Thrombectomy with Conscious Sedation Compared with General Anesthesia: A DEFUSE 3 Analysis.

BACKGROUND AND PURPOSE: The optimal patient sedation during mechanical thrombectomy for ischemic stroke in the extended time window is unknown. The purpose of this study was to assess the impact of patient sedation on outcome in patients undergoing thrombectomy 6-16 hours from stroke onset. MATERIALS AND METHODS: Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 (DEFUSE 3) was a multicenter, randomized, open-label trial of thrombectomy for ICA and M1 occlusions in patients 6-16 hours from stroke onset. Subjects underwent thrombectomy with either general anesthesia or conscious sedation at the discretion of the treating institution. RESULTS: Of the 92 patients who were randomized to intervention, 26 (28%) underwent thrombectomy with general anesthesia and 66 (72%) underwent thrombectomy with conscious sedation. Baseline clinical and imaging characteristics were similar among all groups. Functional independence at 90 days was 23% for general anesthesia, 53% for conscious sedation, and 17% for medical management (P = .009 for general anesthesia versus conscious sedation). Conscious sedation was associated with a shorter time from arrival in the angiosuite to femoral puncture (median, 14 versus 18 minutes; P = 0.05) and a shorter time from femoral puncture to reperfusion (median, 36 versus 48 minutes; P = .004). Sixty-six patients were treated at sites that exclusively used general anesthesia (n = 14) or conscious sedation (n = 52). For these patients, functional independence at 90 days was significantly higher in the conscious sedation subgroup (58%) compared with the general anesthesia subgroup (21%) (P = .03). CONCLUSIONS: Patients who underwent thrombectomy with conscious sedation in the extended time window experienced a higher likelihood of functional independence at 90 days, a lower NIHSS score at 24 hours, and a shorter time from femoral puncture to reperfusion compared with those who had general anesthesia. This effect remained robust in institutions that only treated patients with a single anesthesia technique.

Epidemiology of classical risk factors in stroke patients in the Middle East.

The Middle East (ME) is an ethnically and economically diverse region. A systematic review of all stroke studies conducted in the ME was carried out, with the aim of determining the prevalence of classic vascular risk factors (CRFs) across this region. Additionally, the prevalence of CRFs in the ME was compared to that of a US cohort. Prospective and retrospective ME stroke studies published from 1994 to 2014 were searched for that specifically reported on the prevalence of CRFs. The Z test for proportions was used to determine the significance of differences in CRF rates between the ME and non-ME studies. A total of 21,724 stroke patients from 13 nations in the ME were included. The prevalence rates for CRFs in the ME stroke population were hypertension, 62.1%; diabetes, 33.1%; dyslipidaemia, 36.8%; ischaemic heart disease, 24.6%; smoking, 19.3%; and atrial fibrillation, 13.6%. Compared to the US cohort, ME patients had a lower prevalence of all CRFs except diabetes (P < 0.0001) and smoking (P = 0.05). Compared with stroke patients in the USA, those in the ME have a significantly higher prevalence of diabetes and smoking. Education and lifestyle modification is perhaps the most effective strategy in reducing the risk of stroke in this population.

Self-sampling for community respiratory illness: a new tool for national virological surveillance.

This report aims to evaluate the usefulness of self-sampling as an approach for future national surveillance of emerging respiratory infections by comparing virological data from two parallel surveillance schemes in England. Nasal swabs were obtained via self-administered sampling from consenting adults (≥ 16 years-old) with influenza symptoms who had contacted the National Pandemic Flu Service (NPFS) health line during the 2009 influenza pandemic. Equivalent samples submitted by sentinel general practitioners participating in the national influenza surveillance scheme run jointly by the Royal College of General Practitioners (RCGP) and Health Protection Agency were also obtained. When comparable samples were analysed there was no significant difference in results obtained from self-sampling and clinician-led sampling schemes. These results demonstrate that self-sampling can be applied in a responsive and flexible manner, to supplement sentinel clinician-based sampling, to achieve a wide spread and geographically representative way of assessing community transmission of a known organism.

