Optimising the oral midazolam dose for premedication in people with intellectual disabilities and/or autism spectrum disorder.

BACKGROUND: In people with intellectual disabilities and/or autism spectrum disorder, oral midazolam (OM) is very effective as premedication for facilitating medical treatment. In this retrospective study, we investigated the optimal dosage of OM for premedication. METHODS: Patients with intellectual disability and/or autism spectrum disorder who were given OM as a premedication were selected from anaesthesia records. The primary outcome variable was the dose of OM (mg/kg) required to produce an adequate sedation. RESULTS: The mean OM dose required was 0.32 ± 0.10 mg/kg. The required OM dose decreased significantly as age and weight increased, and age and weight were also shown to be significantly associated with the dose of OM in the multivariate linear regression analysis. CONCLUSION: The dosage of OM to achieve adequate sedation should decrease as the patient ages. Furthermore, adequate sedation can be achieved with even lower doses of OM in obese people.

Anesthetic Management Using Remimazolam in a Hemodialysis Patient.

Remimazolam, an ultra-short-acting benzodiazepine, is a new intravenous anesthetic used for sedation and general anesthesia. Because remimazolam is primarily metabolized by carboxylesterases in the liver and other tissues including the lung and has metabolites with little or no bioactivity, its anesthetic effect is not significantly influenced by renal dysfunction. Therefore, remimazolam may be considered an appropriate agent for hemodialysis patients and may have added benefits beyond midazolam and propofol. Remimazolam has also been suggested to cause less cardiac depression than propofol. This case report presents an 82-year-old female hemodialysis patient with chronic heart failure who underwent partial glossectomy for squamous cell carcinoma of the tongue under general anesthesia with remimazolam and remifentanil. Hemodynamic control was stable during the anesthetic, which was safely completed without any adverse events and resulted in a rapid, clear emergence without flumazenil. Remimazolam and remifentanil may be appropriate as first-line general anesthetic agents for hemodialysis patients with heart failure.

Evaluation of Sedation Levels Using SedLine During Intravenous Sedation for Dental Procedures: A Case-Series Study.

The Patient State Index (PSI) is the numerical value of anesthesia depth as measured using a SedLine Sedation Monitor (Masimo Corporation). In this pilot study, we evaluated PSI values captured during intravenous (IV) moderate sedation for dental treatment. During the dental treatment, a dental anesthesiologist maintained the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score at 3 to 4 by adjusting the administration of midazolam and propofol while PSI values were recorded. The mean (SD) and median (25th percentile, 75th percentile) PSI values during dental treatment under IV moderate sedation were 72.7 (13.6) and 75 (65, 85), respectively.

The clinical advantage of nasal high-flow in respiratory management during procedural sedation: A scoping review on the application of nasal high-flow during dental procedures with sedation.

Structured summary: Rationale: Nasal high-flow (NHF), a new method for respiratory management during procedural sedation, has greater advantages than conventional nasal therapy with oxygen. However, its clinical relevance for patients undergoing oral maxillofacial surgery and/or dental treatment remains uncertain and controversial, due to a paucity of studies. This scoping review compared and evaluated NHF and conventional nasal therapy with oxygen in patients undergoing oral maxillofacial surgery and/or dental treatment. Materials and methods: A literature search of two public electronic databases was conducted, and English writing randomized controlled trials (RCTs) of nasal high flow during dental procedure with sedation reviewed. The primary and secondary outcomes of interest were the incidence of hypoxemia and hypercapnia during sedation and the need for intervention to relieve upper airway obstruction, respectively. Results: The search strategy yielded 7 studies, of which three RCTs met our eligibility criteria, with a total of 78 patients. Compared with conventional nasal therapy with oxygen, NHF significantly reduced the incidence of hypoxemia and hypercapnia during procedural sedation. Conclusion: NHF can maintain oxygenation and possibly prevent hypercapnia in patients undergoing dental treatment. Additional RCTs are needed to clarify and confirm these findings.

Capsaicin May Improve Swallowing Impairment in Patients with Amyotrophic Lateral Sclerosis: A Randomized Controlled Trial.

