Leptin receptor blockade reduces intrahepatic vascular resistance and portal pressure in an experimental model of rat liver cirrhosis.
Increased hepatic vascular resistance mainly due to elevated vascular tone and to fibrosis is the primary factor in the development of portal hypertension in cirrhosis. Leptin, a hormone associated with reduction in nitric oxide bioavailability, vascular dysfunction, and liver fibrosis, is increased in patients with cirrhosis. We aimed at evaluating whether leptin influences the increased hepatic resistance in portal hypertension. CCl4-cirrhotic rats received the leptin receptor-blocker ObR antibody, or its vehicle, every other day for 1 wk. Hepatic and systemic hemodynamics were measured in both groups. Hepatic nitric oxide production and bioavailability, together with oxidative stress, nitrotyrosinated proteins, and liver fibrosis, were evaluated. In cirrhotic rats, leptin-receptor blockade significantly reduced portal pressure without modifying portal blood flow, suggesting a reduction in the intrahepatic resistance. Portal pressure reduction was associated with increased nitric oxide bioavailability and with decreased O2(-) levels and nitrotyrosinated proteins. No changes in systemic hemodynamics and liver fibrosis were observed. In conclusion, the present study shows that blockade of the leptin signaling pathway in cirrhosis significantly reduces portal pressure. This effect is probably due to a nitric oxide-mediated reduction in the hepatic vascular tone.


The Use of Complementary and Alternative Medicine by the General Population in the Czech Republic: A Follow-Up Study.
The prevalence of complementary and alternative medicine (CAM) ranges between 0.3% and 86% in most highly developed countries. In the Czech Republic, CAM is used by 76% of the general population. Our aim was to examine patterns in CAM use among a representative sample of the general population in the Czech Republic, for 2011 and 2014. A cross-sectional survey was conducted. A sex-, age- and region-stratified sample of citizens aged 15 years and older was randomly selected from the 2014 voter registration lists (n = 8,395,132). A comparative analysis of data collected in 2011 and 2014 was performed. Overall, 76.0% (N = 1,365) versus 87.0% (N = 1,565) of the respondents reported use of 1 or more CAM modalities during the past 30 days, in 2011 and 2014, respectively (p < 0.001). In both years, the top 4 CAM modalities used were vitamins/minerals, herbal teas, massage, and relaxation. Yoga replaced dietary supplements excluding vitamins/minerals in the 5th position. Nevertheless, only herbal teas (48.0% vs. 53.0%, p = 0.002), massage (20.0% vs. 26.0%, p < 0.001), relaxation (10.0% vs. 19.0%, p < 0.001), and yoga (3.7% vs. 7.1%, p < 0.001) showed a significant increase in use. The prevalence of CAM use in the Czech Republic is increasing, especially among people who use biological, body- and mind-based CAM therapies. There is a great need to educate students and health care professionals about the efficacy and safety of CAM in order to meet the patients' demands on CAM.


My-Forensic-Loci-queries (MyFLq) framework for analysis of forensic STR data generated by massive parallel sequencing.
Forensic scientists are currently investigating how to transition from capillary electrophoresis (CE) to massive parallel sequencing (MPS) for analysis of forensic DNA profiles. MPS offers several advantages over CE such as virtually unlimited multiplexy of loci, combining both short tandem repeat (STR) and single nucleotide polymorphism (SNP) loci, small amplicons without constraints of size separation, more discrimination power, deep mixture resolution and sample multiplexing. We present our bioinformatic framework My-Forensic-Loci-queries (MyFLq) for analysis of MPS forensic data. For allele calling, the framework uses a MySQL reference allele database with automatically determined regions of interest (ROIs) by a generic maximal flanking algorithm which makes it possible to use any STR or SNP forensic locus. Python scripts were designed to automatically make allele calls starting from raw MPS data. We also present a method to assess the usefulness and overall performance of a forensic locus with respect to MPS, as well as methods to estimate whether an unknown allele, which sequence is not present in the MySQL database, is in fact a new allele or a sequencing error. The MyFLq framework was applied to an Illumina MiSeq dataset of a forensic Illumina amplicon library, generated from multilocus STR polymerase chain reaction (PCR) on both single contributor samples and multiple person DNA mixtures. Although the multilocus PCR was not yet optimized for MPS in terms of amplicon length or locus selection, the results show excellent results for most loci. The results show a high signal-to-noise ratio, correct allele calls, and a low limit of detection for minor DNA contributors in mixed DNA samples. Technically, forensic MPS affords great promise for routine implementation in forensic genomics. The method is also applicable to adjacent disciplines such as molecular autopsy in legal medicine and in mitochondrial DNA research.


