The risks following the exposure to radiation associated with the surgical correction of limb deformities in children are minimal.
The aim of this study was to quantify the risk of developing cancer from the exposure to radiation associated with surgery to correct limb deformities in children. A total of 35 children were studied. There were 19 girls and 16 boys. Their mean age was 11.9 years (2 to 18) at the time of surgery. Details of the radiological examinations were recorded during gradual correction using a Taylor Spatial Frame. The dose area product for each radiograph was obtained from the Computerised Radiology Information System database. The effective dose in millisieverts (mSv) was calculated using conversion coefficients for the anatomical area. The lifetime risk of developing cancer was calculated using government-approved Health Protection Agency reports, accounting for the age and gender of the child. Correction was undertaken in five femurs, 18 tibiae, and 12 feet. The median duration of treatment was 45 months (11 to 118). The mean effective dose was 0.31 mSv (0.05 to 0.64) for the femur, 0.29 mSv (0.01 to 0.97) for the tibia, and 0.027 mSv (0.001 to 0.161) for the foot. The cumulative exposure gave 'negligible' risk in 26 children and 'minimal' risk in nine children, according to Public Health England categories. These results are below the mean annual background radiation in the United Kingdom. The lifetime attributable risk of developing cancer from repeated exposure to radiation was negligible or minimal in all children. This is the first study to quantify the exposure to radiation from serial radiographs in children with limb deformities who are treated surgically using circular external fixation, linking this to the risk of developing cancer. Cite this article: Bone Joint J 2019;101-B:241-245.


Standards for systems biology.
High-throughput technologies are generating large amounts of complex data that have to be stored in databases, communicated to various data analysis tools and interpreted by scientists. Data representation and communication standards are needed to implement these steps efficiently. Here we give a classification of various standards related to systems biology and discuss various aspects of standardization in life sciences in general. Why are some standards more successful than others, what are the prerequisites for a standard to succeed and what are the possible pitfalls?


[Prevalence and socio-economic relevance of allergies in Germany].
Within the last five decades, the worldwide prevalence of allergic diseases such as asthma, hay fever, or food allergies has increased dramatically. Germany follows a similar trend; several studies have shown increased numbers of allergic diseases in this period. Although allergic diseases do not exhibit high mortality rates, the loss of quality of life as shown by studies conducted by the World Health Organization (WHO) is considerable. Additional health-economical analyses documented that allergic patients more frequently occupy services of the health care system in Germany. The treatment of allergies and the increasing consultation rates cause rising costs and an increasing burden for the national economy. Currently it is possible to control allergic diseases such as asthma by a precise diagnosis or identification of the causative allergen. However, a considerable reduction in the prevalence of allergic disease and its therapy costs can only be expected if causative therapies and effective prevention strategies are available.


Randomised double-blind trial of the effect of vitamin A supplementation of Indonesian pregnant women on morbidity and growth of their infants during the first year of life.
To investigate whether supplementation with vitamin A together with iron of Indonesian pregnant women decreases morbidity and improves growth of their infants during the first year of life. Women from a rural area in West Java, Indonesia, were randomly assigned on an individual basis to double-blind supplementation once weekly from approximately 18 weeks of pregnancy until delivery. Supplementation comprised 120 mg iron and 500 microg folic acid with or without 4800 RE vitamin A. Their newborn infants were followed up during the first year of life: weight, length, morbidity and food intake were assessed monthly. Infants whose mothers had taken vitamin A supplements during pregnancy had similar weight, length, weight gain and growth as their counterparts during the follow-up period. The proportions of infants with reported symptoms of morbidity were similar in the vitamin A plus iron group and the iron group. In addition immunisation coverage and feeding mode did not differ between the groups. All infants were breast-fed, but exclusive breast-feeding rapidly declined at 4 months of age. Infants with serum retinol concentrations >0.70 micromol/l increased their weight and length more during the first 6 months of life and had higher weight-for-age Z-scores during the first year of life than infants with serum retinol concentrations <or=0.70 micromol/l. Serum retinol concentrations were not associated with morbidity. In this study, vitamin A supplementation in conjunction with iron supplementation of pregnant women did not improve growth or reduce morbidity of their infants during the first year of life.


Can MR neurography of the common peroneal nerve predict a residual motor deficit in patients with foot drop?
To determine if MR neurography of the common peroneal nerve (CPN) predicts a residual motor deficit at 12-month clinical follow-up in patients presenting with foot drop. A retrospective search for MR neurography cases evaluating the CPN at the knee was performed. Patients were included if they had electrodiagnostic testing (EDX) within 3 months of imaging, ankle and/or forefoot dorsiflexion weakness at presentation, and at least 12-month follow-up. Two radiologists individually evaluated nerve size (enlarged/normal), nerve signal (T2 hyperintense/normal), muscle signal (T2 hyperintense/normal), muscle bulk (normal/Goutallier 1/Goutallier > 1), and nerve and muscle enhancement. Discrepancies were resolved via consensus review. Multivariable logistical regression was used to evaluate for association between each imaging finding and a residual motor deficit at 12-month follow-up. Twenty-three 3 T MRIs in 22 patients (1 bilateral, mean age 52 years, 16 male) met inclusion criteria. Eighteen cases demonstrated common peroneal neuropathy on EDX, and median duration of symptoms was 5 months. Six cases demonstrated a residual motor deficit at 12-month follow-up. Fourteen cases underwent CPN decompression (1 bilateral) within 1 year of presentation. Three cases demonstrated Goutallier > 1 anterior compartment muscle bulk. Multivariable logistical regression did not show a statistically significant association between any of the imaging findings and a residual motor deficit at 12-month follow-up. MR neurography did not predict a residual motor deficit at 12-month follow-up in patients presenting with foot drop, though few patients demonstrated muscle atrophy in this study.


Cerebrospinal Fluid Profiles in Parkinson's Disease: No Accumulation of Glucosylceramide, but Significant Downregulation of Active Complement C5 Fragment.
As mutations in glucocerebrosidase 1 (GBA1) are a major risk factor for Parkinson's disease (PD), decreased GBA1 activity might play an important role in the pathogenesis of the disease. However, there are currently no reports on glucosylceramide levels in the cerebrospinal fluid (CSF) in PD. We investigated whether glucosylceramide accumulation and abnormal immune status in the brain are associated with PD. We measured glucosylceramide by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) as well as levels of the active fragment of complement C5, C5a, in the CSF of 33 PD, 15 amyotrophic lateral sclerosis (ALS) and 22 neurologically normal control (NNC) subjects. Serum C5a levels in all PD and ALS cases and in a limited number of NNC subjects (n = 8) were also measured. C5a levels in CSF were significantly downregulated in PD compared with NNC. Moreover, CSF C5a/serum C5a ratio showed pronounced perturbations in PD and ALS patients. LC-ESI-MS/MS revealed a statistically significant accumulation of a specific subspecies of glucosylceramide (d18 : 1/C23 : 0 acyl chain fatty acid) in ALS, but not in PD. Interestingly, CSF glucosylceramide (d18 : 1/C23 : 0) exhibited a significant correlation with CSF C5a levels in PD, but not ALS. No correlation was observed between C5a levels or glucosylceramide subspecies content and disease duration, levodopa equivalent daily dose or Hoehn & Yahr staging in PD. Our findings demonstrate complement dysregulation without glucosylceramide accumulation in PD CSF. Furthermore, we found an association between a specific glucosylceramide subspecies and immune status in PD.


No bioaccumulation of Cry protein in the aphidophagous predator Harmonia axyridis.
The uptake of insecticidal Cry1Ab from genetically engineered (GE) maize, via herbivore Rhopalosiphum padi, to a predator Harmonia axyridis and its potential intergenerational transfer were investigated. Cry1Ab concentration was found to be 400-fold lower in R. padi compared to GE maize, and more than two-fold lower in H. axyridis. For 62% of H. axyridis samples, Cry1Ab was under the limit of detection (LOD), for another 13% were under the limit of quantification (LOQ). The concentration of Cry1Ab was similar between H. axyridis exposed short-term and long-term with the exception of adults after long-term. There was no correlation between Cry1Ab in females and eggs and neonates. The performance of H. axyridis was comparable between Cry1Ab and control. Histological investigation did not show any pathological changes in the digestive and reproductive systems. The detected route of exposure is unlikely to be important for functional biological control by H. axyridis in agroecosystem.


Substituted hydroxyapatites for bone repair.
Calcium phosphates such as hydroxyapatite have a wide range of applications both in bone grafts and for the coating of metallic implants, largely as a result of their chemical similarity to the mineral component of bone. However, to more accurately mirror the chemistry, various substitutions, both cationic (substituting for the calcium) and anionic (substituting for the phosphate or hydroxyl groups) have been produced. Significant research has been carried out in the field of substituted apatites and this paper aims to summarise some of the key effect of substitutions including magnesium, zinc, strontium, silicon and carbonate on physical and biological characteristics. Even small substitutions have been shown to have very significant effects on thermal stability, solubility, osteoclastic and osteoblastic response in vitro and degradation and bone regeneration in vivo.


HCC Liver Transplantation Wait List Dropout Rates Before and After the Mandated 6-Month Wait Time.
Studies have shown significant improvement in hepatocellular carcinoma (HCC) recurrence rates after liver transplantation since the united network of organ sharing (UNOS) implementation of a 6-month wait period prior to accrued exception model for end-stage liver disease (MELD) points enacted on October 8, 2015. However, few have examined the impact on HCC dropout rates for patients awaiting liver transplant. Our objective is to evaluate the outcomes of HCC dropout rates before and after the mandatory 6-month wait policy enacted. We conducted a retrospective cohort study on adult patients added to the liver transplant wait list between January 1, 2012, and March 8, 2019 (n = 767). Information was obtained through electronic medical records and organ procurement and transplant network (OPTN) publicly available national data reports. In response to the 2015 UNOS-mandated 6-month wait time, dropout rates in the HCC patient population at our center increased from 12% pre-mandate to 20.8% post-mandate This increase was similarly reflected in the national dropout rate, which also increased from 26.3% pre-mandate to 29.0% post-mandate. From these changes, it is evident that the UNOS mandate achieved its goal of increasing equity of liver organ allocation, but HCC patients are nonetheless dropping off of the wait list at an increased rate and are therefore disadvantaged.


