Evaluating the Effectiveness of the Driving Resumption Assessment in Brain Disorders: Insights From a Retrospective Observational Study.

Objectives For patients with brain disorders, regaining the ability to drive is crucial to their reintegration into society. Despite the existence of numerous assessment methods for determining the ability to resume driving, the most effective approach remains unclear. This study evaluated patients with brain disorders who had received support for driving resumption. We examined the factors influencing the acquisition of driving ability in this specific population. Methods This retrospective observational study was conducted from July 2019 to March 2022. Initially, a desk-based assessment was conducted using neuropsychological tests. Successful candidates subsequently underwent an on-road assessment at an affiliated driving school. Patients who passed both assessments were granted permission to resume driving. The participants were categorized into pass and fail groups based on their assessments, and a comparative analysis was conducted. Age, sex, type of brain disorder, functional independence measures (FIMs), assessments of higher cognitive skills, and physical function test results were evaluated. Results Forty-five patients (average age: 62±13 years) underwent evaluation. Logistic regression analysis for the desk-based assessment identified the Rey-Osterrieth complex figure test (ROCFT) (three-minute delayed recall) as the most influential factor (cutoff value: 21.5 points; sensitivity: 65%; specificity, 72.7%). In the on-road assessment, the 10-m walking test was significantly faster in the passing group than in the failing group (p<0.005). Conclusions We demonstrated that the ROCFT (three-minute delayed recall) was the most effective neuropsychological assessment tool for evaluating driving resumption. The assessment of walking speed may also be able to predict the resumption of driving in patients with brain disorders.

Safety and efficacy of restarting immune checkpoint inhibitors in non-small cell lung cancer patients following immune-related adverse events: a systematic review and meta-analysis.

OBJECTIVE: This meta-analysis aims to evaluate the safety and efficacy of restarting immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC) after experiencing immune-related adverse events (irAEs). METHODS: A comprehensive search of PubMed, Web of Science, Embase, and the Cochrane Library was conducted to identify studies investigating the safety and efficacy of restarting ICIs in NSCLC patients after irAEs. Outcome measures, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) after ICI restarting, were extracted. Meta-analysis was performed using the R meta-package. RESULTS: Four studies involving a total of 326 subjects were included, comprising 137 patients who restarted ICI treatment after irAEs and 189 patients who did not restart ICI treatment. The results revealed that ICI restarting was associated with an increased ORR (OR = 2.36, 95% CI 1.49-3.84), prolonged PFS (HR = 0.60, 95% CI 0.42-0.86), and prolonged OS (HR = 0.65, 95% CI 0.43-0.99) compared to non-restarting. The incidence of irAEs after ICI restarting was 45% (95% CI 0.27-0.63). CONCLUSION: Restarting ICI treatment after discontinuation due to previous irAEs appears to be a reasonable option for NSCLC patients. However, a comprehensive assessment of the potential benefits and risks to individual patients is crucial, and close monitoring of irAEs is warranted.

Maternal Postpartum Work Resumption Stress: Questionnaire Development and Validation.

Transitioning back to work after maternity leave is increasingly common. While differences exist, for many mothers this transition represents a stressor. This study aimed to define the construct of maternal postpartum work resumption stress and develop and validate a self-report measure in a low-risk sample of Dutch mothers. First, the item pool (N = 71) and face and content validity of the questionnaire were established. Next, two independent samples of mothers returning to work (N = 298, N = 291) were recruited to identify factor structure, reduce the number of items, and assess the dimensionality, reliability, convergent and discriminant validity of the questionnaire. Based on exploratory and confirmatory factor analyses, the reliable and valid REturn to Work INventory (REWINd) with 30 items across three factors was established. While further validation is needed, REWINd can be used to further study the nature and consequences of maternal postpartum work resumption stress.

Reversal and resumption of anticoagulants in patients with anticoagulant-associated intracerebral hemorrhage.

