Exploring the disruptions of the neurophysiological organization in Alzheimer's disease: An integrative approach.

BACKGROUND AND OBJECTIVE: Alzheimer's disease (AD) is a neurological disorder that impairs brain functions associated with cognition, memory, and behavior. Noninvasive neurophysiological techniques like magnetoencephalography (MEG) and electroencephalography (EEG) have shown promise in reflecting brain changes related to AD. These techniques are usually assessed at two levels: local activation (spectral, nonlinear, and dynamic properties) and global synchronization (functional connectivity, frequency-dependent network, and multiplex network organization characteristics). Nonetheless, the understanding of the organization formed by the existing relationships between these levels, henceforth named neurophysiological organization, remains unexplored. This work aims to assess the alterations AD causes in the resting-state neurophysiological organization. METHODS: To that end, three datasets from healthy controls (HC) and patients with dementia due to AD were considered: MEG database (55 HC and 87 patients with AD), EEG1 database (51 HC and 100 patients with AD), and EEG2 database (45 HC and 82 patients with AD). To explore the alterations induced by AD in the relationships between several features extracted from M/EEG data, association networks (ANs) were computed. ANs are graphs, useful to quantify and visualize the intricate relationships between multiple features. RESULTS: Our results suggested a disruption in the neurophysiological organization of patients with AD, exhibiting a greater inclination towards the local activation level; and a significant decrease in the complexity and diversity of the ANs (p-value ¡ 0.05, Mann-Whitney U-test, Bonferroni correction). This effect might be due to a shift of the neurophysiological organization towards more regular configurations, which may increase its vulnerability. Moreover, our findings support the crucial role played by the local activation level in maintaining the stability of the neurophysiological organization. Classification performance exhibited accuracy values of 83.91%, 73.68%, and 72.65% for MEG, EEG1, and EEG2 databases, respectively. CONCLUSION: This study introduces a novel, valuable methodology able to integrate parameters characterize different properties of the brain activity and to explore the intricate organization of the neurophysiological organization at different levels. It was noted that AD increases susceptibility to changes in functional neural organization, suggesting a greater ease in the development of severe impairments. Therefore, ANs could facilitate a deeper comprehension of the complex interactions in brain function from a global standpoint.

AG-920 (Articaine) Ophthalmic Solution: A Masked, Active-Controlled Evaluation of Its Local Anesthetic Efficacy and Safety in Pediatric Patients.

Purpose: The safety and efficacy of a novel topical ocular anesthetic (AG-920 sterile ophthalmic solution, 8%) was previously evaluated in adults. For both clinical and regulatory purposes, this new agent was evaluated in children. Methods: This was a Phase 3, randomized, active-controlled, single-masked, parallel-group design study in healthy pediatric subjects performed at a private practice retina clinic in the United States. The safety and anesthetic efficacy of AG-920 was compared with proparacaine hydrochloride ophthalmic solution 0.5% in 60 children undergoing ophthalmic examinations. The primary efficacy endpoint was whether the investigator was able to perform the eye examination. Results: In all subjects in each treatment group, the investigator was able to perform the eye examination without additional local anesthetic. There were no adverse events reported in this study. In both the study eye and fellow eye, there were no notable changes after dosing, and both treatment groups were similar. All external eye exams in all subjects in both treatment groups were normal. Conclusions: In this pediatric population aged 7 months to >11 years, AG-920 was therapeutically equivalent to marketed proparacaine with respect to having an ophthalmic examination performed without needing additional local anesthetic. Further, AG-920 was well tolerated, and there were no clinically significant safety findings.

Low-Density Lipoproteins Increase Proliferation, Invasion, and Chemoresistance via an Exosome Autocrine Mechanism in MDA-MB-231 Chemoresistant Cells.

