Betaine improves appetite regulation and glucose-lipid metabolism in mandarin fish (Siniperca chuatsi) fed a high-carbohydrate-diet by regulating the AMPK/mTOR signaling.

Diets with high carbohydrate (HC) was reported to have influence on appetite and intermediary metabolism in fish. To illustrate whether betaine could improve appetite and glucose-lipid metabolism in aquatic animals, mandarin fish (Siniperca chuatsi) were fed with the HC diets with or without betaine for 8 weeks. The results suggested that betaine enhanced feed intake by regulating the hypothalamic appetite genes. The HC diet-induced downregulation of AMPK and appetite genes was also positively correlated with the decreased autophagy genes, suggesting a possible mechanism that AMPK/mTOR signaling might regulate appetite through autophagy. The HC diet remarkably elevated transcriptional levels of genes related to lipogenesis, while betaine alleviated the HC-induced hepatic lipid deposition. Additionally, betaine supplementation tended to store the energy storage as hepatic glycogen. Our findings proposed the possible mechanism for appetite regulation through autophagy via AMPK/mTOR, and demonstrated the feasibility of betaine as an aquafeed additive to regulate appetite and intermediary metabolism in fish.

Dietary Betaine Attenuates High-Carbohydrate-Diet-Induced Oxidative Stress, Endoplasmic Reticulum Stress, and Apoptosis in Mandarin Fish (Siniperca chuatsi).

To investigate the impact of betaine on high-carbohydrate-diet-induced oxidative stress and endoplasmic reticulum (ER) stress, mandarin fish (Siniperca chuatsi) (23.73 ± 0.05 g) were fed with control (NC), betaine (BET), high carbohydrate (HC), and high carbohydrate + betaine (HC + BET) diets for 8 weeks. The results showed that betaine significantly promoted the growth of mandarin fish irrespective of the dietary carbohydrate levels. The HC diet induced oxidative stress, as evidenced by significantly elevated MDA levels. The HC diet significantly stimulated the mRNA levels of genes involved in ER stress (ire1, perk, atf6, xbp1, eif2α, atf4, chop), autophagy (ulk1, becn1, lc3b), and apoptosis (bax). However, betaine mitigated HC-diet-induced oxidative stress by modulating antioxidant enzymes and alleviated ER stress by regulating the mRNA of genes in the PERK-eIF2a-ATF4 pathway. Additionally, betaine significantly reduced the mRNA levels of becn1 and bax, along with the apoptosis rate, indicating a mitigating effect on autophagy and apoptosis. Overall, dietary betaine improved growth, attenuated HC-diet-induced oxidative stress and ER stress, and ultimately alleviated apoptosis in mandarin fish. These findings provide evidence for the use of betaine in aquafeeds to counter disruptive effects due to diets containing high carbohydrate levels.

Automated mandatory bolus versus basal infusion for maintenance of epidural analgesia in labour.

