Cycle Disturbances Research Articles

Does the COVID-19 Vaccines Effect on the Menstrual Cycle, Cross-Sectional Study Among Adult Females at King Saud University

COVID-19 vaccinations have been associated with irregularities in the menstrual cycle and symptoms occurring pre and post-menstruation, affecting women’s reproductive health. This study aimed to demonstrate the impact of COVID-19 vaccines on women’s reproductive health by examining the association between COVID-19 vaccines and disturbed menstrual cycles. This cross-sectional survey-based study was conducted among adult females at King Saud University, Saudi Arabia, from April 2022 to August 2022. A total of 380 participants were selected through a stratified random sampling technique. Ethical approval was obtained from the Deanship of Scientific Research at King Saud University. The data were analysed using descriptive statistics and appropriate statistical tests. The results revealed that 53.9% of the participants experienced disturbances in the menstrual cycle after receiving the COVID-19 vaccination. Adult females aged 18-25 showed the highest rate of disorders. Menstrual disruptions were substantially correlated with marital status (p = 0.05), with a significant association between the number of COVID-19 vaccine doses and the occurrence of menstrual disturbances (p = 0.001). The administration of the vaccination during menstruation was linked to a notable occurrence of menstrual disturbances, although the p-value showed no statistical significance. A significant correlation was examined (p < 0.05) between pre-existing menstrual problems and the occurrence of disorders after receiving the COVID-19 vaccine (p < 0.05). The study emphasised the importance of tailored healthcare treatments for women following COVID-19 vaccination and the need for regular evaluation of reproductive health outcomes post-COVID-19 vaccination.

Metabolic Syndrome Severity Score in Subjects with and without Poly Cystic Ovarian Syndrome

Objective: To compare polycystic ovarian syndrome and their defining criteria with metabolic syndrome severity score among females with and without polycystic ovarian syndrome. Study Design: Comparative cross-sectional study. Place and Duration of Study: Naval Hospital Islamabad, from Jan 2018 to Dec 2021. Methodology: We evaluated 293 female subjects for Poly Cystic Ovarian Syndrome after several exclusions who presented with an initial complaint of disturbances in menstrual cycles. These subjects underwent clinical examination including blood pressure and anthropometric indices and measurements of modified Ferriman Gallway score. Biochemical measurements included fasting plasma glucose, HDL cholesterol, triglycerides and insulin measurement. These parameters were measured for various components included in defining the Poly Cystic Ovarian Syndrome as per Rotterdam criteria and Metabolic Syndrome Severity Score equation to compare metabolic syndrome severity and insulin resistance among subjects with Poly Cystic Ovarian Syndrome and without Poly Cystic Ovarian Syndrome. Results: Mean age among participants were 29.46±6.74 years. Disturbances in menstrual cycle reporting oligo/anovulation was reported by (181/293) 61.8% in comparison to (112/293) 38.2%. Hirsutism (modified Ferriman Gallway score>8) was present in (142/293) 48.5%. Radiological findings pointing towards Poly Cystic Ovarian Syndrome diagnosis were found in (72/293) 24.6%. Metabolic Syndrome Severity Score showed higher correlation with age, and insulin resistance in contrast to hirsutism and free androgen indices. Hirsutism was higher among oligo/anovulation females than participants without menstrual complaints (14.17+8.99 vs. 11.16+7.88, p=0.004). Similarly, bioc Conclusion: Metabolic Syndrome Severity Score equation does not associate with Poly Cystic Ovarian Syndrome criteria as defined by Rotterdam. Insulin resi

Effects of puerarin on gait disturbance in a 6-hydroxydopamine mouse model of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder caused by dopamine (DA) neuronal dysfunction. Although DA agonists and N-methyl-D-aspartate receptor (NMDAR) antagonists are used to treat PD, chronic use causes severe side effects. Puerarin (PUE) is a natural bioactive compound that affects the DA system; however, its effect on PD-associated motor functions is unknown. Therefore, we investigated whether PUE treatment in a 6-hydroxydopamine (6-OHDA) PD mouse model affects motor dysfunction. Adult male ICR mice received unilateral 6-OHDA microinfusion into the right medial forebrain bundle. After a 2-week recovery period, PUE (20 or 50mg/kg) or the vehicle (saline, VEH) was administered intraperitoneally once daily for 21 days. Motor dysfunction was assessed using the locomotion, gait cycle, and rotation tests. Local field potentials (LFPs) were measured in the substantia nigra compacta (SNc), striatum (STR), subthalamic nucleus (STN), and primary motor cortex. 6-OHDA-lesioned PD mice showed increased gait cycle disturbance and unidirectional rotation. PUE treatment ameliorated the gait cycle disturbance, but not unidirectional rotation of PD mice. These effects differed with DA agonist treatment (which improved PD symptoms) and NMDAR antagonist treatment (which aggravated PD symptoms). Moreover, locomotion was increased only in NMDAR antagonist treatment. PUE treatment induced no changes in the attenuated LFP of the beta wave in the STR and STN, and SNc-STN delta-wave coherence was shown in PD animals. This study suggests that PUE is a beneficial co-therapeutic agent for alleviating gait cycle disturbance in PD symptoms.

