Lowered circulating apelin is significantly associated with an increased risk for hypertension: A meta-analysis.
Apelin is a bioactive peptide manifesting a potent vasodilatory property. In this meta-analysis, we aimed to investigate for the first time whether circulating apelin differed significantly between hypertensive patients and normotensive controls. Both PubMed and Embase were searched for eligible articles. Eligibility evaluation and data collection were done independently by two investigators. Weighted mean difference (WMD) with 95% confidence interval (CI) was calculated under random-effects model by STATA. Ten studies were synthesized finally, including 1610 patients and 1105 controls. Overall analysis revealed that circulating apelin was significantly lowered in patients than in controls (WMD = -39.85 pg/mL, 95% CI: -65.56 to -14.15; P = 0.002), with significant heterogeneity (I2 = 89.4%). By race, patients had lower circulating apelin than controls in Caucasian populations (WMD = -79.82 pg/mL, 95% CI: -105.80 to -53.85; P < 0.001), without heterogeneity (I2=0.0%), while no significance was observed in Chinese and African-Americans. Further grouping studies by source of controls found a significant reduction in circulating apelin in studies with hospital-based controls (WMD = -96.28 pg/mL, 95% CI: -129.67 to -62.88; P < 0.001) (I2 = 49.4%), but not in studies with population-based controls. Via a meta-analysis of 10 studies and on 2715 subjects, our findings demonstrated that lowered circulating apelin was significantly associated with an increased risk for hypertension, especially in Caucasian populations.


Novel inorganic host layered double hydroxides intercalated with guest organic inhibitors for anticorrosion applications.
Zn-Al and Mg-Al layered double hydroxides (LDHs) loaded with quinaldate and 2-mercaptobenzothiazolate anions were synthesized via anion-exchange reaction. The resulting compounds were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy/energy-dispersive X-ray spectroscopy. Spectrophotometric measurements demonstrated that the release of organic anions from these LDHs into the bulk solution is triggered by the presence of chloride anions, evidencing the anion-exchange nature of this process. The anticorrosion capabilities of LDHs loaded with organic inhibitors toward the AA2024 aluminum alloy were analyzed by electrochemical impedance spectroscopy. A significant reduction of the corrosion rate is observed when the LDH nanopigments are present in the corrosive media. The mechanism by which the inhibiting anions can be released from the LDHs underlines the versatility of these environmentally friendly structures and their potential application as nanocontainers in self-healing coatings.


Evolution of the Resistance of Botrytis cinerea to Carbendazim and the Current Efficacy of Carbendazim Against Gray Mold After Long-Term Discontinuation.
Gray mold caused by Botrytis cinerea is a fungal disease that critically threatens agricultural production, and carbendazim was the first fungicide used to control B. cinerea. However, B. cinerea developed serious resistance to carbendazim, and this fungicide has thus rarely been used in the past decade in China. Due to the extended discontinuation of carbendazim use, the evolution of the resistance of B. cinerea to carbendazim in recent years is unclear, and whether carbendazim can effectively control gray mold is largely unknown. Therefore, this study determined the sensitivity of 407 B. cinerea isolates collected from 2014 to 2018 to carbendazim and the ability of carbendazim to control gray mold in the field. The results showed that the frequency of B. cinerea isolates resistant to carbendazim remained above 95%. Three different mutation types responsible for the resistance of B. cinerea to carbendazim were identified at codon 198 in the β-tubulin gene sequence: E198V (changed from GAG to GTG), E198A (changed from GAG to GCG), and E198K (changed from GAG to AAG). Over the last 5 years, E198V was the major mutation. However, an analysis of its evolution revealed that the percentage of the E198V mutation declined after 2017 to 56.5% in 2018. In addition, the proportion of isolates with the E198K mutation decreased over time, and no isolates with this mutation were found in either 2017 or 2018. The proportion of the E198A mutation increased over the 5-year test period to reach 43.5% in 2018. Furthermore, three greenhouse experiments demonstrated that carbendazim has lost its ability to control gray mold. We attribute the above findings to our results showing that the carbendazim-resistant isolates had no fitness penalties compared with the carbendazim-sensitive isolates for sporulation and mycelial growth. In particular, the E198A mutant isolates exhibited a strong ability to sporulate, suggesting that the E198A mutation might become dominant in the future. Interestingly, the results showed that carbendazim-sensitive isolates could be easily controlled by four conventional fungicides, namely boscalid, procymidone, iprodione, and pyrimethanil, with mean EC50 values of 0.71 ± 0.2 mg liter-1, 1.33 ± 0.39 mg liter-1, 0.59 ± 0.33 mg liter-1, and 6.02 ± 3.02 mg liter-1, respectively. In conclusion, carbendazim has lost its application value and is ineffective for the control of gray mold.


Socioeconomic, health, and psychosocial mediators of racial disparities in cognition in early, middle, and late adulthood.
Racial disparities in cognitive performance exist across the life course, but it is not known whether mediators of disparities differ by age. Understanding sources of cognitive disparities at different ages can inform policies and interventions. Data were obtained for non-Hispanic Black and White respondents to The National Survey of Midlife Development in the United States from 3 age groups: 28-44 (N = 1210; 20% Black); 45-64 (N = 2693; 15% Black); and 65-85 (N = 1298; 11% Black). Moderated mediation models characterized direct and indirect effects of race on episodic memory and executive function composite scores through economic, health, and psychosocial variables as a function of age group. Education, income, chronic health conditions, and external locus of control mediated cognitive disparities across the life course, although income was a stronger mediator at younger ages. Perceived discrimination was a weaker mediator among young adults due to an absence of racial differences in perceived discrimination in that group. Despite multiple indirect effects, there were still significant unexplained effects of race on cognition that were not moderated by age group. Interventional work is needed to determine whether increasing educational attainment and income, and reducing chronic health conditions and perceived constraints among Blacks, reduce cognitive disparities. Targeting income inequality and discrimination (or buffering the impact of those variables) may be differently effective at reducing cognitive disparities at different stages of the adult life course. (PsycINFO Database Record


The new LassoLoop360° technique for biomechanically superior tissue grip.
Suprapectoral tenodesis is a frequently used technique for treating pathologies of the long head of the biceps brachii (LHBB) tendon. However, so far, no Gold Standard treatment exist. Hence, the arthroscopic LassoLoop360 (LL360) technique is introduced aiming to provide secure fixation and improved biomechanical properties. It was hypothesized, that the LL360 technique would show superior biomechanical response to cyclic loading and ultimate load-to-failure testing compared to the commonly used simple Lasso Loop (SLL). Twenty-two porcine superficial flexor digitorum tendons were prepared using a No. 2 suture according to either the SLL or the LL360 technique. Displacement after cyclic loading (1.000 cycles) between 5 and 30 N, ultimate load-to-failure (ULTF), mode of failure as well as the construct stiffness were tested. Significantly less displacement was found in the LL360 group (SLL 2.25 ± 0.51 mm; LL360 1.67 ± 0.37 mm; p = 0.01). Ultimate Load to Failure was significantly higher in the LL360 (168.6 ± 29.6 N) as compared to the SLL (124.1 ± 25.8 N, p = 0.02). The LL360 also revealed a significant higher stiffness compared to the SLL (SLL 13.1 ± 0.9 N/mm vs. LL360 19.1 ± 1.0 N/mm, p < 0.001). The most common mode of failure was the suture cutting through the tendon, with a significantly less suture cutting through for the LL360 compared with the SLL (p < 0.05). The LassoLoop360-technique offers superior biomechanical characteristics regarding the tendon-suture-interface compared to the SLL. In the initial healing phase, the suture-tendon-interface is the most vulnerable part of the tendon-suture-anchor construct, the aim of this new technique is to reduce this weakest part of the chain (Ponce et al., Am J Sports Med 39:188-194, 2011). This technique may therefore be beneficial for arthroscopic suprapectoral biceps tenodesis at the entrance of the bicipital groove.


Serological and electrophoretic typing of red clover mottle virus isolates.
Serological and immunoelectrophoretic properties of 22 RCMV isolates from Czechoslovakia were determined. Based on the differences among the isolates, two electrophoretic types were established: type I--isolates with one non-separable electrophoretic form, and type II--isolates with two electrophoretic forms. Depending on the mobility of the electrophoretic forms these types could be subdivided further into two subtypes each. In all selected isolates representing the individual electrophoretic types and subtypes two isoelectric points were determined at pH 5.2 and pH 5.6.


Evaluation of a network of medical abortion providers in two districts of Maharashtra, India.
The objective of this study was to examine experiences and service delivery of private medical doctors participating in a professional network designed to improve knowledge and service quality of medical abortion (MA) procedures. A cross-sectional assessment of 87 Medical Abortion Provider Network (MAPnet) participants was conducted between December 2006 and January 2007 to describe participants' service delivery and network experiences. After participating in MAPnet, providers reported a statistically significant amount of more MA services (92%), national protocol adherence for timing of drug administration (93%) and drug dosage protocols (82%) when compared to their reports before MAPnet affiliation. In addition, MAPnet providers offered contraceptive counselling (100%) and pain management (54%). Nearly three-quarters of providers were interested in continuing their association with the network initiatives. However, the network failed to adequately facilitate inter-network sharing of knowledge and experiences. These findings suggest that establishing and nurturing a network of private medical doctors can improve availability and quality of safe and early abortion services through MA.


Behavioural phenotyping of casper mutant and 1-pheny-2-thiourea treated adult zebrafish.
The ability to visualise neural circuits in zebrafish in vivo is one of the most useful aspects of this model organism in neuroscience. To maintain the transparency of embryos, however, drugs, such as 1-pheyl-2-thiourea (PTU) must be added, or researchers can use mutants that do not develop pigment (e.g., the casper). The behavioural characteristics of such strains, however, have not been documented. Here, we tested adult zebrafish from the casper line, as well as wild-type (Tübingen, TU) and wild-types treated as embryos with PTU on three commonly used behavioural endpoints in neuroscience: novel tank test (similar to open-field in rodents), conditioned place preference for nicotine, and social cohesion (using a new method of cluster analysis). We found no differences between the casper and the TU, but the adult TU treated with PTU as embryos showed a marked increase in anxiety during the novel tank test. These data suggest that where possible, labs interested in analysis of developmental processes involved in adult phenotypes should avoid the use of PTU in favour of transparent mutants, such as casper.


