Radical hysterectomy case volume and cervical cancer treatment in the era of COVID-19: A multi-site analysis of National Cancer Institute-designated Comprehensive Cancer Centers.

OBJECTIVE: To compare radical hysterectomy case volume, cancer stage, and biopsy-to-treatment time of invasive cervical cancer diagnosed before and after onset of the COVID-19 pandemic. METHODS: In a multi-institution retrospective cohort study conducted at 6 large, geographically diverse National Cancer Institute-designated cancer centers, patients treated for newly diagnosed invasive cervical cancer were classified into 2 temporal cohorts based on date of first gynecologic oncology encounter: (1) Pre-Pandemic: 3/1/2018-2/28/2020; (2) Pandemic & Recovery: 4/1/2020-12/31/2021. The primary outcome was total monthly radical hysterectomy case volume. Secondary outcomes were stage at diagnosis and diagnosis-to-treatment time. Statistical analyses used chi-squared and two sample t-tests. RESULTS: Between 3/1/2018-12/31/2021, 561 patients were diagnosed with cervical cancer. The Pre-Pandemic and Pandemic & Recovery cohorts had similar age, race, ethnicity, smoking status, and Body Mass Index (BMI). During Pandemic & Recovery, the mean monthly radical hysterectomy case volume decreased from 7[SD 2.8] to 5[SD 2.0] (p = 0.001), the proportion of patients diagnosed with Stage I disease dropped from 278/561 (49.5%) to 155/381 (40.7%), and diagnosis of stage II-IV disease increased from 281/561 (50.1%) to 224/381 (58.8%). Primary surgical management was less frequent (38.3% Pandemic & Recovery versus 46.7% Pre-Pandemic, p = 0.013) and fewer surgically-treated patients received surgery within 6 weeks of diagnosis (27.4% versus 38.9%; p = 0.025). CONCLUSIONS: Lower radical hysterectomy case volume, a shift to higher cervical cancer stage, and delay in surgical therapy were observed across the United States following the COVID-19 outbreak. Decreased surgical volume may result from lower detection of early-stage disease or other factors.

Feeding Black Pepper (Piper nigrum) or Exogenous Xylanase Improves the Blood Lipid Profile of Broiler Chickens Fed Wheat-Based Diets.

This study aimed to determine the impact of dietary black peppercorn (BP) and xylanase (XYL) alone or in combination on growth performance, dietary energy, nutrient digestibility and blood lipid profile when fed to male Ross 308 broiler chickens from the ages of 7 to 21 d. A wheat-soy-based basal feed that was formulated to be 0.42 MJ lower in metabolizable energy (ME) was mixed. The basal feed was then split into four batches, with the first batch set aside as the basal control; the second batch was supplemented with freshly milled BP; the third batch was supplemented with XYL; the fourth batch was supplemented with both BP and XYL, as in the previous two batches. Each diet was fed to eight pens, with two birds in a pen, following randomization. Feeding BP reduced bird growth and most of the digestibility coefficients but increased blood high-density lipoprotein (p < 0.05). Dietary XYL increased bird growth, dietary ME and nutrient digestibility (p < 0.05). In addition, XYL increased hepatic carotenoids and coenzyme Q10, but reduced blood low-density lipoprotein (p < 0.05). There were no BP by XYL interactions (p > 0.05) observed. Further research is needed to identify the optimum level of BP in broiler diets.

Stevia (Stevia rebaudiana) Improves Carotenoid Content in Eggs When Fed to Laying Hens.

