Structure of a Pancreatic ATP-Sensitive Potassium Channel.

ATP-sensitive potassium channels (KATP) couple intracellular ATP levels with membrane excitability. These channels play crucial roles in many essential physiological processes and have been implicated extensively in a spectrum of metabolic diseases and disorders. To gain insight into the mechanism of KATP, we elucidated the structure of a hetero-octameric pancreatic KATP channel in complex with a non-competitive inhibitor glibenclamide by single-particle cryoelectron microscopy to 5.6-Å resolution. The structure shows that four SUR1 regulatory subunits locate peripherally and dock onto the central Kir6.2 channel tetramer through the SUR1 TMD0-L0 fragment. Glibenclamide-bound SUR1 uses TMD0-L0 fragment to stabilize Kir6.2 channel in a closed conformation. In another structural population, a putative co-purified phosphatidylinositol 4,5-bisphosphate (PIP2) molecule uncouples Kir6.2 from glibenclamide-bound SUR1. These structural observations suggest a molecular mechanism for KATP regulation by anti-diabetic sulfonylurea drugs, intracellular adenosine nucleotide concentrations, and PIP2 lipid.

Personalized Therapeutics for KATP-Dependent Pathologies.

Ubiquitously expressed throughout the body, ATP-sensitive potassium (KATP) channels couple cellular metabolism to electrical activity in multiple tissues; their unique assembly as four Kir6 pore-forming subunits and four sulfonylurea receptor (SUR) subunits has resulted in a large armory of selective channel opener and inhibitor drugs. The spectrum of monogenic pathologies that result from gain- or loss-of-function mutations in these channels, and the potential for therapeutic correction of these pathologies, is now clear. However, while available drugs can be effective treatments for specific pathologies, cross-reactivity with the other Kir6 or SUR subfamily members can result in drug-induced versions of each pathology and may limit therapeutic usefulness. This review discusses the background to KATP channel physiology, pathology, and pharmacology and considers the potential for more specific or effective therapeutic agents.

Sulfonylurea receptor 2 (SUR2), intricate sensors for intracellular Mg-nucleotides.

SUR2, similar to SUR1, is a regulatory subunit of the ATP-sensitive potassium channel (KATP), which plays a key role in numerous important physiological processes and is implicated in various diseases. Recent structural studies have revealed that, like SUR1, SUR2 can undergo ligand-dependent dynamic conformational changes, transitioning between an inhibitory inward-facing conformation and an activating occluded conformation. In addition, SUR2 possesses a unique inhibitory Regulatory helix (R helix) that is absent in SUR1. The binding of the activating Mg-ADP to NBD2 of SUR2 competes with the inhibitory Mg-ATP, thereby promoting the release of the R helix and initiating the activation process. Moreover, the signal generated by Mg-ADP binding to NBD2 might be directly transmitted to the TMD of SUR2, prior to NBD dimerization. Furthermore, the C-terminal 42 residues (C42) of SUR2 might allosterically regulate the kinetics of Mg-nucleotide binding on NBD2. These distinctive properties render SUR2 intricate sensors for intracellular Mg-nucleotides.

Novel loss-of-function variants expand ABCC9-related intellectual disability and myopathy syndrome.

Loss-of-function mutation of ABCC9, the gene encoding the SUR2 subunit of ATP sensitive-potassium (KATP) channels, was recently associated with autosomal recessive ABCC9-related intellectual disability and myopathy syndrome (AIMS). Here we identify nine additional subjects, from seven unrelated families, harbouring different homozygous loss-of-function variants in ABCC9 and presenting with a conserved range of clinical features. All variants are predicted to result in severe truncations or in-frame deletions within SUR2, leading to the generation of non-functional SUR2-dependent KATP channels. Affected individuals show psychomotor delay and intellectual disability of variable severity, microcephaly, corpus callosum and white matter abnormalities, seizures, spasticity, short stature, muscle fatigability and weakness. Heterozygous parents do not show any conserved clinical pathology but report multiple incidences of intra-uterine fetal death, which were also observed in an eighth family included in this study. In vivo studies of abcc9 loss-of-function in zebrafish revealed an exacerbated motor response to pentylenetetrazole, a pro-convulsive drug, consistent with impaired neurodevelopment associated with an increased seizure susceptibility. Our findings define an ABCC9 loss-of-function-related phenotype, expanding the genotypic and phenotypic spectrum of AIMS and reveal novel human pathologies arising from KATP channel dysfunction.

