Homeostatic metaplasticity induced by the combination of two inhibitory brain stimulation techniques: Continuous theta burst and transcranial static magnetic stimulation.

Aftereffects of non-invasive brain stimulation techniques may be brain state-dependent. Either continuous theta-burst stimulation (cTBS) as transcranial static magnetic field stimulation (tSMS) reduce cortical excitability. Our objective was to explore the aftereffects of tSMS on a M1 previously stimulated with cTBS. The interaction effect of two inhibitory protocols on cortical excitability was tested on healthy volunteers (n = 20), in two different sessions. A first application cTBS was followed by real-tSMS in one session, or sham-tSMS in the other session. When intracortical inhibition was tested with paired-pulse transcranial magnetic stimulation, LICI (ie., long intracortical inhibition) increased, although the unconditioned motor-evoked potential (MEP) remained stable. These effects were observed in the whole sample of participants regardless of the type of static magnetic field stimulation (real or sham) applied after cTBS. Subsequently, we defined a group of good-responders to cTBS (n = 9) on whom the unconditioned MEP amplitude reduced after cTBS and found that application of real-tSMS (subsequent to cTBS) increased the unconditioned MEP. This MEP increase was not found when sham-tSMS followed cTBS. The interaction of tSMS with cTBS seems not to take place at inhibitory cortical interneurons tested by LICI, since LICI was not differently affected after real and sham tSMS. Our results indicate the existence of a process of homeostatic plasticity when tSMS is applied after cTBS. This work suggests that tSMS aftereffects arise at the synaptic level and supports further investigation into tSMS as a useful tool to restore pathological conditions with altered cortical excitability.

Lrp10 suppresses IL7R limiting CD8 T cell homeostatic expansion and anti-tumor immunity.

Signals emanating from the T-cell receptor (TCR), co-stimulatory receptors, and cytokine receptors each influence CD8 T-cell fate. Understanding how these signals respond to homeostatic and microenvironmental cues can reveal new ways to therapeutically direct T-cell function. Through forward genetic screening in mice, we discover that loss-of-function mutations in LDL receptor-related protein 10 (Lrp10) cause naive and central memory CD8 T cells to accumulate in peripheral lymphoid organs. Lrp10 encodes a conserved cell surface protein of unknown immunological function. T-cell activation induces Lrp10 expression, which post-translationally suppresses IL7 receptor (IL7R) levels. Accordingly, Lrp10 deletion enhances T-cell homeostatic expansion through IL7R signaling. Lrp10-deficient mice are also intrinsically resistant to syngeneic tumors. This phenotype depends on dense tumor infiltration of CD8 T cells, which display increased memory cell characteristics, reduced terminal exhaustion, and augmented responses to immune checkpoint inhibition. Here, we present Lrp10 as a new negative regulator of CD8 T-cell homeostasis and a host factor that controls tumor resistance with implications for immunotherapy.

Oxidative Stress in Prediabetic Young Adults.

Background Malondialdehyde (MDA) and nitric oxide (NO) are considered specific biomarkers for oxidative stress. Oxidative stress in prediabetics with an augmented potential for the onset of diabetes is at least partly responsible for the various complications of diabetes. Evidence shows that the early features of cell injury are due to transient acute elevations in blood glucose. This study aims to determine whether oxidative stress in prediabetic young adults increases the risk of developing diabetes. Aim and objectives We envisaged a study to determine whether the parameters representing oxidative stress are deranged in prediabetics. Materials and methods The study was conducted on prediabetic young individuals from 18 to 35 years, screened from the tertiary-level hospital, and a similar group of non-prediabetic young individuals identified from the same in a tertiary-level hospital in India. Results We observed significant elevations in prediabetics in the following oxidative stress parameters: MDA (P= <0.001), and NO (P= <0.001); indicating that these parameters were significantly higher among the prediabetics than the controls. We also observed significantly greater body weight, waist circumference, and BMI among the prediabetics than the controls. Conclusion Early identification and appropriate treatment of hyperglycemia in prediabetics is essential, as impairments in pancreatic beta-cell functioning and resistance to insulin are already present before the onset of type 2 diabetes mellitus (T2DM). Owing to the high potential for mortality and morbidity due to cardiovascular diseases (CVDs) as a complication of diabetes, treatment plans must be put in place early enough so that complications can be prevented. Inflammation and oxidative stress may be viewed as valuable targets to hinder the evolution of T2DM from prediabetes.

