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Abstract Background Exposure to extreme heat impacts millions of people worldwide and outdoor workers are among the populations most affected by hot temperatures. Heat stress induces several biological responses in humans, including the production of heat shock proteins (HSP) and antibodies against HSP (anti-HSP) which may play a central role in the body’s cellular response to a hot environment. Objective This longitudinal study investigated the impact of elevated temperatures and humidity on the presence of HSP70 and anti-HSP70 and examined relationships with markers of kidney function in an at-risk workforce under conditions of extreme heat and exertion in Guatemala. Methods We collected ambient temperature and relative humidity data as well as biomarkers and clinical data from 40 sugarcane workers at the start and the end of a 6-month harvest. We used generalized mixed-effects models to estimate temperature effects on HSP70 and anti-HSP70 levels. In addition, we examined trends between HSP70 and anti-HSP70 levels and markers of kidney function across the harvest. Results At the end of the harvest, temperatures were higher, and workers had, on average, higher levels of HSP70 and anti-HSP70 compared to the beginning of the season. We observed significant increasing trends with temperature indices, heat index, and HSP70 levels. Maximum temperature was associated with HSP70 increments after controlling for age, systolic and diastolic blood pressure (β: 0.21, 95% Confidence Interval: 0.09, 0.33). Kidney function decline across the harvest was associated with both higher levels of anti-HSP70 levels at the end of the harvest as well as greater increases in anti-HSP70 levels across the harvest. Conclusions These results suggest that workplace heat exposure may increase the production of HSP70 and anti-HSP70 levels and that there may be a relationship between increasing anti-HSP70 antibodies and the development of renal injury. HSP70 holds promise as a biomarker of heat stress in exposed populations.

The aim of this article is to elucidate the rational foundations upon which personalist bioethics is built, thereby enhancing understanding regarding its place within the broader discourse of secular bioethics. Personalist bioethics, as a dynamic pursuit, actively engages with scientific discoveries, periodically revisiting them and considering contemporary individualsʼ diverse perceptions of identity and values. It integrates two foundational trunks: personalism and Aristotelian-Thomistic theology with metaphysical reference. The method employed by personalist bioethics is illustrated through triangulation: the exposition of biomedical reality, an in-depth study of anthropological significance, and the identification of values at stake. Rooted in a substantialist concept of the human person, it follows a systematic interaction of various knowledge spheres, aiming not only to describe problematic relations but also to propose prescriptive solutions. Personalism maintains that the human person is valuable for who he is and not only for the choices he makes; he is a source from which the choices proceed. According to personalist ethics, the ethical value of an act will have to be considered under the subjective aspect of intentionality, but it will also have to be considered in terms of its objective content and its consequences. The natural moral law that urges every conscience to do good and avoid evil, therefore, becomes concrete in respect for the human person in all the fullness of his values, his essence, and ontological dignity.

Peru reported the second-highest COVID-19 cases in Latin America, after Brazil. The first COVID-19 wave occurred between March–December 2020, and the second occurred between January–September 2021. The differences between these waves remain largely unknown, and there is no comparison between them in Peru. We evaluated the variation in the clinical and epidemiological components of COVID-19-affected patients in both waves in northern Peru by a retrospective study using the clinical follow-up database of Lambayeque and the epidemiological notification form database of NotiWeb. The COVID-19-associated factors during the two waves were determined using simple and multiple regression analysis, and the prevalence ratio (PR) was estimated. During the second wave of COVID-19, there was an increase in cough symptoms in 12.1%, odynophagia in 5.0%, and chills in 16.0% compared with the first wave. The second wave was marked by a higher proportion of affected adolescents and children and a greater percentage of respiratory symptoms than the first wave.

Abstract Background Emerging zoonotic diseases arise from cross-species transmission events between wild or domesticated animals and humans, with bats being one of the major reservoirs of zoonotic viruses. Viral metagenomics has led to the discovery of many viruses, but efforts have mainly been focused on some areas of the world and on certain viral families. Methods We set out to describe full-length genomes of new picorna-like viruses by collecting feces from hundreds of bats captured in different regions of Spain. Viral sequences were obtained by high-throughput Illumina sequencing and analyzed phylogenetically to classify them in the context of known viruses. Linear discriminant analysis (LDA) was performed to infer likely hosts based on genome composition. Results We found five complete or nearly complete genomes belonging to the family Picornaviridae, including a new species of the subfamily Ensavirinae. LDA suggested that these were true vertebrate viruses, rather than viruses from the bat diet. Some of these viruses were related to picornaviruses previously found in other bat species from distant geographical regions. We also found a calhevirus genome that most likely belongs to a proposed new family within the order Picornavirales, and for which genome composition analysis suggested a plant host. Conclusions Our findings describe new picorna-like viral species and variants circulating in the Iberian Peninsula, illustrate the wide geographical distribution and interspecies transmissibility of picornaviruses, and suggest new hosts for calheviruses.

Abstract The Philippines is a high-incidence country for tuberculosis, with the increasing prevalence of multi- (MDR-TB) and extensively-drug (XDR-TB) resistant Mycobacterium tuberculosis strains posing difficulties to disease control. Understanding the genetic diversity of circulating strains can provide insights into underlying drug resistance mutations and transmission dynamics, thereby assisting the design of diagnostic tools, including those using next generation sequencing (NGS) platforms. By analysing genome sequencing data of 732 isolates from Philippines drug-resistance survey collections spanning from 2011 to 2019, we found that the majority belonged to lineages L1 (531/732; 72.5%) and L4 (European-American; n = 174; 23.8%), with the Manila strain (L1.2.1.2.1) being the most prominent (475/531). Approximately two-thirds of isolates were found to be at least MDR-TB (483/732; 66.0%), and potential XDR-TB genotypic resistance was observed (3/732; 0.4%), highlighting an emerging problem in the country. Genotypic resistance was highly concordant with laboratory drug susceptibility testing. By finding isolates with (near-)identical genomic variation, five major clusters containing a total of 114 isolates were identified: all containing either L1 or L4 isolates with at least MDR-TB resistance and spanning multiple years of collection. Closer inspection of clusters revealed transmission in prisons, some involving isolates with XDR-TB, and mutations linked to third-line drug bedaquiline. We have also identified previously unreported mutations linked to resistance for isoniazid, rifampicin, ethambutol, and fluoroquinolones. Overall, this study provides important insights into the genetic diversity, transmission and circulating drug resistance mutations of M. tuberculosis in the Philippines, thereby informing clinical and surveillance decision-making, which is increasingly using NGS platforms.

