Search

There is conflicting literature evidence regarding the independent effects of insulin resistance and concomitant hyperinsulinemia on bone mineral density. In addition, it is still under debate whether the net effect is favorable or unfavorable for the fracture risk. Therefore, we conducted a cross-sectional study.

Aim: To evaluate the efficacy and safety of onabotulinumtoxinA for treating upper and lower limb spasticity among pediatric patients in 2 open-label extension trials., Methods: Patients aged <18 years received ≤5 doses of onabotulinumtoxinA (maximum: 8 U/kg [300 U], cycle 1; 10 U/kg [340 U], cycles 2-5) over 60 weeks. Week 6 efficacy endpoints included mean change from baseline in Modified Ashworth Scale-Bohannon and Modified Tardieu Scale scores, and mean Clinical Global Impression of Overall Change score. Adverse events and laboratory assessments of bone health were monitored., Results: A total of 580 patients received onabotulinumtoxinA. Modified Ashworth Scale-Bohannon change from baseline ranged from -1.01 to -1.9. Modified Tardieu Scale change from baseline was 13.6 to 18.1 (ankle), 25.8 to 44.1 (elbow), and -5.0 to -26.3 (wrist). Clinical Global Impression of Overall Change scores were 1.5 to 2.2. The most common treatment-emergent adverse events were upper respiratory tract infection (16.9%) and nasopharyngitis (15.7%)., Interpretation: Repeat administration of onabotulinumtoxinA was safe and efficacious for treating upper and lower limb spasticity in children., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Mark Gormley is an advisory board member and serves on the speaker's bureau for Allergan, an AbbVie Company. Heakyung Kim has received an honorarium from AAPM&R and is an advisory board member and consultant for Allergan, an AbbVie company, Ipsen, Merz, and Pacira Biosciences, Inc. Marcin Bonikowski serves as advisory board member, consultant, and speaker for Allergan, an AbbVie company, Ipsen, and Merz. Marta Banach serves as a speaker for Allergan, an AbbVie company, Ipsen, Kedrion, Merz, and Shire and is an advisory board member and consultant for Merz. Fatma Gul receives research support from AbbVie, Ipsen, Merz, and Supernus, and is a consultant to Medisys Consultants. Jill Meilahn receives research support and dedicated research time funding through Marshfield Clinic Research Institute. Darcy Fehlings and Brad Racette have no interests that might be perceived as posing a conflict or bias. Nuoyu Huang, Xiaomeng Niu, Lynn M. James, and Rozalina Dimitrova are employees of AbbVie and may hold AbbVie stock.

Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case-control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen's d=-0.232; P=3.50 × 10-7) and thalamus (d=-0.148; P=4.27 × 10-3) and enlarged lateral ventricles (d=-0.260; P=3.93 × 10-5) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons.

The profile of brain structural abnormalities in schizophrenia is still not fully understood, despite decades of research using brain scans. To validate a prospective meta-analysis approach to analyzing multicenter neuroimaging data, we analyzed brain MRI scans from 2028 schizophrenia patients and 2540 healthy controls, assessed with standardized methods at 15 centers worldwide. We identified subcortical brain volumes that differentiated patients from controls, and ranked them according to their effect sizes. Compared with healthy controls, patients with schizophrenia had smaller hippocampus (Cohen's d=-0.46), amygdala (d=-0.31), thalamus (d=-0.31), accumbens (d=-0.25) and intracranial volumes (d=-0.12), as well as larger pallidum (d=0.21) and lateral ventricle volumes (d=0.37). Putamen and pallidum volume augmentations were positively associated with duration of illness and hippocampal deficits scaled with the proportion of unmedicated patients. Worldwide cooperative analyses of brain imaging data support a profile of subcortical abnormalities in schizophrenia, which is consistent with that based on traditional meta-analytic approaches. This first ENIGMA Schizophrenia Working Group study validates that collaborative data analyses can readily be used across brain phenotypes and disorders and encourages analysis and data sharing efforts to further our understanding of severe mental illness.

Previous studies indicate that school climate is important for student health and academic achievement. This study concerns the validity and reliability of the student edition a Swedish instrument for measuring pedagogical and social school climate (PESOC). Data were collected from 5,745 students at 97 Swedish secondary schools. Multilevel confirmatory factor analyses were conducted, and multilevel composite reliability estimates, as well as correlations with school-level achievement indicators, were calculated. The results supported an 8-factor structure at the student level and 1 general factor at the school level. Factor loadings and composite reliability estimates were acceptable at both levels. The school-level factor was moderately and positively correlated with school-level academic achievement. The student PESOC is a promising instrument for studying school climate.

