Developing Predictive Models to Anticipate Shunt Complications in 33,248 Pediatric Patients with Shunted Hydrocephalus Utilizing Machine Learning.

INTRODUCTION: Hydrocephalus is a common pediatric neurosurgical pathology, typically treated with a ventricular shunt, yet approximately 30% of patients experience shunt failure within the first year after surgery. As a result, the objective of the present study was to validate a predictive model of pediatric shunt complications with data retrieved from the Healthcare Cost and Utilization Project (HCUP) National Readmissions Database (NRD). METHODS: The HCUP NRD was queried from 2016 to 2017 for pediatric patients undergoing shunt placement using ICD-10 codes. Comorbidities present upon initial admission resulting in shunt placement, Johns Hopkins Adjusted Clinical Groups (JHACG) frailty-defining criteria, and Major Diagnostic Category (MDC) at admission classifications were obtained. The database was divided into training (n = 19,948), validation (n = 6,650), and testing (n = 6,650) datasets. Multivariable analysis was performed to identify significant predictors of shunt complications which were used to develop logistic regression models. Post hoc receiver operating characteristic (ROC) curves were created. RESULTS: A total of 33,248 pediatric patients aged 6.9 ± 5.7 years were included. Number of diagnoses during primary admission (OR: 1.05, 95% CI: 1.04-1.07) and initial neurological admission diagnoses (OR: 3.83, 95% CI: 3.33-4.42) positively correlated with shunt complications. Female sex (OR: 0.87, 95% CI: 0.76-0.99) and elective admissions (OR: 0.62, 95% CI: 0.53-0.72) negatively correlated with shunt complications. ROC curve for the regression model utilizing all significant predictors of readmission demonstrated area under the curve of 0.733, suggesting these factors are possible predictors of shunt complications in pediatric hydrocephalus. CONCLUSION: Efficacious and safe treatment of pediatric hydrocephalus is of paramount importance. Our machine learning algorithm delineated possible variables predictive of shunt complications with good predictive value.

N-Terminomic Changes in Neurons During Excitotoxicity Reveal Proteolytic Events Associated With Synaptic Dysfunctions and Potential Targets for Neuroprotection.

Excitotoxicity, a neuronal death process in neurological disorders such as stroke, is initiated by the overstimulation of ionotropic glutamate receptors. Although dysregulation of proteolytic signaling networks is critical for excitotoxicity, the identity of affected proteins and mechanisms by which they induce neuronal cell death remain unclear. To address this, we used quantitative N-terminomics to identify proteins modified by proteolysis in neurons undergoing excitotoxic cell death. We found that most proteolytically processed proteins in excitotoxic neurons are likely substrates of calpains, including key synaptic regulatory proteins such as CRMP2, doublecortin-like kinase I, Src tyrosine kinase and calmodulin-dependent protein kinase IIß (CaMKIIß). Critically, calpain-catalyzed proteolytic processing of these proteins generates stable truncated fragments with altered activities that potentially contribute to neuronal death by perturbing synaptic organization and function. Blocking calpain-mediated proteolysis of one of these proteins, Src, protected against neuronal loss in a rat model of neurotoxicity. Extrapolation of our N-terminomic results led to the discovery that CaMKIIα, an isoform of CaMKIIß, undergoes differential processing in mouse brains under physiological conditions and during ischemic stroke. In summary, by identifying the neuronal proteins undergoing proteolysis during excitotoxicity, our findings offer new insights into excitotoxic neuronal death mechanisms and reveal potential neuroprotective targets for neurological disorders.

Dopamine Circuit Mechanisms of Addiction-Like Behaviors.

Addiction is a complex disease that impacts millions of people around the world. Clinically, addiction is formalized as substance use disorder (SUD), with three primary symptom categories: exaggerated substance use, social or lifestyle impairment, and risky substance use. Considerable efforts have been made to model features of these criteria in non-human animal research subjects, for insight into the underlying neurobiological mechanisms. Here we review evidence from rodent models of SUD-inspired criteria, focusing on the role of the striatal dopamine system. We identify distinct mesostriatal and nigrostriatal dopamine circuit functions in behavioral outcomes that are relevant to addictions and SUDs. This work suggests that striatal dopamine is essential for not only positive symptom features of SUDs, such as elevated intake and craving, but also for impairments in decision making that underlie compulsive behavior, reduced sociality, and risk taking. Understanding the functional heterogeneity of the dopamine system and related networks can offer insight into this complex symptomatology and may lead to more targeted treatments.