Abstract Despite substantial growth in wind energy technology in recent decades, aerodynamic modeling of wind turbines relies on momentum models derived in the late 19th and early 20th centuries, which are well-known to break down under flow regimes in which wind turbines often operate. This gap in theoretical modeling for rotors that are misaligned with the inflow and also for high-thrust rotors has resulted in the development of numerous empirical corrections which are widely applied in textbooks, research articles, and open-source and industry design codes. This work reports a Unified Momentum Model to efficiently predict power production, thrust force, and wake dynamics of rotors under arbitrary inflow angles and thrust coefficients without empirical corrections. The Unified Momentum Model is additionally coupled with a blade element model to enable blade element momentum modeling predictions of wind turbines in high thrust coefficient and yaw misaligned states without using corrections for these states. This Unified Momentum Model can form a new basis for wind turbine modeling, design, and control tools from first principles and may enable further development of innovations necessary for increased wind production and reliability to respond to 21st century climate change challenges.

We report the rediscovery, a century after its last record, of two specimens of Pristimantis ruidus from approximately 6 km northeast of its type locality, in a montane forest from the western Andes of southern Ecuador. This species, described by John D. Lynch in 1979, based on specimens collected in 1922 by George H. Tate, was previously known only from the type series, all specimens originating from a single locality (Molleturo, Provincia Azuay, Ecuador, 2317 m elev.). The rediscovery occurred in November 2022 in the Reserva de Conservación Quitahuaycu, Molleturo Parish, Azuay Province. The two specimens, both females, are characterised by rough skin with numerous rounded low warts and tubercles on their dorsum, a W-shaped occipital fold, tympanum and tympanic ring not externally visible and by the lack of cranial crests, characters that correspond with the description of the holotype. We evaluate the phylogenetic relationships, based on two mitochondrial genes (12S and 16S rRNA) and one nuclear gene (RAG-1). These analyses reveal Pristimantis ruidus as a member of the subgenus Huicundomantis, being most closely related to P. philipi, a species with a distribution restricted to the paramo of the same mountain region (Macizo del Cajas). Pristimantis ruidus co-exists with Pristimantis jimenezi, three additional species of Pristimantis and one Noblella with uncertain taxonomic status. This rediscovery underscores the urgency of implementing effective conservation and monitoring measures for the few remnants of the original ecosystems from western Ecuador, which face ongoing anthropogenic threats and harbour a diversity that remains insufficiently studied.

Abstract Background Critical care management heavily relies on accurate cardiac output (CO) measurement. Echocardiography has been a mainstay in non-invasive cardiac monitoring; however, its comparability to invasive methods warrants further exploration. Recent studies have suggested the potential of carotid Doppler measurements as a promising approach to estimate CO. Despite this potential, the literature presents mixed outcomes regarding its reliability and accuracy. This study aims to evaluate the correlation and concordance between carotid Doppler ultrasonography and invasive hemodynamic monitoring in estimating CO in critically ill patients. Furthermore, it assesses the concordance and correlation between echocardiography CO and the standard invasive CO measurements. Methods This concordance study involved critically ill adults requiring invasive CO measurement. Patients with arrhythmias, severe valvulopathy, pregnancy, and poor acoustic window were excluded. Statistical analyses comprised univariate analysis, Wilcoxon signed-rank test, Spearman correlation, and intraclass correlation coefficient. Ethical approval was granted by the institution’s ethics committee. Results A total of 49 critically ill patients were included, predominantly male (63.27%), with a median age of 57 years. Diagnoses included subarachnoid hemorrhage (53.06%) and heart failure (8.16%). Mean cardiac index was 3.36 ± 0.81 L/min/m2 and mean cardiac output was 5.98 ± 1.47 L/min. Spearman correlation coefficient between echocardiography and invasive CO measurements was 0.58 (p-value = p

Abstract Background Diet and exercise are important components of treatment for complex chronic conditions, however access to allied health support is limited. When available, support is often siloed and fragmented. Digital health incorporating patient choice may help to align health care services with preferences and goals. This study evaluated the implementation of a ubiquitously accessible patient-centred digital health diet and exercise service. Methods U-DECIDE was a single-centre, 26-week randomised controlled trial set in kidney and liver disease clinics in a tertiary hospital in Brisbane, Australia. Participants were adults with a complex chronic condition referred for dietetic consultation with at least one feature of the metabolic syndrome. All participants received a dietary consultation, an activity monitor and usual care. Intervention participants were offered one text message per week and access to additional digital health options (increased text message frequency, nutrition app, exercise app, group-based diet and/or exercise video consultations). The primary outcome of feasibility was determined by safety (study-related serious adverse events: SRSAEs), recruitment (≥ 50% eligible patients), retention (≥ 70%), exposure uptake (≥ 75% of intervention group had greater access to health professional contact than comparator) and video consultation adherence (≥ 80% attendance). Secondary outcomes included process evaluation metrics and clinical outcomes. Results Of 67 participants (intervention n = 33, comparator n = 34), 37 (55%) were men, median (IQR) age was 51 (41–58) years. The most chosen digital health options were the nutrition app (n = 29, 88%) and exercise video consultations (n = 26, 79%). Only one participant chose no additional digital health options. The intervention group had no SRSAEs. The study exceeded targets for recruitment (52%), retention (81%) and exposure uptake (94%). Video consultation adherence was 42%. Engagement across digital health options was inconsistent. Conclusions Digital health options incorporating patient choice were feasible and can be offered to people with complex chronic disease as a service model option. Trial registration Australia and New Zealand Trials Register: Trial Registration Number: ACTRN12620001282976. Registered 27th November 2020.

Abstract Background Congenital Myasthenic Syndromes (CMS) are rare genetic diseases, which share as a common denominator muscle fatigability due to failure of neuromuscular transmission. A distinctive clinical feature of presynaptic CMS variants caused by defects of the synthesis of acetylcholine is the association with life-threatening episodes of apnea. One of these variants is caused by mutations in the SLC5A7 gene, which encodes the sodium-dependent HC-3 high-affinity choline transporter 1 (CHT1). To our knowledge there are no published cases of this CMS type in Latin America. Case presentation We present two cases of CHT1-CMS. Both patients were males presenting with repeated episodes of apnea, hypotonia, weakness, ptosis, mild ophthalmoparesis, and bulbar deficit. The first case also presented one isolated seizure, while the second case showed global developmental delay. Both cases, exhibited incomplete improvement with treatment with pyridostigmine. Conclusions This report emphasizes the broad incidence of CMS with episodic apnea caused by mutations in the SLC5A7 gene and the frequent association of this condition with serious manifestations of central nervous system involvement.

