bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced microglia activation following metformin administration or microglia ablation is sufficient to prevent functional deficits in a mouse model of neonatal stroke
Authors: Bourget Clara , Adams Kelsey V. , Morshead Cindi M. 
Published: June 2022

Abstract
Background
Neonatal stroke is a devastating insult that can lead to life-long impairments. In response to hypoxic–ischaemic injury, there is loss of neurons and glia as well as a neuroinflammatory response mediated by resident immune cells, including microglia and astrocytes, which can exacerbate damage. Administration of the antidiabetic drug metformin has been shown to improve functional outcomes in preclinical models of brain injury and the cellular basis for metformin-mediated recovery is unknown. Given metformin’s demonstrated anti-inflammatory properties, we investigated its role in regulating the microglia activation and used a microglia ablation strategy to investigate the microglia-mediated outcomes in a mouse model of neonatal stroke.

Methods
Hypoxia-ischaemia (H-I) was performed on post-natal day 8. Metformin was administered for one week, starting one day after injury. Immunohistochemistry was used to examine the spatiotemporal response of microglia and astrocytes after hypoxia-ischaemia, with or without metformin treatment. To evaluate the effects of microglia depletion after hypoxia-ischaemia, we delivered Plexxikon 5622 for 1 or 2 weeks post-injury. The regional pattern of microglia and astrocyte depletion was assessed through immunohistochemistry. Motor behaviour was assessed with the righting reflex, hindlimb suspension, grip strength and cylinder tests.

Results
Herein, we revealed a spatiotemporally regulated response of microglia and astrocytes after hypoxia-ischaemia. Metformin treatment after hypoxia-ischaemia had no effect on microglia number and proliferation, but significantly reduced microglia activation in all regions examined, concomitant with improved behavioural outcomes in injured mice. Plexxikon 5622 treatment successfully ablated microglia, resulting in a > 90% depletion in microglia in the neonatal brain. Microglia rapidly repopulated upon treatment cessation of Plexxikon. Most interesting, microglia ablation was sufficient to reduce functional deficits after hypoxia-ischaemia, mimicking the effects of 1 week of metformin treatment post-injury.

Conclusion
These results highlight the importance of regulating the neuroinflammatory response after neonatal stroke to promote recovery.
Superior control of inflammatory pain by corticotropin-releasing factor receptor 1 via opioid peptides in distinct pain-relevant brain areas
Authors: Mousa Shaaban A. , Khalefa Baled I. , Shaqura Mohammed , Al-Madol Mohammed , Treskatsch Sascha , Schäfer Michael 
Published: June 2022

Abstract
Background
Under inflammatory conditions, the activation of corticotropin-releasing factor (CRF) receptor has been shown to inhibit pain through opioid peptide release from immune cells or neurons. CRF’s effects on human and animal pain modulation depend, however, on the distribution of its receptor subtypes 1 and 2 (CRF-R1 and CRF-R2) along the neuraxis of pain transmission. The objective of this study is to investigate the respective role of each CRF receptor subtype on centrally administered CRF-induced antinociception during inflammatory pain.

Methods
The present study investigated the role of intracerebroventricular (i.c.v.) CRF receptor agonists on nociception and the contribution of cerebral CRF-R1 and/or CRF-R2 subtypes in an animal model of Freund’s complete adjuvant (FCA)-induced hind paw inflammation. Methods used included behavioral experiments, immunofluorescence confocal analysis, and reverse transcriptase-polymerase chain reaction.