Hemoglobin a1c levels and the risk of cardiovascular disease in people without known diabetes: a population-based cohort study in Japan.
High hemoglobin A1c (HbA1c) levels are strongly associated with an increased risk of cardiovascular disease (CVD) in people with and without diabetes. However, information regarding the relationship between low HbA1c levels and the risk of CVD among people without known diabetes is limited. The aim of this large-scale, prospective, population-based cohort study was to clarify the association between HbA1c levels and CVD risk among people without known diabetes.We followed-up 10,980 men and 18,079 women (46-80 years old and free of CVD and cancer at baseline) in the Japan Public Health Center-based Prospective Study. Using Cox models, we estimated the hazard ratios for CVD risk with adjustments for age, sex, geographic areas, body mass index, smoking status, sports and physical exercise, alcohol intake, systolic blood pressure, non-high-density lipoprotein cholesterol, and high-density lipoprotein cholesterol.During the median follow-up of 9.4 years, 935 CVD events (770 strokes and 165 coronary heart diseases) occurred. We observed a nonlinear association between HbA1c levels and CVD risk in participants without known diabetes. Compared with HbA1c levels of 5.0 to 5.4% (31-36 mmol/mol), the hazard ratios for CVD in participants without known diabetes were 1.50 (95% confidence interval: 1.15-1.95), 1.01 (0.85-1.20), 1.04 (0.82-1.32), and 1.77 (1.32-2.38) for HbA1c levels of <5.0% (<31 mmol/mol), 5.5 to 5.9% (37-41 mmol/mol), 6.0 to 6.4% (42-47 mmol/mol), and ≥6.5% (≥48 mmol/mol), respectively (P value for nonlinear trend: <0.001). In addition, the hazard ratio for CVD was 1.81 (1.43-2.29) in patients with known diabetes compared with participants with HbA1c levels of 5.0 to 5.4% and without known diabetes. This nonlinear relation persisted after excluding people with kidney dysfunction, liver dysfunction, anemia, body mass index <18.5 kg/m, or early events within 3 years of follow-up (P value for nonlinear trend: <0.01 for all tests).In conclusion, both low and high levels of HbA1c were associated with a higher risk of CVD in a Japanese general population without known diabetes.


An automated technique for the analysis of plasma guanidino acids, and some findings in chronic renal disease.
A sensitive method for the quantitative determination of all guanidino compounds in human serum, including basic compounds such as methylguanidine, was developed by the adaptation of the Technicon automatic amino acid analyzer. Elution buffers with very high pH and molarity are employed for the elution of very basic compounds from the column. Automatic quantitative determination of the plasma guanidino compounds was performed with biacetyl alpha-naphthol, a specific reagent for the guanidino group. This method permitted the quantitative automatic determination of guanidino compounds in less than 1 ml of serum of normal or uremic patients. Guanidino propionic acid and guanidino succinic acid were identified in high concentrations in uremic sera. Methyl guanidine, and guanidine were in smaller concentrations. Guanidino acetic acid and guanidino butyric acid were present in normal plasma in quantities not significantly different from those in uremic plasma.


Potential of water-washing of rape straw on thermal properties and interactions during co-combustion with bituminous coal.
The aim of this work was to study the thermal properties and interactions during co-combustion of rape straw (RS) before and after water-washing with bituminous coal. A series of experiments was conducted to investigate the properties and interactions during co-combustion of RS with bituminous coal (at 10, 20, 40 and 60% RS). The feasibility and potential of water-washing as an RS pre-treatment was also explored. Reactivity and the amount of heat released followed a quadratic trend, while changes to the degree of interactions between the fuels conformed to a cosine curve. Water-washing increased the ignition and burn-out temperatures and slightly decreased reactivity. Demineralization negatively affected the previously synergistic co-firing relationship, nevertheless, the amount of heat released increased by 10.28% and the average activation energy (146kJ/mol) was lower than that of the unwashed blend (186kJ/mol). Overall, water-washing of RS could prove a useful pre-treatment before co-combustion with bituminous coal.


Genetic regulation of iron homeostasis in sideropenic patients with mild COVID-19 disease under a new oral iron formulation: Lessons from a different perspective.
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) needs iron to replicate itself. Coronaviruses are able to upregulate Chop/Gadd153 and Arg1 genes, consequently leading to CD8 lymphocytes decrease, degradation of asparagine and decreased nitric oxide (NO), thus impairing immune response and antithrombotic functions. Little is known about regulation of genes involved in iron metabolism in paucisymptomatic patients with COVID-19 disease or in patients with iron deficiency treated with sucrosomial iron. Whole blood was taken from the COVID-19 patients and from patients with sideropenic anemia, treated or not (control group) with iron supplementations. Enrolled patients were: affected by COVID19 under sucrosomal iron support (group A), affected by COVID-19 not under oral iron support (group B), iron deficiency not under treatment, not affected by COVID19 (control group). After RNA extraction and complementary DNA (cDNA) synthesis of Arg1, Hepcidin and Chop/Gadd153, gene expression from the 3 groups was measured by qRT-PCR. M2 macrophages were detected by cytofluorimetry using CD163 and CD14 markers. Forty patients with COVID-19 (group A), 20 patients with iron deficiency treated with sucrosomial iron (group B) and 20 patients with iron deficiency not under treatment (control group) were enrolled. In all the patients supported with oral sucrosomial iron, the gene expression of Chop, Arg1 and Hepcidin genes was lower than in sideropenic patients not supported with iron, M1 macrophages polarization and functional iron deficiency was also lower in group A and B, than observed in the control group. New oral iron formulations, as sucrosomial iron, are able to influence the expression of genes like Chop and Arg1 and to influence M2 macrophage polarization mainly in the early phase of COVID-19 disease.


The effects of age on carbamazepine pharmacokinetics and adverse effects.
The pharmacokinetics and effect of single oral doses of carbamazepine (400 mg) were compared in a group of six young volunteers aged between 20 and 25 years, and a second group of five elderly volunteers aged between 66 and 84 years. No age related changes in salivary or plasma pharmacokinetics or in psychomotor function were detected.


Oat β-glucan alleviates muscle atrophy via promoting myotube formation and suppressing protein degradation.
The dangerous inducers of muscle atrophy are inflammatory reaction, oxidative stress, and cachexia, etc. β-Glucan, an important food derived active ingredient, has been reported to exert anti-inflammatory effects, however, its effects on regulating myoblast differentiation and protein degradation are unclear. This study is aimed to investigate the mechanism of oat β-glucan on alleviating muscle atrophy. The results showed that oat β-glucan treatment reversed tumor necrosis factor-α (TNF-α) induced abnormal myoblast differentiation and reduced muscle atrophy related MuRF-1 and Atrogin-1 protein expression. The similar phenomenon was observed after using MCC950 (NLRP3 specific inhibitor) or AS1842856 (FoxO1 specific inhibitor) to suppress NLRP3 and FoxO1 expression, respectively. Exposure to β-glucan or AS1842856 also inhibited TNF-α induced the activation of TLR4/NF-κB pathway by inactivating FoxO1, and subsequently suppressed the expression of NLRP3. Our results indicate that oat β-glucan exerts essential roles in promoting myoblast differentiation and alleviating muscle atrophy via inactivating FoxO1 and NLRP3 inflammasome signal pathway. © 2023 Society of Chemical Industry.


DNA content in Acanthamoeba during two stress defense reactions: Encystation, pseudocyst formation and cell cycle.
During environmental stress, the vegetative cells of the facultative pathogenic amoeba Acanthamoeba castellanii reversibly differentiate into resistant dormant stages, namely, cysts or pseudocysts. The type of resistant stage depends on the nature and duration of the stressor. Cell differentiation is accompanied by changes in morphology and cellular metabolism. Moreover, cell differentiation is also expected to be closely linked to the regulation of the cell cycle and, thus, to cellular DNA content. While the existence of the resistant stages in A. castellanii is well known, there is no consensus regarding the relationship between differentiation and cell cycle progression. In the present work, we used flow cytometry analysis to explore the changes in the DNA content during Acanthamoeba encystation and pseudocyst formation. Our results strongly indicate that A. castellanii enters encystation from the G2 phase of the cell cycle. In contrast, differentiation into pseudocysts can begin in the G1 and G2 phases. In addition, we present a phylogenetic analysis and classification of the main cell cycle regulators, namely, cyclin-dependent kinases and cyclins that are found in the genome of A. castellanii.


Television viewing and snacking.
With the rise in obesity in America, the search for potential causes for this epidemic has begun to include a focus on environmental factors. Television (TV) viewing is one such factor, partially due to its potential as a stimulus for eating. The current study investigated the relationship between food intake and self-reported TV viewing in an effort to identify the impact of TV viewing on specific eating behaviors. Seventy-four overweight women seeking obesity treatment completed questionnaires assessing dietary habits and TV viewing behaviors. Results suggest that snacking, but not necessarily eating meals, while watching TV is associated with increased overall caloric intake and calories from fat. Therefore, interventions targeting stimulus control techniques to reduce snacking behavior may have an impact on overall caloric intake.


Giant cross-Kerr effect for propagating microwaves induced by an artificial atom.
We investigate the effective interaction between two microwave fields, mediated by a transmon-type superconducting artificial atom which is strongly coupled to a coplanar transmission line. The interaction between the fields and atom produces an effective cross-Kerr coupling. We demonstrate average cross-Kerr phase shifts of up to 20 degrees per photon with both coherent microwave fields at the single-photon level. Our results provide an important step toward quantum applications with propagating microwave photons.


Treatment progress of spinal metastatic cancer: a powerful tool for improving the quality of life of the patients.
Spinal metastasis is a common secondary malignant tumor of the bone, often resulting in spinal cord and nerve root compression, leading to obvious pain and related compression symptoms. This condition has a high incidence and mortality rate. The treatment approach for most patients with spinal metastasis is primarily palliative. Consultation with a multidisciplinary team is widely accepted as a comprehensive treatment approach for patients with spinal metastases. With advancements in research and technology, the evaluation and treatment of spinal metastatic cancer are continuously evolving. This study provides an overview of surgical treatment, minimally invasive treatment, and radiotherapy for spinal metastatic cancer and also analyzes the clinical effects, advantages, and current limitations associated with various treatment approaches.


