Use of donepezil for neurocognitive recovery after brain injury in adult and pediatric populations:a scoping review

There are few pharmacologic options for the treatment of cognitive deficits associated with traumatic brain injury in pediatric patients.Acetylcholinesterase inhibitors such as donepezil have been evaluated in adult patients after traumatic brain injury,but relatively less is known about the effect in pediatric populations.The goal of this review is to identify knowledge gaps in the efficacy and safety of acetylcholinesterase inhibito rs as a potential a djuvant treatment fo r neurocognitive decline in pediatric patients with traumatic brain injury.Investigators queried PubMed to identify literature published from database inception thro ugh June 2023 desc ribing the use of donepezil in young adult traumatic brain injury and pediatric patients with predefined conditions.Based on preselected search criteria,340 unique papers we re selected for title and abstra ct screening.Thirty-two reco rds were reviewed in full after eliminating preclinical studies and pape rs outside the scope of the project.In adult traumatic brain injury,we review results from 14 papers detailing 227 subjects where evidence suggests donepezil is well tole rated and shows both objective and patient-reported efficacy for reducing cognitive impairment.In children,3 pape rs report on 5 children recovering from traumatic brain injury,showing limited efficacy.An additional 15 pediatric studies conducted in populations at risk for cognitive dysfunction provide a broader look at safety and efficacy in 210 patients in the pediatric age group.Given its promise for efficacy in adults with traumatic brain injury and tole rability in pediatric patients,we believe further study of donepezil for children and adolescents with traumatic brain injury is warranted.

Review of the genetic basis of emotion dysregulation in children and adolescents

Previous evidence suggests that emotion dysregulation may have different biological correlates between adults and children/adolescents. Although the role of genetic factors has been extensively studied in adult-onset emotion dysregulation, the genetic basis for pediatriconset emotion dysregulation remains elusive. The current review article presents a summary of previous studies that have suggested a few genetic variants associated with pediatric emotion dysregulation. Among these candidate loci, many prior studies have been focused on serotonin transporter promoter gene polymorphism 5-HTTLPR. Certain alleles of the 5-HTTLPR gene polymorphism have been found to be associated with traits associated with emotion dysregulation, such as aggression, affect reactivity, and insecure attachment. Additionally, genetic variants involving dopamine and neurophysiological biomarkers like the COMT Val158Met(rs460) and dopamine receptor D2/ ankyrin repeat and kinase domain containing one polymorphisms may play a role in emotion dysregulation. Inconsistent findings have been noted, possibly due to the heterogeneity in study designs and characteristics of different populations. Further research on the role of genetic predetermination of emotion dysregulation in children and adolescents is warranted.

A Theory-Based Dietary Intervention for Overweight, Postpartum Mothers and Their Children Improves Maternal Vegetable Intake

Objective: To evaluate the effectiveness of a dietary intervention to increase target vegetable intake in overweight, postpartum mothers;and their children. Methods: Overweight mothers attending their six-week postpartum follow-up visit and their infants (n = 104 pairs) were randomized to intervention or usual care groups during the time period 2008-2011. Mothers received four 60 minute education sessions with a nutrition professional and eight monthly follow-up phone calls. Counseling began at the obstetrician office and continued at the regularly scheduled pediatric visits. The primary study outcome was the change in maternal target vegetable intake. Secondary outcomes included child target vegetable intake and whether child vegetable intake was modified by exposure to breastfeeding. Mother/child energy intake and weight indices were also assessed. Outcomes were measured at baseline (6-weeks postpartum), 6, 12 (post-intervention), and 18 (follow-up) months. Mixed-effects models were used to estimate the impact of the dietary intervention on study outcomes relative to usual care. Results: Mothers randomized to the intervention had greater consumption of target vegetables at 6, 12 and 18 months (P P P = 0.03, respectively). There were no differences between groups in maternal energy intake, body mass index, or child target vegetable or energy intake. The child’s target vegetable intake at 12 months was related to the mother’s intake at 6 months (P = 0.03), however, this relationship was not modified by exposure to breastfeeding. Conclusion: A dietary intervention targeting the diet of the mother/child dyad resulted in improved maternal vegetable intake.

