Proliferation of myeloid lineage cells and apoptosis of lymphoblastic leukemic cells induced by short-course high-dose methylprednisolone in patients with acute lymphoblastic leukemia.
In this paper, we investigated the effects of short-course high-dose methylprednisolone (HDMP) treatment on the proliferation of myeloid lineage cells and on apoptosis of blast cells in eight children with acute lymphoblastic leukemia (ALL). The patients were given the HDMP treatment (30 mg/kg/d, perorally) before 9:00 a.m. for seven days. Bone marrow (BM) aspiration was done at days 0 and 3 of the HDMP treatment in all patients and at the 7th day of the HDMP treatment in six patients. Bone marrow blast cells had gradually decreased after the HDMP treatment by the 7th day. There were statistically significant differences between the mean percentages of BM blast cells at days 0 and 3, days 0 and 7, and at days 3 and 7 (p<0.05). The mean percentages of blast cell apoptosis at the 3rd day was significantly higher than at days 0 and 7, and apoptosis at day 0 was significantly lower than at the 7th day (p<0.05). The mean percentages of BM myeloid lineage cells at the 7th day was significantly higher than at days 0 and 3 (p<0.05), and the mean percentage at day 0 was significantly lower than at the 3rd day (p<0.05). These findings indicate that short-course HDMP treatment causes apoptosis on lymphoblasts and increases the proliferation of myeloid lineage cells in children with ALL.


Structural characterization of two interchangeable conformations of a 2-aminofluorene-modified DNA oligomer by NMR and energy minimization.
One- and two-dimensional NMR spectroscopy and energy minimization calculations were used to investigate the conformation of a 2-aminofluorene- (AF-) modified model human c-H-ras1 protooncogene codon 61 deoxyoligonucleotide duplex, d(C1-A2-C3-C4-A5- [AF-G6]-G7-A8-A9-C10).-d(G11-T12-T13-C14-C15-T16 -G17-G18-T19-G20), in which the AF adduct is located at the third base of codon 61 with cytosine as the complementary nucleotide. Two interchangeable conformations of the AF-modified duplex, referred to as the external-AF conformation and the inserted-AF conformation, were determined from the NMR data. An analysis of the coalescence of resonances led to the estimation that the chemical exchange lifetime is greater than 3 ms but less than 20 ms at 30 degrees C, pH 7. In the external-AF conformation, Watson-Crick base-pair formation is observed for all 10 complementary nucleotides, including the AF-G6.C15 base pair. In the inserted-AF conformation, 9 of the 10 complementary bases form Watson-Crick base pairs; the AF-G6 imino proton exhibits no evidence of hydrogen bond formation with its complementary cytosine. Several NOEs between aminofluorene protons and DNA protons show that the AF moiety in the inserted-AF conformation stacks between the adjacent A5.T16 and G7.C14 base pairs. Solvated energy minimization calculations using distance restraints obtained from NOESY data at 2 degrees C with a 100-ms mixing time were performed to obtain representative structures of the external-AF and inserted-AF conformations. The external-AF conformer has the AF moiety protruding out of the major groove of a relatively unperturbed DNA duplex, leaving intact Watson-Crick base pairing for the AF-G6.C15 bases. Thus, the external-AF conformer may represent a visualization of a conformation that allows faithful replication. The inserted-AF conformer has the AF moiety stacked within the DNA helix, breaking the Watson-Crick base pairing of the modified guanine and its complementary cytosine and displacing the guanine and cytosine into the grooves. We label the inserted-AF conformer as a premutagenic conformation to reflect the displacement of the modified guanine. Interconversion between the structurally distinct external-AF and inserted-AF conformers takes place on a time scale of the same order as DNA replication. We have labeled this interconversion as a mutagenic switch to highlight a possible conformational equilibrium that may be important in replication.


Stabilisation patterns of hourly urban sound levels.
In this paper, the stabilisation times for all 24 h of the day are analysed for 12 measurement stations located in the Spanish town of Malaga and throughout 5 years (2007-2011) of sampling environmental noise levels. For the results to be generalised to sound level measurements made in other streets or cities where there have been no long-term measurements, this study was developed for different road types and urban shapes. This distinction was made according to the types of roads indicated in other studies in which a statistically significant relationship was found between noise levels and the road type. The final objective of the study is to determine the capacity to estimate and approximate the real equivalent hourly noise level (L Aeq,1h) from the integration of a number of consecutive minutes (short-term measurements) less than 60 (L Aeq,1h ≈ L Aeq,T being T ≤ 60 min). Clearly, this strategy would save time and resources by making measurements of reduced duration. In summary and according to this analysis, a short-time measurement of 15 min is adequate to work with 90% confidence levels and errors of ±2 dB, with 80% confidence levels and errors of ±1 dB, and 50% confidence levels and errors of ±0.5 dB. However, it is necessary to consider the measurement hour period to achieve these levels of confidence due to the high variability throughout the day.


Detection of Toxoplasma gondii in venous blood from AIDS patients by polymerase chain reaction.
Detection of Toxoplasma gondii in blood by means of the polymerase chain reaction (PCR) may facilitate the diagnosis and follow-up of cerebral toxoplasmosis in patients with AIDS. We evaluated this approach with seven patients with tissue culture-proven parasitemia, 14 patients with presumptive cerebral toxoplasmosis, and 17 healthy human immunodeficiency virus-positive controls. Each sample of blood was assayed on three different occasions by a PCR assay based on detection of the gene encoding the P30 surface protein. A positive PCR diagnosis required positivity in at least two of the three PCR tests. None of the controls had a positive PCR diagnosis, but six of the seven patients with parasitemia did. Cerebral toxoplasmosis was confirmed in 13 of the 14 patients with a presumptive diagnosis; diagnosis by PCR was positive before treatment for 9 of these 13 patients, whereas tissue culture was positive for only 1 patient. During treatment, blood samples were taken from 14 patients at regular intervals until day 12. PCR diagnosis became negative on ethidium-stained gels, but persistent signals were observed after hybridization, in some cases, for up to 12 days after initiation of therapy. PCR on venous blood could thus be a sensitive and noninvasive method for the diagnosis of cerebral and disseminated toxoplasmosis in AIDS patients and could be a potential tool for monitoring the effects of treatment.


Assessing the quality of initial consultations regarding adjuvant colon cancer therapy.
Adjuvant chemotherapy prevents colon cancer recurrence in a subset of treated patients; however, decisions about whether to receive chemotherapy are complex. Adequate information exchange (IE) and informed decision making (IDM) between patient and physician are essential, particularly in the elderly. A total of 35 patients with stage II and III colon cancer were asked on a questionnaire if they discussed specific colon cancer-related information and elements of IDM with their doctors during their initial adjuvant chemotherapy consultations. On average, patients reported discussing 14.6 (SD +/- 6.6) of 28 information items with their doctors. Basic items about cancer stage, prognosis, and treatment were discussed more commonly (mean, 9 of 12) than information about short-term (mean, 3.5 of 8) and long-term (mean, 2.3 of 8) effects of therapy. Patients aged >or= 70 years reported discussing fewer information items with their physicians than patients aged < 70 years (mean, 11 items vs. 16.2 items; P = .06). Patients reported discussing an average of 5.1 (SD +/- 1.3) of 7 IDM elements with their physicians. Thirty-four percent of the patients did not recall being asked their preference about chemotherapy, and 23% did not recall their doctor checking to ensure that they understood the discussion. Concordance with patient report and coded transcripts was good among 5 available patient-transcript pairs. By patient report, IE and IDM quality appeared to be very good in initial adjuvant therapy consultations, though attention to patient preference could be an area for improvement. Differences in decision quality between younger and older patients are an important area for future study.


Career paths of graduates of a degree-linked nursing course.
The aim of this study was to follow the career development of all 103 former students of the BSc (Hons) degree in human biology at the University of Surrey who also took the nursing option leading to qualification as SRN, at St George's School of Nursing, London. These individuals qualified between 1970 and 1980. A postal questionnaire was used and a 97% response was obtained. The employment of each respondent was recorded at various time intervals after qualification and categorized to facilitate analysis. Findings were generally in accordance with the preliminary findings of the Universities of Manchester and Edinburgh follow-up studies. The majority of respondents chose and followed careers in nursing. The most common categories of employment for the first 5 years after qualification were hospital and community nursing. Sixty-two percent had taken further training in various fields of nursing. A larger proportion of human biologist nurse graduates had selected careers in community nursing, nursing research and nursing education than had Edinburgh nurse graduates. There was support for the suggestion that nurse graduates choose to consolidate their experience before breaking their career on account of motherhood. Between 9 and 31% were in non-nursing employment during the first 5 years of employment. Most of these were studying or working in health related fields. This figure was higher than that found in Edinburgh and reflects the nature of the degree-linked human biology/nursing option course.


Expertise differences in cognitive interpreting: A meta-analysis of eye tracking studies across four decades.
This meta-analytic research delves into the influence of expertise on cognitive interpreting, emphasizing time efficiency, accuracy, and cognitive effort, in alignment with prevailing expertise theories that link professional development and cognitive efficiency. The study assimilates empirical data from 18 eye-tracking studies conducted over the past four decades, encompassing a sample of 1581 interpreters. The objective is to elucidate the role of expertise in interpretative performance while tracing the evolution of these dynamics over time. Findings suggest that expert interpreters outperform novices in time efficiency and accuracy and exhibit lower cognitive effort, especially in sight and consecutive interpreting. This effect is particularly pronounced in the English-Chinese language pair and with the use of E-prime and Tobii eye-tracking systems. Further, fixation count and pupil size are essential metrics impacting cognitive effort. These findings have vital implications for interpreter training programs, suggesting a focus on expertise development to enhance efficiency and accuracy, reduce cognitive load, and emphasize the importance of sight interpreting as a foundational skill. The selection of technology and understanding of specific ocular metrics also emerged as essential for future research and practical applications in the interpreting industry. This article is categorized under: Psychology > Theory and Methods Linguistics > Cognitive.


