Regular Cycles Research Articles

Alterations in Circadian Rhythms, Sleep, and Physical Activity in COVID-19: Mechanisms, Interventions, and Lessons for the Future.

Although the world is acquitting from the throes of COVID-19 and returning to the regularity of life, its effects on physical and mental health are prominently evident in the post-pandemic era. The pandemic subjected us to inadequate sleep and physical activities, stress, irregular eating patterns, and work hours beyond the regular rest-activity cycle. Thus, perturbing the synchrony of the regular circadianclock functions led to chronic psychiatric and neurological disorders and poor immunological response in several COVID-19 survivors. Understanding the links between the host immune system and viral replication machinery from a clock-infection biology perspective promises novel avenues of intervention. Behavioral improvements in our daily lifestyle can reduce the severity and expedite the convalescent stage of COVID-19 by maintaining consistent eating, sleep, and physical activity schedules. Including dietary supplements and nutraceuticals with prophylactic value aids in combating COVID-19, as their deficiency can lead to a higher risk of infection, vulnerability, and severity of COVID-19. Thus, besides developing therapeutic measures, perpetual healthy practices could also contribute to combating the upcoming pandemics. This review highlights the impact of the COVID-19 pandemic on biological rhythms, sleep-wake cycles, physical activities, and eating patterns and how those disruptions possibly contribute to the response, severity, and outcome of SARS-CoV-2 infection.

Hybrid non-technical-loss detection in fog-enabled smart grids

Electricity theft is one of the major factors contributing to non-technical-losses (NTLs) in power distribution networks. NTL fraud includes frauds in which consumers profit unlawfully by manipulating smart meters (SMs), intruding networks, and so forth. This unlawful act not only undermines people’s efforts to conserve energy but also disrupts the regular billing cycle for power utilities, causing financial losses. In order to help utility companies solve the problems of inefficient electricity inspection and irregular power consumption, two NTL Detection schemes are proposed for NTL fraud prediction. Both schemes employed the auto-regressive integrated moving average (ARIMA) and the machine learning technique to predict the consumer behavior fraud pattern efficiently. Furthermore, extensive simulations are conducted on real-world electricity consumption data sets, which show that the proposed schemes outperformed state-of-the-art solutions and achieved an accuracy of 98%, a precision of 98.6%, a recall of 98.2%, an AUC of 97.9%, and an F1 score of 98.4%.

Determinants of menstrual dysfunction in the female athlete triad: A cross-sectional study in Italian athletes.

BackgroundIn 1992 the American College of Sports Medicine first described the Female Athlete Triad. The Triad is a metabolic injury involving three distinct clinical traits: low energy availability, with possible eating disorder, low bone mineral density and menstrual dysfunction (MD). Although the estimated prevalence of the Triad is low (1.2 %), single factors are common in female athletes, at all competitive levels and ages. Even though the Triad was described over two decades ago, the interrelation of the three diagnostics components is still debated: additional evidence is required to improve the multidisciplinary treatment approach for this complex condition. MD is one of the first signs of energy impairment. The present study aims at investigating MD determinants and predictors in female athletes, to allow an early diagnosis of the Triad and to implement adequate preventive strategies. Materials and methodsAn original structured questionnaire was composed to detect the presence of MD risk factors. Included participants were active female athletes within reproductive age range (15–40 years old). Anthropometric parameters and training-related factors, possibly affecting the regularity of the menstrual cycle, were investigated. ResultsRespondents were 288 female athletes. Among them, 73.3 % were under 25 years of age; 6.6 % resulted underweight; 30.6 % reported to follow a meal plan/diet and 13.9 % declared to be a smoker. Lean sports were practiced by 30.6 % of responders. Body-weight congruence was detected in in 79.9 % of participants, whereas overestimation of body image was found in 16.3 % of athletes. Irregular menstrual cycle, a possible MD predictor, was present in 33.0 % of athletes, with 41.1 % practicing some lean sport (p = 0.007). Also, overestimation of body image suggested an increased risk of menstrual irregularity (p = 0.001). BMI <18.5 or BMI >30 could also act as risk factor, although significance was not fully obtained (p = 0.053). Overall, practice of lean sports and overestimation of body image appeared good determinants of increased menstrual irregularity (AOR 2.02 and 3.83, respectively). ConclusionsMenstrual irregularity in female athletes can be considered an early predictor of MD: risk is further increased in athletes of lean sports and reporting an overestimation of self-perceived body image. Screenings and awareness programs should specifically address female athletes, because of their vulnerable-group profile. In order to define a standardized at-risk profile for Triad onset and sequelae likelihood, evaluation of menstrual regularity should especially be considered, in conjunction with the assessment of other indicators of energy availability (e.g. TEE, lean and fat mass, BMC). Testing for sport-derived stress and disordered eating attitudes is also recommended. Preventive strategy should involve the proactive engagement of sport clubs and periodic competitive sport medical assessment.

