Short- and Long-Term High-Fat Diet Exposure Differentially Alters Phasic and Tonic GABAergic Signaling onto Lateral Orbitofrontal Pyramidal Neurons.

The chronic consumption of caloric dense high-fat foods is a major contributor to increased body weight, obesity, and other chronic health conditions. The orbitofrontal cortex (OFC) is critical in guiding decisions about food intake and is altered with diet-induced obesity. Obese rodents have altered morphologic and synaptic electrophysiological properties in the lateral orbitofrontal cortex (lOFC). Yet the time course by which exposure to a high-fat diet (HFD) induces these changes is poorly understood. Here, male mice are exposed to either short-term (7 d) or long-term (90 d) HFD. Long-term HFD exposure increases body weight, and glucose signaling compared with short-term HFD or a standard control diet (SCD). Both short and long-term HFD exposure increased the excitability of lOFC pyramidal neurons. However, phasic and tonic GABAergic signaling was differentially altered depending on HFD exposure length, such that tonic GABAergic signaling was decreased with early exposure to the HFD and phasic signaling was changed with long-term diet exposure. Furthermore, alterations in the short-term diet exposure were transient, as removal of the diet restored electrophysiological characteristics similar to mice fed SCD, whereas long-term HFD electrophysiological changes were persistent and remained after HFD removal. Finally, we demonstrate that changes in reward devaluation occur early with diet exposure. Together, these results suggest that the duration of HFD exposure differentially alters lOFC function and provides mechanistic insights into the susceptibility of the OFC to impairments in outcome devaluation.SIGNIFICANCE STATEMENT This study provides mechanistic insight on the impact of short-term and long-term high-fat diet (HFD) exposure on GABAergic function in the lateral orbitofrontal cortex (lOFC), a region known to guide decision-making. We find short-term HFD exposure induces transient changes in firing and tonic GABA action on lOFC pyramidal neurons, whereas long-term HFD induces obesity and has lasting changes on firing, tonic GABA and inhibitory synaptic transmission onto lOFC neurons. Given that GABAergic signaling in the lOFC can influence decision-making around food, these results have important implications in present society as palatable energy dense foods are abundantly available.

Post-activation depression from primary afferent depolarization (PAD) produces extensor H-reflex suppression following flexor afferent conditioning.

Suppression of the extensor H-reflex by flexor afferent conditioning is thought to be produced by a long-lasting inhibition of extensor Ia afferent terminals via GABAA receptor-activated primary afferent depolarization (PAD). Given the recent finding that PAD does not produce presynaptic inhibition of Ia afferent terminals, we examined in 28 participants if H-reflex suppression is instead mediated by post-activation depression of the extensor Ia afferents triggered by PAD-evoked spikes and/or by a long-lasting inhibition of the extensor motoneurons. A brief conditioning vibration of the flexor tendon suppressed both the extensor soleus H-reflex and the tonic discharge of soleus motor units out to 150 ms following the vibration, suggesting that part of the H-reflex suppression during this period was mediated by postsynaptic inhibition of the extensor motoneurons. When activating the flexor afferents electrically to produce conditioning, the soleus H-reflex was also suppressed but only when a short-latency reflex was evoked in the soleus muscle by the conditioning input itself. In mice, a similar short-latency reflex was evoked when optogenetic or afferent activation of GABAergic (GAD2+ ) neurons produced a large enough PAD to evoke orthodromic spikes in the test Ia afferents, causing post-activation depression of subsequent monosynaptic EPSPs. The long duration of this post-activation depression and related H-reflex suppression (seconds) was similar to rate-dependent depression that is also due to post-activation depression. We conclude that extensor H-reflex inhibition by brief flexor afferent conditioning is produced by both post-activation depression of extensor Ia afferents and long-lasting inhibition of extensor motoneurons, rather than from PAD inhibiting Ia afferent terminals. KEY POINTS: Suppression of extensor H-reflexes by flexor afferent conditioning was thought to be mediated by GABAA receptor-mediated primary afferent depolarization (PAD) shunting action potentials in the Ia afferent terminal. In line with recent findings that PAD has a facilitatory role in Ia afferent conduction, we show here that when large enough, PAD can evoke orthodromic spikes that travel to the Ia afferent terminal to evoke EPSPs in the motoneuron. These PAD-evoked spikes also produce post-activation depression of Ia afferent terminals and may mediate the short- and long-lasting suppression of extensor H-reflexes in response to flexor afferent conditioning. Our findings highlight that we must re-examine how changes in the activation of GABAergic interneurons and PAD following nervous system injury or disease affects the regulation of Ia afferent transmission to spinal neurons and ultimately motor dysfunction in these disorders.

