Gross motor change after inpatient rehabilitation for children with acquired brain injury: A 10-year retrospective review.

AIM: To estimate gross motor change in inpatient school-aged children with subacute acquired brain injury (ABI), identify factors associated with gross motor change, and describe inpatient physiotherapy focus. METHOD: This retrospective chart review involved inpatient children (5-18 years) with subacute ABI who had either two Gross Motor Function Measure (GMFM-88) assessments or one GMFM-88 with another pre/post gross motor outcome measure. Outcome change scores and Goal Attainment Scaling (GAS) T scores were calculated. Regression analyses examined factors predicting gross motor change. GAS goal areas were analysed to determine physiotherapy focus. RESULTS: Of the 546 charts screened, 266 (118 female) met study criteria. The GMFM-88 was generally administered first, followed by other measures. GMFM-88 (n = 202), Community Balance and Mobility Scale (n = 89), and Six-Minute Walk Test (6MWT) (n = 98) mean change scores were 18.03% (SD 19.34), 17.85% (SD 10.77), and 142.3 m (SD 101.8) respectively. The mean GAS T score was 55.06 (SD 11.50). Lower baseline scores and increased time between assessments were most predictive of greater GMFM-88 change (r ≥ 0.40). Twenty-five percent of GAS goals were ambulation-based. INTERPRETATION: Appropriate outcome measure selection is integral to detecting gross motor change in pediatric inpatient ABI rehabilitation. Mean change score estimates can be used to compare standard inpatient rehabilitation with new treatment approaches.

MRI monitoring of transplanted neonatal porcine islets labeled with polyvinylpyrrolidone-coated superparamagnetic iron oxide nanoparticles in a mouse model.

Islet transplantation is a potential treatment option for certain patients with type 1 diabetes; however, it still faces barriers to widespread use, including the lack of tools to monitor islet grafts post-transplantation. This study investigates whether labeling neonatal porcine islets (NPI) with polyvinylpyrrolidone-coated superparamagnetic iron oxide nanoparticles (PVP-SPIO) affects their function, and whether this nanoparticle can be utilized to monitor NPI xenografts with magnetic resonance imaging (MRI) in a mouse model. In vitro, PVP-SPIO-labeled NPI in an agarose gel was visualized clearly by MRI. PVP-SPIO-labeled islets were then transplanted under the kidney capsules of immunodeficient nondiabetic and diabetic mice. All diabetic mice that received transplantation of PVP-SPIO-labeled islets reached normoglycemia. Grafts appeared as hypo-intense areas on MRI and were distinguishable from the surrounding tissues. Following injection of spleen cells from immunocompetent mice, normoglycemic recipient mice became diabetic and islet grafts showed an increase in volume, accompanied by a mixed signal on MRI. Overall, this study demonstrates that PVP-SPIO did not affect the function of NPI that PVP-SPIO-labeled islets were easily seen on MRI, and changes in MRI signals following rejection suggest a potential use of PVP-SPIO-labeled islets to monitor graft viability.

18F-Sodium Fluoride Imaging of Coronary Atherosclerosis in Ambulatory Patients With Diabetes Mellitus.

Objective- Although patients with diabetes mellitus (DM) are considered at high risk of cardiovascular events, there is growing evidence that this notion is incorrect. Atherosclerosis imaging may identify patients at risk. Approach and Results- We performed coronary atherosclerosis with 18F-sodium fluoride (NaF) positron emission tomography/computed tomography and gated chest computed tomography for coronary artery calcium in 88 consecutive ambulatory patients with DM on a stable medical regimen. NaF has been shown to localize avidly in culprit lesions of patients with acute coronary syndromes and may identify unstable plaques. NaF activity was measured as target (coronary arteries)-to-background (left ventricular pool) ratio (TBR). High TBR was defined as ≥1.5. The mean age of the cohort was 54±14 years, 55% had type 2 DM, 65% were men, the median HgbA1c (hemoglobin A1c) and LDL (low-density lipoprotein) cholesterol were 7.5% (interquartile range, 7.1-8.5) and 1.9 mmol/L (interquartile range, 1.5-2.6), respectively. Mean coronary artery calcium score was 374±773, and median TBR was 1.2. Coronary artery TBR ≥1.5 was detected in 13 (15%) patients. In univariable analyses, male sex ( P=0.0002), estimated glomerular filtration rate ( P=0.02), and total coronary artery calcium score ( P=0.04) were associated with TBR. In multivariable analyses, TBR >median was associated with male sex ( P=0.0001) and statin use ( P=0.042). Conclusions- In ambulatory patients with DM asymptomatic for cardiovascular disease, the prevalence of potentially vulnerable plaques detected with NaF was low, but in the absence of follow-up data at this stage, we cannot assess the import of this information. Future research will establish whether NaF imaging helps risk stratify patients with DM. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT03530176.