Stevia rebaudiana Bertoni is a shrub with leaves that have a high concentration of carotenoids such as lutein and zeaxanthin. Egg yolks are a bioavailable source of lutein and zeaxanthin. The consumption of these carotenoids has been linked with improved human health. To investigate the impact of dried stevia leaves at 0%, 1% and 2% on the quality variables, the chemical composition and antioxidant content of eggs, the experiment involved 90 Hy-Line Brown laying hens, housed in 30 enriched layer cages, in groups of three from 22 to 26 weeks of age. The impact on the internal qualities of stored eggs was also examined. Yolks from hens fed stevia had an enriched color compared with the controls. At the end of the experiment, the whole egg, without shell, of birds fed 2% stevia had a higher total carotenoid content (p < 0.001) compared with birds fed 1% and 0% stevia, i.e., 5.16 (µg/g), 4.23 (µg/g) and 2.96 (µg/g), respectively. Storage reduced albumen height and increased albumen pH (p < 0.001). Stevia supplementation did not interact (p > 0.05) with storage time among the egg quality variables. Consuming eggs from hens fed stevia may increase carotenoids in human diet.

Antioxidant status and growth performance of broiler chickens fed diets containing graded levels of supplementary dihydroquercetin.

Dihydroquercetin (DHQ), also known as taxifolin, is a natural antioxidant that can be commercially obtained by extraction from Siberian Larch (Larix sibirica). Four wheat-soy based diets, formulated to contain 0, 0.5, 1.5 and 4.5 g/kg of supplementary DHQ were prepared. Each diet was fed ad libitum to birds in seven pens (three birds in each pen) in a randomised block design from 7 to 21 days of age. The effect of DHQ on weight gain was not significant overall (P > 0.05), although there was an indication of a linear increase (L < 0.05). The blood glutathione peroxidase responded (P < 0.001) in a curvilinear manner (L < 0.001 and Q < 0.05) to increased dietary DHQ. The results from this study indicate that dietary DHQ supplementation may be beneficial at levels greater than 1.5 g/kg feed, due to improved bird antioxidant status. Further research to define an upper inclusion level and optimal timing for phase feeding programmes is warranted.

Feeding dry stevia leaf (Stevia rebaudiana) or xylanase improves the hepatic antioxidative status of broiler chickens.

Four diets, formulated with and without stevia and with and without exogenous xylanase, following a 2 × 2 factorial design, were prepared. Each diet was fed ad libitum to birds in eight pens (three birds in each pen) in a randomised block design. It was found that birds fed xylanase grew faster, used the feed more efficiently and had an increased concentration of hepatic α-tocopherol and vitamin E concentrations (P < 0.05). Feeding stevia did not affect growth performance (P > 0.05), but increased hepatic CoQ10 (P = 0.05), lutein, zeaxanthin and total carotenoids (P < 0.001) concentrations. There were no dietary stevia by xylanase interactions (P > 0.05) for any of the studied variables. The results showed that alone, dietary stevia and dietary xylanase can improve the antioxidative status of birds through enhancing dietary antioxidant availability.

Feeding dihydroquercetin and vitamin E to broiler chickens reared at standard and high ambient temperatures.

The use of natural antioxidants, in particular polyphenols such as dihydroquercetin (DHQ), in animal nutrition has recently increased in popularity. This may partly be due to the risk of increased incidences of heat stress associated with raising livestock in warmer ambient temperatures, facilitated by global warming, reducing antioxidant capacity. The current research demonstrates the effect of dietary DHQ, vitaminEand standard or high ambient temperatures on growth performance, energy and nutrient metabolism, gastrointestinal tract (GIT) development, jejunal villus morphometry and antioxidant status in broiler chickens. Each of the four experimental diets was fed to 16 pens of five birds, which were allocated to four rooms (four pens in each room). The temperature in two rooms was maintained at aconstant 35°C (high temperature; HT), and the temperature in the other two rooms was gradually reduced from 27°C at 7 dof age to 22°C at 20 dof age (standard temperature; ST). Rearing birds at HT reduced feed intake, weight gain, weight of small intestine, total GIT, liver, spleen, heart, villus height, villus surface area and lowered blood glutationperoxidase (GSH-Px). Dietary DHQ increased blood GSH-Px and total antioxidant status, increased heart weight and reduced caecal size. When fed separately, DHQ and vitamin E improved hepatic vitamin E concentration. Feeding vitamin Eincreased spleen and liver weights. When fed together, DHQ and vitamin Ereduced villus height, villus height to crypt depth ratio and villus surface area. Temperature and antioxidants did not affect energy and nutrient metabolism. There were no effects of dietary antioxidants on growth performance of broiler chickens and there were no mortalities. At present, it is unclear if feeding antioxidants (in particular DHQ) at different levels, using different dietary formulations, and rearing birds under arange of environmental conditions may be effective at enhancing production performance and bird health in hot ambient climates.