Does migraine-related stroke occur in childhood?
This report concerns seven children who had at least one episode of infarct, possibly during an attack of migraine. They fulfilled the following criteria: presence of acute neurological deficit associated with headache or other symptoms characteristic of migraine attacks; a history of migraine; evidence of infarct on CT scan; and no other evident cause of the stroke. CT showed that the area of infarction was in the distribution of the posterior cerebral artery in three cases. Four of the children have been followed for at least 23 months and none has severe residual deficit. An aetiological relationship between migraine and stroke could not be demonstrated. However, epidemiological data suggest that childhood migraine can be a contributory risk-factor for strokes.


High throughput selection of antibiotic-resistant transgenic Arabidopsis plants.
Kanamycin resistance is the most frequently used antibiotic-resistance marker for Arabidopsis transformations, however, this method frequently causes escape of untransformed plants, particularly at the high seedling density during the selection. Here we developed a robust high-density selection method using top agar for Arabidopsis thaliana. Top agar effectively suppressed growth of untransformed wild-type plants on selection media at high density. Survival of the transformed plants during the selection were confirmed by production of green true leaves and expression of a firefly luciferase reporter gene. Top agar method allowed selection using a large amount of seeds in Arabidopsis transformation.


Licensed DNA Vaccines against Infectious Hematopoietic Necrosis Virus (IHNV).
This article reviews some of the recent patents on DNA vaccines against fish viruses, in particular against the novirhabdovirus infectious hematopoitic necrosis virus (IHNV). Although very effective in protecting fish against IHNV, only one DNA vaccine has been approved to date for use in Canada. In Europe and in US, its commercialization is restricted due to safety concerns.


Effect of bulk-fill base material on fracture strength of root-filled teeth restored with laminate resin composite restorations.
To evaluate the effect of using a bulk-fill flowable base material on fracture strength and fracture patterns of root-filled maxillary premolars with MOD preparations restored with laminate restorations. Fifty extracted maxillary premolars were selected for the study. Standardized MOD cavities with endodontic treatment were prepared for all teeth, except for intact control. The teeth were divided randomly into five groups (n=10); (Group 1) sound teeth, (Group 2) unrestored teeth; (Group 3) MOD cavities with Vitrebond base and resin-based composite (Ceram. X One Universal); (Group 4) MOD cavities with 2mm GIC base (Fuji IX GP) and resin-based composite (Ceram. X One Universal) open laminate, (Group 5) MOD cavities were restored with 4mm of bulk-fill flowable base material (SDR) and resin-based composite (Ceram. X One Universal). All teeth were thermocycled and subjected to a 45° ramped oblique load in a universal testing machine. Fracture load and fracture patterns were recorded. Data were analyzed using one-way ANOVA and Dunnett's T3 test. Restoration in general increased the fracture strength compared to unrestored teeth. The fracture strength of group 5 (bulk-fill) was significantly higher than the fracture strength of the GIC laminate groups and not significantly different from the intact teeth (355±112N, P=0.118). The type of failure was unfavorable for most of the groups, with the majority being mixed failures. The use of a bulk-fill flowable base material significantly increased the fracture strength of extracted root-filled teeth with MOD cavities; however it did not improve fracture patterns to more favorable ones. Investigating restorative techniques that may improve the longevity of root-filled premolar teeth restored with direct resin restorations.


Rapid eye movement sleep behavior disorder in children with autism.
We performed nocturnal polysomnography on 11 children with autism who had symptoms of disrupted sleep and nocturnal awakenings. We identified rapid eye movement (REM) sleep behavior disorder in 5 of these 11 patients. Since REM sleep behavior disorder typically affects elderly males with neurodegenerative diseases, the identification of this phenomenon in autistic children could have profound implications for our understanding of the neurochemical and neurophysiologic bases of autism. Further, accurate diagnosis of REM sleep behavior disorder would enable specific treatment with clonazepam and help the family and the child consolidate sleep and improve daytime performance.


Diagnostic of charge balance in high-temperature tungsten plasmas using LLNL EBIT.
Diagnostic of high-temperature M-shell W plasmas is challenging because of contribution of numerous ionization stages in a relatively narrow x-ray spectral region. A method using LLNL EBIT data generated at different electron beam energies has been established for the identification of prominent spectral features and for the determination of charge balance in x-ray M-shell W spectra between 3.5 and 8.5 A. It extends previous work [A. S. Safronova et al., Can. J. Phys. 86, 267 (2008)] which used only Ni-like lines to include the neighboring ionization stages. This diagnostic procedure was tested with results from Z-pinch plasmas produced on the 1 MA pulse power generator Zebra at UNR. These results are of particular importance for fusion research.


Inhibition of glycogen synthesis by fatty acid in C(2)C(12) muscle cells is independent of PKC-alpha, -epsilon, and -theta.
We have previously shown that glycogen synthesis is reduced in lipid-treated C(2)C(12) skeletal muscle myotubes and that this is independent of changes in glucose uptake. Here, we tested whether mitochondrial metabolism of these lipids is necessary for this inhibition and whether the activation of specific protein kinase C (PKC) isoforms is involved. C(2)C(12) myotubes were pretreated with fatty acids and subsequently stimulated with insulin for the determination of glycogen synthesis. The carnitine palmitoyltransferase-1 inhibitor etomoxir, an inhibitor of beta-oxidation of acyl-CoA, did not protect against the inhibition of glycogen synthesis caused by the unsaturated fatty acid oleate. In addition, although oleate caused translocation, indicating activation, of individual PKC isoforms, inhibition of PKC by pharmacological agents or adenovirus-mediated overexpression of dominant negative PKC-alpha, -epsilon, or -theta mutants was unable to prevent the inhibitory effects of oleate on glycogen synthesis. We conclude that neither mitochondrial lipid metabolism nor activation of PKC-alpha, -epsilon, or -theta plays a role in the direct inhibition of glycogen synthesis by unsaturated fatty acids.


Proteochemometrics-Based Prediction of Peptide Binding to HLA-DP Proteins.
Human leukocyte antigens (HLA) class II proteins are involved in the antigen processing in the antigen presenting cells. They form complexes with antigen peptide fragments. The peptide-HLA protein complexes are presented on the cell surface where they are recognized by helper T cells (Th cells). HLA-DP is one of the three HLA class II loci. The HLA-DP proteins are associated with a significant number of autoimmune diseases, as well as with a susceptibility or resistance to a number of infectious agents. In the present study, we apply proteochemometrics-a method for bioactivity modeling of multiple ligands binding to multiple target proteins-to derive and validate a robust model for peptide binding prediction to the 7 most frequent HLA-DP proteins. The model is able to identify 86% of the binders in the top 10% of the best predicted nonamers generated from one protein.


Risk stratification theme for congenital heart surgery.
Surgical practice is changing and auto-evaluation of quality of care, organized by scientific societies, is very likely to become an obligation during this new decade. This evaluation requires a common nomenclature, a registry, and risk stratification. The primary purpose of risk stratification is to offer the possibility of objective analysis of surgical outcomes according to the complexity of the pathology treated. Registries, databases containing select essential data on a complete population, are not able to produce a statistically reliable risk stratification model. Academic databases, like that of the Congenital Heart Surgeons Society, contain comprehensive data on select patients, and are able to produce risk stratification, but only very slowly. The absence of risk discrimination in current registries penalizes centers treating complex pathologies. They may be reluctant to release their results without the security of risk stratification. Given the diversity of congenital heart surgery, a new method has been developed to stratify risks: the complexity score. This approach is based on the perceived opinions of a group of 50 internationally recognized surgeons and centers. It allows a hierarchical classification of surgical procedures according to mortality, morbidity, and surgical difficulty. Surgical procedures are scored globally on simple pathologies and in detail according to seven categories of risks. The complexity score in congenital heart surgery, also known as the Aristotle Score, is currently being developed as a collaborative effort of the members of the European Association for Cardio-thoracic Surgery, the Society of Thoracic Surgeons, the Congenital Heart Surgeons Society, and the European Congenital Heart Surgeons Foundation, and should be available next year.


Correlation of Visuospatial Ability and EEG Slowing in Patients with Parkinson's Disease.
Background. Visuospatial dysfunction is among the first cognitive symptoms in Parkinson's disease (PD) and is often predictive for PD-dementia. Furthermore, cognitive status in PD-patients correlates with quantitative EEG. This cross-sectional study aimed to investigate the correlation between EEG slowing and visuospatial ability in nondemented PD-patients. Methods. Fifty-seven nondemented PD-patients (17 females/40 males) were evaluated with a comprehensive neuropsychological test battery and a high-resolution 256-channel EEG was recorded. A median split was performed for each cognitive test dividing the patients sample into either a normal or lower performance group. The electrodes were split into five areas: frontal, central, temporal, parietal, and occipital. A linear mixed effects model (LME) was used for correlational analyses and to control for confounding factors. Results. Subsequently, for the lower performance, LME analysis showed a significant positive correlation between ROCF score and parietal alpha/theta ratio (b = .59, p = .012) and occipital alpha/theta ratio (b = 0.50, p = .030). No correlations were found in the group of patients with normal visuospatial abilities. Conclusion. We conclude that a reduction of the parietal alpha/theta ratio is related to visuospatial impairments in PD-patients. These findings indicate that visuospatial impairment in PD-patients could be influenced by parietal dysfunction.


Dacron patch infection following carotid endarterectomy: a systematic review of the literature.
Our report encompasses two cases of Dacron patch infection following carotid endarterectomy and a systematic review of the literature. Particular attention is placed on the incidence, aetiology, investigation, presentation and management dilemmas of this rare complication of carotid surgery. We present all known cases of synthetic patch infection following carotid endarterectomy over the last 12 years. 14 publications have been identified totalling 77 cases of graft infection. Approximately 0.25-0.5% of all Dacron patches appear to get infected. Infection may present early or late and appears to have a bi-modal distribution depending on the presence of low- or high-grade infection. Post-operative complications especially wound haematoma is associated with the later development of infection. Most patients present with pseudoaneurysm formation, neck swelling or a draining local sinus and are infected with either Staphylococcus epidermidis or Staphylococcus aureus. Duplex ultrasound is the investigation of choice and complete excision of all infected material and arterial reconstruction with a vein patch or graft is recommended. Dacron patch infection is a rare but recognised complication of carotid surgery and knowledge of this condition is vital for vascular surgeons and other speciality surgeons to whom cases may present.