Initially Asymmetrical Function on MAG3 Renography Increases Incidence of Adverse Outcomes.

PURPOSE: To discriminate pathological from physiological hydronephrosis (99m)Tc-mercaptoacetyltriglycine (MAG3) diuretic renography is a fundamental imaging modality. Initial asymmetrical differential function or decreasing function on serial MAG3 scans is a classic surgical indication. However, prognostic evidence supporting this is limited. Therefore, we examined the association between initial function and outcomes. We hypothesized that patients with initially asymmetrical function would have higher odds of functional decline, and experience symptoms and surgical intervention compared to patients with initially symmetrical scans. MATERIALS AND METHODS: We retrospectively reviewed the charts of 1,124 pediatric patients with hydronephrosis seen at Stollery Children's Hospital from 2000 to 2014. A total of 387 cases of unilateral ureteropelvic junction obstruction were grouped by initial postnatal differential function with asymmetrical defined as a greater than 10% difference in relative function. Postnatal surveillance, followup MAG3 results, pyeloplasty rates and post-pyeloplasty outcomes were compared. RESULTS: Of 387 patients 143 (37%) had initially asymmetrical function. Of those undergoing MAG3 scan surveillance 17% experienced a 10% or greater decline in ipsilateral differential function vs a 6% rate of function loss in the initially symmetrical group (OR 3.2, 95% CI 1.6-6.4, p = 0.0008). The overall pyeloplasty rate in patients with asymmetrical and symmetrical function was 27% and 16%, respectively (OR 1.9, 95% CI 1.1-3.2, p = 0.013). Patients with initially asymmetrical function had an increased rate of pyeloplasty secondary to symptoms compared to those with initially symmetrical function (16% vs 8%, OR 2.1, 95% CI 1.1-4.0, p = 0.019). Mean time to functional decline and pyeloplasty was 19 and 17 months, respectively. CONCLUSIONS: Patients with initially asymmetrical differential function had increased ORs for subsequent renal decline, symptom onset and pyeloplasty.

Psychosocial consequences of mild traumatic brain injury in children: results of a systematic review by the International Collaboration on Mild Traumatic Brain Injury Prognosis.

OBJECTIVE: To synthesize the best available evidence regarding psychosocial consequences of mild traumatic brain injury (MTBI) in children. DATA SOURCES: MEDLINE, Embase, CINAHL, PsycINFO, and SPORTDiscus were searched (2001-2012). Inclusion criteria included published peer-reviewed reports in English, French, Norwegian, Spanish, Swedish, and Danish. References were also identified from relevant reviews and meta-analyses, and the bibliographies of eligible articles. STUDY SELECTION: This article presents an update of a previous review with a much larger scope, of which this topic is a small subset of the questions addressed by that review. Controlled trials and cohort and case-control studies were selected according to predefined criteria. Two independent reviewers used modified Scottish Intercollegiate Guidelines Network criteria to critically appraise eligible studies. A total of 77,914 records were screened; 101 of these articles were deemed scientifically admissible, of which 6 investigated the psychosocial consequences of MTBI in children. DATA EXTRACTION: Two reviewers independently extracted data from accepted studies into evidence tables. DATA SYNTHESIS: We conducted a best-evidence synthesis by linking our conclusions to the evidence tables. Most accepted studies were exploratory rather than confirmatory. Preliminary evidence suggests that most children recover within 3 months post-MTBI. After 1 year, the prevalence of postconcussion symptoms and syndrome is similar between children with MTBI and children with orthopedic injuries. The functional status of children with MTBI improves over a 30-month follow-up period, but further research is needed to investigate the possibility that children with MTBI experience greater rates of psychiatric illness during the 3 years after their injury. CONCLUSIONS: The prognosis of MTBI is favorable in children. Most appear to recover functionally from a physical and psychological perspective. However, future research should investigate the risk for psychiatric illness.

