Resistance Training With Elastic Tubing Improves Muscle Strength, Exercise Capacity, and Post-Exercise Creatine Kinase Clearance in Subjects With COPD.
Among the types of physical exercise, resistance exercises have been gaining significant attention in the COPD population. The aim of this study was to compare effects of conventional resistance training and of training by using elastic tubes on muscle strength, exercise capacity, and creatine kinase clearance in subjects with COPD. Twenty-eight subjects with COPD were randomized into the following: resistance training with the elastic tubing group and resistance training with the weight-machine training group (conventional resistance group), performed 3 times a week for 12 weeks. The subjects were submitted to spirometry, functional exercise capacity (the 6-min walk test), muscle strength (dynamometry), and the repetition maximum test. Differences between the initial and final evaluations (Δ) and the (final - initial evaluations)/initial evaluations ×100 (Δ%) of each group were expressed as mean [95% CI]. Nineteen subjects (FEV1 % predicted, 52 ± 18; years, 65 ± 8) completed the training program. Similar improvements were observed in both modalities on muscle strength (knee extension, Δ%18 [6 to 29]; knee flexion, Δ%35 [17 to 54]; elbow flexion, Δ%28 [9 to 48]; shoulder abduction, Δ%41 [25 to 58] and shoulder flexion, Δ%31 [11 to 51] in the weight-machine training group (conventional resistance group); knee extension, Δ%15 [8 to 21]; knee flexion, Δ%28 [15 to 41]; elbow flexion, Δ%36 [22 to 51]; and shoulder abduction, Δ%43 [32 to 55] and shoulder flexion, Δ%43 [25 to 61] in the elastic tubing group, P < .05 for intra-group analysis and P > .05 for between groups analysis), 6-min walk test (baseline 493 ± 67m vs 12 weeks 526 ± 78 in the weight-machine training group (P = .10); baseline 493 ± 71 vs 12 weeks 524 ± 68 in the elastic tubing group (P < .01), P = .88 between groups). The elastic tubing group had lower accumulated creatine kinase levels between 24 and 72 h ((Δ%-24 [-31 to 16] than subjects in the weight-machine training group Δ%3 [-21 to 28], P = .042 between the groups. Training with elastic resistance provided similar changes in muscle strength and exercise capacity to conventional resistance group in the subjects with COPD. The elastic tubing group had faster creatine kinase clearance after a training session than the weight-machine training group (conventional resistance group). The ease of its application associated with similar training benefits to conventional training supported its application in clinical routine.


Perioperative Rosuvastatin in Cardiac Surgery.
Complications after cardiac surgery are common and lead to substantial increases in morbidity and mortality. Meta-analyses of small randomized trials have suggested that perioperative statin therapy can prevent some of these complications. We randomly assigned 1922 patients in sinus rhythm who were scheduled for elective cardiac surgery to receive perioperative rosuvastatin (at a dose of 20 mg daily) or placebo. The primary outcomes were postoperative atrial fibrillation within 5 days after surgery, as assessed by Holter electrocardiographic monitoring, and myocardial injury within 120 hours after surgery, as assessed by serial measurements of the cardiac troponin I concentration. Secondary outcomes included major in-hospital adverse events, duration of stay in the hospital and intensive care unit, left ventricular and renal function, and blood biomarkers. The concentrations of low-density lipoprotein cholesterol and C-reactive protein after surgery were lower in patients assigned to rosuvastatin than in those assigned to placebo (P<0.001). However, the rate of postoperative atrial fibrillation did not differ significantly between the rosuvastatin group and the placebo group (21.1% and 20.5%, respectively; odds ratio 1.04; 95% confidence interval [CI], 0.84 to 1.30; P=0.72), nor did the area under the troponin I-release curve (102 ng×hour per milliliter and 100 ng×hour per milliliter, respectively; between-group difference, 1%; 95% CI, -9 to 13; P=0.80). Subgroup analyses did not indicate benefit in any category of patient. Rosuvastatin therapy did not result in beneficial effects on any of the secondary outcomes but was associated with a significant absolute (±SE) excess of 5.4±1.9 percentage points in the rate of postoperative acute kidney injury (P=0.005). In this trial, perioperative statin therapy did not prevent postoperative atrial fibrillation or perioperative myocardial damage in patients undergoing elective cardiac surgery. Acute kidney injury was more common with rosuvastatin. (Funded by the British Heart Foundation and others; STICS ClinicalTrials.gov number, NCT01573143.).


The WHEAT pilot trial-WithHolding Enteral feeds Around packed red cell Transfusion to prevent necrotising enterocolitis in preterm neonates: a multicentre, electronic patient record (EPR), randomised controlled point-of-care pilot trial.
Necrotising enterocolitis (NEC) is a potentially devastating neonatal disease. A temporal association between red cell transfusion and NEC is well described. Observational data suggest that withholding enteral feeds around red cell transfusions may reduce the risk of NEC but this has not been tested in randomised trials; current UK practice varies. Prevention of NEC is a research priority but no appropriately powered trials have addressed this question. The use of a simplified opt-out consent model and embedding trial processes within existing electronic patient record (EPR) systems provide opportunities to increase trial efficiency and recruitment. We will undertake a randomised, controlled, multicentre, unblinded, pilot trial comparing two care pathways: continuing milk feeds (before, during and after red cell transfusions) and withholding milk feeds (for 4 hours before, during and for 4 hours after red cell transfusions), with infants randomly assigned with equal probability. We will use opt-out consent. A nested qualitative study will explore parent and health professional views. Infants will be eligible if born at <30+0 gestational weeks+days. Primary feasibility outcomes will be rate of recruitment, opt-out, retention, compliance, data completeness and data accuracy; clinical outcomes will include mortality and NEC. The trial will recruit in two neonatal networks in England for 9 months. Data collection will continue until all infants have reached 40+0 corrected gestational weeks or neonatal discharge. Participant identification and recruitment, randomisation and all trial data collection will be embedded within existing neonatal EPR systems (BadgerNet and BadgerEPR); outcome data will be extracted from routinely recorded data held in the National Neonatal Research Database. This study holds Research Ethics Committee approval to use an opt-out approach to consent. Results will inform future EPR-embedded and data-enabled trials and will be disseminated through conferences, publications and parent-centred information. ISRCTN registry ISRCTN62501859; Pre-results.


Rapid diagnosis of myocardial injury with troponin T and CK-MB relative index.
Current hospital practice involves protracted observation of chest-pain patients to rule out myocardial infarction. Concurrent measurement of multiple biomarkers may increase sensitivity and make rapid diagnosis feasible. We sought to determine the optimal biomarker strategy for highly sensitive, early diagnosis of myocardial injury. A prospective evaluation of 171 acute coronary syndrome patients admitted to a single university medical center was performed. Blood tests for creatine kinase (CK), CK myocardial band isoenzyme (CK-MB), and troponin T were obtained at 0, 3, 6, 8, and 16 hours after presentation to the emergency department. Myocardial injury was defined as a troponin T level of >or=0.03 ng/mL. Troponin T had sensitivities of 79.7%, 95.7%, and 98.4% at the time of initial presentation, 3 and 6 hours after presentation, respectively. Using a combination of troponin T and CK-MB relative index, sensitivity on presentation was increased to 90.6%. The sensitivity was improved to 97.9% and 100% at 3 and 6 hours, respectively. This study demonstrates that the diagnosis of myocardial injury can be accurately excluded within 6 hours of admission with high sensitivity using troponin T. The combination of troponin T and CK-MB relative index provided the largest improvement in diagnostic sensitivity at patient arrival. These results support the feasibility of rapid, efficient triage for the emergent presentation of patients with chest pain.


Role of immunoproteasomes in cross-presentation.
The evidence that proteasomes are involved in the processing of cross-presented proteins is indirect and based on the in vitro use of proteasome inhibitors. It remains, therefore, unclear whether cross-presentation of MHC class I peptide epitopes can occur entirely within phagolysosomes or whether it requires proteasome degradation. To address this question, we studied in vivo cross-presentation of an immunoproteasome-dependent epitope. First, we demonstrated that generation of the immunodominant HY Uty(246-254) epitope is LMP7 dependent, resulting in the lack of rejection of male LMP7-deficient (LMP7(-/-)) skin grafts by female LMP7(-/-) mice. Second, we ruled out an altered Uty(246-254)-specific T cell repertoire in LMP7(-/-) female mice and demonstrated efficient Uty(246-254) presentation by re-expressing LMP7 in male LMP7(-/-) cells. Finally, we observed that LMP7 expression significantly enhanced cross-priming of Uty(246-254)-specific T cells in vivo. The observations that male skin grafts are not rejected by LMP7(-/-) female mice and that presentation of a proteasome-dependent peptide is not efficiently rescued by alternative cross-presentation pathways provide strong evidence that proteasomes play an important role in cross-priming events.


Bisphenol A Release: Survey of the Composition of Dental Composite Resins.
Bisphenol A (BPA) is an endocrine disruptor with potential toxicity. Composite resins may not contain pure BPA, but its derivatives are widely used. Several studies found doses of BPA or its derivatives in saliva or urine of patients after composite resin placement. The aims of this study were to establish an exhaustive list of composite resins marketed in Europe and their composition, and to assess the extent of BPA derivatives used. A research on manufacturers' websites was performed to reference all composite resins marketed in Europe, then their composition was determined from both material safety data sheets and a standardized questionnaire sent to manufacturers. Manufacturers had to indicate whether their product contained the monomers listed, add other monomers if necessary, or indicate "not disclosed". 160 composite resins were identified from 31 manufacturers and 23 manufacturers (74.2%) responded to the survey. From the survey and websites, the composition of 130 composite resins (81.2%) was: 112 (86.2%) based on BPA derivatives, 97 (74.7%) on bis-GMA, 17 (13.1%) without monomer derived from BPA (UDMA, sometimes with TEGDMA) and 6 (4.6%) with UDMA (only); 1 (0.8%) did not contain a BPA derivative or UDMA or TEGDMA. Pure BPA was never reported. This work has established a list of 18 composite resins that contain no BPA derivative. Manufacturers should be required to report the exact composition of their products as it often remains unclear or incomplete.