Effect of zileuton in radicular pain induced by herniated nucleus pulposus in rats.
Arachidonic acid metabolites, prostaglandins and leukotrienes are detected in clinical cases of herniated nucleus pulposus. However, little is known about their role in the associated symptoms like radicular pain. The aim of the present study was to examine the role of leukotrienes in an animal model of hyperalgesia induced by application of autologus nucleus pulposus to sciatic nerve in rats. Hyperalgesia was assessed employing noxious mechanical and thermal stimuli. Zileuton, a 5-lipoxygenase inhibitor, dose dependently (25-100 mg/kg, p.o.), and indomethacin (2 mg/kg, p.o.), a non-selective cyclooxygenase inhibitor, significantly (P > 0.05) decreased mechanical as well as thermal hyperalgesia on postoperative days 3, 5 and 7 as compared to the nucleus pulposus group. Further, co-administration of zileuton (25 mg/kg, p.o.) with indomethacin (2 mg/kg, p.o.) showed enhanced anti-hyperalgesic effect in both the paradigms as compared to effect per se. The present study, thus, suggested that leukotrienes as well as prostaglandins might play a significant role in hyperalgesia induced by autologus nucleus pulposus in rats. The results suggested that dual inhibition approach of 5-lipoxygenase and cyclooxygenase enzymes may prove beneficial in such conditions.


Fabrication of Titanium-Niobium-Zirconium-Tantalium Alloy (TNZT) Bioimplant Components with Controllable Porosity by Spark Plasma Sintering.
Spark Plasma Sintering (SPS) is used to fabricate Titanium-Niobium-Zirconium-Tantalum alloy (TNZT) powder-based bioimplant components with controllable porosity. The developed densification maps show the effects of final SPS temperature, pressure, holding time, and initial particle size on final sample relative density. Correlations between the final sample density and mechanical properties of the fabricated TNZT components are also investigated and microstructural analysis of the processed material is conducted. A densification model is proposed and used to calculate the TNZT alloy creep activation energy. The obtained experimental data can be utilized for the optimized fabrication of TNZT components with specific microstructural and mechanical properties suitable for biomedical applications.


[Expression of BMP-2/7 heterodimers with potent ability to stimulate osteogenic differentiation in CHO cells].
Coding sequences of BMP-2 and BMP-7 were amplified using PCR and ligated with a DNA sequence encoding a flexible peptide (Gly4Ser)5. The fusion gene was inserted into plasmid pIRESneo3. The expression level of BMP2/7 heterodimers in the transfected CHO-K1 cells was 230.75+/-13.34 ng/mL. Culture medium of stably tansfected clone pool was collected as conditional medium to treat osteoblast MC3T3 cells. Staining of Alkalin phosphatase and Alizarin red demonstrated that the conditional medium significantly promoted osteogenic differentiation to a higher extent than BMP-2 homodimers expressed in either CHO-K1 cells or E. coli. Transcriptional levels of Osteogenic phenotype-related molecular markers such as OC, ALP, Runx2 and Osx were increased (P<0.05), and BMP/Smad signal activities were significantly enhanced by BMP-2/7 heterodimers, comparing with BMP-2 homodimers (P<0.05). The results demonstrate that BMP-2/7 heterodimers expressed in CHO-K1 cells have potent ability to stimulate osteogenic differentiation.


A mitogen- and anisomycin-stimulated kinase phosphorylates HMG-14 in its basic amino-terminal domain in vivo and on isolated mononucleosomes.
The rapid, transient induction of 80-100 immediate-early (IE) genes upon mitogenic stimulation occurs irrespective of protein synthesis and is mediated by modification of existing proteins. Two mechanisms, not mutually exclusive, involving modification either of sequence-specific transcription factors or of structural chromatin proteins primed by pre-association with responsive effectors are conceivable. Here, we show that upon IE gene induction, the non-histone high-mobility-group protein HMG-14, but not the related protein HMG-17, becomes serine phosphorylated in its basic, amino-terminal region close to where it binds nucleosomal DNA. Phosphorylation, normally transient, occurs independent of transcription and is quantitative and prolonged during superinduction. Brief micrococcal nuclease digestion substantially releases HMG-14 from nuclei in the mononucleosome-bound state. Finally, mononucleosomes prepared from mitogen-stimulated, but not control, cells contain a mitogen-activated kinase that phosphorylates HMG-14 in vitro on the same site(s) as in intact cells. The association of HMG-14 and its mitogen-activated kinase with nuclease-sensitive mononucleosomes has implications for models of mitogen-stimulated IE gene induction.


Inflammatory bowel disease and the genes for the natural resistance-associated macrophage protein-1 and the interferon-gamma receptor 1.
The genes for the interferon-gamma receptor 1 and the natural resistance-associated macrophage protein 1 (NRAMP1) control the immune response to intracellular microbial pathogens. Such pathogens, in particular Mycobacterium paratuberculosis, have been implicated in the pathogenesis of Crohn's disease. We studied markers in the genes for NRAMP1 and two mutations in the interferon-gamma receptor in relation to inflammatory bowel disease (IBD) in the following groups: 270 healthy individuals, 74 patients with Crohn's disease, 72 patients with ulcerative colitis, and 40 patients with primary sclerosing cholangitis. We studied the allele frequencies of two restriction fragment length polymorphisms in the gene for NRAMP1 and the prevalence of two mutations in the interferon-gamma receptor 1 gene. The markers in the NRAMP1 gene were not associated with inflammatory bowel disease. Also, the mutations in the interferon-gamma receptor 1 were not found in the 186 IBD patients. Genetic markers in NRAMP1 are thus not associated with IBD. Therefore this gene is not likely to play a role in the pathogenesis of IBD. The mutation in the interferon-gamma receptor was not found in our IBD patients group.


Evaluation of cell-mediated immunity and circulating immune complexes as prognostic indicators in cancer patients.
Cell-mediated immunity (CMI) and circulating immune complexes (CIC) were estimated in 55 cancer patients and 25 control volunteers to evaluate their prognostic significance. Cancer patients comprised head and neck cancer (11), breast cancer (13), gastrointestinal cancer (10), genitourinary cancer (11), and lymphomas and sarcomas (10). CMI was tested in vitro by early rosette-forming cells (ARFC) and total rosette-forming cell (TRFC) counts. ARFC count in control group was 758.1 +/- 78.09 cells/cumm. In advancing clinical stages of cancer (I-IV), ARFC counts were decreased (i.e., 601.12 +/- 74.96 [p < 0.01]; 494.8 +/- 71.83 [p < 0.001]; 432.44 +/- 36.05 [p < 0.001], and 438.55 +/- 69.99 [p < 0.001] cells/cumm, respectively). TRFC count in control group was 1029 +/- 88.39 cells/cumm. In cancer stages I through IV, these counts decreased significantly (i.e., 699.63 +/- 66.24; 597.55 +/- 82.9; 505.11 +/- 52.56; and 501.55 +/- 69.99 cells/cumm, respectively [p < 0.001]. Dinitrochlorobenzene cutaneous reactivity in vivo was 100% positive in control group, 62.5% positive in cancer stage I, 5% positive in stage II, and negative in stages III and IV. CIC of intermediate size were estimated by polyethylene glycol precipitation (PEG pptn) technique, which detects CIC in the ratio of 2:1 (Ag2Ab). Mean PEG index in control group was 39.5 +/- 4.65; sequential increase in CIC was observed in advancing clinical stages of cancer (I-IV)(i.e., 49 +/- 7.03 [p < 0.01]; 75.38 +/- 44.01 [p < 0.001]; 93.38 +/- 44.57 [p < 0.001]; and 216.00 +/- 147.05 [p < 0.001], respectively). Latex agglutination inhibition (LAI) titer was done to detect CIC as small as 8s, which constitute the opposite polar end of CIC spectrum. LAI titers in control group were nil. However, LAI titers in cancer stages I through IV were 1 +/- 2.64; 8.6 +/- 5.6 (p < 0.001); 12.00 +/- 8.11 (p < 0.001); and 25.77 +/- 9.06 (p < 0.001), respectively. Decrease in CMI and subsequent increase in CIC indicate unfavorable prognosis in cancer patients, and also precede clinical manifestation of increased tumor mass in vivo.


Reemergence of an epidemic coxsackievirus B5 genotype.
Outbreaks of coxsackievirus B5 (CB5) infections occur primarily during peak epidemic years, with comparatively few cases occurring during intervening years. This pattern of periodic CB5 epidemicity is quite distinct from the general endemicity typical of other group B coxsackieviruses. To determine the genetic relationships among CB5 isolates from different outbreaks, we compared viral RNAs by ribonuclease T1 oligonucleotide fingerprinting. Isolates obtained within an epidemic year had very similar fingerprints, an observation indicating that they were closely related variants of a single genotype. CB5 isolates from the major 1972 epidemic were not closely related to the genotype associated with the preceding epidemic of 1967. However, isolates from the most recent CB5 epidemic year, 1983, had fingerprints nearly identical to those of the 1967 strains. These findings provide clear evidence for epidemic reemergence of the 1967 genotype and suggest that the virus was maintained under conditions approaching evolutionary stasis during the intervening 16-year period.


Local Structure and Magnetism of Fe2O3 Maghemite Nanocrystals: The Role of Crystal Dimension.
Here we report on the impact of reducing the crystalline size on the structural and magnetic properties of γ-Fe2O3 maghemite nanoparticles. A set of polycrystalline specimens with crystallite size ranging from ~2 to ~50 nm was obtained combining microwave plasma synthesis and commercial samples. Crystallite size was derived by electron microscopy and synchrotron powder diffraction, which was used also to investigate the crystallographic structure. The local atomic structure was inquired combining pair distribution function (PDF) and X-ray absorption spectroscopy (XAS). PDF revealed that reducing the crystal dimension induces the depletion of the amount of Fe tetrahedral sites. XAS confirmed significant bond distance expansion and a loose Fe-Fe connectivity between octahedral and tetrahedral sites. Molecular dynamics revealed important surface effects, whose implementation in PDF reproduces the first shells of experimental curves. The structural disorder affects the magnetic properties more and more with decreasing the nanoparticle size. In particular, the saturation magnetization reduces, revealing a spin canting effect. Moreover, a large effective magnetic anisotropy is measured at low temperature together with an exchange bias effect, a behavior that we related to the existence of a highly disordered glassy magnetic phase.


Storage on Maternal Plants Affects Temperature Requirements during Germination in Rumex obtusifolius.
Aerial seed banks facilitate population persistence by extending the temporal range of seed dispersal. Knowing the temporal range of germination will improve our understanding of the relationship between seed germination dynamics and aerial seed bank storage duration. We tested the effects of temperature (12/12 h of 5/10, 10/20, 20/30 and 25/35 °C) and light variation (12 h light/12 h darkness and 24 h darkness per day) on germination of Rumex obtusifolius L. seeds retained in an aerial seed bank for 0, 2, 4, 6, 8 and 10 months. Freshly harvested R. obtusifolius were non-dormant and exhibited germination rates of up to 92%. Overall, seeds of R. obtusifolius germinated reliably at all but the lowest temperature (5/10 °C). Seeds maintained high viability throughout the collection period, indicating that fluctuating weather conditions had little influence on seed germination. Thus, the species can maintain viable seeds in aerial storage for up to 10 months and contribute viable seeds to the soil seed bank year-round. This ability to maintain a renewed soil seed bank contributes to the species' strong resilience in colonizing disturbed areas and makes it a difficult weed to control.


