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Objective To investigate whether epileptiform discharge burden can identify those at risk for delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH). Methods Retrospective analysis of 113 moderate to severe grade SAH patients who had continuous EEG (cEEG) recordings during their hospitalization. We calculated the burden of epileptiform discharges (ED), measured as number of ED per hour. Results We find that many SAH patients have an increase in ED burden during the first 3–10 days following rupture, the major risk period for DCI. However, those who develop DCI have a significantly higher hourly burden from days 3.5–6 after SAH vs. those who do not. ED burden is higher in DCI patients when assessed in relation to the onset of DCI (area under the receiver operator curve 0.72). Finally, specific trends of ED burden over time, assessed by group-based trajectory analysis, also help stratify DCI risk. Conclusions These results suggest that ED burden is a useful parameter for identifying those at higher risk of developing DCI after SAH. The higher burden rate associated with DCI supports the theory of metabolic supply-demand mismatch which contributes to this complication. Significance ED burden is a novel biomarker for predicting those at high risk of DCI.

Objective Electroencephalography (EEG) is an important tool for neurological outcome prediction after cardiac arrest. However, the complexity of continuous EEG data limits timely and accurate interpretation by clinicians. We develop a deep neural network (DNN) model to leverage complex EEG trends for early and accurate assessment of cardiac arrest coma recovery likelihood. Methods We developed a multiscale DNN combining convolutional neural networks (CNN) and recurrent neural networks (long short-term memory [LSTM]) using EEG and demographic information (age, gender, shockable rhythm) from a multicenter cohort of 1,038 cardiac arrest patients. The CNN learns EEG feature representations while the multiscale LSTM captures short-term and long-term EEG dynamics on multiple time scales. Poor outcome is defined as a Cerebral Performance Category (CPC) score of 3-5 and good outcome as CPC score 1-2 at 3-6 months after cardiac arrest. Performance is evaluated using area under the receiver operating characteristic curve (AUC) and calibration error. Results Model performance increased with EEG duration, with AUC increasing from 0.83 (95% Confidence Interval [CI] 0.79-0.87 at 12h to 0.91 (95%CI 0.88-0.93) at 66h. Sensitivity of good and poor outcome prediction was 77% and 75% at a specificity of 90%, respectively. Sensitivity of poor outcome was 50% at a specificity of 99%. Predicted probability was well matched to the observation frequency of poor outcomes, with a calibration error of 0.11 [0.09-0.14]. Conclusions These results demonstrate that incorporating EEG evolution over time improves the accuracy of neurologic outcome prediction for patients with coma after cardiac arrest.

Ya Bin Zhou,* Yuan Yuan Xiao,* Jin Jing Chao, Lin Ma Department of Dermatology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuan Yuan XiaoDepartment of Dermatology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, People’s Republic of ChinaTel +86 10 59616884Fax +86 10 59718700Email xyy81924@126.comAbstract: Tinea capitis is a common dermatophytosis predominantly occurring in children, which needs oral antifungal drug therapy. Itraconazole pulse therapy has been widely applicated in the treatment of adult onychomycosis. However, only a few studies are available for the treatment of pediatric tinea capitis with itraconazole pulse therapy. The therapy schedules vary with respect to dose and intermission. Here, we report four cases of tinea capitis that were treated with a novel high-dose itraconazole pulse therapy (6– 10 mg/kg/d with 3 weeks off between consecutive pulses). After 2– 3 pulses therapy, all the patients were cured and no adverse reactions were observed. We demonstrate the efficacy and safety of this novel itraconazole pulse therapy schedule. It may be a promising therapy in the treatment of tinea capitis in children.Keywords: tinea capitis, itraconazole pulse therapy, children, Microsporum canis, Nannizzia gypsea

This study was undertaken to determine the dose-response relation between epileptiform activity burden and outcomes in acutely ill patients.A single center retrospective analysis was made of 1,967 neurologic, medical, and surgical patients who underwent16 hours of continuous electroencephalography (EEG) between 2011 and 2017. We developed an artificial intelligence algorithm to annotate 11.02 terabytes of EEG and quantify epileptiform activity burden within 72 hours of recording. We evaluated burden (1) in the first 24 hours of recording, (2) in the 12-hours epoch with highest burden (peak burden), and (3) cumulatively through the first 72 hours of monitoring. Machine learning was applied to estimate the effect of epileptiform burden on outcome. Outcome measure was discharge modified Rankin Scale, dichotomized as good (0-4) versus poor (5-6).Peak epileptiform burden was independently associated with poor outcomes (p 0.0001). Other independent associations included age, Acute Physiology and Chronic Health Evaluation II score, seizure on presentation, and diagnosis of hypoxic-ischemic encephalopathy. Model calibration error was calculated across 3 strata based on the time interval between last EEG measurement (up to 72 hours of monitoring) and discharge: (1) 5 days between last measurement and discharge, 0.0941 (95% confidence interval [CI] = 0.0706-0.1191); 5 to 10 days between last measurement and discharge, 0.0946 (95% CI = 0.0631-0.1290);10 days between last measurement and discharge, 0.0998 (95% CI = 0.0698-0.1335). After adjusting for covariates, increase in peak epileptiform activity burden from 0 to 100% increased the probability of poor outcome by 35%.Automated measurement of peak epileptiform activity burden affords a convenient, consistent, and quantifiable target for future multicenter randomized trials investigating whether suppressing epileptiform activity improves outcomes. ANN NEUROL 2021;90:300-311.

Purpose Migraine is often accompanied with chronic tinnitus that will affect the cerebral blood flow (CBF) and exacerbate the tinnitus distress. However, the potential relationship between migraine and tinnitus remains unclear. This study will investigate whether aberrant CBF patterns exist in migraine patients with tinnitus and examine the influence of migraine on CBF alterations in chronic tinnitus. Materials and methods Participants included chronic tinnitus patients (n = 45) and non-tinnitus controls (n = 50), matched for age, sex, education, and hearing thresholds. CBF images were collected and analyzed using arterial spin labeling (ASL) perfusion functional magnetic resonance imaging (fMRI). Regions with major CBF differences between tinnitus patients and non-tinnitus controls were first detected. The effects of migraine on tinnitus for CBF alterations were further examined. Correlation analyses illustrated the association between CBF values and tinnitus severity as well as between CBF and severity of migraine. Results Compared with non-tinnitus controls, chronic tinnitus patients without migraine exhibited decreased CBF, primarily in right superior temporal gyrus (STG), bilateral middle frontal gyrus (MFG), and left superior frontal gyrus (SFG); decreased CBF in these regions was correlated with tinnitus distress. There was a significant effect of migraine on tinnitus for CBF in right STG and MFG. Moreover, the severity of migraine correlated negatively with CBF in tinnitus patients. Conclusions Chronic tinnitus patients exhibited reduced CBF in the auditory and prefrontal cortex. Migraine may facilitate a CBF decrease in the setting of tinnitus, which may underlie the neuropathological mechanisms of chronic tinnitus comorbid with migraine.

Stopping maneuver is an important research topic in ship maneuverability. The stopping ability of ship is not only related to the hydrodynamic characteristics of hull, rudder and propeller, but also related to the capacity of main engine. However, there are few researches on the capacity of main engine under reversed propulsion condition. In the paper, a numerical water tank is established to simulate the propeller loads using the computational fluid dynamics (CFD) software STAR CCM+. The numerical model is firstly validated by experimental data, and then is used to investigate the propeller loads on a full-scale model with different ship speed and propeller speed. By dimensionless, the relations between the advance coefficient and the load coefficients are shown as J - KT curves and J - KQ curves. Furtherly, the flow structures near the propeller and the pressure on the propeller with different J values are investigated. The simulations reveal that the flow velocities induced by the reversed propulsion of the propeller is similar to the wake flow by ship with J = -0.49. That is the reason for the minimum points of J - KT and J - KQ curve occurring in cases with J = -0.49. Subsequently, the capacity of the main engine and the output load of the propeller are considered comprehensively. The relations between the ship speeds and the maximum output loads on the propeller are discussed in details.