A novel ABCC9 variant in a Greek family with Cantu syndrome affecting multiple generations highlights the functional role of the SUR2B NBD1.

Cantu syndrome (CS) (OMIM #239850) is an autosomal dominant multiorgan system condition, associated with a characteristic facial phenotype, hypertrichosis, and multiple cardiovascular complications. CS is caused by gain-of-function (GOF) variants in KCNJ8 or ABCC9 that encode pore-forming Kir6.1 and regulatory SUR2 subunits of ATP-sensitive potassium (KATP) channels. A novel heterozygous ABCC9 variant, c.2440G>T; p.Gly814Trp, was identified in three individuals from a four generation Greek family. The membrane potential in cells stably expressing hKir6.1 and hSUR2B with p.Gly814Trp was hyperpolarized compared to cells expressing WT channels, and inside-out patch-clamp assays of KATP channels formed with hSUR2B p.Gly814Trp demonstrated a decreased sensitivity to ATP inhibition, confirming a relatively mild GOF effect of this variant. The specific location of the variant reveals an unrecognized functional role of the first glycine in the signature motif of the nucleotide binding domains in ATP-binding cassette (ABC) protein ion channels.

Mitotic spindle positioning protein serves as prognostic biomarker in patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) ranks among the most aggressive types of cancer globally. Currently, clinical tumor prognostic biomarkers still lack accuracy. Mitotic spindle positioning (MISP) protein connects microtubules to the actin cytoskeleton and adhesive plaques, playing a critical role in spindle positioning, orientation, and the process of cell division. MISP can regulate the malignant biological functions of pancreatic cancer and intrahepatic cholangiocarcinoma and it acts as biomarker for prognosis, but its role in CRC remains unclear. METHODS: This study has collected 37 CRC tissue samples and 37 corresponding adjacent nontumor tissue samples, and 57 additional CRC tissues samples. Clinical data were obtained from the patients with CRC. MISP mRNA and protein expression levels were analyzed in normal control and CRC tissues using the GEPIA and Human Protein Atlas website. MISP protein levels in the collected tissues were analyzed using immunohistochemistry. RESULTS: MISP mRNA and protein expression levels were significantly increased in CRC tissues compared to adjacent nontumor tissues. Higher MISP protein levels were associated with distant metastasis, recurrence, and lower survival rates. Kaplan-Meier analysis showed that high expression levels of MISP protein were associated with recurrence and death in CRC patients. In addition, a high expression level of MISP protein, lymph node metastasis, and distance metastasis were risk factors for recurrence and a poor prognosis in patients with CRC. CONCLUSION: Elevated MISP protein correlated with tumor metastasis, recurrence, and lower survival rates in patients with CRC, and thus, MISP has the potential to become a prognostic marker for CRC.

The scope of empowerment for conservation and communities.

Conservationists increasingly position conservation that is mutually beneficial to people and biodiversity on the promise of empowerment of people through participatory discourse, metrics, processes, and outcomes. Empowerment represents multidimensional concepts and theories that permeate the interlinking levels of power, from the psychological to the political, and social scales in which conservation operates. The multifaceted nature of empowerment makes it challenging to understand, pursue, and evaluate as a central philosophical commitment and goal-oriented practice in conservation. Moreover, definitional and methodological uncertainty may disempower interested and affected groups because they can foster conceptual assumptions that reinforce institutionalized barriers to systemic changes. Despite these complexities, there are no targeted reviews of empowerment in conservation. We conducted a scoping review of the conservation literature to synthesize the meanings and uses of empowerment in the field. We reviewed 121 of the most cited conservation articles that invoked or assessed empowerment from 1992 to 2017 to document geographic, conceptual, and methodological trends in the scales and theories of empowerment deployed by conservationists. Research claiming or assessing empowerment through conservation often focused on communities in the Global South. Most studies relied on qualitative and mixed methods (78%) collected largely from male or non-Indigenous participants. Few studies (30%) defined the 20 types of empowerment they referenced. Fewer studies (3%) applied empowerment theories in their work. Our findings show that empowerment discourse of local and Indigenous communities permeates the discourse of people-centered conservation. Yet, overreliance on empowerment's rhetorical promise and minimal engagement with theory (e.g., postcolonial theory) risks disempowering people by obscuring empowerment's foundational value to conservation and communities and oversimplifying the complex realities of people-centered conservation. Lasting change could come from more meaningful engagement with empowerment, including coproducing definitions and measures with and for disempowered social groups to tackle widespread power disparities in conservation today.