A longitudinal study of infections and injuries of Ranger students.
Causes of medical attrition and their implications for medical support for the U.S. Army Ranger course are considered, based on data collected from 190 students in a summer class. In the second half of the course, an increase in documented infection rates, notably cellulitis of the lower extremities and Streptococcus carriage prevalence, coincided with indications of compromised immune function. The authors suggest that aggressive treatment in the field, including liberal use of antibiotics, and periodic examination of each student by medical personnel are critical factors which will minimize medical attrition and ensure safe participation of soldiers in this and other stressful and sustained field exercises.


Necrotizing meningoencephalitis in a cow.
An 18-month-old Charolais cow developed depression and drooling and was submitted for necropsy after euthanasia. The cow was 1 of 50 moved between 2 farms approximately 5 days before the onset of clinical disease. Gross findings included swollen and hemorrhagic areas of malacia in the frontal, temporal, and parietal lobes of the cerebral cortex. Microscopically there was a necrotizing meningoencephalitis with intranuclear astrocytic and neuronal eosinophilic viral inclusions in the frontal, temporal, and parietal cerebral cortex as well as in the basal nuclei and thalamus. The gross and microscopic findings were consistent with necrotizing meningoencephalitis caused by bovine herpesvirus (BHV-1 or BHV-5), and the diagnosis was confirmed by detection of bovine herpesviral antigen on fresh samples of brain via fluorescent antibody test using a monoclonal antibody against BHV-1 glycoprotein C.


The role of the Ikaros gene in lymphocyte development and homeostasis.
The Ikaros gene, which encodes a family of hemopoietic-specific zinc finger proteins, is described as a central regulator of lymphocyte differentiation. During fetal development, it is required at the earliest stage of T cell and B cell specification. In the adult, however, lymphoid lineages rely on Ikaros at distinct phases of their development. Its activity is essential for the generation of B cell but not of T cell precursors, although the differentiation of the latter is not normal. A significant increase in CD4 thymocytes and their immediate precursors is detected, and because these cells lack markers that correlate with positive selection, a deregulation in their maturation process is suggested. Furthermore, Ikaros-null thymocytes hyperproliferate in response to T cell receptor (TCR) signaling; within days after their appearance in the thymus, clonally expanding populations are detected. Deregulated TCR-mediated responses and the fast kinetics of tumor development in these mutant thymocytes implicate Ikaros as a central tumor suppressor gene for the T cell lineage. In addition, lack of natural killer cells and selective defects in gamma delta T cells and dendritic antigen-presenting cells point to Ikaros as an essential factor for the establishment of early branchpoints of the T cell pathway. The dominant interference activity of Ikaros isoforms unable to bind DNA and their effects in lymphocyte development suggest that Ikaros works in concert with other factors. The role of Aiolos, a lymphoid-restricted and structurally related gene, in lymphoid differentiation is discussed. A model is proposed that defines Ikaros as the backbone of a complex regulatory protein network that controls cell fate decisions and regulates homeostasis in the hemo-lymphoid system. Changes in this regulatory network may reflect differentiation and proliferation adjustments made in hemo-lymphoid progenitors and precursors as they give rise to the cells of our immune system.


Photodissociation dynamics and the dissociation energy of vanadium monoxide, VO, investigated using velocity map imaging.
Velocity map imaging has been employed to study multi-photon fragmentation of vanadium monoxide (VO) via the C 4Σ- state. The fragmentation dynamics are interpreted in terms of dissociation at the three-photon level, with the first photon weakly resonant with transitions to vibrational energy levels of the C 4Σ- state. The dissociation channels accessed are shown to depend strongly on the vibrational level via which excitation takes place. Analysis of the evolution of the kinetic energy release spectrum with photon energy leads to a refined value for the dissociation energy of ground state VO of D0(VO) = 53 126 ± 263 cm-1.


Pulmonary benign metastasizing leiomyoma: a case report.
Pulmonary benign metastasizing leiomyoma (PBML) is a rare entity usually occurring in females with history of uterine leiomyoma, and it is preferential to metastasize to the lung and appears as a histopathologic benign tumor of smooth muscle origin. In this article, the clinical and pathological data from 1 patient with PBML were analyzed. Chest CT scan showed that multiple well-defined nodules in the both lobes of the lungs. The tumor cells in the lung were well differentiated, and the pattern of tumor was similar to the original tumor. IHC identified it originated from smooth muscle cells, consistent with the diagnosis of PBML. Positive staining of estrogen and progestogen receptors was detected in both the leiomyoma and the metastasizing lesions. During two years of observation, pulmonary function parameters were within normal limits and there was no evidence of tumor recurrence.


Prostaglandins for Postpartum Hemorrhage: Pharmacology, Application, and Current Opinion.
Postpartum hemorrhage (PPH) remains a common cause of maternal mortality worldwide. Medical intervention plays an important role in the prevention and treatment of PPH. Prostaglandins (PGs) are currently recommended as second-line uterotonics, which are applied in cases of persistent bleeding despite oxytocin treatment. PG agents that are constantly used in clinical practice include carboprost, sulprostone, and misoprostol, representing the analogs of PGF2α, PGE2, and PGE1, respectively. Injectable PGs, when used to treat PPH, are effective in reducing blood loss but probably induce cardiovascular or respiratory side effects. Misoprostol is characterized by oral administration, low cost, stability in storage, broad availability, and minimal side effects. It remains a treatment option for uterine atony in low-resource settings, but its effectiveness as a uterotonic for independent application may be limited. Key Messages: The present review article discusses the physiological roles of various natural PGs, evaluates the existing evidence of PG analogs in the prevention and treatment of PPH, and finally provides a reference to assist obstetricians in selecting appropriate uterotonics.


Proline carrier mutant of Escherichia coli K-12 with altered cation sensitivity of substrate-binding activity: cloning, biochemical characterization, and identification of the mutation.
Two putP mutants of Escherichia coli K-12 that were defective in proline transport but retained the binding activities of the major proline carrier were isolated (T. Mogi, H. Yamamoto, T. Nakao, I. Yamato, and Y. Anraku, Mol. Gen. Genet. 202:35-41, 1986). One of these mutations and three null-type mutations (K. Motojima, I. Yamato, and Y. Anraku, J. Bacteriol. 136:5-9, 1978) were cloned into a pBR322 putP+ hybrid plasmid (pTMP5) by in vivo recombination. Cytoplasmic membrane vesicles were prepared from the mutant strains and strains harboring pTMP5 putP plasmids, and the properties of the proline-binding reaction of the mutant putP carriers in membranes were examined under nonenergized conditions. The putP19, putP21, and putP22 mutations, which were mapped in the same DNA segment of the putP gene (Mogi et al., Mol. Gen. Genet. 202:35-41, 1986), caused the complete loss of proline carrier activity. The proline carriers encoded by the mutant putP genes, putP9 and putP32, and putP32 in pTMP5-32, which was derived from in vivo recombination with the putP32 mutation, had altered sodium ion and proton dependence of binding affinities for proline and were resistant to N-ethylmaleimide inactivation without changes in the specificities for substrates and alkaline metal cations. The nucleotide sequence of the putP32 lesion located on the 0.35-megadalton RsaI-PvuII fragment in the putP gene in pTMP5-32 was determined; the mutation changed a cytosine at position 1001 to a thymine, causing the alteration of arginine to cysteine at amino acid position 257 in the primary structure of the proline carrier. It was shown that this one point mutation was enough to produce the phenotype of pTMP5-32 by in vitro DNA replacement of the AcyI-PvuII fragment of the wild-type putP gene with the DNA fragment containing the mutated nucleotide sequence.


Comparison of complications and long-term survival after minimally invasive esophagectomy versus open esophagectomy in patients with esophageal cancer and chronic obstructive pulmonary disease.
To compare the complications and long-term survival of esophageal cancer patients with chronic obstructive pulmonary disease (COPD) after minimally invasive esophagectomy (MIE) versus open esophagectomy (OE) using propensity score matching (PSM). Esophageal cancer patients who underwent esophagectomy at the Thoracic Surgery Department of the First Affiliated Hospital of Hebei North University from January 2010 to December 2018 were retrospectively enrolled. The incidence of postoperative complications and prognosis of the MIE (n = 132) and OE (n = 138) groups were compared. To reduce bias, 1:1 PSM was adopted for the analysis. The median disease-free survival (DFS) of the MIE and OE groups were 24 months and 26 months, respectively, and neither group reached median survival. There was no significant difference between the two groups in terms of 3-year DFS and overall survival (OS). The stratification of the patients on the basis of the percentage of estimated forced expiratory volume in the first second (%FEV1) did not result in significant differences in the survival rates. A total of 42 patients (50%) in the MIE group and 55 patients (65.48%) in the OE group experienced complications, and the difference was statistically significant (OR=0.527, 95% CI: 0.283-0.981, P=0.042). The incidence of acute COPD exacerbation (OR=0.213, 95% OR, CI: 0.068-0.666, P=0.004) and pulmonary atelectasis requiring bronchoscopic aspiration (OR=0.232, 95% OR, CI: 0.082-0.659, P=0.004) were significantly higher in the OE versus the MIE group. In addition, the distribution of the various grades of complications also differed significantly between the two groups (P=0.016). While the incidence of minor complications (≤Grade II) was similar in both groups (P=0.503), that of severe complications (≥Grade III) was markedly higher in the OE group (P=0.002) and the Grade-IIIa complications were predominant (P=0.001). The severity of complications was correlated with the postoperative duration of hospital stay in both groups (r=0.187, P=0.015). No significant difference was observed in the incidence of minor complications (≤Grade II) between the two groups following stratification on the basis of %FEV1, whereas severe complications were more frequent in the OE group among patients with %FEV1 between 60% and 70% (P=0.001<0.05). There was no significant difference in the postoperative DFS and OS of esophageal cancer patients with COPD after undergoing MIE or OE. However, MIE significantly reduced the incidence of severe postoperative complications among patients with %FEV1 between 60% and 70%.