Objective The aim was to evaluate the efficacy, safety and completion rate of 3-month, once-weekly rifapentine and isoniazid for tuberculosis (TB) prevention among Chinese silicosis patients. Methods Male silicosis patients without human immunodeficiency virus infection, aged 18 years to 65 years, with or without latent TB infection, were randomized 1:1 to receive rifapentine/isoniazid under direct observation (3RPT/INH group) or were untreated (observation group). Active TB incidence was compared between the two groups with 37 months of follow-up. Safety profile and complete rates were evaluated. Results A total of 1227 adults with silicosis were screened; 513 eligible participants were enrolled and assigned to 3RPT/INH (n = 254) vs. observation (n = 259). Twenty-eight participants were diagnosed with active TB, and 9 and 19 in the 3RPT/INH group and observation groups, respectively. In the intention-to-treat analysis, the cumulative active TB rate was 3.5% (9/254) in the 3RPT/INH group and 7.3% (19/259) in the observation group (log rank p 0.055). On per protocol analysis, the cumulative active TB rates were 0.7% (1/139) and 7.3% (19/259), respectively (log rank p 0.01). Owing to an unexpected high frequency of adverse events (70.4%) and Grade 3 or 4 AEs (7.9%), the completion rate of the 3RPT/INH regimen was 54.7% (139/254). Twenty-six (10.8%) participants had flu-like systemic drug reactions; five (2.1%) experienced hepatotoxicity. Discussion Weekly rifapentine/isoniazid prophylaxis prevented active TB among Chinese people with silicosis when taken, irrespective of LTBI screening; efficacy was reduced by lack of compliance. The regimen must be used with caution because of the high rates of adverse effects. Clinical trial registration ClinicalTrials.gov number: NCT02430259

Aims/Introduction The association between plasma irisin and glucose levels in the general population is controversial, and few studies have longitudinally detected this correlation. We aimed to examine whether irisin in pregnancy was associated with postpartum glucose levels among Chinese women and explore the modifiable factors. Materials and Methods We carried out a prospective cohort study in Guangzhou, China, during 2017 and 2018, and 453 pregnant women (20–28 weeks) were enrolled. Plasma irisin levels in pregnancy were tested. At 6–8 weeks after delivery, 93 women with gestational diabetes mellitus (GDM) underwent a 75‐g oral glucose tolerance test, and the other 360 women had a fasting blood glucose (FBG) test. Multivariable linear, quantile and logistic regressions were carried out. Results The mean plasma irisin in mid‐pregnancy was 13.73 ng/mL. We observed a significantly negative association between mid‐pregnancy irisin and postpartum FBG (β: −0.056 ± 0.024). However, quantile regression showed the association was only significant in high percentiles of FBG levels (P 50 to P 95), and the magnitude showed an increasing trend. Higher baseline irisin was also associated with a lower risk of postpartum impaired fasting glucose (relative risk 0.563, 95% confidence interval 0.384–0.825). Furthermore, we found significant interactions between irisin and predominant breast‐feeding on FBG and impaired fasting glucose (both P interaction, The present study suggested that plasma irisin levels in mid‐pregnancy were negatively associated with FBG and IFG at 6‐8 weeks postpartum among Chinese women, and stronger associations were observed in women with higher FBG values. Moreover, breast‐feeding may modify this relationship. The results implied that irisin may play a protective role on glucose levels in postpartum women, especially in women with impaired glucose levels.

OBJECTIVE: The aim was to determine the prevalence and risk factors for electrographic seizures and other electroencephalographic (EEG) patterns in patients with Coronavirus disease 2019 (COVID-19) undergoing clinically indicated continuous electroencephalogram (cEEG) monitoring and to assess whether EEG findings are associated with outcomes. METHODS: We identified 197 patients with COVID-19 referred for cEEG at 9 participating centers. Medical records and EEG reports were reviewed retrospectively to determine the incidence of and clinical risk factors for seizures and other epileptiform patterns. Multivariate Cox proportional hazards analysis assessed the relationship between EEG patterns and clinical outcomes. RESULTS: Electrographic seizures were detected in 19 (9.6%) patients, including nonconvulsive status epilepticus (NCSE) in 11 (5.6%). Epileptiform abnormalities (either ictal or interictal) were present in 96 (48.7%). Preceding clinical seizures during hospitalization were associated with both electrographic seizures (36.4% in those with vs 8.1% in those without prior clinical seizures, odds ratio [OR] 6.51, p = 0.01) and NCSE (27.3% vs 4.3%, OR 8.34, p = 0.01). A pre-existing intracranial lesion on neuroimaging was associated with NCSE (14.3% vs 3.7%; OR 4.33, p = 0.02). In multivariate analysis of outcomes, electrographic seizures were an independent predictor of in-hospital mortality (hazard ratio [HR] 4.07 [1.44-11.51], p < 0.01). In competing risks analysis, hospital length of stay increased in the presence of NCSE (30 day proportion discharged with vs without NCSE: HR 0.21 [0.03-0.33] vs 0.43 [0.36-0.49]). INTERPRETATION: This multicenter retrospective cohort study demonstrates that seizures and other epileptiform abnormalities are common in patients with COVID-19 undergoing clinically indicated cEEG and are associated with adverse clinical outcomes. ANN NEUROL 2021;89:872-883.

Background. Mutations in insulin receptor genes can cause severe insulin resistance syndrome. Compared with Rabson-Mendenhall Syndrome and Donohue’s Syndrome, type A insulin resistance syndrome is generally not serious. The main manifestations in woman with type A insulin resistance syndrome are hyperinsulinemia, insulin resistance, acanthosis nigricans, hyperandrogenism, and polycystic ovary. Case Presentation. A 13-year-old girl (Han nationality) visited the hospital due to hairiness and acanthosis nigricans. Further examination revealed severe hyperinsulinemia, insulin resistance, elevated blood glucose, hyperandrogenism, and polycystic ovary. Analysis of the insulin receptor gene by sequencing showed the presence of a nucleotide change in intron 7 (c. 1610+1G > A). The mutation was a splicing mutation, which can obviously affect the mRNA splicing of the insulin receptor and cause its function loss. The patient was finally diagnosed with type A insulin resistance syndrome. After 2 months of metformin treatment, the patient had spontaneous menstrual cramps and significantly improved acanthosis nigricans and sex hormones. Conclusion. We report for the first time a new splicing mutation on the insulin receptor gene at the 7th intron (c.1610+1G > A), which leads to type A insulin resistance syndrome. In clinically suspected patients with polycystic ovary syndrome, if there are extremely high blood levels of insulin in the blood, genetic testing should be performed to detect insulin receptor gene mutation of type A insulin resistance syndrome.

Aim To determine the effects of glycine powder air-polishing (GPAP) as an adjunct to full-mouth scaling and root planing (SRP) on clinical, inflammatory and microbiological outcomes in patients with untreated periodontitis. Materials and methods Forty-one patients were randomly assigned to the control group A (SRP) and test groups B1 (subgingival GPAP right after SRP) and B2 (subgingival GPAP right before SRP). Clinical examinations and sample collections (saliva, subgingival plaque, serum and gingival crevicular fluid) were performed at assessment visits and before therapies at clinical visits of baseline, 6-week and 3-month. C-reactive protein, IL-6 and TNF-α were assessed in serum and gingival crevicular fluid, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum were measured in saliva and subgingival plaque. Results Patients in control and test groups did not significantly differ by age, sex and disease severity at baseline. Participants in control and intervention groups had similar improvements in clinical parameters (PD, BOP, PLI and BI). All groups had a similar percentage of sites showing PD reduction of ≥2 mm between baseline and follow-up visits, with a few exceptions. Reduced C-reactive protein, IL-6 and TNF-α in serum were found after treatments. Conclusion Full-mouth SRP with and without GPAP resulted in largely similar clinical, inflammatory and microbiological outcomes in the care of untreated periodontitis.

This study aimed to examine individual and combined associations between after-school sedentary time (ST) and daily physical activity (PA) with executive function development in children.The study included 4304 children aged 6 to 12 years. ST and PA were assessed using the International Physical Activity Questionnaire Short Form, and executive function was assessed using the Behavior Rating Inventory of Executive Function (Parent Version). Participants were classified as low (2 h per day) or high (≥2 h per day) ST and low (not meeting guidelines) or high (meeting guidelines) PA. Resulting groups were defined as 1) low ST/high PA, 2) low ST/low PA, 3) high ST/high PA, and 4) high ST/low PA.Children in group 4 had the highest mean T-scores for BRIEF indices (48.23 ± 8.44, indicating increased symptoms of executive function dysfunction), followed by those in group 3 (47.10 ± 8.05), group 2 (45.81 ± 7.78), and group 1 (44.41 ± 7.31). ST was positively related to the T-score of all indices, independent of moderate-to-vigorous physical activity (MVPA). Significantly negative associations were observed between MVPA and Metacognition Index only in the high ST subgroup.Low ST and high PA were positively associated with executive function development in children. Notably, children with high ST and high PA demonstrated more significant deficits in executive function than those with low ST and low PA, suggesting that intervention efforts should focus on ST reduction in addition to promoting PA.

