Simultaneous monitoring of oxidation, deamidation, isomerization, and glycosylation of monoclonal antibodies by liquid chromatography-mass spectrometry method with ultrafast tryptic digestion.
Monoclonal antibodies are subjected to a wide variety of post-translational modifications (PTMs) that cause structural heterogeneity. Characterization and control of these modifications or quality attributes are critical to ensure antibody quality and to define any potential effects on the ultimate safety and potency of antibody therapeutics. The biopharmaceutical industry currently uses numerous tools to analyze these quality attributes individually, which requires substantial time and resources. Here, we report a simple and ultrafast bottom-up liquid chromatography-mass spectrometry (uLC-MS) method with 5 min tryptic digestion to simultaneously analyze multiple modifications, including oxidation, deamidation, isomerization, glycation, glycosylation, and N-terminal pyro-glutamate formation, which can occur during antibody production in mammalian cell culture, during purification and/or on storage. Compared to commonly used preparation procedures, this uLC-MS method eliminates assay artifacts of falsely-increased Met oxidation, Asp isomerization, and Asn deamidation, a problem associated with long digestion times in conventional LC-MS methods. This simple, low artifact multi-attribute uLC-MS method can be used to quickly and accurately analyze samples at any stage of antibody drug development, in particular for clone and media selection during cell culture development.


Maintaining and attaining educational expectations: A two-cohort longitudinal study of Hispanic youth.
Hispanic adolescents have high expectations for their own educational attainment, but educational attainment outcomes for Hispanic young adults are relatively low on average. Limited scholarship links Hispanic adolescents' educational expectations with attainment in adulthood. Using a longitudinal within-group approach, the authors examined changes in Hispanic adolescents' educational expectations from 10th to 12th grade as well as the discrepancy between educational expectations and later attainment in 2 cohorts (N = 1,372 and N = 1,521). Based on national surveys approximately 12 years apart (NELS:88 and ELS:02), expectations of a college degree became more common for Hispanic adolescents. Most Hispanic young adults attained less education than they expected, and this expectations-attainment gap grew over time, consistent with U.S. national trends. Parent education was positively associated with attaining expectations, and family income became more important for attaining expectations over time. Consistent with the immigrant paradox and immigrant optimism hypothesis, second-generation youth came closer to attaining their expectations than third- or higher-generation youth of equal positioning. Educational expectations and attainment patterns also varied by cohort: for instance, immigrants in the more recent cohort had an absolute disadvantage in terms of attaining their expectations compared with their other-generation counterparts. Finally, parental involvement in education (e.g., parents' educational aspirations) was associated with educational expectations and attainment outcomes. This study advances knowledge of factors that contribute to maintaining and attaining educational expectations for Hispanic youth and how these factors have changed over time. Study results inform efforts to support Hispanic adolescents' and young adults' educational potential. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


The Role of Physiotherapy in Pediatric Palliative Care: A Systematic Review.
Pediatric palliative care (PPC) is a set of actions aimed at children who suffer from a severe or life-threatening disease to alleviate the symptoms of the disease and improve the quality of life of both the child and his/her family. One of the tools used to control symptoms is physiotherapy; however, its application in the child population has not been thoroughly studied. The main objective of this study was to gather, analyze, and critically evaluate the available scientific evidence on physiotherapy in children who require palliative care through a systematic review of the studies published in the last 10 years in the following databases: PubMed, Cochrane Library, PEDro, CINAHL, and Scopus. Of a total of 622 studies, the inclusion criteria were only met by seven articles, which were focused on the relationship between physiotherapy and PPC. This study analyzed: (1) the main pathologies treated, with a predominance of cerebral palsy and cancer; (2) the interventions applied, such as respiratory physiotherapy, neurological physiotherapy, therapeutic massage, and virtual reality; (3) the effects achieved in the child and his/her family, highlighting the control of symptoms and the improvement of the quality of life; and (4) the knowledge of the physiotherapists on PPC, observing that most of the professionals had not received training in this scope. The findings of this review indicate a lack of an adequate evidence foundation for physiotherapy in PPC.


Participants' recall and understanding of genomic research and large-scale data sharing.
As genomic researchers are urged to openly share generated sequence data with other researchers, it is important to examine the utility of informed consent documents and processes, particularly as these relate to participants' engagement with and recall of the information presented to them, their objective or subjective understanding of the key elements of genomic research (e.g., data sharing), as well as how these factors influence or mediate the decisions they make. We conducted a randomized trial of three experimental informed consent documents (ICDs) with participants (n = 229) being recruited to genomic research studies; each document afforded varying control over breadth of release of genetic information. Recall and understanding, their impact on data sharing decisions, and comfort in decision making were assessed in a follow-up structured interview. Over 25% did not remember signing an ICD to participate in a genomic study, and the majority (54%) could not correctly identify with whom they had agreed to share their genomic data. However, participants felt that they understood enough to make an informed decision, and lack of recall did not impact final data sharing decisions or satisfaction with participation. These findings raise questions about the types of information participants need in order to provide valid informed consent, and whether subjective understanding and comfort with decision making are sufficient to satisfy the ethical principle of respect for persons.


The MicroRNA Interaction Network of Lipid Diseases.
Background: Dyslipidemia is one of the major forms of lipid disorder, characterized by increased triglycerides (TGs), increased low-density lipoprotein-cholesterol (LDL-C), and decreased high-density lipoprotein-cholesterol (HDL-C) levels in blood. Recently, MicroRNAs (miRNAs) have been reported to involve in various biological processes; their potential usage being a biomarkers and in diagnosis of various diseases. Computational approaches including text mining have been used recently to analyze abstracts from the public databases to observe the relationships/associations between the biological molecules, miRNAs, and disease phenotypes. Materials and Methods: In the present study, significance of text mined extracted pair associations (miRNA-lipid disease) were estimated by one-sided Fisher's exact test. The top 20 significant miRNA-disease associations were visualized on Cytoscape. The CyTargetLinker plug-in tool on Cytoscape was used to extend the network and predicts new miRNA target genes. The Biological Networks Gene Ontology (BiNGO) plug-in tool on Cytoscape was used to retrieve gene ontology (GO) annotations for the targeted genes. Results: We retrieved 227 miRNA-lipid disease associations including 148 miRNAs. The top 20 significant miRNAs analysis on CyTargetLinker provides defined, predicted and validated gene targets, further targeted genes analyzed by BiNGO showed targeted genes were significantly associated with lipid, cholesterol, apolipoprotein, and fatty acids GO terms. Conclusion: We are the first to provide a reliable miRNA-lipid disease association network based on text mining. This could help future experimental studies that aim to validate predicted gene targets.


[Jejunal ulcer--therapeutical and diagnosis difficulties].
We present a female patient of 70 years, admitted in emergency department for signs of high bowel obstruction. After preoperative intensive care, surgical intervention was performed. A complete stenosis of the bowel lumen was found about 15 cm from the duodenojejunal angle, due to a process of sclerosis. Segmental enterectomy was performed with lateroterminal enteroenteralanastomosys, with poor outcome due to a lung infection, which occurred amid COPD. The patient died in intensive care unit requiring mechanical ventilation postoperative. Jejunal ulcer diagnosis was established after pathological examination. Particular issues in discussion are: etiological, clinical, diagnostic and therapeutic ones, that this rare condition posed in practical care.


Identification of key genes in endometrioid endometrial adenocarcinoma via TCGA database.
Understanding the molecular mechanisms is important in development and therapy of endometrioid endometrial adenocarcinoma. To identify key genes in endometrioid endometrial adenocarcinoma. The data of mRNA, miRNA and DNA methylation were downloaded from The Cancer Genome Atlas (TCGA) database and differential analysis was performed. Then, bioinformatic analysis was used to explore the regulatory mechanisms of miRNA and DNA methylation on gene expression. The regulatory network between differentially expressed miRNAs and target genes was established. Finally, the quantitative RT-PCR was applied to validate the bioinformatics results. We obtained biological omics data of 381 patients with endometrioid endometrial adenocarcinoma from TCGA data portal. After data processing, up to 2068 DEGs and 69 differentially expressed miRNAs were identified. Prediction and correlation analysis revealed that 175 DEGs that were not only the target genes but also negatively correlated with the screened differentially expressed miRNAs. After the integrated analysis of differentially methylated CpG islands and DEGs, 16 related genes were obtained. The quantitative RT-PCR results were roughly consistent with the bioinformatics analysis. The altered DEGs (ZEB1, ZEB2, TIMP2, TCF4, CYP1B1, PITX1, PITX2, ZNF154 and TSPYL5) may be involved in tumor differentiation of endometrioid endometrial adenocarcinoma and could be used as potential therapeutic targets for the disease.


Pretransplant blood transfusions can harm matched kidneys in dogs.
The effect of pretransplant blood transfusion (PBT) and histocompatibility matching on kidney allograft survival was studied in immunosuppressed dogs. PBT was found to be beneficial for related and unrelated mismatched kidney grafts. In contrast, after withdrawal of the immunosuppressants, transfused recipients of related and unrelated matched grafts rejected the kidney significantly more often than non-transfused dogs. Crossimmunisation for minor histocompatibility antigens may be responsible for this adverse effect, but could not be demonstrated in vitro by serology or mixed lymphocyte reactions. The possible deleterious effect of PBT in this model argues against the routine use of pretransplant blood transfusions in man.


Brachial neuritis.
Brachial neuritis is a rare disorder of unknown etiology that causes pain and weakness of the shoulder and upper extremity. There have been many descriptions of the disorder in the literature. The classic symptoms begin with an acute onset of sharp pain in the shoulder girdle. As the pain subsides, weakness occurs. The diagnosis often is difficult to make in the acute setting. Diagnostic tests typically are not helpful, although electromyography may be useful. The treatment is chiefly supportive with analgesics initially followed by range of motion exercises. Full functional recovery is expected in most patients, although the interval may be protracted. Understanding the disorder of brachial neuritis and its course will assist in the diagnosis and treatment.


Synthesis, characterization and opto-electrical properties of ternary Zn2SnO4 nanowires.
Ternary oxides have the potential to display better electrical and optical properties than the commonly fabricated binary oxides. In our experiments, Zn(2)SnO(4) (ZTO) nanowires were synthesized via thermal evaporation and vapor phase transport. The opto-electrical performance of the nanowires was investigated. An individual ZTO nanowire field-effect transistor was successfully fabricated for the first time and shows an on-off ratio of 10(4) and transconductance of 20.6 nS, which demonstrates the promising electronic performance of ZTO nanowire in an electrical device. Field emission experiments on ZTO nanowire film also indicate their potential application as a field emission electron source.


