Phase Of Cycle Research Articles

Population Dynamics and the Microbiome in a Wild Boreal Mammal: The Snowshoe Hare Cycle and Impacts of Diet, Season and Predation Risk.

The North American boreal forest is a massive ecosystem, and its keystone herbivore is the snowshoe hare (Lepus americanus). Hares are exposed to considerable environmental extremes in diet and weather, food availability, and predation risk. Gut microbiomes have been suggested to facilitate adaptive animal responses to environmental change, but severe environmental challenges to homeostasis can also disrupt host-microbiome relationships. To better understand gut microbiome contributions to animal acclimation, we studied the faecal bacterial microbiome of wild hares across two types of extreme environmental change that are integral to their natural history: (1) seasonal transitions between summer and winter, and (2) changes over the ~10 year 'boom-bust' population cycles that are characterised by shifting food resource availability and predation pressure. When compared to summer, hares in winter had lower bacterial richness and were depleted in 20 families (including Oxalobacteraceae and Christensenellaceae) but enriched for Ruminococcaceae (a family which contains plant fibre degrading bacteria) alongside nine other bacterial groups. Marked bacterial microbiome differences also occurred across phases of the population cycle. Bacterial microbiomes were lower in richness and compositionally distinct in the peak compared to the increase or decline phases of the population cycle. Direct measures of host physiology and diet quality (faecal fibre contents) most strongly supported food resource availability as a mechanism underlying phase-based differences in bacterial communities, but faecal fibre contents could not fully account for bacterial microbiome variation across phases.

MULTI-PROXY PALEOENVIRONMENTAL AND PALEOECOLOGICAL RECONSTRUCTION OF THE FOREMOST FORMATION (UPPER CRETACEOUS, CAMPANIAN) OF ALBERTA

Abstract The Foremost Formation of southern Alberta, Canada, is the basal member of the Cretaceous (Campanian) Belly River Group and has been understudied relative to the overlying Oldman and Dinosaur Park formations of this group. Here we describe and analyze the sedimentology, foraminiferal micropaleontology, vertebrate microsite paleoecology, and paleoenvironmental conditions of the Foremost Formation. Outcrop of the Foremost Formation is characterized by estuarine and shallow marine facies that transition upward into coastal/fluvial facies that accumulated during the Claggett marine regression of the Western Interior Seaway (WIS). This is consistent with at least two rapid transgressive events driven by local subsidence interrupting the overall regressive phase of the Claggett marine cycle, creating the aggrading profile in the lower portion of the sections measured here, and suggesting that orogenic buildup in the Rocky Mountains and its associated basin subsidence were a controlling factor of local deposition in the WIS. A low abundance, low diversity agglutinated benthic foraminiferal fauna suggests frequently stressed oxygen and salinity conditions in marginal marine environments. Vertebrate microsite faunas display a mixed freshwater to brackish water environmental influence, with an increase in diversity upsection in conjunction with increased freshwater influence. Among dinosaurs, ceratopsids and ankylosaurs experience notable relative abundance decreases through the Foremost Formation and into the lower Oldman Formation, potentially reflecting preference for coastal habitats and/or plant resources relative to other terrestrial herbivores.

The effect of lysophosphatidic acid on myometrial contractility and the mRNA transcription of its receptors in the myometrium at different stages of endometrosis in mares

BackgroundEndometrosis (chronic degenerative endometritis) results in morphological changes in the equine endometrium and impairs its secretory function. However, the effect of this condition on the myometrium remains unclear. Lysophosphatidic acid (LPA) may affect female reproductive function and embryo transport by influencing uterine contractility through its receptors (LPARs). The objective of this study was to determine myometrial LPAR1–6 mRNA transcription, and the effects of LPA on myometrial contractions in mares with endometrosis during the mid-luteal and follicular phases of the estrous cycle.ResultsA reduction in myometrial LPAR1 mRNA transcription was observed in mares with endometrosis during the mid-luteal phase, in comparison to those with category I endometria (P < 0.05). While, upregulation of myometrial LPAR3 or LPAR6 mRNA transcription was observed in mares with category III or IIB endometria; respectively (P < 0.05). An increase in myometrial LPAR1, LPAR3 and LPAR5 mRNA transcription was observed during the follicular phase in mares with category IIA endometrium in comparison to their expression in category I endometrium (P < 0.05). During endometrosis progression LPA reduced the force of myometrial contractions in both phases of the estrous cycle (P < 0.05). However, in mares with category IIA endometrium during the follicular phase, LPA was found to increase the force of contraction of myometrial strips in comparison to mares with category I endometrium (P < 0.01).ConclusionIn the course of endometrosis in mares, a disruption in the myometrial mRNA transcription of LPARs has been observed. This is the first study to examine the impact of LPA on myometrial contractility at diffrent stage of endometrosis. However, it is essential to consider that multiple factors may contribute to this process. Alternations in contractile activity and changes in myometrial LPARs mRNA transcription may indicate impaired LPA-signaling mechanisms in equine myometrium during endometrosis.

Feasibility of volumetric-modulated arc therapy gating for cardiac radioablation using real-time ECG signal acquisition and a dynamic phantom.