Patients with neurodegenerative diseases are at an increased risk of dysphagia and aspiration pneumonia. In this study, we examined whether ingestion of capsaicin prior to swallowing changes the temporal dynamics of swallowing in such patients. In a crossover, randomized controlled trial, 29 patients with neurodegenerative diseases were given a soluble wafer containing 1.5 µg capsaicin or an identical placebo 20 min prior to testing. For evaluation with video fluoroscopy (VF), patients consumed a barium-containing liquid plus thickening material. The durations of the latency, elevating and recovery periods of the hyoid were assessed from VF. Overall, no significant differences were observed in the duration of each period between capsaicin and placebo treatments. However, reductions in the latency and elevating periods were positively correlated with baseline durations. In subgroup analyses, that correlation was observed in patents with amyotrophic lateral sclerosis (ALS) but not in patients with Parkinson's disease. The consumption of wafer paper containing capsaicin before the intake of food may be effective in patients with dysphagia related with certain neurodegenerative diseases, particularly ALS patients. Further studies will be needed to validate this finding.

Patient satisfaction with deep versus light/moderate sedation for non-surgical procedures: A systematic review and meta-analysis.

BACKGROUND: Deep sedation relieves a patient's anxiety and stress during the procedure by inducing patient unconsciousness. However, it remains unclear whether deep sedation actually improves patient satisfaction with the procedure. Therefore, we performed a systematic review and meta-analysis to compare the satisfaction of patients undergoing deep sedation with that of those undergoing light/moderate sedation during non-surgical procedures. METHODS: A comprehensive literature search was performed using electronic databases (search until September 2020). The primary outcome was whether patient satisfaction was higher after deep sedation or light/moderate sedation. The secondary outcome was the relative safety of deep sedation compared with light/moderate sedation in terms of oxygen saturation, systolic blood pressure, and heart rate. The tertiary outcomes were the relative procedure and recovery times for deep versus light/moderate sedation.Data from each of the trials were combined, and calculations were made using DerSimonian and Laird random effects models. The pooled effect estimates for patient satisfaction were evaluated using relative risk (RR) with the 95% confidence interval (CI). The pooled effect estimates for continuous data are expressed as weighted mean difference with the 95% CI. We assessed heterogeneity with the Cochrane Q statistic and the I2 statistic. The risk of bias assessment and Grading of Recommendations Assessment, Development and Evaluation approach were used as the quality assessment method. RESULTS: After removing unrelated studies and applying the exclusion criterion, 5 articles satisfied the inclusion criteria. Patient satisfaction was significantly higher in those who received deep sedation compared with light/moderate sedation (relative risk = 1.12; 95% CI, 1.04-1.20; P = .003; Cochrane Q = 25.0; I2 = 76%).There was no significant difference in oxygen saturation, systolic blood pressure, heart rate, and procedure times according to whether the procedures were performed under deep or light/moderate sedation. However, the recovery time was significantly prolonged in patients under deep sedation. CONCLUSIONS: Our meta-analysis suggests that deep sedation resulted in improved patient satisfaction compared with light/moderate sedation. Deep sedation is recommended for patients undergoing procedures because it improves patient satisfaction. However, respiration and circulation should be carefully monitored both intra-operatively and postoperatively.

Comparison of Oxygen Saturation Between Nasal High-Flow Oxygen and Conventional Nasal Cannula in Obese Patients Undergoing Dental Procedures With Deep Sedation: A Randomized Crossover Trial.

PURPOSE: In anesthetic management, it is widely accepted that obese patients are more likely to suffer airway obstructions and reductions in arterial oxygen saturation (SpO2). Therefore, it is important to take special measures to prevent oxygen desaturation during the deep sedation of obese patients. This clinical study examined whether the use of nasal high-flow systems (NHFS) keep higher SpO2 and reduced hypoxemia than conventional nasal cannula during the deep sedation of obese patients with intellectual disabilities for dental treatment. MATERIALS AND METHODS: Eighteen obese patients (body mass index: >25) with intellectual disabilities who underwent dental sedation were enrolled. In each case, sedation was induced using propofol and maintained at a bispectral index of 50 to 70. The subjects were randomly assigned to the control oxygen administration (5 L/min via a nasal cannula) or NHFS (40% O2, 40 L/min, 37 °C) arm in alternate shifts as a crossover trial. The primary endpoint was the minimum SpO2 value, and the incidence of hypoxemia during dental treatment was also evaluated. RESULTS: The mean minimum SpO2 value was significantly higher in the NHFS arm than in the control arm (95.8 ± 2.1 % vs 93.6 ± 4.1 %, P = 0.0052, 95% confidence interval: 0.608-3.947). Hypoxemic episodes (SpO2: ≤94%) occurred 3 cases (16.7%) in the NHFS arm and 11 cases (61.1%) in the control arm (P = 0.0076, odds ratio: 0.127, 95% confidence interval 0.0324 - 0.630). CONCLUSION: NHFS resulted in higher minimum SpO2 and reduced hypoxemia than nasal cannula in obese patients during deep sedation for dental treatment.

