Effect of replacing dicalcium phosphate with mono-dicalcium phosphate to supplement phosphorus on laying performance, phosphorus-calcium metabolism and bone metabolism of aged laying hens.

The objective of this study was to evaluate the effect of replacing dicalcium phosphate (DCP) with mono-dicalcium phosphate (MDCP) to formulate low-phosphorus (P) diets on laying performance, egg quality, phosphorus-calcium metabolism, and bone metabolism of 69-78-week-old aged laying hens. Hy-Line Brown laying hens (n = 1,350, 69 weeks old) were randomly assigned to six treatments, each with five replicates of 45 hens. A corn-soybean meal-based diet was formulated to contain 0.12% non-phytate phosphorus (NPP), 3.81% calcium (Ca), and 1,470 FTU/kg phytase. The control group (CON) was supplemented with DCP inorganic phosphorus (Pi) at the NPP level of 0.20% (dietary NPP levels of 0.32%). Test groups (T1-T5) were supplemented with MDCP Pi at NPP levels of 0.07%, 0.11%, 0.15%, 0.18, and 0.20% (dietary NPP levels of 0.19, 0.23, 0.27, 0.30, and 0.32%, respectively). Calcium carbonate levels were adjusted to ensure all experimental diets contained the same Ca levels (3.81%). The feeding trial lasted 10 weeks, with hens increasing in age from 69 to 78 weeks. When supplemented with 1,470 FTU/kg phytase, extra DCP Pi or MDCP Pi did not affect (p > 0.05) laying performance (day laying rate, average egg weight, feed intake, feed-to-egg mass ratio, broken egg rate), egg quality (eggshell strength, albumen height, haugh units), or serum P, Ca, copper (Cu), iron (Fe), zinc (Zn), and manganese (Mn) levels. However, when laying hens were fed MDCP Pi (NPP levels of 0.07 to 0.20%), yolk color improved (p = 0.0148). The tibia breaking strength was significantly higher (p < 0.05) in the 0.18 and 0.20% NPP MDCP Pi groups than in the 0.20% NPP DCP Pi group. The breaking strength, Ca content, and P content of tibia in 0.11% and 0.15% NPP MDCP Pi hens were not significantly (p > 0.05) different from those in 0.20% NPP DCP Pi hens. Hens fed 0.07% NPP MDCP Pi had higher (p < 0.01) serum levels of osteoprotegerin (OPG), type-I collagen c-telopeptide (CTX-I), and tartrate-resistant acid phosphatase 5b (TRACP-5b) than those in all other groups. Serum levels of TRACP-5b and CTX-I in the 0.11% and 0.15% NPP MDCP Pi group were significantly lower than those in 0.18 and 0.20% NPP MDCP Pi groups and the 0.20% NPP DCP Pi group (p < 0.0001). Hens fed 0.07% and 0.11% NPP MDCP Pi had higher (p < 0.05) serum levels of parathyroid hormone (PTH) than those in all other groups. No differences were detected in serum calcitonin (CT), 1,25-dihydroxy-vitamin D3 (1,25-(OH)2D3), bone alkaline phosphatase (BAP), osteocalcin(OCN), and osteopontin (OPN) among all groups (p > 0.05). The expression of P transporters type IIa Na/Pi cotransporter (NaPi-IIa) in 0.11% and 0.15% NPP MDCP Pi hens were higher than those in 0.20% NPP MDCP Pi group and 0.20% NPP DCP Pi group (p < 0.05). The results indicated that both renal P reabsorption and bone resorption were involved in adapting to a low-P diet. In summary, when MDCP was used instead of DCP to supplement P, NPP levels could be reduced to 0.11% (dietary NPP level of 0.23%) without negative effects on laying performance and skeletal health of aged hens. In addition, MDCP was more beneficial than DCP for tibia quality. The results of the current study would provide references for the application of MDCP in low-P diets of aged laying hens.

Inhibition of gingival fibroblast necroptosis mediated by RIPK3/MLKL attenuates periodontitis.

