Abnormal Tone Research Articles

ESG performance and disclosure quality: does a well-balanced board of directors matter when impression management occurs?

PurposeThis paper explores how the disclosure quality, measured by the abnormal tone of environmental and social report, may determine the environmental, social and corporate governance (ESG) performance of the firm. This study also investigates the impact of the moderator “board of directors” to explore the extent to which a well-balanced board of directors may affect this association within an impression management strategy.Design/methodology/approachThis work uses a sample of 616 firm-year observations using a sample of French firms indexed on SBF120 index from 2010 to 2017. To test the developed hypotheses, the GLS regression is applied and to control for endogeneity issue and sample selection bias, the authors used, respectively, the two stage least square (2SLS) procedure and the Heckman model.FindingsFindings suggest that a well-balanced board of directors moderates the relationship between the ESG performance and the disclosure quality. The positive effect of abnormal tone management on ESG is weakened by the presence of a good structure of the board, attenuating impression management initiatives.Research limitations/implicationsThe research provides evidence of the impact of corporate social responsibility (CSR) reporting quality, in particular disclosure tone management, on the level of ESG performance in the French context. As the board of directors may have a major impact on weakening impression management strategies in particular tone management practices, in order to improve CSR report quality, the authors recommend French companies to ensure a well-balanced board of directors.Originality/valueThis study helps investors to comprehensively evaluate the information disclosed on CSR reports. It unveils that a strong board composition induces better quality of CSR report and brings better ESG performance. Thus, the study results point to the importance of a well-balanced board of directors and the regulation of the narrative disclosure of CSR information.

Safety and efficacy of cardioneuroablation for vagal bradycardia in a single arm prospective study

Cardioneuroablation (CNA) is currently considered as a promising treatment option for patients with symptomatic bradycardia caused by vagotonia. This study aims to further investigate its safety and efficacy in patients suffering from vagal bradycardia. A total of 60 patients with vagal bradycardia who underwent CNA in the First Affiliated Hospital of Xinjiang Medical University from November 2019 to June 2022. Preoperative atropine tests revealed abnormal vagal tone elevation in all patients. First, the electroanatomic structures of the left atrium was mapped out by using the Carto 3 system, according to the protocol of purely anatomy-guided and local fractionated intracardiac electrogram-guided CNA methods. The upper limit of ablation power of superior left ganglion (SLGP) and right anterior ganglion (RAGP) was not more than 45W with an ablation index of 450.Postoperative transesophageal cardiac electrophysiological examination was performed 1 to 3 months after surgery. The atropine test was conducted when appropriate. Twelve-lead electrocardiogram, Holter electrocardiogram, and skin sympathetic nerve activity were reviewed at 1, 3, 6 and 12 months after operation. Adverse events such as pacemaker implantation and other complications were also recorded to analyze the safety and efficacy of CNA in the treatment of vagus bradycardia. Sixty patients were enrolled in the study (38 males, mean age 36.67 ± 9.44, ranging from 18 to 50 years old). None of the patients had a vascular injury, thromboembolism, pericardial effusion, or other surgical complications. The mean heart rate, minimum heart rate, low frequency, low/high frequency, acceleration capacity of rate, and skin sympathetic nerve activity increased significantly after CNA. Conversely, SDNN, PNN50, rMSSD, high frequency, and deceleration capacity of rate values decreased after CNA (all P < 0.05). At 3 months after ablation, the average heart rate, maximum heart rate, and acceleration capacity of heart rate remained higher than those before ablation, and the deceleration capacity of heart rate remained lower than those before ablation and the above results continued to follow up for 12 months after ablation (all P < 0.05). There was no significant difference in other indicators compared with those before ablation (all P > 0.05). The remaining 81.67% (49/60) of the patients had good clinical results, with no episodes of arrhythmia during follow-up. CNA may be a safe and effective treatment for vagal-induced bradycardia, subject to confirmation by larger multicenter trials.

