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Background: Currently, there is no consensus on the optimal management of women with low prognosis in ART. In this Delphi consensus, a panel of international experts provided real-world clinical perspectives on a series of literature-supported consensus statements regarding the overall relevance of the POSEIDON criteria for women with low prognosis in ART. Methods: Using a Delphi-consensus framework, twelve experts plus two Scientific Coordinators discussed and amended statements and supporting references proposed by the Scientific Coordinators (Round 1). Statements were distributed via an online survey to an extended panel of 53 experts, of whom 36 who voted anonymously on their level of agreement or disagreement with each statement using a six-point Likert-type scale (1 = Absolutely agree; 2 = More than agree; 3 = Agree; 4 = Disagree; 5 = More than disagree; 6 = Absolutely disagree) (Round 2). Consensus was reached if > 66% of participants agreed or disagreed. Results: The extended panel voted on seventeen statements and subcategorized them according to relevance. All but one statement reached consensus during the first round; the remaining statement reached consensus after rewording. Statements were categorized according to impact, low-prognosis validation, outcomes and patient management. The POSEIDON criteria are timely and clinically sound. The preferred success measure is cumulative live birth and key management strategies include the use of recombinant FSH preparations, supplementation with r-hLH, dose increases and oocyte/embryo accumulation through vitrification. Tools such as the ART Calculator and Follicle-to-Oocyte Index may be considered. Validation data from large, prospective studies in each POSEIDON group are now needed to corroborate existing retrospective data. Conclusions: This Delphi consensus provides an overview of expert opinion on the clinical implications of the POSEIDON criteria for women with low prognosis to ovarian stimulation. [ABSTRACT FROM AUTHOR]

Leucine-rich repeat kinase-2 (LRRK2), a gene mutated in familial and sporadic Parkinson's disease (PD), controls multiple cellular processes important for GLIA physiology. Interestingly, emerging studies report that LRRK2 is highly expressed in oligodendrocyte precursor cells (OPCs) compared to the pathophysiology of other brain cells and oligodendrocytes (OLs) in PD. Altogether, these observations suggest crucial function(s) of LRRK2 in OPCs/Ols, which would be interesting to explore. In this study, we investigated the role of LRRK2 in OLs. We showed that LRRK2 knock-out (KO) OPC cultures displayed defects in the transition of OPCs into OLs, suggesting a role of LRRK2 in OL differentiation. Consistently, we found an alteration of myelin basic protein (MBP) striosomes in LRRK2 KO mouse brains and reduced levels of oligodendrocyte transcription factor 2 (Olig2) and Mbp in olig2:EGFP and mbp:RFP transgenic zebrafish embryos injected with lrrk2 morpholino (MO). Moreover, lrrk2 knock-down zebrafish exhibited a lower amount of nerve growth factor (Ngf) compared to control embryos, which represents a potent regulator of oligodendrogenesis and myelination. Overall, our findings indicate that LRRK2 controls OL differentiation, affecting the number of mature OLs. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases (NDs) are characterized by abnormalities within neurons of the brain or spinal cord that gradually lose function, eventually leading to cell death. Upon examination of affected tissue, pathological changes reveal a loss of synapses, misfolded proteins, and activation of immune cells--all indicative of disease progression--before severe clinical symptoms become apparent. Early detection of NDs is crucial for potentially administering targeted medications that may delay disease advancement. Given their complex pathophysiological features and diverse clinical symptoms, there is a pressing need for sensitive and effective diagnostic methods for NDs. Biomarkers such as microRNAs (miRNAs) have been identified as potential tools for detecting these diseases. We explore the pivotal role of miRNAs in the context of NDs, focusing on Alzheimer's disease, Parkinson's disease, multiple sclerosis, Huntington's disease, and Amyotrophic Lateral Sclerosis. The review delves into the intricate relationship between aging and NDs, highlighting structural and functional alterations in the aging brain and their implications for disease development. It elucidates how miRNAs and RNA-binding proteins are implicated in the pathogenesis of NDs and underscores the importance of investigating their expression and function in aging. Significantly, miRNAs exert substantial influence on post-translational modifications (PTMs), impacting not just the nervous system but a wide array of tissues and cell types as well. Specific miRNAs have been found to target proteins involved in ubiquitination or de-ubiquitination processes, which play a significant role in regulating protein function and stability. We discuss the link between miRNA, PTM, and NDs. Additionally, the review discusses the significance of miRNAs as biomarkers for early disease detection, offering insights into diagnostic strategies. [ABSTRACT FROM AUTHOR]

Background: The DuoStim protocol has been proposed as an alternative to conventional single and double stimulation cycles in the treatment of infertility. However, its efficacy in improving pregnancy outcomes remains uncertain., Objective: To systematically evaluate the impact of the DuoStim protocol on pregnancy outcomes in infertile patients by comparing it with single and double conventional stimulation cycles., Methods: An online systematic search was conducted using PubMed, Cochrane Library, and EMBASE databases, covering the period from their inception to March 2024. Randomized controlled trials (RCTs) comparing the DuoStim protocol with single and double conventional stimulation cycles in infertile patients were identified. Data were extracted by two independent investigators who screened the literature and assessed the quality of the studies. Meta-analysis was performed using RevMan 5.4 software., Results: A total of six RCTs involving 414 infertile patients were included. The DuoStim protocol significantly increased the total number of oocytes compared to single and double conventional stimulation (MD =  - 1.47; 95% CI, - 2.12 to - 0.82; P < 0.00001). There were no statistically significant differences in the number of MII oocytes, total embryos, pregnancy rate, and live birth rate. Subgroup Analysis: compared to single stimulation, the DuoStim protocol significantly increased the number of MII oocytes (MD = 1.71; 95% CI, 0.77 to 2.66; P = 0.0004) and total embryos (MD = 1.34; 95% CI, 0.61 to 2.08; P = 0.0003). There were no significant differences in pregnancy rate and live birth rate. Secondary outcomes showed the effect of the DuoStim protocol in patients undergoing preimplantation genetic testing for aneuploidies (PGT-A). The time to obtain euploid blastocysts was significantly reduced in the DuoStim group compared to the control group (23.3 ± 2.8 days vs. 44.1 ± 2.0 days; P < 0.001)., Conclusions: The DuoStim protocol shows a significant advantage in increasing the total number of oocytes, MII oocytes, and embryos compared to single stimulation. However, it does not significantly improve pregnancy and live birth rates. The protocol also shortens the time to obtain euploid blastocysts in patients undergoing PGT-A, indicating potential benefits for specific patient groups. Further research is needed to confirm these findings and evaluate long-term outcomes. Thus, the quality of evidence should be considered moderate, warranting cautious interpretation of the results., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: This study is to evaluate the effectiveness of a PPOS protocol in poor prognosis patients undergoing IVF with DuoStim and PGT-A versus the conventional protocol with GnRH antagonist., Methods: Retrospective cohort study encompassing 444 couples obtained matching one PPOS-DuoStim with two antagonist-DuoStim cycles at a private IVF center between 2020 and 2023 (average maternal age: 40 years, average cumulus-oocyte complexes collected after the first stimulation: 5). The study was powered to exclude a two-sided different euploid blastocyst rate per MII oocytes (EBR per MII) in the two groups (alpha = 0.05, power = 0.9, effect size = 0.3). All cycles involved ICSI, blastocyst stage PGT-A, and single vitrified-warmed euploid transfers. We compared all embryological and clinical outcomes within each group (first vs. second stimulations), and among the two study arms (first stimulation vs. first stimulation; second stimulations vs. second stimulation; overall). The overall EBR per MII was the primary study outcome. The cumulative-live-birth-rate per concluded cycles (CLBR) was the main secondary outcome., Results: In the second stimulations, we obtained a greater number of COCs and MIIs in both antagonist- and PPOS-DuoStim groups. No difference was observed for all embryological and clinical outcomes when comparing the two stimulations within each group. All embryological and clinical outcomes were comparable also between the two groups, including the EBR per MII. To date, 285 and 121 antagonist- and PPOS-DuoStim cycles were concluded. The CLBR was comparable between the groups: 26% vs. 29%., Conclusions: PPOS-DuoStim holds potential for being an efficient, patient-friendly, and possibly cost-effective approach that does not compromise treatment efficacy. Future investigations must explore PPOS effect on follicular recruitment, neonatal, and long-term outcomes., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: It is difficult to obtain healthy oocytes in poor ovarian responders with conventional treatment methods. Thus, the need to investigate new methods is essential. This study aims to investigate ovulation induction outcomes in patients with decreased ovarian reserve (DOR) in two groups treated with double stimulation (DuoStim) during the follicular and luteal phases in comparison with the antagonist cycle. Materials and Methods: This was a randomised clinical trial that enrolled the patients with reduced ovarian reserve. The patients referred for in vitro fertilization (IVF) at Molud Infertility Clinic, Ali Ebn Abitalib (AS) Hospital, Zahedan, Iran from 2020 to 2021. Participants were randomly divided into two groups, those who underwent treatment with DuoStim during the follicular and luteal phase (case group) and those who received the conventional antagonist cycle (control group). Results: The mean number of metaphase II (MII) eggs was 7.7 ± 3.1 in the case group and 6.1 ± 3.9 in the control group (P=0.063). The mean total number of retrieved eggs in the case group was 9.2 ± 3.7 and in the control group, it was 6.9 ± 4.4 (P=0.023). The mean number of embryos obtained in the case group was 6.5 ± 3.9; in the control group, it was 4.7 ± 2.8 (P=0.016). Conclusion: The DuoStim method can effectively play a role in increasing the total number of retrieved eggs and embryos (registration number: IRCT20120817010617N8). [ABSTRACT FROM AUTHOR]