Translation, cultural adaptation and validation of the Systemic Lupus Erythematosus Activity Questionnaire (SLAQ) in a cohort of Italian systemic lupus erythematosus patients.

Introduction The Systemic Lupus Erythematosus Activity Questionnaire (SLAQ) is a patient-reported instrument for the assessment of disease activity in systemic lupus erythematosus (SLE). The aims of the present study are translation, cultural adaptation and validation of an Italian version: the SLAQit. Methods The process of translation and cultural adaptation followed published guidelines. SLAQit was pretested in a group of 35 SLE patients to evaluate acceptability, comprehension and feasibility. Internal consistency, test-retest validity and external validity were tested on consecutive SLE patients attending the clinic. Results In total, 135 SLE patients were enrolled in this study. The pilot test provided a 99.9% response rate and demonstrated feasibility and comprehensibility of the questionnaire. A good internal consistency was found among the three components of the score (SLAQ score, numerical rating scale (NRS), patient global assessment question (PGA); α = 0.79). SLAQit showed very high reliability (test-retest α > 0.8). NRS and PGA showed a strong positive correlation with both Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) ( p = 0.002 and p < 0.001, respectively) and European Consensus Lupus Measurement (ECLAM) scores ( p = 0.01 and p < 0.001, respectively), while the SLAQ score did not. A significant agreement was observed between the physician's intention to treat and both the NRS and PGA scores, while no significant association was reported with the SLAQ score. Conclusions SLAQit was demonstrated to be a reliable and valid instrument for self-assessment of disease activity in SLE patients.

Intensity-dependent effects of aerobic training on pressure pain threshold in overweight men: A randomized trial.

PURPOSE: To investigate the chronic and acute effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on pressure pain thresholds (PPT) in overweight men. METHODS: Twenty-eight participants performed stationary cycling exercise three times per week for 6 weeks. Participants were randomly allocated to HIIT (10 × 1-min intervals at 90% peak heart rate) or MICT (30 min at 65-75% peak heart rate). PPTs were assessed over the rectus femoris, tibialis anterior and upper trapezius before and after the 6-week training programme (chronic effect) as well as before and after the first, middle and final exercise sessions (acute effect). RESULTS: For chronic exercise, PPTs increased more after MICT compared to HIIT over the rectus femoris (p = 0.009, effect size r = 0.54) and tibialis anterior (p = 0.012, r = 0.54), but not the trapezius (p = 0.399, r = 0.29). The effect of acute exercise on PPT was more varied and ranged from moderate hypoalgesia to moderate hyperalgesia. Overall, however, there was no consistent change in PPT after acute exercise for HIIT or MICT (p ≥ 0.231, r ≥ -0.31 and ≤0.31). CONCLUSION: Six weeks of MICT cycling (chronic exercise) increased PPT for the lower body, but not upper body, in overweight men, whereas HIIT did not provide any hypoalgesic effect for chronic exercise. The acute effect of exercise on PPT was highly variable and negligible overall. SIGNIFICANCE: This study shows that aerobic training increases pressure pain threshold in pain-free adults. This effect was observed only for MICT over-exercised muscles, implying intensity- and site-specific effects of exercise training on pain threshold.

Combined Laminoplasty and Posterior Fusion for Cervical Spondylotic Myelopathy Treatment: A Literature Review.

STUDY DESIGN: A literature review. PURPOSE: To explore the utility of laminoplasty in combination with instrumented fusion, with a focus on neurological outcomes and changes in kyphotic deformity. OVERVIEW OF LITERATURE: Management of cervical spondylotic myelopathy (CSM) to reduce morbidity within the neurosurgical population. METHODS: A US National Library of Medicine PubMed search was conducted for manuscripts pertaining to cervical laminoplasty and fusion for the management of CSM. Several relevant studies were shortlisted for review, and the bibliographies of the articles were searched for additional references. The search was limited to human studies, English-language literature, and reports on more than one patient. RESULTS: Combined laminoplasty and fusion was found to provide at least comparable, if not superior, neurological outcomes in specific patient populations with CSM. The Japanese Orthopedic Association scores, local kyphosis, and C2-C7 angle have been reviewed in several manuscripts, and improvement in each of these categories was found with laminoplasty and fusion. CONCLUSIONS: The treatment of CSM necessitates an individualized approach based on the pathoanatomical variation. Laminoplasty and fusion can be appropriately used for patients with CSM in a setting of local kyphotic deformity, ossification of the posterior longitudinal ligament, associated segmental instability, and the need for strong stabilization.