Spindles in WAG/Rij Rats with Absence Epilepsy and Comorbid Depression

WAG/Rij rats are a valid model of absence epilepsy and comorbid depression. We have previously shown that WAG/Rij rats have disturbances in the sleep-wake cycle and changes in the characteristics of sleep spindles. A negative correlation was also found between the number of spike-wave discharges (SWD) and the duration of rapid eye movement (REM) sleep. Clinical evidence suggests that the traditional antidepressants imipramine and fluoxetine are effective in suppressing symptoms of depression, but may have a negative impact on the sleep-wake cycle and comorbid epilepsy in patients. Our previous studies in WAG/Rij rats showed that imipramine, when administered chronically, increases the number of SWDs, while fluoxetine at the same dose reduces their number, although both antidepressants have a pronounced antidepressant effect. Comparison of the effects of the antidepressants imipramine and fluoxetine on the sleep-wake cycle and sleep spindles in WAG/Rij rats remains unstudied. The purpose of this work is to find out: 1) what effects do imipramine and fluoxetine have on the sleep-wake cycle and the characteristics of sleep spindles in WAG/Rij rats and 2) whether there are differences in their effects. To achieve this goal, the characteristics of the sleep-wake cycle and sleep spindles were compared in WAG/Rij rats after chronic administration of antidepressants and saline and in non-epileptic Wistar rats. Administration of imipramine led to a significant decrease in the duration of REM sleep. The administration of imipramine, compared with fluoxetine, also increased the latency of the transition to sleep and the transition to REM sleep. Sleep spindle amplitude was significantly increased by both antidepressants. However, the spectral power density of “slow” and “medium” spindles, which predominate in WAG/Rij rats compared to Wistar rats, was significantly higher after administration of imipramine than fluoxetine. The results suggest that imipramine causes greater negative changes in the sleep-wake cycle and sleep spindles than fluoxetine. Studies in the WAG/Rij rat model indicate that fluoxetine is more preferable antidepressant for the treatment of depressive disorders comorbid with absence epilepsy, since it does not cause a significant deterioration in sleep quality. These results are consistent with clinical data.

Systemic messenger RNA replacement therapy is effective in a novel clinically relevant model of acute intermittent porphyria developed in non-human primates

ObjectiveAcute intermittent porphyria (AIP) is a rare metabolic disorder caused by haploinsufficiency of hepatic porphobilinogen deaminase (PBGD), the third enzyme of the heme biosynthesis. Individuals with AIP experience neurovisceral attacks...

An integrated metabolomics and proteomics analysis reveals copper‑zinc alloy surface contact-mediated metabolic disruption, lipid peroxidation, and osmotic imbalance of Cryptocaryon irritans tomonts