Systematic review of the clinical course, natural history, and prognosis for pediatric mild traumatic brain injury: results of the International Collaboration on Mild Traumatic Brain Injury Prognosis.

OBJECTIVE: To synthesize the best available evidence on prognosis after pediatric mild traumatic brain injury (MTBI). DATA SOURCES: We searched MEDLINE, Embase, PsycINFO, CINAHL, and SPORTDiscus (2001-2012), as well as reference lists of eligible articles, and relevant systematic reviews and meta-analyses. STUDY SELECTION: Controlled trials and cohort and case-control studies were selected according to predefined criteria. Studies had to have a minimum of 30 MTBI pediatric cases. After 77,914 records were screened for the entire review, 299 studies were eligible and assessed for scientific rigor. DATA EXTRACTION: Eligible studies were critically appraised using the Scottish Intercollegiate Guidelines Network (SIGN) criteria. Two reviewers independently reviewed each study and extracted data from accepted articles into evidence tables. DATA SYNTHESIS: Evidence from 25 accepted articles was synthesized qualitatively according to SIGN criteria, and prognostic information was prioritized according to design as exploratory or confirmatory. Most studies show that postconcussion symptoms and cognitive deficits resolve over time. Limited evidence suggests that postconcussion symptoms may persist in those with lower cognitive ability and intracranial pathology on neuroimaging. Preliminary evidence suggests that the risk of epilepsy is increased for up to 10 years after MTBI; however, there is insufficient high-quality evidence at this time to support this link. CONCLUSIONS: Common post-MTBI symptoms and deficits in children are not specific to MTBI and appear to resolve with time; however, limited evidence suggests that children with intracranial pathology on imaging may experience persisting symptoms or deficits. Well-designed, long-term studies are needed to confirm these findings.

Systematic review of prognosis and return to play after sport concussion: results of the International Collaboration on Mild Traumatic Brain Injury Prognosis.

OBJECTIVE: To synthesize the best available evidence on prognosis after sport concussion. DATA SOURCES: MEDLINE and other databases were searched (2001-2012) with terms including "craniocerebral trauma" and "sports." Reference lists of eligible articles were also searched. STUDY SELECTION: Randomized controlled trials and cohort and case-control studies were selected according to predefined criteria. Studies had to have a minimum of 30 concussion cases. DATA EXTRACTION: Eligible studies were critically appraised using a modification of the Scottish Intercollegiate Guidelines Network (SIGN) criteria. Two reviewers independently reviewed and extracted data from accepted studies into evidence tables. DATA SYNTHESIS: Evidence was synthesized qualitatively according to modified SIGN criteria, and studies were categorized as exploratory or confirmatory based on the strength of their design and evidence. After 77,914 records were screened, 52 articles were eligible for this review, and 24 articles (representing 19 studies) with a low risk of bias were accepted. Our findings are based on exploratory studies of predominantly male football players at the high school, collegiate, and professional levels. Most athletes recover within days to a few weeks, and American and Australian professional football players return to play quickly after mild traumatic brain injury. Delayed recovery appears more likely in high school athletes, in those with a history of previous concussion, and in those with a higher number and duration of postconcussion symptoms. CONCLUSIONS: The evidence concerning sports concussion course and prognosis is very preliminary, and there is no evidence on the effect of return-to-play guidelines on prognosis. Our findings have implications for further research. Well-designed, confirmatory studies are urgently needed to understand the consequences of sport concussion, including recurrent concussion, across different athletic populations and sports.