A Complete Guide to Using the Endothelin-1 Model of Stroke in Conscious Rats for Acute and Long-Term Recovery Studies.

Multiple methods exist to model permanent and transient ischemia under anesthesia in animals, however most human strokes occur while conscious. The use of endothelin-1 as a vasoconstrictor applied to the perivascular surface of the middle cerebral artery is one of the only methods for inducing stroke in conscious animals. Here, we describe standard operating procedures for stereotaxic placement of an ET-1 guide probe above the middle cerebral artery, induction of stroke in conscious rats, predictive outcome scoring during stroke, and neurological behavioral tests that we use to monitor transient and continuing deficits. The inclusion of long term neurological assessment is of particular importance when taking into consideration the effects of stroke on brain remodeling.

Impaired taste sensation in type 2 diabetic patients without chronic complications: a case-control study.

PURPOSE: Few and contradictory data suggest changes in taste perception in type 2 diabetes (T2DM), potentially altering food choices. We, therefore, analyzed taste recognition thresholds in T2DM patients with good metabolic control and free of conditions potentially impacting on taste, compared with age-, body mass index-, and sex-matched normoglycemic controls. METHODS: An ascending-concentration method was used, employing sucrose (sweet), sodium chloride (salty), citric acid (sour), and quinine hydrochloride (bitter), diluted in increasing concentration solutions. The recognition threshold was the lowest concentration of correct taste identification. RESULTS: The recognition thresholds for the four tastes were higher in T2DM patients. In a multiple regression model, T2DM [ß = 0.95; 95% CI 0.32-1.58; p = 0.004 (salty); ß = 0.61; 0.19-1.03; p = 0.006 (sweet); ß = 0.78; 0.15-1.40; p = 0.016 (sour); ß = 0.74; 0.22-1.25; p = 0.006 (bitter)] and waist circumference [ß = 0.05; 0.01-0.08; p = 0.012 (salty); ß = 0.03; 0.01-0.05; p = 0.020 (sweet); ß = 0.04; 0.01-0.08; p = 0.020 (sour); ß = 0.04; 0.01-0.07; p = 0.007 (bitter)] were associated with the recognition thresholds. Age was associated with salty (ß = 0.06; 0.01-0.12; p = 0.027) and BMI with sweet thresholds (ß = 0.06; 0.01-0.11; p = 0.019). CONCLUSIONS: Taste recognition thresholds were higher in uncomplicated T2DM, and central obesity was significantly associated with this impairment. Hypogeusia may be an early sign of diabetic neuropathy and be implicated in the poor compliance of these patients to dietary recommendations.

Pseudogout of the cervical and thoracic spine mimicking infection after lumbar fusion: case report.

Pseudogout is a form of acute calcium pyrophosphate deposition (CPPD) disease that typically afflicts the elderly. CPPD commonly involves larger joints, such as the knees, wrists, shoulders, and hips, and has been known to involve the spine. The authors report the case of a 66-year-old woman with a recent history of lumbar laminectomy and fusion who presented 5 weeks postprocedure with a clinical and radiographic picture consistent with multilevel skip lesions involving the cervical and thoracic spine, thoracic discitis, and epidural abscess. Serial blood cultures and repeat biopsy samples were sterile. Subsequent wrist and ankle erythema, pain, and swelling led to synovial fluid analysis, and pseudogout was diagnosed. She was treated with an interleukin-1 inhibitor with immediate symptom relief. To the authors' knowledge, this is only the second report of spinal pseudogout presenting with a clinical and radiographic picture consistent with discitis and epidural abscess. This report is the first to report skip lesions of pseudogout occurring throughout the spine that are uniquely remote from a recent lumbar surgery.

Preoperative oral immunonutrition versus standard preoperative oral diet in well nourished patients undergoing pancreaticoduodenectomy.

