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nd the validity of the InSIDE assumption. Down-sampling analysis can be used in large GWAS for the possible detection of bias in the MR methods.Nicotinamide adenine dinucleotide (NAD) is a coenzyme in metabolic reactions and cosubstrate in signaling pathways of cells. While the intracellular function of NAD is well described, much less is known about its importance as an extracellular molecule. Moreover, there is only little information about the concentration of extracellular NAD and the ratio between its oxidized (NAD+) and reduced (NADH) form in humans. Therefore, our study aimed at the analysis of total NAD and NAD+/NADH ratio in human plasma depending on sex and age. First, an enzymatic assay was established for detecting NAD+ and NADH in human plasma samples. Then, plasma NAD was analyzed in 205 probands without severe diseases (91 men, 114 women) being 18-83 years old. The total plasma NAD concentration was determined with median 1.34 µM (0.44-2.88 µM) without difference between men and women. Although the amounts of NAD+ and NADH were nearly balanced, women had higher plasma NAD+/NADH ratios than men (median 1.33 vs. 1.09, P less then 0.001). The sex-related difference in the plasma NAD+/NADH ratio reduces with increasing age, an effect that was more obvious for two parameters of the biological age (skin autofluorescence, brachial-femoral pulse wave velocity (PWV)) than for the chronological age. However, plasma values for total NAD and NAD+/NADH ratio did not generally alter with increasing age. In conclusion, human plasma contains low micromolar concentrations of total NAD with higher NAD+/NADH redox ratios in adult but not older women compared with same-aged men.This parallel group randomized controlled clinical trial compared intubation duration and success using video laryngoscopy (VL) versus direct laryngoscopy (DL) during routine nasotracheal intubation. Fifty patients undergoing oral and maxillofacial surgery under general anesthesia were randomly assigned into 2 groups receiving either VL or DL to facilitate nasotracheal intubation. The primary outcome was the amount of time required to complete nasotracheal intubation. The secondary outcomes included the success of first attempt at intubation and the use of Magill forceps. Results demonstrated a mean time to intubation of 142 seconds in the DL group and 94 seconds in the VL group (p = .011). First attempt intubation success was 92.0% in the VL group and 84.0% in the DL group (p = .34). The use of Magill forceps was significantly increased in the DL group (p = .007). VL for routine nasotracheal intubation in oral and maxillofacial surgery procedures results in significantly faster intubation times and decreased use of Magill forceps compared with traditional DL.This is a case report of a 75-year-old man scheduled for apical resection and cystectomy of odontogenic cysts involving both maxillary central incisors who presented with a previously unknown laryngeal mass that was discovered prior to intubation. Following induction and easy mask ventilation, direct laryngoscopy revealed a large mass on the right side of the glottis that impeded passage of a standard oral endotracheal tube. LOXO-305 chemical structure Successful atraumatic intubation was performed with the combination of a video laryngoscope (King Vision, Ambu Inc, Ballerup, Denmark) and a gum elastic bougie (GEB). Although a GEB may not be used routinely for tracheal intubation, it facilitated smooth advancement of the endotracheal tube without damaging the laryngeal mass when used in combination with video laryngoscopy.Due to the ongoing nature of the COVID-19 pandemic, I have decided to print the following commentary to help provide another alternative for reducing potential exposure to and incidental transmission of SARS-CoV-2 during the provision of anesthesia for dentistry. -Kyle J. Kramer, Editor-in-Chief.One century after the clinical introduction of cocaine, local anesthesia remains the most important method of pain control in dentistry. Many local anesthetics have been marketed since 1884, and it is likely that attempts to produce drugs that enhance anesthetic efficacy, reduce systemic and local toxicity, and increase nociceptive selectivity, will continue. In addition, new methods of drug administration have been and will be developed to achieve these goals. Of fundamental importance to such improvements are investigations into the pharmacology of drugs with local anesthetic activity and anatomical and physiologic studies pertaining to the reasons why local anesthetics sometimes fail to achieve desired results. This paper reviews recent advances in our understanding of these drugs and their clinical use.A 20-year-old woman with glycogen storage disease type 0 (GSD-0) underwent velopharyngeal closure for velopharyngeal insufficiency following palatoplasty. To reduce the risk of complications attributed to GSD-0, general anesthesia was administered using a total intravenous anesthesia (TIVA) technique with propofol and remifentanil, along with supplemental glucose-containing intravenous fluids. Her blood glucose remained stable, intraoperative body temperature ranged from 36.5 to 37.2°C, and the velopharyngeal closure was completed without any adverse events.Restless legs syndrome (RLS) is a neurological sensory disorder associated with sensory and motor symptoms that most commonly occur at night and during periods of rest. It is characterized by altered or abnormal sensations primarily in the legs and the urge to move the associated limbs. Perioperative procedures, including general anesthesia, can cause exacerbations of RLS. This is a case report of a suspected RLS exacerbation in a 22-year-old woman who had no formal diagnosis of RLS despite reporting symptoms that met all essential diagnostic criteria by the International RLS Study Group. Despite her previous diagnoses of dehydration induced-muscle pain or nocturnal cramps, we suspected her to have RLS. The patient underwent general anesthesia for a bilateral sagittal split ramus osteotomy using a combined inhalational and intravenous anesthetic technique with sevoflurane, propofol, remifentanil, and dexmedetomidine. After successful completion of the surgery and returning to the ward, she began moving her lower extremities and complaining of unpleasant sensations in both ankles.