Partially divided caging reduces overall aggression and anxiety which may indicate improved welfare in group housed male C57BL/6J mice.

Deciding which environmental enrichment is used in mouse caging is often subjective, with cost frequently prevailing over welfare benefits, including aggression and anxiety. While many devices introduced to encourage natural behaviors and reduce aggression show mixed results, we have previously demonstrated significant reductions in aggressive behavior between group-housed male mice housed in partially divided caging. To further assess behavior, we have raised male C57BL/6J mice in either partially divided caging or in standard caging with no divider. Animal behavior was tested on rotarod, open field, novel object recognition, elevated plus maze, and Y maze. Body weights were taken weekly beginning at weaning and bite wounds were counted weekly beginning at 133 days old. Aggressive behavior was recorded weekly beginning at 133 days old. Results indicated significantly less anxiety in the elevated-plus maze, statistically fewer bite wounds, and a statistically significant decrease in aggressive behaviors of mice in partially divided caging compared to mice in standard cages. We conclude that reductions in anxiety, aggressive behavior, and bite wounds may indicate improved overall welfare for non-sibling, group housed male mice.

Relation of pain sensitization to self-reported and performance-based measures of physical functioning: the Multicenter Osteoarthritis (MOST) study.

OBJECTIVE: It is unclear if alterations in nociceptive signaling contribute to poor physical functioning in persons with knee osteoarthritis (OA). We aimed to characterize the relation of pain sensitization to physical functioning in persons with or at risk for knee OA, and determine if knee pain severity mediates these relationships. MATERIALS AND METHODS: We used cross-sectional data from the Multicenter Osteoarthritis Study, a cohort study of persons with or at risk for knee OA. Pressure pain thresholds (PPTs) and temporal summation (TS) were assessed with quantitative sensory testing. Self-reported function was quantified with the Western Ontario and McMaster Universities Arthritis Index function subscale (WOMAC-F). Walking speed was determined during a 20-m walk. Knee extension strength was assessed with dynamometry. Relations of PPTs and TS to functional outcomes were examined with linear regression. The mediating role of knee pain severity was assessed with mediation analyses. RESULTS: Among 1560 participants (60.5% female, mean age (SD) 67 (8), body mass index (BMI) 30.2 (5.5) kg/m2), lower PPTs and the presence of TS were associated with worse WOMAC-F scores, slower walking speeds, and weaker knee extension. The extent of mediation by knee pain severity was mixed, with the greatest mediation observed for self-report function and only minimally for performance-based function. CONCLUSIONS: Heightened pain sensitivity appears to be meaningfully associated with weaker knee extension in individuals with or at risk for knee OA. Relations to self-reported physical function and walking speed do not seem clinically meaningful. Knee pain severity differentially mediated these relationships.

Peg Forest Rehabilitation - A novel spatial navigation based cognitive rehabilitation paradigm for experimental neurotrauma.

Traumatic brain injury (TBI) results from mechanical forces applied to the head. Ensuing cascades of complex pathophysiology transition the injury event into a disease process. The enduring constellation of emotional, somatic, and cognitive impairments degrade quality of life for the millions of TBI survivors suffering from long-term neurological symptoms. Rehabilitation strategies have reported mixed results, as most have not focused on specific symptomatology or explored cellular processes. The current experiments evaluated a novel cognitive rehabilitation paradigm for brain-injured and uninjured rats. The arena is a plastic floor with a cartesian grid of holes for plastic dowels to create new environments with the rearrangement of threaded pegs. Rats received either two weeks of Peg Forest rehabilitation (PFR) or open field exposure starting at 7 days post-injury; or one week starting at either day 7 or 14 post-injury; or served as caged controls. Cognitive performance was assessed on a battery of novel object tasks at 28 days post-injury. The results revealed that two weeks of PFR was required to prevent the onset of cognitive impairments, while one week of PFR was insufficient regardless of when rehabilitation was initiated after injury. Further assessment of the task showed that novel daily arrangements of the environment were required to impart the cognitive performance benefits, as exposure to a static arrangement of pegs for PFR each day did not improve cognitive performance. The results indicate that PFR prevents the onset of cognitive disorders following acquired a mild to moderate brain injury, and potentially other neurological conditions.

Depressive symptoms and multi-joint pain partially mediate the relationship between obesity and opioid use in people with knee osteoarthritis.

