Phase Of Cycle Research Articles

Examining the upper frequency limit of dynamic cerebral autoregulation: Considerations across the cardiac cycle during eucapnia.

There are differences within the literature regarding the upper frequency cut-off point of the dynamic cerebral autoregulation (CA) high-pass filter. The projection pursuit regression approach has demonstrated that the upper frequency limit is ∼0.07Hz, whereas another approach [transfer function analysis (TFA) phase approaching zero] indicated a theoretical upper frequency limit for the high-pass filter of 0.24Hz. We investigated how these limits accurately represent the CA upper frequency limit, in addition to extending earlier findings with respect to biological sexes and across the cardiac cycle. Sixteen participants (nine females and seven males) performed repeated squat-stand manoeuvres at frequencies of 0.05, 0.10, 0.15, 0.20 and 0.25Hz, with insonation of the middle and posterior cerebral arteries. Linear regression modelling with adjustment for sex and order of squat completion was used to compared TFA gain and phase with 0.25Hz (above the theoretical limit of CA). The upper frequency limit of CA with TFA gain was within the range of 0.05-0.10Hz, whereas TFA phase was within the range of 0.20-0.25Hz, and consistent between vessels, between sexes and across the cardiac cycle. Females displayed greater middle cerebral artery gain compared with males (all P<0.047), and no phase differences were present (all P>0.072). Although sex-specific differences were present for specific TFA metrics at a given frequency, the upper frequency limit of autoregulation was similar between cerebral conduit vessels, cardiac cycle phase and biological sex. Future work is warranted to determine whether an upper frequency limit exists with respect to hysteresis analyses.

Stress-induced phosphoprotein 1 expression in the endometrium and myometrium of patients with adenomyosis

BACKGROUND: The study of stress-induced phosphoprotein 1 in the pathogenesis of adenomyosis is not only of theoretical interest, but this protein may be also considered as a potential biomarker of the disease. AIM: The aim of this study was to evaluate stress-induced phosphoprotein 1 expression in the endometrium and heterotopic foci in women with isolated adenomyosis and in combination with benign hyperproliferative diseases of the reproductive organs. MATERIALS AND METHODS: This study enrolled 66 women aged 21 to 47 years (34.9 ± 6.7 years), including 49 patients with adenomyosis and 17 women in the control group. The main group was divided into subgroups depending on the concomitant hyperproliferative disease such as isolated adenomyosis (n = 36), adenomyosis combined with uterine fibroids (n = 8), and adenomyosis combined with endometriosis (n = 5). The patients underwent endometrial biopsy and multifocal myometrial biopsy. Histological and immunohistochemical studies were performed to assess stress-induced phosphoprotein 1 expression in the glandular and stromal components of the endometrium and ectopic endometrial tissue within the uterine myometrium. RESULTS: We found increased stress-induced phosphoprotein 1 expression in the adenomyosis lesion compared to that in the myometrium of the control group, regardless of the phase of the menstrual cycle (p 0.001). When studying stress-induced phosphoprotein 1 expression in the endometrium of the main group in the proliferative phase of the menstrual cycle, an increase was found, but the differences were not significant. Stress-induced phosphoprotein 1 expression in the secretory phase of the menstrual cycle was higher in the glandular component of the endometrium of patients with adenomyosis compared to the levels in women in the control group (p 0.05). CONCLUSIONS: The increased expression of stress-induced phosphoprotein 1 in the glandular component of the adenomyosis lesion indicates a potential role of the protein in the pathogenesis of the disease. However, further research is needed to determine its practical significance.

Immune Modulation by Epstein–Barr Virus Lytic Cycle: Relevance and Implication in Oncogenesis

EBV infects more than 90% of people globally, causing lifelong infection. The phases of the EBV life cycle encompass primary infection, latency, and subsequent reactivation or lytic phase. The primary infection usually happens without noticeable symptoms, commonly in early life stages. If it manifests after childhood, it could culminate in infectious mononucleosis. Regarding potential late consequences, EBV is associated with multiple sclerosis, rheumatoid arthritis, chronic active EBV infection, lymphomas, and carcinomas. Previous reports that the lytic phase plays a negligible or merely secondary role in the oncogenesis of EBV-related tumors are steadily losing credibility. The right mechanisms through which the lytic cycle contributes to carcinogenesis are still unclear, but it is now recognized that lytic genes are expressed to some degree in different cancer-type cells, implicating their role here. The lytic infection is a persistent aspect of virus activity, continuously stimulating the immune system. EBV shows different strategies to modulate and avoid the immune system, which is thought to be a key factor in its ability to cause cancer. So, the principal goal of our review is to explore the EBV’s lytic phase contribution to oncogenesis.