Prediabetes: A Benign Intermediate Stage or a Risk Factor in Itself?

Prediabetes is a condition when the blood glucose levels are above the normal range but below the threshold for defining diabetes. Previously considered benign, it is now recognized to be associated with various macrovascular and microvascular complications, with increases in the risk of cardiovascular events, nephropathy neuropathy, and retinopathy. Early identification of prediabetics may help detect the risk for these future complications at an earlier stage. Moreover, therapeutic options for prediabetes are available, which can retard its progression to diabetes and the subsequent development of complications. Hence, we make a case for the early identification of prediabetes through screening methods and appropriate institution of management strategies.

Anxiety is related to slower RSA oscillation during stress response and regulation.

Respiratory sinus arrhythmia (RSA), an index of the parasympathetic nervous system activity, has been considered indicative of stress response and emotion regulation. However, the relationship between RSA and anxiety remains inconclusive, partly because previous research has primarily focused on static RSA levels. In this nonclinical sample (N = 75, Mage = 20.89 ± 1.72 SD, 48 males), we used a damped oscillator model to characterize RSA dynamics across 30-s epochs while participants completed the Trier social stress test. Results showed that RSA constantly oscillated during the three periods of TSST (namely Rest, Stress, and Recovery). Importantly, slower RSA oscillation in the Stress period was related to elevated state anxiety, whereas in the Recovery period, it was related to higher trait anxiety. These findings demonstrated the dynamic nature of RSA during the whole course of stress response. Slower RSA oscillation may indicate inflexible and tardy physiological regulation which may give rise to anxiety issues.

Homeostatic Synaptic Plasticity of Miniature Excitatory Postsynaptic Currents in Mouse Cortical Cultures Requires Neuronal Rab3A.

Following prolonged activity blockade, amplitudes of miniature excitatory postsynaptic currents (mEPSCs) increase, a form of plasticity termed "homeostatic synaptic plasticity." We previously showed that a presynaptic protein, the small GTPase Rab3A, is required for full expression of the increase in miniature endplate current amplitudes following prolonged blockade of action potential activity at the mouse neuromuscular junction in vivo (Wang et al., 2011), but it is unknown whether this form of Rab3A-dependent homeostatic plasticity shares any characteristics with central synapses. We show here that homeostatic synaptic plasticity of mEPSCs is impaired in mouse cortical neuron cultures prepared from Rab3A-/- and mutant mice expressing a single point mutation of Rab3A, Rab3A Earlybird mice. To determine if Rab3A is involved in the well-established homeostatic increase in postsynaptic AMPA-type receptors (AMPARs), we performed a series of experiments in which electrophysiological recordings of mEPSCs and confocal imaging of synaptic AMPAR immunofluorescence were assessed within the same cultures. We found that Rab3A was required for the increase in synaptic AMPARs following prolonged activity blockade, but the increase in mEPSC amplitudes was not always accompanied by an increase in postsynaptic AMPAR levels, suggesting other factors may contribute. Finally, we demonstrate that Rab3A is acting in neurons because only selective loss of Rab3A in neurons, not glia, disrupted the homeostatic increase in mEPSC amplitudes. This is the first demonstration that neuronal Rab3A is required for homeostatic synaptic plasticity and that it does so partially through regulation of the surface expression of AMPA receptors.

GluN2A- and GluN2B-containing pre-synaptic N-methyl-d-aspartate receptors differentially regulate action potential-evoked Ca2+ influx via modulation of SK channels.