Fluctuation-induced interaction between randomly charged dielectrics.
Monopolar charge disorder effects are studied in the context of fluctuation-induced interactions between neutral dielectric slabs. It is shown that quenched bulk charge disorder gives rise to an additive contribution to the net interaction force which decays as the inverse distance between the slabs and may thus completely mask the standard Casimir-van der Waals force at large separations. By contrast, annealed (bulk or surface) charge disorder leads to a net interaction force whose large-distance behavior agrees with the universal Casimir force between ideal conductors, which scales as the inverse cubic distance, and the dielectric properties enter only in the subleading corrections.


Outcomes following single, caudally based bilateral versus unilateral frontonasal sinusotomy for treatment of equine paranasal sinus disease.
Bilateral sinus disease is relatively uncommon in horses, accounting for 3%-4.5% of horses with sinonasal disease, but may require bilateral paranasal surgery for complete resolution. Complications and recurrence following bilateral sinusotomy have not been reported or compared to those following unilateral procedures. To describe clinical features and outcomes in horses undergoing standing single, caudally based bilateral frontonasal sinusotomy compared to unilateral frontonasal surgery. Records of horses (n = 37) undergoing surgical treatment for sinus disease (five bilateral, 32 unilateral) were retrospectively reviewed (2010-2017) for signalment, presenting complaint, duration of signs preoperatively, diagnostic imaging, treatments administered, duration hospitalization, complications, and owner satisfaction with the procedure. Mann-Whitney testing was used to compare age, duration of hospitalization, and follow-up time in horses undergoing unilateral or bilateral procedures. Fisher's exact testing was used to determine if sex predilection was present for unilateral or bilateral disease. Survival time and time to recurrence were compared by Kaplan-Meier survival curves and log-rank curve comparison testing. Significance was assessed at p < 0.05. Length of signs prior to admission did not differ between horses with unilateral and bilateral disease (p = 0.09), but there was a tendency for horses with bilateral disease to have clinical signs for longer. Age (p = 0.19) and hospitalization duration (p = 0.53) did not differ between horses undergoing unilateral versus bilateral procedures. Recurrence or failure to resolve signs was reported in 11/32 (34%) of unilateral and 0/5 bilateral cases (p = 0.07). The bilateral single, caudally based sinusotomy approach may be considered to effectively treat bilateral paranasal sinus disease without concern for increased risk of life-threatening complications or longer hospitalization duration than would be typical for unilateral sinusotomy procedures.


Abnormal ER quality control of neural GPI-anchored proteins via dysfunction in ER export processing in the frontal cortex of elderly subjects with schizophrenia.
Abnormalities of posttranslational protein modifications (PTMs) have recently been implicated in the pathophysiology of schizophrenia. Glycosylphosphatidylinositols (GPIs) are a class of complex glycolipids, which anchor surface proteins and glycoproteins to the cell membrane. GPI attachment to proteins represents one of the most common PTMs and GPI-associated proteins (GPI-APs) facilitate many cell surface processes, including synapse development and maintenance. Mutations in the GPI processing pathway are associated with intellectual disability, emphasizing the potential role of GPI-APs in cognition and schizophrenia-associated cognitive dysfunction. As initial endoplasmic reticulum (ER)-associated protein processing is essential for GPI-AP function, we measured protein expression of molecules involved in attachment (GPAA1), modification (PGAP1), and ER export (Tmp21) of GPI-APs, in homogenates and in an ER enriched fraction derived from dorsolateral prefrontal cortex (DLPFC) of 15 matched pairs of schizophrenia and comparison subjects. In total homogenate we found a significant decrease in transmembrane protein 21 (Tmp21) and in the ER-enriched fraction we found reduced expression of post-GPI attachment protein (PGAP1). PGAP1 modifies GPI-anchors through inositol deacylation, allowing it to be recognized by Tmp21. Tmp21 is a component of the p24 complex that recognizes GPI-anchored proteins, senses the status of the GPI-anchor, and regulates incorporation into COPII vesicles for export to the Golgi apparatus. Together, these proteins are the molecular mechanisms underlying GPI-AP quality control and ER export. To investigate the potential consequences of a deficit in export and/or quality control, we measured cell membrane-associated expression of known GPI-APs that have been previously implicated in schizophrenia, including GPC1, NCAM, MDGA2, and EPHA1, using Triton X-114 phase separation. Additionally, we tested the sensitivity of those candidate proteins to phosphatidylinositol-specific phospholipase C (PI-PLC), an enzyme that cleaves GPI from GPI-APs. While we did not observe a difference in the amount of these GPI-APs in Triton X-114 phase separated membrane fractions, we found decreased NCAM and GPC1 within the PI-PLC sensitive fraction. These findings suggest dysregulation of ER-associated GPI-AP protein processing, with impacts on post-translational modifications of proteins previously implicated in schizophrenia such as NCAM and GPC1. These findings provide evidence for a deficit in ER protein processing pathways in this illness.


Evaluating mobilization and transport of arsenic in sediments and groundwaters of Aquia aquifer, Maryland, USA.
Groundwater and sediment samples were collected along a flow path in the Aquia aquifer (Paleocene), Maryland in order to examine and study the factors influencing "evolution" of arsenic (As) in these groundwaters. The Aquia crops out near Washington, DC, where it is unconfined, and extends approximately 90 km down dip to the south and east towards and beneath the Chesapeake Bay. The studied flow path was chosen owing to (i) the number of accessible wells, (ii) differences in total dissolved As concentrations in groundwaters from some of the sampled wells, which reach values > or =667 nmol kg(-1) or > or =50 ppb, and (iii) the distinct difference in total dissolved As concentrations in Aquia groundwaters between the northern and southern portions of the study area. In groundwater samples, in situ separation of inorganic As species [As(III) and As(V)] were performed by using anion exchange chromatography. Subsequently, As concentrations were determined by inductively coupled plasma mass spectrometry. In situ measurements of Fe concentrations and speciation, dissolved S(-II) concentrations, pH, alkalinity, and oxidation-reduction potential (Eh) were determined to establish the oxidation-reduction conditions and solution chemistry along the flow path. Concentrations of As in 12 analyzed groundwater samples range from approximately 0.75 to 1 072 nmol kg(-1), and As(III) concentrations ranging from 0.24 to 980 nmol kg(-1) appears to be the dominant form of As in solution. 50% of the studied wells yielded groundwaters with concentrations that exceed the US EPA's Maximum Contaminant Level for As in drinking water of 133 nmol kg(-1) or 10 ppb. In order to examine the solid phase speciation of As within the aquifer sediments, we collected a number of Aquia sediment samples from a drill core that was archived at the Maryland Geological Survey. These sediment samples were evaluated using a previously established sequential extractions procedure. Solid phase As concentrations range between 973 and 2,012 nmol kg(-1). Additionally, petrographic, X-Ray diffraction and diffuse reflectance spectroscopy analyses of the Aquia sediments reveal presence of glauconite, and smectite along with goethite and hematite within the samples. Here, we present the possible mechanisms responsible for the elevated As concentrations in the studied groundwaters of the Aquia aquifer.


Epidemiology and mortality in patients hospitalized for burns in Catalonia, Spain.
Burn injuries are one of the leading causes of morbidity worldwide. Although the overall incidence of burns and burn-related mortality is declining, these factors have not been analysed in our population for 25 years. The aim of this study has been to determine whether the epidemiological profile of patients hospitalized for burns has changed over the past 25 years. We performed a retrospective cohort study of patients hospitalised between 1 January 2011 and 31 December 2018 with a primary diagnosis of burns. The incidence of burns in our setting was 3.68/105 population. Most patients admitted for burns were men (61%), aged between 35 and 45 years (16.8%), followed by children aged between 0 and 4 years (12.4%). Scalding was the most prevalent mechanism of injury, and the region most frequently affected was the hands. The mean burned total body surface (TBSA) area was 8.3%, and the proportion of severely burned patients was 9.7%. Obesity was the most prevalent comorbidity (39.5%). The median length of stay was 1.8 days. The most frequent in-hospital complications were sepsis (16.6%), acute kidney injury (7.9%), and cardiovascular complications (5.9%). Risk factors for mortality were advanced age, high abbreviated burn severity index score, smoke inhalation, existing cardiovascular disease full-thickness burn, and high percentage of burned TBSA. Overall mortality was 4.3%. Multi-organ failure was the most frequent cause of death, with an incidence of 49.5%. The population has aged over the 25 years since the previous study, and the number of comorbidities has increased. The incidence and severity of burns, and the percentage of burned TBSA have all decreased, with scalding being the most prevalent mechanism of injury. The clinical presentation and evolution of burns differs between children and adults. Risk factors for mortality were advanced age, smoke inhalation, existing cardiovascular disease, full-thickness burn, and high percentage of burned TBSA.


Alternative Treatment Regimens With the PCSK9 Inhibitors Alirocumab and Evolocumab: A Pharmacokinetic and Pharmacodynamic Modeling Approach.
Alirocumab and evolocumab are 2 human monoclonal antibodies that inhibit the proprotein convertase subtilisin/kexin type 9 (PCSK9). These antibodies can potently lower low-density lipoprotein cholesterol (LDLc) serum concentrations. The aims of this analysis were to develop a pharmacokinetic (PK) and pharmacodynamic (PD) model for both antibodies, to simulate and investigate different dosage and application regimens, and finally, to note the effects on LDLc levels. Alirocumab was clinically studied and approved with 2 doses, 75 and 150 mg every 2 weeks (Q2W), whereas evolocumab was tested and approved with 2 dosing intervals, 140 mg Q2W and 420 mg Q4W. Data were digitized from published studies describing alirocumab and evolocumab PK, as well as LDLc levels in humans for various single and multiple doses. Alirocumab dosages ranged between 75 and 300 mg and evolocumab from 7 to 420 mg. The analysis was performed using a nonlinear mixed-effects modeling technique. A 2-compartment model with first-order absorption and saturable elimination described the PK of both antibodies best. LDLc levels were described by a turnover model with zero-order synthesis rate decreased by the antibodies and a first-order degradation rate that was increased by the antibodies. Simulations show a comparable effectiveness for alirocumab 75 mg Q2W and 150 mg Q3W as well as evolucmab 140 mg Q2W and 420 mg Q5W, respectively. This is the first PK/PD model describing the link between alirocumab and evolocumab PK and LDLc concentrations. The model may serve as an important tool to simulate different dosage regimens in order to optimize therapy.