Estradiol-mediated enhancement of the human ectocervical epithelial barrier correlates with desmoglein-1 expression in the follicular menstrual phase

BackgroundThe cervicovaginal epithelial barrier is crucial for defending the female reproductive tract against sexually transmitted infections. Hormones, specifically estradiol and progesterone, along with their respective receptor expressions, play an important role in modulating this barrier. However, the influence of estradiol and progesterone on gene and protein expression in the ectocervical mucosa of naturally cycling women is not well understood.MethodsMucosal and blood samples were collected from Kenyan female sex workers at high risk of sexually transmitted infections. All samples were obtained at two time points, separated by two weeks, aiming for the follicular and luteal phases of the menstrual cycle. Ectocervical tissue biopsies were analyzed by RNA-sequencing and in situ immunofluorescence staining, cervicovaginal lavage samples (CVL) were evaluated using protein profiling, and plasma samples were analyzed for hormone levels.ResultsUnsupervised clustering of RNA-sequencing data was performed using Weighted gene co-expression network analysis (WGCNA). In the follicular phase, estradiol levels positively correlated with a gene module representing epithelial structure and function, and negatively correlated with a gene module representing cell cycle regulation. These correlations were confirmed using regression analysis including adjustment for bacterial vaginosis status. Using WGCNA, no gene module correlated with progesterone levels in the follicular phase. In the luteal phase, no gene module correlated with either estradiol or progesterone levels. Protein profiling on CVL revealed that higher levels of estradiol during the follicular phase correlated with increased expression of epithelial barrier integrity markers, including DSG1. This contrasted to the limited correlations of protein expression with estradiol levels in the luteal phase. In situ imaging analysis confirmed that higher estradiol levels during the follicular phase correlated with increased DSG1 expression.ConclusionWe demonstrate that estradiol levels positively correlate with specific markers of ectocervical epithelial structure and function, particularly DSG1, during the follicular phase of the menstrual cycle. Neither progesterone levels during the follicular phase nor estradiol and progesterone levels during the luteal phase correlated with any specific sets of gene markers. These findings align with the expression of estradiol and progesterone receptors in the ectocervical epithelium during these menstrual phases.

Silmitasertib in Combination With Cabozantinib Impairs Liver Cancer Cell Cycle Progression, Induces Apoptosis, and Delays Tumor Growth in a Preclinical Model.

The rising incidence of hepatocellular carcinoma (HCC) is a global problem. Several approved treatments, including immune therapy and multi-tyrosine kinase inhibitors, are used for treatment, although the results are not optimum. There is an unmet need to develop highly effective chemotherapies for HCC. Targeting multiple pathways to attack cancer cells is beneficial. Cabozantinib is an orally available bioactive multikinase inhibitor and has a modest effect on HCC treatment. Silmitasertib is an orally bioavailable, potent CK2 inhibitor with a direct role in DNA damage repair and is in clinical trials for other cancers. In this study, we planned to repurpose these existing drugs on HCC treatment. We observed a stronger antiproliferative effect of these two combined drugs on HCC cells generated from different etiologies as compared to the single treatment. Global RNA-seq analyses revealed a decrease in the expression of G2/M cell cycle transition genes in HCC cells following combination treatment, suggesting G2 phase cell arrest. We observed G2/M cell cycle phase arrest in HCC cells upon combination treatment compared to the single-treated or vehicle-treated control cells. The downregulation of CCNA2 and CDC25C following combination therapy further supported the observation. Subsequent analyses demonstrated that combination treatment inhibited 70 kDa ribosomal protein S6 kinase (p70S6K) phosphorylation, and increased Bim expression. Apoptosis of HCC cells were accompanied by increased poly (ADP-ribose) polymerase cleavage and caspase-9 activation. Next, we observed that a combination therapy significantly delayed the progression of HCC xenograft growth as compared to vehicle control. Together, our results suggested combining cabozantinib and silmitasertib would be a promising treatment option for HCC.