Stereotactic arrythmia radioablation (STAR) is a noninvasive technique to treat ventricular tachycardia (VT). Management of cardiorespiratory motion plays an essential role in VT-STAR treatments to improve treatment outcomes by reducing positional uncertainties and increasing dose conformality. Use of an electrocardiogram (ECG) signal, acquired in real-time, as a surrogate to gate the beam has the potential to fulfil that intent. To investigate the gated delivery of volumetric-modulated arc therapy (VMAT) for STAR on a TrueBeam linear accelerator (linac) using a real-time acquired ECG signal and a dynamic cardiac phantom. Dosimetric characteristics of a 6 MV flattening filter free (FFF) beam from a Varian TrueBeam linac were initially evaluated under high-frequency gating scenarios relevant to cardiac rhythms with respect to dose linearity, beam output, and energy quality. A microcontroller board was used to interface and gate the linac, sending a beam on/off signal. For real-time cardiac gated measurements, an AD8232 Heart Monitor board was used to acquire the ECG signal and synchronize the VMAT delivery to an ArcCHECK detector to a specific phase of the cardiac cycle. Gated dose distributions were compared against those acquired for a non-gated delivery mode. An in-house dynamic cardiac phantom was developed to simulate cardiorespiratory motion that correlates target position with the signal to gate the beam. Measured dose distributions using gafchromic film were also compared against the static (reference) mode in different scenarios with and without gating. Maximum difference in dose per monitor unit (MU) was found to be no greater than 1% as compared to static mode with variation in the chamber response within 0.2% in the range of 50 MUs to 200 MUs. Maximum percentage differences for the beam output and beam qualiy index (TPR20,10) between gated and non-gated modes were 0.91% and -0.44%, respectively. Comparison of delivered dose distributions for the VMAT plan without gating versus ECG synchronized gating modes provided a passing rate 98% for the gamma analysis with 1% relative dose difference, 1mm distance-to-agreement criteria. For the synchronization of dose delivery with target position, passing rates were 98%, 97%, and 99% for the axial, coronal, and sagittal planes, respectively, when gating the beam based on target position for cardiac motion only, for 3%, 3mm tolerance as compared to static mode. Without gating the beam, passing rates of the respective plans are 97%, 94%, and 99% for the cardiac motion only, and 67%, 57%, and 55% when including respiratory component of motion. A 6 MV-FFF TrueBeam is stable for performing gating in STAR under high-frequency gate windows within typical cardiac cycles. Agreement between measured dose distributions for a VMAT plan in static and ECG-synchronized deliveries and between static and target-position gated modes shows that the proposed methodology is feasible and can be implemented on a TrueBeam platform.

Hypoxic conditions affect transcriptome of endometrial stromal cells in endometriosis and promote TGFBI axis

BackgroundEndometriosis is characterized by the ectopic growth of endometrial-like cells, causing chronic pelvic pain, adhesions and impaired fertility in women of reproductive age. Usually, these lesions grow in the peritoneal cavity in a hypoxic environment. Hypoxia is known to affect gene expression and protein kinase (PK) activity. We aimed to explore the changes in the transcriptome and PK activity characteristic of eutopic and ectopic endometrium in endometriosis under hypoxia.MethodsEutopic (EuESCs) and ectopic (EcESCs) endometrial stromal cells were exposed to hypoxia (1% O2) or normoxia (20% O2) for 48 hours. We assessed PK activity and examined transcriptome using mRNA-seq in cells cultured under hypoxic or normoxic conditions. Enzyme-linked immunosorbent assay, quantitative reverse transcription-PCR and immunohistochemistry were performed for the downstream analysis of Transforming Growth Factor Beta Induced (TGFBI) expression.ResultsThe kinase assay revealed a minor decrease in cAMP-dependent PK (PKAc) and Akt activity and a trend towards an increase in Rho-dependent PK (ROCK) activity in response to exposure to hypoxic conditions in EcESCs. A wider examination of the hypoxia-mediated changes in transcriptomes of cultured cells revealed that the genes related to aerobic glycolysis and cellular metabolism were upregulated in EuESCs exposed to hypoxia. In contrast, EcESCs had a single differentially expressed gene (TGFBI) upregulated under hypoxic conditions. This gene was also found to be overexpressed in EuESCs exposed to hypoxia vs normoxia, and in EcESCs vs EuESCs in normoxia. The level of secreted TGFBI in the spent culture media was accordingly high in the EcESC cultures and in the EuESC culture exposed to hypoxia. In the eutopic endometrial tissue biopsies, TGFBI mRNA and protein expression depended on the menstrual cycle phase, with higher levels observed in the proliferative phase. TGFBI staining showed the protein localized to the stroma and around the blood vessels. In the secretory phase, TGFBI protein expression was stronger in ectopic endometrium compared to paired eutopic endometrium.ConclusionsWithin this study, we showed hypoxia-mediated transcriptome changes characteristic of EuESCs and EcESCs and identified TGFBI as a potential therapeutic target for endometriosis due to its role in fibrosis and angiogenesis.

Functional, instrumental test of flexion-extension movements of the wrist joint. Normative parameters.

