PURPOSE:To investigate the association of retinal and choroidal vessel density with renal function using optical coherence tomographic angiography (OCTA). METHOD:The present study prospectively recruited consecutive diabetes patients admitted to Beijing Liangxiang Hospital from October 2023 to March 2024. All participants underwent comprehensive ophthalmologic examinations and laboratory analysis at the first visit. Quantitative parameters of OCTA scans included retinal superficial vascular complex (SVC) and deep vascular complex (DVC) vessel densities, and choriocapillaris flow deficits (CCFD%). RESULTS:A total of 85 patients were included in the present study. After adjusting for severity of diabetic retinopathy and other confounding factors, every 1 % increased SVC within in ETDRS grid was associated with reduced incidence of CKD (OR=0.86 95 %CI:[0.73-1.01]), decreased urine albumin-to-creatinine ratio (ACR, coefficient=-0.65, 95 %CI:[-1.22, -0.08]), and increased eGFR (coefficient=1.55, 95 %CI:[0.14, 2.96]). Every 1 % increased CCFD% was significantly associated with increased incidence of CKD (OR=1.72, 95 %CI:[1.14-2.58]) and decrease eGFR (coefficient=-6.47, 95 %CI:[-9.68, -3.26]). Non-linear regression revealed that SVC vessel density was associated with eGFR among patients with advanced retinal microvasculature damage. CONCLUSIONS:Retina and choroid blood flow were associated with the onset and severity of CKD. Decreased SVC and decreased CCFD% can be used for non-invasively screening CKD in diabetes patients.

Background Despite growing interest in the intergenerational impacts of adversity, evidence on the association between parental adverse childhood experiences (ACEs) on offspring mortality remains limited, and the potential mediating role of parental education is underexplored. Objectives To investigate associations of parental ACEs with offspring mortality, and to explore whether parental educational level mediates these associations. Participants and setting This cross-sectional study included 6052 fathers (corresponding to 15,493 offspring) and 6679 mothers (corresponding to 17,687 offspring) from the 2014 life history survey of the China Health and Retirement Longitudinal Study. Methods Data on parental exposure to 12 ACEs, educational levels, and offspring mortality were collected via questionnaire. Multilevel logistic regression models were constructed to examine the associations of paternal and maternal ACEs with offspring mortality, respectively. Mediation analyses were conducted using generalized structural equation models. Results Parents with four or more ACEs had the highest odds of offspring mortality compared to those with no ACEs (paternal ACEs: odds ratio [OR] = 1.98, 95 % confidence interval [CI] [1.44, 2.74]; maternal ACEs: OR = 1.98, 95 % CI [1.52, 2.57]). Parental educational level partially mediated these associations, accounting for 23.8 % and 35.3 % of the total effects for paternal and maternal ACEs, respectively. Conclusions Both paternal and maternal ACEs were intergenerationally associated with increased risk of offspring mortality, with part of the association explained by parental educational disadvantage. These findings underscore the need for trauma-informed, family-based interventions that support both mothers and fathers with ACE histories, and for policies that promote educational equity.

BackgroundWeak handgrip strength (HGS) has been linked to adverse health outcomes including stroke. However, the joint associations of HGS weakness and asymmetry between limbs with stroke incidence remain underexplored.MethodsThis cohort study analyzed data of participants aged ≥45 years from three waves (2011, 2013, and 2015) of the China Health and Retirement Longitudinal Study. Weak HGS was defined according to the recommendation of European Working Group on Sarcopenia in Older People. Asymmetric HGS was defined if the HGS ratio of both hands was over 1.1 or below 0.9. New-onset stroke was confirmed through self-report of physician’s diagnosis.ResultsA total of 10,966 participants without stroke at baseline were included in the analysis. During the 4 years follow-up, there were 262 (2.39%) new-onset stroke cases. Compared to individuals with non-weak and symmetric HGS, those with HGS asymmetry alone and weakness alone were associated with hazards of 1.09 (95% confidence interval [CI]: 0.80–1.48) and 1.27 (95%CI: 0.86–1.88) for new-onset stroke, respectively, while co-occurrence of both HGS asymmetry and weakness was associated with 1.80 (95%CI: 1.24–2.60) greater hazard for new-onset stroke after controlling for confounders. Such associations were consistent in older adults aged ≥60 years, but not in those aged<60 years.ConclusionIndividuals with both weak and asymmetric HGS tended to have greater risk of new-onset stroke, compared to those with normal HGS, or with either weak or asymmetric HGS alone. Our finding suggested that examining HGS asymmetry alongside weakness may help to improve the risk-stratification and target prevention of stroke, particularly in the older population.