Impact of Prolonged Pregnancy on Mode of Delivery and Fetal Outcome

Background: The “term pregnancy” is defined as the pregnancy that ends between 259 and 294 days (37-42 weeks) of pregnancy from the 1st day of last menstrual period. If the pregnancy continues beyond this mentioned period, it is called prolonged pregnancy. Post-term Pregnancy is one of the commonest obstetric conditions which associated with an increased risk of fetal and neonatal mortality and morbidity as well as an increased maternal morbidity.Objectives: The aim of this study is to determine the frequency of mode of delivery and fetal outcomes in prolonged pregnancy.Material and Methods: It is a Descriptive cross sectional study, conducted from 28th Aug, 2019 to 28thFeb, 2020 at Department of Obs &amp; Gynae, MTI-HMC Peshawar. Sample size was 125 keeping 11% proportion of patients having poor apgar score with 95% confidence interval, 5% level of significance.5% margin of error. Sample collection was accomplished by non-probability, consecutive sampling technique. All patients between 18-40 years of age with 42 weeks of gestation or more by dates or dating scan admitted to Gynae Ward/Labour room, having regular cycles were included in the study.Results: As per descriptive statistics, mean and SDs for age was 25±4.90. Mean and SDs for gravidity was recorded as 2±0.58. Mean and SDs for parity was 2±0.58. Mean and SDs for Apgar score was recorded as 8±0.89. 28 (22.4%) patients were obese. In this study 14 (11.2%) neonates had poor apgar score. Normal vaginal delivery 66(52.8%) was the Frequent mode of delivery followed by assisted vaginal deliveries 48(38.4%) and Caesarean section11(8.8%).Conclusion: In this study, we have concluded that pregnancy should not be allowed to go post-term due to association of higher neonatal morbidity and mortality rate, and should be managed before 42 weeks of gestation.Keywords: Fetal outcome, Post term pregnancy, Poor Apgar Score

Dehydroepiandrosterone with a high-fat diet treatment at inducing polycystic ovary syndrome in rat model

ObjectiveThis study aimed to evaluate the effects of dehydroepiandrosterone (DHEA) and DHEA combined with a high-fat diet (HFD) treatment of reproductive and endocrine metabolism in rats and then identify an ideal model of polycystic ovary syndrome (PCOS). MethodsThree-week-old female Sprague–Dawley rats were injected subcutaneously with DHEA or oil, fed with or without a HFD, for 21 days, during which body weight, feed intake, and estrous cycle monitoring were carried out. Fasting blood glucose was measured, and serum fasting insulin, testosterone, dihydrotestosterone (DHT), estradiol, progesterone, luteinizing hormone (LH), anti-Müllerian hormone (AMH), and follicle-stimulating hormone (FSH) were estimated by ELISA. Serum total cholesterol (TC), total triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured by colorimetric assay. Whereas, histologic changes in rat ovaries were evaluated by H&E staining. Ovarian steroid hormone synthases and their protein levels (StAR, 3β-HSD2, 17β-HSD1, CYP11A1, CYP17A1, and CYP19A1) were examined by Western blotting. ResultsBoth DHEA and DHEA + HFD-treated rats lost a regular estrous cycle; had polycystic ovarian changes, significantly higher serum fasting insulin and testosterone levels; and increased ovarian StAR, 3β-HSD2, and CYP11A1 protein levels. Additionally, rats in the DHEA + HFD-treated group were obese; had elevated fasting blood glucose, TG, DHT, AMH levels and LH:FSH ratios; increased ovarian 17β-HSD1 protein levels. ConclusionDHEA combined with HFD treatment is more effective at inducing PCOS than DHEA alone. The reproductive and endocrine metabolic aspects of this method are more consistent with the clinical characteristics of PCOS patients.