Determination of thiol-disulphide homeostasis in premenstrual syndrome during adolescence

Background. Premenstrual syndrome (PMS) characterized by cyclic symptoms during the luteal phase of the menstrual cycle, presents an uncertain etiology in adolescents involving hormonal fluctuations and serotonin-related neurotransmitters with a limited existing literature on the impact of oxidative stress. This study aimed to explore the potential association between PMS and oxidative stress in adolescents. Methods. In a cross-sectional study conducted at a university hospital, involving 45 adolescent girls aged 12 to 18, participants were categorized based on the presence or absence of PMS using the cut-off point of 110 on the PMS Scale developed by Gençdoğan. Oxidative stress was assessed through dynamic thiol-disulfide homeostasis. The shift from the balance towards disulfide form is associated with oxidative stress, whereas towards thiol it shows a greater antioxidant capacity. Results. Thirty out of the forty-five participants were found to have PMS with a mean age of 15.5 years. The PMS group demonstrated a significant increase in antioxidant markers, specifically elevated native (631.6±57.55 vs 598.2±41.08, p=0.048) and total thiol levels (675.15±3.4 vs 639.3±44.9, p=0.031). Despite a significant increase in thiol, thiol to disulfide ratio was not found to be significant (p=0.849). Conclusion. Contradictory to other studies in adults, we have demonstrated an increase in the antioxidant markers in adolescents with PMS. Elevated antioxidant status in adolescents with PMS may be an adaptive response to acute cyclic inflammation in the adolescent period, which might decrease with the progression of age. Further research is needed to investigate the complex interaction between oxidative stress and PMS across different age groups.

СОЦІАЛЬНО-ЕКОНОМІЧНІ ЦИКЛИ: ТЕОРЕТИЧНА ІНТЕРПРЕТАЦІЯ ТА СТАТИСТИЧНЕ ОЦІНЮВАННЯ

Sustainable national economic development requires a balance of aggregate demand and aggregate supply. The country's government is working out economic and legal mechanisms to achieve macroeconomic balance against factors that can disrupt it. The preconditions of macroeconomic instability include exogenous (natural and military-political) and endogenous (macroeconomic cyclical development). Due to the combination of these factors, achieving national macroeconomic balance is an urgent scientific and practical task for economists, scientists who study macroeconomics, as well as politicians and government officials. The key questions that need to be answered are the length of the cycle, the pace of the recession, and most importantly, the development of effective mechanisms for restoring macroeconomic balance and its long-term maintenance. The study of sustainable national economic development assumes cyclicality. It can be considered an independent process from the point of view of the manifestation of self-regulation of the market economy, when the equilibrium will be restored after a certain period of time by the action of market mechanisms, and also as a process of decline in business activity, which can be scientifically and practically studied as a phenomenon and, accordingly, an effective macroeconomic strategy of government policy can be identified. With the aim of accelerated and controlled passage of the economic cycle and development of effective government instruments, scientists study the essence and causes of macroeconomic instability, manifestations of unemployment and inflation. Cyclicality should be considered as a movement of the national economy, a form of its development and improvement. The socio-economic cycle involves fluctuations in the macroeconomic situation (level of employment, production and prices) from recession to upswing against the background of the general trend of the dynamics of the gross domestic product. The success of the government's macroeconomic policy is determined by the cause of the crisis, the degree of state regulation of the economy, opportunities to use the results of scientific and technical development, and the ratio of the shares of the real and non-productive sectors of the economy. This approach involves theoretical interpretation and statistical evaluation of socio-economic cycles. The article considers the main aspects of the theoretical interpretation of socio-economic cycles. A review of the scientific works of leading macroeconomists regarding the study of the essence and manifestations of cyclicality in the economy, social life of society was carried out, and attention was also paid to the issues of the interrelationship of the development of the economies of different countries in the conditions of globalization. The main factors of cyclical fluctuations and their periodicity are highlighted, the main theoretical provisions of economic cyclicality are given. The article provides a methodology for statistical evaluation of socio-economic cycles and the selection of its individual phases (recession, boom) based on the application of the method of statistical equations of dependencies and the method of complex statistical coefficients. Using the method of statistical equations of dependence, the existence of a relationship between the result indicator (GDP, billion US dollars, y) and two factors: "External debt, billion US dollars, x", "Number of registered unemployed, thousands of people, z" was established . It was determined that the factor "External debt, billion US dollars, x" plays the main role in the formation of the output indicator (GDP). It is substantiated that when the value of "GDP, billion US dollars" increases by 1 billion dollars. In the USA, the factor "External debt, billion US dollars" is expected to increase by 0.63 billion US dollars, and with an increase in the value of "GDP, billion US dollars" by 1 billion dollars. In the USA, the value of the factor "Number of registered unemployed, thousands of persons" is expected to decrease. for 5.43 thousand persons. Cyclicality was studied on the basis of the two mentioned methods and two phases of the economic development cycle of Ukraine were identified: 2008-2009 and 2013-2015. A generalization was obtained regarding the existence of a phase of the seven-year economic cycle.