ImportanceStudies investigating the association of threat-related and deprivation-related adverse childhood experiences (ACEs) with later-life cognitive decline are lacking.ObjectivesTo evaluate the independent association of threat-related and deprivation-related ACEs with cognitive decline over time among middle-aged and older Chinese adults and to examine the modifying role of social isolation in such associations.Design, Setting, and ParticipantsThis prospective cohort study used cognitive data from the China Health and Retirement Longitudinal Study (CHARLS) baseline survey that was administered between June 1, 2011, and March 31, 2012, and the CHARLS follow-up survey administered between July 1 and September 30, 2015. The life history survey with information of ACEs was additionally administered between June 1 and December 31, 2014. Statistical analysis was performed from March 1 to July 31, 2022. The study population consisted of middle-aged and older adults (age range, 45-97 years) with complete data on ACEs and 2 cognitive assessments and without cognitive impairment at baseline.ExposuresFive threat-related ACEs (ie, physical abuse, household substance abuse, domestic violence, unsafe neighborhood, and bullying) and 5 deprivation-related ACEs (ie, emotional neglect, household mental illness, incarcerated household member, parental separation or divorce, and parental death) before 17 years of age were queried by questionnaires. The cumulative scores of the 2 ACE dimensions were calculated and grouped into 3 categories as 0, 1, and 2 or more in main analyses.Main Outcomes and MeasuresCognitive function was measured by episodic memory and executive function. Global cognition was further calculated as the total score of these 2 dimensions. The raw scores of each cognitive test were standardized to z scores using baseline means and SDs. Linear mixed-effects models were constructed to examine the association between 2 dimensions of ACEs and the rate of annual cognitive decline. The modifying role of baseline social isolation in such associations was assessed with 3-way interaction tests.ResultsOf the 6466 participants included in main analyses, 3301 (51.1%) were men and the mean (SD) age was 57.2 (8.3) years. Compared with no exposures, experience of 1 deprivation-related ACE was associated with faster cognitive decline in global cognition (β = −0.012 [95% CI, −0.022 to −0.002] SD/y) and executive function (β = −0.010 [95% CI, −0.020 to −0.00002] SD/y), whereas individuals with at least 2 childhood deprivations had faster cognitive declines in all cognitive tests (β = −0.035 [95% CI, −0.050 to −0.019] SD/y for global cognition; β = −0.047 [95% CI, −0.068 to −0.025] SD/y for episodic memory; β = −0.019 [95% CI, −0.034 to −0.004] SD/y for executive function). However, such an association was not observed for threat-related ACEs. In addition, baseline social isolation was a significant modifier in the associations between deprivation-related ACEs and cognitive declines in global cognition (β = −0.033 [95% CI, −0.061 to −0.005] SD/y; P = .02 for 3-way interaction) and executive function (β = −0.032 [95% CI, −0.059 to −0.005] SD/y; P = .02 for 3-way interaction).Conclusions and RelevanceDeprivation-related ACEs, but not threat-related ACEs, were associated with faster decline in later-life cognitive function, whereas social isolation could modify such detrimental impact. These findings highlight the potential benefits of promoting social integration in maintaining later-life cognitive function among individuals who have experienced childhood deprivation.