Hemoglobin pretreatment endows rat cortical astrocytes resistance to hemin-induced toxicity via Nrf2/HO-1 pathway.
Oxidative stress mediated secondary injury contributes to neurological deterioration after intracerebral hemorrhage (ICH). Astrocytes, the most dominant cells in the central nervous system (CNS), play key roles in maintaining redox homeostasis by providing oxidative stress defense. Hemoglobin (Hb), the primary component released by hemolysis, is an effective activator of astrocytes. Hemin, the product of Hb degradation, is highly toxic due to the induction of reactive oxygen species (ROS). We speculate that Hb-activated astrocytes are resistant to hemin-induced toxicity. To verify our speculation, Hb-pretreated astrocytes were exposed to hemin, intracellular ROS accumulation and cell apoptosis were evaluated. Heme oxygenase 1 (HO-1) and nuclear transcription factor-erythroid 2 related factor (Nrf2) expression were observed to explore the potential mechanism. The results demonstrated that Hb induced upregulation and nuclear translocation of Nrf2 in astrocytes, resulted in HO-1 upregulation, which contributed to reduced ROS accumulation and apoptosis rate. Knocking down Nrf2 expression by siRNA suppressed Hb-induced upregulation of HO-1 expression and increased the susceptibility of Hb-pretreated astrocytes to hemin-induced toxicity. Taken together, Hb-activated astrocytes acquired resistance to hemin-induced toxicity via Nrf2/HO-1 pathway. This phenomenon can be considered as the adaptive self-defense in the pathological process of ICH. Hb pre-warned astrocytes and enhanced their capability of handling the coming hemin "flood". Nrf2/HO-1 may be employed as a target for neuroprotection after ICH.


The crystal structure of the herpes simplex virus 1 ssDNA-binding protein suggests the structural basis for flexible, cooperative single-stranded DNA binding.
All organisms including animal viruses use specific proteins to bind single-stranded DNA rapidly in a non-sequence-specific, flexible, and cooperative manner during the DNA replication process. The crystal structure of a 60-residue C-terminal deletion construct of ICP8, the major single-stranded DNA-binding protein from herpes simplex virus-1, was determined at 3.0 A resolution. The structure reveals a novel fold, consisting of a large N-terminal domain (residues 9-1038) and a small C-terminal domain (residues 1049-1129). On the basis of the structure and the nearest neighbor interactions in the crystal, we have presented a model describing the site of single-stranded DNA binding and explaining the basis for cooperative binding. This model agrees with the beaded morphology observed in electron micrographs.


Influence of temperature gradients on leaf water potential.
Water potential was monitored at nine locations along single maize (Zea mays L.) leaf blades with aluminum block in situ thermocouple hygrometers. Water potential showed a continuous decrease toward the tip, with a 2- to 4-bar difference between leaf base and tip under both moist and dry soil conditions. The water potential difference between the soil and the leaf base was about 4 bars. Water potentials decreased during the day and during a drying cycle, and increased at night and after irrigation. Heating a band of a leaf to 40 C or cooling it to 7 C had no influence on the water potential of the affected portion when this was corrected for hygrometer output over standard calibrating solutions at the respective temperatures. Heating or cooling a portion of a leaf had neither short nor long term effects on water potential of more distal leaf portions continuously monitored by hygrometers in dew point readout. Water potential fluctuated with an amplitude of about 1.5 bars and an irregular period of 10 to 30 minutes. Measurements with silver foil in situ psychrometers gave similar results.


Association Between Anxiety and Depression and Nonalcoholic Fatty Liver Disease.
Backgrounds: Depression and anxiety disorder are frequently seen in patients with nonalcoholic fatty liver disease (NAFLD). However, the associations between mood disorders and NAFLD have not been fully evaluated. In this study, we investigated the relationship between NAFLD and depression or anxiety in a Korean population. Methods: We conducted a retrospective cross-sectional study that included subjects who underwent abdominal ultrasonography and completed a symptom questionnaire for a routine health check-up. NAFLD was diagnosed and graded according to the ultrasonography findings. Depression and anxiety were assessed using the Beck Depression Inventory and State-Trait Anxiety Inventory, respectively. Results: Among the total of 25,333 subjects, the mean age was 47 years (men, 56.2%), and the prevalence rate of NAFLD was 30.9%. In the multivariate analysis, NAFLD showed a significant association with depression [adjusted odds ratio (OR) 1.43 and 95% confidence interval (CI) 1.14-1.80, p = 0.002] in women. Severe NAFLD significantly correlated with state anxiety and trait anxiety (adjusted OR 1.84 and 95% CI 1.01-3.37, p = 0.047 and adjusted OR 2.45 and 95% CI 1.08-4.85, p = 0.018, respectively) in women. Conclusions: There was a higher tendency of women with NAFLD to suffer from depression with increase in steatosis, and severe stage of steatosis was significantly associated with anxiety in the female compared to non-NAFLD. Understanding the association between NAFLD and mood disorders may have clinical implications for reducing the prevalence of comorbidities.


[The contribution of the new scale for assessing disability].
The assessment of disability and its management is complex and problematic. With a view to ensuring equality of opportunity between disabled people and others, a new law adopted in August 2005 proposed a new method for assessing disability is applicable on a wider scale by GPs. Assessing the contribution of the new scale for assessing disability in patients suffering from debilitating diseases, to verify compliance in Tunisia. Cross-sectional study on 60 hemiplegic, paraplegic and post traumatic head injuries. The patients underwent clinical evaluation and a functional assessment. The assessment tools used were: the classification of the American Spinal Injury Association, the Barthel Index, Glasgow Outcome Scale, Functional Independence Measure, the Health Assessement Questionnaire and the Social Function-36. Patients were also evaluated with the new scale of disability. concerning paraplegic patients, limitation of activity concerned mobility, maintenance staff, domestic life, social relationships, community life and major areas of life. On the hemiplegic, areas related to communication, mobility, maintenance staff, domestic life, social relationships, community life and major areas of life have been affected. We have noted a correlation between the new scale and the Barthel Index. Regarding traumatic brain injury, the areas most affected were those related to mobility, maintenance staff, domestic life and the major areas of life. A correlation was found between the new scale and the Functional Independence Measure in three populations, as well as the quality of life that has been correlated with disability. Disability was observed in 90% of paraplegics, 80% and 50% of hemiplegic patients with severe brain injury. The handicap was the heaviest seen in traumatic brain injury patients with a frequency of 20%. The new scale for assessing disability has reproduced disability and special needs of paraplegic patients, stroke patients and traumatic brain injury.


Validity of an inertial system for measuring velocity, force, and power during hamstring exercises performed on a flywheel resistance training device.
Inertial hamstring exercises promote functional changes leading to lower rates of hamstring injuries. However, variable training measurement systems have not been specifically validated for hamstring exercises. Accordingly, this study aimed to evaluate the validity of the Inertial Measurement System (IMS) to measure the velocity, force, and power during the performance of different hamstring exercises on a flywheel resistance training device. Fifteen males (average age: 22.4 ± 2.5 years; body mass: 77.3 ± 9.8 kg; height: 179.5 ± 7.4 cm; weekly physical activity: 434.0 ± 169.2 min; years of strength training: 4.3 ± 2.2 years) performed the bilateral stiff-leg deadlift (SDL), 45° hip extension (HE), and unilateral straight knee bridge (SKB) in two sessions (familiarization and evaluation) with a 1-week interval between them. The velocity, force, and power (average and peak values) in the concentric and eccentric phases for each of the exercises were recorded simultaneously with IMS and MuscleLab. Consistency between IMS and MuscleLab was good to excellent for all variables, with r ranges from 0.824 to 0.966 in SDL, from 0.822 to 0.971 in HE, and from 0.806 to 0.969 in SKB. Acceptable levels of agreement between devices were observed in general for all exercises, the "bias" ranging from 1.1% to 13.2%. Although MuscleLab showed higher values than IMS for peak velocity, force and power values, the effect size was only relevant for 5 of the 36 parameters. IMS is a new and valid system to monitor inertial hamstring exercises on a new flywheel device. In this way, IMS could have potential practical applications for any professional or athlete who wants to monitor inertial hamstring exercises.


[Effects of intercropping Sedum plumbizincicola in wheat growth season under wheat-rice rotation on the crops growth and their heavy metals uptake from different soil types].
A pot experiment with heavy metals- contaminated black soil from Heilongjiang Province, alluvial soil from Henan Province, and paddy soil from Zhejiang Province was conducted to study the effects of intercropping Sedum plumbizincicola in wheat growth season under wheat (Triticum aestivum) - rice (Oryza sativa) rotation on the growth of the crops and their heavy metals uptake, aimed to explore the feasibility of simultaneous grain production and heavy metals-contaminated soil phytoremediation in main food crop production areas of this country. Comparing with monoculture T. aestivum, intercropping S. plumbizincicola increased the soil NaNO3 -extractable Zn and Cd significantly, with the increment of extractable Zn in test paddy soil, alluvial soil, and black soil being 55%, 32% and 110%, and that of extractable Cd in test paddy soil and black soil being 38% and 110%, respectively. The heavy metals concentration in T. aestivum shoots under intercropping S. plumbizincicola was 0.1-0.9 times higher than that under monoculture T. aestivum, but the intercropping had little effects on the rice growth and its heavy metals uptake. Though the Cd concentration in rice grain after S. plumbizincicola planting was still higher than 0.2 mg kg(-1) (the limit of Cd in food standard), it presented a decreasing trend, as compared with that after monoculture T. aestivum. Therefore, intercropping S. plumbizincicola in wheat growth season under wheat-rice rota- tion could benefit the phytoremediation of heavy metals-contaminated soil, and decrease the food-chain risk of rotated rice.