Background: Stroke is a significant medical and social issue due to its high incidence and mortality rates, with a trend toward increasing overall cases. In 80% of patients, upper limb dysfunction persists. Existing methods, such as clinical scales and questionnaires, are criticized for their subjectivity and lack of precision. There is a need to develop an instrumental method for assessing upper limb function that can be applied in clinical settings. Aims: To develop a functional test for the objective diagnosis of wrist joint function applicable in clinical settings. Methods: A functional test was proposed to assess the biomechanics of the wrist joint using inertial sensors. The study involved 15 healthy volunteers (5 men and 10 women, aged 23 to 33), with no joint diseases or neurological disorders. The study was conducted over one year (2022–2023). The primary endpoint was to determine the amplitude, time, and trajectory of wrist joint movements during two tests—"Wrist-0" and "Wrist-Flex." Evaluation was based on the duration of the movement cycle, maximum amplitude, and movement phase. Results: Assessment of upper limb function using clinical scales (ARAT, FMA-UE, MRC) showed that parameters were consistent with those of healthy individuals. In the "Wrist-0" test, movement amplitude was significantly lower compared to the "Wrist-Flex" test (p0.05). There were no statistically significant differences in movement amplitude between the right and left limbs in either test (p0.05). The phase of maximum flexion in the "Wrist-0" test occurred significantly earlier than in the "Wrist-Flex" test for the right hand (p0.05). The movement cycle duration did not differ significantly between tests for the right hand (p0.05) but was significantly longer in the "Wrist-Flex" test for the left hand (p0.05). Conclusions: Normative parameters for the functional test have been established. Minor differences in function between the right and left wrist joints were observed. The proposed test requires minimal time to administer and can be used for the objective diagnosis of wrist joint function in patients.

A study on anxiety and depression symptoms among menopausal women: a web based cross sectional survey

BackgroundAn essential part of aging is menopause, which indicates the final phase of the female reproductive cycle. The objective of this research was to assess anxiety and depressive symptoms among menopausal women in Asir region, Saudi Arabia.MethodsThe cross-sectional survey was carried out in February to June 2024, using a random sampling procedure, study participants were selected. All menopausal women including &amp;lt;50 and ≥60 years old, were included, and symptoms of depression and anxiety were collected using Patient Health Questionnaire-9 (PHQ-9) Generalized Anxiety Disorder-7 (GAD-7) respectively.ResultsOf the 396 menopausal women, the majority 170 (42.9%) were &amp;lt;50 years old and 92 (23.2%) were between 50 and 54 years old. Two hundred eighty-one were married (71%) and 273 (68.9%) were literate. Most of them, 229 (57.8%) got married at &amp;lt;18 years and 196 (49.5%) have a parity of 3–5 and 189 (47.7%) women attained menopause at &amp;lt;50 years old. In terms of menopausal symptoms, 268 (67.7%) women experienced hot flushes; 252 (63.6%) had night sweats and were more irritable 256 (64.6%) followed by 244 (61.6%) had decreased sexual desire. In general, 258 (65.2%) and 206 (52.02%) menopausal women reported having depression and anxiety symptoms, respectively. Married (OR = 0.317; 95% CI = 0.182–0.551, p = 0.000) and literate (OR = 0.518; 95% CI = 0.309–0.868, p = 0.013) are less likely to be in depression compared to widowed/separated individuals. Literates (OR = 0.271; 95% CI = 0.165–0.443, p = 0.000), are less likely to have anxiety compared to illiterates.ConclusionThe study found that a significant percentage of menopausal women had depression and anxiety symptoms. These results emphasize the significance of screening and assessing women experiencing anxiety and depression symptoms throughout the menopausal transition. To alleviate menopausal symptoms, it is also suggested to conduct activities to educate menopausal women, such as a health awareness program in shopping centers and other public places, etc.

Influence of Oestradiol Fluctuations in the Menstrual Cycle on Respiratory Exchange Ratio at Different Exercise Intensities: A Systematic Review, Meta-Analysis and Pooled-Data Analysis