Quantitation of mRNAs for M(1) to M(5) subtypes of muscarinic receptors in rat heart and brain cortex.
It has been generally accepted that, of the five subtypes of muscarinic receptors (M(1)-M(5)), only the M(2) subtype is expressed in mammalian heart. This notion has recently been challenged by a series of reports indicating that mRNAs for some or all non-M(2) subtypes are also present in mammalian heart, in parallel with the M(2) mRNA. However, the quantities of relevant mRNAs reported to be present in the heart are not known, which makes it difficult to evaluate their likely significance. We measured the concentrations of the five muscarinic mRNAs by competitive reverse transcription-polymerase chain reaction and discovered that the M(2) mRNA represents more than 90% of total muscarinic mRNAs in rat atria and in either ventricle. The concentrations of total muscarinic mRNAs and of the M(2) mRNA were more than twice as high in the atria than in the ventricles. mRNAs for all non-M(2) muscarinic receptor subtypes were also detected but represented less than 1% (M(1) and M(4)), less than 3% (M(3)), and less than 5% (M(5)) of total muscarinic RNAs in the atria and ventricles. The findings support the concept of the prevalent role of the M(2) muscarinic receptors in the cholinergic control of the heart. When the same method of quantitation was applied to rat cerebral cortex, mRNAs for individual subtypes were found to represent 36% (M(1)), 21% (M(2)), 25% (M(3)), 11% (M(4)), and 7% (M(5)) of total muscarinic mRNAs.


Electroencephalography in acute head injury.
The established uses of standard and computerized EEG in acute head injury are outlined. Emphasis is placed on EEG correlation with level of consciousness, rostrocaudal deterioration, brainstem lesions, and prognosis. The utility of the standard EEG in seizures and toxic metabolic states accompanying severe head injury is also discussed.


Application of Porcine Kidney-Derived Extracellular Matrix as Coating, Hydrogel, and Scaffold Material for Renal Proximal Tubular Epithelial Cell.
Human renal proximal tubular epithelial (RPTE) cell is a very useful tool for kidney-related experiments in vitro/ex vivo. However, only a few primary RPTE cells can be obtained through kidney biopsy, the proliferation rate of primary cell is very low, and the cultured cell properties are easily altered in artificial conditions. Thus, RPTE cell usage is very tricky; we applied porcine kidney-derived extracellular matrix (renal ECM) as coating, hydrogel, and scaffold material to increase cell proliferation and maintain cellular properties providing three-dimensional (3D) niche, which can be a valuable cell delivery vehicle. Porcine renal ECM was prepared by decellularization using 1% Triton X-100, solubilized with 0.5 M acetic acid. The final protein concentration was adjusted to 10 μg/μL (pH 7.0). The efficacies as coating, hydrogel, and scaffold materials were analyzed through cell morphology, proliferation rate, renal-associated gene expressions, chemical composition, and microstructure evaluation. The efficacies as a coating material were compared with Matrigel, collagen type 1 (col1), gelatin, fibrinogen, and thrombin. After confirmation of coating effects, the effective concentration range was decided. The efficacies as hydrogel and scaffold materials were compared with hyaluronic acid (HA) and col1, respectively. As the coating material, renal ECM showed a higher cell proliferation rate compared to other materials, except for Matrigel. Renal-associated gene expressions were significantly enhanced in the renal ECM than other materials. Coating effect on cell proliferation was dependent on the renal ECM concentration, and the effective concentration ranged from 30 to 100 μg. As the hydrogel material, renal ECM showed a distinct inner cell network morphology and significantly increased renal-associated gene expressions, compared to HA hydrogel. As the scaffold material, renal ECM showed specific amide peaks, enhanced internal porosity, cell proliferation rate, and renal-associated gene expression compared to the col1 scaffold. We concluded that renal ECM can be a suitable material for RPTE cell culture and usage. More practically, the coated renal ECM stimulates RPTE cell proliferation, and the hydrogel and scaffold of renal ECM provide useful 3D culture niche and cell delivery vehicles maintaining renal cell properties.


Detection of binaural interaction in free-field evoked auditory brainstem responses by time-scale representations.
The so called β-wave of the binaural interaction component (BIC) in auditory brainstem responses (ABR) has been shown to be an objective measure for binaural interaction (BI). This component is the arithmetical difference between the sum of the monaurally evoked ABRs and the binaurally evoked ABR. Unfortunately, these neural responses are known to be very fragile and as a result the calculated BIC. An additional issue is, that the findings of this measurement are predominantly needed in people with hearing loss who may use hearing devices like hearing aids (HA) or cochlear implants (CI), thus they are not able to use headphones (like in conventional ABR measurements) during the detection of possible BI. This is a crucial problem, because it is known that factors like the interaural time delay (ITD) between the receiving ears are responsible for solving tasks like sound source localization or sound source separation, but specially designed measurements to coordinate the fitting of HAs or CIs with respect to BI are still missing. In this paper, we introduce a new measurement setup that is able to detect BI depending on different ITDs in free-field evoked responses by using the more reliable instantaneous phase in the time-scale representation. With this pilot study we are able to demonstrate a decreasing BI with an increasing ITD using the wavelet phase synchronization stability analysis in ten normal hearing subjects.


Different patterns of p16INK4A and p53 protein expressions in intraductal papillary-mucinous neoplasms and pancreatic intraepithelial neoplasia.
To examine aberrations and differences of cell cycle regulatory proteins between intraductal papillary-mucinous neoplasms (IPMNs) and pancreatic intraepithelial neoplasias (PanINs). In total, 47 IPMN lesions and 42 PanIN lesions were obtained from 26 patients with IPMN and 16 patients who underwent pancreatic surgery for invasive pancreatic ductal cancer or other diseases. They were subjected to conventional hematoxylin-eosin staining and immunostaining for p16INK4A and p53. The percentages of immunohistochemical positivity or negativity were compared between IPMN and PanIN, in accordance with the same histological grade of atypia. The Ki-67 labeling index was also counted in each lesion. Either the loss of p16INK4A expression or the overexpression of p53 was much more frequently observed among PanIN-3 than among carcinoma in situ in IPMN (P = 0.046 and 0.008, respectively). The Ki-67 labeling index was correlated with the histological grades of both PanINs and IPMNs (P = 0.0001 and P = 0.0001, respectively). There are different immunohistochemical expression patterns of p16INK4A and p53 between IPMNs and PanINs. These may substantiate their different genetic progressions to invasive carcinoma.


Mutations affecting regulation of the Klebsiella pneumoniae nifH (nitrogenase reductase) promotor.
Starting with plasmid pSA30 which contains an intact nifHDKY operon, we selected mutants that no longer inhibited nitrogen fixation in Klebsiella pneumoniae. Three categories of mutants were found among eight mutant plasmids examined in detail. Three mutant plasmids carried a single-base-pair (bp) change at position -12 or -14 relative to the nifH transcription start site. These mutations were located in a previously described consensus sequence found in the -10 to -15 region of nif promoters. Four of the mutant plasmids contain lesions considerably upstream from the start point of transcription. Two of these upstream mutations are identical 112-bp deletions of nucleotides -72 to -184, and two others are a single-bp change at position -136. The final plasmid does not contain a mutation within a 525-bp region which includes 289 bp upstream from the nifH ATG initiation codon and which extends 69 codons into the nifH gene. All eight of the mutant pSA30 plasmids failed to complement a chromosomal nifH mutation, suggesting that the mutations that block inhibition of nif expression also prevent transcription of the nifHDKY operon.


Diabetic Neuropathies.
This article provides an up-to-date review of the diagnosis and management of the most common neuropathies that occur in patients with diabetes. The prevalence of diabetes continues to grow worldwide and, as a result, the burden of diabetic neuropathies is also increasing. Most diabetic neuropathies are caused by hyperglycemic effects on small and large fiber nerves, and glycemic control in individuals with type 1 diabetes reduces neuropathy prevalence. However, among people with type 2 diabetes, additional factors, particularly metabolic syndrome components, play a role and should be addressed. Although length-dependent distal symmetric polyneuropathy is the most common form of neuropathy, autonomic syndromes, particularly cardiovascular autonomic neuropathy, are associated with increased mortality, whereas lumbosacral radiculoplexus neuropathy and treatment-induced neuropathy cause substantial morbidity. Recent evidence-based guidelines have updated the recommended treatment options to manage pain associated with distal symmetric polyneuropathy of diabetes. Identifying and appropriately diagnosing the neuropathies of diabetes is key to preventing progression. Until better disease-modifying therapies are identified, management remains focused on diabetes and metabolic risk factor control and pain management.


Metric development and score reporting in Rasch measurement.
This article: 1) describes problems in score reporting with the True-Score Model, 2) presents a definition of the Rasch measurement unit, the logit, 3) reviews various transformations of the logit metric, and 4) provides examples of score reporting procedures. Two data sets are used. The first contains dichotomous data drawn from responses to a multiple-response statistics examination taken by Ph.D. students; the second contains polychotomous data from a self-efficacy assessment given to war veterans suffering from Post Traumatic Stress Disorder.


Identification of novel compound heterozygous variants in the DNAH1 gene of a Chinese family with left-right asymmetry disorder.
Most internal organs in humans and other vertebrates exhibit striking left-right asymmetry in position and structure. Variation of normal organ positioning results in left-right asymmetry disorders and presents as internal organ reversal or randomization. Up to date, at least 82 genes have been identified as the causative genetic factors of left-right asymmetry disorders. This study sought to discover potential pathogenic variants responsible for left-right asymmetry disorder present in a Han-Chinese family using whole exome sequencing combined with Sanger sequencing. Novel compound heterozygous variants, c.5690A>G (p.Asn1897Ser) and c.7759G>A (p.Val2587Met), in the dynein axonemal heavy chain 1 gene (DNAH1), were found in the proband and absent in unaffected family members. Conservation analysis has shown that the variants affect evolutionarily conserved residues, which may impact the tertiary structure of the DNAH1 protein. The novel compound heterozygous variants may potentially bear responsibility for left-right asymmetry disorder, which results from a perturbation of left-right axis coordination at the earliest embryonic development stages. This study broadens the variant spectrum of left-right asymmetry disorders and may be helpful for genetic counseling and healthcare management for the diagnosed individual, and promotes a greater understanding of the pathophysiology.


SERS enhancement induced by the Se vacancy defects in ultra-thin hybrid phase SnSex nanosheets.
Improving the photo-induced charge transfer (PICT) efficiency by adjusting the energy levels difference between adsorbed probe molecules and substrate materials is a key factor for boosting the surface enhanced Raman scattering (SERS) based on the chemical mechanism (CM). Herein, a new route to improve the SERS activity of two-dimensional (2D) selenium and tin compounds (SnSex, 1 ≤ x ≤ 2) by the hybrid phase materials is researched. The physical properties and the energy band structure of SnSex were analyzed. The enhanced SERS activity of 2D SnSex can be attribute to the coupling of the PICT resonance caused by the defect energy levels induced by Se vacancy and the molecular resonance Raman scattering (RRS). This established a relationship between the physical properties and SERS activity of 2D layered materials. The resonance probe molecule, rhodamine (R6G), which is used to detect the SERS performance of SnSex nanosheets. The enhancement factor (EF) of R6G on the optimized SnSe1.35 nanosheets can be as high as 2.6 × 106, with a detection limit of 10-10 M. The SERS result of the environmental pollution, thiram, shows that the SnSex nanosheets have a practical application in trace SERS detection, without the participation of metal particles. These results demonstrate that, through hybrid phase materials, the SERS sensitivity of 2D layered nanomaterials can be improved. It provides a kind of foreground non-metal SERS substrate in monitoring or detecting and provide a deep insight into the chemical SERS mechanism based on 2D layered materials.