Few studies have suggested that long-term adherence to low-carbohydrate diets (LCD) may affect maternal glucose metabolism in Western countries. We aimed to investigate the association between LCD during pregnancy and glucose metabolism in a Chinese population. A total of 1018 women in mid-pregnancy were recruited in 2017–2018. Participants underwent a 75 g oral glucose tolerance test (OGTT). Daily dietary intakes over the past month were accessed using a validated FFQ. The overall, animal and vegetable LCD scores which represent adherence to different low-carbohydrate dietary patterns were calculated. Mixed linear regression and generalised linear mixed regression were conducted to evaluate the associations between LCD scores and maternal glucose metabolism. Of the 1018 subjects, 194 (19·1 %) were diagnosed with gestational diabetes mellitus (GDM). The overall LCD score (β: 0·024, se 0·008, PFDR = 0·02) and animal LCD score (β: 0·023, se 0·008, PFDR = 0·02) were positively associated with OGTT 1-h glucose. No significant associations were found between the three different LCD scores with fasting plasma glucose, OGTT 2-h glucose, or insulin resistance, respectively. Compared with the lowest quartile, the crude OR of GDM for the highest quartile were 1·84 (95 % CI 1·14, 2·95) for overall LCD score (Pfor trend = 0·02) and 1·56 (95 % CI 1·00, 2·45) for animal LCD score (Pfor trend = 0·02). However, these associations became non-significant after adjustment for covariates. In conclusion, a low-carbohydrate dietary pattern with high animal protein and fat is associated with higher postprandial 1-h glucose levels in Chinese pregnant women.

Acute lung injury (ALI) and the subsequent acute respiratory distress syndrome remain devastating diseases with high mortality rates and poor prognoses among patients in intensive care units. The present study is aimed at investigating the role and underlying mechanisms of microRNA-31-5p (miR-31-5p) on lipopolysaccharide- (LPS-) induced ALI. Mice were pretreated with miR-31-5p agomir, antagomir, and their negative controls at indicated doses for 3 consecutive days, and then they received a single intratracheal injection of LPS (5 mg/kg) for 12 h to induce ALI. MH-S murine alveolar macrophage cell lines were cultured to further verify the role of miR-31-5p in vitro. For AMP-activated protein kinase α (AMPKα) and calcium-binding protein 39 (Cab39) inhibition, compound C or lentiviral vectors were used in vivo and in vitro. We observed an upregulation of miR-31-5p in lung tissue upon LPS injection. miR-31-5p antagomir alleviated, while miR-31-5p agomir exacerbated LPS-induced inflammation, oxidative damage, and pulmonary dysfunction in vivo and in vitro. Mechanistically, miR-31-5p antagomir activated AMPKα to exert the protective effects that were abrogated by AMPKα inhibition. Further studies revealed that Cab39 was required for AMPKα activation and pulmonary protection by miR-31-5p antagomir. We provide the evidence that endogenous miR-31-5p is a key pathogenic factor for inflammation and oxidative damage during LPS-induced ALI, which is related to Cab39-dependent inhibition of AMPKα.

Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset neurodevelopmental disorder that usually persists into adulthood. However, limited evidence is available regarding its influence on adult health outcomes beyond neuropsychiatric comorbidities. This study aimed to examine the association of ADHD with diabetes in US adults.We analyzed data from the National Health Interview Survey (NHIS), a leading health survey of a nationally representative sample in the United States. We included adults aged 20-79 years who participated in the NHIS 2007 and 2012. Physician-diagnosed ADHD and diabetes were reported during an in-person household interview. Logistic regression with survey sampling weights was used to estimate the odds ratio (OR) and 95% confidence interval (CI) of diabetes.This analysis included 52 821 adults (weighted mean age 45.5 years; 48.6% males). Among them, 1642 participants reported a diagnosis of ADHD and 4631 reported a diagnosis of diabetes. In the multivariable analysis adjusting for age, sex, race/ethnicity, education level, family income level, smoking, alcohol drinking, physical activity, and body mass index, the OR of diabetes among adults with ADHD vs those without ADHD was 1.54 (95% CI, 1.16-2.04). In the stratified analyses, the significant association of ADHD with diabetes remained in most strata, and the associations were not significantly modified by age, sex, race/ethnicity, or obesity status.In a nationally representative sample of US adults, we found a significant association between a history of ADHD diagnosis and diabetes.背景: 注意缺陷力/多动症(ADHD)是一种儿童期出现并通常持续到成年的一种神经发育障碍。除外神经精神病合并症以外, ADHD对患者长期健康结局影响的研究证据非常有限。本项研究旨在了解美国成人ADHD与糖尿病的关系。 方法: 美国国家健康访谈调查(NHIS)是一项针对美国全国代表性样本的健康调查。我们纳入了2007年和2012参加这项调查的20-79岁成年人。在面对面的家庭访谈中收集了ADHD和糖尿病的诊断信息。用纳入了调查样本权重的逻辑回归分析来估计糖尿病的优势比(OR)和95%置信区间(CI)。 结果: 这项分析包括52821名成年人(加权平均年龄45.5岁；48.6%为男性)。其中, 有1642名受试者报告了ADHD的诊断, 4631名受试者报告了糖尿病的诊断。在对年龄, 性别, 种族/族裔, 教育程度, 家庭收入水平, 吸烟, 饮酒, 体育锻炼和体重指数进行校正的多变量分析中, 患有ADHD的成年人与未患ADHD的成年人相比, 其糖尿病OR为1.54(95 % CI:1.16-2.04)。在分层分析中, ADHD与糖尿病之间的显著关联存在于大多数层级中, 并且该关联并未因年龄, 性别, 种族/民族或肥胖状况有明显改变。 结论: 在美国成年人的全国代表性样本中, 我们发现了ADHD的诊断历史与糖尿病之间存在显著关联。.

OBJECTIVE: Childhood epilepsy with centrotemporal spikes (CECTS) is a common, focal, transient, developmental epilepsy syndrome characterized by unilateral or bilateral, independent epileptiform spikes in the Rolandic regions of unknown etiology. Given that CECTS presents during a period of dramatic white matter maturation and thatspikes in CECTS are activated during non–rapid eye movement (REM) sleep, we hypothesized that children with CECTS would have aberrant development of white matter connectivity between the thalamus and the Rolandic cortex. We further tested whether Rolandic thalamocortical structural connectivity correlates with spike rate during non-REM sleep. METHODS: Twenty-three children with CECTS (age = 8-15 years) and 19 controls (age = 7-15 years) underwent 3-T structural and diffusion-weighted magnetic resonance imaging and 72-electrode electroencephalographic recordings. Thalamocortical structural connectivity to Rolandic and non-Rolandic cortices was quantified using probabilistic tractography. Developmental changes in connectivity were compared between groups using bootstrap analyses. Longitudinal analysis was performed in four subjects with 1-year follow-up data. Spike rate was quantified during non-REM sleep using manual and automated techniques and compared to Rolandic connectivity using regression analyses. RESULTS: Children with CECTS had aberrant development of thalamocortical connectivity to the Rolandic cortex compared to controls (P = .01), where the expected increase in connectivity with age was not observed in CECTS. There was no difference in the development of thalamocortical connectivity to non-Rolandic regions between CECTS subjects and controls (P = .19). Subjects with CECTS observed longitudinally had reductions in thalamocortical connectivity to the Rolandic cortex over time. No definite relationship was found between Rolandic connectivity and non-REM spike rate (P > .05). SIGNIFICANCE: These data provide evidence that abnormal maturation of thalamocortical white matter circuits to the Rolandic cortex is a feature of CECTS. Our data further suggest that the abnormalities in these tracts do not recover, but are increasingly dysmature over time, implicating a permanent but potentially compensatory process contributing to disease resolution.