Effective doses due to external irradiation from the Chernobyl accident for different population groups of Ukraine.
A model for the external exposure of the Ukrainian population after the Chernobyl accident was developed. It is based on extensive measurements of external gamma-exposure rates (EGER) in air and of external effective doses of members of five population groups. Questionnaires were used to determine the occupancy times of members of the population groups at three types of locations; inside houses, outdoors, and outside of the home settlement. Behavior factors are defined as the ratio of individual external doses to a reference dose for a phantom standing permanently over an open field with the same average 137Cs activity per unit area as in the settlement. The behavior factors were derived for five population groups (children younger than seven years, the age group from eight to seventeen years, employees, agricultural workers, and pensioners) by two methods: first from direct measurements of individual doses by thermoluminescent dosimetry and an experimental determination of the average 137Cs activity per unit area in the settlement of interest; and second from external gamma-exposure rates in air at various types of locations and from the questionnaire data. The methods were found to be consistent and the results were used to calculate external exposures of the five population groups in the years 1987 through 1991.


[Effectiveness of Nd: YAG laser therapy on Japanese cedar pollinosis].
Many have reported on the effectiveness of laser surgery therapy for perennial allergic rhinitis. However, the suppressive effects of laser irradiation on allergic rhinitis and its symptoms have not been reported in patients with pollinosis. This is because therapeutic effects on pollinosis are difficult to evaluate. The amount of pollen in the air varies during the year, and from year to year. Also, allergic symptoms develop due to exposure to the amount of pollen which is markedly influenced by the weather. In this study, the severity of allergic symptoms in the pollen season was compared between patients treated with early medication, non-treated patients and patients treated with preseasonal contact Nd: YAG laser surgery. Results suggests that laser surgery was effective in reducing the severity of symptoms in patients with cedar pollinosis. Symptoms were milder in the laser group than in the medication group and non-treated group for 3-4 weeks after the start of seasonal pollinosis, although no differences were noted in the early weeks. This may be explained by the fact that laser irradiation reduces the lamina propria of the nasal mucosa, the site of allergic reactions. This also suggests that allergic pollen can't penetrate the mucosal surface which shows squamous epithelization after laser irradiation.


CT and ultrasound findings of surgically retained sponges and towels.
The CT and ultrasound features of retained sponges (gossypibomas) are described in six patients. They are well-circumscribed cystic masses without surrounding edema. The retained sponges or towels were correctly identified in only three cases. In the other three cases retained sponges were organized and lost their original configuration. Gas was seen in one case and calcification in two cases. Gossypibomas should be included in the differential diagnosis in all patients with a well-circumscribed cystic mass in the abdomen and with a history of previous laparotomy.


The trough-to-peak ratio as an instrument to evaluate antihypertensive drugs. The APTH Investigators. Ambulatory Blood Pressure and Treatment of Hypertension Trial.
The U.S. Food and Drug Administration designed the trough-to-peak ratio as an instrument for the evaluation of long-acting antihypertensive drugs, but the ratios are usually reported without accounting for interindividual variability. This study investigated how the trough-to-peak ratio would be affected by interindividual and intraindividual variability and by smoothing of the diurnal blood pressure profiles. The ambulatory blood pressure was recorded on placebo in 143 hypertensive patients (diastolic pressure on conventional measurement > 95 mm Hg). After 2 months, the recordings were repeated on 10 mg (n = 66) or 20 mg (n = 77) lisinopril given once daily between 7 and 11 PM. The baseline-adjusted trough-to-peak ratios were determined from diurnal blood pressure profiles with 1-hour precision. Lisinopril reduced (+/- SD) the 24-hour pressure by 16 +/- 17 mm Hg for systolic and 10 +/- 10 mm Hg for diastolic (P < .001). According to the usual approach, disregarding interindividual variability, the trough-to-peak ratio was 0.72 for systolic pressure and 0.67 for diastolic pressure. In the 143 patients the ratios were not normally distributed. They were the same on both lisinopril doses. When interindividual variability was accounted for, the median trough-to-peak ratio was 0.34 (P5 to P95 interval, -0.46 to 0.87) for systolic pressure and 0.26 (-0.44 to 0.84) for diastolic pressure. In 66 patients examined twice on 10 mg lisinopril at a median interval of 32 days, the trough-to-peak ratios were characterized by large intraindividual variability.(ABSTRACT TRUNCATED AT 250 WORDS)