Aerobic physiology of redox-engineered Saccharomyces cerevisiae strains modified in the ammonium assimilation for increased NADPH availability.
Recombinant strains altered in the ammonium assimilation pathways were constructed with the purpose of increasing NADPH availability. The NADPH-dependent glutamate dehydrogenase encoded by GDH1, which accounts for a major fraction of the NADPH consumption during growth on ammonium, was deleted, and alternative pathways for ammonium assimilation were overexpressed: GDH2 (NADH-consuming) or GLN1 and GLT1 (the GS-GOGAT system). The flux through the pentose phosphate pathway during aerobic growth on glucose decreased to about half that of the reference strain Saccharomyces cerevisiae CEN.PK113-7D, indicating a major redox alteration in the strains. The basic growth characteristics of the recombinant strains were not affected to a great extent, but the dilution rate at which the onset of aerobic fermentation occurred decreased, suggesting a relation between the onset of the Crabtree effect and the flux through the Embden-Meyerhof-Parnas pathway downstream of glucose 6-phosphate. No redox effect was observed in a strain containing a deletion of GLR1, encoding glutathione reductase, an enzyme that is NADPH-consuming.


Helicases - feasible antimalarial drug target for Plasmodium falciparum.
Of the four Plasmodium species that cause human malaria, Plasmodium falciparum is responsible for the most severe form of the disease and this parasite is developing resistance to the major antimalarial drugs. Therefore, in order to control malaria it is necessary to identify new drug targets. One feasible target might be helicases, which are important unwinding enzymes and required for almost all the nucleic acid metabolism in the malaria parasite.


In vitro biological responses of plasma nanocoatings for coronary stent applications.
In-stent restenosis and thrombosis remain to be long-term challenges in coronary stenting procedures. The objective of this study was to evaluate the in vitro biological responses of trimethylsilane (TMS) plasma nanocoatings modified with NH3 /O2 (2:1 molar ratio) plasma post-treatment (TMS + NH3 /O2 nanocoatings) on cobalt chromium (CoCr) alloy L605 coupons, L605 stents, and 316L stainless steel (SS) stents. Surface properties of the plasma nanocoatings with up to 2-year aging time were characterized by wettability assessment and x-ray photoelectron spectroscopy (XPS). It was found that TMS + NH3 /O2 nanocoatings had a surface composition of 41.21 ± 1.06 at% oxygen, 31.90 ± 1.08 at% silicon, and 24.12 ± 1.7 at% carbon, and very small but essential amount of 2.77 ± 0.18 at% nitrogen. Surface chemical stability of the plasma coatings was noted with persistent O/Si atomic ratio of 1.292-1.413 and N/Si atomic ratio of ~0.087 through 2 years. The in vitro biological responses of plasma nanocoatings were studied by evaluating the cell proliferation and migration of porcine coronary artery endothelial cells (PCAECs) and smooth muscle cells (PCASMCs). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay results revealed that, after 7-day incubation, TMS + NH3 /O2 nanocoatings maintained a similar level of PCAEC proliferation while showing a decrease in the viability of PCASMCs by 73 ± 19% as compared with uncoated L605 surfaces. Cell co-culture of PCAECs and PCASMCs results showed that, the cell ratio of PCAEC/PCASMC on TMS + NH3 /O2 nanocoating surfaces was 1.5-fold higher than that on uncoated L605 surfaces, indicating enhanced selectivity for promoting PCAEC growth. Migration test showed comparable PCAEC migration distance for uncoated L605 and TMS + NH3 /O2 nanocoatings. In contrast, PCASMC migration distance was reduced nearly 8.5-fold on TMS + NH3 /O2 nanocoating surfaces as compared to the uncoated L605 surfaces. Platelet adhesion test using porcine whole blood showed lower adhered platelets distribution (by 70 ± 16%), reduced clotting attachment (by 54 ± 12%), and less platelet activation on TMS + NH3 /O2 nanocoating surfaces as compared with the uncoated L605 controls. It was further found that, under shear stress conditions of simulated blood flow, TMS + NH3 /O2 nanocoating significantly inhibited platelet adhesion compared to the uncoated 316L SS stents and TMS nanocoated 316L SS stents. These results indicate that TMS + NH3 /O2 nanocoatings are very promising in preventing both restenosis and thrombosis for coronary stent applications.


Increase in pharmacodynamic tolerance after repeated antidepressant trials in treatment-responsive bipolar I depressed subjects: An exploratory study.
This study examined the presence of increased pharmacodynamic tolerance with reduced effectiveness following repeated antidepressant trials over the course of the affective illness in subjects with treatment-responsive bipolar II depression. Data were derived from the open-label phase of a prospective, randomized, placebo-controlled trial of long-term fluoxetine versus lithium monotherapy in 148 subjects >=18 years old with treatment-responsive bipolar II depression, who were initially administered open-label fluoxetine monotherapy for 12 weeks. Response was defined as >=50% reduction in baseline Hamilton Rating Scale for Depression (HRSD) score, and remission was defined as a final HRSD score =<8. Subjects reported a mean (SD) total of 1.61 (1.85) (range: 0-9) prior adequate, antidepressant trials over the course of their affective illness, before study enrollment. There was a 25% reduction in the likelihood of fluoxetine response (p < 0.01) and a 22% lower likelihood of remission (p = 0.02), respectively, with each increase in the number of prior antidepressant treatment trials over the illness course. There was no clinically meaningful correlation between fluoxetine response or remission and any other baseline clinical or demographic variable. Thus, only the number of prior antidepressant trials meaningfully impacted the likelihood of fluoxetine response or remission. Limitations. This was an exploratory study of post hoc, analyses, and the trial was not specifically powered to test the development of increased pharmacodynamic tolerance. Disease heterogeneity or inter-individual differences in antidepressant responsiveness may have influenced fluoxetine effectiveness. Conclusion. These results confirm prior observations of an increased pharmacodynamic tolerance after repeated antidepressant administration, resulting in a step-wise loss of antidepressant effectiveness over the course of the illness.


Towards a comprehensive characterization of durum wheat landraces in Moroccan traditional agrosystems: analysing genetic diversity in the light of geography, farmers' taxonomy and tetraploid wheat domestication history.
Crop diversity managed by smallholder farmers in traditional agrosystems is the outcome of historical and current processes interacting at various spatial scales, and influenced by factors such as farming practices and environmental pressures. Only recently have studies started to consider the complexity of these processes instead of simply describing diversity for breeding purposes. A first step in that aim is to add multiple references to the collection of genetic data, including the farmers' varietal taxonomy and practices and the historical background of the crop. On the basis of interview data collected in a previous study, we sampled 166 populations of durum wheat varieties in two traditional Moroccan agrosystems, in the Pre-Rif and Atlas Mountains regions. Using a common garden experiment, we detected a high phenotypic variability on traits indicative of taxonomical position and breeding status, namely spike shape and plant height. Populations often combined modern (short) with traditional-like (tall) statures, and classical durum squared spike shape (5 flowers/spikelet) with flat spike shape (3 flowers/ spikelet) representative of primitive domesticated tetraploid wheat (ssp. dicoccum). By contrast, the genetic diversity assessed using 14 microsatellite markers was relatively limited. When compared to the genetic diversity found in a large collection of tetraploid wheat, it corresponded to free-threshing tetraploid wheat. Within Morocco, the two studied regions differed for both genetic diversity and variety names. Within regions, neither geography nor variety names nor even breeding status constituted strong barriers to gene exchange despite a few significant patterns. This first assessment of morphological and genetic diversity allowed pointing out some important factors that may have influenced the structure and evolutionary dynamics of durum wheat in Morocco: the significance of variety names, the occurrence of mixtures within populations, the relative strength of seed exchange between farmers and local adaptation, as well as the fate of modern varieties once they have been introduced. Further, multidisciplinary studies at different spatial scales are needed to better understand these complex agrosystems of invaluable importance for food security.


Sickle cell disease: a clinical and histopathologic study of the liver in living children.
To study hepatic lesions in living children with sickle cell disease. Although such lesions are well known, the possibility of chronic persistent damage to the parenchyma resulting from the disease itself or iron overload is controversial. Sixteen children with sickle cell disease aged 15 months to 18 years were prospectively investigated out of 741 patients younger than 20 years registered at Hemominas Foundation, Brazil. Inclusion criteria for biopsy were as follows: five had positive anti-hepatitis C virus (HCV) antibody, two had positive hepatitis B virus (HBV) surface antigen and persistently increased levels of aminotransferases, and nine underwent biopsy during abdominal surgery. Children with B or C hepatitis were significantly older than the others and also had increased levels of both alanine and aspartate aminotransferases. Lobular architecture was preserved in all nonviral cases; mild to moderate sinusoidal dilatation was present in eight, hepatocellular regenerative activity in six, and focal necrosis and corresponding mild inflammatory infiltrate in three. No fibrosis or bile duct damage was observed. Mild to severe hemosiderosis was present in all children except one. The degree of iron overload was clearly associated with the number of previous blood transfusions. All five children with HCV had chronic hepatitis. One of the children with HBV had incomplete and the other had definite cirrhosis. These data indicate that chronic hepatic lesions in children with sickle cell disease may be caused by viral damage. Patients without evidence for viral etiology had reversible vascular lesions. Follow-up studies would be necessary to confirm this hypothesis but are precluded for ethical reasons. Hemosiderosis was not associated with fibrosis in any nonviral cases, but a larger number of patients would be necessary to establish valid conclusions.