RESUMEN Introducción y objetivos: La mayoría de los pacientes con embolia pulmonar (EP) aguda reciben únicamente anticoagulación. La reperfusión es necesaria en los pacientes con EP de alto riesgo y en una minoría de pacientes con EP de riesgo intermedio-alto. La trombólisis sistémica (TS) es el tratamiento de reperfusión de primera línea, pero debido a las contraindicaciones y a la preocupación por las hemorragias graves, las terapias dirigidas por catéter (TDC) están surgiendo como una alternativa adecuada. El objetivo del presente estudio fue detectar predictores del uso de TDC con respecto a otras terapias en pacientes con EP aguda. Métodos: Este registro incluyó pacientes consecutivos con EP de riesgo intermedio y alto en dos centros terciarios, con un equipo de respuesta a la EP, desde 2014 hasta 2022. Los pacientes se agruparon según la terapia inicial: solo anticoagulación, TDC o TS; y se evaluaron los predictores de selección de terapia y variables de seguridad. Resultados: Se incluyó a un total de 274 pacientes. De ellos, 112 recibieron solo anticoagulación, 96 recibieron TS como tratamiento primario y 66 fueron sometidos a TDC en un primer momento. Las comorbilidades fueron mayores en el grupo TDC que en los otros dos. Los pacientes sometidos a TS o TDC presentaban mayores parámetros de gravedad de la EP al ingreso hospitalario. Tras el análisis multivariable, el índice de comorbilidad de Charlson (OR = 1,29; IC95%, 1,05-1,59), la cirugía reciente (OR = 11,07; IC95%, 3,07-39,87) y la EP central bilateral (OR = 2,42; IC95%, 1,10-5,32) siguieron siendo predictores independientes del uso de TDC. En cuanto a los resultados precoces de seguridad, sólo se produjeron hemorragias intracraneales en el grupo TS (1,8% de los pacientes). Conclusiones: Este registro contemporáneo utilizó TDC como terapia inicial en el 24% de los pacientes de riesgo intermedio y alto, principalmente en pacientes comórbidos y posquirúrgicos. La TDC fue una alternativa segura y eficaz al tratamiento médico en pacientes seleccionados.

ABSTRACT Introduction and objectives: Most patients with acute pulmonary embolism (PE) receive anticoagulation only. Reperfusion is required in high-risk and a minority of intermediate-risk PE patients. Systemic thrombolysis (ST) is the first-line reperfusion therapy, but due to contraindications and major bleeding concerns, the use of catheter-directed therapies (CDT) is increasing as a suitable alternative. The objective of the present study was to detect predictors of the use of CDT compared with other therapies in patients with acute PE. Methods: This registry included consecutive intermediate- and high-risk PE patients in 2 tertiary centers with a 24/7 PE response team from 2014 to 2022. The patients were grouped according to the primary treatment: anticoagulation only, CDT, or ST. We evaluated predictors of treatment assignment and safety endpoints. Results: A total of 274 patients were included. Of them, 112 received anticoagulation only, 96 received ST as the primary treatment, and 66 underwent CDT first. Comorbidities were higher in the CDT group than in the other 2 groups. Patients undergoing ST/CDT had higher PE severity parameters at hospital admission. On multivariable analysis, independent predictors for the use of CDT were Charlson Comorbidity Index (OR, 1.29; 95%CI, 1.05-1.59), recent surgery (OR, 11.07; 95%CI, 3.07-39.87), and bilateral central PE (OR, 2.42; 95%CI, 1.10-5.32). Analysis of early safety outcomes showed that intracranial bleeding occurred only in the ST group (1.8% of patients). Conclusions: This contemporary registry used CDT as the primary treatment in 24% of intermediate- and high-risk patients, mainly in comorbid and postsurgical patients. CDT was a safe and effective alternative to medical therapy in selected patients.

Abstract Background Repetitive Transcranial Magnetic Stimulation (rTMS) and EEG-guided neurofeedback techniques can reduce motor symptoms in Parkinson’s disease (PD). However, the effects of their combination are unknown. Our objective was to determine the immediate and short-term effects on motor and non-motor symptoms, and neurophysiological measures, of rTMS and EEG-guided neurofeedback, alone or combined, compared to no intervention, in people with PD. Methods A randomized, single-blinded controlled trial with 4 arms was conducted. Group A received eight bilateral, high-frequency (10 Hz) rTMS sessions over the Primary Motor Cortices; Group B received eight 30-minute EEG-guided neurofeedback sessions focused on reducing average bilateral alpha and beta bands; Group C received a combination of A and B; Group D did not receive any therapy. The primary outcome measure was the UPDRS-III at post-intervention and two weeks later. Secondary outcomes were functional mobility, limits of stability, depression, health-related quality-of-life and cortical silent periods. Treatment effects were obtained by longitudinal analysis of covariance mixed-effects models. Results Forty people with PD participated (27 males, age = 63 ± 8.26 years, baseline UPDRS-III = 15.63 ± 6.99 points, H&Y = 1–3). Group C showed the largest effect on motor symptoms, health-related quality-of-life and cortical silent periods, followed by Group A and Group B. Negligible differences between Groups A-C and Group D for functional mobility or limits of stability were found. Conclusions The combination of rTMS and EEG-guided neurofeedback diminished overall motor symptoms and increased quality-of-life, but this was not reflected by changes in functional mobility, postural stability or depression levels. Trial registration NCT04017481.

Abstract Public engagement with research (PEwR) has become increasingly integral to research practices. This paper explores the process and outcomes of a collaborative effort to address the ethical implications of PEwR activities and develop tools to navigate them within the context of a University Medical School. The activities this paper reflects on aimed to establish boundaries between research data collection and PEwR activities, support colleagues in identifying the ethical considerations relevant to their planned activities, and build confidence and capacity among staff to conduct PEwR projects. The development process involved the creation of a taxonomy outlining key terms used in PEwR work, a self-assessment tool to evaluate the need for formal ethical review, and a code of conduct for ethical PEwR. These tools were refined through iterative discussions and feedback from stakeholders, resulting in practical guidance for researchers navigating the ethical complexities of PEwR. Additionally, reflective prompts were developed to guide researchers in planning and conducting engagement activities, addressing a crucial aspect often overlooked in formal ethical review processes. The paper reflects on the broader regulatory landscape and the limitations of existing approval and governance processes, and prompts critical reflection on the compatibility of formal approval processes with the ethos of PEwR. Overall, the paper offers insights and practical guidance for researchers and institutions grappling with ethical considerations in PEwR, contributing to the ongoing conversation surrounding responsible research practices.

Chitons are molluscs with scarce world records in estuaries. In the present study, we provide the first records of two species of Polyplacophora in the Coreaú River estuary, Camocim, Ceará, Brazil: Ischnochiton striolatus and Ischnoplax pectinata. The data shows these animals thrive in estuary coastal regions. The taxonomic data together with the ecological data presented in this study, it is possible to conclude that this research represents a significant milestone in understanding the biodiversity of Brazilian estuarine areas.

