The longitudinal effects of a physical activity programme on the physical fitness and disability of back pain patients: Service evaluation.
To evaluate the longitudinal effect of a group physical activity service to help patients self-manage un-resolving back pain. Back pain is one of the most common and costly conditions. Large scale trials have demonstrated a role for less traditional treatment including exercise, yet the long term effects of patient centred, group physical activity programmes remains unclear. One hundred and eighty-one un-resolving back pain patients (aged 53 ± 17 years) completed a 6 × 2 h physical activity programme. All activities were relevant to activities of daily living and incorporated activities to develop aerobic fitness, flexibility, core activation, and muscular strength and endurance. Dietary advice, home diaries and pedometers were provided. Measures of back pain, aerobic fitness, muscular endurance and body composition showed significant (p< 0.05) pre-post intervention improvements. Disability rating decreased by 19% alongside improvements in aerobic fitness (15%), back extension (36%) back flexion (16%) and grip strength (5%). Six month follow up identified (p< 0.05) reductions in body fat (6.5%) whilst aerobic fitness, disability rating and muscular strength and endurance remained stable. Group physical activity programmes could contribute to the self-management of back pain, enabling sustained improvements in fitness, physical activity and body fatness.


Comparative insecticidal power of three pyrethroids on netting.
Adult mosquitoes, Anopheles gambiae Giles and Culex quinquefasciatus Say (Diptera: Culicidae), were exposed for 3 min to replicate samples of polyester netting cut from replicate bednets treated with pyrethroid insecticide formulations at the recommended concentration (alphacypermethrin SC at 40mg ai/m2; cyfluthrin EW at 50 mg ai/m2; deltamethrin WT at 25 mg ai/m2), or treated with only a quarter of those dosages. After 4 months domestic use of the bednets in Malawi, chemical assays showed that pyrethroid deposits on the netting were somewhat less than the target concentrations. Comparing the pyrethroid bioassay results with Anopheles at both treatment concentrations, deltamethrin gave significantly higher mortality (99.7-100%) than the other compounds (alphacypermethrin 94-96%, cyfluthrin 80-89%). Culex bioassay mortality was lower (alphacypermethrin 56-74%; cyfluthrin 63-65%; deltamethrin 50-81 %) and results with the three pyrethroid insecticides at their recommended doses did not differ significantly.


Normal kinematics of the unconstrained glenohumeral joint under coupled moment loads.
The glenohumeral joint presents difficult experimental challenges, large ranges of motion, coupled motions, and multi-planar motions. Many biomechanical tests performed on the glenohumeral joint constrain it or provide conditions that might not be reproducible within and among specimens or treatments. The goal of this study was to determine a means to test the glenohumeral joint in vitro with coupled moments applied to the unconstrained humerus and recording its "6 degrees of freedom" motion relative to the glenoid. This procedure was achieved with the development of a new testing apparatus. Kinematics were described in abduction-adduction, flexion-extension, and abduction, extension, and external rotation, simulating the cocked phase of throwing. The advantage of the techniques was that only the glenohumeral capsule and articular surface contact control the motion of the humerus in response to the applied loading pattern. Also, the motions were unconstrained by the loading apparatus, allowing coupling of rotations and translations and multiplanar motions. Rotations were found to be coupled with translations. For adduction-abduction and flexion-extension, the humeral head was found to translate first in 1 direction, opposite the direction of increasing rotation, at low moments. Then, with increasing moment and angle of rotation, translations changed direction and moved with the primary motion. This occurrence indicates the existence of a region of joint laxity or neutral zone. Rotations were found to be coupled during motion to the cocked position of throwing, as the humerus adducted with extension from full abduction and then adducted further and extends with external rotation. Changes in these motion patterns with pathologic conditions may provide useful information about the nature of shoulder dysfunction and provide insight into appropriate means of repair.


Determination of the internal pair production branching ratio of 90Y.
The National Institute of Standards and Technology (NIST) measured the internal pair production branching ratio of 90Y using two sources and four high purity germanium (HPGe) detectors to detect the resulting annihilation radiation. The internal pair production branching ratio determined from these measurements, (32.0 ± 1.5) × 10-6 (k = 1), agrees within 1 standard uncertainty with the recommended value of (32.6 ± 0.7) × 10-6 (k = 1) from the DDEP database.


Monoclonal anti-idiotypic antibodies that recognize the binding site for nicotine on rat brain receptor.
Anti-idiotypic monoclonal antibodies have been prepared that represent the internal image of nicotine and are specific for the nicotine binding site on rat brain receptor. Specificity of these antibodies for the combining site on anti-nicotine was demonstrated by their ability to inhibit binding of monoclonal anti-nicotine to immobilized nicotine-polylysine. Furthermore, purified rat brain nicotine receptor but not acetylcholine receptor from fish electric organ effectively competed with anti-nicotine for immobilized nicotine and for immobilized anti-idiotype. Only 9 pmoles of naturally occurring (-)-nicotine inhibited idiotype-anti-idiotype binding by 50% whereas 11 times more (+)-nicotine was required. Acetylcholine, several cholinergic agonists and antagonists, nicotine metabolites, and other structurally related compounds were poor inhibitors.


Leishmania donovani promastigotes induce periphagosomal F-actin accumulation through retention of the GTPase Cdc42.
Leishmania donovani promastigotes inhibit phagosome maturation and induce the accumulation of periphagosomal F-actin during the establishment of infection within macrophages. These events are mediated by the surface glycolipid lipophosphoglycan (LPG), but the underlying mechanisms remain to be elucidated. In this study, we addressed the role of the Rho-family GTPases RhoA, Rac1 and Cdc42 in the uptake of L. donovani promastigotes and in the accumulation of periphagosomal F-actin. Confocal microscopy analyses revealed that association of both Rac1 and RhoA to phagosomes containing L. donovani promastigotes was independent of the presence of LPG. In contrast, Cdc42 and proteins required for F-actin assembly (Arp2/3, WASP, Myosin, alpha-actinin) were retained on phagosomes in a LPG-dependent manner. Expression of the RhoA inhibitor C3-transferase blocked the internalization of complement-opsonized promastigotes, whereas the dominant-negative Rac1N17 blocked the uptake of unopsonized promastigotes. The dominant-negative Cdc42N17 inhibited LPG-mediated phagosomal accumulation of F-actin and retention of Arp2/3 and Myosin. Thus, our data suggest that the effect of LPG on the accumulation of periphagosomal F-actin is the consequence of an abnormal retention or activation of Cdc42 at the phagosome.


Pertussis toxin catalyzed ADP-ribosylation of a 41 kDa G-protein impairs insulin-stimulated glucose metabolism in BC3H-1 myocytes.
In this study, we examined the effects of pertussis toxin (PT) on the ADP-ribosylation of guanine nucleotide binding proteins (G-proteins) and various insulin-stimulated processes in cultured BC3H-1 myocytes. Treatment of intact myocytes with 0.1 microgram/ml PT for 24 hours resulted in the complete ribosylation of a 41 kDa protein. The 41 kDa PT substrate was immunoprecipitated with antibodies directed against a synthetic peptide corresponding to a unique sequence in the alpha subunit of Gi-proteins. PT treatment of intact cells had no effect on insulin receptor binding or internalization. However, PT inhibited insulin-stimulated glucose transport at all insulin-concentrations tested (1-100 ng/ml). Maximally stimulated glucose transport was reduced by 50% +/- 15%. Insulin-stimulated glucose oxidation was also decreased by 31% +/- 8%. The toxin had no significant effect on the basal rates of glucose transport and glucose oxidation. The time course of PT-induced inhibition on glucose transport correlated with the time course of the "in vivo" ADP-ribosylation of the 41 kDa protein. The results suggest that a 41 kDa PT-sensitive G-protein, identical or very similar to Gi, is involved in the regulation of glucose metabolism by insulin in BC3H-1 cells.


Association of hsp70-2 (+1267A/G), hsp70-hom (+2437T/C), HMOX-1 (number of GT repeats) and TNF-alpha (+489G/A) polymorphisms with COPD in Croatian population.
To test for possible association of hsp70-2 (+1267A/G), hsp70-hom (+2437T/C), HMOX-1 (number of GT repeats) and TNF-α (+489G/A) polymorphisms with chronic obstructive pulmonary disease (COPD) in Croatian population. Genotyping of DNA isolated from whole blood of 130 COPD patients (as defined by spirometry) and 95 healthy controls was performed. Fragment size analysis upon restriction enzyme digestion and/or sequencing was used for genotype/allele definition. Significance of findings was tested using χ(2) test. hsp70-2 (+1267A/G) polymorphism was significantly associated with COPD. Results of genotyping analysis indicated that a genotype carrying G allele was preferentially associated with COPD; odds ratio (OR)=1.50, 95% confidence interval (CI)=1.00-2.24 and P=0.061. OR for the GG genotype was 3.47 with CI=1.26-9.56 and P=0.04. No association for hsp70-hom (+2437T/C), TNF-α (+489G/A) and HMOX-1 (number of GT repeats) polymorphisms were found. In addition, comparison of genotype frequencies among different stages of disease severity (GOLD II-IV) revealed no discrimination for any of the tested polymorphisms. This study is supporting the association of hsp70-2 (+1267A/G) polymorphism and COPD. Higher frequency of G allele and GG genotype in Croatian COPD patients was observed. There was no evidence for the association of hsp70-hom (+2437T/C), TNF-α (+489G/A) SNPs and HMOX-1 (number of GT repeats) polymorphism with COPD. Allele and genotype frequencies for all of the tested polymorphisms show no association with disease severity (GOLD II-IV).


[Mathematical methods of analysing the heart rhythm in assessing the function of the cardiovascular system in workers manufacturing kormolizin].
A mathematical analysis of the cardiac rhythm carried out in 89 workers of a biochemical plant allowed to evaluate the state of regulatory mechanisms of workers engaged in cormolysin production. The functional state proved to be tense in most young workers. This is suggested to be the result of inadequate reaction to loads and inadequate adaptation of the workers to the working conditions.


Moral judgment in retarded and nonretarded school age children.
The moral judgment of 135 normal, educable retarded, and trainable retarded boys and girls (ages 6-10, 11-13, and 14-16) was individually assessed to determine the significance of chronological age and IQ on moral development. The results indicated significant differences in mean normal judgment between the groups and each age level. The findings were interpreted as substantiating Piaget's stage theory of moral development and suggesting that within the retarded population, level of intellectual ability is also significantly related to moral judgment.