Visualization and microscopic quantification of HCMV-peptide-specific cytotoxic T lymphocytes using tetramer binding.
To monitor the frequencies of virus-specific cytotoxic T lymphocytes (CTLs), FACS analyses were performed detecting lymphocyte-specific surface molecules and tetramer binding, as marker for peptide-specificity. Aim of this investigation was to establish an alternative protocol for the quantification of virus-specific CTLs using tetramer binding and microscopic analyzing. The frequencies of HCMV-pp65-peptide-specific CTLs in the blood of eight different HLA-A*0201-positive, HCMV-IgG antibody-positive donors were analyzed with both methods. Using FACS analyses, a median of 0.8% and, using the microscopic analyses, a median of 3.0% was detected in the CD3+CD8+ cells. After enrichment of HCMV-pp65-peptide-specific CTLs using the interferon-gamma secretion assay followed by expansion in cell culture, a median of 90.6% using FACS analyses and a median of 87.1% using the microscopic analyses was detected. Thus, the staining protocol presented in this investigation is an alternative approach to detect and to quantify virus-specific CTLs in low as well as in high frequencies.


miR-769-5p suppressed cell proliferation, migration and invasion by targeting TGFBR1 in non-small cell lung carcinoma.
MicroRNAs (miRNAs) are key regulators of multiple cancers, including non-small cell lung carcinoma (NSCLC). The aim of this study was to determine the expression pattern of miR-769-5p in NSCLC and to investigate its biological role during tumorigenesis. We showed that miR-769-5p was significantly downregulated and predicted poor prognosis in NSCLC compared with corresponding normal tissues. We then investigated its function and found that miR-769-5p significantly inhibited cell proliferation, migration and invasion in vitro and reduced tumor growth and metastasis in vivo. Furthermore, we explored the molecular mechanisms by which miR-769-5p contributes to NSCLC suppression and identified TGFBR1 as a direct target gene of miR-769-5p. Finally, we showed that TGFBR1 had opposite effects to those of miR-769-5p on lung cancer cells, suggesting that miR-769-5p might inhibit lung tumorigenesis by silencing TGFBR1. Taken together, our results demonstrated that miR-769-5p plays a pivotal role in NSCLC by inhibiting cell proliferation, migration and invasion by targeting TGFBR1.


An altered cellular response to interferon and up-regulation of interleukin-8 induced by the hepatitis C viral protein NS5A uncovered by microarray analysis.
There is evidence for an inhibition of interferon-alpha antiviral activity by the hepatitis C viral protein, NS5A. To identify the mechanisms through which NS5A blocks interferon activity, we compared the gene expression profile of interferon-treated Huh7 cells, stably expressing NS5A with control, using microarrays. Following interferon treatment, 50 genes were up-regulated by at least twofold in control clones, whereas induction of 9 of the 50 genes was significantly reduced in NS5A-expressing clones. The strongest effect of NS5A on interferon response was observed for the OAS-p69 gene. Remarkably, Huh7 cells expressing NS5A showed an up-regulation of interleukin-8. Up-regulation of interleukin-8 was also observed upon transient expression of NS5A mutants isolated from patients responsive or resistant to interferon therapy. Addition of interleukin-8 to Huh7 cells inhibited the antiviral activity of interferon and, similarly to NS5A, reduced the induction by interferon-alpha of selective genes including OAS-p69. Our findings provide a mechanism for NS5A-mediated interferon resistance.


Enhancer-mediated enrichment of interacting JMJD3-DDX21 to ENPP2 locus prevents R-loop formation and promotes transcription.
ENPP2, which encodes for the enzyme autotaxin (ATX), is overexpressed during chronic inflammatory diseases and various cancers. However, the molecular mechanism involved in the ENPP2 transcription remains elusive. Here, in HEK 293T cells, we demonstrated that lipopolysaccharide (LPS) increased the transcription process at ENPP2 locus through a NF-кB pathway and a reduction of H3K27me3 level, a histone repressive mark, by the demethylase UTX. Simultaneously, the H3K27me3 demethylase JMJD3/KDM6B was recruited to the transcription start site (TSS), within the gene body and controlled the expression of ENPP2 in a non-enzymatic manner. Mass spectrometry data revealed a novel interaction for JMJD3 with DDX21, a RNA helicase that unwinds R-loops created by nascent transcript and DNA template. Upon LPS treatment, JMJD3 is necessary for DDX21 recruitment at ENPP2 locus allowing the resolution of aberrant R-loops. CRISPR-Cas9-mediated deletion of a distant-acting enhancer decreased the expression of ENPP2 and lowered the recruitment of JMJD3-DDX21 complex at TSS and its progression through the gene body. Taken together, these findings revealed that enhancer-mediated enrichment of novel JMJD3-DDX21 interaction at ENPP2 locus is necessary for nascent transcript synthesis via the resolution of aberrant R-loops formation in response to inflammatory stimulus.


Aggressive amelanotic lentigo maligna.
A 66-year-old woman had a long-standing, scaly erythematous lesion on her left temple which histologically showed features of amelanotic lentigo maligna. It had recurred on numerous occasions over a period of 17 years, in spite of multiple attempts at curative surgery. There were also recurrences within a skin graft which, to our knowledge, has not been documented previously with lentigo maligna. In spite of the prolonged course, and extensive intraepidermal melanocytic proliferation amounting to melanoma in situ, there has been no evidence of dermal invasion. The lack of pigmentation in such lesions means that clinical definition of margins is highly inaccurate. In view of the aggressive horizontal growth phase of this lesion, with rapid recurrence following surgery, it was treated with electron beam therapy, and this has resulted in complete clinical remission. This most unusual case illustrates the potential difficulties in diagnosis and management of amelanotic lentigo maligna.


Safety assessment for hair-spray resins: risk assessment based on rodent inhalation studies.
The methods involved in the safety assessment of resins used in hair-spray products have received little peer review, or debate in the published literature, despite their widespread use, in both hairdressing salons and the home. The safety assessment for these resins currently involves determining the type of lung pathology that can be caused in animal inhalation exposure studies, and establishing the no-observable-effect level (NOEL) for these pathologies. The likely human consumer exposure is determined by techniques that model the simulated exposure under "in use" conditions. From these values it is then possible to derive the likely safety factors for human exposure. An important part of this process would be to recognize the intrinsic differences between rodents and humans in terms of the respiratory doses that each species experiences during inhalation exposures, for the purpose of the safety assessment. Interspecies scaling factors become necessary when comparing the exposure doses experienced by rats, compared to humans, because of basic differences between species in lung clearance rates and the alveolar area in the lungs. The rodent inhalation data and modeled human exposure to Resin 6965, a resin polymer that is based on vinyl acetate, has been used to calculate the safety factor for human consumer exposure to this resin, under a range of "in use" exposure conditions. The use of this safety assessment process clearly demonstrates that Resin 6965 is acceptable for human consumer exposure under the conditions considered in this risk assessment.


Safety of oral intake of vitamin E.
A review of the literature concerning the safety of oral intake of vitamin E indicated that the toxicity of vitamin E is low. Vitamin E supplementation has resulted in inconsistent effects in serum lipid and lipoprotein levels. Animal studies showed that vitamin E is not mutagenic, carcinogenic, or teratogenic. In human studies with double-blind protocols and in large population studies, oral vitamin E supplementation resulted in few side effects even at doses as high as 3200 mg/d (3200 IU/d).


Prediction of Signal Peptide Cleavage Sites with Subsite-Coupled and Template Matching Fusion Algorithm.
Fast and effective prediction of signal peptides (SP) and their cleavage sites is of great importance in computational biology. The approaches developed to predict signal peptide can be roughly divided into machine learning based, and sliding windows based. In order to further increase the prediction accuracy and coverage of organism for SP cleavage sites, we propose a novel method for predicting SP cleavage sites called Signal-CTF that utilizes machine learning and sliding windows, and is designed for N-termial secretory proteins in a large variety of organisms including human, animal, plant, virus, bacteria, fungi and archaea. Signal-CTF consists of three distinct elements: (1) a subsite-coupled and regularization function with a scaled window of fixed width that selects a set of candidates of possible secretion-cleavable segment for a query secretory protein; (2) a sum fusion system that integrates the outcomes from aligning the cleavage site template sequence with each of the aforementioned candidates in a scaled window of fixed width to determine the best candidate cleavage sites for the query secretory protein; (3) a voting system that identifies the ultimate signal peptide cleavage site among all possible results derived from using scaled windows of different width. When compared with Signal-3L and SignalP 4.0 predictors, the prediction accuracy of Signal-CTF is 4-12 %, 10-25 % higher than that of Signal-3L for human, animal and eukaryote, and SignalP 4.0 for eukaryota, Gram-positive bacteria and Gram-negative bacteria, respectively. Comparing with PRED-SIGNAL and SignalP 4.0 predictors on the 32 archaea secretory proteins of used in Bagos's paper, the prediction accuracy of Signal-CTF is 12.5 %, 25 % higher than that of PRED-SIGNAL and SignalP 4.0, respectively. The predicting results of several long signal peptides show that the Signal-CTF can better predict cleavage sites for long signal peptides than SignalP, Phobius, Philius, SPOCTOPUS, Signal-CF and Signal-3L. These results show that Signal-CTF is more accurate and flexible in predicting signal peptides of different characteristics for many organisms. Signal-CTF is freely available as a web-server at http://darwin2.cbi.utsa.edu/minniweb/index.html.


Generation and screening of recombinant inbred lines of rice for yellow stemborer resistance.
Based on the results of studies on varietal screening, antixenosis (egg laying preference) and antibiosis (larval survival and adult emergence), rice varieties W1263 and CO43 were selected as resistant and susceptible parents, respectively, for yellow stemborer (YSB) infestation. A mapping population was developed using above parents following single seed descent method. Screening for YSB reaction in F1 and F2, generations under field and glasshouse conditions for both dead hearts and white ears, established the polygenic nature of inheritance for YSB resistance. Field screening for YSB resistance at F9 generation revealed the difference in the reactions among recombinant inbred lines (RILs) between vegetative and reproductive stages. The experiments under field and glasshouse screening of RILs for dead hearts showed significant positive association. However, the reaction was more towards susceptibility in glasshouse screening due to no choice test. Scoring of 250 RILs (F8) for various morphological traits showed wide range of variation indicating the suitability for QTL mapping.


Detecting dentinal sclerosis in decalcified sections with the Pollak trichrome connective tissue stain.
The supply of young human teeth for controlled human pulp studies is inadequate. Dentinal sclerosis in older teeth modifies the expected pulpal responses. Decalcification, necessary to interpret pulpal responses, destroys the primary evidence of sclerosis. At present we are unable to detect the degree of sclerosis and the pulp response in the same preparation. Valid interpretations on older teeth cannot be accomplished until this problem is resolved. Fifty-seven teeth, normal and carious, representing a wide age span were fixed, embedded in Bioplastic and sectioned with the Bronwill Model No. 77 through the middle of the M-D plane on the labio-lingual plane to obtain an undecalcified ground section for examination with reflected and transmitted light and Faxitron 805 microradiography. The remaining portions of the tooth were decalcified, processed in paraffin and subjected to a variety of histochemical reactions including the Pollak trichrome stain. The Pollak trichrome and the Pollak trichrome solution No. 6 modification stains provided the greatest correlations with the sclerotic areas in the radiographs of the ground sections. Areas of dentin indicative of sclerosis prior to decalcification stained orange-red with the Pollak trichrome stain and deep orange with the Pollak trichrome solution No. 6 modification.