Abstract Intracortical microelectrodes (IMEs) are devices designed to be implanted into the cerebral cortex for various neuroscience and neuro-engineering applications. A critical feature of IMEs is their ability to detect neural activity from individual neurons. Currently, IMEs are limited by chronic failure, largely considered to be caused by the prolonged neuroinflammatory response to the implanted devices. Over the past few years, the characterization of the neuroinflammatory response has grown in sophistication, with the most recent advances focusing on mRNA expression following IME implantation. While gene expression studies increase our broad understanding of the relationship between IMEs and cortical tissue, advanced proteomic techniques have not been reported. Proteomic evaluation is necessary to describe the diverse changes in protein expression specific to neuroinflammation, neurodegeneration, or tissue and cellular viability, which could lead to the further development of targeted intervention strategies designed to improve IME functionality. In this study, we have characterized the expression of 62 proteins within 180 μm of the IME implant site at 4-, 8-, and 16-weeks post-implantation. We identified potential targets for immunotherapies, as well as key pathways that contribute to neuronal dieback around the IME implant.

Abstract Recent discoveries in biology have highlighted the importance of protein and RNA-based condensates as an alternative to classical membrane-bound organelles. Here, we demonstrate the design of pure RNA condensates from nanostructured, star-shaped RNA motifs. We generate condensates using two different RNA nanostar architectures: multi-stranded nanostars whose binding interactions are programmed via linear overhangs, and single-stranded nanostars whose interactions are programmed via kissing loops. Through systematic sequence design, we demonstrate that both architectures can produce orthogonal (distinct and immiscible) condensates, which can be individually tracked via fluorogenic aptamers. We also show that aptamers make it possible to recruit peptides and proteins to the condensates with high specificity. Successful co-transcriptional formation of condensates from single-stranded nanostars suggests that they may be genetically encoded and produced in living cells. We provide a library of orthogonal RNA condensates that can be modularly customized and offer a route toward creating systems of functional artificial organelles for the task of compartmentalizing molecules and biochemical reactions.

Abstract Background To report the risk of exudation recurrence and long-term outcomes in patients with choroidal neovascularization secondary to angioid streaks, according to its morphology and characteristics by optical coherence tomography angiography. Methods Retrospective analysis of electronic medical records from three hospitals. We enrolled patients with a clinical diagnosis of angioid streaks choroidal neovascularization that had a minimum follow-up of 12 months. From each record, we extracted general demographic data, best corrected visual acuity (baseline, before and after each disease recurrence and last on file), type of treatment, time between last intravitreal injection and disease recurrence, and classification of the neovascular lesion morphology by optical coherence tomography, and optical coherence tomography angiography. Patients with myopic choroidal neovascularization were used as controls. Interobserver agreement was assessed with a Cohen-Kappa test. The Odds ratio was calculated with a chi2 test for significance. Visual acuity change through time was evaluated with an ANOVA for repeated measurements with an alpha value of 0.05 for statistical significance. Results We enrolled 30 patients in the study group and 14 in the control group. In the study group, the baseline and final BCVA were 0.861 ± 0.59 and 1.095 ± 0.61 logMAR (p = 0.1) respectively. Control group: 1.045 ± 0.57 and 0.617 ± 0.53 logMAR (p

El objetivo de un Presupuesto por Resultados es mejorar la eficiencia y eficacia del gasto público, utilizando la información de desempeño para la toma de decisiones presupuestarias, es por ello que la investigación tuvo como objetivo determinar la relación entre el presupuesto por resultados y la gestión gerencial en la Municipalidad Distrital de Ascensión. La metodología utilizada fue de nivel descriptivo-correlacional y diseño no experimental-transversal, se empleó la técnica de la encuesta, cuyo cuestionario fue aplicado a los 55 trabajadores nombrados en la Municipalidad Distrital de Ascensión. Los resultados mostraron que la relación entre ambas variables se vincula positiva y significativamente, contando con una intensidad del 79,2% de acuerdo al coeficiente de Spearman, concluyendo que a medida que los presupuestos por resultados sean bien ejecutados, la gestión gerencial de la municipalidad distrital de Ascensión será más eficiente, direccionando los fondos hacia la solución de problemas que incidan el bienestar social.

El desarrollo de los recursos humanos es un aspecto crucial de cualquier organización, que implica la gestión y el desarrollo de los empleados para garantizar que tengan las habilidades y la motivación para contribuir al éxito de la empresa. El objetivo del artículo es determinar de qué manera se relaciona el desarrollo de recursos humanos y los indicadores de desempeño del personal de la Universidad Nacional de Huancavelica, año 2022. La metodología es investigación aplicada, correlacional; la población es el total de personal docente y administrativo de la Universidad Nacional de Huancavelica, el muestreo no probabilístico e intencionado. La técnica de recolección de información fue encuesta y el instrumento un cuestionario. Los resultados indican la presencia de una asociación entre las dos variables subsistema de desarrollo de recursos humanos e indicadores de desempeño del personal de la Universidad Nacional de Huancavelica, Año 2022. Se concluye que, el coeficiente de correlación hallada es de rho=0,546** que tiene asociado una probabilidad p.=0,000

Abstract Background Firearm homicide and opioid overdoses were already leading causes of death in the U.S. before both problems surged during the COVID-19 pandemic. Firearm violence, overdoses, and COVID-19 have all disproportionately harmed communities that are socially and economically marginalized, but the co-occurrence of these problems in the same communities has received little attention. To describe the co-occurrence of firearm homicides and opioid overdose deaths with COVID-19 mortality we used 2017–2021 medical examiner’s data from Chicago, IL. Deaths were assigned to zip codes based on decedents’ residence. We stratified zip codes into quartiles by COVID-19 mortality rate, then compared firearm homicide and fatal opioid overdose rates by COVID-19 quartile. Findings Throughout the study period, firearm homicide and opioid overdose rates were highest in the highest COVID-19 mortality quartile and lowest in the lowest COVID-19 mortality quartile. Increases in firearm homicide and opioid overdose were observed across all COVID-19 mortality quartiles. Conclusions High co-occurrence of these deaths at the community level call for addressing the systemic forces which made them most vulnerable before the pandemic. Such strategies should consider the environments where people reside, not only where fatal injuries occur.

Abstract Background Quality of life (QoL) is an important determinant of physical and mental health. QoL in head and neck cancer tends to deteriorate due to changes in the physical, functional, psychological aspects. EORTC-QLQ-H&N35 is an instrument that measure the QoL specifically in head and neck cancer patients. EORTC-QLQ-H&N35 give a numeric value to QoL of patients with high value correspond to better QoL. Objective The aim of present study was to find out the cut-off points of numeric values of EORTC-QLQ-H&N35 to categorize QoL impairment into different categories (normal, mild, moderate, and severe). Present study also aims analyze the QoL among head and neck cancer patients under these new categories. Methodology Total 205 patients of head and neck cancer visiting to the outpatient unit were enrolled in this study. Hindi version of EORTC-QLQ-H&N35 was used to evaluate the QoL. Total 9 classification schemes were created with different cut-off points to classify the global QoL score into normal, mild, moderate and severe categories. QoL data was then analyze using the scheme having highest F value in ANOVA test. Results Classification scheme having cut-off values 76–100 for normal QoL, 51–75 for mild QoL impairment, 26–50 for moderate and 0–25 for severe QoL impairment found to have highest F value (729.915) in ANOVA test. The mean QoL score among total 205 patients were 60.08 ± 19.06. Based on the new classification scheme, QoL was normal in 46 (22.4%) patients whereas QoL was impaired to mild level in 76 (37.1%) patients, to moderate level in 76 (37.1%) and to severe level in 7 (3.4%) patients. Role functioning, emotional functioning and social functioning was impaired to severe level in 4 (2.0%), 13 (6.3%) and 3 (1.5%) patients respectively. Conclusion EORTC-QLQ-H&N35 offer a comprehensive review of QoL in head and neck cancer patients. By designating the QoL score into different categories, it will become easier for clinician to have a better idea of QoL of head and neck cancer patients.

