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Aim: To assess the predictive capabilities of the Baby Observational Selective Control AppRaisal (BabyOSCAR) tool, administered at 3 months corrected age, in determining spastic cerebral palsy (CP) outcome, functional abilities, and body topography at 2 years of age or later., Method: Independent joint motions were measured at age 10 to 16 weeks from video recordings of spontaneous movement using BabyOSCAR in a sample of 75 infants. All included infants had known 2-year outcomes (45 with spastic CP and 30 without CP) including Gross Motor Functional Classification System (GMFCS) levels and CP body distribution. Receiver operating characteristic curves and cut points indicating greatest sensitivity and specificity were generated for predictive performance., Results: Total BabyOSCAR score was a strong predictor of future outcome of spastic CP (cut score of 22.5, sensitivity = 98%, specificity = 100%, area under the curve = 0.99), and was able to distinguish children classified in GMFCS levels I and II from those in III to V (cut score of 13.5, sensitivity = 92%, specificity = 89%, area under the curve = 0.94). Having an (absolute) asymmetry score on the BabyOSCAR of more than 5 was a predictor of having unilateral CP at age 2 years (sensitivity = 56%, specificity = 100%, area under the curve = 0.86)., Interpretation: BabyOSCAR scores are predictors of diagnosis, body distribution, and future gross motor function in infants with spastic CP at 2 years of age or later., What This Paper Adds: Decreased independent joint movement at 3 months predicts spastic cerebral palsy (CP) at 2 years. Baby Observational Selective Control AppRaisal (BabyOSCAR) scores ≤13 are predictive of Gross Motor Function Classification System (GMFCS) levels III to V. BabyOSCAR scores of 14 to 22 are predictive of GMFCS levels I and II. A BabyOSCAR total asymmetry score >5 predicts unilateral CP. Stereotyped movements are more prominent in those who will be diagnosed with spastic CP at 2 years., (© 2024 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

Aim: To describe the development of an observational measure of spontaneous independent joint motion in infants with spastic cerebral palsy (CP), the Baby Observational Selective Control AppRaisal (BabyOSCAR), and to test its convergent validity and reliability., Method: A retrospective sample of 75 infants (45 with spastic CP and 30 without CP) at 3 months of age were scored with the BabyOSCAR and compared with diagnosis of spastic CP, limbs affected, and Gross Motor Function Classification level at 2 years of age or later for convergent validity using t-tests, Kruskal-Wallis tests, and Spearman's rank correlation coefficients. BabyOSCAR interrater and test-retest reliability was also evaluated using intraclass correlation coefficients., Results: Infants with spastic CP had significantly lower BabyOSCAR scores than children without CP (p < 0.001) and scores were significantly correlated with Gross Motor Function Classification System levels (p < 0.001). Children with unilateral CP had significantly higher asymmetry scores than children with bilateral CP or no CP (p < 0.01). Interrater and test-retest reliabilities were good to excellent., Interpretation: Reductions in independent joint control measured in infancy are a hallmark of eventual diagnosis of spastic CP, and influence gross motor function later in childhood (with or without a diagnosis of CP)., What This Paper Adds: Early brain injury causing spastic cerebral palsy results in fewer independent joint movements in infants. Baby Observational Selective Control AppRaisal (BabyOSCAR) score at 3 months depends on limbs affected by early brain injury. BabyOSCAR scores at 3 months correlate with Gross Motor Function Classification System level at ≥2 years. BabyOSCAR has excellent interrater reliability. BabyOSCAR, scored with a 1-minute video recording, has good to excellent test-retest reliability., (© 2024 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

