Essential oil composition of Alseodaphne perakensis (Gamble) Kosterm from Malaysia.
The chemical composition of the essential oil from the leaves of Alseodaphne perakensis (Gamble) Kosterm (Lauraceae) growing in Perak, Malaysia was investigated for the first time. The essential oil was obtained by hydrodistillation and fully characterized by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). A total of 37 components (90.9 ± 2.5%) were successfully identified in the essential oil which were characterized by high proportions of bicyclogermacrene (15.8 ± 0.5%), δ-cadinene (11.7 ± 0.2%), γ-cadinene (6.3 ± 0.4%), and aromadendrene (5.6 ± 0.5%).


Optimizing the Extraction and Enrichment of Luteolin from Patrinia villosa and Its Anti-Pseudorabies Virus Activity.
Luteolin from Patrinia villosa exhibits strong antiviral activity. Here, the conditions for extracting and enriching luteolin from P. villosa were optimized. Response surface methodology was used to determine the optimal extraction parameters in terms of reflux time, solvent ratio, extraction temperature, material-to-liquid ratio, and number of extractions. Thereafter, a macroporous resin method was used to enrich luteolin from P. villosa. Finally, the following optimal extraction and enrichment conditions were established: an extraction time of 43.00 min, a methanol/hydrochloric acid solvent ratio of 13:1, an extraction temperature of 77.60 °C, a material/liquid ratio of 1:22, and a total of two extractions. NKA-9 was determined to be the most appropriate resin for enrichment. The ideal adsorption conditions were as follows: a pH of 5.0, a temperature of 25 °C, an initial luteolin concentration of 19.58 µg/mL, a sample loading volume of 2.9 BV, and a sample loading rate of 2 BV/h. The ideal desorption conditions were as follows: distilled water, 30% ethanol and 80% ethanol elution, and 5 BV at a flow rate of 2 BV/h. After optimization, the enrichment recovery rate was 80.06% and the luteolin content increased 3.8-fold. Additionally, the enriched product exhibited a significant inhibitory effect on PRV (Porcine pseudorabies virus) in vitro and in vivo, providing data for developing and applying luteolin from P. villosa.


Silica based hybrid materials for drug delivery and bioimaging.
Silica hybrid materials play an important role in improvement of novel progressive functional nanomaterials. Study in silica hybrid functional materials is supported by growing interest in providing intelligent materials that combine best of the inorganic silica structure along with organic or biological realms. Hybrid silica materials do not only provide fantastic opportunities for the design of novel materials for research but their represented unique properties open versatile applications specifically in nanomedicine since it was recognized by US FDA as a safe material for human trials. By combining various materials with different characteristics along with silica NPs as building blocks, silica-based hybrid vehicles were developed. In this regard, silica-based hybrid materials have shown great capabilities as unique carriers for bioimaging and/or drug delivery purposes. In the aforementioned hybrid systems, silica was preferred as a main building block of the hybrid structure, which is easily functionalized with different materials, bio-molecules and targeting ligands while providing biocompatibility for the system. This review will cover a full description of different hybrids of silica nanoparticles including silica-polymer, silica-protein, silica-peptide, silica-nucleic acid, silica-gold, silica-quantum dot, and silica-magnetic nanoparticles and their applications as therapeutic or imaging systems.


Regenerative Therapy for the Permanent Immature Teeth: A Long Term Study. An Original Research.
Endodontics faces several clinical difficulties while treating young necrotic permanent teeth. The use of regenerative endodontic procedures (REPs) enables apical closure, improved canal wall thickness, and root growth. The objective of this study was to assess the effects of these regenerative procedures on immature necrotic permanent teeth. This prospective clinical study was conducted at the tertiary care hospital for the study period of 2 years. This study includes 30 necrotic permanent immature teeth that were studied in 30 subjects of both genders. A standard REP protocol was used to treat every tooth. A follow-up visit was scheduled for each patient at timely intervals. Various study parameters as well as the demographics were assessed at each visit. To examine various parameters, a calibrated endodontist also performed a radiographic evaluation. Our findings point to excellent rates of survival, clinical success, and apical pathological resolution for 29 teeth. After 2 years, there were significant variations in the root thickness area and the average root length. The apical diameter significantly decreased during the research period, with 30.8% of the instances exhibiting full apical closure. Apical diameter, root length, and thickness changed more frequently in teeth with the level of the immaturity of the root, although the variations were not significant. REP treatment for teeth preceded symptom relief. Increased root thickness, root length, and apical closure were seen at 30 months, even if the clinically meaningful change was not attained in all patients.


Cost of skeletal-related events in European patients with solid tumours and bone metastases: data from a prospective multinational observational study.
Patients with bone metastases often experience skeletal-related events (SREs: radiation or surgery to bone, pathologic fracture, and spinal cord compression). This study examined health resource utilization and costs associated with SREs. Data presented are from the European cohort (Germany, Italy, Spain, and the UK) of patients with solid tumours enrolled in a multi-national, prospective, observational study in patients with solid tumours or multiple myeloma. Patients with Eastern Cooperative Oncology Group score 0-2 and life expectancy ≥6 months, who experienced an SRE up to 97 days before enrolment, were eligible. Health resource utilization associated with SREs (including number/length of inpatient stays, numbers of procedures and outpatient visits) were collected through chart review for up to 97 days before enrolment and prospectively during follow-up. Country-specific cost calculations were performed. In total, 478 eligible patients contributed 893 SREs to this analysis. Radiation to bone occurred most frequently (66% of total). Spinal cord compression (7%) and surgery to bone (10%) were the least common events, but most likely to require inpatient stays. The most costly SREs were also spinal cord compression (mean per SRE across countries, €4884-€12,082) and surgery to bone (€3348-€9407). Inpatient stays were the main cost drivers. Health resource utilization used to calculate the costs associated with SREs may have been under-estimated as a result of exclusion of patients with low performance status or life expectancy; unavailable information and exclusion of resource consumption associated with pain. Thus, the estimate of associated costs is likely to be conservative. SREs result in considerable health resource utilization, imposing a substantial financial burden driven by inpatient stays. Treatments that prevent/delay SREs may help ease this burden, thereby providing cost savings across European healthcare systems.


Salivary IgA and serum IgA and IgG antibodies to Candida albicans in HIV-infected subjects.
This study sought to determine IgA, IgG antibodies to Candida albicans in whole saliva and serum from HIV-infected patients and to compare them to a group of healthy controls. The study population consisted of 34 HIV-infected individuals free of any other systemic diseases and thirty healthy controls. IgA concentrations in saliva and IgA and IgG concentrations in serum were measured by a micro enzyme-linked immunosorbent assay. No significant differences were observed in salivary and serum IgA antibodies to C. albicans between the two study groups. Serum IgG antibodies were found to be significantly lower in the HIV-infected (P < 0.05). No significant changes were observed in the specific activity of anti-Candida IgA and IgG antibodies in saliva and serum, in both the study groups. The undifferentiated levels of secretory-IgA antibodies to C. albicans in the patients' and the controls' saliva could be an indicator of the high immune response to opportunistic infections of the HIV-infected subjects, a fact that is verified by the lack of oral candidiasis in the patients' group. The low levels of IgG antibodies in the serum of the HIV-infected patients confirm the high immune response of them.


IL-1β increases urinary corin in patients with primary proteinuric kidney diseases and in 293 cells.
Corin is a serine protease that is important for the regulation of blood pressure and water balance. Corin was initially discovered in the heart, however, it has also been detected in kidney cells, though its function in the kidneys is unclear. To further investigate the function of corin in the kidney, the present study analyzed the levels of corin in urine and blood samples collected from normal individuals and patients with primary proteinuric diseases. The associations between the levels of corin, and the cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were then assessed. The results demonstrated that corin was detectable in the urine and plasma following an enzyme-linked immunosorbent assay; the level of corin in the urine was associated with the level of urinary β2-microglobulin (P=0.01), which was indicative of renal tubular injury. When compared with normal individuals, the levels of urinary corin in proteinuric patients were markedly increased (P=0.02), and were also associated with IL-1β (P=0.03). This correlation between corin and IL-1β was confirmed in vitro using 293 cells. As the IL-1β concentrations increased (0, 0.1, 1, 10 ng/ml), an elevation in the level of corin was observed in the culture medium (P<0.01); however, the amount of corin was not markedly altered in the cell lysate (P>0.05). In addition, when TNF-α reached 10 ng/ml, the level of corin in the medium increased significantly when compared with the control group (0 ng/ml; P=0.02), however, no significant difference in corin levels was detected in the cell lysate. The results suggest that the cytokines IL-1β and TNF-α may increase urinary corin in patients with primary proteinuric kidney diseases. Cytokines may accelerate corin shedding from the cell membrane of renal tubule epithelial cells. These findings indicate that corin may be associated with kidney inflammation and injury.


Cathepsin D repairing role in photodamaged skin barrier.
BACKGROUNDS/OBJECTIVES: Cathepsin D plays an important part in maintaining a normal skin barrier. Our previous study found that cathepsin D decreased in chronic photodamaged skin. This study investigated the cathepsin D content change in the stratum corneum (SC) and the repairing role of cathepsin D in chronic photodamaged skin barrier via the application of cathepsin D gel. Cathepsin D gel (0.001%) was applied to chronic photodamaged (sun-exposed forearm) human skin on identical sites (1 cm(2)/area) twice daily for 2 weeks. At 30 min and at 1, 3, 7, and 14 days, skin hydration and transepidermal water loss (TEWL) average values were detected via noninvasive skin detection equipment. Cathepsin D and transglutaminase (TGase)-1 in the skin sublayers were separated and detected via tape stripping, ELISA and Western blot. After 2 weeks of cathepsin D gel application, the skin moisture value increased from 86.8 ± 1.2 to 95.2 ± 2.7 (p < 0.05), while TEWL decreased from 17.88 ± 1.87 to 11.58 ± 2.14 (p < 0.05). Cathepsin D protein was detected in the upper epidermis (12.6 ± 2.6 ng/cm(2)), mid-epidermis (8.4 ± 0.8 ng/cm(2)) and deep epidermis (16.2 ± 2.6 ng/cm(2)) in the cathepsin D gel group compared to the control group (2.2 ± 0.7, 3.0 ± 1.1 and 3.85 ± 1.4 ng/cm(2), respectively; p < 0.05). TGase-1 enzyme expression was upregulated 2.54 ± 0.19 times in the matrix gel-treated skin. These data suggest that cathepsin D gel could increase the SC cathepsin D content and repair the epidermal barrier in chronic photodamaged skin. The mechanism might be related to increasing TGase-1 expression and activity.