Progressive damage along the optic nerve following induction of crush injury or rodent anterior ischemic optic neuropathy in transgenic mice.
To characterize the histological changes that occur in response to induction of ischemic or mechanical optic nerve damage in transgenic mice. Either optic nerve crush injury or rodent anterior ischemic optic neuropathy (rAION) were induced in the right eye of mice transgenic for the Thy1 gene promoter expressing cyan fluorescent protein (CFP; n=40) and mice transgenic for the cyclic nucleotide phosphodiesterase (CNPase) gene promoter expressing green fluorescent protein (GFP; n=40). The left eye served as a control. The mice were euthanized at different times after injury. Eyes were enucleated, and the brain together with the optic nerves was completely dissected. Cryopreserved sections of both optic nerves were analyzed by fluorescence microscopy. In addition, flat-mounted retinas from the Thy1-CFP mice were analyzed for retinal ganglion cell (RGC) loss. Axonal loss was detected in the right eye of the Thy1-CFP mice, and demyelination was detected in the CNPase-GFP mice. Both processes occurred simultaneously in the two models of injury. The damage proceeded retrogradely and, in the crush-injury group, crossed the chiasm within 4 days. At 21 days after injury, RGC loss measured 70% in the crush-injury group and 25% in the rAION group. Axonal injury and demyelination along the optic nerves occur simultaneously in transgenic mice exposed to ischemic or crush injury. The degree of RGC loss reflects the severity of the injury. Loss of oligodendrocytes and myelin apparently leads to axonal loss. Transgenic mice offer a promising model for exploring the damage caused by optic nerve injury. Use of fluorescence labeling makes it possible to better understand the underlying pathophysiology, which can help researchers formulate neuroprotective agents.


[Perspective and application of metabonomics in modern study of traditional Chinese medicine].
Metabonomics is a new method to study on the metabolic network and the relationship between body and environment, which conforms to the way of traditional Chinese medicine (TCM) research. In the study process of modernization of traditional Chinese medicine, effectively conjunction with metabonomics method will facilitate the integration of TCM with modern biological science and technology, and promote the modernization of TCM. This paper introduce the application of metabonomics in the research of toxicity mechanism of TCM, compatibility mechanism of TCM formula, pharmacology effect of TCM and processing mechanism of TCM. This paper summarize the problems in the TCM metabonomics research and prospect its bright future.


Hydroxypropyl methylcellulose 2% for dry eye prevention during phacoemulsification in senile and diabetic patients.
To assess the effect of hydroxypropyl methylcellulose (HPMC) 2% to prevent dry eye during phacoemulsification in senile and diabetic patients. This prospective interventional case series comprised 60 eyes (44 patients) with age-related cataract scheduled for standardized phacoemulsification surgery. The patients were assigned to receive either balanced saline solution (BSS, 30 eyes) or HPMC 2% (30 eyes) during surgery. Preoperative and postoperative examinations (1, 3, 7 and 30 days) included measurements of automatic noninvasive tear film breakup time (NITBUT), fluorescein staining, Schirmer I test, tear meniscus height, depth and area and subjective symptoms. Intraoperative application frequency was also assessed. The mean age of patients was 68.7 ± 2.3 years. The application frequency of BSS during surgery was significantly reduced in HPMC group (P = 0.001). The incidence of dry eye syndrome (DES) was significantly reduced in HPMC group in both senile and diabetic patients. Scores of subjective symptoms were significantly higher in the BSS group in 1 day (P = 0.003) and 3 days (P = 0.043) postoperatively. The first and average NITBUT were significantly higher in HPMC group in 1 day and 3 days after surgery, respectively (P = 0.012 and P = 0.024, respectively). NITBUT values did not significantly change postoperatively in the HPMC group (P > 0.05), while they were significantly lower postoperatively in the BSS group. Application of HPMC 2% during phacoemulsification reduced the incidence of DES and improved patients' satisfaction in both senile and diabetic cataract patients. It was also effective in maintaining corneal hydration and was able to significantly reduce the application frequency intraoperatively.


[Clinical use of cefoxitin in respiratory tract infections].
Cefoxitin (CFX) was used in 9 patients who had respiratory tract infections and following results were obtained: CFX was used in 2 patients with acute pneumonia, 2 with lung abscess, 3 with a mixed infection of lung cancer, 1 with a mixed infection of pulmonary tuberculosis and 1 with empyema. The overall efficacy rate was 77.8%; results were excellent in 2, good in 5 and poor in 2. Bacteriologically, all strains except P. aeruginosa were eradicated after treatment. No side effects were observed. A slight transient elevation of transaminase was observed in 1 patient after doses of 4 approximately 8 g daily. From the above, CFX seems to be a useful and safe drug as an initial choice in the treatment of respiratory tract infections.


Root Resorption with Orthodontic Mechanics: Pertinent Areas Revisited.
Root resorption can occur at any time during orthodontic treatment and lead to a compromise in the prognosis of the tooth and the stability of the treatment results. Recent research has focused more on the cause and effect relationship as well as preventive or treatment options to combat this unwelcome event. Investigations have highlighted the genetic as well as molecular aspects of the process and enabled clinicians to determine which patients might be susceptible. A proper medical history, an assessment of predisposing factors, a radiographic evaluation for alterations in root morphology and careful planning and execution of orthodontic mechanics may reduce the incidence of root resorption. The current review is aimed at providing clinicians and academics with an insight into the process of root resorption, the methods of identification during its early stages and intervention at the right time to reduce its severity.


Functional nano-systems for transdermal drug delivery and skin therapy.
Transdermal drug delivery is one of the least intrusive and patient-friendly ways for therapeutic agent administration. Recently, functional nano-systems have been demonstrated as one of the most promising strategies to treat skin diseases by improving drug penetration across the skin barrier and achieving therapeutically effective drug concentrations in the target cutaneous tissues. Here, a brief review of functional nano-systems for promoting transdermal drug delivery is presented. The fundamentals of transdermal delivery, including skin biology and penetration routes, are introduced. The characteristics of functional nano-systems for facilitating transdermal drug delivery are elucidated. Moreover, the fabrication of various types of functional transdermal nano-systems is systematically presented. Multiple techniques for evaluating the transdermal capacities of nano-systems are illustrated. Finally, the advances in the applications of functional transdermal nano-systems for treating different skin diseases are summarized.


Anthelmintic efficacy of oxibendazole against some important nematodes in dogs and cats.
The anthelmintic efficacy and safety of the oxibendazole component in a combination oxibendazole-niclosamide paste were investigated in dogs and cats and in litters of pups with naturally acquired nematode infections. A single dose of 15 mg oxibendazole/kg body weight given to 70 dogs and to 29 cats reduced faecal worm egg counts (EPG) by 97.6% for Toxocara canis, 95.7% for Trichuris vulpis, 94.6% for Ancylostoma caninum, and 100% for Toxascaris leonina. In cats, 96.7% efficacy was demonstrated against Toxocara cati. In a second trial, 119 pups in 22 litters were treated with the same dosage at 2, 4, and 6 weeks of age. After treatment on two consecutive days, 95% of the pups did not shed T. canis eggs, compared with 85% after only a single treatment. Side effects were rare and only recorded in young animals. A 2-day treatment schedule is recommended for unweaned pups.


Patient-Perceived Outcomes and Quality of Life in ALS.
A variety of outcome measures are used in clinical practice and in research to assess patients with amyotrophic lateral sclerosis (ALS). However, there may be discordance between traditional outcome measures such as strength and physical function, and patient-perceived measures of well-being. One such self-perceived measure, reflecting the patient's view, is quality of life (QOL). QOL in patients with severe medical disorder is often underestimated by others. Patients with ALS often have high QOL, and this may persist throughout the disease due to shifting expectations and to reprioritization of factors contributing to QOL. QOL instruments can measure health-related QOL (HRQOL) or global QOL, and can be generic or disease-specific. HRQOL refers primarily to physical and mental health. Global QOL is much broader, and is also determined by non-health-related factors. The choice of a QOL instrument depends on whether the setting is routine patient care or clinical research, whether or not the outcome of a specific intervention is being assessed, and upon the expected efficacy or toxicity of the intervention. Global QOL instruments are best for individual clinical patient care or for comparing groups. HRQOL or a combination of HRQOL and global QOL instruments are most appropriate for assessing specific interventions.


Fengycin C produced by Bacillus subtilis EA-CB0015.
Bacillus subtilis EA-CB0015 was isolated from the phyllosphere of a banana plant and tested for its potential to produce bioactive compounds against Mycosphaerella fijiensis. Using a dual plate culture technique the cell-free supernatant of B. subtilis EA-CB0015 produced inhibition values of 89 ± 1%. The active compounds were purified by solid-phase extraction and HPLC, and their primary structures determined using mass spectrometry and amino acid analysis. A new fengycin isoform, fengycin C, with the amino acid sequence Glu-Orn-Tyr-Thr-Glu-Val-Pro-Gln-Thr-Ile was isolated. The peptidic moiety differs from fengycin B at position 9 and from fengycin A at positions 6 and 9. The β-hydroxy fatty acyl chain is connected to the N-terminal of the decapeptide and can be saturated or unsaturated, ranging from 14 to 18 carbons. The C-terminal residue of the peptidic moiety is linked to the tyrosine residue at position 3, forming the branching point of the acyl peptide and the eight-membered cyclic lactone.


[Intraoperative fluorescein angiography with an ultrasensitive imaging tube].
Fluorescein angiographic examination may be prevented by vitreous hemorrhage or opacities in vitreoretinal diseases before vitrectomy. We performed intraoperative fluorescein angiography for such cases, using a conventional light source and an ultrasensitive video camera equipped with a silicone intensifier target tube to avoid retinal phototoxicity. Intraoperative fluorescein angiograms allowed evaluation of neovascular vessels, proliferative tissues, and avascular areas associated with diabetic retinopathy. Indentation of the pars plicata enabled us to also record fluorescein images of the area. This device may aid intraoperative assessment of vitreoretinal diseases including diabetic retinopathy.