A heterogeneity-based genome search meta-analysis for autism-spectrum disorders.
Autism and autism-spectrum disorders exhibit high heritability, although specific susceptibility genes still remain largely elusive. We performed a heterogeneity-based genome search meta-analysis (HEGESMA) of nine genome scans on autism or autism-spectrum disorders. Each genome scan was separated in 30 cM bins and the maximum linkage statistic from each bin was ranked. Significance for each bin's average rank and for between-scan heterogeneity (dis-similarity in the average ranks) was obtained through Monte Carlo tests. For autism, data from 771 affected sibpairs were synthesized across six separate genome scans. Region 7q22-q32 reached genome-wide significance both in weighted and unweighted analyses, with evidence for significantly low between-scan heterogeneity. The flanking chromosomal region 7q32-qter reached the less stringent threshold of suggestive significance, with no evidence for low between-scan heterogeneity. For autism-spectrum disorders (634 affected sibpairs from five separate scans), no chromosomal region reached genome-wide significance. However, suggestive significance was reached for the chromosomal regions 17p11.2-q12 and 10p12-q11.1 in weighted analyses. There was evidence for significantly high between-scan heterogeneity for the former region. The meta-analysis suggests that the 7q22-q32 region should be further scrutinized for autism susceptibility genes, while autism-spectrum disorders seem to have quite diverse linkage signals across scans, possibly suggesting genetic heterogeneity across subsyndromes and subpopulations.


Toxic effects of the wastewater produced by underwater hull cleaning equipment on the copepod Tigriopus japonicus.
Unmanaged disposal of wastewater produced by underwater hull cleaning equipment (WHCE) is suspected to induce toxic effects to marine organisms because wastewater contains several anti-fouling compounds. To investigate the effects of WHCE on marine copepod, we examined the toxicity on life parameters (e.g. mortality, development, and fecundity) and gene expression changes of Tigriopus japonicus as model organism. Significant mortality and developmental time changes were observed in response to wastewater. No significant differences in fecundity were observed. Transcriptional profiling with differentially expressed genes from WHCE exposed T. japonicus showed WHCE may induce genotoxicity associated genes and pathways. In addition, potentially neurotoxic effects were evident following exposure to WHCE. The findings suggest that wastewater released during hull cleaning should be managed to reduce physiological and molecular deleterious effects in marine organisms.


Biological activity and magnetic resonance imaging of superparamagnetic iron oxide nanoparticles-labeled adipose-derived stem cells.
No comparative study of adipose-derived stem cells (ADSCs) and bone marrow mesenchymal stem cells (BMSCs) by using superparamagnetic iron oxide nanoparticles (SPIOs)-labeling and magnetic resonance imaging (MRI) has been performed. We studied the biological activity and MRI of ADSCs by labeling them with SPIOs and comparing them with BMSCs. After incubating the cells in culture medium with different levels of SPIOs (control group: 0 μg/ml; Groups 1 to 3: 25, 50, and 100 μg/ml) for 24 hours, we compared ADSCs with BMSCs in terms of intracellular iron content, labeling efficiency, and cell viability. Stem cells in the culture medium containing 50 μg/ml SPIOs were induced into osteoblasts and fat cells. Adipogenic and osteogenic differentiation potentials were compared. R2* values of MRI in vitro were compared. The results showed that labeling efficiency was highest in Group 2. Intracellular iron content and R2* values increased with increasing concentrations of SPIOs, whereas cell viability decreased with increasing concentrations of SPIOs, and adipogenic and osteogenic differentiation potentials decreased. However, we found no significant difference between the two kinds of cells for any of these indexes. ADSCs can be labeled and traced as easily as BMSCs in vitro. Given their abundance and higher proliferative capacity, as was previously shown, ADSCs may be better suited to stem cell therapy than are BMSCs.


Ultrasound evaluation of deeply infiltrative endometriosis: technique and interpretation.
Endometriosis is a common benign gynecological condition defined as the presence of endometrial tissue located outside the uterus and frequently associated with chronic pelvic pain and infertility. It is a polymorphic disease that can be presented as superficial implants, endometriomas and deep lesions that infiltrate the peritoneal surface associated with fibrosis and inflammatory reaction. Diagnosis of deep endometriosis is difficult and delayed, frequently missed in a routine ultrasound. Transvaginal ultrasound is the first-line imaging modality to investigate endometriosis and when performed by an expert in female pelvic imaging can provide a reliable mapping of the affected sites. Bowel preparation can be used to improve the detection of bowel lesions as well as the other sites affected by eliminating artifacts. Surgery has been the mainstay to treat symptomatic endometriosis and preoperative imaging mapping is crucial for better results and to reduce residual disease. The goals of surgery include radical removal of all lesions and the restoration of normal pelvic anatomy. The author describes technical aspects and imaging interpretation of the transvaginal sonography to investigate deeply infiltrative endometriosis.


Effect of molecular weight of starch on the properties of cassava starch microspheres prepared in aqueous two-phase system.
Starch microspheres (SMs) were fabricated in an aqueous two-phase system (ATPS). A series of starch samples with different molecular weight were prepared by acid hydrolysis, and the effect of molecular weight of starch on the fabrication of SMs were investigated. Scanning electron microscopy (SEM) showed that the morphologies of SMs varied with starch molecular weight, and spherical SMs with sharp contours were obtained while using starch samples with weight-average molecular weight (M¯w)≤1.057×105g/mol. X-ray diffraction (XRD) results revealed that crystalline structure of SMs were different from that of native cassava starch, and the relative crystallinity of SMs increased with the molecular weight of starch decreasing. Differential scanning calorimetry (DSC) results showed peak gelatinization temperature (Tp) and enthalpy of gelatinization (ΔH) of SMs increased with decreased M¯wof starch. Stability tests indicated that the SMs were stable under acid environment, but not stable under α-amylase hydrolysis.


An overlap of Brugada syndrome and arrhythmogenic right ventricular cardiomyopathy/dysplasia.
Overlapping characteristics of Brugada syndrome (BrS) and arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) have been reported in recent studies, but little is known about the overlapping disease state of BrS and ARVC/D. A 36-year-old man, hospitalized at our institution for syncope, presented with this overlapping disease state. The electrocardiogram showed spontaneous coved-type ST-segment elevation, and ventricular fibrillation was induced by right ventricular outflow tract stimulation in an electrophysiological study. BrS was subsequently diagnosed; additionally, the presence of epsilon-like waves and right ventricular structural abnormalities met with the 2010 revised task force criteria for ARVC/D. After careful investigation for both BrS and ARVC/D, an implantable cardioverter defibrillator was inserted in the patient. This case revealed 2 important clinical findings: (1) BrS and ARVC/D clinical features can coexist in a single patient, and EPS might be useful for determining the phenotype of overlapping disease (e.g., BrS-like or ARVC/D-like). (2) An overlapping disease state of BrS and ARVC/D can change phenotypically during its clinical course. Therefore, careful examination and attentive follow-up are required for patients with BrS or ARVC/D.


Mechanobiologic influences in long bone cross-sectional growth.
We developed a computer model to simulate the interaction of biological and mechanobiological factors in the development of the cross-sectional morphology of long bones. The model incorporated a strong influence of biologically induced bone formation during early development. In addition, an assumed mechanical loading history during growth and development corresponding to age-related changes in body weight and muscle mass was applied. Based on the bone stress stimulus generated by the assumed loads, mechanically induced apposition and resorption rates were calculated at the periosteal and endosteal surfaces using a previously developed bone modeling theory. These methods successfully emulated the growth-related changes seen in long bone diaphyseal structure as well as changes observed in mature bones during aging. The simulations recreated the rapid increase in bone dimensions during development, stabilizing at maturity, and then the gradual, age-related subperiosteal expansion and cortical thinning. Throughout the growth, development, and aging simulations, the values of the bone radii, area, moments of inertia, and apposition rates corresponded well with measurements documented by other researchers.


[Anisocoria and nausea].
We present the case of a 40-year-old female patient with sudden onset of anisocoria and unilateral ptosis of the left eye. With the exception of several previous episodes of nausea and vomiting, mild headache and tiredness, combined with the early death of the patient's mother following aortic rupture, patient history and clinical condition showed no pathological findings. Following indicative findings on duplex sonography, a dissection of the left internal carotid artery from its origin to its distal section was detected on CT angiography of the brain vessels and the diagnosis of Horner syndrome due to internal carotid artery dissection was made. Since this condition is associated with serious embolic complications, prompt treatment following diagnosis is of utmost importance. Our patient was treated conservatively using PTT (partial thromboplastin time)-effective heparinisation. Regular checks including kidney ultrasound, blood pressure measurement, imaging and continuous therapy with acetylsalicylic acid are recommended.


Association between antibiotic resistance and increasing ambient temperature in China: An ecological study with nationwide panel data.
Antibiotic resistance leads to longer hospital stays, higher medical costs, and increased mortality. However, research into the relationship between climate change and antibiotic resistance remains inconclusive. This study aims to address the gap in the literature by exploring the association of antibiotic resistance with regional ambient temperature and its changes over time. Data were obtained from the China Antimicrobial Surveillance Network (CHINET), monitoring the prevalence of carbapenem-resistant Acinetobacter baumannii (CRAB), Klebsiella pneumoniae (CRKP) and Pseudomonas aeruginosa (CRPA) in 28 provinces/regions over the period from 2005 to 2019. Log-linear regression models were established to determine the association between ambient temperature and antibiotic resistance after adjustment for variations in socioeconomic, health service, and environmental factors. A 1 °C increase in average ambient temperature was associated with 1.14-fold increase (95%-CI [1.07-1.23]) in CRKP prevalence and 1.06-fold increase (95%-CI [1.03-1.08]) in CRPA prevalence. There was an accumulative effect of year-by-year changes in ambient temperature, with the four-year sum showing the greatest effect on antibiotic resistance. Higher prevalence of antibiotic resistance was also associated with higher antibiotic consumption, lower density of health facilities, higher density of hospital beds and higher level of corruption. Higher prevalence of antibiotic resistance is associated with increased regional ambient temperature. The development of antibiotic resistance under rising ambient temperature differs across various strains of bacteria. The National Key R&D Program of China (grant number: 2018YFA0606200), National Natural Science Foundation of China (grant number: 72074234), Fundamental Scientific Research Funds for Central Universities, P.R. China (grant number: 22qntd4201), China Medical Board (grant number: CMB-OC-19-337).