Abstract To inform clinical trial design and real-world precision pediatric oncology practice, we classified diagnoses, assessed the landscape of mutations, and identified genomic variants matching trials in a large unselected institutional cohort of solid tumors patients sequenced at Dana-Farber / Boston Children’s Cancer and Blood Disorders Center. Tumors were sequenced with OncoPanel, a targeted next-generation DNA sequencing panel. Diagnoses were classified according to the International Classification of Diseases for Oncology (ICD-O-3.2). Over 6.5 years, 888 pediatric cancer patients with 95 distinct diagnoses had successful tumor sequencing. Overall, 33% (n = 289/888) of patients had at least 1 variant matching a precision oncology trial protocol, and 14% (41/289) were treated with molecularly targeted therapy. This study highlights opportunities to use genomic data from hospital-based sequencing performed either for research or clinical care to inform ongoing and future precision oncology clinical trials. Furthermore, the study results emphasize the importance of data sharing to define the genomic landscape and targeted treatment opportunities for the large group of rare pediatric cancers we encounter in clinical practice.

Introduction Dengue disease represents a large and growing global threat to public health, accounting for a significant burden to health systems of endemic countries. The World Health Organization’s (WHO) Strategic Advisory Group of Experts (SAGE) and the European Medicines Agency (EMA) currently recommend the use of TAK-003 dengue vaccine in high dengue burden and transmission settings for countries considering vaccination as part of their integrated management strategy for prevention and control of Dengue.Areas covered This paper describes the main conclusions of a workshop held by the Arbovirus Committee of the Latin American Society of Pediatric Infectious Diseases (SLIPE) in November 2023, to generate consensus recommendations on the introduction of this new vaccine in the region. Considerations were made regarding the molecular epidemiology of dengue infection in the Americas and the need for more precise phylogenetic classification and correlation with clinical outcome and disease severity.Expert opinion Introduction of dengue vaccine should be considered as an strategy for health entities in the region, with participation of social sectors, scientific societies, and ministries of health that could be able to create a successful vaccination program.

Purpose: To summarize the results of Chile's 2022 Report Card (RC) on physical activity (PA) for Children and Adolescents. Methods: Chile's 2022 RC included ten core PA indicators common to the Global Matrix 4.0. Evidence from scientific articles, reports, and databases published between 2018 and January 2022 was included for each indicator. The data were collected and analyzed by a national scientific committee, which assigned letter grades (A to F) using a consensus based on benchmarks defined and revised by the Active Healthy Kids Global Alliance. Results: The committee assigned the following grades: Overall PA, D−; Organized Sports and Physical Activity Participation, C−; Active Play, Incomplete; Active Transportation, D; Sedentary Behavior, D−; Physical Fitness, Incomplete; Family and Peers, D; School, C; Community and Environment, D+; Government, A−. Conclusions: Chile's 2022 RC, like its previous versions, shows persistently low grades for most indicators. Overall PA remained nearly unchanged, while Community and Environment scored lower. Slight improvements were seen in Organized Sports, Family and Peers, and School Environment. While Chile has endeavored to increase children's activity levels, policies require implementation through a systemic, coherent framework to promote sustainable changes and reach a larger portion of children and youth.

The article addresses the diagnostic value of the combined use of computed tomography (CT) perfusion and dual-energy CT (DECT) in patients with neuroendocrine tumors. It emphasizes the heterogeneity and complexity of these neoplasms, primarily affecting the gastrointestinal tract, bronchopulmonary system, and pancreas. While conventional CT is widely employed in their diagnosis, the combination of CT perfusion and dual-energy CT offers greater precision, particularly in detecting synchronous tumors and characterizing their vascularization. A clinical case of a patient with chronic abdominal symptoms, whose diagnosis was facilitated using both combined techniques, is presented. The discussion explores how CT perfusion assesses tumor vascularization and how dual-energy CT improves soft tissue differentiation, resulting in increased diagnostic accuracy. It is highlighted that this approach not only enhances detection rates but also positively impacts clinical management and healthcare costs. Therefore, the importance of considering these advanced tools in the diagnosis of neuroendocrine tumors to improve diagnostic precision and efficiency in patient care is underscored.

Introducción. Colombia alberga dos millones de indígenas, que viven en condiciones de pobreza y tienen deficiencias en salud, por lo cual están expuestos a contraer infecciones virales como la hepatitis B. El departamento del Amazonas presenta una gran prevalencia del virus y barreras para acceder a la vacunación; por esto, parte de la población es propensa a la infección. Objetivo. Identificar factores asociados con la infección por el virus de la hepatitis B en indígenas colombianos. Materiales y métodos. Se llevó a cabo un estudio de casos y controles en mayores de 18 años de cuatro departamentos del país. Los casos se identificaron mediante el registro nacional de notificación de hepatitis B (2015-2022). Los controles seleccionados de manera concurrente fueron pareados con los casos por edad, sexo, etnia y departamento. En una encuesta se consignaron las características sociodemográficas, los factores asociados con el contacto con sangre y fluidos, las prácticas socioculturales y los antecedentes de vacunación. El proyecto fue aprobado por Comité de Ética de la Universidad de Antioquia. Resultados. Participaron 75 casos y 150 controles de 13 grupos étnicos. El departamento del Amazonas aportó el 49 % de los participantes (83 % mujeres) con una mediana de edad de 30 años (RIC = 27-37). Los factores asociados con una mayor probabilidad de contraer la infección fueron el antecedente de algún familiar infectado con el virus de la hepatitis B (OR ajustado = 2,61) (IC95%: 1,09-6,27) y número de embarazos en mujeres, (OR ajustado = 1,61) (IC95%: 1,02-2,54). La vacunación mostró un efecto protector sin asociación significativa. Conclusión. Los aspectos asociados con la convivencia familiar y el número de embarazos contribuyen a una potencial transmisión vertical y horizontal del virus. No se identificaron prácticas culturales asociadas. Se requieren estrategias novedosas y diferenciales para reducir la transmisión del virus de la hepatitis B en poblaciones indígenas.