Correlations of plasma lipid metabolites with hibernation and lactation in wild black bears Ursus americanus.
During the denning period, black bears (Ursus americanus) are capable of enduring several months without food. At the same time, female bears that are pregnant or lactating have an added metabolic stress. Based on laboratory studies, much of the energy required to support metabolism and lactation during denning in black bears comes from lipid reserves. These lipid reserves are mobilized and the most metabolically active lipid fraction in the blood are nonesterified fatty acids (NEFA). Therefore, we hypothesized that plasma NEFAs would be higher in denning relative to active bears and in lactating relative to non-lactating female bears. We further hypothesized that in bears with elevated plasma NEFA levels, other lipid-related parameters (e.g., ketone bodies, albumin, cholesterol, lipase) would also be elevated in the plasma. Denning bears had significantly increased NEFA levels in all classes (saturates, monoenes, and polyenes). A doubling of plasma NEFA levels and a 33% increase in albumin, the plasma fatty acid binding protein, in denning bears, resulted in NEFA/albumin ratios that were higher in denning bears (4:1) compared to those of active bears (3:1). Bears became relatively ketonemic with a 17-fold increase in D-beta-hydroxybutyrate levels during the denning period. Plasma cholesterol approximately doubled and lipase was ten-fold lower in denning relative to active bears. These findings indicate a strong correlation between plasma lipid metabolites and the denning period in a wild population of black bears.


Location-dependent signaling of the group 1 metabotropic glutamate receptor mGlu5.
Although G protein-coupled receptors are primarily known for converting extracellular signals into intracellular responses, some receptors, such as the group 1 metabotropic glutamate receptor, mGlu5, are also localized on intracellular membranes where they can mediate both overlapping and unique signaling effects. Thus, besides "ligand bias," whereby a receptor's signaling modality can shift from G protein dependence to independence, canonical mGlu5 receptor signaling can also be influenced by "location bias" (i.e., the particular membrane and/or cell type from which it signals). Because mGlu5 receptors play important roles in both normal development and in disorders such as Fragile X syndrome, autism, epilepsy, addiction, anxiety, schizophrenia, pain, dyskinesias, and melanoma, a large number of drugs are being developed to allosterically target this receptor. Therefore, it is critical to understand how such drugs might be affecting mGlu5 receptor function on different membranes and in different brain regions. Further elucidation of the site(s) of action of these drugs may determine which signal pathways mediate therapeutic efficacy.


Isomer resolution by micelle-assisted diffusion-ordered spectroscopy.
Diffusion-ordered NMR spectroscopy ("DOSY") is a useful tool for the identification of mixture components. In its basic form it relies on simple differences in hydrodynamic radius to distinguish between different species. This can be very effective where species have significantly different molecular sizes, but generally fails for isomeric species. The use of surfactant co-solutes can allow isomeric species to be distinguished by virtue of their different degrees of interaction with micelles or reversed micelles. The use of micelle-assisted DOSY to resolve the NMR spectra of isomers is illustrated for the case of the three dihydroxybenzenes (catechol, resorcinol, and hydroquinone) in aqueous solution containing sodium dodecyl sulfate micelles, and in chloroform solution containing AOT reversed micelles.


The effects of Panax notoginseng on delayed onset muscle soreness and muscle damage in well-trained males: a double blind randomised controlled trial.
The aim of the study was to determine if Panax notoginseng is effective in reducing pain, indicators of inflammation and muscle damage, and in turn improve performance in well trained males who underwent a bout of eccentric exercise designed to induce delayed onset muscle soreness (DOMS). A double blind randomised placebo controlled trial. Twenty well trained male volunteers, matched by maximum aerobic capacity were randomly assigned to consume a regime of 4000 mg of P. notoginseng capsules or an indistinguishable placebo before and after a downhill treadmill running episode designed to induce DOMS. Performance measures (Kin-Com, counter movement and squat jump), pain assessments (visual analogue scale (VAS), algometer) and blood analyses (interleukin-1, interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), C-reactive protein, myoglobin, creatine kinase) were assessed at 7 time points over 5 days (pre, post, 4, 24, 48, 72 and 96 h after the downhill run). The placebo group demonstrated a significant decrease in squat jump performance immediately post the downhill run, with a mean change ± 95% confidence interval (CI) of 0.8 cm (-3.53 to 1.93). The placebo group also experienced increased pain in the quadriceps 96 h after the downhill run, with a mean VAS change ± 95% CI of -0.32 cm (-0.34 to 0.98).The serum concentration of IL-6 and TNF-α were significantly lower in the placebo group 24h after the downhill run. Mean IL-6 change ± 95% CI of 0.50 pg/mL (-1.59 to 0.59), and mean TNF-α change ± 95% CI was 0.98 pg/mL (-2.04 to 0.09). No other significant differences were identified between the groups for any other outcome measure. Considering all data from this study, P. notoginseng did not convincingly have an effect on performance, muscular pain or assessed blood markers in well-trained males after an intense bout of eccentric exercise that induced DOMS.


Molecular mechanisms of renin release.
Renin secretion from renal juxtaglomerular cells is controlled by the intrarenal blood pressure, sodium chloride load of the organism, sympathetic nerve activity, and a number of hormones. The mechanisms by which these parameters exert their effects are not well understood. However, it is reasonable to assume that they act via signal transduction systems, implying the role of second messenger molecules in the control of renin secretion. This article summarizes present knowledge about the cellular mechanisms of renin secretion. Moreover, current concepts about the mechanisms by which the blood pressure and the sodium chloride load could influence renin secretion are discussed.


Evaluation of the cytogenetic damage induced by the organophosphorous insecticide acephate.
The organophosphorous insecticide acephate was tested for its ability to induce in vitro cytogenetic effect in human peripheral lymphocytes by using the chromosomal aberrations (CAs), sister chromatid exchange (SCE) and micronuclei (MN) assay. The level of nuclear DNA damage of acephate was evaluated by using the comet assay. Concentrations of 12.5, 25, 50, 100 and 200 mug mL(-1) of acephate were used. All concentrations of acephate induced significant increase in the frequency of CAs and in the formation of MN dose dependently (r = 0.92 at 24 h, r = 0.95 at 48 h for CAs, r = 0.87 for MN). A significant increase was observed in induction of SCE at 50, 100 and 200 mug mL(-1) concentrations during 24 h treatment and at all concentrations (except 12.5 mug mL(-1)) during 48 h treatment period in a dose-dependent manner (r = 0.84 at 24 h, r = 0.88 at 48 h). Acephate did not affect the replicative index and cytokinesis-block proliferation index (CBPI). However, it significantly decreased the mitotic index at all three highest concentrations (50, 100, 200 mug mL(-1)) for 24 h treatment and at all concentrations (except 12.5 mug mL(-1)) for 48 h treatment, dose-dependently (r = 0.94 at 24 h, r = 0.92 at 48 h). A significant increase in mean comet tail length was observed at 100 and 200 mug mL(-1) concentrations compared with negative control in a concentration-dependent manner (r = 0.94). The mean comet tail intensity was significantly increased at only 200 mug mL(-1) concentration. The present results indicate that acephate is a clastogenic, cytotoxic agent and it causes DNA damage at high concentrations in human lymphocytes in culture.


Can ethograms be automatically generated using body acceleration data from free-ranging birds?
An ethogram is a catalogue of discrete behaviors typically employed by a species. Traditionally animal behavior has been recorded by observing study individuals directly. However, this approach is difficult, often impossible, in the case of behaviors which occur in remote areas and/or at great depth or altitude. The recent development of increasingly sophisticated, animal-borne data loggers, has started to overcome this problem. Accelerometers are particularly useful in this respect because they can record the dynamic motion of a body in e.g. flight, walking, or swimming. However, classifying behavior using body acceleration characteristics typically requires prior knowledge of the behavior of free-ranging animals. Here, we demonstrate an automated procedure to categorize behavior from body acceleration, together with the release of a user-friendly computer application, "Ethographer". We evaluated its performance using longitudinal acceleration data collected from a foot-propelled diving seabird, the European shag, Phalacrocorax aristotelis. The time series data were converted into a spectrum by continuous wavelet transformation. Then, each second of the spectrum was categorized into one of 20 behavior groups by unsupervised cluster analysis, using k-means methods. The typical behaviors extracted were characterized by the periodicities of body acceleration. Each categorized behavior was assumed to correspond to when the bird was on land, in flight, on the sea surface, diving and so on. The behaviors classified by the procedures accorded well with those independently defined from depth profiles. Because our approach is performed by unsupervised computation of the data, it has the potential to detect previously unknown types of behavior and unknown sequences of some behaviors.


Embryonal feather growth in the chicken.
Prenatal feather growth development in the chicken was studied in 7 body regions in HH stages 27-45, using direct measurements, specific histological and immunohistochemical methods, and scanning electron microscopy. The results from measurements of absolute length values, and, particularly, growth rate development in each HH stage revealed a distinct phase of most intensive growth in HH stage 40-41, which was preceded by feather follicle insertion and accompanied by the occurrence of alpha-keratins in barbule cells. Specific regional evaluation demonstrated that growth in the feather follicles of abdominal skin generally showed the slowest progression from absolute values and that in the feather filaments of the developing wings the most rapid progression occurred during HH stage 40-41 from growth rate values.


Effect of short-chain fructooligosaccharides and cellulose on cecal enzyme activities in rats.
The effect of fructooligosaccharides (FOS) on cecal enzyme activity was studied. Adult male Wistar rats were fed a fiber-free diet supplemented with 5% cellulose, a 5% mixture (1:1) of cellulose and FOS or 5% FOS as a source of fiber for 4 weeks. The cecal content was used to measure azoreductase, beta-glucuronidase, beta-glucosidase, nitrate reductase and nitroreductase activities. Cellulose-fed diet increased significantly body weight gain, food intake and fecal stool weight compared to FOS-fed diet. No differences in food intake between FOS-containing diets were found. FOS-containing diets showed statistically higher weight of cecal content and weight of cecal wall compared with the cellulose group. There were significant differences in cecal enzyme activities between cellulose-fed rats and FOS-fed rats. Cellulose-FOS-fed diet decreased significantly nitroreductase, beta-glucuronidase and beta-glucosidase enzymes, but did not differ statistically in azoreductase and nitrate reductase compared with the control group. FOS-fed diet increased significantly reductive enzymes and decreased hydrolytic enzymes compared with the cellulose group. The incorporation of cellulose in diet seems to affect the prebiotic effect of FOS, since both cellulose and FOS are possible substrates for bifidobacteria proliferation. The results suggest that a mixture of cellulose and FOS as a source of dietary fiber could have a healthier effect on bacterial enzyme activities than each type of dietary fiber alone.