A Team-Based Activity to Support Knowledge Transfer and Experimental Design Skills of Undergraduate Science Students.
Experimental design may be considered an essential learning objective of undergraduate science education. This skill not only requires learners to be able to identify novel questions, generate hypotheses, create experimental models, and anticipate data outcomes but also demands that students are able to effectively transfer and apply knowledge from previous learning experiences to novel contexts. Here, I describe a team-based activity for upper-level undergraduate science courses that aims to strengthen students' skills in experimental design and transfer of knowledge. Instructional resources are provided to facilitate straightforward application in courses of diverse science disciplines and delivery modes.


Evaluation of gemeprost vaginal pessaries in the termination of abnormal intra-uterine pregnancies at twelve teaching hospitals in Indonesia.
Vaginal pessaries, up to a maximum of 5, each containing 1 mg of 16,16-dimethyl-trans-delta squared-prostaglandin E1, ester (Gemeprost) were inserted as high as possible into the posterior fornix of the vagina at 3 hourly intervals in 459 women with abnormal intrauterine pregnancies presenting for termination of the pregnancy. There were 145 missed abortions (31.6%), 207 intrauterine fetal deaths (45.1%), 86 molar pregnancies (18.7%), 5 anencephalics (1.1%), and 16 others (3.5%). The study was conducted from July 1981-March 1982. 402 women (87.6%) underwent abortion within the 30 hour observation period, including 139 women (30.3%) who required additional procedures to complete evacuation of the uterus. Expulsion of the uterine contents failed to occur within 30 hours in 57 women (12.4%) and alternative procedures were employed. These failures consisted of 37 missed abortions, 17 intrauterine fetal deaths, 2 molar pregnancies, and 1 pregnancy with an IUD in situ. Side effects caused by the drug were basically tolerable. 234 women (51.0%) had 1 or more side effects, gastrointestinal tract disturbances (nausea, vomiting, and diarrhea) being the most frequently observed, and moderate fever the next most frequent. There was 1 ruptured uterus.


Outcomes in obstetric fistula care: a literature review.
To highlight the lack of consistency in the terminology and indicators related to obstetric fistula care and to put forward a call for consensus. Recent studies show at least some degree of statistical correlation between outcome and the following clinical factors: degree of scarring/fibrosis, fistula location, fistula size, damage to the urethra, presence of circumferential fistula, bladder capacity, and prior attempt at fistula repair. Consensus about basic definitions of clinical success does not yet exist. Opinions vary widely about the prognostic parameters for success or failure. Commonly agreed upon definitions and outcome measures will help ensure that site reviews are accurate and conducted fairly. To properly compare technical innovations with existing methods, agreement must be reached on definitions of success. Standardized indicators for mortality and morbidity associated with fistula repair will improve the evidence base and contribute to quality of care.


A length-based hierarchical model of brown trout (Salmo trutta fario) growth and production.
We present a hierarchical Bayesian model (HBM) to estimate the growth parameters, production, and production over biomass ratio (P/B) of resident brown trout (Salmo trutta fario) populations. The data which are required to run the model are removal sampling and air temperature data which are conveniently gathered by freshwater biologists. The model is the combination of eight submodels: abundance, weight, biomass, growth, growth rate, time of emergence, water temperature, and production. Abundance is modeled as a mixture of Gaussian cohorts; cohorts centers and standard deviations are related by a von Bertalanffy growth function; time of emergence and growth rate are functions of water temperature; water temperature is predicted from air temperature; biomass, production, and P/B are subsequently computed. We illustrate the capabilities of the model by investigating the growth and production of a brown trout population (Neste d'Oueil, Pyrénées, France) by using data collected in the field from 2005 to 2010.