Monitoring the spread of meticillin-resistant Staphylococcus aureus in The Netherlands from a reference laboratory perspective.
In The Netherlands, efforts to control meticillin-resistant Staphylococcus aureus (MRSA) in hospitals have been largely successful due to stringent screening of patients on admission and isolation of those that fall into defined risk categories. However, Dutch hospitals are not free of MRSA, and a considerable number of cases are found that do not belong to any of the risk categories. Some of these may be due to undetected nosocomial transmission, whereas others may be introduced from unknown reservoirs. Identifying multi-institutional clusters of MRSA isolates to estimate the contribution of potential unobserved reservoirs in The Netherlands. We applied a clustering algorithm that combines time, place, and genetics to routine data available for all MRSA isolates submitted to the Dutch Staphylococcal Reference Laboratory between 2008 and 2011 in order to map the geo-temporal distribution of MRSA clonal lineages in The Netherlands. Of the 2966 isolates lacking obvious risk factors, 579 were part of geo-temporal clusters, whereas 2387 were classified as MRSA of unknown origin (MUOs). We also observed marked differences in the proportion of isolates that belonged to geo-temporal clusters between specific multi-locus variable number of tandem repeat analysis (MLVA) clonal complexes, indicating lineage-specific transmissibility. The majority of clustered isolates (74%) were present in multi-institutional clusters. The frequency of MRSA of unknown origin among patients lacking obvious risk factors is an indication of a largely undefined extra-institutional but genetically highly diverse reservoir. Efforts to understand the emergence and spread of high-risk clones require the pooling of routine epidemiological information and typing data into central databases.


Viability of anastomoses with coupler in extra-intracranial bypass: cadaveric study.
The time required to perform an anastomosis in extra-intracranial bypass is approximately 20 to 60 minutes. The search for alternative methods to reduce the ischemic time remains vital. To evaluate Coupler anastomosis for extra-intracranial bypass in cadavers. In 8 fresh adult cadavers, the saphenous vein and radial artery were used as donor vessels. The superficial temporal and the extracranial internal and external carotid arteries were dissected. A wide craniotomy with a sylvian fissure opening was performed, exposing the middle cerebral and supraclinoid internal carotid arteries. The Coupler devices were tested in all 8 cadavers. The diameter of the donor and recipient vessels as well as the time required to perform the anastomosis were measured. Bypass permeability was evaluated by injecting saline solution under pressure, checking for leaks. The anastomoses were successfully performed in all specimens. The size of the head of the fitting Coupler required the performance of a wide craniotomy (6 × 6 cm) and a wide opening of the sylvian fissure. The time required to perform each anastomosis ranged from 4 to 7 minutes, being easier with the radial artery than with the saphenous vein. Coupler devices are helpful to perform the anastomoses, because they significantly reduce ischemia time. Their use is easier at the M1 segment, just before the bifurcation and after takeoff of the lenticulostriate arteries, and in the M2 segment. It would be advisable to have a smaller coupling system, allowing maneuverability in the deeper areas where space is limited.


NO binding kinetics in myoglobin investigated by picosecond Fe K-edge absorption spectroscopy.
Diatomic ligands in hemoproteins and the way they bind to the active center are central to the protein's function. Using picosecond Fe K-edge X-ray absorption spectroscopy, we probe the NO-heme recombination kinetics with direct sensitivity to the Fe-NO binding after 532-nm photoexcitation of nitrosylmyoglobin (MbNO) in physiological solutions. The transients at 70 and 300 ps are identical, but they deviate from the difference between the static spectra of deoxymyoglobin and MbNO, showing the formation of an intermediate species. We propose the latter to be a six-coordinated domed species that is populated on a timescale of ∼ 200 ps by recombination with NO ligands. This work shows the feasibility of ultrafast pump-probe X-ray spectroscopic studies of proteins in physiological media, delivering insight into the electronic and geometric structure of the active center.


Genome-wide association studies of MRI-defined brain infarcts: meta-analysis from the CHARGE Consortium.
Previous studies examining genetic associations with MRI-defined brain infarct have yielded inconsistent findings. We investigated genetic variation underlying covert MRI infarct in persons without histories of transient ischemic attack or stroke. We performed meta-analysis of genome-wide association studies of white participants in 6 studies comprising the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. Using 2.2 million genotyped and imputed single nucleotide polymorphisms, each study performed cross-sectional genome-wide association analysis of MRI infarct using age- and sex-adjusted logistic regression models. Study-specific findings were combined in an inverse-variance-weighted meta-analysis, including 9401 participants with mean age 69.7 (19.4% of whom had >or=1 MRI infarct). The most significant association was found with rs2208454 (minor allele frequency, 20%), located in intron 3 of MACRO domain containing 2 gene and in the downstream region of fibronectin leucine-rich transmembrane protein 3 gene. Each copy of the minor allele was associated with lower risk of MRI infarcts (odds ratio, 0.76; 95% confidence interval, 0.68-0.84; P=4.64x10(-7)). Highly suggestive associations (P<1.0x10(-5)) were also found for 22 other single nucleotide polymorphisms in linkage disequilibrium (r(2)>0.64) with rs2208454. The association with rs2208454 did not replicate in independent samples of 1822 white and 644 black participants, although 4 single nucleotide polymorphisms within 200 kb from rs2208454 were associated with MRI infarcts in the black population sample. This first community-based, genome-wide association study on covert MRI infarcts uncovered novel associations. Although replication of the association with top single nucleotide polymorphisms failed, possibly because of insufficient power, results in the black population sample are encouraging, and further efforts at replication are needed.


Hybrid Vibrio vulnificus.
The recent emergence of the human-pathogenic Vibrio vulnificus in Israel was investigated by using multilocus genotype data and modern molecular evolutionary analysis tools. We show that this pathogen is a hybrid organism that evolved by the hybridization of the genomes from 2 distinct and independent populations. These findings provide clear evidence of how hybridization between 2 existing and nonpathogenic forms has apparently led to the emergence of an epidemic infectious disease caused by this pathogenic variant. This novel observation shows yet another way in which epidemic organisms arise.


Femoral Neck Fracture After Arthroscopic Femoroplasty of the Hip.
Hip arthroscopy is an increasingly common procedure, particularly for the treatment of femoroacetabular impingement. Various complications have been previously reported, and the authors sought to further evaluate the safety of this procedure. This study was conducted to identify the incidence of femoral neck fracture as well as treatment and outcomes after arthroscopic femoroplasty. In April 2013, a survey was administered to 28 established hip arthroscopists regarding the breadth of their experience, including the total number of hip arthroscopies and proximal femoroplasties performed and the number of postoperative femoral neck fractures. Fracture type, patient age, patient sex, time to fracture, comorbidities, treatments, and outcomes were queried. The study identified 27,200 total arthroscopies and 14,945 proximal femoroplasties performed by the surgeons, with 11 postoperative proximal femur fractures. The incidence of proximal femur fracture after arthroscopic femoroplasty was 0.07%, based on combined data of high-volume hip arthroscopists at multiple medical centers. Mean time to fracture after arthroscopic femoroplasty was 40.5 (±26.6) days postoperatively. The male-to-female ratio was approximately 1:3 for those with fracture, and mean patient age was 52 (±13) years. More than half of the fractures were caused by violation of weight-bearing precautions. All patients had improvement in symptoms after treatment. Femoral neck fracture after arthroscopic femoroplasty is a rare complication for established hip arthroscopists. It is most common in women and patients older than 50 years. Treatment is based on the severity of the fracture, and patients have improved outcomes after treatment.


5-lipoxygenase inhibitor (AA-861) attenuates neutrophil-mediated oxidative stress on the venular endothelium in endotoxemia.
Neutrophil-mediated oxidative stress on the rat mesenteric microcirculation was studied in the experimental model of endotoxin-induced disseminated intravascular coagulation (DIC) by using an intravital fluorescent microscope equipped with a Silicon Intensifier Target Image Tube camera and luminol-dependent chemiluminescence (ChL) analysis. Leukocytes adhering to the venules were visualized by the injection of acridine orange, a fluorochrome tracer which shows high affinity to white cells. Endotoxin (E. coli, O-111 B4) was administered intravenously at a dose of 2 mg/kg/hour. After starting the infusion of endotoxin, the number of adherent cells gradually increased in the venular endothelium and was followed by a transient neutropenia. ChL activities from neutrophils were also significantly elevated, which may reflect the enhanced ability to generate oxygen-radicals. To elucidate the role of 5-lipoxygenase products in the locomotive and metabolic changes of neutrophils, the effects of AA-861, a specific inhibitor of 5-lipoxygenase was tested. In addition prednisolone and indomethacin were evaluated. AA-861 and prednisolone reduced neutropenia, leukocyte adhesion to the venular walls and ChL activities from neutrophils. It was concluded that 5-lipoxygenase may modulate neutrophil-mediated oxidative stress on microvasculature in endotoxin-induced DIC.


Aβ1-42 and Tau as Potential Biomarkers for Diagnosis and Prognosis of Amyotrophic Lateral Sclerosis.
Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease, but its definitive diagnosis delays around 12 months. Although the research is highly active in the biomarker field, the absence of specific biomarkers for diagnosis contributes to this long delay. Another strategy of biomarker identification based on less specific but sensitive molecules may be of interest in clinical practice. For example, markers related to other neurodegenerative diseases such as Alzheimer's disease (AD) could be fully explored. Here, we compared baseline levels of amyloidβ1-42 (Aβ1-42), total Tau, and phosphorylated-Tau (phospho-Tau) protein in the cerebrospinal fluid (CSF) of ALS patients to controls and correlated it with clinical parameters of ALS progression collected over 12 months. We observed increased levels of Aβ1-42 (controls: 992.9 ± 358.3 ng/L; ALS: 1277.0 ± 296.6 ng/L; p < 0.0001) and increased Aβ1-42/phospho-Tau ratio and Innotest Amyloid Tau Index (IATI) (both p < 0.0001). IATI and the phospho-Tau/total Tau ratio correlated positively with ALSFRS-R and weight at baseline. Multivariate analysis revealed that baseline ALSFRS-R was associated with Aβ1-42 and phospho-Tau/total Tau ratio (p = 0.0109 and p = 0.0013, respectively). Total Tau and phospho-Tau levels correlated negatively with ALSFRS-R variation at months 6 and 9, respectively (p = 0.02 and p = 0.04, respectively). Phospho-Tau/total Tau ratio correlated positively with ALSFRS-R variation at month 9 (p = 0.04). CSF levels of Aβ1-42 could be used as a complementary tool to ALS diagnosis, and total Tau and phospho-Tau levels may help establishing the prognosis of ALS. Further studies merit exploring the pathophysiological mechanisms associated with these markers. Despite their lack of specificity, phospho-Tau/total Tau and Aβ1-42 should be combined to other biological and clinical markers in order to improve ALS management.