El alcance del empoderamiento para la conservación y las comunidades Resumen Con frecuencia los conservacionistas posicionan a la conservación como benéfica para las personas y la biodiversidad mediante discursos, medidas, procesos y resultados participativos que prometen el empoderamiento de la gente. El empoderamiento representa conceptos y teorías multidimensionales que permean los niveles interconectados de poder, desde el psicológico al político, y las escalas sociales en las que opera la conservación. La naturaleza multifacética del empoderamiento complica que se entienda, se dé seguimiento y se evalúe como un compromiso filosófico central y una práctica orientada hacia las metas dentro de la conservación. Además, la incertidumbre metodológica y de definición pueden restar autoridad a los grupos interesados o afectados pues pueden promover suposiciones conceptuales que refuerzan las barreras institucionales de los cambios sistémicos. A pesar de estas complejidades, no existen revisiones focalizadas del empoderamiento en la conservación. Realizamos una revisión de alcance de la literatura de conservación para sintetizar los significados y usos de la palabra empoderamiento en este campo. Revisamos 121 de los artículos sobre conservación más citados que invocaron o evaluaron el empoderamiento entre 1992 y 2017 para documentar las tendencias geográficas, conceptuales y metodológicas en las escalas y teorías del empoderamiento usadas por los conservacionistas. La mayoría de los artículos que afirmaban o evaluaban el empoderamiento por medio de la conservación se enfocaron en comunidades del Sur Global. La mayoría de los estudios dependieron de métodos cualitativos y mixtos (78%) tomados principalmente de participantes masculinos o no indígenas. Pocos estudios (30%) definieron los 20 tipos de empoderamiento que referenciaron. Todavía menos estudios (3%) aplicaron las teorías de empoderamiento a su trabajo. Nuestros descubrimientos muestran que el discurso de empoderamiento de las comunidades locales e indígenas permea el discurso de la conservación centrada en la gente. Sin embargo, depender en exceso de la promesa retórica del empoderamiento e involucrarse en lo mínimo con la teoría (p. ej.: teoría postcolonial) arriesga que la gente se pierda autoridad al oscurecer el valor fundamental que tiene el empoderamiento para la conservación y las comunidades y simplificar sobremanera las realidades complejas de la conservación centrada en las personas. El cambio duradero podría venir de involucrarse de forma más significativa con el empoderamiento, lo que incluye la coproducción de definiciones y medidas con y para los grupos sociales no empoderados para resolver la disparidad de poder que existe hoy en día en la conservación.

A data-driven approach to multiple-stressor impact assessment for a marine protected area.

The coastal environment is not managed in a way that considers the impact of cumulative threats, despite being subject to threats from all realms (marine, land, and atmosphere). Relationships between threats and species are often nonlinear; thus, current (linear) approaches to estimating the impact of threats may be misleading. We developed a data-driven approach to assessing cumulative impacts on ecosystems and applied it to explore nonlinear relationships between threats and a temperate reef fish community. We used data on water quality, commercial fishing, climate change, and indicators of recreational fishing and urbanization to build a cumulative threat map of the northern region in New South Wales, Australia. We used statistical models of fish abundance to quantify associations among threats and biophysical covariates and predicted where cumulative impacts are likely to have the greatest impact on fish. We also assessed the performance of no-take zones (NTZs), to protect fish from cumulative threats across 2 marine protected area networks (marine parks). Fishing had a greater impact on fish than water quality threats (i.e., percent increase above the mean for invertivores was 337% when fishing was removed and was 11% above the mean when water quality was removed inside NTZs), and fishing outside NTZs affected fish abundances inside NTZs. Quantifying the spatial influence of multiple threats enables managers to understand the multitude of management actions required to address threats.