Cryptocaryon irritans cause massive losses in the mariculture industry and are among the most threatening pathogens affecting teleost species. Copper‑zinc alloy (CZA) surface contact effectively kills C. irritans within minutes. Thus, this study employed integrated metabolomics and proteomics analysis to investigate the killing mechanism of CZA against C. irritans. Moreover, malondialdehyde contents, CuZn-SOD, and ATPase activities were evaluated. Proteomics analysis identified 142 differentially expressed proteins (DEPs), including 91 (59 upregulated, 32 downregulated), 92 (42 upregulated, 50 downregulated), and 43 (17 upregulated, 26 downregulated) DEPs at 0.5 h, 1 h, and 0.5 h vs 1 h of contact treatment with the CZA surface, respectively. Similarly, the metabolomic analysis identified 377 differentially expressed metabolites (DEMs). There were 237 (94 upregulated, 143 downregulated), 264 (112 upregulated, 152 downregulated), and 193 (101 upregulated, 92 downregulated) DEMs at 0.5 h, 1 h, and 0.5 h vs 1 h of contact treatment with the CZA surface, respectively. KEGG-based integrative analyses revealed that CZA exposure significantly enriched proteins and metabolites involved in oxidative phosphorylation, purine, pyrimidine, cysteine, and methionine metabolism. Notably, CZA exposure inhibited the TCA cycle, disrupting energy metabolism, as evidenced by downregulation of key TCA proteins, including citrate synthase and malate dehydrogenase, and metabolites like succinic and malic acids at both 0.5 h and 1 h of CZA treatment. Prolonged CZA exposure also affected protein metabolism, with significant downregulation of ribosomal protein S3a (RPS3a) and proteasome activity. Additionally, CZA surface contact downregulated key proteins involved in pyrimidine (DHFR-TS), purine (RRM1), and cysteine and methionine metabolism (AHCY), leading to disturbances in the methionine cycle, suppression of glutathione metabolism, and alterations in cellular redox status. Quantitative polymerase chain reaction (qPCR) analysis confirmed the upregulation of citrate synthase, proteasome subunit alpha type, and adenosylhomocysteinase with prolonged CZA exposure. Additionally, extended CZA exposure significantly decreased the MDA content due to the increased CuZn-SOD activity. Moreover, CZA exposure reduced Ca2+/Mg2+-ATPase and Na+/K+-ATPase activities. Altogether, CZA surface contact caused metabolic disruption, lipid peroxidation, and osmotic imbalance of C. irritans tomonts, highlighting the broad molecular impact of CZA on cellular processes.

The effect of norepinephrine on ovarian dysfunction by mediating ferroptosis in mice model.

Studies have shown that stress is associated with ovarian dysfunction. Norepinephrine (NE), a classic stress hormone involved in the stress response, is less recognized for its role in ovarian function. In this study, an NE-treated mouse model is induced by intraperitoneal injection of NE for 4 weeks. Compared with normal control mice, NE-treated mice show disturbances in the estrous cycle, decreased levels of anti-Mullerian hormone (AMH) and estradiol (E2), and increased level of follicle-stimulating hormone (FSH). Additionally, the numbers of primordial follicles, primary follicles, secondary follicles, and antral follicles are decreased, whereas the number of atretic follicles is increased in NE-treated mice, indicating NE-induced ovarian dysfunction. RNA sequencing further reveals that genes associated with ferroptosis are significantly enriched in NE-treated ovarian tissues. Concurrently, the levels of reactive oxygen species (ROS), ferrous ions, and malondialdehyde (MDA) are increased, whereas the expression level of glutathione peroxidase 4 (GPX4) is decreased. To elucidate the mechanism of NE-induced ferroptosis in ovaries and the potential reversal by Coenzyme Q10 (CoQ10), an antioxidant, we conduct both in vitro and in vivo experiments. In vitro, the granulosa cell line KGN, when treated with NE, shows decreased cell viability, reduced expression of GPX4, elevated levels of ferrous ion and ROS, and increased MDA level. However, these NE-induced changes are reversed by the addition of CoQ10. Compared with the NE group, the NE-treated mice supplemented with CoQ10 present increased GPX4 level and decreased iron, ROS, and MDA levels. Moreover, the differential expression of genes associated with ferroptosis induced by NE is ameliorated by CoQ10 in NE-treated mice. Additionally, CoQ10 improves ovarian function, as evidenced by increased ovarian weight, more regular estrous cycles, and an increase in follicles at various stages of growth in NE-treated mice. In conclusion, NE induces ovarian dysfunction by triggering ferroptosis in ovarian tissues, and CoQ10 represents a promising approach for protecting reproductive function by inhibiting ferroptosis.