Effect of adult leader participation on physical activity in children

Background: Participation in physically active games is one way to increase energy expendture in children. However, it is unknown whether adult leader participation (LP) in games can impact children’s physical activity (PA) levels. The purpose of this study was to examine the influence of LP compared to no LP on PA levels among children participating in organized active games. Methods: Children (n = 14) in grades 4-6 (Male = 42.8%, White = 50%, Overweight/ Obese = 42.8%) participated in four active games across two consecutive days. Each day, children participated in two 16-minute games and received verbal encouragement from an adult leader. Each game was divided into four-minute intervals alternating between LP or no LP. LP was counter-balanced across two days. Each child wore an Actigraph GT1M accelerometer. Time spent in moderate-to-vigorous PA (MVPA), vigorous PA (VPA), and sedentary behavior (SB) was determined by Freedson’s MET prediction. Data were analyzed using a condition (LP or no LP) by game repeated-measures ANCOVA. Results: Children participated in MVPA 52.3% of game time across all games. There were no differences in MVPA, VPA, and SB by gender, weight status, or ethnicity. LP and no LP conditions were not different for MVPA, VPA, or SB. Conclusions: These results show no effect of LP on PA in children during active games. It may be that LP could not increase PA because the children were already exhibiting high levels of MVPA.

Impact of Motor Speech Intervention on Neural Activity in Children with Speech Sound Disorders: Use of Magnetoencephalography

We present the novel use of a neuroimaging technique, magnetoenceph-alography (MEG), for examining therapy-related changes in neural activity during a speech and a non-speech motor task in children with speech sound disorders (SSD). Nine children (mean age = 4.2 years) with SSD were scanned in the MEG before and after an eight-week course of intensive motor speech therapy. MEG tasks involved an oromotor and a syllable production task. MEG analyses identified significant post-therapy changes in brain regions related to oromotor control and speech production. Behavioral assessments showed significant improvements on measures of motor speech skills and articulation following intervention. This is the first demonstration of the ability of MEG to: 1) capture brain activations resulting from oromotor movements and simple syllable production in young children, and 2) capture brain changes related to speech therapy. As the findings from this study are promising, we discuss directions for the design of future studies to further examine specific neural dysfunctions in speech sound disorders.

Retrospective analysis of early COVID-19 vaccine efficacy in older individuals receiving primary cycle, first booster and second booster

Background:We analysed data garnered during the ongoing Italian nationwide coronavirus disease 2019(COVID-19)vaccination campaign for comparing early COVID-19 monovalent vaccine efficacy in older persons who received the primary vaccination cycle,the first vaccine booster,and the second vaccine booster.Methods:We conducted a retrospective analysis of early COVID-19 monovalent vaccine efficacy(i.e.,within 120 days)against COVID-19 related hospitalizations,intensive care unit(ICU)admissions and deaths in older persons(i.e.,aged≥80 years),by accessing official data of the COVID-19 national integrated surveillance program instituted by the Italian National Institute of Health.Vaccine efficacy was compared(odds ratio;OR)among cohorts receiving the primary vaccination cycle,the first vaccine booster,and the second vaccine booster.Results:A consistent decline could be seen in the rate of COVID-19 hospitalizations,ICU admissions and deaths with increasing number of monovalent immunizations.Within 120 days of administration,the first and second vaccine boosters had superior efficacy compared to the primary vaccination cycle,reducing the odds of all endpoints between 62%-71%and 69%-84%,respectively.A modestly superior early efficacy could also be noted for the second versus the first monovalent vaccine booster(ORs of all endpoints further reduced by 18%-48%).Conclusion:Since an increasing number of immunizations is associated with a lower risk of unfavourable COVID-19 outcomes,vaccine boosters may be useful for limiting the clinical burden of this infectious disease in elderly populations.

Harmonization of SARS-CoV-2 antigen immunoassays:are they measuring the same“thing”?