Hypoxic Radioresistance: Can ROS Be the Key to Overcome It?
Radiotherapy is a mainstay treatment for many types of cancer and kills cancer cells via generation of reactive oxygen species (ROS). Incorporating radiation with pharmacological ROS inducers, therefore, has been widely investigated as an approach to enhance aerobic radiosensitization. However, this strategy was overlooked in hypoxic counterpart, one of the most important causes of radiotherapy failure, due to the notion that hypoxic cells are immune to ROS insults because of the shortage of ROS substrate oxygen. Paradoxically, evidence reveals that ROS are produced more in hypoxic than normoxic cells and serve as signaling molecules that render cells adaptive to hypoxia. As a result, hypoxic tumor cells heavily rely on antioxidant systems to sustain the ROS homeostasis. Thereby, they become sensitive to insults that impair the ROS detoxification network, which has been verified in diverse models with or without radiation. Of note, hypoxic radioresistance has been overviewed in different contexts. To the best of our knowledge, this review is the first to systemically summarize the interplay among radiation, hypoxia, and ROS, and to discuss whether perturbation of ROS homeostasis could provide a new avenue to tackle hypoxic radioresistance.


Racial disparities in melanoma survival.
Melanoma is a cutaneous malignancy common in the white population but can also occur in other racial groups. We sought to evaluate survival across racial groups in patients given a diagnosis of malignant melanoma. The Surveillance, Epidemiology, and End Results database was used to populate a cohort of 96,953 patients given a diagnosis of cutaneous melanoma as their primary cancer, from 1992 to 2009. White patients had the longest survival time (P < .05), followed by Hispanic (P < .05), Asian American/Native American/Pacific Islander (P < .05), and black (P < .05) patients, respectively. Survival stratified by race and stage showed that for stages I and III, blacks had a significantly lower survival (P < .05), and increased hazard ratios (stage I hazard ratio, 3.037 [95% confidence interval, 2.335-3.951]; stage III hazard ratio, 1.864 [95% confidence interval, 1.211-2.87]). The proportion of later stage cutaneous melanoma (stages II-IV) was greater in blacks compared with whites. Despite higher incidence of cutaneous melanoma in whites, overall survival for cutaneous melanoma in non-whites was significantly lower. Our results suggest that more emphasis is needed for melanoma screening and awareness in non-white populations to improve survival outcomes.


Accessibility of Protein-Bound Chlorophylls Probed by Dynamic Electron Polarization.
The possibility to probe the accessibility of sites of proteins represents an important point to explore their interactions with specific substrates in solution. The dynamic electron polarization of nitroxide radicals induced by excited triplet states of organic molecules is a phenomenon that is known to occur in aqueous solutions. The interaction within the radical-triplet pair causes a net emissive dynamic electron polarization of the nitroxide radical, that can be detected by means of time-resolved electron paramagnetic resonance (TR-EPR) spectroscopy. We have exploited this effect to prove the accessibility of chlorophylls bound to a protein, namely, the water-soluble chlorophyll protein WSCP. The results have important implications for topological studies in macromolecules.


Exploring candidate genes for pericarp russet pigmentation of sand pear (Pyrus pyrifolia) via RNA-Seq data in two genotypes contrasting for pericarp color.
Sand pear (Pyrus pyrifolia) russet pericarp is an important trait affecting both the quality and stress tolerance of fruits. This trait is controlled by a relative complex genetic process, with some fundamental biological questions such as how many and which genes are involved in the process remaining elusive. In this study, we explored differentially expressed genes between the russet- and green-pericarp offspring from the sand pear (Pyrus pyrifolia) cv. 'Qingxiang' × 'Cuiguan' F1 group by RNA-seq-based bulked segregant analysis (BSA). A total of 29,100 unigenes were identified and 206 of which showed significant differences in expression level (log2fold values>1) between the two types of pericarp pools. Gene Ontology (GO) analyses detected 123 unigenes in GO terms related to 'cellular_component' and 'biological_process', suggesting developmental and growth differentiations between the two types. GO categories associated with various aspects of 'lipid metabolic processes', 'transport', 'response to stress', 'oxidation-reduction process' and more were enriched with genes with divergent expressions between the two libraries. Detailed examination of a selected set of these categories revealed repressed expressions of candidate genes for suberin, cutin and wax biosynthesis in the russet pericarps.Genes encoding putative cinnamoyl-CoA reductase (CCR), cinnamyl alcohol dehydrogenase (CAD) and peroxidase (POD) that are involved in the lignin biosynthesis were suggested to be candidates for pigmentation of sand pear russet pericarps. Nine differentially expressed genes were analyzed for their expressions using qRT-PCR and the results were consistent with those obtained from Illumina RNA-sequencing. This study provides a comprehensive molecular biology insight into the sand pear pericarp pigmentation and appearance quality formation.


Molecular‑cytogenetic study of de novo mosaic karyotype 45,X/46,X,i(Yq)/46,X,idic(Yq) in an azoospermic male: Case report and literature review.
The present study describes a 36‑year‑old male with the 45,X/46,X,i(Yq)/46,X,idic(Yq) karyotype, who suffered from azoospermia attributed to maturation arrest of the primary spermatocyte. To the best of our knowledge, this rare karyotype has not yet been reported in the literature. The results of detailed molecular‑cytogenetic studies of isodicentric (idic)Y chromosomes and isochromosome (iso)Y, which are identified in patient with complex mosaic karyotypes, are presented. The presence of mosaicism of the three cell lines 45,X, 46,X,i(Yq) and 46,X,idic(Yq) may be a contributing factor for spermatogenic failure, in addition to the instability of iso/idic Y chromosomes to pass the spermatogenesis process. Possible mechanisms of the formation of the mosaic karyotype and karyotype‑phenotype correlations are discussed. The current study highlights that routine karyotype analysis and fluorescent in situ hybridization‑based technology are more useful in detecting mosaic chromosomal abnormality, predicting the clinical features of patients during genetic counseling and improving artificial reproductive technologies.


High-Throughput Architecture for Discovering Combination Cancer Therapeutics.
The amount of available next-generation sequencing data of tumors, in combination with relevant molecular and clinical data, has significantly increased in the last decade and transformed translational cancer research. Even with the progress made through data-sharing initiatives, there is a clear unmet need for easily accessible analyses tools. These include capabilities to efficiently process large sequencing database projects to present them in a straightforward and accurate way. Another urgent challenge in cancer research is to identify more effective combination therapies. We have created a software architecture that allows the user to integrate and analyze large-scale sequencing, clinical, and other datasets for efficient prediction of potential combination drug targets. This architecture permits predictions for all genes pairs; however, Food and Drug Administration-approved agents are currently lacking for most of the identified gene targets. By applying this approach, we performed a comprehensive study and analyzed all possible combination partners and identified potentially synergistic target pairs for 38 approved targets currently in clinical use. We further showed which genes could be synergistic prediction markers and potential targets with MAPK/ERK inhibitors for the treatment of melanoma. Moreover, we integrated a graph analytics technique in this architecture to identify pathways that could be targeted synergistically to enhance the efficacy of certain therapeutics in cancer. The architecture and the results presented provide a foundation for discovering effective combination therapeutics.


Blood pressure and hypertension distribution in a lower middle class urban community in Pakistan.
To determine the awareness level, blood pressure profile and its correlates in Metroville Health Study and to compare the results with those of Pakistan National Health Survey and National Health and Nutrition Examination Survey of USA. Sample consisted of 400 households of Metroville, included after informed consent. Demographic data was collected and Blood pressure, Cholesterol, Blood Glucose, Height and weight were measured. Obesity was calculated as BMI. The results were compared with those of the Pakistan National Health Survey and National Health and Nutrition Examination Survey of USA. For both sexes and all age groups, hypertension was more prevalent in MHS than Pakistan National Health Survey (PNHS) and U.S. MHS hypertensives were more likely to be aware of and treated for their condition than hypertensives of PNHS, but less likely than U.S. hypertensives. Systolic and diastolic blood pressure (DBP) rose with increased age in all three populations. Blood pressure also rose with increased body mass index (BMI) in MHS as well as PNHS and NHANES, with little differences in the degree of rise among them. A one-kg/Height (in m approximately) increment in BMI was associated with a 0.40-0.67 mmHg increment in systolic pressure in men and a 0.56-0.74 mmHg increment in women. The main difference between USA and two Pakistani surveys was the level of DBP, which was significantly higher in Pakistani Surveys than NHANES, for both men and women. The prevalence of Hypertension in Metroville was high. It showed a quantitative relationship to increasing age and BMI. Hypertension and obesity were the major public health problems in the lower middle class community of Metroville. It is recommended that awareness should be increased and preventive measures implemented.


Femoral Nerve Block versus Adductor Canal Block for Analgesia after Total Knee Arthroplasty.
Inadequate pain management after total knee arthroplasty (TKA) impedes recovery, increases the risk of postoperative complications, and results in patient dissatisfaction. Although the preemptive use of multimodal measures is currently considered the principle of pain management after TKA, no gold standard pain management protocol has been established. Peripheral nerve blocks have been used as part of a contemporary multimodal approach to pain control after TKA. Femoral nerve block (FNB) has excellent postoperative analgesia and is now a commonly used analgesic modality for TKA pain control. However, FNB leads to quadriceps muscle weakness, which impairs early mobilization and increases the risk of postoperative falls. In this context, emerging evidence suggests that adductor canal block (ACB) facilitates postoperative rehabilitation compared with FNB because it primarily provides a sensory nerve block with sparing of quadriceps strength. However, whether ACB is more appropriate for contemporary pain management after TKA remains controversial. The objective of this study was to review and summarize recent studies regarding practical issues for ACB and comparisons of analgesic efficacy and functional recovery between ACB and FNB in patients who have undergone TKA.