Aim: To explore the diagnostic value of serum-derived exosomal miRNAs and predict the roles of their target genes in Alzheimer's disease (AD) based on the expression of miRNAs in AD patients. Methods: We determined the relative concentration of exosomal miRNAs by High-throughput Second-generation Sequencing and real-time quantitative real-time PCR. Results: 71 AD patients and 71 ND subjects were collected. The study demonstrated that hsa-miR-125b-1-3p, hsa-miR-193a-5p, hsa-miR-378a-3p, hsa-miR-378i and hsa-miR-451a are differentially expressed in the serum-derived exosomes of AD patients compared with healthy subjects. According to ROC analysis, hsa-miR-125b-1-3p has an AUC of 0.765 in the AD group compared to the healthy group with a sensitivity and specificity of 82.1– 67.7%, respectively. Enrichment analysis of its target genes showed that they were related to neuroactive ligand-receptor interactions, the PI3K-Akt signaling pathway, the Hippo signaling pathway and nervous system-related pathways. And, hsa-miR-451a had an AUC of 0.728 that differentiated the AD group from the healthy group with a sensitivity and specificity of 67.9% and 72.6%, respectively. Enrichment analysis of its target genes showed a relationship with cytokine-cytokine receptor interactions and the PI3K-Akt signaling pathway. Conclusion: The dysregulation of serum exosomal microRNAs in patients with AD may promote the diagnosis of AD. The target genes of miRNAs may be involved in the occurrence and development of AD through various pathways. [ABSTRACT FROM AUTHOR]

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There is a growing body of research showing that cerebral pathophysiological processes triggered by pediatric mild traumatic brain injury (pmTBI) may extend beyond the usual clinical recovery timeline. It is paramount to further unravel these processes, because the possible long‐term cognitive effects resulting from ongoing secondary injury in the developing brain are not known. In the current fMRI study, neural processes related to cognitive control were studied in 181 patients with pmTBI at sub‐acute (SA; ~1 week) and early chronic (EC; ~4 months) stages post‐injury. Additionally, a group of 162 age‐ and sex‐matched healthy controls (HC) were recruited at equivalent time points. Proactive (post‐cue) and reactive (post‐probe) cognitive control were examined using a multimodal attention fMRI paradigm for either congruent or incongruent stimuli. To study brain network function, the triple‐network model was used, consisting of the executive and salience networks (collectively known as the cognitive control network), and the default mode network. Additionally, whole‐brain voxel‐wise analyses were performed. Decreased deactivation was found within the default mode network at the EC stage following pmTBI during both proactive and reactive control. Voxel‐wise analyses revealed sub‐acute hypoactivation of a frontal area of the cognitive control network (left pre‐supplementary motor area) during proactive control, with a reversed effect at the EC stage after pmTBI. Similar effects were observed in areas outside of the triple‐network during reactive control. Group differences in activation during proactive control were limited to the visual domain, whereas for reactive control findings were more pronounced during the attendance of auditory stimuli. No significant correlations were present between task‐related activations and (persistent) post‐concussive symptoms. In aggregate, current results show alterations in neural functioning during cognitive control in pmTBI up to 4 months post‐injury, regardless of clinical recovery. We propose that subacute decreases in activity reflect a general state of hypo‐excitability due to the injury, while early chronic hyperactivation represents a compensatory mechanism to prevent default mode interference and to retain cognitive control. [ABSTRACT FROM AUTHOR]

Background: The debate on how to manage women affected by multiple sclerosis (MS) during reproductive age is still open, as is the issue of fertility in such patients. Main issue regard the identification of the optimal window for pregnancy and how to deal with medical therapy before and during conception. The aim of this Delphi consensus was to collect the opinions of a multidisciplinary group, involving reproductive medicine specialists and neurologists with experience in the management of multiple sclerosis women with reproductive desire. Methods: Four experts plus scientific coordinators developed a questionnaire distributed online to 10 neurologists and later discussed the responses and amended a list of statements. The statements were then distributed via an online survey to 23 neurologists (comprising the first 10), who voted on their level of agreement/disagreement with each statement. Consensus was achieved if agreement or disagreement with a statement exceeded 66%. Results: Twenty-one statements reached consensus after two rounds of voting, leading to the following main recommendations: (1) Fertility evaluation should be suggested to wMS, in case of the need to shorten time to pregnancy and before treatment switch in women on DMTs contraindicated in pregnancy, particularly in case of highly active disease and age > 35 years. (2) ART should not be discouraged in wMS, but the use of DMTs until pregnancy confirmation should be suggested; ART may be considered in order to reduce time to pregnancy in MS women with a reduced ovarian reserve and/or age > 35 years, but in case of an expected poor ART prognosis and the need for more than one ART cycle, a switch to a highefficacy DMD before ART should be offered. (3) Oocyte cryopreservation may be considered in women with reduced ovarian reserve, with unpredictable time to complete diagnostic workup and achieve disease control; a risk/cost-benefit analysis must be performed in women >35 years, considering the diminished ovarian reserve. Conclusion: This consensus will help MS neurologists to support family planning in wMS, respecting MS therapeutic needs while also taking into account the safety and impact of advancing age on fertility. [ABSTRACT FROM AUTHOR]

Racial, ethnic, and gender disparities have received focused attention recently, as they became more visible in the COVID era. We continue to learn more about how healthcare disparities manifest for our patients and, more broadly, the structural underpinnings that result in predictable outcomes gaps. This review summarizes what we know about disparities relevant to interventional radiologists. The prevalence and magnitude of disparities are quantified and discussed where relevant. Specific examples are provided to demonstrate how factors like gender, ethnicity, social status, geography, etc. interact to create inequities in the delivery of interventional radiology (IR) care. Understanding and addressing health disparities in IR is crucial for improving real-world patient outcomes and reducing the economic burden associated with ineffective and low-value care. Finally, the importance of intentional mentorship, outreach, education, and equitable distribution of high-quality healthcare to mitigate these disparities and promote health equity in interventional radiology is discussed. [ABSTRACT FROM AUTHOR]