The use of a resorbable membrane in mucogingival surgery. Case series.
A surgical technique involving a resorbable membrane was used to treat 3 to 7 mm localized human buccal recessions on 10 consecutive patients. The exposed root surface was scaled and a trapezoidal mucoperiosteal flap was elevated after de-epithelization of the papillae. The space between the root and the membrane was created using a bur to form a concavity on the root and by bending the membrane with a suture. The flap was positioned as coronally as possible covering the membrane. The sutures were removed 15 days postsurgery and tetracycline therapy prescribed for 10 days. The results were evaluated at 12 months. The surgical procedure resulted in a significant reduction in recession (2.9 mm +/- 1.3) as well as a gain in attachment (3.4 mm +/- 2.1). Calculation of mean root coverage was 59.6%. There was no significant change of the keratinized tissue width. For therapeutic reasons, re-entry was performed in 2 cases: newly formed tissue was observed on the previously exposed roots. Guided tissue regeneration using a resorbable membrane appears to provide good results in cases of localized buccal recession.


Host-parasite associations and host-specificity in haemoparasites of reed bed passerines.
The host specificity and host sharing of avian haemoparasites (genera Haemoproteus and Plasmodium) is still poorly known, although they infect a large proportion of several studied bird populations. This study used molecular techniques to detect haemoparasites in marsh warblers and in other passerines that feed in reed beds, at 4 sites in Portugal. The host-specificity of the parasite lineages was analysed and compared with other cases described in the literature to assess whether apparent host specificity changes according to the studied system. Nine lineages of Haemoproteus and 15 of Plasmodium were found, of which only 10 Plasmodium were proven to have local transmission. Each lineage was confined to a distinct set of host species. The distribution of parasites in the host species was non-nested, meaning that specialist lineages did not always share hosts with generalists. The most prevalent lineages were those with a wider host range, indicating that the ability to infect more hosts will enhance a parasite's prevalence in its entire host range. We also found that in our areas, a specialist parasite (H. MW1) appears to have a more generalist character than described in the literature, suggesting that a parasite's apparent specialization can depend on the type of host species sampled.


An Actual Natural Setting Improves Mood Better Than Its Virtual Counterpart: A Meta-Analysis of Experimental Data.
Accumulating evidence indicates that simulated natural settings can engage mechanisms that promote health. Simulations offer alternatives to actual natural settings for populations unable to travel outdoors safely; however, few studies have contrasted the effects of simulations of natural settings to their actual outdoor counterparts. We compared the impacts of simulated and actual natural settings on positive and negative affect (mood) levels using a pooled sample of participants enrolled in extant experimental studies. Relevant articles were identified from a review of research published/in press by March 2020 and updated during the peer review of the current study. Of 16 articles identified, 6 met the inclusion criteria and administered a single cross-cutting, standardized instrument [the Positive and Negative Affect Schedule (PANAS)] before and after exposure. Random effects meta-analysis of pooled effects showed that positive affect increased in the actual settings but not in their simulated counterparts (Hedge's g = 0.87; 95% CI, 0.54, 1.20). We observed little difference in effects on negative affect change scores (g = -0.28; 95% CI, -0.62, 0.06), with studies generally showing reductions in negative affect in both settings. Further research with additional populations, settings, antecedent conditions, and durations would provide a more robust understanding of differences in effects between these two ways to enhance mood by viewing nature.


Antimicrobial activity of subinhibitory concentrations of aminoglycosides against Pseudomonas aeruginosa as determined by the killing-curve method and the postantibiotic effect.
This investigation used the postantibiotic effect (PAE) and killing curves to provide data on the antimicrobial activity of subinhibitory (1/8x, 1/4x and 1/2x minimum inhibitory concentration; MIC) and inhibitory (1x MIC) concentrations of amikacin, gentamicin and tobramycin against Pseudomonas aeruginosa. Subinhibitory concentrations (1/4x and 1/2x MIC) of aminoglycosides demonstrated a reproducible PAE. At 1/4x MIC, the order of duration of the PAE was approximately 15 min for all aminoglycosides, while at 1/2x MIC all three aminoglycosides displayed a similar PAE of approximately 40 min. Killing-curve studies demonstrated that subinhibitory concentrations of aminoglycosides either decrease bacterial growth for several hours (1/4x and 1/2x MIC) or produce stasis of growth for several hours (1/8x MIC). Only inhibitory aminoglycoside concentrations (1x MIC) proved to be bactericidal. Subinhibitory concentrations of aminoglycosides decrease bacterial growth and produce a PAE against P. aeruginosa.


Anterior cervical discectomy with freeze-dried fibula allograft. Overview of 317 cases and literature review.
A retrospective review of 317 patients to determine the efficacy of allogeneic fibula arthrodesis after anterior cervical discectomy. To examine the efficacy of allogeneic fibula as an alternative fusion substrate after anterior cervical discectomy, and to determine the effects of cigarette smoking on the healing of fibula allografts. The use of autogeneic iliac crest is associated with graft harvest complications in up to 20% of patients. Most studies reporting on the use of allogeneic iliac crest cite a high collapse rate. Few studies exist that note the efficacy of allogeneic fibula in this procedure and the effects of cigarette smoking on fusion rate. From 1988 to 1993, 317 patients underwent grafting by the Smith-Robinson technique with allogeneic fibula after anterior cervical discectomy. Patients who described themselves as habitual cigarette smokers or who smoked during the perioperative or postoperative period were categorized as smokers. All patients were immobilized in a rigid cervical orthosis (Philadelphia collar) for at least 10 weeks postoperatively. A minimum of 2 years follow-up was achieved in 289 patients. In all, 162 men and 127 women had a total of 311 levels grafted, and the mean follow-up period was 33 months (range, 24 to 51 months). Of patients who received allogeneic fibula at one level, 90% (242/269) achieved radiologic fusion. The fusion rate was 92% (182/198) among nonsmokers compared with 85% (60/71) among smokers (not a statistically significant difference; P = 0.120). After two-level procedures, 72% (13/18) of the patients showed fusion. The fusion rate was 50% (2/4) among smokers compared with 79% (11/14) among nonsmokers (P = 0.53). When one-level arthrodesis (90%) was compared with two-level arthrodesis (72%), the difference approached statistical significance (P = 0.054). Neither of the two patients, both nonsmokers, who received grafts at three levels achieved fusion. There were no infections, and no grafts collapsed. Two grafts extruded (0.6%), but these were partial and did not require reoperation. Both patients fused and constituted the only patients with more than 10 degrees of angulation in the series. Graft subsidence occurred in 5% (17/311) of the grafts, mostly in the beginning of the series, and was not problematic. This phenomenon was thought to have been caused by overaggressive removal of the cortical endplate. Allogeneic fibula is an effective substrate for use in achieving fusion after anterior cervical discectomy. Maximal results are achieved with its use at one level in nonsmokers. Cigarette smoking decreased the fusion rate with allogeneic fibula in the anterior cervical spine, but not by a statistically significant amount.


[Molecular analysis of the parental origin of trisomy in two families with two children having regular trisomy 21].
In order to investigate the parental origin of the trisomy in two families with two free trisomy 21 affected siblings, cytogenetic and molecular analyses were performed. In each case the parental origin was the same for both patients. In one of the families an association between the concordance of the paternal origin of the trisomy and the existence of mosaicism in the blood was established. The various etiologies which may account for recurrence are discussed.


Development of drainage water quality from a landfill cover built with secondary construction materials.
The aim of this study was to evaluate the drainage water quality from a landfill cover built with secondary construction materials (SCM), fly ash (FA), bottom ash (BA) sewage sludge, compost and its changes over time. Column tests, physical simulation models and a full scale field test were conducted. While the laboratory tests showed a clear trend for all studied constituents towards reduced concentrations over time, the concentrations in the field fluctuated considerably. The primary contaminants in the drainage water were Cl(-), N, dissolved organic matter and Cd, Cu, Ni, Zn with initial concentrations one to three orders of magnitude above the discharge values to the local recipient. Using a sludge/FA mixture in the protection layer resulted in less contaminated drainage water compared to a sludge/BA mixture. If the leaching conditions in the landfill cover change from reduced to oxidized, the release of trace elements from ashes is expected to last about one decade longer while the release of N and organic matter from the sludge can be shortened with about two-three decades. The observed concentration levels and their expected development over time require drainage water treatment for at least three to four decades before the water can be discharged directly to the recipient.


Gender and pregnancy affect neuropeptide responses of the rabbit Achilles tendon.
Tendons such as the Achilles tendon are complex structures that are hypocellular, hypovascular, and hyponeural. The development of pathophysiologic function in this tendon because of overuse is relatively common; however, the mechanisms responsible for the development of paratenonitis and tendinosis remain primarily undefined. To understand better a possible regulatory role for neuropeptides (substance P and calcitonin gene related peptide) known to be present in this tissue, the influence of substance P and calcitonin gene related peptide on messenger ribonucleic acid levels for numerous inflammatory molecules, growth factors, and proteinases and inhibitors have been assessed using a semiquantitative reverse transcription-polymerase chain reaction method and explants of paratenon and Achilles tendon midsubstance tissue from adolescent male and female rabbits and tissue from primigravida females. Most of the significant (p < 0.01) changes observed were at the level of the growth factor transcripts and transcripts for proteinases and inhibitors. Twenty-one significant differences in the responsiveness between tissues from male and female rabbits were observed, and 12 significant differences in responsiveness between virgin females and primigravida rabbits were seen. Differences between paratenon and midsubstance responsiveness to the neuropeptides also were observed within each group of animals. The midsubstance tissue from pregnant animals was hyporesponsive to both neuropeptides. These results indicate that neurotransmitter responsiveness of Achilles tendon tissue differs in a gender specific manner and is influenced by pregnancy associated factors.


Emerging Alzheimer's disease therapies: inhibition of beta-secretase.
Among the approaches towards disease modifying treatment of Alzheimer's disease blocking the initial step of the amyloid cascade, Abeta42 generation, has received most attention. Abeta42 generation requires two proteases, beta- and gamma-secretase, and inhibition of these enzymes is a key focus of AD drug development. Progress in this area has been slow, because these enzymes were not identified. Using an expression cloning strategy we have identified a novel membrane bound aspartic protease, BACE1, as beta-secretase. The enzyme has been characterized in detail. The x-ray crystal structure, which is critical for rational inhibitor design, has been solved and shown to be similar to that of other pepsin family members. Our recent knockout studies show that BACE1 is critical for Abeta generation, but the knockout mice show an otherwise normal phenotype, raising the possibility that therapeutic BACE1 inhibition could be accomplished without major mechanism based toxicity. However, target-mediated toxicity of beta-secretase inhibition cannot be ruled out, as long as the major substrates of this enzyme are unknown. While various peptidic beta-secretase inhibitors have been published, the key challenge now is the generation of more drug-like compounds that could be developed for therapeutic purposes.