Dynamic variations of plasma and urine metabolic profiles in left anterior descending coronary artery ligation-induced myocardial infarction rats and the regulatory effects of Chinese patent medicine Xin-Ke-Shu

Myocardial infarction (MI) is one of the most severe cardiovascular diseases (CVD). Traditional Chinese medicines have unique advantages in the treatment of CVD, with Xin-Ke-Shu (XKS) being a commonly used Chinese patent medicine for the prevention and treatment of MI patients. This study aimed to investigate the dynamic metabolic profiles of plasma and urine in left anterior descending coronary artery ligation (LAD) -induced MI rats at days 3, 12, and 21 after surgery, and to evaluate the regulatory effects of XKS at these time points using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) metabolomics. The metabolic profiles of plasma and urine in the LAD-induced MI rats showed significant variations at days 3, 12, and 21 after MI. We identified a total of 23 plasma metabolites and 12 urine metabolites as potential pathological markers related to MI progression. These metabolites were mainly involved in pathways such as TCA cycle, arachidonic acid metabolism, glutathione metabolism, glycerophospholipid metabolism, sphingolipid metabolism, and fatty acid metabolism, all of which were associated with imbalance of myocardial energy metabolism, oxidative stress, and calcium overload. Disturbances in the TCA cycle, arachidonic acid metabolism, glutathione metabolism, and purine metabolism in plasma and urine were observed as early as day 3 after MI. By day 12, we noted significant changes in fatty acid metabolism in plasma and urine, along with notable alterations in sphingolipid metabolism in plasma. Disorders in plasma glycerophospholipid metabolism were first evident at day 12 and reached their peak severity by day 21. Treatments with XKS significantly regulated the disturbances in the plasma and urine metabolic profiles of MI rats at days 3, 12, and 21, with medium dose of XKS displaying a particularly strong regulatory effect, especially at day 12. Our study demonstrates that host metabolism undergoes dynamical changes following MI with most metabolic disorders manifesting in the early stage of MI. XKS effectively regulates nearly all of these disturbances and can be administered as soon as possible after MI. These findings provide valuable insights into the metabolic progression of MI and highlight the therapeutic potential of XKS in the treatment of MI.

Targeting ATR Kinase as a Strategy for Canine Lymphoma and Leukaemia Treatment.

Ataxia telangiectasia and Rad3-related (ATR) kinase is one of the main regulators of cell response to DNA damage and replication stress. Effectiveness of ATR targeting in human cancers has been confirmed in preclinical studies and ATR inhibitors are currently developed clinically in human oncology. In the presented study, we tested the anticancer efficacy of ATR inhibitor berzosertib in an in vitro model of canine haematopoietic cancers. Using MTT assay and flow cytometry, we assessed the cytotoxicity of berzosertib in four established canine lymphoma and leukaemia cell lines and compared it with its activity against noncancerous canine cells. Further, we estimated the level of apoptosis in berzosertib-treated cells via flow cytometry and assessed H2AX phosphorylation as a marker of DNA damage using western blot technique. In flow-cytometric analysis, we also evaluated potential synergism between berzosertib and chlorambucil and assessed the influence of berzosertib on cell cycle disturbances induced by the drug. The results demonstrated that berzosertib, even without additional DNA damaging agent, can be effective against canine lymphoma and leukaemia cells at concentrations that were harmless for noncancerous cells, although sensitivity of individual cancer cell lines varied greatly. Cell death occurred through caspase-dependent apoptosis via induction of DNA damage. Berzosertib also acted synergistically with chlorambucil, probably by preventing DNA damage repair as a consequence of S-phase arrest abrogation. In conclusion, ATR inhibition may provide a new therapeutic option for the treatment of canine lymphomas and leukaemias, but further studies are required to determine potential biomarkers of their susceptibility.

Circumscribed Alopecia Areata Incognita and Response to Tofacitinib

<b><i>Introduction:</i></b> Alopecia areata incognita (AAI) remains a subject of ongoing debate in the literature, with some authors advocating its classification as a subtype of alopecia areata. A localized form of this condition, entitled circumscribed AAI, has been rarely reported in the literature. We report an unusual case of circumscribed AAI treated with oral tofacitinib. <b><i>Case Report:</i></b> A 21-year-old woman presented with a large patch of localized hair thinning on the parietal area. Trichoscopy revealed yellow dots and short thin hairs. A diagnosis of circumscribed AAI was established. Due to the frequent relapses to conventional treatment and associated weight gain secondary to oral dexamethasone, oral tofacitinib 5 mg twice daily was started with a sustained response. <b><i>Discussion:</i></b> AAI is a controversial condition, and its circumscribed variant is scarcely reported in the literature. We hypothesize that AAI clinical presentation may be secondary to cycle disturbance leading to rapid and incomplete hair follicle cycling. Most papers established that the best treatment for AAI is corticosteroids, either topical, intralesional or systemic. <b><i>Conclusion:</i></b> Oral tofacitinib represents a potential treatment for AAI cases that do not present a sustained response to corticosteroids.