Locomotor-related propriospinal V3 neurons produce primary afferent depolarization and modulate sensory transmission to motoneurons.

When a muscle is stretched, sensory feedback not only causes reflexes but also leads to a depolarization of sensory afferents throughout the spinal cord (primary afferent depolarization, PAD), readying the whole limb for further disturbances. This sensory-evoked PAD is thought to be mediated by a trisynaptic circuit, where sensory input activates first-order excitatory neurons that activate GABAergic neurons that in turn activate GABAA receptors on afferents to cause PAD, though the identity of these first-order neurons is unclear. Here, we show that these first-order neurons include propriospinal V3 neurons, as they receive extensive sensory input and in turn innervate GABAergic neurons that cause PAD, because optogenetic activation or inhibition of V3 neurons in mice mimics or inhibits sensory-evoked PAD, respectively. Furthermore, persistent inward sodium currents intrinsic to V3 neurons prolong their activity, explaining the prolonged duration of PAD. Also, local optogenetic activation of V3 neurons at one segment causes PAD in other segments, due to the long propriospinal tracts of these neurons, helping to explain the radiating nature of PAD. This in turn facilitates monosynaptic reflex transmission to motoneurons across the spinal cord. In addition, V3 neurons directly innervate proprioceptive afferents (including Ia), causing a glutamate receptor-mediated PAD (glutamate PAD). Finally, increasing the spinal cord excitability with either GABAA receptor blockers or chronic spinal cord injury causes an increase in the glutamate PAD. Overall, we show the V3 neuron has a prominent role in modulating sensory transmission, in addition to its previously described role in locomotion.NEW & NOTEWORTHY Locomotor-related propriospinal neurons depolarize sensory axons throughout the spinal cord by either direct glutamatergic axoaxonic contacts or indirect innervation of GABAergic neurons that themselves form axoaxonic contacts on sensory axons. This depolarization (PAD) increases sensory transmission to motoneurons throughout the spinal cord, readying the sensorimotor system for external disturbances. The glutamate-mediated PAD is particularly adaptable, increasing with either an acute block of GABA receptors or chronic spinal cord injury, suggesting a role in motor recovery.

Associations between overactive bladder and sleep patterns: a cross-sectional study based on 2007-2014 NHANES.

OBJECTIVES: To determine whether relationship exists between overactive bladder (OAB) and sleep patterns through the cross-sectional study. PATIENTS AND METHODS: Patients from the National Health and Nutrition Examination Survey (NHANES) 2007-2014 were included in this study. Data were extracted through questionnaires, including demographics, dietary and health-related behaviors, body measurements and disease information. Three sleep factors were included to aggregate overall sleep scores, ranging from 0 to 3. A sleep score of 0 to 1, 2 or 3 was expressed as a bad, intermediate or healthy sleep pattern, respectively. The Overactive Bladder Symptom Score (OABSS) scale was applied to quantify the severity of OAB for each participant. Weighted logistic regression models were used to investigate the associations between sleep and OAB. RESULTS: A total of 16,978 participants were enrolled in this study. The relationship between OAB and sleep patterns was statistically significant. After fully adjusting for confounding factors, the OAB risk of patients with intermediate and poor sleep patterns obviously increased by 26% and 38%, respectively, and mild (OR = 1.21, 95% CI [1.03,1.42]), moderate (OR = 1.45, 95% CI [1.27,1.66]) and severe (OR = 1.57, 95% CI [1.18,2.09]) OAB were significantly associated with sleep pattern grouping. The prevalence of OAB is significantly higher in patients with bad sleep patterns, and vice versa. CONCLUSION: This study indicated that there is a positive relationship between OAB and worse sleep-related issues.

The effect of applying telehealth education to home care of infants after congenital heart disease surgery.