The chronic pain syndrome: a physical and psychologic challenge.
The chronic pain syndrome differs from chronic pain. The syndrome is a psychologic stress state that can produce physical-type illness, often with musculoskeletal manifestations. It tends to strike the "worried well," by nature hysterical, depressed, hypochondriacal, and dependent. Standard medical, surgical, and psychologic treatments do not alleviate the pain. The chronic pain syndrome progresses only with enablement by the physician or indiscriminate use of ancillary services. An early complete history and physical examination are the basis from which the physician draws logical conclusions about the patient to prevent progression. The long-range solution lies in a dynamically structured, progressive physical and mental reactivation program implemented by a highly trained interdisciplinary team of professionals using a holistic approach.


Changes in fecal microbiota composition and the cytokine expression profile in school-aged children with depression: A case-control study.
Depression in childhood negatively affects the growth and development, school performance, and peer or family relationships of affected children, and may even lead to suicide. Despite this, its etiology and pathophysiology remain largely unknown. Increasing evidence supports that gut microbiota plays a vital role in the development of childhood depression. However, little is known about the underlying mechanisms, as most clinical studies investigating the link between gut microbiota and depression have been undertaken in adult cohorts. In present study, a total of 140 school-aged children (6-12 years) were enrolled, including 92 with depression (male/female: 42/50) and 48 healthy controls (male/female: 22/26) from Lishui, Zhejiang, China. Illumina sequencing of the V3-V4 region of the 16S rRNA gene was used to investigate gut microbiota profiles while Bio-Plex Pro Human Cytokine 27-plex Panel was employed to explore host immune response. We found that, compared with healthy controls, children with depression had greater bacterial richness and altered β-diversity. Pro-inflammatory genera such as Streptococcus were enriched in the depression group, whereas anti-inflammatory genera such as Faecalibacterium were reduced, as determined by linear discriminant analysis effect size. These changes corresponded to altered bacterial functions, especially the production of immunomodulatory metabolites. We also identified the presence of a complex inflammatory condition in children with depression, characterized by increased levels of pro-inflammatory cytokines such as IL-17 and decreased levels of anti-inflammatory cytokines such as IFN-γ. Correlation analysis demonstrated that the differential cytokine abundance was closely linked to changes in gut microbiota of children with depression. In summary, key functional genera, such as Streptococcus and Faecalibacterium, alone or in combination, could serve as novel and powerful non-invasive biomarkers to distinguish between children with depression from healthy ones. This study was the first to demonstrate that, in Chinese children with depression, gut microbiota homeostasis is disrupted, concomitant with the activation of a complex pro-inflammatory response. These findings suggest that gut microbiota might play an important role in the pathogenesis of depression in school-aged children, while key functional bacteria in gut may serve as novel targets for non-invasive diagnosis and patient-tailored early precise intervention in children with depression.


Canine reference intervals for the Sysmex XT-2000iV hematology analyzer.
The laser-based Sysmex XT-2000iV hematology analyzer is increasingly used in veterinary clinical pathology laboratories, and instrument-specific reference intervals for dogs are not available. The purpose of this study was to establish canine hematologic reference intervals according to International Federation of Clinical Chemistry and Clinical and Laboratory Standards Institute guidelines using the Sysmex XT-2000iV hematology analyzer. Blood samples from 132 healthy purebred dogs from France, selected to represent the most prevalent canine breeds in France, were analyzed. Blood smears were scored for platelet (PLT) aggregates. Reference intervals were established using the nonparametric method. PLT and RBC counts obtained by impedance and optical methods were compared. Effects of sex and age on reference intervals were determined. The correlation between impedance (I) and optical (O) measurements of RBC and PLT counts was excellent (Pearson r=.99 and .98, respectively); however, there were significant differences between the 2 methods (Student's paired t-test, P<.0001). Differences between sexes were not significant except for HCT, PLT-I, and PLT-O. WBC, lymphocyte, and neutrophil counts decreased significantly with age (ANOVA, P<.05). Median eosinophil counts were higher in Brittany Spaniels (1.87 × 10(9) /L), Rottweilers (1.41 × 10(9) /L), and German Shepherd dogs (1.38 × 10(9) /L) than in the overall population (0.9 × 10(9) /L). PLT aggregates were responsible for lower PLT counts by the impedance, but not the optical, method. Reference intervals for hematologic analytes and indices were determined under controlled preanalytical and analytical conditions for a well-characterized population of dogs according to international recommendations.


