A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong disability.Currently,there are no FDA-approved therapies available to promote nerve regeneration.Tacrolimus accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve surgery.The authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug exposure.Tacrolimus is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 days.Size and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible byproducts.Tacrolimus released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic delivery.Given its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

Encouraging kids to hop,skip,and jump：Emphasizing the need for higher-intensity physical activity in childcare

1.Introduction Daily physical activity（PA）participation is crucial to the health and well-being of young children.Along with total physical activity（TPA;all-intensity）,moderate-to-vigorous physical activity（MVPA）,or energetic play,is associated with greater health benefits,particularly for preschoolers（3-4 years）,including but not limited to improved bone and skeletal properties and cognitive and psychosocial health.1 Centered on this,both Canada and Australia have recently established 24-Hour Movement Guidelines for the Early Years,recommending that.

Compound Heterozygous PLD1 Variants in Right-Sided Heart Malformations

We report a three-year-old male child who presented with congenital valvular defects,right ventricular malformation,and initial developmental delay.Genome sequencing showed rare deleterious biallelic missense variants in PLD1.In his parents’second pregnancy,echocardiogram at 13 weeks gestation revealed right-sided cardiac malformations resembling the clinical presentation of the family’s first child.Targeted DNA analysis showed that the fetus carried the same biallelic PLD1 variants as their older sibling.This case helps to further delineate the clinical spectrum of PLD1-related defects and highlights the value of both genome sequencing in congenital heart disease and early fetal echocardiography to establish phenotype.

More to it than meets the eye: a case report of incomitant esotropia in a child caused by a giant basilar aneurysm

Background:Esotropia is a common concern in pediatric ophthalmology consultations.While most cases stem from strabismus,it is crucial for physicians to differentiate atypical features that might indicate underlying organic causes,such as VI nerve palsy,hinting at the presence of intracranial spaceoccupying lesions.Although the occurrence of cerebral aneurysms in children is rare,they can have severe consequences.Case Description:Here,we described an extremely rare case of giant basilar fusiform aneurysm measuring 4.0 cm×3.9 cm×3.9 cm in an otherwise healthy 8-year-old child,and analyzed its atypical features that suggested an intracranial etiology.We further described an endovascular approach,performed by interventional radiologists,and discussed its advantages over the conventional neurosurgery.The patient continued to be followed by our multidisciplinary team.He had a stable post-operative course and made an excellent recovery neurologically.At the 1-year follow-up,he was orthophoria with excellent vision and stereopsis.Conclusions:To our knowledge,this is the first pediatric case in Canada where a giant intracranial aneurysm was treated endovascularly.The salient red flags—progressive incomitant esotropia and diplopia,the presence of myopia(rather than hyperopia),nystagmus and abnormal saccadic movements—should be astutely recognized by clinicians as intracranial giant aneurysms carry a poor prognosis.A multidisciplinary approach is essential for the management of such cases.

Intermittent fasting-a double edged sword for atherosclerosis

The impact of alternate-day fasting(ADF)on atherosclerosis remains poorly understood,particularly in high-risk populations.In a recent paper published in Life Metabolism,Deng et al.revealed that ADF exacerbated both early and advanced atherosclerotic lesion development in Apoe^(-/-)mice through suppression of hepatic activating transcription factor 3(ATF3)and consequent dysregulation of cholesterol metabolism.

关注孕产期用药——加拿大“motherisk”项目简介

孕产期用药的安全性是一个值得关注的课题,因其对儿童健康的影响不可忽视。加拿大多伦多大学附属儿童病院于1985年发起的"Motherisk"研究项目,集临床治疗、研究及教育为一体,旨在为医护人员及患者提供证据充分的怀孕及哺乳期用药安全及风险的信息和指南,并对孕妇提供实用的咨询和帮助。本文结合实际的研究事例,从该项目的基本背景和研究内容及应用情况做一简要介绍。

Hepatocellular adenoma in the paediatric population:Molecular classification and clinical associations

Hepatocellular adenomas(HCAs)represent rare,benign liver tumours occurring predominantly in females taking oral contraceptives.In children,HCAs comprise less than 5%of hepatic tumours and demonstrate association with various conditions.The contemporary classification of HCAs,based on their distinctive genotypes and clinical phenotypes,includes hepatocyte nuclear factor 1 homeobox alpha-inactivated HCAs,beta-catenin-mutated HCAs,inflammatory HCAs,combined beta-catenin-mutated and inflammatory HCAs,sonic hedgehogactivated HCAs,and unclassified HCAs.In children,there is a lack of literature on the characteristics and distribution of HCA subtypes.In this review,we summarized different HCA subtypes and the clinicopathologic spectrum of HCAs in the paediatric population.