BACKGROUND: Pancreaticoduodenectomy is still associated to high morbility, especially due to pancreatic surgery related and infectious complications: many risk factors have already been advocated. Aim of this study is to evaluate the role of preoperative oral immunonutrition in well nourished patients scheduled for pancreaticoduodenectomy. METHODS: From February 2014 to June 2015, 54 well nourished patients undergoing pancreaticoduodenectomy were enrolled for 5 days preoperative oral immunonutrition. A series of consecutive patients submitted to the same intervention in the same department, with preoperative standard oral diet, was matched 1:1. For analysis demographic, pathological and surgical variables were considered. Mortality rate, overall postoperative morbility, pancreatic fistula, post pancreatectomy haemorrhage, delayed gastric emptying, infectious complications and length of hospital stay were described for each groups. Chi squared test, Fisher's Exact test and Student's T test were used for comparison. Differences were considered statistically significant at p < 0.05. Statistics was performed using a freeware Microsoft Excel (®) based program and SPSS v 10.00. RESULTS: No statistical differences in term of mortality (2.1% in each groups) and overall morbility rate (41.6% vs 47.9%) occurred between the groups as well as for pancreatic surgery related complications. Conversely, statistical differences were found for infectious complications (22.9% vs 43.7%, p = 0.034) and length of hospital stay (18.3 ± 6.8 days vs 21.7 ± 8.3, p = 0.035) in immunonutrition group. CONCLUSION: Preoperative oral immunonutrition is effective for well nourished patients scheduled for pancreaticoduodenectomy; it helps to reduce the risk of postoperative infectious complications and length of hospital stays.

Modulating Astrocyte Transition after Stroke to Promote Brain Rescue and Functional Recovery: Emerging Targets Include Rho Kinase.

Stroke is a common and serious condition, with few therapies. Whilst previous focus has been directed towards biochemical events within neurons, none have successfully prevented the progression of injury that occurs in the acute phase. New targeted treatments that promote recovery after stroke might be a better strategy and are desperately needed for the majority of stroke survivors. Cells comprising the neurovascular unit, including blood vessels and astrocytes, present an alternative target for supporting brain rescue and recovery in the late phase of stroke, since alteration in the unit also occurs in regions outside of the lesion. One of the major changes in the unit involves extensive morphological transition of astrocytes resulting in altered energy metabolism, decreased glutamate reuptake and recycling, and retraction of astrocyte end feed from both blood vessels and neurons. Whilst globally inhibiting transitional change in astrocytes after stroke is reported to result in further damage and functional loss, we discuss the available evidence to suggest that the transitional activation of astrocytes after stroke can be modulated for improved outcomes. In particular, we review the role of Rho-kinase (ROCK) in reactive gliosis and show that inhibiting ROCK after stroke results in reduced scar formation and improved functional recovery.

Insomnia symptoms, perceived stress and coping strategies in patients with systemic lupus erythematosus.

OBJECTIVE: The aim of this study is to evaluate perceived stress and coping strategies in individuals with systemic lupus erythematosus (SLE) according to the presence of insomnia symptoms, using a set of variables that include anxiety and depressive symptoms evaluation. METHODS: Ninety SLE women were evaluated in a cross-sectional study using the Perceived Stress Scale (PSS), Brief COPE, Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Beck Depression Inventory (BDI) and Self-rating Anxiety Scale (SAS). RESULTS: Individuals with insomnia symptoms (n = 57, 66%) presented higher PSS (p < 0.001), PSQI (p < 0.0001), BDI, (p < 0.0001) scores and showed less-effective coping strategies such as the use of behavioral disengagement (p = 0.04), self-blame (p = 0.02) and emotional-focused coping (p = 0.001). In a multi-regression model ISI was the independent determinant of high PSS and of behavioral disengagement; PSQI was the only determinant of self-blame (p = 0.02) and emotional-focused coping. CONCLUSIONS: SLE individuals with insomnia symptoms show high levels of perceived stress and more frequent use of disengaging and emotional-focused coping strategies. This body of evidence suggests that individuals with SLE and comorbid insomnia symptoms may therefore require additional interventions for insomnia.

Risk factors for osteoporosis and fragility fractures in patients with systemic lupus erythematosus.