Comparative study of preclinical mouse models of high-grade glioma for nanomedicine research: the importance of reproducing blood-brain barrier heterogeneity.

The clinical translation of new nanoparticle-based therapies for high-grade glioma (HGG) remains extremely poor. This has partly been due to the lack of suitable preclinical mouse models capable of replicating the complex characteristics of recurrent HGG (rHGG), namely the heterogeneous structural and functional characteristics of the blood-brain barrier (BBB). The goal of this study is to compare the characteristics of the tumor BBB of rHGG with two different mouse models of HGG, the ubiquitously used U87 cell line xenograft model and a patient-derived cell line WK1 xenograft model, in order to assess their suitability for nanomedicine research. Method: Structural MRI was used to assess the extent of BBB opening in mouse models with a fully developed tumor, and dynamic contrast enhanced MRI was used to obtain values of BBB permeability in contrast enhancing tumor. H&E and immunofluorescence staining were used to validate results obtained from the in vivo imaging studies. Results: The extent of BBB disruption and permeability in the contrast enhancing tumor was significantly higher in the U87 model than in rHGG. These values in the WK1 model are similar to those of rHGG. The U87 model is not infiltrative, has an entirely abnormal and leaky vasculature and it is not of glial origin. The WK1 model infiltrates into the non-neoplastic brain parenchyma, it has both regions with intact BBB and regions with leaky BBB and remains of glial origin. Conclusion: The WK1 mouse model more accurately reproduces the extent of BBB disruption, the level of BBB permeability and the histopathological characteristics found in rHGG patients than the U87 mouse model, and is therefore a more clinically relevant model for preclinical evaluations of emerging nanoparticle-based therapies for HGG.

A digital media attention diversion improves mood and fear in patients receiving chemotherapy for recurrent gynecologic malignancies: results of a randomized trial.

BACKGROUND: Recurrent gynecologic cancer patients experience symptoms that affect psychologic, emotional, social, and physical well-being. Chemotherapy can further exacerbate these symptoms. Poor mood, pain, and fatigue are linked and are detrimental to quality of life. Interventions targeting these symptoms may improve patient-reported outcomes and performance status. OBJECTIVES: To determine the ability of a humorous digital media attention diversion to improve symptom domains of positive and negative mood during chemotherapy for patients with recurrent gynecologic cancers. STUDY DESIGN: This randomized, crossover clinical trial enrolled women with recurrent gynecologic cancers. Subjects participated over three cycles of chemotherapy. The primary outcome was the change in mood on the validated Positive and Negative Affect Scale-Extended (PANAS-X) instrument, which measures positive and negative affect domains. All subjects completed the PANAS-X after receiving chemotherapy during cycle 1 on study. In atudy arm 1, subjects watched their choice of humorous movies on a digital media device while receiving chemotherapy during cycle 2 on study. They selected from non-humorous movies during cycle 3 on study. In arm 2, the order of movies was reversed. After each cycle, mood, fatigue, and other patient-reported outcomes were assessed for comparison with baseline measurements. RESULTS: The target enrollment of 66 subjects was achieved. Subjects watched humorous content for an average of 96.0 min and non-humorous content for an average of 62.5 min. Negative mood improved after exposure to humorous (p=0.017) and non-humorous content (p=0.001). Patient-reported fear also improved after exposure to both humorous (p=0.038) and non-humorous content (p=0.002). Subjects reported higher use of affiliating and self-effacing humor types. CONCLUSIONS: Offering patients a choice of digital media during chemotherapy significantly improved negative mood and fear. This was seen with both humorous and non-humorous content. This low-cost and low-risk intervention should be implemented as an attention diversion to improve negative mood and fear for patients receiving chemotherapy.

