Unraveling the Influence of Litter Size, Maternal Care, Exercise, and Aging on Neurobehavioral Plasticity and Dentate Gyrus Microglia Dynamics in Male Rats.

This study explores the multifaceted influence of litter size, maternal care, exercise, and aging on rats' neurobehavioral plasticity and dentate gyrus microglia dynamics. Body weight evolution revealed a progressive increase until maturity, followed by a decline during aging, with larger litters exhibiting lower weights initially. Notably, exercised rats from smaller litters displayed higher body weights during the mature and aged stages. The dentate gyrus volumes showed no significant differences among groups, except for aged sedentary rats from smaller litters, which exhibited a reduction. Maternal care varied significantly based on litter size, with large litter dams showing lower frequencies of caregiving behaviors. Behavioral assays highlighted the detrimental impact of a sedentary lifestyle and reduced maternal care/large litters on spatial memory, mitigated by exercise in aged rats from smaller litters. The microglial dynamics in the layers of dentate gyrus revealed age-related changes modulated by litter size and exercise. Exercise interventions mitigated microgliosis associated with aging, particularly in aged rats. These findings underscore the complex interplay between early-life experiences, exercise, microglial dynamics, and neurobehavioral outcomes during aging.

Characterisation of the novel HLA-B*35:593 allele using short and long-read sequencing technologies.

The novel HLA-B*35:593 allele, first described in a potential bone marrow donor from Brazil.

Characterisation of the novel HLA-A*30:218 allele using two different sequencing technologies.

The novel HLA-A*30:218 allele, first described in a potential bone marrow donor from Brazil.

Determining the Optimal Methodology for Identifying Incident Stroke Deaths Using Administrative Datasets Within Australia.

BACKGROUND AND AIM: Quantifying stroke incidence and mortality is crucial for disease surveillance and health system planning. Administrative data offer a cost-effective alternative to "gold standard" population-based studies. However, the optimal methodology for establishing stroke deaths from administrative data remains unclear. We aimed to determine the optimal method for identifying stroke-related deaths in administrative datasets as the fatal component of stroke incidence, comparing counts derived using underlying and all causes of death (CoD). METHOD: Using whole-population multijurisdictional person-level linked data from hospital and death datasets from South Australia, the Northern Territory, and Western Australia, we identified first-ever stroke events between 2012 and 2015, using underlying CoD and all CoD to identify fatal stroke counts. We determined the 28-day case fatality for both counts and compared results with gold standard Australian population-based stroke incidence studies. RESULTS: The total number of incident stroke events was 16,150 using underlying CoD and 18,074 using all CoD. Case fatality was 24.7% and 32.7% using underlying and all CoD, respectively. Case fatality using underlying CoD was similar to that observed in four Australian "gold standard" population-based studies (20%-24%). CONCLUSIONS: Underlying CoD generates fatal incident stroke estimates more consistent with population-based studies than estimates based on stroke deaths identified from all-cause fields in death registers.

Novel artificial intelligence-based hypodensity detection tool improves clinician identification of hypodensity on non-contrast computed tomography in stroke patients.

Introduction: In acute stroke, identifying early changes (parenchymal hypodensity) on non-contrast CT (NCCT) can be challenging. We aimed to identify whether the accuracy of clinicians in detecting acute hypodensity in ischaemic stroke patients on a non-contrast CT is improved with the use of an Artificial Intelligence (AI) based, automated hypodensity detection algorithm (HDT) using MRI-DWI as the gold standard. Methods: The study employed a case-crossover within-clinician design, where 32 clinicians were tasked with identifying hypodensity lesions on NCCT scans for five a priori selected patient cases, before and after viewing the AI-based HDT. The DICE similarity coefficient (DICE score) was the primary measure of accuracy. Statistical analysis compared DICE scores with and without AI-based HDT using mixed-effects linear regression, with individual NCCT scans and clinicians as nested random effects. Results: The AI-based HDT had a mean DICE score of 0.62 for detecting hypodensity across all NCCT scans. Clinicians' overall mean DICE score was 0.33 (SD 0.31) before AI-based HDT implementation and 0.40 (SD 0.27) after implementation. AI-based HDT use was associated with an increase of 0.07 (95% CI: 0.02-0.11, p = 0.003) in DICE score accounting for individual scan and clinician effects. For scans with small lesions, clinicians achieved a mean increase in DICE score of 0.08 (95% CI: 0.02, 0.13, p = 0.004) following AI-based HDT use. In a subgroup of 15 trainees, DICE score improved with AI-based HDT implementation [mean difference in DICE 0.09 (95% CI: 0.03, 0.14, p = 0.004)]. Discussion: AI-based automated hypodensity detection has potential to enhance clinician accuracy of detecting hypodensity in acute stroke diagnosis, especially for smaller lesions, and notably for less experienced clinicians.