Dyslipidemias involving high concentrations of low-density lipoproteins (LDLs) increase the risk of developing triple-negative breast cancer (TNBC), wherein cholesterol metabolism and protein translation initiation mechanisms have been linked with chemoresistance. Doxorubicin (Dox) treatment, a member of the anthracycline family, represents a typical therapeutic strategy; however, chemoresistance remains a significant challenge. Exosomes (Exs) secreted by tumoral cells have been implicated in cell communication pathways and chemoresistance mechanisms; the content of exosomes is an outcome of cellular cholesterol metabolism. We previously induced Dox resistance in TNBC cell models, characterizing a variant denominated as variant B cells. Our results suggest that LDL internalization in parental and chemoresistant variant B cells is associated with increased cell proliferation, migration, invasion, and spheroid growth. We identified the role of eIF4F translation initiation factor and the down-regulation of tumor suppressor gene PDCD4, an inhibitor of eIF4A, in chemoresistant variant B cells. In addition, the exomes secreted by variant B cells were characterized by the protein content, electronic microscopy, and cell internalization assays. Critically, exosomes purified from LDL-treated variant B cell promoted cell proliferation, migration, and an increment in lactate concentration. Our results suggest that an autocrine phenomenon induced by exosomes in chemoresistant cells may induce modifications on signaling mechanisms of the p53/Mdm2 axis and activation of p70 ribosomal protein kinase S6. Moreover, the specific down-regulated profile of chaperones Hsp90 and Hsp70 secretion inside the exosomes of the chemoresistant variant could be associated with this phenomenon. Therefore, autocrine activation mediated by exosomes and the effect of LDL internalization may influence changes in exosome chaperone content and modulate proliferative signaling pathways, increasing the aggressiveness of MDA-MB-231 chemoresistant cells.

Exploring antioxidant strategies in the pathogenesis of ALS.

The central nervous system is essential for maintaining homeostasis and controlling the body's physiological functions. However, its biochemical characteristics make it highly vulnerable to oxidative damage, which is a common factor in neurodegenerative diseases like amyotrophic lateral sclerosis (ALS). ALS is a leading cause of motor neuron disease, characterized by a rapidly progressing and incurable condition. ALS often results in death from respiratory failure within 3-5 years from the onset of the first symptoms, underscoring the urgent need to address this medical challenge. The aim of this study is to present available data supporting the role of oxidative stress in the mechanisms underlying ALS and to discuss potential antioxidant therapies currently in development. These therapies aim to improve the quality of life and life expectancy for patients affected by this devastating disease.

Reshaping Smart Cities through NGSI-LD Enrichment.

The vast amount of information stemming from the deployment of the Internet of Things and open data portals is poised to provide significant benefits for both the private and public sectors, such as the development of value-added services or an increase in the efficiency of public services. This is further enhanced due to the potential of semantic information models such as NGSI-LD, which enable the enrichment and linkage of semantic data, strengthened by the contextual information present by definition. In this scenario, advanced data processing techniques need to be defined and developed for the processing of harmonised datasets and data streams. Our work is based on a structured approach that leverages the principles of linked-data modelling and semantics, as well as a data enrichment toolchain framework developed around NGSI-LD. Within this framework, we reveal the potential for enrichment and linkage techniques to reshape how data are exploited in smart cities, with a particular focus on citizen-centred initiatives. Moreover, we showcase the effectiveness of these data processing techniques through specific examples of entity transformations. The findings, which focus on improving data comprehension and bolstering smart city advancements, set the stage for the future exploration and refinement of the symbiosis between semantic data and smart city ecosystems.

Bees display limited acclimation capacity for heat tolerance.