N-methyl-d-aspartate receptors (NMDARs) play a pivotal role in synaptic plasticity. While the functional role of post-synaptic NMDARs is well established, pre-synaptic NMDAR (pre-NMDAR) function is largely unexplored. Different pre-NMDAR subunit populations are documented at synapses, suggesting that subunit composition influences neuronal transmission. Here, we used electrophysiological recordings at Schaffer collateral-CA1 synapses partnered with Ca2+ imaging and glutamate uncaging at boutons of CA3 pyramidal neurones to reveal two populations of pre-NMDARs that contain either the GluN2A or GluN2B subunit. Activation of the GluN2B population decreases action potential-evoked Ca2+ influx via modulation of small-conductance Ca2+-activated K+ channels, while activation of the GluN2A population does the opposite. Critically, the level of functional expression of the subunits is subject to homeostatic regulation, bidirectionally affecting short-term facilitation, thus providing a capacity for a fine adjustment of information transfer. This article is part of a discussion meeting issue 'Long-term potentiation: 50 years on'.

Relevance of the Adjuvant Effect between Cellular Homeostasis and Resistance to Antibiotics in Gram-Negative Bacteria with Pathogenic Capacity: A Study of Klebsiella pneumoniae.

Antibiotic resistance has become a global issue. The most significant risk is the acquisition of these mechanisms by pathogenic bacteria, which can have a severe clinical impact and pose a public health risk. This problem assumes that bacterial fitness is a constant phenomenon and should be approached from an evolutionary perspective to develop the most appropriate and effective strategies to contain the emergence of strains with pathogenic potential. Resistance mechanisms can be understood as adaptive processes to stressful conditions. This review examines the relevance of homeostatic regulatory mechanisms in antimicrobial resistance mechanisms. We focus on the interactions in the cellular physiology of pathogenic bacteria, particularly Gram-negative bacteria, and specifically Klebsiella pneumoniae. From a clinical research perspective, understanding these interactions is crucial for comprehensively understanding the phenomenon of resistance and developing more effective drugs and treatments to limit or attenuate bacterial sepsis, since the most conserved adjuvant phenomena in bacterial physiology has turned out to be more optimized and, therefore, more susceptible to alterations due to pharmacological action.

Retinoic acid-mediated homeostatic plasticity in the nucleus accumbens core contributes to incubation of cocaine craving.

RATIONALE: Incubation of cocaine craving refers to the progressive intensification of cue-induced craving during abstinence from cocaine self-administration. We showed previously that homomeric GluA1 Ca2+-permeable AMPARs (CP-AMPAR) accumulate in excitatory synapses of nucleus accumbens core (NAcc) medium spiny neurons (MSN) after ∼1 month of abstinence and thereafter their activation is required for expression of incubation. Therefore, it is important to understand mechanisms underlying CP-AMPAR plasticity. OBJECTIVES: We hypothesize that CP-AMPAR upregulation represents a retinoic acid (RA)-dependent form of homeostatic plasticity, previously described in other brain regions, in which a reduction in neuronal activity disinhibits RA synthesis, leading to GluA1 translation and CP-AMPAR synaptic insertion. We tested this using viral vectors to bidirectionally manipulate RA signaling in NAcc during abstinence following extended-access cocaine self-administration. RESULTS: We used shRNA targeted to the RA degradative enzyme Cyp26b1 to increase RA signaling. This treatment accelerated incubation; rats expressed incubation on abstinence day (AD) 15, when it is not yet detected in control rats. It also accelerated CP-AMPAR synaptic insertion measured with slice physiology. CP-AMPARs were detected in Cyp26b1 shRNA-expressing MSN, but not control MSN, on AD15-18. Next, we used shRNA targeted to the major RA synthetic enzyme Aldh1a1 to reduce RA signaling. In MSN expressing Aldh1a1 shRNA, synaptic CP-AMPARs were reduced in late withdrawal (AD42-60) compared to controls. However, we did not detect an effect of this manipulation on incubated cocaine seeking (AD40). CONCLUSIONS: These findings support the hypothesis that increased RA signaling during abstinence contributes to CP-AMPAR accumulation and incubation of cocaine craving.