AIM: Necroptosis participates in the pathogenesis of many inflammatory diseases, including periodontitis. Here, we aimed to investigate the role and mechanism of necroptosis inhibitors in attenuating periodontitis. MATERIALS AND METHODS: The Gene Expression Omnibus (GEO) dataset GSE164241 was re-analysed to identify the role of necroptosis in periodontitis. Gingival specimens from healthy subjects or periodontitis patients were collected to evaluate the expression level of necroptosis-associated proteins. The therapeutic effect of necroptosis inhibitors on periodontitis was assessed in vivo and in vitro. Moreover, Transwell assays and Western blotting and siRNA transfection were used to identify the effects of necroptotic human gingival fibroblasts (hGFs) on THP-1 macrophages. RESULTS: Re-analysis revealed that gingival fibroblasts (GFs) in periodontitis gingiva showed the highest area under the curve score of necroptosis. Elevated levels of necroptosis-associated proteins were identified in GFs in periodontitis gingiva collected from patients and mice. In ligature-induced periodontitis mice, local administration of receptor interacting protein kinase 3(RIPK3) inhibitor GSK'872 or sh-mixed-lineage kinase domain-like pseudokinase (Mlkl) markedly abrogated necroptosis and rescued periodontitis. Analogously, necroptosis inhibitors alleviated the inflammatory response and release of damage-associated molecular patterns in lipopolysaccharide- or LAZ (LPS + AZD'5582 + z-VAD-fmk, necroptosis inducer)-induced GFs and then reduced THP-1 cell migration and M1 polarization. CONCLUSIONS: Necroptosis in GFs aggravated gingival inflammation and alveolar bone loss. Necroptosis inhibitors attenuate this process by modulating THP-1 macrophage migration and polarization. This study offers novel insights into the pathogenesis and potential therapeutic targets of periodontitis.

AdipoAI suppresses osteoclastogenesis by activating AdipoR1/APPL1: An in vivo experimental study in diabetes-associated peri-implantitis.

AIM: Diabetics experience severe peri-implant inflammatory bone damage. We aimed to provide powerful evidence supporting the novel adiponectin receptor agonist AdipoAI in treating diabetes-associated peri-implantitis. MATERIALS AND METHODS: Twenty-four ZDF-Leprfa/Crl rats were randomly allocated to three groups (N = 8). After feeding with a high-fat diet to establish diabetic rats, experimental peri-implantitis was induced by implanting titanium rods (1.5 mm diameter and 20 mm length) contaminated with Staphylococcus aureus into the femurs. Radiographic evaluation, microCT, histological analyses and qRT-PCR were used to detect inflammatory infiltration and bone destruction. In vitro, the inhibition by AdipoAI of osteoclastogenesis, including the number and function of osteoclasts, was investigated by TRAP staining, immunofluorescence, qRT-PCR and Western blotting. Immunofluorescence, qRT-PCR and Western blotting were also utilized to explore AdipoR1, APPL1, NF-κB and Wnt5a-Ror2 signalling molecules in this process. One-way ANOVA with Tukey's post hoc test was used to compare the data. RESULTS: AdipoAI reduced inflammation and bone destruction caused by peri-implantitis in diabetic rats, which were manifested by a reduction in F4/80-positive macrophage infiltration by 72%, the number of osteoclasts by 58% and the levels of cytokines (p < .05) in disease group. In vitro, 1 µM AdipoAI decreased the number of osteoclasts to 51%, inhibited F-actin ring formation and reduced the levels of related markers (p < .05). Mechanistically, AdipoAI activated AdipoR1/APPL1 and conversely suppressed the phosphorylation of IκB-α, nuclear translocation of P65 and the Wnt5a-Ror2 signalling pathway (p < .05). CONCLUSIONS: AdipoAI suppressed osteoclastogenesis in diabetes-associated peri-implantitis by inhibiting the NF-κB and Wnt5a-Ror2 pathways via the AdipoR1/APPL1 axis.

Effects of Low-Phosphorus Diets Supplemented with Phytase on the Production Performance, Phosphorus-Calcium Metabolism, and Bone Metabolism of Aged Hy-Line Brown Laying Hens.