Combination of Articaine and Ketamine V/S Articaine Alone After Surgical Extraction of Impacted Third Molars.
Local anesthetics are the most effective drugs available for the management of pain while performing operative procedures. This study was performed to compare the clinical efficacy of treatment with local anesthetic articaine (4%) with ketamine and local anesthetic articaine alone (4%) for the relief or prevention of postoperative pain, swelling, and trismus after the surgical extraction of impacted mesioangular third molars. Sixty patients undergoing the extraction of impacted mesioangular mandibular third molars were included in the study. The patients were randomly divided into two groups: local anesthetic alone (LAA) and local anesthetic plus ketamine (LAK). Facial swelling following surgery on postoperative days was significantly lower in the LAK group than in the LAA group on 3rd and 7th postoperative days (P < 0.05). Mouth opening on the postoperative days was significantly greater in the LAK group than in the LAA group on 3rd and 7th postoperative days (P < 0.05). The pain scores on the visual analog scale at 30 min and 1 h, 4 h, 12 h, and 24 h after the surgery were significantly higher in the LAA group than in the LAK group and there was no significant difference in heart rate, oxygen saturation, and blood pressure in both the groups. In this present study, the effect of articaine with ketamine in comparison with articaine alone intraoperatively and postoperatively was observed, and it revealed that the combination of articaine with ketamine produced good local anesthesia and provide good postoperative analgesia with less swelling and significantly less trismus.


Abrupt upwelling and CO2 outgassing episodes in the north-eastern Arabian Sea since mid-Holocene.
Identifying the causes and consequences of natural variations in ocean acidification and atmospheric CO2 due to complex earth processes has been a major challenge for climate scientists in the past few decades. Recent developments in the boron isotope (δ11B) based seawater pH and pCO2 (or pCO2sw) proxy have been pivotal in understanding the various oceanic processes involved in air-sea CO2 exchange. Here we present the first foraminifera-based δ11B record from the north-eastern Arabian Sea (NEAS) covering the mid-late Holocene (~ 8-1 ka). Our record suggests that the region was overall a moderate to strong CO2 sink during the last 7.7 kyr. The region behaved as a significant CO2 source during two short intervals around 5.5-4 ka and 2.8-2.5 ka. The decreased pH and increased CO2 outgassing during those abrupt episodes are associated with the increased upwelling in the area. The upwelled waters may have increased the nutrient content of the surface water through either increased supply or weaker export production. This new dataset from the coastal NEAS suggests that, as a potential result of changes in the strength of the El-Nino Southern Oscillation, the region experienced short episodes of high CO2 outgassing and pre-industrial ocean acidification comparable to or even greater than that experienced during the last ~ 200 years.


DRGs and prospective payment: an introduction to the issues facing clinical engineering programs.
DRGs--these letters, spoken as frequently as they now are, may sound familiar and perhaps even sinister. They have rapidly become the driving force of the health care system. Medicare is the largest purchaser of health care and has engineered a financing program based upon DRGs. Since other insurers are joining the program, the health care industry, along with its suppliers and clients, will never again be treated as it was in the past. As participants in the system, our work and our careers will also be changed. Yet, as with any change, there will be opportunities to acquire knowledge, to grow professionally, and to contribute to society. If hospitals are to provide quality care in a cost-effective and efficient manner, it will be both because of and in spite of technology. The appropriate selection, use, and maintenance of technology is an intrinsic part of the system. The clinical engineer's role will be to contribute technical and managerial expertise in support of the institution--in other words, in the management of technology.


Arabidopsis thaliana centromere regions: genetic map positions and repetitive DNA structure.
The genetic positions of the five Arabidopsis thaliana centromere regions have been identified by mapping size polymorphisms in the centromeric 180-bp repeat arrays. Structural and genetic analysis indicates that 180-bp repeat arrays of up to 1000 kb are found in the centromere region of each chromosome. The genetic behavior of the centromeric arrays suggests that recombination within the arrays is suppressed. These results indicate that the centromere regions of A. thaliana resemble human centromeres in size and genomic organization.