Objective: The objective of this study was to investigate the influences on motor development in infants who are at low risk from Belgium, India, Norway, and the United States using the General Movement Assessment at 10-16 weeks postterm age., Methods: This was a cross-sectional study of prospectively enrolled full-term infants at low risk (n = 186). Certified General Movement Assessment observers rated the fidgety movements, quality of the movement patterns, age-adequacy of the movement repertoire, postural patterns, movement character, and overall Motor Optimality Score-Revised (MOS-R). Scores were evaluated for associations with sex, birth weight category, gestational age, postterm age at video, and country., Results: The majority of infants had normal fidgety movements (179/186, 96.2%). This did not vary by sex, birth weight, gestational age, postterm age at video, or country. All infants showed normal>atypical movement patterns. Variability was seen for age adequacy (optimal: 137/183, 74.9%), postural patterns (normal>atypical: 164/183, 89.6%), and smooth/ fluent movement character (138/183, 75.4%). Gestational age and postterm age at video were associated with atypical postural patterns, but in multivariable regression, only younger postterm age retained significance (OR = 2.94, 95% CI = 1.05-8.24). Lack of age adequacy was associated with postterm age (OR = 13.15, 95% CI = 4.36-39.72) and country (compared with Norway; Belgium OR = 3.38 95% CI = 12.4-9.22; India OR = 3.16, 95% CI = 1.01-9.87; United States not significant). Infants from India also showed lower rates of an optimal MOS-R (25-28) than infants from Norway., Conclusion: The normality and temporal organization of fidgety movements did not differ by sex, birth weight, postterm age, or country, suggesting that the fidgety movements are free of cultural and environmental influences. The majority of full-term infants who were healthy in this cohort showed normal scores for all aspects of motor development tested using the MOS-R. Differences in age adequacy and MOS-R by country warrant investigation with larger cohorts and longitudinal follow-up., Impact: Understanding variations in typical motor development is essential to interpreting patterns of movement and posture in infants at risk for atypical development. Using the framework of Prechtl's General Movement Assessment, this study showed that the development of movement and posture in healthy infants was affected by age and country of birth, but the development of the fidgety movements appeared to be free of these influences. Local norms may be needed to interpret the Motor Optimality Score-Revised in all populations, but further research on this topic is needed., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), characterised by hepatic lipid accumulation, causes inflammation and oxidative stress accompanied by cell damage and fibrosis. Liver injury (LI) is also frequently reported in patients hospitalised with coronavirus disease 2019 (COVID-19), while pre-existing MASLD increases the risk of LI and the development of COVID-19-associated cholangiopathy. Mechanisms of injury at the cellular level remain unclear, but it may be significant that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes COVID-19, uses angiotensin-converting expression enzyme 2 (ACE2), a key regulator of the 'anti-inflammatory' arm of the renin-angiotensin system, for viral attachment and host cell invasion., Aim: To determine if hepatic ACE2 levels are altered during progression of MASLD and in patients who died with severe COVID-19., Methods: ACE2 protein levels and localisation, and histological fibrosis and lipid droplet accumulation as markers of MASLD were determined in formalin-fixed liver tissue sections across the MASLD pathological spectrum (isolated hepatocellular steatosis, metabolic dysfunction-associated steatohepatitis (MASH) +/- fibrosis, end-stage cirrhosis) and in post-mortem tissues from patients who had died with severe COVID-19, using ACE2 immunohistochemistry and haematoxylin and eosin and picrosirius red staining of total collagen and lipid droplet areas, followed by quantification using machine learning-based image pixel classifiers., Results: ACE2 staining is primarily intracellular and concentrated in the cytoplasm of centrilobular hepatocytes and apical membranes of bile duct cholangiocytes. Strikingly, ACE2 protein levels are elevated in non-fibrotic MASH compared to healthy controls but not in the progression to MASH with fibrosis and in cirrhosis. ACE2 protein levels and histological fibrosis are not associated, but ACE2 and liver lipid droplet content are significantly correlated across the MASLD spectrum. Hepatic ACE2 levels are also increased in COVID-19 patients, especially those