Bees are essential pollinators and understanding their ability to cope with extreme temperature changes is crucial for predicting their resilience to climate change, but studies are limited. We measured the response of the critical thermal maximum (CTMax) to short-term acclimation in foragers of six bee species from the Greek island of Lesvos, which differ in body size, nesting habit, and level of sociality. We calculated the acclimation response ratio as a metric to assess acclimation capacity and tested whether bees' acclimation capacity was influenced by body size and/or CTMax. We also assessed whether CTMax increases following acute heat exposure simulating a heat wave. Average estimate of CTMax varied among species and increased with body size but did not significantly shift in response to acclimation treatment except in the sweat bee Lasioglossum malachurum. Acclimation capacity averaged 9% among species and it was not significantly associated with body size or CTMax. Similarly, the average CTMax did not increase following acute heat exposure. These results indicate that bees might have limited capacity to enhance heat tolerance via acclimation or in response to prior heat exposure, rendering them physiologically sensitive to rapid temperature changes during extreme weather events. These findings reinforce the idea that insects, like other ectotherms, generally express weak plasticity in CTMax, underscoring the critical role of behavioral thermoregulation for avoidance of extreme temperatures. Conserving and restoring native vegetation can provide bees temporary thermal refuges during extreme weather events.

Manipulating the insulating post arrangement in DC-biased AC-iEK devices to improve microparticle separations.

There is a growing interest in the advancement of microscale electrokinetic (EK) systems for biomedical and clinical applications, as these systems offer attractive characteristics such as portability, robustness, low sample requirements and short response time. The present work is focused on manipulating the characteristics of the insulating post arrangement in insulator-based EK (iEK) systems for separating a binary mixture of spherical microparticles with same diameter (5.1 µm), same shape, made from the same substrate material and only differing in their zeta potential by ∼14 mV. This study presents a combination of mathematical modeling and experimental separations performed by applying a low-frequency alternating current (AC) voltage in iEK systems with 12 distinct post arrangements. These iEK devices were used to systematically study the effect of three spatial characteristics of the insulating post array on particle separations: the horizontal separation and the vertical separation between posts, and introducing an offset to the posts arrangement. Through normalization of the spatial separation between the insulating posts with respect to particle diameter, guidelines to improve separation resolution for different particle mixtures possessing similar characteristics were successfully identified. The results indicated that by carefully designing the spatial arrangement of the post array, separation resolution values in the range of 1.4-2.8 can be obtained, illustrating the importance and effect of the arrangement of insulating posts on improving particle separations. This study demonstrates that iEK devices, with effectively designed spatial arrangement of the insulating post arrays, have the capabilities to perform discriminatory separations of microparticles of similar characteristics.

Suppression of Dexter transfer by covalent encapsulation for efficient matrix-free narrowband deep blue hyperfluorescent OLEDs.

Hyperfluorescence shows great promise for the next generation of commercially feasible blue organic light-emitting diodes, for which eliminating the Dexter transfer to terminal emitter triplet states is key to efficiency and stability. Current devices rely on high-gap matrices to prevent Dexter transfer, which unfortunately leads to overly complex devices from a fabrication standpoint. Here we introduce a molecular design where ultranarrowband blue emitters are covalently encapsulated by insulating alkylene straps. Organic light-emitting diodes with simple emissive layers consisting of pristine thermally activated delayed fluorescence hosts doped with encapsulated terminal emitters exhibit negligible external quantum efficiency drops compared with non-doped devices, enabling a maximum external quantum efficiency of 21.5%. To explain the high efficiency in the absence of high-gap matrices, we turn to transient absorption spectroscopy. It is directly observed that Dexter transfer from a pristine thermally activated delayed fluorescence sensitizer host can be substantially reduced by an encapsulated terminal emitter, opening the door to highly efficient 'matrix-free' blue hyperfluorescence.

Public support for and concerns regarding pediatric dose optimization for seizures in emergency medical services: An exception from informed consent (EFIC) trial.