The use of anticoagulants has become more frequent due to the progressive aging population and increased thromboembolic events. Consequently, the proportion of anticoagulant-associated intracerebral hemorrhage (AAICH) in stroke patients is gradually increasing. Compared with intracerebral hemorrhage (ICH) patients without coagulopathy, patients with AAICH may have larger hematomas, worse prognoses, and higher mortality. Given the need for anticoagulant reversal and resumption, the management of AAICH differs from that of conventional medical or surgical treatments for ICH, and it is more specific. Understanding the pharmacology of anticoagulants and identifying agents that can reverse their effects in the early stages are crucial for treating life-threatening AAICH. When patients transition beyond the acute phase and their vital signs stabilize, it is important to consider resuming anticoagulants at the right time to prevent the occurrence of further thromboembolism. However, the timing and strategy for reversing and resuming anticoagulants are still in a dilemma. Herein, we summarize the important clinical studies, reviews, and related guidelines published in the past few years that focus on the reversal and resumption of anticoagulants in AAICH patients to help implement decisive diagnosis and treatment strategies in the clinical setting.

Resumption of ovulation in anovulatory women with PCOS and obesity is associated with reduction of 11ß-hydroxyandrostenedione concentrations.

STUDY QUESTION: Is resumption of ovulation after a 6-month lifestyle intervention in women with PCOS and obesity associated with differential changes in endocrine and metabolic parameters (weight, insulin resistance, anti-Müllerian hormone (AMH), and androgens) compared to women with PCOS who remained anovulatory? SUMMARY ANSWER: Resumption of ovulation after a 6-month lifestyle intervention in women with PCOS and obesity is associated with changes in serum 11ß-hydroxyandrostenedione (11OHA4) concentrations. WHAT IS KNOWN ALREADY: Lifestyle interventions have been shown to reduce clinical and biochemical hyperandrogenism in women with PCOS. Weight loss of 5-10% may reverse anovulatory status, thereby increasing natural conception rates. However, the mechanisms underlying why some women with PCOS remain anovulatory and others resume ovulation after weight loss are unclear. Reproductive characteristics at baseline and a greater degree of change in endocrine and metabolic features with lifestyle intervention may be crucial for ovulatory response. STUDY DESIGN, SIZE, DURATION: We used data and samples originating from an earlier randomized controlled trial (RCT), which examined the efficacy of a 6-month lifestyle intervention prior to infertility treatment compared to prompt infertility treatment on live birth rate in women with obesity. A total of 577 women with obesity (BMI > 29 kg/m2) were randomized between 2009 and 2012. Anovulatory women with PCOS who were allocated to the intervention arm of the original RCT (n = 95) were included in the current analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: We defined women as having resumed ovulation (RO+) based on the following criteria: spontaneous pregnancy; or assignment to expectant management; or IUI in natural cycles as the treatment strategy after lifestyle intervention. Steroid hormones were measured using liquid chromatography tandem mass spectrometry. Generalized estimating equations with adjustment for baseline measures and interaction between group and time was used to examine differences in changes of endocrine and metabolic parameters between RO+ (n = 34) and persistently anovulatory women (RO-, n = 61) at 3 and 6 months after intervention. MAIN RESULTS AND THE ROLE OF CHANCE: At baseline, the mean ± SD age was 27.5 ± 3.6 years in the RO+ group and 27.9 ± 4.1 years in the RO- group (P = 0.65), and the mean ± SD weights were 101.2 ± 9.5 kg and 105.0 ± 14.6 kg, respectively (P = 0.13). Baseline AMH concentrations showed significant differences between RO+ and RO- women (median and interquartile range [IQR] 4.7 [3.2; 8.3] versus 7.2 [5.3; 10.8] ng/ml, respectively). Baseline androgen concentrations did not differ between the two groups. During and after lifestyle intervention, both groups showed weight loss; changes in 11OHA4 were significantly different between the RO+ and RO groups (P-value for interaction = 0.03). There was a similar trend for SHBG (interaction P-value = 0.07), and DHEA-S (interaction P-value = 0.06), with the most pronounced differences observed in the first 3 months. Other parameters, such as AMH and FAI, decreased over time but with no difference between the groups. LIMITATIONS, REASONS FOR CAUTION: No high-resolution transvaginal ultrasonography was used to confirm ovulatory status at the end of the lifestyle program. The small sample size may limit the robustness of the results. WIDER IMPLICATIONS OF THE FINDINGS: Reduction of androgen concentrations during and after lifestyle intervention is associated with recovery of ovulatory cycles. If our results are confirmed in other studies, androgen concentrations could be monitored during lifestyle intervention to provide individualized recommendations on the timing of resumption of ovulation in anovulatory women with PCOS and obesity. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by a grant from ZonMw, the Dutch Organization for Health Research and Development (50-50110-96-518). The Department of Obstetrics and Gynecology of the UMCG received an unrestricted educational grant from Ferring Pharmaceuticals BV, The Netherlands. A.H. reports consultancy for the development and implementation of a lifestyle App MyFertiCoach developed by Ferring Pharmaceutical Company. All other authors have no conflicts to declare. TRIAL REGISTRATION NUMBER: The LIFEstyle RCT was registered at the Dutch trial registry (NTR 1530).