To investigate the independent impact of threat-related and deprivation-related adverse childhood experiences (ACEs) on depressive symptoms among middle-aged and older adults, and to evaluate the moderating role of current economic status in these associations. This cross-sectional study included 11,048 participants aged ≥ 45 years from the China Health and Retirement Longitudinal Study. We captured five threat-related ACEs and five deprivation-related ACEs by questionnaires. Depressive symptoms were assessed using the 10-item Centre for Epidemiological Studies Depression Scale. Current economic status was reflected by annual per capita household consumption expenditure. We performed logistic regression analyses to evaluate the independent association of childhood threat and deprivation with depressive symptoms, and conducted stratified analyses and tests for interaction to explore the moderation effect of current economic status in such associations. Compared with the nonexposed group, the experience of both childhood threat and deprivation were independently associated with greater risks of depressive symptoms later in life (odds ratio [OR] 1.75, 95

Fetuin-A has been linked to insulin resistance and obesity. Its role in the pathogenesis of type 2 diabetes (T2DM) has also been discussed. We aimed to investigate the prospective association of fetuin-A and the risk of T2DM in a systematic review and meta-analysis.

Objective: To investigate the association between daytime napping and prevalent/incident diabetes mellitus (DM) based on systematic review and meta-analytic data.Methods: The electronic databases of Embase, Medline, Pubmed and Web of Science were searched. Relevant studies were extracted by two reviewers independently. The associations between daytime napping (irrespective of duration), long nap (>= 1 h/day) and short nap (< 1 h/day), and risk of DM were assessed according to study types. Overall estimates were pooled using either fixed-or random-effect with inverse variance meta-analysis. Heterogeneity of included studies was assessed using the I-2 test and possible cause of the heterogeneity was examined by meta-regression analyses.Results: Ten studies (four cross-sectional and six longitudinal cohort) comprising a total of 304,885 individuals and 20,857 cases of DM were included in the systematic review, with an average napping prevalence of 47%. Nappers were found to have increased risk of DM in both cross-sectional and cohort studies. However, significant heterogeneity was present. Long nap (>= 1 h/day) was associated with both prevalent and incident DM; in particular, those with a daily nap over 1 h had a 31% increased risk of developing DM during follow-up (95% confidence interval: 2-67%). Conversely, no such association was found in individuals with short naps (< 1 h/day) in cohort studies.Conclusions: Long daytime napping over 1 h per day was associated with increased risk of both prevalent and incident DM. Further studies are needed to confirm the findings. (C) 2017 Elsevier B.V. All rights reserved.

Human brain imaging studies have revealed the anterior cingulate cortex (ACC) as a key brain region for mediating visceral-pain-cognitive interactions. Recently, we characterized impairments of long-term potentiation and spike-field coherence in the basolateral amygdala (BLA)-ACC network in association with a decision-making deficit in rats with visceral hypersensitivity (VH). Now, by combining integrative neurobiological approaches, we show that ACC-reactive astrogliosis and activity-dependent impairment of lactate release occur in VH rats. Exogenous lactate supply rescues chronic-visceral-pain-caused impairments of ACC phase locking and decision making, which can be mimicked by optogenetic activation of ACC astrocytes. Large-scale electrophysiological recordings in free-moving animals during a decision-making task indicate that optogenetic astrocytic activation improves decision-making performance and engages ACC phase locking and BLA-to-ACC information flow. Collectively, these observations support the idea of an “astrocyte-neuron l-lactate shuttle” and suggest that targeting astrocytes may help with cognitive dysfunctions under chronic visceral pain.

