Correction to: Expanding the genetic heterogeneity of intellectual disability.

Variant nomenclature discrepancy was identified in the article.

Expanding the genetic heterogeneity of intellectual disability.

Intellectual disability (ID) is a common morbid condition with a wide range of etiologies. The list of monogenic forms of ID has increased rapidly in recent years thanks to the implementation of genomic sequencing techniques. In this study, we describe the phenotypic and genetic findings of 68 families (105 patients) all with novel ID-related variants. In addition to established ID genes, including ones for which we describe unusual mutational mechanism, some of these variants represent the first confirmatory disease-gene links following previous reports (TRAK1, GTF3C3, SPTBN4 and NKX6-2), some of which were based on single families. Furthermore, we describe novel variants in 14 genes that we propose as novel candidates (ANKHD1, ASTN2, ATP13A1, FMO4, MADD, MFSD11, NCKAP1, NFASC, PCDHGA10, PPP1R21, SLC12A2, SLK, STK32C and ZFAT). We highlight MADD and PCDHGA10 as particularly compelling candidates in which we identified biallelic likely deleterious variants in two independent ID families each. We also highlight NCKAP1 as another compelling candidate in a large family with autosomal dominant mild intellectual disability that fully segregates with a heterozygous truncating variant. The candidacy of NCKAP1 is further supported by its biological function, and our demonstration of relevant expression in human brain. Our study expands the locus and allelic heterogeneity of ID and demonstrates the power of positional mapping to reveal unusual mutational mechanisms.

Parental Attitudes and Hesitancy About COVID-19 vs. Routine Childhood Vaccinations: A National Survey.

Objectives: To quantify parental acceptance of the COVID-19 vaccine and assess the vaccine hesitancy (VH) for COVID-19 vs. childhood vaccines. Methods: Eight vaccine hesitancy scale (VHS) items, adopted from WHO's Strategic Advisory Group of Immunization (SAGE), were used to assess VH for COVID-19 vaccine vs. routine childhood vaccines. We distributed the online survey to parents with the commence of the national childhood COVID-19 vaccination program in Saudi Arabia. Results: Among 3,167 parents, 47.6% are decided to vaccinate their children against COVID-19. The most common reasons for refusal were inadequate safety information (69%) and worry about side effects (60.6%). Parents have a significantly greater positive attitudes toward children's routine vaccines vs. the COVID-19 vaccine, with higher mean VHS (±SD) = 2.98 ± 0.58 vs. 2.63 ± 0.73, respectively (p-value < 0.001). Parents agreed more that routine childhood vaccines are more essential and effective as compared to the COVID-19 vaccine (Cohen's D: 0.946, and 0.826, consecutively; T-test p-value < 0.00). There is more parental anxiety about serious side effects of the COVID-19 vaccine vs. routine childhood vaccines (Cohen's D = 0.706, p-value < 0.001). Parents who relied on the Ministry of Health information were more predicted (OR = 1.28, p-value = 0.035) to intend to vaccinate as opposed to those who used the WHO website (OR = 0.47, -53%, p-value < 0.001). In a multivariate logistic regression analysis, the factors associated with intention to vaccinate children were parents who received COVID-19 vaccine, older parents, having children aged 12-18, and parents with lower education levels. Conclusions: Significant proportion of parents are hesitant about the COVID-19 vaccine because they are less confident in its effectiveness, safety, and whether it is essential for their children. Relying on the national official healthcare authority's website for the source of information was associated with increased acceptance of childhood COVID-19 vaccination. As parental intention to vaccinate children against COVID-19 is suboptimal, healthcare authorities could boost vaccine uptake by campaigns targeting hesitant parents.

Comparison of neurological outcomes in patients undergoing conventional coronary artery bypass grafting, on-pump beating heart coronary bypass, and off-pump coronary bypass.