Efficacy and uterine bleeding patterns in initiating goserelin therapy during different menstrual phases in patients with adenomyosis: a prospective cohortstudy.

We carried out this study to explore the possibility of initiating goserelin therapy during the non-menstrual period in patients diagnosed with adenomyosis. 115 premenopausal adenomyosis patients were enrolled and divided into three groups based on their menstrual cycle phase during the initial outpatient visit: menstrual, follicular, and luteal. Each received a 3.6 mg subcutaneous dose of goserelin monthly for three months. The endpoints encompassed alterations in uterine volume, dysmenorrhea Numerical Rating Scale (NRS) score, CA125 level, hemoglobin (HGB) after a 12-week treatment course, and the occurrence and duration of uterine hemorrhage during the first treatment cycle. Analysis revealed that the timing of goserelin therapy initiation in the menstrual cycle did not significantly impact its effectiveness in reducing uterine size, alleviating pain, lowering CA125 levels, or improving hemoglobin concentrations. However, patients starting treatment during the luteal phase experienced increased uterine bleeding (reference: menstrual period, OR = 4.33, 95% CI 1.23-15.25, p = .023). The results suggested non-inferiority of goserelin therapy initiated during the non-menstrual period, but the uterine bleeding rate was higher in the luteal phase group. Therefore, goserelin treatment for outpatient adenomyosis patients should not be limited to starting during the menstrual period; it can also be initiated outside the menstrual period, providing more convenience for patients as most consultations occur outside the menstrual period. However, the use of goserelin during the luteal phase should be avoided to reduce the risk of exacerbated bleeding, especially in anemic patients with heavy menstrual bleeding. This study highlights the importance of individualizing treatment initiation based on the patient's health profile to optimize therapeutic outcomes and minimize adverse effects. ChiCTR2200059548.

7975 TLR4 Signaling Modulates Reproductive and Metabolic Outcomes in a Mouse Model of Polycystic Ovary Syndrome

Abstract Disclosure: K.D. Wiggins: None. Z. Del Mundo: None. J.A. Ayala Angulo: None. M. Lopez: None. C. Garcia: None. C. Nguyen: None. J. De La Torre: None. A. Saba: None. D. Trinh: None. D. Nicholas: None. Polycystic Ovarian Syndrome (PCOS), characterized by disruptions in both reproductive and metabolic functions, is associated with abnormal immune system activity and chronic inflammation. Although the precise mechanistic drivers of chronic inflammation in PCOS are not fully elucidated, elevated serum levels of lipopolysaccharide (LPS) have been observed. We propose that Toll-like receptor 4 (TLR4) signaling, influenced by dysregulated LPS levels, is a central driver of chronic inflammation affecting both reproductive and metabolic pathways. To investigate this hypothesis, we subcutaneously implanted a nonsteroidal aromatase inhibitor, Letrozole (LET), in pubertal TLR4 knockout mice (TLR4KO) and C57BL/6J (wild type) mice. Our five-week LET treatment revealed that TLR4KO mice successfully entered all phases of the estrous cycle, with normalized Luteinizing Hormone (LH) and increased Follicle Stimulating Hormone (FSH) levels. These findings highlight TLR4's role in shaping cycling patterns and regulating fundamental hormonal pathways vital for reproductive health. Despite the genetic manipulation of the inflammatory pathway leading to a reduction in overall body weight gain, it had no discernible impact on the overall body composition of fat and lean mass. Additionally, our study found that dysregulation of blood glucose levels over time was independent of reduced body weight. TLR4KO mice demonstrated inefficient glucose clearance compared to wild-type mice, hinting at potential increases in insulin resistance, imbalances in adipose tissue inflammation, or possible alterations in the gut microbiota. Our study underscores the significance of disrupting the pro-inflammatory TLR4 pathway in shaping the reproductive and metabolic phenotypes in Letrozole-induced PCOS. The investigation into TLR4 becomes pivotal for comprehending the role of chronic inflammation in PCOS development or progression, offering valuable insights into potential therapeutic targets. Presentation: 6/2/2024

Model of “secular” cycle of financial capital accumulation

Crises hitting the world economy since the end of the previous century need a deeper explanation than effects of numerous sudden shocks. According to G. Arrighi’s theory, they manifest the final phase of North-American cycle of capital accumulation. Although analytically promising, the theory doesn’t meet broad recognition. A reason could be its weak formalization. This article addresses this problem by developing a mathematical model of capital growth rates. They are measured by nominal yield and interest rates which represent increments of capital in its general, financial form. If capital level follows a logistic path then its growth rate should be described by logistic differential equation. The model is brought to data on government bonds yields in Great Britain in XVIII– XIX centuries and USA — in XX century up to now. The study provides evidence for the pivotal role of financial-capital accumulation in systemic cycles and its S-shaped form. Besides, it reveals importance of trade balance in specifying cycle phases of domestic and global capital expansion.