BACKGROUND: The purpose of this study was to investigate the effect of applying telehealth education to home care of infants after congenital heart disease (CHD) surgery. METHODS: A prospective randomized controlled study was conducted from July 2020 to February 2021 in Fujian Children's Hospital to compare the home care condition of infants after CHD surgery between the intervention group and the control group. RESULTS: At 3 months after discharge, parents' caring ability and CHD knowledge in the intervention group were significantly better than those in the control group and were significantly improved compared with those at discharge time (P < 0.05). The parental care burden in the intervention group was significantly lower than that in the control group and was significantly lower than that at discharge time (P < 0.05). During the follow-up period, the rate of loss of follow-up and complications in the intervention group were significantly lower than those in the control group (P < 0.05). CONCLUSION: Telehealth education via WeChat can effectively improve the knowledge of disease and home care ability of parents of infants after CHD surgery and reduce their home care burden, which can effectively reduce the incidence of complications and lost to follow-up rate after discharge.

Rescue high-frequency oscillatory ventilation combined with intermittent mandatory ventilation for infants with acute respiratory distress syndrome after congenital heart surgery.

BACKGROUND: This study aimed to evaluate the efficacy and safety of high-frequency oscillation ventilation combined with intermittent mandatory ventilation in infants with acute respiratory distress syndrome after congenital heart surgery. METHODS: We retrospectively analysed the clinical data of 32 infants who were ventilated due to acute respiratory distress syndrome after congenital heart surgery between January, 2020 and January, 2022. We adopted high-frequency oscillation ventilation combined with intermittent mandatory ventilation as the rescue ventilation mode for infants who were failing conventional mechanical ventilation. RESULTS: After rescue high-frequency oscillation ventilation combined with intermittent mandatory ventilation, the dynamic compliance (Cdyn), PaO2 and PaO2/FiO2 ratio of the infants improved compared with conventional mechanical ventilation (p < 0.05). Moreover, high-frequency oscillation ventilation combined with intermittent mandatory ventilation resulted in a significant decrease in arterial-alveolar oxygen difference (AaDO2), FiO2, and oxygenation index (p < 0.05). No significant effect on haemodynamic parameters was observed. Moreover, no serious complications occurred in the two groups. CONCLUSION: Rescue high-frequency oscillation ventilation combined with intermittent mandatory ventilation significantly improved oxygenation in infants who failed conventional mechanical ventilation for acute respiratory distress syndrome after congenital heart surgery. Thus, this strategy is considered safe and feasible. However, further studies must be conducted to confirm the efficacy and safety of high-frequency oscillation ventilation combined with intermittent mandatory ventilation as a rescue perioperative respiratory support strategy for CHD.

The Association Between Religious Belief and Postoperative Psychological Status and Quality of Life of Parents of Children with Congenital Heart Disease: A Single Center Experience in Southeast China.

This study aimed to investigate the association of religious belief on the postoperative psychological status and quality of life of parents of children with congenital heart disease (CHD). This was a cross-sectional study conducted at a provincial children's hospital in Fujian Province, China. Parents of postoperative children with CHD in the early postoperative period were included in this study between January 2020 and September 2020. The parents were divided into a religious belief group (n = 39) and a nonreligious belief group (n = 42) depending on whether they had religious beliefs. The Religious Coping Questionnaire, WHOQOL-BREF scale, Self-rating depression scale (SDS), and Self-rating anxiety scale (SAS) were used to evaluate psychological status and quality of life. The results showed that the SDS and SAS scores in the religious belief group were significantly lower than those in the nonreligious belief group (P = 0.012 and P = 0.003, respectively). The WHOQOL-BREF scale results showed that the religious belief group's score was significantly higher than those in the nonreligious belief group on the subscale scores of physiology, psychology, social relations, and environment on the WHOQOL-BREF. The total score of quality of life in the religious belief group was significantly higher than that in the nonreligious belief group. Religious belief was associated with lower SDS score (ß = - 0.324, P = 0.005) and SAS score (ß = - 0.245, P = 0.026), while religious belief was positively correlated with the score of WHOQOL-BREF (ß = 0.506, P < 0.001). In this study, we concluded that comparing to those with no religious beliefs, parents with religious belief experienced more positive emotions and higher quality of life when taking care of children in the early postoperative period after congenital heart surgery.

Effect of High-Frequency Oscillatory Ventilation, Combined With Prone Positioning, in Infants With Acute Respiratory Distress Syndrome After Congenital Heart Surgery: A Prospective Randomized Controlled Trial.