Background: Oestradiol has been implicated as a factor in substrate utilisation in male and mouse studies but the effect of acute changes during the menstrual cycle is yet to be fully understood. Objective: To determine the role of oestradiol in respiratory exchange ratio (RER) during exercise at various intensities. Methods: This systematic review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. From inception to November 2023, four online databases (Cochrane, SPORTDiscus, MEDline and Web of Science) were searched for relevant articles. Studies that reported a resting oestradiol measurement in naturally menstruating women with exercise at a percentage of maximal aerobic capacity (%V˙O2max) were included. Mean and standard deviation for oestradiol, RER and exercise intensity were extracted and study quality assessed using a modified Downs and Black checklist. Risk of bias was assessed using I2 measure of heterogeneity and Egger’s regression test, assessment of bias from methodological quality was identified by sensitivity analysis. Eligible datasets were extracted for pairwise comparisons within a meta-analysis and correlation between change in oestradiol and change in RER. Data were also pooled to produce a mean and standard deviation for RER for menstrual stage and for low and high oestradiol groups. Results: Twenty-four articles were identified, over 50% were identified as high quality. Sixteen articles included datasets eligible for meta-analysis. Eleven articles utilised a submaximal constant-load exercise intensity, finding a standardised mean difference of − 0.09 ([CI: −0.35–0.17], p = 0.5) suggesting no effect of menstrual phase on constant-load exercise RER. In six articles using incremental exercise tests to exhaustion, a standardised mean difference of 0.60 ([CI 0.00–1.19], p = 0.05) was identified towards a higher maximal RER attained in follicular compared to luteal phase. There was no correlation (R = −0.26, p = 0.2) between change in oestradiol and change in RER between phases. All 24 articles, totalling 650 participants, were included in pooled analysis. When grouped by menstrual cycle phase or when grouped by oestradiol levels, RER was higher in the follicular phase than the luteal phase at low and high constant load exercise intensities. Discussion: Findings from the pooled-analysis and meta-analysis suggest that there may be menstrual cycle phase differences in RER that are intensity dependent. These differences may be related to sex hormone levels, but this was not supported by evidence of correlation between differences in RER and differences in oestradiol. At present, it remains best practice to assess performance in the same menstrual cycle phase if seeking to assess change from baseline.

Comparing the Waste and Environmental Impact of Blepharoplasty at an Office-based Operating Room Versus an Ambulatory Surgery Center in the United States.

The aim of the study was to evaluate the environmental impact of a blepharoplasty as performed by a single surgeon at an office-based operating room (OR) versus at an ambulatory surgery center. We employed life cycle analyses on routine, uncomplicated bilateral upper lid blepharoplasties as performed by a single surgeon. Life cycle phases of production, use, and end-of-life treatment were included. Study boundaries encompassed all waste products exiting the OR in addition to utility energy and water use. We conducted waste audits to collect data on surgical waste by item, material, and weight. Building energy and water use were approximated using data obtained from utility companies. Environmental impact is reported as global warming potential (GW100a; kg carbon dioxide equivalents). The office-based OR generated 784 g of physical waste per blepharoplasty as compared to 1323 g at the ambulatory surgery center. The life cycle analyses found that a blepharoplasty contributed a total of 6.42 kg carbon dioxide equivalents at the office-based OR and 7.78 at the ambulatory surgery center. The production phase contributed the majority of these carbon dioxide equivalents. Plastic supplies contributed the most waste by weight and emissions associated with production. Nonwoven polypropylene contributed the largest waste and emissions by material. The ambulatory surgery center produces more waste and carbon dioxide equivalents per blepharoplasty than the office-based OR. Use of supplies including drapes and gowns made of nonwoven polypropylene can be reduced to increase the environmental sustainability of blepharoplasty.

Cogwheel phase cycling in population-detected optical coherent multidimensional spectroscopy.

An integral procedure in every coherent multidimensional spectroscopy experiment is to suppress undesired background signals. For that purpose, one can employ a particular phase-matching geometry or phase cycling, a procedure that was adapted from nuclear magnetic resonance (NMR) spectroscopy. In optical multidimensional spectroscopy, phase cycling has been usually carried out in a "nested" fashion, where pulse phases are incremented sequentially with linearly spaced increments. Another phase-cycling approach that was developed for NMR spectroscopy is "cogwheel phase cycling," where all pulse phases are varied simultaneously in increments defined by so-called "winding numbers." Here we explore the concept of cogwheel phase cycling in the context of population-based coherent multidimensional spectroscopy. We derive selection rules for resolving and extracting fourth-order and higher-order nonlinear signals by cogwheel phase cycling and describe how to perform a numerical search for the winding numbers for various population-detected 2D spectroscopy experiments. We also provide an expression for a numerical search for nested phase-cycling schemes and predict the most economical schemes of both approaches for a wide range of nonlinear signals. The signal selectivity of the technique is demonstrated experimentally by acquiring rephasing and nonrephasing fourth-order signals of a laser dye by both phase-cycling approaches. We find that individual nonlinear signal contributions are, in most cases, captured with fewer steps by cogwheel phase cycling compared to nested phase cycling.

Changing economic environment and expected return proxies

PurposeWe aim to examine two issues. First, we intend to identify the best performing expected return proxies. Second, we investigate whether the expected return proxies for individual stocks can track the corresponding realized returns during extremely good or extremely bad times of the economic environment related to business conditions, stock market valuation and broad market performance.Design/methodology/approachWe construct four sets of expected return proxies, including: (1) characteristic-based proxies; (2) standard risk-factor-based proxies; (3) risk-factor-based proxies that allow betas to vary with firm characteristics and (4) macroeconomic-variable-based proxies. First, we estimate expected returns for individual stocks using newly developed methods and evaluate the performance of these expected return proxies based on the minimum variance criterion of Lee et al. (2020). Second, we regress expected return proxies and realized returns on indicator variables that capture the extreme phases of the economic environment. Then we compare the estimated coefficients from these two sets of regressions and see if they are similar in magnitude via formal hypothesis testing.FindingsWe find that characteristic-based proxies and risk-factor-based proxies that allow betas to vary with firm characteristics are the two best performing proxies. Therefore, it is important to allow betas to vary with firm characteristics in constructing expected return proxies. We also find that model-based expected return proxies do a reasonably good job capturing actual returns during extremely bad and extremely good phases of business cycles measured by leading economic indicators, consumer confidence and business confidence. However, there is a large gap between the adjustment of model-based expected returns and realized returns during extreme episodes of stock market valuation or broad market performance.Originality/valueWe examine four types of expected return proxies and use the newly developed methodology as in Lee et al. (2020) to see which one is the best. In addition, we document whether model-based expected returns from individual stocks adjust partially or fully to keep pace with actual returns in response to changing economic conditions. No prior studies have examined these two issues.