Assessing disease activity using the pediatric Crohn’s disease activity index:Can we use subjective or objective parameters alone?

BACKGROUND The pediatric Crohn’s disease activity index(PCDAI)is used as a standard tool to assess disease activity in clinical trials for pediatric Crohn’s disease.AIM To examine which items on the PCDAI drive assessment of disease activity,and how subgroups of subjective and objective items reflect change in disease state over time.METHODS Selective raw data from three prospectively collected datasets were combined,including 703 children with full PCDAI data at baseline,at 3-mo(Q1,n=670),and 1-year(Q4,n=474).Change in individual PCDAI scores from baseline to Q1 and to Q4 were examined using the non-weighted PCDAI.RESULTS Abdominal pain,well-being,weight,and stooling had the highest change scores over time.Objective indicators including albumin,abdominal exam,and height velocity followed.Change scores for well-being and abdominal exam did not explain significant variance at Q1 but were significant predictors at Q4(P<0.001 and P<0.05).Subjective and objective subgroups of items predicted less variance(18%and 22%)on total PCDAI scores at Q1 and Q4 compared to the full PCDAI,or a composite scale(both 32%)containing significant predictors.CONCLUSION Although subjective items on the PCDAI change the most over time,the full PCDAI or a smaller composite of items including a combination of subjective and objective components classifies disease activity better than a subgroup of either subjective or objective items alone.Reliance on subjective or objective items as stand-alone proxies for disease activity measurement could result in misclassification of disease state.

Magnetic resonance imaging of the transplanted pediatric heart as a potential predictor of rejection

AIM To evaluate cardiac magnetic resonance imaging(CMR) as a non-invasive tool to detect acute cellular rejection(ACR) in children after heart transplant(HT).METHODS Thirty pediatric HT recipients underwent CMR at the time of surveillance endomyocardial biopsy(EMB) and results were compared to 14 non-transplant controls. Biventricular volumes, ejection fractions(EFs), T2-weighted signal intensities, native T1 times, extracellular volumes(ECVs) and presence of late gadolinium enhancement(LGE) were compared between patients and controls and betweenpatients with International Society of Heart and Lung Transplantation(ISHLT) grade ≥ 2R rejection and those with grade 0/1R. Heart rate(HR) and brain natriuretic peptide(BNP) were assessed as potential biomarkers.RESULTS Significant ACR(ISHLT grade ≥ 2R) was an infrequent event in our population(5/30, 17%). Ventricular volumes,EFs, LGE prevalence, ECVs, native T1 times, T2 signal intensity ratios, HR and BNP were not associated with the presence of ≥ 2R ACR.CONCLUSION In this pilot study CMR did not reliably identify ACRrelated changes in pediatric HT patients.

Adiponectin and the regulation of gastric content volume in the newborn rat

BACKGROUND Oral intake is dependent on the gastric ability to accommodate the food bolus.Comparatively,neonates have a smaller gastric capacity than adults and this may limit the volume of their milk intake.Yet,we previously reported that the newborn rat gastric milk volume is greatest after birth and,when normalized to body weight,decreases with postnatal age.Such age-dependent changes are not the result of intake differences,but greater gastric accommodation and reduced emptying rate.AIM Hypothesizing that breastmilk-derived adiponectin is the factor regulating gastric accommodation in neonates,we comparatively evaluated its effects on the rat fundic muscle tone at different postnatal ages.METHODS In freshly dispersed smooth muscle cells(SMC),we measured the adiponectin effect on the carbachol-induced length changes.RESULTS Adiponectin significantly reduced the carbachol-stimulated SMC shortening independently of age.In the presence of the inhibitor iberiotoxin,the adiponectin effect on SMC shortening was suppressed,suggesting that it is mediated via largeconductance Ca^(2+)sensitive K^(+)channel activation.Lastly,we comparatively measured the newborn rat gastric milk curd adiponectin content in one-and twoweek-old rats and found a 50%lower value in the latter.CONCLUSION Adiponectin,a major component of breastmilk,downregulates fundic smooth muscle contraction potential,thus facilitating gastric volume accommodation.This rodent’s adaptive response maximizes breastmilk intake volume after birth.