OBJECTIVES: To assess the relation of obesity to opioid use in people with or at risk of knee osteoarthritis (OA), and the extent to which this association is mediated by number of painful joints or depressive symptoms. METHODS: We used data from the Multicenter Osteoarthritis Study, a longitudinal cohort of older adults with or at risk of knee OA. Opioid use was identified by prescription medications and self-report. Obesity was defined as BMI ≥ 30 kg/m2. Multi-joint pain was assessed using a standardized body homunculus, and depressive symptoms using the Center for Epidemiological Studies Depression scale. We quantified the direct and indirect effect of obesity on opioid use through the number of painful joints or depressive symptoms using causal mediation analysis by natural-effects models. RESULTS: We studied 2,335 participants (mean age: 68; mean BMI 31 kg/m2; 60% women). Persons with obesity had ∼50% higher odds of opioid use than those without. Estimates of indirect (mediated) effect by the number of painful joints and depressive symptoms suggested an increased odds of opioid use by 34% (odds ratio [OR] = 1.34, 95% CI: 1.04, 1.70) and 35% (OR 1.35, 95% CI: 1.05, 1.71), respectively, in obese vs non-obese individuals. The total effect of obesity on opioid use was higher in women than in men. CONCLUSIONS: Multi-joint pain and depressive symptoms partially explained greater opioid use among obese persons with knee OA, demonstrating that the negative impact of obesity on knee OA extends beyond its influence on knee pain and structural progression.

Time Course of Remote Neuropathology Following Diffuse Traumatic Brain Injury in the Male Rat.

Traumatic brain injury (TBI) can affect different regions throughout the brain. Regions near the site of impact are the most vulnerable to injury. However, damage to distal regions occurs. We investigated progressive neuropathology in the dorsal hippocampus (near the impact) and cerebellum (distal to the impact) after diffuse TBI. Adult male rats were subjected to midline fluid percussion injury or sham injury. Brain tissue was stained by the amino cupric silver stain. Neuropathology was quantified in sub-regions of the dorsal hippocampus at 1, 7, and 28 days post-injury (DPI) and coronal cerebellar sections at 1, 2, and 7 DPI. The highest observed neuropathology in the dentate gyrus occurred at 7 DPI which attenuated by 28 DPI, whereas the highest observed neuropathology was at 1 DPI in the CA3 region. There was no significant neuropathology in the CA1 region at any time point. Neuropathology was increased at 7 DPI in the cerebellum compared to shams and stripes of pathology were observed in the molecular layer perpendicular to the cerebellar cortical surface. Together these data show that diffuse TBI can result in neuropathology across the brain. By describing the time course of pathology in response to TBI, it is possible to build the temporal profile of disease progression.

Chronic Cognitive and Cerebrovascular Function after Mild Traumatic Brain Injury in Rats.

Severe traumatic brain injury (TBI) results in cognitive dysfunction in part due to vascular perturbations. In contrast, the long-term vasculo-cognitive pathophysiology of mild TBI (mTBI) remains unknown. We evaluated mTBI effects on chronic cognitive and cerebrovascular function and assessed their interrelationships. Sprague-Dawley rats received midline fluid percussion injury (n = 20) or sham (n = 21). Cognitive function was assessed (3- and 6-month novel object recognition [NOR], novel object location [NOL], and temporal order object recognition [TOR]). Six-month cerebral blood flow (CBF) and cerebral blood volume (CBV) using contrast magnetic resonance imaging (MRI) and ex vivo circle of Willis artery endothelial and smooth muscle-dependent function were measured. mTBI rats showed significantly impaired NOR, with similar trends (non-significant) in NOL/TOR. Regional CBF and CBV were similar in sham and mTBI. NOR correlated with CBF in lateral hippocampus, medial hippocampus, and primary somatosensory barrel cortex, whereas it inversely correlated with arterial smooth muscle-dependent dilation. Six-month baseline endothelial and smooth muscle-dependent arterial function were similar among mTBI and sham, but post-angiotensin 2 stimulation, mTBI showed no change in smooth muscle-dependent dilation from baseline response, unlike the reduction in sham. mTBI led to chronic cognitive dysfunction and altered angiotensin 2-stimulated smooth muscle-dependent vasoreactivity. The findings of persistent pathophysiological consequences of mTBI in this animal model add to the broader understanding of chronic pathophysiological sequelae in human mild TBI.