This study was conducted to evaluate the effects of phytase supplementation in low-phosphorus diets on the production performance, phosphorus-calcium metabolism, and bone metabolism in laying hens from 69 to 78 weeks of age. Hy-Line Brown laying hens (n = 1350) were assigned randomly to six treatments with five replicates of 45 birds. A corn-soybean meal-based diet with no inorganic phosphates was formulated to contain 0.12% non-phytate phosphorus (NPP) and 1470 FTU/kg phytase (Released phytate phosphorus content ≥ 0.1%). Inorganic phosphorus (dicalcium phosphate) was supplemented into the basal diet to construct five test diets (level of NPP supplementation = 0.10%, 0.15%, 0.20%, 0.25%, and 0.30%). The level of calcium carbonate was adjusted to ensure that all six experimental diets contained the same calcium percentage (3.81%). The feeding trial lasted 10 weeks (hens from 69 to 78 weeks of age). Upon supplementation with phytase (1470 FTU/kg), supplemental inorganic phosphates (dicalcium phosphate) had no significant effects (p > 0.05) on the production performance or egg quality. Significant differences in serum levels of calcium, phosphorus, copper, iron, zinc, or manganese were not detected across treatments (p > 0.05). Hens fed NPP (0.15%, 0.20%, 0.25%, and 0.30%) had higher levels (p < 0.0001) of tibial ash, calcium, and phosphorus than those not fed inorganic phosphates. The tibial breaking strength of the group without inorganic phosphates was significantly lower than that of the other groups (p < 0.01). Dietary supplementation with inorganic phosphates had no effect (p > 0.05) on serum levels of calcitonin (CT) and 1,25-dihydroxy-vitamin D3 (1,25-(OH)2D3). Hens that did not receive supplementation with inorganic phosphates had higher serum levels of parathyroid hormone (PTH), osteoprotegerin (OPG), type-I collagen c-telopeptide (CTX-I), and tartrate-resistant acid phosphatase 5b (TRACP-5b) compared with those in the other groups (p < 0.01). Serum levels of CTX-I and TRACP-5b were significantly lower in the NPP-supplementation groups of 0.25% and 0.30% than in the 0.10% NPP-supplementation group (p < 0.01). Dietary supplementation with inorganic phosphates had no effect (p > 0.05) on serum levels of bone-alkaline phosphatase (BAP), osteocalcin (OCN), or osteopontin (OPN). Hens not fed inorganic phosphate had the highest renal expression of phosphorus transporter type IIa Na/Pi cotransporter (NaPi-Ⅱa). Renal expression of NaPi-Ⅱa was increased significantly in NPP-supplementation groups of 0.10-0.20% compared with that in NPP-supplementation groups of 0.25% and 0.30% (p < 0.0001). The results indicated that a reduction in NPP supplementation to 0.15% (dietary NPP level = 0.27%) with phytase inclusion did not have an adverse effect on the production performance or bone health of laying hens from 69 to 78 weeks of age, which might be attributed to renal phosphorus reabsorption and bone resorption. These findings could support the application of low-phosphorus diets in the poultry industry.

Effect of Sugammadex During Transcranial Electrical Motor Evoked Potentials Monitoring in Spinal Surgery: A Randomized Controlled Trial.

INTRODUCTION: Neuromuscular blockade suppresses transcranial electrical motor evoked potential (TceMEP) amplitude and is usually avoided during TceMEP monitoring. In this randomized controlled trial, we investigated whether rocuronium-induced suppression of TceMEP amplitude could be reversed by sugammadex in patients undergoing spine surgery. METHODS: Seventy-six patients undergoing spinal surgery were randomly allocated into sugammadex and control groups. In the sugammadex group, a rocuronium infusion was titrated to maintain moderate neuromuscular blockade (2 twitches on train-of-four) until dural opening when the rocuronium infusion was discontinued and 2 mg/kg sugammadex administered. In the control group, no neuromuscular blockade was administered after induction of anesthesia. The primary outcome was a comparison between sugammadex and control groups of mean TceMEP amplitudes in the abductor pollicis brevis muscles of both upper extremities 5 minutes after dural. Secondary outcomes included TceMEP amplitudes at 10, 20, 30, and 60 minutes after dural opening. RESULTS: Sixty-six patients were included in the analysis. TceMEP amplitudes were significantly greater in the sugammadex group (629 µV, interquartile range: 987 µV) than in the control group (502 µV, interquartile range: 577 µV; P =0.033) at 5 minutes after dural opening. TceMEP amplitudes were also greater in the sugammadex group at 10 minutes ( P =0.0010), 20 minutes ( P =0.003), 30 minutes ( P =0.001), and 60 minutes ( P =0.003) after dural opening. CONCLUSIONS: Moderate neuromuscular blockade induced by continuous infusion of rocuronium was effectively reversed by sugammadex. This suggests that sugammadex could be used to enhance TceMEP waveform monitoring during spine surgery requiring muscle relaxation.

Identification of nine signature proteins involved in periodontitis by integrated analysis of TMT proteomics and transcriptomics.