BACKGROUND: Epidural analgesia is often used for pain relief during labour and childbirth, and involves administration of local anaesthetics (LA) into the epidural space resulting in sensory blockade of the abdomen, pelvis, and perineum. Epidural opioids are often co-administered to improve analgesia. Administration of epidural medications can be accomplished by basal infusion (BI) or automated mandatory bolus (AMB). With BI, medications are administered continuously, while AMB involves injecting medications at set time intervals. Patient-controlled epidural analgesia (PCEA) on top of AMB or BI enables patients to initiate additional boluses of epidural medications.  The superior method of delivering epidural medications would result in lower incidence of pain requiring anaesthesiologist intervention (breakthrough pain). Also, it should be associated with lower incidence of epidural-related adverse effects including caesarean delivery, instrumental delivery (use of forceps or vacuum devices), prolonged duration of labour analgesia, and LA consumption. However, clear evidence of the superiority of one technique over the other is lacking. Also, differences in the initiation of epidural analgesia such as combined spinal-epidural (CSE) (medications given into the intrathecal space in addition to the epidural space) compared to epidural only, and medications used (types and doses of LA or opioids) may not have been accounted for in previous reviews.  Our prior systematic review suggested that AMB reduces the incidence of breakthrough pain compared to BI with no significant difference in the incidence of caesarean delivery or instrumental delivery, duration of labour analgesia, and LA consumption. However, several studies comparing AMB and BI have been performed since then, and inclusion of their data may improve the precision of our effect estimates. OBJECTIVES: To assess the benefits and harms of AMB versus BI for maintaining labour epidural analgesia in women at term. SEARCH METHODS: We searched CENTRAL, Wiley Cochrane Library), MEDLINE, (National Library of Medicine), Embase(Elseiver), Web of Science (Clarivate), the WHO-ICTRP (World Health Organization) and ClinicalTrials.gov (National Library of Medicine) on 31 December 2022. Additionally, we screened the reference lists of relevant trials and reviews for eligible citations, and we contacted authors of included studies to identify unpublished research and ongoing trials. SELECTION CRITERIA: We included all randomised controlled studies that compared bolus dosing AMB with continuous BI during epidural analgesia. We excluded studies of women in preterm labour, with multiple pregnancies, with fetal malposition, intrathecal catheters, those that did not use automated delivery of medications, and those where AMB and BI were combined. DATA COLLECTION AND ANALYSIS: We used standard methodology for systematic review and meta-analysis described by Cochrane. Primary outcomes included: incidence of breakthrough pain requiring anaesthesiologist intervention; incidence of caesarean delivery; and incidence of instrumental delivery. Secondly, we assessed the duration of labour; hourly LA consumption in bupivacaine equivalents, maternal satisfaction after fetal delivery, and neonatal Apgar scores.  The following subgroup analyses were chosen a priori: epidural alone versus CSE technique; regimens that used PCEA versus those that did not; and nulliparous versus combination of nulli- and multi-parous women. We used the GRADE system to assess the certainty of evidence associated with our outcome measures. MAIN RESULTS: We included 18 studies of 4590 women, of which 13 enrolled healthy nulliparous women and five included healthy nulli- and multiparous women. All studies excluded women with preterm or complicated pregnancies. Techniques used to initiate epidural analgesia differed between the studies: seven used combined spinal epidural, 10 used epidural, and one used dural puncture epidural (DPE). There was also variation in analgesics used. Eight studies utilised ropivacaine with fentanyl, three used ropivacaine with sufentanil, two utilised levobupivacaine with sufentanil, one used levobupivacaine with fentanyl, and four utilised bupivacaine with fentanyl. Most of the studies were assessed to have low risk of randomisation, blinding, attrition, and reporting biases, except for allocation concealment where eight studies were assessed to have uncertain risk and three with high risk. Our results showed that AMB was associated with lower incidence of breakthrough pain compared to BI (risk ratio (RR) 0.71; 95% confidence interval (CI) 0.55 to 0.91; I2 = 57%) (16 studies, 1528 participants), and lower hourly LA consumption in bupivacaine equivalents (mean difference (MD) -0.84 mg/h; 95% CI -1.29 to -0.38, I2 = 87%) (16 studies, 1642 participants), both with moderate certainty. AMB was associated with an estimated reduction in breakthrough pain incidence of 29.1% (incidence 202 per 1000, 95% CI 157 to 259), and was therefore considered clinically significant. The incidence of caesarean delivery (RR 0.85; 95% CI 0.69 to 1.06; I2 = 0%) (16 studies, 1735 participants) and instrumental delivery (RR 0.85; 95% CI 0.71 to 1.01; I2 = 0%) (17 studies, 4550 participants) were not significantly, both with moderate certainty. There was no significant difference in duration of labour analgesia (MD -8.81 min; 95% CI -19.38 to 1.77; I2 = 50%) (17 studies, 4544 participants) with moderate certainty. Due to differences in the methods and timing of outcome measurements, we did not pool data for maternal satisfaction and Apgar scores. Results reported narratively suggest AMB may be associated with increased maternal satisfaction (eight studies reported increased satisfaction and six reported no difference), and all studies showed no difference in Apgar scores. WIth the exception of epidural alone versus CSE which found significant subgroup differences in LA consumption between AMB and BI, no significant differences were detected in the remaining subgroup analyses. AUTHORS' CONCLUSIONS: Overall, AMB is associated with lower incidence of breakthrough pain, reduced LA consumption, and may improve maternal satisfaction. There were no significant differences between AMB and BI in the incidence of caesarean delivery, instrumental delivery, duration of labour analgesia, and Apgar scores. Larger studies assessing the incidence of caesarean and instrumental delivery are required.