The effects of repeated idea elaboration on unconscious plagiarism.
Unconscious plagiarism occurs in a recall task when someone presents someone else's idea as his or her own. Recent research has shown that the likelihood of such an error is inflated if the idea is improved during the retention interval, but not if it is imagined. Here, we explore the effects of repeating the elaboration phase during the retention interval. Participants in a group first generated alternate uses to common objects before elaborating the ideas either by imagining them or by improving them. This elaboration phase occurred once, twice, or not at all. Later, they attempted to recall their original ideas and generate new ideas. Repeated imagery did not inflate unconscious plagiarism on either task. In contrast, repeating the improvement phase increased plagiarism to dramatically high levels in the recall task. The latter effect might be particularly pertinent to real-world cases of plagiarism in which the ideas under dispute have been the subject of creative development over many occasions.


CDC42 regulates PYRIN inflammasome assembly.
The PYRIN inflammasome pathway is part of the innate immune response against invading pathogens. Unprovoked continuous activation of the PYRIN inflammasome drives autoinflammation and underlies several autoinflammatory diseases, including familial Mediterranean fever (FMF) syndrome. PYRIN inflammasome formation requires PYRIN dephosphorylation and oligomerization by molecular mechanisms that are poorly understood. Here, we use a functional genetics approach to find regulators of PYRIN inflammasome function. We identify the small Rho GTPase CDC42 to be essential for PYRIN activity and oligomerization of the inflammasome complex. While CDC42 catalytic activity enhances PYRIN phosphorylation, thereby inhibiting it, the inflammasome-supportive role of CDC42 is independent of its GDP/GTP binding or hydrolysis capacity and does not affect PYRIN dephosphorylation. These findings identify the dual role of CDC42 as a regulator of PYRIN and as a critical player required for PYRIN inflammasome assembly in health and disease.


Differential costs of sexual and vegetative reproduction in wild strawberry populations.
The CO2 costs of producing sexual and vegetative reproductive propagules were calculated for two species of wild strawberry, Fragaria virginiana and F. vesca. Five populations on sites representing a gradient of successional regrowth near Ithaca, New York, USA, were studied for two or three years each. Field studies of phenology, biomass, demography, and environment and laboratory studies of CO2 exchange were integrated using a computerbased model of CO2 dynamics to estimate costs of propagules.The percentage of plants flowering and the number of flower buds produced were highest in an open, recently disturbed habitat and lowest in a forest habitat. The openhabitat plants had the greatest success in converting flower buds into ripe fruits and also produced the highest numbers of runners and runner plantlets. On the basis of total investments in structure and respiration minus any photosynthetic gain of all reproductive structures, the cost per seed was lowest in the most open habitats and highest and increasingly variable in the more closed habitats. The cost of plantlets also was lowest in the most open habitat. The differences among habitats in cost of plantlets alive after one or two growing seasons increased due to differential survivorship of plantlets, with the open habitat continuing to have the lowest cost per plantlet. Theoretical treatments of life history characteristics such as reproductive effort should recognize that costs of equivalent type and size of propagule may vary among environments.


Survival in Alzheimer's disease is shorter in women carrying heterozygosity at codon 129 of the PRNP gene and no APOE epsilon 4 allele.
We assessed the role of the APOE genotype and prion protein polymorphism at codon 129 in predicting the clinical duration of 92 neuropathologically confirmed sporadic Alzheimer's disease patients. Analyses of survival showed that the absence of the APOE epsilon 4 allele in heterozygous codon 129 PRNP carriers is a negative predictor of survival. When this subgroup of patients was stratified by sex, the effect of APOE was observed in women, but not in men.


Myositis ossificans traumatica (circumscripta) and return to sport: A retrospective series of 19 cases.
Myositis ossificans is a worrisome complication of muscle lesions in sports medicine. Our goal is to specify clinical, paraclinical and therapeutic elements to guide a myositis ossificans traumatica patient back into sport. All patients having consulted between January 2006 and December 2012 presenting myositis ossificans with a recent muscle injury from playing sports were included. We excluded patients with myositis ossificans without an identified trauma, or from an old injury (>6 months). Ultrasound images were captured on a Philips(®) Sparq ultrasound machine with a linear probe (4-12MHz). The diagnosis of myositis ossificans was performed on 2 ultrasound criteria in context of recent muscle trauma: presence of ossification or calcification within a muscle on axial and longitudinal sections using B-mode and hyperactivity in power Doppler mode around the ossification/calcification. Clinical signs and treatment were collected systematically at inclusion, 6 months and 1 year. Among the 22 myositis ossificans cases diagnosed between January 2006 and December 2012, 19 were of traumatic origin, on a recent muscle lesion and were included in the study. Our patients resumed light physical activities 3 months after diagnosis for 89.5% of them (100% at 10 months) and returned to their earlier level 6 months after myositis ossificans diagnosis for also 89.5% of them (all patients having resumed sport at their earlier levels 12 months after diagnosis). Therapeutic abstention and persistence of ossification do not seem to be detrimental factors for resuming a sport at the earlier level with ultrasound monitoring.


[Vaccinations Before and During Pregnancy].
Vaccinations before and during pregnancy are of great significance-through a consistent vaccination strategy, infections can be totally prevented or the course of a disease can be attenuated and risks for mother and child avoided. The recommendations for immunizations before pregnancy are adapted to the general vaccination recommendations. Two vaccinations are explicitly recommended during pregnancy. On the one hand this is immunization against seasonal influenza, which protects the pregnant woman against infection as she has a higher risk for a serious course of disease and for complications. On the other hand vaccination against pertussis is recommended, which provides protection for the newborn in the first months of life. During breastfeeding, insufficient vaccination status should be completed according to the general recommendations.


Impact of plasma and intracellular exposure and CYP3A4, CYP3A5, and ABCB1 genetic polymorphisms on vincristine-induced neurotoxicity.
The aim of this study was to investigate the impact of plasma and intracellular exposure and CYP3A4, CYP3A5, and ABCB1 polymorphisms on vincristine neurotoxicity. We subsequently assessed the impact of ABCB1 polymorphisms on intracellular vincristine accumulation. Children treated for solid tumors were enrolled in the study (n = 26) and received 1.5 mg/m² of vincristine per course. Individual pharmacokinetic parameters and CYP3A4, CYP3A5, and ABCB1 genotypes were available from a previous analysis. A global toxicity score (pain, peripheral neurotoxicity, and gastrointestinal toxicity) was collected at each course. Vincristine in plasma and PBMCs were quantified by LC-MS/MS. Vincristine plasma and intracellular concentrations ranged from 0.40 to 89.6 ng/ml and from 0.00225 to 1.85 ng/10(6) cells over a 24-h interval, respectively. The global toxicity score ranged from 0 to 6 and was not correlated with individual pharmacokinetics parameters. Neurotoxicity events (global score ≥ 3) were observed in 8 patients but the incidence was not influenced by the different studied polymorphisms. The global toxicity score was correlated with age, body surface area, and dose in mg. A trend to higher intracellular/plasma ratio of vincristine was found for patients with heterozygous diplotype (CGC-TTT) of ABCB1. None of the different genetic covariates nor plasma and intracellular exposure was predictive of the observed neurotoxicity in our pediatric population. Nevertheless, the heterozygote diplotype of ABCB1 appears to influence the intracellular accumulation of vincristine. Owing to the small sample size, further evaluations are needed in a larger patient cohort.


Intensive chemotherapy improved treatment outcome for Chinese children and adolescents with lymphoblastic lymphoma.
Lymphoblastic lymphoma (LBL) is a highly aggressive lymphoma, for which intensive chemotherapy is necessary. This study was designed to evaluate the efficacy and toxicity of a modified acute lymphoblastic leukemia (ALL)-Berlin-Frankfurt-Münster (BFM)-90-based protocol in Chinese children and adolescents with LBL. From March 1998 to November 2006, 60 untreated patients with LBL (age <18 years) from a single institution were enrolled. All patients were treated with the modified ALL-BFM-90 protocol, and prophylactic cranial radiotherapy was omitted. The median age of the patients was 10 years (range, 2.5-18 years). Forty-eight (80%) patients had T-cell LBL, and 59 (98.3%) of the patients were stage III/IV. At the end of induction remission Ia (day 33), 3 patients had died of treatment-related toxicity. In the remaining 57 patients, complete remission (CR) or CR undetermined (CRu) had occurred in 47 (82.45%), who were designated as the moderate-risk group and partial remission (PR) had occurred in 10 patients (17.54%), who were designated the high-risk group. All patients experienced grade 3-4 hematological toxicity. At a median follow-up of 35 months, event-free survival was 78.81%+/-0.05 for all patients; the figure was 88.34%+/-0.05 for the moderate-risk group (90.91%+/-0.08 for stage III, 87.68%+/-0.06 for stage IV, 100% for those with B-cell LBL, 84.78%+/-0.06 for those with T-cell LBL, and 82.94%+/-0.08 for stage IV patients with more than 25% blast cells in bone marrow [BM]). The event-free survival in the high-risk group was 60%+/-0.15. This modified ALL-BFM-90 protocol is an effective regimen and it greatly improved the survival rate of Chinese children and adolescents with LBL compared with the ALL protocols used previously.


Validation of beat by beat fetal heart signals acquired from four-channel fetal phonocardiogram with fetal electrocardiogram in healthy late pregnancy.
Fetal heart rate monitoring is an essential obstetric procedure, however, false-positive results cause unnecessary obstetric interventions and healthcare cost. In this study, we propose a low cost and non-invasive fetal phonocardiography based signal system to measure the fetal heart sounds and fetal heart rate. Phonocardiogram (PCG) signals contain acoustic information reflecting the contraction and relaxation of the heart. We have developed a four-channel recording device with four separated piezoelectric sensors harnessed by a cloth sheet to record abdominal phonogram signals. A multi-lag covariance matrix based eigenvalue decomposition technique was used to extract fetal and maternal heart sounds as well as maternal breathing movement. In order to validate the fetal heart sounds extracted by PCG signal processing, 10 minutes' simultaneous recordings of fetal Electrocardiogram (fECG) and abdominal phonogram from 15 pregnant women (27 ± 5-year-old) with fetal gestation ages between 33 and 40 weeks were obtained and processed. Highly significant (p < 0.01) correlation (r = 0.96; N = 270) was found between beat to beat fetal heart rate (FHRECG) from fECG and the same (FHRPCG) from fetal PCG signals. Bland-Altman plot of FHRECG and FHRPCG shows good agreement (<5% difference). We conclude that the proposed beat to beat fetal heart rate measurement system would be useful for monitoring fetal neurological wellbeing as a better alternative to traditional cardiotocogram based antenatal fetal heart rate monitoring.