Recently, there are many researches on signature molecules of periodontitis derived from different periodontal tissues to determine the disease occurrence and development, and deepen the understanding of this complex disease. Among them, a variety of omics techniques have been utilized to analyze periodontitis pathology and progression. However, few accurate signature molecules are known and available. Herein, we aimed to screened and identified signature molecules suitable for distinguishing periodontitis patients using machine learning models by integrated analysis of TMT proteomics and transcriptomics with the purpose of finding novel prediction or diagnosis targets. Differential protein profiles, functional enrichment analysis, and protein-protein interaction network analysis were conducted based on TMT proteomics of 15 gingival tissues from healthy and periodontitis patients. DEPs correlating with periodontitis were screened using LASSO regression. We constructed a new diagnostic model using an artificial neural network (ANN) and verified its efficacy based on periodontitis transcriptomics datasets (GSE10334 and GSE16134). Western blotting validated expression levels of hub DEPs. TMT proteomics revealed 5658 proteins and 115 DEPs, and the 115 DEPs are closely related to inflammation and immune activity. Nine hub DEPs were screened by LASSO, and the ANN model distinguished healthy from periodontitis patients. The model showed satisfactory classification ability for both training (AUC=0.972) and validation (AUC=0.881) cohorts by ROC analysis. Expression levels of the 9 hub DEPs were validated and consistent with TMT proteomics quantitation. Our work reveals that nine hub DEPs in gingival tissues are closely related to the occurrence and progression of periodontitis and are potential signature molecules involved in periodontitis.

L-Selenocysteine induced HepG-2 cells apoptosis through reactive oxygen species-mediated signaling pathway.

BACKGROUND: Currently, Liver cancer is the fifth most common tumor and the second most important reason for cancer-related death in the world. However, there are still many limitations of the clinical treatment of liver cancer, and new treatment options are clearly needed. Fortunately, studies have shown that L-Selenocysteine has a certain effect on cancer. This study was to investigate the effects of L-Selenocysteine on the inhibition of cell proliferation and the promotion of apoptosis of HepG-2 cells through ROS mediated fine signaling pathway. MATERIALS AND METHODS: CCK-8 assay was applied to evaluating the cytotoxic effect of L-Selenocysteine on HepG-2 cells. Electron microscopy, flow cytometry and Western Blot was utilization in further researching cells signaling pathways. RESULTS: The growth of HepG-2 cells was inhibited by L-selenocysteine ​​treatment in a dose-dependent manner. The cell viability decreased to 52.20%, 43.20% and 30.83% under the treatment of 4, 8, 16 µM L-selenocysteine, respectively. L-Selenocysteine had higher cytotoxicity towards HepG-2 cells than normal cells. L-Selenocysteine can induce the apoptosis of HepG-2 cells by increasing the DNA fragmentation, and activating the Caspase-3. In addition, it was found that the mechanism of the induction to HepG-2 cell apoptosis by L-Selenocysteine was closely related to the overproduction of ROS and promoted apoptosis through the Bcl-2 signaling pathway. CONCLUSIONS: Our data suggest that L-selenocysteine ​​may cause mitochondrial damage and subsequently stimulate ROS production. ROS can damage cellular DNA and mediate the production of Casapase-8, Bid, Bcl-2 and other proteins, affecting downstream signaling pathways, and ultimately induced apoptosis.

Exosomes from LPS-Stimulated hDPSCs Activated the Angiogenic Potential of HUVECs In Vitro.

BACKGROUND: Exosomes from human dental pulp stem cells (hDPSCs) were indicated to play a positive role in vascular regeneration processes. But the angiogenic capabilities of exosomes from inflammatory hDPSCs and the underlying mechanism remain unknown. In this study, the inflammatory factor lipopolysaccharide (LPS) was used to stimulate hDPSCs, and exosomes were extracted from these hDPSCs. The proangiogenic potential of exosomes was examined, and the underlying mechanism was studied. METHOD: Exosomes were isolated from hDPSCs with or without LPS stimulation (N-EXO and LPS-EXO) and cocultured with human umbilical vein endothelial cells (HUVECs). The proangiogenic potential of exosomes was evaluated by endothelial cell proliferation, migration, and tube formation abilities in vitro. To investigate the proangiogenic mechanism of LPS-EXO, microRNA sequencing was performed to explore the microRNA profile of N-EXO and LPS-EXO. Gene Ontology (GO) analysis was used to study the functions of the predicted target genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was used to estimate the signaling pathways associated with the inflammation-induced angiogenesis process. RESULT: Compared to the uptake of N-EXO, uptake of LPS-EXO activated the angiogenic potential of HUVECs by promoting the proliferation, migration, and tube formation abilities in vitro. The mRNA expression levels of vascular endothelial growth factor (VEGF) and kinase-insert domain-containing receptor (KDR) in the LPS-EXO group were significantly higher than those in the N-EXO group. MicroRNA sequencing showed that 10 microRNAs were significantly changed in LPS-EXO. Pathway analysis showed that the genes targeted by differentially expressed microRNAs were involved in multiple angiogenesis-related pathways. CONCLUSION: This study revealed that exosomes derived from inflammatory hDPSCs possessed better proangiogenic potential in vitro. This is the first time to explore the role of exosomal microRNA from hDPSCs in inflammation-induced angiogenesis. This finding sheds new light on the effect of inflammation-stimulated hDPSCs on tissue regeneration.