Follicle stimulating hormone receptor: impact of genetic variations and gene expression levels in fertility

To date, Assisted Reproductive Technologies (ARTs) increase the probability of conception starting from the collection of more than a single oocyte produced in a regular ovulatory cycle. To achieve this aim many ovarian stimulation protocols have been proposed, some with very good performances but also with some important side effects and, more important, with not many possibilities to personalize the hormonal treatment according to patients characteristics. Although the hormonal and clinical parameters remain the only proven factors to aid in the selection of the best possible hormone stimulation for each patient, none of the commonly used markers has an optimal predictive value if considered individually. Therefore, a complementary strategy that is emerging in recent years is pharmacogenetics. The candidate genes to date are follicle hormone (FSH) and its receptor (FSHR), in which single nucleotide polymorphisms (SNPs) are able to modulate the expression and functions of the genes. The FSH-FSHR complex initiates a cascade of molecular events in the gonads, from the increase of cyclic AMP (cAMP) to the transduction of enzyme-encoding mRNA products, which modulate the synthesis of steroid hormones. In this way, FSH stimulates folliculogenesis and steroidogenesis in the ovary and testicular development and spermatogenesis in the testis. The administration of FSH in the treatment of infertility, in both sexes, aims to induce these activities in order to allow infertile couples to carry out the pregnancy. Many studies on the genetic polymorphisms of FSH and its receptor identified which of these variants could be considered as a marker able to predict the individual responses of patients undergoing ovarian stimulation. KEY WORDS: Clinical embryology, FSH, Polymorphism, Ovarian functions.

Repeated-dose toxicity and toxicokinetic study of isobutylparaben in rats subcutaneously treated for 13weeks.

Parabens have historically served as antimicrobial preservatives in a range of consumables such as food, beverages, medications, and personal care products due to their broad-spectrum antibacterial and antifungal properties. Traditionally, these compounds were believed to exhibit low toxicity, causing minimal irritation, and possessing limited sensitization potential. However, recent evidence suggests that parabens might function as endocrine-disrupting chemicals (EDCs). Consequently, extensive research is underway to elucidate potential human health implications arising from exposure to these substances. Among these parabens, particular concerns have been raised regarding the potential adverse effects of iso-butylparaben (IBP). Studies have specifically highlighted its potential for inducing hormonal disruption, significant ocular damage, and allergic skin reactions. This study aimed to evaluate the prolonged systemic toxicity, semen quality, and estrus cycle in relation to endocrine disruption endpoints, alongside assessing the toxicokinetic behavior of IBP in Sprague-Dawley rats following a 13-week repeated subcutaneous administration. The rats were administered either the vehicle (4% Tween 80) or IBP at dosage levels of 2, 10, and 50mg/kg/day for 13weeks. Blood collection for toxicokinetic study was conducted on three specified days: day 1 (1st), day 30 (2nd), and day 91 (3rd). Systemic toxicity assessment and potential endocrine effects were based on various parameters including mortality rates, clinical signs, body weights, food and water consumption, ophthalmological findings, urinalysis, hematological and clinical biochemistry tests, organ weights, necropsy and histopathological findings, estrus cycle regularity, semen quality, and toxicokinetic behavior. The findings revealed that IBP induced local irritation at the injection site in males at doses ≥ 10mg/kg/day and in females at 50mg/kg/day; however, systemic toxicity was not observed. Consequently, the no-observed-adverse-effect level (NOAEL) for IBP was determined to be 50mg/kg/day in rats of both sexes, indicating no impact on the endocrine system. The toxicokinetics of IBP exhibited dose-dependent systemic exposure, reaching a maximum dose of 50mg/kg/day, and repeated administration over 13weeks showed no signs of accumulation.

Evaluation of wheat (Triticum aestivium L) diet on reproductive functions of adult female rats

