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Using longitudinal surveys on married Singaporean women of childbearing ages, we compared self-reported changes to fertility plans among 407 and 345 respondents after the 2016–2017 Zika and 2020 COVID-19 outbreaks, respectively. Zika associated with intentions to delay but not reduce childbearing, while COVID-19 was associated with both. Some women reported accelerating and increasing childbearing during COVID-19, with more intending to bring forward births as the pandemic persisted. Education was more predictive of changes in fertility plans during the pandemic compared to the Zika epidemic, and women who delayed childbearing due to Zika were more likely to further adjust timing of childbearing during COVID-19. We considered three possible explanations for changes to fertility plans: fear of infection, change in subjective wellbeing, and income loss, and find stronger effects of perceptions of the virus on downward revisions of fertility plans after the Zika epidemic but a larger role for stress and income loss during the pandemic, reflecting the latter's wider economic and social impacts. [ABSTRACT FROM AUTHOR]

Background: Steroid-induced osteonecrosis of the femoral head (SONFH) is a challenging and debilitating orthopedic condition with a rising incidence in recent years. Shuanghe Decoction (SHD), a traditional Chinese medicine formula, has shown significant efficacy in treating SONFH, though its underlying mechanisms remain unclear. Purpose: This study aims to elucidate the therapeutic effects and potential mechanisms of SHD on SONFH through in vivo experiments, combined with network pharmacology, metabolomics, and gut microbiota analysis. Materials and methods: Forty male Sprague-Dawley rats (300 ± 20 g) were randomly assigned to four groups: Control, Model, SHD-L, and SHD-H, with 10 rats each. SONFH was induced in all groups except the Control group using lipopolysaccharide and methylprednisolone. The SHD-L and SHD-H groups were treated with Shuanghe decoction at doses of 4.86 g/kg/day and 9.72 g/kg/day, respectively, for eight weeks. Bone morphology, pathological changes, and osteogenic factors were evaluated using Micro-CT, histological staining, and immunohistochemistry. Network pharmacology, metabolomics, and gut microbiota analyses were conducted to explore SHD's mechanisms. Results: SHD improved bone morphology and increased osteogenic factor expression (RUNX2, OCN, COL-I). Network pharmacology indicated that metabolic pathways play a key role in SHD's therapeutic effects. Metabolomic analysis identified 14 differential metabolites, including 21-hydroxypregnenolone and tyramine, which were restored to normal levels by SHD. Gut microbiota analysis revealed that SHD modulated bacterial abundance, particularly Verrucomicrobia, Allobaculum, and Burkholderiales. A comprehensive network identified two key metabolites (tyramine, 21-hydroxypregnenolone), seven targets (CYP19A1, CYP1A2, CYP1B1, CYP2C9, CYP3A4, MIF, and HSD11B1), two metabolic pathways (tyrosine metabolism, steroid hormone biosynthesis), and four bacterial taxa (Jeotgalicoccus, Clostridium, Corynebacterium, rc4-4) as central to SHD against SONFH. Conclusion: SHD alleviates SONFH by reshaping gut microbiota, reversing metabolic imbalances, and enhancing osteogenesis. Our findings provide novel insights into the pharmacological mechanisms of SHD, laying a foundation for its clinical application in treating SONFH. [ABSTRACT FROM AUTHOR]

Background/Objectives: Pre-operative radiation (Pre-RT) decreases local recurrence following soft tissue sarcoma (STS) resection but carries the risk of wound healing complications (WHCs). This study evaluated skin specimens and clinical characteristics of STS patients to (1) compare patients with and without Pre-RT, (2) compare Pre-RT patients with and without WHCs, and (3) explore associations between clinical characteristics and WHCs. Methods: This retrospective study included 54 adults who underwent STS resection with primary closure (Pre-RT n = 30). A pathologist who was blinded to the clinical outcomes evaluated the skin specimens microscopically. Results: Irradiated skin had lower vessel density and was more likely to lack hair follicles and sebaceous glands, consistent with the effects of radiation. Irradiated skin was also more likely to include plasma cells. Irradiated skin demonstrated higher mean TAZ H-scores; however, within the Pre-RT subset, those patients who developed WHCs demonstrated comparatively lower TAZ. Conclusions: This novel finding may suggest that higher TAZ in irradiated skin reflects a response to injury but that comparatively lower TAZ in irradiated skin might contribute to WHCs. Future studies should consider more focused evaluation of TAZ in STS resections with Pre-RT as they may help to predict WHCs when used in combination with other histologic factors and could suggest a therapeutic target. [ABSTRACT FROM AUTHOR]