Investigating motivations to eat: Refining and validating a framework of Eating Behaviour Traits in dieters and the general population.

Due to relationships between diet and health including obesity, there is a need to examine the explanatory power of factors that motivate people to (over or under) eat. In a previous investigation, a four-factor subscale-based model of eating behaviour traits (EBTs) was developed which identified individual differences in psychological factors influencing motivations to eat and some residual uncertainties. The current study used a data-driven and theory-driven approach, including individual items to refine and extend previous EBT models. The aim was to examine and validate the domain structure of a framework for EBTs. The analysis used two samples including a representative sample of the UK population (n = 2010, 51% female, 49% male, 18-88 years), and members of a weight management program (n = 2317, 96.6% female, 2.8% male, 21-84 years), who completed 5 questionnaires including 10 EBTs. The results found some support for a 6-factor model, encompassing reactive eating, negative emotional eating, positive emotional eating, restricted eating, homeostatic eating, and body-food choice congruence (data-driven model) or eating for health (theory-driven model). There were differences between the data-driven model and the theory-driven model regarding the 6th factor. Additionally, the data-driven model did not distinguish between eating for pleasure and reactive eating. The models demonstrated that the eating behaviour factors were significantly associated with BMI category. Overall, this research contributes to a more structured understanding of the dimensions of motivation underlying EBTs, emphasising the utility of this framework for identifying at-risk individuals and tailoring interventions to meet specific individual needs.

Enhanced Synaptic Inhibition in the Dorsolateral Geniculate Nucleus in a Mouse Model of Glaucoma.

Elevated intraocular pressure (IOP) triggers glaucoma by damaging the output neurons of the retina called retinal ganglion cells (RGCs). This leads to the loss of RGC signaling to visual centers of the brain such as the dorsolateral geniculate nucleus (dLGN), which is critical for processing and relaying information to the cortex for conscious vision. In response to altered levels of activity or synaptic input, neurons can homeostatically modulate postsynaptic neurotransmitter receptor numbers, allowing them to scale their synaptic responses to stabilize spike output. While prior work has indicated unaltered glutamate receptor properties in the glaucomatous dLGN, it is unknown whether glaucoma impacts dLGN inhibition. Here, using DBA/2J mice, which develop elevated IOP beginning at 6-7 months of age, we tested whether the strength of inhibitory synapses on dLGN thalamocortical relay neurons is altered in response to the disease state. We found an enhancement of feedforward disynaptic inhibition arising from local interneurons along with increased amplitude of quantal inhibitory synaptic currents. A combination of immunofluorescence staining for the γ-aminobutyric acid (GABA)A-α1 receptor subunit, peak-scaled nonstationary fluctuation analysis, and measures of homeostatic synaptic scaling pointed to an ∼1.4-fold increase in GABA receptors at postsynaptic inhibitory synapses, although several pieces of evidence indicate a nonuniform scaling across inhibitory synapses within individual relay neurons. Together, these results indicate an increase in inhibitory synaptic strength in the glaucomatous dLGN, potentially pointing toward homeostatic compensation for disruptions in network and neuronal function triggered by increased IOP.

GABAergic synaptic scaling is triggered by changes in spiking activity rather than AMPA receptor activation.

Homeostatic plasticity represents a set of mechanisms that are thought to recover some aspect of neural function. One such mechanism called AMPAergic scaling was thought to be a likely candidate to homeostatically control spiking activity. However, recent findings have forced us to reconsider this idea as several studies suggest AMPAergic scaling is not directly triggered by changes in spiking. Moreover, studies examining homeostatic perturbations in vivo have suggested that GABAergic synapses may be more critical in terms of spiking homeostasis. Here, we show results that GABAergic scaling can act to homeostatically control spiking levels. We found that perturbations which increased or decreased spiking in cortical cultures triggered multiplicative GABAergic upscaling and downscaling, respectively. In contrast, we found that changes in AMPA receptor (AMPAR) or GABAR transmission only influence GABAergic scaling through their indirect effect on spiking. We propose that GABAergic scaling represents a stronger candidate for spike rate homeostat than AMPAergic scaling.