Results
Intracerebroventricular, but systemically inactive, doses of CRF elicited potent, dose-dependent antinociceptive effects in inflammatory pain which were significantly antagonized by i.c.v. CRF-R1-selective antagonist NBI 27914 (by approximately 60%) but less by CRF-R2-selective antagonist K41498 (by only 20%). In line with these findings, i.c.v. administration of CRF-R1 agonist stressin I produced superior control of inflammatory pain over CRF-R2 agonist urocortin-2. Intriguingly, i.c.v. opioid antagonist naloxone significantly reversed the CRF as well as CRF-R1 agonist-elicited pain inhibition. Consistent with existing evidence of high CRF concentrations in brain areas such as the thalamus, hypothalamus, locus coeruleus, and periaqueductal gray following its i.c.v. administration, double-immunofluorescence confocal microscopy demonstrated primarily CRF-R1-positive neurons that expressed opioid peptides in these pain-relevant brain areas. Finally, PCR analysis confirmed the predominant expression of the CRF-R1 over CRF-R2 in representative brain areas such as the hypothalamus.

Conclusion
Taken together, these findings suggest that CRF-R1 in opioid-peptide-containing brain areas plays an important role in the modulation of inflammatory pain and may be a useful therapeutic target for inflammatory pain control.
Individual experience influences reconstruction of division of labour under colony disturbance in a queenless ant species
Authors: Tanaka Yasunari , Hojo Masaru K. , Shimoji Hiroyuki 
Published: June 2022

Abstract
Background
Division of labour (DOL) is ubiquitous across biological hierarchies. In eusocial insects, DOL is often characterized by age-related task allocation, but workers can flexibly change their tasks, allowing for DOL reconstruction in fluctuating environments. Behavioural change driven by individual experience is regarded as a key to understanding this task flexibility. However, experimental evidence for the influence of individual experience is remains sparse. Here we tested the effect of individual experience on task choice in the queenless ponerine ant, Diacamma cf. indicum from Japan.

Results
We confirmed that both nurses and foragers shifted to vacant tasks when the colony composition was biased to one or the other. We also found that nurses which are induced to forage readily revert to nursing when reintroduced into balanced colonies. In contrast, foragers which are induced to revert to nursing very rarely return to a foraging role, even 19 days post reintroduction to their original colony.

Conclusions
Taken together, our results suggest that individual experience decreases the response threshold of original foragers, as they continue to be specialist nurses in a disturbed colony. However, original nurses do not appear strongly affected by having forager experience and revert to being nurses. Therefore, while individual experience does have an effect, other factors, such as reproductive ability, are clearly required to understand DOL maintenance in fluctuating environments.
Murine in utero exposure to simulated complex urban air pollution disturbs offspring gut maturation and microbiota during intestinal suckling-to-weaning transition in a sex-dependent manner
Authors: Guilloteau Eva , Coll Patrice , Lu Zhuyi , Djouina Madjid , Cazaunau Mathieu , Waxin Christophe , Bergé Antonin , Caboche Ségolène , Gratien Aline , Al Marj Elie , Hot David , Dubuquoy Laurent , Launay David , Vignal Cécile , Lanone Sophie , Body-Malapel Mathilde 
Published: June 2022

Abstract
Background
Emerging data indicate that prenatal exposure to air pollution may lead to higher susceptibility to several non-communicable diseases. Limited research has been conducted due to difficulties in modelling realistic air pollution exposure. In this study, pregnant mice were exposed from gestational day 10–17 to an atmosphere representative of a 2017 pollution event in Beijing, China. Intestinal homeostasis and microbiota were assessed in both male and female offspring during the suckling-to-weaning transition.

Results
Sex-specific differences were observed in progeny of gestationally-exposed mice. In utero exposed males exhibited decreased villus and crypt length, vacuolation abnormalities, and lower levels of tight junction protein ZO-1 in ileum. They showed an upregulation of absorptive cell markers and a downregulation of neonatal markers in colon. Cecum of in utero exposed male mice also presented a deeply unbalanced inflammatory pattern. By contrast, in utero exposed female mice displayed less severe intestinal alterations, but included dysregulated expression of Lgr5 in colon, Tjp1 in cecum, and Epcam, Car2 and Sis in ileum. Moreover, exposed female mice showed dysbiosis characterized by a decreased weighted UniFrac β-diversity index, a higher abundance of Bacteroidales and Coriobacteriales orders, and a reduced Firmicutes/Bacteroidetes ratio.