Background: Diabetic retinopathy (DR) is linked to increased risk of cardiovascular (CV) disease. However, the effect size of the association was not consistent. In this study, we performed a systematic review and meta-analysis of available cohort studies to determine the association between DR and CV disease, and to investigate the factors that influence the association. Methods: Terms related to DR and CV disease were searched from MEDLINE and EMBASE database. High-quality articles (Newcastle-Ottawa scales above 6) conducted in cohort studies reporting the association between DR and CV disease were identified. Study-specific estimates were pooled using random effects with inverse variance meta-analysis. Subgroup analysis was performed according to diabetes types. Heterogeneity of included studies was assessed using the I-2 test. The cause of the heterogeneity was examined using metaregression analyses. Results: A total of 13 studies representing 17,611 patients without CV disease at baseline were included. At follow-up, there were 1457 CV disease-related incidences. Overall, DR was associated with increased risk of CV disease (relative risk [RR]: 2.42, 95% confidence interval [CI]: 1.77-3.31) in diabetes. Specifically, the RR was 3.59 (95% CI: 1.79-7.20) for type 1 diabetes and 1.81 (95% CI: 1.47-2.23) for type 2 diabetes. Significant heterogeneity was found in studies with type 1 diabetes. Metaregression analysis showed that baseline systolic blood pressure was a key factor leading to the heterogeneity. Conclusion: In conclusion, DR is significantly associated with CV disease incidence and CV disease-related mortality in diabetes. Patients with DR may need more intensive management to control future CV disease attacks. (C) 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Vagus nerve stimulation (VNS) can enhance memory and cognitive functions in both rats and humans. Studies have shown that VNS influenced decision-making in epileptic patients. However, the sites of action involved in the cognitive-enhancement are poorly understood. By employing a conscious rat model equipped with vagus nerve cuff electrode, we assess the role of chronic VNS on decision-making in rat gambling task (RGT). Simultaneous multichannel-recordings offer an ideal setup to test the hypothesis that VNS may induce alterations of in both spike-field-coherence and synchronization of theta oscillations across brain areas in the anterior cingulate cortex (ACC) and basolateral amygdala (BLA). Daily VNS, administered immediately following training sessions of RGT, caused an increase in 'good decision-maker' rats. Neural spikes in the ACC became synchronized with the ongoing theta oscillations of local field potential (LFP) in BLA following VNS. Moreover, cross-correlation analysis revealed synchronization between the ACC and BLA. Our results provide specific evidence that VNS facilitates decision-making and unveils several important roles for VNS in regulating LFP and spike phases, as well as enhancing spike-phase coherence between key brain areas involved in cognitive performance. These data may serve to provide fundamental notions regarding neurophysiological biomarkers for therapeutic VNS in cognitive impairment.

Ciguatoxins are marine biotoxins that induce the human poisoning syndrome known as ciguatera fish poisoning (CFP). In humans, different kinds of neurological symptoms have been reported after CFP, including anxiety, depression and memory loss. Repetitive exposures to sub-threshold levels of ciguatera toxins may cause irreversible sub-clinical damage, and eventually cause more severe illness. Our previous study has shown that an acute single dose of Pacific ciguatoxin-1 (P-CTX-1) induced synaptic facilitation and blockage of the induction of electrical stimulation-induced long-term potentiation in the medial thalamus- anterior cingulate cortex pathway. Reactive astrogliosis was detected in acute ciguatera poisoning. Despite the reports of complex and prolonged neurological symptoms in patients, few studies have been conducted in animal models to investigate the emotional and cognitive deficits after chronic exposure to ciguatoxin. In the present study, using a rat model with repeated exposures to low dosage of P-CTX-1, we observed development of anxiety-like behavior by open field test and elevated plus maze test, and learning and memory deficits by the Morris water maze; further, decision-making impairment was determined in the chronic P-CTX-1-treated rats by the rats gambling task. We conclude that chronic ciguatera poisoning leads to anxiety, and to impairment of spatial reference memory and decision-making behavior.

Visceral hypersensitivity (VH) is a key factor of irritable bowel syndrome (IBS). Previous studies have identified an enhanced response of anterior cingulate cortex (ACC) to colorectal distension in VH rats, which can be observed up to 7weeks following colonic anaphylaxis, independent of colonic inflammation. The induction of VH produces a change in the ability to induce subsequent synaptic plasticity at the ACC circuitry. In clinical practice, a positive link between IBS and cognitive impairments has been noted for years, but no animal model has been reported. Decision-making is a valuable model for monitoring higher-order cognitive functions in animals, which depends on the integrated function of several sub-regions of the ACC and amygdala. Using rat gambling task (RGT) in the present study, we observed an impairment of decision-making behavior in VH rats. Electrophysiological study showed a reduction of long-term potentiation in the basolateral amygdala (BLA)-ACC synapses in VH rats. Multiple-electrode array recordings of local field potential (LFP) in both BLA and ACC were also performed in freely behaving rats. Spike-field coherence (SFC) analysis revealed chronic visceral pain led to disruption of ACC spike timing and BLA local theta oscillation. Finally, cross-correlation analysis revealed that VH was associated with suppressed synchronization of theta oscillation between the BLA and ACC, indicating reduced neuronal communications between these two regions under the VH state. The present results demonstrate that functional disturbances in BLA-ACC neural circuitry may be relevant causes for the deficits in decision-making in chronic pain state.