Changes in Imaging and Cognition in Juvenile Rats After Whole-Brain Irradiation.
In pediatric cancer survivors treated with whole-brain irradiation (WBI), long-term cognitive deficits and morbidity develop that are poorly understood and for which there is no treatment. We describe similar cognitive defects in juvenile WBI rats and correlate them with alterations in diffusion tensor imaging and magnetic resonance spectroscopy (MRS) during brain development. Juvenile Fischer rats received clinically relevant fractionated doses of WBI or a high-dose exposure. Diffusion tensor imaging and MRS were performed at the time of WBI and during the subacute (3-month) and late (6-month) phases, before behavioral testing. Fractional anisotropy in the splenium of the corpus callosum increased steadily over the study period, reflecting brain development. WBI did not alter the subacute response, but thereafter there was no further increase in fractional anisotropy, especially in the high-dose group. Similarly, the ratios of various MRS metabolites to creatine increased over the study period, and in general, the most significant changes after WBI were during the late phase and with the higher dose. The most dramatic changes observed were in glutamine-creatine ratios that failed to increase normally between 3 and 6 months after either radiation dose. WBI did not affect the ambulatory response to novel open field testing in the subacute phase, but locomotor habituation was impaired and anxiety-like behaviors increased. As for cognitive measures, the most dramatic impairments were in novel object recognition late after either dose of WBI. The developing brains of juvenile rats given clinically relevant fractionated doses of WBI show few abnormalities in the subacute phase but marked late cognitive alterations that may be linked with perturbed MRS signals measured in the corpus callosum. This pathomimetic phenotype of clinically relevant cranial irradiation effects may be useful for modeling, mechanistic evaluations, and testing of mitigation approaches.


Effects of extracts of spices on rumen methanogenesis, enzyme activities and fermentation of feeds in vitro.
An experiment was conducted to study the effects of boiling water, methanol and ethanol extracts (0, 0.25 and 0.50 mL) of seeds of Foeniculum vulgare (fennel), flower buds of Syzygium aromaticum (clove), bulbs of Allium sativum (garlic), bulbs of Allium cepa (onion) and roots of Zingiber officinalis (ginger) on rumen methanogenesis, fibrolytic enzyme activities and fermentation characteristics in vitro. Ethanol and methanol extracts of fennel, clove and garlic at 0.50 mL and clove at 0.25 mL inhibited (P < 0.05) methane production. Carboxymethylcellulase activity was reduced (P < 0.05) by ethanol and methanol extracts (0.50 mL) of fennel and clove (0.25 and 0.50 mL). The extracts of clove reduced (0.25 and 0.50 mL) xylanase and acetylesterase activities, and the fennel extract (0.50 mL) reduced (P < 0.05) xylanase activity. However, the extracts of garlic (0.50 mL) increased (P < 0.05) acetylesterase activity. Concentrations of volatile fatty acids were reduced (P < 0.05) by the extracts of garlic and onion. The extracts of garlic caused a decrease (P < 0.05) in acetate:propionate ratio (A:P) at 0.50 mL, whereas A:P was increased (P < 0.05) by the inclusion of 0.50 mL extracts of clove. Methanol and ethanol extracts of clove decreased (P < 0.05) in vitro organic matter degradability. Extracts (0.50 mL) of clove decreased (P < 0.05) the numbers of total protozoa, small entodiniomorphs and holotrichs, whereas extracts of onion, ginger and garlic enhanced (P < 0.05) protozoal numbers (both entodiniomorphs and holotrichs). Ethanol and methanol extracts of fennel and garlic have potential to inhibit rumen methanogenesis without adversely affecting rumen fermentation.


Upper Gastrointestinal Tract Hemorrhage: Unexpected Discovery.
Pica is a serious condition that is characterized by ingesting inedible things which can prove to be fatal (glass, pebbles, etc.) We present the case of a 64-year-old male patient who is admitted to the emergency room with the following complaints: upper GI tract bleeding manifested through hematemesis and melena, epigastric pain, lack of bowel movements. A contrast computed tomograohy is performed showing the presence of a hyper-dense stomach content, gastric wall thickening, abdominal fluid but with no signs of intestinal occlusion. A laparotomy is performed and ollowing an anterior gastrotomy a large quantity of pebbles is found along with a hemorrhagic and stenotic tumor of the lesser curvature. Taking into account the intraoperative aspect the decision was made to perform an end-to-side stapled esophago-jejunal anastomosis on an omega loop with a Braun entero-entero anastomosis following total gastric resection and D1 lymphadenectomy. Postoperative course is uneventful. A barium swallow carried out on the 10th day following surgery shows a functional anastomosis without leakage. On day 11, the patient is discharged. Pica is usually discovered by accident, most frequently on the operating table which is why thorough preoperative examination and investigations are required.


Work-Life Balance, Burnout, and Physician Wellness.
Work-life balance, burnout, and physician wellness have become an important focus over the last 20 years in the field of medicine. Significant work design and cultural changes are to blame for these newly recognized aspects of a physician's career and life as a whole. Unique aspects of the work environment in the United States not only contribute to these issues in the field of medicine, but also affect the US workforce at large. Stagnant responses from governmental bodies and private organizations have allowed the issue to worsen over time. Now with added attention from some leaders, both inside and outside the health care industry, along with the increasing body of research to guide these changes, there is hope for the necessary cultural change to address work-life balance, burnout, and physician wellness. Studies are available to identify the negative contributing factors, establish evidence-based prevention strategies, and help physicians to find their ideal work-life balance, avoid burnout, and achieve overall wellness. This article seeks to provide a brief background in the area of work-life balance, burnout, and physician wellness. It will also review key points of the current literature and provide a combination of solutions suggested by experts in the field.


Free amino acids in the Arctic snow and ice core samples: Potential markers for paleoclimatic studies.
The role of oceanic primary production on climate variability has long been debated. Defining changes in past oceanic primary production can help understanding of the important role that marine algae have in climate variability. In ice core research methanesulfonic acid is the chemical marker commonly used for assessing changes in past primary production. However, other organic compounds such as amino acids, can be produced and emitted into the atmosphere during a phytoplankton bloom. These species can be transported and deposited onto the ice cap in polar regions. Here we investigate the correlation between the concentration of chlorophyll-a, marker of marine primary production, and amino acids present in an ice core. For the first time, free l- and d-amino acids in Arctic snow and firn samples were determined by a sensitive and selective analytical method based on liquid chromatography coupled with tandem mass spectrometry. The new method for the determination of free amino acids concentrations was applied to firn core samples collected on April 2015 from the summit of the Holtedahlfonna glacier, Svalbard (N 79'08.424, E 13'23.639, 1120m a.s.l.). The main results of this work are summarized as follows: (1) glycine, alanine and proline, were detected and quantified in the firn core samples; (2) their concentration profiles, compared with that of the stable isotope δ18O ratio, show a seasonal cycling with the highest concentrations during the spring and summer time; (3) back-trajectories and Greenland Sea chlorophyll-a concentrations obtained by satellite measurements were compared with the amino acids profile obtained from ice core samples, this provided further insights into the present results. This study suggests that the amino acid concentrations in the ice samples collected from the Holtedahlfonna glaciers could reflect changes in oceanic phytoplankton abundance.


Impact of tuberculosis on glycaemic status: A neglected association.
Diabetes mellitus (DM) is an important risk factor for tuberculosis and has received increasing emphasis. However, the reverse association of tuberculosis impacting blood sugar levels has not been well studied. The present study was conducted to evaluate the prevalence of hyperglycemia in patients with tuberculosis and assess its resolution following successful treatment of tuberculosis. In this prospective study, a total of 582 patients with tuberculosis were evaluated for hyperglycaemia [DM or impaired glucose tolerance (IGT)] with random blood sugar (RBS) and all patients with RBS >100 mg/dl were subjected to a 75 g oral glucose tolerance test (OGTT). All patients received thrice weekly intermittent Directly Observed Treatment Short Course (DOTS) for tuberculosis. Patients with hyperglycaemia were re-evaluated at the end of anti-tuberculosis treatment with an OGTT and glycated hemoglobin (HbA1c) levels to assess for glycaemic status. In the present study, 41 of the 582 patients were found to have DM [7%, 95% confidence interval (CI) (5.2, 9.4)] while 26 patients were found to have IGT [4.5%, 95% CI (3, 6.5)]. Three patients were lost to follow up. Of the 26 patients with IGT, 17 [65.4%, 95% CI (46.1, 80.7)] reverted to euglycaemic status following successful treatment of tuberculosis, while the blood sugar levels improved in all patients with DM following treatment of tuberculosis. Our study results show that tuberculosis adversely impacts glycaemic status with improvement in blood sugar levels at the end of successful treatment of tuberculosis. Longitudinal studies with large sample size are required to confirm these findings.


Vectors to target protein domains to different cellular compartments.
The pcDNA3 mammalian expression vector uses the cytomegalovirus (CMV) promoter to express proteins cloned into an adjacent polylinker. We have modified this vector to create three different targeting constructs: Go to Plasma Membrane (pGTM), Go to Nucleus (pGTN) and Go to Nucleus, Activate Transcription (pGTNAT). pGTM expresses a protein as a fusion to a myristic acid attachment signal, which targets proteins to the cell membranes. pGTN expresses an inserted protein as a fusion to a nuclear localization sequence (NLS), targeting it to the nucleus. pGTNAT incorporates an NLS (directing proteins to the nuclear compartment), an acid blob (a transcriptional activation domain) and a hemagglutinin epitope tag, creating a 107-amino acid fusion domain. We then cloned green fluorescent protein (GFP) into the three novel vectors and pcDNA3, and we transfected HeLa cells to test the new targeting constructs. Immunofluorescence analysis showed that the GFP protein localizes to the nucleus when over-expressed in pGTN and pGTNAT, localizes to the plasma membrane and perinuclear membrane when in pGTM and is ubiquitous through the cell in pcDNA3. We anticipate that these new vectors will prove very useful in future expression studies to examine the function of particular proteins when they are localized to specific cellular compartments.