Osteoporosis is an inflammatory disease characterised by low bone mass and quality, resulting in weaker bone strength and fragility fractures. Periostin is a matricellular protein expressed in the periosteum of bone by osteoblasts. It regulates cell recruitment and differentiation in response to fracture and contributes to extracellular matrix (ECM) formation. The aim of the following study was to determine the splice variants of Periostin expressed in human osteoblasts and Periostin's function in the pathophysiology of osteoporosis. Osteoblasts isolated from femoral heads from 29 patients with or without osteoporosis were utilised. Periostin splice variants were compared by quantitative real-time polymerase chain reaction (qPCR). Furthermore, the effect of Periostin inhibition on osteoblast differentiation was investigated using alizarin red S staining. Lastly, the interaction of IL-6 and Periostin and their effect on osteoprotegerin (OPG) secretion were analysed with the implantation of enzyme-linked immunosorbent assays (ELISAs). It could be demonstrated that human osteoblasts preferentially express Periostin isoform 4, even if splice variant expression was not altered in osteoporosis conditions, indicating that Periostin's functions in bone are primarily attributable to this isoform. The inhibition of Periostin resulted in significantly reduced osteoblast differentiation. However, Periostin was secreted in significantly higher amounts in osteoblasts from patients with osteoporosis. Additionally, Periostin significantly reduces OPG secretion and, thereby, rather promotes bone resorption. Furthermore, it could be determined that Periostin and IL-6 induce each other, and both significantly decrease OPG secretion. A positive feedback loop exacerbates the dysregulation found in human osteoblasts from patients with osteoporosis, thereby contributing to bone loss. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis (OP) frequently occurs in post-menopausal women, increasing the risk of fracture. Early screening OP could improve the prevention of fractures.This study focused on the significance of miR-208a-3p in diagnosing OP and development regulation, aiming to explore a novel biomarker and therapeutic target for OP. Methods: The study enrolled a total of 154 post-menopausal women and grouping was performed based on the incidence of OP and fracture. The significance of miR-208a-3p was evaluated from the perspectives of menopausal correlation, OP diagnosis, and fracture prediction. In mechanism, the regulatory effect and mechanism of miR-208a-3p on osteoclast activation was investigated. Results: miR-208a-3p was menopause-related showing a negative correlation with E2 and positive correlations with FSH and LH. Significant upregulation of miR-208a-3p was observed in post-menopausal women with OP and showed significant diagnostic potential. Increasing miR-208a-3p was positively correlated with bone metabolism markers and negatively correlated with BMD of post-menopausal women with OP. Moreover, miR-208a-3p was also identified as a risk factor for fracture. STC1 was identified as a direct target of miR-208a-3p and was negatively regulated by miR-208a-3p. Silencing miR-208a-3p significantly alleviated macrophage inflammation and osteoblast activation, which was reversed by the knockdown of STC1. Conclusion: Serum miR-208a-3p served as a diagnostic biomarker for OP and a risk factor for fracture in post-menopausal women. miR-208a-3p regulated macrophage inflammation and further mediated osteoclast activation via targeting STC1. [ABSTRACT FROM AUTHOR]

Background: For patients with epilepsy, antiseizure medication remains the primary treatment; however, it is ineffective in approximately 30% of cases. These patients experience progressive neuronal damage and poor outcomes. Therefore, there is an urgent need for disease-modifying therapy (DMT) that targets the pathogenesis of epilepsy. Glycyrrhizin has shown potential as a DMT in epilepsy due to its multiple targets and diverse mechanisms. Previous studies suggest that glycyrrhizin may regulate key processes involved in epilepsy pathogenesis, such as neuroinflammation and cell death, but its effects on pyroptosis have not been reported. Methods: This study employed bioinformatics techniques to identify potential molecular targets for glycyrrhizin in epilepsy treatment and then validated using a kainic acid-induced status epilepticus mouse model. Results: Glycyrrhizin treatment significantly prolonged seizure latency, reduced seizure duration, and alleviated neuronal damage in the status epilepticus mouse model. Molecular experiments indicated that glycyrrhizin may regulate pyroptosis through mediation of the high mobility group box 1 (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling pathway. Conclusion: Glycyrrhizin exerts neuroprotective and anticonvulsant effects in epilepsy by regulating pyroptosis via the HMGB1/TLR4/NF-κB signaling pathway, offering novel insights into its potential as a DMT for epilepsy. [ABSTRACT FROM AUTHOR]