Update in three-dimensional imaging in facial plastic surgery.
Facial plastic surgeons have always relied on photography for preoperative and postoperative analysis, medicolegal documentation, and communication. The current standards for analysis and documentation of facial structures have been determined by obtaining measurements and parameters from two-dimensional photographs or radiographs. However, the face and neck are three-dimensional structures and require manipulation in three planes within the constraints of esthetics, stability, and function. Recent advances in technology have made three-dimensional imaging and analysis possible. The ability to capture images in three dimensions has opened up new avenues for observation and has increased the ability to analyze changes after surgery. Whereas only linear distances, angles, and areas can be determined by use of two-dimensional images, soft tissue volumetric data and surface topography can also be measured accurately; this can be helpful in validating changes in patients undergoing aging facial or orthognathic procedures. Recent studies have focused on descriptions of imaging techniques, validation of measurements, and the creation of normative data and its applications in surgery. The availability of three-dimensional imaging and software systems presents new opportunities for the facial cosmetic surgeon to plan, execute, and assess the outcomes in patients undergoing surgery of the face and neck.


Allogeneic Decellularized Muscle Scaffold Is Less Fibrogenic and Inflammatory than Acellular Dermal Matrices in a Rat Model of Skeletal Muscle Regeneration.
Skeletal muscle trauma can produce grave functional deficits, but therapeutic options remain limited. The authors studied whether a decellularized skeletal muscle scaffold would provide benefits in inducing skeletal muscle regeneration over acellular dermal matrices. Eighty-two rat muscle defects were surgically created and assigned to no intervention or implantation of AlloDerm, Strattice, decellularized rat muscle, or decellularized rat dermis to 30 or 60 days. Decellularized rat muscle and dermis were prepared using a negative pressure-assisted protocol. Assessment for cellularity, neovascularization, myogenesis, inflammation and fibrosis were done histologically and by polymerase chain reaction. Histology showed relative hypercellularity of AlloDerm (p < 0.003); Strattice appeared encapsulated. Immunofluorescence for CD31 and myosin heavy chain in decellularized rat muscle revealed dense microvasculature and peripheral islands of myogenesis. MyoD expression in muscle scaffolds was 23-fold higher than in controls (p < 0.01). Decellularized rat muscle showed no up-regulation of COX-2 (p < 0.05), with less expression than decellularized rat dermis and Strattice (p < 0.002). Decellularized rat muscle scaffolds expressed tumor necrosis factor-α less than Strattice, AlloDerm, and decellularized rat dermis (p < 0.01); collagen-1a less than decellularized rat dermis and Strattice (p < 0.04); α-smooth muscle actin 7-fold less than AlloDerm (p = 0.04); and connective tissue growth factor less than Strattice, AlloDerm, and decellularized rat dermis (p < 0.02). Decellularized muscle matrix appears to reduce inflammation and fibrosis in an animal muscle defect as compared with dermal matrices and promotes greater expression of myocyte differentiation-inducing genes.


Physical and chemical properties of DMP 504, a polyalkylammonium-based bile acid sequestrant.
The purpose of this study was to characterize the physicochemical properties of DMP 504 and lay the foundation for formulation development. Thermal properties were characterized by DSC and TGA and moisture sorption and desorption by TGA. The association rate and equilibrium binding capacity of the polymer for a prototype bile acid was evaluated using cholic acid, and solid state stability was examined at 25 degrees C, 40 degrees C (with and without 5% added water), 60 degrees C, and 600 foot candles/25 degrees C. The solid state excipient compatibility of binary mixtures of DMP 504 and several commonly used pharmaceutical excipients was also evaluated. Thermal analysis of the polymer showed a glass transition temperature at approximately 95 degrees C and no melting point, indicating a highly amorphous macromolecular structure with thermal stability up to 250 degrees C. Moisture sorption and desorption isotherms at controlled humidity ranging from 11% to 97% RH did not display hysteresis. Cholic acid associated with DMP 504 extremely rapidly so that binding was essentially complete within 5 min. Scatchard analysis of the equilibrium binding of cholic acid to DMP 504 was unconventional, and indicated that the system was exhibiting positive cooperative behavior. Modeling the binding curve for a system exhibiting cooperative behavior indicated a maximum binding capacity of DMP 504 for cholic acid in phosphate buffered saline (pH 7.0) of 4.9 mumol/mg, and a cooperativity value, P, of 2.2 implying that binding of one molecule promotes the binding of additional molecules. DMP 504, a hygroscopic, amorphous cross-linked polymer with a tendency to gain or lose moisture with ease, is stable in the solid state, either drug substance alone or in presence of excipients, at normal storage temperatures and light, and under controlled conditions of humidity.


Mass spectral properties of volatile derivatives of thyronine (T0) and use of these in the study of thyronine excretion in eu-, hyper- and hypothyroidism.
The mass spectral properties of four classes of derivatives of thyronine are discussed ( oxazolidinone , O-methyl oxazolidinone , O-acetyl oxazolidinone and N,O- diheptafluorobutyryl methyl ester). An assay for thyronine in human urine is described based on the N,O- diheptafluorobutyryl methyl ester. Results of T0 excretion in euthyroid humans were compared with those obtained previously using an assay based on the O-acetyl oxazolidinone derivative. Patients with frank hyperthyroidism had significantly higher T0 excretion than euthyroid subjects (2 alpha less than 0.002) and hypothyroid patients lower T0 excretions than euthyroid subjects (2 alpha less than 0.002). Some overlap between the two pathological ranges and the normal euthyroid range was evident.


Overview of on-farm bioremediation systems to reduce the occurrence of point source contamination.
Contamination of ground and surface water puts pressure on the use of pesticides. Pesticide contamination of water can often be linked to point sources rather than to diffuse sources. Examples of such point sources are areas on farms where pesticides are handled and filled into sprayers, and where sprayers are cleaned. To reduce contamination from these point sources, different kinds of bioremediation system are being researched in various member states of the EU. Bioremediation is the use of living organisms, primarily microorganisms, to degrade the environmental contaminants into less toxic forms. The systems available for biocleaning of pesticides vary according to their shape and design. Up till now, three systems have been extensively described and reported: the biobed, the Phytobac and the biofilter. Most of these constructions are excavations or different sizes of container filled with biological material. Typical overall clean-up efficiency exceeds 95%, realising even more than 99% in many cases. This paper provides an overview of the state of the art of these bioremediation systems and discusses their construction, efficiency and drawbacks.


Biodiversity and Resilience of Ecosystem Functions.
Accelerating rates of environmental change and the continued loss of global biodiversity threaten functions and services delivered by ecosystems. Much ecosystem monitoring and management is focused on the provision of ecosystem functions and services under current environmental conditions, yet this could lead to inappropriate management guidance and undervaluation of the importance of biodiversity. The maintenance of ecosystem functions and services under substantial predicted future environmental change (i.e., their 'resilience') is crucial. Here we identify a range of mechanisms underpinning the resilience of ecosystem functions across three ecological scales. Although potentially less important in the short term, biodiversity, encompassing variation from within species to across landscapes, may be crucial for the longer-term resilience of ecosystem functions and the services that they underpin.


Apoptosis induced by DNA primase inhibitor 3,3'-diethyl-9-methylthia-carbocyanine iodide in human leukemia HL-60 cells.
To investigate apoptosis induced by 3,3'-diethyl-9-methylthia-carbocyanine iodide (DMTCCI), an inhibitor of DNA primase found in our previous study, and the mechanism of DMTCCI in human myelogenous leukemia HL-60 cells. HL-60 cells were cultured in RPMI-1640 medium and treated with different concentrations of DMTCCI. MTT assay was used to detect growth inhibition. Flow cytometry and DNA ladders were used to detect apoptosis. Western blotting was used to observe the expression of survivin, Bcl-xL, Bad, Bax, Bcl-2, caspase-9, caspase-3, caspase-6, PARP, DFF45 and lamin B protein. Caspase-3 activity was measured by ApoAlert Caspase-3 Assay Kit. DMTCCI inhibited proliferation of human leukemia HL-60 cells with IC50 value of 0.24 micromol x L(-1). The results of flow cytometry and DNA ladders showed that DMTCCI could induce apoptosis of HL-60 cells. The expression levels of protein survivin and Bcl-xL were down-regulated, Bad and Bax were up-regulated, while Bcl-2 protein had no change in response to DMTCCI treatment in HL-60 cells. Treatment of HL-60 cells with DMTCCI induced the proteolytic cleavage of caspase-9, caspase-3, caspase-6, PARP, DFF45 and lamin B protein. Caspase-3 activity apparently increased at 3 h and reached a peak at 12 h after exposure to 1 micromol x L(-1) of DMTCCI in HL-60 cells. DMTCCI inhibited proliferation and induced apoptosis of human leukemia HL-60 cells. Bcl-2 family proteins, survivin and caspases family proteins might play a role in the apoptosis process induced by DMTCCI.


Characterization of amino cross-linked soy protein hydrogels.
This study focused on amino cross-linking as means of forming soy protein hydrogels with modifiable properties. The efficiency of glyceraldehyde, a potential food-grade cross-linking agent, was compared to glutaraldehyde, a well-known dialdehyde. The influence of the concentration of these agents on the degree of cross-linking as well as macroscopic and supramolecular properties was studied. The effect of increasing the cross-linker concentration was mainly an increase in degree of cross-linking and gel storage modulus (G') and a decrease in gel swelling ratio and increase in gel deswelling ratio. However, the cross-linking influence was less pronounced in the case of glyceraldehyde. Glutaraldehyde displayed greater ability to form hydrogels with modifiable properties. Finally, electron micrographs suggested that cross-linking agent type had no impact on gel microstructure.


Selective Blockade of the Metabotropic Glutamate Receptor mGluR5 Protects Mouse Livers in In Vitro and Ex Vivo Models of Ischemia Reperfusion Injury.
2-Methyl-6-(phenylethynyl)pyridine (MPEP), a negative allosteric modulator of the metabotropic glutamate receptor (mGluR) 5, protects hepatocytes from ischemic injury. In astrocytes and microglia, MPEP depletes ATP. These findings seem to be self-contradictory, since ATP depletion is a fundamental stressor in ischemia. This study attempted to reconstruct the mechanism of MPEP-mediated ATP depletion and the consequences of ATP depletion on protection against ischemic injury. We compared the effects of MPEP and other mGluR5 negative modulators on ATP concentration when measured in rat hepatocytes and acellular solutions. We also evaluated the effects of mGluR5 blockade on viability in rat hepatocytes exposed to hypoxia. Furthermore, we studied the effects of MPEP treatment on mouse livers subjected to cold ischemia and warm ischemia reperfusion. We found that MPEP and 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) deplete ATP in hepatocytes and acellular solutions, unlike fenobam. This finding suggests that mGluR5s may not be involved, contrary to previous reports. MPEP, as well as MTEP and fenobam, improved hypoxic hepatocyte viability, suggesting that protection against ischemic injury is independent of ATP depletion. Significantly, MPEP protected mouse livers in two different ex vivo models of ischemia reperfusion injury, suggesting its possible protective deployment in the treatment of hepatic inflammatory conditions.