Conclusion
Prenatal realistic modelling of an urban air pollution event induced sex-specific precocious alterations of structural and immune intestinal development in mice.
The impact of neoliberal generative mechanisms on Indigenous health: a critical realist scoping review
Authors: Poirier Brianna , Sethi Sneha , Haag Dandara , Hedges Joanne , Jamieson Lisa 
Published: June 2022

AbstractThe pervasive nature and colonial foundations of neoliberalism has significant ramifications for Indigenous health, globally. Not only does neoliberalism undermine Indigenous collectivist values by emphasising personal autonomy, but the exploitation of natural resources has unique implications for Indigenous wellbeing. Therefore, this scoping review aims to synthesise evidence that articulates the impacts of neoliberalism on global Indigenous health inequities. Two reviewers searched PubMed, Embase, Scopus, Web of Science, and ProQuest Central to identify records eligible for inclusion. The search was not restricted by geographic location or language. Using principles of qualitative meta-aggregation, generative mechanism summaries and illustrations were extracted from each of the included articles, synthesised into broader categories, then considered in the context of neoliberal ideologies. The systematic search identified 9952 unique records, of which 38 fully satisfied the inclusion criteria. Findings represented 23 Indigenous communities across 12 countries and considered the impacts of neoliberalism across 16 health outcomes. Eighty-eight generative mechanisms of neoliberalism and 12 generative mechanisms of resistance were extracted from the included articles and mapped against four core principles of neoliberalism: competitive and private markets, reduced public expenditure on infrastructure, personal autonomy, and deregulation that facilitates economic activity. Overwhelmingly, neoliberalism has manifest impacts, through various pathways, on poor health outcomes and experiences for Indigenous communities included in this review. Importantly, Indigenous communities continue to resist the impacts of neoliberalism through advocacy, reclamation of traditional practices, and opposition to industrial development. Consideration and investigation of neoliberal structures and ideologies must become common practice in health equity scholarship. Actors within neoliberal societies must resist dominant epistemological, ontological, and praxiological stances that reinforce the supremacy of colonial values and subalternation of Indigenous ways of knowing, being, and doing to begin effectively addressing Indigenous health inequities.
Breastfeeding and humanitarian emergencies: the experiences of pregnant and lactating women during the earthquake in Abruzzo, Italy
Authors: Giusti Angela , Marchetti Francesca , Zambri Francesca , Pro Elide , Brillo Eleonora , Colaceci Sofia 
Published: June 2022

Abstract
Background
Emergencies have a great impact on infant and young child feeding. Despite the evidence, the recommended feeding practices are often not implemented in the emergency response, undermining infant and maternal health. The aim of this study was to explore the experiences of pregnant and lactating women during the earthquake emergency that occurred in L’Aquila on 6 April 2009.

Methods
The study design was qualitative descriptive. Data were collected by individual semi-structured interviews, investigating the mother’s experiences of pregnancy, childbirth, breastfeeding, infant formula or complementary feeding during the emergency and the post emergency phase. Data analysis was categorical and was performed by using N-Vivo software.

Results
Six women who were pregnant at the time of the earthquake were interviewed in January 2010. In addition to the essential needs of pregnant and lactating women, such as those related to the emergency shelters conditions, the main findings emerged from this study were: the reconfiguration of relationships and the central role of partners and family support; the need of spaces for sharing experiences and practices with other mothers; the lack of breastfeeding support after the hospital discharge; the inappropriate donations and distribution of Breast Milk Substitutes.