Introduction: Neoadjuvant radiotherapy (NART) is often used in the treatment of extremity soft tissue sarcomas (STS) including myxoid liposarcoma (MLS). Postoperative major wound complications (WC) are a well-recognised problem following NART. Aims: A review of the literature regarding the definition and incidence of WC following NART and surgery for STS and a retrospective review of a single surgeon series of 25 MLS. Methods: A literature search for papers focusing on MLS, NART and WC was performed, with 12 papers being reviewed. Retrospective data from a single surgeon series of 25 patients with MLS, treated with NART and surgery, were reviewed, focussing on WC. Results: The average rate of WC from the 12 papers included was 29·4% (20–47%), and the average rate of reoperation was 15·6% (7·3–24%). There were a range of definitions used for WC, most commonly O'Sullivan's definition. In the single surgeon series, two patients (8%) developed WC and were treated conservatively, and there were no reoperations within 120 days. Conclusion: This literature review identified that there was a lack of consistency between the definitions used for major WC. The single surgeon series of MLS showed WC that were lower when compared to the reviewed literature (8% versus 29·4%). [ABSTRACT FROM AUTHOR]

The autonomic regulation of the pulmonary vasculature has been under‐appreciated despite the presence of sympathetic and parasympathetic neural innervation and adrenergic and cholinergic receptors on pulmonary vessels. Recent clinical trials targeting this innervation have demonstrated promising effects in pulmonary hypertension, and in this context of reignited interest, we review autonomic pulmonary vascular regulation, its integration with other pulmonary vascular regulatory mechanisms, systemic homeostatic reflexes and their clinical relevance in pulmonary hypertension. The sympathetic and parasympathetic nervous systems can affect pulmonary vascular tone and pulmonary vascular stiffness. Local afferents in the pulmonary vasculature are activated by elevations in pressure and distension and lead to distinct pulmonary baroreflex responses, including pulmonary vasoconstriction, increased sympathetic outflow, systemic vasoconstriction and increased respiratory drive. Autonomic pulmonary vascular control interacts with, and potentially makes a functional contribution to, systemic homeostatic reflexes, such as the arterial baroreflex. New experimental therapeutic applications, including pulmonary artery denervation, pharmacological cholinergic potentiation, vagal nerve stimulation and carotid baroreflex stimulation, have shown some promise in the treatment of pulmonary hypertension. What is the topic of this review?This review examines our understanding of the autonomic control of pulmonary circulation, with an emphasis on its clinical relevance and potential therapeutic targeting in pulmonary hypertension.What advances does it highlight?The sympathetic and parasympathetic nervous systems both regulate pulmonary vascular tone and stiffness, in integration with systemic autonomic homeostasis. Pulmonary vascular afferents responsive to pulmonary arterial pressure produce distinct pulmonary baroreflex responses. Dysfunction in autonomic control both to and from the pulmonary vasculature might contribute to pulmonary hypertension, and new approaches targeting this have demonstrated early success. [ABSTRACT FROM AUTHOR]