Una estrategia basada en datos para la evaluación de impacto de múltiples estresores en un área marina protegida Resumen Los ambientes costeros no se manejan de manera que se considere el impacto de las amenazas acumulativas, a pesar de que se enfrentan a amenazas de todos los entornos (marinas, terrestres y atmosféricas). Las relaciones entre las amenazas y las especies casi siempre son no lineales; por lo tanto, las estrategias actuales (lineales) para estimar el impacto de las amenazas pueden ser engañosas. Desarrollamos una estrategia basada en datos para evaluar el impacto acumulativo sobre los ecosistemas y la aplicamos para explorar las relaciones no lineales entre las amenazas y la comunidad de peces de arrecifes templados. Usamos datos de la calidad del agua, pesca comercial, cambio climático e indicadores de pesca recreativa y urbanización para construir un mapa acumulativo de amenazas de la región norte de Nueva Gales del Sur, Australia. Usamos modelos estadísticos de la abundancia de peces para cuantificar las asociaciones entre las amenazas y las covarianzas biofísicas y pronosticamos en dónde es probable que los impactos acumulativos sean mayores sobre los peces. También evaluamos el desempeño de las zonas de veda para así proteger a los peces de las amenazas acumulativas en dos redes de áreas marinas protegidas (parques marinos). La pesca tuvo un mayor impacto que la calidad del agua sobre los peces (es decir, el incremento del porcentaje por encima de la media de depredadores de invertebrados fue de 337% cuando se eliminó la pesca y fue de 11% por encima de la media cuando se eliminó la calidad del agua dentro de las zonas de veda) y la pesca fuera de las zonas de veda afectó la abundancia de los peces dentro de ellas. La cuantificación de la influencia espacial de las múltiples amenazas permite que los gestores entiendan la multitud de acciones de manejo que se requieren para abordar las amenazas.

Strategies for advancing inclusive biodiversity research through equitable practices and collective responsibility.

Biodiversity research is essential for addressing the global biodiversity crisis, necessitating diverse participation and perspectives of researchers from a wide range of backgrounds. However, conservation faces a significant inclusivity problem because local expertise from biodiversity-rich but economically disadvantaged regions is often underrepresented. This underrepresentation is driven by linguistic bias, undervalued contributions, parachute science practices, and capacity constraints. Although fragmented solutions exist, a unified multistakeholder approach is needed to address the interconnected and systemic conservation issues. We devised a holistic framework of collective responsibility across all research participants and tailored strategies that embrace diversity and dismantle systemic barriers to equitable collaboration. This framework delineates the diverse actors and practices required for promoting inclusivity in biodiversity research, assigning clear responsibilities to researchers, publishers, institutions, and funding bodies. Strategies for researchers include cultivating self-awareness, expanding literature searches, fostering partnerships with local experts, and promoting knowledge exchange. For institutions, we recommend establishing specialized liaison roles, implementing equitable policies, allocating resources for diversity initiatives, and enhancing support for international researchers. Publishers can facilitate multilingual dissemination, remove financial barriers, establish inclusivity standards, and ensure equitable representation in peer review. Funders must remove systemic barriers, strengthen research networks, and prioritize equitable resource allocation. Implementing these stakeholder-specific strategies can help dismantle deep-rooted biases and structural inequities in biodiversity research, catalyzing a shift toward a more inclusive and representative model that amplifies diverse perspectives and maximizes collective knowledge for effective global conservation.

Estrategias para las prácticas equitativas y la responsabilidad colectiva en la investigación de la biodiversidad Resumen La investigación sobre biodiversidad es esencial para hacer frente a la crisis mundial de la biodiversidad, por lo que requiere la participación y la variedad de perspectivas de investigadores de diferente procedencia. Sin embargo, la conservación se enfrenta a un importante problema de inclusión, ya que los expertos locales de regiones ricas en biodiversidad, pero con economías desfavorecidas suelen estar infrarrepresentados. Esta infrarrepresentación se debe a prejuicios lingüísticos, contribuciones infravaloradas, prácticas científicas paracaidistas y limitaciones de capacidad. Aunque existen soluciones fragmentadas, se necesita un enfoque unificado de los múltiples actores para abordar los problemas de conservación interconectados y sistémicos. Ideamos un marco holístico de responsabilidad colectiva de todos los participantes en la investigación y estrategias a medida que abarcan la diversidad y desmantelan las barreras sistémicas a la colaboración equitativa. Se necesitan diversos actores y estrategias para promover la inclusión en la investigación sobre biodiversidad, y deben asignarse claramente las responsabilidades de investigadores, editores, instituciones y organismos de financiación. Las estrategias para los investigadores incluyen fomentar la autoconciencia, ampliar las búsquedas bibliográficas, fomentar las asociaciones con expertos locales y promover el intercambio de conocimientos. Para las instituciones, recomendamos establecer funciones de enlace especializadas, aplicar políticas equitativas, asignar recursos a iniciativas de diversidad y mejorar el apoyo a los investigadores internacionales. Las editoriales pueden facilitar la difusión multilingüe, eliminar barreras financieras, establecer normas de inclusión y garantizar una representación equitativa en la revisión por pares. Los financiadores deben eliminar las barreras sistémicas, reforzar las redes de investigación y dar prioridad a la asignación equitativa de recursos. La aplicación de estas estrategias específicas puede ayudar a desmantelar prejuicios profundamente arraigados y desigualdades estructurales en la investigación de la biodiversidad, catalizando un cambio hacia un modelo más inclusivo y representativo que amplifique las diversas perspectivas y maximice el conocimiento colectivo para una conservación global eficaz.