Background:This study was planned to assess the accuracy and comparability of two commercially available,laboratory-based SARS-CoV-2(severe acute respiratory syndrome)antigen(Ag)immunoassays.Methods:We studied a cohort of subjects with acute SARS-CoV-2 infection,from whom a nasopharyngeal swab was taken and tested with a molecular assay(Altona Diagnostics RealStar SARS-CoV-2 RT-PCR Kit)and two laboratory-based,fully automated SARS-CoV-2 Ag immunoassays(Fujirebio Lumipulse G SARS-CoV-2 Ag and Roche Elecsys SARS-CoV-2 Ag).Results:The final population consisted in 93 subjects testing positive for SARS-CoV-2 RNA,34 with cycle threshold(Ct)values<29.5.The results of the two SARS-CoV-2 Ag immunoassays were significantly intercorrelated(r=0.77;P<0.001)in the entire cohort,though such correlation considerably improved in patients with high viral load(cycle threshold values<29.5:r=0.96;P<0.001).The accuracy for identifying samples with high viral load was excellent for both Lumipulse G SARS-CoV-2 Ag(AUC,0.99;P<0.001)and Elecsys SARS-CoV-2 Ag(AUC,0.99;P<0.001),with best cut-offs of 2.03 ng/mL for Lumipulse G SARS-CoV-2 Ag(1.00 sensitivity and 0.88 specificity)and 0.70 COI for Elecsys SARS-CoV-2 Ag(1.00 sensitivity and 0.80 specificity),respectively.Conclusion:The results of this study provide valuable support to usability of fully-automated,rapid,high throughput and accurate SARS-CoV-2 Ag immunoassays for complementing molecular assays.

Pooled analysis of efficacy of the fourth mRNA-based COVID-19 vaccine dose in eliciting anti-SARS-CoV-2 serum antibody response in the general immunocompetent population

Objective:Since the opportunity of widespread administration of the fourth mRNA-based coronavirus disease 2019(COVID-19)vaccine dose remains controversial,this article provides a pooled analysis of the efficacy of the second COVID-19 mRNA-based homologous vaccine booster in eliciting anti-SARS-CoV-2 serum antibody response in general immunocompetent populations.Methods:We conducted a digital search in Medline using the keywords"fourth dose"or"second booster"and"antibodies"and"COVID-19"or"SARS-CoV-2"and"BNT162b2"or"mRNA-1273",to identify all clinical studies which evaluated the anti-SARS-CoV-2 serum antibody response after the fourth mRNA-based COVID-19 homologous vaccine dose administration in general immunocompetent populations compared to the response seen before its administration and after the first booster.Results:Four studies totaling 571 recipients of the second mRNA-based COVID-19 vaccine booster were finally included in our analysis.The weighted mean difference(WMD)ratio of anti-SARS-CoV-2 serum antibodies levels measured after and before administration of the fourth vaccine dose was 9.7(95%CI,6.5-12.9)in those receiving BNT162b2 and 12.0(95%CI,5.8-18.2)in those receiving mRNA-1273,respectively.The WMD ratio of anti-SARS-CoV-2 serum antibodies levels measured at the peak of the fourth and third vaccine doses was 1.4(95%CI,1.2-1.7)in those receiving BNT162b2 and 1.9(95%CI,1.5-2.4)in those receiving mRNA-1273,respectively.Conclusion:Our data confirm the efficacy of the fourth mRNA-based COVID-19 vaccine dose in restoring a satisfactory level of anti-SARS-CoV-2 serum antibodies,though such effectiveness seems only marginally superior to that of the first booster.

Monitoring humoral and cellular immunity over 6 months after mRNA-based bivalent COVID-19 vaccine administration

Dear Editor,Although the World Health Organization(WHO)has declared an end to the global emergency for coronavirus disease 2019(COVID-19)[1],the clinical burden of severe acute respiratory syndrome coronavirus disease(SARS-CoV-2)has not yet subsided[2,3],especially after the emergence of new variants such as EG.5 and BA.2.86,whose genetic leap is so large that it may contribute to increase the number of new COVID-19 cases,hospitalizations,and deaths[3].Some physical preventive measures,such as mask-wearing,hand hygiene,and isolation of positive cases,play an important role.However,widespread vaccination remains the cornerstone to contain the spread of the virus and mitigate the potential harm to human health.