Beyond the Motor Domain: Exploring the Secondary Effects of a Fundamental Motor Skill Intervention for Children With Autism Spectrum Disorder.
Early motor skill interventions have been shown to improve the motor skill proficiency of children with autism spectrum disorder; however, little is known about the secondary effects associated with these types of interventions (e.g., influence on behavior, social skills, family dynamics). The purpose of this qualitative study was to (a) investigate parents' perceptions of the child-level benefits associated with a fundamental motor skill intervention for their 4-year-olds with autism spectrum disorder and (b) explore how child-level benefits influenced the family unit. Eight parents (N = 8) were interviewed (semistructured) about their experiences with the intervention for their child(ren); the study was grounded in phenomenology. Five main child-level benefits emerged, including improvements with (a) motor skills, (b) social skills, (c) listening skills, (d) turn-taking skills, and (e) transition skills. The child-level benefits then extended to family members in a number of ways (e.g., more positive sibling interactions). These findings highlight several important secondary effects that should be investigated in future research.


Psychosocial factors of deliberate self-harm in Afghanistan: a hospital based, matched case-control study.
Deliberate self-harm is not only a major global public health problem but also an important index of psychological distress and a risk factor for suicide. We aimed to determine the psychosocial risk factors for deliberate self-harm in patients aged ≥ 16 years presenting to tertiary care hospitals in Kabul, Afghanistan. A matched case-control study was conducted from February 2015 to May 2015. We recruited 185 cases (patients with deliberate self-harm) and 555 age- and sex-matched controls (patients with general medical conditions) from 4 tertiary care hospitals in Kabul. We developed a questionnaire to record the sociodemographic characteristics of the participants, history of domestic violence, drug abuse and details about the act of deliberate self-harm, including the methods used. To assess depression and anxiety, we used the WHO self-reporting questionnaire (SRQ-20). Matched odds ratios with 95% confidence interval using conditional logistic regression were used to determine statistically significant associations between psychosocial factors and deliberate self-harm. Family conflicts, domestic violence, interpersonal arguments and living in extended families were found to be significantly associated with deliberate self-harm. In Afghanistan, deliberate self-harm appears to be predominately related to interpersonal problems and family conflicts. About two-thirds of females and more than half of males scored positive for depression, yet none were receiving treatment for this. These findings have important policy implications for mental health and suicide prevention programmes in the country.


Preventable factors in hospital admissions for asthma.
Asthma remains the second most common cause for admissions to a paediatric hospital bed. The aim of this study was to describe the characteristics of children admitted to hospital with an acute asthma attack and to identify factors that may prevent future hospital admissions. Parents of all children aged 3 to 15 years admitted to hospital for acute asthma were interviewed and the child's case record reviewed. Children were recruited consecutively in two groups: 141 summer/autumn and 125 winter/spring 1996. According to the pattern of symptoms in the previous 12 months, 61% of the children had infrequent episodic asthma, 26% had frequent episodic asthma, and 13% persistent asthma. Only 8% of children aged 8 years or less had persistent asthma, in contrast to 22% of those aged > 8 years. There was evidence of both inadequate prescription of preventive treatment and poor compliance in the frequent episodic and persistent asthma groups. Of the whole group, 44% had previously been given an acute asthma management plan, but only 9% of them used it before the current hospital admission. There was a delay in seeking medical advice (> 24 hours after the onset of symptoms) in 27% of all admissions. This study has identified potential areas where intervention may reduce the number of future admissions.


Development of a sensitive, multiplexed immunoassay using xMAP beads for detection of serotype-specific streptococcus pneumoniae antigen in urine samples.
In support of the surveillance of pneumococcal infections in the era of conjugate vaccines, a sensitive and specific multiplex immunoassay using xMAP beads has been developed for direct detection of pneumococcal serotype-specific polysaccharides in clinical samples, particularly urine. The assay was tested on panels of spiked urine specimens, clinical urine specimens and bacterial isolates. Each of the 14 serotypes in the multiplex assay can be detected to 0.1 ng purified polysaccharide ml(-1), or less. Testing of a panel of urine specimens from patients with culture-confirmed pneumococcal or non-pneumococcal disease indicated that the multiplex assay is both sensitive and specific. The correct pneumococcal serotype was identified directly from urine in 46/58 (79.3 %) patients who had a contemporaneous blood culture isolate of a multiplex assay serotype. Furthermore, the specificity of the assay on this panel of samples was 99.3 % (145/146). This multiplex assay could be useful, in conjunction with the pneumococcal screening test Binax NOW, in urine for diagnosis of pneumococcal disease and the identification of the aetiological serotype, and potentially be of benefit in culture-negative patients.


Association between sympathetic nerve activity and cerebrovascular protection in young spontaneously hypertensive rats.
The purpose of this study was to determine resting and maximal superior cervical sympathetic nerve activity in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) at five and ten weeks of age as hypertension was developing. Basal cervical sympathetic nerve activity (SNA) of five week SHR was 58 +/- 3 muv* which was significantly elevated over age-matched WKY (SNA = 30 +/- 4 muv, *p less than 0.001) and ten week SHR (SNA = 30 +/- 4 muv, *p less than 0.001) as well as ten week WKY (SNA = 24 +/- 4 muv, *p less than 0.001). Thus, during basal conditions five week SHR nerve traffic was approximately two times that found in age-matched WKY as well as in ten week SHR and WKY. The peak sympathetic nerve activity in response to rapid hemorrhage in five week SHR (215 +/- 16 muv*) was significantly elevated over the maximal response of WKY (140 +/- 23 muv) (*p less than 0.02). Ten week SHR also reached a maximal sympathetic nerve activity (187 +/- 28 muv*) that was significantly elevated over WKY (100 +/- 15 muv) (*p less than 0.02). Thus, both five and ten week SHR had a greater capacity for elevated nerve activity following rapid hemorrhage than age-matched WKY. The elevation in resting cervical sympathetic activity in five week SHR, and the elevated capacity for sympathetic neural response in both five as well as ten week SHR, are consistent with a central nervous system abnormality in SHR that could relate to the previously described protective influence of sympathetic nerves on SHR cerebral blood vessels as hypertension is developing.


Secondary transfer effects of intergroup contact: Alternative accounts and underlying processes.
Although intergroup contact is one of the most prominent interventions to reduce prejudice, the generalization of contact effects is still a contentious issue. This research further examined the rarely studied secondary transfer effect (STE; Pettigrew, 2009), by which contact with a primary outgroup reduces prejudice toward secondary groups that are not directly involved in the contact. Across 3 cross-sectional studies conducted in Cyprus (N = 1,653), Northern Ireland (N = 1,973), and Texas (N = 275) and 1 longitudinal study conducted in Northern Ireland (N = 411), the present research sought to systematically rule out alternative accounts of the STE and to investigate 2 potential mediating mechanisms (ingroup reappraisal and attitude generalization). Results indicated that, consistent with the STE, contact with a primary outgroup predicts attitudes toward secondary outgroups, over and above contact with the secondary outgroup, socially desirable responding, and prior attitudes. Mediation analyses found strong evidence for attitude generalization but only limited evidence for ingroup reappraisal as an underlying process. Two out of 3 tests of a reverse model, where contact with the secondary outgroup predicts attitudes toward the primary outgroup, provide further evidence for an indirect effect through attitude generalization. Theoretical and practical implications of these results are discussed, and directions for future research are identified.


Investigation into the scattering of light by human hair.
We describe a general investigation into the scattering of light by human hair. The main features of the intensity distribution produced by light scattered by an individual hair are identified. Qualitative explanations for the features are advanced in terms of the arrangement of the outer structure of the hair and its level of pigmentation. Contrast gloss values are calculated in an attempt to quantify the appearance of hair. These values are found to depend not only on the properties of hair, such as color and condition, but also on the direction and polarization state of the incident light. In assessing the effects of cosmetic treatments on hair, gloss values are shown to be useful where readings from treated hairs are compared with those from a control sample investigated in the same conditions.


Dopamine Transporter SPECT Imaging in Corticobasal Syndrome.
To investigate dopaminergic function in a large cohort of patients with corticobasal syndrome (CBS) and describe its relationship with clinical features in comparison to Parkinson's disease and healthy control subjects. In addition, we assessed prevalence and features of individuals with CBS and in vivo evidence of preserved nigral neuronal density. Substantia nigra pars compacta (SNc) neuronal degeneration is a mandatory pathological criterion for definite corticobasal degeneration, though sporadic autopsy-proven cases with ante-mortem imaging evidence of preserved nigral terminals have been recently described. In this multicenter study, we investigated presynaptic nigrostriatal function in 36 outpatients fulfilling clinical criteria for "probable corticobasal degeneration" (age 71±7.3 years; disease duration 3.9±1.6 years), 37 PD and 24 healthy control subjects using FP-CIT single photon emission computed tomography. Clinical, neuropsychological, and magnetic resonance imaging assessment was performed to characterize CBS patients. Linear discriminant analysis was used to categorize normal vs. pathological scans. FP-CIT binding reduction in patients with CBS was characterized by larger variability, more uniform reduction throughout the striatum and greater hemispheric asymmetry compared to PD. Moreover, there was no significant correlation between tracer uptake values and clinical features such as disease duration and severity. Despite all CBS subjects showed obvious bilateral extrapyramidal signs, FP-CIT uptake was found to be normal bilaterally in four CBS patients and only unilaterally in other four cases. Extensive clinical, neuropsychological and imaging assessment did not reveal remarkable differences between CBS subjects with normal vs. pathological FP-CIT uptake. Our findings support the hypothesis that extrapyramidal motor symptoms in CBS are not invariably associated with SNc neuronal degeneration and that supranigral factors may play a major role in several cases. CBS individuals with normal FP-CIT uptake do not show any clinical or cognitive feature suggesting a different pathology than CBD.