Inconsistent Regulatory Mapping Quietly Threatens Rivers and Streams.

Even the most stringent environmental law cannot protect a river if its tributaries remain exposed to pollution and other threats upstream. Excluding a subset of watercourses from legal protection therefore threatens to alter freshwater ecosystems across entire river networks and the services they provide, such as drinking water and flood regulation. Considerable attention has been devoted to defining the scope of environmental laws protecting watercourses. Yet how these definitions are implemented through regulatory mapping, the cartography of waterbodies that legally qualify as watercourses and are thus protected, has not been examined outside of the United States. Here, we demonstrate the consequences of regulatory mapping on the extent of river networks that are protected, using France as a case study. By assembling the first map of France's watercourses protected under the Water Law, we estimate that a quarter of previously mapped hydrographic segments were excluded from protection and found stark geographical variations in the extent of protected ecosystems. Headwater and nonperennial segments are disproportionately excluded by 28% compared to their prevalence (67%) in the overall hydrographic network, with potentially far-reaching implications for biodiversity and people. We expect regulatory frameworks in most countries to be equally susceptible to local interpretation of legal definitions.

Baicalein attenuates rotenone-induced SH-SY5Y cell apoptosis through binding to SUR1 and activating ATP-sensitive potassium channels.

Dopaminergic neurons in the substantia nigra (SN) expressing SUR1/Kir6.2 type ATP-sensitive potassium channels (K-ATP) are more vulnerable to rotenone or metabolic stress, which may be an important reason for the selective degeneration of neurons in Parkinson's disease (PD). Baicalein has shown neuroprotective effects in PD animal models. In this study, we investigated the effect of baicalein on K-ATP channels and the underlying mechanisms in rotenone-induced apoptosis of SH-SY5Y cells. K-ATP currents were recorded from SH-SY5Y cells using whole-cell voltage-clamp recording. Drugs dissolved in the external solution at the final concentration were directly pipetted onto the cells. We showed that rotenone and baicalein opened K-ATP channels and increased the current amplitudes with EC50 values of 0.438 µM and 6.159 µM, respectively. K-ATP channel blockers glibenclamide (50 µM) or 5-hydroxydecanoate (5-HD, 250 µM) attenuated the protective effects of baicalein in reducing reactive oxygen species (ROS) content and increasing mitochondrial membrane potential and ATP levels in rotenone-injured SH-SY5Y cells, suggesting that baicalein protected against the apoptosis of SH-SY5Y cells by regulating the effect of rotenone on opening K-ATP channels. Administration of baicalein (150, 300 mg·kg-1·d-1, i.g.) significantly inhibited rotenone-induced overexpression of SUR1 in SN and striatum of rats. We conducted surface plasmon resonance assay and molecular docking, and found that baicalein had a higher affinity with SUR1 protein (KD = 10.39 µM) than glibenclamide (KD = 24.32 µM), thus reducing the sensitivity of K-ATP channels to rotenone. Knockdown of SUR1 subunit reduced rotenone-induced apoptosis and damage of SH-SY5Y cells, confirming that SUR1 was an important target for slowing dopaminergic neuronal degeneration in PD. Taken together, we demonstrate for the first time that baicalein attenuates rotenone-induced SH-SY5Y cell apoptosis through binding to SUR1 and activating K-ATP channels.

Medical Assistance in Dying for Mental Illness as a Sole Underlying Medical Condition and Its Relationship to Suicide: A Qualitative Lived Experience-Engaged Study: Aide Médicale à Mourir Pour Maladie Mentale Comme Seule Condition Médicale Sous-Jacente et Son Lien Avec le Suicide: Une Etude Qualitative Engagée Dans l'Expérience Vécue.