Metabolic Messengers: itaconate.

The metabolite itaconate has emerged as an important immunoregulator with roles in antibacterial defence, inhibition of inflammation and, more recently, as an inhibitory factor in obesity. Itaconate is one of the most upregulated metabolites in inflammatory macrophages. It is produced owing to the disturbance of the tricarboxylic acid cycle and the diversion of aconitate to itaconate via the enzyme aconitate decarboxylase 1. In immunology, initial studies concentrated on the role of itaconate in inflammatory macrophages where it was shown to be inhibitory, but this has expanded as the impact of itaconate on other cell types is starting to emerge. This review focuses on itaconate as a key immunoregulatory metabolite and describes its diverse mechanisms of action and its many impacts on the immune and inflammatory responses and in cancer. We also examine the clinical relevance of this immunometabolite and its therapeutic potential for immune and inflammatory diseases.

Investigation of cannabidiol-induced cytotoxicity in human hepatic cells

Cannabidiol (CBD) is one of the primary cannabinoids present in extracts of the plant Cannabis sativa L. A CBD-based drug, Epidiolex, has been approved by the U.S. FDA for the treatment of seizures in childhood-onset epileptic disorders. Although CBD-associated liver toxicity has been reported in clinical studies, the underlying mechanisms remain unclear. In this study, we demonstrated that CBD causes cytotoxicity in primary human hepatocytes and hepatic HepG2 cells. A 24-h CBD treatment induced cell cycle disturbances, cellular apoptosis, and endoplasmic reticulum (ER) stress in HepG2 cells. A potent ER stress inhibitor, 4-phenylbutyrate, markedly attenuated CBD-induced apoptosis and cell death. Additionally, we investigated the role of cytochrome P450 (CYP)-mediated metabolism in CBD-induced cytotoxicity using HepG2 cell lines engineered to express 14 individual CYPs. We identified CYP2C9, 2C19, 2D6, 2C18, and 3A5 as participants in CBD metabolism. Notably, cells overexpressing CYP2C9, 2C19, and 2C18 produced 7-hydroxy-CBD, while cells overexpressing CYP2C9, 2C19, 2D6, and 2C18 generated 7-carboxy-CBD. Furthermore, CBD-induced cytotoxicity was significantly attenuated in the cells expressing CYP2D6. Taken together, these data suggest that cell cycle disturbances, apoptosis, and ER stress are associated with CBD-induced cytotoxicity, and CYP2D6-mediated metabolism plays a critical role in decreasing the cytotoxicity of CBD.

Effects of COVID-19 Vaccination on Menstrual Cycle Disturbance in Female Population

Effects of COVID-19 Vaccination on Menstrual Cycle Disturbance in Female Population

Effect of COVID-19 Vaccination on Menstrual Cycle Patterns of Reproductive-age Women: A Multi-centric Observational Study.

The study was conducted to know the impact of COVID-19 vaccination on menstrual cycle patterns and pre- and post-menstrual symptoms in women aged 18-45 years. COVID-19 vaccination was introduced to combat the dreadful impacts of human coronavirus infection. The two indigenously developed COVID-19 vaccines approved for use in India are COVISHIELD and COVAXIN. To investigate the effects of COVID-19 vaccination on the menstrual cycle, pre- and post-menstrual symptoms and to establish the correlation with the type of vaccine received. Multi-centric observational study conducted in six institutes of national importance in different states of India over one year. A total of 5709 female participants fulfilling inclusion criteria were enrolled. Data about the impact of vaccines (COVISHIELD and COVAXIN) and prior COVID-19 infection on the menstrual cycle and its associated symptoms were obtained using all participants' online and offline interviews. Of 5709 participants, 78.2% received COVISHIELD and 21.8% COVAXIN. Of the total 5709 participants, 333 (5.8%) developed post-vaccination menstrual disturbances, with 32.7% having frequent cycles, 63.7% prolonged cycles, and 3.6% inter-menstrual bleeding. A total of 301 participants noticed changes in the amount of bleeding, with 50.2% excessive, 48.8% scanty, and 0.99% amenorrhea followed by heavy bleeding. Furthermore, the irregularities of the menstrual cycle (p = 0.011) and length (0.001) were significantly higher in the COVAXIN group (7.2%) as compared to the COVISHIELD (5.3%) group. A total of 721 participants complained of newly developed/worsening pre- and post-menstrual symptoms. These symptoms were significantly higher in the COVISHIELD group (p = 0.031), with generalized weakness and body pains as the main complaints (p = 0.001). No significant difference was observed in the incidence of COVID-19 infection with these vaccines. No significant associations were observed when comparing menstrual abnormalities among those with COVID-19 infection (p > 0.05). COVISHIELD and COVAXIN vaccines were associated with menstrual cycle disturbances and pre-and post-menstrual symptoms in a small proportion of participants, with 94.7% having no change in the amount of bleeding during menstruation post-vaccination. The menstrual irregularities observed were significantly higher with the COVAXIN vaccine. Others: Further, long-term studies are required to confirm that the impact of COVID-19 vaccination on the menstrual cycle may be short-lasting, with no severe effects on women's menstrual health.