OBJECTIVES: This study aimed to evaluate the effect of high-frequency oscillatory ventilation, (HFOV) combined with prone positioning, on oxygenation and pulmonary ventilation in infants with acute respiratory distress syndrome (ARDS) after congenital heart surgery. DESIGN: A randomized controlled trial. SETTING: A single-center study at a tertiary teaching hospital. PARTICIPANTS: Patients with postoperative ARDS after congenital heart disease were divided randomly into the following 2 groups: HFOV combined with prone position (HFOV-PP), and HFOV combined with supine position (HFOV-SP). INTERVENTIONS: The primary outcomes were the PaO2/FIO2 ratio and the oxygenation index after the intervention, and the secondary outcomes were respiratory variables, hemodynamics, complications, and other short-term outcomes. RESULTS: Sixty-five eligible infants with ARDS were randomized to either the HFOV-PP (n = 32) or HFOV-SP (n = 33) group. No significant difference in baseline data was found between the 2 groups (p > 0.05). Oxygenation was improved in both groups after HFOV intervention. Compared with the HFOV-SP group, the HFOV-PP group had significantly increased PaO2/FIO2 and oxygenation index and a shorter duration of invasive ventilation and length of cardiac intensive care unit stay. No serious complications occurred in the 2 groups. CONCLUSION: HFOV-PP significantly improved oxygenation in infants with ARDS after cardiac surgery and had no serious complications.

Unplanned Return to Cardiac Intensive Care Unit of Children After Congenital Heart Surgery: Incidence, Outcomes, and Risk Factors.

OBJECTIVE: Factors leading to an unplanned return to the cardiac intensive care unit (CICU) in children after congenital heart disease and their impact on mortality have not been well characterized. We sought to determine the incidence and outcomes of unplanned return to the CICU. A secondary objective was to identify risk factors. METHODS: Retrospective analysis of the registration data collected by our unit. The study subjects included postoperative patients with congenital heart disease who survived to initial transfer out of the CICU. Patients who unexpectedly returned to the CICU due to an acute change in clinical status were defined as unplanned returns. Demographic, preoperative, intraoperative, and postoperative variables were assessed. Univariate comparisons were performed between the return group and non-return group, and multivariate regression analysis was performed to identify potential risk factors for unplanned return to the CICU. RESULTS: Of the 531 children who met the inclusion criteria, 29 were unplanned returns to the CICU. Respiratory symptoms (41.4%) and cardiac symptoms (44.8%) were the most common reasons for returning to the CICU. Patients with unplanned returns had a higher mortality rate (13.8% vs. 0.56%, P < 0.01). In multivariate analysis, unplanned CICU admission was associated with chromosomal abnormalities (P < 0.01), longer ventilator duration (P < 0.01), and more prolonged cardiopulmonary bypass (P < 0.01) was associated with a return to independence. CONCLUSIONS: Unplanned return to the CICU during the same hospital stay was uncommon but associated with higher mortality. Chromosomal abnormalities, longer ventilator use duration, and prolonged CPB were significant risk factors for the entire cohort. We hope to minimize the impact of unplanned return after congenital heart disease surgery by changing the process of transferring these high-risk postoperative patients out of the CICU and early postoperative care.

Short-Term Nutritional Support Improves The Preoperative Nutritional Status of Infants With Non-Restrictive Ventricular Septal Defect: A Prospective Controlled Study.

OBJECTIVE: To investigate the effect of short-term nutritional support on improving preoperative nutritional status of infants with non-restrictive ventricular septal defect. METHODS: A prospective randomized controlled study was conducted from June 2021 to December 2021 at a provincial children's hospital in China. The difference of nutritional status between the intervention group and the control group after short-term nutritional support was compared. RESULTS: After one month of nutritional support, the weight, STRONGkids score, albumin, prealbumin, and hemoglobin in the intervention group significantly were higher than those in the control group (P < 0.05). The postoperative intensive care time and discharge time of the two groups significantly were lower in the intervention group than those in the control group (P < 0.05). CONCLUSION: The preoperative nutritional support of 1 month for infants with non-restrictive ventricular septal defect can effectively improve their preoperative nutritional status and promote postoperative recovery.