showing evidence of LI, but are not correlated with the presence of SARS-CoV-2 virus in the liver. However, there is a clear association between the hepatic lipid droplet content and the presence of the virus, suggesting a possible functional link., Conclusion: Hepatic ACE2 levels were elevated in nonfibrotic MASH and COVID-19 patients with LI, while lipid accumulation may promote intra-hepatic SARS-CoV-2 replication, accelerating MASLD progression and COVID-19-mediated liver damage., Competing Interests: Conflict-of-interest statement: No conflict of interest has been declared by any of the authors impacting on the work presented in this manuscript., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Managing diagnostic uncertainty is a major challenge in primary care due to factors such as the absence of definitive tests, variable symptom presentations and disease evolution. Maintaining patient trust during a period of investigative uncertainty, whilst minimising scope for diagnostic error is a challenge. Mismanagement can lead to diagnostic errors, treatment delays, and suboptimal patient outcomes., Objective: Our aim was to explore how UK primary care physicians (GPs) address and communicate diagnostic uncertainty in practice., Design: This qualitative study used video and audio-recordings. Verbatim transcripts were coded with a modified, validated tool to capture GPs' actions and communication in primary care consultations that included diagnostic uncertainty. The tool includes items relating to advice regarding new symptoms or symptom deterioration (sometimes called 'safety netting'). Video data was analysed to identify GP and patient body postures during and after the delivery of the management plan., Participants: All patient participants had a consultation with a GP, were over the age of 50 and had (1) at least one new presenting problem or (2) one persistent problem that was undiagnosed., Approach: Data collection occurred in GP-patient consultations during 2017-2018 across 7 practices in UK during 2017-2018., Key Results: GPs used various management strategies to address diagnostic uncertainty, including (1) symptom monitoring without treatment, (2) prescribed treatment with symptom monitoring, and (3) addressing risks that could arise from administrative tasks. GPs did not make management plans for potential treatment side effects. Specificity of uncertainty management plans varied among GPs, with only some offering detailed actions and timescales. The transfer of responsibility for the management plan to patients was usually delivered rather than negotiated, with most patients confirming acceptance before concluding the discussion., Conclusions: We offer guidance to healthcare professionals, improving awareness of using and communicating management plans for diagnostic uncertainty., (© 2024. The Author(s).)

Aims: Evaluate the association between cumulative tobacco consumption (CTC; packs-year) and atherosclerosis in type 1 diabetes (T1D), and study whether the inclusion of CTC in the Steno T1 Risk Engine (ST1RE) equation improves the identification of plaques., Methods: Cross-sectional study in T1D patients without cardiovascular disease (CVD), with ≥ 1 of the following: ≥40 years-old, diabetic kidney disease, and/or T1D duration ≥ 10 years + cardiovascular risk factors.Preclinical atherosclerosis was evaluated by carotid ultrasonography., Results: N = 584 patients were included (46.1 % women, age 48.7 ± 10.5 years, T1D duration 27.3 ± 10.8 years, 26.2 % active smokers). The overall plaque prevalence was 40.9 %. In models adjusted for age, sex, lipids, blood pressure, kidney function, statin use, microvascular complications and HbA 1c , CTC was dose-dependently associated with the number of plaques (none, 1-2, ≥3) overall and in both active and former smokers (p < 0.001). This association remained after adjusting for ST1RE (OR 1.11 [1.02-1.19]). Although the inclusion of CTC in the ST1RE did not improve plaque identification overall (p = 0.180), it did so when analyzing active smokers separately (AUC 0.738 vs. 0.768; p < 0.01)., Conclusions: In T1D patients, CTC is dose-dependently associated with atherosclerosis. Further prospective studies are needed to determine if CTC could identify T1D individuals more prone to accelerated atherosclerosis., 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 © 2024. Published by Elsevier B.V.)