Aging can cause the decline of balance ability, which can lead to increased falls and decreased mobility. This work aimed to discern differences in balance control between healthy older and younger adults. Foot force data of 38 older and 65 younger participants (older and younger than 60 yr, respectively) were analyzed. To first determine whether the two groups exhibited any differences, this study incorporated the orientation of the foot-ground interaction force in addition to its point of application. Specifically, the frequency dependence of the "intersection point" of the lines of actions of the foot-ground interaction forces was evaluated. Results demonstrated that, like the mean center-of-pressure speed, a traditionally employed measure, the intersection-point analysis could distinguish between the two participant groups. Then, to further explore age-specific control strategies, simulations of standing balance were conducted. An optimal controller stabilized a double-inverted-pendulum model with torque-actuated ankle and hip joints corrupted with white noise. The experimental data were compared with the simulation results to identify the controller parameters that best described the human data. Older participants showed significantly more use of the ankle than hip compared with younger participants. Best-fit controller gains suggested increased preference for asymmetric inter-joint neural feedback, possibly to compensate for the effects of aging such as sarcopenia. These results underscore the advantages of the intersection-point analysis to quantify possible shifts in inter-joint control with age, thus highlighting its potential to be used as a balance assessment tool in research and clinical settings. NEW & NOTEWORTHY Age groups were distinguished by analyzing foot-ground force data during quiet standing in older and younger adults to calculate the foot-force vector intersection point that emerges across frequency bands. Modeling balance and comparing the simulations' outcomes to experimental results suggested that older adults increased reliance on neural feedback, possibly compensating for muscle strength deficiency. This novel analysis also quantified the apparent balance controller for each participant, highlighting its potential as a balance assessment tool.

A recent line of work suggests that the net behavior of the foot-ground interaction force provides insight into quiet-standing-balance dynamics and control. Through human-subject experiments, Boehm et al. found that the relative variations of the center of pressure and force orientation emerge as a distinct pattern in the frequency domain, termed the "intersection-point (IP) height." Subsequent empirical and simulation-based studies showed that different control strategies are reflected in the distribution of intersection-point height across frequency. To facilitate understanding of the strengths and limitations of the intersection-point height in describing the dynamics and control of standing, the present work establishes a spectral-based method that also enables derivation of a closed-form estimate of the intersection-point height from any linear model of quiet stance. This new method explained observations from prior work, including how the measure captures aspects of control and physiological noise. The analysis presented herein highlights the utility of the frequency-dependent foot-force dynamics in probing the balance controller and provides a tool for model development and validation to further our understanding of the neuromotor control of natural upright posture in humans. NEW & NOTEWORTHY The present work details a closed-form analytical result that reveals a direct link between frequency-domain patterns in the foot-force line-of-action and the closed-loop frequency response function of human upright stance. The analytical method developed herein dramatically simplifies the identification of the intersection-point-height measure of standing balance, and further demonstrates that the net behavior of the foot-ground interaction force quantifies essential characteristics of the underlying neuromotor control of human quiet standing.

Congenital heart disease is associated with impaired early brain development and adverse neurodevelopmental outcomes. This study investigated how individualized measures of preoperative cortical gyrification index differ in 142 infants with congenital heart disease, using a normative modelling approach with reference data from 320 typically developing infants. Gyrification index Z -scores for the whole brain and six major cortical areas were generated using two different normative models: one accounting for post-menstrual age at scan, post-natal age at scan and sex, and another additionally accounting for supratentorial brain volume. These Z -scores were compared between congenital heart disease and control groups to test the hypothesis that cortical folding in infants with congenital heart disease deviates from the normal developmental trajectory. The relationships between whole-brain gyrification index Z -scores from the two normative models and both cerebral oxygen delivery and neurodevelopmental outcomes were also investigated. Global and regional brain gyrification was significantly reduced in neonates with congenital heart disease, but not when supratentorial brain volume was accounted for. This finding suggests that whilst cortical folding is reduced in congenital heart disease, it is primarily driven by a reduction in brain size. There was a significant positive correlation between cerebral oxygen delivery and whole-brain gyrification index Z -scores in congenital heart disease, but not when supratentorial brain volume was accounted for. Cerebral oxygen delivery is therefore likely to play a more important role in the biological processes underlying volumetric brain growth than cortical folding. No significant associations between whole-brain gyrification index Z -scores and motor/cognitive outcomes or autism traits were identified in the 70 infants with congenital heart disease who underwent neurodevelopmental assessment at 22-months. Our results suggest that chronic in utero and early post-natal hypoxia in congenital heart disease is associated with reductions in cortical folding that are proportional to reductions in supratentorial brain volume., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