OBJECTIVE: This lived experience-engaged study aims to understand patient and family perspectives on the relationship between suicidality and medical assistance in dying when the sole underlying medical condition is mental illness (MAiD MI-SUMC). METHOD: Thirty individuals with mental illness (age M = 41.8 years, SD = 14.2) and 25 family members (age M = 47.5 years, SD = 16.0) participated in qualitative interviews examining perspectives on MAiD MI-SUMC and its relationship with suicide. Audio recordings were transcribed and analysed using reflexive thematic analysis. People with lived experience were engaged in the research process as team members. RESULTS: Four main themes were developed, which were consistent across individuals with mental illness and family members: (a) deciding to die is an individual choice to end the ongoing intolerable suffering of people with mental illness; (b) MAiD MI-SUMC is the same as suicide because the end result is death, although suicide can be more impulsive; (c) MAiD MI-SUMC is a humane, dignified, safe, nonstigmatized alternative to suicide; and (4) suicidality should be considered when MAiD MI-SUMC is requested, but suicidality's role is multifaceted given its diverse manifestations. CONCLUSION: For patient-oriented mental health policy and treatment, it is critical that the voices of people with lived experience be heard on the issue of MAiD MI-SUMC. Given the important intersections between MAiD MI-SUMC and suicidality and the context of suicide prevention, the role that suicidality should play in MAiD MI-SUMC is multifaceted. Future research and policy development are required to ensure that patient and family perspectives guide the development and implementation of MAiD MI-SUMC policy and practice.

Patient Perceptions of Microbiome-Based Therapies as Novel Treatments for Mood Disorders: A Mixed Methods Study: Perceptions des patients sur les thérapies basées sur le microbiome pour les troubles de l'humeur : une étude à méthodes mixtes.

OBJECTIVE: Medications are critical for treating major depressive disorder (MDD) and bipolar disorder (BD). Unfortunately, 30% to 40% of individuals do not respond well to current pharmacotherapy. Given the compelling growing body of research on the gut-brain axis, this study aims to assess patient perspectives regarding microbiome-based therapies (MBT) such as probiotics, prebiotics, dietary changes, or fecal microbiota transplantation (FMT) in the management of MDD and BD. METHODS: This single-centred observational study used quantitative and qualitative assessments to examine patient perceptions of MBT. Participants diagnosed with MDD or BD completed an anonymous questionnaire obtaining demographics, prior medication history, and symptom burden. Self-assessment questionnaires specific to each diagnosis were also used: Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR), Altman Self-Rating Mania Scale (ASRM), and General Anxiety Disorder Questionnaire (GAD-7). A logistic regression model analysed the association of MBT acceptance with disorder type, QIDS-SR, and GAD-7 scores. A bootstrap method assessed the proportion of MBT acceptance. The qualitative assessment consisted of 30-minute interviews to elicit perceptions and attitudes towards MBT. RESULTS: The qualitative assessment achieved information power with n = 20. Results from the 63-item MBT questionnaire (n = 43) showed probiotics (37.2%) as the top choice, followed by FMT (32.6%), dietary change (25.6%), and prebiotics (4.6%). A majority of participants (72.1%) expressed willingness to try MBT for their mood disorder, however, logistic regression analysis did not identify statistically significant predictors for MBT acceptance among disorder type, QIDS-SR, and GAD-7. CONCLUSION: There is an increased focus on the gut microbiota's role in mood disorders' etiology and treatment. Promising research and patient interest underscore the necessity for exploring and educating on patient perspectives and the factors influencing attitudes towards MBT.

Gestational age, maternal smoking, neurological lesion and retinopathy predict strabismus at age 5.5 in preterm children.

AIM: Prematurity is a risk factor for strabismus, but the roles of intermediate factors like retinopathy of prematurity (ROP) and neurological lesions are less understood. We aimed to identify neonatal risk factors for strabismus at age 5.5 in preterm children. METHODS: Data were extracted from the étude épidémiologique sur les petits âges gestationnels 2 cohort, a French prospective population-based study of preterm children born in 2011 with gestational age of 34 weeks or less. Strabismus was recorded during a medical interview at 5.5 years. Using a directed acyclic graph, intermediate and confounding factors were identified. Total and direct effects of gestational age on strabismus risk were analysed using generalised estimating equation. RESULTS: Among 2419 children assessed, 274 (52.6% male) presented strabismus at 5.5 years. The direct effect of gestational age remained significant after adjustment (p < 0.001). In the complete imputed model: maternal smoking during pregnancy (odds ratio, OR 1.8; 95% confident interval, 95% CI 1.3-2.6), neonatal severe cerebral lesions (OR 2.9, 95% CI 1.8-4.6) and severe ROP (OR 4.2, 95% CI 1.9-9.0) were independent risk factors. CONCLUSION: Special attention is needed regarding strabismus screening at age 5.5 in preterm children, even without severe cerebral lesions and ROP. Smoking cessation during pregnancy should be encouraged.