UGT2B13 and UGT2C1 are involved in lambda-cyhalothrin resistance in Rhopalosiphum padi.
Uridine diphosphate-glucuronosyltransferases (UGTs) are major multifunctional detoxification phase II enzymes involved in the metabolic detoxification of xenobiotics. However, their roles in insecticides resistance are still unclear. In this study, we identified two UGTs genes (UGT2B13 and UGT2C1) in Rhopalosiphum padi, a serious insect pest of wheat worldwide. Bioassays results showed that the resistance ratio of R. padi resistance strain (LC-R) to lambda-cyhalothrin (LC) was 2963.8 fold. The roles of UGT2B13 and UGT2C1 in lambda-cyhalothrin resistance were evaluated. Results indicated that the UGTs contents were significantly increased in the LC resistant strain of R. padi. UGT2B13 and UGT2C1 were significantly overexpressed in the LC-R strain. Transcription levels of UGT2B13 and UGT2C1 were relatively higher in the gut of LC-R strain. RNA interference (RNAi) of UGT2B13 or UGT2C1 significantly decreased the UGTs contents of the LC-R aphids and increased mortality of R. padi exposure to the LC50 concentration of LC. This study provides a new view that UGTs are involved in LC resistance of R. padi. The findings will promote further work to detailed the functions of UGTs in the metabolism resistance of insects to insecticides.


IGF-1 stimulated upregulation of cyclin D1 is mediated via STAT5 signaling pathway in neuronal cells.
Signal Transducer and Activator of Transcription (STATs) regulate various target genes such as cyclin D1, MYC, and BCL2 in nonneuronal cells which contribute towards progression as well as prevention of apoptosis and are involved in differentiation and cell survival. However, in neuronal cells, the role of STATs in the activation and regulation of these target genes and their signaling pathways are still not well established. In this study, a robust cyclin D1 expression was observed following IGF-1 stimulation in SY5Y cells as well as neurospheres. JAK/STAT pathway was shown to be involved in this upregulation. A detailed promoter analysis revealed that the specific STAT involved was STAT5, which acted as a positive regulatory element for cyclin D1 expression. Overexpression studies confirmed increase in cyclin D1 expression in response to STAT5a and STAT5b constructs when compared to dominant-negative STAT5. siRNA targeting STAT5, diminished the cyclin D1 expression, further confirming that STAT5 specifically regulated cyclin D1 in neuronal cells. Together, these findings shed new light on the mechanism of IGF-1 mediated upregulation of cyclin D1 expression in neural cell lines as well as in neural stem cells via the JAK/STAT5 signaling cascade.


Comparative pharmacokinetic studies of 14C-octamethylcyclotetrasiloxane (14C-D4) in Fischer 344 and Sprague Dawley CD rats after single and repeated inhalation exposure.
Octamethylcyclotetrasiloxane (D4) is a high production volume chemical that has been subject to thorough toxicological investigations. Animal studies with the substance were conducted with either Fischer 344 or Sprague Dawley CD rats. While the pharmacokinetic fate of D4 in Fischer rats is well understood, little information exists on Sprague Dawley CD rats, where reproductive effects have been demonstrated. The objective of this study was to explore the pharmacokinetic behavior in both rats, and to identify potential strain-specific differences. Fischer and Sprague Dawley CD rats were exposed for six hours to 700 ppm of 14C-D4 vapor either with or without preceding 14-day exposure to non-radiolabeled D4. Time-course data in blood, tissues and excreta were obtained through 168 h post-exposure and analyzed for both total radioactivity and parent D4. The data confirm that repeated exposure results in increased metabolism in both rat strains, confirming the findings of earlier studies of auto-induction of CYP2B1/2 by D4. The results also indicate that D4 is subject to strain-specific pharmacokinetic behavior, and that Fischer rats appear to metabolize D4 to a greater extent than Sprague Dawley CD rats.


Examining the sustainability of effects of early childhood obesity prevention interventions: Follow-up of the EPOCH individual participant data prospective meta-analysis.
Although early childhood obesity prevention has become an important issue internationally, little evidence exists regarding longer term effects (i.e., sustainability) of early interventions. To determine whether intervention benefits at 2 years of age were sustained at 3.5 and 5 years. Follow-up of the Early Prevention of Obesity in Children (EPOCH) individual participant data prospective meta-analysis of four randomized controlled trials including 2196 mother-child dyads at baseline. Interventions were home- or community-based, commenced within 6 months of birth, ended by 2 years of age, and comprised multiple sessions. Controls received standard care. BMI z-score (primary outcome), other anthropometric measures and weight-related behaviours were initially measured at 1.5-2 years and followed up at 3.5 and 5 years. Positive intervention effects on BMI z-scores at 1.5-2 years of age were not apparent by 3.5 years (-0.04 adjusted mean difference; 95% CI:-0.14, 0.06; p = 0.424), and 5 years (0.03; 95% CI: -0.08, 0.14; p = 0.60). While prolonged intervention benefits were detected for a few, but not the majority of, weight-related behaviours at 3.5 years, these effects diminished over time. This meta-analysis found that initial positive effects of childhood obesity interventions faded out after interventions ended, pointing toward the importance of a suite of interventions implemented at multiple stages across childhood.


Factors associated with early dramatic recovery following successful recanalization of occluded artery by endovascular treatment in anterior circulation stroke.
Endovascular treatment (EVT) significantly increases the recanalization rate and improves functional outcomes in acute ischemic stroke. However, despite successful recanalization by EVT, some stroke patients demonstrate no early dramatic recovery (EDR). We assessed factors associated with EDR following recanalization by EVT. We included subjects with anterior circulation stroke treated with EVT who met the following criteria: Thrombolysis in Cerebral Ischemia scores (TICI) 2b-3 after EVT, lesion volume <70mL as seen on the pre-treatment diffusion-weighted imaging (DWI) scan and a baseline NIHSS score ≥6. EDR was defined as a ≥8-point reduction in the NIHSS score, or NIHSS score of 0 or 1 measured 24h following treatment. Multivariate regression analyses were performed to identify the predictors associated with EDR. Of the 102 patients (mean age, 64.3years; median National Institutes of Health Stroke Scale score, 14), EDR was achieved in 39 patients (38.2%). The median DWI lesion volume was 12mL (interquartile range, 5-25mL). Median onset-to-recanalization time in these patients was 320min (interquartile range, 270-415min). Logistic regression analysis identified a higher initial NIHSS score (OR 1.17, 95% CI 1.03-1.33, P=0.016) and shorter time from onset to recanalization (OR 0.99, 95% CI 0.986-0.997, P=0.003), to be independently associated with EDR. In the setting of pretreatment DWI lesion volume <70mL, a higher initial NIHSS score and faster time from onset to recanalization may be important predictors of EDR following successful EVT.


The multiplicity and stoichiometry of the prosthetic groups in QH2: cytochrome c oxidoreductase as studied by EPR.
1. The EPR signal in the g = 2 region of the reduced QH2: cytochrome c oxidoreductase as present in submitochondrial particles and the isolated enzyme is an overlap of two signals in a 1 : 1 weighted ratio. Both signals are due to [2Fe-2S]+1 centers. 2. From the signal intensity it is computed that the concentration of each Fe-S center is half that of cytochrome c1. 3. The line shape of one of the Fe-S centers, defined as center 1, is reversibly dependent on the redox state of the b-c1 complex. The change of the line shape cannot be correlated with changes of the redox state of any of the cytochromes in QH2: cytochrome c oxidoreductase. 4. Lie the optical spectrum, the EPR spectrum of the cytochromes is composed of the absorption of at least three different b cytochromes and cytochrome c1. 5. The molar ratio of the prosthetic groups was found to be c1 : b-562 : b-566 : b-558 : center 1 : center 2 = 2 : 2 : 1 : 1 : 1 : 1. The consequences of this stoichiometry are discussed in relation to the basic enzymic unit of QH2 : cytochrome c oxidoreductase.


Comparative evaluation of eight serological assays for diagnosing Chlamydophila abortus infection in sheep.
Chlamydophila abortus is one of the principal causes of late-term abortion (enzootic abortion of ewes or EAE) in sheep across Europe. Serological diagnosis of EAE is routinely carried out by the complement fixation test, although the interpretation of results can often be difficult because of cross reaction with Chlamydophila pecorum, which also commonly infects sheep. The purpose of this study was to evaluate and compare four ELISAs developed at Moredun Research Institute and based on whole C. abortus elementary bodies (EBs), an outer membrane preparation of the whole organism (SolPr) and two recombinant polymorphic outer membrane protein fragments (rOMP90-3 and rOMP90-4), with 3 commercial tests, the CHEKIT Chlamydophila Abortus, Pourquier ELISA Chlamydophila abortus and ImmunoComb Ovine Chlamydophila Antibody tests. The tests were evaluated using a panel of 202 sera from experimentally and naturally infected animals, as well as from EAE-free flocks. The EB, SolPr and CHEKIT ELISAs performed similarly to the CFT, all lacking in specificity by cross reacting with sera from C. pecorum infected animals. The ImmunoComb also lacked specificity with C. pecorum sera, but also badly cross reacted with sera from EAE-free flocks. The rOMP90-3, rOMP90-4 and Pourquier ELISAs were the most specific, although the Pourquier test appeared less sensitive with sera from naturally infected animals. Overall, the rOMP90-3 ELISA performed the best, with high sensitivity (96.8%) and no cross reaction with sera from C. pecorum infected animals or from EAE-free flocks (100% specificity) and so would be a suitable alternative to the CFT for the serological diagnosis of EAE.


Utilisation of Rep-PCR to track microbes in aerosols collected adjacent to their source, a saline lake in Victoria, Australia.
Dust storms are a major source of aerosolized bacteria, especially in the drought conditions experienced in Australia in the decade to 2009. The major aims of this project were to identify the culturable bacteria in environmental samples and to genetically fingerprint all isolates using repetitive element PCR (Rep-PCR) to investigate the possibility of tracking isolates from their source into the atmosphere. Four field trips were conducted to a dry lake in western Victoria, Australia to sample aerosols and sediments. Aerosols were collected at heights up to 150 m using vacuum pumps with filters attached to a tethered helium balloon, while corresponding sediments were collected in sterile polypropylene tubes. Isolates were cultivated on Tryptic Soy Agar, R2 Agar and Marine Agar, and grown in dark conditions at ambient temperature. By sequencing the 16S rRNA gene of 270 isolates, fifteen different bacterial families were identified, with both the aerosols and sediments dominated by the Bacillaceae family. Four sets of Rep-PCR primers were tested, with the ERIC and (GTG)5 primers proving to be the most suitable for fingerprinting the cultured taxa. Rep-PCR revealed very high strain diversity in the samples collected, however some strains were still able to be tracked from sediments up to 150 m in height. This shows the potential of Rep-PCR, however very large reference databases would be required for the technique to be more useful.