Community perception of school-based mass drug administration program for soil-transmitted helminths and Schistosomiasis in Ogun State, Nigeria.
Neglected tropical diseases, such as soil-transmitted helminths and Schistosomiasis, are prevalent in sub-Saharan Africa, particularly Ogun State, Nigeria. School-based mass drug administration program is the primary control intervention, but the coverage and uptake of this intervention have been inadequate. This study aimed to investigate community perceptions of school-based mass drug administration programs for these infections in Ogun State, Nigeria, and identify the barriers to their uptake and coverage. The study used a qualitative research approach involving focus group discussions and in-depth interviews with community members and stakeholders engaged in neglected tropical disease control programs in Ogun State, Nigeria. A semi-structured questionnaire guided the exploration of ideas, and the data were analyzed using the QRS Nvivo 12 software package. The study found several barriers, such as the influence of parents, lack of sufficient knowledge, and side effects. The study recommended strategies such as improving community sensitization and engagement, drug distribution and performance, and enhancing partner collaboration and coordination to improve the school-based mass drug administration programs. The study revealed correct perceptions of transmission but some misconceptions about disease causation, transmission, and drug safety. Participants expressed a desire for better sensitization campaigns and more assurances of their safety. The study recommends strengthening health education messages and increasing the visibility of on-site medical personnel. The findings have implications for improving the performance of these programs and reducing the burden of intestinal parasitic infections in the community. The study highlights the need for community engagement and education, health system support, and partner collaboration to successfully implement mass drug administration programs.


Skin microbiota dynamics following B. subtilis formulation challenge: an in vivo study in mice.
Modulating the microbiota is a leading-edge strategy for the restoration and maintenance of a healthy, balanced environment. The use of health-promoting bacteria has demonstrated some potential benefits as an alternative for skin microbiota intervention. Here, we investigate the manipulation of mice skin microbiota using B. subtilis incorporated into a supportive Pluronic F-127 hydrogel formulation. The formula plays an important role in delivering the bacteria to the desired action site. The B. subtilis challenge induced a shift in the composition and abundance of the skin microbiota. Containment of B. subtilis in the Pluronic F-127 hydrogel accelerated bacterial modulation compared with free B. subtilis. The abundance of both Staphylococcus and Corynebacterium spp. was altered as a result of the live bacterial intervention: the abundance of Corynebacterium increased while that of Staphylococcus decreased. Four days after last application of the B. subtilis formulation, B. subtilis counts returned to its initial level. B. subtilis intervention can induce a shift in the skin microbiota, influencing the abundance of commensal, beneficial, and pathogenic bacteria. Containment of B. subtilis in Pluronic hydrogel accelerates the microbial alteration, probably by facilitating bacterial attachment and supporting continuous growth. Our results reveal the ability of B. subtilis in Pluronic to modulate the skin microbiota composition, suggesting that the formulation holds therapeutic potential for skin disease treatment.


Torricelli and the ocean of air: the first measurement of barometric pressure.
The recognition of barometric pressure was a critical step in the development of environmental physiology. In 1644, Evangelista Torricelli described the first mercury barometer in a remarkable letter that contained the phrase, "We live submerged at the bottom of an ocean of the element air, which by unquestioned experiments is known to have weight." This extraordinary insight seems to have come right out of the blue. Less than 10 years before, the great Galileo had given an erroneous explanation for the related problem of pumping water from a deep well. Previously, Gasparo Berti had filled a very long lead vertical tube with water and showed that a vacuum formed at the top. However, Torricelli was the first to make a mercury barometer and understand that the mercury was supported by the pressure of the air. Aristotle stated that the air has weight, although this was controversial for some time. Galileo described a method of measuring the weight of the air in detail, but for reasons that are not clear his result was in error by a factor of about two. Torricelli surmised that the pressure of the air might be less on mountains, but the first demonstration of this was by Blaise Pascal. The first air pump was built by Otto von Guericke, and this influenced Robert Boyle to carry out his classical experiments of the physiological effects of reduced barometric pressure. These were turning points in the early history of high-altitude physiology.


Flunitrazepam as an induction agent in children. A clinical and pharmacokinetic study.
Flunitrazepam was studied as an induction agent in paediatric patients. The onset of action was slow and its efficacy uncertain following single doses of 0.03 mg kg-1(n = 4), or 0.04 mg kg-1 (n = 6) i.v. Long-lasting sedative effects were observed following operation. A strong anterograde but not retrograde amnesic effect was obtained, and a possible analgesic sparing property. Flunitrazepam has a faster and more extensive tissue distribution and a more rapid elimination (half-life about 12 h) in children than in adults.


Nuclear factor-kB in thyroid carcinogenesis and progression: a novel therapeutic target for advanced thyroid cancer.
Apoptosis is an essential physiological process of elimination of destined cells during the development and differentiation or after damage from external stresses such as ionizing radiation or chemotherapeutic agents. Disruption of apoptosis is proved to cause various diseases including cancer. Among numerous molecules involved in diverse anti- or pro-apoptotic signaling pathways, NF-kappaB is one of the key factors controlling anti-apoptotic responses. Its anti-apoptotic effect is thought to be mediated through not only transcriptional activation of dependent genes but also by crosstalking with the JNK pathway. Oncogenic proteins such as Ret/PTC, Ras and BRAF can induce NF-kappaB activation making it an important change in thyroid cancer. A number of specific or non-specific NF-kappaB inhibitors have been tried to take over the cascade in in vitro and in vivo experiments. These agents can induce massive apoptosis especially in combination with radio- or chemotherapy. Current results suggest that the inhibition of the NF-kappaB may be a promising strategy for advanced thyroid cancer treatment but further investigations are warranted to develop specific and clinically effective NF-kappaB inhibitors in future.


MicroRNAs in hematological malignancies: a novel approach to targeted therapy.
MicroRNAs (miRNAs) are about 19-24 nucleotide small single-stranded noncoding RNAs that are involved in crucial cell processes such as proliferation, apoptosis, and differentiation. Several studies reported show the involvement of miRNA in cancer. It has been suggested that miRNA profiling has the potential to classify a variety of tumors and possibly predict outcome. MicroRNA can act as an oncogene as well as tumor suppressor gene and this dual function of miRNA can be utilized as a therapeutic tool. The oncogenic character of miRNA can be silenced through various RNA interference-type strategies. The involvement of miRNA in the tumorogenesis processes makes them an important therapeutic tool and a novel biomarker. In this review, we have highlighted the role of miRNA in hematological malignancies and its utility in targeted therapy.


Neuropsychological weaknesses in adult ADHD; cognitive functions as core deficit and roles of them in persistence to adulthood.
Prior investigations have shown that individuals with attention deficit hyperactivity disorder (ADHD) have impaired neuropsychological functions. This study had two aims, first to investigate weakened cognitive functions in adult ADHD (aADHD), and second, to investigate difference between persisters (those having persistently ongoing ADHD diagnosis in adulthood), and remitters (those having ADHD diagnosis only in childhood and not in adulthood), in terms of cognitive deficits. We evaluated performance on a comprehensive neuropsychological battery in three groups including 34 persisters, 35 remitters, and 35 healthy control group (absence of childhood and adulthood ADHD diagnosis). Our findings showed that adults with ADHD have inefficient attention, interference control and set-shifting functions, which may be revealed on neuropsychological tests that require greater cognitive demand. Given the finding that interference control deficit exists across the lifespan in people with ADHD, we suggest that interference control-associated functional weakness may be a core deficit for ADHD. (JINS, 2012, 18, 1-8).


Case report Iatrogenic parasitic leiomyoma: the surgeon's invisible hand.
Uterine leiomyoma is the most common benign tumour of the uterus in women of reproductive age. When removed surgically, a mini-invasive procedure is preferentially used (laparoscopic or robotic) and the extraction of the specimen can be managed by power morcellation. In this consecutive case-series, we present three cases of parasitic leiomyoma that appeared following previous surgical management of leiomyoma using the technique of laparoscopic myomectomy with uncontained power morcellation. The time frame in between the initial surgery and the diagnosis of the parasitic leiomyoma was 5.7 years. All three patients were diagnosed with endometriosis: 2 cases prior to the initial surgery and 1 case after the initial surgery. One hypothesis could be that, due to pelvic inflammation, endometriosis is a risk factor for iatrogenic parasitic leiomyoma development in case of uncontained morcellation of leiomyoma during myomectomy.


MP1 homologue-based multilocus sequence system for typing the pathogenic fungus Penicillium marneffei: a novel approach using lineage-specific genes.
A highly reproducible and discriminative typing system is essential for better understanding of the epidemiology of Penicillium marneffei, the most important thermal dimorphic fungus causing respiratory, skin, and systemic mycosis in Southeast Asia. The sequences of 11 housekeeping genes were identical among 10 strains of P. marneffei, but those of MP1 and its 13 homologues, a novel superfamily of mannoproteins in the subdivision Pezizomycotina of Ascomycetes, mostly species of Penicillium and Aspergillus, showed significant variations. Therefore, a multilocus sequence typing (MLST) system for P. marneffei was constructed using MP1 (549 bp) and the four of its homologues (MPLP4 [337 bp], MPLP7 [347 bp], MPLP10 [546 bp], and MPLP13 [422 bp]) that showed the greatest variations. Among the 2,201 bp of the five loci, 183 polymorphic sites were observed in 44 strains of P. marneffei. The median number of alleles at each locus was five (range, 5 [MPLP4, MPLP7, and MPLP13] to 15 [MPLP10]). Four of the five genes had nonsynonymous substitution/synonymous substitution (d(n)/d(s)) ratios of >1. A total of 35 different sequence types (STs) were assigned to the 44 P. marneffei isolates, with 28 of the 35 STs identified only once. The discriminatory power was 0.9884. MP1 and its homologues were better than housekeeping genes for MLST in P. marneffei. Due to their more rapid evolutionary rates, lineage-specific genes may be better candidates than housekeeping genes for sequence-based typing, especially in microbes that evolve slowly or have evolved recently.


Systems-based analysis of RIG-I-dependent signalling identifies KHSRP as an inhibitor of RIG-I receptor activation.
Retinoic acid-inducible gene I (RIG-I) receptor recognizes 5'-triphosphorylated RNA and triggers a signalling cascade that results in the induction of type-I interferon (IFN)-dependent responses. Its precise regulation represents a pivotal balance between antiviral defences and autoimmunity. To elucidate the cellular cofactors that regulate RIG-I signalling, we performed two global RNA interference analyses to identify both positive and negative regulatory nodes operating on the signalling pathway during virus infection. These factors were integrated with experimentally and computationally derived interactome data to build a RIG-I protein interaction network. Our analysis revealed diverse cellular processes, including the unfolded protein response, Wnt signalling and RNA metabolism, as critical cellular components governing innate responses to non-self RNA species. Importantly, we identified K-Homology Splicing Regulatory Protein (KHSRP) as a negative regulator of this pathway. We find that KHSRP associates with the regulatory domain of RIG-I to maintain the receptor in an inactive state and attenuate its sensing of viral RNA (vRNA). Consistent with increased RIG-I antiviral signalling in the absence of KHSRP, viral replication is reduced when KHSRP expression is knocked down both in vitro and in vivo. Taken together, these data indicate that KHSRP functions as a checkpoint regulator of the innate immune response to pathogen challenge.