Lower extremity dexterity is associated with agility in adolescent soccer athletes.

Agility is important for sport performance and potentially injury risk; however, factors affecting this motor skill remain unclear. Here, we evaluated the extent to which lower extremity dexterity (LED) and muscle performance were associated with agility. Fourteen male and 14 female soccer athletes participated. Agility was evaluated using a hopping sequence separately with both limbs and with the dominant limb only. The LED test evaluated the athletes' ability to dynamically regulate foot-ground interactions by compressing a spring prone to buckling with the lower limb. Muscle performance included hip and knee isometric strength and vertical jump height. Correlation analyses were used to assess the associations between muscle performance, LED, and agility. Multiple regression models were used to determine whether linear associations differed between sexes. On average, the female athletes took longer to complete the agility tasks than the male athletes. This difference could not be explained by muscle performance. Conversely, LED was found to be the primary determinant of agility (double limb: R(2) = 0.61, P < 0.001; single limb: R(2) = 0.63, P < 0.001). Our findings suggest that the sensorimotor ability to dynamically regulate foot-ground interactions as assessed by the LED test is predictive of agility in soccer athletes. We propose that LED may have implications for sport performance, injury risk, and rehabilitation.

Hip and knee kinematics are associated with pain and self-reported functional status in males and females with patellofemoral pain.

Altered hip and knee kinematics in the frontal and transverse planes may increase patellofemoral joint stress and contribute to the development of patellofemoral pain. The purpose of this cross-sectional study was to evaluate the association among hip and knee kinematics, pain, and self-reported functional status in males and females with patellofemoral pain. 20 males and 20 females with patellofemoral pain participated in this study. 3-dimensional hip and knee kinematics were quantified while performing a step-down task. A visual analogue scale was used to evaluate usual knee pain. The anterior knee pain scale was used to evaluate the knee functional score. For both groups combined, greater usual pain was associated with greater peak hip adduction, hip internal rotation and knee abduction (r=0.54-0.57, P<0.001). Also, modest to low correlations (r=-0.48 to - 0.37, P=0.03-0.08) were found among hip and knee kinematics and functional score. Stepwise regression revealed that peak hip internal rotation and hip adduction were significant predictors of pain, while peak hip adduction was the only predictor of function. Greater hip adduction, hip internal rotation and knee abduction are associated with higher levels of pain and reduced function in males and females with patellofemoral pain.

The influence of sex and maturation on landing biomechanics: implications for anterior cruciate ligament injury.

During landing and cutting, females exhibit greater frontal plane moments at the knee (internal knee adductor moments or external knee abduction moments) and favor the use of the knee extensors over the hip extensors to attenuate impact forces when compared with males. However, it is not known when this biomechanical profile emerges. The purpose of this study was to compare landing biomechanics between sexes across maturation levels. One hundred and nineteen male and female soccer players (9-22 years) participated. Subjects were grouped based on maturational development. Lower extremity kinematics and kinetics were obtained during a drop-land task. Dependent variables included the average internal knee adductor moment and sagittal plane knee/hip moment and energy absorption ratios during the deceleration phase of landing. When averaged across maturation levels, females demonstrated greater internal knee adductor moments (0.06±0.03 vs 0.01±0.02 N m/kg m; P<0.005), knee/hip extensor moment ratios (2.0±0.1 vs 1.4±0.1 N m/kg m; P<0.001) and knee/hip energy absorption ratios (2.9±0.1 vs 1.96±0.1 N m/kg m; P<0.001) compared with males. Higher knee adductor moments combined with disproportionate use of knee extensors relative to hip extensors observed in females reflect a biomechanical pattern that increases anterior cruciate ligament loading. This biomechanical strategy already was established in pre-pubertal female athletes.