We assessed the feasibility of obtaining parent-collected General Movement Assessment videos using the Baby Moves app. Among 261 participants from 4 Chicago NICUs, 70% submitted videos. Families living in higher areas of childhood opportunity used the app more than those from areas of lower opportunity., Competing Interests: Declaration of Competing Interest Peyton and Spittle are members of the General Movements Trust Speakers Bureau. deRegnier is an Associate Editor for The Journal of Pediatrics. This project was generously supported by Northwestern University Department of Physical Therapy and Human Movement Science and the Shirley Ryan Ability Lab. CP receives support from National Center for Advancing Translational Sciences, Grant KL2TR001424. Michael Msall was supported in part by T73 Leadership Education in Neurodevelopmental and Related Disorders Training Program (LEND, T73MC11047) and the Health Resources and Services Administration of the US Department of Health and Human Services (UA6MC32492), the Life Course Intervention Research Network. Preterm Research Node: Engaging Families of Preterm Babies to Optimize Thriving and Well-Being., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The Motor Optimality Score-Revised (MOS-R) is a clinical test of infant spontaneous movement at 3-5 months of age and has been associated with neurodevelopmental outcomes in infants with medical complexity. However the stability of the MOS-R tested at different developmental ages is not yet known., Aim: To determine if the repeated scoring of the MOS-R remained consistent when tested at two developmental ages in young infants., Study Design: In this prospective cohort study, infants were tested twice with the MOS-R between 12 and 13 weeks corrected age (CA) and 14-16 weeks CA. Bland Altman Plots were used to calculate agreement between the scores. Infants were grouped as having higher or lower medical complexity. MOS-R threshold scores were analyzed to assess changes over time within each group using Fisher's exact test., Subjects: 85 infants with history of hospitalization in a neonatal intensive care unit (NICU)., Results: The MOS-R scores had a high agreement with negligible bias (0.058) between timepoints (95 % CI -1.10, 1.22). Using a MOS-R cut point of 19, infants with higher medical complexity were more likely to change groups between timepoints than infants with lower medical complexity (p = 0.008), but this was not significantly different using cut points of 20 or 21., Conclusion: The MOS-R scores were stable when measured repeatedly in infants who were hospitalized in a NICU. Infants with high medical complexity had less stable MOS-R scores using certain cut points than infants with lower medical complexity., Competing Interests: Declaration of competing interest Colleen Peyton is a member of the General Movements Trust speaker's bureau., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: We compared hair cortisol (HC) with classic tests of the hypothalamic-pituitary-adrenal (HPA) axis in chronic kidney disease (CKD) and assessed its association with kidney and cardiometabolic status., Design and Methods: A cross-sectional study of 48 patients with CKD stages I-IV, matched by age, sex, and BMI with 24 healthy controls (CTR) was performed. Metabolic comorbidities, body composition, and HPA axis function were studied., Results: A total of 72 subjects (age 52.9 ± 12.2 years, 50% women, BMI 26.2 ± 4.1 kg/m 2 ) were included. Metabolic syndrome features (hypertension, dyslipidaemia, glucose, HOMA-IR, triglycerides, waist circumference) and 24-h urinary proteins increased progressively with worsening kidney function (p < 0.05 for all). Reduced cortisol suppression after 1-mg dexamethasone suppression (DST) (p < 0.001), a higher noon (12:00 h pm) salivary cortisol (p = 0.042), and salivary cortisol AUC (p = 0.008) were seen in CKD. 24-h urinary-free cortisol (24-h UFC) decreased in CKD stages III-IV compared with I-II (p < 0.001); higher midnight salivary cortisol (p = 0.015) and lower suppressibility after 1-mg DST were observed with declining kidney function (p < 0.001). Cortisol-after-DST cortisol was >2 mcg/dL in 23% of CKD patients (12.5% in stage III and 56.3% in stage IV); 45% of them had cortisol >2 mcg/dL after low-dose 2-day DST, all in stage IV (p < 0.001 for all). Cortisol-after-DST was lineally inversely correlated with eGFR (p < 0.001). Cortisol-after-DST (OR 14.9, 95% CI 1.7-103, p = 0.015) and glucose (OR 1.3, 95% CI 1.1-1.5, p = 0.003) were independently associated with eGFR <30 mL/min/m 2 ). HC was independently correlated with visceral adipose tissue (VAT) (p = 0.016). Cortisol-after-DST (p = 0.032) and VAT (p < 0.001) were independently correlated with BMI., Conclusion: Cortisol-after-DST and salivary cortisol rhythm present progressive alterations in CKD patients. Changes in cortisol excretion and HPA dynamics in CKD are not accompanied by significant changes in long-term exposure to cortisol evaluated by HC. The clinical significance and pathophysiological mechanisms explaining the associations between HPA parameters, body composition, and kidney damage warrant further study., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Boswell, Vega-Beyhart, Blasco, Quintana, Rodríguez, Díaz-Catalán, Vilardell, Claro, Mora, Amor, Casals and Hanzu.)