Denominators: An attempt to adjust for cancer incidence and mortality rates and its role in cancer registries.
Cancer is an important public health burden in India and around the Globe. Incident cases of cancer are reported continuously, and trends in incidence rates vary among five yearly age group. In India National census is carried out after every 10 years since 1951, the latest census is carried out in 2011. As Incident cases of cancer are reported continuously for 5 year age group and estimation of rates and trends for a given year of interest fall in-between two census period population estimation of five yearly age group, which serves as Denominator sense importance. Denominator serves as the most essential part of any cancer registry program as it used for calculation of various rates for five yearly age group such as age-standardized rate, crude rate, truncated rate, cumulative risk etc., Calculated by different registries and Individual Researchers, Government organizations, etc. Currently most of the registries used individual exponential growth rate and differential distribution method to estimate the growth rate. However, it is found that the calculated rates and risk be suffering from bias most of the time since some method over and underestimate the growth rate while some does not able to maintain consistency. Here, an attempt is made to adjust the world standard population with two census period to estimate the five yearly age group for a given year of interest of a geographical region falls in-between two census period. It is also shown here that how the proposed model "age-adjusted population growth model" maintain the overall growth as in exponential growth model and difference distribution method also maintains the estimated growth rate is as found in difference distribution method. Further, it is tried to highlight the points how these method overcomes the problems compared with other methods that are currently used by registries.


Crystal structure of an integrin-binding fragment of vascular cell adhesion molecule-1 at 1.8 A resolution.
The cell-surface glycoprotein vascular cell adhesion molecule-1 (VCAM-1; ref. 1) mediates intercellular adhesion by specific binding to the integrin very-late antigen-4 (VLA-4, alpha 4 beta 1; ref. 3). VCAM-1, with the intercellular adhesion molecules ICAM-1, ICAM-2, ICAM-3 and the mucosal vascular addressin MAd-CAM-1, forms an integrin-binding subgroup of the immunoglobulin superfamily. In addition to their clinical relevance in inflammation, these molecules act as cellular receptors for viral and parasitic agents. The predominant form of VCAM-1 in vivo has an amino-terminal extracellular region comprising seven immunoglobulin-like domains. Functional studies have identified a conserved integrin-binding motif in domains 1 and 4, variants of which are present in the N-terminal domain of all members of the immunoglobulin superfamily subgroup. We report here the crystal structure of a VLA-4-binding fragment composed of the first two domains of VCAM-1. The integrin-binding motif (Q38IDSPL) is highly exposed and forms the N-terminal region of the loop between beta-strands C and D of domain 1. This motif exhibits a distinctive conformation which we predict will be common to all the integrin-binding IgSF molecules. These, and additional data, map VLA-4 binding to the face of the CFG beta-sheet, the surface previously identified as the site for intercellular adhesive interactions between members of the immunoglobulin superfamily.


The unfolding action of GroEL on a protein substrate.
A molecular dynamics simulation of the active unfolding of denatured rhodanese by the chaperone GroEL is presented. The compact denatured protein is bound initially to the cis cavity and forms stable contacts with several of the subunits. As the cis ring apical domains of GroEL undergo the transition from the closed to the more open (ATP-bound) state, they exert a force on rhodanese that leads to the increased unfolding of certain loops. The contacts between GroEL and rhodanese are analyzed and their variation during the GroEL transition is shown. The major contacts, which give rise to the stretching force, are found to be similar to those observed in crystal structures of peptides bound to the apical domains. The results of the simulation show that multidomain interactions play an essential role, in accord with experiments. Implications of the results for mutation experiments and for the action of GroEL are discussed.


A dsDNA model optimized for electrokinetic applications.
We present a coarse-grained (CG) model of a charged double-stranded DNA immersed in an electrolyte solution that can be used for a variety of electrokinetic applications. The model is based on an earlier rigid and immobile model of Weik et al. and includes now semi-flexibility and mobility, so that DNA dynamics can be sufficiently captured to simulate a full nanopore translocation process. To this end we couple the DNA hydrodynamically via a raspberry approach to a lattice-Boltzmann fluid and parametrize the counterions with a distant dependent friction. The electrokinetic properties of the CG DNA model inside an infinite cylinder is fitted against experimental data from Smeets et al. and all-atom simulation data from Kesselheim et al. The stiffness of our CG DNA is modeled via a harmonic angle potential fitted against experimental data of Brunet et al. Finally, the quality of our tuned parameters is tested by measuring the electrophoretic mobility of our DNA model for various numbers of base pairs and salt concentrations. Our results compare excellently with the experimental data sets of Stellwagen et al. and Hoagland et al.


Serverification of molecular modeling applications: the Rosetta Online Server that Includes Everyone (ROSIE).
The Rosetta molecular modeling software package provides experimentally tested and rapidly evolving tools for the 3D structure prediction and high-resolution design of proteins, nucleic acids, and a growing number of non-natural polymers. Despite its free availability to academic users and improving documentation, use of Rosetta has largely remained confined to developers and their immediate collaborators due to the code's difficulty of use, the requirement for large computational resources, and the unavailability of servers for most of the Rosetta applications. Here, we present a unified web framework for Rosetta applications called ROSIE (Rosetta Online Server that Includes Everyone). ROSIE provides (a) a common user interface for Rosetta protocols, (b) a stable application programming interface for developers to add additional protocols, (c) a flexible back-end to allow leveraging of computer cluster resources shared by RosettaCommons member institutions, and (d) centralized administration by the RosettaCommons to ensure continuous maintenance. This paper describes the ROSIE server infrastructure, a step-by-step 'serverification' protocol for use by Rosetta developers, and the deployment of the first nine ROSIE applications by six separate developer teams: Docking, RNA de novo, ERRASER, Antibody, Sequence Tolerance, Supercharge, Beta peptide design, NCBB design, and VIP redesign. As illustrated by the number and diversity of these applications, ROSIE offers a general and speedy paradigm for serverification of Rosetta applications that incurs negligible cost to developers and lowers barriers to Rosetta use for the broader biological community. ROSIE is available at http://rosie.rosettacommons.org.


Internet-based treatment for older adults with depression and co-morbid cardiovascular disease: protocol for a randomised, double-blind, placebo controlled trial.
Depression, cardiovascular disease (CVD) risk factors and cognitive impairment are important causes of disability and poor health outcomes. In combination they lead to an even worse prognosis. Internet or web-based interventions have been shown to deliver efficacious psychological intervention programs for depression on a large scale, yet no published studies have evaluated their impact among patients with co-existing physical conditions. The aims of this randomised controlled trial are to determine the effects of an evidence-based internet intervention program for depression on depressive mood symptoms, cognitive function and treatment adherence in patients at risk of CVD. This study is an internet-based, double-blind, parallel group randomised controlled trial. The trial will compare the effectiveness of online cognitive behavioural therapy with an online attention control placebo. The trial will consist of a 12-week intervention phase with a 40-week follow-up. It will be conducted in urban and rural New South Wales, Australia and will recruit a community-based sample of adults aged 45 to 75 years. Recruitment, intervention, cognitive testing and follow-up data collection will all be internet-based and automated. The primary outcome is a change in severity of depressive symptoms from baseline to three-months. Secondary outcomes are changes in cognitive function and adherence to treatment for CVD from baseline to three, six and 12-months. Prior studies of depression amongst patients with CVD have targeted those with previous vascular events and major depression. The potential for intervening earlier in these disease states appears to have significant potential and has yet to be tested. Scalable psychological programs using web-based interventions could deliver care to large numbers in a cost effective way if efficacy were proved. This study will determine the effects of a web-based intervention on depressive symptoms and adherence to treatment among patients at risk of CVD. In addition it will also precisely and reliably define the effects of the intervention upon aspects of cognitive function that are likely to be affected early in at risk individuals, using sensitive and responsive measures. Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12610000085077.


Amelioration effects of berberine on diabetic microendothelial injury model by the combination of high glucose and advanced glycation end products in vitro.
Microvascular complications are much earlier and common in diabetes. Advanced glycation end products (AGEs), together with high glucose, play a key role in the endothelial dysfunction of diabetic vascular complications. So it is of more significance to expedite the therapies to block the formation and/or the effects of AGEs. Berberine has been showed to have anti-diabetic effects, however the effects on diabetic complications were less explored, especially the effects on the microvascular complications and the formation and pathways of AGEs which have not been reported. Therefore, the present study established an in vitro model of diabetic microendothelial (microEC) injury by the combination of high glucose and AGEs to mimic the clinical situations and examine the effects and mechanisms of berberine on high glucose-AGEs-induced microEC injuries and on the formation of AGEs. We prepared AGEs, established the high glucose-AGEs injured microEC models by MTT assay, which was further supported by significantly decreased nitric oxide (NO) release, NO synthase (NOS) and thrombomodulin production with ELISA, western blot and RT-PCR analysis. Berberine treatments showed significant improvements as indicated by significantly increased NO release, NOS and thrombomodulin production. Moreover, we also observed significant inhibition effects of berberine on AGEs formation. We concluded that the in vitro model of diabetic microEC injury could be established by the combination treatments of high glucose and AGEs, while berberine could improve the diabetic microvascular injury in vitro and inhibit the formation of AGEs, suggesting the potential clinical therapies with berberine for diabetes and its vascular complications.