Clinicobiochemical Profile and Outcome of Children with Small Molecule Neurometabolic Disorders: A Tertiary Care Hospital Experience from India

AbstractInborn Errors of Metabolism (IEM), though heterogenous, are not uncommon. Neurologic manifestations predominate. Without universal newborn screening, early diagnosis and treatment may lessen neuromorbidity. Hence, this study was done to understand small molecule neurometabolic disorders' presentation, diagnostic clues, and outcome.Small molecule neurometabolic disorder was diagnosed in 45 children (postneonatal onset) over 14 years (2008–2022) in a tertiary care hospital. Clinical and laboratory data were retrospectively analyzed.There were 26 boys and 19 girls. The median age at diagnosis was 19 months (interquartile range [IQR] 8–38 months). The median diagnostic delay was 12 months in chronic encephalopathy (IQR 1–24 months) and 1 month (IQR 0.2–5.5 months) in the acute encephalopathy group (p ≤ 0.01). The presentation mode was chronic encephalopathy/myopathy in 29 (64.4%) and acute encephalopathy in 11 (24.4%). Diagnostic clues included unexplained developmental delay (n = 27, 60%), tone abnormalities (n = 26, 57.7%), movement disorder and ataxia (n = 16, 35.5%), acute encephalopathy (n = 11, 24.4%), neuroregression (n = 10, 22.2%), macrocephaly (n = 10, 22.2%), and alopecia (n = 4, 8.9%). Diagnostic/suggestive blood-spot tandem mass spectrometry (TMS) was seen in 34/38 (89.5%) children. Neuroimaging helped clinch the diagnosis in 17 (47%) children. Diagnostic categories were organic acidemias (n = 25, 55.6%), urea cycle disorders (n = 11, 24.4%), aminoacidopathies (n = 5, 11.1%), and fatty acid oxidation disorders (n = 4, 8.9%). The neurodevelopmental outcome was normal in 13 (28.8%), mild delay in 12 (26.6%), severe delay in 11 (24.4%), 3 deaths (6.6%), and 6 (13.3%) children being lost to follow-up. Overall, the outcome was favorable in 55% of cases.Unexplained developmental delay with tone abnormalities with or without movement disorders is a joint presentation of late-onset neurometabolic diseases. Neuroimaging studies and laboratory tests like blood-spot TMS help identify many small molecule disorders.

Yield and Utility of Routine Epilepsy Panel Genetic Testing Among Young Patients With Seizures.

Objective: We examined the yield of routine epilepsy panel genetic testing in pediatric patients. Methods: We retrospectively reviewed epilepsy genetic panel results routinely performed in the hospital or clinic on patients <8 years old from July 2021 to July 2023. We evaluated demographics, family history, seizure type, severity, and frequency, development, tone and movement abnormalities, dysmorphism, and electroencephalography (EEG) or magnetic resonance imaging (MRI) results as predictors of results. Results: 65 patients were included with mean age 4.5 years. Sixty percent of patients were male; 11 patients had pathogenic variants (16.9%), 7 were carriers for autosomal recessive conditions (10.8%), 36 had variants of uncertain significance (55.4%), and 11 tested negative (16.9%). Pathogenic variants and variants of uncertain significance were unassociated with demographics, clinical features, imaging, or family history. Conclusion: Variants identified have potential implications for treatment (SCN1), comorbidity screening (TSC1), reproduction (ATAD1, PSAT1, and CLN8), and prognostication (FOXG1). Patients not routinely screened for a genetic cause of epilepsy by our standard practices had clinically relevant results.

Media abnormal tone and cross section of stock returns: Evidence from China

AbstractThis paper introduces an innovative methodology for extracting information from textual data to explain cross‐sectional stock returns, addressing limitations of conventional media tone measures. We find firms exhibiting higher media abnormal tone yield lower future returns in the Chinese market, even when controlling for common risk factors. This effect is more pronounced among firms with low investment, low profitability, and high short‐term reversal. We also find the negative premium generated by media abnormal tone results from mispricing, highlighting investor overreaction despite media's role in disseminating concurrent firm information. Furthermore, the tendency for media outlets to follow suit exacerbates investor overreaction.