There is considerable evidence to suggest early life experiences, such as maternal separation (MS), play a role in the prevalence of emotional dysregulation and cognitive impairment. At the same time, optimal decision making requires functional integrity between the amygdala and anterior cingulate cortex (ACC), and any dysfunction of this system is believed to induce decision-making deficits. However, the impact of MS on decision-making behavior and the underlying neurophysiological mechanisms have not been thoroughly studied. As such, we consider the impact of MS on the emotional and cognitive functions of rats by employing the open-field test, elevated plus-maze test, and rat gambling task (RGT). Using multi-channel recordings from freely behaving rats, we assessed the effects of MS on the large scale synchrony between the basolateral amygdala (BLA) and the ACC; while also characterizing the relationship between neural spiking activity and the ongoing oscillations in theta frequency band across the BLA and ACC. The results indicated that the MS rats demonstrated anxiety-like behavior. While the RGT showed a decrease in the percentage of good decision-makers, and an increase in the percentage of poor decision-makers. Electrophysiological data revealed an increase in the total power in the theta band of the LFP in the BLA and a decrease in theta power in the ACC in MS rats. MS was also found to disrupt the spike-field coherence of the ACC single unit spiking activity to the ongoing theta oscillations in the BLA and interrupt the synchrony in the BLA-ACC pathway. We provide specific evidence that MS leads to decision-making deficits that are accompanied by alteration of the theta band LFP in the BLA-ACC circuitries and disruption of the neural network integrity. These observations may help revise fundamental notions regarding neurophysiological biomarkers to treat cognitive impairment induced by early life stress.

BACKGROUND:Patients following prolonged cancer chemotherapy are at high risk of emotional and cognitive deficits. Research indicates that the brain neuronal temporal coding and synaptic long-term potentiation (LTP) are critical in memory and perception. We studied the effects of cisplatin on induction of LTP in the basolateral amygdala (BLA)-anterior cingulate cortex (ACC) pathway, characterized the coordination of spike timing with local theta oscillation, and identified synchrony in the BLA-ACC network integrity.RESULTS:In the study presented, the impacts of cisplatin on emotional and cognitive functions were investigated by elevated plus-maze test, Morris water maze test, and rat Iowa gambling task (RGT). Electrophysiological recordings were conducted to study long-term potentiation. Simultaneous recordings from multi-electrodes were performed to characterize the neural spike firing and ongoing theta oscillation of local field potential (LFP), and to clarify the synchronization of large scale of theta oscillation in the BLA-ACC pathway. Cisplatin-treated rats demonstrated anxiety- like behavior, exhibited impaired spatial reference memory. RGT showed decrease of the percentage of good decision-makers, and increase in the percentage of maladaptive behavior (delay-good decision-makers plus poor decision-makers). Cisplatin suppressed the LTP, and disrupted the phase-locking of ACC single neural firings to the ongoing theta oscillation; further, cisplatin interrupted the synchrony in the BLA-ACC pathway.CONCLUSIONS:We provide the first direct evidence that the cisplatin interrupts theta-frequency phase-locking of ACC neurons. The block of LTP and disruption of synchronized theta oscillations in the BLA-ACC pathway are associated with emotional and cognitive deficits in rats, following cancer chemotherapy.