BACKGROUND: Federal regulations allow exception from informed consent (EFIC) to study emergent conditions when obtaining prospective consent is not feasible. Little is known about public views on including children in EFIC studies. The Pediatric Dose Optimization for Seizures in EMS (PediDOSE) trial implements age-based, standardized midazolam dosing for pediatric seizures. The primary objective of this study was to determine public support for and concerns about the PediDOSE EFIC trial. The secondary objective was to assess how support for PediDOSE varied by demographics. METHODS: We conducted a mixed-methods study in 20 U.S. communities. Participants reviewed information about PediDOSE before completing an online survey. Descriptive data were generated. Univariable and multivariable logistic regression analysis identified factors associated with support for PediDOSE. Reviewers identified themes from free-text response data regarding participant concerns. RESULTS: Of 2450 respondents, 79% were parents/guardians, and 20% had a child with previous seizures. A total of 96% of respondents supported PediDOSE being conducted, and 70% approved of children being enrolled without prior consent. Non-Hispanic Black respondents were less likely than non-Hispanic White respondents to support PediDOSE with an adjusted odds ratio (aOR) of 0.57 (95% CI 0.42-0.75). Health care providers were more likely to support PediDOSE, with strongest support among prehospital emergency medicine clinicians (aOR 5.82, 95% CI 3.19-10.62). Age, gender, parental status, and level of education were not associated with support of PediDOSE. Common concerns about PediDOSE included adverse effects, legal and ethical concerns about enrolling without consent, and potential racial bias. CONCLUSIONS: In communities where this study will occur, most respondents supported PediDOSE being conducted with EFIC and most approved of children being enrolled without prior consent. Support was lowest among non-Hispanic Black respondents and highest among health care providers. Further research is needed to determine optimal ways to address the concerns of specific racial and ethnic groups when conducting EFIC trials.

A Connector for Integrating NGSI-LD Data into Open Data Portals.

Nowadays, there are plenty of data sources generating massive amounts of information that, combined with novel data analytics frameworks, are meant to support optimisation in many application domains. Nonetheless, there are still shortcomings in terms of data discoverability, accessibility and interoperability. Open Data portals have emerged as a shift towards openness and discoverability. However, they do not impose any condition to the data itself, just stipulate how datasets have to be described. Alternatively, the NGSI-LD standard pursues harmonisation in terms of data modelling and accessibility. This paper presents a solution that bridges these two domains (i.e., Open Data portals and NGSI-LD-based data) in order to keep benefiting from the structured description of datasets offered by Open Data portals, while ensuring the interoperability provided by the NGSI-LD standard. Our solution aggregates the data into coherent datasets and generate high-quality descriptions, ensuring comprehensiveness, interoperability and accessibility. The proposed solution has been validated through a real-world implementation that exposes IoT data in NGSI-LD format through the European Data Portal (EDP). Moreover, the results from the Metadata Quality Assessment that the EDP implements, show that the datasets' descriptions generated achieve excellent ranking in terms of the Findability, Accessibility, Interoperability and Reusability (FAIR) data principles.

Assessment of risk-adjusted mortality ratio (RAMR) in bloodstream infections using all-patient refined diagnosis-related groups (APR-DRGs).

OBJECTIVES: To calculate a risk-adjusted mortality ratio (RAMR) for bloodstream infections (BSIs) using all-patient refined diagnosis-related groups (APR-DRGs) and compare it with the crude mortality rate (CMR). METHODS: Retrospective observational study of prevalent BSI at our institution from January 2019 to December 2022. In-hospital mortality was adjusted with a binary logistic regression model adjusting for sex, age, admission type and mortality risk for the hospitalization episode according to the four severity levels of APR DRGs. The RAMR was calculated as the ratio of observed to expected in-hospital mortality, and the CMR was calculated as the proportion of deaths among all bacteraemia episodes. RESULTS: Of 2939 BSIs, 2541 were included: Escherichia coli (n = 1310), Klebsiella pneumoniae (n = 428), Pseudomonas aeruginosa (n = 209), Staphylococcus aureus (n = 498) and candidaemia (n = 96). A total of 436 (17.2%) patients died during hospitalization and 279 died within the first 14 days after the onset of BSI. Throughout the period, all BSI cases had a mortality rate above the expected adjusted mortality (RAMR value greater than 1), except for Escherichia coli (1.03; 95% CI 0.86-1.21). The highest overall RAMR values were observed for P. aeruginosa, Candida and S. aureus with 2.06 (95% CI 1.57-2.62), 1.99 (95% CI 1.3-2.81) and 1.8 (95% CI 1.47-2.16), respectively. The temporal evolution of CMR may differ from RAMR, especially in E. coli, where it was reversed. CONCLUSIONS: RAMR showed higher than expected mortality for all BSIs studied except E. coli and provides complementary to and more clinically comprehensive information than CMR, the currently recommended antibiotic stewardship programme mortality indicator.