Radiological Findings in Patients Presenting with Brief Resolved Unexplained Events (BRUEs)

Background/Hypothesis: Brief resolved unexplained events (BRUEs) are events in infants characterized by cyanosis, abnormal breathing, abnormal tone, and altered responsiveness. Practice guidelines define high-risk and low-risk BRUEs and do not recommend imaging in low-risk patients. We evaluated imaging in these patients and hypothesized that high-risk patients would have more imaging studies and abnormalities.&#x0D; Methods: Using the radiology information system, a retrospective review was performed between 2016-2022 for patients &lt;1 year presenting with BRUE. Defined search terms were used to identify imaging within one week of presentation. Patients were evaluated for clinical presentation, medical history, physical examination, imaging studies ordered, and final diagnoses.&#x0D; Results: 126 patients were identified. 113 patients (46 female; 93 high-risk), between 3 and 355 days old (average age 97 days), met inclusion criteria. Imaging included chest radiographs (99), head CTs (24), brain MRIs (19), skeletal surveys (16), and others (22). There was no difference in the number of imaging studies obtained between these groups (p=0.423, Mann-Whitney U test). However, a greater proportion of high-risk patients had imaging abnormalities (p=0.023, Fisher’s exact test). Only 1/20 (5%) low-risk patients had abnormal imaging (PCR proven viral bronchiolitis). 26/93 (28%) high-risk patients had abnormal findings, most commonly on chestradiographs (15), brain MRIs (9), head CTs (4), and skeletal surveys (3). 18/26 high-risk patients had imaging abnormalities leading to a diagnosis other than BRUE (viral bronchiolitis, bronchopulmonary dysplasia, nonaccidental trauma, perinatal HSV infection, ventricular septal defect, double aortic arch, intestinal malrotation, and neurofibromatosis). Overall, 7/93 (7.5%) high-risk BRUE patients had significant pathology.&#x0D; Conclusion: High-risk patients were more likely to have an imaging abnormality compared to low-risk patients, which is consistent with current imaging recommendations given only one low-risk imaging abnormality. Interestingly, 7.5% of the high-risk patients had significant pathology diagnosed by imaging.

Effectiveness of Art Therapy and Physical Activity in Improving Quality of Sleep in Children with Hemiplegic Cerebral Palsy: A Quasi-experimental Pilot Study

Introduction: Hemiplegic Cerebral Palsy (CP) is characterised by abnormalities in movement and posture, along with sensory and tone abnormalities. It also represents significant impairments in cognition and sleep quality. Art activity involves playfulness, creativity, improvisation, and brings benefits to cognition and the alleviation of mental suffering. Physical activity shows considerable improvement in sleep quality as it concentrates on cardiorespiratory fitness and increases total energy expenditure. Aim: To evaluate the effect of art therapy and physical activity on sleep quality in children with hemiplegic CP. Materials and Methods: This quasi-experimental pilot study was performed among six ambulant children with hemiplegic CP in December 2022 at MGM School of Physiotherapy, Aurangabad, Maharashtra, India. Both male and female children aged between 4 to 12 years were included in the study. Pretest scores were recorded using the Paediatric Sleep Questionnaire (PSQ). The participants then underwent a physiotherapy protocol lasting one hour, which included art therapy along with upper limb physical activities for four weeks. Art therapy included colouring pictures, drawing geometrical shapes, line-drawing connections, thumbprints, and vegetable prints. The protocol was given for one month, which included three sessions of art therapy and physical activity each week. Parents and children were encouraged to follow the protocol before sleep. At the end of one month, postscoring of all outcome measures was calculated, and statistical analysis was done using the paired t-test. Results: From the results, the median pretest and post-test PSQ scores were 0.68 and 0.49, respectively. Interquartile Range (IQR) value for the outcome measure was 0.0675 and 0.0775, which was significant. Conclusion: Art therapy, along with physical activity, improved sleep quality in children with hemiplegic CP.

Pulmonary hypertension and the potential of 'drug' repurposing: A case for African medicinal plants.