Introduction: The relationships between wheat diet, sex hormone and the estrous cycle are important from the perspective of fertility. Aim: This study aims to investigate the effect of wheat diet on weight, estrous cycle, reproductive hormones and histology of the ovary of female Sprague-Dawley rats. Methods: Prior to the test, vaginal smear was monitored daily for 16 days period to select females with normal (regular) estrous cycle. A total of twenty rats with regular estrous cycle weighing between 170-200 g were randomized into four sets of 5 animals each. Group A is the female control and was fed with rat chow, group B, C and D was given 40%, 60%, 100% of wheat diet respectively. The wheat diet was giving respectively for a period of 4 weeks. Estrous cycle pattern was monitored using the vaginal smear for 16 days. At the end of the experiment, the rats were sacrificed and the blood sample were taken for follicle stimulating hormone, luteinizing hormones, estradiol, and progesterone analysis. The histology of the ovary were carried out. Results: The result showed that there was an increase in the weight of the rats that was fed with wheat and the increase was diet dependent. The wheat diets disrupt the order of appearance of normal estrous cycle stages, hence; there was no constancy in the frequency of all cycle stages in the wheat groups, mostly the 100% wheat group. No significant endocrine or histological differences noticed between control and wheat diets groups. Therefore photomicrograph of wheat diet shows large corpus luteum, thick germinal epithelium, zona granulosa and oocyte. Conclusion: Wheat diets disrupt the estrous cycle of the rats; however no adverse effect was noticed on the circulating reproductive hormones and histology of the ovary. However, high consumption of wheat should be taken with precaution.

Testing the Adaptive Sterilization Hypothesis in mice inoculated with Chlamydia muridarum.

The "adaptive sterilization hypothesis" argues that the tendency of sexually transmitted infections (STIs) to cause infertility likely reflects an evolutionary adaptation of these pathogens. For example, some STIs can lead to bilateral occlusions of the oviducts and sterile matings. Cycling females that do not spend time gestating and lactating are ready to mate sooner than fertile females, and therefore, likely to mate more frequently and possibly more promiscuously. These sexual activities are associated with enhanced transmissibility of STIs, and tubal occlusion is a proximate mechanism by which STIs can increase fitness. Our principal objectives were to determine whether female mice inoculated with Chlamydia muridarum mate more frequently than mice inoculated with sterile saline and to test the hypothesis that tubal occlusion following C. muridarum infection modulates mating behavior in a manner that might increase transmissibility of Chlamydia. Similar to C. trachomatis infections in human females, C. muridarum can ascend the reproductive tract of mice, damage and occlude the oviducts, and cause infertility. However, ovarian function and mating activity are maintained following tubal occlusion. Twenty C57Bl/6 mice with regular estrous cycles were given intra-vaginal inocula of C. muridarum and 32 days later paired with a male for 90 days. Nine saline-treated females served as controls. Three Chlamydia-inoculated females were rendered infertile due to bilateral oviductal damage and mated 8 (±0.0) times. Control females mated on average 4.6 (±0.3) times, and 17 Chlamydia-inoculated fertile females, including six females with only a single oviduct occluded, mated on average 4.7 (±0.2) times. Chlamydia-inoculated fertile females with unilateral oviductal damage had significantly smaller average litter sizes as compared to females inoculated with saline. Females with unilateral tubal occlusion also tended to wean fewer pups than saline controls over the course of 90 days. Female mice with Chlamydia-induced tubal infertility mated more frequently (approximately every 11 d) than did fertile females (approximately every 20 d), which is consistent with the adaptive sterilization hypothesis. To determine whether Chlamydia-induced sterilization is truly adaptive, future studies will need to demonstrate increased sexual transmissibility, and possibly increased promiscuity, within populations of freely breeding mice.

Melatonin modulates lipopolysaccharides-induced inflammatory response and maintains circadian rhythm associated with histone H3 acetylation in bovine mammary epithelial cells

Lipopolysaccharides (LPS) can disrupt the barrier function of mammary epithelial cells, leading to mastitis. The protective effects of melatonin (MT) have been demonstrated against various infections, but the underlying mechanism remains unclear in LPS-induced bovine mastitis. This study, therefore, aimed to investigate the modulatory effect of melatonin (MT) on LPS-induced inflammation in bovine mammary epithelial cells (BMECs), its influence on the disruption of circadian rhythms triggered by this inflammation, and the potential underlying molecular mechanisms. BMECs extracted from lactating cows underwent one of 4 treatments in triplicates for 12 h simultaneously: Control (CON), LPS (exposed to LPS at 1 μg/mL), MT (exposed to MT at 40 μmol/L), or LPS + MT (LMT, exposed to both LPS at 1 μg/mL and MT at 40 μmol/L). The flow cytometry results demonstrated that MT reduced the ratios of cells in the G0/G1 phase but increased those in the G2/M phase (P < 0.05). Additionally, MT inhibited p65 phosphorylation levels, leading to a decreased cellular inflammatory response (P < 0.05). Treatment with MT elevated the acetylation levels of histone H3 in BMECs compared to the LPS treatment (P < 0.05). The circadian rhythm analysis revealed a significant increase in the gene expression levels of BMAL1, PER1, CRY1, and CRY2 at the 12 h mark in LMT compared to the LPS treatment (P < 0.05). Additionally, this study assessed the fluctuations in clock-related genes PER2 and CLOCK over 24 h under various treatment conditions. The results demonstrated that BMECs exposed to LMT treatment exhibited a significant increase in the expression levels of CLOCK and PER2 genes from 4 to 24 h in comparison to the LPS treatment (P < 0.05). Moreover, cells in the LMT treatment displayed a more regular circadian rhythm cycle compared to those in the LPS treatment. Overall, the data suggest that MT could alleviate the inflammatory response in BMECs by upregulating histone H3 acetylation, thereby maintaining the physiological circadian rhythm of BMECs.