Long non­coding RNAs are novel players in oral inflammatory disorders, potentially premalignant oral epithelial lesions and oral squamous cell carcinoma (Review).

In recent years, a large number of studies have shown that the abnormal expression of long non­coding (lnc)RNAs can lead to a variety of different diseases, including inflammatory disorders, cardiovascular disease, nervous system diseases, and cancers. Recent research has demonstrated the biological characteristics of lncRNAs and the important functions of lncRNAs in oral inflammation, precancerous lesions and cancers. The present review aims to explore and discuss the potential roles of candidate lncRNAs in oral diseases by summarizing multiple lncRNA profiles in diseased and healthy oral tissues to determine the altered lncRNA signatures. In addition, to highlight the exact regulatory mechanism of lncRNAs in oral inflammatory disorders, potentially premalignant oral epithelial lesions and oral squamous cell carcinoma. The detection of lncRNAs in oral samples has the potential to be used as a diagnostic and an early detection tool for oral diseases. Furthermore, lncRNAs are promising future therapeutic targets in oral diseases, and research in this field may expand in the future.

Genome-wide identification of long noncoding RNAs and their competing endogenous RNA networks involved in the odontogenic differentiation of human dental pulp stem cells.

BACKGROUND: Long noncoding RNAs (lncRNAs) play an important role in the multiple differentiations of mesenchymal stem cells (MSCs). However, few studies have focused on the regulatory mechanism of lncRNAs in the odontogenic differentiation of human dental pulp stem cells (hDPSCs). METHODS: hDPSCs were induced to differentiate into odontoblasts in vitro, and the expression profiles of lncRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs) in differentiated and undifferentiated cells were obtained by microarray. Bioinformatics analyses including Gene Ontology (GO) analysis, pathway analysis, and binding site prediction were performed for functional annotation of lncRNA. miRNA/odontogenesis-related gene networks and lncRNA-associated ceRNA networks were constructed. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to verify the expression of selected genes. RNA fluorescence in situ hybridization (FISH), qRT-PCR, and western blot analysis were used to explore the location and function of lncRNA-G043225. Dual-luciferase reporter assay was performed to confirm the binding sites of miR-588 with G043225 and Fibrillin 1 (FBN1). RESULTS: We identified 132 lncRNAs, 114 miRNAs, and 172 mRNAs were differentially expressed. GO analysis demonstrated that regulation of the neurogenic locus notch homolog (Notch), Wnt, and epidermal growth factor receptor (ERBB) signaling pathways and activation of mitogen-activated protein kinase (MAPK) activity were related to odontogenic differentiation. Pathway analysis indicated that the most significant pathway was the forkhead box O (FoxO) signaling pathway, which is related to odontogenic differentiation. Two odontogenesis-related gene-centered lncRNA-associated ceRNA networks were successfully constructed. The qRT-PCR validation results were consistent with the microarray analysis. G043225 mainly locating in cytoplasm was proved to promote the odontogenic differentiation of hDPSCs via miR-588 and FBN1. CONCLUSION: This is the first study revealing lncRNA-associated ceRNA network during odontogenic differentiation of hDPSCs using microarray, and it could provide clues to explore the mechanism of action at the RNA-RNA level as well as novel treatments for dentin regeneration based on stem cells.

Adenosine at the Interphase of Hypoxia and Inflammation in Lung Injury.

Hypoxia and inflammation often coincide in pathogenic conditions such as acute respiratory distress syndrome (ARDS) and chronic lung diseases, which are significant contributors to morbidity and mortality for the general population. For example, the recent global outbreak of Coronavirus disease 2019 (COVID-19) has placed viral infection-induced ARDS under the spotlight. Moreover, chronic lung disease ranks the third leading cause of death in the United States. Hypoxia signaling plays a diverse role in both acute and chronic lung inflammation, which could partially be explained by the divergent function of downstream target pathways such as adenosine signaling. Particularly, hypoxia signaling activates adenosine signaling to inhibit the inflammatory response in ARDS, while in chronic lung diseases, it promotes inflammation and tissue injury. In this review, we discuss the role of adenosine at the interphase of hypoxia and inflammation in ARDS and chronic lung diseases, as well as the current strategy for therapeutic targeting of the adenosine signaling pathway.