While national healthcare expenditures per capita in the United States exceed those in all other Organisation for Economic Co-operation and Development (OECD) countries, measures of health outcomes in the United States lag behind those in peer nations. This combination of high healthcare spending and relatively poor health has led to attempts to identify high- and low-value healthcare services and to develop mechanisms to reimburse health care providers based on the value of the care delivered. This article investigates the meaning of value in healthcare and identifies specific services delivered by interventional radiologists that have accrued evidence that they meet criteria for high-value services. Recognizing the shift in reimbursement to high-value care, it is imperative that interventional radiology (IR) develop the evidence needed to articulate to all relevant stakeholders how IR contributes value to the system. [ABSTRACT FROM AUTHOR]

The aim of the present study was to examine the association between miRNA levels in extracellular vesicles (EVs) from serum and the severity of Major Depression (MD). Patient sera from 16 MD cases were collected at our university hospital. The miRNAs contained in EVs were extracted using a nanofiltration method, and their expression levels were analyzed using miRNA microarrays. Intergroup comparisons were performed to validate the diagnostic performance of miRNAs in EVs. Furthermore, candidate miRNAs in EVs were added to neural progenitor cells, astrocytes, and microglial cells in vitro, and the predicted target genes of the candidate miRNAs were extracted. The predicted target genes underwent enrichment analysis. The expression levels of hsa-miR-6813-3p and hsa-miR-2277-3p were significantly downregulated with increasing depression severity of MD. The pathway enrichment analysis suggests that hsa-miR-6813-3p may be involved in glucocorticoid receptor and gamma-aminobutyric acid receptor signaling. Additionally, hsa-miR-2277-3p was found to be involved in the dopaminergic neural pathway. The analysis of serum miRNAs in EVs suggests that hsa-miR-6813-3p and hsa-miR-2277-3p could serve as novel biomarkers for MD, reflecting its severity. Moreover, these miRNAs in EVs could help understand MD pathophysiology. [ABSTRACT FROM AUTHOR]

Sports‐related concussions (SRCs) are associated with neuromuscular control deficits in athletes following return to play. However, the connection between SRC and potentially disrupted neural regulation of lower extremity motor control has not been investigated. The purpose of this study was to investigate brain activity and connectivity during a functional magnetic resonance imaging (fMRI) lower extremity motor control task (bilateral leg press) in female adolescent athletes with a history of SRC. Nineteen female adolescent athletes with a history of SRC and nineteen uninjured (without a history of SRC) age‐ and sport‐matched control athletes participated in this study. Athletes with a history of SRC exhibited less neural activity in the left inferior parietal lobule/supramarginal gyrus (IPL) during the bilateral leg press compared to matched controls. Based upon signal change detected in the brain activity analysis, a 6 mm region of interest (seed) was defined to perform secondary connectivity analyses using psychophysiological interaction (PPI) analyses. During the motor control task, the left IPL (seed) was significantly connected to the right posterior cingulate gyrus/precuneus cortex and right IPL for athletes with a history of SRC. The left IPL was significantly connected to the left primary motor cortex (M1) and primary somatosensory cortex (S1), right inferior temporal gyrus, and right S1 for matched controls. Altered neural activity in brain regions important for sensorimotor integration and motor attention, combined with unique connectivity to regions responsible for attentional, cognitive, and proprioceptive processing, indicate compensatory neural mechanisms may underlie the lingering neuromuscular control deficits associated with SRC. Our research provides a new perspective on motor control alterations in female adolescent athletes with a history of sports‐related concussion (SRC), by identifying neural alterations via functional magnetic resonance imaging during lower extremity movement. This work complements previous evidence of neuromuscular control impairments in athletes following a concussion and identifies a potential underlying mechanism for lower extremity injury risk in female adolescent athletes with a history of SRC. [ABSTRACT FROM AUTHOR]

Background—Screening programs for colorectal cancer are implemented due to their ability to reduce mortality. The Endocuff Vision is a new endoscopic device that significantly improves the adenoma detection rate. The primary outcome was to assess the efficacy of ECV in improving stability and reducing operation time during difficult colon polypectomies in a multicenter randomized prospective study. Methods—In a randomized multicenter pilot study, two groups of patients who underwent difficult polypectomies with and without the assistance of Endocuff Vision were compared. Demographics and clinical characteristics of patients were obtained, and polyps' size, morphology, site, and access (SMSA); polypectomy time; and endoscope stability were evaluated. Results—From October 2016 to April 2020, 32 patients were enrolled. In total, 12 patients underwent Endocuff Vision polypectomy, and 20 patients underwent standard polypectomy by using a computer-generated random number table. No statistical differences were found in clinical characteristics, SMSA, and polypectomy time. The most interesting findings were the positive correlations between shaking and SMSA (r = 0.55, p = 0.005) and shaking and polypectomy time (r = 0.745, p < 0.0001). Conclusion—Endocuff Vision seems to be adequately stable during difficult endoscopic resection procedures. The new parameter proposed that shaking is strongly correlated to the stability of the endoscope, the difficulty of the resection (SMSA), and the polypectomy time. [ABSTRACT FROM AUTHOR]

The field of discrete-event simulation for medical disaster management is relatively new. In such simulations, human victims are generated using pre-determined transitions from one health state to the next, based on a set of triggers that correspond to treatment or the clinical progression of untreated injuries or diseases. However, this approach does not account for subtle differences in clinical progression. We propose a parameter-based model to characterize the evolution of symptoms at first for physical and nerve agent chemical injuries. We used a Gompertz function to predict the time of death in trauma based on forensic data. Then we separately considered the effects of the chemical warfare agent sarin (GB) being the origin of the chemical injuries for the purpose of modelling a GB attack in a metro station. We emphasize that our approach can be extended to other CBRN threats pending knowledge of clinical progressions available in the literature for the purpose of casualty estimations. The intent is to provide an estimate of time to death without any treatment and overlay this model with a treatment model, improving the evolution of the health state. A modification for non-life-threatening injuries is included without losing generality. Improvement functions modelling medical treatment are proposed. We argue that the availability of injury scores vs mortality can greatly enhance the validity of the model. [ABSTRACT FROM AUTHOR]

Chronic neuroinflammation plays a crucial role in the progression of several neurodegenerative diseases (NDDs), including Parkinson's disease (PD) and Alzheimer's disease (AD). Intriguingly, in the last decade, leucine-rich repeat kinase-2 (LRRK2), a gene mutated in familial and sporadic PD, was revealed as a key mediator of neuroinflammation. Therefore, the anti-inflammatory properties of LRRK2 inhibitors have started to be considered as a disease-modifying treatment for PD; however, to date, there is little evidence on the beneficial effects of targeting LRRK2-related neuroinflammation in preclinical models. In this study, we further validated LRRK2 kinase modulation as a pharmacological intervention in preclinical models of AD- and PD-related neuroinflammation. Specifically, we reported that LRRK2 kinase inhibition with MLi2 and PF-06447475 (PF) molecules attenuated neuroinflammation, gliosis and cytotoxicity in mice with intracerebral injection of Aβ1-42 fibrils or α-syn preformed fibrils (pffs). Moreover, for the first time in vivo, we showed that LRRK2 kinase activity participates in AD-related neuroinflammation and therefore might contribute to AD pathogenesis. Overall, our findings added evidence on the anti-inflammatory effects of LRRK2 kinase inhibition in preclinical models and indicate that targeting LRRK2 activity could be a disease-modifying treatment for NDDs with an inflammatory component. [ABSTRACT FROM AUTHOR]