Differentiation between non-hypervascular pancreatic neuroendocrine tumors and mass-forming pancreatitis using contrast-enhanced computed tomography.
Non-hypervascular pancreatic neuroendocrine tumors (PNETs) showed slight or iso-enhancement in contrast-enhanced computed tomography (CE-CT), which shared similar imaging findings with mass-forming pancreatitis (MFPs). To explore the value of CT imaging features in differentiating the two diseases. Fifty-one patients with histologically proved MFPs (n = 27) or non-hypervascular PNETs (n = 24) were included. Two radiologists reviewed CT imaging findings and clinical features. Logistic regression analysis was performed to identify relevant features in differentiating non-hypervascular PNETs and MFPs. Receiver operating characteristic (ROC) curve analysis was used to show the performance of the optimal parameters in differentiating non-hypervascular PNETs and MFPs. A well-defined margin was more common in non-hypervascular PNETs (P < 0.05) than that in MFPs. MFPs often occurred in older people (P < 0.01) and the head-neck of the pancreas compared with non-hypervascular PNETs (P < 0.05). Metastases only presented in non-hypervascular PNETs (P < 0.05). CT values at venous phase and delay phase of MFPs were higher (P = 0.010 and P = 0.029) than those in non-hypervascular PNETs. Logistic analysis showed gender, tumor margin, CT values at venous phase, and tumor components were independent predictors in differentiating the two lesions. The area under the curve (AUC) was 0.938 with a sensitivity of 87.5% and specificity of 92.6% for combined predicators. Gender, tumor margin, CT values at venous phase, and tumor components were useful predicators in differentiating non-hypervascular PNETs and MFPs.


Generating EQ-5D-3L Utility Scores from the Dermatology Life Quality Index: A Mapping Study in Patients with Psoriasis.
To develop an algorithm to predict the three-level EuroQol five-dimensional questionnaire (EQ-5D-3L) utility scores from the Dermatology Life Quality Index (DLQI) in psoriasis. This mapping study used data from the British Association of Dermatologists Biologic Interventions Register-a pharmacovigilance register comprising patients with moderate to severe psoriasis on systemic therapies. Conceptual overlap between the EQ-5D-3L and DLQI was assessed using Spearman rank correlation coefficients and exploratory factor analysis. Six regression methods to predict the EQ-5D-3L index (direct mapping) and two regression methods to predict EQ-5D-3L domain responses (response mapping) were tested. Random effects models were explored to account for repeated observations from the same individual. Estimated and actual EQ-5D-3L utility scores were compared using 10-fold cross-validation (in-sample) to evaluate predictive performance. Final models were selected using root mean squared error, mean absolute error, and mean error. The data set comprised 22,085 observations for which DLQI and EQ-5D-3L were recorded on the same day. A moderate correlation was found between the measures (r = -0.47). Exploratory factor analysis showed that two EQ-5D-3L domains (pain/discomfort and depression/anxiety) were associated with all six DLQI domains. The best-performing model used ordinary least squares with DLQI items, age, and sex as explanatory variables (with squared, cubic, and interaction terms). A tool was produced to allow users to map their data to the EQ-5D-3L, and includes algorithms that require fewer variables (e.g., total DLQI scores). This study produced mapping algorithms that can generate EQ-5D-3L utility scores from DLQI data for economic evaluations of health interventions for patients with psoriasis.


Neurogenic appendicopathy: clinical, macroscopic, and histopathological presentation in pediatric patients.
The proliferation of nerve fibers in the appendix, in association with an increase of the neuropeptides such as vasoactive intestinal peptide and substance P characterizes neurogenic appendicopathy (NA), which may mimic the symptoms of acute appendicitis (AA). It may be difficult to differentiate this little known distinct pathological entity clinically from AA. The aim of this study is to describe the epidemiology, clinical signs, and histological description of NA in pediatric patients. After institutional review board approval, all appendiceal specimens from children who underwent appendectomy between February 2006 and December 2008 were analyzed. Analysis included age, gender, clinical symptoms, blood tests, intraoperative macroscopic assessment of the appendix, and the histopathological type of NA. NA was diagnosed by hematoxylin-eosin staining and /or S-100 immunochemistry and then classified into different histopathological groups. Of the 385 appendix specimens examined, 29 (7.5%) met the histopathological criteria of NA. The median duration of abdominal pain was 2 days (range, 1 to 7). The surgeon characterized the appendix as follows: not inflamed in 5 (17.2%), acute in 17 (58.6%), phlegmonous in 4 (13.8%), and perforated in 3 patients (10.4%). Histopathological diagnosis of NA classified the specimen as axial neuroma in 2 (7%), mucosal in 12 (41%), and submucosal in 15 cases (52%). NA is a relatively common diagnosis in children. NA must be considered in patients with recurrent right lower quadrant pain or signs of AA, even if intraoperative findings are normal. For these patients, we recommend appendectomy and consideration of a subsequent histopathological workup.


Validity of the Myotest® in measuring force and power production in the squat and bench press.
The purpose of this study was to verify the concurrent validity of a bar-mounted Myotest® instrument in measuring the force and power production in the squat and bench press exercises when compared to the gold standard of a computerized linear transducer and force platform system. Fifty-four men (bench press: 39-171 kg; squat: 75-221 kg) and 43 women (bench press: 18-80 kg; squat: 30-115 kg) (age range 18-30 years) performed a 1 repetition maximum (1RM) strength test in bench press and squat exercises. Power testing consisted of the jump squat and the bench throw at 30% of each subject's 1RM. During each measurement, both the Myotest® instrument and the Celesco linear transducer of the directly interfaced BMS system (Ballistic Measurement System [BMS] Innervations Inc, Fitness Technology force plate, Skye, South Australia, Australia) were mounted to the weight bar. A strong, positive correlation (r) between the Myotest and BMS systems and a high correlation of determination (R2) was demonstrated for bench throw force (r = 0.95, p < 0.05) (R2 = 0.92); bench throw power (r = 0.96, p < 0.05) (R2 = 0.93); squat jump force (r = 0.98, p < 0.05) (R2 = 0.97); and squat jump power (r = 0.91, p < 0.05) (R2 = 0.82). In conclusion, when fixed on the bar in the vertical axis, the Myotest is a valid field instrument for measuring force and power in commonly used exercise movements.


The complete mitochondrial genome of Boccardiella hamata (Annelida: Polychaeta: Spionida).
In this study, the complete mitogenome sequence of Korean Boccardiella hamata was determined. This is the first complete mitogenome in the order Spionida. The complete mitogenome of B. hamata is 17,561 bp in length with 12 protein-coding genes (atp8 gene absent), 23 transfer RNAs, 2 ribosomal RNAs, and 1 control region. Interestingly, the gene arrangement of the 12 PCGs of B. hamata is unique, which is very different from that of the other polychaetes currently known. The phylogenetic tree supported the traditional taxonomic position of Spionidae within subclass Sedentaria.


Pharmacokinetics and safety of injected ornidazole compared to its enantiomer levornidazole in healthy Chinese subjects.
To compare the pharmacokinetics of levornidazole and ornidazole in healthy Chinese subjects after a single intravenous injection, and to determine whether the chiral inversion of levornidazole occurs in vivo. The study was a randomized, open-label, two-period crossover, single-dose design. A total of 12 subjects were enrolled in this study. Subjects received an intravenous injection of either levornidazole sodium chloride injection (200 mL: 0.5 g) or ornidazole sodium chloride injection (200 mL: 0.5 g) once per period. The plasma concentrations of levornidazole, ornidazole, and their metabolites were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Phenix WinNolin software (version 6.4) was used to calculate the pharmacokinetic parameters of levornidazole, ornidazole, and their metabolites. Dexornidazole was not detected in the plasma or urine. After a single intravenous injection of levornidazole or ornidazole, there was no significant difference in Cmax between the two drugs (p < 0.05). The AUC0-∞ and AUC0-t of levornidazole were slightly lower than those of ornidazole. Metabolites M1 and M4 were detected in the plasma of both drugs, and their pharmacokinetic parameters were similar. Metabolites M1, M2, and M4 were present in urine. The average cumulative urinary excretion rates of levornidazole and its metabolites M1 and M4 were: during 0 - 24 hours (8.14 ± 0.80%, 0.560 ± 0.072%, and 1.42 ± 0.19%) and 0 - 60 hours (10.5 ± 1.0%, 0.960 ± 0.084%, and 2.52 ± 0.20%), the average cumulative urinary excretion rates of ornidazole and its metabolites M1 and M4 were: 0 - 24 hours (8.64 ± 0.98%, 0.486 ± 0.074%, and 1.46 ± 0.21%), 0 - 60 hours (11.8 ± 1.0%, 0.888 ± 0.070%, and 2.76 ± 0.20%). The incidence of adverse reactions was similar between the two drugs. No chiral inversion of levornidazole occurred in vivo after intravenous administration of levornidazole. The pharmacokinetic parameters and cumulative excretion rates of levornidazole and ornidazole were similar. The safety results were basically consistent between the two drugs.


Pulmonary Eosinophilic Inflammatory Infiltration Post-Intensive Care in a Nearly Drowned Young Man with Papillary Fibroelastoma: A Rare Complication Discovered by Forensic Autopsy.
Papillary fibroelastoma is a rare benign lesion of heart (1). It is the second most common primary cardiac neoplasm, accounting for 4.4-8% of all tumors of the heart (2). We described a forensic autopsy of a nearly drowned young man with cardiac papillary fibroelastoma who died because of a pulmonary inflammatory infiltration rich in granulocytes after intensive care. This occurrence is rare but possible and should be kept in mind because a lung inflammatory infiltrate rich in eosinophilic granulocytes can be present in different pathological conditions and differential diagnoses are often difficult to do.