Tamoxifen regulation of bone growth and endocrine function in the ovariectomized rat: discrimination of responses involving estrogen receptor α/estrogen receptor ß, G protein-coupled estrogen receptor, or estrogen-related receptor γ using fulvestrant (ICI 182780).

Tamoxifen is a selective estrogen receptor (ER) modulator, but it is also a deactivating ligand for estrogen-related receptor-γ (ERRγ) and a full agonist for the G protein-coupled estrogen receptor (GPER). Fulvestrant is a selective ER down-regulator that lacks agonist effects on ERα/ERß, is inactive on ERRγ, but acts as a full agonist on GPER. Fulvestrant effects on tamoxifen actions on uterine and somatic growth, bone, the growth hormone (GH)-insulin-like growth factor I (IGF-I) axis, and pituitary prolactin were analyzed to pharmacologically discriminate tamoxifen effects that may be mediated by ERα/ERß versus ERRγ versus GPER. Ovariectomized rats received tamoxifen (0.6 mg/kg/daily) plus fulvestrant at 0, 3, 6, or 12 mg/kg/daily for 5 weeks; controls received vehicle or 6 mg/kg fulvestrant daily. Tamoxifen effects to increase uterine weight, decrease serum IGF-I, increase pituitary prolactin, and increase bone mineral density could be fully blocked by fulvestrant, indicating mediation by ERα/ERß. Tamoxifen effects to decrease pituitary GH, tibia length, and body weight were only partially blocked by fulvestrant, indicating involvement of mechanisms unrelated to ERα/ERß. Fulvestrant did not inhibit tamoxifen actions to reduce total pituitary protein, again indicating effects not mediated by ERα/ERß. Tamoxifen actions to reduce serum GH were mimicked rather than inhibited by fulvestrant, pharmacological features consistent with GPER involvement. However, fulvestrant alone increased IGF-I and also blocked tamoxifen-evoked IGF-I decreases; thus fulvestrant effects on serum GH might reflect increased IGF-I feedback inhibition. Fulvestrant alone had no effect on the other parameters. The findings indicate that mechanisms unrelated to ERα/ERß contribute to tamoxifen effects on body weight, bone growth, and pituitary function.

The influence of classroom aggression and classroom climate on aggressive-disruptive behavior.

Research suggests that early classroom experiences influence the socialization of aggression. Tracking changes in the aggressive behavior of 4,179 children from kindergarten to second-grade (ages 5-8), this study examined the impact of 2 important features of the classroom context--aggregate peer aggression and climates characterized by supportive teacher-student interactions. The aggregate aggression scores of children assigned to first-grade classrooms predicted the level of classroom aggression (assessed by teacher ratings) and quality of classroom climate (assessed by observers) that emerged by the end of Grade 1. Hierarchical linear model analyses revealed that first-grade classroom aggression and quality of classroom climate made independent contributions to changes in student aggression, as students moved from kindergarten to second grade. Implications for policy and practice are discussed.

Individuals with patellofemoral pain exhibit greater patellofemoral joint stress: a finite element analysis study.

OBJECTIVE: To test the hypothesis that individuals with patellofemoral pain (PFP) exhibit greater patellofemoral joint stress profiles compared to persons who are pain-free. METHODS: Ten females with PFP and ten gender, age, and activity-matched pain-free controls participated. Patella and femur stress profiles were quantified utilizing subject-specific finite element (FE) models of the patellofemoral joint at 15° and 45° of knee flexion. Input parameters for the FE model included: (1) joint geometry, (2) quadriceps muscle forces, and (3) weight-bearing patellofemoral joint kinematics. Using a nonlinear FE solver, quasi-static loading simulations were performed to quantify each subject's patellofemoral joint stress profile during a static squatting maneuver. The patella and femur peak and mean hydrostatic pressure as well as the peak and mean octahedral shear stress for the elements representing the chondro-osseous interface were quantified. RESULTS: Compared to the pain-free controls, individuals with PFP consistently exhibited greater peak and mean hydrostatic pressure as well as peak and mean octahedral shear stress for the elements representing the patella and femur chondro-osseous interface across the two knee flexion angles tested (15° and 45°). CONCLUSIONS: The combined finding of elevated hydrostatic pressure and octahedral shear stress across the two knee flexion angles supports the premise that PFP may be associated with elevated joint stress. Therefore, treatments aimed at decreasing patellofemoral joint stress may be indicated in this patient population.