Unveiling of the anti-tumor activity of green synthesized zinc nanoparticles against Ehrlich solid tumors in mice

Cancer as a threat to human life disease is considered by the disturbance of the normal cell cycle, which results in the spontaneous growth of cell growth, the lack of differentiation, and consequently malignant growths. Nowadays, various synthetic agents are applied for cancer therapy; nevertheless, the reports confirmed that these chemical agents are related to various adverse complications. This experimental study was designed to assess the anti-tumor activities of zinc nanoparticles (ZnNP) green synthesized by the Astragalus maximus against the Ehrlich solid tumors (EST) in mice. To induce the EST model, 0.2 ml of cell suspension was intramuscularly injected into the right thigh of the mice. Five-day post-injection, the mice were allocated into five groups (containing 8 mice/each group) including EST mice treated with normal saline, EST mice orally treated ZnNP 10 mg/kg/day, EST mice orally treated ZnNP 25 mg/kg/day, and EST mice orally treated ZnNP 50 mg/kg/day for 14 days. Then, the volume of the tumor, tumor growth inhibition, body weight, the tumor markers, oxidant/antioxidant markers, and tumor necrosis factor-alpha level (TNF-α), were assessed in tested mice. Our results showed that after the treatment of EST mice with CYC and ZnNPs at 10, 25, and 50 mg/kg, the volume of tumor and serum amount of tumor markers of AFP and CEA were significantly reduced (p<0.001). We found that ZnNPs at 10, 25, and 50 mg/kg markedly declined the oxidative markers and increased the level of antioxidant enzyme of SOD and GPx in comparison with the control group received normal saline (p<0.001). To conclude, we reported the unveiling of the anti-tumor activity of ZnNPs green synthesized by A. maximus extract mainly at the doses 50 mg/kg against Ehrlich solid tumors (EST) in mice; however, further supplementary studies are required to clear all anti-tumor aspects of these nanoparticles.

Menstrual Cycle Disturbances after COVID-19 Vaccination: A Cross-Sectional Study.

Following COVID-19 vaccination, some women suffered from menstrual cycle disturbances. This study aimed to investigate menstrual cycle disturbances after COVID-19 vaccination in women of reproductive age. This cross-sectional study was performed on 407 vaccinated women in the vaccination center of Imam Hossein Hospital (Tehran, Iran) between October 2021 and October 2022. They were interviewed based on a research-made checklist which consisted of two areas of questions about the baseline characteristics of participants and menstrual cycle characteristics to explore menstrual characteristics following COVID-19 vaccination. The prevalence of menstrual disturbances was higher after the third dose (38.3%) compared with the second (27.9%) and first (17.7%) doses (P<0.001). After the first dose, a history of polycystic ovarian syndrome [PCOS, odds ratio (OR)=7.35, 95% confidential interval (CI)= (3.64-14.82), P<0.001] and menstrual disturbances with unknown etiology [OR=15.23, 95% CI=(6.30-36.80), P<0.001] could predict menstrual disturbances. After the second dose, a history of menstrual disturbances with unknown etiology [OR=3.83, 95% CI=(1.47-9.94), P=0.006] and menstrual disturbances after the first dose [OR=201.96, 95% CI= (40.99-994.90), P<0.001] were predictors of menstrual disturbances. After the third dose, a history of menstrual disturbances with unknown etiology [OR=3.09, 95% CI= (1.00-9.52), P=0.048], menstrual disturbances after the first [OR=9.82, 95% CI=(1.38-69.69), P=0.022] and second [OR=7.83, 95% CI=(1.46-41.92), P=0.016] doses could predict menstrual disturbances. We detected that many women experienced various menstrual disturbances after vaccination against SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). Furthermore, a history of menstrual abnormalities (before COVID-19 vaccination and following the previous doses of these vaccines) was associated with developing menstrual disturbances.