Conclusions
During and after L’Aquila earthquake, several aspects of infant and young child feeding did not comply with standard practices and recommendations. The response system appeared not always able to address the specific needs of pregnant and lactating women. It is urgent to develop management plans, policies and procedures and provide communication, sensitization, and training on infant and young child feeding at all levels and sectors of the emergency response.
Healing of joint capsule after hip arthroscopy using interportal capsulotomy and capsular closure influences clinical outcomes
Authors: Gao Guanying , Jiao Chenbo , Liu Jiayang , Zhou Chang , Liu Yuhao , Ao Yingfang , Xu Yan 
Published: June 2022

Abstract
Background
Hip arthroscopy for treatment of femoroacetabular impingement (FAI) has developed rapidly and has been shown to significantly decrease pain and improve hip function. However, the relationship between hip capsule characteristics and healing after arthroscopic surgery and changes in patient-reported outcomes scores (PROs) for postoperative pain, function, and symptoms is still uncertain.

Methods
We retrospectively evaluated consecutive patients who were diagnosed with FAI and underwent hip arthroscopy for treatment in our hospital between May 2018 and November 2020. All patients had preoperative MRI and postoperative MRI at least 6 months after arthroscopy. Hip capsular thickness was measured at the proximal, middle, and distal site of the capsule. PROs and PROs at final follow-up were obtained, including visual analog scale (VAS) for pain and modified Harris Hip Score (mHHS).

Results
A total of 194 patients were included in this study. The mean MRI follow-up time was 14.3 (range, 6–37) months, and the mean clinical follow-up time was 26.1 (range, 12–43) months. Postoperative capsular thickness or net change were not correlated with postoperative PROs and VAS (P > .05). Capsular defect was observed in 17 (8.8%) patients. Patients with capsular defect had a relatively higher BMI (P < .05). Patients with capsular defect had a significant lower mHHS and higher VAS compared with patients with continuous capsule (P < .05). Ninety-one percentage of patients with continuous capsule surpassed minimal clinically important difference (MCID) and 80.8% achieved PASS, but only 58.8% of patients with capsular defect surpassed MCID and 47.1% achieved patient acceptable symptom state (PASS).

Conclusions
Postoperative capsular thickness may not have influence on the clinical outcomes of hip arthroscopy for treatment of FAI. Some capsule of patients who underwent arthroscopic interportal capsulotomy and repair could not heal. Postoperative capsular continuity had a great impact on the clinical outcomes of hip arthroscopy for FAI. Patients with higher BMI may be more likely to have capsule failure to heal.
Templated freezing: a simple method may increase gripping force of the clamp on the tendon
Authors: Wang T. , Yu H. 
Published: June 2022

Abstract
Purpose
To evaluate the effectiveness of combining a customized mold with frozen conventional clamps against other freezing and non-freezing methods.

Methods
Forty-five porcine and 45 chicken tendons were evenly divided into five groups (n = 9 + 9/group): control group, non-freezing with gauze placed between tendon and clamp (gauze), non-freezing with suture fixation at tendon ends (suture), freezing with dry ice pocket placed at the clamps (pocket), and freezing using a templated liquid nitrogen clamp with a customized mold (mold). Tension tests were used to measure failure modes and loads.

Result
Slippage and avulsion were observed in non-freezing groups with significantly lower failure loads compared to freezing methods. With freezing, rupture occurred near the central point only in the mold group. The failure loads for porcine tendons in the mold group were higher (2121.651 ± 73.101 N) than the pocket group (1746.337 ± 68.849 N). The failure loads of chicken tendons in the mold (243.552 ± 15.881 N) and pocket groups (260.647 ± 22.161 N) were not statistically different.

Conclusion
Freezing clamps represent the better choice for soft tissue clamping. The customized mold method could improve gripping effectiveness.
Calcium-dependent cytosolic phospholipase A2 activation is implicated in neuroinflammation and oxidative stress associated with ApoE4
Authors: Wang Shaowei , Li Boyang , Solomon Victoria , Fonteh Alfred , Rapoport Stanley I. , Bennett David A. , Arvanitakis Zoe , Chui Helena C. , Sullivan Patrick M. , Yassine Hussein N. 
Published: June 2022

Abstract
Background
Apolipoprotein E4 (APOE4) is associated with a greater response to neuroinflammation and the risk of developing late-onset Alzheimer’s disease (AD), but the mechanisms for this association are not clear. The activation of calcium-dependent cytosolic phospholipase A2 (cPLA2) is involved in inflammatory signaling and is elevated within the plaques of AD brains. The relation between APOE4 genotype and cPLA2 activity is not known.