OBJECTIVE: To study the differences in the prevalence of neurological complications following coronary artery bypass (CAB) carried out by conventional, on-pump beating and off-pump techniques. METHODS: A retrospective analysis of all isolated coronary bypass operations (n=127) performed in King Fahad Cardiac Center, Riyadh over a period of one year starting from January 2005. Out of 127 patients, 73 underwent conventional CAB graft (CABG), 33 patents on-pump beating heart coronary bypass, and 21 had off pump coronary bypass grafting (OPCAB). All patients had preoperative carotid scans and those who developed neurological complications underwent CT-brain and expert neuro-psychiatric assessment. RESULTS: Preoperative characteristics of patients in all 3 groups were similar. The bypass times in the conventional CABG group were significantly longer than the on-pump beating group. The maximum number of grafts was in the on-pump beating group, followed by the conventional CABG, and the least in the OPCAB group. Seven out of 73 cases in the conventional bypass group developed neurological events of various severities. Only one out of 33 patients developed acute confusional state in the on-pump beating group and no neurological events were noticed in 21 patients operated by the OPCAB technique. Low ejection fraction, preoperative congestive cardiac failure, non-elective surgery and preoperative catastrophic state were found to be significant risk factors independent of the bypass technique. CONCLUSION: This study shows no significant difference in the prevalence of neurological complications among different types of bypass surgery in our institution. There was a trend towards less neurological outcomes in the OPCAB and on-pump beating groups.

The effects of melatonin premedication on propofol and thiopental induction dose-response curves: a prospective, randomized, double-blind study.

BACKGROUND: The effect of melatonin on the intraoperative requirements for i.v.anesthetics has not been documented. We studied the effect of melatonin premedication on the propofol and thiopental dose-response curves for abolition of responses to verbal commands and eyelash stimulation. METHODS: This prospective, randomized, double-blind study included 200 adults with ASA physical status I. Patients received either 0.2 mg/kg melatonin or a placebo orally for premedication (n = 100 per group). Approximately 50 min later, subgroups of 10 melatonin and 10 placebo patients were administered various doses of propofol (0.5, 1.0, 1.5, 2.0, or 2.4 mg/kg) or thiopental (2.0, 3.0, 4.0, 5.0, or 6.0 mg/kg) for anesthetic induction. The ability of each patient to respond to the command, "open your eyes," and the disappearance of the eyelash reflex were assessed 60 s after the end of the injection of propofol or thiopental. Dose-response curves were determined by probit analysis. RESULTS: Melatonin premedication decreased thiopental ED50 values for loss of response to verbal command and eyelash reflex from 3.4 mg/kg (95% confidence interval, 3.2-3.5 mg/kg) and 3.7 mg/kg (3.5-3.9 mg/kg) to 2.7 mg/kg (2.6-2.9 mg/kg) and 2.6 mg/kg (2.5-2.7 mg/kg), respectively (P < 0.05). Corresponding propofol ED50 values decreased from 1.5 mg/kg (1.4-1.6 mg/kg) and 1.6 mg/kg (1.5-1.7 mg/kg) to 0.9 mg/kg (0.8-0.96 mg/kg) and 0.9 mg/kg (0.8-0.95 mg/kg), respectively (P < 0.05). CONCLUSIONS: Melatonin premedication significantly decreased the doses of both propofol and thiopental required to induce anesthesia.

Does the use of ketamine or nitroglycerin as an adjuvant to lidocaine improve the quality of intravenous regional anesthesia?