Surgical Treatment in Post-Stroke Spastic Hands: A Systematic Review.

Background: For more than two decades, the surgical treatment of post-stroke spastic hands has been displaced by botulinum toxin therapy and is currently underutilized. Objectives: This article aimed to assess the potential of surgery for treating a post-stroke spastic upper extremity through a systematic review of the literature on surgical approaches that are adopted in different profiles of patients and on their outcomes and complications. Methods: Medline PubMed, Web of Science, SCOPUS, and Cochrane Library databases were searched for observational and experimental studies published in English up to November 2022. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluations (GRADE) system. Results: The search retrieved 501 abstracts, and 22 articles were finally selected. The GRADE-assessed quality of evidence was low or very low. The results of the reviewed studies suggest that surgery is a useful, safe, and enduring treatment for post-stroke spastic upper extremities, although most studied patients were candidates for hygienic improvements alone. Patients usually require an individualized combination of techniques. Over the past ten years, interest has grown in procedures that act on the peripheral nerve. Conclusions: Despite the lack of comparative studies on the effectiveness, safety, and cost of the treatments, botulinum toxin has displaced surgery for these patients. Studies to date have found surgery to be an effective and safe approach, but their weak design yields only poor-quality evidence, and clinical trials are warranted to compare these treatment options.

Incidence of Stroke in Indigenous Populations of Countries With a Very High Human Development Index: A Systematic Review.

BACKGROUND AND OBJECTIVES: Cardiovascular disease contributes significantly to disease burden among many Indigenous populations. However, data on stroke incidence in Indigenous populations are sparse. We aimed to investigate what is known of stroke incidence in Indigenous populations of countries with a very high Human Development Index (HDI), locating the research in the broader context of Indigenous health. METHODS: We identified population-based stroke incidence studies published between 1990 and 2022 among Indigenous adult populations of developed countries using PubMed, Embase, and Global Health databases, without language restriction. We excluded non-peer-reviewed sources, studies with fewer than 10 Indigenous people, or not covering a 35- to 64-year minimum age range. Two reviewers independently screened titles, abstracts, and full-text articles and extracted data. We assessed quality using "gold standard" criteria for population-based stroke incidence studies, the Newcastle-Ottawa Scale for risk of bias, and CONSIDER criteria for reporting of Indigenous health research. An Indigenous Advisory Board provided oversight for the study. RESULTS: From 13,041 publications screened, 24 studies (19 full-text articles, 5 abstracts) from 7 countries met the inclusion criteria. Age-standardized stroke incidence rate ratios were greater in Aboriginal and Torres Strait Islander Australians (1.7-3.2), American Indians (1.2), Sámi of Sweden/Norway (1.08-2.14), and Singaporean Malay (1.7-1.9), compared with respective non-Indigenous populations. Studies had substantial heterogeneity in design and risk of bias. Attack rates, male-female rate ratios, and time trends are reported where available. Few investigators reported Indigenous stakeholder involvement, with few studies meeting any of the CONSIDER criteria for research among Indigenous populations. DISCUSSION: In countries with a very high HDI, there are notable, albeit varying, disparities in stroke incidence between Indigenous and non-Indigenous populations, although there are gaps in data availability and quality. A greater understanding of stroke incidence is imperative for informing effective societal responses to socioeconomic and health disparities in these populations. Future studies into stroke incidence in Indigenous populations should be designed and conducted with Indigenous oversight and governance to facilitate improved outcomes and capacity building. REGISTRATION INFORMATION: PROSPERO registration: CRD42021242367.