Methods
Mouse primary astrocytes, mouse and human brain samples differing by APOE genotypes were collected for measuring cPLA2 expression, phosphorylation, and activity in relation to measures of inflammation and oxidative stress.

Results
Greater cPLA2 phosphorylation, cPLA2 activity and leukotriene B4 (LTB4) levels were identified in ApoE4 compared to ApoE3 in primary astrocytes, brains of ApoE-targeted replacement (ApoE-TR) mice, and in human brain homogenates from the inferior frontal cortex of persons with AD dementia carrying APOE3/4 compared to APOE3/3. Higher phosphorylated p38 MAPK but not ERK1/2 was found in ApoE4 primary astrocytes and mouse brains than that in ApoE3. Greater cPLA2 translocation to cytosol was observed in human postmortem frontal cortical synaptosomes with recombinant ApoE4 than ApoE3 ex vivo. In ApoE4 astrocytes, the greater levels of LTB4, reactive oxygen species (ROS), and inducible nitric oxide synthase (iNOS) were reduced after cPLA2 inhibition.

Conclusions
Our findings implicate greater activation of cPLA2 signaling system with APOE4, which could represent a potential drug target for mitigating the increased neuroinflammation with APOE4 and AD.
Genome-wide translation control analysis of developing human neurons
Authors: Lins Érico Moreto , Oliveira Natássia Cristina Martins , Reis Osvaldo , Ferrasa Adriano , Herai Roberto , Muotri Alysson R. , Massirer Katlin Brauer , Bengtson Mário Henrique 
Published: June 2022

AbstractDuring neuronal differentiation, neuroprogenitor cells become polarized, change shape, extend axons, and form complex dendritic trees. While growing, axons are guided by molecular cues to their final destination, where they establish synaptic connections with other neuronal cells. Several layers of regulation are integrated to control neuronal development properly. Although control of mRNA translation plays an essential role in mammalian gene expression, how it contributes temporarily to the modulation of later stages of neuronal differentiation remains poorly understood. Here, we investigated how translation control affects pathways and processes essential for neuronal maturation, using H9-derived human neuro progenitor cells differentiated into neurons as a model. Through Ribosome Profiling (Riboseq) combined with RNA sequencing (RNAseq) analysis, we found that translation control regulates the expression of critical hub genes. Fundamental synaptic vesicle secretion genes belonging to SNARE complex, Rab family members, and vesicle acidification ATPases are strongly translationally regulated in developing neurons. Translational control also participates in neuronal metabolism modulation, particularly affecting genes involved in the TCA cycle and glutamate synthesis/catabolism. Importantly, we found translation regulation of several critical genes with fundamental roles regulating actin and microtubule cytoskeleton pathways, critical to neurite generation, spine formation, axon guidance, and circuit formation. Our results show that translational control dynamically integrates important signals in neurons, regulating several aspects of its development and biology.
Management of avian malaria in populations of high conservation concern
Authors: Miranda Paez Andrea , Chalkowski Kayleigh , Zohdy Sarah , Willoughby Janna R. 
Published: June 2022

AbstractAvian malaria is a vector-borne disease that is caused by Plasmodium parasites. These parasites are transmitted via mosquito bites and can cause sickness or death in a wide variety of birds, including many threatened and endangered species. This Primer first provides contextual background for the avian malaria system including the life cycle, geographic distribution and spread. Then, we focus on recent advances in understanding avian malaria ecology, including how avian malaria can lead to large ecosystem changes and variation in host immune responses to Plasmodium infection. Finally, we review advances in avian malaria management in vulnerable bird populations including genetic modification methods suitable for limiting the effects of this disease in wild populations and the use of sterile insect techniques to reduce vector abundance.
Graphical Abstract