Understanding the impact of bilateral brain injury in children with unilateral cerebral palsy.

The presence of bilateral brain injury in patients with unilateral cerebral palsy (CP) may impact neuroplasticity in the ipsilateral hemisphere; however, this pattern of injury is typically under-analyzed due to the lack of methods robust to severe injury. In this study, injury-robust methods have been applied to structural brain magnetic resonance imaging (MRI) data of a cohort of 91 children with unilateral CP (37 with unilateral and 54 with bilateral brain injury, 4-17 years) and 44 typically developing controls (5-17 years), to determine how brain structure is associated with concurrent motor function, and if these associations differ between patients with unilateral or bilateral injury. Regression models were used to associate these measures with two clinical scores of hand function, with patient age, gender, brain injury laterality, and interaction effects included. Significant associations with brain structure and motor function were observed (Pearson's r = .494-.716), implicating several regions of the motor pathway, and demonstrating an accurate prediction of hand function from MRI, regardless of the extent of brain injury. Reduced brain volumes were observed in patients with bilateral injury, including volumes of the thalamus and corpus callosum splenium, compared to those with unilateral injury, and the healthy controls. Increases in cortical thickness in several cortical regions were observed in cohorts with unilateral and bilateral injury compared to controls, potentially suggesting neuroplasticity might be occurring in the inferior frontal gyrus and the precuneus. These findings identify prospective useful target regions for transcranial magnetic stimulation intervention.

The effects of supercritical carbon dioxide extraction and cold-pressed hexane extraction on the chemical composition and feeding value of rapeseed meal for broiler chickens.

The chemical characteristics of rapeseed meal (RSM) produced from two cultivars of UK-grown rapeseed, by both supercritical carbon dioxide extraction (ScCO2) and cold-pressed hexane extraction (CpHe) were examined. Their nutritional value, with and without protease, was then assessed in a broiler digestibility trial. Basal feed was substituted with one of four RSM batches (200 g/kg) following adjustments for dry matter (DM) and ether extract (EE) content. Half of each diet was supplemented with a mono-component protease derived from Bacillus subtilis (Axtra®PRO, Danisco Animal Nutrition, Malborough, UK) giving a total of eight test diets. Two control diets, with and without protease were also fed. At 13 d age male Ross 308 broilers were randomly allocated to seven replicate pens (five birds per pen) and assigned to one of 10 diets. Total excreta were collected from 17 to 21 d age and feed intake was recorded. Pre-caecal protein digestibility (pcPd) was determined using TiO2 as an indigestible marker. Colourimetrically CpHe RSM was substantially darker than ScCO2 counterparts. The influence of oil recovery method (ORM) was also evident in DM, EE, ash free neutral detergent fibre (aNDFom), neutral detergent insoluble crude protein (NDICP) and glucosinolate content (GLS). The content of DM, EE and GLS was higher in ScCO2 RSM whereas aNDFom and NDICP levels were greater in CpHe RSM. Protein solubility in KOH was greater in ScCO2 RSM whilst levels of NDICP were lower. Collectively these results suggest that less heat damage was incurred to the RSM during ScCO2 extraction. There was no significant main effect of cultivar nor were any significant interactions observed between treatment factors. Rapeseed meal ScCO2 produced greater metabolisable energy, pcPd, nitrogen retention and energy metabolisability (p < 0.05). Protease supplementation increased pcPd (p < 0.05) irrespective of ORM and cultivar. The key implications of these findings are that by adopting oil recovery methods that minimise the exposure of RSM to thermal treatments and by adding a compatible protease there is scope to increase the nutritional value of RSM for broilers and increase its utilisation in modern poultry production.