Do Carolina chickadees (Poecile carolinensis) and tufted titmice (Baeolophus bicolor) use predator eyes in risk assessment?
Previous studies have found that Carolina chickadees and tufted titmice use a predator's head orientation to determine risk, taking fewer seeds from a feeder if an avian predator model's head is facing the feeder while ignoring the head orientation. In addition to head orientation, eyes are a cue of predator risk. In the current study, I examined whether or not chickadees and titmice used the presence of eyes of a predator model to determine when to forage for food. Plastic owl models, with their eyes covered or uncovered, were presented to wild flocks of chickadees and titmice. To test whether or not chickadees and titmice would respond to the presence of eyes, the number of seeds taken and the calling behavior of birds were compared between the two types of predator presentations (eyes covered or uncovered). Chickadees and titmice took fewer seeds when the eyes were uncovered than when they were covered. Chickadees also gave significantly more introductory notes, often used in association with the presence of predators or risk, in their calls when the eyes were visible than when the eyes of the predator model were covered. The results indicate that chickadees and titmice can use the presence of eyes on predators to determine predation risk and possibly use eye gaze to determine where a predator is looking.


The Impact of Depression in Patients Undergoing Emergency Abdominal Surgery: An Exploratory Study.
Depression is associated with poorer outcomes in many disease states. However, its significance in abdominal surgery is unknown. This study investigated rates of depression in emergency abdominal surgery patients and its effects on outcomes. A retrospective cohort study was conducted across two UK sites and included all adult patients undergoing emergency abdominal surgery. Primary outcome was the complication rate in depressed patients, including the incidence of post-operative delirium. Secondary outcomes included mortality, time to oral intake and analgesia. Two hundred and ten patients were identified. The commonest indication for surgery was appendicitis (53.3%) followed by small bowel obstruction (9.5%). There was a 17% (n = 36) incidence of depression amongst patients, most of whom (n = 26, 72.2%) were taking antidepressants. Depression was associated with male sex (M:F 27:9 p = 0.003), higher median BMI (28 vs. 25 p = 0.013) and previous surgery (47.2% vs. 28.7% p = 0.032). Despite a higher incidence of post-operative delirium, increased time to oral analgesia and greater 30-day readmission rates in the depression cohort, multivariate analyses showed depression was not a significant independent predictor of these (OR 2.181, 95%CI 0.310-15.344; p = 0.433, OR 0.07, 95%CI 0.499-1.408; p = 0.348 and OR 1.367, 95%CI 0.102-18.34, respectively). Complication and mortality rates between depressed and non-depressed individuals were similar. Significant numbers of patients undergoing emergency abdominal surgery have depression, but this did not adversely affect post-operative outcomes. The study included relatively small numbers of participants undergoing procedures with straightforward recovery. Larger population studies are therefore required and should focus on investigating the association between major emergency surgeries with post-operative delirium and uncontrolled pain.


Evidence of two different molecular mechanisms as a consequence of an isolated 20q- abnormality in a case of multiple myeloma accompanied with myelodysplastic syndrome.
The deletion of the long arm of chromosome 20 is a characteristic cytogenetic marker of myeloid disorders. Rarely, it is also found in lymphoproliferative diseases, including multiple myeloma (MM). The role of 20q- in MM is not fully understood. In the cases of MM which co-exist with primary or therapy-related dysplasia, this anomaly is mostly linked to the occurrence of myeloid neoplasms. On the other hand 20q- is found as an isolated anomaly in cases with MM that have no dysplastic features or is not accompanied with other hematological diseases which suggests that the 20q deletion is also important for the development of MM. This report describes an isolated 20q- anomaly in a case of a light chain myeloma co-existing with myelodysplastic syndrome (MDS). Fluorescent in situ hybridization (FISH) experiments have demonstrated the presence in the patient's bone marrow of a basic clone (stemline) with deletion of the PTPRT gene (located at 20q13.11) and two sidelines: one with deletion of the PTPRT and MAPRE1 genes (located at 20q11.12) found in the mature granulocytes and one with deletion of PTPRT and duplication of MAPRE1 found in the myeloma cells. These data have indicated that 20q- has appeared in the multipotent precursor cells and affects both myeloid and lymphoid lineage by two different molecular mechanisms - one possibly related to the pathogenesis of the MDS and another to the pathogenesis of the MM.


Alanine scan reveals modifiable residues in teixobactin.
An alanine scan of Lys10-teixobactin reveals that a cationic residue at position 10 is not necessary for antibiotic activity and that position 3 tolerates substitution without loss of activity. An unexpected correlation between poor aqueous solubility and better antibiotic activity of the teixobactin analogues is observed.


Upregulation of torso-like protein (perforin) and granzymes B and G in non-adherent, lymphocyte-like haemocytes during a WSSV infection in shrimp.
Invertebrates only have an innate immunity in which haemocytes play an important role. In our lab, 5 subpopulations of haemocytes were identified in the past by an iodixanol density gradient: hyalinocytes, granulocytes, semi-granulocytes and two subpopulations of non-phagocytic cells. For the two latter subpopulations, the haemocytes have small cytoplasm rims, do not adhere to the bottom of plastic cell-culture grade wells and present folds in the nucleus. These characteristics are similar to those of mammalian lymphocytes. Therefore, they were designated lymphocyte-like haemocytes. Although little is known about their function, we hypothesize, based on their morphology, that they may have a cytotoxic activity. First, a fast isolation technique was developed to separate the non-adherent haemocytes from the adherent haemocytes. After 60 min incubation on cell culture plates, the non-adherent haemocytes were collected. The purity reached 93% as demonstrated by flow cytometry and light microscopy upon a Hematoxylin and Eosin (H&E) staining. Cytotoxicity by lymphocytes is mediated by molecules such as perforin and granzymes and therefore, we searched for their genes in the shrimp genome. Genes coding for a torso-like protein, granzyme B and granzyme G were identified. Primers were designed and RT-PCR/RT-qPCR assays were developed. The results demonstrated that torso-like protein, granzyme B and granzyme G were mainly expressed in non-adherent haemocytes. The shrimp torso-like protein gene was most related to that of the crab torso-like protein; granzyme B gene was most related to that of mouse granzyme B and granzyme G gene was most related to that of zebrafish granzyme G. In a 72-hour in vivo WSSV infection challenge, the mRNA expression of shrimp torso-like protein, granzyme B and granzyme G in haemocytes was increasing over time, which indicated that torso-like protein, granzyme B and granzyme G of shrimp haemocytes are involved in the immune response during a viral infection. In the future, antibodies will be raised against these proteins for more in-depth functional analyses.


Inferior Alveolar Nerve Lateralization and Transposition for Dental Implant Placement. Part II: a Systematic Review of Neurosensory Complications.
This article, the second in a two-part series, continues the discussion of inferior alveolar nerve lateralization/transposition for dental implant placement. The aim of this article is to review the scientific literature and clinical reports in order to analyse the neurosensory complications, risks and disadvantages of lateralization/transposition of the inferior alveolar nerve followed by implant placement in an edentulous atrophic posterior mandible. A comprehensive review of the current literature was conducted according to the PRISMA guidelines by accessing the NCBI PubMed and PMC databases, as well as academic sites and books. The articles were searched from January 1997 to July 2014. Articles in English language, which included adult patients between 18 - 80 years of age who had minimal residual bone above the mandibular canal and had undergone inferior alveolar nerve (IAN) repositioning, with minimum 6 months of follow-up, were included. A total of 21 studies were included in this review. Ten were related to IAN transposition, 7 to IAN lateralization and 4 to both transposition and lateralization. The IAN neurosensory disturbance function was present in most patients (99.47% [376/378]) for 1 to 6 months. In total, 0.53% (2/378) of procedures the disturbances were permanent. Inferior alveolar nerve repositioning is related to initial transient change in sensation in the majority of cases. The most popular causes of nerve damage are spatula-caused traction in the mucoperiosteal flap, pressure due to severe inflammation or retention of fluid around the nerve and subsequent development of transient ischemia, and mandibular body fracture.


The heat-stable cytosolic factor that promotes glucocorticoid receptor binding to DNA is neither thioredoxin nor ribonuclease.
Treatment of rat liver cytosol containing temperature-transformed [3H]dexamethasone-bound receptors at 0 degree C with the sulfhydryl modifying reagent methyl methanethiosulfonate (MMTS) inhibits the DNA-binding activity of the receptor, and DNA-binding activity is restored after addition of dithiothreitol (DTT). However, transformed receptors that are treated with MMTS and then separated from low Mr components of cytosol by passage through a column of Sephadex G-50 have very little DNA-binding activity when DTT is added to regenerate sulfhydryl moities. The receptors will bind to DNA if whole liver cytosol or boiled liver cytosol is added in addition to DTT. The effect of boiled cytosol is mimicked by purified rat thioredoxin or bovine RNase A in a manner that does not reflect the reducing activity of the former or the catalytic activity of the latter. This suggests that the reported ability of each of these heat-stable peptides to stimulate DNA binding by glucocorticoid receptors is not a biologically relevant action. We suggest that stimulation of DNA binding of partially purified receptors by boiled cytosol does not constitute a reconstitution of a complete cytosolic system in which the dissociated receptor must associate with a specific heat-stable accessory protein required for DNA binding, as has been suggested in the "two-step" model of receptor transformation recently proposed by Schmidt et al. (Schmidt T.J., Miller-Diener, A., Webb M.L. and Litwack G. (1985) J. biol. Chem. 260, 16255-16262).


Profiling cellular and inflammatory changes in the airway wall of mild to moderate COPD.
The objective of this study was to enumerate total cells and the number of inflammatory cell differentials in large airways (LAs) versus small airways (SAs) of mild-moderate COPD, and against appropriate controls. For LA, we used endobronchial biopsies and for SA resected lung tissues. Immunostaining was enumerated (cells per mm2 ) for macrophages, neutrophils, CD4 and CD8 T cells in the lamina propria (LP) up to 150 µM deep for LA and full wall thickness for SA. We confirmed hypocellularity in the LA and in the SA wall in smokers and COPD (P < 0.001). LA cellularity was least in current smokers with COPD (COPD-CS) (P < 0.01), while SA cellularity was similar across smoker/COPD groups. LA neutrophils were decreased in COPD-CS (P < 0.01), while SA neutrophil counts were unchanged. Compared with controls, LA macrophage numbers in COPD were significantly lower (P < 0.05), with SA macrophage numbers unchanged. A significant increase was observed in SA CD8+ cells in both normal smokers (P < 0.01) and COPD-CS (P < 0.001) but not in LA. These unique data indicate that the current model for airway wall inflammation in COPD is oversimplified, and contrast with innate inflammatory activation in the lumen, at least in mild-moderate disease. Any abnormalities in airway wall cell differentials are small, although exaggerated in percentage terms.