AIMS: To compare and evaluate the effect of adding ketamine or nitroglycerin (NTG) as adjuncts to lidocaine for intravenous regional anesthesia (IVRA) on intraoperative and postoperative analgesia, sensorial and motor block onset times, and tourniquet pain. SETTINGS AND DESIGN: A prospective, randomized, double-blind study was carried out. MATERIALS AND METHODS: Seventy-five patients undergoing hand surgery were divided into three groups as follows: control group receiving lidocaine 2%, LK group receiving lidocaine 2% with ketamine, and LN group administered lidocaine 2% with NTG. Sensory and motor blocks' onset and recovery times were recorded. Visual analog scale (VAS) for tourniquet pain was measured after tourniquet application and it was also used to measure postoperative pain. Analgesic consumption for tourniquet pain and postoperatively were recorded. RESULTS: Sensory block onset times were shorter in the LK (4.4 ± 1.2 minutes) and LN (3.5 ± 0.9 minutes) groups compared with the control group (6.5 ± 1.1 minute) (P < 0.0001) and motor block onset times were shorter in the LK (7.3 ± 1.6 minutes) and LN (3.6 ± 1.2 minutes) groups compared with the control group (10.2 ± 1.5 minutes) (P< 0.0001). Sensory recovery time prolonged in the LK (6.7 ± 1.3 minutes) and LN (6.9 ± 1.1 minutes) groups compared with the control group (5.3 ± 1.4 minutes) (P = 0.0006 and < 0.0001, respectively). Motor recovery time prolonged in the LK (8.4 ± 1.4 minutes) and LN (7.9 ± 1.1 minutes) groups compared with the control group (7.1 ± 1.3 minutes) (P = 0.0014 and 0.023, respectively). The sensory and motor block onset times were also shorter in LN group than in the LK group (3.5 ± 0.9 versus 4.4 ± 1.2 minutes, P=0.004; and 3.6 ± 1.2 versus 7.3 ± 1.6 minutes, P < 0.0001, respectively). The amount of fentanyl required for tourniquet pain was less in adjuvant groups when compared with control group. It was 13.6 ± 27.9 and 27.6 ± 34.9 µg in LK group and LN groups, respectively, versus 54.8 ± 28 µg in the control group. VAS scores of tourniquet pain were higher at 10, 20, 30, 40 minutes in the control group compared with the other study groups (P < 0.0001). It was also higher in LN group compared with LK group at 30 and 40 minutes (P < 0.001). Postoperative VAS scores were higher for the first 4 h in control group compared with the other study groups (P< 0.0001). CONCLUSIONS: The adjuvant drugs (ketamine or NTG) when added to lidocaine in IVRA were effective in improving the overall quality of anesthesia, reducing tourniquet pain, increasing tourniquet tolerance and improving the postoperative analgesia in comparison to the control group. Ketamine as an adjuvant produced better tolerance to tourniquet than the other groups. NTG as an adjuvant produced faster onset of sensory and motor blockades in comparison to other groups.

Timing of revascularization after acute myocardial infarction.

The optimal timing of surgical revascularization after acute myocardial infarction remains controversial. Higher mortality after emergency coronary artery bypass has been documented. We retrospectively reviewed 278 patients who underwent coronary artery bypass between 2005 and 2007. The time from onset of myocardial infarction to surgical revascularization was the basis for dividing patients into 3 groups: surgery was performed within 24 h in group 1, at 24-72 h in group 2, and after 14 days in group 3. There was a definite relationship between the timing of revascularization and the outcome of surgery. Group 1 had a mortality rate of 11.7%, group 2 had 7% mortality, and group 3 had 2.5% mortality. Group 1 had the highest incidence of postoperative complications. Surgical revascularization within 24 h of acute myocardial infarction was associated with significantly higher risks of mortality and morbidity than procedures performed after 72 h.

Mixed venous versus central venous oxygen saturation in patients undergoing on pump beating coronary artery bypass grafting.

OBJECTIVE: To examine the validity of central venous oxygen saturation (ScvO(2)) as a numerical substitution of mixed venous oxygen saturation (SvO(2)) in adult patients undergoing normothermic on pump beating coronary artery bypass grafting (CABG). MATERIALS AND METHODS: Prospective clinical observational study was done at King Khalid University Hospital, King Saud University, Riyadh, Kingdom of Saudi Arabia. Thirty four adult patients scheduled for coronary artery surgery were included. Patients were monitored by a pulmonary artery catheter (PAC) as a part of our routine intraoperative monitoring. SvO(2) and ScvO(2) were simultaneously measured 15 minutes (T1) and 30 minutes (T2) after induction of anesthesia, 15 and 30 minutes after initiation of cardiopulmonary bypass (T3 and T4), and 15 and 30 minutes after admission to intensive care unit (T5 and T6). RESULTS: ScvO(2) showed higher reading than SvO(2) all through our study. Our results showed perfect positive statistically significant correlation between SvO(2) and ScvO(2) at all data points. Individual mean of difference (MOD) between both the readings at study time showed MOD of 1.34 and 1.44 at T1 and T2 simultaneously. This MOD was statistically insignificant, but after on pump beating normothermic bypass was initiated; MOD was 5.2 and 4.4 at T3 and T4 with high statistical significance. In ICU, MOD continues to have high statistical significance, MOD was 6.3 at T5 and at T6 it was 4.6. CONCLUSIONS: In on pump beating CABG patients; ScvO(2) and SvO(2) are not interchangeable numerically. ScvO(2) is useful in the meaning of trend; our data suggest that ScvO(2) is equivalent to SvO(2) , only in the course of clinical decisions as long as absolute values are not required.