Poco se sabe cómo operan los mercados de carne de monte en la Amazonía peruana y la influencia que tienen sobre los niveles de extracción con fines alimenticios y comerciales. La investigación analiza cómo el precio de la carne de monte se relaciona con la intensidad de caza en comunidades nativas cercanas a la ciudad de Pucallpa. El estudio confirma que la extracción, comercio y uso de carne de monte en estas comunidades están relacionados con la comercialización del recurso en la ciudad. La cantidad de carne compartida, carne vendida y el precio promedio influyen sobre la cantidad total de carne cazada. Si los precios varían, las cantidades de carne cazada para la venta varían también. Se recomienda promover la autorregulación local, mediante la cual las propias comunidades se organizan asegurando la permanencia de poblaciones saludables de fauna silvestre y beneficiarse sin perjudicar el ecosistema. Se sugiere promover la venta legal de carne de monte de especies manejadas en los mercados formales de Pucallpa para que el comercio pueda estar sujeto a mayor control y permitir que los precios logren un nivel de equilibrio sostenible en la extracción y venta de carne de monte.

Recent empirical research in policy design has shown the relevance of micro-level components, particularly specification and calibration, in shaping policy outcomes. Additionally, research highlights the importance that understanding the mechanisms underlying the policy process has for effective policy design. Yet, a gap persists in how to effectively calibrate and specify policies for specific cases, with a theoretical grounding and guidance for practitioners. This paper addresses this need by applying a process theory of change to delineate the key episodes that constitute the mechanisms of a plausible pathway for an effective Program for Ecosystem Services (PES), an incentives-based instrument focused on conserving forests producing carbon sequestration, biodiversity protection, and water infiltration, among other services. Specifically, the paper uses the well-documented Mexican PES to illustrate how to derive the mechanisms and use them for calibration and specification. The paper provides valuable theoretical insights drawn from the case study, contributing to the field of micro-policy design with a mechanistic approach.

Summary: Background: Bacterial biofilm communities are embedded in a protective extracellular matrix comprised of various components, with its' integrity largely owed to a 3-dimensional lattice of extracellular DNA (eDNA) interconnected by Holliday Junction (HJ)-like structures and stabilised by the ubiquitous eubacterial DNABII family of DNA-binding architectural proteins. We recently showed that the host innate immune effector High Mobility Group Box 1 (HMGB1) protein possesses extracellular anti-biofilm activity by destabilising these HJ-like structures, resulting in release of biofilm-resident bacteria into a vulnerable state. Herein, we showed that HMGB1's anti-biofilm activity was completely contained within a contiguous 97 amino acid region that retained DNA-binding activity, called ‘mB Box-97’. Methods: We engineered a synthetic version of this 97-mer and introduced a single amino acid change which lacked any post-translational modifications, and tested its activity independently and in combination with a humanised monoclonal antibody that disrupts biofilms by the distinct mechanism of DNABII protein sequestration. Findings: mB Box-97 disrupted and prevented biofilms, including those formed by the ESKAPEE pathogens, and importantly reduced measurable proinflammatory activity normally associated with HMGB1 in a murine lung infection model. Interpretation: Herein, we discuss the value of targeting the ubiquitous eDNA-dependent matrix of biofilms via mB Box-97 used singly or in a dual host-augmenting/pathogen-targeted cocktail to resolve bacterial biofilm infections. Funding: This work was supported by NIH/NIDCD R01DC011818 to L.O.B. and S.D.G. and NIH/NIAID R01AI155501 to S.D.G.

Soil salinity, a major environmental stress, restricts agricultural production worldwide. Gynura divaricata (L.) DC. is widely cultivated on tropical islands in China and has both edible and medicinal value. NaCl stress and growth indicators, antioxidant enzyme activity, as well as MDA, proline, and soluble sugar content, were determined. Based on the transcriptomic data of tissue-cultured G. divaricata plantlets grown in control (0 mM NaCl) and salt stress (50 and 200 mM NaCl) conditions, gene expression patterns were examined. KEGG enrichment analysis of differentially expressed genes indicated significant enrichment of plant hormone signaling, MAPK signaling, and starch and sucrose metabolism pathways. These findings allowed key biological pathways and salt stress-responsive genes to be identified, thus providing a molecular basis for breeding salt-tolerant G. divaricata varieties. This transcriptomic analysis revealed a complex tolerance mechanism of G. divaricata in response to NaCl, laying a foundation for screening and cloning key genes related to NaCl tolerance and studying their interactions. These findings would allow the molecular basis of NaCl tolerance to be explored, with the aim of breeding NaCl-tolerant varieties.

Objectives: Identifying host response biomarkers implicated in the emergence of organ failure during infection is key to improving the early detection of this complication. Methods: Twenty biomarkers of innate immunity, T-cell response, endothelial dysfunction, coagulation, and immunosuppression were profiled in 180 surgical patients with infections of diverse severity (IDS) and 53 with no infection (nIDS). Those better differentiating IDS/nIDS in the area under the curve were combined to test their association with the sequential organ failure assessment score by linear regression analysis in IDS. Results were validated in another IDS cohort of 174 patients. Results: C-reactive protein, procalcitonin, pentraxin-3, lipocalin-2 (LCN2), tumoral necrosis factor-α, angiopoietin-2, triggering receptor expressed on myeloid cells-1 (TREM-1) and interleukin (IL)-15 yielded an area under the curve ≥0.75 to differentiate IDS from nIDS. The combination of LCN2, IL-15, TREM-1, angiopoietin-2 (Dys-4) showed the strongest association with sequential organ failure assessment score in IDS (adjusted regression coefficient; standard error; P): Dys-4 (3.55;0.44;

Objectives: To determine the associated pathogen during the 2023 conjunctivitis outbreak in Vietnam Methods: RNA-sequencing was used to identify pathogens before and during the outbreak. Results: 24 patients with infectious conjunctivitis between March and October 2023 from Hai Yen Vision Institute in Vietnam were swabbed. Coxsackievirus A24v was the most common pathogen identified. Phylogenetic analysis of these strains demonstrates similarities to the Coxsackievirus identified in the 2022 India outbreak. Human adenovirus D was also circulating. Ocular findings of tearing, purulence, and itching were common in this outbreak. Conclusions: Multiple viruses can co-circulate during conjunctivitis outbreaks. Hemorrhagic conjunctivitis, commonly associated with coxsackievirus conjunctivitis, was not a common clinical sign in this outbreak. Repeat genetic surveillance, with the notable inclusion of RNA virus detection strategies, is important for outbreak detection.

The increase of antibiotic-resistant bacteria has become a global health emergency and the need to explore alternative therapeutic options arises. Phage therapy uses bacteriophages to target specific bacterial strains. Phages are highly specific and can target resistant bacteria. Currently, research in this regard is focused on ensuring reliability and safety to bring this tool into clinical practice. The first step is to conduct comprehensive preclinical research. In this work, we present two novel bacteriophages vB_Kpn_F13 and vB_Kpn_F14 isolated against clinical carbapenem-resistant Klebsiella pneumoniae strains obtained from hospital sewage. Multiple studies in vitro were conducted, such as sequencing, electron microscopy, stability, host range infectivity, planktonic effect and biofilm inhibition in order to discover their ability to be used against carbapenem-resistant K. pneumoniae pathogens causing difficult-to-treat infections.