Pulmonary hypertension (PH) is a haemodynamic disorder in which elevated blood pressure in the pulmonary circulation is caused by abnormal vascular tone. Despite advances in treatment, PH mortality remains high, and drug repurposing has been proposed as a mitigating approach. This article reviews the studies that have investigated drug repurposing as a viable option for PH. We provide an overview of PH and highlight pharmaceutical drugs with repurposing potential, based on limited evidence of their mechanisms of action. Moreover, studies have demonstrated the benefits of medicinal plants in PH, most of which are of Indian or Asian origin. Africa is a rich source of many medicinal plants that have been scientifically proven to counteract myriad pathologies. When perusing these studies, one will notice that some African medicinal plants can counteract the molecular pathways (e.g. proliferation, vasoconstriction, inflammation, oxidative stress and mitochondrial dysfunction) that are also involved in the pathogenesis of PH. We review the actions of these plants with actions applicable to PH and highlight that they could be repurposed as adjunct PH therapies. However, these plants have either never been tested in PH, or there is little evidence of their actions against PH. We therefore encourage caution, as more research is needed to study these plants further in experimental models of PH while acknowledging that the outcomes of such proof of-concept studies may not always yield promising findings. Regardless, this article aims to stimulate future research that could make timely contributions to the field. What the study adds. Pulmonary hypertension (PH) remains a fatal disease, and 80% of the patients live in developing countries where resources are scarce and specialised therapies are often unavailable. Drug repurposing is a viable option to try to improve treatment outcomes.Implications of the findings. We propose that another form of 'drug' repurposing is the use of medicinal plants, many of which have demonstrated benefits against pathological processes that are also key in PH, e.g. apoptosis, tumour-like growth of cells, proliferation, oxidative stress and mitochondrial dysfunction.

The Abnormal Tone of CEO Letters in ESG Reports: What Does it Tell us about Future ESG and Financial Performance?

The Abnormal Tone of CEO Letters in ESG Reports: What Does it Tell us about Future ESG and Financial Performance?

Abnormal Disclosure Tone in MD&A and Analysts’ Earnings Forecast: Evidence from China

ABSTRACT This study examines the association between abnormal disclosure tone in the Management Discussion and Analysis (MD&A) section of annual reports and analysts’ forecasting behavior. Using analysts’ forecast data of Chinese listed firms from 2008 to 2020, we find that analysts can discern abnormal tone in managers’ disclosures, leading to a downward revision of earnings estimates and an enhancement of forecast accuracy. Moreover, we observe that abnormal tone in the MD&A section attracts analysts’ attention as they navigate the challenges posed by tone management and diminished information transparency. Collectively, this paper enhances our understanding of analysts’ forecasting behavior concerning the extent of tone management observed in MD&A disclosures within emerging markets.

Do abnormal accruals influence abnormal tone in the CEO statements of the top 40 JSE-listed companies?

The aim of this study is to examine the effect of abnormal accruals on abnormal tone in the Chief Executive Officer (CEO) statements of South Africa’s (SA) top 40 Johannesburg Stock Exchange (JSE) listed businesses in the 2021 financial year. This study employs the quantile regression analysis and the generalised linear regression model. For this evaluation, the Top 40 JSE-listed firms' integrated annual reports (IARs), which include the annual financial statements and CEO statements, were extracted from the companies' official web pages. Findings revealed that abnormal accruals have a negative relationship with the abnormal tone used in the CEO statements of the top 40 JSE-listed companies. i.e., anomalous accruals and irregular tone move in different directions, as abnormal accruals increase, the abnormal tone in CEO statements decreases. This suggests that abnormal accruals and abnormal tone do not co-occur and that companies with abnormal accruals do not conceal them using abnormal tone in their CEO statements. We recommend that the amount of flexibility and judgment given to preparers of annual financial statements be reduced to lessen the use of earnings management practices. The research adds to the sparse literature on tone management and earnings management in developing nations, particularly SA.