One-step optimization strategy in the simulated moving bed process with asynchronous movement of ports: A VariCol case study.
The VariCol process is a variant of the conventional simulated moving bed (SMB) process, distinguished by the asynchronous shifting of the inlet and outlet ports of the chromatographic column train. This feature allows for a more flexible operation in column utilization and can also achieve higher separation performances. However, to take full benefit out of it, the operating parameters, such as the strategy for port switching, must be optimal. in this paper, a novel methodology for optimizing those parameters, based on a single NLP (non-linear programming), is proposed. The main advantage of this approach is that it significantly reduces the complexity of the original MINLP (mixed-integer non-linear programming) formulation currently discussed in the literature. The proposed optimization problem is built, considering that the average column configuration of three zones provides the necessary and sufficient information to describe the VariCol process. Several optimization scenarios for the enantioseparation of 1,1´-bi-2-naphthol and aminoglutethimide were considered to evaluate the proposed methodology and to compare the performance of VariCol and SMB processes. The results have shown that with the single NLP approach, it is possible to explore the optimal solution in all the VariCol process domains with less computational effort than other optimization strategies reported in the literature. That is a great advantage, especially in the context of real-time applications.


Application of MRI-based partial-volume correction to the analysis of PET images of mu-opioid receptors using statistical parametric mapping.
The accurate quantification of brain radioactivity concentration is limited by the spatial resolution of the PET scanner for structures smaller than 2-3 times the resolution. In the presence of enlarged cerebrospinal fluid spaces or regions of cortical neuronal loss, a significant underestimation of gray-matter radioactivity concentration due to the resulting partial-volume averaging can potentially occur. To recover the true radioactivity concentration from PET data, algorithms that use the high-resolution anatomic information provided by MRI have been developed. Their effect on PET quantification has been assessed using regions of interest and non-operator-dependent voxel-based analyses such as statistical parametric mapping (SPM), although the mechanisms that lead to an improvement in PET quantification after partial-volume correction (PVC), compared with no PVC, have not been addressed. We studied the influence of our previously described MRI-based PVC algorithm on SPM analysis of age effects on mu-opioid receptor (mu -OR) binding using (11)C-carfentanil PET in 14 healthy subjects (age range, 29-74 y). Mu-OR binding increased with age at a rate of about 0.9% per year in the left temporal cortex after PVC, consistent with the results obtained from human autoradiographic studies. Without PVC, no significant relationship with age was observed. PVC decreased mainly the residual variability of voxel mu-OR binding values around the age regression line. MRI-based PVC improves the sensitivity and accuracy of voxel-based statistical analysis of PET data.


Simultaneous quantification of labeled (2)H5-glycerol, (13)C6-glucose, and endogenous D-glucose in mouse plasma using liquid chromatography tandem mass spectrometry.
Monitoring the level of glucose and glycerol or their labeled derivatives in biological fluid for kinetic studies has always been challenging, especially in mice, because of the limited volume in addition to the complexity of plasma. For such application, we developed a simple, fast, and sensitive method for the simultaneous measurement of absolute concentrations of labeled (2)H5-glycerol and (13)C6-glucose as well as endogenous D-glucose using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). In our study, 15.0 μL of mouse plasma was processed by a one-step protein precipitation, followed by LC-MS/MS analysis. The quantification of the analytes was carried out by monitoring the product ion scan of their corresponding deprotonated molecular ions and constructing the extracted ion fragmentogram by choosing a specific product ion for each analyte (equivalent to precursor ion to product ion transitions). The limit of detection (LOD) was evaluated to be 1.0 μM for both (2)H5-glycerol and (13)C6-glucose, and the limit of quantitation (LOQ) was observed to be 5.0 μM for both (2)H5-glycerol and (13)C6-glucose in diluted mice plasma that corresponds to 50 μM in plasma or 4.60 and 9.01 mg/dL of glycerol and glucose in plasma, respectively. The extraction recoveries are 81.9 % (CV = 8.1 %) for (2)H5-glycerol and 26.2 % (CV = 13.6 %) for (13)C6-glucose.


Strategic Scientific and Technological Capacity-Building in Clinical Medicine in China: Taking the Innovative Development of Reproductive Medicine at Peking University Third Hospital as an Example.
Based on the macroanalysis of the unbalanced development of the "demand side" and the "supply side" of clinical medicine in China, this paper elucidates the stakeholders, resources, and ecosystem of the strategic scientific and technological capacity-building and calls for a larger coverage, smoother supply chain, and more sustainable ecosystem to ensure the development of clinical medicine. Furthermore, focusing on the establishment and development of clinical reproductive health in China, the authors introduce the strategic scientific and technological capacity-building of reproductive medicine in Peking University Third Hospital, with an attempt to inform similar efforts in other fields and even the whole clinical medicine in China.


Determinants of survival in children with brain tumors.
A study was conducted in metropolitan Baltimore to examine time trends in survival and factors which influence survival of children with brain tumors. One hundred eighty-four cases diagnosed from 1960 to 1975 were identified; 76.5% occurred in white children and 48% were girls. Five-year survival rates were 35% for children diagnosed in 1960-64, 34% in 1965-69, and 49% in 1970-74. Girls had consistently better survival rates than boys. White children experienced consistently better survival rates than blacks. Of those who survived the first year, children with supratentorial tumors had better five-year survival rates (46%) than those which with infratentorial tumors (27%). Of those who survived the first year, children with astrocytomas had better survival rates than those with other types of tumors.


The Brazillian version of the hand mobility in scleroderma (HAMIS) test: translation and validation.
The Hand Mobility in Scleroderma (HAMIS) test was created to measure the degree of dysfunction of hand movements imposed by systemic sclerosis (SSc). The modified version (mHAMIS), with 4 of the 9 original items, was developed later. The goal of the present study was to translate and validate HAMIS and mHAMIS into Brazilian Portuguese and culture. After direct and reverse translation and comprehension test in 10 SSc patients, HAMIS-Br was applied to another 32 patients with SSc. To evaluate internal consistency, intraobserver and interobserver agreement, and intraobserver and interobserver reliability, we used respectively the Cronbach's α coefficient, kappa concordance and intraclass correlation (ICC). The correlation between HAMIS-Br and mHAMIS-Br was evaluated and a factorial analysis was performed. HAMIS-Br showed excellent internal consistency (Cronbach's α = 0.997), good intraobserver agreement (kappa between 0.78 [95%CI =0.57-0.99] and 1) and intraobserver and interobserver reliability (ICC = 0.993, 95% CI = 0.973-0.993 and ICC = 0.994, 95% CI = 0.987-0.997, respectively). The mHAMIS-Br presented similar results and excellent correlation with HAMIS-Br (r = 0.923). The factorial analysis extracted three groups of questions that explain 84.4% of the total variance, and that can be understood through the influence of certain movements in the interpretation of others: [1] questions whose interpretation is influenced by the extension of the fingers, [2] questions whose interpretation is influenced by flexion of the fingers, [3] volar flexion of the fingers, with similar correlation with both other factors. HAMIS-Br and mHAMIS-Br showed good agreement, intraobserver and interobserver reliability, and internal validity. It is necessary to be attentive to the influence of certain limitations of movements in the interpretation of others.


Cordyceps: a traditional Chinese medicine and another fungal therapeutic biofactory?
Traditional Chinese medicines (TCM) are growing in popularity. However, are they effective? Cordyceps is not studied as systematically for bioactivity as another TCM, Ganoderma. Cordyceps is fascinating per se, especially because of the pathogenic lifestyle on Lepidopteron insects. The combination of the fungus and dead insect has been used as a TCM for centuries. However, the natural fungus has been harvested to the extent that it is an endangered species. The effectiveness has been attributed to the Chinese philosophical concept of Yin and Yang and can this be compatible with scientific philosophy? A vast literature exists, some of which is scientific, although others are popular myth, and even hype. Cordyceps sinensis is the most explored species followed by Cordyceps militaris. However, taxonomic concepts were confused until a recent revision, with undefined material being used that cannot be verified. Holomorphism is relevant and contamination might account for some of the activity. The role of the insect has been ignored. Some of the analytical methodologies are poor. Data on the "old" compound cordycepin are still being published: ergosterol and related compounds are reported despite being universal to fungi. There is too much work on crude extracts rather than pure compounds with water and methanol solvents being over-represented in this respect (although methanol is an effective solvent). Excessive speculation exists as to the curative properties. However, there are some excellent pharmacological data and relating to apoptosis. For example, some preparations are active against cancers or diabetes which should be fully investigated. Polysaccharides and secondary metabolites are of particular interest. The use of genuine anamorphic forms in bioreactors is encouraged.


The radiofrequency frontier: a review of radiofrequency and combined radiofrequency pulsed-light technology in aesthetic medicine.
Radiofrequency (RF) and combined RF light source technologies have established themselves as safe and effective treatment modalities for several dermatologic procedures, including skin tightening, hair and leg vein removal, acne scarring, skin rejuvenation, and wrinkle reduction. This article reviews the technology, clinical applications, and recent advances of RF and combined RF light/laser source technologies in aesthetic medicine.


Comparing optimal and empirical stomatal conductance models for application in Earth system models.
Earth system models (ESMs) rely on the calculation of canopy conductance in land surface models (LSMs) to quantify the partitioning of land surface energy, water, and CO2 fluxes. This is achieved by scaling stomatal conductance, gw , determined from physiological models developed for leaves. Traditionally, models for gw have been semi-empirical, combining physiological functions with empirically determined calibration constants. More recently, optimization theory has been applied to model gw in LSMs under the premise that it has a stronger grounding in physiological theory and might ultimately lead to improved predictive accuracy. However, this premise has not been thoroughly tested. Using original field data from contrasting forest systems, we compare a widely used empirical type and a more recently developed optimization-type gw model, termed BB and MED, respectively. Overall, we find no difference between the two models when used to simulate gw from photosynthesis data, or leaf gas exchange from a coupled photosynthesis-conductance model, or gross primary productivity and evapotranspiration for a FLUXNET tower site with the CLM5 community LSM. Field measurements reveal that the key fitted parameters for BB and MED, g1B and g1M, exhibit strong species specificity in magnitude and sensitivity to CO2 , and CLM5 simulations reveal that failure to include this sensitivity can result in significant overestimates of evapotranspiration for high-CO2 scenarios. Further, we show that g1B and g1M can be determined from mean ci /ca (ratio of leaf intercellular to ambient CO2 concentration). Applying this relationship with ci /ca values derived from a leaf δ13 C database, we obtain a global distribution of g1B and g1M , and these values correlate significantly with mean annual precipitation. This provides a new methodology for global parameterization of the BB and MED models in LSMs, tied directly to leaf physiology but unconstrained by spatial boundaries separating designated biomes or plant functional types.