Osteoporosis (OP) and fragility fractures (FFx) are a known comorbidity in patients with systemic lupus erythematosus (SLE). This work aimed at evaluating (1) the prevalence of OP and FFx in a cohort of SLE and (2) the risk factors associated with both OP and FFx. The following data were collected from clinical charts: age, sex, menopausal status (MP), body mass index, smoking habits, disease duration, daily dose and cumulative glucocorticoids (GCs), type of organ involvement, comorbidities and medications. Data on bone metabolism, calcium and vitamin D supplementation and treatment with bisphosphonates, teriparatide or denosumab were collected, together with bone mineral density (BMD) values (measured by dual-energy X-ray absorptiometry (DXA)) and history of FFx (occurred after the onset of SLE and unrelated to trauma). OP and reduced BMD were defined according to the WHO. 186 patients were included (women 175, men 11; mean age 46.4±13 years, mean disease duration 14.9±9 years). At their last visit, 97 patients (52.2%) had a reduced BMD and 52 (27.9%) had OP. 22 patients (11.8%), all women, had at least one FFx; six patients (27.3%) were pre-menopausal. On univariate analysis, age, cumulative dose of GC, MP, therapy with antiepileptics and chronic renal failure (CRF) were correlated with OP (p<0.03); age, total amount of GC, MP, CRF, anticoagulants (AC) and antiepileptic therapy were correlated with FFx (p<0.05). The multivariate logistic model confirmed a direct association of OP and age, MP and antiepileptic therapy (p≤0.01) and of FFx and age, chronic therapy with AC and antiepileptics (p<0.03). In conclusion, low BMD is frequently observed in SLE, and FFx are observed also in premenopausal patients. Together with traditional risk factors (age, MP and GC), CRF and chronic treatments with AC or antiepileptics seem to be associated with a higher risk profile for OP and FFx occurrence.

Pre-differentiation of human neural stem cells into GABAergic neurons prior to transplant results in greater repopulation of the damaged brain and accelerates functional recovery after transient ischemic stroke.

INTRODUCTION: Despite attempts to prevent brain injury during the hyperacute phase of stroke, most sufferers end up with significant neuronal loss and functional deficits. The use of cell-based therapies to recover the injured brain offers new hope. In the current study, we employed human neural stem cells (hNSCs) isolated from subventricular zone (SVZ), and directed their differentiation into GABAergic neurons followed by transplantation to ischemic brain. METHODS: Pre-differentiated GABAergic neurons, undifferentiated SVZ-hNSCs or media alone were stereotaxically transplanted into the rat brain (n=7/group) 7 days after endothelin-1 induced stroke. Neurological outcome was assessed by neurological deficit scores and the cylinder test. Transplanted cell survival, cellular phenotype and maturation were assessed using immunohistochemistry and confocal microscopy. RESULTS: Behavioral assessments revealed accelerated improvements in motor function 7 days post-transplant in rats treated with pre-differentiated GABAergic cells in comparison to media alone and undifferentiated hNSC treated groups. Histopathology 28 days-post transplant indicated that pre-differentiated cells maintained their GABAergic neuronal phenotype, showed evidence of synaptogenesis and up-regulated expression of both GABA and calcium signaling proteins associated with neurotransmission. Rats treated with pre-differentiated cells also showed increased neurogenic activity within the SVZ at 28 days, suggesting an additional trophic role of these GABAergic cells. In contrast, undifferentiated SVZ-hNSCs predominantly differentiated into GFAP-positive astrocytes and appeared to be incorporated into the glial scar. CONCLUSION: Our study is the first to show enhanced exogenous repopulation of a neuronal phenotype after stroke using techniques aimed at GABAergic cell induction prior to delivery that resulted in accelerated and improved functional recovery.

Blood pressure and sodium intake from snacks in adolescents.

BACKGROUND/OBJECTIVES: The relationship between sodium intake and arterial blood pressure (BP) values in adolescence is still controversial. The intake of high-sodium processed foods as snacks has gone up worldwide. The purpose of the present cross-sectional study was to analyze the association between BP values and sodium intake from snacks. SUBJECTS/METHODS: The mean weekly consumption of snacks was evaluated in 1200 randomly selected adolescents aged 11-13 years by a food-frequency questionnaire; their anthropometric and BP values were measured by trained researchers. A dietary 24-h food-recall questionnaire was randomly given to 400 of the 1200 adolescents. RESULTS: Mean sodium intake from snacks was 1.4 g/day. Systolic and diastolic BP (SBP and DBP, respectively) significantly increased from the lower to the higher tertile of sodium from snacks and with increasing frequency of salty snacks consumption. In a multiple logistic regression model, both being in the highest SBP quartile and in the highest DBP quartile were significantly associated with the intake of sodium from snacks (odds ratio (OR)=1.48; 95% confidence interval (CI) 1.14-1.91 and OR=2.17; 95% CI 1.68-2.79, respectively), the consumption of >2/day salty snacks (OR=1.86; 95% CI 1.32-2.63 and OR=2.38; 95% CI 1.69-3.37, respectively) and body mass index (OR=1.26; 95% CI 1.22-1.31 and OR=1.14; 95% CI 1.10-1.18, respectively) but not with age, sex or exercise levels. In the 400 individuals, the average total sodium intake was 3.1 g/day and was significantly higher in individuals belonging to the highest quartile of SBP and DBP. CONCLUSIONS: Sodium intake from snacks was almost half of the average daily sodium consumption and was significantly associated with BP values in adolescents.