Emergency contraception for individuals weighing 80 kg or greater: A randomized trial of 30 mg ulipristal acetate and 1.5 mg or 3.0 mg levonorgestrel

ObjectiveTo compare the efficacy of oral emergency contraception (EC) regimens used within 72 hours of unprotected intercourse in individuals weighing >80 kg. Study DesignWe enrolled healthy women aged 18-40 years with a weight of at least 80 kg requesting EC in a multi-center, single-blind, randomized study of levonorgestrel 1.5 mg (LNG1X) and 3.0 mg (LNG2X) and ulipristal acetate 30 mg (UPA) (enrollment goal 1200). Key eligibility requirements included regular cycles, unprotected intercourse within 72 hours of enrollment, no use of hormonal contraception since last menstrual period, a negative urine pregnancy test (UPT), and willingness to abstain from intercourse until next menses. Study staff directly observed EC ingestion. To assess our primary outcome of incidence of pregnancy, participants completed home UPTs; if no menses by 2-weeks post-treatment, or a positive UPT, they returned for an in person visit with quantitative serum human chorionic gonadotropin (hCG) and ultrasound. ResultsWe enrolled and randomized 532; 44 were not dosed or not evaluable for primary end-point, leaving an analyzable sample of 488 (173 LNG1X, 158 LNG2X, 157 UPA) with similar demographics between groups [mean age 29.6 years (5.74), BMI 37.09 kg/m2 (6.95)]. Five pregnancies occurred during the study (LNG1X n = 1, LNG2X n = 1, UPA n = 3); none occurred during the highest at-risk window relative to estimated day of ovulation (day of ovulation and the 3 days prior). We closed the study prior to achieving our enrollment goal because the low pregnancy rate in all groups established futility based on an interim blinded analysis. ConclusionAlthough slow enrollment limited our study power, we found no differences in pregnancy rates between oral EC regimens among women weighing 80 kg or more. Our results are not able to refute or support differences between the three treatment arms. ImplicationsWomen weighing 80 kg or more experienced no differences in pregnancy rates between oral EC regimens but due to several significant study limitations including sample size and the lack of a study population at high risk of pregnancy, our results are not able to determine if differences in treatment effectiveness exist.

Attributes of Menstruation among Young Physical Therapy Female Students of Karachi

The average age of menarche is between 9 to 14 years of age. Menarche is considered a normal milestone of every female's life. This period is supposed like a special period of every girl's life because in this stage girl is converted to the woman's age. Menarche is the indicator sign of a female that is ready to take part in reproduction activity. Objective:To determine the attributes of menstruation among young physical therapy female students of Karachi. Methods: This cross-sectional study was done among 385 young physical therapy female students in Karachi-Pakistan to reveal the age, duration, symptoms, and length of the menstruation cycle. The duration of the study was between June to November 2023. A non-probability purposive sampling technique was used. The validated questionnaire was used from a previous study done in 2016. Data were analyzed through SPSS version 23.0 software. Results: A total number of 385 young females was included in this study. The mean age of menarche revealed 187 (48.57%) found between 11 to 13 years. The regularity of menses was found in 299 (77.66%)participants. The average days of menstruation flow were about 6 to 8 days in 218 (56.62%) of research participants. The average length of the menstrual cycle was 21 to 35 days in 221 (57.40%) while the most common symptom found in research participants was lower abdominal pain in 187 (48.57%). Conclusions:There were significant differences between the characteristics of every young female related to the pattern, duration, age, regularity, and cycle length of the menstrual cycle.   