Molecular mechanisms of action of curaxin CBL0137 on breast cancer cells in vitro

Introduction. Breast cancer (BC) represents a group of malignant neoplasms with various molecular profiles, which are characterized by aberrations in the mechanisms of epigenetic transcription regulation. One of these disruptions associated with a worse prognosis is the overexpression of the BET protein family, responsible for the interaction of transcription factors with histone-rich acetylated regions. Previously, for the multitargeted epigenetically active agent curaxin CBL0137 (CBL), we have shown the ability to inhibit the expression of BRD2, BRD3, BRD4 proteins in HeLa TI cells and BRD3, BRD4 proteins in BC cells.Aim. To analyze the molecular mechanisms of CBL0137 action on BC cells in vitro, including: 1) assessment of cytotoxicity, 2) analysis of the effect on the cell cycle, 3) assessment of the ability to trigger apoptosis, 4) cause DNA damage, and 5) analyze the effect on the expression of genes involved in proliferation, apoptosis and repair processes.Materials and methods. The cytotoxicity of CBL on BC cells (MCF7, MDA-MB-231, SKBR3) was assessed using the MTT assay. The effect of the agent on the cell cycle and activation of apoptosis was analyzed by flow cytometry. Analysis of DNA damage under the action of CBL was performed using the comet assay. Changes in the expression of genes associated with proliferation, repair and apoptosis were evaluated using real-time polymerase chain reaction.Results. The half maximal inhibitory concentration (IC50) on BC cells under the action of CBL0137 were 1 μM at 72-hour exposure, 14–25 μM at 24-hour. Curaxin CBL (0.5 and 1 μM) caused G2/M cell cycle arrest, and also triggered apoptosis in all cell lines. Under the action of 1 μM CBL, an increase in the degree of DNA damage in MCF7 and SKBR3 cells was recorded, and under the action of both concentrations in MDA-MB-231 cells. The gene expression profile involved in proliferation also corresponded to the arrest in the G2/M phase of the cell cycle. Also, under the action of CBL, the activation of p53-dependent repair genes occurred. An increase in the expression of pro-apoptotic and a decrease in anti-apoptotic genes was shown.Conclusion. Curaxin CBL0137 showed differential effects on molecular processes in BC cells. We have identified a cytostatic effect of the compound, confirmed at various molecular levels. The data obtained indicate the ability of CBL0137 to inhibit tumor processes in BC cells, which makes it a potentially interesting agent for combination therapy.

New thiazolidin-4-ones as anti-cervical cancer agents targeting EGFR: design, synthesis, and computational studies.

A new series of 3,4-dihydronaphthalen-1(2 h)-ylidene)hydrazineylidene)-5-substituted thiazolidin-4-one derivatives were designed and synthesized. The new compounds were screened for in vitro antitumor activity against Hela cancer cell line. The compounds 7b, 7 h, and 7i produced more potent cytotoxicity than doxorubicin with IC50 values of 1.83 ± 0.1, 2.54 ± 0.14, 2.75 ± 0.15, and 3.63 ± 0.2 μM, respectively. They also showed a promising safety profile against WI-38 normal cells. In addition, compound 7b produced a promising multi-kinase inhibition against EGFR (WT) while being very selective toward the mutant forms (L858R and T790M) with IC50 values of 0.099 ± 0.006, 0.064 ± 0.006, and 0.026 ± 0.007 μM, respectively, in comparison to gefitinib and osimertinib. A study of the cell cycle in Hela cells showed that 7b arrests cell cycle in the pre-G1 phase and causes early and late apoptosis. Eventually, the molecular docking results showed that 7b had good-binding interactions with EGFRWT, EGFRL858R, and EGFRT790M. Compound 7b was predicted to have promising oral absorption, good drug-likeness, and low toxicity risks in humans. Moreover, MD simulations confirmed the stable complexes of 7b with EGFRWT, EGFRL858R, and EGFRT790M (with RMSD 0.12-0.35 nm, RMSF 0.2-0.55 nm, SASA 140-150, and Rg 1.80-2.00 nm).