Exercise conditioning and intraocular pressure.
We studied the intraocular pressure response to short-term maximal aerobic exertion before and after exercise conditioning in ten healthy sedentary volunteers. Before exercise conditioning, mean intraocular pressure +/- S.E.M. decreased by 5.9 +/- 0.6 mm Hg after short-term maximal aerobic exercise, returning to baseline in a mean of 37 +/- 4 minutes. After four months of exercise conditioning, this ocular hypotensive response was significantly dampened, with a mean intraocular pressure reduction of only 1.6 +/- 0.4 mm Hg after short-term maximal aerobic exercise (P less than .01). Additionally, a significant reduction in baseline intraocular pressure occurred, with a mean intraocular pressure of 14.3 +/- 0.7 mm Hg before exercise conditioning, declining to a mean intraocular pressure of 13 +/- 0.9 mm Hg (P less than .02) after four months of physical training. Exercise conditioning may significantly reduce baseline intraocular pressure and attenuate the hypotensive response to short-term maximal aerobic exercise.


Potential fatality reductions through eliminating occupant ejection from cars.
The percent of occupant fatalities preventable by eliminating ejection is calculated using Fatal Accident Reporting System (FARS) data for 1975 through 1986. The calculation requires estimates of two quantities. First, the fraction of all fatally injured occupants who were ejected; this is obtained directly from the FARS data. Second, the probability that an ejected occupant was killed compared to the probability that the occupant would have been killed in a similar crash in the absence of ejection; this quantity is estimated using the double pair comparison method, and its dependence on occupant age and sex and on car mass and model year is examined. High precision estimates of the reduction in fatalities that would result from eliminating ejection as functions of these same variables are thereby obtained. These estimates depend on assuming that whatever method is used to prevent ejection would cause the formerly ejected occupant to acquire the same fatality risk as a nonejected occupant in a similar crash; the study does not address how to prevent ejection. It is concluded that ejection elimination would decrease fatalities to unrestrained car occupants by 18 +/- 1%. The fatality reductions are independent of car seating position (19%, 19%, 17%, 16%, 19%, and 18% for drivers, middle front, right front, left rear, middle rear, and right rear passengers, respectively); they decrease with driver age, from 25% at age 18 years to 7% at 70 years; they decrease with increasing mass, but remained relatively independent of car model year since the early 1970s, being somewhat higher for earlier model years.


A Silastic stent for palliation of extrinsic tracheal compression or unresectable tracheobronchial obstruction.
A silicone rubber stent has been used successfully in the treatment of patients with unresectable major airways obstruction. Silicone rubber does not generate secretions in the tracheobronchial tree and may be left in situ for long periods without complications. With effective relief for asphyxia, radiotherapy can be employed safely.


Magnitude and factors associated with intimate partner violence in mainland Tanzania.
In Tanzania like in many sub-Saharan countries the data about Intimate Partner Violence (IPV) are scarce and diverse. This study aims to determine the magnitude of IPV and associated factors among ever partnered women in urban mainland Tanzania. Data for this report were extracted from a big quasi-experimental survey that was used to evaluate MAP (MAP - Men as Partners) project. Data were collected using standard questions as those in big surveys like Demographic and Health Surveys. Data analyses involved descriptive statistics to characterize IPV. Associations between IPV and selected variables were based on Chi-square test and we used binary logistic regression to assess factors associated with women's perpetration to physical IPV and Odds Ratio (OR) as outcome measures with their 95 % confidence intervals (CI). The lifetime exposure to IPV was 65 % among ever-married or ever-partnered women with 34, 18 and 21 % reporting current emotional, physical and sexual violence respectively. Seven percent of women reported having ever physically abused partners. The prevalence of women perpetration to physical IPV was above 10 % regardless to their exposure to emotional, physical or sexual IPV. IPV towards women in this study was high. Although rates are low, there is some evidence to suggest that women may also perpetrate IPV against their partners. Based on hypothesis of IPV and HIV co-existence, there should be strategies to address the problem of IPV especially among women.


Measurement of cyclobutane thymidine dimers in melanocytic nevi and surrounding epidermis in human skin in situ.
The numbers of melanocytic nevi, localized benign proliferations of melanocytes, have been shown to be associated with an increased risk for development of melanoma. In the present study we have developed an alternative post-labelling method for determination of levels of cyclobutane thymidine dimers (T=T) as dinucleotides at sensitivities sufficient for analysis of human skin samples. Using the developed method, the induction of T=T was determined in melanocytic nevi in situ and surrounding skin, obtained from seven subjects, after exposure to solar simulating radiation. The T=T level in nevi was found to be 1- to 4.5-fold lower than that in surrounding skin and the difference was statistically significant (Student's t-test, P < 0.05).


Respiratory muscle rigidity in a preterm infant after use of fentanyl during Caesarean section.
Fentanyl is in many neonatal intensive care units the sedative of choice. One side-effect is, however, the possibility of muscle and/or chest wall rigidity. A pregnant woman with a critical pulmonary valve stenosis had a balloon dilatation at 26 weeks of gestation. She was put on propranolol, but went into a severe cardiac failure. In week 31, she developed pregnancy induced hypertension. Periodically absent diastolic flow in the umbilical cord was demonstrated. A Caesarean section was performed using fentanyl as analgesia. A boy weighing 1440 g, had a 1 min Apgar score of 3 without respiratory movements. Mask ventilation was tried, but chest wall expansion was not achieved despite using high pressures. He was intubated and positive pressure ventilation attempted, with the same result. Despite the use of high pressures up to 60-70 cm H2O, no chest movement could be achieved. An intravenous line was established in order to give naloxone and pancuronium. Just before the drugs were given, chest wall movements were achieved and the heart rate normalized. This is the first report on chest wall rigidity in a neonate after administration of fentanyl to the mother during Caesarean section.


The Colonic Crypt Protects Stem Cells from Microbiota-Derived Metabolites.
In the mammalian intestine, crypts of Leiberkühn house intestinal epithelial stem/progenitor cells at their base. The mammalian intestine also harbors a diverse array of microbial metabolite compounds that potentially modulate stem/progenitor cell activity. Unbiased screening identified butyrate, a prominent bacterial metabolite, as a potent inhibitor of intestinal stem/progenitor proliferation at physiologic concentrations. During homeostasis, differentiated colonocytes metabolized butyrate likely preventing it from reaching proliferating epithelial stem/progenitor cells within the crypt. Exposure of stem/progenitor cells in vivo to butyrate through either mucosal injury or application to a naturally crypt-less host organism led to inhibition of proliferation and delayed wound repair. The mechanism of butyrate action depended on the transcription factor Foxo3. Our findings indicate that mammalian crypt architecture protects stem/progenitor cell proliferation in part through a metabolic barrier formed by differentiated colonocytes that consume butyrate and stimulate future studies on the interplay of host anatomy and microbiome metabolism.


Hemodynamic effects of alcohol at rest and during upright exercise in coronary artery disease.
The hemodynamic effects of acute alcohol intoxication were studied at rest and during upright exercise in 28 patients with coronary artery disease by right-sided heart catheterization and radionuclide cardiography. The mean arterial blood pressure at rest was reduced by 5% and the left ventricular ejection fraction at rest decreased 2% because of end-systolic dilation during intoxication (serum ethanol 21 mmol/liter). No changes were observed in heart rate, stroke volume, pulmonary artery pressure, pulmonary artery wedge pressure or total peripheral resistance. No significant changes occurred in plasma catecholamines, and no changes occurred in any variable during mild exercise corresponding to a 30 to 40% heart rate increase. Thus, alcohol ingested in moderate doses causes slight impairment of left ventricular emptying and a reduction in the arterial blood pressure at rest in patients with coronary artery disease. A mild exercise load can be tolerated during alcohol intoxication without hemodynamic changes.


Potential preventive properties of GLP-1 receptor agonists against prostate cancer: a nationwide cohort study.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been suggested to possess antineoplastic properties against prostate cancer. We examined the association between GLP-1RA use and prostate cancer risk in a real-world setting. We performed a nationwide register-based cohort study using an active-comparator, new-user design. We included all men in Denmark aged ≥50 years who commenced use of GLP-1RAs or basal insulin during 2007-2019. HRs and 95% CIs for incident prostate cancer were estimated using multivariable Cox regression in 'intention-to-treat' (ITT)- and 'per-protocol'-like analyses. Among 14,206 initiators of GLP-1RAs and 21,756 initiators of basal insulin, we identified 697 patients with prostate cancer during a mean follow-up period of about 5 years from initiation of the study drugs. In comparison with basal insulin use, GLP-1RA use was associated with an adjusted HR of 0.91 (95% CI 0.73, 1.14) in the 'ITT' analysis and 0.80 (95% CI 0.64, 1.01) in the 'per-protocol' analysis. Stronger inverse associations were seen among older men (≥70 years) ('ITT' HR 0.56; 95% CI 0.38, 0.82; 'per-protocol' HR 0.47; 95% CI 0.30, 0.74), and in patients with CVD ('ITT' HR 0.75; 95% CI 0.53, 1.06; 'per-protocol' HR 0.60; 95% CI 0.39, 0.91). GLP-1RA use was inversely associated with prostate cancer risk compared with use of basal insulin in the 'per-protocol' analysis. Older men and patients with CVD exhibited stronger inverse associations in both the 'ITT' and 'per-protocol' analyses. Our results may indicate that GLP-1RA use could protect against prostate cancer.


A balanced scorecard approach in assessing IT value in healthcare sector: an empirical examination.
Healthcare sector indicates human-based and knowledge-intensive property. Massive IT investments are necessary to maintain competitiveness in this sector. The justification of IT investments is the major concern of senior management. Empirical studies examining IT value have found inconclusive results with little or no improvement in productivity. Little research has been conducted in healthcare sector. The balanced scorecard (BSC) strikes a balance between financial and non-financial measure and has been applied in evaluating organization-based performance. Moreover, healthcare organizations often consider their performance goal at customer satisfaction in addition to financial performance. This research thus proposed a new hierarchical structure for the BSC with placing both finance and customer at the top, internal process at the next, and learning and growth at the bottom. Empirical examination has found the importance of the new BSC structure in assessing IT investments. Learning and growth plays the initial driver for reaching both customer and financial performance through the mediator of internal process. This can provide deep insight into effectively managing IT resources in the hospitals.