Exploring salivary exosomes as early predictors of oral cancer in susceptible tobacco consumers: noninvasive diagnostic and prognostic applications.
Salivary exosome analysis provides a noninvasive and comprehensive approach with potential applications in oral cancer diagnosis and prognosis. The early detection of oral cancer has remained a critical concern in enhancing the quality of life, especially for individuals who consume tobacco and are at greater risk of developing the disease. The current study investigates the potential of salivary exosomes in screening smokers for early signs and transformations of oral cancer. Morphological characterization of salivary exosomes among three study groups (non-smokers as control, smokers as high-risk tobacco consumers, and Oral cancer) (n = 120) was carried out through dynamic light scattering, and nanoparticle tracking analysis. For molecular characterization, EXOCET and Fourier transform infrared spectroscopy methods were utilized. The expression of the exosomal surface protein CD63 was evaluated using Western blotting. Salivary exosomes exhibit noticeable differences in size between control group and tobacco consumers. The differentiation extended beyond exosome size and included variations in concentration and bio-molecular composition, as determined by FTIR screening. Tobacco consumers and oral cancer groups showed significantly larger and more concentrated exosomes compared to the healthy group. Our study provides strong evidence that the properties of salivary exosomes can serve as reliable noninvasive biomarkers for distinguishing tobacco consumers from non-smokers and oral cancer patients. Our results underscore the potential of exosome-based diagnostics in early oral cancer detection for high-risk individuals. The larger size and higher concentration of exosomes in tobacco consumers indicate early changes in cell secretions associated with the transformation from healthy to abnormal cells.


Inhibition of cytokine signaling by ruxolitinib and implications for COVID-19 treatment.
Approximately 15% of patients with coronavirus disease 2019 (COVID-19) experience severe disease, and 5% progress to critical stage that can result in rapid death. No vaccines or antiviral treatments have yet proven effective against COVID-19. Patients with severe COVID-19 experience elevated plasma levels of pro-inflammatory cytokines, which can result in cytokine storm, followed by massive immune cell infiltration into the lungs leading to alveolar damage, decreased lung function, and rapid progression to death. As many of the elevated cytokines signal through Janus kinase (JAK)1/JAK2, inhibition of these pathways with ruxolitinib has the potential to mitigate the COVID-19-associated cytokine storm and reduce mortality. This is supported by preclinical and clinical data from other diseases with hyperinflammatory states, where ruxolitinib has been shown to reduce cytokine levels and improve outcomes. The urgent need for treatments for patients with severe disease support expedited investigation of ruxolitinib for patients with COVID-19.


QUANTITATIVE GENETICS IN PLANTS: THE EFFECT OF THE BREEDING SYSTEM ON GENETIC VARIABILITY.
The expected effects of breeding system on quantitative genetic variation under various models for the maintenance of such variation are examined, with particular emphasis on the contrast between randomly mating and highly self-fertilizing populations. Estimates of quantitative genetic parameters from plant populations are reviewed. There is some evidence for reduced within-population genetic variance in highly inbreeding populations, compared with outbreeders, but more empirical work appears necessary. Although the estimate of the magnitude of the effect of breeding system is subject to considerable error, the reduction in genetic variance in inbreeding populations appears greater than expected if the variation were maintained by overdominance, or if it were due to neutral mutations. It is more consistent with models involving mutation-selection balance, although a rather larger reduction in genetic variance is estimated than is expected theoretically. We discuss some possible reasons for the lower level of genetic variance in selfers than is predicted by such models.


Single-nucleotide polymorphisms in genes related to the hypothalamic-pituitary-adrenal axis as risk factors for posttraumatic stress disorder.
Posttraumatic stress disorder (PTSD) is a common psychiatric disorder. The etiology of PTSD is multifactorial, depending on many environmental and genetic risk factors, and the exposure to life or physical integrity-threatening events. Several studies have shown significant correlations of many neurobiological findings with PTSD. Hypothalamic-pituitary-adrenal (HPA) axis dysfunction is strongly correlated with this disorder. One hypothesis is that HPA axis dysfunction may precede the traumatic event, suggesting that genes expressed in the HPA axis may be involved in the development of PTSD. This article reviews molecular genetic studies related to PTSD collected through a literature search performed in PubMed, MEDLINE, ScienceDirect, and Scientific Electronic Library Online (SciELO). The results of these studies suggest that several polymorphisms in the HPA axis genes, including FKBP5, NR3C1, CRHR1, and CRHR2, may be risk factors for PTSD development or may be associated with the severity of PTSD symptoms.


Reports of social circles' and own vaccination behavior: A national longitudinal survey.
Flu vaccinations are recommended for almost everyone, but uptake may vary because of perceived social norms. We aimed to examine the relationship between perceived social circle vaccine coverage (including family, friends, and acquaintances) and own vaccination behavior as well as potential mediators. In 2011, 357 participants from RAND's American Life Panel reported perceived social circle vaccine coverage for the 2010-2011 flu season, own vaccination behavior for the 2009-2010 and 2010-2011 flu seasons, perceived flu risk without and with vaccination, and perceived vaccine safety. In 2012 and 2016, respectively, participants returned to report their own vaccination behavior for the 2011-2012 flu season (N = 338) and 2015-2016 flu season (N = 216). Perceiving greater percentage of 2010-2011 social circle vaccine coverage was associated with a greater likelihood of getting vaccinated in the 2010-2011 flu season (odds ratio [OR] = 1.03, 95% confidence interval [CI] = 1.01, 1.04) and the subsequent 2011-2012 flu season (OR = 1.02, 95% CI = 1.01, 1.03) but not the 2015-2016 flu season (OR = 1.00, 95% CI = .99, 1.01), as seen in logistic regressions that controlled for demographics and 2009-2010 vaccination behavior. All significant relationships between social circle vaccine coverage and own vaccination behavior were mediated by perceived flu risk without vaccination. Perceived social circle vaccine coverage is associated with own vaccination behavior in the current and subsequent flu season, establishing behavior patterns that may persist into the future. People's vaccination decisions may be informed by their perceptions of their peers' beliefs and behaviors. We discuss intervention strategies for promoting vaccine uptake by counteracting negative and promoting positive perceived social norms. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Phenotypic Analysis of Growth and Morphological Traits in Miniature Breeds of Japanese Indigenous Chickens.
Japanese indigenous chickens include approximately 50 breeds exhibiting various morphological traits, such as a long tail. These genetic resources will be important for revealing the genetic basis of morphological traits in the future. However, little is known about the phenotypic characteristics of each breed during the growth stages. To understand age-dependent changes in growth and morphological traits, we investigated tail length, tail number, body weight, and shank length at several time points using three genetically distinct Japanese indigenous chicken breeds. A total of 155 birds from the Tosa-jidori, Chabo, and Minohikichabo breeds were used for trait measurements from 1 to 36 weeks of age to reveal breed and sex effects. Significant sex differences through the growth stages were observed for all traits except for tail number. Although there were no clear breed differences in tail length traits at the 6- and 20-week stages, Minohikichabo ultimately had a significantly longer tail due to extended tail feather growth at later stages (28 and 36 weeks). By measuring two tail length variables (central and maximum), it was revealed that the shape of the tail feathers varies with the growth stage. Minohikichabo's tail number was higher than that of Tosajidori and Chabo at earlier ages (8 and 16 weeks), which leads to an elegant visual in Minohikichabo. Tosa-jidori's body weight was higher than that of Chabo and Minohikichabo, whereas the shank lengths of Chabo and Minohikichabo were shorter than those of Tosa-jidori. These differences in body weight and shank length were consistent from the early to late growth stages. These results revealed the age-dependency of growth and morphological trait breed characteristics.


Mercury toxicity and dental amalgam.
There is adequate evidence that dental amalgam restorations, during and after placement, results in the release of Hg into the patient's body. Whether the Hg released from amalgam is due to placement procedures, surface abrasion, or later corrosion breakdown, there is evidence that a low level Hg release continues for years. It is generally agreed that if amalgam was introduced today as a restorative material, they would never pass F.D.A. approval. With new and more accurate techniques of measuring Hg levels, especially in tissue and blood, additional studies are necessary to relate blood-Hg levels with dental amalgam restorations. Studies must relate existing restorations as well as the placement of new restorations to body-Hg levels. It is possible that we have accepted a potentially dangerous material as being safe.


Quitting marijuana.
Marijuana quitters, continuing users and never-users were compared. Never-users are found to be more conservative, traditional, and strongly identified with their parental role models. Continuing users are more unconventional, involved in risk-taking behavior, and lacking a stable identity. Quitters are intermediate in cultural attitudes and stance. They have the highest rate of determined ego identify, but have more often reported problems with intimacy and have more often sought help for emotional problems. Three types of quitters are identified: the experimenter whose use was a social accident, the ex-rebel who used marijuana during the post adolescent stage of psychosocial moratorium, and the emotionally fragile individual for whom marijuana was psychologically threatening.


Chronic myelocytic leukemia: eosinophils involved in the malignant clone.
Chronic myelocytic leukemia (CML) is a clonal disorder involving neutrophil, monocyte, erythrocyte, and platelet precursors. In order to determine if the eosinophils are also involved in the leukemic clone, we purified the eosinophils from a woman heterozygous for the common electrophoretic variants of the G6PD gene. Only type B enzyme was demonstrable in the eosinophils, neutrophils, and red cells, but both A and B enzymes were found in the fibroblasts. The data provide evidence that the eosinophil is involved in the malignant clone.