Expert consensus on the monitoring and treatment of sepsis-induced immunosuppression

Emerged evidence has indicated that immunosuppression is involved in the occurrence and development of sepsis.To provide clinical practice recommendations on the immune function in sepsis,an expert consensus focusing on the monitoring and treatment of sepsis-induced immunosuppression was developed.Literature related to the immune monitoring and treatment of sepsis were retrieved from PubMed,Web of Science,and Chinese National Knowledge Infrastructure to design items and expert opinions were collected through an online questionnaire.Then,the Delphi method was used to form consensus opinions,and RAND appropriateness method was developed to provide consistency evaluation and recommendation levels for consensus opinions.This consensus achieved satisfactory results through two rounds of questionnaire survey,with 2 statements rated as perfect consistency,13 as very good consistency,and 9 as good consistency.After summarizing the results,a total of 14 strong recommended opinions,8 weak recommended opinions and 2 non-recommended opinions were produced.Finally,a face-to-face discussion of the consensus opinions was performed through an online meeting,and all judges unanimously agreed on the content of this consensus.In summary,this expert consensus provides a preliminary guidance for the monitoring and treatment of immunosuppression in patients with sepsis.

基于16S rRNA和recA香鱼鳗利斯顿氏菌的分离鉴定

为研究引起香鱼(Plecoglossus altivelis)出血溃烂症病因及致病菌系统发育地位,本研究从患病香鱼的肝脏、肾脏及体表分离到11株病原菌(编号:X0901-X0911),运用常规细菌生理生化方法鉴定致病菌所属种类;运用16SrRNA基因、recA基因序列分析方法研究致病菌的系统发育地位。细菌生理生化鉴定结果表明:致病菌为鳗利斯顿氏菌,11株细菌生理生化结果相同,均为革兰氏阴性杆菌、氧化酶阳性、接触酶阳性、吲哚阳性、精氨酸脱羧酶阳性、精氨酸双水解酶阳性、硝酸盐还原阳性、甘露醇阳性、MR测定阳性;H2S阴性、V-P测定阴性等。根据16SrRNA基因、recA基因序列分别构建弧菌科常见细菌系统进化树,结果表明:致病菌与鳗利斯顿氏菌(Listonella anguillarum)均聚为一枝,聚类结果与细菌生理生化鉴定结果相符。致病菌与鳗利斯顿氏菌16SrRNA基因、recA基因的同源性分别为99.9%、99.8%。以recA基因构建的系统进化树的拓扑学结构与16SrRNA基因建树结果相类似。此外,与16SrRNA基因相比,recA基因在不同物种之间具有更高的鉴别能力,本研究表明recA基因适合作为弧菌科常见细菌物种间进化关系研究的标记。

与氨基糖甙类抗生素耳毒性相关的线粒体12S rRNA突变的流行病学特征

线粒体DNA(mtDNA)12SrRNA是氨基糖甙类抗生素导致的非综合征型听力损失的一个突变热点区域。在这些突变位点中,位于12SrRNA高度保守的解码区的同质性的A1555G和C1494T突变与耳聋相关,这两个突变导致很多患者的氨基糖甙类抗生素中毒性耳聋。A1555G突变和C1494T突变会在12SrRNA的高度保守的A位形成新的1494C-G1555或1494U-A1555碱基对。这些改变使得12SrRNA在二级结构上与细菌的16SrRNA的相应区域的二级结构更加相似,因此,由于C1494T和A1555G突变在12SrRNA形成U-A和G-C配对使得氨基糖甙类抗生素的结合更加容易,这就是为何携带这些突变的人在接触了氨基糖甙类抗生素时会出现或加重耳聋的原因。携带C1494T和A1555G突变的细胞的生化特征是线粒体蛋白质合成的异常并随之引起细胞的呼吸功能异常。而且,当用含高浓度的巴龙霉素或新霉素的DMEM培养基来培养携带这两个突变的细胞系时,可以观察到这些细胞与对照细胞系相比会出现生长缺陷和线粒体内蛋白的翻译异常。这些观察为以下结论提供了直接的遗传和生化方面的证据,即A1555G和C1494T突变是导致氨基糖甙类抗生素诱导的非综合征型耳聋的致病性的mtDNA突变。而且,这些研究数据还为我们进行以下预测提供了有价值的信息和方法:(1)哪些患者有耳毒性风险;(2)提高使用氨基糖甙类抗生素治疗时的安全性;(3)逐渐减少耳聋的发生率。