Efficacy and Safety of Early Treatment with Glibenclamide in Patients with Aneurysmal Subarachnoid Hemorrhage: A Randomized Controlled Trial.

BACKGROUND: This study aims to investigate the efficacy and safety of glibenclamide treatment in patients with acute aneurysmal subarachnoid hemorrhage (aSAH). METHODS: The randomized controlled trial was conducted from October 2021 to May 2023 at two university-affiliated hospitals in Beijing, China. The study included patients with aSAH within 48 h of onset, of whom were divided into the intervention group and the control group according to the random number table method. Patients in the intervention group received glibenclamide tablet 3.75 mg/day for 7 days. The primary end points were the levels of serum neuron-specific enolase (NSE) and soluble protein 100B (S100B) between the two groups. Secondary end points included evaluating changes in the midline shift and the gray matter-white matter ratio, as well as assessing the modified Rankin Scale scores during follow-up. The trial was registered at ClinicalTrials.gov (identifier NCT05137678). RESULTS: A total of 111 study participants completed the study. The median age was 55 years, and 52% were women. The mean admission Glasgow Coma Scale was 10, and 58% of the Hunt-Hess grades were no less than grade III. The baseline characteristics of the two groups were similar. On days 3 and 7, there were no statistically significant differences observed in serum NSE and S100B levels between the two groups (P > 0.05). The computer tomography (CT) values of gray matter and white matter in the basal ganglia were low on admission, indicating early brain edema. However, there were no significant differences found in midline shift and gray matter-white matter ratio (P > 0.05) between the two groups. More than half of the patients had a beneficial outcome (modified Rankin Scale scores 0-2), and there were no statistically significant differences between the two groups. The incidence of hypoglycemia in the two groups were 4% and 9%, respectively (P = 0.439). CONCLUSIONS: Treating patients with early aSAH with oral glibenclamide did not decrease levels of serum NSE and S100B and did not improve the poor 90-day neurological outcome. In the intervention group, there was a visible decreasing trend in cases of delayed cerebral ischemia, but no statistically significant difference was observed. The incidence of hypoglycemia did not differ significantly between the two groups.

In Vitro and In Silico Studies of the Biological Activities of Some Secondary Metabolites Belonging to Ficus sur Forssk (Moraceae): Towards Optimization of Wighteone Metabolite.

Based on ethnomedicinal and chemotaxonomic records of Ficus plants, Ficussur Forssk was studied in the search for bioactive compounds. Eleven known compounds including mixture α -amyrin acetate and ß -amyrin acetate (1 and 2), lupeol (3), 3ß-acetoxy-olean-12-en-11-one (4), lupenyl acetate (5), taraxastan-3,20-diol (6), 3'- (3-methylbut-2-enyl) biochanin A (7), derrone (8), quercetin (9), stigmasterol (10), and stigmasterol glycoside (11) were isolated from stem barks of Ficus sur Forssk. Their structures were obtained through analysis of spectroscopic data (1D and 2D NMR), mass spectrometry, and by comparison of these data with the literature. Nine isolated compounds (1-7, 10, 11) were tested as the active wighteone metabolite previously isolated from the roots of this plant against the human HepG2 hepatocellular carcinoma cells and a small panel of sensitive microbial strains for structure- activity relationship purpose. The compounds didn't show any activity. With the aim of understanding the impact of the structural difference between wighteone metabolite and its analogs, the former were cross-docked to evaluate their anticancer properties via the apoptosis pathway. Wighteone metabolite proved to be the best ligand confirming its previous bioassay result. Thus, the current study lays the framework for the further optimization of wighteone metabolite regarding its anticancer activity.

Sur lies élevage practice to modulate the features of red wines from calcareous soils with different textures.

BACKGROUND: In Sicilian calcareous soils, red wines often display unripeness and bitterness features. To enhance wine quality, we employed the 'sur lies élevage' technique, involving prolonged contact of dead yeast cells with the wine to favor the extraction of yeast cellular components through cell lysis. The 7 month treatment utilized two types of Chardonnay lies: fresh and previously matured. To overcome challenges in retrieving lies from red winemaking, we have recovered the lies from a white winemaking. Additionally, the lies underwent a preliminary passage on a red wine to minimize color adsorption on yeast cell walls. RESULTS: The sur lies treatment effectively reduced astringency, bitterness, and brown pigment in wines, with partial removal of red color. It successfully eliminated quercetin aglycone and induced remarkable changes in the aromatic profile, showing increased ethyl esters and relative fatty acids. Sensory evaluations revealed sur lies-treated wines had fruitier and more complex characteristics compared to untreated wines. Matured lies had a greater impact on enhancing fruitiness than fresh lies. CONCLUSIONS: The treatments mitigated the unripeness and bitterness of studied wines. Sur lies treatment improved the aromatic profile, leading to fruitier and more complex notes, enhancing overall sensory quality. Matured lies showed greater efficacy in elevating fruitiness than fresh lies. These findings highlight the value of the sur lies technique in enhancing the quality and sensory attributes of Nero d'Avola and Syrah wines from Sicilian calcareous soils. © 2023 Society of Chemical Industry.