High-spin states (S >/= 5/2) of the photosystem II manganese complex.
The Mn4 complex which is involved in water oxidation in photosystem II (PSII) is known to exhibit two types of EPR signals in the S2 state, one of the five redox states of the enzyme cycle: either a multiline signal (S = 1/2) or a signal at g = 4.1 (S = 3/2 or S= 5/2). The S = 1/2 state can be converted to that responsible for the g = 4.1 signal upon the absorption of near-infrared (IR) light [Boussac, A., Girerd, J.-J., and Rutherford, A.W. (1996) Biochemistry 35, 6984-6989]. It is shown here that a third state gives rise to signals at g = 10 and 6. This state is formed by IR illumination of the S = 1/2 state at 65 K, a temperature where IR illumination leads to the loss of the S = 1/2 signal but to no formation of the g = 4.1 state. On the basis of the corresponding decrease of the S = 1/2 state, the new state can be trapped in approximately 40% of the PSII centers. Warming of the sample above 65 K, in the dark, leads to the loss of the g = 10 and 6 resonances with the corresponding appearance of the g = 4.1 signal. It is suggested that the IR-induced conversion of the S = 1/2 state into the g = 4.1 state at 150 K involves the transient formation of the new state. The new state is attributed to a S = 5/2 state of the Mn4 complex (although a S value > 5/2 is also a possibility). Spectral simulations indicate an E/D ratio of -0.05 with D </= 1 cm-1. The resonances at g = 10 and 6 correspond to the gz of the +/-5/2 and +/-3/2 transition, respectively. The temperature-dependent conversion of this S = 5/2 state into the g = 4.1 state is proposed to be due to relaxation of the ligand environment around the Mn4 cluster that leads to a change in the zero field splitting parameters, assuming an S = 5/2 value for the g = 4.1 state. The new form of the S2 state reported here may explain some earlier data where the S2 state was present and yet not detectable as either a S = 1/2 or a g = 4.1 EPR signal.


Evaluation by double-blind placebo-controlled oral challenge of the clinical relevance of IgE antibodies against plant glycans.
The clinical relevance of immunoglobulin E (IgE) to plant glycans is a longstanding debate. We sought to evaluate their clinical reactivity using the human glycoprotein lactoferrin expressed in rice. Allergic patients with IgE antibodies against plant glycans were analyzed for the presence of IgE against rice-produced lactoferrin. The potency of IgE to induce mediator release was assessed by basophil histamine release and skin prick tests (SPTs). Clinical relevance was evaluated by double-blind placebo-controlled oral challenge (DBPCOC). Twenty-four of 29 sera (82.7%) with IgE antibodies against plant glycans demonstrated IgE binding to transgenic lactoferrin. In three of five cases transgenic lactoferrin induced histamine release. Compared to a control major grass pollen allergen lactoferrin concentrations needed for biological activity of IgE were 5-6 orders of magnitude higher. Skin prick test and DBPCOC were negative in five patients with potential clinical reactivity that volunteered to undergo these in vivo challenges. Poor or no biological activity and lack of clinical relevance of IgE-binding plant glycans (five out of five) was demonstrated using human lactoferrin expressed in rice as a model.


Nidotherapy in the successful management of comorbid depressive and personality disorder.
Nidotherapy is a new form of psychological therapy that aims to improve mental health by a systematic and collaborative manipulation of the environment in all its forms without focusing on alleviation of symptoms. Following treatment with nidotherapy, we describe a dramatic, and continuing, improvement in a woman with comorbid severe depressive illness and borderline personality disorder. She had made repeated serious suicide attempts over the previous 25 years and had received many drug and psychological treatments without success. The nidotherapy solution enabled her to leave home and achieve greater autonomy. Prior to this, she had been demeaned and undermined in her role as a family carer, and no health professionals had appreciated previously the restrictions it had placed on her health and well-being. Nidotherapy effected a smooth and orderly transition with family approval; the reasons for this seem to lie in the emotional neutrality of nidotherapy as a purely environmental intervention. Without this approach, we judge that separation from the family would not have been possible. Copyright © 2017 John Wiley & Sons, Ltd.


Association Between Motor Competence, Physical Fitness, and Academic Achievement in Physical Education in 13- to 16-Year-Old School Children.
In physical education (PE), both assessment practices and choice of teaching content indicate that pupil-related factors such as motor competence and physical fitness potentially influence pupils' academic achievement in PE. However, neither of these factors are explicitly expressed as assessment criteria in the Norwegian PE-curriculum. Hence, the aim of the current study was to investigate potential differences in motor competence and physical fitness between pupils with different academic achievements in PE. Forty-five boys and 31 girls (N = 76) from grades 8 to 10 in the lower secondary school participated in this study. In addition to collecting pupils' final grade in PE, as a proxy for academic achievement, they were assessed on the Test of Motor Competence (placing bricks, building bricks, heal-to-toe-walking, and walking/running in slopes) and four task items from the Test of Physical fitness (standing broad jump, pushing medicine ball, running 20 m as fast as possible, and reduced Cooper test). In the main analysis, the total score for motor competence and physical fitness, as well as their respective task items, were compared between pupils with different grades (i.e., 3 or 4, 5, 6). A one-way ANOVA revealed neither significant difference between pupils with different grades in overall motor competence (total score) nor the respective task items for fine motor assessment or the gross motor task heal-to-toe-walking. However, there was a large difference between pupils with different grades in performance of the gross motor task walking/running in slopes, where pupils receiving a grade of 6 and 5 completed the task significantly faster compared to their peers with a grade of 3 or 4. Furthermore, a one-way ANOVA indicated moderate-to-large differences between pupils with different grades in the total score of physical fitness and performance in three of the four respective task items (i.e., standing broad jump, running 20 m as fast as possible, and reduced Cooper test). Pupils with a grade of 6 had a significantly greater total score of physical fitness and jumped longer compared to pupils with a grade of 5 and 3 or 4. Additionally, pupils with a grade of 6 ran significantly faster as opposed to pupils with a grade of 3 or 4. Performance on the reduced Cooper test was significantly different between all groups of grades, with the distance covered being progressively increased from pupils receiving a grade of 3 or 4 to 6, respectively. These results indicate that physical fitness levels and one component of motor competence may influence pupils' academic achievement in PE. Since neither certain levels of gross motor competence nor physical fitness are explicitly stated as assessment criteria in the Norwegian PE curriculum, these findings may indicate a lack of alignment between PE-teachers' assessment practice and the curriculum's intentions. It is argued that PE-teachers should be aware of how these individual constraints may influence pupils' academic achievement in PE so that all pupils are given equal opportunities to meet the described learning outcomes.


[Microwave tumor coagulation (MTC) in liver tumor: indication and percutaneous approach].
Indications for microwave tumor coagulation (MTC) and percutaneous approach in liver tumor were investigated. The study population comprised 26 patients with unresectable liver tumor (4 with hepatocellular carcinoma, 22 with metastatic liver tumor) who underwent MTC at our department after April 1990. Concomitant therapies were alcohol injection in 2 patients, hepatectomy in 12 and selective arterial chemotherapy in 20. Percutaneous MTC was performed on 2 patients with a single lesion under general anesthesia. Following tip coagulation electrode penetration under echo guidance, the lesion was thermally coagulated at 60W. To establish indications for MTC by the effect of thermal coagulation, survival periods were compared by underlying disease, number of masses coagulated, and maximum tumor size, in 23 patients who had undergone MTC at least 1 year previously. Thirteen of these 23 survived for 1 year or longer, including all 3 with hepatocellular carcinoma, 3 with breast cancer, 2 with leiomyosarcoma (gastric, small intestine), 4 of the 10 with colon cancer and 1 of the 2 with pancreatic cancer. According to evaluation of the degree of coagulation, complete coagulation was obtained in 11 of 23, all of whom had at most 6 tumor masses (of up to 3 cm in diameter) coagulated, and 9 of whom survived for 1 year or longer. Percutaneous MTC, of low invasiveness, proved useful as a tool of regional cancer therapy.


Treatment of periodontal intrabony defects using β-TCP alone or in combination with rhPDGF-BB: a randomized controlled clinical and radiographic study.
The need to increase the predictability of periodontal regeneration has encouraged clinicians and researchers to employ cell-stimulating proteins in combination with osteoconductive scaffolds, based on the principles of tissue engineering. The purpose of this clinical and radiographic study was to compare the regenerative potential of the combination of β-tricalcium phosphate (β-TCP) and recombinant human platelet-derived growth factor BB (rhPDGF-BB) in the grafting of intraosseous defects with the established technique of bone grafting with (β-TCP alone. A total of 30 sites from 15 patients with infrabony defects in two different quadrants were selected, and the sites were randomly divided into test sites (rhPDGF + β-TCP) and control sites (β-TCP alone) using a split-mouth design. Clinical parameters, including probing pocket depth, clinical attachment level, and gingival recession, were recorded at baseline, 6 months, and 9 months. Radiographic evaluation was carried out to evaluate defect fill, change in alveolar crest height, and percentage of defect fill at baseline, 6 months, and 9 months. Both the experimental groups showed statistically significant reduction in probing pocket depth and gain in clinical attachment level. On intergroup comparison, sites treated with rhPDGF + β-TCP demonstrated a significantly greater pocket depth reduction (P < .05) and greater gain in clinical attachment level (P < .01). Mean percentage defect fill was significantly greater in test sites as compared with control sites at 6 and 9 months (P < .01). rhPDGF + β-TCP-treated sites demonstrated a significant gain in mean alveolar crest height at 6 and 9 months (P < .05), while β-TCP-treated sites demonstrated crestal resorption. Both groups demonstrated potential in enhancing periodontal regeneration; however, on comparison between the two groups, the results obtained by rhPDGF + β-TCP were significantly better with respect to both clinical and radiographic parameters.


Particulate Matter 2.5 Induced Developmental Cardiotoxicity in Chicken Embryo and Hatchling.
Particulate matter poses health risk to developing organisms. To investigate particulate matters with a diameter smaller than 2.5 um (PM2.5)-induced developmental cardiotoxicity, fertile chicken eggs were exposed to PM2.5 via air cell injection at doses of 0.05, 0.2, 0.5, 2, and 5 mg/egg kg. Morphological changes in the embryonic day four (ED4) and hatchling hearts were assessed with histological techniques. Heart rates of hatchling chickens were measured with electrocardiography. The protein expression levels of nuclear factor kappa-light-chain-enhancer of activated B cells p65 (NF-kb p65), inducible nitric oxide synthase (iNOS), and matrix metallopeptidase 9 (MMP9) were assessed with immunohistochemistry or western blotting in hatchling hearts. PM2.5 exposure elevated areas of heart in ED4 embryo, increased heart rate, and thickened right ventricular wall thickness in hatchling chickens. Immunohistochemistry revealed enhanced NF-kb p65 expression in hatchling hearts. Western blotting results indicated that both iNOS and MMP9 expression were enhanced by lower doses of PM2.5 exposure (0.2 and 0.5 mg/kg) but not 2 mg/kg. In summary, developmental exposure to PM2.5 induced developmental cardiotoxicity in chicken embryo and hatchling chickens, which is associated with NF-kb p65, iNOS, and MMP9.