The temperament of a total of 30 small puppies of 4 breeds in the period of their primary socialization was typified. The number of sanguines, cholerics, phlegmatics and melancholics was determined separately according to the breed of the animals along with the possibility of building a successful behavioral model for representatives of different breeds according to their temperament. The fastest socialization was reported in Shih Tzu puppies, followed by Bichon Frise, Pekingese, Dachshund, and lastly Poodle. There was a relationship between temperament and breed in dogs. [ABSTRACT FROM AUTHOR]

The increased life expectancy of PLHIV (People Living with HIV) and the successful highly combined antiretroviral therapy (cART) poses new clinical challenges regarding aging and its co-morbid condition. It is commonly believed that HIV infection "accelerates" aging. Human immunodeficiency virus type 1 (HIV-1) infection is characterized by inflammation and immune activation that persists despite cART, and that may contribute to the development of co-morbid conditions. In this regard, we aimed to compare current cART regimens in light of premature aging to evaluate differences in their ability to reduce immune activation and inflammation in virologically suppressed patients. We studied a panel of biomarkers (IFN-γ, IL-1β, IL-12p70, IL-2, IL-4, IL-5, IL-6, IL-13, IL-18, GM-CSF, TNF-α, C-reactive protein, D-dimer, soluble CD14), which could provide a non-invasive and affordable approach to monitor HIV-related chronic inflammation. The results of the current study do not provide hard evidence favoring a particular cART regimen, although they show a less favorable regimen profile containing a protease inhibitor. Our data suggest an incomplete reduction of inflammation and immune activation in terms of the effective cART. It is likely that the interest in various biomarkers related to immune activation and inflammation as predictors of clinical outcomes among PLHIV will increase in the future.

Alpha oscillations play a vital role in managing the brain's resources, inhibiting neural activity as a function of their phase and amplitude, and are changed in many brain disorders. Developing minimally invasive tools to modulate alpha activity and identifying the parameters that determine its response to exogenous modulators is essential for the implementation of focussed interventions. We introduce Alpha Closed-Loop Auditory Stimulation (αCLAS) as an EEG-based method to modulate and investigate these brain rhythms in humans with specificity and selectivity, using targeted auditory stimulation. Across a series of independent experiments, we demonstrate that αCLAS alters alpha power, frequency, and connectivity in a phase, amplitude, and topography-dependent manner. Using single-pulse-αCLAS, we show that the effects of auditory stimuli on alpha oscillations can be explained within the theoretical framework of oscillator theory and a phase-reset mechanism. Finally, we demonstrate the functional relevance of our approach by showing that αCLAS can interfere with sleep onset dynamics in a phase-dependent manner., Competing Interests: N.G. is part in a patent application on the ecHT technology, assigned to MIT, and is a founder in a company that utilises it., (Copyright: © 2024 Hebron et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The motor neuroscience literature suggests that the central nervous system may encode some motor commands in terms of velocity. In this work, we tackle the question: what consequences would velocity commands produce at the behavioral level? Considering the ubiquitous presence of noise in the neuromusculoskeletal system, we predict that velocity commands affected by stationary noise would produce "random walks", also known as Brownian processes, in position. Brownian motions are distinctively characterized by a linearly growing variance and a power spectral density that declines in inverse proportion to frequency. This work first shows that these Brownian processes are indeed observed in unbounded motion tasks e.g., rotating a crank. We further predict that such growing variance would still be present, but bounded, in tasks requiring a constant posture e.g., maintaining a static hand position or quietly standing. This hypothesis was also confirmed by experimental observations. A series of descriptive models are investigated to justify the observed behavior. Interestingly, one of the models capable of accounting for all the experimental results must feature forward-path velocity commands corrupted by stationary noise. The results of this work provide behavioral support for the hypothesis that humans plan the motion components of their actions in terms of velocity., (© 2024. The Author(s).)