7241 Catamenial Diabetic Ketoacidosis

Abstract Disclosure: L. Javed: None. A. Rehan: None. L. Hashim: None. J. Lim: None. Introduction: Diabetic ketoacidosis (DKA) is a common cause of hospitalization and readmission in patients with diabetes mellitus. Etiologies are generally due to medication non-adherence, trauma, infection, or other precipitating illness. In approximately 10% of DKA cases, no discernible precipitating cause can be determined. The word catamenial is derived from a Greek word meaning monthly. It is used to describe the monthly occurrence of menstruation. Catamenial hyperglycemia is a phenomenon in which blood glucose levels change with the different phases in the menstrual cycle. This can precipitate recurrent, unexplained episodes of DKA. Here, we present a similar case. Case description:A 19-year-old woman with type 1 diabetes, gastroparesis, hypertension, dysmenorrhea and cyclical vomiting disorder presented with unrelenting nausea and vomiting for one day. Other symptoms included abdominal &amp; chest pain that the patient attributed to premenstrual symptoms. She is afebrile, doesn’t have any other symptoms of infection and no recent sick contacts. She is compliant with her home insulin regimen of Insulin detemir 20 units BID and pre meal 8 units insulin aspart. Further interrogation reveals she has regular menstrual cycles and has been hospitalized three times in the last three months due to DKA coinciding with premenstrual symptoms, specifically severe abdominal pain and vomiting, typically starting five days before the onset of her menstrual cycle. She is hemodynamically stable and physical exam is significant for mid epigastric tenderness. Significant labs: WBC 16.52 (N&amp;lt;11 K/mm3), glucose 457 mg/dl, anion gap 23, K 4.1 (mmol/L), bicarbonate 18 (≥19 mmol/L), lactate 3.2 (N ≤ 1.9 mmol/L), beta hydroxybutyarate 4.0 (N ≤ 0.27 mmol/L), trop T 6 (N&amp;lt;10 ng/L), BHCG negative . Hba1c a month ago was 9.6%. Infectious work up was negative. EKG showed no signs of ischemia. She was treated per DKA protocol which results in resolution of symptoms and normalization of labs. Since no other precipitating factors for DKA are identified, and her symptoms corresponded with her menstrual periods, she is given a diagnosis of Catamenial DKA and scheduled for regular follow up in endocrinology clinic. Conclusion: This case highlights the importance of considering the association betweenmenstrual cycle phases and blood sugar levels as a possible trigger, underscoring the role of a thorough menstrual history in patients presenting with DKA. The impact of menstrual cycle fluctuations on glycemic control varies among patients however glucose profiles seem to be consistent across cycles for each individual woman. This highlights the need for personalized management strategies including patient education and adjustment of insulin during these periods. Addressing this adequately will improve overall glycemic control, reduce hospitalizations, and help improve the quality of life. Presentation: 6/1/2024

Super-resolved analysis of colocalization between replication and transcription along the cell cycle in a model of oncogene activation

To understand how oncogenes affect genome organization, it is essential to visualize fundamental processes such as DNA replication and transcription at high resolution in intact cells. At the same time, it is important to determine the progression of the cell along the cell cycle, as cell cycle regulation is crucial for the control of cell proliferation and oncogenesis. Here, we present a super-resolution imaging-based method to analyze single cell nuclei sorted according to specific phases of the cell cycle. The sorting is based on the evaluation of the number and the intensity of pixels in the replication foci image and the colocalization analysis is based on image cross-correlation spectroscopy (ICCS). We evaluate the colocalization between replication and transcription, at different cell cycle phases, in a model of PML-RARα oncogene activation. We find that colocalization between replication and transcription is higher in cells in early S phase compared to cells in middle and late S phase. When we turn on the PML-RARα oncogene, this colocalization pattern is preserved but we detect an increase of colocalization between replication and transcription in the early S phase which points to an effect of the PML-RARα oncogene on the coordination between replication and transcription.

Early menstrual cycle impacts of oestrogen and progesterone on the timing of the fertile window.