Dexmedetomidine inhibits LPS-induced inflammatory responses through peroxisome proliferator-activated receptor gamma (PPARγ) activation following binding to α2 adrenoceptors.

Over the past decade, dexmedetomidine (DEX) has been found to possess an anti-inflammatory effect. However, the local anti-inflammatory mechanism of DEX has not been fully clarified. Some intracellular inflammatory pathways lead to negative feedback during the inflammatory process. The cyclooxygenase (COX) cascade synthesizes prostaglandins (PGs) and plays a key role in inflammation, but is known to also have anti-inflammatory properties through an alternative route of a PGD2 metabolite, 15-deoxy-delta-12,14-prostaglandin J2 (15d-PGJ2), and its receptor, peroxisome proliferator-activated receptor gamma (PPARγ). Therefore, we hypothesized that DEX inhibits LPS-induced inflammatory responses through 15d-PGJ2 and/or PPARγ activation, and evaluated the effects of DEX on these responses. The RAW264.7 mouse macrophage-like cells were pre-incubated with DEX, followed by the addition of LPS to induce inflammatory responses. Concentrations of TNFα, IL-6, PGE2, and 15d-PGJ2 in the supernatants of the cells were measured, and gene expressions of PPARγ and COX-2 were evaluated in the cells. Furthermore, we evaluated whether a selective α2 adrenoceptor antagonist, yohimbine or a selective PPARγ antagonist, T0070907, reversed the effects of DEX on the LPS-induced inflammatory responses. DEX inhibited LPS-induced TNFα, IL-6, and PGE2 productions and COX-2 mRNA expression, and the effects of DEX were reversed by yohimbine. On the other hand, DEX significantly increased 15d-PGJ2 production and PPARγ mRNA expression, and yohimbine reversed these DEX's effects. Furthermore, T0070907 reversed the anti-inflammatory effects of DEX on TNFα and IL-6 productions in the cells. These results suggest that DEX inhibits LPS-induced inflammatory responses through PPARγ activation following binding to α2 adrenoceptors.

Assessing the Effectiveness of Combined Analgesics for Bilateral Ramus Osteotomies.

Pain management is important for alleviating patients' suffering and early recovery. Although analgesic combinations are known to be effective, a comparison of the effectiveness of different combinations has never been performed specifically for ramus osteotomy procedures. Therefore, the purpose of this observational retrospective cohort study was to identify an effective combination for pain management throughout the intraoperative and immediate postoperative period for patients undergoing bilateral ramus osteotomy procedures. Inclusion criteria consisted of patients who had undergone bilateral mandibular ramus osteotomies over a 2-year period. The analyzed predictor variables included patient gender, age, body weight, operation, anesthetic method, duration of operation, intraoperative use of fentanyl, nonsteroidal anti-inflammatory drugs (NSAIDs), and intravenous acetaminophen administered in the operating room at the end of the surgery. The outcome variable was the necessity for additional rescue analgesics (yes/no) in the recovery room. Bivariate statistics and multivariate analysis were computed with a p-value of <0.05. The study sample was comprised of 78 patients requiring bilateral mandibular ramus osteotomies. From the multivariate analysis, the combination of NSAIDs-acetaminophen-fentanyl was an independent factor for no additional rescue analgesics during the first 1 hour after bilateral ramus osteotomies, indicating that the combination is significantly effective for bilateral ramus osteotomies compared with the other combinations. Considering that this study consisted of a small sample size, the results of this study suggest that some of the combinations, particularly NSAIDs-acetaminophen-fentanyl, are more effective than NSAIDs alone for postoperative pain control immediately following bilateral ramus osteotomy procedures.

Metabolic alterations caused by the mutation and overexpression of the Tmem135 gene.

IMPACT STATEMENT: Mitochondria are dynamic organelles undergoing fission and fusion. Proper regulation of this process is important for healthy aging process, as aberrant mitochondrial dynamics are associated with several age-related diseases/pathologies. However, it is not well understood how imbalanced mitochondrial dynamics may lead to those diseases and pathologies. Here, we aimed to determine metabolic alterations in tissues and cells from mouse models with over-fused (fusion > fission) and over-fragmented (fusion < fission) mitochondria that display age-related disease pathologies. Our results indicated tissue-dependent sensitivity to these mitochondrial changes, and metabolic pathways likely affected by aberrant mitochondrial dynamics. This study provides new insights into how dysregulated mitochondrial dynamics could lead to functional abnormalities of tissues and cells.