What Evidence?: Qualitative Publishing in the Canadian Journal for Dietetic Practice and Research.

Background: Qualitative research involves the analysis of data in various forms (i.e., written text such as interview transcripts, literature, or a personal diary; visual media such as photographs, maps, or memes; and audio materials such as podcasts, music, or voice notes) to describe and/or interpret phenomena and humans' perceptions and experiences of the world, including of food, health, and well-being. Dietetic-scholars have raised concerns about the dearth and quality of qualitative dietetic research.Objective: To document the availability and quality of qualitative research published in Canadian dietetic literature.Methods: A manifest content analysis of articles published in the Canadian Journal of Dietetic Research and Practice (CJDRP) between 2012 and 2021.Results: In total, 340 articles were published between 2012 and 2021 of which 43 (12.6%) used qualitative methods. Overall, the quality of qualitative articles was poor; articles frequently failed to report the methodological approach or a theoretical framework. Methods of data collection, data analysis, and strategies to ensure rigor were seldom described in detail. Reported limitations were often inappropriate for qualitative research.Discussion: Qualitative research is markedly underrepresented in the CJDPR. Efforts are needed to ensure that high-quality qualitative research evidence and publishing opportunities are available to Canadian dietetic practitioners and researchers. This study provides baseline data to evaluate the impact of future efforts.

Land2Lab Project: Reflections on Learning about Mi'kmaw Foodways.

Land2Lab is an evolving community-based intergenerational program that brings together Elders and youth on the land and in the kitchen and lab to share and celebrate Mi'kmaw foodways. Rooted in an Etuaptmumk-Two Eyed Seeing (E-TES) perspective, which acknowledges both Indigenous and Western ways of knowing, the project to date has featured seasonal food workshops, involvement in a children's summer math camp, a food safety training workshop for teens, and the development of an online toolkit. The project was guided by the Mi'kmaw principle of Netukulimk, which reinforces respect for Mother Earth and stewardship of the land, water, and air for subsequent generations. Involvement of community leaders has been key to successful planning and implementation. While technology plays an important role, lessons learned on the land are critical and will inform efforts to include language and ceremony in future programming. Dietitians are encouraged to support Indigenous-led land-based learning in support of the profession's commitment to reconciliation.

Canadian Dietary Intakes Assessed by Nutrient Profiling Models and Association with Mortality and Cardiovascular Disease.

Purpose: Nutrient profiling (NP) ranks foods according to nutritional composition and underpins policies (e.g., front-of-package (FOP) labelling). This study aimed to evaluate Canadian adults' dietary intakes using proposed Canadian FOP "high-in" labelling thresholds and international NP models (i.e., Ofcom, FSANZ, and Nutri-Score) and examine the association between intakes using international NP models and all-cause mortality and cardiovascular disease (CVD).Methods: Intakes from the Canadian Community Health Survey-Nutrition (CCHS-Nutrition) 2004 and 2015 were given NP scores and assessed against FOP thresholds. CCHS-Nutrition 2004 was linked with death records (Canadian Vital Statistics Database, n = 6767) and CVD incidence and mortality (hospital Discharge Abstract Database, n = 6420) until December 2017.Results: Foods that would require FOP labels, should there be such regulation in Canada, contributed 38% of calories. Association between NP scores and mortality was significant for Ofcom, FSANZ, and Nutri-Score (hazard ratio (HR) in highest quintile (lowest quality): 1.73, 95%CI [1.20-2.49], 1.59[1.15-2.21], and 1.75[1.18-2.59], respectively), and for CVD incidence, among males (HR in highest quintile: 2.11[1.15-3.89], 1.74[1.07-2.84], and 2.29[1.24-4.24], respectively).Conclusions: Canadians had moderately healthy intakes. NP systems could discriminate between low and high dietary quality such that adults with the lowest diet quality were more likely to experience all-cause mortality and CVD events (for males).