Impaired granulocyte-macrophage colony-stimulating factor bioactivity accelerates surgical recurrence in ileal crohn's disease

AIM To examine the relationship between elevated granulocyte-macrophage colony-stimulating factor(GMCSF) auto-antibodies(Ab) level and time to surgical recurrence after initial surgery for Crohn's disease(CD). METHODS We reviewed 412 charts from a clinical database at tertiary academic hospital. Patients included in the study had ileal or ileocolonic CD and surgical resection of small bowel or ileocecal region for management of disease. Serum samples were analyzed for serological assays including GM-CSF cytokine, GM-CSF Ab, ASCA Ig G and Ig A, and genetic markers including SNPs rs2066843, rs2066844, rs2066845, rs2076756 and rs2066847 in NOD2, rs2241880 in ATG16 L1, and rs13361189 in IRGM. Cox proportional-hazards models were used to assess the predictors of surgical recurrence.RESULTS Ninety six percent of patients underwent initial ileocecal resection(ICR) or ileal resection(IR) and subsequently 40% of patients required a second ICR/IR for CD. GMCSF Ab level was elevated at a median of 3.81 mcg/mL. Factors predicting faster time to a second surgery included elevated GM-CSF Ab [hazard ratio(HR) 3.52, 95%CI: 1.45-8.53, P = 0.005] and elevated GM-CSF cytokine(HR = 2.48, 95%CI: 1.31-4.70, P = 0.005). Factors predicting longer duration between first and second surgery included use of Immunomodulators(HR = 0.49, 95%CI: 0.31-0.77, P = 0.002), the interaction effect of low GM-CSF Ab levels and smoking(HR = 0.60, 95%CI: 0.45-0.81, P = 0.001) and the interaction effect of low GM-CSF cytokine levels and ATG16 L1(HR = 0.65, 95%CI: 0.49-0.88, P = 0.006).CONCLUSION GM-CSF bioavailability plays a critical role in maintaining intestinal homeostasis. Decreased bioavailability coupled with the genetic risk markers and/or smoking results in aggressive CD behavior.

Mitochondrial DNA A1555G mutation screening using a testing kit method and its significance in preventing aminoglycoside-related hearing loss

To report a new screening method for mitochondrial DNA 1555A→G mutation and the results of genotype analysis in 19 maternal inherited deafness pedigrees. Method Five hundred and forty-six non-syndromic neuro-sensory hearing loss patients were tested for 1555A→G mutation using a new compact testing kit, which allows clear distinction between wild type and 1555 A→G mutated mtDNAs. Results Nineteen subjects among the 546 patients (3.48%) were found to carry mtDNA A1555G mutation. The results were confirmed by sequencing in an ABI 3100 Avant sequencer. Conclusions Maternal inherited deafness families are a frequently seen in outpatient group. The detection of mtDNA 1555 A→G mutation with a low cost, ready to use detection kit is needed and suitable in China for large scale screening and preventive testing before usage of aminoglycoside antibiotics.