Brain fingerprint and subjective mood state across the menstrual cycle

BackgroundBrain connectome fingerprinting represents a recent and valid approach in assessing individual identifiability on the basis of the subject-specific brain functional connectome. Although this methodology has been tested and validated in several neurological diseases, its performance, reliability and reproducibility in healthy individuals has been poorly investigated. In particular, the impact of the changes in brain connectivity, induced by the different phases of the menstrual cycle (MC), on the reliability of this approach remains unexplored. Furthermore, although the modifications of the psychological condition of women during the MC are widely documented, the possible link with the changes of brain connectivity has been poorly investigated.MethodsWe conducted the Clinical Connectome Fingerprint (CCF) analysis on source-reconstructed magnetoencephalography signals in a cohort of 24 women across the MC.ResultsAll the parameters of identifiability did not differ according to the MC phases. The peri-ovulatory and mid-luteal phases showed a less stable, more variable over time, brain connectome compared to the early follicular phase. This difference in brain connectome stability in the alpha band significantly predicted the self-esteem level (p-value &amp;lt;0.01), mood (p-value &amp;lt;0.01) and five (environmental mastery, personal growth, positive relations with others, purpose in life, and self-acceptance) of the six dimensions of well-being (p-value &amp;lt;0.01, save autonomy).ConclusionThese results confirm the high reliability of the CCF as well as its independence from the MC phases. At the same time the study provides insights on changes of the brain connectome in the different phases of the MC and their possible role in affecting women’s subjective mood state across the MC. Finally, these changes in the alpha band share a predictive power on self-esteem, mood and well-being.

Effective combination therapy for telogen hair loss

Background. Telogen hair loss is one of the most common forms of alopecia, associated with a disruption in the phases of the hair growth cycle – specifically, the premature transition of the hair follicle into the telogen phase. The primary causes are the influence of triggering factors such as increased stress levels and previous illnesses. The main goal of therapy is to prolong the anagen phase and stimulate hair growth through the use of topical peptides and a multivitamin complex.Objective. To study the effectiveness of a hair growth restoration method in the treatment of telogen alopecia using cosmetic hair growth products and dietary supplements.Methods. The study involved 20 patients diagnosed with telogen alopecia who received treatment with the topical cosmetic products «Time to Grow» and the dietary supplement «Thick and Strong Hair» for 9 weeks. The effectiveness of the treatment was assessed at 3, 6, and 9 weeks after the start of therapy.Results. The analysis of the study showed statistically significant changes in trichoscopy indicators in patients with telogen alopecia, demonstrating the effectiveness of using hair growth cosmetics (p&lt;0.05). At the final assessment point, a reduction in hair loss was observed in 100 % of the subjects, along with improvements in hair quality and volume. A survey evaluating the participants’ subjective experiences demonstrated satisfaction with the treatment and adherence to the therapy.Conclusion. The use of hair growth products and the dietary supplement «Time to Grow» has proven effectiveness in the treatment of telogen hair loss.

N-Glycoside of Indolo[2,3-a]pyrrolo[3,4-c]carbazole LCS1269 Exerts Anti-Glioblastoma Effects by G2 Cell Cycle Arrest and CDK1 Activity Modulation: Molecular Docking Studies, Biological Investigations, and ADMET Prediction

Background/Objectives: Indolo[2,3-a]pyrrolo[3,4-c]carbazole scaffold is successfully used as an efficient structural motif for the design and development of different antitumor agents. In this study, we investigated the anti-glioblastoma therapeutic potential of glycosylated indolocarbazole analog LCS1269 utilizing in vitro, in vivo, and in silico approaches. Methods: Cell viability was estimated by an MTT assay. The distribution of cell cycle phases was monitored using flow cytometry. Mitotic figures were visualized by fluorescence microscopy. Quantitative RT-PCR was used to evaluate the gene expression. The protein expression was assessed by Western blotting. Molecular docking and computational ADMET were approved for the probable protein target simulations and predicted pharmacological assessments, respectively. Results: Our findings clearly suggest that LCS1269 displayed a significant cytotoxic effect against diverse glioblastoma cell lines and patient-derived glioblastoma cultures as well as strongly suppressed xenograft growth in nude mice. LCS1269 exhibited more potent anti-proliferative activity toward glioblastoma cell lines and patient-derived glioblastoma cultures compared to conventional drug temozolomide. We further demonstrated that LCS1269 treatment caused the severe G2 phase arrest of cell cycle in a dose-dependent manner. Mechanistically, we proposed that LCS1269 could affect the CDK1 activity both by targeting active site of this enzyme and indirectly, in particular through the modulation of the Wee1/Myt1 and FOXM1/Plk1 signaling pathways, and via p21 up-regulation. LCS1269 also showed favorable pharmacological characteristics in in silico ADME prediction in comparison with staurosporine, rebeccamycin, and becatecarin as reference drugs. Conclusions: Further investigations of LCS1269 as an anti-glioblastoma medicinal agent could be very promising.