First- and second-generation integrated process for bioethanol production: Fermentation of molasses diluted with hemicellulose hydrolysate by recombinant Saccharomyces cerevisiae.

The integration of first- (1G) and second-generation (2G) ethanol production by adding sugarcane juice or molasses to lignocellulosic hydrolysates offers the possibility to overcome the problem of inhibitors (acetic acid, furfural, hydroxymethylfurfural and phenolic compounds), and add nutrients (such as salts, sugars and nitrogen sources) to the fermentation medium, allowing the production of higher ethanol titers. In this work, an 1G2G production process was developed with hemicellulosic hydrolysate (HH) from a diluted sulfuric acid pretreatment of sugarcane bagasse and sugarcane molasses. The industrial Saccharomyces cerevisiae CAT-1 was genetically modified for xylose consumption and used for co-fermentation of sucrose, fructose, glucose, and xylose. The fed-batch fermentation with high cell density that mimics an industrial fermentation was performed at bench scale fermenter, achieved high volumetric ethanol productivity of 1.59 g L-1 h-1, 0.39 g g-1 of ethanol yield, and 44.5 g L-1 ethanol titer, and shown that the yeast was able to consume all the sugars present in must simultaneously. With the results, it was possible to establish a mass balance for the global process: from pretreatment to the co-fermentation of molasses and HH, and it was possible to establish an effective integrated process (1G2G) with sugarcane molasses and HH co-fermentation employing a recombinant yeast.

Effect of Different Substitutions at the 1,7-Bay Positions of Perylenediimide Dyes on Their Optical and Laser Properties.

Perylenediimide (PDI) compounds are widely used as the active units of thin-film organic lasers. Lately, PDIs bearing two sterically hindering diphenylphenoxy groups at the 1,7-bay positions have received attention because they provide a way to red-shift the emission with respect to bay-unsubstituted PDIs, while maintaining a good amplified spontaneous emission (ASE) performance at high doping rates. Here, we report the synthesis of a series of six PDI derivatives with different aryloxy groups (PDI 6 to PDI 10) or ethoxy groups (PDI 11) at the 1,7 positions of the PDI core, together with a complete characterization of their optical properties, including absorption, photoluminescence, and ASE. We aim to stablish structure-property relationships that help designing compounds with optimized ASE performance. Film experiments were accomplished at low PDI concentrations in the film, to resemble the isolated molecule behaviour, and at a range of increasing doping rates, to investigate concentration quenching effects. Compounds PDI 10 and PDI 7, bearing substituents in the 2' positions of the benzene ring (the one contiguous to the linking oxygen atom) attached to the 1,7 positions of the PDI core, have shown a better threshold performance, which is attributed to conformational (steric) effects. Films containing PDI 11 show dual ASE.

Panchromatic Light-Capturing Bis-styryl BODIPY-Perylenediimide Donor-Acceptor Constructs: Occurrence of Sequential Energy Transfer Followed by Electron Transfer.

Invited for the cover of this issue are the groups of Fernando Fernández-Lázaro and Ángela Sastre-Santos at the Universidad Miguel Hernández, Elche, Spain, and Francis D'Souza at the University of North Texas at Denton, Texas, USA. The image depicts the structure and properties of bis-styryl BODIPY-perylenediimide donor-acceptor constructs. Read the full text of the article at 10.1002/chem.202301686.

Upper-Limb Disability and the Severity of Lymphedema Reduce the Quality of Life of Patients with Breast Cancer-Related Lymphedema.