What is the effect of oestrogen and progesterone at the beginning of the menstrual cycle in delaying entry into the fertile window? Both oestrogen and progesterone contribute to a delay in the onset of the fertile window. Oestrogen enhances cervical mucus secretion while progesterone inhibits it. Observational study. Daily observation of 220 menstrual cycles contributed by 88 women with no known menstrual cycle disorder. Women recorded cervical mucus daily and collected first-morning urine samples for analysis of oestrone-3-glucuronide, pregnanediol-3-alpha-glucuronide (PDG), FHS, and LH. They underwent serial ovarian ultrasound examinations. The main outcome measure was the timing within the cycle of the onset of the fertile window, as identified by the appearance of mucus felt or seen at the vulva. Low oestrogen secretion and persistent progesterone secretion during the first week of the menstrual cycle both negatively affect mucus secretion. Doubling oestrogen approximately doubled the odds of entering the fertile window (OR: 1.82 95% CI=1.23; 2.69). Increasing PDG from below 1.5 to 4µg/mg creatinine was associated with a 2-fold decrease in the odds of entering the fertile window (OR: 0.51 95% CI=0.31; 0.82). Prolonged progesterone secretion during the first week of the menstrual cycle was also statistically significantly associated with higher LH secretion. Finally, the later onset of the fertile window was associated with statistically significant persistently elevated LH secretion during the luteal phase of the previous menstrual cycle. This post hoc study was conducted to assess the potential impact of residual progesterone secretion at the beginning of the menstrual cycle. It was conducted on an existing data set because of the scarcity of data available to answer the question. Analysis with other datasets with similar hormone results would be useful to confirm these findings. This study provides evidence for residual progesterone secretion in the early latency phase of some menstrual cycles, which may delay the onset of the fertile window. This progesterone secretion may be supported by subtly increased LH secretion during the few days before and after the onset of menses, which may relate to follicular waves in the luteal phase. Persistent progesterone secretion should be considered in predicting the onset of the fertile window and in assessing ovulatory dysfunction. The authors declare no conflicts of interest. No funding was provided for this secondary data analysis. N/A.

Role of the Kölliker-Fuse/Parabrachial Complex in generation of post-inspiratory vagal and sympathetic nerve activities.

In the rat, the activity of laryngeal adductor muscles, the crural diaphragm, and sympathetic vasomotor neurons is entrained to the post-inspiratory (post-I) phase of the respiratory cycle, a mechanism thought to enhance cardiorespiratory efficiency. The identity of the central neurons responsible for transmitting respiratory activity to these outputs remains unresolved. Here we explore the contribution of the Kölliker-Fuse/Parabrachial nuclei (KF-PBN) in the generation of post-I activity in vagal and sympathetic outputs under steady-state conditions and during acute hypoxemia, a condition that potently recruits post-I activity. In artificially ventilated, vagotomised and urethane-anesthetised rats, bilateral KF-PBN inhibition by microinjection of the GABAA receptor agonist isoguvacine evoked stereotypical responses on respiratory pattern, characterised by a reduction in phrenic nerve burst amplitude, a modest lengthening of inspiratory time, and an increase in breath-to-breath variability, while post-I vagal nerve activity was abolished and post-I sympathetic nerve activity diminished. During acute hypoxemia, KF-PBN inhibition attenuated tachypnoeic responses and completely abolished post-I vagal activity while preserving respiratory-sympathetic coupling. Furthermore, KF-PBN inhibition disrupted the decline in respiratory frequency that normally follows resumption of oxygenation. These findings suggest that the KF-PBN is a critical hub for the distribution of post-I activities to vagal and sympathetic outputs and is an important contributor to the dynamic adjustments to respiratory patterns that occur in response to acute hypoxia. While KF-PBN appears essential for post-I vagal activity, it only partially contributes to post-I sympathetic nerve activity, suggesting the contribution of multiple neural pathways to respiratory-sympathetic coupling.