Nox2 knockout delays infarct progression and increases vascular recovery through angiogenesis in mice following ischaemic stroke with reperfusion.

Evidence suggests the NADPH oxidases contribute to ischaemic stroke injury and Nox2 is the most widely studied subtype in the context of stroke. There is still conjecture however regarding the benefits of inhibiting Nox2 to improve stroke outcome. The current study aimed to examine the temporal effects of genetic Nox2 deletion on neuronal loss after ischaemic stroke using knockout (KO) mice with 6, 24 and 72 hour recovery. Transient cerebral ischaemia was induced via intraluminal filament occlusion and resulted in reduced infarct volumes in Nox2 KO mice at 24 h post-stroke compared to wild-type controls. No protection was evident at either 6 h or 72 h post-stroke, with both genotypes exhibiting similar volumes of damage. Reactive oxygen species were detected using dihydroethidium and were co-localised with neurons and microglia in both genotypes using immunofluorescent double-labelling. The effect of Nox2 deletion on vascular damage and recovery was also examined 24 h and 72 h post-stroke using an antibody against laminin. Blood vessel density was decreased in the ischaemic core of both genotypes 24 h post-stroke and returned to pre-stroke levels only in Nox2 KO mice by 72 h. Overall, these results are the first to show that genetic Nox2 deletion merely delays the progression of neuronal loss after stroke but does not prevent it. Additionally, we show for the first time that Nox2 deletion increases re-vascularisation of the damaged brain by 72 h, which may be important in promoting endogenous brain repair mechanisms that rely on re-vascularisation.

Neuropsychiatric questionnaires in systemic lupus erythematosus.

Patients with systemic lupus erythematosus (SLE) can be affected by a multitude of neurologic and psychiatric symptoms with a wide range of prevalence and severity. Irrespectively from attribution to SLE or other causes, neuropsychiatric (NP) symptoms strongly impact short-term and long-term outcomes, thus NP evaluation during routine clinical practice in SLE should be undertaken regularly. The assessment of NP involvement in SLE patients is challenging and the available diagnostic tools fail to guarantee optimal diagnostic accuracy, sensitivity to changes as well as feasibility in routine clinical care. Standardised questionnaires (both physician-administered and self-reported) can offer valuable help to the treating physician to capture all possible NP syndromes; few SLE-specific NP questionnaire have been developed but validation in large cohort or cross-cultural adaptations are still pending. On the other hand, general instruments have been largely applied to SLE patients. Both kinds of questionnaires can address all possible NP manifestations either globally or, more frequently, focus on specific NP symptoms. These latter have been mainly used in SLE to detect and classify mild and subtle symptoms, more likely to be overlooked during routine clinical assessment such as headache, cognitive impairment and psychiatric manifestations. In conclusion, this literature review highlights a clear case for validation studies in this area and the wider implementation of questionnaires to assess NP involvement is still warranted. The broader use of such instruments could have important consequences; first of all, by standardising symptom assessment, a better definition of the prevalence of NP manifestation across different centres could be achieved. Secondly, prospective studies could allow for the evaluation of clinical significance of mild symptoms and their impact on the patient's function and quality of life.

Brain remodelling following endothelin-1 induced stroke in conscious rats.