Human gamma delta T-cell recognition of Yersinia enterocolitica.
We have studied the human gamma delta T-cell response to Yersinia enterocolitica, a facultative intracellular bacterium which causes gastroenteritis and, particularly in human leucocyte antigen (HLA)-B27+ individuals, reactive arthritis (ReA). A marked proliferation of that cytotoxic gamma delta T cells is seen when Yersinia-infected lymphoblastoid cell lines or fixed intact Yersinia are added to cultures of mononuclear cells derived from the synovial fluid of ReA patients or from the peripheral blood of healthy donors. In contrast, heat-inactivated Yersinia fail to stimulate the gamma delta T-cell response. The gamma delta T-cell lines generated killed both autologous and allogeneic infected cell lines. Interestingly, a T-cell line generated from synovial fluid mononuclear cells (SFMC) killed infected autologous cell lines and a cell line matched for HLA-B27 less well than infected allogeneic target cells. gamma delta T-cell clones isolated from this line were found to express V gamma 9V delta 2 T-cell receptor (TCR) and also killed infected mismatched cells more efficiently than autologous targets. Moreover, from experiments using major histocompatability complex (MHC)-deficient cell lines, it was apparent that target cell recognition was MHC independent. Our results suggest that gamma delta T cells can be involved in immunity to Yersinia enterocolitica and should be taken into account when considering immunopathological mechanisms leading to reactive arthritis.


Ultrastructure of spermiogenesis in the American alligator, Alligator mississippiensis (Reptilia, Crocodylia, Alligatoridae).
Testicular samples were collected to describe the ultrastructure of spermiogenisis in Alligator mississipiensis (American Alligator). Spermiogenesis commences with an acrosome vesicle forming from Golgi transport vesicles. An acrosome granule forms during vesicle contact with the nucleus, and remains posterior until mid to late elongation when it diffuses uniformly throughout the acrosomal lumen. The nucleus has uniform diffuse chromatin with small indices of heterochromatin, and the condensation of DNA is granular. The subacrosome space develops early, enlarges during elongation, and accumulates a thick layer of dark staining granules. Once the acrosome has completed its development, the nucleus of the early elongating spermatid becomes associated with the cell membrane flattening the acrosome vesicle on the apical surface of the nucleus, which aids in the migration of the acrosomal shoulders laterally. One endonuclear canal is present where the perforatorium resides. A prominent longitudinal manchette is associated with the nuclei of late elongating spermatids, and less numerous circular microtubules are observed close to the acrosome complex. The microtubule doublets of the midpiece axoneme are surrounded by a layer of dense staining granular material. The mitochondria of the midpiece abut the proximal centriole resulting in a very short neck region, and possess tubular cristae internally and concentric layers of cristae superficially. A fibrous sheath surrounds only the axoneme of the principal piece. Characters not previously described during spermiogenesis in any other amniote are observed and include (1) an endoplasmic reticulum cap during early acrosome development, (2) a concentric ring of endoplasmic reticulum around the nucleus of early to middle elongating spermatids, (3) a band of endoplasmic reticulum around the acrosome complex of late developing elongate spermatids, and (4) midpiece mitochondria that have both tubular and concentric layers of cristae.


Haloperidol prevents ketamine- and phencyclidine-induced HSP70 protein expression but not microglial activation.
Noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists, inclu ding ketamine and phencyclidine (PCP), produce abnormal intracellular vacuoles in posterior cingulate and retrosplenial cortical neurons in the rat. Ketamine also induces 70-kDa heat shock protein (HSP70) expression in pyramidal neurons in the posterior cingulate and retrosplenial cortex and, as shown by this study, activates microglia in the retrosplenial cortex of the rat. Whereas HSP70 protein expression was induced with ketamine doses of 40 mg/kg (ip) and higher, doses of 80 mg/kg and higher were required to activate microglia. HSP70-positive neurons were observed in 30- to 90-day-old rats but not in younger, 10- to 20- day old animals following ketamine (80 mg/kg, ip). Pretreatment with the antipsychotic drug haloperidol at doses of 1.0 mg/kg and above abolished all HSP70 immunostaining produced by ketamine (80 mg/kg). However, a single dose of haloperidol (5 mg/kg, im) did not decrease the number of microglia activated in retrosplenial cortex by ketamine (80-140 mg/kg). Similarly, PCP (10 and 50 mg/kg, ip)-induced microglial activation in the posterior cingulate and retrosplenial cortex of adult rats was not blocked by haloperidol (10 mg/kg, im, 1 h prior to PCP). These results suggest that ketamine and PCP injure neurons in the posterior cingulate and retrosplenial cortex of adults rats. Though haloperidol may afford some protection against this injury since it inhibits induction of HSP70 expression, the failure to prevent microglial activation suggests that single doses of haloperidol do not completely protect neurons from NMDA antagonist toxicity.