The solar wind heavy ion composition in the ascending phases of the solar cycles 23 and 25

The approximately 11-year solar cycle has been shown to impact the heavy ion composition of the solar wind, even when accounting for streams of differing speeds; however, the heavy ion composition observed between the same specific phases of a past solar cycle and the current cycle has rarely, if ever, been compared. Here, we compare the heavy ion composition of the solar wind, as measured in situ during the solar cycle 23 and 25 ascending phases. We examine the mean iron and oxygen charge state composition and the O7+/O6+ ratio in multiple ranges of associated bulk wind speeds. Then, we compare the iron and oxygen charge state composition and relative abundance of iron to oxygen in the traditionally defined fast and slow solar wind. Finally, to determine the impact of individual ion contributions on the solar wind iron abundance, we examine individual ratios of iron and oxygen ions. Although the charge state composition remained broadly similar between these two ascending phases, both the O7+/O6+ ratio and iron fractionation in fast-speed streams were higher in the solar cycle 25 ascending phase than they were during the solar cycle 23 ascending phase, suggesting that equatorial coronal hole fields more frequently reconnected with helmet streamers or active regions in the latter of the two ascending phases; however, more work will need to be done to connect these observations back to their coronal origins. The individual ion ratios used in this work provided a spectrum to analyze the aggregate elemental abundances, and this work, as a whole, is an important step in determining how conditions in the corona may vary between solar cycles between the same phases.

How does Public Financial Management (PFM) influence health system efficiency: A scoping review

Background Effective Public Financial Management (PFM) approaches are imperative in the quest for efficiency in health service delivery. Reviews conducted in this area have assessed the impact of PFM approaches on health system efficiency but have left out the mechanisms through which PFM influences efficiency. This scoping review aims to synthesize evidence on the mechanisms by which PFM influences health system efficiency. Methods We searched databases of PubMed and Google Scholar and websites of the World Health Organization (WHO), World Bank and Overseas Development Institute (ODI) for peer-reviewed and grey literature articles that provided data on the relationship between PFM and health system efficiency. Three reviewers screened the articles for eligibility with the inclusion criteria. Data on PFM and health system efficiency was charted and summarized. We then reported the mechanisms by which PFM influence efficiency. Results PFM processes and structures influence health system efficiency by influencing; the alignment of resources to health system needs, the cost of inputs, the motivation of health workers, and the input mix. Conclusion The entire budget process influences health system efficiency. However, most of the findings are drawn from studies that focused on aspects of the budget process. Studies that look at PFM in totality will help explore other cross-cutting issues within sections of the budget cycle; they will also bring out the relationship between the different phases of the budget cycle.

Effect of Cucurbita pepo (Pumpkin) seed extracts on the cyclicity and reproductive hormones of female Wistar rats

Introduction: Despite the traditional use of Cucurbita pepo seed in pregnancy, its effects on female reproduction remain scarce. This study evaluated the impacts of n-hexane, dichloromethane (DCM), and aqueous ethanol extracts of C. pepo seed on the cyclicity and reproductive hormones of female Wistar rats. Methods: Ten groups of four rats received seed extracts or tween 80 orally for 21 days: A (control)= 0.5 mL tween 80 (vehicle); B, C, &amp; D= 142.86, 285.71, and 428.57 mg/kg nHE; E, F, &amp; G= 142.86, 285.71, 428.57 mg/kg of DCM; and H, I, &amp; J= 142.86, 285.71, 428.57 mg/kg of aqueous ethanol extracts, respectively. Vaginal cytology monitored the estrous cycle daily, and blood samples were obtained for follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen, and progesterone at various oestrus cycle phases. Results: Compared to the control, the estrous cycle phases did not change significantly (P&gt;0.05). FSH levels significantly increased (P&lt;0.05) with DCM and aqueous ethanol extracts of C. pepo seed during proestrus and estrus phases compared to the control. A significant (P&lt;0.05) increase in LH was observed with n-hexane, DCM, and aqueous ethanol extracts during all estrous cycle phases compared to the control. All extracts significantly increased estrogen levels (P&lt;0.05) during all phases. DCM and aqueous ethanol extracts reduced substantially the estrus-phase progesterone. Conclusion: Cucurbita pepo may stimulate the hypothalamic-pituitary-gonadal axis in female reproduction. Further studies should be conducted using various phytoestrogen compounds to gain useful knowledge about the effectiveness, safety, and long-term effects of C. pepo seed extracts in regulating hormonal balance.

Spatially restricted ecto-5'-nucleotidase expression promotes the growth of uterine leiomyomas by modulating Akt activity.