Effects of polysaccharides-riched Prunus mume fruit juice concentrate on uric acid excretion and gut microbiota in mice with adenine-induced chronic kidney disease.
The present study aimed to determine the effects of polysaccharides-riched Prunus mume fruit juice concentrate (PFC) on uric acid (UA) excretion and the gut microbiota in mice with chronic kidney disease (CKD). C57BL/6 mice were randomly allocated to four groups: two that were fed AIN93M diet, one of which was administered 500 mg/kg PFC, and two that were fed AIN93M diet containing 0.2% adenine, one of which was administered 500 mg/kg PFC. PFC promoted UA excretion, which may have been mediated through increases in the protein expression of ATP-binding cassette transporter G2 (ABCG2), organic anion transporter 1 (OAT1), organic carnitine transporter 2 (OCTN2), and reductions in the protein expression of glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1) in kidneys of CKD mice. ABCG2 expression in the intestine was also increased by PFC administration. Additionally, PFC significantly increased large intestinal short-chain fatty acids (SCFAs) concentrations, and the number of gut microbial species, and reduced the abundance of the genera Bacteroides, Pseudoflavonifractor, Helicobacter, Clostridium_IV and Allobaculum, which have a negative effect on UA excretion. In conclusion, PFC may promote UA excretion in CKD mice by altering the expression of urate transporters and regulating the gut microbiota.


Isolation and Whole-Genome Sequencing of Four Antibiotic-Producing Pseudomonas Strains.
Here, we report the isolation, whole-genome sequencing, and annotation of four novel Pseudomonas isolates. We also evaluate the biosynthetic potential of each genome.


Using geographic information systems to map older people's emergency department attendance for future health planning.
This study aimed to assess the pattern of use of EDs, factors contributing to the visits, geographical distribution and outcomes in people aged 65 years or older to a large hospital in Dublin. A retrospective analysis of 2 years of data from an urban university teaching hospital ED in the southern part of Dublin was reviewed for the period 2014-2015 (n=103 022) to capture the records of attenders. All ED presentations by individuals 65 years and older were extracted for analysis. Address-matched records were analysed using QGIS, a geographic information systems (GIS) analysis and visualisation tool to determine straight-line distances travelled to the ED by age. Of the 49 538 non-duplicate presentations in the main database, 49.9% of the total are women and 49.1% are men. A subset comprised of 40 801 had address-matched records. When mapped, the data showed a distinct clustering of addresses around the hospital site but this clustering shows different patterns based on age cohort. Average distances travelled to ED are shorter for people 65 and older compared with younger patients. Average distances travelled for those aged 65-74 was 21 km (n=4177 presentations); for the age group 75-84, 18 km (n=2518 presentations) and 13 km for those aged 85 and older (n=2104 presentations). This is validated by statistical tests on the clustered data. Self-referral rates of about 60% were recorded for each age group, although this varied slightly, not significantly, with age. Health planning at a regional level should account for the significant number of older patients attending EDs. The use of GIS for health planning in particular can assist hospitals to improve their understanding of the origin of the cohort of older ED patients.


Dielectric laser acceleration of sub-100 keV electrons with silicon dual-pillar grating structures.
We present the demonstration of high-gradient laser acceleration and deflection of electrons with silicon dual-pillar grating structures using both evanescent inverse Smith-Purcell modes and coupled modes. Our devices accelerate subrelativistic 86.5 and 96.3 keV electrons by 2.05 keV over 5.6 μm distance for accelerating gradients of 370 MeV/m with a 3 nJ mode-locked Ti:sapphire laser. We also show that dual pillars can produce uniform accelerating gradients with a coupled-mode field profile. These results represent a significant step toward making practical dielectric laser accelerators for ultrafast, medical, and high-energy applications.


Gradient-echo imaging of hemorrhage at 1.5 Tesla.
We report in vitro and in vivo MR studies of hemorrhage using the gradient-echo pulse sequence, FISP (steady state free precession) and FLASH (spoiling of transverse magnetization) at 1.5 Tesla. Phantoms containing methemoglobin, ferromagnetic particles, human serum and blood clot were scanned using both spin-echo and gradient-echo techniques. FLASH signal intensities were more sensitive to methemoglobin concentration than high T1-weighted spin-echo images. FISP showed little change in signal intensity with varying concentrations of methemoglobin and a contrast relationship similar to T2-weighted spin-echo techniques. FISP and FLASH showed intensity changes at lower concentrations of ferromagnetic material than T2-weighted spin-echo sequences. In vitro blood clot was less intense when observed by FISP and FLASH sequences than on the T2-weighted spin-echo sequences. Maximum contrast between clot and other blood components occurred at a flip angle of 45 degrees for FLASH and 60 degrees for FISP. FISP and FLASH scans of patients with hemorrhage demonstrated a marked decrease in signal intensity in the region of blood clot. This decrease was more pronounced with the gradient-echo sequences than with T2-weighted spin-echo images. We conclude that FLASH is useful for detecting methemoglobin and that both FISP and FLASH are useful for evaluating hemorrhage because of their sensitivity to methemoglobin.


From farm accountancy data to environmental indicators: Assessing the environmental performance of Spanish agriculture at a regional level.
Understanding the environmental impacts of current agricultural practices is a starting point for transitioning towards sustainable agriculture, which is a goal to be achieved by the European Union. This study aims to provide a set of environmental impact indicators with which to assess and compare the environmental performance of a broad group of agricultural reference holdings at the Spanish NUTS 2 level. A life cycle assessment approach based on statistical data on farm accountancy is applied. The unit of analysis is a reference holding on which a specific crop is grown in a NUTS 2 and follows a specific management system (open-field irrigated, open-field rainfed, or greenhouse). The system boundaries are set at the farm gate, and the impact results are expressed per 1 € of net value added. For most reference holdings, the EF scores per net value added are similar regardless of their EF scores per kg commodity, suggesting a correspondence between the use of resources and the economic results. The environmental footprint is clustered into four groups. The first one accounts for 78 % of the sample and represents the holdings with the lowest impact (between 9.7·10-5 and 2.88·10-3 EF score·NVAfc-1); the second cluster groups seven reference holdings (3 herbaceous and 4 Mediterranean perennial crops) with an environmental footprint of between 3.04·10-3 and 9.01·10-3 EF score·NVAfc-1; the third group comprises four irrigated herbaceous crops holdings with the highest impact (between 1.37·10-2 and 2.13·10-2 EF score·NVAfc-1); and the last group corresponds to the holdings with economic losses (mostly herbaceous and two Mediterranean perennial crops). This research highlights the challenge of improving the competitiveness and profitability of Spanish farming. In this way, agricultural practices that generate environmental impacts without achieving their economic goals would be avoided.


A Prospective Study of Social Needs Associated with Mental Health among Postpartum Patients Living in Underserved Communities.
Given the rising rates of maternal morbidity and mortality in the United States and the contribution of mental illness, especially among individuals living in underresourced communities, the objective was to evaluate the prevalence of unmet health-related social needs and their impact on perinatal mental health outcomes. This was a prospective observational study of postpartum patients residing within regions with increased rates of poor perinatal outcomes and sociodemographic disparities. Patients were enrolled in a multidisciplinary public health initiative "extending Maternal Care After Pregnancy (eMCAP)" between October 1, 2020 and October 31, 2021. Unmet health-related social needs were assessed at delivery. Symptoms of postpartum depression and anxiety were evaluated at 1 month postpartum utilizing the Edinburgh Postnatal Depression Scale (EPDS) and Generalized Anxiety Disorder-7 (GAD7) screening tools, respectively. Mean EPDS and GAD7 scores and odds of screening positive (scoring ≥ 10) were compared among individuals with and without unmet health-related social needs with p < 0.05 considered significant. Of participants enrolled in eMCAP, 603 completed at least one EPDS or GAD7 at 1 month. Most had at least one social need, most commonly dependence on social programs for food (n = 413/603; 68%). Individuals lacking transportation to medical (odds ratio [OR]: 4.0, 95% confidence interval [CI]: 1.2-13.32) and nonmedical appointments (OR: 4.17, 95% CI: 1.08-16.03) had significantly higher odds of screening positive on EPDS while participants lacking transportation to medical appointments (OR: 2.73, 95% CI: 0.97-7.70) had significantly higher odds of screening positive on GAD7. Among postpartum individuals in underserved communities, social needs correlate with higher depression and anxiety screening scores. This highlights the need to address social needs to improve maternal mental health. · Social needs are prevalent among underserved patients.. · Needs can be assessed in a structured or freeform manner.. · Unmet needs correlate with poor mental health outcomes.. · Similar needs correlate with depression and anxiety..


The pattern of paediatric trauma on operations.
Recent military campaigns in Iraq and Afghanistan have resulted in the treatment of children in British Medical facilities. In order to determine how care for children may develop in the future, it is necessary to understand the current situation. The aim of this article is to examine the pattern of paediatric trauma on recent operations in Iraq and Afghanistan. Data was requested from the Joint Theatre Trauma Registry, held at the Royal Centre for Defence Medicine in Birmingham, on all trauma calls for patients aged under 16 between the dates 21/3/03 and 31/8/09. Data included age, gender, theatre of operation, injury mechanism and type, trauma scores and destination of the child. 176 children were identified with 16.5% from Iraq and 83.5% from Afghanistan. The overall survival rate was 88.6% with survival rates in Iraq of 89.7% and in Afghanistan of 88.4%. Males accounted for 66.5% of admissions and the commonest age group was age 6-8 years. In 59.1% of total admissions the mechanism of injury was related to explosives. This differed between theatres with explosive injury causing 27.6% of admissions in Iraq and 63.5% in Afghanistan. Injury Severity Scores (ISS) showed equal numbers of minor and severe injuries with fewer moderately injured patients. The median ISS of all data was nine. The median ISS from Iraq was 16 and the median ISS from Afghanistan was nine. The treatment of children in British medical facilities whilst deployed on operations is likely to continue. An assessment of the injury patterns of paediatric patients on current deployments allows development of training and an understanding of logistic requirements. Data collection will also need to be adapted to meet the needs of paediatric patients. These remain issues that are being addressed by the Defence Medical Services.


Temperature effects on the quenching of the 5D0-->7F2 emission of Eu(6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionate)3 by a Cu(II) macrocycle.
Luminescence quenching of Eu(fod)3(fod = 6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionate) by a Cu(II) macrocycle was studied at 25, 35 and 45 degrees C by steady-state and flash luminescence techniques, varying the Cu(II) concentration between 0.2 and 20 mM. Experimental variation of the observed rate constant with the quencher concentration is rationalized in terms of a mechanism involving the quenching of two unequilibrated species by the Cu(II) macrocycle.