RE-START: Exploring the effectiveness of anti-calcitonin gene-related peptide resumption after discontinuation in migraine.

BACKGROUND AND PURPOSE: According to the latest European guidelines, discontinuation of monoclonal antibodies against calcitonin gene-related peptide (anti-CGRP MAb) may be considered after 12-18 months of treatment. However, some patients may worsen after discontinuation. In this study, we assessed the response following treatment resumption. METHODS: This was a prospective study conducted in 14 Headache Units in Spain. We included patients with response to anti-CGRP MAb with clinical worsening after withdrawal and resumption of treatment. Numbers of monthly migraine days (MMD) and monthly headache days (MHD) were obtained at four time points: before starting anti-CGRP MAb (T-baseline); last month of first treatment period (T-suspension); month of restart due to worsening (T-worsening); and 3 months after resumption (T-reintroduction). The response rate to resumption was calculated. Possible differences among periods were analysed according to MMD and MHD. RESULTS: A total of 360 patients, 82% women, with a median (interquartile range [IQR]) age at migraine onset of 18 (12) years. The median (IQR) MHD at T-baseline was 20 (13) and MMD was 5 (6); at T-suspension, the median (IQR) MHD was 5 (6) and MMD was 4 (5); at T-worsening, the median (IQR) MHD was 16 (13) and MMD was 12 (6); and at T-reintroduction, the median (IQR) MHD was 8 (8) and MHD was 5 (5). In the second period of treatment, a 50% response rate was achieved by 57.4% of patients in MHD and 65.8% in MMD. Multivariate models showed significant differences in MHD between the third month after reintroduction and last month before suspension of first treatment period (p < 0.001). CONCLUSION: The results suggest that anti-CGRP MAb therapy is effective after reintroduction. However, 3 months after resumption, one third of the sample reached the same improvement as after the first treatment period.

Granulosa Cells Alone, Without Theca Cells, Can Mediate LH-induced Oocyte Meiotic Resumption.

Signaling in the granulosa cells of mammalian ovarian follicles is necessary for maintaining prophase arrest in the oocyte and for mediating the resumption of meiosis in response to luteinizing hormone (LH). However, the follicle also includes an outer layer of theca cells, some of which express receptors for LH. To investigate whether theca cells are required for maintaining meiotic arrest and reinitiating meiosis in response to LH, we mechanically separated the granulosa cells and oocyte from the theca and basal lamina. This was accomplished by cutting a slit in the outer surface of isolated follicles such that the mural granulosa cells and cumulus-oocyte complex were extruded from the theca shell, forming a lawn of cells on an organotypic membrane. The remnant of theca cells and basal lamina was then removed. The separation of the granulosa cells from the theca cells and basal lamina was demonstrated by immunofluorescence localization of endomucin (blood vessels of the theca) and laminin gamma (basal lamina). Cells comprising these granulosa cell-oocyte complexes expressed LH receptors and were connected by gap junctions. Oocytes within these granulosa cell complexes maintained meiotic arrest and resumed meiosis in response to LH, showing that the granulosa cells alone, without theca cells, transduce these signals. This semi-intact and mostly 2-dimensional preparation could facilitate imaging studies of follicle physiology.