Enhancing ACLF prediction by integrating sarcopenia assessment and frailty in liver transplant candidates on the waiting list.

Background & Aims: Malnutrition, sarcopenia, and frailty are prevalent in cirrhosis. We aimed to assess the correlation between assessment tools for malnutrition, sarcopenia, and frailty in patients on the liver transplant (LT) waiting list (WL), and to identify a predictive model for acute-on-chronic liver failure (ACLF) development. Methods: This prospective single-center study enrolled consecutive patients with cirrhosis on the WL for LT (May 2019-November 2021). Assessments included subjective global assessment, CT body composition, skeletal muscle index (SMI), ultrasound thigh muscle thickness, sarcopenia HIBA score, liver frailty index (LFI), hand grip strength, and 6-minute walk test at enrollment. Correlations were analyzed using Pearson's correlation. Competing risk regression analysis was used to assess the predictive ability of the liver- and functional physiological reserve-related variables for ACLF. Results: A total of 132 patients, predominantly with decompensated cirrhosis (87%), were included. Our study revealed a high prevalence of malnutrition (61%), sarcopenia (61%), visceral obesity (20%), sarcopenic visceral obesity (17%), and frailty (10%) among participants. Correlations between the assessment tools for sarcopenia and frailty were poor. Sarcopenia by SMI remained prevalent when frailty assessments were not usable. After a median follow-up of 10 months, 39% of the patients developed ACLF on WL, while 28% experienced dropouts without ACLF. Multivariate analysis identified MELD-Na, SMI, and LFI as independent predictors of ACLF on the WL. The predictive model MELD-Na-sarcopenia-LFI had a C-statistic of 0.85. Conclusions: The poor correlation between sarcopenia assessment tools and frailty underscores the importance of a comprehensive evaluation. The SMI, LFI, and MELD-Na independently predicted ACLF development in WL. These findings enhance our understanding of the relationship between sarcopenia, frailty, and ACLF in patients awaiting LT, emphasizing the need for early detection and intervention to improve WL outcomes. Impact and implications: The relationship between sarcopenia and frailty assessment tools, as well as their ability to predict acute-on-chronic liver failure (ACLF) in patients on the liver transplant (LT) waiting list (WL), remains poorly understood. Existing objective frailty screening tests have limitations when applied to critically ill patients. The correlation between sarcopenia and frailty assessment tools was weak, suggesting that they may capture different phenotypes. Sarcopenia assessed by skeletal muscle index, frailty evaluated using the liver frailty index, and the model for end-stage liver disease-Na score independently predicted the development of ACLF in patients on the WL. Our findings support the integration of liver frailty index and skeletal muscle index assessments at the time of inclusion on the WL for LT. This combined approach allows for the identification of a specific patient subgroup with an increased susceptibility to ACLF, underscoring the importance of early implementation of targeted treatment strategies to improve outcomes for patients awaiting LT.

Neuropeptide expression and action in the reproductive system of the starfish Asterias rubens.

