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Youth with brachial plexus birth injuries (BPBI) have an increased risk of mental health issues such as depression, anxiety, and diminished self-confidence. Despite this evidence, current standards of care focus on physical interventions. Evaluation of psychological and emotional concerns is rarely prioritized in clinical settings. Therefore, mental health needs are unmet and poorly understood.
Premature birth is a major risk factor for multiple brain pathologies, notably periventricular leukomalacia (PVL), which is distinguished by bilateral necrosis of neural tissue around the ventricles and a sequela of neurological disturbances. The 2 hallmarks of brain pathologies of prematurity are a restricted gestational window of vulnerability and confinement of injury to a specific cerebral region. Here, we examined the proposition that both of these features are determined by the state of blood vessel immaturity. We developed a murine genetic model that allows for inducible and reversible VEGF blockade during brain development. Using this system, we determined that cerebral vessels mature in a centrifugal, wave-like fashion that results in sequential acquisition of a functional blood-brain barrier and exit from a VEGF-dependent phase, with periventricular vessels being the last to mature. This developmental program permitted selective ablation of periventricular vessels via episodic VEGF blockade within a specific, vulnerable gestational window. Enforced collapse of ganglionic eminence vessels and resultant periventricular neural apoptosis resulted in a PVL-like phenotype that recapitulates the primary periventricular lesion, ventricular enlargement, and the secondary cortical deficit in out-migrating GABAergic inhibitory interneurons. These findings provide an animal model that reproduces the temporal and spatial specificities of PVL and indicate that damage to VEGF-dependent, immature periventricular vessels contributes to PVL development.
Stem cells have a high therapeutic potential for the treatment of spinal cord injury (SCI). We have shown previously that endogenous stem cell potential is confined to ependymal cells in the adult spinal cord which could be targeted for non-invasive SCI therapy. However, ependymal cells are an understudied cell population. Taking advantage of transgenic lines, we characterize the appearance and potential of ependymal cells during development. We show that spinal cord stem cell potential in vitro is contained within these cells by birth. Moreover, juvenile cultures generate more neurospheres and more oligodendrocytes than adult ones. Interestingly, juvenile ependymal cells in vivo contribute to glial scar formation after severe but not mild SCI, due to a more effective sealing of the lesion by other glial cells. This study highlights the importance of the age-dependent potential of stem cells and post-SCI environment in order to utilize ependymal cell's regenerative potential.
Birth-related fractures are an important differential diagnosis of child abuse in early infancy. While fractures associated to vaginal deliveries are well known, cesarean section is not necessarily known to cause such injuries. Nevertheless neonatal fractures have been described after cesarean sections. To give an overview over the frequency and typical locations of such fractures, the appearance of symptoms and the timespan until diagnosis, a literature research was conducted via Google scholar and Pubmed, using the key words "cesarean section" and "fractures". Birth-related fractures after cesarean sections are rare but can occur, with the long bones being particularly affected. Therefore, birth injuries should always be considered in the forensic medical assessment of fractures in early infancy, even after cesarean section. To enable a differentiation between birth trauma and physical abuse, birth and operation records should be checked for surgical manoeuvres, possible difficulties during the procedure or other risk factors. Birth-related fractures are usually detected early; in rare cases, the diagnosis is made only weeks after birth.
Right obstetric brachial plexus injuries (OBPI) often lead to left-handedness before limb function is restored post-surgery. A pertinent question arises about promoting a transition from left to right-handedness. We hypothesized that, with the decrease in neuroplasticity, handedness switching is not only difficult, but also reduces handedness-speech lateralization, impaired motor adaptability, and compromised language proficiency.