The rodent anterior cingulate cortex (ACC) is critical for visceral pain and pain-related aversive response in chronic visceral hypersensitive (VH) state. Long-term potentiation (LTP), induced by theta burst stimulation (TBS) in the medial thalamus (MT)-ACC pathway, is blocked in VH rats. However, the neuronal intrinsic firing characteristics and the MT-ACC connectivity have not been investigated in visceral pain. Using repetitive distension of the colon and rectum (rCRD) as a sensitization paradigm, we have identified that the spontaneous firing rates of ACC neurons and the CRD-stimulated neuronal firings were increased after repetitive visceral noxious stimulation. This correlates with increases in visceral pain responses (visceromotor responses, VMRs). Two multichannel arrays of electrodes were implanted in the MT and ACC. Recordings were performed in free-moving rats before and after repeated CRD treatment. Power spectral density analysis showed that the local field potential (LFP) recorded in the ACC displayed increases in theta band power (4-10 Hz) that were modulated by rCRD. Neural spike activity in the ACC becomes synchronized with ongoing theta oscillations of LFP. Furthermore, cross correlation analysis showed augmented synchronization of thalamo-ACC theta band LFPs, which was consistent with an increase of neuronal communication between the two regions. In conclusion, these results reveal theta oscillations and theta-frequency phase-locking as prominent features of neural activity in the ACC and a candidate neural mechanism underlying acute visceral pain. (C) 2015 The Authors. Published by Elsevier Ltd. on behalf of IBRO.

Human studies have shown that multiple teeth loss was significantly associated with cognitive impairment, dementia and Alzheimer's disease. However, the causal relationship between tooth loss and cognitive deficits has not been clarified. Rodents demonstrate human-like cognitive faculties. In this study by performing rat gambling task (RGT), we reported that prolonged tooth loss condition by extracting all left molars in the rats led to an increase in the proportion of poor decision-makers, and decrease in the proportion of good decision-makers compared with controls. No influence was detected on the general activity and motivation after tooth loss. Recent experiments have shown that decision-making performances in the RGT rely on the functional integrity of the amygdala and anterior cingulate cortex (ACC). The theta band brain oscillation has been acknowledged for extensive cognitive functions. Here, we performed multiple-electrode array recordings of local field potential (LFP) in anesthetized rats. The results exhibited an increase in accumulative power of the theta frequency of LFP in the basolateral amygdala (BLA) and decrease of theta power in the ACC in tooth loss rats. Furthermore, cross-correlation analysis displayed that tooth loss suppressed the synchronization of theta frequency of LFP between the BLA and ACC, indicating reduced neuronal communications between these two regions. In conclusion, we demonstrate for the first time that tooth loss leads to higher-order cognitive deficits accompanied by the alteration of theta frequency of LFP in brain circuitries and disruption of neural network integrity.

Objective. Although electrode size should be miniaturized to provide higher selectivity for neural signal recording and to avoid tissue damage, small sized electrodes induce high impedance, which decreases recording quality. In this work, the electrode surface was modified to increase the effective surface area to lower the electrode impedance and to improve the neural signal detection quality by optimizing plasma conditions. Approach. A tetrafluoromethane (CF4) plasma was used to increase the effective surface area of gold electrode sites of polyimide-based neural probes. In vitro electrode impedance and in vivo neural signal recording and stimulation were characterized. Main results. For 15 mu m diameter (dia.) electrode size, the average surface roughness could be increased from 1.7 to 22 nm after plasma treatment, and the electrode impedance was decreased by 98%. Averaged background noise power in the range of 1 to 1000 Hz was decreased to -106 dB after the 30 mu m dia. electrodes were plasma modified-lower than the noise level of -86 dB without plasma treatment. Neural probes with plasma-modified electrode sites of 15 and 30 mu m dia. were implanted to the anterior cingulate cortex (ACC) region for acute recording of spontaneous and electrical evoked local field potential (LFP) of neural signals. Spontaneous LFP recorded in vivo by the plasma-modified electrodes of 30 mu m dia. was two times higher compared to electrodes without treatment. For a stimulation current of 400 mu A, electrically evoked LFP recorded by the plasma-modified electrodes was seven times higher than those without plasma exposure. Significance. A controllable technology was developed to increase the effective surface area of electrodes using a CF4 plasma. Plasma-modified electrodes improved the quality of the neural probe recording and more sensitive to record spontaneous and evoked LFP in the ACC region.