Resuming peritoneal dialysis after secondary embedding of the peritoneal dialysis catheter in the end-of-life period: A case report.

Secondary embedding of a peritoneal dialysis (PD) catheter has been performed for patients whose kidney function has improved enough to stop dialysis but recovery is not expected to be long term. In addition, we have also performed the procedure for patients who have poor general condition due to severe cerebrovascular and/or cardiac disease or who wish to have PD again at the end of life. Here, we report the case of the first terminal haemodialysis (HD) patient who resumed PD using a secondarily embedded catheter as an end-of-life choice. The patient had undergone secondary embedding of a PD catheter and had been transferred to HD, during which time multiple pulmonary metastases of thyroid cancer were observed. She hoped to resume PD in the end-of-life period, and the catheter was subsequently externalised. The catheter was used immediately, and the patient has continued on PD over the past 1 month without infectious or mechanical complications. For elderly end-stage kidney disease patients with progressive disease and cancer, secondary embedding of the PD catheter may be an option to permit them to live the remainder of their lives at home.

Examining the cognitive processes underlying resumption costs in task-interruption contexts: Decay or inhibition of suspended task goals?

To examine whether an ongoing primary task is inhibited when switching to an interruption task, we implemented the n - 2 backward inhibition paradigm into a task-interruption setting. In two experiments, subjects performed two primary tasks (block-wise manipulation) consisting of a predefined sequence of three subtasks. The primary tasks differed regarding whether the last subtask switched or repeated relative to the penultimate subtask, resulting in n - 1 switch subtasks (e.g., ABC) and n - 1 repetition subtasks (e.g., ACC) as the last subtask of the primary task. Occasionally, an interruption task was introduced before the last subtask of a primary task, changing the last subtask of the primary task from a n - 1 switch subtask to a n - 2 switch subtask (e.g., AB → secondary task → C) and from a n - 1 repetition subtask to a n - 2 repetition subtask (e.g., AC → secondary task → C). In two experiments with different degrees of response-set overlap between the interruption task and the subtasks of the primary task, we observed that switching back from the interruption task to the primary task resulted in n - 2 switch costs in the first subtask after the interruption (i.e., worse performance in n - 2 switch subtasks than in n - 2 repetition subtasks). This n - 2 switch cost was replicated in a third experiment in which we used a predefined sequence of four subtasks instead of three subtasks. Our finding of n - 2 switch costs suggest that the last subtask performed before the interruption remains activated when switching to the interruption task.

Arf1 GTPase Regulates Golgi-Dependent G2/M Transition and Spindle Organization in Oocyte Meiosis.

ADP-ribosylation factor 1 (Arf1) is a small GTPase belonging to the Arf family. As a molecular switch, Arf1 is found to regulate retrograde and intra-Golgi transport, plasma membrane signaling, and organelle function during mitosis. This study aimed to explore the noncanonical roles of Arf1 in cell cycle regulation and cytoskeleton dynamics in meiosis with a mouse oocyte model. Arf1 accumulated in microtubules during oocyte meiosis, and the depletion of Arf1 led to the failure of polar body extrusion. Unlike mitosis, it finds that Arf1 affected Myt1 activity for cyclin B1/CDK1-based G2/M transition, which disturbed oocyte meiotic resumption. Besides, Arf1 modulated GM130 for the dynamic changes in the Golgi apparatus and Rab35-based vesicle transport during meiosis. Moreover, Arf1 is associated with Ran GTPase for TPX2 expression, further regulating the Aurora A-polo-like kinase 1 pathway for meiotic spindle assembly and microtubule stability in oocytes. Further, exogenous Arf1 mRNA supplementation can significantly rescue these defects. In conclusion, results reported the noncanonical functions of Arf1 in G2/M transition and meiotic spindle organization in mouse oocytes.

Exploring return to work for patients with head and neck cancer.