Experimental induction of pulmonary fibrosis in horses with the gammaherpesvirus equine herpesvirus 5.
Gammaherpesviruses (γHV) are implicated in the pathogenesis of pulmonary fibrosis in humans and murine models of lung fibrosis, however there is little direct experimental evidence that such viruses induce lung fibrosis in the natural host. The equine γHV EHV 5 is associated with equine multinodular pulmonary fibrosis (EMPF), a progressive fibrosing lung disease in its natural host, the horse. Experimental reproduction of EMPF has not been attempted to date. We hypothesized that inoculation of EHV 5 isolated from cases of EMPF into the lungs of clinically normal horses would induce lung fibrosis similar to EMPF. Neutralizing antibody titers were measured in the horses before and after inoculation with EHV 5. PCR and virus isolation was used to detect EHV 5 in antemortem blood and BAL samples, and in tissues collected postmortem. Nodular pulmonary fibrosis and induction of myofibroblasts occurred in EHV 5 inoculated horses. Mean lung collagen in EHV 5 inoculated horses (80 µg/mg) was significantly increased compared to control horses (26 µg/mg) (p < 0.5), as was interstitial collagen (32.6% ± 1.2% vs 23% ± 1.4%) (mean ± SEM; p < 0.001). Virus was difficult to detect in infected horses throughout the experiment, although EHV 5 antigen was detected in the lung by immunohistochemistry. We conclude that the γHV EHV 5 can induce lung fibrosis in the horse, and hypothesize that induction of fibrosis occurs while the virus is latent within the lung. This is the first example of a γHV inducing lung fibrosis in the natural host.


Endothelial nitric oxide synthase targeting to caveolae. Specific interactions with caveolin isoforms in cardiac myocytes and endothelial cells.
The endothelial isoform of nitric oxide synthase (eNOS) modulates cardiac myocyte function and is expressed in the particulate subcellular fraction. We have previously shown that eNOS is targeted to plasmalemmal caveolae in endothelial cells. Caveolae, specialized domains of the plasma membrane, may serve to sequester signaling proteins; a family of transmembrane proteins, the caveolins, form a key structural component of these microdomains. Caveolae in cardiac tissues contain the muscle-specific isoform caveolin-3, and caveolae in endothelial cells contain the widely expressed isoform caveolin-1, which shares limited sequence identity with caveolin-3. Our immunohistochemical analyses of rat cardiac muscle used isoform-specific caveolin antibodies to reveal prominent caveolin-3 staining in myocyte sarcolemmal membranes and at intercalated discs, whereas caveolin-1 staining was prominent in the vascular endothelium. Caveolin or eNOS antibodies were utilized to immunoprecipitate cardiac myocyte or cultured aortic endothelial cell lysates, which then were analyzed in immunoblots. In endothelial cells, we found that eNOS is quantitatively immunoprecipitated by antibodies to caveolin-1. In cardiac myocyte lysates, nearly all the eNOS is immunoprecipitated instead by antibodies to caveolin-3 and, conversely, eNOS antiserum immunoprecipitated primarily caveolin-3. These studies establish expression of eNOS in cardiac myocyte caveolae and document tissue-specific and quantitative associations of eNOS with caveolin. These findings may have important implications for the regulation of eNOS by caveolin isoforms and by other signaling proteins targeted to caveolae.


[Effects of somatostatin and its analog on gastric secretion. An application of the secretagogues to gastric secretion].
A simple technique to examine the effects of drugs on the gastric secretion response to the secretagogues without anesthesia was shown in this paper. The administration of bethanechol (1 mg/kg, s.c.), histamine (15 mg/kg, s.c.) or pentagastrin (0.25 mg/kg, i.p.) significantly increased the gastric volume and the total acid output in the pylorus-ligated rat. These responses to the secretagogues were inhibited by N-butylscopolamine, urogastrone or cimetidine dose-dependently. N-butylscopolamine (0.5 mg/kg, i.p.) inhibited the response to bethanechol but not that to pentagastrin or histamine. Cimetidine (5 mg/kg, i.p.) inhibited not only the response to histamine but also the acid response to bethanechol or pentagastrin. Urogastrone (5 mg/kg, i.p.) inhibited the response to these three secretagogues. The ratio of the total acid output to the gastric volume was also examined in each of the cases. Somatostatin (0.1 mg/kg, i.p.) inhibited the response to pentagastrin, but not that to bethanechol or histamine. On the other hand, an analogue of somatostatin (SS-1; 0.1 mg/kg, i.p.) inhibited the response to bethanechol but not that to pentagastrin or histamine.


The rising impact of mathematical modelling in epidemiology: antibiotic resistance research as a case study.
Mathematical modelling of infectious diseases has gradually become part of public health decision-making in recent years. However, the developing status of modelling in epidemiology and its relationship with other relevant scientific approaches have never been assessed quantitatively. Herein, using antibiotic resistance as a case study, 60 published models were analysed. Their interactions with other scientific fields are reported and their citation impact evaluated, as well as temporal trends. The yearly number of antibiotic resistance modelling publications increased significantly between 1990 and 2006. This rise cannot be explained by the surge of interest in resistance phenomena alone. Moreover, modelling articles are, on average, among the most frequently cited third of articles from the journal in which they were published. The results of this analysis, which might be applicable to other emerging public health problems, demonstrate the growing interest in mathematical modelling approaches to evaluate antibiotic resistance.


PdCu alloy nanoparticle-decorated copper nanotubes as enhanced electrocatalysts: DFT prediction validated by experiment.
In order to combine the advantages of both 0D and 1D nanostructured materials into a single catalyst, density functional theory (DFT) calculations have been used to study the PdCu alloy NP-decorated Cu nanotubes (PdCu@CuNTs). These present a significant improvement of the electrocatalytic activity of formic acid oxidation (FAO). Motivated by our theoretical work, we adopted the seed-mediated growth method to successfully synthesize the nanostructured PdCu@CuNTs. The new catalysts triple the catalytic activity for FAO, compared with commercial Pd/C. In summary, our work provides a new strategy for the DFT prediction and experimental synthesis of novel metal NP-decorated 1D nanostructures as electrocatalysts for fuel cells.


Ultra-low lattice thermal conductivity and anisotropic thermoelectric transport properties in Zintl compound β-K2Te2.
A good thermoelectric (TE) performance is usually the result of the coexistence of an ultralow thermal conductivity and a high TE power factor in the same material. In this paper, we investigate the thermal transport and TE properties of the Zintl compound β-K2Te2 based on a combination of first-principles calculations and the Boltzmann transport equation. Remarkably, the calculated lattice thermal conductivity κL in hexagonal β-K2Te2 is ultralow with a value of 0.19 (0.30) W m-1 K-1 along the c (a and b) axis at 300 K due to the small phonon group velocity and phonon lifetime, which is comparable to the κL for wood and promises possible good TE performance. By taking the fully anisotropic acoustic deformation potential scattering, polar optical phonon scattering, and ionized impurity scattering into account, the rational electron scattering and transport properties are captured, which indicates a power factor exceeding 2.0 mW m-1 K-2. As a result, the anomalously high n-type ZT of 2.62 and p-type ZT of 3.82 at 650 K along the c axis are obtained in the hexagonal β-K2Te2, breaking the long-term record of ZT < 3.5 in the majority of the reported TE materials until now. These findings support that hexagonal β-K2Te2 is a potential candidate for high-efficiency TE applications.


The Toll-like Receptor 2 (TLR2)-related Immunopathological Responses in the Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis.
Toll-like receptors (TLRs) play principle roles in recognition of autologous components which have been pointed as the danger-associated molecular patterns (DAMP) and microbial components which are identified as pathogen associated molecular patterns (PAMP).The infiltration of various inflammatory cells such as dendritic cells, lymphocytes (CD4+ T, CD8+ T as well as B cells), monocytes and macrophages occur into the central nervous sys-tem (CNS) during multiple sclerosis (MS) and its animal model named experimental autoimmune encephalomyelitis (EAE). The infiltrated leukocytes and residential cells of the CNS express several TLRs (especially TLR2) and their expression are elevated in MS and EAE. TLR2 recognizes a large variety DAMP and PAMP molecules due to its ability to create heterodimers with TLR1, TLR6 and probably TLR10. A wide spectrum of DAMP molecules, including heat shock protein 60 (HSP60), HSP70, high mobility group box 1 (HMGB1), β-defensin 3, surfactant protein A and D, eosinophil-derived neurotoxin, gangliosides, serum amyloid A, hyaluronic acid and biglycan are identified by TLR2, whose their expression is increased in MS patients. TLR2 may contribute in the development of MS and EAE diseases through the reinforcement of Th1/Th17 cell-related responses, downregulation of regulatory T cells, induction of IL-17+ γδ T cells, inhibition of oligodendrocyte maturation, induction of poly ADP-ribose polymerase-1 (PARP-1)-dependent pathway in microglia, macrophages and astrocytes and inhibition of type I interferons expression. The contribution of TLR2-related immunopathological responses in the MS and EAE pathogenesis and its possible targeting as promising therapeutic potentials are considered in this review.


Reliability of air displacement plethysmography in a large, heterogeneous sample.
Several studies have assessed the validity of air displacement plethysmography (ADP), but few have assessed the reliability of ADP using a large, heterogeneous sample. This study was conducted to determine the reliability of ADP using the Bod Pod in a large, heterogeneous sample. A total of 980 healthy men and women (30 +/- 15 yr, mean +/- SD) completed two body composition assessments separated by 15-30 min. All testing was done in accordance with the manufacturer's instructions. A significant correlation (r = 0.992, P = 0.001) was found between body density (BD) 1 (1.046 +/- 0.001 kg.L(-1); mean +/- SEM) and BD 2 (1.046 +/- 0.001 kg.L(-1). A paired t-test revealed no significant difference between BD 1 and 2 (P = 0.935). The coefficient of variation (CV) for BD was 0.15%. A significant intraclass correlation coefficient (ICC) was found for BD (ICC = 0.996, P = 0.001), and the standard error of measurement (SEM) was 0.001 kg.L(-1). Body mass (BM) 1 and 2 were correlated significantly (r = 0.999, P = 0.001); however, a significant (P = 0.001) decrease was seen from BM 1 (75.510 +/- 0.461 kg) to BM 2 (75.497 +/- 0.461 kg). Body volume (BV) tended to decrease (P = 0.08) from BV 1 (69.900 +/- 0.449 L) to BV 2 (69.884 +/- 0.449 L). ADP using the Bod Pod appears to assess BD reliably; however, the observed CV suggests that multiple trials are necessary to detect small treatment effects.