SiC formation for a solar cell passivation layer using an RF magnetron co-sputtering system.
In this paper, we describe a method of amorphous silicon carbide film formation for a solar cell passivation layer. The film was deposited on p-type silicon (100) and glass substrates by an RF magnetron co-sputtering system using a Si target and a C target at a room-temperature condition. Several different SiC [Si1-xCx] film compositions were achieved by controlling the Si target power with a fixed C target power at 150 W. Then, structural, optical, and electrical properties of the Si1-xCx films were studied. The structural properties were investigated by transmission electron microscopy and secondary ion mass spectrometry. The optical properties were achieved by UV-visible spectroscopy and ellipsometry. The performance of Si1-xCx passivation was explored by carrier lifetime measurement.


Active switching and tuning of sharp Fano resonances in the mid-infrared spectral region.
We propose and analyze a scheme for active switching and spectral tuning of mid-infrared Fano resonances. We consider dielectric resonators made of semiconductor cylinder arrays and block pairs, and theoretically investigate their optical response change due to carrier generation. Owing to sharp optical resonances in these structures and large dielectric constant variations with carrier densities, the significant spectral tuning of Fano resonances is achievable. Furthermore, selective optical pumping in coupled semiconductor structures can even enable dynamic switching of Fano resonances. This leads to a drastic change in the scattering spectra as well as in the near-field intensity. We also observe a stark difference between Fano resonances in cylinder arrays and block pairs. To understand this unusual behavior, we adopt the two coupled oscillator model, and extract the relevant Fano resonance parameters that explain this difference. Our findings and in-depth analyses can be useful for molecular sensors and switching devices in the technologically important mid-infrared spectral region.


A gene signature to predict high tumor-infiltrating lymphocytes after neoadjuvant chemotherapy and outcome in patients with triple-negative breast cancer.
In patients with triple-negative breast cancer (TNBC), the extent of tumor-infiltrating lymphocytes (TILs) in the residual disease after neoadjuvant chemotherapy (NACT) is associated with better prognosis. Our objective was to develop a gene signature from pretreatment samples to predict the extent of TILs after NACT and then to test its prognostic value on survival. Using 99 pretreatment samples, we generated a four-gene signature associated with high post-NACT TILs. Prognostic value of the signature on distant relapse-free survival (DRFS) was first assessed on the training set (n = 99) and then on an independent validation set (n = 115). A four-gene signature combining the expression levels of HLF, CXCL13, SULT1E1, and GBP1 was developed in baseline samples to predict the extent of lymphocytic infiltration after NACT. In a multivariate analysis performed on the training set, this signature was associated with DRFS [hazard ratio (HR): 0.28, for a one-unit increase in the value of the four-gene signature, 95% confidence interval (CI): 0.13-0.63)]. In a multivariate analysis performed on an independent validation set, the four-gene signature was significantly associated with DRFS (HR: 0.17, 95% CI: 0.06-0.43). The four-gene signature added significant prognostic information when compared with the clinicopathologic pretreatment model (likelihood ratio test in the training set P = 0.004 and in the validation set P = 0.002). A four-gene signature predicts high levels of TILs after anthracycline-containing NACT and outcome in patients with TNBC and adds prognostic information to a clinicopathological model at diagnosis.