The composition of grape seeds from two white dessert (‘Bolgar’ and ‘Super ran Bolgar’) and two red wine Bulgarian varieties (‘Mavroud’ and ‘Shiroka melnishka loza’) was investigated. The content of proteins was established by Kjeldhal method and was found to be 6.3 – 8.9%. The content of carbohydrates - calculated as the difference of mean values: 100 - (amount in percentage of oil, moisture, protein and ash) - was 65.5 – 70.9%. The content of oil – by extraction with n-hexane - was 11.6 - 16.5%. The content of phospholipids was determined spectrophotometrically after isolation by chromatographic methods and was found to be 0.6 - 0.9%, including phosphatidylcholine, phosphatidylinositol and phosphatidic acids. The sterol content determined by gas chromatography was 0.3 – 0.4% while β-sitosterol (70.0 – 72.1%) and campesterol (18.5 – 19.9%) were the major components. In the phospholipids and sterol esters, saturated and monounsaturated fatty acids presented higher amount than the triacylglycerols. Fatty acids of sterol esters and phospholipids were determined by gas chromatography after isolation. The quantity of palmitic acid in the phospholipid fraction was 43.4 – 59.4%, the content of oleic acid was 9.0 – 14.0% and the content of linoleic acid was 10.0 – 24.5% while in the sterol esters, the predominant ones were mainly linoleic (40.7 – 53.8%), oleic (24.9 – 35.5%) and palmitic acids (13.0 – 16.7%). Linoleic (68.5 – 72.3%) and oleic acids (16.3 – 18.7%) were found to be the main components of the triacylglycerols. The tocopherol content varied from 67.7 mg kg-1 to 290.5 mg kg-1 where α-tocopherol (74.8 – 84.4%) was the predominant component.

A methodology has been developed for obtaining of porous castings from Al and aluminium A356 alloy. The methodology includes introduction of Ca into the melt for viscosity increasing and homogenization by mechanical stirring. This is followed by addition of TiH2, homogenization, subsequent formation of the porous structure and crystallization. A tomographic analysis of the porous samples was carried out and the main characteristics of their structure were determined. Tests were carried out on specimens of the castings involving abrasive wearing under dry friction conditions on a surface with hard-attached abrasive particles. [ABSTRACT FROM AUTHOR]

Brain dynamic functional connectivity characterises transient connections between brain regions. Features of brain dynamics have been linked to emotion and cognition in adult individuals, and atypical patterns have been associated with neurodevelopmental conditions such as autism. Although reliable functional brain networks have been consistently identified in neonates, little is known about the early development of dynamic functional connectivity. In this study we characterise dynamic functional connectivity with functional magnetic resonance imaging (fMRI) in the first few weeks of postnatal life in term-born (n = 324) and preterm-born (n = 66) individuals. We show that a dynamic landscape of brain connectivity is already established by the time of birth in the human brain, characterised by six transient states of neonatal functional connectivity with changing dynamics through the neonatal period. The pattern of dynamic connectivity is atypical in preterm-born infants, and associated with atypical social, sensory, and repetitive behaviours measured by the Quantitative Checklist for Autism in Toddlers (Q-CHAT) scores at 18 months of age., (© 2024. The Author(s).)

Coronavirus Anxiety Scale (CAS) is a widely used measure that captures somatic symptoms of coronavirus-related anxiety. In a large-scale collaboration spanning 60 countries ( N total = 21,513), we examined the CAS's measurement invariance and assessed the convergent validity of CAS scores in relation to the fear of COVID-19 (FCV-19S) and the satisfaction with life (SWLS-3) scales. We utilized both conventional exact invariance tests and alignment procedures, with results revealing that the single-factor model fit the data well in almost all countries. Partial scalar invariance was supported in a subset of 56 countries. To ensure the robustness of results, given the unbalanced samples, we employed resampling techniques both with and without replacement and found the results were more stable in larger samples. The alignment procedure demonstrated a high degree of measurement invariance with 9% of the parameters exhibiting noninvariance. We also conducted simulations of alignment using the parameters estimated in the current model. Findings demonstrated reliability of the means but indicated challenges in estimating the latent variances. Strong positive correlations between CAS and FCV-19S estimated with all three different approaches were found in most countries. Correlations of CAS and SWLS-3 were weak and negative but significantly differed from zero in several countries. Overall, the study provided support for the measurement invariance of the CAS and offered evidence of its convergent validity while also highlighting issues with variance estimation. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