Feeding value of field beans (Vicia faba L. var. minor) with and without enzyme containing tannase, pectinase and xylanase activities for broilers.

Effects of field beans with various tannin content and exogenous enzyme mixture containing tannase, pectinase and xylanase activities on N-corrected dietary apparent metabolisable energy (AMEn), coefficients of dry matter (DMR) and nitrogen retention (NR), fat digestibility, gastrointestinal tract (GIT) development, jejunal villus morphometry, ileal digesta viscosity and sialic acid were examined. Birds' growth performance and energy conversion ratio (ECR) were also measured. Birds were fed one of eight mash diets. The Control diet contained as major ingredients wheat (400 g/kg) and soybean meal (SBM) (127 g/kg and 221 g crude protein/kg and 12.83 MJ AMEn/kg. To reduce nutrient density, the Control diet also contained washed sand at 119 g/kg. Another three diets containing 300 g/kg of each of three experimental field bean cultivar samples in replacement for SBM and sand were also mixed. Each diet was fed to nine pens with two male Ross 308 broilers. Diets high in tannin had low AMEn, ECR, DMR and NR (p < 0.001). Feeding field beans increased (p < 0.001) the weights of the pancreas and the proventriculus and gizzard (PG) of the birds. Supplementing diets with the enzyme mixture improved (p < 0.001) feed conversion efficiency, AMEn and all nutrient utilisation coefficients despite the tannins in diets. The enzyme mixture reduced ileal digesta viscosity (p < 0.001) and the weight of pancreas, total GIT and PG (p < 0.05) of the birds. It can be concluded that the feeding value of field beans with different tannin contents may vary when fed to broilers. The supplementation of the enzyme mixture improved the feeding value of diets for broilers. The beneficial effect of the addition of the enzyme mixture seems to be mediated through reduced ileal digesta viscosity and improved nutrient availability.

PREMM: preterm early massage by the mother: protocol of a randomised controlled trial of massage therapy in very preterm infants.

BACKGROUND: Preterm infants follow an altered neurodevelopmental trajectory compared to their term born peers as a result of the influence of early birth, and the altered environment. Infant massage in the preterm infant has shown positive effects on weight gain and reduced length of hospital stay. There is however, limited current evidence of improved neurodevelopment or improved attachment, maternal mood or anxiety. The aim of this study is to investigate the effects of infant massage performed by the mother in very preterm (VPT) infants. Effects on the infant will be assessed at the electrophysiological, neuroradiological and clinical levels.  Effects on maternal mood, anxiety and mother-infant attachment will also be measured. METHODS/DESIGN: A randomised controlled trial to investigate the effect of massage therapy in VPT infants. Sixty VPT infants, born at 28 to 32 weeks and 6 days gestational age, who are stable, off supplemental oxygen therapy and have normal cranial ultrasounds will be recruited and randomised to an intervention (infant massage) group or a control (standard care) group. Ten healthy term born infants will be recruited as a reference comparison group. The intervention group will receive standardised massage therapy administered by the mother from recruitment, until term equivalent age (TEA). The control group will receive care as usual (CAU). Infants and their mothers will be assessed at baseline, TEA, 12 months and 24 months corrected age (CA), with a battery of clinical, neuroimaging and electrophysiological measures, as well as structured questionnaires, psychoanalytic observations and neurodevelopmental assessments. DISCUSSION: Optimising preterm infant neurodevelopment is a key aim of neonatal research, which could substantially improve long-term outcomes and reduce the socio-economic impact of VPT birth. This study has the potential to give insights into the mother-baby relationship and any positive effects of infant massage on neurodevelopment. An early intervention such as massage that is relatively easy to administer and could alter the trajectory of preterm infant brain development, holds potential to improve neurodevelopmental outcomes in this vulnerable population. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12612000335897 . Date registered: 22/3/2012.

Nutritional value of raw and micronised field beans (Vicia faba L. var. minor) with and without enzyme supplementation containing tannase for growing chickens.