To explore the repair effect of lycium barbarum polysaccharide (LBP) on ovarian injuries induced by repeated superovulation in mice, a model of ovarian injury was established, and ovarian repair was assessed after intragastric administration of LBP. The oocyte quality and blastocyst rates of pronuclear embryos in vitro were observed. The levels of 8-hydroxydeoxyguanosine (8-OHdG) and lipid peroxide (LPO) in ovarian tissue were measured, and ovarian damage was assessed in paraffin sections. The groups with significant injury were selected according to the above observation, mice in the significant injury group were intragastrically administered with LBP (low dose, 25 mg/kg; medium dose, 35 mg/kg; and high dose, 45 mg/kg) for 30 days. The above measurements and anti-Müllerian hormone (AMH) expression were detected in the mouse ovaries and the breeding verification was carried out. Our results showed that repeated superovulation could cause mouse oocyte quality to drop, significant differences started from 4 superovulation events (P < 0.05). The levels of 8-OHdG and LPO in the ovary increased gradually as the number of superovulation events increased, and significant differences were observed after 4-6 superovulations (P < 0.05). The ratios of primordial follicles, primary, tertiary and mature follicles decreased and the ratio of atresia follicles increased as the number of superovulation events increased, especially in 4-6 superovulation groups. Thus, the groups of superovulation 4-6 events were considered as significant injury groups. LBP-medium dose groups significantly improved the number and quantity of oocytes and embryo blastocyst rate (P < 0.05), significantly decreased 8-OHdG and LPO levels in mice ovary (P < 0.05), also improved the ratios of all stages follicles and reduced the rate of atresia follicles, increased the numbers of litter size, live birth, weaning survival, and repaired the expression of AMH in ovary significantly (P < 0.05). In conclusion, the degree of ovarian injury was affected by the number of superovulation. LBP repaired ovarian injuries most likely through scavenging oxidative products 8-OHdG and LPO and increasing AMH protein expression.
Road traffic injuries (RTIs) have become a considerable issue for children. In China, RTIs are among the top 3 contributors to injury-related mortality and disability-adjusted life years. The present study aimed to evaluate social and environmental factors that may contribute to RTIs among children under 5 in rural areas of China.
Bronchopulmonary dysplasia (BPD) is one of the most common complications of prematurity, occurring in 30% of very low birth weight infants. The benefits of dietary intake of polyunsaturated fatty acids ω-3 (PUFA ω-3) during pregnancy or the perinatal period have been reported. The aim of this study was to assess the effects of maternal PUFA ω-3 supplementation on lung injuries in newborn rats exposed to prolonged hyperoxia. Pregnant female Wistar rats (n = 14) were fed a control diet (n = 2), a PUFA ω-6 diet (n = 6), or a PUFA ω-3 diet (n = 6), starting with the 14th gestation day. At Day 1, female and newborn rats (10 per female) were exposed to hyperoxia (O₂, n = 70) or to the ambient air (Air, n = 70). Six groups of newborns rats were obtained: PUFA ω-6/O₂ (n = 30), PUFA ω-6/air (n = 30), PUFA ω-3/O₂ (n = 30), PUFA ω-3/air (n = 30), control/O₂ (n = 10), and control/air (n = 10). After 10 days, lungs were removed for analysis of alveolarization and pulmonary vascular development. Survival rate was 100%. Hyperoxia reduced alveolarization and increased pulmonary vascular wall thickness in both control (n = 20) and PUFA ω-6 groups (n = 60). Maternal PUFA ω-3 supplementation prevented the decrease in alveolarization caused by hyperoxia (n = 30) compared to PUFA ω-6/O₂ (n = 30) or to the control/O₂ (n = 10), but did not significantly increase the thickness of the lung vascular wall. Therefore, maternal PUFA ω-3 supplementation may protect newborn rats from lung injuries induced by hyperoxia. In clinical settings, maternal PUFA ω-3 supplementation during pregnancy and during lactation may prevent BPD development after premature birth.
The hexapeptide WKYMVm, which is a strong formyl peptide receptor (FPR) 2 agonist, exhibits pro-angiogenic, anti-inflammatory and anti-apoptotic properties. However, its therapeutic efficacy in bronchopulmonary dysplasia (BPD) has not been tested to date. Here, we investigated whether WKYMVm attenuates hyperoxia-induced lung inflammation and ensuing injuries by upregulating FPR2. The proliferation and tube formation ability of human umbilical vein endothelial cells (HUVECs), along with the level of extracellular signal regulated kinase (ERK) phosphorylation, were evaluated in vitro. Newborn mice were randomly exposed to 80% oxygen or room air for 14 days starting at birth. WKYMVm (2.5 mg/kg) was intraperitoneally administrated daily from postnatal day (P) 5 to P8. At P14, mice were sacrificed for histopathological and morphometric analyses. Along with upregulation of FPR2 and p-ERK, WKYMVm promoted HUVEC cell proliferation and tube formation in vitro. Additionally, WKYMVm promoted proliferation of human pulmonary microvascular endothelial cells (HULEC-5a) and murine pulmonary endothelial and epithelial cells in vitro. WKYMVm significantly attenuated hyperoxia-induced lung inflammation, as evidenced by increased inflammatory cytokines, neutrophils, and alveolar macrophages, and resultant lung injuries, which included impaired alveolarization and angiogenesis, an increased number of apoptotic cells, and reduced levels of growth factors in vivo, such as vascular endothelial growth factor and hepatocyte growth factor. WKYMVm attenuates hyperoxia-induced lung injuries and lung inflammation by upregulating FPR2 and p-ERK.