Multi-drug therapy for epilepsy influenced bispectral index after a bolus propofol administration without affecting propofol's pharmacokinetics: a prospective cohort study.

Some previous studies have indicated that valproate (VPA) might change the pharmacokinetics and enhance the effects of propofol. We evaluated whether clinical VPA therapy affected the propofol blood level, the protein-unbound free propofol level, and/or the anesthetic effects of propofol in the clinical setting. The subjects were divided into the control group (not medicated with antiepileptics), the mono-VPA group (medicated with VPA alone), and the poly-VPA group (medicated with VPA, other antiepileptics, and/or psychoactive drugs). General anesthesia was induced via the administration of a single bolus of propofol and a remifentanil infusion, and when the bispectral index (BIS) exceeded 60 sevoflurane was started. There were no significant differences in the total blood propofol level at 5, 10, 15, and 20 min or the protein-unbound free propofol level at 5 min after the intravenous administration of propofol between the 3 groups. However, the minimum BIS was significantly lower and the time until the BIS exceeded 60 was significantly longer in the poly-VPA group. In the multivariate regression analysis, belonging to the poly-VPA group was found to be independently associated with the minimum BIS value and the time until the BIS exceeded 60. Clinical VPA therapy did not influence the pharmacokinetics of propofol. However, multi-drug therapy involving VPA might enhance the anesthetic effects of propofol.

Pulmonary Aspiration During Induction of General Anesthesia.

Perioperative pulmonary aspiration of gastric contents can induce complications of varying severity, including aspiration pneumonitis or pneumonia, which may be lethal. A 34-year-old man with no significant medical history presented to Okayama University Hospital for extraction of the third molars and incisive canal cystectomy under general anesthesia. He experienced pulmonary aspiration of clear stomach fluid during mask ventilation after induction. After aspiration occurred, the patient was immediately intubated, and suctioning was performed through the endotracheal tube (ETT). An anteroposterior (AP) chest radiograph was obtained that demonstrated atelectasis in the left lower lobe, in addition to increased peak airway pressures being noted, although SpO2 remained at 96% to 99% at an FiO2 of 1.0. The decision was made to proceed, and the scheduled procedures were completed in approximately 2 hours. A repeat AP chest radiograph obtained at the end of the operation revealed improvement of the atelectasis, and no residual atelectasis was observed on the next day. Although the patient reported following standard preoperative fasting instructions (no fluids for 2 hours preoperatively), more than 50 mL of clear fluid remained in his stomach. Because vomiting can occur despite following NPO guidelines, the need for continued vigilance by anesthesia providers and proper timely management is reinforced.

Locally injected ivabradine inhibits carrageenan-induced pain and inflammatory responses via hyperpolarization-activated cyclic nucleotide-gated (HCN) channels.

BACKGROUND: Recently, attention has been focused on the role of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in the mechanism of and as a treatment target for neuropathic and inflammatory pain. Ivabradine, a blocker of HCN channels, was demonstrated to have an effect on neuropathic pain in an animal model. Therefore, in the present study, we evaluated the effect of ivabradine on inflammatory pain, and under the hypothesis that ivabradine can directly influence inflammatory responses, we investigated its effect in in vivo and in vitro studies. METHODS: After approval from our institution, we studied male Sprague-Dawley rats aged 8 weeks. Peripheral inflammation was induced by the subcutaneous injection of carrageenan into the hindpaw of rats. The paw-withdrawal threshold (pain threshold) was evaluated by applying mechanical stimulation to the injected site with von Frey filaments. Ivabradine was subcutaneously injected, combined with carrageenan, and its effect on the pain threshold was evaluated. In addition, we evaluated the effects of ivabradine on the accumulation of leukocytes and TNF-alpha expression in the injected area of rats. Furthermore, we investigated the effects of ivabradine on LPS-stimulated production of TNF-alpha in incubated mouse macrophage-like cells. RESULTS: The addition of ivabradine to carrageenan increased the pain threshold lowered by carrageenan injection. Both lamotrigine and forskolin, activators of HCN channels, significantly reversed the inhibitory effect of ivabradine on the pain threshold. Ivabradine inhibited the carrageenan-induced accumulation of leukocytes and TNF-alpha expression in the injected area. Furthermore, ivabradine significantly inhibited LPS-stimulated production of TNF-alpha in the incubated cells. CONCLUSION: The results of the present study demonstrated that locally injected ivabradine is effective against carrageenan-induced inflammatory pain via HCN channels. Its effect was considered to involve not only an action on peripheral nerves but also an anti-inflammatory effect.