Traumatic stress is the main environmental risk factor for the development of psychiatric disorders. We have previously shown that acute footshock (FS) stress in male rats induces rapid and long-lasting functional and structural changes in the prefrontal cortex (PFC), which are partly reversed by acute subanesthetic ketamine. Here, we asked if acute FS may also induce any changes in glutamatergic synaptic plasticity in the PFC 24 h after stress exposure and whether ketamine administration 6 h after stress may have any effect. We found that the induction of long-term potentiation (LTP) in PFC slices of both control and FS animals is dependent on dopamine and that dopamine-dependent LTP is reduced by ketamine. We also found selective changes in ionotropic glutamate receptor subunit expression, phosphorylation, and localization at synaptic membranes induced by both acute stress and ketamine. Although more studies are needed to understand the effects of acute stress and ketamine on PFC glutamatergic plasticity, this first report suggests a restoring effect of acute ketamine, supporting the potential benefit of ketamine in limiting the impact of acute traumatic stress. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Is the total number of oocytes retrieved with dual ovarian stimulation in the same cycle (duostim) higher than with two consecutive antagonist cycles in poor responders? SUMMARY ANSWER Based on the number of total and mature oocytes retrieved in women with poor ovarian response (POR), there is no benefit of duostim versus two consecutive antagonist cycles. WHAT IS KNOWN ALREADY Recent studies have shown the ability to obtain oocytes with equivalent quality from the follicular and the luteal phase, and a higher number of oocytes within one cycle when using duostim. If during follicular stimulation smaller follicles are sensitized and recruited, this may increase the number of follicles selected in the consecutive luteal phase stimulation, as shown in non-randomized controlled trials (RCT). This could be particularly relevant for women with POR. STUDY DESIGN, SIZE, DURATION This is a multicentre, open-labelled RCT, performed in four IVF centres from September 2018 to March 2021. The primary outcome was the number of oocytes retrieved over the two cycles. The primary objective was to demonstrate in women with POR that two ovarian stimulations within the same cycle (first in the follicular phase, followed by a second in the luteal phase) led to the retrieval of 1.5 (2) more oocytes than the cumulative number of oocytes from two consecutive conventional stimulations with an antagonist protocol. In a superiority hypothesis, with power 0.8 alpha-risk 0.05 and a 35% cancellation rate, 44 patients were needed in each group. Patients were randomized by computer allocation. PARTICIPANTS/MATERIALS, SETTING, METHODS Eighty-eight women with POR, defined using adjusted Bologna criteria (antral follicle count ≤5 and/or anti-Müllerian hormone ≤1.2 ng/ml) were randomized, 44 in the duostim group and 44 in the conventional (control) group. HMG 300 IU/day with flexible antagonist protocol was used for ovarian stimulation, except in luteal phase stimulation of the duostim group. In the duostim group, oocytes were pooled and inseminated after the second retrieval, with a freeze-all protocol. Fresh transfers were performed in the control group, frozen embryo transfers were performed in both control and duostim groups in natural cycles. Data underwent intention-to-treat and per-protocol analyses. MAIN RESULTS AND THE ROLE OF CHANCE There was no difference between the groups regarding demographics, ovarian reserve markers, and stimulation parameters. The mean (SD) cumulative number of oocytes retrieved from two ovarian stimulations was not statistically different between the control and duostim groups, respectively, 4.6 (3.4) and 5.0 (3.4) [mean difference (MD) [95% CI] +0.4 [−1.1; 1.9], P  = 0.56]. The mean cumulative numbersof mature oocytes and total embryos obtained were not significantly different between groups. The total number of embryos transferred by patient was significantly higher in the control group 1.5 (1.1) versus the duostim group 0.9 (1.1) (P  = 0.03). After two cumulative cycles, 78% of women in the control group and 53.8% in the duostim group had at least one embryo transfer (P  = 0.02). There was no statistical difference in the mean number of total and mature oocytes retrieved per cycle comparing Cycle 1 versus Cycle 2, both in control and duostim groups. The time to the second oocyte retrieval was significantly longer in controls, at 2.8 (1.3) months compared to 0.3 (0.5) months in the duostim group (P  < 0.001). The implantation rate was similar between groups. The cumulative live birth rate was not statistically different, comparing controls versus the duostim group, 34.1% versus 17.9%, respectively (P  = 0.08). The time to transfer resulting in an ongoing pregnancy did not differ in controls 1.7 (1.5) months versus the duostim group, 3.0 (1.6) (P  = 0.08). No serious adverse events were reported. LIMITATIONS, REASONS FOR CAUTION The RCT was impacted by the coronavirus disease 2019 pandemic and the halt in IVF activities for 10 weeks. Delays were recalculated to exclude this period; however, one woman in the duostim group could not have the luteal stimulation. We also faced unexpected good ovarian responses and pregnancies after the first oocyte retrieval in both groups, with a higher incidence in the control group. However, our hypothesis was based on 1.5 more oocytes in the luteal than the follicular phase in the duostim group, and the number of patients to treat was reached in this group (N = 28). This study was only powered for cumulative number of oocytes retrieved. WIDER IMPLICATIONS OF THE FINDINGS This is the first RCT comparing the outcome of two consecutive cycles, either in the same menstrual cycle or in two consecutive menstrual cycles. In routine practice, the benefit of duostim in patients with POR regarding fresh embryo transfer is not confirmed in this RCT: first, because this study demonstrates no improvement in the number of oocytes retrieved in the luteal phase after follicular phase stimulation, in contrast to previous non-randomized studies, and second, because the freeze-all strategy avoids a pregnancy with fresh embryo transfer after the first cycle. However, duostim appears to be safe for women. In duostim, the two consecutive processes of freezing/thawing are mandatory and increase the risk of wastage of oocytes/embryos. The only benefit of duostim is to shorten the time to a second retrieval by 2 weeks if accumulation of oocytes/embryos is needed. STUDY FUNDING/COMPETING INTERESTS This is an investigator-initiated study supported by a research Grant from IBSA Pharma. N.M. declares grants paid to their institution from MSD (Organon France); consulting fees from MSD (Organon France), Ferring, and Merck KGaA; honoraria from Merck KGaA, General Electrics, Genevrier (IBSA Pharma), and Theramex; support for travel and meetings from Theramex, Merck KGaG, and Gedeon Richter; and equipment paid to their institution from Goodlife Pharma. I.A. declares honoraria from GISKIT and support for travel and meetings from GISKIT. G.P.-B. declares Consulting fees from Ferring and Merck KGaA; honoraria from Theramex, Gedeon Richter, and Ferring; payment for expert testimony from Ferring, Merck KGaA, and Gedeon Richter; and support for travel and meetings from Ferring, Theramex, and Gedeon Richter. N.C. declares grants from IBSA pharma, Merck KGaA, Ferring, and Gedeon Richter; support for travel and meetings from IBSA pharma, Merck KGaG, MSD (Organon France), Gedeon Richter, and Theramex; and participation on advisory board from Merck KGaA. E.D. declares support for travel and meetings from IBSA pharma, Merck KGaG, MSD (Organon France), Ferring, Gedeon Richter, Theramex, and General Electrics. C.P.-V. declares support for travel and meetings from IBSA Pharma, Merck KGaA, Ferring, Gedeon Richter, and Theramex. M.Pi. declares support for travel and meetings from Ferring, Gedeon Richetr, and Merck KGaA. M.Pa. declares honoraria from Merck KGaA, Theramex, and Gedeon Richter; support for travel and meetings from Merck KGaA, IBSA Pharma, Theramex, Ferring, Gedeon Richter, and MSD (Organon France). H.B.-G. declares honoraria from Merck KGaA, and Gedeon Richter and support for travel and meetings from Ferring, Merck KGaA, IBSA Pharma, MSD (Organon France), Theramex, and Gedeon Richter. S.G. and M.B. have nothing to declare. TRIAL REGISTRATION NUMBER Registration number EudraCT: 2017-003223-30. ClinicalTrials.gov identifier: NCT03803228. TRIAL REGISTRATION DATE EudraCT: 28 July 2017. ClinicalTrials.gov: 14 January 2019. DATE OF FIRST PATIENT'S ENROLMENT 3 September 2018. [ABSTRACT FROM AUTHOR]