Noncoding RNAs: new insights into the odontogenic differentiation of dental tissue-derived mesenchymal stem cells.

Odontoblasts are cells that contribute to the formation of the dental pulp complex. The differentiation of dental tissue-derived mesenchymal stem cells into odontoblasts comprises many factors and signaling pathways. Noncoding RNAs (ncRNAs), comprising a substantial part of poly-A tail mature RNAs, are considered "transcriptional noise." Emerging evidence has shown that ncRNAs have key functions in the differentiation of mesenchymal stem cells. In this review, we discussed two major types of ncRNAs, including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), in terms of their role in the odontogenic differentiation of dental tissue-derived stem cells. Recent findings have demonstrated important functions for miRNAs and lncRNAs in odontogenic differentiation. It is expected that ncRNAs will become promising therapeutic targets for dentin regeneration based on stem cells.

Vacuolar protein sorting 4B regulates the proliferation and odontoblastic differentiation of human dental pulp stem cells through the Wnt-ß-catenin signalling pathway.

Our previous studies have revealed that a dominant mutation in vacuolar protein sorting 4B (VPS4B), a member of the AAA ATPase family, causes dentin dysplasia type I. The purpose of the present study was to investigate the roles of VPS4B in human dental pulp stem cells (hDPSCs) and to elucidate the underlying molecular mechanisms. In this study, we found that VPS4B was highly expressed in the dental pulp cells of the mouse molar tooth germ, and the expression of VPS4B increased significantly during the odontoblastic differentiation of hDPSCs. VPS4B downregulation inhibited the proliferation, migration, and odontoblastic differentiation of hDPSCs. Moreover, treatment with lithium chloride, an agonist of the Wnt-ß-catenin signalling pathway, partially reversed the VPS4B knockdown-driven suppression of proliferation and of odontoblastic differentiation of hDPSCs. Collectively, our findings indicate that VPS4B, via Wnt-ß-catenin signalling, acts as a regulator of the proliferation and differentiation of hDPSCs. Our results suggest potential therapeutic avenues for dentin formation and regenerative endodontics in patients with dentin dysplasia type I.

Midazolam Sedation Induces Upper Limb Coordination Deficits That Are Reversed by Flumazenil in Patients with Eloquent Area Gliomas.

BACKGROUND: Midazolam has been found to exacerbate or unmask limb motor dysfunction in patients with brain tumors. This study aimed to determine whether the exacerbated upper limb motor-sensory deficits are mediated through benzodiazepine sites by demonstrating reversibility by flumazenil in patients with gliomas in eloquent areas. METHODS: This was an interventional, parallel assignment, nonrandomized trial. Study subjects were admitted in the operating room. Patients with supratentorial eloquent area gliomas and volunteers of similar age without neurologic disease were sedated with midazolam, but still responsive and cooperative. Motor and sensory functions for upper extremities were evaluated by the Nine-Hole Peg Test before and after midazolam, as well as after flumazenil reversal. RESULTS: Thirty-two cases were included: 15 in the glioma group and 17 in the control group. The total dose of midazolam and flumazenil were comparable between the groups. In the glioma group, the times to task completion after midazolam in the contralateral hand (P = 0.001) and ipsilateral hand (P = 0.002) were 26.5 (95% CI, 11.3 to 41.7) and 13.7 (95% CI, 5.0 to 22.4) seconds slower than baseline, respectively. After flumazenil reversal, the contralateral hand (P = 0.99) and ipsilateral hand (P = 0.187) performed 1.2 (95% CI, -3.3 to 5.8) and 1.5 (95% CI, -0.5 to 3.5) seconds slower than baseline, respectively. In the control group, the dominant (P < 0.001) and nondominant hand (P = 0.006) were 2.9 (95% CI, 1.4 to 4.3) and 1.7 (95% CI, 0.5 to 2.9) seconds slower than baseline, respectively. After flumazenil, the dominant hand (P = 0.99) and nondominant hand (P = 0.019) performed 0.2 (95% CI, -0.7 to 1.0) and 1.3 (95% CI, -0.2 to 2.4) seconds faster than baseline, respectively. CONCLUSIONS: In patients with eloquent area gliomas, mild sedation with midazolam induced motor coordination deficits in upper limbs. This deficit was almost completely reversed by the benzodiazepine antagonist flumazenil, suggesting that this is a reversible abnormality linked to occupation of the receptor by midazolam.

Preoperative Gabapentin Administration Improves Acute Postoperative Analgesia in Patients Undergoing Craniotomy: A Randomized Controlled Trial.