Association of Pain Catastrophizing with Postnatal Depressive States in Nulliparous Parturients: A Prospective Study.

PURPOSE: Postnatal depression (PND) is associated with maternal morbidity and socioeconomic burden. Recent studies have shown an association between pain catastrophizing, increased labor pain, and subsequent adverse postnatal adjustment; however, little is known on its role in PND development. We aimed to investigate the association between pain catastrophizing and probable PND. METHODS: Parturients planning to undergo epidural labor analgesia were recruited. Predelivery questionnaires, including the Pain Catastrophizing Scale (PCS) and Edinburgh Postnatal Depression Scale (EPDS), were administered during early labor. A phone survey at 5- 9 weeks postdelivery was conducted to determine postdelivery EPDS and Spielberger's State-Trait-Anxiety Inventory scores. The primary outcome was a binary variable of postdelivery EPDS with cutoff of ≥10, whereas the secondary outcome was a continuous variable on increases in EPDS score. RESULTS: Probable PND (EPDS ≥10) occurred in 10.5% (95% CI 8.0%-13.5%, 55 of 525) of women who underwent epidural labor analgesia. We found that high pain catastrophizing (PCS ≥25) was associated with increased postdelivery EPDS scores (adjusted ß estimate 0.36, 95% CI 0.15-0.57; p=0.0008), but did not meet significance for increased risk of probable PND (p=0.1770). Additionally, presence of breakthrough pain during epidural analgesia (adjusted ß estimate 0.24, 95% CI 0.02-0.46; p=0.0306) and lower BMI at term (adjusted ß estimate -0.04, 95% CI -0.07 to -0.01; p=0.0055) were associated with increased postdelivery EPDS scores. CONCLUSION: No significant association was found between high pain catastrophizing and probable PND; however, high predelivery pain catastrophizing, presence of breakthrough pain during epidural analgesia, and lower BMI at term were associated with increased postdelivery EPDS scores. Further research will be needed to validate this association in the context of the risk of PND development.

Automated mandatory bolus versus basal infusion for maintenance of epidural analgesia in labour.