Association between hamstring coactivation during isokinetic quadriceps strength testing and knee cartilage worsening over 24 months.

OBJECTIVE: This study aimed to determine longitudinal associations, including sex-specific differences, between greater knee flexor antagonist coactivation and worsening cartilage morphology in knees with or at risk for osteoarthritis (OA). DESIGN: Baseline measurements were collected at the 60-month visit of a longitudinal osteoarthritis study following community-dwelling participants (MOST). Knee flexor and extensor muscle activity were measured with surface electromyography during a maximal isokinetic knee extension task. MRI analyzed knee cartilage morphology at baseline and 24-month follow-up. Multivariable adjusted logistic regression models were used to assess associations between coactivation level and cartilage morphology worsening. RESULTS: Analysis of 373 women (mean ± SD age 67.4 ± 7.3 years and BMI 29.7 ± 5.0 kg/m2) and 240 men (66.5 ± 7.8 years and 29.9 ± 4.5 kg/m2) revealed that women had greater medial (P < 0.001), lateral (P < 0.001), and combined (P < 0.001) hamstring coactivation than men. In both sexes, combined hamstring coactivation was associated with patellofemoral cartilage morphology worsening [1.23 (1.02, 1.49)] and to a less significant degree with whole knee cartilage morphology worsening [1.21 (0.98, 1.49)]. In men, greater combined hamstring coactivation was associated with increased risk for whole knee [1.59 (1.06, 2.39)] and patellofemoral [1.38 (1.01, 1.88)] cartilage morphology worsening and point estimates suggested association between medial hamstring coactivation and medial tibiofemoral cartilage morphology worsening. No significant associations were detected between greater hamstring coactivation and cartilage morphology worsening in women. CONCLUSIONS: These findings suggest a longitudinal relationship between antagonist hamstring coactivation during isokinetic knee extensor testing and worsening of cartilage morphology over 24 months in men with or at risk for knee OA.

The limbic memory circuit and the neural basis of contextual memory.

The hippocampus, retrosplenial cortex and anterior thalamus are key components of a neural circuit known to be involved in a variety of memory functions, including spatial, contextual and episodic memory. In this review, we focus on the role of this circuit in contextual memory processes. The background environment, or context, is a powerful cue for memory retrieval, and neural representations of the context provide a mechanism for efficiently retrieving relevant memories while avoiding interference from memories that belong to other contexts. Data from experimental lesions and neural manipulation techniques indicate that each of these regions is critical for contextual memory. Neurophysiological evidence from the hippocampus and retrosplenial cortex suggest that contextual information is represented within this circuit by population-level neural firing patterns that reliably differentiate each context a subject encounters. These findings indicate that encoding contextual information to support context-dependent memory retrieval is a key function of this circuit.

Does weight-bearing versus non-weight-bearing pain reflect different pain mechanisms in knee osteoarthritis?: the Multicenter Osteoarthritis Study (MOST).

OBJECTIVE: Knee osteoarthritis (OA) is predominantly characterized by pain with weight-bearing activities. Pain at rest also occurs but the mechanisms for this are not clear. We evaluated the relations of nociceptive signal alterations to weight-bearing and non-weight-bearing pain in knee OA. DESIGN: We used data from a NIH-funded longitudinal cohort of older adults with or at risk of knee OA. We evaluated quantitative sensory testing (QST) measures (pressure pain threshold (PPT) at patellae and the wrist; mechanical temporal summation (TS); conditioned pain modulation (CPM)). Each WOMAC pain question was dichotomized as having at least moderate pain, and we further categorized them as weight-bearing pain and non-weight-bearing pain. We evaluated the relation of QST measures to each pain outcome using logistic regression, adjusting for potential confounders. RESULTS: 2,749 participants (5,479 knees) were included (mean age 64 ± 11, 57% female). Each SD unit decrease in patellar PPT was associated with greater odds of both weight-bearing pain (OR 1.51 (95% CI 1.27, 1.79)) and non-weight-bearing pain (OR 1.46 (1.20-1.77)), while wrist PPT was associated with greater odds of weight-bearing pain (OR 1.27 (1.15, 1.39)) but only with pain during sitting/lying (OR 1.20 (1.01, 1.43)). TS was significantly associated with greater odds of pain with walking and stairs (OR 1.11 (1.01, 1.23), 1.11 (1.03, 1.20), respectively). CPM was not associated with any pain outcomes. CONCLUSIONS: Our findings challenge the hypothesis that non-weight-bearing pain may reflect greater pain sensitization and/or inefficient CPM than weight-bearing pain in knee OA, suggesting other mechanisms are likely responsible.