Aim: The adenoma detection rate (ADR) is an important quality measure, with a high ADR reflecting high‐quality colonoscopy. This systematic review and meta‐analysis aimed to assess the effects of Endocuff™/Endocuff Vision™‐assisted colonoscopy (EAC) versus standard colonoscopy (SC) on ADR and other clinical, patient and resource‐use outcomes. Method: MEDLINE, EMBASE, Web of Science, Scopus and the Cochrane Central Register of Controlled Trials were searched for full papers reporting randomized studies comparing EAC with SC. The primary outcome was ADR. Secondary outcomes comprised key polyp/adenoma detection, procedure‐related, patient‐related and health economic measures. Random effects meta‐analyses provided pooled estimates of outcomes [risk ratio (RR) or mean difference (MD), with 95% confidence intervals (CI)]. Results: Twelve parallel‐group randomized controlled trials (RCTs) and three crossover RCTs with data on 9140 patients were included. EAC significantly increased the ADR (RR 1.18, 95% CI 1.09–1.29), mean adenomas per procedure (MAP) (MD 0.19, 95% CI 0.06–0.33), polyp detection rate (PDR) (RR 1.20, 95% CI 1.10–1.30) and mean polyps per procedure (MPP) (MD 0.39, 95% CI 0.14–0.63) versus SC. EAC significantly increased segmental PDR versus SC in the sigmoid (RR 2.02, 95% CI 1.64–2.49), transverse (RR 1.63, 95% CI 1.09–2.42), ascending (RR 1.74, 95% CI 1.26–2.41) and caecal segments (RR 1.91, 95% CI 1.29–2.82). Procedure‐related variables did not differ between arms. There were insufficient data for meta‐analysis of health economic or patient‐centred outcomes. Conclusions: EAC increased ADR, MAP, PDR and MPP versus SC without detrimental effects on procedure measures. Cost‐effectiveness and patient experience data are lacking and would be valuable to inform practice recommendations. [ABSTRACT FROM AUTHOR]

Double ovarian stimulation (DuoStim), initially only suggested for fertility preservation in cancer patients, is now increasingly also used in routine clinical IVF, especially in poor responders. The claimed rational for this is the alleged existence of multiple follicular waves in a single intermenstrual interval, allowing for retrieval of more oocytes in a single IVF cycle. This commentary argues that this expansion of purpose lacks rationale, evidence, and follow-up. Consequently, we suggest that, unless valid clinical indications have been established, DuoStim be only subject of controlled clinical trials with appropriate experimental consents. [ABSTRACT FROM AUTHOR]

Mood disorders are the most prevalent psychiatric disorders associated with significant disability, morbidity, and mortality. The risk of suicide is associated with severe or mixed depressive episodes in patients with mood disorders. However, the risk of suicide increases with the severity of depressive episodes and is often presented with higher incidences in bipolar disorder (BD) patients than in patients with major depression (MDD). Biomarker study in neuropsychiatric disorders is critical for developing better treatment plans by facilitating more accurate diagnosis. At the same time, biomarker discovery also provides more objectivity to develop state-of-the-art personalized medicine with increased accuracy through clinical interventions. Recently, colinear changes in miRNA expression between brain and systemic circulation have added great interest in examining their potential as molecular markers in mental disorders, including MDD, BD, and suicidality. A present understanding of circulating miRNAs in body fluids implicates their role in managing neuropsychiatric conditions. Most notably, their use as prognostic and diagnostic markers and their potential role in treatment response have significantly advanced our knowledge base. The present review discusses circulatory miRNAs and their underlying possibilities to be used as a screening tool for assessing major psychiatric conditions, including MDD, BD, and suicidal behavior. [ABSTRACT FROM AUTHOR]

Study Question: Are the IVF parameters and the steroidogenic luteal characteristics of random-start IVF cycles different from conventional cycles in cancer patients?Summary Answer: No; controlled ovarian stimulation cycles randomly started at late follicular phase (LFP) and luteal phase (LP) are totally comparable to those conventional IVF cycles started at early follicular phase (EFP) in terms of the expression of the enzymes involved in cholesterol utilization and steroid hormone biosynthesis pathways, gonadotropin receptor expression and, estradiol (E2) and progesterone (P4) production in addition to the similarities in ovarian response to gonadotropin stimulation, oocyte yield, fertilization rate and embryo development competency in cancer patients.What Is Known Already: Random start ovarian stimulation protocols are commonly employed for oocyte and embryo freezing for fertility preservation in cancer patients with time constraints who do not have sufficient time to undergo ovarian stimulation initiated conventionally at EFP of the next cycle. No data is available regarding the molecular steroidogenic features of these cycles analyzed together with the clinical IVF characteristics in cancer patients. We aimed to address this question in this study to help understand how similar the random start cycles are to the conventional start ones.Study Design, Size, Duration: A clinical translational research study conducted in 62 cancer patients undergoing IVF for fertility preservation between the years 2017 and 2022.Participants/materials, Setting, Methods: Sixty-two patients who were diagnosed with different types of cancer and underwent ovarian stimulation for oocyte (n = 41) and embryo (n = 21) cryopreservation using GnRH antagonist protocol and human menopausal gonadotropins before receiving cancer treatment/surgery were enrolled in the study. For patients with breast cancer and endometrial cancer the aromatase inhibitor letrozole was used with gonadotropin stimulation. Ovarian stimulation was initiated conventionally at EFP in 22 patients and served as control while it was started at LFP in 20, and mid-LP in the other 20 patients. The luteinized granulosa cells (GCs) were recovered from follicular aspirates during oocyte retrieval procedure and used for the experiments separately for each individual patient. The expression of the enzymes involved in sex steroid biosynthesis (StAR, 3β-HSD, Aromatase) and cholesterol synthesis (3-hydroxy 3-methylglutaryl Co-A reductase (HMG-Co-A reductase)), utilization (hormone sensitive lipase (HSL)), and storage (Acetyl-Coenzyme A acetyltransferase 1 (ACAT-1)), and gonadotropin receptor expression status were analyzed using immunoblotting and RT-PCR methods. Laser confocal immunofluorescence imaging was applied to analyze and compare the expression patterns of the steroidogenic enzymes and their relation with mitochondria. In vitro E2 and P4 production by the cells were compared among the groups.Main Results and the Role Of Chance: Baseline demographic and IVF characteristics of the patients undergoing the conventional start and random start IVF cycles were similar. Duration of gonadotropin stimulation was significantly longer in LFP and LP start cycles in comparison to the conventional ones. Ovarian response to gonadotropin stimulation, mature and total oocyte yield, fertilization and Day 5 blastulation rates of the embryos were comparable between the conventional versus random start cycles. When the luteal GCs of these random start cycles were analyzed we could not find any gross differences between these cycles in terms of the viability index and gross light microscopic morphologic features. More detailed analysis of the molecular luteal characteristics of the cells using RT-PCR, immunoblotting methods revealed that the expression profiles of the gonadotropin receptors, and the enzymes involved in sex steroid biosynthesis and cholesterol synthesis/utilization, and the steroidogenic activity of the luteal GCs of the random start cycles are almost identical to those of the conventional start cycles. Confocal image analysis demonstrated similar patterns in the signal expression profiles of the steroidogenic enzymes and their co-localization within mitochondria.Large Scale Data: N/A.Limitations, Reasons For Caution: Caution should be exercised when interpreting our data and counseling cancer patients seeking fertility preservation because it is still unclear if previous exposure to cancer drugs, different ovarian pathologies or infertility etiologies, previous ovarian surgery and/or any other underlying diseases that are concomitantly present with cancer may cause a difference between conventional and random start stimulation protocols in terms of IVF parameters, luteal function and reproductive outcome. Relatively low number of patients in each stimulation protocol and pooling of luteal GCs for each patient rather than individual analysis of each follicle and oocyte are additional limitations of our study.Wider Implications Of the Findings: Our findings provide reassurance that random start protocol offers cancer patients an equally good prospect of fertility preservation as conventional IVF.Study Funding/competing Interest(s): Funded by the School of Medicine, the Graduate School of Health Sciences of Koc University and Koç University Research Center for Translational Medicine (KUTTAM), equally funded by the Republic of Turkey Ministry of Development Research Infrastructure Support Program. All authors declare no conflict of interest.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Simple Summary: With this review, the authors aim at providing the reader a concise biological and biomechanical description of the main contributions in the field of traumatic brain injuries and neurodegenerative outcomes for women, especially related to chronic traumatic encephalopathy. A review on numerical models created to address these issues is also performed, discussing the use (or the lack of use) of sex-specific validation experiments to validate those models. A discussion is also performed to alert to some considerations to be taken in account when numerically modelling those same injury scenarios. The biomechanics of traumatic injuries of the human body as a consequence of road crashes, falling, contact sports, and military environments have been studied for decades. In particular, traumatic brain injury (TBI), the so-called "silent epidemic", is the traumatic insult responsible for the greatest percentage of death and disability, justifying the relevance of this research topic. Despite its great importance, only recently have research groups started to seriously consider the sex differences regarding the morphology and physiology of women, which differs from men and may result in a specific outcome for a given traumatic event. This work aims to provide a summary of the contributions given in this field so far, from clinical reports to numerical models, covering not only the direct injuries from inertial loading scenarios but also the role sex plays in the conditions that precede an accident, and post-traumatic events, with an emphasis on neuroendocrine dysfunctions and chronic traumatic encephalopathy. A review on finite element head models and finite element neck models for the study of specific traumatic events is also performed, discussing whether sex was a factor in validating them. Based on the information collected, improvement perspectives and future directions are discussed. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurological disease that worsens with time. The hallmark illnesses include extracellular senile plaques caused by ß-amyloid protein deposition, neurofibrillary tangles caused by tau protein hyperphosphorylation, and neuronal loss accompanying glial cell hyperplasia. Noncoding RNAs are substantially implicated in related pathophysiology, according to mounting data. However, the function of these ncRNAs is mainly unclear. Circular RNAs (circRNAs) include many miRNA-binding sites (miRNA response elements, MREs), which operate as miRNA sponges or competing endogenous RNAs (ceRNAs). The purpose of this study was to look at the role of circular RNAs (circRNAs) andmicroRNAs (miRNAs) in Alzheimer's disease (AD) as possible biomarkers. The Gene Expression Omnibus (GEO) database was used to obtain an expression profile of Alzheimer's disease patients (GSE5281, GSE122603, GSE97760, GSE150693, GSE1297, and GSE161435). Through preliminary data deletion, 163 genes with significant differences, 156 miRNAs with significant differences, and 153 circRNAs with significant differences were identified. Then, 10 key genes, led by MAPT and AP2M1, were identified by the mediation center algorithm, 34miRNAs with obvious prognosis were identified by the cox regression model, and 16 key circRNAs were selected by the database. To develop competitive endogenous RNA (ceRNA) networks, hub circRNAs andmRNAs were used. Finally, GO analysis and clinical data verification of key genes were carried out. We discovered that a down-regulated circRNA (has_circ_002048) caused the increased expression of numerous miRNAs, which further inhibited the expression of a critical mRNA (AP2M1), leading to Alzheimer's disease pathology. The findings of this work contribute to a better understanding of the circRNA-miRNA-mRNA regulating processes in Alzheimer's disease. Furthermore, the ncRNAs found here might become novel biomarkers and potential targets for the development of Alzheimer's drugs. [ABSTRACT FROM AUTHOR]