Reproductive processes are regulated by a variety of neuropeptides in vertebrates and invertebrates. In starfish (phylum Echinodermata), relaxin-like gonad-stimulating peptide triggers oocyte maturation and spawning. However, little is known about other neuropeptides as potential regulators of reproduction in starfish. To address this issue, here, we used histology and immunohistochemistry to analyze the reproductive system of the starfish Asterias rubens at four stages of the seasonal reproductive cycle in male and female animals, investigating the expression of eight neuropeptides: the corticotropin-releasing hormone-type neuropeptide ArCRH, the calcitonin-type neuropeptide ArCT, the pedal peptide-type neuropeptides ArPPLN1b and ArPPLN2h, the vasopressin/ocytocin-type neuropeptide asterotocin, the gonadotropin-releasing hormone-type neuropeptide ArGnRH, and the somatostatin/allatostatin-C-type neuropeptides ArSS1 and ArSS2. The expression of five neuropeptides, ArCRH, ArCT, ArPPLN1b, ArPPLN2h, and asterotocin, was detected in the gonoducts and/or gonads. For example, extensive ArPPLN2h expression was revealed in the coelomic epithelial layer of the gonads throughout the seasonal reproductive cycle in both males and females. However, seasonal and/or sexual differences in the patterns of neuropeptide expression were also observed. Informed by these findings, the in vitro pharmacological effects of neuropeptides on gonad preparations from male and female starfish were investigated. This revealed that ArSS1 causes gonadal contraction and that ArPPLN2h causes gonadal relaxation, with both neuropeptides being more effective on ovaries than testes. Collectively, these findings indicate that multiple neuropeptide signaling systems are involved in the regulation of reproductive function in starfish, with some neuropeptides exerting excitatory or inhibitory effects on gonad contractility that may be physiologically relevant when gametes are expelled during spawning.

Ocular, Visual, and Anatomical Outcomes in Eyes Requiring Incisional Intraocular Pressure-Lowering Surgery Following the 0.19-mg Fluocinolone Acetonide Intravitreal Implant.

BACKGROUND AND OBJECTIVE: To assess ocular, visual, and anatomical outcomes following the 0.19-mg fluocinolone acetonide (FAc) intravitreal implant (ILUVIEN®) and incisional intraocular pressure (IOP)-lowering surgery in diabetic macular edema. PATIENTS AND METHODS: From a 36-month, phase 4, open-label, observational study (N = 202 eyes, 159 patients), 8 eyes (7 patients) required IOP-lowering surgery post-FAc; eyes were segregated by FAc-induced (n = 5, 2.47%) versus neovascular glaucoma (NVG)-related (n = 3, 1.49%) IOP elevations and assessed for IOP, best corrected visual acuity (BCVA), central subfield thickness (CST), and cup-to-disc ratio (c/d). RESULTS: Changes at 36 months were +5.4 letters BCVA (P > 0.05) and +0.09 c/d (P = 0.0217); IOP and CST were unchanged. FAc-induced-group eyes required fewer IOP-lowering medications than NVG-group eyes (2.0 versus 4.0; P < 0.01) but for longer duration (15.2 versus 2.6 months; P < 0.001). CONCLUSIONS: Post-FAc IOP-lowering surgery, regardless of cause, largely did not affect the outcomes measured; these procedures, then, may not meaningfully threaten positive outcomes. [Ophthalmic Surg Lasers Imaging Retina 2024;55:22-29.].

Relation between task-related activity modulation and cortical inhibitory function in schizophrenia and healthy controls: a TMS-EEG study.