An experiment examined the effects of two field bean cultivar samples with different tannin contents, the effect of heat treatment (micronising) and the effect of dietary supplementation of a proprietary enzyme preparation containing tannase, pectinase, and xylanase activities on metabolisable energy (ME), total tract dry matter digestibility (DMD) and ether extract digestibility (EED), nitrogen retention (NR), tannin degradability, gastrointestinal tract (GIT) development, and endogenous mucin losses excretion in broiler chickens. The Control diet contained per kg 221 g crude protein and 12.83 MJ ME. Four additional diets contained 300 g/kg of each of the two untreated or micronised experimental field bean cultivar samples. Each diet was then split into two batches and one of them was supplemented with 3400 units tannase per kg diet resulting in 10 diets in total. Each diet was fed to seven pens with two randomly selected male broilers each. Birds fed the high tannin bean sample had a lower weight gain (p < 0.001), and a lower determined apparent ME (p < 0.05), and DMD (p < 0.001) but a higher tannin degradability (p < 0.001). Compared to the Control diet, feeding field beans increased (p < 0.001) the weights of the proventriculus and gizzard of the birds, and also increased endogenous mucin losses (p < 0.05). Supplementing diets with the tannase-containing enzyme preparation improved dietary ME (p < 0.001), DMD (p < 0.001), NR (p < 0.001) and DEE (p < 0.05), but did not change tannin degradability. Heat treatment of the beans reduced the degradability of condensed tannins and increased endogenous mucin losses (p < 0.05). The differences in the feeding value of the different field bean samples were not improved by heat treatment, but enzyme supplementation improved the feeding value of all diets regardless of the bean samples or heat treatment. Further research is warranted to study the effectiveness of tannase supplementation in poultry diet formulations by dose response trials with purified tannase preparations.

Extent of altered white matter in unilateral and bilateral periventricular white matter lesions in children with unilateral cerebral palsy.

AIMS: To investigate the extent of white matter damage in children with unilateral cerebral palsy (UCP) caused by periventricular white matter lesions comparing between unilateral and bilateral lesions; and to investigate a relationship between white matter microstructure and hand function. METHODS AND PROCEDURES: Diffusion MRI images from 46 children with UCP and 18 children with typical development (CTD) were included. Subjects were grouped by side of hemiparesis and unilateral or bilateral lesions. A voxel-wise white matter analysis was performed to identify regions where fractional anisotropy (FA) was significantly different between UCP groups and CTD; and where FA correlated with either dominant or impaired hand function (using Jebsen Taylor Hand Function Test). OUTCOMES AND RESULTS: Children with unilateral lesions had reduced FA in the corticospinal tract of the affected hemisphere. Children with bilateral lesions had widespread reduced FA extending into all lobes. In children with left hemiparesis, impaired hand function correlated with FA in the contralateral corticospinal tract. Dominant hand function correlated with FA in the posterior thalamic radiations as well as multiple other regions in both left and right hemiparesis groups. CONCLUSIONS AND IMPLICATIONS: Periventricular white matter lesions consist of focal and diffuse components. Focal lesions may cause direct motor fibre insult resulting in motor impairment. Diffuse white matter injury is heterogeneous, and may contribute to more global dysfunction.

Mitii™ ABI: study protocol of a randomised controlled trial of a web-based multi-modal training program for children and adolescents with an Acquired Brain Injury (ABI).