Hyperoxia reduces salivary secretion by inducing oxidative stress in mice.

OBJECTIVE: The aim of this study was to determine the effects of prolonged hyperoxia on salivary glands and salivary secretion in mice. DESIGN: Male C57BL/6 J mice were kept in a 75% oxygen chamber (hyperoxia group) or a 21% oxygen chamber for 5 days. We measured the secretion volume, protein concentration, and amylase activity of saliva after the injection of pilocarpine. In addition, we evaluated the histological changes induced in the submandibular glands using hematoxylin and eosin and Alcian blue staining and assessed apoptotic changes using the TdT-mediated dUTP nick end labeling (TUNEL) assay. We also compared the submandibular gland expression levels of heme oxygenase-1 (HO-1), superoxide dismutase (SOD)-1, and SOD-2 using the real-time polymerase chain reaction. RESULTS: In the hyperoxia group, salivary secretion was significantly inhibited at 5 and 10 min after the injection of pilocarpine, and the total salivary secretion volume was significantly decreased. The salivary protein concentration and amylase activity were also significantly higher in the hyperoxia group. In the histological examinations, enlargement of the mucous acini and the accumulation of mucins were observed in the submandibular region in the hyperoxia group, and the number of TUNEL-positive cells was also significantly increased in the hyperoxia group. Moreover, the expression levels of HO-1, SOD-1, and SOD-2 were significantly higher in the hyperoxia group. CONCLUSION: Our results suggest that hyperoxia reduces salivary secretion, and oxidative stress reactions might be involved in this.

Remifentanil suppresses increase in interleukin-6 mRNA in the brain by inhibiting cyclic AMP synthesis.

PURPOSE: Neuronal inflammation is caused by systemic inflammation and induces cognitive dysfunction. IL-6 plays a crucial role in therapies for neuronal inflammation and cognitive dysfunction. Remifentanil, an ultra-short-acting opioid, controls inflammatory reactions in the periphery, but not in the brain. Therefore, the anti-inflammatory effects of remifentanil in neuronal tissue and the involvement of cAMP in these effects were investigated in the present study. METHODS: Mice were divided into 4 groups: control, remifentanil, LPS, and LPS + remifentanil. Brain levels of pro-inflammatory cytokine mRNA, and serum levels of corticosterone, catecholamine and IL-6 were measured in the 4 groups. The co-localization of IL-6 and astrocytes in the mouse brain after the LPS injection was validated by immunostaining. LPS and/or remifentanil-induced changes in intracellular cAMP levels in cultured glial cells were measured, and the effects of cAMP on LPS-induced IL-6 mRNA expression levels were evaluated. RESULTS: Remifentanil suppressed increase in IL-6 mRNA levels in the mouse brain, and also inhibited the responses of plasma IL-6, corticosterone, and noradrenaline in an inflammatory state. In the hypothalamus, IL-6 was localized in the median eminence, at which GFAP immunoreactivity was specifically detected. In cultured cells, remifentanil suppressed increase in IL-6 mRNA levels and intracellular cAMP levels after the administration of LPS, and this enhanced IL-6 mRNA expression in response to LPS. CONCLUSION: Remifentanil suppressed increase in IL-6 mRNA levels in the brain in an inflammatory state, and this effect may be attributed to its direct action on neuronal cells through the inhibition of intracellular cAMP rather than corticosterone.

The effect of Tmem135 overexpression on the mouse heart.

Tissues with high-energy demand including the heart are rich in the energy-producing organelles, mitochondria, and sensitive to mitochondrial dysfunction. While alterations in mitochondrial function are increasingly recognized in cardiovascular diseases, the molecular mechanisms through which changes in mitochondria lead to heart abnormalities have not been fully elucidated. Here, we report that transgenic mice overexpressing a novel regulator of mitochondrial dynamics, transmembrane protein 135 (Tmem135), exhibit increased fragmentation of mitochondria and disease phenotypes in the heart including collagen accumulation and hypertrophy. The gene expression analysis showed that genes associated with ER stress and unfolded protein response, and especially the pathway involving activating transcription factor 4, are upregulated in the heart of Tmem135 transgenic mice. It also showed that gene expression changes in the heart of Tmem135 transgenic mice significantly overlap with those of aged mice in addition to the similarity in cardiac phenotypes, suggesting that changes in mitochondrial dynamics may be involved in the development of heart abnormalities associated with aging. Our study revealed the pathological consequence of overexpression of Tmem135, and suggested downstream molecular changes that may underlie those disease pathologies.