Schizophrenia has been associated with a reduced task-related modulation of cortical activity assessed through electroencephalography (EEG). However, to the best of our knowledge, no study so far has assessed the underpinnings of this decreased EEG modulation in schizophrenia. A possible substrate of these findings could be a decreased inhibitory function, a replicated finding in the field. In this pilot study, our aim was to explore the association between EEG modulation during a cognitive task and the inhibitory system function in vivo in a sample including healthy controls and patients with schizophrenia. We hypothesized that the replicated decreased task-related activity modulation during a cognitive task in schizophrenia would be related to a hypofunction of the inhibitory system. For this purpose, 27 healthy controls and 22 patients with schizophrenia (including 13 first episodes) performed a 3-condition auditory oddball task from which the spectral entropy modulation was calculated. In addition, cortical reactivity-as an index of the inhibitory function-was assessed by the administration of 75 monophasic transcranial magnetic stimulation single pulses over the left dorsolateral prefrontal cortex. Our results replicated the task-related cortical activity modulation deficit in schizophrenia patients. Moreover, schizophrenia patients showed higher cortical reactivity following transcranial magnetic stimulation single pulses over the left dorsolateral prefrontal cortex compared to healthy controls. Cortical reactivity was inversely associated with EEG modulation, supporting the idea that a hypofunction of the inhibitory system could hamper the task-related modulation of EEG activity.

Self-Diagnosis of SARS-CoV-2 from Saliva Samples at Home: Isothermal Amplification Enabled by Do-It-Yourself Portable Incubators and Laminated Poly-ethyl Sulfonate Membranes.

COVID-19 made explicit the need for rethinking the way in which we conduct testing for epidemic emergencies. During the COVID-19 pandemic, the dependence on centralized lab facilities and resource-intensive methodologies (e.g., RT-qPCR methods) greatly limited the deployment of widespread testing efforts in many developed and underdeveloped countries. Here, we illustrate the development of a simple and portable diagnostic kit that enables self-diagnosis of COVID-19 at home from saliva samples. We describe the development of a do-it-yourself (DIY) incubator for Eppendorf tubes that can be used to conduct SARS-CoV-2 detection with competitive sensitivity and selectivity from saliva at home. In a proof-of-concept experiment, we assembled Eppendorf-tube incubators at our home shop, prepared a single-tube mix of reagents and LAMP primers in our lab, and deployed these COVID-19 detection kits using urban delivery systems (i.e., Rappifavor or Uber) to more than 15 different locations in Monterrey, México. This straightforward strategy enabled rapid and cost-effective at-home molecular diagnostics of SARS-CoV-2 from real saliva samples with a high sensitivity (100%) and high selectivity (87%).

Fitness benefits of alternated chick provisioning in cooperatively breeding carrion crows.

In most bird species, parents raise offspring cooperatively. In some cases, this cooperation extends to helpers-at-the-nest who assist the breeders with a range of tasks. While cooperative food provisioning might merely arise incidentally, as a result of the efforts of carers that act independently from each other, recent studies suggest that birds may coordinate by taking turns in visiting the nest. However, evidence that such coordination emerges because individuals actively respond to each other's behaviour is controversial, and the potential benefits of carers' alternation remain unknown. We addressed this knowledge gap by analysing a multiyear dataset for cooperatively breeding carrion crows Corvus corone, comprising 8693 nest visits across 50 groups. Our results reveal that turn-taking does occur in this species and that all group members, regardless of their sex and social role (breeder/helper), tend to alternate at the nest with other carers rather than to make repeat visits. Importantly, we found that the body mass of nestlings increased significantly with the degree of carers' alternation, possibly because well-coordinated groups provided food at more regular intervals. Using earlier monitoring data, the observed increase in body mass is predicted to substantially boost postfledging survival rates. Our analyses demonstrate that alternation in nestling provisioning has measurable fitness benefits in this study system. This raises the possibility that cooperatively breeding carrion crows, as well as other bird species with similarly coordinated brood provisioning, exhibit specialized behavioural strategies that enable effective alternation.