Sub-clinical infection with Salmonella in chickens differentially affects behaviour and welfare in three inbred strains.

1. Much evidence exists detailing how animals respond to pathogen challenge, yet information explaining how the various behavioural, immunological, and physiological systems in chickens interplay during such challenges remains limited. 2. To gain an understanding of this interplay while controlling for genetic variation, the current study collected a variety of behavioural, physiological and immunological measures from three inbred lines (P, O and N) of laying hens before and after a sub-clinical infection with Salmonella enterica Typhimurium at 56 d of age. For comparison, an equal number of control birds were inoculated with a Salmonella-free broth. To identify an underlying profile, which might result in reduced susceptibility to infection, data were also collected in the pre-infection period. Post-infection blood and faeces were collected at 1-d post infection (dpi) and faeces again at 8 dpi. Animals were killed 15 d after infection and faeces, caecal contents, and spleen were examined for the presence of Salmonella. 3. Statistical analysis was performed to identify pre- and post-infection differences between genetic lines, changes in bird behavioural patterns between the two periods, and associations between a positive test for Salmonella and the various response measures. 4. Tissues from Line P birds were more often negative for Salmonella than those from birds of other lines, though this was inconsistent and tissue-dependent. The P line was also characterised by relatively greater serum concentrations of immunoglobulins at 1 dpi and α(1)-acid glycoprotein at 15 dpi. In addition, P line birds were more timid and their growth was reduced during the pre-infection period suggesting the possibility of a profile with reduced susceptibility to the bacterial challenge. 5. The current work has identified correlations between attributes of chicken strains and improved clearance. Future work using hypothesis-based testing will be required to determine whether the identified correlations are causally related.

Association between patella alta and the prevalence and worsening of structural features of patellofemoral joint osteoarthritis: the multicenter osteoarthritis study.

OBJECTIVE: To examine the relationship between patella alta and the prevalence and worsening at followup of structural features of patellofemoral joint (PFJ) osteoarthritis (OA) on magnetic resonance imaging (MRI). METHODS: The Multicenter Osteoarthritis Study is a cohort study of persons ages 50-79 years with or at risk for knee OA. Patella alta was measured using the Insall-Salvati ratio (ISR) on the baseline lateral radiograph, and cartilage damage, bone marrow lesions (BMLs), and subchondral bone attrition (SBA) were graded on MRI at baseline and at 30 months of followup in the PFJ. We examined the association of the ISR with the prevalence and worsening of cartilage damage, BMLs, and SBA in the PFJ using logistic regression. RESULTS: A total of 907 knees were studied (mean age 62 years, body mass index 30 kg/m(2), ISR 1.10), 63% from female subjects. Compared with knees in the lowest ISR quartile at baseline, those in the highest quartile had 2.4 (95% confidence interval [95% CI] 1.7-3.3), 2.9 (95% CI 2.0-4.3), and 3.5 (95% CI 2.3-5.5) times the odds of having lateral PFJ cartilage damage, BMLs, and SBA, respectively, and 1.5 (95% CI 1.1-2.0), 1.3 (95% CI 0.9-1.8), and 2.2 (95% CI 1.4-3.4) times the odds of having medial PFJ cartilage damage, BMLs, and SBA, respectively. Similarly, those with high ISRs were also at risk for worsening of cartilage damage and BMLs over time than those with low ISRs. CONCLUSION: A high ISR, indicative of patella alta, is associated with structural features of OA in the PFJ. Additionally, the same knees have an increased risk of worsening of these same features over time.