Infant cholestasis patient with a novel missense mutation in the AKR1D1 gene successfully treated by early adequate supplementation with chenodeoxycholic acid: A case report and review of the literature

Steroid 5β-reductase [aldo-keto reductase family 1 member D1(AKR1D1)] is essential for bile acid biosynthesis. Bile acid deficiency caused by genetic defects in AKR1D1 leads to life-threatening neonatal hepatitis and cholestasis. There is still limited experience regarding the treatment of this disease. We describe an infant who presented with hyperbilirubinemia and coagulopathy but normal bile acid and γ-glutamyltransferase. Gene analysis was performed using genomic DNA from peripheral lymphocytes from the patient, his parents, and his elder brother. The patient was compound heterozygous for c.919C>T in exon 8 and exhibited a loss of heterozygosity of the AKR1D1 gene, which led to an amino acid substitution of arginine by cysteine at amino acid position 307(p.R307C). Based on these mutations, the patient was confirmed to have primary 5β-reductase deficiency. Ursodeoxycholic acid(UDCA) treatment did not have any effect on the patient. However, when we changed to chenodeoxycholic acid(CDCA) treatment, his symptoms and laboratory tests gradually improved. It is therefore crucial to supplement with an adequate dose of CDCA early to improve clinical symptoms and to normalize laboratory tests.

Ponseti method compared with soft-tissue release for the management of clubfoot:A meta-analysis study

AIM: To compare the functional outcomes of patients who underwent open surgery vs Ponseti method for the management of idiopathic clubfoot and to determine whether correlations exist between functional outcome and radiographic measurements.METHODS: A meta-analysis of the literature was conducted for studies concerning primary treatment of patients with idiopathic clubfoot. We searched PubM ed Medline, EMBASE, and the Cochrane Library databases from January 1950 to October 2011. Meta-analyses were performed on outcomes from 12 studies. Pooled means, SDs, and sample sizes were either identified in the results or calculated based on the results of each study.RESULTS: Overall, 835 treated idiopathic clubfeet in 516 patients were reviewed. The average follow-up was 15.7 years. Patients managed with Ponseti method did have a higher rate of excellent or good outcome than patients treated with open surgery(0.76 and 0.62, respectively), but not quite to the point of statistical significance(Q = 3.73, P = 0.053). Age at surgery wasnot correlated with the functional outcome for the surgically treated patients(r =-0.32, P = 0.68). A larger anteroposterior talocalcaneal angle was correlated with a higher rate of excellent or good outcomes(r = 0.80, P = 0.006). There were no other significant correlations between the functional and radiographic outcomes.CONCLUSION: The Ponseti method should be considered the initial treatment of idiopathic clubfeet, and open surgery should be reserved for clubfeet that cannot be completely corrected.

Human small intestine is capable of restoring barrier function after short ischemic periods

AIM To assess intestinal barrier function during human intestinal ischemia and reperfusion(IR).METHODS In a human experimental model,6 cm of jejunum was selectively exposed to 30 min of ischemia(I) followed by 30 and 120 min of reperfusion(R). A sham procedure was also performed. Blood and tissue was sampled at all-time points. Functional barrier function was assessed using dual-sugar absorption tests with lactulose(L) and rhamnose(R). Plasma concentrations of citrulline,an amino acid described as marker for enterocyte function were measured as marker of metabolic enterocytes restoration. Damage to the epithelial lining was assessed by immunohistochemistry for tight junctions( TJs),by plasma marker for enterocytes damage(I-FABP) and analyzed by electron microscopy(EM) using lanthanum nitrate as an electrondense marker.RESULTS Plasma L/R ratio's were significantly increased after 30 min of ischemia(30 I) followed by 30 min of reperfusion(30 R) compared to control(0.75 ± 0.10 vs 0.20 ± 0.09,P < 0.05). At 120 min of reperfusion(120 R),ratio's normalized(0.17 ± 0.06) and were not significantly different from control. Plasma levels of I-FABP correlated with plasma L/R ratios measured at the same time points(correlation: 0.467,P < 0.01). TJs staining shows distortion of staining at 30 I. An intact lining of TJs was again observed at 30 I120 R. Electron microscopy analysis revealed disrupted TJs after 30 I with paracellular leakage of lanthanum nitrate,which restored after 30 I120 R. Furthermore,citrulline concentrations closely paralleled the histological perturbations during intestinal IR.CONCLUSION This study directly correlates histological data with intestinal permeability tests,revealing that the human gut has the ability of to withstand short episodes of ischemia,with morphological and functional recovery of the intestinal barrier within 120 min of reperfusion.