Application of High-Frequency Oscillation Ventilation Combined With Volume Guarantee in Preterm Infants With Acute Hypoxic Respiratory Failure After Patent Ductus Arteriosus Ligation.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of high-frequency oscillation ventilation combined with volume guarantee (HFOV-VG) in preterm infants with acute hypoxemic respiratory failure (AHRF) after patent ductus arteriosus ligation. METHODS: We retrospectively analyzed the clinical data of 41 preterm infants, who were ventilated for AHRF after patent ductus arteriosus ligation between January 2020 and January 2022. HFOV alone was used in 20 of the 41 infants, whereas HFOV-VG was used in the other 21 infants. RESULTS: There was no statistically significant difference in the demographic information and baseline characteristics of preterm infants included in the study. The average frequency tidal volume (VThf) of the HFOV-VG group was lower than that of the HFOV group (2.6 ± 0.6 mL versus 1.9 ± 0.3 mL, P < .001). In addition, the incidence of hypocapnia and hypercapnia in infants supported with HFOV-VG was significantly lower (15 versus 8, P < .001; 12 versus 5, P < .001). Furthermore, the duration of invasive ventilation in the HFOV-VG group also was lower than in the HFOV group (3.7 ± 1.2 days versus 2.1 ± 1.0 days, P < .01). CONCLUSION: Compared with HFOV alone, HFOV-VG decreases VThf levels and reduces the incidence of hypercapnia and hypocapnia in preterm infants with acute hypoxic respiratory failure after patent ductus arteriosus ligation.

The Interventricular Septal Hematoma Following Surgical Correction of Ventricular Septal Defect in Infants: A Single-Center Experience.

OBJECTIVE: To review and analyze the cases of interventricular septal hematoma (IVSH) following surgical correction of the ventricular septal defect (VSD) in infants in our center. METHODS: Retrospective analysis was performed on five infants with IVSH after surgical correction of VSD in our center from January 2020 to January 2022. The general preoperative information and intraoperative and postoperative results were collected and analyzed. RESULTS: All five infants with VSD were repaired under cardiopulmonary bypass and occurred IVSH. The cardiac arrest occurred in one patient five hours after return to the intensive care unit (ICU). The patient's hemodynamics were difficult to maintain after cardiopulmonary resuscitation, and the patient died. Two other patients had arrhythmia and unstable hemodynamics during the perioperative period, the hematoma puncture was performed, and the patients' symptoms lessened. Perioperative and postoperative echocardiography showed that the hematoma gradually was shrunk, and the hemodynamics became stable. The hemodynamics were stable in the remaining two infants during the perioperative period. No specific medical intervention was required other than clinical observation in these two patients. Finally, the four infants successfully were discharged with good clinical results. CONCLUSION: IVSH is a rare complication of surgical repair of VSD. Prevention and early detection of IVSH during operation in infants with VSD are essential.

Subepicardial lipoma of the posterior atrioventricular sulcus in children: a case report and review of the literature.

Cardiac lipoma is rarely reported in the pediatric population. We reported a case of subepicardial lipoma of the posterior atrioventricular sulcus in a child. The tumor was resected successfully and the patient recovered well after the operation.

5-HT1D receptors inhibit the monosynaptic stretch reflex by modulating C-fiber activity.

The monosynaptic stretch reflex (MSR) plays an important role in feedback control of movement and posture but can also lead to unstable oscillations associated with tremor and clonus, especially when increased with spinal cord injury (SCI). To control the MSR and clonus after SCI, we examined how serotonin regulates the MSR in the sacrocaudal spinal cord of rats with and without a chronic spinal transection. In chronic spinal rats, numerous 5-HT receptor agonists, including zolmitriptan, methylergonovine, and 5-HT, inhibited the MSR with a potency highly correlated to their binding affinity to 5-HT1D receptors and not other 5-HT receptors. Selective 5-HT1D receptor antagonists blocked this agonist-induced inhibition, although antagonists alone had no action, indicating a lack of endogenous or constitutive receptor activity. In normal uninjured rats, the MSR was likewise inhibited by 5-HT, but at much higher doses, indicating a supersensitivity after SCI. This supersensitivity resulted from the loss of the serotonin transporter SERT with spinal transection, because normal and injured rats were equally sensitive to 5-HT after SERT was blocked or to agonists not transported by SERT (zolmitriptan). Immunolabeling revealed that the 5-HT1D receptor was confined to superficial lamina of the dorsal horn, colocalized with CGRP-positive C-fibers, and eliminated by dorsal rhizotomy. 5-HT1D receptor labeling was not found on large proprioceptive afferents or α-motoneurons of the MSR. Thus serotonergic inhibition of the MSR acts indirectly by modulating C-fiber activity, opening up new possibilities for modulating reflex function and clonus via pain-related pathways. NEW & NOTEWORTHY Brain stem-derived serotonin potently inhibits afferent transmission in the monosynaptic stretch reflex. We show that serotonin produces this inhibition exclusively via 5-HT1D receptors, and yet these receptors are paradoxically mostly confined to C-fibers. This suggests that serotonin acts by gating of C-fiber activity, which in turn modulates afferent transmission to motoneurons. We also show that the classic supersensitivity to 5-HT after spinal cord injury results from a loss of SERT, and not 5-HT1D receptor plasticity.