Experimental disseminated strongyloidiasis in Erythrocebus patas. I. Pathology.
Fatal disseminated disease was induced in ten patas monkeys infected with two Southeast Asian strains of Strongyloides stercoralis. While some animals died within 6 weeks after infection, others controlled their infections until placed on high doses of corticosteroids. Larvae were first noted in the stools 11-20 days after transcutaneous exposure to filariform larvae. Daily larval counts tended to increase as the infections progressed, but the number of larvae in the stool was not predictive of whether a monkey would control his infection or succumb to fatal disease. Hyperinfection was confirmed in the six monkeys in which counts were made of the adult female parasites in the duodenum at postmortem, as well as by pathologic findings in all animals. Clinical signs of disease were vague until dyspnea induced by terminal pulmonary hemorrhage occurred. Eosinophilia and/or basophilia were noted intermittently in some infections. Severe necrotizing duodenitis, colitis, and pulmonary hemorrhage were the most conspicuous postmortem findings. Hyperinfection has been predictably induced in a cercopithecoid monkey for the first time; a species which may lend itself to further investigations into the pathogenesis of disseminated strongyloidiasis .


Different effects of the TAR structure on HIV-1 and HIV-2 genomic RNA translation.
The 5'-untranslated region (5'-UTR) of the genomic RNA of human immunodeficiency viruses type-1 (HIV-1) and type-2 (HIV-2) is composed of highly structured RNA motifs essential for viral replication that are expected to interfere with Gag and Gag-Pol translation. Here, we have analyzed and compared the properties by which the viral 5'-UTR drives translation from the genomic RNA of both human immunodeficiency viruses. Our results showed that translation from the HIV-2 gRNA was very poor compared to that of HIV-1. This was rather due to the intrinsic structural motifs in their respective 5'-UTR without involvement of any viral protein. Further investigation pointed to a different role of TAR RNA, which was much inhibitory for HIV-2 translation. Altogether, these data highlight important structural and functional differences between these two human pathogens.


Molecular genetics of nicotine dependence and abstinence: whole genome association using 520,000 SNPs.
Classical genetic studies indicate that nicotine dependence is a substantially heritable complex disorder. Genetic vulnerabilities to nicotine dependence largely overlap with genetic vulnerabilities to dependence on other addictive substances. Successful abstinence from nicotine displays substantial heritable components as well. Some of the heritability for the ability to quit smoking appears to overlap with the genetics of nicotine dependence and some does not. We now report genome wide association studies of nicotine dependent individuals who were successful in abstaining from cigarette smoking, nicotine dependent individuals who were not successful in abstaining and ethnically-matched control subjects free from substantial lifetime use of any addictive substance. These data, and their comparison with data that we have previously obtained from comparisons of four other substance dependent vs control samples support two main ideas: 1) Single nucleotide polymorphisms (SNPs) whose allele frequencies distinguish nicotine-dependent from control individuals identify a set of genes that overlaps significantly with the set of genes that contain markers whose allelic frequencies distinguish the four other substance dependent vs control groups (p < 0.018). 2) SNPs whose allelic frequencies distinguish successful vs unsuccessful abstainers cluster in small genomic regions in ways that are highly unlikely to be due to chance (Monte Carlo p < 0.00001). These clustered SNPs nominate candidate genes for successful abstinence from smoking that are implicated in interesting functions: cell adhesion, enzymes, transcriptional regulators, neurotransmitters and receptors and regulation of DNA, RNA and proteins. As these observations are replicated, they will provide an increasingly-strong basis for understanding mechanisms of successful abstinence, for identifying individuals more or less likely to succeed in smoking cessation efforts and for tailoring therapies so that genotypes can help match smokers with the treatments that are most likely to benefit them.


Clinical complexity and the effectiveness of an intervention for depressed diabetes patients.
In a trial completed in 2010, US patients with diabetes and depression were randomized to usual care or telephone cognitive behavioural therapy that emphasized physical activity. Twelve-month intervention effects were observed for blood pressure, depression, and pedometer-measured step-counts. This study examined variation in intervention effects across patient subgroups defined by a measure of clinical complexity. Three groups of patients were identified at baseline using the Vector Model of Complexity that recognizes socioeconomic, biological, behavioural, and other determinants of treatment response. Complexity-by-intervention interactions were examined using regression models. Intervention effects for blood pressure, depression, and step-counts differed across complexity levels (each p < 0.01). Effects on Beck Depression Inventory scores were greater in the low-complexity group (-8.8) than in the medium- (-3.2) or high-complexity groups (-2.7). Physical activity effects also were greatest in the low-complexity group (increase of 1498 steps per day). In contrast, systolic blood pressure effects were greater among intervention patients with high complexity (-8.5 mmHg). This intervention had varying impacts on physical and mental health depending on patients' clinical complexity. Physical activity and depressive symptom gains may be more likely among less complex patients, although more complex patients may achieve cardiovascular benefits through decreased blood pressures.


Muscle metabolism during overground walking in persons with poststroke hemiparesis.
Muscle energy metabolism is associated with speed, endurance, and effort during walking, yet data regarding muscle metabolism during walking in persons with poststroke hemiparesis have not been published. The primary purpose of this study was to compare the energy metabolism during overground walking in persons with poststroke hemiparesis to controls. The secondary purpose was to determine whether the walking behavior of persons with poststroke hemiparesis conforms to the fuel selection patterns previously observed in controls. O2 consumption and CO2 production were measured as 7 individuals with poststroke hemiparesis and 7 age-matched controls walked at self-selected preferred and fast speeds. Indirect calorimetry was used to measure fuel oxidation. Walking speeds and economy were lower in the clinical cohort, although VO2 and fuel oxidation were consistent between groups. Fat was the dominant fuel source at preferred speeds; whereas, carbohydrate rates increased substantially at fast speeds. Within each condition, similar contributions of fat and carbohydrate were observed despite a wide disparity in speeds. It is hypothesized that fuel selection contributed to preferred walking speeds in the individuals with poststroke hemiparesis and that high rates of carbohydrate oxidation may have prevented higher, more functional, preferred walking speeds.


Transient corticosteroid treatment permanently amplifies the Th2 response in a murine model of asthma.
Corticosteroids (CS) remain the most efficacious pharmacotherapeutic option for the management of asthma. Although the acute anti-inflammatory effects of CS treatment have been amply documented both clinically and experimentally, recent human data intimate that exposure to CS may be associated with retrograde immune phenomena, including enhanced synthesis of IgE in vivo and elevated Th2 cytokine production in vitro. We have investigated the long-term immunologic effects of CS treatment in a murine model of allergic airway inflammation. CS treatment during initial exposure to OVA or upon long-term Ag rechallenge remarkably attenuated eosinophilic airway inflammation and airway hyperresponsiveness. Interestingly, however, Th2 cytokine production by cultured splenocytes from CS-treated mice was significantly elevated, while IFN-gamma synthesis was depressed. Moreover, mice rechallenged with OVA several weeks after CS intervention during allergic sensitization not only developed airway inflammation, but also exhibited enhanced Th2 cytokine production in lymphoid tissues and OVA-specific IgE in serum. This amplification of the systemic immune response was associated with an intact APC compartment during CS-conditioned sensitization to OVA. These data indicate that immune processes underlying the allergic phenotype remain impervious to CS treatment and raise the possibility that treatment with CS during sensitization may amplify elements of the allergen-specific immune response.


A data repository and analysis framework for spontaneous neural activity recordings in developing retina.
During early development, neural circuits fire spontaneously, generating activity episodes with complex spatiotemporal patterns. Recordings of spontaneous activity have been made in many parts of the nervous system over the last 25 years, reporting developmental changes in activity patterns and the effects of various genetic perturbations. We present a curated repository of multielectrode array recordings of spontaneous activity in developing mouse and ferret retina. The data have been annotated with minimal metadata and converted into HDF5. This paper describes the structure of the data, along with examples of reproducible research using these data files. We also demonstrate how these data can be analysed in the CARMEN workflow system. This article is written as a literate programming document; all programs and data described here are freely available. 1. We hope this repository will lead to novel analysis of spontaneous activity recorded in different laboratories. 2. We encourage published data to be added to the repository. 3. This repository serves as an example of how multielectrode array recordings can be stored for long-term reuse.


Symptoms before periapical surgery related to histologic diagnosis and postoperative healing at 12 months for 178 periapical lesions.
To compare the preoperative signs and symptoms with the histologic diagnosis and postoperative healing at 12 months for 178 periapical lesions. A total of 152 patients who had undergone periapical surgery from 2005 to 2008 were studied. The study included patients presenting with signs and symptoms before periapical surgery with a sufficient tissue sample (periapical lesion) for histologic analysis and a minimal follow-up of 12 months. The signs and symptoms present in the soft tissues at the initial examination were recorded. The histologic analysis established the diagnosis as granuloma, cyst, or scar tissue. The postoperative healing at 12 months was evaluated according to the criteria of von Arx and Kurt. Of the 152 patients, 147, with 178 periapical lesions, were included in the present study. No significant relationship was found between the preoperative signs and symptoms, lesion type, and evolution. However, scar tissues were asymptomatic in 78.1%, and 36.4% of granulomas were painful. Of the 8 cysts, 50% were asymptomatic and 50% caused pain. Fibrous scars created no soft tissue alterations in 68.7%. Granulomas had fistulized in 31.7%, and 75% of cysts had produced no alterations. The lesions with swelling had worse healing, and those with no soft tissue alterations had better postoperative healing. Chronic periapical lesions (granuloma, cyst, and scar tissue) are usually asymptomatic and do not create soft tissue alterations. However, they can deteriorate, producing pain and fistulization. Worse postoperative healing was observed for lesions with swelling, although the difference was not significant.


The cerebellar nodulus: perceptual and ocular processing of graviceptive input.
Current concepts postulate a decisive role of the cerebellar nodulus in the processing of otolith input. We hypothesized that nodular lesions abolish otolith-perceptual integration, predicting alignment of perceived direction of earth vertical with the z-axis of the head and not with gravity. In an 80-year-old patient with acute heminodular infarction, the subjective visual vertical deviated contralesionally by -21.1° when the patient was upright. After subtracting this offset, perceived vertical closely matched the patient's head orientation when the patient was roll-tilted. Otolith-ocular reflexes remained normal. This is the first report on abolished earth verticality perception in heminodular stroke and underlines the importance of the nodulus in spatial orientation.