Cycling and heart failure: A 2-sample Mendelian randomization.

Heart failure (HF) is a major cause of mortality worldwide. Cycling, an aerobic exercise, is believed to have a more effective rehabilitative impact on patients with heart failure. Previous studies have demonstrated the benefits of exercise in patients with HF. However, a precise causal relationship remains unknown. Two-sample Mendelian randomization (MR) was used to investigate the potential causal relationship between regular cardiac cycling and heart failure (HF) development. Data from the IEU OpenGWAS project, an extensive genetic study involving a diverse group of European males and females was used to determine how choices related to physical activity, such as cycling, impact cardiovascular well-being. To ensure reliability and robustness, the MR-Egger regression, weighted median, and random effects with inverse variance weighting methods were used. The key findings were summarized using odds ratio (OR) and 95% confidence intervals (CI). The MR-Egger, weighted mean, and inverse variance weighted (IVW) estimated superiority ratios were 0.960 (95% CI: 0.909-1.013), 0.985 (95% CI: 0.962-1.009), and 0.982 (95% CI: 0.966-0.998), respectively, indicating a significant association between cycling and a decreased risk of heart failure. These findings suggest that cycling, a form of moderate and easily accessible physical activity, may be a protective factor against HF. These findings correlate with those of previous studies regarding the crucial role of regular physical activity for the prevention and management of cardiovascular disease. The outcomes of this MR analysis can be used in the development of public health policies and aid individuals making lifestyle choices that promote heart health.

Altered Grooming Cycles in Transgenic Drosophila.

Head grooming in Drosophila consists of repeated sweeps of the legs across the head, comprising regular cycles. We used the GAL4-UAS system to study the effects of overexpressing shibirets1 and of Adar knockdown via RNA interference, on the period of head-grooming cycles in Drosophila. Overexpressing shibirets1 interferes with synaptic vesicle recycling and thus with cell communication, while Adar knockdown reduces RNA editing of neuronal transcripts for a large number of genes. All transgenic flies and their controls were tested at 22° to avoid temperature effects; in wild type, cycle frequency varied with temperature with a Q10 of 1.3. Two experiments were performed with transgenic shibirets1: (1) each fly was heat-shocked for 10min at 30° immediately before testing at 22° and (2) flies were not heat shocked. In both experiments, cycle period was increased when shibirets1 was overexpressed in all neurons, but was not increased when shibirets1 was overexpressed in motoneurons alone. We hypothesize that grooming cycles in flies overexpressing shibirets1 are lengthened because of synaptic impairment in neural circuits that control head-grooming cycles. In flies with constitutive, pan-neuronal Adar knockdown, cycle period was more variable within individuals, but mean cycle period was not significantly altered. We conclude that RNA editing is essential for the maintenance of within-individual stereotypy of head-grooming cycles.

Assessment of polyethylene wear in dual mobility implant for Asians on various head-to-liner ratios: A finite-element analysis

Based on several references, Asians carry out several daily activities that are different from Westerners, which require a greater range of motion. Because of that, a dual mobility (DM) implant was created that was adapted to the activities of Asian people. One of the factors that might shorten the life of a hip implant is wear. Simulations of wear that are based on computation can guide product design to reduce the amount of adhesive and abrasive wear. Even though advanced modeling approaches have been established, a great deal of wear is still not understood, especially regarding the metal-on-polyethylene articulations found on DM cups. It is critical to examine the wear on the DM cup's head-to-liner ratio to determine the proper head diameter and liner thickness for this DM cup. In this work, wear was analyzed using finite-element analysis and compared between three different femoral head diameters matched with different thicknesses of the polyethylene liner on DM cups. Wear was analyzed throughout the regular walking cycle at each head-to-liner ratio. The findings of this study can be used to develop a dual-mobility artificial hip joint for Asians with the slightest wear.