Locomotor-related V3 interneurons initiate and coordinate muscles spasms after spinal cord injury.

Spinal cord injury leads to a devastating loss of motor function and yet is accompanied by a paradoxical emergence of muscle spasms, which often involve complex muscle activation patterns across multiple joints, reciprocal muscle timing, and rhythmic clonus. We investigated the hypothesis that spasms are a manifestation of partially recovered function in spinal central pattern-generating (CPG) circuits that normally coordinate complex postural and locomotor functions. We focused on the commissural propriospinal V3 neurons that coordinate interlimb movements during locomotion and examined mice with a chronic spinal transection. When the V3 neurons were optogenetically activated with a light pulse, a complex coordinated pattern of motoneuron activity was evoked with reciprocal, crossed, and intersegmental activity. In these same mice, brief sensory stimulation evoked spasms with a complex pattern of activity very similar to that evoked by light, and the timing of these spasms was readily reset by activation of V3 neurons. Given that V3 neurons receive abundant sensory input, these results suggest that sensory activation of V3 neurons is alone sufficient to generate spasms. Indeed, when we silenced V3 neurons optogenetically, sensory evoked spasms were inhibited. Also, inhibiting general CPG activity by blocking N-methyl-d-aspartate (NMDA) receptors inhibited V3 evoked activity and associated spasms, whereas NMDA application did the opposite. Furthermore, overwhelming the V3 neurons with repeated optogenetic stimulation inhibited subsequent sensory evoked spasms, both in vivo and in vitro. Taken together, these results demonstrate that spasms are generated in part by sensory activation of V3 neurons and associated CPG circuits. NEW & NOTEWORTHY We investigated whether locomotor-related excitatory interneurons (V3) play a role in coordinating muscle spasm activity after spinal cord injury (SCI). Unexpectedly, we found that these neurons not only coordinate reciprocal motor activity but are critical for initiating spasms, as well. More generally, these results suggest that V3 neurons are important in initiating and coordinating motor output after SCI and thus provide a promising target for restoring residual motor function.

Extrasynaptic α5GABAA receptors on proprioceptive afferents produce a tonic depolarization that modulates sodium channel function in the rat spinal cord.

Activation of GABAA receptors on sensory axons produces a primary afferent depolarization (PAD) that modulates sensory transmission in the spinal cord. While axoaxonic synaptic contacts of GABAergic interneurons onto afferent terminals have been extensively studied, less is known about the function of extrasynaptic GABA receptors on afferents. Thus, we examined extrasynaptic α5GABAA receptors on low-threshold proprioceptive (group Ia) and cutaneous afferents. Afferents were impaled with intracellular electrodes and filled with neurobiotin in the sacrocaudal spinal cord of rats. Confocal microscopy was used to reconstruct the afferents and locate immunolabelled α5GABAA receptors. In all afferents α5GABAA receptors were found throughout the extensive central axon arbors. They were most densely located at branch points near sodium channel nodes, including in the dorsal horn. Unexpectedly, proprioceptive afferent terminals on motoneurons had a relative lack of α5GABAA receptors. When recording intracellularly from these afferents, blocking α5GABAA receptors (with L655708, gabazine, or bicuculline) hyperpolarized the afferents, as did blocking neuronal activity with tetrodotoxin, indicating a tonic GABA tone and tonic PAD. This tonic PAD was increased by repeatedly stimulating the dorsal root at low rates and remained elevated for many seconds after the stimulation. It is puzzling that tonic PAD arises from α5GABAA receptors located far from the afferent terminal where they can have relatively little effect on terminal presynaptic inhibition. However, consistent with the nodal location of α5GABAA receptors, we find tonic PAD helps produce sodium spikes that propagate antidromically out the dorsal roots, and we suggest that it may well be involved in assisting spike transmission in general. NEW & NOTEWORTHY GABAergic neurons are well known to form synaptic contacts on proprioceptive afferent terminals innervating motoneurons and to cause presynaptic inhibition. However, the particular GABA receptors involved are unknown. Here, we examined the distribution of extrasynaptic α5GABAA receptors on proprioceptive Ia afferents. Unexpectedly, these receptors were found preferentially near nodal sodium channels throughout the afferent and were largely absent from afferent terminals. These receptors produced a tonic afferent depolarization that modulated sodium spikes, consistent with their location.