Intestinal helminth infection triggers a type 2 immune response that promotes a 'weep-and sweep' response characterised by increased mucus secretion and intestinal hypermotility, which function to dislodge the worm from its intestinal habitat. Recent studies have discovered that several other pathogens cause intestinal dysmotility through major alterations to the immune and enteric nervous systems (ENS), and their interactions, within the gastrointestinal tract. However, the involvement of these systems has not been investigated for helminth infections. Eosinophils represent a key cell type recruited by the type 2 immune response and alter intestinal motility under steady-state conditions. Our study aimed to investigate whether altered intestinal motility driven by the murine hookworm, Nippostrongylus brasiliensis, infection involves eosinophils and how the ENS and smooth muscles of the gut are impacted. Eosinophil deficiency did not influence helminth-induced intestinal hypermotility and hypermotility did not involve gross structural or functional changes to the ENS. Hypermotility was instead associated with a dramatic increase in smooth muscle thickness and contractility, an observation that extended to another rodent nematode, Heligmosomoides polygyrus. In summary our data indicate that, in contrast to other pathogens, helminth-induced intestinal hypermotility is driven by largely by myogenic, rather than neurogenic, alterations with such changes occurring independently of eosinophils. (

Degradation of heparan sulfate (HS), a glycosaminoglycan (GAG) comprised of repeating units of N-acetylglucosamine and glucuronic acid, begins in the cytosol and is completed in the lysosomes. Acetylation of the terminal non-reducing amino group of α-D-glucosamine of HS is essential for its complete breakdown into monosaccharides and free sulfate. Heparan-α-glucosaminide N-acetyltransferase (HGSNAT), a resident of the lysosomal membrane, catalyzes this essential acetylation reaction by accepting and transferring the acetyl group from cytosolic acetyl-CoA to terminal α-D-glucosamine of HS in the lysosomal lumen. Mutation-induced dysfunction in HGSNAT causes abnormal accumulation of HS within the lysosomes and leads to an autosomal recessive neurodegenerative lysosomal storage disorder called mucopolysaccharidosis IIIC (MPS IIIC). There are no approved drugs or treatment strategies to cure or manage the symptoms of, MPS IIIC. Here, we use cryo-electron microscopy (cryo-EM) to determine a high-resolution structure of the HGSNAT-acetyl-CoA complex, the first step in the HGSNAT-catalyzed acetyltransferase reaction. In addition, we map the known MPS IIIC mutations onto the structure and elucidate the molecular basis for mutation-induced HGSNAT dysfunction.

Abstract. Trauma is a leading cause of mortality and morbidity worldwide with high rates of disability in survivors. With improvements in care, rehabilitation of the trauma patient is a cornerstone to reducing sequelae. A lack of well-established hospital rehabilitation units and standardized protocols for managing posttraumatic injuries is a common problem in Latin American countries. Future studies should seek to understand the barriers and gaps in care so that consensus and ultimately best practice guidelines can be developed and included in rehabilitation programs throughout trauma centers in Latin America.

Abstract Objectives Providing personal demographic information is routine practice in the United States, and yet, little is known about the impacts of this process. This study aims to examine the experiences and perspectives of Multiracial/ethnic adults in the United States when disclosing racial/ethnic identity. Methods Seventeen semistructured interviews were conducted with adults identifying as Multiracial/ethnic. The Multiracial/ethnic identities of participants included Black or African American and White; Black or African American, American Indian or Alaska Native (AI/AN) and Hispanic or Latino; Black or African American and Hispanic or Latino; Black or African American and AI/AN; AI/AN and White and Asian, Native Hawaiian or Pacific Islander and White. Multiple participants reported identifying with multiple ethnic groups for any single broad category. Three identified as sexual minorities. Nine were Millennials; six were Gen X; one was Gen Z; one was Baby Boomer. Qualitative data were analyzed using staged hybrid inductive–deductive thematic analysis. Results Disclosure of racial and ethnic identities presents a unique stressor for Multiracial/ethnic populations due to methods used to obtain data, perceived mismatch of identity and phenotype and exposure to prejudice. Social norms, constructs and movements impact the categories that a Multiracial/ethnic person indicates to external parties. Conclusions The stress and negative feelings that Multiracial/ethnic adults face when identifying their race/ethnicity underscore the broader implications of standard demographic questions on feelings of inclusivity and visibility within a population. Patient or Public Contribution Gathering data on individuals' racial and ethnic backgrounds is a standard practice, and yet, it can pose challenges for those who identify with multiple groups or do not see their identities reflected in the options provided. Such individuals may feel excluded or experience unfair treatment when disclosing their identity, leading to significant stress. As the frequency of this data collection increases, it is essential that the questions are posed empathetically and equitably, with a strong commitment to enhancing inclusivity throughout the process.

key Clinical Message Constrictive Pericarditis is a rare fibrotic conversion of the pericardium that results in non‐specific clinical symptoms such as hepatomegaly, ascites, pleural effusions, and lower extremity edema. A multi‐modal diagnostic approach with cardiac imaging tools, cardiac hemodynamic measurements, and tissue biopsy can be used to diagnose Constrictive Pericarditis. Abstract Constrictive Pericarditis is a rare complication resulting in the fibrotic conversion of the pericardium secondary to idiopathic, infective, post‐surgical, or post‐radiation etiologies. The rigid and restrictive nature of the pericardium can result in non‐specific symptoms of volume overload that can mimic liver cirrhosis or congestive heart failure. We present the case of a 73‐year‐old female with constrictive pericarditis who presented with vague symptoms of abdominal pain, abdominal bloating, and bilateral lower extremity edema. This case report highlights the clinical manifestation, invasive, and non‐invasive diagnostic work‐up, and management of constrictive pericarditis.

Centrolenidae is a Neotropical family widely distributed in Central and South America, with its species richness concentrated in the tropical Andes. Several taxonomic problems have been identified within this family, mostly related to species with broad geographic distributions. In this study, we assessed and redefined the species boundaries of the Centrolene buckleyi species complex, and formally described two new species from the Andes of Ecuador. These new taxa are recognized by a combination of morphometric, osteological, acoustic, and genetic data. Following IUCN criteria, we propose that the two new species should to be considered as Endangered (EN), mainly because of their small distributions and habitat loss. The C. buckleyi complex provides insights into the biogeography of closely related Andean species. As in other glassfrogs, speciation in Centrolene seems to be mediated by the linearity of the Andes, where gene flow can be restricted by topography and, also, local extinctions.