Developmental biology: regulation by selective gene localization.
Recent studies have shown that, early during sporulation in Bacillus subtilis, the temporary exclusion of 70% of the chromosome from the forespore compartment is critical to the regulated activation of two major transcription factors, sigma(F) and sigma(E).


Convexity, Jensen's inequality and benefits of noisy mechanical ventilation.
Mechanical ventilators breathe for you when you cannot or when your lungs are too sick to do their job. Most ventilators monotonously deliver the same-sized breaths, like clockwork; however, healthy people do not breathe this way. This has led to the development of a biologically variable ventilator--one that incorporates noise. There are indications that such a noisy ventilator may be beneficial for patients with very sick lungs. In this paper we use a probabilistic argument, based on Jensen's inequality, to identify the circumstances in which the addition of noise may be beneficial and, equally important, the circumstances in which it may not be beneficial. Using the local convexity of the relationship between airway pressure and tidal volume in the lung, we show that the addition of noise at low volume or low pressure results in higher mean volume (at the same mean pressure) or lower mean pressure (at the same mean volume). The consequence is enhanced gas exchange or less stress on the lungs, both clinically desirable. The argument has implications for other life support devices, such as cardiopulmonary bypass pumps. This paper illustrates the benefits of research that takes place at the interface between mathematics and medicine.


Current topics on inhibitors of respiratory complex I.
There are a variety of chemicals which regulate the functions of bacterial and mitochondrial complex I. Some of them, such as rotenone and piericidin A, have been indispensable molecular tools in mechanistic studies on complex I. A large amount of experimental data characterizing the actions of complex I inhibitors has been accumulated so far. Recent X-ray crystallographic structural models of entire complex I may be helpful to carefully interpret this data. We herein focused on recent hot topics on complex I inhibitors and the subjects closely connected to these inhibitors, which may provide useful information not only on the structural and functional aspects of complex I, but also on drug design targeting this enzyme. This article is part of a Special Issue entitled Respiratory complex I, edited by Volker Zickermann and Ulrich Brandt.


Transcatheter coil occlusion of perimembranous ventricular septal defects.
Our purpose was to determine the feasibility and safety of transcatheter coil occlusion of a perimembranous VSD. Transcatheter coil occlusion of a perimembranous ventricular septal defect (VSD) may be a useful treatment; however, there are few reports on its technical aspects and outcome. We attempted coil closure of a perimembranous VSD in 41 patients. We approached the VSD via the right ventricle (RV) in 16, via the left ventricle (LV) in 16, simultaneously deployed two coils from the RV (RV/RV) in three, and simultaneously deployed two, three, or four coils from the RV and LV (RV/LV) in six. Coils (0.038'' flipper, 0.052'' Gianturco, or 0.035'' platinum coil) were placed into the defect through the delivery catheter until any flow through the VSD disappeared or became trivial on angiography. We achieved 100% complete closure in all patients in whom coils were deployed, although some patients required a second session. A flipper coil used alone was insufficient to completely occlude VSDs larger than 2.5 mm. Transcatheter coil occlusion of a VSD can be performed reliably and safely by selecting appropriate embolic coils. Small defects (<2.5 mm) can be closed with a flipper coil, but defects >or=2.5 mm require a 0.052'' coil.


Efficacy and tolerability of 5-day azacytidine dose-intensified regimen in higher-risk MDS.
Higher-risk myelodysplastic syndromes (MDS) are aggressive disorders with rapid progression to AML and short survival. Azacitidine has shown unprecedented survival advantage in these patients but its treatment schedule involves daily hospital administrations for 7 days every 4 weeks. Due to patient and staffing constraints, we have treated 50 patients with a 5-day dose-intensified (500 mg/m(2) total monthly dose divided in 5 days) azacitidine schedule in our center. The regimen was well tolerated, with Grade 3/4 adverse events seen in 24 % patients and only two discontinuations due to toxicity. The response rate was similar to that reported with the 7-day schedule: 16 % complete remissions, 32 % partial remissions, and 62 % transfusion independence. The median survival was 19.2 months from diagnosis. In addition, this regimen reduced hospital visits by 28 % and drug use by 30 %. Our results demonstrate the safety and efficacy of a dose-intensified 5-day regimen.


Easy alternatives to difficult clamping of distal vessels of the leg.
Control of proximal and back bleeding following an arteriotomy can be challenging when tibial or pedal vessels are noncompressible owing to calcification. We present two easy, inexpensive, and available solutions using a simple intravenous cannula to facilitate clamping of the distal vessels during below-knee revascularization.


Longterm impact of abdominal decompression: a prospective comparative analysis.
Abdominal decompression is widely used to treat end-organ dysfunction associated with intraabdominal hypertension (IAH) and abdominal compartment syndrome (ACS). The longterm impact of abdominal decompression on physical and mental health, quality of life, and subsequent employment remains unclear. A prospective cohort study was performed at a tertiary referral/Level I trauma center. All patients who required abdominal decompression for more than 48 hours were asked to complete the SF-36v2 health survey at regular intervals for 2 years postdecompression. Patients discharged with a chronic incisional hernia (OPEN) were compared with those discharged with primary fascial closure (CLOSED) and with the general population. Quality-adjusted life years (QALYs) and successful return to employment were determined. From June 2002 to May 2005, 245 consecutive patients required abdominal decompression for intraabdominal hypertension and abdominal compartment syndrome. Forty-four patients (30 OPEN, 14 CLOSED) met inclusion criteria and completed their health surveys. At 6 months postdecompression, physical and social functioning were significantly decreased among OPEN, but not CLOSED, patients when compared with the general population. By 18 months, OPEN patients demonstrated normal physical and mental health perception. OPEN and CLOSED patients exhibited decreased, but identical, quality-adjusted life years (1.20+/-0.11 versus 1.23+/-0.25 [mean +/- SD]; p=0.39) and similar ability to resume employment (41% versus 55%; p=0.49). Abdominal decompression does not have a negative impact on longterm physical or mental health perception. Quality of life and ability to resume employment are not improved by same-admission primary fascial closure. Abdominal decompression is not as debilitating and life altering as might be expected.


Validation of automatic wear-time detection algorithms in a free-living setting of wrist-worn and hip-worn ActiGraph GT3X.
Wrist-worn accelerometers are increasingly used in epidemiological studies to record physical activity. The accelerometer data are usually only analyzed if the convention for compliant wear time is met (i.e. ≥ 10 h per day) but the algorithms to detect wear time have been developed based on data from hip-worn devices only and have not been tested in a free-living setting. The aim of this study was to validate the automatic wear time detection algorithms of one of the most frequently used devices in a free-living setting. Sixty-eight adults wore one ActiGraph GT3X+ accelerometer on the wrist and one on the hip and additionally recorded wear times for each device separately in a diary. Monitoring phase was during three consecutive days in a free-living setting. Wear time was computed by the algorithms of Troiano and Choi and compared to the diary recordings. Mean wear time was over 1420 min per day for both devices on all days. Lin's concordance correlation coefficient for the wrist-worn wear time was 0.73 (0.60; 0.82) when comparing the diary with Troiano and 0.78 (0.67; 0.86) when comparing the diary with Choi. For hip-worn devices the respective values were 0.23 (0.13; 0.33) for Troiano and 0.92 (0.88; 0.95) for Choi. Mean and standard deviation values for absolute percentage errors for wrist-worn devices were - 1.3 ± 8.1% in Troiano and 0.9 ± 7.7% in Choi. The respective values for hip-worn devices were - 17.5 ± 10% in Troiano and - 0.8 ± 4.6% in Choi. Hip worn devices may be preferred due to their higher accuracy in physical activity measurement. Automatic wear-time detection can show high errors in individuals, but on a group level, type I, type II, and total errors are generally low when the Choi algorithm is used. In a real-life setting and participants with a high compliance, the algorithm by Choi is sufficient to distinguish wear time from non-wear time on a group level.


Rapid evaluation of tetanus immunity by a haemagglutination test in the injured at a hospital emergency unit.
A turkey red blood cell haemagglutination assay (TRBC HA) allowing rapid measurement of the antibodies against tetanus has been set recently. Its feasibility was evaluated in injured patients admitted into an emergency unit during summer 1987. TRBC HA was performed by the same physician who questioned the patient on his/her previous vaccinations and evaluated his/her immunization status. The rapid HA test practiced in emergency was controlled by TRBC HA and ELISA measurement of antibodies carried out in the laboratory. Each method was compared to the others: the results were fitted and no significant difference was found. The preventive procedures which would have followed the antibody measurement by immediate TRBC HA were compared to the decision resulting from clinical evaluation. The immunoprophylactic attitude would have been the same in 82% of cases. TRBC HA is a reliable test, and feasible in an emergency: it could help in making the appropriate decision for immunoprophylaxis to be applied to the injured and other patients at risk of tetanus.


Flow cytometric detection of liposomal cytarabine in cerebrospinal fluid of patients treated with intrathecal chemotherapy.
We report the unusual flow cytometric detection of liposomes in the cerebrospinal fluid of patients with aggressive non-Hodgkin's lymphoma and acute myeloid leukemia, treated with intrathecal liposomal cytarabine.


The Effects of Intestinal Nematode L4 Stage on Mouse Experimental Autoimmune Encephalomyelitis.
Helminths use various immunomodulatory and anti-inflammatory strategies to evade immune attack by the host. During pathological conditions, these strategies alter the course of disease by reducing immune-mediated pathology. The study examines the therapeutic effect of the nematode L4 stage based on an in vivo model of multiple sclerosis, monophasic encephalomyelitis (EAE), induced by sensitization with MOG35-55 peptide in C57BL/6 female mice infected with the intestinal nematode Heligmosomoides polygyrus. The EAE remission was correlated with altered leukocyte number identified in the central nervous system (CNS), and temporary permeability of the blood-brain barrier at the histotrophic phase of infection. At 6 days post-infection, when the L4 stage had almost completely attenuated the clinical severity and pathological signs of EAE, CD25+ cell numbers expanded significantly, with parallel growth of CD8+ and CD4+, both CD25+Foxp3+ and CD25+Foxp3- subsets and alternatively activated macrophages. The phenotypic changes in distinct subsets of cerebrospinal fluid cells were correlated with an inhibited proliferative response of encephalitogenic T cells and elevated levels of nerve growth factor and TGF-β. These results enhance our understanding of mechanisms involved in the inhibition of immune responses in the CNS during nematode infection.