Breast cancer-related lymphedema (BCRL) is characterized by arm swelling, pain, and discomfort, reducing the quality of life (QoL) of affected individuals. BRCL is caused via the blockage or disruption of the lymphatic vessels following cancer treatments, leading to an accumulation of fluid in the affected arm. While current BCRL rehabilitation treatments seek to reduce arm swelling, our study aimed to examine the impact of both the magnitude of lymphedema (ΔVolume) and arm disability on three dimensions of QoL: social, physical, and psychological. Using the Disabilities of the Arm, Shoulder, and Hand questionnaire (DASH) and the Upper Limb Lymphedema 27 questionnaire (ULL) in a group of 30 patients, we found that the magnitude of lymphedema (ΔVolume) was associated with the social dimension of QoL (r = 0.37, p = 0.041), but not with other dimensions. On the other hand, arm disability was associated with all evaluated dimensions of QoL (social, physical, and psychological: p < 0.001, p = 0.019, and p = 0.050 (borderline), respectively). These findings suggest that BCRL rehabilitation strategies should not only aim to reduce the magnitude of lymphedema but should also seek to improve or preserve arm functionality to enhance the QoL of BCRL patients.

Abnormal functional connectivity in radiologically isolated syndrome: A resting-state fMRI study.

BACKGROUND: Radiologically isolated syndrome (RIS) patients might have psychiatric and cognitive deficits, which suggests an involvement of major resting-state functional networks. Notwithstanding, very little is known about the neural networks involved in RIS. OBJECTIVE: To examine functional connectivity differences between RIS and healthy controls using resting-state functional magnetic resonance imaging (fMRI). METHODS: Resting-state fMRI data in 25 RIS patients and 28 healthy controls were analyzed using an independent component analysis; in addition, seed-based correlation analysis was used to obtain more information about specific differences in the functional connectivity of resting-state networks. Participants also underwent neuropsychological testing. RESULTS: RIS patients did not differ from the healthy controls regarding age, sex, and years of education. However, in memory (verbal and visuospatial) and executive functions, RIS patients' cognitive performance was significantly worse than the healthy controls. In addition, fluid intelligence was also affected. Twelve out of 25 (48%) RIS patients failed at least one cognitive test, and six (24.0%) had cognitive impairment. Compared to healthy controls, RIS patients showed higher functional connectivity between the default mode network and the right middle and superior frontal gyri and between the central executive network and the right thalamus (pFDR < 0.05; corrected). In addition, the seed-based correlation analysis revealed that RIS patients presented higher functional connectivity between the posterior cingulate cortex, an important hub in neural networks, and the right precuneus. CONCLUSION: RIS patients had abnormal brain connectivity in major resting-state neural networks and worse performance in neurocognitive tests. This entity should be considered not an "incidental finding" but an exclusively non-motor (neurocognitive) variant of multiple sclerosis.

Left ventricular structural abnormalities in the assessment of diastolic function in the elderly: source of discrepancies between the 2009 and 2016 criteria.

Diastolic dysfunction (DD) is routinely evaluated in echocardiography to support diagnosis, prognostication, and management of heart failure, a condition highly prevalent in elderly patients. Clinical guidelines were published in 2009, and updated in 2016, pursuing to standardize and improve DD categorization. We aimed to assess the concordance of DD between these two documents in an elderly population and to investigate how left ventricular structural abnormalities (LVSA) impact the reclassification. To evaluate this we analyzed the 308 consecutive transthoracic echocardiograms in patients older than 60 years (70.4 ± 7.7 years-old, 59% women) that fulfilled the inclusion criteria out of the 1438 echocardiograms performed in a tertiary hospital. We found that the prevalence of DD was lower according to the 2016 criteria (64% vs. 91%; p < 0.001), with 207 (67.2%) patients changing category, indicating poor agreement between the guidelines (kappa = 0.21). There were 188 (61%) patients with LVSA, which drove most of the reclassifications in 2016 Grade I DD cases. The prevalence of elevated filling pressures by Doppler halved in this elderly population using the updated recommendations (20.9% vs. 39.2%; p < 0.001). In conclusion the prevalence of DD was lower applying the 2016 guidelines, with a poor agreement with 2009 guidelines in all DD grades. The role of LVSA in reclassifications was particularly evident in Grade I DD, while Doppler parameters drove reclassifications among the more severe grades. If not properly addressed, these discrepancies may undermine the reliance on DD as a diagnostic and prognostic tool, particularly in an elderly population at a higher risk of heart failure.

Persistent pain management in an oncology population through pain neuroscience education, a multimodal program: PaiNEd randomized clinical trial protocol.