False-positive Findings of Large Vessel Vasculitis on FDG-PET in Patients Treated With Immune Checkpoint Inhibitors.

Fluorine-18 fluorodeoxygluocose positron emission tomography (FDG-PET) is increasingly used in the evaluation of response to immune checkpoint inhibitor (ICI) therapy. Incidental findings of increased vessel wall uptake may prompt the concern for ICI-induced large vessel vasculitis (LVV). Precise radiographic and clinical evaluation is required to determine if this represents true vasculitis, as use of immune suppression and ICI discontinuation can have significant impacts on patient outcomes. We performed a retrospective case analysis of 4 consecutive patients referred to 2 rheumatology clinics treated with ICI with incidental findings of LVV on FDG-PET, reviewing their clinical course and radiographic findings. All 4 cases had FDG-PET scans for routine oncology indications and had no associated clinical features of LVV. One patient was treated with corticosteroids and no patients developed any clinical evidence of vasculitis during a mean follow-up period of 17 months (range: 7-33 mo). All FDG-PET images reporting LVV underwent a standardized analysis to identify any technical issues or concerns with interpretation. In review of imaging, 3 of the cases may have been due to delayed tracer to scan interval leading to misinterpretation of vascular uptake as suspected LVV. Recognition of technical pitfalls in FDG-PET interpretation is crucial to inform the need for immunosuppression and the safety of continued ICI therapy.

Fluorine-18 Prostate-Specific Membrane Antigen-1007 PET/CT vs Multiparametric MRI for Locoregional Staging of Prostate Cancer.

Importance: Prostate-specific membrane antigen (PSMA) demonstrates overexpression in prostate cancer and correlates with tumor aggressiveness. PSMA positron emission tomography (PET) is superior to conventional imaging for the metastatic staging of prostate cancer per current research but studies of second-generation PSMA PET radioligands for locoregional staging are limited. Objective: To determine the accuracy of fluorine-18 PSMA-1007 PET/computed tomography (18F-PSMA-1007 PET/CT) compared to multiparametric magnetic resonance imaging (MRI) in the primary locoregional staging of intermediate-risk and high-risk prostate cancers. Design, Setting, and Participants: The Next Generation Trial was a phase 2 prospective validating paired cohort study assessing the accuracy of 18F-PSMA-1007 PET/CT and MRI for locoregional staging of prostate cancer, with results of histopathologic examination as the reference standard comparator. Radiologists, nuclear medicine physicians, and pathologists were blinded to preoperative clinical, pathology, and imaging data. Patients underwent all imaging studies and radical prostatectomies at 2 tertiary care hospitals in Alberta, Canada. Eligible participants included men with intermediate-risk or high-risk prostate cancer who consented to radical prostatectomy. Participants who underwent radical prostatectomy were included in the final analysis. Patients were recruited between March 2022 and June 2023, and data analysis occurred between July 2023 and December 2023. Exposures: All participants underwent both 18F-PSMA-1007 PET/CT and MRI within 2 weeks of one another and before radical prostatectomy. Main Outcomes and Measures: The primary outcome was the correct identification of the prostate cancer tumor stage by each imaging test. The secondary outcomes were correct identification of the dominant nodule, laterality, extracapsular extension, and seminal vesical invasion. Results: Of 150 eligible men with prostate cancer, 134 patients ultimately underwent radical prostatectomy (mean [SD] age at prostatectomy, 62.0 [5.7] years). PSMA PET was superior to MRI for the accurate identification of the final pathological tumor stage (61 [45%] vs 38 [28%]; P = .003). PSMA PET was also superior to MRI for the correct identification of the dominant nodule (126 [94%] vs 112 [83%]; P = .01), laterality (86 [64%] vs 60 [44%]; P = .001), and extracapsular extension (100 [75%] vs 84 [63%]; P = .01), but not for seminal vesicle invasion (122 [91%] vs 115 [85%]; P = .07). Conclusions and Relevance: In this phase 2 prospective validating paired cohort study, 18F-PSMA-1007 PET/CT was superior to MRI for the locoregional staging of prostate cancer. These findings support PSMA PET in the preoperative workflow of intermediate-risk and high-risk tumors.