Field and physical properties of carbonatoblastites (known as carbonatites): rock forests

Until today, it was known that carbonites developed in the form of magmatic origin intrusions, carbonatite dykes, pegmatitic, heads, stocks, veins and lenses, which are rarely seen in nature. However, as a result of our research (field, petrography, mineralogy etc.), it was determined that carbonatites are definitely not magmatic in origin. On the contrary, carbonatites are formed from pure-impure carbonate/limestones with different units of metamorphic, rootless, primary source rocks derived in solid phase and in-situ within the regional dynamo-thermal Tarhan metamorphism cycle. Within the regional dynamothermal Tarhan metamorphism cycle, different age, environment and origin primary rock units (cosmic upper mantle peridotites, terrestrial magmatic rock series/ocean crust series/ophiolite series, volcanosedimentary series, different volcanic and different sedimentary rocks etc.) were enriched and dominated by granite mineralogical rock-forming main-secondary-trace crystalloblast neominerals and were formed, metamorphic origin, rootless leucocratoblastic metablastic rock series and their derivatives / metablastites / metablastic rocks (known as granite/granitoid, gabbro/gabbroid, diorite/dioritoid, charnockite/charnockite and carbonatite/carbonatoid intrusion, pluton and batholith type magmatic origin plutonic/plutonic rocks) were determined to be a type of new modern metamorphic rock. For this reason, it has been determined and suggested that carbonatoblastic rock series and their derivatives / carbonatoblastites / carbonatoblastic rocks are a type of metablastic rocks with different primary rocks. Carbonatoblastites (known as carbonatites of magmatic origin, rarely seen in nature); developed in the second and last stage of the regional dynamothermal Tarhan metamorphism cycle, and developed in the changing physical conditions (P/T) of the facies and sub-facies of Abukuma type reversed regional regressive dynamothermal metamorphism, where temperatures are effective compared to pressures (T&gt;P, T: Temperature; P: Pressure; Temperatures put their stamp/seal on metamorphism). They are derived from the pure and impure carbonate/limestones, which are the primary source rock units, and the pure and impure marbles, which are the metamorphic equivalents of the regional progressive dynamothermal metamorphism of the Barrow type, where the pressures are effective in proportion to the temperatures developed in the first phase of the regional dynamothermal Tarhan metamorphism cycle of the primary source rock units (P/T, pressures put their stamp on the metamorphism), in solid phase and in situ from the mentioned rock units. Carbonatoblastites are metamorphic equivalents of pure-impure carbonate/limestones with different primary source rocks, metamorphic origin, rootless, new type of metamorphic rocks, modern metablastic rock series and their derivatives / metablastites / metablastic rocks (known as granite/granitoid, gabbro/gabbroid, diorite/dioritoid, charnockite/charnockite, carbonatite/carbonatoid intrusion, pluton, batholith type magmatic origin pluton/deep rocks) defined and named under the general name, forming different types. Under the name of carbonatoblastites, many carbonatoblastite type metablastic rocks (alkali metablastites, syenitoblastite, monzonitoblastite, calcitoblastite, calcito-dolomitoblastite, dolomitoblastite, sideritoblastite, stroncianitoblastite etc.) and carbonate-originated rock-forming main-secondary-trace crystalloblast neominerals (calcitoblast, dolomitoblast, witheritoblast, stroncianitoblast etc.) forming different carbonatoblastites have been etymologically redefined, named, classified and their physical-chemical properties have been determined. Depending on the compositions and contents of pure-impure carbonate/limestones which are primary source rocks and pure-impure marbles which are metamorphic equivalent rock units of the mentioned primary source rock units, different pure-impure carbonatoblastite type metablastic rocks which are rootless, metamorphic origin, a kind of new modern metamorphic rocks develop. Depending on the mineralogical composition of carbonatoblastites; especially calcitoblastite-dolomitoblastite type metablastic rock types formed by calcitoblast-dolomitoblast crystalloblast neominerals, pure-impure carbonatoblastites formed by two or more main rock-forming carbonatoblast crystalloblast neominerals with different physical properties, develop strange vertical structural geomorphological shapes in topography/morphology (eroded cone stalagmites, fairy chimneys etc.) as a result of different erosions, meltings and dissolutions due to external factors (wind, snow-rain water etc.). Because the physical properties of the rock-forming main calcitoblast and dolomitoblast crystalloblast neominerals are different and their resistance to external factors will be different, they cause the development of different karst formations (erect cones, caves, grooves, abrasions, cavities, etc.) on the outer surface of the carbonatoblastite type rock they form due to different abrasion/erosion, melting and dissolution in the calcitoblastite-dolomitoblastite type carbonatoblastite type metablastic rocks they form. In addition, carbonatoblastites are a new type of 3rd generation metablastic rock types of modern metamorphic origin, developed within the regional dynamothermal Tarhan metamorphism cycle, and correspond to the 5th classical state of matter, which developed spontaneously in nature and can be seen in every phase of our daily lives. Such geomorphological formations are known as "rock forests", which are widely developed in many countries. In addition, pure and impure carbonatoblastites contain precious and semi-precious stones, ornamental stones (Gemology), radioactive and heavy and light rare earth elements/REE, the world's richest potential metablastic ore/mineral deposits. They contain carbonate-based metallic-non-metallic ores and strategic minerals.