Similar costs and outcomes for differentiated service delivery models for HIV treatment in Uganda.
This cost-outcome study estimated, from the perspective of the service provider, the total annual cost per client on antiretroviral therapy (ART) and total annual cost per client virally suppressed (defined as < 1000 copies/ml at the time of the study) in Uganda in five ART differentiated service delivery models (DSDMs). These included both facility- and community-based models and the standard of care (SOC), known as the facility-based individual management (FBIM) model. The Ministry of Health (MOH) adopted guidelines for DSDMs in 2017 and sought to measure their costs and outcomes, in order to effectively plan for their resourcing, implementation, and scale-up. In Uganda, the standard of care (FBIM) is considered as a DSDM option for clients requiring specialized treatment and support, or for those who select not to join an alternative DSDM. Note that clients on second-line regimes and considered as "established on treatment" can join a suitable DSDM.Using retrospective client record review of a cohort of clients over a two-year period, with bottom-up collection of clients' resource utilization data, top-down collection of above-delivery level and delivery-level providers' fixed operational costs, and local unit costs. Forty-seven DSDMs located at facilities or community-based points in the four regions of Uganda were included in the study, with 653 adults on ART (> 18 years old) enrolled in a DSDM. The study found that retention in care was 98% for the sample as a whole [96-100%], and viral suppression, 91% [86-93%]. The mean cost to the provider (MOH or NGO implementers) was $152 per annum per client treated, ranging from $141 to $166. Differences among the models' costs were largely due to clients' ARV regimens and the proportions of clients on second line regimens. Service delivery costs, excluding ARVs, other medicines and laboratory tests, were modest, ranging from $9.66-16.43 per client per year. We conclude that differentiated ART service delivery in Uganda achieved excellent treatment outcomes at a cost similar to the standard of care. While large budgetary savings might not be immediately realized, the reallocation of "saved" staff time could improve health system efficiency and with their equivalent or better outcomes and large benefits to clients, client-centred differentiated models would nevertheless add great societal value.


Comparison of ultrasound colored image views produced by application of statistical analysis of radio-frequency signals and histological findings in patients with chronic hepatitis C.
To assess the tissue characteristics of chronic liver disease, we statistically analyzed the speckle signal from liver parenchyma. Analysis was performed for 65 patients with biopsy-proven chronic hepatitis C; individuals with fatty liver, heavy drinkers, and those with a thick abdominal wall were excluded. The probability density function of radio-frequency signal amplitude was statistically analyzed using a new analytical method. We focused on strong signals which deviated remarkably from the Rayleigh distribution. By applying the analytical results, lesions that caused the strong signals were displayed as red scatter overlaid on B-mode images (we called the red scatter "US-Red" in this study). US-Red% occupancy on the color image was statistically compared with pathological findings. US-Red suggests the existence of an acoustic reflectional plane mainly formed of fibrous bridge and septa. US-Red% increased significantly with progression of liver fibrosis stage. US-Red% varied widely in cirrhosis, and US-Red% in the large nodule group was significantly higher than that in the small nodule group. The results suggest that US-Red% is useful for evaluating liver fibrosis stage (F1-3) and the size of nodules in cirrhosis. In addition, visually detecting the acoustic reflectional plane, which increases with progression of disease, as color images will be clinically beneficial.


Gait analysis on the treadmill - monitoring exercise in the treatment of paraplegia.
A prospective study was performed to evaluate the gait training of seven consecutive spinal cord injured patients and 10 controls on a treadmill using instrumented gait analysis and video documentation. To determine whether it is possible to maintain gait motion within physiological limits during treadmill training. Primary and secondary care unit for spinal cord injury, Heidelberg, Germany. Treadmill training was instituted as early as possible. Gait analysis was performed when the patients were stable enough to walk without manual aid from therapists and enough endurance to allow measurements. A control group of healthy volunteers were examined as well. Video documentation and a camera system using passive markers were employed. Treadmill training started with weight reduction of 25% of bodyweight (18 (0-35) kg), maximum walking speed 0.28 (0.15-0.7) m/s and maximum walking duration 4.7 (3-7) min. At the end of the training, weight reduction decreased to 9.3 (0-20) kg, maximum walking speed increased to 0.67 (0.23-1.1) ms with a maximum walking duration of 11 (8-15) min. 3-D motion analysis of hip, knee and ankle demonstrated joint excursions almost entirely within the limits of normal gait. Exceptions were due to fixed contractures. Our data suggests that it is possible to perform early gait training on a treadmill with no supportive orthoses within the physiologic range of joint motion. The risk for repetitive stress injuries or other negative effects is low.


Practical use of chemical shift databases for protein solid-state NMR: 2D chemical shift maps and amino-acid assignment with secondary-structure information.
We introduce a Python-based program that utilizes the large database of (13)C and (15)N chemical shifts in the Biological Magnetic Resonance Bank to rapidly predict the amino acid type and secondary structure from correlated chemical shifts. The program, called PACSYlite Unified Query (PLUQ), is designed to help assign peaks obtained from 2D (13)C-(13)C, (15)N-(13)C, or 3D (15)N-(13)C-(13)C magic-angle-spinning correlation spectra. We show secondary-structure specific 2D (13)C-(13)C correlation maps of all twenty amino acids, constructed from a chemical shift database of 262,209 residues. The maps reveal interesting conformation-dependent chemical shift distributions and facilitate searching of correlation peaks during amino-acid type assignment. Based on these correlations, PLUQ outputs the most likely amino acid types and the associated secondary structures from inputs of experimental chemical shifts. We test the assignment accuracy using four high-quality protein structures. Based on only the Cα and Cβ chemical shifts, the highest-ranked PLUQ assignments were 40-60 % correct in both the amino-acid type and the secondary structure. For three input chemical shifts (CO-Cα-Cβ or N-Cα-Cβ), the first-ranked assignments were correct for 60 % of the residues, while within the top three predictions, the correct assignments were found for 80 % of the residues. PLUQ and the chemical shift maps are expected to be useful at the first stage of sequential assignment, for combination with automated sequential assignment programs, and for highly disordered proteins for which secondary structure analysis is the main goal of structure determination.


Difficulties in retrieving specific details of autobiographical memories and imagining positive future events in individuals with acute but not remitted anorexia nervosa.
The factors that contribute to the maintenance of anorexia nervosa (AN) are not fully understood, although it is generally accepted that depression is a core feature and contributes to poor prognosis. Individuals with depression tend to have difficulties in producing specific details of autobiographical memories and future episodes. Our aim was to investigate autobiographical memory and episodic future thinking (EFT) in individuals with AN (n = 46), people recovered from AN (recAN; n = 40), and non-affected controls (n = 35). Using a remotely administered computerised version of the autobiographical memory test and episodic future thinking task, we measured six aspects of memory retrieval and EFT generation: specificity, detailedness, difficulty in remembering/imagining, positivity, vividness and realism. Memory and EFT cue valence was manipulated; cues were either positive, neutral, or disorder-related/negative. As the production of EFTs is theoretically linked to the ability to retrieve autobiographical memories, the relationship between autobiographical memory specificity and EFT specificity was explored. To investigate whether autobiographical memory and EFT performance were independent of performance on other forms of cognition, working memory, verbal fluency and cognitive flexibility were measured. People with AN had difficulties retrieving specific details of autobiographical memories and rated autobiographical memories as less positive overall, and less vivid when primed by positive cues. People with a lifetime diagnosis (currently ill or recovered) reported greater difficulty in retrieving memories. The AN group generated less positive EFTs, particularly to positive and neutral cues. Comorbid depressive symptoms had some contribution to the observed findings. Lastly, in all groups autobiographical memory specificity predicted EFT specificity. Problems with retrieving specific details of autobiographical memories and simulating positive EFTs may be a state feature of AN. Treatments targeted at alleviating depressive symptoms, as well those targeted towards facilitating memory retrieval or reconsolidation, and the construction of positive EFTs, may contribute to hope for recovery and strengthen the sense of self beyond the disorder.


Dissolved carbon dioxide accumulation in a large scale and high density production of TGFβ receptor with baculovirus infected Sf-9 cells.
Production of a TGFβ receptor with high density baculovirus infected Sf-9 cells (7×10(6)cells ml(-1)) served as a test run for a retrofitted 150 L microbial fermentor. The entire 110 L batch run was performed in serum free medium, with an addition of a concentrated amino acid and yeastolate mixture at the time of infection. This addition strategy has been proven effective at a small scale by enabling cultures to maintain maximum product yield. In the bioreactor however, while cellular growth was comparable to that of the smaller scale control, TGFβ receptor production was three fold below the control. To minimize the mechanical stress, low flow rate of pure oxygen was used to control the dissolved oxygen at 40%. As a consequence, it seems that this aeration strategy involved an accumulation of dissolved carbon dioxide that in turn inhibited the protein production. A model has been developed that estimated the CO(2) partial pressure in the culture to be in the vicinity of 0.15 atm. The effect of dissolved CO(2) at this concentration has been assessed at smaller scale for TGFβ receptor and β-gal expression, in controlled atmosphere incubators.


A phase I/II study of carfilzomib 2-10-min infusion in patients with advanced solid tumors.
Tolerability, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of carfilzomib, a selective proteasome inhibitor, administered twice weekly by 2-10-min intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 in 28-day cycles, were assessed in patients with advanced solid tumors in this phase I/II study. Adult patients with solid tumors progressing after ≥1 prior therapies were enrolled. The dose was 20 mg/m(2) in week 1 of cycle 1 and 20, 27, or 36 mg/m(2) thereafter. The maximum tolerated dose or protocol-defined maximum planned dose (MPD) identified during dose escalation was administered to an expansion cohort and to patients with small cell lung, non-small cell lung, ovarian, and renal cancer in phase II tumor-specific cohorts. Fourteen patients received carfilzomib during dose escalation. The single dose-limiting toxicity at 20/36 mg/m(2) was grade 3 fatigue, establishing the MPD as the expansion and phase II dose. Sixty-five additional patients received carfilzomib at the MPD. Adverse events included fatigue, nausea, anorexia, and dyspnea. Carfilzomib PK was dose proportional with a half-life <1 h. All doses resulted in at least 80 % proteasome inhibition in blood. Partial responses occurred in two patients in phase I, with 21.5 % stable disease after four cycles in evaluable patients in the expansion and phase II cohorts. Carfilzomib 20/36 mg/m(2) was well tolerated when administered twice weekly by 2-10-min IV infusion. At this dose and infusion rate, carfilzomib inhibited the proteasome in blood but demonstrated limited antitumor activity in patients with advanced solid tumors.


Using stainless steel tape and artery clips to hold miniplates.
A technique for holding Champy miniplates is described and illustrated.