Prevalence of dance-related injuries and associated risk factors among children and young Chinese dance practitioners.

While Chinese dance is a popular dance genre among Chinese teenagers and adults, little is known regarding the prevalence of dance-related injuries or factors associated with such injuries among Chinese dance practitioners. The current cross-sectional study aimed to determine the prevalence of dance-related injuries and their associated risk factors among young Chinese dance practitioners in Hong Kong. Online surveys were distributed to dancers through local dance associations, while paper-based surveys were distributed to young Chinese dance performers during the 54th School Dance Festival in Hong Kong. Self-reported hours of dancing, injuries in the last 12 months, injury sites, and related factors were collected. The injury rate, 12-month prevalence of dance-related injuries were determined. Risk factors for common dance injuries were analyzed using separate multivariate regression models. A total of 175 children (aged 10-14 years) and 118 young (aged 15-24 years) Chinese dance practitioners provided their dance injury information. Young dancers had a significantly higher injury rate (6.5 injuries vs 4.6 injuries/1000 dance hours) and 12-month prevalence (52.5% vs 19.4%) than their child counterparts. The most commonly injured sites were the knee (children:7.4%; young:15.3%), lower back (children: 4.6%; young: 9.5%), and ankles (children: 5.1%; young: 16.9%). Age was a significant independent risk factor for dance-related injuries to the upper back, lower back, and pelvis/buttock (odds ratios ranging from 1.2 to 1.3/additional years). Additionally, height was a significant independent risk factor for lower limb injury (odds ratios ranging from 1.0-1.1/additional centimeter). Collectively, young Chinese dance practitioners are more vulnerable to dance-related injuries than are child dancers. Older age increases the risk of trunk injuries, whereas taller dancers are more likely to sustain lower-limb injuries. Future research should determine the mechanisms underlying dance-related injuries among these dancers.

Optimization of myocardial nulling in pediatric cardiac MRI.

BACKGROUND: Current protocols to determine optimal nulling time in late enhancement imaging using adult techniques may not apply to children. OBJECTIVE: To determine the optimal nulling time in anesthetised children, with the hypothesis that this occurs earlier than in adults. MATERIALS AND METHODS: Sedated cardiac MRI was performed in 12 children (median age: 12 months, range: 1-60 months). After gadolinium administration, scout images at 2, 3, 4 and 10 min and phase sensitive inversion recovery (PSIR) images from 5 to 10 min were obtained. Signal-to-noise ratio (SNR) and inversion time (TI) were determined. Quality of nulling was assessed according to a grading score by three observers. Data was analysed using linear regression, Kruskal-Wallis and quadratic-weighted kappa statistics. RESULTS: One child with a cardiomyopathy had late enhancement. Good agreement in nulling occurred for scout images at 2 (κ = 0.69) and 3 (κ = 0.66) min and moderate agreement at 4 min (κ = 0.57). Agreement of PSIR images was moderate at 7 min (κ = 0.44) and poor-fair at other times. There were significant correlations between TI and scout time (r = 0.61, P < 0.0001), and SNR and kappa (r = 0.22, P = 0.017). CONCLUSION: Scout images at 2-4 min can be used to determine the TI with little variability. Image quality for PSIR images was highest at 7 min and SNR optimal at 7-9 min. TI increases with time and should be adjusted frequently during imaging. Thus, nulling times in children differ from nulling times in adults when using standard adult techniques.

Gastrointestinal neuroendocrine tumor with discordant metastatic disease on 111In-pentetreotide SPECT/CT, 18F-DOPA PET/CT and 68Ga-HA-DOTATATE PET/CT.