Unlocking cognitive potential: a comprehensive review of neurocognitive interventions in Down Syndrome

Background: Down Syndrome (DS) poses unique challenges in cognitive functioning, characterized by deficits in language, memory, and executive functions. This review synthesizes current research across educational, behavioral, pharmacological, and physical interventions to enhance cognitive capabilities in individuals with DS. Methods: A comprehensive literature review was conducted, incorporating studies that explored diverse interventions for cognitive enhancement in DS. Educational interventions, behavioral strategies, pharmacological approaches, and physical modalities were systematically analyzed to provide a holistic overview of the current landscape. Objectives: This review aims to consolidate findings from various intervention studies, offering insights into the efficacy of educational, behavioral, pharmacological, and physical approaches in ameliorating cognitive deficits in DS. The diverse range of interventions and their respective outcomes were critically examined to guide future research and intervention strategies. Discussions: Educational interventions, such as language and speech therapy, technology-assisted learning, and working memory training, displayed promising outcomes. Behavioral approaches, including responsive teaching and motor skill-focused interventions, added valuable insights to cognitive enhancement. Pharmacological interventions exhibited varying degrees of success, emphasizing the need for tailored approaches. Physical interventions, particularly regular physical activity and assisted cycle therapy, emerged as potential catalysts for cognitive improvement. This review highlights the multifaceted nature of cognitive deficits in DS and underscores the importance of personalized perspectives in intervention strategies. The discussions provide a comprehensive understanding of the current interventions' effectiveness, contributing to the ongoing discourse on cognitive enhancement in DS. Future research should focus on personalized approaches, considering the heterogeneity in DS phenotypes, to optimize cognitive outcomes for individuals with DS.

Determination of Maximum Tolerable Cold Ischemia Time in a Mouse Model of Cervical Heterotopic Uterus Transplantation.

Uterus transplantation (UTx) is an emerging treatment for uterine factor infertility. Determining the maximum tolerable cold ischemia time is crucial for successful UTx. However, the limit for cold ischemia in the uterus is unclear. This study aimed to examine cold ischemia's effects on mouse uteri and identify the maximum cold ischemia duration that uteri can endure. We systematically assessed the tolerance of mouse uteri to extended cold ischemia, 24 h, 36 h, and 48 h, using the cervical heterotopic UTx model. Multiple indicators were used to evaluate ischemia-reperfusion injury, including reperfusion duration, macroscopic examination, oxidative stress, inflammation, and histopathology. The function of transplants was evaluated through estrous cycle monitoring and embryo transfer. Mouse uteri subjected to 48 h of cold ischemia exhibited significant delays and insufficiencies in reperfusion, substantial tissue necrosis, and loss of the estrous cycle. Conversely, uteri that underwent cold ischemia within 36 h showed long survival, regular estrous cycles, and fertility. Our study demonstrated that mouse uteri can endure at least 36 h of cold ischemia, extending the known limits for cold ischemia and providing a pivotal reference for research on the prevention and treatment of cold ischemic injury in UTx.

Correlation Between Ultrasonographic Placental Thickness and Adverse Fetal and Neonatal Outcomes.

Introduction The placenta is often overlooked in the routine evaluation of normal gestations, receiving attention only when abnormalities are detected. Placental thickness can serve as a good predictor of fetal growth and birth weight, especially in the second trimester.In this prospective study, we measured placental thickness in the second and third trimesters of singleton pregnancies and identified an association between placental thickness and adverse outcomes such as congenital anomalies, fetal growth restriction (FGR), prematurity, low birth weight, stillbirth, and hydrops fetalis. Methodology A total of 298 patients aged 20 to 33 yearswith a singleton pregnancy and regular cycles, who were sure of the date of their last menstrual period, were observed. Placental thickness was measured by ultrasound at 18-20 and 30-32 weeks, and patients were divided into three groups. Group A consisted of patients with normal placental thickness. Group B included patients with a thin placenta (below the 10th percentile). Group C consisted of patients with a thick placenta (above the 95th percentile). The correlation between placental thickness andthe fetal and neonatal outcome was observed. Results Out of 298 patients, 82 (27.5%) were primigravida and 216 (72.4%) were multigravida. At 18-20 weeks, premature birth was observed in one patient (7.69%) in Group C and six patients (20%) in Group B, compared with eight patients (3.14%) in Group A. At 30-32 weeks, premature birth was seen in two patients (16.67%) in Group C and 11 patients (36.67%) in Group B, compared with two patients (0.78%) in Group A. At 18-20 weeks of gestation, low birth weight was observed for three patients (23.08%) in Group C and 16 patients (53.33%) in Group B, compared with 15 patients (5.88%) in Group A. At 30-32 weeks, low birth weight was observed for four patients (33.33%) in Group C and 19 patients (63.33%) in Group B compared with 11 patients (4.30%) in Group A. A significant association was found between a thin placenta and low birth weight and prematurity at both 18-20 and 30-32 weeks of gestation. Two patients (13.33%) had major congenital abnormalities and a thick placenta at 18-20 weeks. In Group C, hydrops were observed in two patients (15.38%) at 18-20 weeks and two patients (16.67%) at 30-32 weeks. A significant association was found between a thick placenta and hydrops. At 30-32 weeks, 13 patients (43.33%) in Group B had developed FGR compared with six patients (2.34%) with a normal placenta. A significant association was found between a thin placenta and FGR. One patient (7.69%) with a thick placenta had a stillbirth, indicating a nonsignificant association. Conclusions A positive correlation was observed between congenital anomalies and hydrops and a thick placenta, whereas FGR, preterm labor, prematurity, and low birth weight were associated with a thin placenta. Subnormal placental thickness for a particular gestational age may be the earliest sign of FGR. A sonographically identified abnormal placenta should alert clinicians to the possibility of a compromised perinatal outcome and the need for evaluation and close follow-up.