Clinical trial registries may allow for producing a global mapping of health research. However, health conditions are not described with standardized taxonomies in registries. Previous work analyzed clinical trial registries to improve the retrieval of relevant clinical trials for patients. However, no previous work has classified clinical trials across diseases using a standardized taxonomy allowing a comparison between global health research and global burden across diseases. We developed a knowledge-based classifier of health conditions studied in registered clinical trials towards categories of diseases and injuries from the Global Burden of Diseases (GBD) 2010 study. The classifier relies on the UMLS® knowledge source (Unified Medical Language System®) and on heuristic algorithms for parsing data. It maps trial records to a 28-class grouping of the GBD categories by automatically extracting UMLS concepts from text fields and by projecting concepts between medical terminologies. The classifier allows deriving pathways between the clinical trial record and candidate GBD categories using natural language processing and links between knowledge sources, and selects the relevant GBD classification based on rules of prioritization across the pathways found. We compared automatic and manual classifications for an external test set of 2,763 trials. We automatically classified 109,603 interventional trials registered before February 2014 at WHO ICTRP.
Preterm birth (PTB) is the leading cause of perinatal mortality and newborn complications. Bile acids are recognized as signaling molecules regulating a myriad of cellular and metabolic activities but have not been etiologically linked to PTB. In this study, a hospital-based cohort study with 36,755 pregnant women is conducted. We find that serum total bile acid levels directly correlate with the PTB rates regardless of the characteristics of the subjects and etiologies of liver disorders. Consistent with the findings from pregnant women, PTB is successfully reproduced in mice with liver injuries and dysregulated bile acids. More importantly, bile acids dose-dependently induce PTB with minimal hepatotoxicity. Furthermore, restoring bile acid homeostasis by farnesoid X receptor activation markedly reduces PTB and dramatically improves newborn survival rates. The findings thus establish an etiologic link between bile acids and PTB, and open an avenue for developing etiology-based therapies to prevent or delay PTB.
Approximately 15 million babies are born prematurely every year and many will face lifetime motor and/or cognitive deficits. Children born prematurely are at higher risk of developing perinatal brain lesions, especially white matter injuries (WMI). Evidence in humans and rodents demonstrates that systemic inflammation-induced neuroinflammation, including microglial and astrocyte reactivity, is the prominent processes of WMI associated with preterm birth. Thus, a new challenge in the field of perinatal brain injuries is to develop new neuroprotective strategies to target neuroinflammation to prevent WMI. Serotonin (5-HT) and its receptors play an important role in inflammation, and emerging evidence indicates that 5-HT may regulate brain inflammation by the modulation of microglial reactivity and astrocyte functions. The present study is based on a mouse model of WMI induced by intraperitoneal (i.p.) injections of IL-1β during the first 5 days of life. In this model, certain key lesions of preterm brain injuries can be summarized by (i) systemic inflammation, (ii) pro-inflammatory microglial and astrocyte activation, and (iii) inhibition of oligodendrocyte maturation, leading to hypomyelination. We demonstrate that Htr7 mRNA (coding for the HTR7/5-HT7 receptor) is significantly overexpressed in the anterior cortex of IL-1β-exposed animals, suggesting it as a potential therapeutic target. LP-211 is a specific high-affinity HTR7 agonist that crosses the blood-brain barrier (BBB). When co-injected with IL-1β, LP-211 treatment prevented glial reactivity, the down-regulation of myelin-associated proteins, and the apparition of anxiety-like phenotypes. Thus, HTR7 may represent an innovative therapeutic target to protect the developing brain from preterm brain injuries.