A 62-year-old man with resected, pathology-proven small bowel neuroendocrine tumor underwent 111In-pentetreotide SPECT/CT, 18F-DOPA PET/CT and 68Ga-HA-DOTATATE PET/CT to assess metastatic disease. The 111In-pentetreotide SPECT/CT scan showed no metastatic disease. Both 18F-DOPA and 68Ga-HA-DOTATATE PET/CT showed hepatic and peritoneal metastatic disease. However, the burden of 18F-DOPA-avid metastatic disease was far greater compared to the burden of 68Ga-HA-DOTATATE-avid metastatic disease.

Lateralized interictal epileptiform discharges during rapid eye movement sleep correlate with epileptogenic hemisphere in children with intractable epilepsy secondary to tuberous sclerosis complex.

PURPOSE: We assessed lateralization of interictal epileptiform discharges (IEDs) in children with intractable epilepsy secondary to tuberous sclerosis complexes (TSCs) during rapid eye movement sleep (R), compared with non-rapid eye movement sleep (NR) and wakefulness (W), to determine epileptogenicity of R-IEDs. METHODS: We retrospectively studied 23 children with TSC, who underwent prolonged scalp video-electroencephalography (EEG) and magnetic resonance imaging (MRI). We determined the lateralization of ictal EEG, clinical semiology, and the largest tuber on MRI. We analyzed a minimum of 100 IEDs during R, NR, and W to classify right/left/generalized spikes to compare the lateralization with ictal EEG, clinical semiology, and MRI. KEY FINDINGS: R-IEDs were lateralized in 22 patients (96%), W-IEDs in 19 (83%), and NR-IEDs in 16 (70%). Ictal EEGs were lateralized in 15 patients (65%) and clinical semiology in 5 (22%). Ictal EEG lateralization was concordant to R-IEDs in 14 patients (93%), W-IEDs in 11 (73%), and NR-IEDs in 10 (67%). The lateralization of clinical semiology was concordant with R-IEDs in 4 (80%), W-IEDs in 3 (60%), and NR-IEDs in 2 (40%). MRI lateralization of the largest tuber was concordant with R-IEDs in 16 (70%), W-IEDs in 12 (52%), and NR-IEDs in 11 (48%). Thirteen patients (57%) underwent resective surgery, the hemisphere of which was concordant with R-IEDs in 13 (100%), W-IEDs in 8 (62%), and NR-IEDs in 8 (62%). Nine (69%) of them achieved good seizure control after surgery. SIGNIFICANCE: R provoked the most lateralized IEDs compared to NR and W in children with TSC. Lateralization of R-IEDs corresponded with the hemisphere of ictal EEG and largest tuber, and can be used to identify surgical candidacy in TSC children with intractable epilepsy.

Reliability and validity of Six-Spot Step Test (SSST) in stroke survivors.

BACKGROUND: The Six-Spot Step Test (SSST) was originally developed to assess walking ability while challenging balance during walking in patients with multiple sclerosis. It provides more comprehensive information on ambulatory abilities than several existing measures such as the Timed Up and Go test (TUG test), the Functional Gait Assessment, and the Dynamic Gait Index. To assess the advanced balance control ability of stroke survivors, we modified the SSST to serve this purpose. AIM: The aim of this study was to expand the current understanding of the psychometric properties of the SSST using healthy older adults and stroke survivors. DESIGN: This study adopted an experimental design. SETTING: University-affiliated neurorehabilitation laboratory. POPULATION: A total of 50 study participants, including 25 chronic stroke survivors and 25 healthy older adults, were recruited from the community. METHODS: The SSST was administered to the stroke survivors twice (day 1 and 2) with a 1-week interval. The Fugl-Meyer assessment for the lower extremities (FMA-LE), the Berg Balance scale (BBS), the limit of stability (LOS) test, the Timed Up and Go test (TUG test), and the Chinese version of the Community Integration Measures (CIM-C) were assessed on day 1 by random order. The healthy control group was assessed with the Six-Spot Step Test only on day 1. RESULTS: The SSST showed excellent inter-rater, intra-rater, and test-retest reliability (intraclass correlation coefficient >0.95, P<0.001). Significant correlations were found between SSST performance and the FMA-LE results (r=0.517, P<0.05), BBS scores (r=-0.531, P<0.05), and TUG test scores (r=0.828, P<0.001). The MDC in the mean SSST time for the affected leg and the unaffected leg in stroke survivors was 6.05s. The cutoff time was 10.11s (sensitivity, 80%; specificity, 92%) when kicking obstacles with the affected leg and 10.18s (sensitivity, 80%; specificity, 92%) when kicking obstacles with the unaffected leg. CONCLUSIONS: The SSST was a reliable test and showed a significant correlation with FMA-LE scores, BBS scores, and TUG test times in stroke survivors. CLINICAL REHABILITATION IMPACT: The SSST can be used to assess the advanced balance control of stroke survivors.