National trends in main causes of hospitalization: a multi-cohort register study of the finnish working-age population, 1976-2010.
The health transition theory argues that societal changes produce proportional changes in causes of disability and death. The aim of this study was to identify long-term changes in main causes of hospitalization in working-age population within a nation that has experienced considerable societal change. National trends in all-cause hospitalization and hospitalizations for the five main diagnostic categories were investigated in the data obtained from the Finnish Hospital Discharge Register. The seven-cohort sample covered the period from 1976 to 2010 and consisted of 3,769,356 randomly selected Finnish residents, each cohort representing 25% sample of population aged 18 to 64 years. Over the period of 35 years, the risk of hospitalization for cardiovascular diseases and respiratory diseases decreased. Hospitalization for musculoskeletal diseases increased whereas mental and behavioral hospitalizations slightly decreased. The risk of cancer hospitalization decreased marginally in men, whereas in women an upward trend was observed. A considerable health transition related to hospitalizations and a shift in the utilization of health care services of working-age men and women took place in Finland between 1976 and 2010.


The V109G polymorphism of the p27 gene CDKN1B indicates a worse outcome in node-negative breast cancer patients.
Although p27 plays a central role in cell cycle regulation, its role in breast cancer prognosis is controversial. Furthermore, the p27 gene CDKN1B carries a polymorphism with unknown functional relevance. This study was designed to evaluate p27 expression and p27 genotyping with respect to early breast cancer prognosis. 279 patients with infiltrating metastasis-free breast cancer were included in this study. p27 expression was determined in tumor tissue specimens from 261 patients by immunohistochemistry. From 108 patients, the CDKN1B genotype was examined by PCR and subsequent direct sequencing. 55.2% of the tumors were considered p27 positive. p27 expression did not correlate with any of the established parameters except for nodal involvement but significantly correlated to prolonged disease-free survival. In 35% of the tumors analyzed, the CDKN1B gene showed a polymorphism at codon 109 (V109G). The V109G polymorphism correlated with greater nodal involvement. In the node-negative subgroup, V109G correlated significantly with a shortened disease-free survival. In conclusion, the determination of the CDKN1B genotype might be a powerful tool for the prognosis of patients with early breast cancer.


Nanomechanical measurement of adhesion and migration of leukemia cells with phorbol 12-myristate 13-acetate treatment.
The adhesion and traction behavior of leukemia cells in their microenvironment is directly linked to their migration, which is a prime issue affecting the release of cancer cells from the bone marrow and hence metastasis. In assessing the effectiveness of phorbol 12-myristate 13-acetate (PMA) treatment, the conventional batch-cell transwell-migration assay may not indicate the intrinsic effect of the treatment on migration, since the treatment may also affect other cellular behavior, such as proliferation or death. In this study, the pN-level adhesion and traction forces between single leukemia cells and their microenvironment were directly measured using optical tweezers and traction-force microscopy. The effects of PMA on K562 and THP1 leukemia cells were studied, and the results showed that PMA treatment significantly increased cell adhesion with extracellular matrix proteins, bone marrow stromal cells, and human fibroblasts. PMA treatment also significantly increased the traction of THP1 cells on bovine serum albumin proteins, although the effect on K562 cells was insignificant. Western blots showed an increased expression of E-cadherin and vimentin proteins after the leukemia cells were treated with PMA. The study suggests that PMA upregulates adhesion and thus suppresses the migration of both K562 and THP1 cells in their microenvironment. The ability of optical tweezers and traction-force microscopy to measure directly pN-level cell-protein or cell-cell contact was also demonstrated.


Approval and perceived impact of duty hour regulations: survey of pediatric program directors.
To determine pediatric program director (PD) approval and perception of changes to resident training and patient care resulting from 2011 Accreditation Council for Graduate Medical Education (ACGME) Common Program Requirements. All US pediatric PDs (n = 181) were identified from the ACGME. Functional e-mail addresses were identified for 164 (90.6%). Three individualized e-mail requests were sent to each PD to complete an anonymous 32-question Web-based survey. A total of 151 responses were obtained (83.4%). Pediatrics PDs reported approval for nearly all of the 2011 ACGME duty hour regulations except for 16-hour intern shift limits (72.2% disapprove). Regarding the perceived impact of the new standards, many areas were reportedly unchanged, but most PDs reported negative effects on resident education (74.7%), preparation for senior roles (79.9%), resident ownership of patients (76.8%), and continuity of care (78.8%). There was a reported increase in PD workload (67.6%) and use of physician extenders (62.7%). Finally, only 48.3% of PDs reported that their residents are "always" compliant with 2011 requirements. Pediatric PDs think there have been numerous negative consequences of the 2011 Common Program Requirements. These include declines in resident education and preparation to take on more senior roles, as well as diminished resident accountability and continuity of care. Although they support individual aspects of duty hour regulation, almost three-quarters of pediatric PDs say there should be fewer regulations. The opinions expressed by PDs in this study should prompt research using quantitative metrics to assess the true impact of duty hour regulations.


Analysis of a high-speed fiber-optic spectrometer for fiber-optic sensor signal processing.
A novel high-speed fiber-optic spectrometer has been demonstrated in our previous work. The high-speed spectrum measurement is enabled by translating the spectral-domain signal into a time-domain signal through a dispersion element. We present a mathematical model that accurately describes the relationship between the optical spectrum to be measured and the dispersed time-domain signal. Based on the model, the effects of the key parameters on the performance of the spectrometer are investigated in detail using numerical simulation. The analysis is useful for the design and application of such spectrometers.


Large social disparities in spontaneous preterm birth rates in transitional Russia.
This study estimated the effect of maternal sociodemographic, obstetric and lifestyle factors on the risk of spontaneous preterm birth in a Russian town. All women with singleton pregnancies registered at prenatal care centres in Severodvinsk in 1999 comprised the cohort for this study (n=1559). Analysis was based on spontaneous live singleton births at the maternity home (n=1103). Multivariable logistic regression was applied to quantify the effect of the studied factors on the risk of preterm birth. Differences in gestation duration were studied using multiple linear regression. In total, 5.6% of all spontaneous births were preterm. Increased risks of preterm delivery were found in women with lower levels of education and in students. Placental complications, stress and a history of fetal death in previous pregnancies were also associated with elevated risks for preterm delivery. Smoking, hypertension and multigravidity were associated with reduced length of pregnancy in metric form. In addition to medical risk factors, social factors are important determinants of preterm birth in transitional Russia. Large disparities in preterm birth rates may reflect the level of inequalities in transitional Russia. Social variations in pregnancy outcomes should be monitored.


Predictors of pulmonary complications in blunt traumatic spinal cord injury.
Pulmonary complications are the most common acute systemic adverse events following spinal cord injury (SCI), and contribute to morbidity, mortality, and increased length of hospital stay (LOS). Identification of factors associated with pulmonary complications would be of value in prevention and acute care management. Predictors of pulmonary complications after SCI and their effect on neurological recovery were prospectively studied between 2005 and 2009 at the 9 hospitals in the North American Clinical Trials Network (NACTN). The authors sought to address 2 specific aims: 1) define and analyze the predictors of moderate and severe pulmonary complications following SCI; and 2) investigate whether pulmonary complications negatively affected the American Spinal Injury Association (ASIA) Impairment Scale conversion rate of patients with SCI. The NACTN registry of the demographic data, neurological findings, imaging studies, and acute hospitalization duration of patients with SCI was used to analyze the incidence and severity of pulmonary complications in 109 patients with early MR imaging and long-term follow-up (mean 9.5 months). Univariate and Bayesian logistic regression analyses were used to analyze the data. In this study, 86 patients were male, and the mean age was 43 years. The causes of injury were motor vehicle accidents and falls in 80 patients. The SCI segmental level was in the cervical, thoracic, and conus medullaris regions in 87, 14, and 8 patients, respectively. Sixty-four patients were neurologically motor complete at the time of admission. The authors encountered 87 complications in 51 patients: ventilator-dependent respiratory failure (26); pneumonia (25); pleural effusion (17); acute lung injury (6); lobar collapse (4); pneumothorax (4); pulmonary embolism (2); hemothorax (2), and mucus plug (1). Univariate analysis indicated associations between pulmonary complications and younger age, sports injuries, ASIA Impairment Scale grade, ascending neurological level, and lesion length on the MRI studies at admission. Bayesian logistic regression indicated a significant relationship between pulmonary complications and ASIA Impairment Scale Grades A (p = 0.0002) and B (p = 0.04) at admission. Pulmonary complications did not affect long-term conversion of ASIA Impairment Scale grades. The ASIA Impairment Scale grade was the fundamental clinical entity predicting pulmonary complications. Although pulmonary complications significantly increased LOS, they did not increase mortality rates and did not adversely affect the rate of conversion to a better ASIA Impairment Scale grade in patients with SCI. Maximum canal compromise, maximum spinal cord compression, and Acute Physiology and Chronic Health Evaluation-II score had no relationship to pulmonary complications.