The aim of this study was to investigate the influence of calving-related injuries of the vestibulum vaginae and the vagina on fertility measures in heifers. German Holstein heifers (n = 236) were checked for vestibulum vaginae and vaginal injuries. These were scored according to localization, depth and length. The healing process was assessed until day 42 post partum. Calving ease and the occurrence of metritis and endometritis were evaluated. In 160 heifers, the following fertility measures were calculated to assess the reproductive performance of heifers: mean interval from calving to first insemination, mean days open, mean interval from first insemination to conception, mean calving interval, mean pregnancy index, percentage of animals pregnant at 200 days p.p., and first service conception rate. On the one hand, dystocia was a risk factor for injuries of the soft birth canal, and, on the other hand, those injuries were a risk factor for metritis and endometritis. In this study, calving-related injuries of the vestibulum vaginae and the vagina had no statistically significant effect on the reproductive performance of heifers. One reason for this outcome was probably the overall good healing tendencies of those injuries in heifers.
Gas explosions are a recurrent event in coal mining that cause severe pulmonary damage due to shock waves, and there is currently no effective targeted treatment. To illustrate the mechanism of gas explosion-induced lung injury and to explore strategies for blast lung injury (BLI) treatment, the present study used a BLI rat model and supplementation with metformin (MET), an AMP-activated protein kinase (AMPK) activator, at a dose of 10 mg/kg body weight by intraperitoneal injection. Protein expression levels were detected by western blotting. Significantly decreased expression of phosphorylated (p)-AMPK, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) and metabolic activity were observed in the BLI group compared with those in the control group. However, the mitochondrial stability, metabolic activity and expression of p-AMPK and PGC1α were elevated following MET treatment. These results suggested that MET could attenuate gas explosion-induced BLI by improving mitochondrial homeostasis. Meanwhile, high expression of nicotinamide adenine dinucleotide phosphate oxidase (NOX2) and low expression of catalase (CAT) were observed in the BLI group. The expression levels of NOX2 and CAT were restored in the BLI + MET group relative to changes in the BLI group, and the accumulation of oxidative stress was successfully reversed following MET treatment. Overall, these findings revealed that MET could alleviate BLI by activating the AMPK/PGC1α pathway and inhibiting oxidative stress caused by NOX2 activation.
The COVID-19 pandemic provide the opportunities to explore the numerous similarities in clinical symptoms with Kawasaki disease (KD), including severe vasculitis. Despite this, the underlying mechanisms of vascular injury in both KD and COVID-19 remain elusive. To identify these mechanisms, this study employs single-cell RNA sequencing to explore the molecular mechanisms of immune responses in vasculitis, and validate the results through in vitro experiments.
Introduction Birth-related perineal trauma (BPT) is a common consequence of vaginal births. When poorly managed, BPT can result in increased morbidity and mortality due to infections, haemorrhage, and incontinence. This review aims to collect data on rates of BPT in low- and middle-income countries (LMICs), through a systematic review and meta-analysis. Methods The following databases were searched: Medline, Embase, Latin American and Caribbean Health Sciences Literature (LILACs), and the World Health Organization (WHO) regional databases, from 2004 to 2016. Cross-sectional data on the proportion of vaginal births that resulted in episiotomy, second degree tears or obstetric anal sphincter injuries (OASI) were extracted from studies carried out in LMICs by two independent reviewers. Estimates were meta-analysed using a random effects model; results were presented by type of BPT, parity, and mode of birth. Results Of the 1182 citations reviewed, 74 studies providing data on 334,054 births in 41 countries were included. Five studies reported outcomes of births in the community. In LMICs, the overall rates of BPT were 46% (95% CI 36-55%), 24% (95% CI 17-32%), and 1.4% (95% CI 1.2-1.7%) for episiotomies, second degree tears, and OASI, respectively. Studies were highly heterogeneous with respect to study design and population. The overall reporting quality was inadequate. Discussion Compared to high-income settings, episiotomy rates are high in LMIC medical facilities. There is an urgent need to improve reporting of BPT in LMICs particularly with regards to births taking in community settings.
Most cases of traumatic injury during pregnancy involve blunt trauma, with penetrating trauma being uncommonly rare. In glass shard injuries, fragments often penetrate deeply, and multiple injuries may occur simultaneously; attention must be paid to the possibility of organ injury from the residual fragments. However, no case of this occurring during pregnancy has been reported yet.
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