Development of a poly(d,l-lactic-co-glycolic acid) nanoparticle formulation of STAT3 inhibitor JSI-124: implication for cancer immunotherapy.

Constitutively activated signal transducer and activator of transcription-3 (STAT3) in tumor and dendritic cells (DCs) plays a critical role in tumor-induced immunosuppression. This is considered a major challenge in effective immunotherapy of cancer. Herein we describe the development of a polymeric nanocarrier for the delivery of JSI-124 (a small molecule inhibitor of STAT3) to tumor and immunosuppressed DCs using poly(d,l-lactic-co-glycolic acid) nanoparticles (PLGA NPs). For this purpose, JSI-124 was chemically conjugated to PLGA and the PLGA-JSI-124 conjugate was formulated into nanoparticles using the emulsification solvent evaporation method. The attachment of JSI-124 to PLGA was confirmed by a combination of thin layer chromatography and (1)H NMR. The level of JSI-124 in NPs, determined by liquid chromatography-mass spectrometry, was found to be 1.7 +/- 0.3 microg per mg of PLGA. The PLGA-JSI-124 NPs demonstrated a controlled drug release profile over a 1-month period and exhibited potent anticancer and STAT3 inhibitory activity comparable to the soluble JSI-124 after 24 h incubation with B16 melanoma cells, in vitro. Moreover, PLGA-JSI-124 NPs efficiently suppressed the level of p-STAT3 in p-STAT3(high) DCs, generated from mouse bone marrow cells in the presence of conditioned media of B16 cells (B16CM-DCs), and improved their function as assessed by mixed lymphocyte reaction (MLR). Specifically cotreatment of B16CM-DCs with PLGA-JSI-124 NPs and PLGA NPs containing the DC adjuvant CpG resulted in higher levels of T cell proliferation in the MLR assay compared with B16CM-DCs untreated or treated with either CpG NPs or JSI-124 NPs alone. Our results indicate that PLGA NPs containing conjugated JSI-124 can potentially provide a useful platform for sustained JSI-124 release in tumor and its targeted delivery to DCs leading to the modulation of anticancer response by JSI-124 in tumor cells and immunosuppressed DCs, in vitro.

Creating dementia-friendly and inclusive communities for social inclusion: a scoping review protocol.

INTRODUCTION: The number of people with dementia is increasing worldwide, with the majority of people with dementia living at home in the community. WHO calls for global action on the public health response to dementia. Social exclusion is commonly reported by people with dementia and their families. Dementia-friendly and inclusive community has emerged as an idea that holds potential to contribute to the mitigation of social exclusion. The objective of the scoping review is to answer two questions: What social inclusion strategies that have been reported in the dementia-friendly and inclusive communities' literature? What strategies for developing dementia-friendly and inclusive communities that have shown to improve social inclusion? METHODS AND ANALYSIS: This scoping review will follow the Joanna Briggs Institute scoping review methodology and will take place between April and September 2020. The proposed review will consider studies based in community settings with participants living at home with early to late stages of dementia and their families. This includes a three-step search strategy: (1) to identify keywords from MEDLINE and CINAHL; (2) to conduct a second search using all identified keywords and index terms across selected databases (MEDLINE, CINAHL, AgeLine, PsycINFO, Web of Science, ProQuest and Google) and (3) to handsearch the reference lists of all included articles and reports for additional studies. Further, we will search Google for grey literature on published organisational reports. Two researchers will screen titles and abstracts independently and then assess the full text of selected citations against inclusion criteria. Extracted data will be presented in a narrative accompanied by tables that reflect the objective of the review. ETHICS AND DISSEMINATION: As the methodology of this study consists of collecting data from publicly available articles, it does not require ethics approval. This scoping review provides an overview of current evidence on strategies that support dementia-friendly and inclusive communities for social inclusion. The findings will offer insights to inform strategies for education, practice, policy and future research. We will share the scoping review results through conference presentations and an open-access publication in a peer-reviewed journal.