With the COVID-19 pandemic, behavioural scientists aimed to illuminate reasons why people comply with (or not) large-scale cooperative activities. Here we investigated the motives that underlie support for COVID-19 preventive behaviours in a sample of 12,758 individuals from 34 countries. We hypothesized that the associations of empathic prosocial concern and fear of disease with support towards preventive COVID-19 behaviours would be moderated by trust in the government. Results suggest that the association between fear of disease and support for COVID-19 preventive behaviours was strongest when trust in the government was weak (both at individual- and country-level). Conversely, the association with empathic prosocial concern was strongest when trust in the government was high, but this moderation was only found at individual-level scores of governmental trust. We discuss how motivations may be shaped by socio-cultural context, and outline how findings may contribute to a better understanding of collective action during global crises., (© 2023. The Author(s).)

Primary thyroid lymphoma (PTL) is a rare disease characterized by the appearance of a rapidly growing solid mass in the cervical region. A major risk factor is chronic autoimmune thyroiditis with lymphocytes infiltrating the thyroid gland. The lymphoproliferative disease is seen more frequently in the females. PTL usually develops in the sixth and seventh decades of life. We present a case of a 66-year-old woman with diffuse primary B-cell thyroid lymphoma with no prior evidence of underlying autoimmune thyroid pathology. The initial localization of the lymphoproliferative disease was in the thyroid gland, but the involvement of regional cervical lymph nodes was also found at the time of diagnosis. After histological verification with immunohistochemistry and staging by imaging, chemotherapy was initiated according to the R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, Oncovin ® (vincristine), prednisone) protocol. An excellent therapeutic response was achieved with lymphoma remission after six cycles under the mentioned protocol. Thyroid autoantibodies became positive 18 months after rituximab treatment, possibly reflecting the transient suppressive effects of the immunotherapy. The patient was subsequently kept followed up by a multidisciplinary team in the light of possible lymphoma recurrence and/or development of thyroid dysfunction. This case report demonstrates possible challenges for the diagnosis, treatment, and follow-up of this rare thyroid lesion. At the time of diagnosis, the clinical presentation of the disease, the ultrasound image, and the cytological result may be similar to other low-grade thyroid carcinomas or secondary metastatic involvement of the gland. The initial lack of underlying thyroid autoimmunity makes this distinction even more challenging. Furthermore, despite the rapid resolution, regular long-term monitoring for recurrence is required., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Hristozov et al.)

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has brought about significant challenges worldwide. In this study, we present a comprehensive analysis of the genomic epidemiology and lineage dynamics of SARS-CoV-2 in Bulgaria over a three-year period. Through extensive genomic sequencing and data analysis, we investigated the evolution of the virus, the emergence of variants of concern (VOCs), and their impact on the country's pandemic trajectory. We also assessed the relationship between viral diversity and COVID-19 morbidity and mortality in Bulgaria. Our findings shed light on the temporal and spatial distribution of SARS-CoV-2 lineages and provide crucial insights into the dynamics of the pandemic in the country. The interplay between international travel and viral transmission plays a significant role in the emergence and dissemination of different SARS-CoV-2 variants. The observed proportions of exportation to various continents provide insights into the potential pathways through which these lineages spread globally. Understanding the genomic epidemiology of SARS-CoV-2 in Bulgaria is essential for formulating targeted public health strategies, enhancing vaccination efforts, and effectively managing future outbreaks.

Open-cell AMMCs are high-strength and lightweight materials with applications in different types of industries. However, one of the main goals in using these materials is to enhance their tribological behavior, which improves their durability and performance under frictional conditions. This study presents an approach for fabricating and predicting the wear behavior of open-cell AlSn6Cu-SiC composites, which are a type of porous AMMCs with improved tribological properties. The composites were fabricated using liquid-state processing, and their tribological properties are investigated by the pin-on-disk method under different loads (50 N and 100 N) and with dry-sliding friction. The microstructure and phase composition of the composites were investigated by scanning electron microscopy, energy-dispersive X-ray spectroscopy, and X-ray diffraction. The mass wear and coefficient of friction (COF) of the materials were measured as quantitative indicators of their tribological behavior. The results showed that the open-cell AlSn6Cu-SiC composite had an enhanced tribological behavior compared to the open-cell AlSn6Cu material in terms of mass wear (38% decrease at 50 N and 31% decrease at 100 N) while maintaining the COF at the same level. The COF of the composites was predicted by six different machine learning methods based on the experimental data. The performance of these models was evaluated by various metrics (R2, MSE, RMSE, and MAE) on the validation and test sets. Based on the results, the open-cell AlSn6Cu-SiC composite outperformed the open-cell AlSn6Cu material in terms of mass loss under different loads with similar COF values. The ML models that were used can predict the COF accurately and reliably based on features, but they are affected by data quality and quantity, overfitting or underfitting, and load change.