The cardiovascular actions of the volatile oil of the black seed (Nigella sativa) in rats: elucidation of the mechanism of action.
1. The effects of the volatile oil (V.O.) of the black seed (Nigella sativa) on the arterial blood pressure and heart of urethane-anaesthetized rats were investigated and the effects were compared with those of its constituent thymoquinone (T.Q.). 2. Intravenous administration of V.O. in the dose range (4-32 microliters kg.-1) or T.Q. (0.2-1.6 mg kg-1) to rats decreased the arterial blood pressure and the heart rate in a dose-dependent manner. 3. The effects of V.O. were significantly antagonized by treatment of the animals with cyproheptadine, hexamethonium atropine and by spinal pithing. 4. Treatment of the animals with reserpine (5 mg kg- 1 day-1 for 2 days) significantly antagonized the cardiovascular depressant effects induced by 4 and 8 microliters of V.O. kg-1 but not those induced by the larger doses. 5. T.Q.-induced cardiovascular depressant effects were significantly antagonized by atropine and cyproheptadine but not by reserpine. 6. The results suggested that V.O.-induced cardiovascular depressant effects were mediated mainly centrally via indirect and direct mechanisms that involved both 5-hydroxytryptaminergic and muscarinic mechanisms. The direct mechanisms may be due to the presence of T.Q. in the V.O. The V.O. seemed to possess the potential of being a potent centrally acting antihypertensive agent.


Expression of Babesia bovis rhoptry-associated protein 1 (RAP1) in Brucella abortus S19.
Brucella abortus strain 19 (live vaccine) induces a strong humoral and cellular immune response and therefore, it is an attractive vector for the delivery of heterologous antigens. The objective of the present study was to express the rhoptry-associated protein (RAP1) of Babesia bovis in B. abortus S19, as a model for heterologous expression of immunostimulatory antigens from veterinary pathogens. A plasmid for the expression of recombinant proteins fused to the aminoterminal of the outer membrane lipoprotein OMP19 was created, pursuing the objective of increasing the immunogenicity of the recombinant antigen being expressed by its association to a lipid moiety. Recombinant strains of B. abortus S19 expressing RAP1 as a fusion protein either with the first amino acids of beta-galactosidase (S19pBB-RAP1) or B. abortus OMP19 (S19pBB19-RAP1) were generated. Plasmid stability and the immunogenicity of the heterologous proteins were analyzed. Mice immunized with S19pBB-RAP1 or S19pBB19-RAP1 developed specific humoral immune response to RAP1, IgG2a being the predominant antibody isotype. Furthermore, a specific cellular immune response to recombinant RAP1 was elicited in vitro by lymphocytes from mice immunized with both strains. Therefore, we concluded that B. abortus S19 expressing RAP1 is immunostimulatory and may provide the basis for combined heterologous vaccines for babesiosis and brucellosis.


World Health Organization Grade II Meningiomas: The Role of Adjuvant/Salvage Gamma Knife Surgery After Initial Surgery and Prognostic Factor Assessment.
This study was performed to evaluate the efficiency of Gamma Knife surgery (GKS) on reducing recurrence of World Health Organization (WHO) grade II meningiomas after surgery and to define the risk factors associated with tumor recurrence/progression and patient's death. This retrospective study included 75 patients who were diagnosed with WHO grade II meningiomas after initial surgery. The Kaplan-Meier method with a log-rank test was used to calculate the survival curves. Univariate and multivariate Cox proportional hazards model were used to identify the risk factors associated with tumor recurrence/progression and patient's death. The median follow-up period was 70 months. The overall survival (OS) was 97.2% at 2 years and 89.8% at 5 years. The progression-free survival (PFS) at 1, 3, and 5 years was 89.3%, 72.6%, and 59.3%, respectively. Comparing the effects on PFS and OS between different groups, there were no statistically significant differences between the surgery-alone group and the surgery with adjuvant/salvage GKS group (P = 0.512; P = 0.949). In multivariate Cox proportional hazards model analysis, extent of resection (P = 0.001) and tumor location (P = 0.015) were associated with tumor recurrence; only histologic subtypes (P = 0.005) were associated with patient's death. There was no significant PFS or OS benefit for patients with WHO grade II meningiomas treated with adjuvant/salvage GKS postoperatively. Convexity meningiomas with gross total resection tended to benefit PFS. We suggest trying to achieve maximum safe gross total resection for patients with WHO grade II meningiomas, then following up closely.


Select membrane proteins modulate MNV-1 infection of macrophages and dendritic cells in a cell type-specific manner.
Noroviruses cause gastroenteritis in humans and other animals, are shed in the feces, and spread through the fecal-oral route. Host cellular expression of attachment and entry receptors for noroviruses is thought to be a key determinant of cell tropism and the strict species-specificity. However, to date, only carbohydrates have been identified as attachment receptors for noroviruses. Thus, we investigated whether host cellular proteins play a role during the early steps of norovirus infection. We used murine norovirus (MNV) as a representative norovirus, since MNV grows well in tissue culture and is a frequently used model to study basic aspects of norovirus biology. Virus overlay protein binding assay followed by tandem mass spectrometry analysis was performed in two permissive cell lines, RAW264.7 (murine macrophages) and SRDC (murine dendritic cells) to identify four cellular membrane proteins as candidates. Loss-of-function studies revealed that CD36 and CD44 promoted MNV-1 binding to primary dendritic cells, while CD98 heavy chain (CD98) and transferrin receptor 1 (TfRc) facilitated MNV-1 binding to RAW 264.7 cells. Furthermore, the VP1 protruding domain of MNV-1 interacted directly with the extracellular domains of recombinant murine CD36, CD98 and TfRc by ELISA. Additionally, MNV-1 infection of RAW 264.7 cells was enhanced by soluble rCD98 extracellular domain. These studies demonstrate that multiple membrane proteins can promote efficient MNV-1 infection in a cell type-specific manner. Future studies are needed to determine the molecular mechanisms by which each of these proteins affect the MNV-1 infectious cycle.


Prescribing over-the-counter medication in an OMFS department: a service review.
In 2018, NHS England released guidelines restricting the prescription of over-the-counter medicines (OTC). This was a project initially targeted at primary care, but we felt that it could also be used to improve services in secondary or tertiary care. We were interested to investigate our OTC prescribing pattern within a busy maxillofacial department and therefore carried out a service review. All outpatient prescriptions were reviewed between October 2017 and October 2018. The review was then repeated between October 2018 and October 2019. All OTC medications prescribed during these periods and their costs to the Trust were highlighted. Our aim was to improve prescribing patterns based on current guidelines and reduce the departmental spend in this area. The first year of data revealed that a total sum of £2742.75 was spent on OTC medications. Those most frequently prescribed were Difflam™ (Mylan) mouthwash and spray; chlorhexidine mouthwash, and miconazole oral gel. The findings of the service review indicated deficiencies in knowledge with regards to prescribing appropriately. Following departmental training the amount spent reduced from £2742.75 to £1312. There is a need to educate nationally to reduce spending on OTC medications, which would help to relieve financial pressures on other NHS services. As a department, we can also hope for further improvement.


Validation of visual estimation of neonatal jaundice in low-income and middle-income countries: a multicentre observational cohort study.
Determine the sensitivity and specificity of neonatal jaundice visual estimation by primary healthcare workers (PHWs) and physicians as predictors of hyperbilirubinaemia. Multicentre observational cohort study. Hospitals in Chandigarh and Delhi, India; Dhaka, Bangladesh; Durban, South Africa; Kumasi, Ghana; La Paz, Bolivia. Neonates aged 1-20 days (n=2642) who presented to hospitals for evaluation of acute illness. Infants referred for any reason from another health facility or those needing immediate cardiopulmonary resuscitation were excluded. Infants were evaluated for distribution (head, trunk, distal extremities) and degree (mild, moderate, severe) of jaundice by PHWs and physicians. Serum bilirubin level was determined for infants with jaundice, and analyses of sensitivity and specificity of visual estimations of jaundice used bilirubin thresholds of >260 µmol/L (need for phototherapy) and >340 µmol/L (need for emergency intervention in at-risk and preterm babies). 1241 (47.0%) neonates had jaundice. High sensitivity for detecting neonates with serum bilirubin >340 µmol/L was found for 'any jaundice of the distal extremities (palms or soles) OR deep jaundice of the trunk or head' for both PHWs (89%-100%) and physicians (81%-100%) across study sites; specificity was more variable. 'Any jaundice of the distal extremities' identified by PHWs and physicians had sensitivity of 71%-100% and specificity of 55%-95%, excluding La Paz. For the bilirubin threshold >260 µmol/L, 'any jaundice of the distal extremities OR deep jaundice of the trunk or head' had the highest sensitivity across sites (PHWs: 58%-93%, physicians: 55%-98%). In settings where serum bilirubin cannot be measured, neonates with any jaundice on the distal extremities should be referred to a hospital for evaluation and management, where delays in serum bilirubin measurement and appropriate treatment are anticipated following referral, the higher sensitivity sign, any jaundice on the distal extremities or deep jaundice of the trunk or head, may be preferred.


The effect of nigella sativa supplementation on cardiometabolic outcomes in patients with non-alcoholic fatty liver: A randomized double-blind, placebo-controlled trial.
Non-alcoholic fatty liver disease (NAFLD) is one of the metabolic disturbances associated with liver cell inflammation. Nigella sativa (N.sativa) is a widely used medicinal plant known for its anti-inflammatory, antimicrobial, antioxidant, and hepato-protective properties. This study aimed to assess the effect of supplementation of N. sativa oil on plasma levels of adiponectin, leptin, and blood pressure (BP) in patients diagnosed with NAFLD. This randomized, double-blind, placebo-controlled clinical trial was conducted on 44 NAFLD patients. Participants were randomly assigned to two groups (n = 22/group); the experimental group received 1000 mg of N. sativa oil per day, while the control group received a placebo for eight weeks. The primary outcome measures were serum levels of adiponectin, leptin, and systolic and diastolic blood pressure measured at the baseline and the end of the intervention. After eight weeks of supplementation with N. sativa oil, no statistically significant differences were found in serum levels of adiponectin (p = 0.40), leptin (p = 0.89), systolic BP (p = 0.13), and diastolic BP (p = 0.09) between the two groups. Furthermore, after supplementation with N. sativa, no significant changes were observed in leptin (p = 0.07), adiponectin (p = 0.13), systolic BP (p = 0.82), and diastolic BP (p = 0.38) within the two groups. These results indicate that administration of N. sativa oil 1000 mg/day for 8 weeks has no favorable effect on cardiometabolic measures in NAFLD patients. Further studies with higher dosage over a longer period are needed to investigate whether this effect is dose- and time-dependent.