The predictive value of quantitative fibronectin testing in combination with cervical length measurement in symptomatic women.
The combination of the qualitative fetal fibronectin test and cervical length measurement has a high negative predictive value for preterm birth within 7 days; however, positive prediction is poor. A new bedside quantitative fetal fibronectin test showed potential additional value over the conventional qualitative test, but there is limited evidence on the combination with cervical length measurement. The purpose of this study was to compare quantitative fetal fibronectin and qualitative fetal fibronectin testing in the prediction of spontaneous preterm birth within 7 days in symptomatic women who undergo cervical length measurement. We performed a European multicenter cohort study in 10 perinatal centers in 5 countries. Women between 24 and 34 weeks of gestation with signs of active labor and intact membranes underwent quantitative fibronectin testing and cervical length measurement. We assessed the risk of preterm birth within 7 days in predefined strata based on fibronectin concentration and cervical length. Of 455 women who were included in the study, 48 women (11%) delivered within 7 days. A combination of cervical length and qualitative fibronectin resulted in the identification of 246 women who were at low risk: 164 women with a cervix between 15 and 30 mm and a negative fibronectin test (<50 ng/mL; preterm birth rate, 2%) and 82 women with a cervix at >30 mm (preterm birth rate, 2%). Use of quantitative fibronectin alone resulted in a predicted risk of preterm birth within 7 days that ranged from 2% in the group with the lowest fibronectin level (<10 ng/mL) to 38% in the group with the highest fibronectin level (>500 ng/mL), with similar accuracy as that of the combination of cervical length and qualitative fibronectin. Combining cervical length and quantitative fibronectin resulted in the identification of an additional 19 women at low risk (preterm birth rate, 5%), using a threshold of 10 ng/mL in women with a cervix at <15 mm, and 6 women at high risk (preterm birth rate, 33%) using a threshold of >500 ng/mL in women with a cervix at >30 mm. In women with threatened preterm birth, quantitative fibronectin testing alone performs equal to the combination of cervical length and qualitative fibronectin. Possibly, the combination of quantitative fibronectin testing and cervical length increases this predictive capacity. Cost-effectiveness analysis and the availability of these tests in a local setting should determine the final choice.


Impact of aryloxy initiators on the living and immortal polymerization of lactide.
This report describes two different methodologies for the synthesis of aryl end-functionalized poly(lactide)s (PLAs) catalyzed by indium complexes. In the first method, a series of para-functionalized phenoxy-bridged dinuclear indium complexes [(NNO)InCl]2(μ-Cl)(μ-OPhR) (R = OMe (1), Me (2), H (3), Br (4), NO2 (5)) were synthesized and fully characterized. The solution and solid state structures of these complexes reflect the electronic differences between these initiators. The polymerization rates correlate with the electron donating ability of the phenoxy initiators: the para-nitro substituted complex 5 is essentially inactive. However, the para-methoxy variant, while less active than the ethoxy-bridged complex [(NNO)InCl]2(μ-Cl)(μ-OEt) (A), shows sufficient activity. Alternatively, aryl-capped PLAs were synthesized via immortal polymerization of PLA with A in the presence of a range of arylated chain transfer agents. Certain aromatic diols shut down polymerization by chelating one indium centre to form a stable metal complex. Immortal ROP was successful when using phenol, and 1,5-naphthalenediol. These polymers were analysed and chain end fidelity was confirmed using 1H NMR spectroscopy, MALDI-TOF mass spectrometry, and UV-Vis spectroscopy. This study shed light on possible speciation when attempting to generate PLA-lignin copolymers.


Molecular umbrella-amphotericin B conjugates.
A tetrawalled and an octawalled molecular umbrella conjugate of amphotericin B (AmB) have been synthesized. Both conjugates exhibit high water solubility, a low tendency to aggregate, negligible hemolytic activity at 100 μM, and an ability to release a derivative of AmB under reducing conditions that exhibits high antifungal activity. Whereas the larger, octawalled conjugate shows slight adsorption to liposomal membranes and an ability to cross them by passive transport, the tetrawalled analogue shows significant adsorption and much lower bilayer transport activity. The potential of molecular umbrella-AmB conjugates as therapeutic agents is briefly discussed.


Explanation and Elaboration of the Standards of Reporting of Neurological Disorders Checklist: A Guideline for the Reporting of Incidence and Prevalence Studies in Neuroepidemiology.
Incidence and prevalence studies of neurological disorders play an extremely important role in hypothesis-generation, assessing the burden of disease and planning of health services. However, the assessment of disease estimates is hindered by the poor quality of reporting for such studies. We developed the Standards of Reporting of Neurological Disorders (STROND) guideline in order to improve the quality of reporting of neurological disorders from which prevalence, incidence, and outcomes can be extracted for greater generalisability. The guideline was developed using a 3-round Delphi technique in order to identify the 'basic minimum items' important for reporting, as well as some additional 'ideal reporting items.' An e-consultation process was then used in order to gauge opinion by external neuroepidemiological experts on the appropriateness of the items included in the checklist. The resultant 15 items checklist and accompanying recommendations were developed using a similar process and structured in a similar manner to the Strengthening of the Reporting of Observational Studies in Epidemiology checklist for ease of use. This paper presents the STROND checklist with an explanation and elaboration for each item, as well as examples of good reporting from the neuroepidemiological literature. The introduction and use of the STROND checklist should lead to more consistent, transparent and contextualised reporting of descriptive neuroepidemiological studies that should facilitate international comparisons, and lead to more accessible information for multiple stakeholders, ultimately supporting better healthcare decisions for neurological disorders.


A Risk Assessment Scheme of Infection Transmission Indoors Incorporating the Impact of Resuspension.
A new risk assessment scheme was developed to quantify the impact of resuspension to infection transmission indoors. Airborne and surface pathogenic particle concentration models including the effect of two major resuspension scenarios (airflow-induced particle resuspension [AIPR] and walking-induced particle resuspension [WIPR]) were derived based on two-compartment mass balance models and validated against experimental data found in the literature. The inhalation exposure to pathogenic particles was estimated using the derived airborne concentration model, and subsequently incorporated into a dose-response model to assess the infection risk. Using the proposed risk assessment scheme, the influences of resuspension towards indoor infection transmission were examined by two hypothetical case studies. In the case of AIPR, the infection risk increased from 0 to 0.54 during 0-0.5 hours and from 0.54 to 0.57 during 0.5-4 hours. In the case of WIPR, the infection risk increased from 0 to 0.87 during 0-0.5 hours and from 0.87 to 1 during 0.5-4 hours. Sensitivity analysis was conducted based on the design-of-experiments method and showed that the factors that are related to the inspiratory rate of viable pathogens and pathogen virulence have the most significant effect on the infection probability under the occurrence of AIPR and WIPR. The risk assessment scheme could serve as an effective tool for the risk assessment of infection transmission indoors.


TRAF6 is a signal transducer for interleukin-1.
Many cytokines signal through different cell-surface receptors to activate the transcription factor NF-kappaB. Members of the TRAF protein family have been implicated in the activation of NF-kappaB by the tumour-necrosis factor (TNF)-receptor superfamily. Here we report the identification of a new TRAF family member, designated TRAF6. When overexpressed in human 293 cells, TRAF6 activates NF-kappaB. A dominant-negative mutant of TRAF6 inhibits NF-kappaB activation signalled by interleukin-1 (IL-1) but not by TNF. IL-1 treatment of 293 cells induces the association of TRAF6 with IRAK, a serine/threonine kinase that is rapidly recruited to the IL-1 receptor after IL-1 induction. These findings indicate that TRAF proteins may function as signal transducers for distinct receptor families and that TRAF6 participates in IL-1 signalling.


A prospective study of contraceptive use among African women in HIV-1 serodiscordant partnerships.
Dual contraception is important for averting HIV-1 transmission, unintended pregnancy, and maternal-to-child HIV-1 transmission. Few studies have explored contraceptive use in HIV-1 serodiscordant couples, a population at high risk for HIV-1 transmission. Data from a prospective study of 3407 women in HIV-1 heterosexual serodiscordant partnerships were analyzed to describe use and correlates of contraception. Among 2298 HIV-1 seropositive women, 23.5% used contraception at enrollment and 30.2% used contraception after 24 months of follow-up; among 1109 HIV-1 seronegative women, contraceptive use decreased from 21.3% to 14.2%. For both HIV-1 seropositive and seronegative women, contraceptive use was less common among women from East Africa compared to women from southern Africa (adjusted odds ratio [AOR], 0.6; 95% confidence interval [CI], 0.5-0.8 and AOR, 0.6; 95% CI, 0.4-0.8, respectively) and more common among women with at least one child (AOR, 2.4; 95% CI, 1.7-3.4 and AOR, 2.3; 95% CI, 1.2-4.5, respectively). Condom use increased significantly during follow-up from 71.2% to 92.6% and 73.5% to 95.6% among HIV-1 seropositive and HIV-1 seronegative women, respectively, at baseline and 24 months. However, contraceptive use was associated with unprotected sexual activity among both HIV-1 seropositive and seronegative women (AOR, 1.3; 95% CI, 1.1-1.5 and AOR, 1.4; 95% CI, 1.1-1.8, respectively), although not among women who initiated contraception during follow-up. Counseling and provision of dual contraception should receive high priority in programs that care for women in HIV-1 serodiscordant partnerships.


Overexpression of miR-145-5p inhibits proliferation of prostate cancer cells and reduces SOX2 expression.
We aimed to perform functional analysis of miR-145-5p in prostate cancer (PCa) cells and to identify targets of miR-145-5p for understanding its role in PCa pathogenesis. PC3, DU145, LNCaP PCa, and PNT1a nontumorigenic prostate cell lines were utilized for functional analysis of miR-145-5p. Its overexpression caused inhibition of proliferation through apoptosis and reduced migration in PCa cells. SOX2 expression was significantly decreased in both mRNA and protein level in miR-145-5p-overexpressed PCa cells. We proposed that miR-145-5p, being an important regulator of SOX2, carries a crucial role in PCa tumorigenesis.


Reflections on animal selves.
Is self-cognizance a uniquely human attribute, or do other animals also have a sense of self? Although there is considerable interest in this question, answers remain elusive. Progress has been stymied by misunderstandings in terminology, a focus on a narrow range of species, and controversies over key concepts, experimental paradigms and interpretations of data. Here, we propose a new conceptual and terminological framework, emphasizing that degrees of self-cognizance differ among animals because of the cognitive demands that their species-specific social structures and life-history characteristics have placed upon them over evolutionary time. We suggest that the self-cognizance of an organism falls at a point on a continuum of social complexity and conscious involvement.