Effects of restricted vs. step up dietary adaptation for 6 or 9 days on feedlot performance, feeding behaviour, ruminal and blood variables of Nellore cattle.
This study was designed to determine effects of quantitatively restricted intake of the final finishing diet as a means of dietary adaptation compared with diets increasing in concentrate (step up) over periods of 6 and 9 days on feedlot performance, carcass characteristics, feeding behaviour, blood gas profile and rumen morphometrics of Nellore cattle. One hundred twenty 22-month-old Nellore bulls (352 ± 20 kg) were randomly allocated in 24 pens and fed for 84 days. The experimental design was a completely randomized block with 2 × 2 factorial arrangement of treatments: adaptation using either step up protocol for 6 days or 9 days or restriction protocol for 6 days or 9 days, where the pen (five bullocks/pen; six pens/treatment) was considered the experimental unit. Cattle adapted by step up protocol had significantly greater average daily gain throughout the study when compared to those adapted by restriction protocol, regardless of adaptation length. During the adaptation period, a greater dry matter intake fluctuation was observed for animals maintained on restriction programme when compared to those adapted to the finishing diets using step up protocol. In addition, a protocol × length interaction for rumenitis scores was observed, where the level of injuries to the ruminal wall was significantly higher for the cattle adapted by restriction protocol for 9 days and lower for animals submitted for 9 days to the step up programme. Likewise, a protocol × length interaction for mitotic index was observed, in which cattle adapted by step up protocol for 9 days had lower numbers of cells in mitosis. Thus, the step up protocol led to better feedlot performance, and based on this fact, the length of 9 days promoted better rumen epithelium adaptation of Nellore cattle to high-concentrate diets.


Simulation-based skills training: a qualitative interview study exploring surgical trainees' experience of stress.
Stress can affect the ability to acquire technical skills. Simulation-based training (SBT) courses allow surgical trainees to train their technical skills away from stressful clinical environments. Trainees' subjective experiences of stress during SBT courses on laparoscopic surgery remains understudied. Here, we explored the subjective stress experiences of surgical trainees during mandatory laparoscopic SBT courses. We aimed to obtain a broader understanding of which factors of the simulation training the trainees perceived as eliciting stress. A qualitative study with semistructured individual interviews was undertaken to explore trainees' subjective experiences of stress. Twenty surgical trainees participated while attending courses at a national training center for advanced laparoscopic surgery. Questions explored trainees' stress experiences during the SBT courses with a focus on perceived stressors related to laparoscopic simulation training on two box-trainers and one virtual reality simulator. Interview data were analyzed using inductive, qualitative content analysis methods to identify codes, categories, and themes. Findings indicated that trainees have a variety of stress experiences during laparoscopic SBT. Three main themes were identified to be related to stress experiences: simulation task requirements, psychomotor skill levels and internal pressures, with subcategories such as task difficulty and time requirements, unrealistic haptic feedback and realism of graphics, inconsistent and poor technical performance, and self-imposed pressures and socio-evaluative threats. Insights into surgical trainees' experience of stress during laparoscopic SBT courses showed that some stress experiences were directly related to simulation training, while others were of psychological nature. The technical and efficiency requirements of simulation tasks elicited stress experiences among trainees with less laparoscopic experience and lower levels of psychomotor skills. Self-imposed pressures played an integral part in how trainees mobilized and performed during the courses, suggesting that levels of stress might enhance laparoscopic simulation performance. For course facilitators aiming at optimizing future laparoscopic SBT courses, attending to the realism, providing clarity about learning objectives, and having awareness of individual differences among trainees' technical level when designing the simulation tasks, would be beneficial. Equally important to the laparoscopic SBT is to create a psychological safe learning space in order to reduce the internal pressures of trainees.


Synthesis and isolation of non-chromophore cage-rearranged silsesquioxanes from base-catalyzed reactions.
The nucleophilicity of both ortho- and meta-nitrophenolate anions is strong enough to give substituted products, but their basicity also facilitates cage-rearrangement reactions in polyhedral oligomeric silsesquioxanes (POSS). Anions having a stronger basicity, but weaker nucleophilicity, such as CO32-, gave products only from cage-rearrangement, with the cage expansion products being isolable in multi-gram quantities using conventional column chromatography.


[Exudative senile maculopathy, clinical picture, pathogenesis, prognosis and therapy (author's transl)].
From the literature and our own experience it is evident that choriogenic subretinal vascular proliferation is the most important symptom of senile exudative maculopathy. Prior to proliferation a certain percentage of cases develops an isolated detachment of the retinal pigment epithelium. However, there are cases where already in the predisciform stage vascular proliferations are proved histologically. Photocoagulation can be applied to isolated pigment epithelial detachment, to cases with beginning vascular proliferation, and to late stages in order to accelarate the final scaring.


Recurrent invasive meningococcal infections - quantifying the risk, Germany, 2002 to 2018.
IntroductionInvasive meningococcal disease (IMD) is a rare condition with a high case fatality rate. While most patients suffer from one single episode in life, there is anecdotal evidence for recurrent infection.AimThe German National Reference Laboratory for Meningococci and Haemophilus influenzae (NRZMHi) analysed IMD cases from 2002 to 2018 to retrospectively quantify the risk of recurrent infection.MethodsRecurrent IMD was defined as detection of Neisseria meningitidis in a sample of the same patient more than 30 days after the first episode of IMD.ResultsAmong 5,854 patients with a median observation period of 9.4 years, 14 suffered a second IMD episode and one patient a third one. The risk of a recurrent IMD was 29.4 per 100,000 person-years for survivors of the first episode. Rare serogroups (Y, W, E and Z) were more common in patients with recurrent IMD (p < 0.0001).DiscussionPatients surviving IMD were at least at a 50-fold risk of another IMD episode compared with the general population. The study most likely underestimated the risk of recurrent infection. Increased risk may be due to undiagnosed complement deficiencies. The high risk of re-infection argues for vaccination of patients who have survived IMD.


Long-term memory representations influence perception before edges are assigned to objects.
One way to prioritize limited mental resources for perception is to take into account the familiarity of an object to the perceiver. But does an objects' familiarity influence perception only after an object's shape has been determined, or does it influence the decision of which edges are considered part of that object? Here we compare the influence of target familiarity on whole-object masking (object-substitution masking) with its influence on edge-based masking. Two new aspects of edge-based masking are reported. First, we demonstrate that mask and target edges do not only compete (object trimming) but that mask and target edges can also cooperate (object binding), confirming that these masking effects are indeed occurring during the process of object formation and not after object shape has been determined. Second, we find that object trimming and binding are each less likely if the target is linked with a representation already present in long-term memory. Since trimming and binding effects arise very early in visual perception, these data indicate that existing long term memory representations influence the earliest stages of object assembly, before the system has even decided which edges to include in the object.


Thin-layer gel chromatography of dyed proteins.
Plasma chromatography as a method for ultratrace qualitative and quantitative detection of organic compounds is especially well suited for detection of gas chromatographic effluents. The optimum range of sample quantity is 10(-6) to 10(-12) g for detection and identification of a compound by use of its characteristic positive and negative mobility spectra. The type of reference mobility spectra produced by alkanes, aromatics, esters, halogenated compounds, nitrogenated compounds and organic acids have been previously reported. This study presents the reference mobility spectra produced for lysergic acid diethylamide (LSD), delta9-tetrahydrocannabinol (delta9-THC), digitoxigenin and several biochemical compounds of research significance. LSD and delta9-THC in a mixture can be detected and identified by plasma chromatography positive mobility spectra in quantities of 10(-7) g or less. All the compounds investigated in this study display strong MH+ ions along with other ions primarily of the type (M)NO+, (M)2H+. None of these compounds exhibits negative mobility spectra.


Investigating the Mechanism of Palladium-Catalyzed Radical Oxidative C(sp3 )-H Carbonylation: A DFT Study.
Palladium (Pd)-catalyzed radical oxidative C-H carbonylation of alkanes is a useful method for functionalizing hydrocarbons, but there is still a lack of understanding of the mechanism, which restricts the application of this reaction. In this work, density functional theory (DFT) calculations were carried out to study the mechanism for a Pd-catalyzed radical esterification reaction. Two plausible reaction pathways have been proposed and validated by DFT calculations. The computational results reveal that the generated alkyl radical prefers to add to the carbon monoxide (CO) molecule to form a carbonyl radical before bonding with the Pd species. Radical addition onto Pd followed by CO migratory insertion was unfavorable owing to the high energy barrier of the migratory insertion step. The regioselectivity of the C(sp3 )-H carbonylation was also investigated by DFT. The results show that the regioselectivity is controlled by both the bond dissociation energy of the reacting C-H bond and the stability of the corresponding generated carbon radical. Competitive side reactions also affected the yield and regioselectivity owing to the rapid consumption of the stable radical intermediate.


Remodeling of the Photosynthetic Chain Promotes Direct CO2 Conversion into Valuable Aromatic Compounds.
Directing CO2 conversion using photosynthetic microorganisms offers a promising route to couple CO2 sequestration with petrochemical replacement. However, the low-flux shikimate pathway remains largely unexploited for the synthesis of valuable aromatics. In addition, it is unclear how an enhanced low-flux pathway would influence the photosynthetic chain. We created a powerful metabolic sink by introducing the 2-phenylethanol pathway and an artificial feedback-inhibition-resistant cassette to Synechococcus elongatus. More than 30 % of the fixed carbon was redirected to the shikimate pathway for aromatic synthesis, and carbon fixation and O2 evolution increased significantly. A "self-remodeling" mechanism of the photosynthetic chain was discovered, which accelerates electron transport and reduces energy waste. This study represents a significant step toward the industrial viability of CO2 conversion into aromatic compounds and provides design guidance for improving photosynthetic efficiency.


Effects of liraglutide on postprandial insulin and glucagon responses in Japanese patients with type 2 diabetes.
This study assessed the endocrine pancreatic responses to liraglutide (0.9 mg once a day) during normal living conditions in Japanese patients with type 2 diabetes. The study included 14 hospitalized patients with type 2 diabetes. Meal tests were performed after improvement of glycemic control achieved by two weeks of multiple insulin injection therapy and after approximately two weeks of liraglutide treatment. Continuous glucose monitoring was performed to compare daily variation in glycemic control between multiple insulin injection therapy and liraglutide treatment. Liraglutide reduced plasma glucose levels after the test meals (60-180 min; p<0.05), as a result of significant increases in insulin secretion (0-180 min; p<0.05) and decreases in the incremental ratio of plasma glucagon (15-60 min; p<0.05). Continuous glucose monitoring showed that liraglutide treatment was also associated with a decrease in glucose variability. We also demonstrated that optimal glycemic control seen as a reduction in 24-h mean glucose levels and variability was obtained only with liraglutide monotherapy. In conclusion, liraglutide treatment increases insulin secretion and suppresses glucagon secretion in Japanese patients with type 2 diabetes under normal living conditions. The main therapeutic advantages of liraglutide are its use as monotherapy and its ability to decrease glucose variability.