A prognostic mathematical model based on tumor microenvironment-related genes expression for breast cancer patients.
Tumor microenvironment (TME) status is closely related to breast cancer (BC) prognosis and systemic therapeutic effects. However, to date studies have not considered the interactions of immune and stromal cells at the gene expression level in BC as a whole. Herein, we constructed a predictive model, for adjuvant decision-making, by mining TME molecular expression information related to BC patient prognosis and drug treatment sensitivity. Clinical information and gene expression profiles were extracted from The Cancer Genome Atlas (TCGA), with patients divided into high- and low-score groups according to immune/stromal scores. TME-related prognostic genes were identified using Kaplan-Meier analysis, functional enrichment analysis, and protein-protein interaction (PPI) networks, and validated in the Gene Expression Omnibus (GEO) database. Least absolute shrinkage and selection operator (LASSO) Cox regression analysis was used to construct and verify a prognostic model based on TME-related genes. In addition, the patients' response to chemotherapy and immunotherapy was assessed by survival outcome and immunohistochemistry (IPS). Immunohistochemistry (IHC) staining laid a solid foundation for exploring the value of novel therapeutic target genes. By dividing patients into low- and high-risk groups, a significant distinction in overall survival was found (p < 0.05). The risk model was independent of multiple clinicopathological parameters and accurately predicted prognosis in BC patients (p < 0.05). The nomogram-integrated risk score had high prediction accuracy and applicability, when compared with simple clinicopathological features. As predicted by the risk model, regardless of the chemotherapy regimen, the survival advantage of the low-risk group was evident in those patients receiving chemotherapy (p < 0.05). However, in patients receiving anthracycline (A) therapy, outcomes were not significantly different when compared with those receiving no-A therapy (p = 0.24), suggesting these patients may omit from A-containing adjuvant chemotherapy. Our risk model also effectively predicted tumor mutation burden (TMB) and immunotherapy efficacy in BC patients (p < 0.05). The prognostic score model based on TME-related genes effectively predicted prognosis and chemotherapy effects in BC patients. The model provides a theoretical basis for novel driver-gene discover in BC and guides the decision-making for the adjuvant treatment of early breast cancer (eBC).


Dermoscopic patterns of terra firma-forme dermatosis.
Terra firma-forme dermatosis is a relatively common but probably underestimated entity characterized by asymptomatic cutaneous pigmentation resembling dirty skin. Dermoscopy is a non-invasive diagnostic tool used in the diagnosis of many cutaneous conditions. In this study we aimed to reveal dermoscopic patterns of the entity. A total of 10 patients diagnosed with terra firma-forme dermatosis were enrolled. The most common dermoscopic pattern was polygonal brown clods arranged in a mosaic pattern (N=7). The other patterns observed were seborrheic keratosis-like pattern (N=2) and perifollicular hyperpigmentation (N=1). Rubbing with 70% ethyl alcohol resulted in complete resolution of the lesions in all patients.


Hemodialysis in the treatment of severe hypercalcemia.
Severe hypercalcemia is a life-threatening problem that requires prompt therapy. With the exception of diuresis, most forms of therapy are either ineffective, slow in action, or have major serious disadvantages. In some instances diuresis is relatively ineffective. As shown in this case report, hemodialysis with a dialysate low in calcium is rapidly effective in such instances and should be considered for patients with severe hypercalcemia while they are being prepared for surgery or while diagnostic studies are being performed.


Collagen gel contraction induced by retinal pigment epithelial cells and choroidal fibroblasts involves the protein kinase C pathway.
Contraction of intraocular fibrous membranes is an important feature in the pathogenesis of retinal detachment in proliferative vitreoretinopathy (PVR). Collagen gel contraction is a useful in vitro model of membrane contraction in PVR. We studied the role of protein kinase C (PKC) in collagen gel contraction induced by bovine choroidal fibroblasts and retinal pigment epithelial (RPE) cells. Collagen gels embedded with the cells were formed in culture dishes and gel contraction was evaluated. The PKC stimulator, phorbol 12-myristate 13-acetate (PMA), and the protein phosphatase 1 and 2A inhibitor, okadaic acid (OA), were used to evaluate the role of the PKC-mediated phosphorylation system in this gel contraction. Fifteen min incubation with PMA stimulated gel contraction, but 180 min incubation had no effect. Choroidal fibroblast- but not RPE cell-induced gel contraction was stimulated by OA. These effects were inhibited by the broad spectrum protein kinase inhibitor staurosporine and the specific PKC antagonist calphostin C. Transforming growth factor-beta (TGF-beta)1 and TGF-beta 2, which are known to be present in eyes with PVR, were evaluated to determine their effect on gel contraction. Both TGF-beta 1 and 2 had a stimulatory effect on contraction of gels seeded with choroidal fibroblasts and RPE cells, but staurosporine and calphostin C inhibited this TGF-beta-induced gel contraction. These results indicate that activation of PKC/protein phosphorylation is an important factor in gel contraction caused by choroidal fibroblasts and RPE cells, and that TGF-beta-induced gel contraction is mediated at least in part via the PKC pathway.


Comparison of native extracellular matrix with adsorbed protein films using secondary ion mass spectrometry.
In the past decade, the temperature-responsive behavior of poly(N-isopropyl acrylamide) (pNIPAM) has come to be recognized as a convenient method for the nondestructive harvest of confluent cell layers. Recently, we have utilized this nondestructive cell harvest method as a means to ascertain the nature of the extracellular matrix (ECM) secreted from cells. In this work, we compare the ECM obtained after cell liftoff to individual ECM proteins adsorbed directly onto RF-plasma-deposited pNIPAM (ppNIPAM). Using X-ray photoelectron spectroscopy, we find that the composition of ppNIPAM post-cell liftoff surfaces is consistent with those of the ppNIPAM post-protein adsorption surface, both of which differ from control surfaces. Using principal component analysis of positive-ion time-of-flight secondary ion mass spectrometry (ToF-SIMS) data, we show that the major ECM proteins examined can effectively be identified from their amino acid compositions. By comparing the positive-ion ToF-SIMS data from each of the ppNIPAM post-protein adsorption surfaces to that of ppNIPAM post-cell liftoff, we find that ppNIPAM post-cell liftoff surfaces are distinctly separate from fibronectin (FN). This result is consistent with our previous observation using immunoassay that FN is clearly associated with the cell sheet after low-temperature liftoff from ppNIPAM.


[Prevention of lateral cortex fractures in open wedge high tibial osteotomies : The anteroposterior drill hole approach].
In osteotomies with larger correction angles, the capacity for elastic deformation is frequently exceeded, resulting in plastic deformation and fracture of the opposite cortex, which may lead to subsequent loss of correction. An anteroposterior drill hole at the apex of the horizontal osteotomy (= hinge) is supposed to increase the capacity of the bony hinge for elastic deformation and ideally to prevent fractures of the opposite cortex. A high tibial osteotomy (HTO) using standard surgical technique was performed in 20 each of Synbones, Sawbones, and human cadaver tibial specimens. In 10 specimens per group, an additional anteroposterior hinge drilling was performed at the apex of the horizontal osteotomy. All fractures of the opposite cortex were photographically and radiographically documented. All fractures were classified according to fracture types 1-3 of the Takeuchi classification. Regardless of the study group, all tibial bones with an additional hinge drilling achieved larger correction angles during the spreading of the wedge until a fracture of the opposite cortex occurred. The average correction angle of all specimens without the drill hole was 2.7°, which increased to 4.8° with the hinge drill (increase by 77.8%). In correction angles exceeding 5°, all specimen showed a hinge fracture regardless of the presence or absence of a hinge drill. The hinge-protecting effect is restricted to small correction angles, i. e., to unload cartilage repair regions in the absence of severe malalignment. For the treatment of varus gonarthrosis, there is no fracture-protecting effect from a hinge drill.


Viologen-functionalized single-walled carbon nanotubes as carrier nanotags for electrochemical immunosensing. Application to TGF-β1 cytokine.
Viologen-SWCNT hybrids are synthesized by aryl-diazonium chemistry in the presence of isoamyl nitrite followed by condensation reaction of the resulting HOOC-Phe-SWCNT with 1-(3-aminoethyl)-4,4'-bipyridinium bromine and N-alkylation with 2-bromoethylamine. The V-Phe-SWCNT hybrids were characterized by using different spectroscopic techniques (FT-IR, Raman, UV-vis), TGA and Kaiser test. Viologen-SWCNTs were used for the preparation of an electrochemical immunosensor for the determination of the transforming growth factor β1 (TGF-β1) cytokine considered as a reliable biomarker in several human diseases. The methodology involved preparation of V-Phe-SWCNT(-HRP)-anti-TGF conjugates by covalent linkage of HRP and anti-TGF onto V-Phe-SWCNT hybrids. Biotinylated anti-TGF antibodies were immobilized onto 4-carboxyphenyl-functionalized SPCEs modified with streptavidin and a sandwich type immunoassay was implemented for TGF-β1 with signal amplification using V-Phe-SWCNT(-HRP)-anti-TGF conjugates as carrier tags. The analytical characteristics exhibited by the as prepared immunosensor (range of linearity between 2.5 and 1000pgmL-1 TGF-β1; detection limit of 0.95pgmL-1) improve notably those reported with other previous immunosensors or ELISA kits. A great selectivity against other proteins was also found. The prepared immunosensor was validated by determining TGF-β1 in real saliva samples. Minimal sample treatment was required and the obtained results were in excellent agreement with those obtained by using a commercial ELISA kit.


Factors influencing linear growth in Saudi Arabian children aged 6-24 months.
This study was carried out to identify possible factors influencing the growth pattern of Saudi children in the first 2 years of life. The body length and weight of 400 healthy babies attending the well-baby care clinic of King Khalid University Hospital, Riyadh, Saudi Arabia, were measured at various determined ages in a cross-sectional study design. Nutritional indicators were calculated and the proportions with low height-for-age, low weight-for-height and low weight-for-age were compared with the reference population. The results showed a prevalence of 2 per cent of wasted children and 18 per cent of children with stunted growth. A univariate and multivariate analysis of personal and nutritional variables with the standard nutritional indicators identified age, sex, bottle feeding, and type of solid foods as significant risk factors for stunted growth. Stunting increases with age and males have poorer growth pattern than females. Genetic factors and poor feeding practices of the children are suggested reasons for the observed faltering growth between 6 and 24 months of age. A public health education programme for good nutrition is highly recommended.