Neurocognitive contributions to verbal fluency deficits in frontotemporal lobar degeneration.

OBJECTIVE: To test the hypothesis that different neurocognitive networks underlie verbal fluency deficits in frontotemporal lobar degeneration (FTLD). METHODS: Letter ("FAS") and semantic ("animal") fluency tests were administered to patients with a behavioral/dysexecutive disorder (bvFTLD; n = 71), semantic dementia (SemD; n = 21), and progressive nonfluent aphasia (PNFA; n = 26). Tests measuring working memory, naming/lexical retrieval, and semantic knowledge were also obtained. MRI voxel-based morphometry (VBM) studies were obtained on a subset of these patients (bvFTLD, n = 51; PNFA, n = 11; SemD, n = 10). RESULTS: Patients with SemD were disproportionately impaired on the semantic fluency measure. Reduced output on this test was correlated with impaired performance on naming/lexical retrieval tests. VBM analyses related reduced letter and semantic fluency to anterior and inferior left temporal lobe atrophy. Patients with bvFTLD were equally impaired on both fluency tests. Poor performance on both fluency tests was correlated with low scores on working memory and naming/lexical retrieval measures. In this group, MRI-VBM analyses related letter fluency to bilateral frontal atrophy and semantic fluency to left frontal/temporal atrophy. Patients with PNFA were also equally impaired on fluency tests. Reduced semantic fluency output was correlated with reduced performance on naming/lexical retrieval tests. MRI-VBM analyses related semantic fluency to the right frontal lobe and letter fluency to left temporal atrophy. CONCLUSIONS: Distinct neurocognitive networks underlie impaired performance on letter and semantic fluency tests in frontotemporal lobar degeneration subgroups.

IRS1 G972R polymorphism and type 2 diabetes: a paradigm for the difficult ascertainment of the contribution to disease susceptibility of 'low-frequency-low-risk' variants.

AIMS/HYPOTHESIS: The aim of the study was to determine the association between IRS1 G972R polymorphism and type 2 diabetes; published data concerning this association have been conflicting. To obtain further insight into this topic, we performed a meta-analysis of all available case-control studies. METHODS: We performed a meta-analysis of 32 studies (12,076 cases and 11,285 controls). RESULTS: The relatively infrequent R972 variant was not significantly associated with type 2 diabetes (OR 1.09, 95% CI 0.96-1.23, p = 0.184 under a dominant model). Some evidence of heterogeneity was observed across studies (p = 0.1). In the 14 studies (9,713 individuals) in which the mean age at type 2 diabetes diagnosis was available, this variable explained 52% of the heterogeneity (p = 0.03). When these studies were subdivided into tertiles of mean age at diagnosis, the OR for diabetes was 1.48 (95% CI 1.17-1.87), 1.22 (95% CI 0.97-1.53) and 0.88 (95% CI 0.68-1.13) in the youngest, intermediate and oldest tertile, respectively (p = 0.0022 for trend of ORs). CONCLUSIONS/INTERPRETATION: Our findings illustrate the difficulties of ascertaining the contribution of 'low-frequency-low-risk' variants to type 2 diabetes susceptibility. In the specific context of the R972 variant, approximately 200,000 study individuals would be needed to have 80% power to identify a 9% increase in diabetes risk at a genome-wide significance level. Under these circumstances, a strategy aimed at improving outcome definition and decreasing its heterogeneity may critically enhance our ability to detect genetic effects, thereby decreasing the required sample size. Our data suggest that focusing on early-onset diabetes, which is characterised by a stronger genetic background, may be part of such a strategy.

Hyalinizing clear cell carcinoma: report of eight cases and a review of literature.