Immunomodulatory dynamics in the porcine myometrium: global transcriptome analysis, including the effects of PPARγ ligands

BackgroundThe myometrium is involved in many processes during pregnancy and the estrous/menstrual cycle. Peroxisome proliferator-activated receptors (PPARs) can be regulators of the processes occurring in the myometrium. In the present study, we determined the global transcriptome profile of the porcine myometrium during the peri-implantation period and the late luteal phase of the estrous cycle. In addition, we investigated for the first time the influence of PPARγ ligands on the transcriptome profile.ResultsThe myometrium of gilts (n = 3) was collected on days 10–11 and 14–15 of pregnancy and on the corresponding days of the estrous cycle. The expression of PPARγ was confirmed in the tissue. Based on the mRNA level, further studies were conducted on myometrial explants obtained from pigs at days 14–15 of pregnancy and the corresponding days of the estrous cycle. The tissue sections were incubated in vitro for 6 h in the presence of a PPARγ agonist, pioglitazone (P; 10 µM), or antagonist, T0070907 (T; 1 µM). To identify the transcription profile of the myometrium, RNA-Seq was performed on the NovaSeq 6000 Illumina platform. This study identified 1082 differentially expressed genes (DEGs; 609 upregulated and 473 downregulated) in the porcine myometrium on days 14–15 of pregnancy compared with the corresponding days of the estrous cycle. During pregnancy, we detected 6 and 80 DEGs related to PPARγ agonist and antagonist, respectively. During the estrous cycle, we identified 4 and 17 DEGs for P and T vs. the control, respectively.ConclusionsThe results indicate that the DEGs are involved in a number of processes, including the immune response, prostaglandin synthesis, cell differentiation and communication. In addition, the role of PPARγ activity in regulating the expression of genes related to the immune response and hormone synthesis in the porcine myometrium has been demonstrated.

Prostaglandin pathways in equine myometrium regulations: endometrosis progression

IntroductionProstaglandins (PG) are important regulators of the myometrial contractility in mammals. Endometrosis, a condition characterized by morphological changes in the equine endometrium, also affects endometrial secretory function. However, it remains unclear whether and how endometrosis affects myometrial function.MethodsThis study investigated: (i) mRNA transcription of genes encoding specific enzymes responsible for PG synthesis, such as prostaglandin—endoperoxide synthase (PTGS2), PGE2 synthase (PTGES), PGF2α synthase (PTGFS) and PG receptors: PGE2 receptors (PTGER1- 4), and PGF2α receptor (PTGFS) in equine myometrium and, (ii) the effects of PGE2 and PGF2α on myometrial contractile activity, during endometrosis in mares. The myometria used in experiments 1 and 2 were collected from mares in the mid-luteal (n = 23) and follicular (n = 20) phases of the estrous cycle, according to the histological classification of the endometrium (Kenney and Doig categories I, IIA, IIB, and III).ResultsIn experiment 1, changes in mRNA transcription of PG synthase or PG receptors in the myometrium during the course of endometrosis were determined using qPCR. During the mid-luteal phase, myometrial mRNA transcription of PTGES increased in mares with endometrial category IIB compared to category I. However, myometrial mRNA transcription of PTGER1 decreased during the progression of endometrosis compared to category I. During the follicular phase, mRNA transcription of PTGER1 and PTGER2 increased in mares with endometrial categories III or IIA, respectively. In addition, mRNA transcription of PTGFS increased in mares with endometrium category IIA compared to category I. In experiment 2, the force of myometrial contractions was measured using an isometric concentration transducer. In the follicular phase, PGE2 decreased the force of contractions in mares with endometrial categories IIA, IIB, and III compared to the respective control groups. Prostaglandin F2α increased the force of myometrial contractions in mares with category IIA endometrium, whereas it decreased in category IIB compared to the respective control groups.DiscussionWe concluded that in the progression of endometrosis there are changes in the myometrial transcription of mRNA encoding PG synthases and receptors, particularly PTGER1 and PTGER2. Mares with endometrosis had abnormal myometrial contractile responses to PG. These findings suggest that myometrial function may be compromised during the progression of endometrosis.

Impact of a national dementia research consortium: The Canadian Consortium on Neurodegeneration in Aging (CCNA).

The Canadian Consortium on Neurodegeneration in Aging (CCNA) was created by the Canadian federal government through its health research funding agency, the Canadian Institutes for Health Research (CIHR), in 2014, as a response to the G7 initiative to fight dementia. Two five-year funding cycles (2014-2019; 2019-2024) have occurred following peer review, and a third cycle (Phase 3) has just begun. A unique construct was mandated, consisting of 20 national teams in Phase I and 19 teams in Phase II (with research topics spanning from basic to clinical science to health resource systems) along with cross-cutting programs to support them. Responding to the needs of researchers within the CCNA teams, a unique sample of 1173 deeply phenotyped patients with various forms of dementia was accrued and studied over eight years (COMPASS-ND). In the second phase of funding (2019-2024), a national dementia prevention program (CAN-THUMBS UP) was set up. In a short time, this prevention program became a member of the World Wide FINGERS prevention consortium. In this article, the challenges, successes, and impacts of CCNA in Canada and internationally are discussed. Short-term deliverables have occurred, along with considerable promise of impacts in the longer term. The creation of synergy, networking, capacity building, engagement of people with lived experience, and economies of scale have contributed to the considerable success of CCNA by all measures. CCNA is evidence that an organized "centrally-organized" approach to dementia research can catalyze important progress nationally and yield significant and measurable results.