En la mayoría de las especies de aves, los padres cooperan entre sí en el cuidado de sus crías. En algunos casos, la cooperación se extiende a individuos ayudantes que asisten a los reproductores en diferentes tareas. El aprovisionamiento cooperativo de las crías puede darse simplemente como resultado del esfuerzo de cuidadores que actúan de forma independiente, pero estudios recientes sugieren que las aves pueden coordinarse, tomando turnos a la hora de visitar el nido. Sin embargo, las evidencias de que dicha coordinación ocurre porque los individuos realmente responden al comportamiento de los demás es controvertida, y los potenciales beneficios de la alternancia al nido son desconocidos. Nosotros abordamos estos aspectos analizando una base de datos plurianual en la corneja negra Corvus corone, que incluye 8693 visitas al nido en 50 grupos. Nuestros resultados revelan que se produce toma de turnos en esta especie y que todos los miembros del grupo, independientemente del sexo y del estatus social (reproductor / ayudante), tienden a alternarse al nido con otros cuidadores, en vez de repetir visitas. Más importante aún, encontramos que la masa corporal de los polluelos aumentaba de forma significativa al aumentar el grado de coordinación de los cuidadores, posiblemente porque los grupos mejor coordinados aprovisionaban las crías a intervalos más regulares. Basándonos en datos anteriores, pudimos calcular que el incremento observado en masa corporal predice un aumento sustancial de la tasa de supervivencia de los volanderos. Nuestros análisis demuestran, por lo tanto, que la alternancia al nido tiene beneficios medibles en eficacia biológica. Esto conlleva la posibilidad de que las cornejas negras cooperativas, al igual que otras especies de aves con aprovisionamiento coordinado de las crías, exhiban estrategias comportamentales especializadas que permitan una eficiente alternancia al nido.

LIGHTSITE III: 13-Month Efficacy and Safety Evaluation of Multiwavelength Photobiomodulation in Nonexudative (Dry) Age-Related Macular Degeneration Using the Lumithera Valeda Light Delivery System.

PURPOSE: The LIGHTSITE III study evaluated multiwavelength photobiomodulation (PBM) therapy in nonexudative (dry) age-related macular degeneration (AMD) using the LumiThera Valeda Light Delivery System. METHODS: LIGHTSITE III is a randomized, controlled trial to assess the safety and effectiveness of PBM in dry AMD. Subjects were given multiwavelength PBM (590, 660, and 850 nm) or Sham treatment delivered in a series of nine sessions over 3 to 5 weeks every four months over 24 months. Subjects were assessed for efficacy and safety outcomes. Data from the 13-month analysis are presented in this report. RESULTS: A total of 100 subjects (148 eyes) with dry AMD were randomized. LIGHTSITE III met the primary efficacy best-corrected visual acuity endpoint with a significant difference between PBM (n = 91 eyes) and Sham (n = 54 eyes) groups (Between group difference: 2.4 letters (SE 1.15), CI: -4.7 to -0.1, P = 0.02) (PBM alone: 5.4 letters (SE 0.96), CI: 3.5 to 7.3, P < 0.0001; Sham alone: 3.0 letters (SE 1.13), CI: 0.7-5.2, P < 0.0001). The PBM group showed a significant decrease in new onset geographic atrophy ( P = 0.024, Fisher exact test, odds ratio 9.4). A favorable safety profile was observed. CONCLUSION: LIGHTSITE III provides a prospective, randomized, controlled trial showing improved clinical and anatomical outcomes in intermediate dry AMD following PBM therapy.

Trends and challenges in microfluidic methods for protein manipulation-A review.

Proteins are important molecules involved in an immensely large number of biological processes. Being capable of manipulating proteins is critical for developing reliable and affordable techniques to analyze and/or detect them. Such techniques would enable the production of therapeutic agents for the treatment of diseases or other biotechnological applications (e.g., bioreactors or biocatalysis). Microfluidic technology represents a potential solution to protein manipulation challenges because of the diverse phenomena that can be exploited to achieve micro- and nanoparticle manipulation. In this review, we discuss recent contributions made in the field of protein manipulation in microfluidic systems using different physicochemical principles and techniques, some of which are miniaturized versions of already established macro-scale techniques.