Isoflavone-enriched soybean leaves attenuate ovariectomy-induced osteoporosis in rats by anti-inflammatory activity.
With an increasing aging population, postmenopausal osteoporosis has become a global public health problem. Previous evidence has shown that postmenopausal osteoporosis is a skeletal disease mainly caused by estrogen deficiency, generally accompanied by inflammation, and dietary isoflavones may ameliorate postmenopausal osteoporosis by anti-inflammatory activity. We have generated isoflavone-enriched soybean leaves (IESLs), but their anti-inflammatory activity and effect on attenuating osteoporosis are still obscure. Here, we determined the isoflavone profiles of IESLs and evaluated their anti-inflammatory activity in lipopolysaccharide-stimulated RAW 264.7 cells and anti-osteoporotic effects on ovariectomy-induced osteoporosis in rats. IESLs had a high content of total isoflavone. Hydrolysate of IESLs (HIESLs) was rich with the aglycones daidzein and genistein, and HIESLs can significantly inhibit lipopolysaccharide-induced inflammation by reducing messenger RNA expression of iNOS, COX-2, IL6, and IL1β. Moreover, ovariectomized rats receiving aqueous extracts of IESLs (HIESLs) orally maintained more bone mass than control rats did, which was attributed to inhibition of osteoclastogenesis by downregulating the messenger RNA expression of the bone-specific genes RANKL/OPG, OC, and cathepsin K, and the inflammation-related genes IL6, NFκB, and COX-2. IESLs may attenuate postmenopausal osteoporosis by suppressing osteoclastogenesis with anti-inflammatory activity and be a potential source of functional food ingredients for the prevention of osteoporosis. © 2020 Society of Chemical Industry.


Determining extracellular vesicles properties and miRNA cargo variability in bovine milk from healthy cows and cows undergoing subclinical mastitis.
Subclinical mastitis, the inflammation of the mammary gland lacking clinical symptoms, is one of the most prevalent and costly diseases in dairy farming worldwide. Milk microRNAs (miRNAs) encapsulated in extracellular vesicles (EVs) have been proposed as potential biomarkers of different mammary gland conditions, including subclinical mastitis. However, little is known about the robustness of EVs analysis regarding sampling time-point and natural infections. To estimate the reliability of EVs measurements in raw bovine milk, we first evaluated changes in EVs size and concentration using Tunable Resistive Pulse Sensing (TRPS) during three consecutive days of sampling. Then, we analysed daily differences in miRNA cargo using small RNA-seq. Finally, we compared milk EVs differences from naturally infected udder quarters with their healthy adjacent quarters and quarters from uninfected udders, respectively. We found that the milk EV miRNA cargo was very stable over the course of three days regardless of the health status of the quarter, and that infected quarters did not induce relevant changes in milk EVs of adjacent healthy quarters. Chronic subclinical mastitis induced changes in milk EV miRNA cargo, but neither in EVs size nor concentration. We observed that the changes in immunoregulatory miRNAs in quarters with chronic subclinical mastitis were cow-individual, however, the most upregulated miRNA was bta-miR-223-3p across all individuals. Our results showed that the miRNA profile and particle size characteristics remained constant throughout consecutive days, suggesting that miRNAs packed in EVs are physiological state-specific. In addition, infected quarters were solely affected while adjacent healthy quarters remained unaffected. Finally, the cow-individual miRNA changes pointed towards infection-specific alterations.


Association between changes in obesity parameters and incidence of chronic kidney disease in Japanese individuals.
Obesity increases the risk for chronic kidney disease (CKD). By analyzing data on individuals who underwent general health screening in two consecutive years, we investigated whether changes in body mass index (BMI) or waist circumference (WC) were associated with the appearance or disappearance of the CKD components; micro-/macroalbuminuria (> or =30 mg urinary albumin per gram creatinine) and a low estimated glomerular filtration rate (eGFR; <60 ml/min/1.73 m(2)). Logistic regression analysis showed that in men with micro-/macroalbuminuria at the first visit, a BMI reduction of > or =0.42 or a WC reduction of > or =3.0 cm over the 1-year period resulted in a significantly reduced incident of micro-/macroalbuminuria at the second visit. On the other hand, a BMI gain of > or =0.33 over 1 year in men without micro-/macroalbuminuria and a low eGFR at the fist visit significantly increased the incident of micro-/macroalbuminuria and a low eGFR, respectively, at the second visit. These findings indicate that lowering the obesity indexes in men with micro-/macroalbuminuria reduced the incidence of this condition at the 1-year follow-up and that, on the contrary, an increase in BMI in men without micro-/macroalbuminuria and a low eGFR at the first examination increased the risk of these conditions during the 1-year follow-up period.


Development of a sandwich enzyme-linked immunosorbent assay (ELISA) for detection of buckwheat residues in food.
Buckwheat is a pseudocereal (an eudicot with seed qualities and uses similar to those of monocot cereals, family Poaceae) that is consumed in some Asian countries as a staple, and in some western countries as a health food. Allergic reactions to buckwheat are common in some countries. The objective was to develop a specific and sensitive sandwich enzyme-linked immunosorbent assay (ELISA) to detect traces of buckwheat that might inadvertently contaminate other foods in order to assure accurate labeling and consumer protection. Buckwheat-specific antibodies produced in 3 species of animals were tested for specificity and titer by direct ELISA and immunoblot. A sandwich ELISA was developed utilizing pooled rabbit antibuckwheat sera to capture buckwheat proteins and pooled goat antibuckwheat sera, followed by enzyme-labeled rabbit antigoat immunoglobulin G (IgG), to detect bound buckwheat proteins. The lower limit of quantification (LOQ) of the sandwich ELISA was 2 parts per million (ppm) of buckwheat in the presence of complex food matrices. The ELISA is highly specific with no cross-reactivity to any of 80 food ingredients and matrices tested. Validation studies conducted with buckwheat processed into noodles and muffins showed greater than 90% and 60% recovery, respectively. The percent recovery of buckwheat from noodles was similar to that achieved with a commercial buckwheat ELISA kit (ELISA Systems Pty. Ltd., Windsor, Queensland, Australia) at high buckwheat concentrations. However, the sensitivity of this ELISA was greater than the commercial ELISA. This newly developed ELISA is sufficiently specific and sensitive to detect buckwheat residues in processed foods to protect buckwheat-allergic subjects from potential harm. Practical Application: Buckwheat is becoming a common food ingredient in a number of processed foods due to potentially beneficial nutritional properties, without the celiac disease inducing glutenin proteins of wheat and related cereals. However, buckwheat causes allergy in some individuals and must be labeled and tested accurately to protect those with allergy to buckwheat. We describe the development of a new test assay to help food producers ensure that buckwheat is not present in foods that are not intended to contain buckwheat.


Expression of nonmuscle myosin heavy chain B (SMemb) in rat allogeneic kidney transplantation.
Investigators have reported that the nonmuscle myosin heavy chain B (SMemb) expression is enhanced in various types of glomerular diseases which develop into nephrosclerosis. In renal transplantation, transplant glomerulitis is often recognized during acute rejection. Therefore, we hypothesized that SMemb plays important roles in acute kidney rejection. To evaluate the role of SMemb in the development of kidney rejection, we examined its expression in rat kidney transplantation models. We used Lewis rats as recipients and Wistar rats as donors. Group I: controls; group II: isograft model; group III: allograft model; group IV: as group III +10 mg/kg/day of ciclosporin A (CsA), and group V: as group III + CsA administration for 5 days postoperatively. Histopathological and SMemb immunohistochemical studies were completed. Clear enhancement of SMemb expression was found on day 3 in group III. In groups I, II, IV, and V, SMemb was faintly expressed in the glomerular cells. However, after termination of CsA treatment, the SMemb expression increased. The expression of SMemb was higher in the allograft model than in either isograft or CsA-treated models. Immunohistological investigations show that the SMemb expression was significant from an early stage at which histopathological reactions were hardly identifiable. This, therefore, could be useful for an earlier diagnosis of acute rejection.


Nosocomial transmission of Saccharomyces cerevisiae in bone marrow transplant patients.
Saccharomyces cerevisiae is an unusual cause of clinical infection. We describe three bone marrow transplant patients on a haematology unit who developed possible invasive disease with the organism. Two patients died and both these patients appeared to have a related strain of S. cerevisiae. Screening for S. cerevisiae from throat and stool samples revealed four further patients who were carriers. Genotyping of the invasive and carriage strains demonstrated an indistinguishable strain from patients who had been on the unit at the same time, suggesting cross-infection.


Group problems in problem-based learning.
Successful small-group learning in problem-based learning (PBL) educational programmes relies on functional group processes. However, there has been limited research on PBL group problems, and no studies have been conducted on problems as perceived by both students and tutors in the same educational context. The authors investigated PBL group problems in a graduate-entry medical programme, and report the most common group problems, and those that hinder students' learning the most. The possible causes of individual quietness and dominant behaviour, and potential influences that group problems may have on the tutorial process are summarized in an exploratory model of PBL group dysfunction that could be used to guide further research. Specifically, there is a need for further evidence on which to base guidelines for tutors and students to effectively manage group problems.


[Application of direct long-standing electrostimulation in consequences of the sciatic nerve injury].
The results of surgical treatment of 57 patients, suffering consequences of the sciatic nerve injury, using the system for long-lasting electrostimulation "Naysi 3M", were presented. The domestically manufactured system is individual and gives possibility to conduct the direct electrostimulation procedures in the home conditions, several times a day, for a long time. Positive results, consisting of the various degree enhancement of the lower extremities movements volume and strength, the sensitivity restoration and the pain severity reduction or disappearance, were achieved in 46 (81%) patients. In inefficacy of conservative treatment and presence of indications for the operation in patients with sciatic nerve injury the long-lasting electrostimulation secures restoration of the lower extremities lost functions, the pain syndrome and the vegetative-trophic disorders regress.