BACKGROUND: The number of survivors of head and neck cancer (HNC) has steadily increased due to major advances in cancer care. However, cancer survivors who experience job loss face different challenges regarding return to work (RTW). Relatively few studies have integrated the experience encountered by patients. OBJECTIVE: This mixed-methods study aimed to explore the experience and challenges of RTW in patients with HNC. METHODS: Data were collected with structured questionnaires (n = 120) and semi-structured face-to-face interviews (n = 12). RESULTS: Relationships were found between patient's physical status, perceived stress, and social support. Patients who continued work, or not, had significant differences in reported physical function and stress. Four themes emerged from the qualitative data, including the perceived meaning of work, challenges for RTW, preparing for RTW, and social support. After diagnosis and treatment, patients perceived the meaning of work, such as personal value, responsibility, and financial need. They faced many challenges to RTW, including declining physical strength, workload, schedule rearrangement, speech difficulty, and changed appearance. In order to RTW, they prepared extensively and needed support from family and friends. CONCLUSION: This study revealed the experiences and challenges of RTW patients with HNC. The results allowed us to identify patients' concerns and ways that healthcare providers could improve the RTW process. Future studies may develop tailored approaches for RTW in healthcare and government policies.

Comparison of Uterine Involution and the Resumption of Ovarian Cyclicity between Lame and Sound Holstein Cows.

The aim of the study was to examine the effect of lameness and energy status on the involution of the uterus and the resumption of ovarian cyclicity in dairy cows. Lame (lameness score of four and the presence of hoof lesions, n = 22) and sound (normal gait and the absence of hoof lesions, n = 25) multiparous cows with healthy puerperium were enrolled simultaneously in the study and were monitored from day 10 antepartum (ap) to day 50 post-partum (pp). Ultrasonography of the cervix, the formerly gravid uterine horn and the ovarian structures was performed on d 8, 11, 14, 23, 30, and 42 pp. Blood sampling for progesterone, ß-hydroxybutyrate (BHBA), and non-esterified fatty acids (NEFAs) was used to assess cyclicity and energy status. Lame compared to sound cows had higher NEFA concentrations on day 14 pp (0.54 ± 0.05 vs. 0.37 ± 0.05, respectively, p = 0.005), delayed involution of the cervix and the formerly pregnant uterine horn (p = 0.0003 and p = 0.02, respectively), lower ovulation rates within the experimental period (63.6% vs. 88%, respectively, p = 0.05), and higher rates of atresia or cyst formation on day 50 pp (36.4% vs. 12%, respectively, p = 0.05). Independently of lameness status, cows with high NEFA concentrations had lower ovulation rates within the experimental period (65.5% vs. 94.4%, p = 0.02), lower normal ovarian activity on day 50 pp (58.6% vs. 88.9%, p = 0.03), and higher rates of atresia or cyst formation on day 50 pp (34.5% vs. 5.6%, p = 0.02) compared to cows with optimal NEFA concentrations. Furthermore, an interaction between lameness and increased NEFA concentrations was observed regarding the ovulation rate within the experimental period and the percentage of atresia or cyst formation on day 50 pp. Sound cows with low NEFA levels had the lowest mean cervical diameter compared to cows with lameness (both with elevated and optimal NEFA concentrations, p = 0.009 and p = 0.002, respectively). Conclusively, lameness during puerperium negatively affected ovarian function and uterine involution. These effects were exacerbated (through interaction or cumulation) in relation to elevated NEFA concentrations.

Functional recovery after cesarean delivery: a prospective cohort study in rural Rwanda.