Liraglutide Improves PCOS Symptoms in Rats by Targeting FDX1.

Polycystic ovary syndrome (PCOS) is a gynecological endocrine disorder characterized by ovulatory disorders, hyperandrogenemia, and polycystic changes in the ovaries. FDX1 is a ferredoxin-reducing protein on human mitochondria that plays an important role in steroid anabolism. Liraglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), has recently emerged as a potential therapeutic agent for PCOS. Recent studies have suggested that FDX1 may be associated with the development of PCOS. This study aims to explore the pivotal role of FDX1 in the amelioration of PCOS through liraglutide intervention. A PCOS rat model was induced via subcutaneous DHEA injections. Following successful model establishment, the rats were treated with liraglutide combined with metformin, or with each drug individually, over a six-week period. After 6 weeks of treatment, we assessed changes in body weight, fasting blood glucose, sex hormone levels, estrous cycle regularity, ovarian morphology, FDX1 expression in ovarian tissue, and ovarian ROS levels. PCOS rats exhibited significant increases in body weight and fasting blood glucose levels, disrupted estrous cycles, and polycystic ovarian morphology. FDX1 expression was notably reduced in the ovarian tissues of PCOS rats. Treatment with liraglutide, both alone and in combination with metformin, led to improvements in body weight, fasting blood glucose, sex hormone balance, estrous cycle regularity, ovarian morphology, and ovarian ROS levels. Notably, FDX1 expression was significantly restored in all treatment groups, with the most substantial increase observed in the liraglutide-treated group. This study suggests that FDX1 could serve as a potential biomarker for elucidating the underlying mechanisms of liraglutide's therapeutic effects in PCOS management.

Multiple treatments with human embryonic stem cell-derived mesenchymal progenitor cells preserved the fertility and ovarian function of perimenopausal mice undergoing natural aging

ObjectivesCurrently, no approved stem cell-based therapies for preserving ovarian function during aging. To solve this problem, we developed a long-term treatment for human embryonic stem cell-derived mesenchymal progenitor cells (hESC-MPCs). We investigated whether the cells retained their ability to resist ovarian aging, which leads to delayed reproductive senescence.Materials and methodsIn a middle-aged female model undergoing natural aging, we analyzed whether hESC-MPCs benefit the long-term maintenance of reproductive fecundity and ovarian reservoirs and how their transplantation regulates ovarian function.ResultsThe number of primordial follicles and mice with regular estrous cycles were increased in perimenopausal mice who underwent multiple introductions of hESC-MPCs compared to age-matched controls. The estradiol levels in the hESC-MPCs group were restored to those in the young and adult groups. Embryonic development and live birth rates were higher in the hESC-MPC group than in the control group, suggesting that hESC-MPCs delayed ovarian senescence. In addition to their direct effects on the ovary, multiple-treatments with hESC-MPCs reduced ovarian fibrosis by downregulating inflammation and fibrosis-related genes via the suppression of myeloid-derived suppressor cells (MDSCs) produced in the bone marrow.ConclusionsMultiple introductions of hESC-MPCs could be a useful approach to prevent female reproductive senescence and that these cells are promising sources for cell therapy to postpone the ovarian aging and retain fecundity in perimenopausal women.