Pupillometry indexes ocular dominance plasticity.

Short-term monocular deprivation in normally sighted adult humans produces a transient shift of ocular dominance, boosting the deprived eye. This effect has been documented with both perceptual tests and through physiological recordings, but no previous study simultaneously measured physiological responses and the perceptual effects of deprivation. Here we propose an integrated experimental paradigm that combines binocular rivalry with pupillometry, to introduce an objective physiological index of ocular dominance plasticity, acquired concurrently with perceptual testing. Ten participants reported the perceptual dynamics of binocular rivalry, while we measured pupil diameter. Stimuli were a white and a black disk, each presented monocularly. Rivalry dynamics and pupil-size traces were compared before and after 2 h of monocular deprivation, achieved by applying a translucent patch over the dominant eye. Consistent with prior research, we observed that monocular deprivation boosts the deprived-eye signal and consequently increases ocular dominance. In line with previous studies, we also observed subtle but systematic modulations of pupil size that tracked alternations between exclusive dominance phases of the black or white disk. Following monocular deprivation, the amplitude of these pupil-size modulations increased, which is consistent with the post-deprivation boost of the deprived eye and the increase of ocular dominance. This provides evidence that deprivation impacts the effective strength of monocular visual stimuli, coherently affecting perceptual reports and the automatic and unconscious regulation of pupil diameter. Our results show that a combined paradigm of binocular rivalry and pupillometry gives new insights into the physiological mechanisms underlying deprivation effects.

Data-driven mathematical modeling of sleep consolidation in early childhood.

Across early childhood development, sleep behavior transitions from a biphasic pattern (a daytime nap and nighttime sleep) to a monophasic pattern (only nighttime sleep). The transition to consolidated nighttime sleep, which occurs in most children between 2- and 5-years-old, is a major developmental milestone and reflects interactions between the developing homeostatic sleep drive and circadian system. Using a physiologically-based mathematical model of the sleep-wake regulatory network constrained by observational and experimental data from preschool-aged participants, we analyze how developmentally-mediated changes in the homeostatic sleep drive may contribute to the transition from napping to non-napping sleep patterns. We establish baseline behavior by identifying parameter sets that model typical 2-year-old napping behavior and 5-year-old non-napping behavior. Then we vary six model parameters associated with the dynamics of and sensitivity to the homeostatic sleep drive between the 2-year-old and 5-year-old parameter values to induce the transition from biphasic to monophasic sleep. We analyze the individual contributions of these parameters to sleep patterning by independently varying their age-dependent developmental trajectories. Parameters vary according to distinct evolution curves and produce bifurcation sequences representing various ages of transition onset, transition durations, and transitional sleep patterns. Finally, we consider the ability of napping and non-napping light schedules to reinforce napping or promote a transition to consolidated sleep, respectively. These modeling results provide insight into the role of the homeostatic sleep drive in promoting interindividual variability in developmentally-mediated transitions in sleep behavior and lay foundations for the identification of light- or behavior-based interventions that promote healthy sleep consolidation in early childhood.

Inactivity-induced phrenic motor facilitation requires PKCζ activity within phrenic motor neurons.

