Explore the vast range of titles available.

Background Attention-Deficit/Hyperactive Disorder (ADHD) is the neurodevelopmental disorder which commonly occurs in children with the prevalence ranging from 3.4% to 7.2%. It profoundly affects the academic achievement, well-being, and social interactions. As a result, this disorder is of high costs for both individuals and society. Despite the availability of the knowledge regarding the mechanisms of ADHD, the pathogenesis is not clear, hence, existence of many challenges especially on making correct early diagnosis and provision of the accurate management. Objectives We aimed to review the pathogenic pathways of ADHD in children. The major focus was to provide an update on the reported etiologies in humans, animal models, modulators, therapies, mechanisms, epigenetic changes, and the interaction between genetic and environmental factors. Methods References for this review were identified through systematic search in PubMed by using special keywords for all years until January 2022. Results Several genes have been reported to associate with ADHD: DRD1, DRD2, DRD4, DAT1, TPH2, HTR1A, HTR1B, SLC6A4, HTR2A, DBH, NET1, ADRA2A, ADRA2C, CHRNA4, CHRNA7, GAD1, GRM1, GRM5, GRM7, GRM8, TARBP1, ADGRL3, FGF1, MAOA, BDNF, SNAP25, STX1A, ATXN7, and SORCS2. Some of these genes have evidences both from human beings and animal models while others have evidences in either humans or animal models only. Notably, most of these animal models are knockout and do not generate the genetic alteration of the patients. Besides, some of the gene polymorphisms reported differ according to the ethnic groups. Majority of the available animal models are related to the dopaminergic pathway. Epigenetic changes including SUMOylation, methylation and acetylation have been reported in genes related to the dopaminergic pathway. Conclusions Dopaminergic pathway remains to be crucial in the pathogenesis of ADHD. It can be affected by environmental factors and other pathways. Nevertheless, it is still unclear how environmental factors relate with all neurotransmitter pathways thus, more studies are needed. Although several genes have been related to ADHD, there are few animal models studies on majority of the genes, and they do not generate the genetic alteration of the patients. More animal models and epigenetic studies are required.

BackgroundPostoperative nausea and vomiting (PONV) is problematic in bariatric surgery patients and has negative impacts on perioperative outcome. Antiemetic prophylaxis may reduce PONV. Perioperative antiemetic prophylaxis or therapy is crucial and may enhance fast-track bariatric surgery. This study examined the impact of intraoperative multimodal antiemetic prophylaxis on fast-track bariatric surgery.MethodsThis prospective observational clinical study explored the perioperative data of 400 consecutive laparoscopic bariatric surgery patients, over a 6-year period. Perioperative outcomes and variables were analyzed and compared between different intraoperative antiemetic modes.ResultsThe mean BMI was 49, mean age was 42, and male:female ratio was 1:4. About 70% of patients received intraoperative multimodal antiemetic, comprising combinations of prochlorperazine, dexamethasone, ondansetron, or cyclizine. PONV occurred in 19.5% of patients. Intraoperative multimodal antiemetic was associated with significantly less PONV, shorter post-anesthesia care unit duration, earlier postoperative drinking, and shorter hospital stay (p = 0.001). Compared to other multimodal antiemetic modes, dexamethasone + cyclizine + prochlorperazine provided the best prophylaxis and outcome: p = 0.002.ConclusionPONV is a common and peculiar problem in bariatric surgery patients. However, intraoperative multimodal antiemetic prophylaxis effectively minimizes PONV. Intraoperative multimodal antiemetic enhances fast-track bariatric surgical care, patient satisfaction, and perioperative outcomes.

•Shoulder pain is common, but difficult to treat. J Clin Anesth. 2017;41:48-54. J Clin Anesth. 2007;19:296-8.•Suprascapular nerve block may provide temporary shoulder analgesia. J Clin Anesth. 2013;25:347-8.•Previous studies showed perioperative benefit of magnesium, but none for suprascapular block. J Clin Anesth. 2017;39:129-38.•This new study highlights the utility, ease and efficacy of magnesium suprascapular block analgesia for shoulder pain.•It shows that magnesium suprascapular block ensures better analgesia & function for 18wks; & is the first study to show this.