Is the association between physical activity and fatigue mediated by physical function or depressive symptoms in symptomatic knee osteoarthritis? The Multicenter Osteoarthritis Study.

Objectives: To examine whether physical activity (PA) was associated with fatigue, and quantify the extent of potential mediation through depressive symptoms or physical function (PF) on the relationship between PA and fatigue in symptomatic knee osteoarthritis (KOA).Method: This longitudinal study used data from the Multicenter Osteoarthritis Study (n = 484), comprising subjects aged ≥ 50 years. Baseline PA was quantified via an ankle-worn accelerometer. The outcome was fatigue, measured using a 0-10 rating scale at 2 year follow-up. Mediators included gait speed as a measure of PF and depressive symptoms at 2 year follow-up. Mediation analysis was carried out after adjustment for baseline confounders. Stratified analysis by baseline fatigue status [no/low (< 4) and high (≥ 4) fatigue] was performed.Results: A significant direct association was found between PA and fatigue at 2 years [unstandardized coefficient (B) = -0.054; 95% confidence interval (CI) -0.107, -0.002, p = 0.041]. The PA-fatigue relationship was not mediated by gait speed (B = -0.006; 95% CI -0.018, 0.001) or depressive symptoms (B = 0.009; 95% CI 0.009, 0.028). In the subgroup with high baseline fatigue, direct associations were found between PA and fatigue (gait speed model:, B = -0.107; 95% CI -0.212, -0.002, p = 0.046; depressive symptoms model: B = -0.110; 95% CI -0.120, -0.020, p = 0.017); but in the no/low baseline fatigue group, no significant association was found between PA and fatigue.Conclusion: In the symptomatic KOA population, higher baseline PA was directly associated with reduced fatigue 2 years later, especially in those with high baseline fatigue. However, this relationship was not mediated by depressive symptoms or PF.

The association between walking speed from short- and standard-distance tests with the risk of all-cause mortality among adults with radiographic knee osteoarthritis: data from three large United States cohort studies.

OBJECTIVE: Adults with radiographic knee OA (rKOA) are at increased risk of mortality and walking difficulty may modify this relation. Little is known about specific aspects of walking difficulty that increase mortality risk. We investigated the association of walking speed (objective measure of walking difficulty) with mortality and examined the threshold that best discriminated this risk in adults with rKOA. METHODS: Participants with rKOA from the Johnston County Osteoarthritis Project (JoCoOA, longitudinal population-based cohort), Osteoarthritis Initiative and Multicenter Osteoarthritis Study (OAI and MOST, cohorts of individuals with or at high risk of knee OA) were included. Baseline speed was measured via 2.4-meter (m) walk test (short-distance) in JoCoOA and 20-m walk test (standard-distance) in OAI and MOST. To examine the association of walking speed with mortality risk over 9 years, hazard ratios (HR) and 95% confidence intervals (CI) were calculated from Cox regression models adjusted for potential confounders. A Maximal Likelihood Ratio Chi-square Approach was utilized to identify an optimal threshold of walking speed predictive of mortality. RESULTS: Deaths after 9 years of follow-up occurred in 23.3% (290/1244) of JoCoOA and 5.9% (249/4215) of OAI + MOST. Walking 0.2 m/s slower during short- and standard-distance walk tests was associated with 23% (aHR [95%CI]; 1.23 [1.10, 1.39]) and 25% (1.25 [1.09, 1.43]) higher mortality risk, respectively. Walking <0.5 m/s on short-distance and <1.2 m/s standard-distance walk tests, best discriminated those with and without mortality risk. CONCLUSION: Slower walking speed measured via short- and standard-distance walk tests was associated with increased mortality risk in adults with rKOA.

The relation of peripheral and central sensitization to muscle co-contraction: the MOST study.