BACKGROUND: Gabapentin is an adjuvant antiepileptic agent and helps to reduce acute postoperative pain in several surgery settings. However, the effect of gabapentin on postoperative pain from suboccipital or subtemporal craniotomy is not clear. METHODS: The study was a single-center, randomized, placebo-controlled, and double-blinded trial. A total of 122 patients undergoing elective craniotomy by a suboccipital or subtemporal approach were randomly allocated to a placebo group and gabapentin group. The patients received gabapentin (600 mg, orally) the night before surgery and 2 hours before anesthesia induction in the gabapentin group, and patients received vitamin B in the placebo group. The primary outcome was the postoperative pain score on movement at 24 hours. The secondary outcomes included the pain score at other time points, incidence of nausea and vomiting, sedation, and analgesic consumption. RESULTS: Gabapentin significantly decreased the postoperative acute pain scores at rest (P=0.001) and on movement (P=0.000) within 24 hours; however, it did not have an effect at 48 hours. Gabapentin decreased postoperative vomiting (P=0.047) and rescue antiemetic use (P=0.033), whereas it increased the postoperative sedation score at 2 hours (P<0.05). Moreover, gabapentin decreased the mean consumption of intraoperative propofol (0.7 mg/kg/h; P=0.021) and remifentanil (1.3 µg/kg/h; P=0.025); however, it did not influence postoperative opioid consumption. CONCLUSIONS: Preoperative gabapentin significantly alleviated acute postoperative pain and decreased the incidence of vomiting in patients undergoing suboccipital or subtemporal craniotomy. However, more attention should be paid to early postoperative sedation when multimodal analgesia with gabapentin is administered.

Craneotomía en el paciente despierto: Indicaciones, beneficios y técnicas / Awake craniotomy: indications, benefits, and techniques

Abstract Awake craniotomy is mainly used for mapping and resection of lesions in vitally important brain areas where imaging is not sufficiently sensitive. These are most commonly speech and motor areas. The awake approach has become increasingly popular with wider indications due to the advantage of better neurological and other perioperative outcomes including analge sia and postoperative nausea and vomiting. Improvements in anesthetic agents and techniques especially LMA have made a great contribution. Frequently used medications are propofol, dexmedetomidine, and remifentanil. Common anesthetic regi mens range from light-moderate sedation, deep sedation, or general anesthesia during the pre-mapping and postmapping phases. In all sedation-anesthesia techniques, the patients are awake and able to speak and/or move during the mapping phase. This approach to intracranial surgical procedure requires skill, experience, and commitment on the part of the entire OR team. This review, from the point of view of authors, discusses the indications and contraindications, benefits, anesthetic techni ques, challenges, and management, as well as potential future directions of awake craniotomy.

Resumen La craneotomía con el paciente despierto se utiliza fundamen talmente para el mapeo y la resección de lesiones en áreas de vital importancia en el cerebro, en donde las imágenes no son suficientemente sensibles. Se trata por lo general de las áreas del habla y motoras. El abordaje con el paciente despierto ha adquirido cada vez más popularidad y se han ampliado sus indicaciones gracias a la ventaja de mejores desenlaces neurológicos y perioperatorios, entre ellos la analgesia y la náusea y vómito postoperatorios. Los avances en los agentes y las técnicas de anestesia, particularmente la mascarilla laríngea (LMA), han hecho grandes aportes. Los medicamentos de uso frecuente son propofol, dexmedetomidina y remifentanilo. Los esquemas anestésicos comunes van desde la sedación leve a moderada, sedación profunda, o anestesia general durante las fases pre y post-mapeo. En todas las técnicas de sedación - anestesia, los pacientes se encuentran despiertos y con capacidad para hablar y/ o moverse durante la fase de mapeo. Este abordaje al procedi miento quirúrgico intracraneal requiere pericia, experiencia y compromiso por parte de todo el equipo de la sala de cirugía. Esta revisión, desde la perspectiva de los autores, hace referencia a las indicaciones y contraindicaciones, beneficios, técnicas de anestesia, desafíos y manejo, así como a posibles orientaciones a futuro de la craneotomía con el paciente despierto.

Cerebral near-infrared spectroscopy (NIRS) for perioperative monitoring of brain oxygenation in children and adults.