In vitro changes in the proportion of protein-unbound-free propofol induced by valproate.

PURPOSE: It has been reported that oral valproate (VPA) reduces the dose of propofol required for sedation. As  a potential reason for this, it is considered that VPA displaces serum protein-bound propofol and increases the proportion of protein-unbound-free propofol. To examine this hypothesis, the present in vitro study investigated the influence of VPA on the proportion of protein-unbound-free propofol in human serum samples. METHODS: Serum samples were collected from 10 healthy volunteers, who were not taking any medication. VPA (final concentration: 0.05, 0.1 or 1 mg/mL) and propofol (final concentration: 1 or 5 µg/mL) were mixed with serum samples with normal (4.0 g/dL) or low (2.5 g/dL) albumin concentrations. Then, protein-unbound-free propofol was extracted from the samples, and its concentration was measured using high-performance liquid chromatography. We compared the proportion of protein-unbound-free propofol in each of the VPA-containing samples with that in serum samples without VPA (control). RESULTS: In the serum samples with normal albumin concentrations, 1 mg/mL VPA significantly increased the proportion of protein-unbound-free propofol at 1 and 5 µg/mL propofol. Furthermore, in the serum samples with low albumin concentrations, the proportion of protein-unbound-free propofol was significantly increased by both 0.1 and 1 mg/mL VPA at propofol concentrations of 1 and 5 µg/mL. CONCLUSION: VPA might increase the proportion of protein-unbound-free propofol in human serum via displacement reactions.

Clinical Analysis of Analgesics and Steroids Use for Extraction of Teeth in Patients with Intellectual Disability Under General Anesthesia.

BACKGROUND: The extraction of lower wisdom teeth is often performed under general anesthesia in patients with intellectual disabilities. However, the choice of analgesics has not yet been investigated. OBJECTIVE: To analyze the use of analgesics during general anesthesia for extraction including lower wisdom teeth in patients with intellectual disabilities. METHODS: This research is a retrospective observational study. The study population was composed of all patients presenting for extraction of lower wisdom teeth under ambulatory general anesthesia in the clinic of Special Needs Dentistry in Okayama University Hospital from April 2011 to March 2016. The distribution of the combination of analgesics and the relationship between the use of analgesics and the type of extraction were investigated. RESULTS: One hundred and twelve cases were enrolled in this study. Intravenous injections of flurbiprofen, acetaminophen and betamethasone were used in 96 (85.7%), 12 (10.7%) and 26 cases (23.2%), respectively. Flurbiprofen is a non-steroid anti-inflammatory drugs (NSAIDs). Acetaminophen is an old analgesic, but an injection of acetaminophen is new, which was released in 2013 in Japan. And betamethasone is not an analgesic, but a steroid. Betamethasone was used in combination with other analgesics, and was used at a higher dose in a case in which four wisdom teeth were extracted. CONCLUSION: Flurbiprofen was the main analgesic used for extraction of wisdom teeth under general anesthesia in patients with intellectual disabilities. Betamethasone was used to support flurbiprofen or acetaminophen for extractions of multiple wisdom teeth, with the aim of controlling swelling rather than relieving pain.

Mouse Tmem135 mutation reveals a mechanism involving mitochondrial dynamics that leads to age-dependent retinal pathologies.

While the aging process is central to the pathogenesis of age-dependent diseases, it is poorly understood at the molecular level. We identified a mouse mutant with accelerated aging in the retina as well as pathologies observed in age-dependent retinal diseases, suggesting that the responsible gene regulates retinal aging, and its impairment results in age-dependent disease. We determined that a mutation in the transmembrane 135 (Tmem135) is responsible for these phenotypes. We observed localization of TMEM135 on mitochondria, and imbalance of mitochondrial fission and fusion in mutant Tmem135 as well as Tmem135 overexpressing cells, indicating that TMEM135 is involved in the regulation of mitochondrial dynamics. Additionally, mutant retina showed higher sensitivity to oxidative stress. These results suggest that the regulation of mitochondrial dynamics through TMEM135 is critical for protection from environmental stress and controlling the progression of retinal aging. Our study identified TMEM135 as a critical link between aging and age-dependent diseases.