OBJECTIVE: To examine the relation of pain sensitization to altered motor activity in knee OA as assessed by hamstrings muscle co-contraction during maximal effort knee extension. DESIGN: Medial, lateral, and overall hamstring co-contraction was assessed in the Multicenter Osteoarthritis (MOST) Study cohort using electromyography during isokinetic knee extension at 60°/second. Mechanical temporal summation of pain (TS) was assessed at the right wrist and pressure pain thresholds (PPT) were assessed at the patellae; PPTs were categorized into sex-specific tertiles. Muscle co-contraction was categorized into age- and sex-specific tertiles. We evaluated the relation of measures of sensitization to muscle co-contraction using a generalized logistic regression model. RESULTS: 1633 participants were included: mean age and BMI was 67.3 ± 7.7 years and 30.3 ± 5.6 kg/m2, respectively; 58% were female. Presence of TS was associated with higher overall (OR 1.3, 95% confidence interval (CI) (1.0-1.8)), medial (1.4 (1.0-1.9), and lateral (1.3 (1.0, 1.9)) hamstring co-contraction. The lowest PPT tertile (greater sensitivity) was associated with higher overall (1.5 (1.0, 2.3)) and medial (1.5 (1.0, 2.3)) hamstring co-contraction compared with those in the highest PPT tertile. CONCLUSION: Greater pain sensitization, as assessed by presence of TS at the wrist and low patellar PPT, was associated with greater overall and medial hamstring co-contraction during knee extension. This provides support to the possibility that peripheral and/or central nervous system alterations may not only affect pain sensitivity, but also motor function.

Hippocampal state transitions at the boundaries between trial epochs.

The hippocampus encodes distinct contexts with unique patterns of activity. Representational shifts with changes in context, referred to as remapping, have been extensively studied. However, less is known about transitions between representations. In this study, we leverage a large dataset of neuronal recordings taken while rats performed an olfactory memory task with a predictable temporal structure involving trials and intertrial intervals (ITIs), separated by salient boundaries at the trial start and trial end. We found that trial epochs were associated with stable hippocampal representations despite moment-to-moment variability in stimuli and behavior. Representations of trial and ITI epochs were far more distinct than spatial factors would predict and the transitions between the two were abrupt. The boundary was associated with a large spike in multiunit activity, with many individual cells specifically active at the start or end of each trial. Both epochs and boundaries were encoded by hippocampal populations, and these representations carried information on orthogonal axes readily identified using principal component analysis. We suggest that the hippocampus orthogonalizes representations of the trial and ITI epochs and the activity spike at trial boundaries might serve to drive hippocampal activity from one stable state to the other.

Partial cage division significantly reduces aggressive behavior in male laboratory mice.

Aggression in mice often results in injury leading to unplanned euthanasia or the initiation of protocols to isolate animals, thereby increasing research costs and straining resources. Here, we tested if adding a partial cage divider into existing mouse cages affected aggressive-like behavior in group-housed male mice (18 mice; 3 per cage). Mice were randomly assigned to one of two groups upon arrival to the vivarium: (1) standard cage; (2) cage with a partial cage divider. Behavioral observation over 12 hours were conducted at day one, two, and seven after receipt at the facility in order to assess aggression during the course of establishing dominance hierarchies. Observers blinded to study design and hypothesis scored each video for the number and type of aggressive behaviors, which were summed for each hour and analyzed. Results indicated a statistically significant decrease in aggressive behaviors of mice in cages with dividers compared to mice in standard cages. We conclude that cage dividers, which resemble burrows and provide access to common food/water, may promote rigorous research by reducing the number of animals used in a study and refining housing, thus, improving animal welfare.

The small-molecule MERTK inhibitor UNC2025 decreases platelet activation and prevents thrombosis.