Found in as many as 80% of women, uterine leiomyomas are a frequent cause of abnormal uterine bleeding, pelvic pain, and infertility. Despite their significant clinical impact, the mechanisms responsible for driving leiomyoma growth remain poorly understood. After obtaining IRB permission, expression of ecto-5'-nucleotidase (NT5E, CD73) was assessed in matched specimens of myometrium and leiomyoma by real-time qPCR, Western blot, and immunohistochemistry (IHC). Adenosine concentrations were measured by enzyme-linked assay. Primary cultures were used to assess the impact of adenosine and/or adenosine receptor agonists on proliferation, apoptosis, and patterns of intracellular signaling invitro. When compared to matched specimens of healthy myometrium, uterine leiomyomas were characterized by reduced CD73 expression. Largely limited to thin-walled vascular structures and the pseudocapsule of leiomyomas despite diffuse myometrial distribution. Restricted intra-tumoral CD73 expression was accompanied by decreased levels of intra-tumoral adenosine. Invitro, incubation of primary leiomyoma cultures with adenosine or its hydrolysis-resistant analog 2-chloro-adenosine (2-CL-AD) inhibited proliferation, induced apoptosis, and reduced proportion of myocytes in S- and G2-M phases of the cell cycle. Decreased proliferation was accompanied by reduced expression of phospho-Akt, phospho-Cdk2-Tyr15, and phospho-Histone H3. Enforced expression of the A2B adenosine receptor (ADORA2B) and ADORA2B-selective agonists similarly suppressed proliferation and inhibited Akt phosphorylation. Collectively, these observations broadly implicate CD73 and reducedextracellular concentrations ofadenosine as key regulators of leiomyoma growth and potentiallyidentify novel strategies for clinically managing these common tumors.

Mira Variables Based on Emission Lines in LAMOST DR9

We present a sample of 335 Mira variables, extracted from DR9 of the Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) survey. These variables are characterized by the Balmer emissions (Hδ, Hγ, Hβ, and Hα) and the metal emissions (Fe i λ λ 4202, 4308, 4376, and Mg i λ4571) observed in M giant spectra. We distinguished oxygen-rich stars from carbon-rich stars through the identification of carbon molecular bands present in the optical spectra. For the oxygen-rich stars we examined multiple attributes, such as the link between line strength and bolometric luminosity, and the connection between atmospheric parameters and their periods. We observed that Fe i λ λ 4202, 4308 showed a significantly gradual progression, which can be postulated to trace the fluorescent emission resulting from pulsation shocks. Regarding the correlation between T eff and the period, T eff remains relatively constant over varying periods, with no clear trend, while both log g and [Fe/H] show a decreasing trend within a period range of 450 days, and this decreasing of the log g trend is consistent with the results in the literature. To shed more light on the variations of Balmer lines, we showcase time-series spectra for two objects, demonstrating that the Balmer lines reach their peak intensity during the brightest phase of the stellar cycle.

Influence of menstrual cycle and oral contraceptive phases on strength performance, neuromuscular fatigue, and perceived exertion.

The primary aim of the study was to assess differences in strength performance, neuromuscular fatigue, and perceived exertion across phases of the menstrual cycle [MC; early follicular (eFP), late follicular (lFP), and mid-luteal phase (mLP)] and oral contraceptives [OCs; active pill phase (aPP) and nonactive pill phase (nPP)]. The secondary aim was to analyze the influence of fluctuating serum 17β-estradiol and progesterone concentrations on these parameters in naturally menstruating women. Thirty-four women (21 with a natural MC and 13 using OCs) completed three or two experimental sessions, respectively. Mean propulsive velocity (MPVmean) and total number of repetitions (REPtotal) were assessed during a power [3 × 8 at 60% 1RM (one-repetition maximum)] and hypertrophy squat loading (3 sets to failure at 70% 1RM), respectively. Changes in bench press and squat MPV at 60% 1RM in response to the loadings were used as surrogates for nonlocal and local fatigue, respectively. Total blood lactate accumulation (BLAA) and markers of perceived exertion were assessed in each session. No significant differences between any of the MC or OC phases were observed for MPVmean, REPtotal, nonlocal and local fatigue, and markers of perceived exertion (all P > 0.050). A higher intraindividual 17β-estradiol concentration was significantly associated with a lower MPVmean (P = 0.019). BLAA was significantly higher in the lFP than in the mLP (P = 0.019) and negatively associated with the intraindividual progesterone concentration (P = 0.005). Although 17β-estradiol may negatively influence the MPV, it appears that fluctuations of both sex hormones across the MC and OC phases are not prominent enough to induce significant or practically relevant changes in the assessed parameters.NEW & NOTEWORTHY Although a high intraindividual 17β-estradiol concentration was associated with a lower movement velocity, markers of strength performance and surrogates for nonlocal and local fatigue remained unaffected by MC and OC phases. Blood lactate accumulation was significantly reduced in the mLP. Furthermore, our findings suggest that the impact of the MC phases varies greatly among individuals. Individuals with high fluctuations in sex hormone concentrations may experience relevant changes in the assessed parameters.