The extent of stroke damage in patients affects the range of subsequent pathophysiological responses that influence recovery. Here we investigate the effect of lesion size on development of new blood vessels as well as inflammation and scar formation and cellular responses within the subventricular zone (SVZ) following transient focal ischemia in rats (n = 34). Endothelin-1-induced stroke resulted in neurological deficits detected between 1 and 7 days (P<0.001), but significant recovery was observed beyond this time. MCID image analysis revealed varying degrees of damage in the ipsilateral cortex and striatum with infarct volumes ranging from 0.76-77 mm3 after 14 days, where larger infarct volumes correlated with greater functional deficits up to 7 days (r = 0.53, P<0.05). Point counting of blood vessels within consistent sample regions revealed that increased vessel numbers correlated significantly with larger infarct volumes 14 days post-stroke in the core cortical infarct (r = 0.81, P<0.0001), core striatal infarct (r = 0.91, P<0.005) and surrounding border zones (r = 0.66, P<0.005; and r = 0.73, P<0.05). Cell proliferation within the SVZ also increased with infarct size (P<0.01) with a greater number of Nestin/GFAP positive cells observed extending towards the border zone in rats with larger infarcts. Lesion size correlated with both increased microglia and astrocyte activation, with severely diffuse astrocyte transition, the formation of the glial scar being more pronounced in rats with larger infarcts. Thus stroke severity affects cell proliferation within the SVZ in response to injury, which may ultimately make a further contribution to glial scar formation, an important factor to consider when developing treatment strategies that promote neurogenesis.

Risk of radiation-induced malignancies from CT scanning in children who underwent shunt treatment before 6 years of age: a retrospective cohort study with a minimum 10-year follow-up.

OBJECT: A number of mathematical models predict the risk of future cancer from the ionizing radiation exposure of CT scanning. The predictions are alarming. Some models predict 29,000 future cancers and 14,500 deaths in the US will be directly caused by 1 year's worth of CT scanning. However, there are very few clinical data to justify or refute these claims. Young children are theoretically highly susceptible to the damaging effects of radiation. In this study, the authors examined children who underwent CSF shunt placement before 6 years of age. The authors chose to study shunt-treated patients with the assumption that these patients would undergo future imaging, facilitating surveillance. They chose a study period of 1991-2001 to allow more than 10 years of follow-up data. METHODS: The authors studied 104 consecutive children who underwent CSF shunt placement prior to 6 years of age and who had at least 10 years of follow-up data. Sixty-two of these patients underwent shunt placement prior to 1 year of age. The age at the initial scanning session, the number of future CT scanning sessions, diagnosis, and results of any future studies were recorded. The age-specific radiation dose was calculated for children younger than 1 year. Children younger than 1 year at the time of shunt placement were evaluated separately, based on the assumption that they represented the highest risk cohort. The authors examined all data for any evidence of future leukemia or head/neck tumor (benign or malignant). RESULTS: These children underwent a total of 1584 CT scanning sessions over a follow-up period of 1622 person-years. A total of 517 scanning sessions were performed prior to 6 years of age, including 260 in the 1st year of life. Children who underwent shunt placement before 1 year of age underwent an average of 16.3 ± 13.5 CT sessions (range 1-41). Children undergoing placement between 1 and 6 years of age received an average of 14.1 ± 12.5 CT studies (range 5-52). There were no subsequent tumors (benign or malignant) or leukemia detected. CONCLUSIONS: Previously published models predict a significant number of future cancers directly caused by CT scanning. However, there are very few published clinical data. In the authors' study, zero future radiation-induced malignancies were detected after routine CT scanning in a high-risk group. While the authors do not consider their single-institution study adequate to define the actual risk, their data suggest that the overall risk is low. The authors hope this study encourages future collaborative efforts to define the actual risk to patients.

Sleep disorders and systemic lupus erythematosus.

OBJECTIVE: Sleep disturbances are often seen in rheumatic diseases, including systemic lupus erythematosus (SLE). However, the prevalence of sleep disorders in SLE as well as the contributing factors to their occurrence remain poorly understood. The aim of this paper is to review the clinical and psychobiological data on the relationship between sleep disturbances and SLE. METHOD: We performed a systematic search of MEDLINE, EMBASE and PsychINFO, using MeSH headings and keywords for "sleep disorders" and "SLE." RESULTS: Nine studies reporting the relationship between sleep disorders and SLE were found. Prevalence rates of sleep disorders ranged between 55% and 85%; differences in assessment techniques appeared to be a major source of this variability. In the majority of the studies an association between sleep disorders and disease activity, pain and fatigue has been reported. Psychosocial variables, depression, steroid use, and the role that sleep disruption has on pain, inflammation and cytokines, have been hypothesized as possible psychobiological factors. CONCLUSIONS: Sleep disorders appear to occur in more than half of patients with SLE and appear to be associated with disease activity. Pain and fatigue are also related to sleep disorders. Among the hypotheses on the possible mechanisms underlining the association between sleep disorders and SLE, psychosocial/psychological factors, especially depression, were the most frequently reported.