Acute necrotising encephalopathy of childhood – A narrative review

Acute encephalitis syndrome (AES) can pose challenges in diagnosis and management. Infection-associated acute encephalopathies (AEs) are increasingly being recognised and closely mimic AES. We provide an overview of various causes of AE and a detailed review of the clinical laboratory, including neuroradiologic features of acute necrotising encephalopathy (ANE) of childhood, its treatment, and outcome. A literature search was performed using the keywords’ Paediatric acute encephalopathy’ and ‘acute necrotising encephalopathy of childhood’ in PubMed and Google Scholar, and all relevant articles from 2001 to 2021 (including case reports) in the English language were reviewed. Relevant and major articles before 2001 were also reviewed. Infection-associated AEs remain under-recognised and pose a challenge in neurocritical care. Judicious use of neuroimaging and laboratory tests aids diagnosis of specific clinicoradiological AE syndromes. We need to suspect ANE if fever (esp. viral illness) is followed by the rapid deterioration in the sensorium associated with tone abnormalities or seizures. Neuroimaging typically shows symmetric lesions in the thalami, internal capsule or cerebellar white matter and tegmentum. While definite treatment guidelines are not available, several interventions have shown potential benefits in supporting patients with ANE. These include standard supportive care, immunotherapy, especially high-dose pulse methylprednisolone, therapeutic hypothermia initiated before 12 h to reduce cytokines, and anti-oedema measures. However, it is essential to note that outcomes in ANE can be highly variable, with a mortality rate of approximately 30% and only 10% experiencing intact survival. Predictors of poor outcome include age younger than one year, increased cerebrospinal fluid protein/transaminases, the presence of haemorrhage/cavitation/brainstem lesions on neuroimaging, and a high ANE severity score.

Obstructive sleep apneas and cardiovascular diseases

Obstructive sleep apneas (OSA) are a breathing disorder characterized by recurrent apneas and hypopneas associated with complete or partial obstruction of the upper airways during sleep, resulting in disturbed sleep architecture, repeated hypoxemia and awakenings, and daytime sleepiness. OSA syndrome affects up to 34% of men and 17% of women in Western countries. Abnormalities in upper airway anatomy (frequently due to obesity), muscle tone, or neural control of breathing are the main causes. OSA is associated with impaired cognitive function and favors the onset of hypertension, being a major determinant of resistant hypertension, and may favor cardiovascular diseases (e.g., coronary artery disease and heart failure), thereby increasing mortality. Polysomnography and (cardio)-respiratory portable systems are used to diagnose and determine the severity of OSA. Management of OSA includes lifestyle modifications, such as weight loss and avoidance of supine sleep position, and continuous positive airway pressure. Mandibular advancement devices and upper airway surgery may also be appropriate for some patients. Hypoglossal nerve stimulation and pharmacological interventions are currently investigated to improve symptoms and outcomes.

Tone complexity and analyst forecast behaviors: evidence from earnings conference calls

PurposeBoth the SEC (Securities and Exchange Commission) and the popular press have routinely criticized firms for the complexity of their financial disclosures. This study aims to investigate how financial analysts respond to the tone complexity of firm disclosures.Design/methodology/approachUsing approximately 20,000 earnings conference call transcripts of S&P 1,500 firms between 2005 and 2015, the authors first calculate the abnormal negative tone, the measure of tone complexity; then use such tone measure in econometric models to examine analyst forecast behavior. The authors also test the robustness of the results under different model specifications, tone word lists and alternative tone measure calculations.FindingsConsistent with the notion that analysts respond to the information demand from investors and incur more costs and effort to analyze firm disclosure when the tone is more complex, the authors find that higher tone complexity is positively and significantly associated with more analyst following, longer report duration, more forecast revisions, larger forecast error and larger forecast dispersion. In addition, the authors find that tone complexity has a long-term impact on analyst following but has a limited long-term impact on analyst report duration, analyst revision, forecast error and dispersion.Originality/valueThis study complements existing literature by highlighting the information role of financial analysts and by providing evidence that analysts incorporate the management tone disclosed during conference calls to adjust their forecasting behaviors. The results can be used by policymakers as evidence and support for further improving firm communication from a new dimension of disclosure tone.