Enhancer RNA Profiling in Smoking and HPV Associated HNSCC Reveals Associations to Key Oncogenes.
Smoking and HPV infection are known causes for the vast majority of head and neck squamous cell carcinomas (HNSCC) due to their likelihood of causing gene dysregulation and genomic alterations. Enhancer RNAs (eRNAs) are non-coding RNAs that are known to increase nearby and target gene expression, and activity that has been suggested to be affected by genetic and epigenetic alterations. Here we sought to identify the effects of smoking and HPV status on eRNA expression in HNSCC tumors. We focused on four patient cohorts including smoking/HPV+, smoking/HPV-, non-smoking/HPV+, and non-smoking/HPV- patients. We used TCGA RNA-seq data from cancer tumors and adjacent normal tissue, extracted eRNA read counts, and correlated these to survival, clinical variables, immune infiltration, cancer pathways, and genomic alterations. We found a large number of differentially expressed eRNA in each patient cohort. We also found several dysregulated eRNA correlated to patient survival, clinical variables, immune pathways, and genomic alterations. Additionally, we were able to find dysregulated eRNA nearby seven key HNSCC-related oncogenes. For example, we found eRNA chr14:103272042-103272430 (eRNA-24036), which is located close to the TRAF3 gene to be differentially expressed and correlated with the pathologic N stage and immune cell populations. Using a separate validation dataset, we performed differential expression and immune infiltration analysis to validate our results from the TCGA data. Our findings may explain the association between eRNA expression, enhancer activity, and nearby gene dysregulation.


Quality of life and sexual functioning after cervical cancer treatment: a long-term follow-up study.
The purpose of the study was to investigate the long-term treatment side effects on the quality of life (QoL) and sexual functioning of cervical cancer survivors undergoing different treatment regimens. QoL and sexual functioning were measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire, the Cervix Cancer Module, and the Sexual Activity Questionnaire. One hundred twenty-one cervical cancer survivors (63 Surgery, 38 Surgery/CT, and 20 Surgery/RT) participated. Patients in the Surgery/RT Group reported significantly worse QoL outcomes (lower scores on physical, role, cognitive, and social functioning) compared with patients in the Surgery Group or patients in the Surgery/CT Group. The level of symptoms such as nausea/vomiting, pain, appetite loss, frequent urination (p=0.019), leaking of urine (p=0.015), and the feeling of a tight vagina (p=0.018) was significantly higher in irradiated patients. Concerning sexual functioning, patients in the Surgery/RT Group reported a significantly lower sexual activity rate compared with women in the Surgery Group or women in the Surgery/CT group (p<0.05). However, there were no statistically significant differences concerning sexual pleasure and sexual discomfort among the three treatment groups (p>0.05). Cervical cancer survivors treated with adjuvant radiotherapy are more likely at risk for impaired QoL. Survivors treated with surgery or adjuvant chemotherapy return to a similar level of QoL as women without a history of cancer. Although the sexual activity rate is lower in irradiated patients their sexual pleasure is similar to patients after surgery and chemotherapy.


[Our experience with the pectoralis major musculocutaneous flap. Apropos of 57 cases].
One of the most important technical advances in cervicofacial plastic surgery over the last few years is undoubtedly the use of the musculocutaneous flap from pectoralis major. A review of its application in 57 cases showed the flap to be of excellent viability (5% total necrosis of flap), and to offer multiple possibilities during primary surgery or that following radiation. Indications and excision limits can be extended, particularly in buccopharyngeal surgery, providing and appreciable functional gain (particularly disappearance of pain), even though long-term carcinologic advantages are deceiving.


Intracellular pH Regulation during NO(3) Assimilation in Shoot and Roots of Ricinus communis.
Ricinus communis L. was used to test the Dijkshoorn-Ben Zioni hypothesis that NO(3) (-) uptake by roots is regulated by NO(3) (-) assimilation in the shoot. The fate of the electronegative charge arising from total assimilated NO(3) (-) (and SO(4) (2-)) was followed in its distribution between organic anion accumulation and HCO(3) (-) excretion into the nutrient solution. In plants adequately supplied with NO(3) (-), HCO(3) (-) excretion accounted for about 47% of the anion charge, reflecting an excess nutrient anion over cation uptake. In vivo nitrate reductase assays revealed that the roots represented the site of about 44% of the total NO(3) (-) reduction in the plants. To trace vascular transport of ionic and nitrogenous constituents within the plant, the composition of both xylem and phloem saps was thoroughly investigated. Detailed dry tissue and sap analyses revealed that only between 19 and 24% of the HCO(3) (-) excretion could be accounted for from oxidative decarboxylation of shoot-borne organic anions produced in the NO(3) (-) reduction process. The results obtained in this investigation may be interpreted as providing direct evidence for a minor importance of phloem transport of cation-organate for the regulation of intracellular pH and electroneutrality, thus practically eliminating the necessity for the Dijkshoorn-Ben Zioni recycling process.


Dietary High-Oleic Acid Soybean Oil Dose Dependently Attenuates Egg Yolk Content of n-3 Polyunsaturated Fatty Acids in Laying Hens Fed Supplemental Flaxseed Oil.
Chickens can hepatically synthesize eicosapentaenoic acid (20:5 n-3) and docosahexaenoic acid (22:6 n-3) from α-linolenic acid (ALA; 18:3 n-3); however, the process is inefficient and competitively inhibited by dietary linoleic acid (LNA; 18:2 n-6). In the present study, the influence of dietary high-oleic acid (OLA; 18:1 n-9) soybean oil (HOSO) on egg and tissue deposition of ALA and n-3 polyunsaturated fatty acids (PUFA) synthesized from dietary ALA was investigated in laying hens fed a reduced-LNA base diet supplemented with high-ALA flaxseed oil (FLAX). We hypothesized that reducing the dietary level of LNA would promote greater hepatic conversion of ALA to very long-chain (VLC; >20C) n-3 PUFA, while supplemental dietary HOSO would simultaneously further enrich eggs with OLA without influencing egg n-3 PUFA contents. Nine 51-week-old hens each were fed 0, 10, 20, or 40 g HOSO/kg diet for 12 weeks. Within each group, supplemental dietary FLAX was increased every 3 weeks from 0 to 10 to 20 to 40 g/kg diet. Compared to controls, dietary FLAX maximally enriched the total n-3 and VLC n-3 PUFA contents in egg yolk by 9.4-fold and 2.2-fold, respectively, while feeding hens 40 g HOSO/kg diet maximally attenuated the yolk deposition of ALA, VLC n-3 PUFA, and total n-3 PUFA by 37, 15, and 32%, respectively. These results suggest that dietary OLA is not neutral with regard to the overall process by which dietary ALA is absorbed, metabolized, and deposited into egg yolk, either intact or in the form of longer-chain/more unsaturated n-3 PUFA derivatives.


Mortality and sudden death in pediatric left ventricular noncompaction in a tertiary referral center.
Left ventricular noncompaction is a cardiomyopathy characterized by excessive trabeculation of the left ventricle, progressive myocardial dysfunction, and early mortality. Left ventricular noncompaction has a heterogeneous clinical presentation that includes arrhythmia and sudden cardiac death. We retrospectively reviewed all children diagnosed with left ventricular noncompaction at Texas Children's Hospital from January 1990 to January 2009. Patients with congenital cardiac lesions were excluded. Two hundred forty-two children were diagnosed with isolated left ventricular noncompaction over the study period. Thirty-one (12.8%) died, and 13 (5.4%) were received a transplant. One hundred fifty (62%) presented with or developed cardiac dysfunction. The presence of cardiac dysfunction was strongly associated with mortality (hazard ratio, 11; P<0.001). ECG abnormalities were present in 87%, with ventricular hypertrophy and repolarization abnormalities occurring most commonly. Repolarization abnormalities were associated with increased mortality (hazard ratio, 2.1; P=0.02). Eighty children (33.1%) had an arrhythmia, and those with arrhythmias had increased mortality (hazard ratio, 2.8; P=0.002). Forty-two (17.4%) had ventricular tachycardia, with 5 presenting with resuscitated sudden cardiac death. In total, there were 15 cases of sudden cardiac death in the cohort (6.2%). Nearly all patients with sudden death (14 of 15) had abnormal cardiac dimensions or cardiac dysfunction. No patient with normal cardiac dimensions and function without preceding arrhythmias died. Left ventricular noncompaction has a high mortality rate and is strongly associated with arrhythmias in children. Preceding cardiac dysfunction or ventricular arrhythmias are associated with increased mortality. Children with normal cardiac dimensions and normal function are at low risk for sudden death.


[Analysis of the diagnotic results and complications of pneumoconiosis patients with different insurance types].
Objective: By comparing the diagnotic results and complications of pneumoconiosis patients with work-related injury insurance and non-work-related injury insurance, to provide reference for improving the medical insurance of pneumoconiosis patients. Methods: In May 2019, the diagnotic results and complications of 3204 patients with pneumoconiosis who were hospitalized in the second department of Hunan Prevention and Treatment Institute for Occupational Diseases from January 2017 to March 2019 were retrospectively analyzed. Results: Among the 3204 patients, 896 cases (28.0%) were in stage I, 790 cases (24.6%) were in stage II, and 1518 cases (47.4%) were in stage III. 1490 cases (46.5%) of pneumoconiosis patients have complications, mainly chronic obstructive pulmonary disease (COPD) (42.3%, 1354/3204) and lung infection (23.6%, 755/3204) . 584 cases (18.2%) were covered by work-related injury insurance, and the diagnosis of pneumoconiosis patients was mainly in the stage I (61.0%, 356/584) . 2620 cases (81.8%) were covered by non-work-related injury insurance, and the diagnosis of pneumoconiosis patients was mainly in the stage III (56.0%, 1466/2620) . The complication rate of non-work-related injury insurance patients (50.1%, 1312/2620) was higher than that of work-related injury insurance patients (30.5%, 178/584) (χ(2)=73.72, P<0.01) . Conclusion: The inpatients with pneumoconiosis in Hunan Province are still mainly covered by non-work-related injury insurance, and the diagnotic period and complication rate are significantly higher than those of work-related injury insurance patients. Therefore, pneumoconiosis patients should be provided with medical security, early diagnosis and early intervention, to prevent and delay the occurrence of complications.