Cyclophosphamide, doxorubicin, vincristine, and prednisone for primary central nervous system lymphoma: short-duration response and multifocal intracerebral recurrence preceding radiotherapy.
The activity of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in the treatment of primary central nervous system lymphoma (PCNSL) prior to radiotherapy was studied in six patients. Primary lesions were reduced by 80% or more on contrast-enhancing cross-sectional area in four patients and to a lesser extent in two others after two cycles of chemotherapy. The primary lesion sites demonstrated no contrast enhancement in the three patients who completed four cycles of therapy. However, concurrent with response at the primary disease sites, multiple lesions occurred at distant, noncontiguous CNS parenchymal sites in five patients after two to four cycles of chemotherapy. Median survival was 8.5 months for the six enrolled patients and 16.5 months for the four patients completing craniospinal radiotherapy. PCNSL is highly responsive to standard systemic non-Hodgkin's lymphoma chemotherapy regimens, but the pattern and rapidity of relapse suggest mechanisms of failure including inherent or rapidly evolving antineoplastic drug resistance and perhaps limited drug delivery to occult sites of disease in the brain.


Characterization of flagella purified from enterohemorrhagic, vero-cytotoxin-producing Escherichia coli serotype O157:H7.
Escherichia coli of the serotype O157:H7 has recently been isolated in human fecal specimens in association with sporadic cases and outbreaks of hemorrhagic colitis and with the hemolytic uremic syndrome. The aim of this study was to characterize the flagellin protein subunit constituents of flagellar filaments from E. coli O157:H7 strain CL-56. Flagellin isolated from a reference Salmonella enteritidis strain was used for comparison. Flagella were dissociated by incubation of bacteria under acidic conditions, centrifugation, and differential ammonium sulfate precipitation. Reconstituted flagellar filaments were demonstrated by three complementary methods: transmission electron microscopy, antigenic reactivity with H7 antiserum by a dot blot immunoassay, and immunogold localization of antiserum raised to the purified antigen to intact flagella on whole E. coli O157:H7. On sodium dodecyl sulfate-polyacrylamide gels flagellin proteins from E. coli O157:H7 demonstrated an apparent Mr of 66,000. The isoelectric point of E. coli O157:H7 flagellin was 5.42. By immunoblotting, H7 flagellin proteins were shown to be immunogenic. They induced a systemic immune response both in rabbits challenged with whole bacteria and in a human previously infected with E. coli O157:H7.


The Factors Associated With Nonuse of Social Media or Video Communications to Connect With Friends and Family During the COVID-19 Pandemic in Older Adults: Web-Based Survey Study.
Digital technologies have enabled social connection during prolonged periods of physical distancing and travel restrictions throughout the COVID-19 pandemic. These solutions may exclude older adults, who are at higher risk for social isolation, loneliness, and severe outcomes if infected with SARS-CoV-2. This study investigated factors associated with nonuse of social media or video communications to connect with friends and family among older adults during the pandemic's first wave. A web-based, cross-sectional survey was administered to members of a national retired educators' organization based in Ontario, Canada, between May 6 and 19, 2020. Respondents (N=4879) were asked about their use of social networking websites or apps to communicate with friends and family, their internet connection and smartphone access, loneliness, and sociodemographic characteristics. Factors associated with nonuse were evaluated using multivariable logistic regression. A thematic analysis was performed on open-ended survey responses that described experiences with technology and virtual connection. Overall, 15.4% (751/4868) of respondents did not use social networking websites or apps. After adjustment, male gender (odds ratio [OR] 1.60, 95% CI 1.33-1.92), advanced age (OR 1.88, 95% CI 1.38-2.55), living alone (OR 1.68, 95% CI 1.39-2.02), poorer health (OR 1.33, 95% CI 1.04-1.71), and lower social support (OR 1.44, 95% CI 1.20-1.71) increased the odds of nonuse. The reliability of internet connection and access to a smartphone also predicted nonuse. Many respondents viewed these technologies as beneficial, especially for maintaining pre-COVID-19 social contacts and routines, despite preferences for in-person connection. Several factors including advanced age, living alone, and low social support increased the odds of nonuse of social media in older adults to communicate with friends and family during COVID-19's first wave. Our findings identified socially vulnerable subgroups who may benefit from intervention (eg, improved access, digital literacy, and telephone outreach) to improve social connection.


Cyclooxygenase-2 expression in retinoblastoma: an immunohistochemical analysis.
Increased level of cyclooxygenase-2 (COX-2) plays a significant role in the pathogenesis of cancers. High expression of COX-2 has been demonstrated in several cancer types including retinoblastoma. However, the in vivo study did not confirm the anti-proliferative effect of COX-2 inhibitor, celecoxib, on a murine transgenic retinoblastoma model. We, therefore, aim to investigate COX-2 expression in paraffin-embedded retinoblastoma specimens in a larger study group. We reviewed 55 retinoblastoma specimens obtained during 1995 to 2005. Clinical and histopathological data were recorded. Immunohistochemical evaluation of COX-2 expression was performed using a rabbit monoclonal antibody to human cyclooxygenase-2. Forty-four of 55 specimens (80%) showed negative immunoreactivity for COX-2 expression. For the 11 specimens (20%, 95% CI = 11.6-32.4%) with positive COX-2, all immunostainings were less than 50% of tumor area. Demographic data and treatment details were available in 53 specimens. Enucleation was performed as a primary treatment in 43 specimens (81%). Other treatments, mainly systemic chemotherapy, were given prior to enucleation in 10 specimens (19%). There was no statistical difference in COX-2 expression between the specimens identified as primary and secondary enucleation (p = 0.66). Regarding the histopathological findings, there were no significant differences between COX-2 negative and COX-2 positive groups. It appears that COX-2 is not overexpressed in our retinoblastoma specimens, which is different from previous studies. This conflicting data reduces the possibility of introducing Cox-2 inhibitors in the treatment of retinoblastoma.


Immunofluorescence Analysis of Stress Granule Formation After Bacterial Challenge of Mammalian Cells.
Fluorescent imaging of cellular components is an effective tool to investigate host-pathogen interactions. Pathogens can affect many different features of infected cells, including organelle ultrastructure, cytoskeletal network organization, as well as cellular processes such as Stress Granule (SG) formation. The characterization of how pathogens subvert host processes is an important and integral part of the field of pathogenesis. While variable phenotypes may be readily visible, the precise analysis of the qualitative and quantitative differences in the cellular structures induced by pathogen challenge is essential for defining statistically significant differences between experimental and control samples. SG formation is an evolutionarily conserved stress response that leads to antiviral responses and has long been investigated using viral infections1. SG formation also affects signaling cascades and may have other still unknown consequences2. The characterization of this stress response to pathogens other than viruses, such as bacterial pathogens, is currently an emerging area of research3. For now, quantitative and qualitative analysis of SG formation is not yet routinely used, even in the viral systems. Here we describe a simple method for inducing and characterizing SG formation in uninfected cells and in cells infected with a cytosolic bacterial pathogen, which affects the formation of SGs in response to various exogenous stresses. Analysis of SG formation and composition is achieved by using a number of different SG markers and the spot detector plug-in of ICY, an open source image analysis tool.


Size-dependent rate acceleration in the silylation of secondary alcohols: the bigger the faster.
Relative rates for the reaction of secondary alcohols carrying large aromatic moieties with silyl chlorides carrying equally large substituents have been determined in organic solvents. Introducing thoroughly matching pairs of big dispersion energy donor (DED) groups enhanced rate constants up to four times, notably depending on the hydrogen bond donor ability of the solvent. A linear correlation between computed dispersion energy contributions to the stability of the silyl ether products and experimental relative rate constants was found. These results indicate a cooperation between solvophobic effects and DED-groups in the kinetic control of silylation reactions.


Back to the root: a large animal model of the Ross procedure.
The excellent clinical outcomes of the Ross procedure and previous histological studies suggest that the pulmonary autograft has the potential to offer young patients a permanent solution to aortic valve disease. We aim to study the early mechanobiological adaptation of the autograft. To this end, we have reviewed relevant existing animal models, including the canine models which enabled Donald N Ross to perform the first Ross procedure in a patient in 1967. Two research groups recently evaluated the isolated effect of systemic pressures on pulmonary arterial tissue in an ovine model of a pulmonary artery interposition graft in the descending aorta. While this model is ideal to study the artery's biological response and the effect of external support, it does not recreate the complex environment of the aortic root. The freestanding Ross procedure has been performed in pigs and sheep before. These studies offered valuable insights into leaflet growth and histological remodeling, yet may be less relevant to adults undergoing the Ross procedure, as pronounced autograft dilatation was achieved by using small, rapidly growing animals. Therefore, a large animal model remains needed to determine the ideal conditions and surgical technique to ensure long-term autograft remodeling and valve function. We set out to develop an ovine model of the Ross procedure performed as a freestanding root replacement, acknowledging that the sheep's specific anatomy and the setting of an animal laboratory would mandate several modifications in surgical strategy. This article describes the development, surgical technique and early outcomes of our animal model while highlighting opportunities for further research.


The changes of Lp-PLA2 in patients with gestational diabetes and its clinical significance.
Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy and associated with adverse pregnancy outcomes. The aim of this study was to investigate the changes of lipoprotein-associated phospholipaseA2 (Lp-PLA2) level and its correlation with biochemical indexes in patients with GDM.This observational cross-sectional study was performed among 52 GDM and 48 healthy pregnant women. Automatic biochemical analyzer was employed to test the biochemical indexes, including fasting plasma glucose (FPG), Hemoglobin A1c (HbA1c), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). The lipoprotein-associated phospholipaseA2 (Lp-PLA2) level was evaluated by enzyme-linked immunosorbent assay, and homeostatic model assessment for insulin resistance (HOMA-IR) was calculated.The levels of FPG, HbA1c, HOMA-IR, TG, TC and LDL-C were significantly increased while high-density lipoprotein cholesterol (HDL-C) level was significantly decreased in the GDM group when compared with those in the control group. Lp-PLA2 level in maternal blood in the GDM group was significantly higher than that in the control group (199.125 ± 23.494 vs165.825 ± 15.576 ng/mL, P < .05) and logistic regression analysis further confirmed the association of Lp-PLA2 levels with GDM. Furthermore, Lp-PLA2 positively correlated with HOMA-IR, TC, and LDL-C.Our results confirmed the association of Lp-PLA2 with GDM. This broadens our knowledge on the pathophysiology of GDM and provides insights into the development of new targets for the prevention and treatment of GDM.