What is known and objective Drug consultation is an important part of pharmaceutical care offered by clinical pharmacists. We explored the characteristics of telephone drug consultations in an obstetrics and gynaecology speciality hospital to provide a reference as to how to improve drug consultation and pharmaceutical care. Methods We retrospectively analysed records of telephone consultations regarding medication use between 2014 and 2019 in our hospital. Any consultation cases with incomplete records were excluded from our analysis. Of the 1353 consultation cases included in our study, we further classified them into different categories based on the content of the consultations, the type of medications being inquired about, and the groups of people who sought medication guidance. Pareto analysis was performed to separate the main issues the callers were concerned about from the more minor concerns. Results and discussion The medication issues that prompted the caller to consult with our clinical pharmacists could be divided into 12 categories, among which the main issues concerned usage and dosage, choice of drug variety, drug incompatibility (drug mixture in infusion bag or tube), adjustment of the treatment plan, and skin tests (cumulative percentage 76.3%). The minor issues involved medication use during pregnancy and lactation and adverse reactions. The top three types of drugs that callers asked about were antimicrobials (600 cases, 44.4%), anti‐tumour drugs (151 cases, 11.2%) and reproductive system drugs (111 cases, 8.2%). The callers could be divided into four groups as follows: doctors (865 cases, 63.9%), nurses (280 cases, 20.7%), patients (116 cases, 8.6%) and other medical professionals (92 cases, 6.8%). What is new and conclusion Usage and dosage, choice of drug variety, drug incompatibility, adjustment of treatment plan and skin tests represented the main issues for telephone drug consultations in our hospital. Doctors and nurses were most likely to consult clinical pharmacists regarding these issues. Improved drug consultation services are needed to allow more patients to have access to advice from pharmacists. Such access would better enable pharmacists to fulfil their roles in advising the appropriate use of drugs to ensure better patient care and medication compliance.

Background Depression is the most common mental health problem and often co-occurs with dementia in old age. This study investigates the influence of late-life depression on risk of dementia. Methods A total of 16210 dementia-free participants aged 60+ from the Survey of Health, Aging, and Retirement in Europe were followed up for 10 years to detect incident dementia. Depression was assessed by a 12-item Europe-depression scale, dementia was determined by physician diagnosis reported by the participants and their informants. Fine and Gray model was performed to explore the association between depression and incident dementia taking into account competing risk of death. Results During an average of 8 years follow-up, 1030 (6.35%) incident dementia were identified. Late-life depression was related to higher subdistribution hazard ratio (sHR) of dementia (sHR=1.52, 95%CI: 1.32-1.75) after adjusting for age, gender, country, education, smoking, drinking, living arrangement, BMI, chronic disease, and physical activity. Further, the risk was only existed in those below age of 80 (sHR=1.75, 95%CI: 1.47-2.07). In addition, a dose-response association was observed between the severity of depression and dementia risk (p for trend Limitation The ascertainment of depression and dementia was based on information reported by the participants and/or their informants, which might result in information bias. The causal relationship could not be determined because limited follow-up time. Conclusions Late-life depression is associated with higher incidence of dementia in a dose-response fashion. Interventions targeting depression patients aged 60-79 years and those with severe depression may be effective strategies to prevent dementia.

ObjectiveTo examine the relationship between scalp EEG biomarkers of hyperexcitability in Alzheimer disease (AD) and to determine how these electric biomarkers relate to the clinical expression of seizures in AD.MethodsIn this cross-sectional study, we performed 24-hour ambulatory scalp EEGs on 43 cognitively normal elderly healthy controls (HC), 41 participants with early-stage AD with no history or risk factors for epilepsy (AD-NoEp), and 15 participants with early-stage AD with late-onset epilepsy related to AD (AD-Ep). Two epileptologists blinded to diagnosis visually reviewed all EEGs and annotated all potential epileptiform abnormalities. A panel of 9 epileptologists blinded to diagnosis was then surveyed to generate a consensus interpretation of epileptiform abnormalities in each EEG.ResultsEpileptiform abnormalities were seen in 53% of AD-Ep, 22% of AD-NoEp, and 4.7% of HC. Specific features of epileptiform discharges, including high frequency, robust morphology, right temporal location, and occurrence during wakefulness and REM, were associated with clinical seizures in AD. Multiple EEG biomarkers concordantly demonstrated a pattern of left temporal lobe hyperexcitability in early stages of AD, whereas clinical seizures in AD were often associated with bitemporal hyperexcitability. Frequent small sharp spikes were specifically associated with epileptiform EEGs and thus identified as a potential biomarker of hyperexcitability in AD.ConclusionEpileptiform abnormalities are common in AD but not all equivalent. Specific features of epileptiform discharges are associated with clinical seizures in AD. Given the difficulty recognizing clinical seizures in AD, these EEG features could provide guidance on which patients with AD are at high risk for clinical seizures.

The clinical features and immune responses of asymptomatic individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been well described. We studied 37 asymptomatic individuals in the Wanzhou District who were diagnosed with RT-PCR-confirmed SARS-CoV-2 infections but without any relevant clinical symptoms in the preceding 14 d and during hospitalization. Asymptomatic individuals were admitted to the government-designated Wanzhou People's Hospital for centralized isolation in accordance with policy1. The median duration of viral shedding in the asymptomatic group was 19 d (interquartile range (IQR), 15-26 d). The asymptomatic group had a significantly longer duration of viral shedding than the symptomatic group (log-rank P = 0.028). The virus-specific IgG levels in the asymptomatic group (median S/CO, 3.4; IQR, 1.6-10.7) were significantly lower (P = 0.005) relative to the symptomatic group (median S/CO, 20.5; IQR, 5.8-38.2) in the acute phase. Of asymptomatic individuals, 93.3% (28/30) and 81.1% (30/37) had reduction in IgG and neutralizing antibody levels, respectively, during the early convalescent phase, as compared to 96.8% (30/31) and 62.2% (23/37) of symptomatic patients. Forty percent of asymptomatic individuals became seronegative and 12.9% of the symptomatic group became negative for IgG in the early convalescent phase. In addition, asymptomatic individuals exhibited lower levels of 18 pro- and anti-inflammatory cytokines. These data suggest that asymptomatic individuals had a weaker immune response to SARS-CoV-2 infection. The reduction in IgG and neutralizing antibody levels in the early convalescent phase might have implications for immunity strategy and serological surveys.

Objectives Our goal was to explore the pharmaceutical service and teaching methods of obstetric clinical pharmacists to establish standardised pharmaceutical care procedures for obstetric diseases. Methods According to the evidence-based medicine method, the “Standard of Pharmaceutical Care” was established to standardise the procedure and content of the pharmaceutical care procedure including preface, purpose, scope of application, responsibilities, procedures, references, and appendix, with seven parts in total. The object of the pharmaceutical care procedure was selected by the harmfulness of the disease and the drugs used. The clinical pharmacists in obstetrics formulated the pharmaceutical care procedure for each disease according to the standard and carried out clinical practice and teaching. A retrospective study was conducted to investigate the impact of the pharmaceutical care procedure before and after its implementation on both clinical practice and training. Obstetric pharmaceutical consultation and adverse reaction were the key indicators for clinical practice. The graduation assessment for students was strictly carried out in accordance with the regulations of the Chinese Hospital Association Pharmaceutical Affairs Professional Committee including communication and consultation capacity interview, case assessment, and training procedure assessment. Results We established the standards for the pharmaceutical care procedures for three diseases: pregnancy with diabetes; pregnancy with thyroid disease; and pregnancy with hypertensive disorder. The clinical pharmacist conducted the pharmaceutical care procedure, participated in drug treatment management, and improved the recognition of the role of clinical pharmacists by the obstetric clinicians, often inviting the clinical pharmacists to participate in the consultations. The clinical pharmacists discovered and addressed any adverse reactions in a timely manner through patient drug education, subsequently reducing the underreporting of adverse reactions and improving the patient9s medication compliance, which aimed to improve the medical quality of patients in our hospital. Second, the use of the pharmaceutical care procedure as a teaching tool helped to train students to grasp the key points of drug treatment and care of the disease and improve the students9 scores in the graduation assessment (P Conclusions As a pharmacy service and teaching method that can be promoted and implemented, the pharmaceutical care procedure is beneficial for clinical pharmacists to carry out in-depth pharmaceutical services and can also be used as a teaching tool for clinical pharmacist training.