INTRODUCTION: Pain is one of the most persistent symptoms after cancer treatment. The central nervous system can erroneously stay in its alarm phase, altering the pain experience of patients who have cancer. Pain neuroscience education (PNE) with multimodal approaches may benefit these patients. OBJECTIVE: This protocol aims to determine the effectiveness of a PNE tool on pain, physical function and quality of life, as a supplement to a multimodal rehabilitation (MR) program in patients who had breast cancer (BC). METHODS: An 8-week double-blinded randomized controlled trial will be conducted, including 72 participants who had BC and who have persistent pain, randomized into three groups: PNE program + MR program, traditional biomedical information + MR program and control group. The PNE program will include educational content that participants will learn through a mobile app and the MR program will include a concurrent exercise program and manual therapy. The primary outcome will be the perceived pain assessed using the Visual Analogue Scale and secondary outcomes are others related to pain, physical function and quality of life. All outcomes will be evaluated at baseline, at the end of the intervention and 6 months after the end of intervention. DISCUSSION: The proposed study may help BC patients with persistent pain improve their pain experience, quality of life and provide for more adaptive pain-coping strategies. This protocol could propose an action guide to implement different integral approaches for the treatment of sequelae. This treatment option could be offered to this patient profile and it could be easily implemented in the healthcare systems due to its low costs. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04877860. (February18, 2022).

Associations Between Coronary Artery Calcification and Left Ventricular Global Longitudinal Strain and Diastolic Parameters: the ELSA-Brasil Study.

Atherosclerosis burden can be evaluated in asymptomatic patients by measuring coronary artery calcification (CAC), whereas the global longitudinal strain (GLS) and diastolic function parameters (mitral E/e' ratio, septal e', and lateral e') are used to evaluate subclinical left ventricular (LV) dysfunction. We investigated whether subjects with CAC (CAC >0 Agatston units) would present with an impairment in LV functional parameters. Among the participants of the ELSA-Brasil cohort free of clinically prevalent cardiovascular disease who performed cardiac computed tomography and echocardiography within the study protocol, we tested whether those with CAC >0 presented with worse GLS and diastolic function parameters. CAC >0 was present in 203 of the 612 included participants (33.17%; age 51.4 ± 8.6 years, 52.1% women). Absolute CAC values did not correlate with GLS (ro = 0.07, p = 0.105) but did so with E/e' (ro = 0.19, p <0.001), septal e' (ro = 0.28, p <0.001), and lateral e' (ro = 0.30, p <0.001), with stronger correlations in men. Those with CAC >0 had worse mitral E/e' ratios (7.75 ± 0.13 vs 7.01 ± 0.09; p ≤0.001), septal e' (8.25 ± 0.15 vs 9.59 ± 0.11 cm/s; p <0.001), and lateral e' (10.13 ± 0.20 vs 11.99 ± 0.14 cm/s; p ≤0.001), respectively. However, these associations were not independent of diabetes, obesity, hypertension, smoking, and low-density lipoprotein cholesterol, persisting only as significant associations of CAC >0 with mitral E/e' ratio and septal e' in men. There is an association between subclinical coronary atherosclerosis and impaired LV functional parameters. These associations are more likely attributed to the presence of common cardiovascular risk factors in the general population. However, in men, it seems to exist as an independent association.

π-Extended Pyrazinepyrene-Fused Zinc Phthalocyanines: Synthesis and Excited-State Charge Separation Involving Coordinated C60.

A series of pyrazinepyrene-fused zinc phthalocyanines (ZnPc-Pyrn) have been newly synthesized by reacting quinoxaline and the corresponding diamino-functionalized phthalocyanines as a new class of π-extended phthalocyanine systems. Bathochromically shifted absorption as a function of the number of pyrazinepyrene entities due to extended π-conjugation and quenched fluorescence due to the presence of fused pyrazinepyrene were witnessed. The electronic structures of these phthalocyanines were probed by systematic computational and electrochemical studies, while the excited-state properties were examined by pump-probe spectroscopies operating at the femto- and nanosecond time scales. Similar to the excited singlet lifetimes, the excited triplet states also revealed diminished lifetimes with an increased number of pyrazinepyrene entities. Further, the coordinatively unsaturated zinc in these molecules was coordinated with phenyl imidazole-functionalized fullerene, ImC60, to form a new series of donor-acceptor conjugates. Upon full characterization of these conjugates, the occurrence of excited-state charge separation was established by transient pump-probe spectroscopy, covering wide temporal and spatial regions. The lifetime of the final charge-separated states was ∼2 ns and decreased with an increase in the number of fused pyrazinepyrene units.