PROPERTIES OF VOLTAGE-GATED SODIUM CHANNELS IN DEVELOPING AUDITORY NEURONS OF THE MOUSE IN VITRO

Objective. To investigate the properties of voltage-gated sodium (Na+) channels in developing auditoryneurons during early postnatal stages in the mammalian central nervous system.Methods. Using the whole-cell voltage-clamp technique, we have studied changes in the electrophysi-ological properties of Na+ channels in the principal neurons of the medial nucleus of the trapezoid body (MNTB).Results. We found that MNTB neurons already express functional Na+ channels at postnatal day 1 (P1),and that channel density begins to increase at P5 when the neurons receive synaptic innervation andreach its maximum (～3 fold) at P11 when functional hearing onsets. These changes were paralleled byan age-dependent acceleration in both inactivation and recovery from inactivation. In contrast, there wasvery little alteration in the voltage-dependence of inactivation.Conclusion. These profound changes in the properties of voltage-gated Na+ channels may increase theexcitability of MNTB neurons and enhance their phase-locking fidelity and capacity during high-frequencysynaptic transmission.

Surgery for Residual Inferior Left-to-Right Atrial Shunt

We report the case of three female patients who were scheduled for surgical correction of residual left-to-right shunt after initial repair of sinus venosus atrial septal defect(SV-ASD)during childhood.After excluding the possibility of an hemodynamic intervention,all three patients underwent a successful surgical closure through a right mini sub-axillary approach by using total peripheral cannulation for cardiopulmonary bypass and leaving the inferior vena cava completely un-snared allowing for an optimal visualization of the residual atrial septal communication and avoiding extensive dissection of mediastinal structures.

Are potassium levels in children with hemolytic uremic syndrome predictive of outcome?

Objective: To ascertain the role of serum potassium levels in predicting clinical outcomes in diarrhea-associated hemolytic uremic syndrome (HUS D+). Methods: We reviewed clinical and laboratory data from HUS D+ patients at our tertiary care institution from 2001 to 2008. Serum potassium concentration at presentation and during the acute phase of acute renal failure were recorded and related to laboratory parameters and clinical outcomes. Results: 15 HUS D+ cases were identified. E. coli 0157:H7 was found in 9/15 cases (70%). Potassium levels were not predictive of clinical outcomes. Normal serum potassium levels were found in the majority of patients. Potassium levels <3.6 mmol/L were evident at presentation in 3/15 patients (23%), and no patient manifested hyperkalemia even when creatinine levels were concurrently increase. Conclusions: This study suggests the presence of vigorous compensatory mechanisms in the homoestasis of serum potassium levels during HUS D+ disease since neither the increase stool volumes associated with diarrhea nor the presence of renal failure resulted in clinically significant changes in serum potassium levels.

Does Resampled Image Data Offer Quantitative Image Quality Benefit for Pediatric CT?

Acquiring CT images with thin slices can improve resolution and detectability, but cause an increase in the image noise. To compensate for the additional image noise, the kVp or mA can be increased, which carries a dose penalty to the patient. We investigate the image quality achieved in MPR images reformatted from different slice thicknesses 0.625 mm and 5 mm, to determine if a thicker slice could be resampled to smaller thickness with minimal loss of image information. Catphan?600 phantom was imaged using selected kVp/mA settings (80 kVp/250 mA, 100 kVp/ 150 mA and 120 kVp/200 mA) to generate slices with thicknesses of 0.625 mm and 5 mm using a GE Discovery HD750 64-slice CT scanner to investigate the impact of the acquisition slice thickness on the overall image quality in MPRs. Measurements of image noise, uniformity, contrast-to-noise ratio (CNR), low contrast detectability and limiting spatial resolution were performed on axial and coronal multiplanar reformatted images (MPRs). Increased noise, reduced contrast-to-noise ratio, and improved limiting spatial resolution and low contrast detection were observed in 2 mm coronal MPRs generated with 0.625 mm thin slices when compared to the MPRs from 5 mm thick slices. If the 2 mm coronal MPRs acquired with 5 mm slices are resampled to 0.6 mm slice thickness, the reductions in limiting resolution and low contrast detection are compensated, although with reduced uniformity and increased image noise. Thick slice image acquisitions yield better CNR and less noise in the images, whereas thin slices exhibited improved spatial resolution and low contrast detectability. Retrospectively resampling into thinner slices before obtaining the coronal MPRs provided a balance between image smoothness and identifying fine image detail. Which approach provides the optimal image quality may also depend on the imaging task, size and composition of the features of interest, and radiologist preference.

Olanzapine-associated hypothermia in an adolescent anorexic girl

This is a 12th case report on olanzapine induced hypothermia and based on the results of literature search, by far is the youngest case ever is reported. The hypothermia occurred during the refeeding phase, despite a weight gain since increasing the dosage from 5 mg to 7.5 mg olanzapine. Our recent literature search found 11 published cases of olanzapine treatment associated with hypothermia. Olanzapine acts on serotonin or dopamin receptors and has antagonistic properties on histaminergic, muscarinic and α-adrenergic receptors. Olanzapine mediates the hypothermic effect through antagonism at receptors other than dopamine.