Purpose of Review: Chronic axial spinal pain is a leading cause of disability and healthcare spending in the United States. A common source of axial spinal pain is the facet joint. Current treatments for facet joint-mediated pain include conservative treatments and interventions such as intra-articular facet joint injections (FJI), medial branch blocks (MBB), and radiofrequency ablation (RFA). While facet joint interventions are one of the most common spinal procedures, current scientific literature demonstrates conflicting results regarding the use of corticosteroids in these interventions., Recent Findings: A systematic review was conducted to determine the efficacy of local corticosteroid usage in facet joint interventions for treating chronic axial spinal pain. Separate literature searches were performed using PubMed, Google Scholar, Embase, and Cochrane Library to evaluate the use of local corticosteroids in intra-articular FJI, MBB, and for the prevention of post-neurotomy neuritis (PNN). Inclusion criteria included a randomized clinical trial (RCT) or control trial while unique inclusion criteria was used for the differing uses of local corticosteroids. The exclusion criteria for studies included (i) studies written in a non-English language; (ii) articles without full-text access or abstract-only papers; (iii) and studies focused on non-human subjects. Final literature searches were conducted in August 2024. Two studies with 131 patients, four studies with 440 patients, and two studies with 203 patients were selected for the assessment of local corticosteroid use on intra-articular FJI, MBB, and PNN, respectively. A quality assessment tool recommended by The Cochrane Collaboration was used to assess bias risk in included studies. Results were synthesized through a meta-analysis to evaluate intra-articular FJI while a literature analysis was completed to investigate MBB and PNN. This study found that the use of corticosteroid intra-articular FJI and MBB provides significant improvement in pain relief and functionality from baseline for the treatment of lower back pain and chronic axial spinal pain, respectively. However, the use of corticosteroids post-RFA has not been proven to reduce the occurrence of PNN. Limitations to the studies used included blinding bias, absence of placebo groups, subjective inclusion criteria, limited generalizability and small sample sizes., Competing Interests: Declarations. Ethics Approval: This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. Competing interests: ADK is the Editor-in-chief of CPHRs. Human and Animal Rights and Informed Consent: This article does not contain any studies with human or animal subjects performed by any of the authors., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Heart failure (HF) with preserved ejection fraction (HFpEF) is a complex syndrome characterized by symptoms of HF despite normal left ventricular function. It now accounts for >50% of all HF cases, with the only effective treatment (morbidity benefit) so far being sodium-glucose co-transporter-2 inhibitors, finerenone and tirzepatide. Recently, vascular dysfunction has been highlighted as one of the main pathophysiological mechanisms of HFpEF. Recently, a 'two-hit' experimental model of HFpEF was described in which mice fed a high-fat diet (HFD) and l-NAME developed a phenotype that mimics human HFpEF. We further characterize this model by assessing vascular remodelling in the aorta, carotid and femoral arteries. C57BL/6N mice aged 11-12 weeks were fed a HFD and water supplemented with l-NAME 1.5 g/L for 15 weeks. These mice manifested increased body weight and blood pressure, glucose and exercise intolerance, and cardiac structural and functional alterations consistent with HFpEF. Morphometric analyses were performed in the aorta, carotid and femoral arteries, revealing increased media thickness and media-to-lumen ratios. Moreover, we detected evidence of fibrosis in the middle layer of the aorta. A correlation between increased aortic remodelling and fibrosis with diastolic dysfunction was observed. Vascular reactivity studies using wire myography uncovered impaired vasoconstriction and vasodilatation responses, suggesting aortic stiffness. We also detected the presence of a senescence-like phenotype in the aortic wall. Together, these data offer valuable contributions to understanding the vascular mechanisms underlying HFpEF. KEY POINTS: Heart failure with preserved ejection fraction (HFpEF) represents >50% of heart failure patients. Despite its growing prevalence, the aetiology of HFpEF continues to be incompletely understood, mainly due to the lack of reliable animal models. An HFpEF mouse model, obtained by feeding mice a high-fat diet and exposing them to l-NAME, reproduces the majority of the clinical features observed in HFpEF patients. Possible vascular alterations elicited by this model remain unknown. Here, we report that HFpEF mice manifest aortic, carotid and femoral artery remodelling. The aorta also harboured fibrosis plus impaired vasodilatation and vasoconstriction responses. Aortic remodelling and fibrosis correlated with diastolic dysfunction. The aorta from HFpEF mice harboured increased p53, IL-6 and VCAM-1 protein levels, suggesting a senescence-like phenotype. These data reveal that this HFpEF mouse model displays vascular alterations similar to those reported in HFpEF patients. These findings unveil novel insights into the vascular remodelling of HFpEF and, furthermore, validate a reliable animal model that can be used to study HFpEF aetiology and potentially develop future therapeutic approaches., (© 2025 The Authors. The Journal of Physiology © 2025 The Physiological Society.)

Epilepsy which is a chronic neurological disorder is characterized by recurrent seizure poses a significant challenge to healthcare professionals worldwide. Most of antiepileptic drugs have serious side effects that might affect the quality of life such as fatigue, dizziness, weight gain and cognitive impairments. In this context, the search for more effective and potential antiepileptic drug candidate has led to a growing interest in the field of synthesis of heterocyclic compounds. This review will focus on the utilization of heterocyclic moieties including imidazole, indole, thiazole, triazine, quinazoline and oxazole which show remarkable anticonvulsant properties. Furthermore, the exploration of various methodologies for the synthesis of heterocyclic anticonvulsant drugs such as green methodologies and microwave assisted protocols have contributed to the development of environment friendly, more efficient and potential approaches. The review will distinguish from previous ones by specifically focusing on innovative synthetic methodologies, including greener methodologies and micro-assisted techniques, that contribute to eco-friendly and environment benign approaches during 2019-2024. In addition to this, the review will focus on the Structure Activity Relationship (SAR) studies of heterocyclic compounds in order to offer insight into the design of next generation antiepileptic drugs with improved efficacy and reduced side effects., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Proteasomes are the catalytic complexes in eukaryotic cells that decide the fate of proteins involved in various cellular processes in an energy-dependent manner. The proteasomal system performs its function by selectively destroying the proteins labelled with the small protein ubiquitin. Dysfunctional proteasomal activity is allegedly involved in various clinical disorders such as cancer, neurodegenerative disorders, ageing, and so forth, making it an important therapeutic target. Notably, compared to healthy cells, cancer cells have a higher protein homeostasis requirement and a faster protein turnover rate. The ubiquitin-proteasome system (UPS) helps cancer cells increase rapidly and experience less apoptotic cell death. Therefore, understanding UPS is essential to design and discover some effective inhibitors for cancer therapy. Hereby, we have focused on the role of the 26S proteasome complex, mainly the UPS, in carcinogenesis and seeking potential therapeutic targets in treating numerous cancers., (© 2025 Wiley Periodicals LLC.)