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Foam cells in atheroma are engorged with lipid droplets (LDs) that contain esters of regulatory lipids whose metabolism remains poorly understood. LD-associated hydrolase (LDAH) has a lipase structure and high affinity for LDs of foam cells. Using knockout and transgenic mice of both sexes, here we show that LDAH inhibits atherosclerosis development and promotes stable lesion architectures. Broad and targeted lipidomic analyzes of primary macrophages and comparative lipid profiling of atheroma identified a broad impact of LDAH on esterified sterols, including natural liver X receptor (LXR) sterol ligands. Transcriptomic analyzes coupled with rescue experiments show that LDAH modulates the expression of prototypical LXR targets and leads macrophages to a less inflammatory phenotype with a profibrotic gene signature. These studies underscore the role of LDs as reservoirs and metabolic hubs of bioactive lipids, and suggest that LDAH favorably modulates macrophage activation and protects against atherosclerosis via lipolytic mobilization of regulatory sterols.
Asunto(s)
Aterosclerosis , Gotas Lipídicas , Receptores X del Hígado , Macrófagos , Ratones Noqueados , Animales , Aterosclerosis/metabolismo , Aterosclerosis/genética , Aterosclerosis/prevención & control , Aterosclerosis/patología , Receptores X del Hígado/metabolismo , Receptores X del Hígado/genética , Ratones , Masculino , Ligandos , Femenino , Gotas Lipídicas/metabolismo , Macrófagos/metabolismo , Esteroles/metabolismo , Células Espumosas/metabolismo , Ratones Transgénicos , Ratones Endogámicos C57BL , Humanos , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patología , Activación de Macrófagos , Esterol EsterasaRESUMEN
Objective: Peripartum hysterectomy is a major operation and is inevitably performed where certain indications require removal of the uterus at the time of delivery or in the immediate postpartum period. It is a traumatic birth event that affects women's physical, physiological, psychological, social, and sexual health. This study aimed to explore the lived experiences of women undergone peripartum hysterectomy. Materials and methods: Qualitative phenomenological design was adopted to explore the lived experiences of women undergone peripartum hysterectomy. Purposive sampling technique was adopted to enroll the participants and 19 women were interviewed before saturation of responses was reached. All interviews were audio recorded and then transcribed into verbatims. Colaizzi's thematic analysis method was used to analyze the data. Results: Based on participants' verbatims eight major themes emerged: Awareness status regarding peripartum hysterectomy; Body's response to peripartum hysterectomy; Perceived need of support; Facilitators in overcoming post-hysterectomy challenges; Relational turbulence; financial burden; Perceived psychological adaptation; Disturbed body image and low self-esteem. Conclusion: Derived themes in the present study highlighted the multidimensional effects of peripartum hysterectomy. Peripartum hysterectomy affected physical, psychological, sexual and financial health of the women. Increased dependence and changes in the self concept are the other problems faced by peripartum hysterectomy women. Need based individualized psychological therapeutic interventions will facilitate the successful adaptation to the traumatic situation by the reinforcement of positive coping mechanisms.
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Iron-refractory iron deficiency anaemia (IRIDA) is a rare autosomal recessive disorder, distinguished by hypochromic microcytic anaemia, low transferrin levels and inappropriately elevated hepcidin (HEPC) levels. It is caused by mutations in TMPRSS6 gene. Systematic screening of 500 pregnant women with iron deficiency anaemia having moderate to severe microcytosis with no other causes of anaemia were enrolled to rule out oral iron refractoriness. It identified a final cohort of 10 (2.15% prevalence) individuals with IRIDA phenotype. Haematological and biochemical analysis revealed significant differences between iron responders and iron non-responders, with iron non-responders showing lower haemoglobin, red blood cell count, serum iron and serum ferritin levels, along with elevated HEPC (9.47 ± 2.75 ng/mL, p = 0.0009) and erythropoietin (4.58 ± 4.07 µ/mL, p = 0.0196) levels. Genetic sequencing of the TMPRSS6 gene in this final cohort identified 10 novel variants, including seven missense and three frame-shift mutations, with four missense variants showing high functional impact defining the IRIDA phenotype. Structural analysis revealed significant damage caused by two variants (p.L83R and p.S235R). This study provides valuable insights into IRIDA among pregnant women in the Indian subcontinent, unveiling its underlying causes of unresponsiveness, genetic mechanisms and prevalence. Furthermore, research collaboration is essential to validate these findings and develop effective treatments.