DNA microarrays and toxicogenomics: applications for ecotoxicology?
Toxicogenomics attempts to define how the regulation and expression of genes mediate the toxicological effects associated with exposure to a chemical. DNA microarrays are rapidly becoming one of the tools of choice for large-scale toxicogenomic studies. An approach in modern toxicogenomics has been to classify toxicity based on gene transcriptional patterns; comparing the transcriptional responses of a chemical with unknown toxicity to those for which the transcriptional profiles and toxicological endpoints have been well characterized. Recent evidence suggests that gene expression microarrays may be instrumental in defining mechanisms of action of toxicants. However, several assumptions are inherent to a toxicogenomic-based approach in toxicology, many of which remain to be validated. Gene expression profiling using DNA microarrays represents a snapshot of the gene transcriptional responses occurring at a particular time and within a particular tissue. Toxicity, on the other hand, represents a continuum of possible effects governed by both temporal and spatial factors that are inextricably contingent upon the exposure conditions. The perceived toxicological properties of any chemical are dependent on the route, dose, and duration of the exposure, and as such, gene expression patterns are also subject to these variables. Correct interpretation of DNA microarray data for the assessment of the toxicological properties of chemicals will require that temporal and spatial gene expression profiles be accounted for. These considerations are further compounded in ecotoxicological studies, during which altered gene expression patterns induced from exposure to an anthropogenic substance must be discernible over and above the complex effects that phenotypic, genotypic, and environmental variables have on gene expression. To this end, the greatest utility of DNA microarrays in the field of ecotoxicology may be in predicting the toxicological modes of action of anthropogenic substances on host physiology, particularly in non-model organisms. Predictable and accurate assessment of the impacts of a chemical substance in ecotoxicology will require that classical toxicological endpoints be used to validate any effects predicted based on gene expression profiling. Validated expression profiling may subsequently find utility in ecotoxicological-based computer simulation models, such as the Biotic Ligand Model (BLM), in which gene expression information may be integrated with geochemical, pharmacokinetic, and physiological data to accurately assess and predict toxicity of metals to aquatic organisms.


A new species of Passaloecus Shuckard (Hymenoptera, Crabronidae) from China, with a key to Oriental species.
A new species of Passaloecus Shuckard, P.birugatus Bashir & Chen, sp. nov., is described and illustrated from Yunnan Province, China. The new species can be easily distinguished from known species of Passaloecus by its very long petiole, which is distinctly longer than wide, obscure scrobal suture, propodeum rugae and striations, body punctation, and coloration. An identification key to the Oriental species of Passaloecus is given.


Anti-apoptosis effects of codonolactone on cerebral ischemia-reperfusion injury.
Codonolactone is the main biologically active ingredient in Atractylodes lancea Studies have shown various functions of codonolactone, while its protective effect against neurotoxicity caused by ischemic stroke is unclear. This study investigated the roles of codonolactone in inflammation, oxidative stress and apoptosis after cerebral ischemia-reperfusion (I/R) injury. Rats with codonolactone treatment, I/R treatment and the sham operation group were used in this study. After reperfusion for 24 hours, nerve damage was detected by nerve staining, and the neurological deficits of the rats were analyzed. The contents of superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in rat brain tissues were also determined. Western blot analysis was performed to determine the expression levels of Akt/Nrf2 pathway-associated proteins. Compared with the I/R group, the cerebral blood flow, infarct volume, brain water content, coronary blood flow and neurological deficits in the codonolactone treatment group, especially with the 80 mg/kg dosage, were significantly reduced. Codonolactone could significantly reduce the expression levels of caspase-3 and Bax, and significantly increase the expression levels of Bcl-2 after I/R. In addition, codonolactone could significantly reduce MDA content and the expression levels of TNF-α and IL-1β in ischemic brain tissues. It also significantly increased SOD activity, the expression levels of heme oxygenase-1 (HO-1) and the phosphorylation of Akt and Nrf2. Codonolactone ameliorated the cerebral I/R injury by improving anti-oxidant, anti-inflammatory activities and reducing apoptosis. Besides, the Akt/Nrf2 pathway was involved in the pharmacological action of the codonolactone.


Complete coding sequence of Zika virus from Martinique outbreak in 2015.
Zika virus is an Aedes-borne Flavivirus causing fever, arthralgia, myalgia rash, associated with Guillain-Barré syndrome and suspected to induce microcephaly in the fetus. We report here the complete coding sequence of the first characterized Caribbean Zika virus strain, isolated from a patient from Martinique in December, 2015.


Dual renin-angiotensin system blockade for nephroprotection.
In experimental diabetic and nondiabetic chronic kidney disease, angiotensin-converting enzyme (ACE) inhibitor and angiotensin receptor blockers (ARB) combination therapy reduce proteinuria and prevent structural lesions more effectively than either drug alone. Consistently, in humans, a multidrug individually tailored antiproteinuric treatment based on combination therapy with maximum tolerated doses of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers ("Remission Clinic") reduced proteinuria and prevented end-stage renal disease more effectively than angiotensin-converting enzyme/angiotensin receptor blockers monotherapy, in particular in subjects with nondiabetic chronic kidney disease. Fixed doses of an angiotensin-converting enzyme inhibitor or renin inhibitor added-on losartan failed to exert any additional renoprotective effect as compared with losartan monotherapy in patients with type 2 diabetes and overt nephropathy. However, the VA NEPHRON D study found that losartan and lisinopril combination therapy reduced by 34 % the risk of pre-defined reductions in estimated glomerular filtration rate, end-stage renal disease or death as compared to losartan in 1448 type 2 diabetes patients with overt nephropathy. Unfortunately, treatment effect failed to achieve the nominal significance (P=0.07) because of premature trial interruption. Thus, the Remission Clinic protocol is the most powerful tool to prevent progression to end-stage renal disease in nondiabetic proteinuric chronic kidney disease. Results of the ongoing VALID trial will show whether this approach can be safely extended to type 2 diabetes patients.


[Expression of kinesin KIF3A in the kidney of mice with unilateral ureteral obstruction].
To investigate the expression of KIF3A in mice with unilateral ureteral obstruction (UUO) and TGF-β1-induced NRK-52E cells and the role of KIF3A in renal tubular epithelial cell transdifferentiation. Thirty-six C57BL/6J mice were randomly divided into the sham group (n=18) and UUO group (n=18). Six mice in each group were sacrificed at 7, 14 and 21days after the operation. The degree of renal tubulointerstitial fibrosis of the mice was observed by HE staining, Masson trichrome staining and Sirius red staining. The expression and distribution of KIF3A in the kidney of the mice was detected using RT-PCR, Western blotting and immunohistochemistry. Western blotting was used to detect the expression of KIF3A, E-cadherin and α-SMA proteins in the renal tissue of the mice. The expressions of KIF3A, E-cadherin, α-SMA, Wnt4 and β-catenin proteins in NRK-52E cells with TGF-β1-induced transdifferentiation were detected by Western blotting. Compared with the sham-operated mice, the mice with UUO showed worsened renal interstitial fibrosis with the increase of obstruction time, indicating successful modeling. The expressions of KIF3A mRNA and protein increased progressively and reached the peaked level at 21 days after UUO. The expression of α-SMA protein was significantly increased while E-cadherin protein expression was significantly reduced after UUO. The transdifferentiated NRK-52E cells showed significantly increased expressions of KIF3A (P < 0.001), Wnt4 (P < 0.05) and β-catenin proteins (P < 0.0001). KIF3A may participate in the development of renal fibrosis through epithelial-mesenchymal transition mediated by wnt/β-catenin signaling pathway.


Coupled states in dinitrofluorene: relationships between ground state and excited state mixed valence.
The electronic absorption spectrum of 9,9-dimethyl-2,7-dinitrofluorene radical anion in HMPA displays both a NIR intervalence charge transfer and a visible excited state mixed valence transition. These transitions contain a similar vibronic progression resulting from molecular orbitals that are common to both transitions. Vibrational frequency and intensity data are acquired from the resonance Raman spectrum and used to calculate a best fit for the absorption spectrum. The normal coordinate distortions are analyzed in terms of the electronic changes for both transitions to explain their similarity. The Raman scattering intensity decreases at lower excitation wavelength as a result of Raman de-enhancement caused by interference between neighboring excited states.


Trifluoromethylation of Secondary Nitroalkanes.
Using a commercially available Umemoto's reagent, the metal-free trifluoromethylation of nitroalkanes is now possible. This method provides a general, high-yielding synthesis of α-(trifluoromethyl)nitroalkanes. The quaternary α-(trifluoromethyl)nitroalkanes obtained from this transformation can be elaborated to a variety of complex nitrogen-containing molecules, including α-(trifluoromethyl)amines.


Genetic regulation of patterned tubular branching in Drosophila.
A common theme in organogenesis is the branching of epithelial tubes, for example in the lung, liver, or kidney. The later morphogenesis of these branched epithelia dictates the final form and function of the mature tissue. Epithelial branching requires the specification of branch cells, the eversion process itself, and, frequently, patterned morphogenesis to produce branches of specific shape and orientation. Using the branching of renal tubule primordia from the hindgut in Drosophila, we show that these aspects are coordinately regulated. Cell specification depends on Wnt signaling along the tubular gut and results in the spatially restricted coexpression of two transcription factors, Krüppel and Cut, in the hindgut, whose activity drives cells toward renal tubule fate. Significantly, these transcription factors also confer the competence to respond to a second signal; TGF-beta induces branching to form the four renal tubule buds. Differential activation of the TGF-beta pathway also patterns the tubules, resulting in the asymmetry in size and positioning that is characteristic of the two tubule pairs. High levels of TGF-beta promote the expression of Dorsocross1-3 and anterior tubule growth, whereas low levels allow the expression of the transcriptional repressor, Brinker, and thus promote posterior tubule identity. We show that patterning of the tubule primordium into two distinct pairs is critical for the eversion of tubule branches, as well as for their asymmetric morphogenesis.


1-year results using the Opus speech processor with the fine structure speech coding strategy.
In contrast to the Tempo+ the new Opus speech processor stimulates with the new fine structure programming (FSP) speech coding strategy and offers an extended frequency spectrum. A significant improvement in speech perception for sentences at 10 dB SNR (signal to noise ratio) was observable. The aim of this study was to investigate the long-term effects on speech perception in quiet and in noise with the Opus speech processor using FSP. Eight post-lingually deaf patients implanted with Pulsar cochlear implants and fitted with Tempo+ speech processors (both MED-EL) for a minimum of 1 year were tested at baseline with Tempo+ using continuous interleaved sampling (CIS), and at 1 year follow-up with the Opus speech processor using FSP. Monosyllables and sentence tests were performed in quiet, and sentence tests (HSM) in noise with 15, 10 and 5 dB SNR. Mean speech perception scores showed a trend towards improvement for all tests. A statistically significant (p < 0.05) improvement was only observed for the sentence test in noise at 10 dB SNR.


Benign and neoplastic eosinophilic staining cells: an immunofluorescence study.
Deposition of immunoglobulins, complement and fibrinogen on eosinophilic staining cells was investigated using direct immunofluorescence techniques. Serum factor deposition was detected on benign epidermal eosinophilic cells seen in pityriasis lichenoides et varioliformis acuta, sunburn erythema and, in addition, on subepidermal hyaline bodies in lichen planus; no such deposition occurred on neoplastic eosinophilic cells in Bowen's disease and squamous cell carcinoma. The qualitative findings of immunofluorescence microscopy seem to be different in inflammatory and malignant dermatoses.