Autonomic neuro-cardiac profile of electrical, structural and neuronal remodeling in myocardial infarction-induced heart failure.

Heart failure is a clinical syndrome typified by abnormal autonomic tone, impaired ventricular function, and increased arrhythmic vulnerability. This study aims to examine electrophysiological, structural and neuronal remodeling following myocardial infarction in a rabbit heart failure model to establish its neuro-cardiac profile. Weight-matched adult male New Zealand White rabbits (3.2±0.1kg, n=25) were randomized to have coronary ligation surgeries (HF group, n=13) or sham procedures (SHM group, n=12). Transthoracic echocardiography was performed six weeks post-operatively. On week 8, dual-innervated Langendorff-perfused heart preparations were set up for terminal experiments. Seventeen hearts (HF group, n=10) underwent ex-vivo cardiac MRI. Twenty-two hearts (HF group, n=7) were examined histologically. Electrical remodeling and abnormal autonomic profile were evident in HF rabbits with exaggerated sympathetic and attenuated vagal effect on ventricular fibrillation threshold, ventricular refractoriness and restitution curves, in addition to increased spatial restitution dispersion. Histologically, there was significant neuronal enlargement at the heart hila and conus arteriosus in HF. Structural remodeling was characterized by quantifiable myocardial scarring, enlarged left ventricles, altered ventricular geometry and impaired contractility. In an infarct-induced rabbit heart failure model, extensive structural, neuronal and electrophysiological remodeling in conjunction with abnormal autonomic profile provide substrates for ventricular arrhythmias.

Early-infantile developmental and epileptic encephalopathy: the aetiologies, phenotypic differences and outcomes—a prospective observational study

Abstract In this study, we have evaluated the underlying aetiologies, yield of genetic testing and long-term outcomes in patients with early-infantile developmental and epileptic encephalopathies. We have prospectively studied patients with seizure onset before 3 months of age. Based on the clinical details, neuroimaging, metabolic testing and comprehensive genetic evaluation, patients were classified into different aetiological groups. The phenotypic differences between genetic/unknown groups and remaining aetiologies were compared. Factors that could affect seizure control were also assessed. A total of 80 children (M:F ratio—1.5:1) were recruited. The median seizure onset age was 28 days (range, 1–90 days). The aetiologies were confirmed in 66 patients (83%). The patients were further classified into four aetiological groups: genetic (50%), structural (19%), metabolic (14%; all were vitamin responsive) and unknown (17%). On comparing for the phenotypic differences between the groups, children in the ‘genetic/unknown’ groups were more frequently observed to have severe developmental delay (Odds Ratio = 57; P &amp;lt; 0.0001), autistic behaviours (Odds Ratio = 37; P &amp;lt; 0.0001), tone abnormalities (Odds Ratio = 9; P = 0.0006) and movement disorder (Odds Ratio = 19; P &amp;lt; 0.0001). Clonic seizures were more common in the vitamin responsive/structural groups (Risk Ratio = 1.36; P = 0.05) as compared to patients with ‘genetic/unknown’ aetiologies. On the contrary, vitamin responsive/structural aetiology patients were less likely to have tonic seizures (Risk Ratio = 0.66; P = 0.04). Metabolic testing was diagnostic in three out of 41 patients tested (all three had biotinidase deficiency). MRI was abnormal in 35/80 patients (malformation observed in 16/35; 19/35 had non-specific changes that did not contribute to underlying aetiology). A molecular diagnosis was achieved in 53 out of 77 patients tested (69%). Next-generation sequencing had a yield of 51%, while microarray had a yield of 14%. STXBP1 was the most common (five patients) single-gene defect identified. There were 24 novel variants. The mean follow-up period was 30 months (range, 4–72 months). On multivariate logistic regression for the important factors that could affect seizure control (seizure onset age, time lag of first visit to paediatric neurologist and aetiologies), only vitamin responsive aetiology had a statistically significant positive effect on seizure control (P = 0.02). Genetic aetiologies are the most common cause of early-infantile developmental and epileptic encephalopathies. Patients in the genetic/unknown groups had a more severe phenotype. Patients with vitamin responsive epilepsies had the best probability of seizure control.