Impact of Graft Function on Health Status and Quality of Life in Very Long-Term Survivors Who Received an HSCT for Inborn Errors of Immunity, a Prospective Study of the CEREDIH.
The overall survival rate after hematopoietic stem cell transplantation (HSCT) for inborn errors of immunity (IEI) has improved considerably, and its indications have broadened. As a consequence, addressing the issue of long-term health-related quality of life (HRQoL) has become crucial. Our study focuses on the health and HRQoL of post-HSCT survivors. We conducted a multicenter prospective follow-up study enrolling IEI patients who underwent transplantation in childhood before 2009. Self-reported data from the French Childhood Immune Deficiency Long-term Cohort and the 36-item Short Form questionnaires were compiled. One hundred twelve survivors were included with a median duration period from HSCT of 15 years (range 5-37), of whom 55 underwent transplantation for a combined immunodeficiency. We show that in patients evaluated at least 5 years after HSCT, 55% are still affected by a poor or very poor health status. Poor and very poor health status correlated with an abnormal graft function, defined as host or mixed chimerism, abnormal CD3+ count, or diagnosis of chronic graft-versus-host disease (poor health: odds ratio [OR] = 2.6, 95% confidence interval [CI], 1.1-5.9, P = .028; very poor health: OR = 3.6, 95% CI, 1.1-13, P = .049). Poor health was directly linked to a poorer HRQoL. Significant improvements in graft procedures have translated into better survival rates, but we show here that about half of the transplanted patients remain affected by an altered health status with a correlation to both abnormal graft function and impaired HRQoL. Additional studies are needed to confirm the impact of those improvements on long-term health status and HRQoL.


A multigenerational study on phenotypic consequences of the most common causal variant of HNF1A-MODY.
Systematic studies on the phenotypic consequences of variants causal of HNF1A-MODY are rare. Our aim was to assess the phenotype of carriers of a single HNF1A variant and genetic and clinical factors affecting the clinical spectrum. We conducted a family-based multigenerational study by comparing heterozygous carriers of the HNF1A p.(Gly292fs) variant with the non-carrier relatives irrespective of diabetes status. During more than two decades, 145 carriers and 131 non-carriers from 12 families participated in the study, and 208 underwent an OGTT at least once. We assessed the polygenic risk score for type 2 diabetes, age at onset of diabetes and measures of body composition, as well as plasma glucose, serum insulin, proinsulin, C-peptide, glucagon and NEFA response during the OGTT. Half of the carriers remained free of diabetes at 23 years, one-third at 33 years and 13% even at 50 years. The median age at diagnosis was 21 years (IQR 17-35). We could not identify clinical factors affecting the age at conversion; sex, BMI, insulin sensitivity or parental carrier status had no significant effect. However, for 1 SD unit increase of a polygenic risk score for type 2 diabetes, the predicted age at diagnosis decreased by 3.2 years. During the OGTT, the carriers had higher levels of plasma glucose and lower levels of serum insulin and C-peptide than the non-carriers. The carriers were also leaner than the non-carriers (by 5.0 kg, p=0.012, and by 2.1 kg/m2 units of BMI, p=2.2 × 10-4, using the first adult measurements) and, possibly as a result of insulin deficiency, demonstrated higher lipolytic activity (with medians of NEFA at fasting 621 vs 441 μmol/l, p=0.0039; at 120 min during an OGTT 117 vs 64 μmol/l, p=3.1 × 10-5). The most common causal variant of HNF1A-MODY, p.(Gly292fs), presents not only with hyperglycaemia and insulin deficiency, but also with increased lipolysis and markedly lower adult BMI. Serum insulin was more discriminative than C-peptide between carriers and non-carriers. A considerable proportion of carriers develop diabetes after young adulthood. Even among individuals with a monogenic form of diabetes, polygenic risk of diabetes modifies the age at onset of diabetes.


Identification of tryptophan metabolites in the healthy epidermis of diabetics.
The urinary excretion of metabolites of the tryptophan leads to niacin pathway after an L-tryptophan load in patients with potential and latent diabetes, and in a third of those with chemical diabetes, was normal. In the remaining subjects with chemical diabetes and in those with clinical diabetes it was altered and characterized by an increase of xanthurenic acid and by a reduction of kynurenines and 3-hydroxyanthranilic acid. The thin-layer chromatographic pattern of tryptophan metabolites in the epidermis of patients with potential, latent, chemical, clinical diabetes was characterized by the kynurenine pathway metabolites that were also present in the epidermis of healthy subjects. Morevoer, the above pattern was characterized by the appearance of 5-hydroxytrptamine, and in patients with chemical and clinical diabetes by the appearance of xanthurenic acid.


Astigmatic changes after excimer laser refractive surgery.
To compare the astigmatic changes induced by spherical and elliptical excimer laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK). University-based refractive surgery practice. Three-month refractive data from 317 eyes of consecutive patients having spherical PRK, astigmatic PRK (A-PRK), spherical LASIK, and astigmatic LASIK (A-LASIK) by a single surgeon (J.S.P.) using VISX 2020B and Star lasers over 2 years were studied for astigmatic changes resulting from the surgical procedure. At 3 months, the mean change in absolute astigmatism was +0.15 diopter (D) and -0.07 D in the spherical PRK and LASIK groups, respectively. Photorefractive keratectomy tended to induce with-the-rule (WTR) astigmatism, while LASIK was astigmatically neutral. As expected, the eyes treated with A-PRK and A-LASIK achieved a greater reduction in absolute astigmatism (-1.02 D and -1.28 D, respectively) than those treated with spherical PRK and LASIK. The qualitative nature of the astigmatic change was different between flap-based and PRK-based procedures. Spherical PRK is more likely than spherical LASIK to induce astigmatism, with a tendency toward WTR astigmatism. The eyes treated with spherical LASIK had no preponderant change in the direction of astigmatic magnitude or axis. Astigmatic PRK and LASIK effectively reduced astigmatism along the preoperative axis; A-LASIK tended to induce a random resultant axis in most patients.


Circulating secretory immunoglobulins of the A and M isotypes in chronic liver disease.
Serum levels of secretory IgA (SIgA) and secretory IgM (SIgM) were quantified by an enzyme-linked immunosorbent assay in 97 patients with various chronic liver diseases and 17 patients with uncomplicated ulcerative colitis. The values obtained were compared with 89 matched controls and related to other serum variables. All types of liver disease had elevated median levels of serum SIg. Patients with primary biliary cirrhosis (PBC) had the highest SIg levels, particularly SIgM, but increased total serum IgM was slightly more specific for PBC. Thus, the SIg levels did not add more discriminative information than several other variables. Elevated levels of circulating SIgA correlated mainly with variables that indicate reduced liver function. The difference observed between patients with PBC and primary sclerosing cholangitis (PSC) in the alkaline phosphatase (ALP)-to-SIg ratio is discussed.


Clinically comparable impedimetric immunosensor for serum alkaline phosphatase detection based on electrochemically engineered Au-nano-Dendroids and graphene oxide nanocomposite.
In this work, we demonstrate label-free electrochemical impedance spectroscopy (EIS) based alkaline phosphatase (ALP) detection using gold nanoparticles (AuNPs), electrochemically engineered Au-nano-Dendroids, and graphene oxide (GO) nanocomposite. These nanomaterials were sequentially deposited on to the screen-printed carbon electrode (SPCE) and antibodies against ALP (anti-ALP) were immobilized using carbodiimide bioconjugation process. The sensor probe has been characterized extensively using TEM, EDX, SAED, XRD, FE-SEM, FTIR, DIC, and electrochemical techniques. The analytical performance of fabricated biosensor has been evaluated using EIS, where linear dynamic range and limit of detection were obtained to be 100-1000 U/L and 9.10 (±0.12) U/L, respectively. The developed biosensor showed high selectivity towards ALP with negligible interference (ksel « 1; n = 3) due to coexisting molecules. The sensor probe has successfully recovered ALP between 108.84% and 172.50% (n = 3) in human serum samples. The sensor has been used to estimate ALP in clinical serum samples, where the level was found to be 83.15 U/L and was comparable with standard technique used in the hospitals. The shelf life, stability, and reproducibility have also been evaluated.


Hollow hyaluronic acid particles by competition between adhesive and cohesive properties of catechol for anticancer drug carrier.
The marine mussel-inspired properties of catechol, adhesiveness and cohesiveness, have been applied with pH control to fabricate hollow particles using a silica core and catechol-modified hyaluronic acid (HA-CA) shell for an anticancer drug carrier. The competition between adhesive and cohesive properties of catechol with different pH values leads to various structures, a rough catechol modified HA (HA-CA) shell at pH 5.5, monodisperse spherical silica@HA-CA particles at pH 7.4, and an amorphous HA-CA layer at pH 8.5. The redox transition of catechol with pH is a key factor modulating the behavior of the HA-CA shell on the silica core, which induces strong adhesion of HA-CA to silica at pH 5.5 and structural hardness with cohesive coupling at pH 7.4. In addition, after core removal, the hollow HA-CA particles are followed by loading of anticancer drug, doxorubicin (DOX). DOX loaded HA-CA particles show pH-triggered release behavior and dramatic cytotoxic effect indicating that they are a promising novel anticancer drug carrier.


Ecotoxicological characterization of sugarcane vinasses when applied to tropical soils.
The impact of sugarcane vinasse on soil invertebrates was assessed through ecotoxicological assays. Increasing concentrations of two vinasses from different distillery plants (VA and VB), and a vinasse from a laboratory production (VC), were amended on two natural tropical Oxisols (LV and LVA) and a tropical artificial soil (TAS) to characterize the effects of the vinasses on earthworms (Eisenia andrei), enchytraeids (Enchytraeus crypticus), mites (Hypoaspis aculeifer) and collembolans (Folsomia candida). The highest concentrations of VA and VB were avoided by earthworms in all soils and by collembolans especially in the natural soils. The presence of VC in all of the tested soils did not cause avoidance behavior in these species. The reproduction of earthworms, enchytraeids and collembolans was decreased in the highest concentrations of VA and VB in the natural soils. In TAS, VB reduced the reproduction of all test species, whereas VA was toxic exclusively to E. andrei and E. crypticus. The vinasse VC only reduced the number of earthworms in TAS and enchytraeids in LVA. The reproduction of mites was reduced by VB in TAS. Vinasses from distillery plants were more toxic than the vinasse produced in laboratory. The vinasse toxicities were influenced by soil type, although this result was most likely because of the way the organisms are exposed to the contaminants in the soils. Toxicity was attributed to the vinasses' high salt content and especially the high potassium concentrations. Data obtained in this study highlights the potential risk of vinasse disposal on tropical soils to soil biota. The toxic values estimated are even more relevant when considering the usual continuous use of vinasses in crop productions.