Aims/Introduction The role of irisin in maternal glucose metabolism and how it would respond to dietary n‐3 polyunsaturated fatty acid (n‐3 PUFA) intake remains unclear. This study aimed to explore whether maternal plasma irisin is associated with glucose metabolism and whether this association is modified by dietary n‐3 PUFA. Materials and Methods A total of 932 pregnant women (20–28 weeks’ gestation) aged 20–45 years were recruited. Dietary n‐3 PUFA was estimated using a validated quantitative food frequency questionnaire. Plasma irisin and insulin were tested by enzyme‐linked immunosorbent assay, and insulin resistance (IR) was estimated using the homeostatic model assessment (HOMA). Gestational diabetes mellitus was diagnosed with a 75‐g oral glucose tolerance test. Adjusted multivariable linear regression and logistic regression were carried out to examine the associations between plasma irisin and glucose metabolism. The moderating effect of dietary n‐3 PUFA intake was determined by fully multiplicative models by including the interaction term. Results Maternal plasma irisin was negatively associated with HOMA‐IR and oral glucose tolerance test 0 h glucose level (β −0.250, −0.067; corrected P‐value for false discovery rate = 0.012, 0.018, respectively), positively associated with HOMA of insulin sensitivity (β 0.028; corrected P‐value for false discovery rate = 0.012), but not associated with postprandial glucose or the risk of gestational diabetes mellitus. Furthermore, we found a moderating effect of dietary n‐3 PUFA on the relationships of plasma irisin with HOMA‐IR and HOMA of insulin sensitivity; these associations were strengthened with increased n‐3 PUFA intake (β −0.037, 0.004; P = 0.014, 0.041, respectively). Conclusions Plasma irisin was negatively associated with HOMA‐IR and fasting glucose, whereas it was positively associated with HOMA of insulin sensitivity in pregnant women. We first showed that these associations were modified by dietary n‐3 PUFA intake., Plasma irisin was negatively associated with HOMA‐IR while positively associated with HOMA‐IS in pregnant women, and we first demonstrated these associations were modified by dietary n‐3 PUFA intake.

We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT-PCR results and for the identification of asymptomatic infections.

Alzheimer's disease (AD) is a neurodegenerative disease that mainly occurs in old age and involves progressive cognitive impairment. AD has become a major global issue for public health, with approximately 24 million people currently affected by the disease. Estimates indicted that this number will quadruple by 2050. Because of the high incidence of AD, there is an urgent need to develop new strategies to diagnose and treat AD. Many recent studies have indicated the multiple, yet somewhat controversial, roles of exosomes in AD. Although the underlying mechanisms by which exosomes play a role in AD are still unknown, current evidence suggests that exosomes can carry and spread toxic amyloid-beta, and hyperphosphorylated tau, between cells, and then induce apoptosis, thus contributing to the loss of neurons. In addition, exosomes appear to possess the ability to reduce brain amyloid-beta, and tau hyperphosphorylation, and transfer neuroprotective substances between neural cells. The accumulating data brings hope that the application of exosomes may be helpful for early diagnostics and the identification of new therapeutic targets for AD. Here, we summarized the various roles of exosomes, and how they might relate to the pathogenesis of AD. We also highlight the potential application of exosomes as a therapeutic option in AD therapy.

Background The efficacy of the recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV) against virologically-confirmed dengue (VCD) has been documented in a phase 3 trial in Latin America (CYD15, NCT01374516). This is a descriptive secondary analysis of the efficacy and safety of CYD-TDV in participants from Colombia. Methods Data from 9740 Colombian participants 9-16 years of age who were randomized 2:1 to receive CYD-TDV or placebo were assessed to describe the vaccine efficacy of CYD-TDV against VCD and severe VCD. Estimation was made of the relative risk (RR) for hospitalized VCD cases and severe hospitalized VCD cases after the first dose of CYD-TDV, as well as a description of the incidence of hospitalized dengue from the start of the study and per year of the study until study completion. Results During the active phase of the trial in Colombia, the efficacy of CYD-TDV was 67.5% [95% confidence interval (CI): 58.3-74.7] against symptomatic VCD due to any serotype from injection 1 (month 0) to 25 months postinjection 1. Over 6 years, the RR across all 4 serotypes was 0.166 (95% CI: 0.09-0.29) in hospitalized VCD patients and 0.154 (95% CI: 0.04-0.50) in patients with severe hospitalized VCD. Conclusions Analysis of the data from Colombia mimics the efficacy observed in CYD15 during the active surveillance follow-up (25 months), but with a sustained beneficial RR for dengue hospitalizations on the subsequent years of follow-up. In Colombia, where seroprevalence has been demonstrated to be high in several regions of the country, CYD-TDV is a useful tool to consider as part of an integrated control strategy against endemic dengue, a disease with a high economic impact on the health system.

Exposure to silica nanoparticles (SNPs) causes lung fibrosis and threatens human health. However, it is unknown if low-dose radiation (LDR) exposure exacerbates SNP-induced lung dysfunction. Thus, the aim of our study was to determine the combined effect of SNPs and LDR on lung fibrosis and elucidate the potential mechanisms involved. We used SNP-induced A549 cells and mouse models and detected gut microbiota alteration by 16S rDNA amplicon sequencing. Additionally, lung fibrosis-related parameters were also detected using hematoxylin and eosin (H&E) staining, immunofluorescence (IF) staining, qRT-PCR, and western blot analysis. The histopathological and IF staining assays illustrated that co-exposure of mice to SNPs and LDR had a significant deleterious effect on both lung function and lung fibrosis, in comparison to exposure to SNPs or LDR alone. Furthermore, the abundance of Bacteroidetes significantly increased while that of Firmicutes significantly decreased following co-exposure to SNPs and LDR. Mechanistically, the Notch cascade was activated in chronically SNP-exposed mice with lung fibrosis and A549 cells. Additionally, the Notch pathway-associated proteins showed increased expression levels in the lungs following SNP exposure both in vivo and in vitro. Notably, SNP-induced dysbiosis of the gut microbiota promoted lung epithelial damage by triggering the Notch pathway, resulting in SNP-induced lung fibrosis. However, oral administration of probiotics protected the mice from SNP-induced lung injury. Our results strongly indicate that the activation of the gut microbiota-dependent Notch pathway in response to co-exposure to SNPs and LDR results in lung epithelial injury in vivo. Probiotics supplementation is a potential way to protect against SNP- and LDR-induced lung fibrosis.

Objective Develop a high-performing algorithm to detect mesial temporal lobe (mTL) epileptiform discharges on intracranial electrode recordings. Methods An epileptologist annotated 13,959 epileptiform discharges from a dataset of intracranial EEG recordings from 46 epilepsy patients. Using this dataset, we trained a convolutional neural network (CNN) to recognize mTL epileptiform discharges from a single intracranial bipolar channel. The CNN outputs from multiple bipolar channel inputs were averaged to generate the final detector output. Algorithm performance was estimated using a nested 5-fold cross-validation. Results On the receiver-operating characteristic curve, our algorithm achieved an area under the curve (AUC) of 0.996 and a partial AUC (for specificity > 0.9) of 0.981. AUC on a precision-recall curve was 0.807. A sensitivity of 84% was attained at a false positive rate of 1 per minute. 35.9% of the false positive detections corresponded to epileptiform discharges that were missed during expert annotation. Conclusions Using deep learning, we developed a high-performing, patient non-specific algorithm for detection of mTL epileptiform discharges on intracranial electrodes. Significance Our algorithm has many potential applications for understanding the impact of mTL epileptiform discharges in epilepsy and on cognition, and for developing therapies to specifically reduce mTL epileptiform activity.

The checkerboard broth method based on the Clinical and Laboratory Standards Institute M38-A3 document was used in this study to evaluate the in vitro activity of allicin alone and in combination with the antifungal drugs (griseofulvin, fluconazole, itraconazole and terbinafine) against Microsporum canis isolated from patients with tinea capitis. When allicin was used alone, only weak anti-M. canis effects were found. The MIC50, MIC90 and geometric mean (GM) of terbinafine were the lowest among the compounds tested. Synergism was observed for the combinations of allicin with itraconazole and terbinafine. Only indifference was observed for the combinations of allicin with griseofulvin and fluconazole. Our study illustrated the synergism of allicin in combination with itraconazole and terbinafine, which could be a reference for the treatment of tinea capitis due to M. canis.

Objective: The study aimed to examine how the phonological loop influences reading ability and processing in Chinese children with developmental dyslexia (DD).Methods: This study included 30 children with DD and 37 children without DD. Two types of articles (i.e., scenery prose and narrative story) and two conditions (under the conditions of articulatory-suppression and silent reading) were applied. An eye-link II High-Speed Eye Tracker was used to track a series of eye-movement parameters. The data were analyzed by the linear Mixed-Effects model.Results: Compared with children without DD, Children with DD had lower reading achievement (RA), frequency of saccades (FS) and frequency of fixations (FF), longer reading time (RT) and average fixation duration (AFD), slower reading speed (RS), shorter average saccade amplitude (ASA) and fixation distance (FD), more number of fixations (NF), and number of saccades (NS). There were significant interactions between participant group and articulatory suppression on RT and FD. We also observed interaction effects between article types and articulatory suppression on RA, AFD, ASA, and FS.Conclusion: Children DD exhibit abnormal phonological loop and eye movements while reading. The role of articulatory suppression on reading varies with the presentation of DD and the article type.