Study Objectives: Chronic pain is associated with insomnia. The objective of this clinical study was to compare the efficacy and safety of different prescribed doses of zopiclone and clonidine for the management of insomnia in patients with chronic pain. Methods: This prospective observational crossover study included 160 consenting adult patients receiving pain management treatment. For insomnia treatment, each patient ingested different prescribed doses of zopiclone or clonidine on alternate nights. Each patient used a special validated sleep diary to collect data including pain score, sleep scores, sleep duration, sleep medication dose, and adverse effects. Each patient completed the diary for 3 continuous weeks. Pain was measured using a numeric pain rating scale. Sleep score was measured using the Likert Sleep Scale. A change in the pain or sleep scores by 2 points was considered significant. Of the 160 study participants, 150 (93.8%) completed the study successfully, and their data were analyzed with IBM SPSS Statistics 25 (IBM Corporation, Armonk, NY) using Student’s t test, analysis of variance, Pearson chi-square test, and regression analysis. A P value < .05 was considered significant. Results: Pain score was lower with clonidine than zopiclone ( P = .025). Time to fall asleep was shorter with clonidine than zopiclone ( P = .001). Feeling rested on waking in the morning was better with clonidine than zopiclone ( P = .015). Overall sleep quality was better with clonidine than zopiclone ( P = .015). Total Likert sleep score was better with clonidine than zopiclone ( P = .005). Total sleep duration was better with clonidine than zopiclone ( P = .013). Adverse effects were commoner with zopiclone, including collapse, fall, confusion, amnesia, mood disorder, hallucination, nightmare, nocturnal restlessness, locomotor dysfunction, nausea and headache. A minor adverse effect of dry mouth was commoner with clonidine. Conclusions: Clonidine is significantly better than zopiclone with respect to sleep quality, analgesia, tolerability profile, and patient safety. Further studies comparing clonidine with other insomnia medications will be beneficial. Citation: Bamgbade OA, Tai-Osagbemi J, Bamgbade DO, et al. Clonidine is better than zopiclone for insomnia treatment in chronic pain patients. J Clin Sleep Med . 2022;18(6):1565–1571.