Correspondences of hydrostatic pressure in periodontal ligament with regions of root resorption: a clinical and a finite element study of the same human teeth.
The main objectives of this study were to generate individual finite element models of extracted human upper first premolars, and to simulate the distribution of the hydrostatic pressure in the periodontal ligament (PDL) of these models for evaluation of the risk of root resorption. The individual extracted teeth were from a previous in vivo study that investigated root resorption after application of continuous intrusive forces. The results of experimental examination and simulations were compared on these identical tooth roots. The applied force system was 0.5N and 1.0N of intrusive force. The simulated results during intrusion of 0.5N showed regions near the apical thirds of the roots with hydrostatic pressure over the human capillary blood pressure. These regions correlated with the electron microscopies of previous studies performed in Brazil with the identical teeth. An increased force of 1.0N resulted in increased areas and magnitudes of the hydrostatic pressure. The key parameter indicating beginning root resorption used in this study was an increased value for hydrostatic pressure in the PDL.


Interventional bronchoscopy in the management of thoracic malignancy.
Interventional bronchoscopy is a rapidly expanding field in respiratory medicine offering minimally invasive therapeutic and palliative procedures for all types of lung neoplasms. This field has progressed over the last couple of decades with the application of new technology. The HERMES European curriculum recommendations include interventional bronchoscopy skills in the modules of thoracic tumours and bronchoscopy [1]. However, interventional bronchoscopy is not available in all training centres and consequently, not all trainees will obtain experience unless they rotate to centres specifically offering such training. In this review, we give an overview of interventional bronchoscopic procedures used for the treatment and palliation of thoracic malignancy. These can be applied either with flexible or rigid bronchoscopy or a combination of both depending on the anatomical location of the tumour, the complexity of the case, bleeding risk, the operator's expertise and preference as well as local availability. Specialised anaesthetic support and appropriately trained endoscopy staff are essential, allowing a multimodality approach to meet the high complexity of these cases.


Metformin Decouples Phospholipid Metabolism in Breast Cancer Cells.
The antidiabetic drug metformin, currently undergoing trials for cancer treatment, modulates lipid and glucose metabolism both crucial in phospholipid synthesis. Here the effect of treatment of breast tumour cells with metformin on phosphatidylcholine (PtdCho) metabolism which plays a key role in membrane synthesis and intracellular signalling has been examined. MDA-MB-468, BT474 and SKBr3 breast cancer cell lines were treated with metformin and [3H-methyl]choline and [14C(U)]glucose incorporation and lipid accumulation determined in the presence and absence of lipase inhibitors. Activities of choline kinase (CK), CTP:phosphocholine cytidylyl transferase (CCT) and PtdCho-phospholipase C (PLC) were also measured. [3H] Radiolabelled metabolites were determined using thin layer chromatography. Metformin-treated cells exhibited decreased formation of [3H]phosphocholine but increased accumulation of [3H]choline by PtdCho. CK and PLC activities were decreased and CCT activity increased by metformin-treatment. [14C] incorporation into fatty acids was decreased and into glycerol was increased in breast cancer cells treated with metformin incubated with [14C(U)]glucose. This is the first study to show that treatment of breast cancer cells with metformin induces profound changes in phospholipid metabolism.


Absence of histological lesions in primate models of ECT and magnetic seizure therapy.
The authors present preliminary findings from the first nonhuman primate neuropathological study of ECT to use perfusion fixation and adequate controls and the first to compare ECT with magnetic seizure therapy, to their knowledge. Twelve Macaca mullata received 6 weeks of daily ECT, magnetic seizure therapy, or anesthesia alone. After perfusion fixation, their brains were examined while masked to intervention. No identified lesions were attributable to the interventions. Cortical and hippocampal immunoreactivity for glial fibrillary acidic protein (an astrocytic marker) was most intense in the group that received ECT. This small but rigorous primate study supports the view that ECT does not produce histological lesions in the brain and provides the first comparable safety data on magnetic seizure therapy.


Evaluation of spectroscopic properties of Er(3+)/Yb(3+)/Pr(3+): SrGdGa3O7 crystal for use in mid-infrared lasers.
Er(3+)/Yb(3+)/Pr(3+): SrGdGa3O7 crystal was firstly grown by Czochralski method. Detailed spectroscopic analyses of Er(3+)/Yb(3+)/Pr(3+): SrGdGa3O7 were carried out. Besides better absorption characteristic, the spectra of Er(3+)/Yb(3+)/Pr(3+): SrGdGa3O7 show weaker up-conversion and near-infrared emissions as well as superior mid-infrared emission in comparison to Er(3+): SrGdGa3O7 and Er(3+)/Yb(3+): SrGdGa3O7 crystals. Furthermore, the self-termination effect for Er(3+) 2.7 μm laser is suppressed successfully because the fluorescence lifetime of the (4)I(13/2) lower level of Er(3+) decreases markedly while that of the upper (4)I(11/2) level changes slightly in Er(3+)/Yb(3+)/Pr(3+): SrGdGa3O7 crystal. The sensitization effect of Yb(3+) and deactivation effect of Pr(3+) ions as well as the energy transfer mechanism in Er(3+)/Yb(3+)/Pr(3+): SrGdGa3O7 crystal were also studied in this work. The introduction of Yb(3+) and Pr(3+) is favorable for achieving an enhanced 2.7 μm emission in Er(3+)/Yb(3+)/Pr(3+): SrGdGa3O7 crystal which can act as a promising candidate for mid-infrared lasers.


Conservation of repeated DNA sequences in aneuploid human tumor cells.
A series of human neuroectodermal tumors, all containing more than the normal diploid DNA, and each with its own distinct chromosome mode, were studied using restriction enzyme cleavage and specific DNA sequence hybridization. Methods described were quite sensitive and quantitative and as few as 40 molecules with a given restriction site were reproducibly detected in total nuclear DNA. Analysis of several fluorescent gel bands associated with different chromosomal domains revealed no changes between any of the tumor and normal cells. Specific probe hybridization, using purified complex repeating sequences, indicated fidelity of base sequence, as well as preservation of the relative amounts of each of a number of minor related multimers in both the tumor and normal cells. Centromeric regions containing arrays of such sequences may be maintained in these tumor cells and furthermore it is possible that some of these cells are polyploid with respect to DNA sequences, rather than aneuploid as their chromosome profiles suggest.


Role of the endoplasmic reticulum in synaptic transmission.
Neurons possess a complex morphology spanning long distances and a large number of subcellular specializations such as presynaptic terminals and dendritic spines. This structural complexity is essential for maintenance of synaptic junctions and associated electrical as well as biochemical signaling events. Given the structural and functional complexity of neurons, neuronal endoplasmic reticulum is emerging as a key regulator of neuronal function, in particular synaptic signaling. Neuronal endoplasmic reticulum mediates calcium signaling, calcium and lipid homeostasis, vesicular trafficking, and proteostasis events that underlie autonomous functions of numerous subcellular compartments. However, based on its geometric complexity spanning the whole neuron, endoplasmic reticulum also integrates the activity of these autonomous compartments across the neuron and coordinates their interactions with the soma. In this article, we review recent work regarding neuronal endoplasmic reticulum function and its relationship to neurotransmission and plasticity.


The route of lipid administration affects parenteral nutrition-induced hepatic steatosis in a mouse model.
The etiology of parenteral nutrition (PN)-associated hepatic injury remains unresolved. Recent studies have suggested that the intravenous (IV) lipid emulsion administered with PN may contribute to PN-associated hepatic injury. We therefore examined whether the route of lipid administration would affect the development of PN-associated liver injury in a previously established animal model of PN-induced hepatic steatosis. Mice were fed ad libitum PN solution as their only nutritional source for 19 days with lipid supplementation by either the enteral or the IV route. Control mice received chow alone, and a final group received enteral PN solution without lipid supplementation. All mice gained equivalent weight during the study. Mice receiving PN alone or PN with IV lipid developed severe histologic liver damage that was not seen in control mice or in mice receiving PN with enteral lipid. Liver fat content as measured by magnetic resonance spectroscopy was significantly lower in the control and enteral lipid groups when compared with mice receiving PN alone or with IV lipid. Mice receiving enteral lipid had significantly lower levels of serum aspartate aminotransferase and alanine aminotransferase compared with animals receiving PN alone. These data provide preliminary evidence that lipid administered through the enteral route protects against PN-associated hepatic injury in an animal model.


Hydroxyester disaccharides from fruits of cape gooseberry (Physalis peruviana).
The 3-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside of ethyl 3-hydroxyoctanoate and the diastereomeric 3-O-alpha-L-arabinopyranosyl-(1-->6)-beta-D-glucopyranosides of (3R) and (3S)-butyl 3-hydroxybutanoate, respectively, were isolated by chromatographic methods from fruits of cape gooseberry (Physalis peruviana) harvested in Colombia. Their structures were identified by ESI-MS/MS and NMR spectroscopy. The three glycoconjugates can be considered as immediate precursors of ethyl 3-hydroxyoctanoate and butyl 3-hydroxybutanoate, which are important aroma volatiles found in the fruit.


Depletion of Myofibril-Associated Proteins Using Selective Protein Extraction as a Tool in Cardiac Proteomics.
Muscle tissue poses a particular challenge to proteomic analysis due to a very wide range of protein abundances arising from the dominant expression of myofilament-related proteins. We address this issue by describing proteomic analysis with liquid chromatography-mass spectrometry (LC-MS) and sequential window acquisition of all theoretical mass spectra (SWATH), of guinea pig cardiac tissue prepared in two homogenization buffers: (1) An SDS-based buffer designed to extract "all" tissue proteins and (2) a long-established EDTA-containing buffer thought to preferentially extract non-myofibril-related proteins. We use gene ontology (GO) annotation-based assessment of subcellular localization to indicate if these enriched proteins congregate in the cytoplasm or in organellar lumens. This technique results in the preferential quantitation of less abundant non-myofibrillar proteins and, for future studies, offers the opportunity for more complete analyses of changes in heart tissue protein expression with biological circumstance.