INTRODUCTION: Women who deliver via cesarean section (c-section) experience short- and long-term disability that may affect their physical health and their ability to function normally. While clinical complications are assessed, postpartum functional outcomes are not well understood from a patient's perspective or well-characterized by previous studies. In Rwanda, 11% of rural women deliver via c-section. This study explores the functional recovery of rural Rwandan women after c-section and assesses factors that predict poor functionality at postoperative day (POD) 30. METHODS: Data were collected prospectively on POD 3, 11, and 30 from women delivering at Kirehe District Hospital between October 2019 and March 2020. Functionality was measured by self-reported overall health, energy level, mobility, self-care ability, and ability to perform usual activities; and each domain was rated on a 4-point likert scale, lower scores reflecting higher level of difficulties. Using the four functionality domains, we computed composite mean scores with a maximum score of 4.0 and we defined poor functionality as composite score of ≤ 2.0. We assessed functionality with descriptive statistics and logistic regression. RESULTS: Of 617 patients, 54.0%, 25.9%, and 26.8% reported poor functional status at POD3, POD11, and POD30, respectively. At POD30, the most self-reported poor functionality dimensions were poor or very poor overall health (48.1%), and inability to perform usual activities (15.6%). In the adjusted model, women whose surgery lasted 30-45 min had higher odds of poor functionality (aOR = 1.85, p = 0.01), as did women who experienced intraoperative complications (aOR = 4.12, 95% CI (1.09, 25.57), p = 0.037). High income patients had incrementally lower significant odds of poor physical functionality (aOR = 0.62 for every US$1 increase in monthly income, 95% CI (0.40, 0.96) p = 0.04). CONCLUSION: We found a high proportion of poor physical functionality 30 days post-c-section in this Rwandan cohort. Surgery lasting > 30 min and intra-operative complications were associated with poor functionality, whereas a reported higher income status was associated with lower odds of poor functionality. Functional status assessments, monitoring and support should be included in post-partum care for women who delivered via c-section. Effective risk mitigating intervention should be implemented to recover functionality after c-section, particularly among low-income women and those undergoing longer surgical procedures or those with intraoperative complications.

L2 acquisition of Wh-interrogatives at the syntax-discourse interface: interface hypothesis again.

This study sets out to answer one major question: do linguistic phenomena relating to syntax-discourse interface constitute difficulty for Yemeni learners of English? It presents data from an experiment on the acquisition of L2 English wh-interrogatives by L1 Yemeni Arabic speakers, aiming to provide empirical evidence either in support of the Interface Hypothesis (IH) or against it. Two learner groups, intermediate and advanced, were recruited as participants of the study, and a native speaker group of (British) English was also recruited as the control group. The advanced group learners have a near-native proficiency in English. The data utilized consisted of 20 (D-)iscourse linked and non-d-linked wh-interrogatives presented to the three groups in the form of a (decontextualized) bi-modal multiple-choice paced judgement task. Results showed that both learner groups, specifically the advanced learners, performed near-native like in the non-d-linked, but far short of near/native-like performance in the d-linked wh-interrogatives. The study concluded that L2 learners' English is still vulnerable at the syntax-discourse interface, hence supporting the IH.

Policy instruments facilitate China's COVID-19 work resumption.

Governments worldwide have announced stimulus packages to remobilize the labor force after COVID-19 and therefore to cope with the COVID-19-related recession. However, it is still unclear how to facilitate large-scale work resumption. This paper aims to clarify the issue by analyzing the large-scale prefecture-level dataset of human mobility trajectory information for 320 million workers and about 500,000 policy documents in China. We model work resumption as a collective behavioral change due to configurations of capacity, motivation, and policy instruments by using qualitative comparative analysis. We find that the effectiveness of post-COVID-19 recovery stimulus varied across China depending on the fiscal and administrative capacity and the policy motivation of the prefecture. Subnational fiscal and procurement policies were more effective for the wholesale and retail sector and the hotel and catering sector, whereas the manufacturing and business services sectors required more effort regarding employment policies. Due to limited prefectural capacity and wavering policy motivation, the simultaneous adoption of fiscal, employment, and procurement policy interventions endangered post-COVID-19 work resumption. We highlight the necessity of tailored postcrisis recovery strategies based on local fiscal and administrative capacity and the sectoral structure.

Spontaneous Sinus Rhythm Restoration in Patients With Refractory, Permanent Atrial Fibrillation Who Underwent Conduction System Pacing and Atrioventricular Junction Ablation.