Type 1 diabetes mellitus associated with nephrotic syndrome.
Nephrotic syndrome (NS) in a patient with diabetes mellitus (DM) first suggests the diagnosis of diabetic nephropathy. However, glomerular diseases other than diabetic nephropathy have been reported in patients with DM. We present a child with type 1 DM (DM1) associated with NS. A 3 year-old boy who was diagnosed with DM1 developed proteinuria in nephrotic range at the 10th month of follow-up. He had remission on steroid treatment without any problem in glycemic control as he was given tapered daily doses instead of an alternate day regimen. He relapsed at the 7th month of follow-up, and cyclophosphamide treatment brought about remission. He had HLA A24, DR4 and DR53 antigens in common with previously reported cases of DM-NS association. The immunological basis of these diseases may have a causal effect on the association, but the etiopathogenesis is still unclear.


[Decrease in the serum concentration of triiodothyronine in patients with acute edematous pancreatitis].
Serum concentrations of triiodothyronine (T3), Thyroxine (T4) and Thyrotropine (TSH) were measured in ten patients hospitalized in an emergency way due to acute edematose pancreatitis clinically diagnosed and confirmed in the laboratory through the finding of values of amilase higher than 180 I.U. By means of venopunction 5 ml. of blood were taken from each patient in order to determine the thyroidal profile and amilasemia at the moment of internment and after 72 hours of the disease development. Results demonstrated a decrease of the values of T3, 72 hours after the patients entered the hospital, with normal values for T4 and TSH. This decrease reached levels of hypothyroidism with no clinical data of the disease.


Do enrollees in 'look-alike' Medicaid and SCHIP programs really look alike? State Children's Health Insurance Program.
The State Children's Health Insurance Program (SCHIP), passed by Congress in 1997, has been implemented by states in many different forms, thus creating many natural experiments about insurance coverage for low-income children. In Georgia, SCHIP children are enrolled in a Medicaid look-alike program, PeachCare for Kids, with nearly the same administrative rules and providers as in the Medicaid program. Comparing the experiences of PeachCare and Medicaid children thus allows us to examine the impact of population differences on utilization and satisfaction. We find that Medicaid children, controlling for many demographic characteristics, report both less use of services and lower satisfaction with services used. Evidence presented here supports three possible explanations for these differences: Medicaid families are less familiar with and supportive of systems requiring use of an assigned primary care physician, the families face more nonprogram barriers to using care, and physicians have different responses to the two programs.


The impact of extraperitoneal surgical staging on morbidity and tumor recurrence following radiotherapy for cervical carcinoma.
From 1971 through 1981, 83 nonsurgically staged women with cervical cancer received extended-field radiotherapy on the basis of abnormal lymphangiogram, obstruction on intravenous pyelogram, or extensive pelvic tumor volume. From 1978 through 1981, 61 surgically staged patients underwent radiation therapy; of these, the 21 with positive lymph nodes received periaortic radiation. No increase in morbidity was found in these patients. Survival, relapse rate, and sites of treatment failures were similar in the positive lymphangiogram group and in the surgically staged patients with positive nodes.


[The frequency of diagnosis of catatonic schizophrenia in hospitals in Lubliniec (1894-1932, 1934-1936, 1970-1999) and Boleslawiec (1958-1999)].
The analysis of the data from the psychiatric hospitals in Lubliniec (1894-1932, 1934-1936, 1970-1999) and Bolesławiec (1958-1999) proved a decrease in frequency of diagnosis of catatonic schizophrenia, what could testify to a decrease in morbidity with this form of schizophrenia. Basing on the facts from scientific literature there was ascertained that the decrease in frequency of diagnosis of catatonic schizophrenia is connected with following causes: firstly, with the changes in nozology, secondly, with the introduction of a new form of therapy and finally, with the fact that here psychological and sociological factors exist which eliminate catatonia as the most expressive form of schizophrenia.


Schizotypy and mindfulness: Magical thinking without suspiciousness characterizes mindfulness meditators.
Despite growing evidence for demonstrated efficacy of mindfulness in various disorders, there is a continuous concern about the relationship between mindfulness practice and psychosis. As schizotypy is part of the psychosis spectrum, we examined the relationship between long-term mindfulness practice and schizotypy in two independent studies. Study 1 included 24 experienced mindfulness practitioners (19 males) from the Buddhist tradition (meditators) and 24 meditation-naïve individuals (all males). Study 2 consisted of 28 meditators and 28 meditation-naïve individuals (all males). All participants completed the Schizotypal Personality Questionnaire (Raine, 1991), a self-report scale containing 9 subscales (ideas of reference, excessive social anxiety, magical thinking, unusual perceptual experiences, odd/eccentric behavior, no close friends, odd speech, constricted affect, suspiciousness). Participants of study 2 also completed the Five-Facet Mindfulness Questionnaire which assesses observing (Observe), describing (Describe), acting with awareness (Awareness), non-judging of (Non-judgment) and non-reactivity to inner experience (Non-reactivity) facets of trait mindfulness. In both studies, meditators scored significantly lower on suspiciousness and higher on magical thinking compared to meditation-naïve individuals and showed a trend towards lower scores on excessive social anxiety. Excessive social anxiety correlated negatively with Awareness and Non-judgment; and suspiciousness with Awareness, Non-judgment and Non-reactivity facets across both groups. The two groups did not differ in their total schizotypy score. We conclude that mindfulness practice is not associated with an overall increase in schizotypal traits. Instead, the pattern suggests that mindfulness meditation, particularly with an emphasis on the Awareness, Non-judgment and Non-reactivity aspects, may help to reduce suspiciousness and excessive social anxiety.


In Vitro Models for the Study of the Intracellular Activity of Antibiotics.
Intracellular bacteria are poorly responsive to antibiotic treatment. Pharmacological studies are thus needed to determine which antibiotics are most potent or effective against intracellular bacteria as well as to explore the reasons for poor bacterial responsiveness. An in vitro pharmacodynamic model is described, consisting of (1) phagocytosis of pre-opsonized bacteria by eukaryotic cells; (2) elimination of non-internalized bacteria with gentamicin; (3) incubation of infected cells with antibiotics; and (4) determination of surviving bacteria by viable cell counting and normalization of the counts based on sample protein content.


Repeated immobilization stress decreases mRNA and protein levels of the type 1 IP3 receptor in rat heart.
Stress is one of the major contributors to the development of cardiovascular disorders and psychiatric illnesses. Immobilization stress belongs to severe stressors and is known to activate several calcium transport systems. The aim of this work was to determine whether repeated immobilization stress changes mRNA and protein levels of the type 1 and 2 inositol-1,4,5-trisphosphate (IP(3)) receptors in cardiac tissue. Rats were immobilized for 7 days, 2 h daily. After repeated immobilization, increased numbers of collagen fibers were accumulated in the heart atria compared to hearts of the control group of rats. Gene expression was determined after reverse transcription and subsequent real-time polymerase chain reaction, using SYBR Green fluorescent dye. Protein levels were determined by Western blot and hybridization with the primary antibody against IP(3) receptors. Contrary to single immobilization, repeated immobilization decreased a gene expression of the type 1 and 2 IP(3) receptors, and also protein levels of the IP(3) receptors. Although the physiologic relevance of our observations remains to be elucidated, we propose that the decrease in IP(3) receptors may have an impact on the development of the pathophysiologic changes in the heart.


[Genetics and arterial hypertension: 3 approaches to decode a complex disease].
Human arterial hypertension is a complex trait, partly determined by genetic factors. From the analysis of familial studies, it has been estimated that approximately 30% of the blood pressure variance within a population was of genetic origin. Three main types of human studies have been undertaken to try to identify susceptibility genes to hypertension. The first one corresponds to the systematic analysis of the so-called candidate genes, i.e. genes encoding proteins, enzymes, receptors, which are known to belong to pathways controlling blood pressure. Up to now, the most interesting results have been obtained on genes encoding the renin angiotensin system, the a adducin, the G protein subunit beta 3, and adrenergic receptors. The genome wide scan approach corresponds to a systematic analysis of evenly spaced markers throughout the genome in sibling pairs or in more complex families. This second strategy has shown that there was not a single locus that was regularly found by several studies, but rather several possible loci which most often have not been replicated from one study to another one. Among those, the long arm of the human chromosome 17 (17q12-q21) is in synteny with a blood pressure locus found in spontaneously hypertensive rats. The third approach, up to now the most successful, corresponds to the identification of major genes involved in rare Mendelian forms of hypertension. For example, genes responsible for Liddle syndrome, glucocorticoid remediable aldosteronism, apparent mineralocorticoid excess have been characterized and have demonstrated the importance of sodium and water homeostasis in blood pressure control.


Nationwide survey of Baller‑Gerold syndrome in Japanese population.
Baller-Gerold syndrome (BGS) is a rare autosomal genetic disorder characterized by radial aplasia/hypoplasia and craniosynostosis. The causative gene for BGS encodes RECQL4, which belongs to the RecQ helicase family. To understand BGS patients in Japan, a nationwide survey was conducted, which identified 2 families and 3 patients affected by the syndrome. All the three patients showed radial defects and craniosynostosis. In one patient who showed a dislocated joint of the hip and flexion contracture of both the elbow joints and wrists at birth, a homozygous large deletion in the RECQL4 gene was identified. This is the first reported case of BGS in Japan caused by RECQL4 gene mutation.