In Mexico, about 40 % of the mango harvest is lost due to marketing problems. Moreover, the mango industry generates peel and seed waste that ranges from 35 to 60 % of the total weight of processed fruits. This unexploited mango biomass represents a potential resource for producing value-added by-products. A market alternative is exploiting the mango peel as a source of biofunctional compounds, such as pectin. This hydrocolloid has applications in the pharmaceutical, cosmetic, and food industries. This study quantified the peel components of the Ataulfo, Panameño, Manila, and Haden cultivars. The mango peel showed a considerable input of dietary fiber (37–45 % DM), minerals (1018–2156 mg/100 g DM), phenols (2123–4851 mg gallic acid equivalent/100 g DM), flavonoids (0.74–2.7 mg quercetin equivalent/g DM) and antioxidant capacity (375–937 μM Trolox equivalent/g DM). The four cultivars presented high methoxyl pectins (66–71 %). The molecular weight of the pectins analyzed was from 957 to 4859 kDa. The Panameño cultivar showed the highest amount of pectin and viscosity concerning the peel of the other cultivars and a higher content of glucomannans (≈28.21 %). The pectin of the Haden cultivar was the only one with arabinoxylans since xylose was not detected in the pectin of the other cultivars. The chemical characteristics of the studied mango peels are promising for their industrialization.

ObjectiveTo evaluate the safety of COVID-19 vaccines in patients with multiple sclerosis (MS) by assessing their impact on serum neurofilament light chain (sNfL) levels as a marker of neuroaxonal damage.MethodsSingle-center observational longitudinal study including patients with MS who consecutively received their initial vaccination against SARS-CoV-2 at Hospital Universitario Ramón y Cajal, following the first national immunization program in Spain. Serum samples were collected at baseline and after receiving the second dose of the vaccine. sNfL levels were quantified using the single molecule array (SIMOA) technique. Adverse events, including clinical or radiological reactivation of the disease, were recorded.ResultsFifty-two patients were included (median age, 39.7 years [range, 22.5-63.3]; 71.2% female). After SARS-CoV-2 vaccination, no increased inflammatory activity, either determined by the presence of relapses and/or new MRI lesions and/or high sNfL levels, was detected. Accordingly, there was no difference between median sNfL levels before and after vaccination (5.39 vs. 5.76 pg/ml, p=0.6). Despite this, when looking at baseline patient characteristics before vaccination, younger age associated with disease activity after vaccination (OR 0.87, 95% CI: 0.77–0.98, p=0.022). Larger studies are needed to validate these results.ConclusionCOVID-19 vaccines did not cause reactivation of disease at a clinical, radiological or molecular level, thus suggesting that they are safe in MS patients.

The world’s oceans and seas are changing rapidly due to several natural and anthropogenic reasons. Among these, the largest and likely most threatening to marine life being the climate crisis and rising sea temperatures. Studying the dominant primary producers of most marine ecosystems, phytoplankton, and their response to these alterations is challenging, yet essential due to the critical role phytoplankton play in both the oceans and wider biosphere. Satellites are a crucial tool used to study phytoplankton but lack the timespan needed to accurately observe abundance patterns in response to climate change. Historical oceanographic data are increasingly being used to understand changes in the abundance of phytoplankton over the last century. Here, we retrace Secchi depth and Forel-Ule colour scale surveys performed during the “Pola” expeditions between 1890-1898 using contemporary satellite data, to assess changes in water colour and clarity (and by extension phytoplankton abundance) in the Red Sea and the Eastern Mediterranean Sea over the past century. The results show a significant greening of both regions investigated as well as a decrease in water clarity. The Red Sea Forel-Ule colour increased by 0.83 (± 0.08) with an average decrease in Secchi depth of 5.07 m (± 0.44). The Forel-Ule colour in the Eastern Mediterranean increased by 0.50 (± 0.07) and the historic Secchi depth readings were an average of 8.85 m (± 0.47) deeper than present day. Changes in Secchi depth between periods were greater than that which may have been caused by differences in the size of the Secchi disk used on the “Pola” expeditions, estimated using traditional Secchi depth theory. There was no clear change in seasonality of phytoplankton abundance and blooms, although winter months saw many of the largest changes in both measured variables. We discuss potential drivers for this change and the challenges and limitations of combining historical and modern datasets of water clarity and colour.

BackgroundChronic obstructive pulmonary disease (COPD), usually caused by long-term tobacco smoking, is independently associated with systemic inflammation. However, little is known about the systemic inflammatory status of patients with early-stage COPD (classified as GOLD 1) and long-term smokers with normal lung function (LF). Here, we characterised the early changes in the associated inflammatory state in patients with GOLD 1 and in long-term smokers with normal LF.MethodsFresh blood samples from 27 patients with GOLD 1, 27 long-term smokers and 14 non-smokers were analysed.ResultsEx vivo blood analysis revealed greater leucocyte-platelet adhesion to TNFα-stimulated pulmonary endothelium in patients with GOLD 1 than in smokers and non-smokers. In addition, platelet reactivity (platelet count and activation, and fibrinogen levels) and the frequency of leucocyte-platelet aggregates were higher in the GOLD 1 group than in the other groups. Some of these findings correlated with the severity of lung dysfunction, while platelet hyperactivity correlated positively with leucocyte-platelet adhesion. The GOLD 1 group also had a higher Th17/Treg ratio and higher circulating levels of IL-17C and C-reactive protein than the other groups. However, long-term smokers also had higher leucocyte counts and activation, and higher plasma levels of TNFα and IL-6 than non-smokers.ConclusionOur data suggest that the altered inflammatory parameters in long-term smokers may represent early biomarkers of COPD. Accordingly, peripheral immune monitoring based on the above parameters may be useful to prevent disease progression in long-term smokers with normal LF and early COPD.

IntroductionAlemtuzumab is a highly effective pulsed immune reconstitution therapy for multiple sclerosis (MS).AimTo evaluate serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) in patients with relapsing-remitting MS who have been treated with Alemtuzumab over the course of 2 years.MethodsThis prospective study involved MS patients treated with Alemtuzumab at a referral MS center. Both sNfL and sGFAP were analyzed at baseline and then again at 6, 12, and 24 months post-treatment using the single molecule array (SiMoA) technique. We also recruited matched healthy controls (HCs) for comparison.ResultsThe study included 46 patients (with a median age of 34.2 [Interquartile range (IQR), 28.7–42.3] years, 27 of which were women [58%]) and 76 HCs. No differences in demographic characteristics were observed between patients and HC. The median disease duration was 6.22 (IQR, 1.56–10.13) years. The median annualized relapse rate before treatment was 2 (IQR, 1–3). At baseline, sNfL and sGFAP levels were higher in MS patients (median of 18.8 [IQR, 10.7–52.7] pg/ml and 158.9 [IQR, 126.9–255.5] pg/ml, respectively) when compared to HC (6.11 [IQR, 2.03–8.54] pg/ml and 91.0 [72.6–109] pg/ml, respectively) (p