Purpose: The central nervous mechanism of acute tinnitus is different from that of chronic tinnitus, which may be related to the difference of cerebral blood flow (CBF) perfusion in certain regions. To verify this conjecture, we used arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) in this study to compare the CBF alterations of patients with acute and chronic tinnitus.Methods: The current study included patients with chronic tinnitus (n = 35), acute tinnitus (n = 30), and healthy controls (n = 40) who were age-, sex-, and education-matched. All participants underwent MRI scanning and then ASL images were obtained to measure CBF of the entire brain and analyze the differences between groups as well as the correlations with tinnitus characteristics.Results: The chronic tinnitus group showed increased z-CBF in the right superior temporal gyrus (STG) and superior frontal gyrus (SFG) when compared with the acute tinnitus patients. Further connectivity analysis found enhanced CBF connectivity between the right STG and fusiform gyrus (FG), the right SFG and left middle occipital gyrus (MOG), as well as the right parahippocampal gyrus (PHG). Moreover, in the chronic tinnitus group, the tinnitus handicap questionnaire (THQ) score was positively correlated with the normalized z-CBF of right STG (r = 0.440, p = 0.013).Conclusion: Our results confirmed that the CBF changes in some brain regions were different between acute and chronic tinnitus patients, which was correlated with certain tinnitus characteristics. This is of great value to further research on chronicity of tinnitus, and ASL has a promising application in the measurement of CBF.

The reorganization of the limbic regions extend to general cognitive network is believed to exist in the chronicity of tinnitus with particular 'hubs' contributing to a 'noise-cancellation' mechanism. To test this hypothesis, we investigated the topological brain network of tinnitus in different periods.Resting-state functional magnetic resonance imaging were obtained from 32 patients with acute tinnitus, 41 patients with chronic tinnitus and 60 age- and gender- matched healthy controls (HC). The topological features of their brain networks were explored using graph theory analysis.Common small-world attributes were compared between the three groups, all showed a significantly increased values in Cp, Lp, λ (all p 0.05). Significantly increased nodal centralities in the left superior frontal gyrus and the right precuneus, significantly decreased nodal centralities in the right inferior temporal gyrus were observed for acute tinnitus patients compared to HC. While for chronic tinnitus patients, there were significant increased nodal centralities in the left hippocampus, amygdala, and temporal pole, but decreased nodal centralities in the right inferior temporal gyrus. Additionally, significant higher nodal centralities were found in bilateral medial superior frontal gyrus for acute tinnitus patients compared to chronic tinnitus patients. Besides, alterations in rich-club organization were found in acute tinnitus patients and chronic tinnitus patients compared with HC, with increased functional connections among rich-club nodes and peripheral nodes in patients with tinnitus.Brain network topological properties altered across prefrontal-limbic-subcortical regions in tinnitus. The existed hubs in tinnitus might indicate an emotional and cognitive burden in 'noise-cancellation' mechanism.

Background: Early comprehensive treatment models (CTMs) have been developed as effective treatments for children with autism spectrum disorder (ASD). Numerous studies have suggested that CTMs can improve short-term outcomes, but little is known about precise outcome information in childhood. The current meta-analysis reviewed studies reporting broader outcomes in children with ASD who had ever participated in a CTM and examined the predictors of developmental gains.Methods: We searched eight databases up to June 13, 2019, for relevant trials and natural experiments. Longitudinal studies were selected if they investigated the outcomes of CTMs. Two meta-analyses were undertaken to provide a summary estimate of change in treatment outcomes and to evaluate the effect of CTMs; one used the standardized mean change between the pretest and posttest, and the other was a classical meta-analysis. Stratified and random-effects meta-regression analyses were performed to search for outcome differences among studies.Results: Eighteen intervention studies (involving 495 children with ASD) met all the inclusion criteria: 12 used early intensive behavioral intervention (EIBI), and two used the Early Start Denver Model (ESDM). Outcomes were categorized into three parts: cognitive, language and behavioral (e.g., adaptive functioning and symptomatology). Overall, most children with ASD who had ever participated in an early CTM made gains in many areas of functioning, especially in terms of symptom- and language-related outcomes. Stratified analyses indicated that the ESDM displayed the largest effect on IQ improvement (ES = 1.37, 95% CI: 0.95 to 1.80), while EIBI was more effective for symptom reduction (ES = −1.27, 95% CI: −1.96 to −0.58). Further, meta-regression suggested that interventions with parent involvement, higher intensity, and longer treatment hours yielded greater improvements in IQ and social adaptive functioning, respectively.Conclusion: The results demonstrate a positive association between CTMs and better prognosis in childhood, especially regarding symptoms, and language. However, most extant research involves small, non-randomized studies, preventing definitive conclusions from being drawn. Clearly, the outcomes of children with ASD are still far from normal, especially with respect to adaptive functioning, and the four mediating variables pertaining to treatment elements can affect their gains, including approach, implementer, intensity, and total treatment hours.Systematic Review Registration: [www.crd.york.ac.uk/PROSPERO], identifier [CRD42019146859].

Although tinea capitis is common in children, but it is rare in newborns. It should be differentiated with neonatal lupus erythematosus, nummular eczema, psoriasis, seborrheic dermatitis, erythema annular centrifugum, annular urticaria, and annular erythema of infancy. Tinea capitis usually needs oral antifungal therapy, but the data of use in newborn is limited. Here, we report a case of tinea capitis caused by Microsporum canis in a 23-day-old female newborn. The patient was given itraconazole oral solution pulse therapy with an excellent outcome. Itraconazole oral solution pulse therapy may be a promising therapy for tinea capitis in infants, especially in newborns.

Background and PurposeReports have suggested that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes neurologic manifestations including encephalopathy and seizures. However, there has been relatively limited electrophysiology data to contextualize these specific concerns and to understand their associated clinical factors. Our objective was to identify EEG abnormalities present in patients with SARS-CoV-2, and to determine whether they reflect new or preexisting brain pathology.MethodsWe studied a consecutive series of hospitalized patients with SARS-CoV-2 who received an EEG, obtained using tailored safety protocols. Data from EEG reports and clinical records were analyzed to identify EEG abnormalities and possible clinical associations, including neurologic symptoms, new or preexisting brain pathology, and sedation practices.ResultsWe identified 37 patients with SARS-CoV-2 who underwent EEG, of whom 14 had epileptiform findings (38%). Patients with epileptiform findings were more likely to have preexisting brain pathology (6/14, 43%) than patients without epileptiform findings (2/23, 9%; p=0.042). There were no clear differences in rates of acute brain pathology. One case of nonconvulsive status epilepticus was captured, but was not clearly a direct consequence of SARS-CoV-2.Abnormalities of background rhythms were common, and patients recently sedated were more likely to lack a posterior dominant rhythm (p=0.022).ConclusionsEpileptiform abnormalities were common in patients with SARS-CoV-2 referred for EEG, but particularly in the context of preexisting brain pathology and sedation. These findings suggest that neurologic manifestations during SARS-CoV-2 infection may not solely relate to the infection itself, but rather may also reflect patients’ broader, preexisting neurologic vulnerabilities.

Background: Previous studies have suggested that maternal dietary protein was associated with allergic diseases in offspring, but few studies have evaluated the influence of dietary protein patterns. This study aimed to explore the prospective association between maternal dietary protein patterns during pregnancy and the risk of infant eczema.Methods: A total of 713 mother-child pairs from a prospective cohort in Guangzhou, China were recruited. Maternal dietary protein was estimated using a validated face-to-face food frequency questionnaire at 20–28 weeks' gestation from 2017 to 2018. Dietary protein patterns were calculated based on the sources of protein. The data of infant eczema was assessed at 6 months of age using the symptom questionnaire of eczema. Logistic regression was carried out to examine the associations between maternal dietary protein patterns and infant eczema.Results: The cumulative incidence of infant eczema at 6 months of age was 51.19%. Mothers of infants with eczema consumed more protein from poultry source during pregnancy than mothers of infants without eczema, while no statistical differences were observed in maternal intakes of protein from cereals and tubers, vegetables, fruits, red meat, fish and seafood, eggs, dairy, soybean, and nuts and seeds. Four dietary protein patterns were identified and termed poultry, plant, dairy and eggs, and red meat and fish. The cumulative incidence of eczema was 61.2, 45.8, 48.0, 51.4% for these four patterns, respectively. Compared to the poultry dietary pattern, the plant pattern and the dairy and eggs pattern were associated with a reduced risk of infant eczema, and the adjusted odds ratios (95% confidence interval) were 0.572 (0.330–0.992), 0.478 (0.274–0.837), respectively. No such association was observed for the red meat and fish dietary protein pattern.Conclusion: This is the first study that focused on the association between maternal dietary protein during pregnancy from a whole-diet perspective and infant eczema. Compared with the poultry dietary protein pattern, the maternal plant pattern and the dairy and eggs pattern during pregnancy were associated with a reduced risk of infant eczema.