Prolonged inhibition of respiratory neural activity elicits a long-lasting increase in phrenic nerve amplitude once respiratory neural activity is restored. Such long-lasting facilitation represents a form of respiratory motor plasticity known as inactivity-induced phrenic motor facilitation (iPMF). Although facilitation also occurs in inspiratory intercostal nerve activity after diminished respiratory neural activity (iIMF), it is of shorter duration. Atypical PKC activity in the cervical spinal cord is necessary for iPMF and iIMF, but the site and specific isoform of the relevant atypical PKC are unknown. Here, we used RNA interference to test the hypothesis that the zeta atypical PKC isoform (PKCζ) within phrenic motor neurons is necessary for iPMF but PKCζ within intercostal motor neurons is unnecessary for transient iIMF. Intrapleural injections of siRNAs targeting PKCζ (siPKCζ) to knock down PKCζ mRNA within phrenic and intercostal motor neurons were made in rats. Control rats received a nontargeting siRNA (NTsi) or an active siRNA pool targeting a novel PKC isoform, PKCθ (siPKCθ), which is required for other forms of respiratory motor plasticity. Phrenic nerve burst amplitude and external intercostal (T2) electromyographic (EMG) activity were measured in anesthetized and mechanically ventilated rats exposed to 30 min of respiratory neural inactivity (i.e., neural apnea) created by modest hypocapnia (20 min) or a similar recording duration without neural apnea (time control). Phrenic burst amplitude was increased in rats treated with NTsi (68 ± 10% baseline) and siPKCθ (57 ± 8% baseline) 60 min after neural apnea vs. time control rats (-3 ± 3% baseline), demonstrating iPMF. In contrast, intrapleural siPKCζ virtually abolished iPMF (5 ± 4% baseline). iIMF was transient in all groups exposed to neural apnea; however, intrapleural siPKCζ attenuated iIMF 5 min after neural apnea (50 ± 21% baseline) vs. NTsi (97 ± 22% baseline) and siPKCθ (103 ± 20% baseline). Neural inactivity elevated the phrenic, but not intercostal, responses to hypercapnia, an effect that was blocked by siPKCζ. We conclude that PKCζ within phrenic motor neurons is necessary for long-lasting iPMF, whereas intercostal motor neuron PKCζ contributes to, but is not necessary for, transient iIMF.NEW & NOTEWORTHY We report important new findings concerning the mechanisms regulating a form of spinal neuroplasticity elicited by prolonged inhibition of respiratory neural activity, inactivity-induced phrenic motor facilitation (iPMF). We demonstrate that the atypical PKC isoform PKCζ within phrenic motor neurons is necessary for long-lasting iPMF, whereas intercostal motor neuron PKCζ contributes to, but is not necessary for, transient inspiratory intercostal facilitation. Our findings are novel and advance our understanding of mechanisms contributing to phrenic motor plasticity.

Emergence of integrated behaviors through direct optimization for homeostasis.

Homeostasis is a self-regulatory process, wherein an organism maintains a specific internal physiological state. Homeostatic reinforcement learning (RL) is a framework recently proposed in computational neuroscience to explain animal behavior. Homeostatic RL organizes the behaviors of autonomous embodied agents according to the demands of the internal dynamics of their bodies, coupled with the external environment. Thus, it provides a basis for real-world autonomous agents, such as robots, to continually acquire and learn integrated behaviors for survival. However, prior studies have generally explored problems pertaining to limited size, as the agent must handle observations of such coupled dynamics. To overcome this restriction, we developed an advanced method to realize scaled-up homeostatic RL using deep RL. Furthermore, several rewards for homeostasis have been proposed in the literature. We identified that the reward definition that uses the difference in drive function yields the best results. We created two benchmark environments for homeostasis and performed a behavioral analysis. The analysis showed that the trained agents in each environment changed their behavior based on their internal physiological states. Finally, we extended our method to address vision using deep convolutional neural networks. The analysis of a trained agent revealed that it has visual saliency rooted in the survival environment and internal representations resulting from multimodal input.

Facilitation of Early and Middle Latency SEP after tDCS of M1: No Evidence of Primary Somatosensory Homeostatic Plasticity.

Homeostatic plasticity is a mechanism that stabilizes cortical excitability within a physiological range. Most homeostatic plasticity protocols have primed and tested the homeostatic response of the primary motor cortex (M1). This study investigated if a homeostatic response could be recorded from the primary sensory cortex (S1) after inducing homeostatic plasticity in M1. In 31 healthy participants, homeostatic plasticity was induced over M1 with a priming and testing block of transcranial direct current stimulation (tDCS) in two different sessions (anodal and cathodal). S1 excitability was assessed by early (N20, P25) and middle-latency (N33-P45) somatosensory evoked potentials (SEP) extracted from 4 electrodes (CP5, CP3, P5, P3). Baseline and post-measures (post-priming, 0-min, 10-min, and 20-min after homeostatic induction) were taken. Anodal M1 homeostatic plasticity induction significantly facilitated the N20-P25, P45 peak, and N33-P45 early SEP components up to 20-min post-induction, without any indication of a homeostatic response (i.e., reduced SEP). Cathodal homeostatic induction did not induce any significant effect on early or middle latency SEPs. M1 homeostatic plasticity induction by anodal stimulation protocol to the primary motor cortex did not induce a homeostatic response in SEPs.