Ablate and pace (A&P) with conduction system pacing (CSP) improves outcomes in patients with symptomatic permanent atrial fibrillation (AF). Data on spontaneous sinus rhythm restoration (SSRR) in this setting are lacking. This study aimed to assess the incidence and the predictors of SSRR in a population of patients with permanent AF who underwent A&P with CSP. Prospective, observational study, enrolling consecutive patients with symptomatic permanent AF (of documented duration >6 months) and uncontrolled, drug-refractory high ventricular rate, who underwent A&P with CSP. The incidence and predictors of SSRR were prospectively assessed. A total of 107 patients (79.0 ± 9.1 years, 33.6% male, 74.8% with New York Heart Association class ≥III, 56.1% with ejection fraction <40%) were enrolled: 40 received His' bundle pacing, 67 left bundle branch area pacing. During a median follow-up of 12 months SSRR was observed in 14 patients (13.1%), occurring a median of 3 months after A&P (interquartile range 1 to 6; range 0 to 17). Multivariable analysis identified a duration of permanent AF <12 months (hazard ratio 7.7, p = 0.040) and a left atrial volume index <49 ml/m2 (hazard ratio 14.8, p = 0.008) as independent predictors of SSRR. In patients with coexistence of both predictors the incidence of SSRR was of 41.4%. In a population of patients with symptomatic, permanent AF, treated with A&P with CSP, SSRR was observed in 13% of patients during follow-up. A duration of permanent AF <12 months and a left atrial volume index <49 ml/m2 were independent predictors of this phenomenon.

The molecular regulatory mechanisms of meiotic arrest and resumption in Oocyte development and maturation.

In human female primordial germ cells, the transition from mitosis to meiosis begins from the fetal stage. In germ cells, meiosis is arrested at the diplotene stage of prophase in meiosis I (MI) after synapsis and recombination of homologous chromosomes, which cannot be segregated. Within the follicle, the maintenance of oocyte meiotic arrest is primarily attributed to high cytoplasmic concentrations of cyclic adenosine monophosphate (cAMP). Depending on the specific species, oocytes can remain arrested for extended periods of time, ranging from months to even years. During estrus phase in animals or the menstrual cycle in humans, the resumption of meiosis occurs in certain oocytes due to a surge of luteinizing hormone (LH) levels. Any factor interfering with this process may lead to impaired oocyte maturation, which in turn affects female reproductive function. Nevertheless, the precise molecular mechanisms underlying this phenomenon has not been systematically summarized yet. To provide a comprehensive understanding of the recently uncovered regulatory network involved in oocyte development and maturation, the progress of the cellular and molecular mechanisms of oocyte nuclear maturation including meiosis arrest and meiosis resumption is summarized. Additionally, the advancements in understanding the molecular cytoplasmic events occurring in oocytes, such as maternal mRNA degradation, posttranslational regulation, and organelle distribution associated with the quality of oocyte maturation, are reviewed. Therefore, understanding the pathways regulating oocyte meiotic arrest and resumption will provide detailed insight into female reproductive system and provide a theoretical basis for further research and potential approaches for novel disease treatments.

Long-term Discontinuation of Dopamine Agonist Treatment in Patients with Prolactinomas Revisited.

The most common type of functioning pituitary adenomas is prolactinomas; unlike other types, they are treated medically with dopamine agonists (DA). This treatment aims to normalize PRL levels and decrease tumor size by 50% or more. These objectives are typically achieved by 90% of patients with microprolactinoma, two-thirds of those with macroprolactinomas, and about half of those with giant prolactinomas. Life-long pharmacological treatment implies costs, discomfort, and the possibility of side effects, therefore, it has been suggested that DA discontinuation could be attempted in some patients. Long-term remission seems more likely in who, after 2 years of therapy achieve clinical, biochemical, and imaging remission criteria: no evidence of hypogonadism, a normal PRL level (preferably <5 ng/mL), and a >50% of tumor size reduction. Long-term remission seems to be more likely if the patient has been treated with cabergoline (CBG) for a minimum of 2 years, the PRL levels have normalized, tumor size has decreased by at least 50%, and the DA dose can gradually be tapered down to 0.25-0.5 mg per week. After treatment withdrawal, about 65% of patients experience a recurrence of hyperprolactinemia within the first 12 months of DA discontinuation. Although in most patients in whom DA discontinuation has been attempted, the hyperprolactinemia will recur, not all of them will require re-initiation of treatment. A good clinical judgement is crucial to identify those patients who need life-long treatment.