Apparent diffusion coefficient pseudonormalization time in neonatal hypoxic-ischemic encephalopathy.

The apparent diffusion coefficient changes with time after hypoxic-ischemic brain injury. In this study, we quantitatively examined the relationship between the apparent diffusion coefficient and postnatal age for neonates with hypoxic-ischemic encephalopathy and poor outcome, and determined the postnatal age at which these values cannot be distinguished from those of neonates without hypoxic-ischemic encephalopathy (pseudonormalization time). Diffusion-weighted brain images were obtained from clinical scans of term neonates with hypoxic-ischemic encephalopathy and poor outcome (12 neonates, 23 scans) and from control subjects (30 neonates, 31 scans). The correlation between apparent diffusion coefficient and postnatal age was investigated for several brain regions. Pseudonormalization times were determined (1) from the intersection of the regression lines for the hypoxic-ischemic encephalopathy and control groups, as well as (2) from intrasubject apparent diffusion coefficient changes between two scans within a small subgroup. Pseudonormalization times from the regression ranged from 8.3 +/- 1.9 days to 10.1 +/- 2.1 days. Slightly (approximately 1 day) longer values were obtained from the intrasubject analysis. The results suggest that, although abnormally decreased apparent diffusion coefficient values may be evident from approximately 2 days to almost 1 week of postnatal age, abnormally elevated values may not be apparent until late in the second week of life.

Pleomorphic spindle cell sarcoma (PSCS) (formerly known as malignant fibrous histiocytoma, MFH) of the spleen, mimics an atypical haemangioma on 99mTc-RBC, CT and Ultrasound: staging with 18F-FDG PET/CT.

A 63-year-old male was found to have a 7.5-cm splenic mass that had imaging appearances of an atypical haemangioma on CT, ultrasound and a 99mTc-RBC scan, and he was followed conservatively with serial ultrasounds. Sixteen months later, however, the splenic lesion grew and he developed numerous new liver masses which were biopsy confirmed to be a pleomorphic spindle cell sarcoma (PSCS), formerly known as malignant fibrous histiocytoma (MFH). A staging 18F-FDG PET/CT was performed and showed innumerable, mostly necrotic hepatic and splenic masses. The patient passed away a few days after the PET/CT, before a treatment program could be implemented. The use of 18F-FDG PET/CT in the staging of splenic PSCS has not been previously described. We present the 99mTc-RBC and 18F-FDG PET/CT image characteristics of a patient with splenic PSCS.

Pediatric Posttraumatic Headache.

Concussion and mild traumatic brain injury are common injuries in pediatrics, and posttraumatic headache is the most common complaint following them. Although most children and teens recover from a simple, isolated concussion without incidents within 1-2 weeks, some develop symptoms that can last for months. It is important to manage both acute and persistent posttraumatic headaches appropriately to speed recovery, minimize disability, and maximize function. In this article, we review the definitions, epidemiology, and current recommendations for the evaluation and treatment of acute and persistent posttraumatic headaches. Although this is still a developing field and there is much that we still need to learn about concussion and the best strategies to prevent and treat these injuries and their sequelae, we hope that this review will help providers to understand the current evidence and treatment recommendations to improve care for children with concussion and mild traumatic brain injury.