Familial risk for depression is associated with reduced physical activity in young adults: evidence from a wrist-worn actigraphy study

Depression is characterized by reduced physical activity and sleep-wake cycle disturbances, often considered important features of the disease. While a few studies have suggested that self-reported reduced physical activity and sleep-wake cycle disturbances might both be linked to depression vulnerability, actigraphy-based measures in vulnerable samples remain largely unexplored. This study relied on actigraphy-based parameters to test whether these disturbances characterize depression vulnerability. Seven-day actigraphy data were collected from 20 (13 female) university students with a high vulnerability to depression, which was determined by the presence of a family history of the condition but no current symptoms, and 32 (21 female) controls with neither a family history of depression nor current depressive symptoms. Daily physical activity, namely gross motor activity, was quantified as average daily acceleration and time spent engaging in moderate-vigorous physical activity (MVPA). The sleep-wake cycle and circadian rhythms were assessed as total sleep duration per night (in hours), sleep within sleep period time (in hours), sleep efficiency (%), and relative amplitude (i.e., the difference between the activity during the day and the night, which reflects circadian rhythms amplitude). Results showed that individuals with a familial risk for depression exhibited reduced daily acceleration and time spent in MVPA relative to the control group, particularly on the weekend during their free time away from scheduled activities. On the other hand, the two groups were comparable in terms of sleep estimates. Taken together, reduced physical activity, but not sleep-wake disturbances, seem to be associated with vulnerability to depression and might be a viable target for identification and prevention efforts.

The Novel Parallel Closure Technique Compared to Single-Layer Closure of the Uterus After Primary Cesarean Section Decreases the Incidence of Isthmocele Formation and Increases Residual Myometrial Thickness.

Background Isthmocele or a scar defect is a relatively common consequence of cesarean section resulting in menstrual disturbances and infertility and may compromise the myometrial integrity of the uterus in women contemplating subsequent vaginal birth. Several preventive measures have been suggested, including the modification of surgical techniques used for the closure of the uterine incision. The current study aimed to compare the incidence of isthmocele and assess residual myometrial thickness in women who underwent single versus parallel layered closure to approximate the endo-myometrial layer during cesarean section. Methodology This retrospective study evaluated data of women undergoing their first cesarean section under elective conditions (n = 497) where the uterine incision was closed using a single (n = 295) or a parallel layer (n = 202) technique. Patients were evaluated twice, at 3-6 months and 18 months postpartum, with a transvaginal ultrasound noting the presence or absence of an isthmocele and measurement of the residual myometrial thickness. Results Regardless of the closure technique, 64 (12.9%) women had an ultrasound-diagnosed isthmocele. Significantly fewer patients in the parallel-layer closure group presented with an isthmocele both at 3-6 (13.6 vs. 6.9%; p = 0.019) and 18 months (16.3 vs. 7.8%; p = 0.009) postpartum. Residual myometrium was significantly thicker in the parallel-layer closure group (8.0 vs. 13.2 mm at 3-6 months postpartum; p = 0.000 and 7.2 vs. 12.3 mm at 18 months postpartum; p = 0.004). For all patients, a retroverted position of the uterus at 3-6 months follow-up examination significantly increased the frequency of isthmocele (36/395 (9.1%) with an anteverted uterus and 18/102 (17.6%) with a retroverted uterus; p = 0.002). In patients with a single-layer closure, a retroverted uterus at the 3-6-month follow-up was associated with an isthmocele in 29.5% (18/61) of patients, while no isthmocele was recorded when the uterus was retroverted in the parallel-layer closure group (0/41) (p = 0.001). At 18 months postpartum, of the 64 patients with an isthmocele, 26 (40.6%) presented with abnormal uterine bleeding mainly in the form of postmenstrual spotting. Of the 26 patients with abnormal bleeding, 23 were in the single-layer and three were in the parallel-layer closure group. Conclusions The parallel-layer closure when compared to a single-layer closure of the uterine incision in patients undergoing primary cesarean section decreased the incidence of isthmocele formation and increased residual myometrial thickness. More patients in the single-layer closure group had menstrual cycle disturbances at 18 months postpartum.