High and low sodium diets are associated with increased blood pressure and cardiovascular morbidity and mortality. The paradoxical response of elevated BP in low salt diets, aka inverse salt sensitivity (ISS), is an understudied vulnerable 11% of the adult population with yet undiscovered etiology. A linear relationship between the number of single nucleotide polymorphisms (SNPs) in the dopamine D2 receptor (DRD2, rs6276 and 6277), and the sodium myo-inositol cotransporter 2 (SLC5A11, rs11074656), as well as decreased expression of these two genes in urine-derived renal proximal tubule cells (uRPTCs) isolated from clinical study participants suggest involvement of these cells in ISS. Insight into this newly discovered paradoxical response to sodium is found by incubating cells in low sodium (LS) conditions that unveil cell physiologic differences that are then reversed by mir-485-5p miRNA blocker transfection and bypassing the genetic defect by DRD2 re-expression. The renin-angiotensin system (RAS) is an important counter-regulatory mechanism to prevent hyponatremia under LS conditions. Oversensitive RAS under LS conditions could partially explain the increased mortality in ISS. Angiotensin-II (AngII, 10 nmol/L) increased sodium transport in uRPTCs to a greater extent in individuals with ISS than SR. Downstream signaling of AngII is verified by identifying lowered expression of nuclear factor erythroid 2-related factor 2 (NRF2), CCCTC-binding factor (CTCF), and manganese-dependent mitochondrial superoxide dismutase (SOD2) only in ISS-derived uRPTCs and not SR-derived uRPTCs when incubated in LS conditions. We conclude that DRD2 and SLC5A11 variants in ISS may cause an increased low sodium sensitivity to AngII and renal sodium reabsorption which can contribute to inverse salt-sensitive hypertension. [ABSTRACT FROM AUTHOR]

miRNA has been a research hotspot in recent years and its scope of action is very wide, involving the regulation of cell proliferation, differentiation, apoptosis, and other biological behaviors. This study intends to explore the role of miRNA in the lipid metabolism and development of Wilms tumor (WT) by detecting and analyzing the differences in the expression profiles of miRNAs between the tumor and adjacent normal tissue. Gene detection was performed in tumor tissues and adjacent normal tissues of three cases of WT to screen differentially expressed miRNAs (DEMs). According to our previous research, FASN, which participates in the lipid metabolism pathway, may be a target of WT. The starBase database was used to predict FASN-targeted miRNAs. The above two groups of miRNAs were intersected to obtain FASN-targeted DEMs and then GO Ontology (GO) functional enrichment analysis of FASN-targeted DEMs was performed. Finally, the FASN-targeted DEMs were compared and further verified by qRT‒PCR. Through gene sequencing and differential analysis, 287 DEMs were obtained, including 132 upregulated and 155 downregulated miRNAs. The top ten DEMs were all downregulated. Fourteen miRNAs targeted by the lipid metabolism-related gene FASN were predicted by starBase. After intersection with the DEMs, three miRNAs were finally obtained, namely, miR-107, miR-27a-3p, and miR-335-5p. GO enrichment analysis was mainly concentrated in the Parkin-FBXW7-Cul1 ubiquitin ligase complex and response to prostaglandin E. Further experimental verification showed that miR-27a-3p was significantly correlated with WT (P = 0.0018). Imbalanced expression of miRNAs may be involved in the occurrence and development of WT through lipid metabolism. The expression of miR-27a-3p is related to the malignant degree of WT, and it may become the target of diagnosis, prognosis, and treatment of WT in the later stage., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Since depression remains a major public health issue there is a constant need for new and more efficient therapeutic strategies based on the mechanisms involved in the aetiology of depression. Thus, the pathogenic link between depression and inflammation is considered to play a potential key role in the development of such therapies. This review summarizes the results of various pharmacological (non-steroidal anti-inflammatory drugs, aspirin, cyclooxygenase inhibitors, cytokine inhibitors, corticosteroids, statins, minocycline, N-acetyl cysteine, omega-3 fatty acids and probiotics) and non-pharmacological interventions (electroconvulsive therapy, physical exercise and psychological therapy) and outlines their efficacy and discusses potential challenges. Both conventional and non-conventional anti-inflammatory drugs showed promising results according to the specific group of patients. The pre-existing pro-inflammatory status was, in most cases, a predictor for clinical efficacy and, in some cases, a correlation between clinical improvement and changes in various biomarkers was found. Some of the non-pharmacological interventions (physical exercise and electroconvulsive therapy) have also showed beneficial effects for depressive patients with elevated inflammatory markers. Treatments with anti-inflammatory action may improve clinical outcomes in depression, at least for some categories of patients, thus opening the way for a future personalised approach to patients with unipolar depression regarding the inflammation-related mechanism. [ABSTRACT FROM AUTHOR]

