.69 (95% CI 0.40 to 1.20)). The interaction between CRP (per log unit increase) and bDMARD use was also significant for MACE (p=0.011). CRP associated with MACE risk in bDMARD non-users (HR 1.16 (95% CI 1.04 to 1.30)), but not users (HR 0.65 (95% CI 0.36 to 1.17)). No interaction was observed between bDMARD use and DAS28-CRP (p=0.167) or CRP (p=0.237) for iCVE risk. CONCLUSIONS: RA activity and inflammatory markers associated with risk of MACE in bDMARD non-users but not users suggesting the possibility of biological-specific benefits locally on arterial wall independently of effects on systemic inflammation.

As North America is largely industrialized with a variety of available private transportation options, trauma is a common occurrence, resulting in significant burdens of disability and costs to the health care system. To meet increasing trauma care needs, there is a robust organization of trauma and rehabilitation systems, particularly within the United States and Canada. The American and Canadian health care systems share multiple similarities, including well-equipped Level I trauma centers, specialized inpatient rehabilitation units for polytrauma patients, and thorough evaluations for recovery and post-discharge placement. However, they also have several key differences. In Canada, the criteria for admission to inpatient rehabilitation vary by location, and inpatient rehabilitation is universally accessible, whereas outpatient rehabilitation services are generally not covered by insurance. In the United States, these admission criteria for post-acute inpatient rehabilitation are standardized, and both inpatient and outpatient services are covered by private and government-funded insurance with varying durations. Overall, both health care systems face challenges in post-acute rehabilitation, including benefit limitations and limited provider access in rural areas, and must continue to evolve to meet the rehabilitation needs of injured patients as they reintegrate into their communities.

BACKGROUND & AIMS: Metabolic syndrome (MS) is a growing epidemic and a risk factor for the development of hepatocellular carcinoma (HCC). This study investigated the long-term outcomes of liver resection (LR) for HCC in patients with MS. Rates, timing, patterns, and treatment of recurrences were investigated, and cancer-specific survivals were assessed. METHODS: Between 2001 and 2021, data from 24 clinical centers were collected. Overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival were analyzed as well as recurrence patterns and treatment. The analysis was conducted using a competing-risk framework. The trajectory of the risk of recurrence over time was applied to a competing risk analysis. For post-recurrence survival, death resulting from tumor progression was the primary endpoint, whereas deaths with recurrence relating to other causes were considered as competing events. RESULTS: In total, 813 patients were included in the study. Median OS was 81.4 months (range 28.1-157.0 months), and recurrence occurred in 48.3% of patients, with a median RFS of 39.8 months (range 15.7-174.7 months). Cause-specific hazard of recurrence showed a first peak 6 months (0.027), and a second peak 24 months (0.021) after surgery. The later the recurrence, the higher the chance of receiving curative intent approaches (p = 0.001). Size >5 cm, multiple tumors, microvascular invasion, and cirrhosis were independent predictors of recurrence showing a cause-specific hazard over time. RFS was associated with death for recurrence (hazard ratio: 0.985, 95% CI: 0.977-0.995; p = 0.002). CONCLUSIONS: Patients with MS undergoing LR for HCC have good long-term survival. Recurrence occurs in 48% of patients with a double-peak incidence and time-specific hazards depending on tumor-related factors and underlying disease. The timing of recurrence significantly impacts survival. Surveillance after resection should be adjusted over time depending on risk factors. IMPACT AND IMPLICATIONS: Metabolic syndrome (MS) is a growing epidemic and a significant risk factor for the development of hepatocellular carcinoma (HCC). The present study demonstrated that patients who undergo surgical resection for HCC on MS have a good long-term survival and that recurrence occurs in almost half of the cases with a double peak incidence and time-specific hazards depending on tumor-related factors and underlying liver disease. Also, the timing of recurrence significantly impacts survival. Clinicians should therefore adjust follow-up after surgery accordingly, considering timing of recurrence and specific risk factors. Also, the results of the present study might help design future trials on the use of adjuvant therapy following resection.

Peroxiredoxin 6 (Prdx6) repairs peroxidized membranes by reducing oxidized phospholipids, and by replacing oxidized sn-2 fatty acyl groups through hydrolysis/reacylation by its phospholipase A2 (aiPLA2) and lysophosphatidylcholine acyltransferase activities. Prdx6 is highly expressed in the lung, and intact lungs and cells null for Prdx6 or with single-point mutations that inactivate either Prdx6-peroxidase or aiPLA2 activity alone exhibit decreased viability, increased lipid peroxidation, and incomplete repair when exposed to paraquat, hyperoxia, or organic peroxides. Ferroptosis is form of cell death driven by the accumulation of phospholipid hydroperoxides. We studied the role of Prdx6 as a ferroptosis suppressor in the lung. We first compared the expression Prdx6 and glutathione peroxidase 4 (GPx4) and visualized Prdx6 and GPx4 within the lung. Lung Prdx6 mRNA levels were five times higher than GPx4 levels. Both Prdx6 and GPx4 localized to epithelial and endothelial cells. Prdx6 knockout or knockdown sensitized lung endothelial cells to erastin-induced ferroptosis. Cells with genetic inactivation of either aiPLA2 or Prdx6-peroxidase were more sensitive to ferroptosis than WT cells, but less sensitive than KO cells. We then conducted RNA-seq analyses in Prdx6-depleted cells to further explore how the loss of Prdx6 sensitizes lung endothelial cells to ferroptosis. Prdx6 KD upregulated transcriptional signatures associated with selenoamino acid metabolism and mitochondrial function. Accordingly, Prdx6 deficiency blunted mitochondrial function and increased GPx4 abundance whereas GPx4 KD had the opposite effect on Prdx6. Moreover, we detected Prdx6 and GPx4 interactions in intact cells, suggesting that both enzymes cooperate to suppress lipid peroxidation. Notably, Prdx6-depleted cells remained sensitive to erastin-induced ferroptosis despite the compensatory increase in GPx4. These results show that Prdx6 suppresses ferroptosis in lung endothelial cells and that both aiPLA2 and Prdx6-peroxidase contribute to this effect. These results also show that Prdx6 supports mitochondrial function and modulates several coordinated cytoprotective pathways in the pulmonary endothelium.