New Highly Fluorescent Water Soluble Imidazolium-Perylenediimides: Synthesis and Cellular Response.

The synthesis and characterization of two new water soluble 2,6-bis(imidazolylmethyl)-4-methylphenoxy-containing perylenediimides, PDI-1 and PDI-2, are described. These compounds demonstrate a high fluorescence quantum yield in water and were investigated as potential photosensitizers for generating reactive oxygen species with applications in anticancer activities. The HeLa cell line (VPH18) was used to evaluate their efficacy. Fluorescence microscopy was employed to confirm the successful internalization of PDI-1 and PDI-2, while confocal microscopy revealed the specific locations of both PDIs within the lysosomes and mitochondria. In vitro studies were conducted to evaluate the anticancer activity of PDI-1 and PDI-2. Remarkably, these photosensitizers demonstrated a significant ability to selectively eliminate cancer cells when exposed to a specific light wavelength. The water solubility, high fluorescence quantum yield, and selective cytotoxicity of these PDIs toward cancer cells highlight their potential as effective agents for targeted photodynamic therapy. In conclusion, the findings presented here provide a strong foundation for the future exploration and optimization of PDI-1 and PDI-2 as effective photosensitizers in photodynamic therapy, potentially leading to improved treatment strategies for cancer patients.

Biochemical and Biotechnological Insights into Fungus-Plant Interactions for Enhanced Sustainable Agricultural and Industrial Processes.

The literature is full of studies reporting environmental and health issues related to using traditional pesticides in food production and storage. Fortunately, alternatives have arisen in the last few decades, showing that organic agriculture is possible and economically feasible. And in this scenario, fungi may be helpful. In the natural environment, when associated with plants, these microorganisms offer plant-growth-promoting molecules, facilitate plant nutrient uptake, and antagonize phytopathogens. It is true that fungi can also be phytopathogenic, but even they can benefit agriculture in some way-since pathogenicity is species-specific, these fungi are shown to be useful against weeds (as bioherbicides). Finally, plant-associated yeasts and molds are natural biofactories, and the metabolites they produce while dwelling in leaves, flowers, roots, or the rhizosphere have the potential to be employed in different industrial activities. By addressing all these subjects, this manuscript comprehensively reviews the biotechnological uses of plant-associated fungi and, in addition, aims to sensitize academics, researchers, and investors to new alternatives for healthier and more environmentally friendly production processes.

Tunable J-type aggregation of silicon phthalocyanines in a surface-anchored metal-organic framework thin film.

Organic chromophores and semiconductors, like anthracene, pentacene, perylene, and porphyrin, are prone to aggregation, and their packing in the solid state is often hard to predict and difficult to control. As the condensed phase structures of these chromophores and semiconductors are of crucial importance for their optoelectronic functionality, strategies to control their assembly and provide new structural motifs are important. One such approach uses metal-organic frameworks (MOFs); the organic chromophore is converted into a linker and connected by metal ions or nodes. The spatial arrangement of the organic linkers can be well-defined in a MOF, and hence optoelectronic functions can be adjusted accordingly. We have used such a strategy to assemble a phthalocyanine chromophore and illustrated that the electronic inter-phthalocyanine coupling can be rationally tuned by introducing bulky side grounds to increase steric hindrance. We have designed new phthalocyanine linkers and using a layer-by-layer liquid-phase epitaxy strategy thin films of phthalocyanine-based MOFs have been fabricated and their photophysical properties explored. It was found that increasing the steric hindrance around the phthalocyanine reduced the effect of J-aggregation in the thin film structures.