Aims: To explore the relationship between severe hypoglycemia (SH) and hypoglycemia awareness with preclinical atherosclerosis in type 1 diabetes (T1D)., Materials and Methods: Cross-sectional study in patients with T1D without cardiovascular disease (CVD), and with ≥1 of the following: ≥40 years, diabetic kidney disease, or ≥10 years of T1D duration with another risk factor. CVD risk was estimated with the Steno T1 Risk Engine (Steno-Risk). Carotid plaque was evaluated using standardised ultrasonography protocol. Logistic regression models adjusted for CVD risk factors were constructed to test the independent associations with SH or hypoglycemia awareness assessed by the Clarke questionnaire (Clarke). The inclusion of SH and Clarke in Steno-Risk was further evaluated., Results: We included 634 patients (52.4% men, age 48.3 ± 10.8 years, T1D duration 27.4 ± 11.1 years, 39.9% harbouring plaque). A stepped increase in the presence of plaque according to Steno-Risk was observed (13.5%, 37.7%, and 68.7%, for low, moderate, and high risk, respectively; p < 0.001). SH history (OR 4.4 [1.3-14.6]) and Clarke score (OR 1.7 [1.2-2.2]) were associated with plaque in low-risk patients (n = 192). Clarke score was also associated with plaque burden in low-moderate-risk participants (n = 436; ≥2 plaques: OR 1.2 [1.0-1.5], p = 0.031; ≥3 plaques: OR 1.4 [1.1-2.0], p = 0.025). The inclusion of SH and Clarke scores in Steno-Risk significantly improved the identification of low-risk individuals with atherosclerosis (area under the curve: 0.658 vs. 0.576; p = 0.036)., Conclusions: In patients with T1D without an estimated high CVD risk, SH and hypoglycemia awareness assessment score were independently associated with preclinical atherosclerosis and improved identification of patients who would benefit from an intensive approach., (© 2024 John Wiley & Sons Ltd.)

Aims: People with type 1 diabetes (T1D) have an increased risk of cardiovascular disease (CVD). The Mediterranean diet is associated with reduced CVD; however, the evidence in T1D is scarce. We aimed to analyse the relationships between adherence to the energy-restricted Mediterranean diet (erMEDd) and carotid atherosclerosis., Materials and Methods: We included children with T1D without CVD, with ≥1 of the following: age ≥40 years, diabetic kidney disease, or ≥10 years of disease duration with another risk factor. Plaque presence (intima-media thickness ≥1.5 mm) was determined by ultrasonography. The PREDIMED-Plus 17-item questionnaire (PP-17) was used to assess adherence to the erMEDd., Results: Four hundred one individuals were included (48% males, age 48.3 ± 11 years, diabetes duration 26.8 ± 11.4 years). Those harbouring plaques (42%) showed lower adherence to the erMEDd (PP-17: 8.9 ± 2.3 of a maximum of 17 vs. 9.8 ± 2.5, p < 0.001). Greater adherence to the erMEDd was correlated with an overall better metabolic profile. After adjusting for multiple confounders, adherence to the erMEDd was independently associated with carotid atherosclerosis (OR 0.86 [0.77-0.95] for plaque presence and OR 0.85 [0.75-0.97] for ≥2 plaques). The consumption of fruit and nuts and preference of white over red meat was higher in individuals without atherosclerosis (p < 0.05). Fruit and nut consumption was associated with lower plaque prevalence in the fully adjusted models (OR 0.38 [0.19-0.73] and 0.51 [0.29-0.93])., Conclusions: Greater adherence to the erMEDd is associated with less carotid atherosclerosis in children with T1D at high risk of CVD. Strategies to improve and implement healthy dietary patterns in this population should be encouraged., (© 2024 John Wiley & Sons Ltd.)