BACKGROUND: Childbirth may cause the most severe pain some women experience in their lifetime. Epidural analgesia is an effective form of pain relief during labour and is considered to be the reference standard. Traditionally epidural analgesia has been delivered as a continuous infusion via a catheter in the epidural space, with or without the ability for the patient to supplement the analgesia received by activating a programmable pump to deliver additional top-up doses, known as patient-controlled epidural analgesia (PCEA). There has been interest in delivering maintenance analgesic medication via bolus dosing (automated mandatory bolus - AMB) instead of the traditional continuous basal infusion (BI); recent randomized controlled trials (RCTs) have shown that the AMB technique leads to improved analgesia and maternal satisfaction. OBJECTIVES: To assess the effects of automated mandatory bolus versus basal infusion for maintaining epidural analgesia in labour. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, the World Health Organization International Clinial Trials Registry Platform (WHO-ICTRP) and ClinicalTrials.gov on 16 January 2018. We screened the reference lists of all eligible trials and reviews. We also contacted authors of included studies in this field in order to identify unpublished research and trials still underway, and we screened the reference lists of the included articles for potentially relevant articles. SELECTION CRITERIA: We included all RCTs that compared the use of bolus dosing AMB with continuous BI for providing pain relief during epidural analgesia for labour in women. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Our primary outcomes were: risk of breakthrough pain with the need for anaesthetic intervention; risk of caesarean delivery; risk of instrumental delivery. Secondary outcomes included: duration of labour; local anaesthetic consumption. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We included 12 studies with a total of 1121 women. Ten studies enrolled healthy nulliparous women only and two studies enrolled healthy parous women at term as well. All studies excluded women with complicated pregnancies. There were variations in the technique of initiation of epidural analgesia. Seven studies utilized the combined spinal epidural (CSE) technique, and the other five studies only placed an epidural catheter without any intrathecal injection. Seven studies utilized ropivacaine: six with fentanyl and one with sufentanil. Two studies used levobupivacaine: one with sufentanil and one with fentanyl. Three used bupivacaine with or without fentanyl. The overall risk of bias of the studies was low.AMB probably reduces the risk of breakthrough pain compared with BI for maintaining epidural analgesia for labour (from 33% to 20%; risk ratio (RR) 0.60; 95% confidence interval (CI) 0.39 to 0.92, 10 studies, 797 women, moderate-certainty evidence). AMB may make little or no difference to the risk of caesarean delivery compared to BI (15% and 16% respectively; RR 0.92; 95% CI 0.70 to 1.21, 11 studies, 1079 women, low-certainty evidence).AMB may make little or no difference in the risk of instrumental delivery compared to BI (12% and 9% respectively; RR 0.75; 95% CI 0.54 to 1.06, 11 studies, 1079 women, low-certainty evidence). There is probably little or no difference in the mean duration of labour with AMB compared to BI (mean difference (MD) -10.38 min; 95% CI -26.73 to 5.96, 11 studies, 1079 women, moderate-certainty evidence). There is probably a reduction in the hourly consumption of local anaesthetic with AMB compared to BI for maintaining epidural analgesia during labour (MD -1.08 mg/h; 95% CI -1.78 to -0.38, 12 studies, 1121 women, moderate-certainty evidence). Five out of seven studies reported an increase in maternal satisfaction with AMB compared to BI for maintaining epidural analgesia for labour; however, we did not pool these data due to their ordinal nature. Seven studies reported Apgar scores, though there was significant heterogeneity in reporting. None of the studies showed any significant difference between Apgar scores between groups. AUTHORS' CONCLUSIONS: There is predominantly moderate-certainty evidence that AMB is similar to BI for maintaining epidural analgesia for labour for all measured outcomes and may have the benefit of decreasing the risk of breakthrough pain and improving maternal satisfaction while decreasing the amount of local anaesthetic needed.

Early versus late initiation of epidural analgesia for labour.