Essentials Signaling by Gas6 through Tyro3/Axl/Mer receptors is essential for stable platelet aggregation. UNC2025 is a small molecule inhibitor of the Mer tyrosine kinase. UNC2025 decreases platelet activation in vitro and thrombus formation in vivo. UNC2025's anti-platelet effect is synergistic with inhibition of the ADP receptor, P2Y12 . SUMMARY: Background Growth arrest-specific protein 6 signals through the TAM (TYRO-3-AXL-MERTK) receptor family, mediating platelet activation and thrombus formation via activation of the aggregate-stabilizing αIIb ß3 integrin. Objective To describe the antithrombotic effects mediated by UNC2025, a small-molecule MERTK tyrosine kinase inhibitor. Methods MERTK phosphorylation and downstream signaling were assessed by immunoblotting. Light transmission aggregometry, flow cytometry and microfluidic analysis were used to evaluate the impact of MERTK inhibition on platelet activation and stability of aggregates in vitro. The effects of MERTK inhibition on arterial and venous thrombosis, platelet accumulation at microvascular injury sites and tail bleeding times were determined with murine models. The effects of combined treatment with ADP-P2Y1&12 pathway antagonists and UNC2025 were also evaluated. Results and Conclusions Treatment with UNC2025 inhibited MERTK phosphorylation and downstream activation of AKT and SRC, decreased platelet activation, and protected animals from pulmonary embolism and arterial thrombosis without increasing bleeding times. The antiplatelet effect of UNC2025 was enhanced in combination with ADP-P2Y1&12 pathway antagonists, and a greater than additive effect was observed when these two agents with different mechanisms of inhibition were coadministered. TAM kinase signaling represents a potential therapeutic target, as inhibition of this axis, especially in combination with ADP-P2Y pathway antagonism, mediates decreased platelet activation, aggregate stability, and thrombus formation, with less hemorrhagic potential than current treatment strategies. The data presented here also demonstrate antithrombotic activity mediated by UNC2025, a novel translational agent, and support the development of TAM kinase inhibitors for clinical applications.

First trimester screening for pre-eclampsia in Chinese pregnancies: case-control study.

OBJECTIVE: To assess the potential of screening for pre-eclampsia (PE) in a Chinese population. DESIGN: Case-control study. SETTING: Teaching hospital in Hong Kong. POPULATION: A total of 3330 women having a viable singleton pregnancy attending first-trimester Down-syndrome screening. METHODS: Mean arterial pressure (MAP), bilateral uterine artery pulsatility index (UtA-PI), and placental growth factor (PlGF) were measured. Screening markers were transformed to multiples of the gestational median (MoM) and adjusted for maternal and pregnancy characteristics. MoM distributions in PE and non-PE pregnancies were compared with published expected values. PE screening performance was assessed using area under receiver operating curves (AUROC). MAIN OUTCOME MEASURES: PE detection rate. RESULTS: A total of 30 (0.9%) women developed either early (<34 weeks) or late (≥34 weeks) onset PE. MAP was dependent on maternal BMI, UtA-PI on fetal crown rump length, uterine artery peak systolic velocity (UtA-PSV) on maternal age and gestation, and PlGF on gestation in non-PE pregnancies. MoM distributions determined using published Fetal Medicine Foundation models deviated significantly from one for both MAP (P < 0.0001) and PI (P < 0.0001), but not PlGF (P = 0.52) in non-PE pregnancies, whilst PlGF MoM distributions in those who developed early as opposed to late onset PE were significantly higher (P = <0.05). AUROC for any PE using multiple markers was 0.72 (95% CI: 0.64-0.81) with detection rates of 72 and 55% for early and late PE, respectively, for a 10% false positive rate. CONCLUSION: Detection rates for PE in our Chinese population were lower than the expected 90-95% even after adjusting MoM for local women's characteristics. FUNDING: General Research Fund (Project number 470513). TWEETABLE ABSTRACT: Pre-eclampsia screening in the Chinese population had detection rates lower than previously published results.

Rehabilitation modality and onset differentially influence whisker sensory hypersensitivity after diffuse traumatic brain injury in the rat.

BACKGROUND: As rehabilitation strategies advance as therapeutic interventions, the modality and onset of rehabilitation after traumatic brain injury (TBI) are critical to optimize treatment. Our laboratory has detected and characterized a late-onset, long-lasting sensory hypersensitivity to whisker stimulation in diffuse brain-injured rats; a deficit that is comparable to visual or auditory sensory hypersensitivity in humans with an acquired brain injury. OBJECTIVE: We hypothesize that the modality and onset of rehabilitation therapies will differentially influence sensory hypersensitivity in response to the Whisker Nuisance Task (WNT) as well as WNT-induced corticosterone (CORT) stress response in diffuse brain-injured rats and shams. METHODS: After midline fluid percussion brain injury (FPI) or sham surgery, rats were assigned to one of four rehabilitative interventions: (1) whisker sensory deprivation during week one or (2) week two or (3) whisker stimulation during week one or (4) week two. At 28 days following FPI and sham procedures, sensory hypersensitivity was assessed using the WNT. Plasma CORT was evaluated immediately following the WNT (aggravated levels) and prior to the pre-determined endpoint 24 hours later (non-aggravated levels). RESULTS: Deprivation therapy during week two elicited significantly greater sensory hypersensitivity to the WNT compared to week one (p < 0.05), and aggravated CORT levels in FPI rats were significantly lower than sham levels. Stimulation therapy during week one resulted in low levels of sensory hypersensitivity to the WNT, similar to deprivation therapy and naïve controls, however, non-aggravated CORT levels in FPI rats were significantly higher than sham. CONCLUSION: These data indicate that modality and onset of sensory rehabilitation can differentially influence FPI and sham rats, having a lasting impact on behavioral and stress responses to the WNT, emphasizing the necessity for continued evaluation of modality and onset of rehabilitation after TBI.