Resumption of oral anticoagulation in patients with non-valvular atrial fibrillation after intracerebral hemorrhage: A sub-analysis of the PASTA registry study.

PURPOSE: To investigate the rate and timing of oral anticoagulant (OAC) resumption and its safety in patients after intracerebral hemorrhage (ICH) in current clinical practice in Japan. METHODS: We conducted a sub-analysis of the PASTA registry, an observational, multicenter registry of 1043 patients with stroke receiving OACs in Japan, by including patients with ICH on OAC treatment for non-valvular atrial fibrillation (NVAF). The clinical characteristics of the patients in the resumption and non-resumption groups, rate and timing of OAC resumption, its safety, and switching of OACs after ICH were investigated. RESULTS: Of the 160 patients (women, n = 52; median age, 77 years) included, OACs were resumed in 108 (68%) at a median of 7 days (interquartile range, 4-11) after acute ICH onset. The non-resumption group had higher rates of hematoma expansion (21.2% vs. 7.4%; P = 0.0118) and modified Rankin Scale (mRS) scores at discharge (4 (Suda et al., 2019; Steiner et al., 2014 [3, 4]) vs. 4 (Suda et al., 2019; Steiner et al., 2014; Pasquini et al., 2014 [3-5]); P = 0.0302}. The resumption rate in the mRS 0-4 group was higher than that in the mRS 5 group (75.2% vs. 46.5%; P = 0.00006). The number of days to resumption after ICH onset was longer in the mRS 5 than that in the mRS 0-4 group (median 12 days vs. 7 days, P = 0.0065). There were no significant differences in new-onset ICH, symptomatic hematoma expansion, or gastrointestinal bleeding between groups (P > 0.05). CONCLUSIONS: Early resumption of OAC for NVAF in patients after ICH appeared to be safe. Expected functional outcomes at discharge were associated with OAC resumption and with the timing of resumption. REGISTRATION: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034958.

Effects of cyclic adenosine monophosphate modulating agents during oocyte pre-maturation and the role of melatonin on in vitro maturation of bovine cumulus-oocyte complexes.

This study investigated the effects of cyclic adenosine monophosphate modulating during cumulus-oocyte complexes (COCs) pre-maturation and the role of melatonin on in vitro maturation (IVM) of bovine COCs. In experiment one, COCs were pre-matured for 8 h in control medium or with 3-isobutyl-1-methylxanthine (IBMX) and forskolin, IBMX and C-type natriuretic peptide, c-type natriuretic peptide and forskolin or IBMX, forskolin and c-type natriuretic peptide. Then, meiotic progression was evaluated. In experiment two, COCs were pre-matured, followed by IVM in control medium alone or with 10-6, 10-7 or 10-8 M melatonin. After IVM, chromatin configuration, transzonal projections (TZPs), reactive oxygen species, mitochondrial distribution, ultrastructure and mRNA expression for antioxidant enzymes were evaluated. In experiment 1, COCs pre-matured with both C-type natriuretic peptide and forskolin or C-type natriuretic peptide, forskolin and IBMX had lower meiotic resumption rate when compared to control. Considering that IBMX had not an additional effect to potentiate inhibition of meiotic resumption, a combination of C-type natriuretic peptide and forskolin was chosen. In experiment 2, COCs matured with 10-8 M melatonin had greater rates of meiotic resumption when compared to the other treatments (P < 0.05). The COCs matured with 10-7 or 10-8 M melatonin had greater mitochondrial activity (P < 0.05), while those matured with 10-6 or 10-8 M of melatonin had greater levels of TZPs. Ultrastructure of oocyte and cumulus cells after IVM with melatonin was relatively well preserved. COCs matured with 10-8 M melatonin increased mRNA expression for superoxide dismutase (SOD) and catalase (CAT) (P < 0.05), when compared to non-cultured and pre-matured COCs, respectively. In conclusion, bovine COC pre-maturation with C-type natriuretic peptide and forskolin, followed by IVM with 10-8 M melatonin improves meiotic resumption rates, TZPs, mitochondrial distribution and mRNA expression for SOD and CAT.