Hyalinizing clear cell carcinoma (HCCC) is an extremely rare neoplasm with a female predominance, composed of nests of monomorphic clear cells within a hyaline stroma. This tumor often follows an indolent course and treatment includes wide surgical excision with or without adjuvant radiotherapy. We report eight cases of HCCC identified at two academic institutions in six women and two men, ranging in age from 25 to 86 years. Histologically, all cases demonstrated cords, trabeculae, and nests of monomorphic clear cells as well as cells with eosinophilic granular cytoplasm. Mild cellular atypia was occasionally seen and mitoses were very rare. Seven cases demonstrated a hyalinized stroma, and one case, a myxoid stroma. Immunohistochemically, the tumor cells were positive for epithelial markers and negative for desmin and actin. Seven cases were negative for S-100. Cells were also positive for periodic acid-Schiff and negative for mucin. The important clinicopathologic features and the differential diagnoses of HCCC, as well as a review of the literature are discussed.

Cytomegalovirus immune evasion.

Human cytomegalovirus (HCMV) has become a paradigm for viral immune evasion due to its unique multitude of immune-modulatory strategies. HCMV modulates the innate as well as adaptive immune response at every step of its life cycle. It dampens the induction of antiviral interferon-induced genes by several mechanisms. Further striking is the multitude of genes and strategies devoted to modulating and escaping the cellular immune response. Several genes are independently capable of inhibiting antigen presentation to cytolytic T cells by downregulating MHC class I. Recent data revealed an astounding variety of methods in triggering or inhibiting activatory and inhibitory receptors found on NK cells, NKT cells, T cells as well as auxiliary cells of the immune system. The multitude and complexity of these mechanisms is fascinating and continues to reveal novel insights into the host-pathogen interaction and novel cell biological and immunological concepts.

Double Jeopardy: Child and School Characteristics That Predict Aggressive-Disruptive Behavior in First Grade.

High rates of aggressive-disruptive behavior exhibited by children during their initial years of elementary school increase their risk for significant behavioral adjustment problems with teachers and peers. The purpose of the present study was to examine the unique and combined contributions of child vulnerabilities and school context to the development of aggressive-disruptive student behavior during first grade. Parent ratings and child interviews assessed three child characteristics associated with risk for the development of aggressive behavior problems in elementary school (aggressive-disruptive behaviors at home, attention problems, and social cognitions) in a sample of 755 first-grade children in four demographically diverse American communities. Two school characteristics associated with student aggressive-disruptive behavior problems (low-quality classroom context, school poverty levels) were also assessed. Linear and multilevel analyses showed that both child and school characteristics made independent and cumulative contributions to the development of student aggressive-disruptive behavior at school. Although rates of student aggressive-disruptive behavior varied by gender and race, the predictive model generalized across all groups of children in the study.

Examination of PPP1R3B as a candidate gene for the type 2 diabetes and MODY loci on chromosome 8p23.

The product of the PPP1R3B gene (G(L)) is the regulatory subunit of PP1 - a serine/threonine phosphatase involved in the modulation of glycogen synthesis in the liver and skeletal muscle. The PPP1R3B gene is located on chromosome 8p23 in a region that has been linked with type 2 diabetes and maturity-onset diabetes of the young (MODY). We examined whether sequence variants at the PPP1R3B locus are responsible for the linkage with diabetes observed at this location. RT-PCR analysis revealed the existence of two alternative promoters. These and the two exons of this gene were sequenced in the probands of 13 Joslin families showing the strongest evidence of linkage at 8p23. A total of 20 variants were observed: two in the 5' flanking region, one in the intron (9 bp 5' of exon 2), and 17 in the 3' UTR. The intronic variant generated a new acceptor splice site, resulting in an alternative splice variant with a longer 5' UTR. However, neither this nor other variants segregated with diabetes in the 13 'linked' families. Furthermore, allele frequencies were similar in 90 family probands from the Joslin Study and 347 unrelated controls. Thus, genetic variability in the PPP1R3B gene does not appear to contribute to diabetes in our mostly Caucasian families. However, a role cannot be excluded in other populations such as the Japanese, among whom linkage to diabetes is also observed at 8p23 and a non-synonymous mutation has been detected in the PPP1R3B gene.