Role of perinatal long-chain omega-3 fatty acids in cortical circuit maturation:Mechanisms and implications for psychopathology

Accumulating translational evidence suggests that the long-chain omega-3 fatty acid docosahexaenoic acid(DHA) plays a role in the maturation and stability of cortical circuits that are impaired in different recurrent psychiatric disorders. Specifically, rodent and cell culture studies find that DHA preferentially accumulates in synaptic and growth cone membranes and promotes neurite outgrowth, dendritic spine stability, and synaptogenesis. Additional evidence suggests that DHA may play a role in microglia-mediated synaptic pruning, as well as myelin development and resilience. In nonhuman primates n-3 fatty acid insufficiency during perinatal development leads to widespread deficits in functional connectivity in adult frontal cortical networks compared to primates raised on DHA-fortified diet. Preterm delivery in non-human primates and humans is associated with early deficits in cortical DHA accrual. Human preterm birth is associated with longstanding deficits in myelin integrity and cortical circuit connectivity and increased risk for attention deficit/hyperactivity disorder(ADHD), mood, and psychotic disorders. In general, ADHD and mood and psychotic disorders initially emerge during rapid periods of cortical circuit maturation and are characterized by DHA deficits, myelin pathology, and impaired cortical circuit connectivity. Together these associations suggest that early and uncorrected deficits in fetal brain DHA accrual may represent a modifiable risk factor for cortical circuit maturation deficits in psychiatric disorders, and could therefore have significant implications for informing early intervention and prevention strategies.

Vaccinations in immunosuppressive-dependent pediatric inflammatory bowel disease

AIM To determine the vaccination rates in pediatric immunosuppression-dependent inflammatory bowel disease(IBD) and review the safety and efficacy of vaccinations in this population.METHODS The electronic medical records from October 2009 to December 2015 of patients diagnosed with IBD at 10 years of age or younger and prescribed antitumor necrosis factor alpha(anti-TNF-α) therapy were reviewed for clinical history, medication history, vaccination history, and hepatitis B and varicella titers. Literature discussing vaccination response in IBD patients were identified through search of the MEDLINE database and reviewed using the key words "inflammatory bowel disease", "immunization", "vaccination", "pneumococcal", "varicella", and "hepatitis B". Non-human and non-English language studies were excluded. Search results were reviewed by authors toselect articles that addressed safety and efficacy of immunizations in inflammatory bowel disease.RESULTS A total of 51 patients diagnosed with IBD prior to the age of 10 and receiving anti-TNF-α therapy were identified. Thirty-three percent of patients(17/51) had incomplete or no documentation of vaccinations. Sixteen case reports, cohort studies, cross-sectional studies, and randomized trials were determined through review of the literature to describe the safety and efficacy of hepatitis B, pneumococcal, and varicella immunizations in adult and pediatric patients with IBD. These studies showed that patients safely tolerated the vaccines without significant adverse effects. Importantly, IBD patients receiving immunosuppressive medications, particularly anti-TNF-α treatment, have decreased vaccine response compared to controls. However, the majority of patients are still able to achieve protective levels of specific antibodies. CONCLUSION Immunizations have been shown to be well-tolerated and protective immunity can be achieved in patients with IBD requiring immunosuppressive therapy.

Myalgia may not be associated with severity of coronavirus disease 2019 (COVID-19)

Dear editor,A recent study based on the use of experimental artificial intelligence(AI)tool showed 70%–80%accuracy in predicting development of severe disease in coronavirus disease 2019(COVID-19)based on predictive parameters alanine aminotransferase(ALT),myalgia and hemoglobin,whilst only 5 of 53 patients developed acute respiratory distress syndrome(ARDS),2 of whom reporting myalgia.