Background Postoperative pain and analgesia present challenges in bariatric surgery patients. Multimodal analgesia may provide better efficacy, less complications and expedite fast-track bariatric surgical care. There are no studies of the broader topic of perioperative analgesia and the overall impact. This study highlights the impact of multimodal intraoperative analgesia on fast-track bariatric surgery. Methods This observational study examined the perioperative outcome data of 412 consecutive laparoscopic bariatric surgery patients over a 6-year period. Perioperative outcome and variables were analysed and compared between different intraoperative analgesia types. Results Mean BMI was 49, mean age was 42 and male:female ratio was 1:4. About 82% of patients received multimodal intraoperative analgesia, comprising various combinations of bupivacaine infiltration and intravenous acetaminophen, morphine, tramadol, parecoxib or diclofenac. Morphine was administered in 83% of patients and tramadol in 17%. Multimodal intraoperative analgesia provided better postoperative analgesia, shorter postanaesthesia care unit (PACU) duration, lower postoperative opioid requirement, less postoperative vomiting, earlier postoperative oral intake, earlier ambulation and shorter hospital stay compared to unimodal intraoperative morphine analgesia ( p  = 0.0001). Multimodal analgesia comprising tramadol + acetaminophen + diclofenac provided better postoperative analgesia, shorter PACU duration, lower postoperative opioid requirement, earlier ambulation, shorter hospital stay and less postoperative hypopnoea compared to patients who received morphine ( p  = 0.0001). Conclusions Multimodal intraoperative analgesia provides better postoperative analgesia, less complications and better perioperative outcomes and facilitates fast-track bariatric surgical care. Tramadol is suitable, efficacious and safe and associated with the best perioperative outcomes in bariatric surgery patients.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) current reduces dendritic summation, suppresses dendritic calcium spikes, and enables inhibitory GABA-mediated postsynaptic potentials, thereby suppressing epilepsy. However, it is unclear whether increased HCN current can produce epilepsy. We hypothesized that gain-of-function (GOF) and loss-of-function (LOF) variants of HCN channel genes may cause epilepsy. This systematic review aims to summarize the role of HCN channelopathies in epilepsy, update genetic findings in patients, create genotype-phenotype correlations, and discuss animal models, GOF and LOF mechanisms, and potential treatment targets. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, for all years until August 2021. We identified pathogenic variants of ( = 24), ( = 8), ( = 2), and ( = 6) that were associated with epilepsy in 74 cases (43 , 20 , 2 , and 9 ). Epilepsy was associated with GOF and LOF variants, and the mechanisms were indeterminate. Less than half of the cases became seizure-free and some developed drug-resistant epilepsy. Of the 74 cases, 12 (16.2%) died, comprising ( = 4), ( = 2), ( = 2), and ( = 4). Of the deceased cases, 10 (83%) had a sudden unexpected death in epilepsy (SUDEP) and 2 (16.7%) due to cardiopulmonary failure. SUDEP affected more adults ( = 10) than children ( = 2). variants p.M234R, p.C329S, p.V414M, p.M153I, and p.M305L, as well as variants p.S632W and delPPP (p.719-721), were associated with different phenotypes. p.L157V and p.R550C were associated with genetic generalized epilepsy. There are several HCN animal models, pharmacological targets, and modulators, but precise drugs have not been developed. Currently, there are no HCN channel openers. We recommend clinicians to include genes in epilepsy gene panels. Researchers should explore the possible underlying mechanisms for GOF and LOF variants by identifying the specific neuronal subtypes and neuroanatomical locations of each identified pathogenic variant. Researchers should identify specific HCN channel openers and blockers with high binding affinity. Such information will give clarity to the involvement of HCN channelopathies in epilepsy and provide the opportunity to develop targeted treatments.

Background Postoperative complications are undesirable and potentially common in the increasing obese population of surgical patients. There is a scarcity of recent and reliable studies comparing postoperative morbidity and mortality in obese and nonobese patients. The aim of this study was to evaluate the prevalence, pattern, and severity of postoperative complications in obese and nonobese surgical patients. Methods A retrospective review and analysis of adult postoperative complications recorded on an electronic database was conducted. The database covered a period of 4 years and consisted of 7,271 cases of postoperative complications that occurred within 30 days of noncardiac moderate or major surgery. Appropriate data and variables were compared between obese and nonobese patients using the SPSS program. Results The rate of postoperative complications was 7.7%. Obese patients had a higher prevalence of myocardial infarction (P = 0.001), peripheral nerve injury (P = 0.039), wound infection (P = 0.001), and urinary tract infection (P = 0.004). ). Morbidly obese patients had a higher mortality rate of 2.2% compared with 1.2%; for all other patients (P = 0.034) and a higher prevalence of tracheal reintubation (P = 0.009) and cardiac arrest (P = 0.015). Obese patients had higher American Society of Anesthesiologists (ASA) physical status scores than other patients (P = 0.001). Conclusions Obese patients have a significantly higher risk of postoperative myocardial infarction, wound infection, nerve injury, and urinary infection. Obesity is an independent risk factor for perioperative morbidity, and morbid obesity is a risk factor for mortality.