Prospective monitoring of polyomavirus BK replication and impact of pre-emptive intervention in pediatric kidney recipients.
Polyoma BK virus (BKV)-associated nephropathy (PVAN) is a relevant cause of poor renal allograft survival. In a prospective analysis, we monitored BKV DNA in blood and urine samples from 62 consecutive pediatric kidney recipients. In patients with BKV replication, we analyzed the impact of reduction of maintenance immunosuppression on viral load kinetics and PVAN in patients with BKV replication. BKV-specific immunity was concomitantly evaluated on blood samples of viremic patients, by measuring the frequency of BKV-specific interferon-gamma-producing and cytotoxic T cells, and BKV IgG antibody levels. At a median follow-up of 24 months, BK viruria was observed in 39 of 62 patients, while BK viremia developed in 13 patients (21%). In all viremic patients, immunosuppression reduction resulted in the clearance of viremia, and prevented development of PVAN, without increasing the rate of acute rejection or causing graft dysfunction. As a consequence of immunosuppression adjustment, an expansion of BKV-specific cellular immunity was observed that coincided with viral clearance. We conclude that treating pediatric kidney transplant patients pre-emptively with immunosuppression reduction guided by BKV DNA in blood is safe and effective to prevent onset of PVAN. BKV-specific cellular immunity may be useful to guide this intervention.


Fluctuation theorems.
Fluctuation theorems, developed over the past 15 years, have resulted in fundamental breakthroughs in our understanding of how irreversibility emerges from reversible dynamics and have provided new statistical mechanical relationships for free-energy changes. They describe the statistical fluctuations in time-averaged properties of many-particle systems such as fluids driven to nonequilibrium states and provide some of the few analytical expressions that describe nonequilibrium states. Quantitative predictions on fluctuations in small systems that are monitored over short periods can also be made, and therefore the fluctuation theorems allow thermodynamic concepts to be extended to apply to finite systems. For this reason, we anticipate an important role for fluctuation theorems in the design of nanotechnological devices and in the understanding of biological processes. This review discusses these theorems, their physical significance, and results for experimental and model systems.


HbA1c as a predictor of diabetes and as an outcome in the diabetes prevention program: a randomized clinical trial.
Glycated hemoglobin (HbA1c), a standard measure of chronic glycemia for managing diabetes, has been proposed to diagnose diabetes and identify people at risk. The Diabetes Prevention Program (DPP) was a 3.2-year randomized clinical trial of preventing type 2 diabetes with a 10-year follow-up study, the DPP Outcomes Study (DPPOS). We evaluated baseline HbA1c as a predictor of diabetes and determined the effects of treatments on diabetes defined by an HbA1c ≥6.5% (48 mmol/mol). We randomized 3,234 nondiabetic adults at high risk of diabetes to placebo, metformin, or intensive lifestyle intervention and followed them for the development of diabetes as diagnosed by fasting plasma glucose (FPG) and 2-h postload glucose (2hPG) concentrations (1997 American Diabetes Association [ADA] criteria). HbA1c was measured but not used for study eligibility or outcomes. We now evaluate treatment effects in the 2,765 participants who did not have diabetes at baseline according to FPG, 2hPG, or HbA1c (2010 ADA criteria). Baseline HbA1c predicted incident diabetes in all treatment groups. Diabetes incidence defined by HbA1c ≥6.5% was reduced by 44% by metformin and 49% by lifestyle during the DPP and by 38% by metformin and 29% by lifestyle throughout follow-up. Unlike the primary DPP and DPPOS findings based on glucose criteria, metformin and lifestyle were similarly effective in preventing diabetes defined by HbA1c. HbA1c predicted incident diabetes. In contrast to the superiority of the lifestyle intervention on glucose-defined diabetes, metformin and lifestyle interventions had similar effects in preventing HbA1c-defined diabetes. The long-term implications for other health outcomes remain to be determined.


Chronic cannabinoid exposure produces lasting memory impairment and increased anxiety in adolescent but not adult rats.
Although many studies have examined the acute behavioural effects of cannabinoids in rodents, few have examined the lasting effects of cannabinoids at different developmental ages. This study compared lasting effects of cannabinoid exposure occurring in adolescence to that occurring in early adulthood. Forty, 30-day old (adolescent) and 18, 56-day old (adult) female albino Wistar rats were injected with vehicle or incremental doses of the cannabinoid receptor agonist (-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl) cyclohexanol (CP 55,940) once per day for 21 consecutive days (150, 200 and 300 microg/kg i.p. for 3, 8 and 10 days, respectively). Following a 21-day drug-free period, working memory was assessed using an object recognition task. Locomotor activity was also measured in the object recognition apparatus via a ceiling-mounted passive infrared sensor. Three days later, anxiety was assessed using a social interaction test. In the object recognition task, significantly poorer working memory was observed in the adolescent but not adult CP 55,940-treated rats. Adolescent, but not adult CP 55,940-treated rats, also exhibited a significant decrease in social interaction with a novel conspecific. These results suggest that chronic exposure to a cannabinoid receptor agonist well after the immediate postnatal period, but before reaching sexual maturity, can lead to increased anxiety and a lasting impairment of working memory.


Transcutaneous electric nerve stimulation (TENS) for cancer pain in adults.
Cancer-related pain is complex and multi-dimensional but the mainstay of cancer pain management has predominately used a biomedical approach. There is a need for non-pharmacological and innovative approaches. Transcutaneous Electric Nerve Stimulation (TENS) may have a role for a significant number of patients but the effectiveness of TENS is currently unknown. The aim of this systematic review was to determine the effectiveness of TENS for cancer-related pain in adults. We searched The Cochrane Library, MEDLINE, EMBASE, CINAHL, PsychINFO, AMED and PEDRO databases (11/04/08). Only randomised controlled trials (RCTS) investigating the use of TENS for the management of cancer-related pain in adults were included. The search strategy identified 37 possible published studies which were divided between two pairs of review authors that decided on study selection. A study eligibility form was used to screen each abstract and where study eligibility could not be determined from the abstract, the full paper was obtained and assessed by one pair of review authors. A standardised data extraction sheet was used to collect information on the studies and the quality of the studies was assessed independently by two review authors using the validated five-point Oxford Quality Scale. Final scores were discussed and agreed between all four review authors. The small sample sizes and differences in patient study populations of the two included studies prevented meta-analysis. Only two RCTs met the eligibility criteria (64 participants). These studies were heterogenous with respect to study population, sample size, study design, methodological quality, mode of TENS, treatment duration, method of administration and outcome measures used. In one RCT, there were no significant differences between TENS and placebo in women with chronic pain secondary to breast cancer treatment. In the other RCT, there were no significant differences between acupuncture-type TENS and sham in palliative care patients; this study was underpowered. The results of this systematic review are inconclusive due to a lack of suitable RCTs. Large multi-centre RCTs are required to assess the value of TENS in the management of cancer-related pain in adults.


Economic burden for informal caregivers of lung and colorectal cancer patients.
Informal care provides many benefits to cancer patients, but can be costly to caregivers. This study quantified the economic burden for informal caregivers of lung cancer (LC) and colorectal cancer (CRC) patients, examining differences by cancer type, phase of disease, stage at diagnosis, patient age, and relationship. A cross-sectional survey of caregivers of LC and CRC patients participating in the Share Thoughts on Care survey was conducted. Economic burden was calculated using the opportunity cost of caregiver time, the value of work hours lost, and out-of-pocket expenditures. Factors associated with economic burden to caregivers were modeled using fixed-effects generalized least squares estimation. Informal caregivers (1,629) completed mailed surveys. Of these, 663, 822, and 144 were surveyed during the patient's initial phase (first year after diagnosis, not within 6 months of death), continuing phase (after 1 year, not within 6 months of death), and terminal phase (within 6 months of death) of disease, respectively. The accumulated economic burdens for caregivers were $7,028, $19,701, and $14,234 for those evaluated during the patient's initial phase, continuing phase, and terminal phase of disease, respectively. Economic burden was higher for caregivers of LC patients than CRC patients (p = .044) and for caregivers of patients diagnosed at stage 4 versus stage 1 (p = .001). Spouses faced higher economic burden than other relatives (p = .000) or friends (p = .000). Economic burden for informal caregivers of LC and CRC patients is substantial and should be included in estimates of the societal cost of cancer care.


Are we adequately providing support services for optimal infant nutrition in Australia? A study in regional NSW.
Evidence from the literature suggests that parents of infants in Australia may not be receiving appropriate professional assistance to support best practice in infant feeding. This study aimed to investigate whether services for infant nutrition (including breastfeeding, infant formula feeding and support for at-risk infants) complied with current recommendations. Relevant services in a regional area of NSW completed a questionnaire to characterise the assistance they provided for parents of infants in the first 6 months of life. Services for breastfeeding, unlike services for use of infant formula, were consistent with recommendations in the literature. Services were significantly more likely to provide education (χ2 (1, n = 44) = 5.939, P < 0.025) and various forms of professional support (χ2 (1, n = 44) = 20.29, P < 0.0001) for breastfeeding compared with infant formula. At-risk infants were mostly identified through growth monitoring, and extra support services were mostly provided on site. Parents of at-risk infants were encouraged to attend services; strategies included involving family in consultations, offering multiple services on site, free services and home visits. Other important measures recommended in the literature, such as providing continuous care from the antenatal period and transport, were provided infrequently.


Possible involvement of muscarinic receptors in psychiatric disorders: a focus on schizophrenia and mood disorders.
A considerable body of data supports a role for the central cholinergic system in the aetiologies of schizophrenia and mood disorders. There have been breakthroughs in gaining structural data on muscarinic receptors (CHRMs), understanding their role in CNS functioning and in synthesising drugs that can specifically target each of the 5 CHRMs. This means it is opportune to consider the role of specific CHRMs in the pathophysiologies of schizophrenia and mood disorders. This review will focus on data suggesting changes in levels of CHRM1 and CHRM4 implicate these receptors in the pathophysiology of schizophrenia whereas data suggest a role for CHRM2 in mood disorders. There will be a selected reference to recent developments in understanding the roles of CHRM1, 2 and 4 in CNS function and how these predict mechanisms by which these receptors could induce the symptoms prevalent in schizophrenia and mood disorders. Finally, there will be comments on the potential advantages and problems in targeting CHRM1 and CHRM4 to treat the symptoms of schizophrenia and CHRM2 to treat the symptom of depression.