BACKGROUND: Pain during childbirth is arguably the most severe pain some women may experience in their lifetime. Epidural analgesia is an effective form of pain relief during labour. Many women have concerns regarding its safety. Furthermore, epidural services and anaesthetic support may not be available consistently across all centres. Observational data suggest that early initiation of epidural may be associated with an increased risk of caesarean section, but the same findings were not seen in recent randomised controlled trials. More recent guidelines suggest that in the absence of a medical contraindication, maternal request is a sufficient medical indication for pain relief during labour. The choice of analgesic technique, agent, and dosage is based on many factors, including patient preference, medical status, and contraindications. There is no systematically reviewed evidence on the maternal and foetal outcomes and safety of this practice. OBJECTIVES: This systematic review aimed to summarise the effectiveness and safety of early initiation versus late initiation of epidural analgesia in women. We considered the obstetric and fetal outcomes relevant to women and side effects of the treatments, including risk of caesarean section, instrumental birth and time to birth. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (12 February 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 1), MEDLINE (January 1966 to February 2014), Embase (January 1980 to February 2014) and reference lists of retrieved studies. SELECTION CRITERIA: We included all randomised controlled trials involving women undergoing epidural labour analgesia that compared early initiation versus late initiation of epidural labour analgesia. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion, extracted the data and assessed the trial quality. Data were checked for accuracy. MAIN RESULTS: We included nine studies with a total of 15,752 women.The overall risk of bias of the studies was low, with the exception of performance bias (blinding of participants and personnel).The nine studies showed no clinically meaningful difference in risk of caesarean section with early initiation versus late initiation of epidural analgesia for labour (risk ratio (RR) 1.02; 95% confidence interval (CI) 0.96 to 1.08, nine studies, 15,499 women, high quality evidence). There was no clinically meaningful difference in risk of instrumental birth with early initiation versus late initiation of epidural analgesia for labour (RR 0.93; 95% CI 0.86 to 1.01, eight studies, 15,379 women, high quality evidence). The duration of second stage of labour showed no clinically meaningful difference between early initiation and late initiation of epidural analgesia (mean difference (MD) -3.22 minutes; 95% CI -6.71 to 0.27, eight studies, 14,982 women, high quality evidence). There was significant heterogeneity in the duration of first stage of labour and the data were not pooled.There was no clinically meaningful difference in Apgar scores less than seven at one minute (RR 0.96; 95% CI 0.84 to 1.10, seven studies, 14,924 women, high quality evidence). There was no clinically meaningful difference in Apgar scores less than seven at five minutes (RR 0.96; 95% CI 0.69 to 1.33, seven studies, 14,924 women, high quality evidence). There was no clinically meaningful difference in umbilical arterial pH between early initiation and late initiation (MD 0.01; 95% CI -0.01 to 0.03, four studies, 14,004 women, high quality evidence). There was no clinically meaningful difference in umbilical venous pH favouring early initiation (MD 0.01; 95% CI -0.00 to 0.02, four studies, 14,004 women, moderate quality evidence). AUTHORS' CONCLUSIONS: There is predominantly high-quality evidence that early or late initiation of epidural analgesia for labour have similar effects on all measured outcomes. However, various forms of alternative pain relief were given to women who were allocated to delayed epidurals to cover that period of delay, so that is it hard to assess the outcomes clearly. We conclude that for first time mothers in labour who request epidurals for pain relief, it would appear that the time to initiate epidural analgesia is dependent upon women's requests.

The glomic artery supply of carotid body tumors and implications for embolization.

Carotid body tumors (CBT) are rare neuroendocrine neoplasms that usually present in the third or fourth decades of life and are benign in more than 95% of cases. In the angiographic literature, the arterial supply to carotid body tumors is well documented but is often incomplete, with infrequent mention of the glomic artery, a common arterial feeder described in the anatomic and pathologic literature. Through a review of our neuroendovascular patient database, we identified eight patients with CBT undergoing transarterial embolization followed by resection. Mean patient age was 51.5 years (range 29-82), and all patients were female. Mean tumor size was 91.2 cc (standard deviation [SD] 61.1, median 67.7 cc). After embolization, greater than 90% flow reduction was achieved in 5/8 patients (63%); 60-80% flow reduction was achieved in the remaining patients. Mean operative blood loss was 166 cc (SD 100, median 122 cc) and mean operative time was 252 minutes (SD 134.5, median 155 minutes). Pre-embolization angiography was reviewed to identify a glomic artery, defined as a dominant artery supplying the CBT arising from the region of the carotid bifurcation. In six of eight patients (75%) a glomic artery could be identified, arising from the common carotid artery in 4/6 patients and the external carotid artery in 2/6 patients. Thus, glomic artery to supply to CBT was identified in the majority of patients in this series. Knowledge of its presence and identification as a direct supplier, frequently from the common carotid artery itself, provides an avenue for more thorough preoperative embolization of CBT.