Objective Electroencephalogram (EEG) reactivity is a robust predictor of neurological recovery after cardiac arrest, however interrater-agreement among electroencephalographers is limited. We sought to evaluate the performance of machine learning methods using EEG reactivity data to predict good long-term outcomes in hypoxic-ischemic brain injury. Methods We retrospectively reviewed clinical and EEG data of comatose cardiac arrest subjects. Electroencephalogram reactivity was tested within 72 h from cardiac arrest using sound and pain stimuli. A Quantitative EEG (QEEG) reactivity method evaluated changes in QEEG features (EEG spectra, entropy, and frequency features) during the 10 s before and after each stimulation. Good outcome was defined as Cerebral Performance Category of 1–2 at six months. Performance of a random forest classifier was compared against a penalized general linear model (GLM) and expert electroencephalographer review. Results Fifty subjects were included and sixteen (32%) had good outcome. Both QEEG reactivity methods had comparable performance to expert EEG reactivity assessment for good outcome prediction (mean AUC 0.8 for random forest vs. 0.69 for GLM vs. 0.69 for expert review, respectively; p non-significant). Conclusions Machine-learning models utilizing quantitative EEG reactivity data can predict long-term outcome after cardiac arrest. Significance A quantitative approach to EEG reactivity assessment may support prognostication in cardiac arrest.

MicroRNAs (miRNAs) play important roles in maintaining normal heart function. Abnormal expression of miR-331 has been observed in the hearts of patients with atrial fibrillation and Marfan syndrome. However, whether miR-331 regulates cardiac function under physiological and pathological conditions still remains unknown. In the present study, we investigated the function and underlying mechanisms of miR-331 in a pressure overload-induced heart failure model and miR-331 transgenic rat model. First, we found that the expression of miR-331-3p exhibited a 1.7-fold increase in hypertrophy compared with that in the sham group (P

The QRS-T angle is a key ECG predictor for ventricular arrhythmia. Lead has a strong relation with cardiovascular diseases; however, no study has been conducted to investigate the association between lead exposure and QRS-T angle. Thus, we explored this association in a population-based representative sample: NHANES III. We used the standard 12-lead ECGs to calculate Spatial QRS-T angles. Blood lead concentration was measured using graphite furnace atomic absorption spectrophotometry method. We conducted multivariate weighted logistic regression to adjust for impaired fasting glucose, hypertension, poverty index, age, race, and smoking status. We found that when the log of blood lead increased by one unit, the odds of an abnormal QRS-T angle increased by 34% among men and 4% among women. We suggest the use of QRS-T angle deviation among those who are exposed to lead to detect individuals at risk for adverse cardiovascular outcomes such as arrhythmias.

With the increasing number of the one-child family, it is important to investigate whether the only-child status is associated with dyslipidemia. Among a national sample of 65,347 Chinese children aged 6–17 years, 16,100 lipid profiles were available. Children’s height, weight, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured. In comparison to children with siblings, only children (OC) were more likely to be boys and live in urban areas. OC had less physical activity, less fried food intake, but more meat and dairy intakes. OC had significantly higher levels of TC (3.97 ± 0.78 vs. 3.89 ± 0.77) and LDL-C (2.12 ± 0.65 vs. 2.06 ± 0.64) in the overall group, and also in the subgroups of rural boys and girls. The prevalence of hyper-TC (5.48% vs. 4.43%) and hyper-LDL-C (3.97% vs. 2.96%) were significantly higher in OC than their counterparts. Furthermore, we found higher odds of hyper-LDL-C [1.43 (1.12, 1.83)] in OC after adjustments. In the subgroup analysis, only-child status was associated with increased risk of hyper-TC [1.86 (1.06, 3.26)] and hyper-LDL-C [2.65 (1.14, 6.16)] among rural boys, and hyper-LDL-C among rural girls [2.20 (1.14, 4.22)]. In conclusion, higher levels of TC and LDL-C were found in OC especially for rural children. Being an only-child was associated with increased risk of hyper-LDL-C.

Background The prevalence of metabolic syndrome (MetS) rapidly increased over the past decades. However, little evidence exists about the effects of long-term exposure to ambient air pollution on MetS in children and adolescents. Objective This study aims to assess the association between long-term ambient air pollution and the prevalence of MetS in a large population of Chinese children and adolescents. Methods In 2013, a total of 9,897 children and adolescents aged 10 to 18 years were recruited from seven provinces/municipalities in China. MetS was defined based on the recommendation by the International Diabetes Federation (IDF). Satellite based spatio-temporal models were used to estimate exposure to ambient air pollution (including particles with diameters ≤1.0 µm (PM1), ≤2.5 µm (PM2.5), and ≤10 µm (PM10), and nitrogen dioxide (NO2)). Individual exposure was calculated according to 94 schools addresses. After adjustment for a range of covariates, generalized linear mixed-effects models were utilized to evaluate the associations between air pollutants and the prevalence of MetS and its components. In addition, several stratified analyses were examined according to sex, weight status, outdoor physical activity time, and sugar-sweetened beverages (SSBs) intake. Results The prevalence of MetS was 2.8%. The odds ratio of MetS associated with a 10 μg/m3 increase in PM1, PM2.5, PM10 and NO2 was 1.20 (95%CI: 0.99, 1.46), 1.31 (95%CI: 1.05, 1.64), 1.32 (95%CI: 1.08, 1.62), and 1.33 (95%CI: 1.03, 1.72), respectively. Regarding the MetS components, we observed associations between all pollutants and abdominal obesity. In addition, long-term PM1 and NO2 exposures were associated with the prevalence of elevated fasting blood glucose. Stratified analyses detected that the associations between air pollutants and the prevalence of MetS were stronger in boys (Pinteraction Conclusions We found that long-term exposure to PM2.5, PM10, and NO2 were positively associated with the prevalence of MetS in children and adolescents. Our findings may have certain public health implications for some comprehensive strategy of environment improvement and lifestyles changes in order to reduce the burden of non-communicable disease.

Objectives: Seizures and seizure-like electroencephalography (EEG) patterns, collectively referred to as “ictal interictal injury continuum” (IIIC) patterns, are commonly encountered in critically ill patients. Automated detection is important for patient care and to enable research. However, training accurate detectors requires a large labeled dataset. Active Learning (AL) may help select informative examples to label, but the optimal AL approach remains unclear. Methods: We assembled >200,000 h of EEG from 1,454 hospitalized patients. From these, we collected 9,808 labeled and 120,000 unlabeled 10-second EEG segments. Labels included 6 IIIC patterns. In each AL iteration, a Dense-Net Convolutional Neural Network (CNN) learned vector representations for EEG segments using available labels, which were used to create a 2D embedding map. Nearest-neighbor label spreading within the embedding map was used to create additional pseudo-labeled data. A second Dense-Net was trained using real- and pseudo-labels. We evaluated several strategies for selecting candidate points for experts to label next. Finally, we compared two methods for class balancing within queries: standard balanced-based querying (SBBQ), and high confidence spread-based balanced querying (HCSBBQ). Results: Our results show: 1) Label spreading increased convergence speed for AL. 2) All query criteria produced similar results to random sampling. 3) HCSBBQ query balancing performed best. Using label spreading and HCSBBQ query balancing, we were able to train models approaching expert-level performance across all pattern categories after obtaining ∼7000 expert labels. Conclusion: Our results provide guidance regarding the use of AL to efficiently label large EEG datasets in critically ill patients., SCOPUS: ar.j, info:eu-repo/semantics/published

PurposeBoth tinnitus and type 2 diabetes mellitus (T2DM) are linked with cognitive decline and brain dysfunction. This study used arterial spin labeling (ASL) perfusion functional magnetic resonance imaging (fMRI) to examine the abnormal cerebral blood flow (CBF) patterns existed in tinnitus patients and potential relationships between the abnormal CBF and cognitive performance. The impact of T2DM on CBF alterations in tinnitus patients was further explored.MethodsSixty tinnitus patients and 40 non-tinnitus subjects were recruited. CBF images were collected and analyzed using ASL perfusion fMRI. Brain regions with CBF alterations between tinnitus patients and non-tinnitus controls were identified by one-way analysis of variance. Interaction effects between tinnitus and T2DM for CBF changes were also selected. Then, correlation analyses were calculated to specify the link between CBF changes and cognitive performance and between CBF changes and diabetic characteristics.ResultsTinnitus patients showed decreased CBF, primarily in the auditory area and default mode network (DMN), compared with non-tinnitus controls. Decreased CBF in these regions was correlated with executive function and attention. The interaction effect between tinnitus and T2DM was significant in the right medial prefrontal gyrus. Additionally, CBF in the right medial prefrontal gyrus was correlated with tinnitus distress and cognitive performance. In tinnitus patients, Hemoglobin A1c was associated with CBF in the right medial prefrontal gyrus.ConclusionTinnitus affects brain perfusion in the auditory area and DMN. T2DM and uncontrolled glucose levels may aggravate a CBF decrease in tinnitus patients. These new findings implied that tinnitus patients may benefit from blood glucose control in terms of their cognitive function and tinnitus distress.