Prenatal Intravenous Magnesium at 30-34 Weeks’ Gestation and Neurodevelopmental Outcomes in Offspring

Intravenous magnesium sulfate administered to pregnant individuals before birth at less than 30 weeks' gestation reduces the risk of death and cerebral palsy in their children. The effects at later gestational ages are unclear. To determine whether administration of magnesium sulfate at 30 to 34 weeks' gestation reduces death or cerebral palsy at 2 years. This randomized clinical trial enrolled pregnant individuals expected to deliver at 30 to 34 weeks' gestation and was conducted at 24 Australian and New Zealand hospitals between January 2012 and April 2018. Intravenous magnesium sulfate (4 g) was compared with placebo. The primary outcome was death (stillbirth, death of a live-born infant before hospital discharge, or death after hospital discharge before 2 years' corrected age) or cerebral palsy (loss of motor function and abnormalities of muscle tone and power assessed by a pediatrician) at 2 years' corrected age. There were 36 secondary outcomes that assessed the health of the pregnant individual, infant, and child. Of the 1433 pregnant individuals enrolled (mean age, 30.6 [SD, 6.6] years; 46 [3.2%] self-identified as Aboriginal or Torres Strait Islander, 237 [16.5%] as Asian, 82 [5.7%] as Māori, 61 [4.3%] as Pacific, and 966 [67.4%] as White) and their 1679 infants, 1365 (81%) offspring (691 in the magnesium group and 674 in the placebo group) were included in the primary outcome analysis. Death or cerebral palsy at 2 years' corrected age was not significantly different between the magnesium and placebo groups (3.3% [23 of 691 children] vs 2.7% [18 of 674 children], respectively; risk difference, 0.61% [95% CI, -1.27% to 2.50%]; adjusted relative risk [RR], 1.19 [95% CI, 0.65 to 2.18]). Components of the primary outcome did not differ between groups. Neonates in the magnesium group were less likely to have respiratory distress syndrome vs the placebo group (34% [294 of 858] vs 41% [334 of 821], respectively; adjusted RR, 0.85 [95% CI, 0.76 to 0.95]) and chronic lung disease (5.6% [48 of 858] vs 8.2% [67 of 821]; adjusted RR, 0.69 [95% CI, 0.48 to 0.99]) during the birth hospitalization. No serious adverse events occurred; however, adverse events were more likely in pregnant individuals who received magnesium vs placebo (77% [531 of 690] vs 20% [136 of 667], respectively; adjusted RR, 3.76 [95% CI, 3.22 to 4.39]). Fewer pregnant individuals in the magnesium group had a cesarean delivery vs the placebo group (56% [406 of 729] vs 61% [427 of 704], respectively; adjusted RR, 0.91 [95% CI, 0.84 to 0.99]), although more in the magnesium group had a major postpartum hemorrhage (3.4% [25 of 729] vs 1.7% [12 of 704] in the placebo group; adjusted RR, 1.98 [95% CI, 1.01 to 3.91]). Administration of intravenous magnesium sulfate prior to preterm birth at 30 to 34 weeks' gestation did not improve child survival free of cerebral palsy at 2 years, although the study had limited power to detect small between-group differences. anzctr.org.au Identifier: ACTRN12611000491965.

Hemizygous variants in protein phosphatase 1 regulatory subunit 3F (PPP1R3F) are associated with a neurodevelopmental disorder characterized by developmental delay, intellectual disability and autistic features.