BACKGROUND: Acquired brain injury (ABI) refers to multiple disabilities arising from damage to the brain acquired after birth. Children with an ABI may experience physical, cognitive, social and emotional-behavioural impairments which can impact their ability to participate in activities of daily living (ADL). Recent developments in technology have led to the emergence of internet-delivered therapy programs. "Move it to improve it" (Mitii™) is a web-based multi-modal therapy that comprises upper limb (UL) and cognitive training within the context of meaningful physical activity. The proposed study aims to compare the efficacy of Mitii™ to usual care to improve ADL motor and processing skills, gross motor capacity, UL and executive functioning in a randomised waitlist controlled trial. METHODS/DESIGN: Sixty independently ambulant children (30 in each group) at least 12 months post ABI will be recruited to participate in this trial. Children will be matched in pairs at baseline and randomly allocated to receive either 20 weeks of Mitii™ training (30 min per day, six days a week, with a potential total dose of 60 h) immediately, or be waitlisted for 20 weeks. Outcomes will be assessed at baseline, immediately post-intervention and at 20 weeks post-intervention. The primary outcomes will be the Assessment of Motor and Process Skills and 30 s repetition maximum of functional strength exercises (sit-to-stand, step-ups and half kneel to stand). Measures of body structure and functions, activity, participation and quality of life will assess the efficacy of Mitii™ across all domains of the International Classification of Functioning, Disability and Health framework. A subset of children will undertake three tesla (3T) magnetic resonance imaging scans to evaluate functional neurovascular changes, structural imaging, diffusion imaging and resting state functional connectivity before and after intervention. DISCUSSION: Mitii™ provides an alternative approach to deliver intensive therapy for children with an ABI in the convenience of the home environment. If Mitii™ is found to be effective, it may offer an accessible and inexpensive intervention option to increase therapy dose. TRIAL REGISTRATION: ANZCTR12613000403730.

Changes in the integrity of thalamocortical connections are associated with sensorimotor deficits in children with congenital hemiplegia.

Preservation of thalamocortical projections to the sensorimotor cortex is related to improved hand function in children with cerebral palsy (CP). Whether CP is associated with altered microstructure of these sensorimotor projections or other thalamocortical pathways remains unclear. Forty-two children with congenital hemiplegia and fifteen typically developing children (TDC) underwent structural and diffusion-weighted imaging (high-angular-resolution diffusion imaging) using a 3T MRI. Structural T1-images were parcellated into 34 cortical regions and the thalamus per hemisphere. Thalamocortical projections were extracted using probabilistic tractography and the top tan cortical regions with the greatest number of thalamocortical streamlines for the TDC group were selected for further analysis. The thalamus was parcellated based on its cortical connections. Differences between hemispheres for thalamocortical streamline numbers to each cortical region [asymmetry index (AI)], tract volume and tract microstructure [weighted mean fractional anisotropy (FA) and mean diffusivity (MD)] were calculated. Correlations between these measures (AI, FA and MD) and sensorimotor function were performed. Thalamocortical projections showed topographical organisation based on cortical connectivity. Projections to paracentral lobule, pre-central and post-central gyri showed greater AI in CP group, which indicates reduced streamlines on the ipsilesioned hemisphere. Reduced FA, reduced tract volume and increased MD were also found for these thalamocortical projections on the ipsilesioned hemisphere in children with CP. Changes in AI and tract microstructure of these projections were associated with poorer sensorimotor function. The findings suggest CP is associated with reorganisation of thalamocortical projections to the sensorimotor cortex. Integrity in these projections may underpin deficits in sensorimotor function.

Quantitative comparison of cortical and deep grey matter in pathological subtypes of unilateral cerebral palsy.

AIM: The aim of this study was to quantify grey matter changes in children with unilateral cerebral palsy (UCP), differentiating between cortical or deep grey matter (CDGM) lesions, periventricular white matter (PWM) lesions, and unilateral and bilateral lesions. METHOD: In a cross-sectional study we obtained high resolution structural magnetic resonance images from 72 children (41 males, 31 females, mean age 10y 9mo [SD 3y 1mo], range 5y 1mo-17y 1mo) with UCP (33 left, 39 right hemiplegia; Manual Ability Classification System level I n=29, II n=43; Gross Motor Function Classification System level I n=46, II n=26), and 19 children with typical development (CTD; eight males, 11 females, mean age 11y 2mo [SD 2y 7mo], range 7y 8mo-16y 4mo). Images were classified by lesion type and analyzed using voxel-based morphometry (VBM) and subcortical volumetric analysis. RESULTS: Deep grey matter volumes were not significantly different between children with CDGM and PWM lesions, with the thalamus, putamen, and globus pallidus being reduced unilaterally in both groups compared with CTD (p≤0.001). Children with CDGM lesions additionally showed widespread cortical changes involving all lobes using VBM (p<0.01). Children with bilateral lesions had reduced thalamus and putamen volumes bilaterally (p<0.001). The thalamic volume was reduced bilaterally in children with unilateral lesions (p=0.004). INTERPRETATION: Lesions to the PWM cause secondary changes to the deep grey matter structures similar to primary changes seen in CDGM lesions. Despite having a unilateral phenotype, grey matter changes are observed bilaterally, even in children with unilateral lesions.