Inflammation Is Associated With Platelet Coagulation Function Rather Than Enzymatic Coagulation Function in Patients With Takayasu Arteritis.
The integral changes of coagulation and fibrinolysis, and their relationships with inflammation in patients with Takayasu arteritis (TA) remain undetermined. The purpose of this study was to analyze the changes of coagulation and fibrinolysis process in patients with TA by thrombelastography (TEG).A total of 127 patients with TA and 55 healthy controls were enrolled. Patients with TA were grouped according to disease activity. The routine hematological parameters, traditional coagulation assays, and TEG parameters were summarized retrospectively.A shorter K time, larger alpha angle, and higher levels of MA, MA(A), G, and TPI were found in patients with TA, especially in those at the active stage. The R time, EPL, LY30, and CL30 were similar between patients with TA and healthy controls, as well as TA patients with different disease activity. Spearman's correlation showed that ESR was correlated with PLT (r = 0.206, P = 0.020), K (r = -0.353, P < 0.001), alpha angle (r = 0.328, P < 0.001), MA (r = 0.474, P < 0.001), MA (A) (r = 0.623, P < 0.001), G (r = 0.475, P < 0.001), and TPI (r = 0.458, P < 0.001).In conclusion, inflammation was associated with platelet coagulation function rather than enzymatic coagulation function in patients with TA. Physicians should focus on antiplatelet treatment for improving the prognosis of patients with TA.


Trypsin inhibitor polymorphism: multigene family expression and posttranslational modification.
Trypsin inhibitors from winter pea seeds (c.v. Frilene) have been purified and shown to consist of six protease inhibitors (PSTI I, II, III, IVa, IVb, and V). Based on amino acid composition, molecular mass, and N-terminal sequence, the six inhibitors are closely related to one another and belong to the Bowman-Birk family of inhibitors. To define the relations among them, molecular mass and amino acid composition of peptides obtained from digestion with trypsin were determined. The sequence and the biosynthetic mechanism of the isoform formation have been partially resolved for four major isoforms. Two isoinhibitor forms (PSTI IVa, IVb) in pea seeds are due to expression of two distinct genes; PSTI IVa has four amino acid replacements when its sequence is compared with the sequence of PSTI IVb. Two others (PSTI I, II) result from posttranslational proteolytic cleavage of nine C-terminal residues of forms PSTI IVa and IVb, respectively.


Prebiotic selection for motifs in a model of template-free elongation of polymers within compartments.
The transition from prelife where self-replication does not occur, to life which exhibits self-replication and evolution, has been a subject of interest for many decades. Membranes, forming compartments, seem to be a critical component of this transition as they provide several concurrent benefits. They maintain localized interactions, generate electro-chemical gradients, and help in selecting cooperative functions as they arise. These functions pave the way for the emergence and maintenance of simple metabolic cycles and polymers. In the context of origin of life, evolution of information-carrying molecules and RNA based enzymes within compartments has been subject to intensive theoretical and experimental research. Hence, many experimental efforts aim to produce compartments that contain elongating polynucleotides (also referred to as protocells), which store information and perform catalysis. Despite impressive experimental progress, we are still relatively ignorant about the dynamics by which elongating polynucleotides can produce more sophisticated behaviors. Here we perform computer simulations to couple information production through template-free elongation of polymers with dividing compartments. We find that polymers with a simple ability-biasing the concentration of monomers within their own compartment-can acquire a selective advantage in prelife. We further investigate whether such a mechanism allows for cooperative dynamics to dominate over purely competitive ones. We show that under this system of biased monomer addition, even without template-directed self-replication, genetic motifs can emerge, compete, cooperate, and ultimately survive within the population.


[Terahertz Spectrum Modulation with Liquid Crystal Spatial Light Modulator].
Terahertz wave with modulation spectrum is valuable in many fields. Terahertz spectrum has been modulated with a pure-phase liquid crystal spatial light modulator by shaping the femtosecond laser beam profile. In the experiment, terahertz wave is generated by femtosecond laser pulses in mode of Optical Rectification and then its signals are detected by a terahertz time-domain spectroscopy system. Phase maps obtained with the GS algorithm are loaded to get the shaped beam profile. Therefore, Terahertz spectrum has been successfully modulated by changing the detection range and beam profile parameters. Simultaneously, the simulations have been performed with the Fresnel diffraction, and they agree with the experimental results well. The results show that the modulation of the THz spectrum with this method is feasible.


An integrative review of outcomes in patients with acute primary upper extremity deep venous thrombosis following no treatment or treatment with anticoagulation, thrombolysis, or surgical algorithms.
Primary upper extremity deep venous thrombosis (UEDVT) is a rare condition that typically affects young patients and can cause considerable long-term morbidity. Proposed treatments have included rest, heat, elevation of the affected limb, anticoagulation, thrombolysis, surgical decompression, percutaneous transluminal angioplasty (PTA), and stenting. However, the optimal management of primary UEDVT remains controversial. This study was an integrative review of the English-language literature since 1965 on primary UEDVT, with comparison of long-term symptoms, rethrombosis, and pulmonary embolism in 4 treatment algorithms: rest, heat, and elevation alone; anticoagulation alone; surgical decompression without thrombolysis; and algorithms including thrombolysis. Forty-one studies describing 559 patients met the criteria for inclusion. Statistically significant differences were found among the 4 treatment algorithms in the incidence of residual symptoms (p < 0.000), the incidence of pulmonary embolism (p < 0.000), and the incidence of rethrombosis (p < 0.027). Residual symptoms and the severity of residual symptoms were greatest in the rest, heat, and elevation algorithm (74%), followed by the surgical (60%), anticoagulation (44%), and thrombolysis (22%) algorithms. Pulmonary embolism was also greatest in the rest, heat, and elevation algorithm (12%), followed by the anticoagulation (7%), thrombolysis (1%), and surgical algorithms (0%), while rethrombosis was greatest in the thrombolytic algorithm (7%) followed by the surgical (3%), anticoagulation (2%), and rest, heat, and elevation (0%) algorithms. These results support the current clinical practice of a staged, multidisciplinary approach to treatment of primary UEDVT that includes thrombolytic therapy and possible surgical decompression. Further studies are needed to evaluate the natural history of patients treated with thrombolysis alone, to assess the optimal timing of surgical decompression, and to determine the best use of PTA and stenting in the multidisciplinary approach.


Commercial Milk Enzyme-Linked Immunosorbent Assay (ELISA) Kit Reactivities to Purified Milk Proteins and Milk-Derived Ingredients.
Numerous commercial enzyme-linked immunosorbent assay (ELISA) kits exist to quantitatively detect bovine milk residues in foods. Milk contains many proteins that can serve as ELISA targets including caseins (α-, β-, or κ-casein) and whey proteins (α-lactalbumin or β-lactoglobulin). Nine commercially-available milk ELISA kits were selected to compare the specificity and sensitivity with 5 purified milk proteins and 3 milk-derived ingredients. All of the milk kits were capable of quantifying nonfat dry milk (NFDM), but did not necessarily detect all individual protein fractions. While milk-derived ingredients were detected by the kits, their quantitation may be inaccurate due to the use of different calibrators, reference materials, and antibodies in kit development. The establishment of a standard reference material for the calibration of milk ELISA kits is increasingly important. The appropriate selection and understanding of milk ELISA kits for food analysis is critical to accurate quantification of milk residues and informed risk management decisions.


[Analysis of FcgammaRIIIb genotype of periodontal disease in the Han nationality in China].
The purpose of the present study was to compare FcgammaRIIIb genotype of aggressive periodontitis (AgP) with chronic periodontitis (CP) and control group (Cont) in the Han nationality in China. The classification, which was applied in this study, was presented and discussed at the 1999 International Workshop for the Classification of the Periodontal Disease organized by the American Academy of Periodontology (AAP). 23 patients with aggressive periodontitis, including 20 with chronic periodontitis according to the established clinical criteria, and 22 matched healthy controls was included in this study. Peripheral blood samples were taken from all patients and controls, then DNA was isolated from blood using DNA purification kit. And FcgammaRIIIb genotyping was determined by PCR and DNA sequencing. The different results of genotype in all three groups were analysed by chi(2) test. FcgammaRIIIb-NA1, -NA2 (old definition) frequencies didn't equal 1.00 in all 3 groups, and also without -SH, -NA(NULL) genotype. At the same time, many new allele of NA1 and NA2 were found in all groups. However, there were no rules of new alleles in each group and between the groups, no statistical significance as well. The -NA1 of FcgammaRIIIb (new definition) frequency was 0.77, and that of -NA2 (new definition) was 0.23 in this study. Including FcgammaRIIIb-NA1 and -NA2, five alternate allele of -NA1 (-NA1*01b, -NA1*02a, -NA1*02b, -NA1*03a and-NA1*03b) and three alternate allele of -NA2(-NA2*02, -NA2*03 and -NA2*04) were described. The results suggest that FcgammaRIIIb may not be a risk indicator for the susceptibility of periodontitis in the Han nationality of China.


Feedback Blunting: Total Sleep Deprivation Impairs Decision Making that Requires Updating Based on Feedback.
To better understand the sometimes catastrophic effects of sleep loss on naturalistic decision making, we investigated effects of sleep deprivation on decision making in a reversal learning paradigm requiring acquisition and updating of information based on outcome feedback. Subjects were randomized to a sleep deprivation or control condition, with performance testing at baseline, after 2 nights of total sleep deprivation (or rested control), and following 2 nights of recovery sleep. Subjects performed a decision task involving initial learning of go and no go response sets followed by unannounced reversal of contingencies, requiring use of outcome feedback for decisions. A working memory scanning task and psychomotor vigilance test were also administered. Six consecutive days and nights in a controlled laboratory environment with continuous behavioral monitoring. Twenty-six subjects (22-40 y of age; 10 women). Thirteen subjects were randomized to a 62-h total sleep deprivation condition; the others were controls. Unlike controls, sleep deprived subjects had difficulty with initial learning of go and no go stimuli sets and had profound impairment adapting to reversal. Skin conductance responses to outcome feedback were diminished, indicating blunted affective reactions to feedback accompanying sleep deprivation. Working memory scanning performance was not significantly affected by sleep deprivation. And although sleep deprived subjects showed expected attentional lapses, these could not account for impairments in reversal learning decision making. Sleep deprivation is particularly problematic for decision making involving uncertainty and unexpected change. Blunted reactions to feedback while sleep deprived underlie failures to adapt to uncertainty and changing contingencies. Thus, an error may register, but with diminished effect because of reduced affective valence of the feedback or because the feedback is not cognitively bound with the choice. This has important implications for understanding and managing sleep loss-induced cognitive impairment in emergency response, disaster management, military operations, and other dynamic real-world settings with uncertain outcomes and imperfect information.