Bipolar disorder (BD) is a severe, chronic, and disabling neuropsychiatric disorder characterized by recurrent mood disturbances (mania/hypomania and depression, with or without mixed features) and a constellation of cognitive, psychomotor, autonomic, and endocrine abnormalities. The etiology of BD is multifactorial, including both biological and epigenetic factors. Recently, microRNAs (miRNAs), a class of epigenetic regulators of gene expression playing a central role in brain development and plasticity, have been related to several neuropsychiatric disorders, including BD. Moreover, an alteration in the number/distribution and differentiation potential of neural stem cells has also been described, significantly affecting brain homeostasis and neuroplasticity. This review aimed to evaluate the most reliable scientific evidence on miRNAs as biomarkers for the diagnosis of BD and assess their implications in response to mood stabilizers, such as lithium. Neural stem cell distribution, regulation, and dysfunction in the etiology of BD are also dissected. [ABSTRACT FROM AUTHOR]

Objective: We aimed to investigate the effect of differentially methylated genes and chronic childhood stress on the development of depressive symptoms in Chinese adolescents, as well as to test whether methylation at baseline can be used as a predictor of remission at follow-up after six weeks of treatment. Methods: After recruiting 87 MDD patients and 53 healthy controls, we compared demographic and baseline clinical characteristics. The Childhood Chronic Stress Questionnaire was used to assess stress caused by early-life events. MDD patients underwent six weeks of treatment, and response to treatment was assessed using the Beck Depression Inventory-II. In addition, four MDD patients and five controls were randomly chosen for genome-wide methylation analysis. Results: The gene RPS6KA5 showed significant methylation differences between the two groups. Severity of chronic childhood stress was significantly associated with increased risk of depression in adolescents, but not with treatment response. Baseline RPS6KA5 methylation can predict remission after six weeks of treatment. We did not observe any interaction between RPS6KA5 methylation and chronic childhood stress. Conclusions: Our results suggest that RPS6KA5 methylation can be used as a predictor of response to treatment in adolescent MDD patients. Here we offer new evidence for the role of epigenetics in early response to treatment of depression. Trial registration: ChiCTR, ChiCTR2000033402, 31/05/2020, http://www.chictr.org.cn/index.aspx [ABSTRACT FROM AUTHOR]

Objectives: To determine whether follicle-stimulating hormone receptor (FSHR) genotype influences the outcome of ovarian stimulation treatment in luteal phase., Methods: A total of 299 patients were included in a retrospective study between July 2017 and December 2021. These patients carried out a double stimulation protocol and the variant Asn680Ser (rs6166; c.2039A>G) of FSH receptor was genotyped either as part of the pre-treatment fertility tests or for the current study. Patients undergoing a double stimulation treatment who could not be genotyped were excluded from this analysis., Results: The results obtained from ovarian stimulation in luteal phase were better than those obtained in conventional follicular phase. Statistically significant differences ( P  < 0.001) were found in the number of retrieved oocytes (5.47 vs. 4.18), retrieved MII (4.52 vs. 3.29) and fertilised oocytes (3.81 vs. 2.20). Furthermore, these differences remained regardless of the FSH receptor genotype for the 680 position in all groups ( P  < 0.05). In addition, stimulation in luteal phase lasts longer and requires more gonadotropins than in follicular phase. This is especially noteworthy in patients with Ser/Ser genotype, who required a slightly higher dose of gonadotropins compared to other genotypes in luteal phase, as previously observed in the follicular phase for this genotype. No significant differences in age, anti-Müllerian hormone levels, antral follicle count, BMI and type of trigger used in luteal phase were observed among groups of patients with different FSH receptor genotypes., Conclusion: All patients undergoing IVF seem to benefit from luteal phase ovarian stimulation, regardless of their FSHR genotype., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Alzheimer's disease (AD) is a complex, heterogeneous, progressive disease and is the most common type of neurodegenerative dementia. The prevalence of AD is expected to increase as the population ages, placing an additional burden on national healthcare systems. There is a large need for new diagnostic tests that can detect AD at an early stage with high specificity at relatively low cost. The development of modern analytical diagnostic tools has made it possible to determine several biomarkers of AD with high specificity, including pathogenic proteins, markers of synaptic dysfunction, and markers of inflammation in the blood. There is a considerable potential in using microRNA (miRNA) as markers of AD, and diagnostic studies based on miRNA panels suggest that AD could potentially be determined with high accuracy for individual patients. Studies of the retina with improved methods of visualization of the fundus are also showing promising results for the potential diagnosis of the disease. This review focuses on the recent developments of blood, plasma, and ocular biomarkers for the diagnosis of AD. [ABSTRACT FROM AUTHOR]

Fragile X syndrome (FXS) is caused by a mutation in the FMR1 gene which can lead to a loss or shortage of the FMR1 protein. This protein interacts with specific miRNAs and can cause a range of neurological disorders. Therefore, miRNAs could act as a novel class of biomarkers for common CNS diseases. This study aimed to test this theory by exploring the expression profiles of various miRNAs in Iranian using deep sequencing-based technologies and validating the miRNAs affecting the expression of the FMR1 gene. Blood samples were taken from 15 patients with FXS (9 males, 6 females) and 12 controls. 25 miRNAs were differentially expressed in individuals with FXS compared to controls. Levels of 9 miRNAs were found to be significantly changed (3 upregulated and 6 downregulated). In Patients, the levels of hsa-miR-532-5p, hsa-miR-652-3p and hsa-miR-4797-3p were significantly upregulated while levels of hsa-miR-191-5p, hsa-miR-181-5p, hsa-miR-26a-5p, hsa-miR-30e-5p, hsa-miR-186-5p, and hsa-miR-4797-5p exhibited significant downregulation; and these dysregulations were confirmed by RT‐qPCR. This study presents among the first evidence of altered miRNA expression in blood samples from patients with FXS, which could be used for diagnostic, prognostic, and treatment purposes. Larger studies are required to confirm these preliminary results. [ABSTRACT FROM AUTHOR]