[Anatomic study on the design of far-lateral transcondylar transtubercular keyhole approach assisted by neuro-navigation].
To design a new far-lateral transcondylar transtubercular keyhole approach assisted by neuro-navigation system according to the keyhole idea, and to explore the possibility of removing the occipital condyle and jugular tubercle precisely. Navigation data were established on 8 cadaveric heads fixed by formalin and with their intracranial vessels perfused with colored silicone. Before the operation, circumscriptions of the occipital condyle and jugular tubercle were outlined with different colors in the navigation system in order to aid drilling them in operation. A 7 cm longitudinal "S" shaped skin incision was performed with its superior border 2 cm behind the middle point of mastoid and inferior margin at the level of C(2). After inverting the suboccipital muscles and exposing the far lateral part of the occipital bone, occipital condyle, hemilamina of C(1), vertebral artery and posterolateral portion of foramen magnum, a retro-condylar bone flap 3 cm in diameter was cut. Assisted by neuro-navigation, not only were the maximal angle of visual field measured before and after the 1/3 and 1/2 posteromedial occipital condyle removal respectively, but also the anatomic structures were observed and measured. The incision of the retro-condylar keyhole approach fully met the needs of the far-lateral transcondylar transtubercular keyhole approach; partial occipital condyle and jugular tubercle could be precisely drilled with the aid of neuro-navigation, thus avoiding the bewilder in drilling process; the maximal angles of visual field were 39.2 degrees +/- 3.29 degrees (before condyle drilled), 51.5 degrees +/- 2.45 degrees (1/3 condyle drilled) and 57.5 degrees +/- 2.66 degrees (1/2 condyle drilled) respectively, and there were significant difference among them (P < 0.01). It is feasible to perform the far-lateral trascondylar transtubercular keyhole approach; the maximal angle of visual field is obviously increased by drilling partial occipital condyle, and the middle clivus can be increasingly exposed through removal of jugular tubercle.


Role of Anterior Nasal Packing in Endoscopic Skull Base Surgery: Italian Survey.
Nowadays, the endoscopic endonasal approach to sellar and parasellar region tumors is a common technique in neurosurgery, and surgical nuances, complications, and management strategies are shared in a multidisciplinary setting between neurosurgeons and ear, nose, and throat surgeons. Due to the heterogeneity of its variations, the role of the anterior nasal packing in endoscopic endonasal approach to the skull base surgery (EESBS) has not yet been unanimously accepted and no consensus or guidelines on its use exist. A survey containing 10 questions about indications, management advantages, and pitfalls of the use of anterior nasal packing in EESBS was created by using an online open-source tool (SurveyMonkey). The questionnaire was sent to 39 Italian neurosurgical departments, which routinely adopt the endoscopic endonasal approach. Almost half of 39 selected centers (19; 48.7%) answered our survey. The main results can be summarized as 1) anterior nasal packing after EESBS is considered useful by 84% of participants, 2) prevention of epistaxis is the principal indication for anterior nasal packing, 3) the type of approach and skull base reconstruction influence the use of anterior nasal packing, and 4) nasal discomfort is considered the principal negative aspect of nasal packing. Our study identified that anterior nasal packing is commonly adopted in certain conditions, namely when extensive nasal dissection is performed. Furthermore, the choice to adopt or not the anterior nasal packing should be tailored taking in account specific conditions, such as acromegaly and Cushing disease. It represents an important factor in reducing postoperative sinonasal complications of EESB.


Effect of GBR in combination with deproteinized bovine bone mineral and/or enamel matrix proteins on the healing of critical-size defects.
To evaluate the effect of guided bone regeneration (GBR) in combination with or without deproteinized bovine bone mineral (DBBM) and/or an enamel matrix derivative (EMD) on the healing of critical-size calvarial defects. Forty rats were used. In all animals, a standardized critical-size calvarial defect was created surgically. The animals were randomly allocated into 4 groups of 10 animals each. Group A: One calvarial defect was left untreated, while the galeal and the cerebral aspect of the contralateral defect were covered with a bioresorbable membrane (GBR). Group B: One calvarial defect was filled with EMD, while the contralateral defect was treated with GBR and EMD. Group C: One defect was filled with DBBM, while the contralateral defect was treated with combination of GBR and DBBM. Group D: One defect was filled with DBBM combined with EMD, while the contralateral defect was treated with combination of GBR, DBBM and EMD. The healing period was 4 months. Five specimens from each group were macerated and the length, the width and the vertical dimension (thickness) of the remaining defect were evaluated by a stereomicroscope. The remaining specimens in each group were analyzed histologically. The defects of the macerated specimens that were left untreated or were treated only by EMD, DBBM and combination of EMD and DBBM did not present predictably complete healing of the defects. All the defects where GBR was applied alone or combined with DBBM and/or EMD presented always complete healing (P<0.05). The combined use of GBR with EMD and/or DBBM did not offer any significant advantage above GBR alone in terms of healing of the length and the width of the defect. However, the vertical dimension of the defect was significantly higher (P<0.05) in the GBR-treated specimens of Groups C and D. The histological analysis supported these findings. The predictability of bone formation in critical-size defects depends mainly on the presence or absence of barrier membranes (GBR). The combined use with deproteinized bovine bone mineral and/or enamel matrix proteins did not significantly enhance the potential for complete healing provided by the GBR procedure.


The health care system in the year 2000: three scenarios.
Because no one can predict the direction that national health policy might take over the next decade, the author outlines three of the more likely scenarios for the year 2000. He first describes seven major forces that have a stake in national health policy: the federal government, the state governments, business, organized labor, the public at large, the health industry, and the opinion-makers. he next indicates three ways these forces might come together (the scenarios), and last, gives a fuller description of the scenarios and the issues each would raise. He demonstrates in depth how the motivations of most of these forces are in conflict with one another and states that no national health policy is likely to emerge until there is a broad compromise that brings most of those conflicts to some sort of viable consensus. He urges those involved in health care to prepare for a range of possible policies such as, but not limited to, those outlined in this overview, and concludes by maintaining that no matter what health policy emerges, health professionals will use their common sense and good faith to make it work, as they always have.


MMPs and TIMPs--an historical perspective.
There are currently 25 known vertebrate matrix metalloproteinases (MMPs) and 4 tissue inhibitors of metalloproteinases (TIMPs). This article reviews these proteases from an historical perspective in terms of who discovered each protein, when the sequence was established, when action on protein substrates was demonstrated, and what names have been used. A similar approach is taken for the TIMPS, and their multiple functions in addition to protease inhibition are emphasized. MMPs from invertebrates, plants, and bacteria are also discussed. This review is an outgrowth and update of a chapter by the same name originally published in Matrix Metalloproteinase Protocols, pp. 1-23, edited by I. M. Clark and published by Humana Press in 2001.


One hundred consecutive cases of selective termination of an abnormal fetus in a multifetal gestation.
To determine whether transabdominal selective termination of one or more abnormal fetuses in a multifetal pregnancy with dichorionic placentation is a safe and effective procedure. One hundred consecutive selective termination procedures were performed by transabdominal injection of potassium chloride into the heart or umbilical vein of an anomalous fetus in a multifetal pregnancy. All of the abnormal fetuses were presumed to have dichorionic diamniotic placentas, based on an ultrasound evaluation before the procedure. Follow-up data were obtained for each patient regarding the development of postprocedural complications, laboratory or clinical evidence of a coagulopathy, maternal or neonatal morbidity, gestational age at delivery, and birth weight of the infants. Ninety-one sets of twins were reduced to singletons, six sets of triplets were reduced to twins, two sets of triplets were reduced to singletons, and one set of quadruplets was reduced to triplets. The anomalous fetus or fetuses were identified correctly and terminated in each case. Three patients spontaneously aborted, and one women electively terminated her pregnancy 2 weeks after the procedure. The mean gestational age at delivery of the 96 patients who delivered surviving infants was 36.8 weeks, and 85.4% delivered at 32 weeks or later. Three women developed laboratory evidence of a coagulopathy, but there were no cases of clinically evident disseminated intravascular coagulation. This procedure, performed at a single institution by a small number of operators using a common protocol, accomplished its objective in all cases, was accompanied by a low spontaneous loss rate, and resulted in the birth of healthy infants at or near term in the vast majority of cases. This series suggests that selective termination is a reasonable option to consider when one abnormal fetus is found in a multifetal pregnancy with dichorionic placentation.


Agrobacterium tumefaciens-Mediated Transformation of NHEJ Mutant Aspergillus nidulans Conidia: An Efficient Tool for Targeted Gene Recombination Using Selectable Nutritional Markers.
Protoplast transformation for the introduction of recombinant DNA into Aspergillus nidulans is technically demanding and dependant on the availability and batch variability of commercial enzyme preparations. Given the success of Agrobacterium tumefaciens-mediated transformation (ATMT) in diverse pathogenic fungi, we have adapted this method to facilitate transformation of A. nidulans. Using suitably engineered binary vectors, gene-targeted ATMT of A. nidulans non-homologous end-joining (NHEJ) mutant conidia has been carried out for the first time by complementation of a nutritional requirement (uridine/uracil auxotrophy). Site-specific integration in the ΔnkuA host genome occurred at high efficiency. Unlike other transformation techniques, however, cross-feeding of certain nutritional requirements from the bacterium to the fungus was found to occur, thus limiting the choice of auxotrophies available for ATMT. In complementation tests and also for comparative purposes, integration of recombinant cassettes at a specific locus could provide a means to reduce the influence of position effects (chromatin structure) on transgene expression. In this regard, targeted disruption of the wA locus permitted visual identification of transformants carrying site-specific integration events by conidial colour (white), even when auxotrophy selection was compromised due to cross-feeding. The protocol described offers an attractive alternative to the protoplast procedure for obtaining locus-targeted A. nidulans transformants.


Self-management of dietary intake using mindful eating to improve dietary intake for individuals with early stage chronic kidney disease.
Using mindful eating to improve specific dietary recommendations has not been adequately studied. This feasibility study examined an intervention, self-management of dietary intake using mindful eating, with 19 participants that had mild to moderate chronic kidney disease, using a prospective, single group, pretest-posttest design. The intervention had six weekly classes focused on self-management using mindful eating, goal-setting, problem-solving, and food label reading. Weight, body mass index (BMI), 3-day 24-h dietary recalls and fasting blood samples were measured. Participants improved significantly in mean weight (203.21 ± 42.98 vs 199.91 ± 40.36 lbs; P = 0.03) and BMI (32.02 ± 5.22 vs 31.57 ± 5.27 kg/m2; P = 0.04), but not in dietary intake nor blood measures with the exception of cis-beta-carotene levels (0.020 + 0.012 vs 0.026 + 0.012 mcg/mL; P = 0.008), which correlates to fruit and vegetable servings. These promising results warrant further testing of the intervention in randomized control trials.