Irisin alleviated the reproductive endocrinal disorders of PCOS mice accompanied by changes in gut microbiota and metabolomic characteristics

IntroductionFolliculogenesis and oligo/anovulation are common pathophysiological characteristics in polycystic ovary syndrome (PCOS) patients, and it is also accompanied by gut microbiota dysbiosis. It is known that physical activity has beneficial effects on improving metabolism and promoting ovulation and menstrual cycle disorder in PCOS patients, and it can also modulate the gastrointestinal microbiota in human beings. However, the mechanism remains vague. Irisin, a novel myokine, plays a positive role in the mediating effects of physical activity.MethodsMice were randomly divided into the control group, PCOS group and PCOS+irisin group. PCOS model was induced by dehydroepiandrosterone (DHEA) and high-fat diet (HFD). The PCOS+irisin group was given irisin 400μg/kg intraperitoneal injection every other day for 21 days. The serum sex hormones were measured by radioimmunoassay. Hematoxylin and Eosin (H&amp;amp;E) Staining and immunohistochemistry (IHC) were conducted on ovarian tissue. The feces microbiota and metabolomic characteristics were collected by 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC–MS).ResultsIn this study, we demonstrated that irisin supplementation alleviated reproductive endocrine disorders of PCOS mice, including estrous cycle disturbance, ovarian polycystic degeneration, and hyperandrogenemia. Irisin also improved the PCOS follicles dysplasia and ovulation disorders, while it had no significant effect on the quality of oocytes. Moreover, irisin could mitigate the decreased bacteria of Odoribacter and the increased bacteria of Eisenbergiella and Dubosiella in PCOS mice model. Moreover, irisin could alleviate the increased fecal metabolites: Methallenestril and PS (22:5(4Z,7Z,10Z,13Z,16Z)/ LTE4).ConclusionThese results suggest that irisin may alleviate the status of PCOS mice model by modulating androgen-induced gut microbiota dysbiosis and fecal metabolites. Hence, our study provided evidence that irisin may be considered as a promising strategy for the treatment of PCOS.

STRUCTURE AND CHARACTERISTICS OF THE FIRST MODULE IN THE EDUCATIONAL COMPONENT “INDIVIDUAL RESEARCH WORK” FOR EDUCATIONAL PROFESSIONAL PROGRAM “MEDICINE”

The proportion of skills, abilities, and competencies pertaining to the scientific method of understanding reality—comprising principles, rules, norms, and methodologies for acquiring and organizing new knowledge about both objective and subjective realities—represents the scientific aptitude within the educational framework. A robust scientific aptitude within the educational process is a vital prerequisite for students in specific fields of study (specializations) to receive education of requisite quality. The Department of Pathophysiology at Poltava State Medical University is actively engaged in not only fundamental medical and preclinical research but also in ongoing scientific and methodological endeavors aimed at enhancing the educational process departmentally and university-wide. The educational component ‘Individual Research Work” within the educational professional program “Medicine”, developed by the departmental faculty, serves to elevate educational standards by augmenting the scientific aptitude within the educational process. This study aimed to analyze and delineate the structure of the initial module within the educational component “Individual Research Work” of the educational and professional program “Medicine”. In preparing the manuscript of the article, the authors employed several general theoretical research methods, including analysis, synthesis, comparison of concepts, abstraction, and generalization. Module No. 1, titled “Modeling of Typical Pathological Processes in Various Organs and Systems”, within the educational component “Individual Research Work”, spans 120 hours and is structured as follows: 8 lecture hours, 32 hours of practical classes, and 80 hours designated for independent study of module topics. The thematic plan encompasses the exploration of the following topics: 1. Modelling inflammatory processes in various organs; 2. Modelling disturbances in the cell cycle (hypo- and hyperbiotic processes); 3. Modelling systemic metabolic disorders; 4. Modelling functional disorders across various organs and systems. The ultimate outcome of Module No. 1 entails students selecting a topic and experimental model conducive to their research pursuit. The structure and content of this initial module within the educational component “Individual Research Work”, developed by the Department of Pathophysiology at Poltava State Medical University, align with the standards of contemporary higher medical education. The study, along with its inaugural module, is poised to enhance the quality of education for aspiring individuals enrolled in the educational and professional program “Medicine”.