Background and Aims: Recent studies have identified a relationship between innate versus. Adaptative immunity and cardiovascular disease (CVD) in the general population, but information on type 1 diabetes (T1D) is lacking. We aimed to study the relationship between inflammatory biomarkers and preclinical atherosclerosis in this population., Methods and Results: Cross-sectional study in T1D individuals without CVD and with ≥1 of the following: ≥40 years, diabetic kidney disease, or ≥10 years of diabetes duration with classical CVD risk factors. Carotid plaques were evaluated by ultrasonography. C-reactive protein, total leukocyte count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio and systemic immune-inflammation index were assessed as inflammatory markers. Multivariate-adjusted models including age, sex, and other CVD risk factors were constructed to test their independent associations with atherosclerosis burden. We included 602 subjects (52.8% men, 48.7 ± 10.2 years old and 27.0 ± 10.5 years of diabetes duration). Carotid plaques were found in 41.2% of the individuals (12.8%, ≥3 plaques). The number of carotid plaques (none, 1-2, ≥3 plaques), was directly associated with the leukocyte count (6570 [5445-8050], 6640 [5450-8470] and 7310 [5715-8935] per mm 3 , respectively; p for trend = 0.021) and the NLR (1.63 [1.28-2.13], 1.78 [1.38-2.25] and 2.14 [1.58-2.92], respectively; p for trend <0.001), but only the NLR remained directly associated in fully-adjusted models (presence of plaques; OR 1.285 [1.040-1.587]; ≥3 plaques, OR 1.377 [1.036-1.829])., Conclusions: The NLR was independently and directly associated with carotid plaque burden in T1D individuals. Our data support the role of innate versus. Adaptative immunity in atherosclerosis also among the T1D population., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Introduction: An increased midnight cortisol (MC) has been described in end-stage kidney disease (ESKD) and type 1 diabetes (T1D). Lower circulating levels of the cytokine soluble tumor necrosis factor (TNF)-like weak inducer of apoptosis (sTWEAK) have been found in T1D and ESKD and associated with cardiovascular (CV) events in the latter. We aimed to study MC and sTWEAK in simultaneous pancreas-kidney transplant (SPKT) recipients, and the association of these markers with CV risk factors and transplant outcomes., Methods: This was a retrospective cohort study including subjects with T1D who received a first SPKT between 2008 and 2020. MC and sTWEAK at baseline were correlated with CV risk factors and evolution 1 year after SPKT., Results: We included 29 subjects (58.6% women, mean age 43.5 ± 7.5 years, diabetes duration 31.9 ± 9.4 years). Systolic blood pressure (SBP) increased directly with MC quartiles, despite similar hypertension prevalence (p < 0.05). At 1 year, antihypertensive treatment was deintensified in those in lower MC quartiles (p < 0.05). Diabetic neuropathy prevalence decreased progressively in higher cortisol quartiles (p for trend = 0.005). Low MC was associated with delayed kidney graft function (p for trend = 0.044), and high sTWEAK with kidney graft rejection (p for trend = 0.018). In multivariate analyses, MC (standardized-β 0.505, p = 0.004) and age (standardized-β - 0.460, p = 0.040) were independently correlated with SBP, and MC was independently associated with the presence of diabetic neuropathy (OR 0.633, 95% CI 0.425-0.944, p = 0.025), adjusted for confounders., Conclusions: In this exploratory study, lower MC was associated with a lower baseline SBP, an improvement of antihypertensive treatment 1 year after transplant, and a higher diabetic neuropathy prevalence in SPKT recipients., (© 2023. The Author(s).)