Background: Little is still known of how multiple urban exposures interact as health determinants. This study investigated various ways in which greenspace, traffic-related air pollution, and noise could operate together, influencing general health status., Methods: In 2022, a cross-sectional population-based survey was conducted in Sofia, Bulgaria. Included were 917 long-term adult residents who completed questionnaires on poor self-rated health (PSRH), total time spent in physical activity (PA), home garden presence, time spent in urban greenspace and nature, and sociodemographics. Residential greenspace was operationalized using the normalized difference vegetation index (NDVI), tree cover density, number of trees, and access to local greenspace and parks. Nitrogen dioxide (NO 2 ) was modeled for the study area. Road traffic, railway, and aircraft day-evening-night sound levels (L den ) were extracted from EU noise maps. Area-level income and urbanicity were considered. Analyses included multivariate ordinal regressions, interactions, and structural equation modeling (SEM)., Results: Associations with PSRH were per 0.10 NDVI 300 m : OR = 0.65 (0.42-1.01), home garden: OR = 0.72 (0.49-1.07), per 5 μg/m 3 NO 2 : OR = 1.57 (1.00-2.48), per 5 dB(A) L den road traffic: OR = 1.06 (0.91-1.23), railway: OR = 1.11 (1.03-1.20), and aircraft: OR = 1.22 (1.11-1.34). Spending >30 min/week in nature related to better health. In multi-exposure models, only associations with aircraft and railway L den persisted. People with lower education and financial difficulties or living in poorer districts experienced some exposures stronger. In SEM, time spent in nature and PA mediated the effect of greenspace., Conclusions: Greenspace was associated with better general health, with time spent in nature and PA emerging as intermediate pathways. NO 2 , railway, and aircraft noise were associated with poorer general health. These results could inform decision-makers, urban planners, and civil society organizations facing urban development problems. Mitigation and abatement policies and measures should target socioeconomically disadvantaged citizens., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The first recombinant SARS-CoV-2 variants were identified in 2022, causing public health concerns. The importance of recombinant variants has increased especially since the WHO designated the recombinant variant XBB and its lineages as subvariants that require monitoring on 20 November 2022. In this study, we provide the first insights into the new SARS-CoV-2 variant named XAN, a recombinant composed of Omicron sub-lineages BA.2 and BA.5. To our knowledge, this is the first report on the recombinant SARS-CoV-2 XAN variant identified in Bulgaria.

Background Infants with congenital heart disease (CHD) are at risk of neurodevelopmental impairments, which may be associated with impaired brain growth. We characterized how perioperative brain growth in infants with CHD deviates from typical trajectories and assessed the relationship between individualized perioperative brain growth and clinical risk factors. Methods and Results A total of 36 infants with CHD underwent preoperative and postoperative brain magnetic resonance imaging. Regional brain volumes were extracted. Normative volumetric development curves were generated using data from 219 healthy infants. Z- scores, representing the degree of positive or negative deviation from the normative mean for age and sex, were calculated for regional brain volumes from each infant with CHD before and after surgery. The degree of Z -score change was correlated with clinical risk factors. Perioperative growth was impaired across the brain, and it was associated with longer postoperative intensive care stay (false discovery rate P <0.05). Higher preoperative creatinine levels were associated with impaired brainstem, caudate nuclei, and right thalamus growth (all false discovery rate P =0.033). Older postnatal age at surgery was associated with impaired brainstem and right lentiform growth (both false discovery rate P =0.042). Longer cardiopulmonary bypass duration was associated with impaired brainstem and right caudate growth (false discovery rate P <0.027). Conclusions Infants with CHD can have impaired brain growth in the immediate postoperative period, the degree of which associates with postoperative intensive care duration. Brainstem growth appears particularly vulnerable to perioperative clinical course, whereas impaired deep gray matter growth was associated with multiple clinical risk factors, possibly reflecting vulnerability of these regions to short- and long-term hypoxic injury.