Asunto(s)
Anemia Ferropénica , Proteínas de la Membrana , Serina Endopeptidasas , Humanos , Femenino , Embarazo , Anemia Ferropénica/genética , Proteínas de la Membrana/genética , Adulto , Serina Endopeptidasas/genética , Complicaciones Hematológicas del Embarazo/genética , India/epidemiología , Fenotipo , Mutación Missense , Hierro/metabolismo , Genotipo , Mutación , Adulto JovenRESUMEN
This review explores the benefits of yoga during pregnancy and considers its implications for working pregnant women, focusing on safety, future directions, and limitations. The physical and psychological changes experienced during pregnancy can lead to increased stress and discomfort, impacting both maternal and fetal health, which may be further augmented by work stress during pregnancy. To address these challenges, various interventions such as yoga, relaxation techniques, and meditation have been proposed. Although there is evidence to support the benefits of yoga at both physical and psychological levels, there is a lack of proper strategies and guidelines for the implications of these interventions among working pregnant women. Incorporating yoga as a safe and cost-effective intervention for managing work-related distress during pregnancy can have significant benefits for both maternal and fetal health. However, careful consideration of safety guidelines, further research on working pregnant women, and exploring optimal implementation strategies are essential to fully harness the potential of yoga in this context. This review aims to provide a comprehensive overview of the current evidence for the benefits and safety of yoga during pregnancy, with a specific focus on working pregnant women. To ensure the scientific rigor of this review, we conducted a systematic search of the PubMed database for high-quality research studies published in peer-reviewed journals.
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N-acetylaspartate (NAA), the brain's second most abundant metabolite, provides essential substrates for myelination through its hydrolysis. However, activities and physiological roles of NAA in other tissues remain unknown. Here, we show aspartoacylase (ASPA) expression in white adipose tissue (WAT) governs systemic NAA levels for postprandial body temperature regulation. Proteomics and mass spectrometry revealed NAA accumulation in WAT of Aspa knockout mice stimulated the pentose phosphate pathway and pyrimidine production. Stable isotope tracing confirmed higher incorporation of glucose-derived carbon into pyrimidine metabolites in Aspa knockout cells. Additionally, serum NAA positively correlates with the pyrimidine intermediate orotidine and this relationship predicted lower body mass index in humans. Using whole-body and tissue-specific knockout mouse models, we demonstrate that fat cells provided plasma NAA and suppressed postprandial body temperature elevation. Furthermore, exogenous NAA supplementation reduced body temperature. Our study unveils WAT-derived NAA as an endocrine regulator of postprandial body temperature and physiological homeostasis.
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Ovarian cysts exhibit variable clinical presentations depending on their size, type and resulting sequelae. Rupture of ovarian cysts is infrequent, and cyst infections are even rarer. Here, we report an unusual case involving a young, non-pregnant woman who presented acutely with features of peritonitis and sepsis and was found to have a complex adnexal mass. Following a rigorous diagnostic evaluation, which included an urgent exploratory laparotomy and salpingo-oophorectomy, common diagnoses including tubo-ovarian abscess, endometriotic cyst and pelvic tuberculosis were ruled out. Instead, she was diagnosed with an ovarian mucinous cystadenoma that had become infected, possibly due to pelvic inflammatory disease, leading to spontaneous rupture. Such a presentation has rarely been reported, especially in a non-pregnant setting. Therefore, we emphasise the importance of considering this rare complication as a potential differential diagnosis in similar clinical presentations and discuss the management implications, including the importance of adequately treating pelvic inflammatory disease.