Evaluation of a Pediatric Mock Code Educational Training Program at a Large, Tertiary Care Pediatric Hospital

Background: Management of the acutely ill children represents one of the more complex clinical skills required of pediatric physicians. Our goal was to develop and evaluate a multidisciplinary pediatric mock code training program for the pediatric residents in our institution. Methods: We performed a before and after evaluation of pediatric residents. The residents were educated by attending five mock code scenarios, followed by debriefing. Before and after the five sessions, the residents completed a self-assessment questionnaire. Results: Residents reported a significant improvement in their comfort in all aspects of managing pediatric resuscitations, with notable improvement seen in running a resuscitation requiring airway management, managing fluid resuscitation and performing endotracheal intubation. The most prominent change was demonstrated in the comfort level of the overall management of a pediatric resuscitation. Conclusion: The pediatric mock code educational training program improved residents’ self-reported knowledge and comfort level in managing pediatric emergency situations.

Syrup versus Drops of Iron III Hydroxide Polymaltose in the Treatment of Iron Deficiency Anemia of Infancy

Background: Iron deficiency anemia in infants is the most common micronutrient deficiency worldwide. The main cause is low iron intake in the presence of accelerated physiologic growth rate. Objective: The current study aimed at prospectively comparing the efficacy of iron III hydroxide polymaltose syrup (IPS) versus iron III hydroxide polymaltose drops (IPD) in treating iron deficiency among infants attending the hematology outpatient clinic. Our hypothesis was that IPS would be less effective possibly related to the difficulty of giving the medication. Methods: Participants diagnosed with iron deficiency anemia between 11-24 months were randomly assigned to receive either IPS or IPD for 3 months. The main outcome parameter was hemoglobin blood level, while the secondary outcome parameters were: 1) iron;2) ferritin;3) transferrin (i.e.?total iron binding capacity);4) mean corpuscular volume;and 5) red blood cell distribution width. Results: Out of the 104 recruited infants, 55 (52%) completed the study: 29 in the IPS group and26 inthe IPD group. There was no significant difference in the main outcome parameter at either 1 or 3 months of treatment: mean hemoglobin was 10.5 versus 10.7 g/dL within a 1 month treatment, P = 0.4;mean hemoglobin was 11.0 versus 11.1 g/dL within a 3 months of treatment, P = 0.59. Likewise, no significant differences were found with respect to the occurrence of side effects. Conclusion: Oral IPD and IPS are equally effective in treating iron deficiency anemia in infants aged 11 - 24 months.

Radiation compromised survival of patients with heritable retinoblastoma(H1):what will be the long-term consequences of current eye salvage therapies?

Temming and colleagues(1)present important data from the German national retinoblastoma reference center(University Hospital Essen)confirming the previously observed(2)long-term very serious consequence of radiation treatment to save vision for children with heritable retinoblastoma:second cancers.The long-term overall survival of 633 patients with heritable retinoblastoma diagnosed between 1940 and 2008 was studied.Heritable retinoblastoma is initiated by constitutional mutation in the RB1 tumor suppressor gene,indicated as“H1”in the 8th edition of the TNMH cancer staging for retinoblastoma(3).

A decline in snow cover area of Passu and Ghulkin valleys between 1995 and 2022

The global cryosphere is experiencing accelerated melting due to climate change.Currently,the Karakoram anomaly is under discussion with a debate about the possibility that the anomaly may have recently ended.This study aims to evaluate the up-to-date changes in snow cover in the western Karakoram region.We observed the snow cover changes in Passu and Ghulkin valleys in the Hunza River basin(HRB)of the Karakoram through multitemporal Landsat satellite data between 1995 and 2022.We found a significant reduction in snow cover in these valleys,with an average reduction rate of 0.42 km~2/yr,resulting in a total reduction of~11.46 km~2 between 1995 and 2022.This reduction in snow cover is consistent with the mass loss of glaciers in the Karakoram region in recent years.The decline in snow cover in these valleys is also consistent with the meteorological data.The temperature in summer(June)has significantly increased whereas the precipitation in the accumulation season(March)has decreased.These rapid changes suggest that it is crucially important to monitor the snow cover on a regular basis to support downstream management of snowmelt runoff.In addition,there is a need of planning for mitigation and adaptation strategies for snow-related hazards.