MRI structural connectivity, disruption of primary sensorimotor pathways, and hand function in cerebral palsy.

Brain injury and subsequent plasticity of sensory and corticospinal pathways play an integral role in determining paretic hand function in congenital hemiplegia. There is limited knowledge regarding the relationship between the disruption of sensorimotor thalamic pathways projecting into the primary motor cortex and motor control. This study sought to investigate the relationship between the structural connectivity of motor networks that anatomically link the brain stem with the precentral and postcentral gyri with paretic motor sensory function by using an automated analysis strategy. Magnetic resonance imaging structural connectivity was measured by using high-angular-resolution diffusion imaging, probabilistic tractography, and the anatomic parcellation of high-resolution structural images in 16 children with congenital unilateral periventricular white-matter damage. Connectivity of the corticospinal and corticothalamic pathways was determined by using an asymmetry index based on the number of streamlines contained within these projections and compared with measures of paretic hand function and bimanual coordination. For cortical development, the volume of the ipsilesional precentral gyrus was significantly reduced. For connectivity measures, the numbers of streamlines in corticospinal tracts and corticothalamic pathways within the ipsilesional hemisphere were decreased compared with the contralesional side. The sensorimotor thalamic projections were more significantly correlated with paretic hand functions than were the corticospinal tracts. These data support the concept that preservation of sensorimotor thalamic pathways that directly project into the primary motor cortex has more influence on motor function control of the paretic hand than does preservation of corticospinal tracts.

Increased cerebral lactate during hypoxia may be neuroprotective in newborn piglets with intrauterine growth restriction.

Intrauterine growth restriction (IUGR) can increase susceptibility to perinatal hypoxic brain injury for reasons that are unknown. Previous studies of the neonatal IUGR brain have suggested that the cerebral mitochondrial capacity is reduced but the glycolytic capacity increased relative to normal weight (NW) neonates. In view of these two factors, we hypothesized that the generation of brain lactate during a mild hypoxic insult would be greater in neonatal IUGR piglets compared to NW piglets. Brain lactate/N-acetylaspartate (NAA) ratios and apparent diffusion coefficients (ADCs) were determined by proton magnetic resonance spectroscopy and imaging of the brain before, during and after hypoxia in seven neonatal piglets with asymmetric IUGR and six NW piglets. During hypoxia, IUGR piglets had significantly higher brain lactate/NAA ratios than NW piglets (P=0.046). The lactate response in the IUGR piglets correlated inversely with apoptosis in the thalamus and frontal cortex of the brain measured 4 h post hypoxia (Pearson's r=0.86, P<0.05). Apoptosis in IUGR piglets with high brain lactate was similar to that in the NW piglets whereas IUGR piglets with low brain lactate had significantly higher apoptosis than NW piglets (P=0.019). ADCs in the high lactate IUGR piglets were significantly lower during hypoxia than in all the other piglets. This signifies increased diffusion of water into brain cells during hypoxia, possibly in response to increased intracellular osmolality caused by high intracellular lactate concentrations. These findings support previous studies showing increased susceptibility to hypoxic brain injury in IUGR neonates but suggest that increased glycolysis during hypoxia confers neuroprotection in some IUGR piglets.