Objective: Platelets are increasingly considered to play an important role in inflammation and are being regarded as a putative bridge linking mental diseases and inflammatory response. Platelet-associated haematological parameters including mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT), systemic immune-inflammation index (SII), platelet to lymphocyte ratio (PLR), platelet to albumin ratio (PAR) and red blood cell distribution width (RDW) to platelet ratio (RPR), have been recently investigated as simple, easily available, and inexpensive inflammatory markers. In this study, we aimed is to use large-scale clinical data to study platelet parameters in patients with affective disorders, to further investigate the predictive power of platelet parameters for major depressive disorder (MDD) and bipolar disorder (BD). Methods: The retrospective, naturalistic, cross-sectional study analysed the data of 14,007 Chinese affective disorder patients, including 4,801 patients with first-episode MDD, 4,098 patients with recurrent MDD, 3,444 patients with BD manic episodes and 1,664 patients with BD depressive episodes. Meanwhile, 6,847 healthy subjects were served as the control group. The differences in the MPV, PDW, PCT, SII, PLR, PAR, RPR and albumin among different groups were compared, and the contributing factors for the occurrence of MDD or BD were analysed. Results: There were significant differences in MPV, PDW, PCT, SII, PLR, RPR and albumin values among the study groups. In the subjects, patients experiencing BD manic episodes had the highest mean values of MPV and SII, patients experiencing BD depressive episodes had the lowest mean values of platelet counts and PAR, and patients with MDD had the highest mean values of PLR and RDW. The levels of MPV, PDW and albumin were independently correlated with MDD and BD, and they are important predictors for differentiating patients with MDD or BD from healthy controls. Conclusions: Our study demonstrated that different affective disorders have unique platelet parameter variation patterns, highlighting the role of platelet parameters and systemic inflammation in the pathophysiology of MDD and BD. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) is one of the most common psychiatric disorders and is a great disease burden. However, its underlying pathophysiology and aetiology remain poorly understood. Available evidence suggests that circulating microRNAs (miRNAs) are associated with MDD, but it is still unknown whether miRNAs can predict subsequent incident MDD. Methods: In this nested case-control study, a total of 104 individuals, who were free of MDD at baseline, from the Women's Health in Lund Area (WHILA) cohort were included. Among them, 52 individuals developed MDD (cases) during the 5 years follow-up and 52 individuals did not develop MDD (controls). Plasma expression levels of miR-17-5p, miR-134-5p, miR-144-5p, let-7b-5p and let-7c-5p at baseline were assessed using qRT-PCR. Logistic regression was used to estimate the odds of developing MDD among individuals with different levels of miRNA expression. Results: Plasma expression levels of let-7b-5p were significantly lower (p = 0.02) at baseline in cases compared to controls. After adjustment for age and BMI, let-7b-5p was negatively associated with odds for developing MDD (OR = 0.33, p = 0.03, 95% CI = 0.12–0.91). Moreover, let-7b-5p expression levels showed a trend over time with larger differences between cases and controls for the earlier cases (MDD diagnosis <2 years from baseline) than MDD cases developed later (MDD diagnosis 2–5 years from baseline). Conclusions: These findings show that lower plasma levels of let-7b-5p are associated with a higher future risk of MDD. Results need to be validated in a large cohort to examine its potential as a peripheral biomarker for MDD. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a complex mental disorder where the neurochemical, neuroendocrine, immune, and metabolic systems are impaired. The microbiota-gut-brain axis is a bidirectional network where the central and enteric nervous systems are linked through the same endocrine, immune, neural, and metabolic routes dysregulated in MDD. Thus, gut-brain axis abnormalities in MDD patients may, at least in part, account for the symptomatic features associated with MDD. Recent investigations have suggested that the oral microbiome also plays a key role in this complex molecular picture of relationships. As on one hand there is a lot of what we know and on the other hand little of what we still need to know, we structured this review focusing, in the first place, on putting all pieces of this complex puzzle together, underlying the endocrine, immune, oxidative stress, neural, microbial neurotransmitters, and metabolites molecular interactions and systems lying at the base of gut microbiota (GM)–brain-depression interphase. Then, we focused on promising but still under-explored areas of research strictly linked to the GM and potentially involved in MDD development: (i) the interconnection of GM with oral microbiome that can influence the neuroinflammation-related processes and (ii) gut phageome (bacteria-infecting viruses). As conclusions and future directions, we discussed potentiality but also pitfalls, roadblocks, and the gaps to be bridged in this exciting field of research. By the development of a broader knowledge of the biology associated with MDD, with the inclusion of the gut/oral microbiome, we can accelerate the growth toward a better global health based on precision medicine. [ABSTRACT FROM AUTHOR]

Copyright of Revista de Cirugia is the property of Sociedad de Cirujanos de Chile and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

There are accumulating reports regarding poor response to common antidepressant therapy. Antidepressant resistance is often linked to inflammatory system activation and patients displaying inflammation prior to the treatment are less responsive to antidepressants. We hypothesized that the inefficacy of antidepressant therapy in some patients may be attributable to the drugs' inflammatory mode of action, which has been overlooked because of their substantial therapeutic benefit. Bupropion is a commonly prescribed antidepressant that is often used to treat seasonal affective disorders as well. Nevertheless, research suggests that bupropion causes inflammation and worsens depressive symptoms. Therefore, we investigated the impact of bupropion on cytokines of innate and adaptive immunity, as well as immune signaling pathways. We treated lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells (PBMCs) with different doses of bupropion. Pro-/anti-inflammatory cytokines [tumor necrosis factor alpha (TNFα), interleukin-1β (IL-1β), IL-17, and IL-10] were assessed at both transcriptional and translational levels as well as the involvement of JAK2 /STAT3, TLR2, and TLR4 signaling in this process. Bupropion reduced IL-17A, TNFα, and IL-1β protein levels in the cultures. Nonetheless, bupropion increased IL-1β (P < 0.0001), TNFα (P < 0.0001), and IL-17A (P < 0.05) mRNA levels. Treatment enhanced both IL-10 concentration (P < 0.0001) and gene expression (P < 0.0001). TLR2 (P < 0.0001), TLR4 (P < 0.0001), JAK2 (P < 0.0001), and STAT3 (P < 0.0001) gene expression also rose in response to bupropion. The findings imply that bupropion, particularly 50 μM and 100 μM, has pro-inflammatory effects and should be co-administered with anti-inflammatory medications, at least in patients with inflammatory conditions. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) and type 2 diabetes (T2D) are known to be correlated in terms of their epidemiology, histopathology, and molecular and biochemical characteristics. The prevalence of T2D leading to AD is approximately 50–70%. Moreover, AD is often considered type III diabetes because of the common risk factors. Uncontrolled T2D may affect the brain, leading to memory and learning deficits in patients. In addition, metabolic disorders and impaired oxidative phosphorylation in AD and T2D patients suggest that mitochondrial dysfunction is involved in both diseases. The dysregulation of pathways involved in maintaining mitochondrial dynamics, biogenesis and mitophagy are responsible for exacerbating the impact of hyperglycemia on the brain and neurodegeneration under T2D conditions. The first section of this review describes the recent views on mitochondrial dysfunction that connect these two disease conditions, as the pathways are observed to overlap. The second section of the review highlights the importance of different mitochondrial miRNAs (mitomiRs) involved in the regulation of mitochondrial dynamics and their association with the pathogenesis of T2D and AD. Therefore, targeting mitochondrial biogenesis and mitophagy pathways, along with the use of mitomiRs, could be a potent therapeutic strategy for T2D-related AD. The last section of the review highlights the known drugs targeting mitochondrial function for the treatment of both disease conditions. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is a fatal neurodegenerative disorder, and the lesions originate in the entorhinal cortex (EC) and hippocampus (HIP) at the early stage of AD progression. Gaining insight into the molecular mechanisms underlying AD is critical for the diagnosis and treatment of this disorder. Recent discoveries have uncovered the essential roles of microRNAs (miRNAs) in aging and have identified the potential of miRNAs serving as biomarkers in AD diagnosis. Methods: We sought to apply bioinformatics tools to investigate microarray profiles and characterize differentially expressed genes (DEGs) in both EC and HIP and identify specific candidate genes and pathways that might be implicated in AD for further analysis. Furthermore, we considered that DEGs might be dysregulated by miRNAs. Therefore, we investigated patients with AD and healthy controls by studying the gene profiling of their brain and blood samples to identify AD-related DEGs, differentially expressed miRNAs (DEmiRNAs), along with gene ontology (GO) analysis, KEGG pathway analysis, and construction of an AD-specific miRNA–mRNA interaction network. Results: Our analysis identified 10 key hub genes in the EC and HIP of patients with AD, and these hub genes were focused on energy metabolism, suggesting that metabolic dyshomeostasis contributed to the progression of the early AD pathology. Moreover, after the construction of an miRNA–mRNA network, we identified 9 blood-related DEmiRNAs, which regulated 10 target genes in the KEGG pathway. Conclusions: Our findings indicated these DEmiRNAs having the potential to act as diagnostic biomarkers at an early stage of AD. [ABSTRACT FROM AUTHOR]

Copyright of Revista de Cirugia is the property of Sociedad de Cirujanos de Chile and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)