Background CACNA1A variants are associated with severe neurodevelopmental disorders (NDDs), but the underlying mechanisms remain unclear. Our goal was to investigate the molecular mechanisms through which these variants lead to intellectual disability (ID), autism spectrum disorder (ASD), epilepsy, and ataxia. Methods Clinical information was collected from six pediatric patients. Molecular experiments were performed on transfected human embryonic kidney and Chinese hamster ovary cells to study the effect of these variants on mitochondrial and lysosomal function. RT-qPCR, Western blot, apoptosis assay, mitochondrial and lysosomal tracker fluorescence intensity, and mitochondrial calcium concentration tests were performed. Additionally, we examined the levels of reactive oxygen species (ROS), adenosine triphosphate (ATP), and mitochondrial enzymes and copy numbers. Results We identified six variants that downregulated CACNA1A mRNA: p.D1644N, p.Y62C, p.G701R, p.R279C, p.R1664Q, and p.L1422Sfs*8. Five variants down-regulated Ca v 2.1 protein expression, whereas, the p.R279C variant up-regulated it. All variants led to dysfunctions in the autophagy-lysosomal system: p.D1644N, p.R279C, and p.G701R variants blocked the fusion of autophagosomes and lysosomes while p.Y62C, p.R1664Q, and p.L1422Sfs*8 variants displayed increased lysosomal expression. The p.Y62C, p.G701R, p.R279C, p.R1664Q, and p.L1422Sfs*8 variants exhibited defective autophagy. The p.Y62C and p.D1644N variants disrupted mitochondrial function by downregulating mitochondrial enzyme activities and ATP levels, as well as by upregulating mitochondrial copy numbers, calcium levels, and ROS levels. Furthermore, the p.Y62C variant increased mitochondrial expression, fusion, and fission. In contrast, the p.D1644N variant decreased mitochondrial expression, fusion, fission, and mitophagy. The p.G701R, p.R279C, and p.R1664Q variants also interrupted mitochondrial function. These variants down-regulated mitochondrial enzyme activities, fusion and fission, the mitophagy process, and ATP levels while up-regulating mitochondrial copy numbers and ROS levels. The p.L1422Sfs*8 variant increased the expression, fusion and fission of mitochondrial proteins, while decreasing mitochondrial calcium levels and the mitophagy process. The p.R279C variant increased mitochondrial expression and calcium levels while enhancing apoptosis. The p.G701R variant decreased mitochondrial expression and calcium levels while enhancing apoptosis. The p.R1664Q variant increased mitochondrial calcium levels and enhanced apoptosis without changing mitochondrial expression. Conclusions CACNA1A variants may alter mitochondrial and lysosomal function, resulting in the development of NDDs. Graphical abstract

Background: Obstructive sleep apnea (OSA) is prevalent in the surgical patient population and is associated with high risk of perioperative complications. There are limited guidelines and wide practice variations regarding the perioperative care of obese and OSA patients. This is a study of European anesthesiologists' clinical practice of perioperative care of OSA patients. Methods: This survey evaluated United Kingdom anesthesiologists' clinical practice of the perioperative care of OSA patients. Outcomes and variables were compared between 4100 anesthesiologists of different clinical experience and hospital settings. Results: Approximately 45% of respondents manage OSA patients rarely, 42% occasionally, and 13% regularly. Most respondents order OSA screening tests if patients have tonsillar hypertrophy, head/neck tumor, BMI >35, increased neck circumference, craniofacial anomaly, and right-sided electrocardiography (ECG) anomaly. Majority request preoperative polysomnography, ECG, overnight pulse oximetry, and arterial blood gas analysis. Majority recommend preoperative weight loss, optimisation, smoking cessation, reduction of substance use, and regular mask-CPAP use. Majority consider endoscopy, and ophthalmology as appropriate day case procedures, but not laparoscopy. Majority postpone elective airway, laparoscopic, laparotomy, and head/neck surgery; if patients are not optimized preoperatively. For major surgery, combined general + neuraxial anesthesia was ranked as 3rd option. For major limb surgery, neuraxial anesthesia without sedation was ranked as 1st option, nerve block without sedation was ranked 2nd, and general anesthesia + nerve block was ranked 3rd or 4th. At anesthesia emergence, majority ensure that patients have normal consciousness, respiration and neuromuscular function. Majority ensure postoperative oximetry, telemetry, and oxygen supplementation. Conclusion: This study highlights variations in anesthesiologists' perioperative care of OSA patients; even in developed countries with advanced medical training and standards. The study outcomes will improve perioperative care of OSA patients.