BACKGROUND: Various techniques have been employed for the early detection of perioperative cerebral ischaemia and hypoxia. Cerebral near-infrared spectroscopy (NIRS) is increasingly used in this clinical scenario to monitor brain oxygenation. However, it is unknown whether perioperative cerebral NIRS monitoring and the subsequent treatment strategies are of benefit to patients. OBJECTIVES: To assess the effects of perioperative cerebral NIRS monitoring and corresponding treatment strategies in adults and children, compared with blinded or no cerebral oxygenation monitoring, or cerebral oxygenation monitoring based on non-NIRS technologies, on the detection of cerebral oxygen desaturation events (CDEs), neurological outcomes, non-neurological outcomes and socioeconomic impact (including cost of hospitalization and length of hospital stay). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 12), Embase (1974 to 20 December 2016) and MEDLINE (PubMed) (1975 to 20 December 2016). We also searched the World Health Organization (WHO) International Clinical Trials Registry Platform for ongoing studies on 20 December 2016. We updated this search in November 2017, but these results have not yet been incorporated in the review. We imposed no language restriction. SELECTION CRITERIA: We included all relevant randomized controlled trials (RCTs) dealing with the use of cerebral NIRS in the perioperative setting (during the operation and within 72 hours after the operation), including the operating room, the postanaesthesia care unit and the intensive care unit. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies, assessed risk of bias and extracted data. For binary outcomes, we calculated the risk ratio (RR) and its 95% confidence interval (CI). For continuous data, we estimated the mean difference (MD) between groups and its 95% CI. As we expected clinical and methodological heterogeneity between studies, we employed a random-effects model for analyses and we examined the data for heterogeneity (I2 statistic). We created a 'Summary of findings' table using GRADEpro. MAIN RESULTS: We included 15 studies in the review, comprising a total of 1822 adult participants. There are 12 studies awaiting classification, and eight ongoing studies.None of the 15 included studies considered the paediatric population. Four studies were conducted in the abdominal and orthopaedic surgery setting (lumbar spine, or knee and hip replacement), one study in the carotid endarterectomy setting, and the remaining 10 studies in the aortic or cardiac surgery setting. The main sources of bias in the included studies related to potential conflict of interest from industry sponsorship, unclear blinding status or missing participant data.Two studies with 312 participants considered postoperative neurological injury, however no pooled effect estimate could be calculated due to discordant direction of effect between studies (low-quality evidence). One study (N = 126) in participants undergoing major abdominal surgery reported that 4/66 participants experienced neurological injury with blinded monitoring versus 0/56 in the active monitoring group. A second study (N = 195) in participants having coronary artery bypass surgery reported that 1/96 participants experienced neurological injury in the blinded monitoring group compared with 4/94 participants in the active monitoring group.We are uncertain whether active cerebral NIRS monitoring has an important effect on the risk of postoperative stroke because of the low number of events and wide confidence interval (RR 0.25, 95% CI 0.03 to 2.20; 2 studies, 240 participants; low-quality evidence).We are uncertain whether active cerebral NIRS monitoring has an important effect on postoperative delirium because of the wide confidence interval (RR 0.63, 95% CI 0.27 to 1.45; 1 study, 190 participants; low-quality evidence).Two studies with 126 participants showed that active cerebral NIRS monitoring may reduce the incidence of mild postoperative cognitive dysfunction (POCD) as defined by the original studies at one week after surgery (RR 0.53, 95% CI 0.30 to 0.95, I2 = 49%, low-quality evidence).Based on six studies with 962 participants, there was moderate-quality evidence that active cerebral oxygenation monitoring probably does not decrease the occurrence of POCD (decline in cognitive function) at one week after surgery (RR 0.62, 95% CI 0.37 to 1.04, I2 = 80%). The different type of monitoring equipment in one study could potentially be the cause of the heterogeneity.We are uncertain whether active cerebral NIRS monitoring has an important effect on intraoperative mortality or postoperative mortality because of the low number of events and wide confidence interval (RR 0.63, 95% CI 0.08 to 5.03, I2= 0%; 3 studies, 390 participants; low-quality evidence). There was no evidence to determine whether routine use of NIRS-based cerebral oxygenation monitoring causes adverse effects. AUTHORS' CONCLUSIONS: The effects of perioperative active cerebral NIRS monitoring of brain oxygenation in adults for reducing the occurrence of short-term, mild POCD are uncertain due to the low quality of the evidence. There is uncertainty as to whether active cerebral NIRS monitoring has an important effect on postoperative stroke, delirium or death because of the low number of events and wide confidence intervals. The conclusions of this review may change when the eight ongoing studies are published and the 12 studies awaiting assessment are classified. More RCTs performed in the paediatric population and high-risk patients undergoing non-cardiac surgery (e.g. neurosurgery, carotid endarterectomy and other surgery) are needed.