Tinnitus refers to sound perception in the absence of external sound stimulus. It has become a worldwide problem affecting all age groups especially the elderly. Tinnitus often accompanies hearing loss and some mood disorders like depression and anxiety. The comprehensive adverse effects of tinnitus on people determine the severity of tinnitus. Understanding the mechanisms of tinnitus and related discomfort may be beneficial to the prevention and treatment, and then getting patients out of tinnitus distress. Functional magnetic resonance imaging (fMRI) is a powerful technique for characterizing the intrinsic brain activity and making us better understand the tinnitus neural mechanism. In this article, we review fMRI studies published in recent years on the neuroimaging mechanisms of tinnitus. The results have revealed various neural network alterations in tinnitus patients, including the auditory system, limbic system, default mode network, attention system, and some other areas involved in memory, emotion, attention, and control. Moreover, changes in functional connectivity and neural activity in these networks are related to the perception, persistence, and severity of tinnitus. In summary, the neural mechanism of tinnitus is a complex regulatory mechanism involving multiple networks. Future research is needed to study these neural networks more accurately to refine the tinnitus models.

The diagnosis of epilepsy often relies on a reading of routine scalp electroencephalograms (EEGs). Since seizures are highly unlikely to be detected in a routine scalp EEG, the primary diagnosis depends heavily on the visual evaluation of Interictal Epileptiform Discharges (IEDs). This process is tedious, expert-centered, and delays the treatment plan. Consequently, the development of an automated, fast, and reliable epileptic EEG diagnostic system is essential. In this study, we propose a system to classify EEG as epileptic or normal based on multiple modalities extracted from the interictal EEG. The ensemble system consists of three components: a Convolutional Neural Network (CNN)-based IED detector, a Template Matching (TM)-based IED detector, and a spectral feature-based classifier. We evaluate the system on datasets from six centers from the USA, Singapore, and India. The system yields a mean Leave-One-Institution-Out (LOIO) cross-validation (CV) area under curve (AUC) of 0.826 (balanced accuracy (BAC) of 76.1%) and Leave-One-Subject-Out (LOSO) CV AUC of 0.812 (BAC of 74.8%). The LOIO results are found to be similar to the interrater agreement (IRA) reported in the literature for epileptic EEG classification. Moreover, as the proposed system can process routine EEGs in a few seconds, it may aid the clinicians in diagnosing epilepsy efficiently. Ministry of Education (MOE) The research of the project was supported in part by the Ministry of Education, Singapore, under grant AcRF TIER 1- 2019-T1-001-116 (RG16/19). The NUH and NNI dataset collection was supported by the National Health Innovation Centre (NHIC) grant (NHIC-I2D-1608138).

Evidence of the association between common chronic diseases and depression is sparse.Totally 7819 participants aged 45+ without depression at baseline were followed-up (2011-2015) to detect incident depression. Chronic diseases and depression were defined by self-reported diagnosis and the Center for Epidemiological Studies Depression Scale (CES-D10), respectively. Cox proportional hazards model was used to explore the association between chronic diseases and depression adjusting for age, gender, education, marital/living conditions, area, smoking, drinking, economic status, BMI and health insurance.During an average of 3.42 years follow-up, 2271 participants developed depression (85 per 1000 person-year). Chronic diseases were related to significantly higher risk of depression (HR = 1.38). A higher risk of depression was also associated with specific diseases: stomach/other digestive diseases (HR = 1.19), diabetes (HR = 1.22), arthritis/rheumatism (HR = 1.30), and kidney diseases (HR = 1.34) (P0.05). The risk of depression increased with increasing in the number of chronic diseases (1: HR = 1.27, 2: HR = 1.49, and 3+: HR = 1.51, P-trend0.001). No significant difference was observed across age, gender, education, and area.Chronic diseases and depression were based on self-reported diagnosis and measurement scale, respectively, which could lead to information bias. Some unmeasured confounders might have biased the results.The occurrence of depression in people aged 45+ is associated with number of chronic diseases in a dose-response fashion. These results may provide guidance on preventing depression and improving the quality of life in middle and late adulthood.

Background Depressive symptoms and cognitive impairment often coexisted in the elderly. This study investigates the effect of late-life depressive symptoms on risk of mild cognitive impairment (MCI). Methods A total of 14,231 dementia- and MCI free participants aged 60+ from the Survey of Health, Ageing, and Retirement in Europe were followed-up for 10 years to detect incident MCI. MCI was defined as 1.5 standard deviation (SD) below the mean of the standardized global cognition score. Depressive symptoms were assessed by a 12-item Europe-depression scale (EURO-D). Severity of depressive symptoms was grouped as: no/minimal (score 0–3), moderate (score 4–5), and severe (score 6–12). Significant depressive symptoms (SDSs) were defined as EURO-D score ≥ 4. Results During an average of 8.2 (SD = 2.4)-year follow-up, 1,352 (9.50%) incident MCI cases were identified. SDSs were related to higher MCI risk (hazard ratio [HR] = 1.26, 95% confidence intervals [CI]: 1.10–1.44) in total population, individuals aged 70+ (HR = 1.35, 95% CI: 1.14–1.61) and women (HR = 1.28, 95% CI: 1.08–1.51) in Cox proportional hazard model adjusting for confounders. In addition, there was a dose–response association between the severity of depressive symptoms and MCI incidence in total population, people aged ≥70 years and women (p-trend Conclusions Significant depressive symptoms were associated with higher incidence of MCI in a dose–response fashion, especially among people aged 70+ years and women. Treating depressive symptoms targeting older population and women may be effective in preventing MCI.

The research and application of lidar in the establishment of high-precision maps and path planning of intelligent driving vehicles are being developed as a technical support for intelligent driving technology. In this paper we mainly focus on the research and application of lidar real-time positioning and map building technology in intelligent driving vehicles, including the preprocessing of raw data required by Simultaneous Localization and Mapping (SLAM), the front-end algorithm of SLAM, the back-end optimization of SLAM and the final algorithm experiment. In the front-end algorithm of SLAM, we propose a boundary line feature extraction scheme based on the traditional curvature feature point extraction method and Random Sample Consensus (RANSAC) algorithm, and realize point cloud registration and pose estimation based on optimized Iterative Closest Point (ICP). In the back-end processing algorithm, we propose a sparse algorithm of graph nodes for selection, and propose boundary verification based on an improved loop detection and relocation strategy design. The results showed that the algorithm in this paper was less affected by noise, which considerably saves time in the operation of the loop frame determination algorithm and improves the safety of the intelligent vehicle in the process of driving.

Background . Prediction of mortality risk in intensive care units (ICU) is an important task. Data-driven methods such as scoring systems, machine learning methods, and deep learning methods have been investigated for a long time. However, few data-driven methods are specially developed for pediatric ICU. In this paper, we aim to amend this gap—build a simple yet effective linear machine learning model from a number of hand-crafted features for mortality prediction in pediatric ICU. Methods . We use a recently released publicly available pediatric ICU dataset named pediatric intensive care (PIC) from Children’s Hospital of Zhejiang University School of Medicine in China. Unlike previous sophisticated machine learning methods, we want our method to keep simple that can be easily understood by clinical staffs. Thus, an ensemble step-wise feature ranking and selection method is proposed to select a small subset of effective features from the entire feature set. A logistic regression classifier is built upon selected features for mortality prediction. Results . The final predictive linear model with 11 features achieves a 0.7531 ROC-AUC score on the hold-out test set, which is comparable with a logistic regression classifier using all 397 features (0.7610 ROC-AUC score) and is higher than the existing well known pediatric mortality risk scorer PRISM III (0.6895 ROC-AUC score). Conclusions . Our method improves feature ranking and selection by utilizing an ensemble method while keeping a simple linear form of the predictive model and therefore achieves better generalizability and performance on mortality prediction in pediatric ICU.