Correlation between anti-mullerian hormone with insulin resistance in polycystic ovarian syndrome: a systematic review and meta-analysis.

BACKGROUND: Epidemiological studies regarding the correlation between anti-Müllerian hormone (AMH) and insulin resistance (IR) in polycystic ovarian syndrome (PCOS) remain inconsistent. The primary aim of this study was to determine the correlations between AMH and IR in patients with PCOS and to explore the selected factors that influence the correlations. METHODS: We conducted systemic searches of online databases (PubMed, Science Direct, Taylor and Francis, Scopus, and ProQuest) from inception to December 20, 2023 and manual searches of the associated bibliographies to identify relevant studies. We then performed subgroup and sensitivity analyses to explore the sources of heterogeneity, followed by a publication bias risk assessment of the included studies using the Joanna Briggs Institute critical appraisal tool. We used a random-effects model to estimate the pooled correlations between AMH and the homeostatic model assessment for insulin resistance (HOMA-IR) in patients with polycystic ovarian syndrome (PCOS). RESULTS: Of the 4835 articles identified, 22 eligible relevant studies from three regions were included and identified as low risk of bias. The random-effects pooled correlation estimate was 0.089 (95% confidence interval [CI]: -0.040, 0.215), with substantial heterogeneity (I2 = 87%; τ2 = 0.0475, p < .001). Subgroup analyses showed that the study region did not influence the correlation estimates, and sensitivity analysis showed no significant alteration in the pooled correlation estimate or 95% CI values. No publication bias was observed. CONCLUSION: There was a weak, statistically insignificant correlation between AMH and HOMA-IR in patients with PCOS. The correlation estimates did not vary according to the study participants' regions.

Postpartum diabetes and cardiometabolic outcomes among Indian (South Asian) women with early Gestational diabetes mellitus: Insights from the CHIP-F study.

Early GDM is associated with adverse pregnancy outcomes, however data on other outcomes are scarce. We evaluated women with early (n = 117) and classical (n = 412) GDM for long-term postpartum (median 32 months) glycemic and cardiometabolic outcomes and found a significantly higher prevalence of diabetes in the former [22.2 % vs. 12.6 %, p = 0.010].

Building a realistic, scalable memory model with independent engrams using a homeostatic mechanism.

Memory formation is usually associated with Hebbian learning and synaptic plasticity, which changes the synaptic strengths but omits structural changes. A recent study suggests that structural plasticity can also lead to silent memory engrams, reproducing a conditioned learning paradigm with neuron ensembles. However, this study is limited by its way of synapse formation, enabling the formation of only one memory engram. Overcoming this, our model allows the formation of many engrams simultaneously while retaining high neurophysiological accuracy, e.g., as found in cortical columns. We achieve this by substituting the random synapse formation with the Model of Structural Plasticity. As a homeostatic model, neurons regulate their activity by growing and pruning synaptic elements based on their current activity. Utilizing synapse formation based on the Euclidean distance between the neurons with a scalable algorithm allows us to easily simulate 4 million neurons with 343 memory engrams. These engrams do not interfere with one another by default, yet we can change the simulation parameters to form long-reaching associations. Our model's analysis shows that homeostatic engram formation requires a certain spatiotemporal order of events. It predicts that synaptic pruning precedes and enables synaptic engram formation and that it does not occur as a mere compensatory response to enduring synapse potentiation as in Hebbian plasticity with synaptic scaling. Our model paves the way for simulations addressing further inquiries, ranging from memory chains and hierarchies to complex memory systems comprising areas with different learning mechanisms.