Protein phosphatase 1 regulatory subunit 3F (PPP1R3F) is a member of the glycogen targeting subunits (GTSs), which belong to the large group of regulatory subunits of protein phosphatase 1 (PP1), a major eukaryotic serine/threonine protein phosphatase that regulates diverse cellular processes. Here, we describe the identification of hemizygous variants in PPP1R3F associated with a novel X-linked recessive neurodevelopmental disorder in 13 unrelated individuals. This disorder is characterized by developmental delay, mild intellectual disability, neurobehavioral issues such as autism spectrum disorder, seizures and other neurological findings including tone, gait and cerebellar abnormalities. PPP1R3F variants segregated with disease in affected hemizygous males that inherited the variants from their heterozygous carrier mothers. We show that PPP1R3F is predominantly expressed in brain astrocytes and localizes to the endoplasmic reticulum in cells. Glycogen content in PPP1R3F knockout astrocytoma cells appears to be more sensitive to fluxes in extracellular glucose levels than in wild-type cells, suggesting that PPP1R3F functions in maintaining steady brain glycogen levels under changing glucose conditions. We performed functional studies on nine of the identified variants and observed defects in PP1 binding, protein stability, subcellular localization and regulation of glycogen metabolism in most of them. Collectively, the genetic and molecular data indicate that deleterious variants in PPP1R3F are associated with a new X-linked disorder of glycogen metabolism, highlighting the critical role of GTSs in neurological development. This research expands our understanding of neurodevelopmental disorders and the role of PP1 in brain development and proper function.

Sensory integration versus Masgutova neuro-sensorimotor reflex integration program on controlling primitive reflexes and gross motor abilities in children with diplegic cerebral palsy.

An abnormality in muscular tone, lack of postural control, and a lack of coordination are all linked to the retention of primitive and immature postural reflexes. The Purpose of this study aimed of detecting which therapeutic approach is more effective in integrating retained primitive reflexes, either Masgutova neuro-sensorimotor reflex integration or Sensory integration (SI) program. Forty children with spastic diplegic cerebral palsy (CP) (11 girls and 29 boys), involved in the current study and their ages ranged from 3 to 6years old. They were divided at random into two groups (A and B), patients in the study group (A) (n=20) were treated by Masgutova neuro-sensorimotor reflex integration program (MNRI) while those of study group (B) (n=20), were subjected to Sensory integration program (SIP), A standardized physical treatment regimen was provided to both groups (Stretching exercise, Strengthening exercise, and facilitation of developing motor milestones) All children were evaluated by using GMFM-88 and (PDMS-2) reflexes subtest before and after treatment that lasted for three successive months at a frequency of three sessions per week. There was a statistically substantial increase in GMFM scores and control of primitive reflexes post treatment in each group compared to those of the pretreatment mean values (p>0.05). There was also a statistically non-significance difference between group A and group B regarding post treatment results (p>0.05). SI and MNRI programs can equally be used in the treatment of children with spastic CP who suffer from retained primitive reflexes and delayed gross motor function.

Characteristics, Genetic Testing, and Diagnoses of Infants with Neonatal Encephalopathy Not Due to Hypoxic Ischemic Encephalopathy: A Cohort Study

To characterize the presentation and evaluation of infants with neonatal encephalopathy (NE) not due to hypoxic-ischemic encephalopathy (non-HIE NE) and to describe the genetic abnormalities identified. Retrospective cohort study of 193 non-HIE NE neonates admitted to a level IV NICU from 2015 through 2019. For changes in testing over time, Cochrane-Armitage test for trend was used with a Bonferroni-corrected P-value, and comparison between groups was performed using Fisher exact test. The most common symptom of non-HIE NE was abnormal tone in 47% (90/193). Ten percent (19/193) died prior to discharge, and 48% of survivors (83/174) required medical equipment at discharge. Forty percent (77/193) underwent genetic testing as an inpatient. Of 52 chromosomal studies, 54 targeted tests, and 16 exome sequences, 10%, 41%, and 69% were diagnostic, respectively, with no difference in diagnostic rates between infants with and without an associated congenital anomaly and/or dysmorphic feature. Twenty-eight genetic diagnoses were identified. Neonates with non-HIE NE have high rates of morbidity and mortality and may benefit from early genetic testing, even in the absence of other exam findings. This study broadens our knowledge of genetic conditions underlying non-HIE NE, which may enable families and care teams to anticipate the needs of the individual, allow early initiation of targeted therapies, and facilitate decisions surrounding goals of care.