Fractionation and analysis of mitochondria with polycarbonate membrane filters.
Polycarbonate membrane filters were used to fractionate mitochondrial populations depending on their aggregation or association with other subcellular structures. Isolated rat liver mitochondria penetrated through filters which have pore sizes larger than 1 micron. In contrast, mitochondria which were induced to aggregate in vitro by incubation at low pH were retained by the filters and thus could be separated from the single or small aggregates of mitochondria. Use of this membrane filtration method to analyze release of mitochondria from isolated hepatocytes showed that treatment with digitonin at concentrations only sufficient to lyse the plasma membrane did not release mitochondria. Homogenization or sonication following digitonin treatment released 25-50% of the mitochondria, but only a small fraction was intact. A high yield of intact mitochondria was released from digitonin-treated cells by a brief treatment with a low concentration of the proteolytic enzyme nagarse. Thus, this membrane filtration method provides a simple and rapid approach to analyze the extent of mitochondrial aggregation and association with other subcellular structures.


Cutaneous reactive B-cell lymphoid proliferations.
Cutaneous lymphoid hyperplasia (CLH), also known as cutaneous pseudolymphoma, is a spectrum of benign conditions characterized by reactive B- and T-cell cutaneous lymphocytic infiltrates. B-cell lymphoid proliferations are a heterogenous group of non-neoplastic cutaneous diseases that must be histopathologically distinguished from cutaneous B-cell lymphomas. These proliferations can be observed as reactive phenomena to infections, medications, allergens, neoplasms, and more. Furthermore, there are many inflammatory conditions that present with reactive B-cell infiltrates, including actinic prurigo, Zoon balanitis, Rosai-Dorfman disease, and cutaneous plasmacytosis. This review summarizes multiple cutaneous B-cell lymphoid proliferations within the major categories of reactive and disease-associated CLH. Further we discuss major discriminating features of atypical CLH and malignancy. Understanding the specific patterns of B-cell CLH is essential for the proper diagnosis and treatment of patients presenting with such lesions.


The use of RD cells in the isolation of Echo type 30 virus from patients with aseptic meningitis.
Between early July and August 1976, 60 cases of aseptic meningitis and pharyngitis in children from various parts of West Germany were reported to this institute. Successful virus isolation from spinal fluid in 12 out of 36 cases was greatly facilitated by the use of RD cell tissue cultures, whereas isolation attempts in HEL, Vero, and HFDK cells were unsuccessful. In all cases, the isolated virus was identified as ECHO type 30. Neutralization studies with sera of 48 remaining cases also using RD cells clearly indicated that the epidemic outbreak was caused by ECHO type 30 virus.


Neurologic syndromes in hyperammonemic disorders.
This article reviews the neurologic manifestations of hyperammonemic disorders. A variety of inborn errors of metabolism, as well as transient neonatal or acquired hepatic dysfunctions, are identified as causes of hyperammonemia. The pathogenesis of hyperammonemia in these disorders is outlined. Catastrophic hyperammonemia and hyperammonemic coma are described; algorithms to establish specific diagnosis are suggested. Symptoms of less severe ammonia intoxication, which also occur in more common diseases, are described. The need to consider hyperammonemia as a potential etiology for these symptoms is emphasized. Finally, the neurotoxicity of ammonia is discussed.


Comparison of sugammadex and neostigmine-atropine on intraocular pressure and postoperative effects.
During surgery, changes in intraocular pressure (IOP) can be observed resulting from several factors, such as airway manipulations and drugs used. We aimed to investigate the effects of sugammadex and neostigmine on IOP, hemodynamic parameters, and complications after extubation. Our study comprised 60 patients, aged 18-65 years, with a risk status of the American Society of Anesthesiologists I-II who underwent arthroscopic surgery under general anesthesia. The patients were randomly assigned into two groups. At the end of the surgery, the neuromuscular block was reversed using neostigmine (50 μg/kg) plus atropine (15 μg/kg) in Group 1, and sugammadex (4 mg/kg) in Group 2. Neuromuscular blockade was monitored using acceleromyography and a train-of-four mode of stimulation. IOP was measured before induction and at 30 seconds, 2 minutes, and 10 minutes after extubation. A Tono-Pen XL applanation tonometer was used to measure IOP. This showed that elevation in IOP of patients reversed using sugammadex was similar to that recorded in patients reversed using neostigmine-atropine. When heart rate was compared, there was a significant difference between basal values and those obtained at 30 seconds and 10 minutes after extubation in the neostigmine-atropine group. Extubation time (time from withdrawal of anesthetic gas to extubation) was significantly shorter in the sugammadex group (p = 0.003) than in the neostigmine-atropine group. The postextubation IOP values of the sugammadex group were similar to the neostigmine-atropine group. Extubation time (time from withdrawal of anesthetic gas to extubation) was significantly shorter in the sugammadex group (p = 0.003) than in the neostigmine-atropine group.


Comparison of the activity of polyanions and polycations on the classical and alternative pathways of complement.
Polyanions and polycations inhibit activity of the alternative and classical pathways of complement. We compared polyanions (commercial porcine heparin, chondroitin sulfate A, chondroitin sulfate B (dermatan sulfate), chondroitin sulfate C and heparatin sulfate) with polycations (salmon sperm protamine sulfate, poly-L-lysine, poly-L-arginine, polybrene and a synthetically prepared portion of platelet factor 4) for ability to inhibit alternative and classical pathway activity. The polyanions had considerably more activity on the alternative than on the classical pathway, whereas the polycations more profoundly inhibited classical than alternative pathway activity. For example, heparin, a polyanion, at 1.0 micrograms (7.7 x 10(-7) M based upon an Mr average of 13000)/10(7) cellular intermediates, inhibited alternative pathway activity and classical pathway activity by 77 and 14%, respectively, whereas protamine sulfate, a polycation, at 0.25 micrograms/10(7) cellular intermediates, inhibited these two pathways by 34 and 98%, respectively. These studies suggest that the capacity to inhibit complement activity is a common feature of highly charged substances and the polyanions preferentially inhibit the alternative pathway while polycations preferentially inhibit the classical pathway. In vivo these highly charged substances could play an important role in the tissues in regulating the activity of both pathways of complement.


Family morbidity in chronic pain patients.
Family morbidity in chronic pain patients could indicate genetic vulnerability to depressive spectrum disorders or presence of pain behaviour models. Assessment of family morbidity is an area of chronic pain research which has been neglected. In the present study, the frequency and nature of the family psychiatric morbidity of 203 consecutive chronic pain patients has been assessed and compared with that of 140 non-pain psychiatric patients. 30% of chronic pain patients and 33.6% of non-pain psychiatric patients had family psychiatric morbidity. The commonest illness in families of pain patients were found to be alcoholism, psychosomatic disorders and chronic pain. Schizophrenia and affective disorders were reported significantly more often in families of non-pain patients. 53% of psychogenic pain disorder patients had a positive family morbidity. Alcoholism among male relatives, and chronic pain and hypertension more often among female relatives, was another significant observation. No significant difference was found between chronic pain patients with and without family morbidity with regard to socio-demographic variables and clinical diagnosis.


PRISMA-7: a case-finding tool to identify older adults with moderate to severe disabilities.
Many comprehensive rating scales have been developed to assess disabilities. These assessments, which require significant amounts of time, are usually performed by trained professionals. A simple case-finding instrument is needed to quickly identify older persons with potential disabilities, who then should undergo comprehensive assessments. In a cross-sectional study of 594 community-dwelling older subjects, we developed a questionnaire from an initial list of 23 yes/no questions, and compared it with an existing one to determine their relative ability to identify older persons with moderate to severe disabilities. Initially designed to identify older people with any disability, the existing seven-question tool also provided to be a good marker of significant disabilities, with a cut-off score of three or more positive answers. The sensitivity and specificity of this cut-off are 78.3% and 74.7%, respectively. These validity indices support the use of this questionnaire in identifying older persons with potential moderate to severe disabilities with a view to referring them for more comprehensive assessment.


Can faces affect object-based attention? Evidence from online experiments.
This study tested how human faces affect object-based attention (OBA) through two online experiments in a modified double-rectangle paradigm. The results of Experiment 1 revealed that faces did not elicit the OBA effect as non-face objects, which was caused by a longer response time (RT) when attention is focused on faces relative to non-face objects. In addition, by observing faster RTs when attention was engaged horizontally rather than vertically, we found a significant horizontal attention bias, which might override the OBA effect if vertical rectangles were the only items presented; these results were replicated in Experiment 2 (using only vertical rectangles) after directly measuring horizontal bias and excluding its influence on the OBA effect. This study suggested that faces cannot elicit the same-object advantage in the double-rectangle paradigm and provided a method to measure the OBA effect free from horizontal bias.


Indirect measurement of pinch and pull forces at the shaft of laparoscopic graspers.
The grasping instruments used in minimally invasive surgery reduce the ability of the surgeon to feel the forces applied on the tissue, thereby complicating the handling of the tissue and increasing the risk of tissue damage. Force sensors implemented in the forceps of the instruments enable accurate measurements of applied forces, but also complicate the design of the instrument. Alternatively, indirect estimations of tissue interaction forces from measurements of the forces applied on the handle are prone to errors due to friction in the linkages. Further, the force transmission from handle to forceps exhibits large nonlinearities, so that extensive calibration procedures are needed. The kinematic analysis of the grasping mechanism and experimental results presented in this paper show that an intermediate solution, force measurements at the shaft and rod of the grasper, enables accurate measurements of the pinch and pull forces on tissue with only a limited number of calibration measurements. We further show that the force propagation from the shaft and rod to the forceps can be approximated by a linear two-dimensional function of the opening angle of the grasper and the force on the rod.


Developmental trajectories of eye movements in oral and silent reading for beginning readers: a longitudinal investigation.
Eye movements provide a sensitive window into cognitive processing during reading. In the present study, we investigated beginning readers' longitudinal changes in temporal and spatial measures of eye movements during oral versus silent reading, the extent to which variation in eye movements is attributable to individual differences and text differences, and the functional form of growth trajectories of eye-movement variables. Data were from 363 English-speaking children (52% male; 59.8% White) in the US who were followed longitudinally from Grade 1 to Grade 3. Results showed a rapid decrease in temporal eye-movement measures (e.g., first fixation) and an increase in spatial eye-movement measures (initial landing position) in both oral and silent reading. The majority of variance in eye movements was attributable to individual differences whereas some variance in initial landing position was due to text differences. Most eye-movement measures had nonlinear growth trajectories where fast development tapered off near the end of Grade 3 while initial fixation count and total gaze count in silent reading had a linear growth trajectory. The findings provide a first large-scale look into the developmental progression of eye movements during oral and silent reading during a critical period when reading skills rapidly develop.