Identification and validation of cuproptosis and disulfidptosis related genes in colorectal cancer.

Colorectal cancer, the third most prevalent malignant cancer, is associated with poor prognosis. Recent studies have investigated the mechanisms underlying cuproptosis and disulfidptosis in colorectal cancer. However, whether genes linked to these processes impact the prognosis of colorectal cancer patients through analogous mechanisms remains unclear. In this study, we developed a model of cuproptosis and disulfidptosis in colorectal cancer and concurrently explored the role of the pivotal model gene HSPA8 in colorectal cancer cell lines. Our results revealed a positive correlation between cuproptosis and disulfidptosis, both of which are emerging as protective factors for the prognosis of CRC patients. Consequently, a prognostic model encompassing HSPA8, PDCL3, CBX3, ATP6V1G1, TAF1D, RPL4, and RPL14 was constructed. Notably, the key gene in our model, HSPA8, exhibited heightened expression and was validated as a protective prognostic factor in colorectal cancer, exerting inhibitory effects on colorectal cancer cell proliferation. This study offers novel insights into the interplay between cuproptosis and disulfidptosis. The application of the prognostic model holds promise for more effectively predicting the overall survival of colorectal cancer patients.

Tricuspid mechanical valve replacement for severe tricuspid stenosis in a child who underwent surgical correction of complete atrioventricular septal defect, a rare long-term complications.

BACKGROUND: Complete atrioventricular septal defect is a complicated congenital heart malformations, and surgical correction is the best treatment, the severe tricuspid stenosis is a rare long-term complication after the surgery. CASE PRESENTATION: We report a case with the complication of severe tricuspid stenosis 7 years after the surgical correction of complete atrioventricular septal defect in a child. Then the patient underwent tricuspid mechanical valve replacement, Glenn, atrial septostomy, and circumconstriction of the right pulmonary artery. CONCLUSIONS: The patient recovered successfully with good short-term.

Cognitive Impairment Mechanism in Patients with Bipolar Disorder.

Bipolar disorder (BD) is a common chronic mental disorder usually characterized by manic, hypomanic and depressive episodes. Patients diagnosed with BD have cognitive impairments in both the mood attack and remission stages, that is impairment of attention, memory and executive function. Up till the present moment, the causative mechanisms of cognitive impairment in BD patients remain poorly understood. Several studies have demonstrated that cognitive impairment in patients with bipolar disorder is not associated with a single factor, but with gene polymorphism, brain structural and functional variables, inflammatory and metabolic factors. Herein, we reviewed and summarized the recent reports on cognitive impairment mechanisms in patients with BD. To prevent or alleviate cognitive damage at an early stage, we propose that future research should focus on investigating the pathological mechanism of specific cognitive dimension damage as well as the pathological mechanism network between the damage of each dimension. It is crucial to recognize mechanisms of cognitive impairment for improving the symptoms and prognosis of BD patients, restoring their social function and integration.

Parents' understanding and attitudes toward the use of the WeChat platform for postoperative follow-up management of children with congenital heart disease.

OBJECTIVE: This study aimed to investigate parents' understanding and attitudes toward using the WeChat platform for postoperative follow-up management of children with congenital heart disease (CHD). METHODS: A total of 196 children with CHD were followed up using the WeChat platform. A self-designed questionnaire was administered to their parents at discharge. RESULTS: Only 188 parents completed the questionnaire. One hundred nineteen parents (63.3%) confirmed that they heard about using the WeChat platform for postoperative follow-up, and 104 (87.4%) of them expressed that they were willing to accept the WeChat platform for their follow-up. A total of 42 parents (35.3%) were willing to undergo a follow-up of 1 to 3 months, and 32 (26.8%) were willing to undergo a long-term follow-up. Eighty parents (67.2%) had a positive attitude toward the effect of the WeChat platform on follow-up. Parents in rural areas and those educated at the middle school level or below were more willing to engage with the WeChat platform for postoperative follow-up management (P < 0.05). CONCLUSIONS: Although the WeChat platform is an essential tool for daily communication, its application in postoperative follow-up management is still under study. Most parents who participated in the follow-up study had a positive attitude toward the WeChat platform, especially those in rural areas and with lower education levels.