Down syndrome (DS) is the most common genetic cause of intellectual disability with a wide range of neurodevelopmental outcomes. To date, there have been very few in vivo neuroimaging studies of the neonatal brain in DS. In this study we used a cross-sectional sample of 493 preterm- to term-born control neonates from the developing Human Connectome Project to perform normative modeling of regional brain tissue volumes from 32 to 46 weeks postmenstrual age, accounting for sex and age variables. Deviation from the normative mean was quantified in 25 neonates with DS with postnatally confirmed karyotypes from the Early Brain Imaging in DS study. Here, we provide the first comprehensive volumetric phenotyping of the neonatal brain in DS, which is characterized by significantly reduced whole brain, cerebral white matter, and cerebellar volumes; reduced relative frontal and occipital lobar volumes, in contrast with enlarged relative temporal and parietal lobar volumes; enlarged relative deep gray matter volume (particularly the lentiform nuclei); and enlargement of the lateral ventricles, amongst other features. In future, the ability to assess phenotypic severity at the neonatal stage may help guide early interventions and, ultimately, help improve neurodevelopmental outcomes in children with DS., (© The Author(s) 2023. Published by Oxford University Press.)

Upper and lower limb spasticity (ULS, LLS) often occur following a stroke or in patients with other neurological disorders, leading to difficulties in mobility and daily living and decreased quality of life. Prior to the use of onabotulinumtoxinA, antispastic medications had limited efficacy and often caused sedation. Phenol injections were difficult for physicians to perform, painful, and led to tissue destruction. The success of onabotulinumtoxinA in treating cervical dystonia led to its use in spasticity. However, many challenges characterized the development of onabotulinumtoxinA for adult spasticity. The wide variability in the presentation of spasticity among patients rendered it difficult to determine which muscles to inject and how to measure improvement. Another challenge was the initial refusal of the Food and Drug Administration to accept the Ashworth Scale as a primary endpoint. Additional scales were designed to incorporate a goal-oriented, patient-centered approach that also accounted for the variability of spasticity presentations. Several randomized, double-blind, placebo-controlled trials of post-stroke spasticity of the elbow, wrist, and/or fingers showed significantly greater improvements in the modified Ashworth Scale and patient treatment goals and led to the approval of onabotulinumtoxinA for the treatment of ULS in adult patients. Lessons learned from the successful ULS trials were applied to design an LLS trial that led to approval for the latter indication. Additional observational trials mimicking real-world treatment have shown continued effectiveness and patient satisfaction. The use of onabotulinumtoxinA for spasticity has ushered in a more patient-centered treatment approach that has vastly improved patients' quality of life., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Spasticity is a velocity-dependent increase in muscle tone that has a negative effect on quality of life and hinders the ability of others to provide care. In children, most cases are caused by cerebral palsy. Traditionally, many children are treated with surgery, sometimes performed before their limbs had grown sufficiently to permit long-term success. Nonsurgical treatment comprises oral pharmacological options, but their efficacy is limited and side effects such as drowsiness and decreased short-term memory are common; nerve block procedures can cause painful dysesthesias and muscle scarring. OnabotulinumtoxinA was first approved for the treatment of pediatric lower limb spasticity in Europe in the 1990s and is now licensed for use in pediatric patients in over 80 countries worldwide, based on a large body of clinical evidence demonstrating its efficacy and safety. In 2019 the U.S. Food and Drug Administration approved onabotulinumtoxinA for the treatment of pediatric patients with upper or lower limb spasticity. This approval represents 3 decades of work to refine the dose, measurements, patient selection, and muscle selection. The availability of onabotulinumtoxinA as a treatment for pediatric spasticity can have a substantial impact on a patient's quality of life. The use of onabotulinumtoxinA in combination with orthoses and occupational/physical therapy can postpone corrective surgery until growth is nearly complete and minimize the number of corrective surgeries., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Features of brain asymmetry have been implicated in a broad range of cognitive processes; however, their origins are still poorly understood. Here we investigated cortical asymmetries in 442 healthy term-born neonates using structural and functional magnetic resonance images from the Developing Human Connectome Project. Our results demonstrate that the neonatal cortex is markedly asymmetric in both structure and function. Cortical asymmetries observed in the term cohort were contextualized in two ways: by comparing them against cortical asymmetries observed in 103 preterm neonates scanned at term-equivalent age, and by comparing structural asymmetries against those observed in 1,110 healthy young adults from the Human Connectome Project. While associations with preterm birth and biological sex were minimal, significant differences exist between birth and adulthood., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)