Expanded newborn metabolic screening programme in Hong Kong: a three-year journey.

INTRODUCTION: No universal expanded newborn screening service for inborn errors of metabolism is available in Hong Kong despite its long history in developed western countries and rapid development in neighbouring Asian countries. To increase the local awareness and preparedness, the Centre of Inborn Errors of Metabolism of the Chinese University of Hong Kong started a private inborn errors of metabolism screening programme in July 2013. This study aimed to describe the results and implementation of this screening programme. METHODS: We retrieved the demographics of the screened newborns and the screening results from July 2013 to July 2016. These data were used to calculate quality metrics such as call-back rate and false-positive rate. Clinical details of true-positive and false-negative cases and their outcomes were described. Finally, the call-back logistics for newborns with positive screening results were reviewed. RESULTS: During the study period, 30 448 newborns referred from 13 private and public units were screened. Of the samples, 98.3% were collected within 7 days of life. The overall call-back rate was 0.128% (39/30 448) and the false-positive rate was 0.105% (32/30 448). Six neonates were confirmed to have inborn errors of metabolism, including two cases of medium-chain acyl-coenzyme A dehydrogenase deficiency, one case of carnitine-acylcarnitine translocase deficiency, and three milder conditions. One case of maternal carnitine uptake defect was diagnosed. All patients remained asymptomatic at their last follow-up. CONCLUSION: The Centre of Inborn Errors of Metabolism has established a comprehensive expanded newborn screening programme for selected inborn errors of metabolism. It sets a standard against which the performance of other private newborn screening tests can be compared. Our experience can also serve as a reference for policymakers when they contemplate establishing a government-funded universal expanded newborn screening programme in the future.

Triplet pregnancy with fetal reduction: experience in Hong Kong.

INTRODUCTION: Triplet and higher-order multiple pregnancies are well known to be associated with increased adverse outcomes. This study reviewed the perinatal outcomes in women with a triplet pregnancy who underwent fetal reduction versus expectant management at a university hospital in Hong Kong. METHODS: This was a retrospective review of triplet pregnancies at Prince of Wales Hospital in Hong Kong from 1 January 2008 to 30 September 2014. Women carrying a triplet pregnancy were classified as having had expectant management, fetal reduction to twins, or fetal reduction to a singleton. Maternal and pregnancy characteristics were compared. Outcome measures included fetal loss, gestational age at delivery, birth weight, neonatal survival rate, neonatal death, neonatal complications, and need for and length of neonatal intensive care unit stay. RESULTS: A total of 52 triplet pregnancies were identified. One pregnancy that was lost to follow-up and one that was terminated were excluded. The majority of pregnancies (84%) were the result of assisted reproductive technology. Fetal reduction was performed in 26 (52%) pregnancies, of which 22 were reduced to twins and four to a singleton. The mean gestations at delivery were 32.6, 35.2, and 39.6 weeks in the expectant management, fetal reduction to twins, and fetal reduction to a singleton groups, respectively. Significantly more pregnancies with expectant management resulted in a preterm birth. All pregnancies with fetal reduction to a singleton resulted in a term birth. A higher mean birth weight, lower neonatal death rate, and reduced need for admission to and length of stay in the neonatal intensive care unit were observed in the fetal reduction groups. CONCLUSIONS: Approximately 50% of women with a triplet pregnancy in Hong Kong elected to undergo fetal reduction. This was associated with a significant reduction in extreme preterm delivery and associated morbidity and mortality.