An Insight on the Pathways Involved in Crizotinib and Sunitinib Induced Hepatotoxicity in HepG2 Cells and Animal Model.
Both crizotinib and sunitinib, novel orally-active multikinase inhibitors, exhibit antitumor activity and extend the survival of patients with a malignant tumor. However, some patients may suffer liver injury that can further limit the clinical use of these drugs, however the mechanisms underlying hepatotoxicity are still to be elucidated. Thus, our study was designed to use HepG2 cells in vitro and the ICR mice model in vivo to investigate the mechanisms of hepatotoxicity induced by crizotinib and sunitinib. Male ICR mice were treated orally with crizotinib (70 mg/kg/day) or sunitinib (7.5 mg/kg/day) for four weeks. The results demonstrated that crizotinib and sunitinib caused cytotoxicity in HepG2 cells and chronic liver injury in mice, which were associated with oxidative stress, apoptosis and/or necrosis. Crizotinib- and sunitinib-induced oxidative stress was accompanied by increasing reactive oxygen species and malondialdehyde levels and decreasing the activity of superoxide dismutase and glutathione peroxidase. Notably, the activation of the Kelch-like ECH-associated protein-1/Nuclear factor erythroid-2 related factor 2 signaling pathway was involved in the process of oxidative stress, and partially protected against oxidative stress. Crizotinib and sunitinib induced apoptosis via the mitochondrial pathway, which was characterized by decreasing Bcl2/Bax ratio to dissipate the mitochondrial membrane potential, and increasing apoptotic markers levels. Moreover, the pan-caspase inhibitor Z-VAD-FMK improved the cell viability and alleviated liver damage, which further indicated the presence of apoptosis. Taken together, this study demonstrated that crizotinib- and sunitinib-caused oxidative stress and apoptosis finally impaired hepatic function, which was strongly supported by the histopathological lesions and markedly increased levels of serum alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase.


Modeling species' distributions to improve conservation in semiurban landscapes: koala case study.
Models of species' distributions are commonly used to inform landscape and conservation planning. In urban and semiurban landscapes, the distributions of species are determined by a combination of natural habitat and anthropogenic impacts. Understanding the spatial influence of these two processes is crucial for making spatially explicit decisions about conservation actions. We present a logistic regression model for the distribution of koalas (Phascolarctos cinereus) in a semiurban landscape in eastern Australia that explicitly separates the effect of natural habitat quality and anthropogenic impacts on koala distributions. We achieved this by comparing the predicted distributions from the model with what the predicted distributions would have been if anthropogenic variables were at their mean values. Similar approaches have relied on making predictions assuming anthropogenic variables are zero, which will be unreliable if the training data set does not include anthropogenic variables close to zero. Our approach is novel because it can be applied to landscapes where anthropogenic variables are never close to zero. Our model showed that, averaged across the study area, natural habitat was the main determinant of koala presence. At a local scale, however anthropogenic impacts could be more important, with consequent implications for conservation planning. We demonstrated that this modeling approach, combined with the visual presentation of predictions as a map, provides important information for making decisions on how different conservation actions should be spatially allocated. This method is particularly useful for areas where wildlife and human populations exist in close proximity.


Quantitative influence of endogenous salicylic acid level on taxuyunnanine C biosynthesis in suspension cultures of Taxus chinensis.
Intracellular signals are critical to secondary metabolite biosynthesis by plant cells, but their quantitative effects are not yet well understood in plant cell cultures. Using Taxus chinensis suspension culture, which has the potential to provide a sustainable supply of highly useful bioactive taxoids, this work investigated the impact of endogenous salicylic acid (SA) level on taxuyunnanine C (Tc) biosynthesis. It was observed that the Tc accumulation was strongly dependent on the endogenous SA level. Under elicitation with an endogenous SA of 97.1 ± 11.8 µg/g dry weight, a maximal Tc content of 10.3 ± 0.52 mg/g dry weight was obtained. The transcription levels of Tc biosynthetic genes of geranylgeranyl diphosphate synthase and taxadiene synthase were also analyzed, and they were increased with increase of internal SA level. The results demonstrated that manipulation of endogenous SA level could be an efficient strategy for improving secondary metabolite biosynthesis in plant cell culture.


Mechanistic aspects regarding the elimination of H2O2 from C(4a)-hydroperoxyflavin. The role of a proton shuttle required for H2O2 elimination.
DFT calculations presented for C(4a)-hydroperoxyflavin (C(4a)-FLHOOH) at the B3LYP/6-311+G(d,p) level suggest a new mechanism for the elimination of H2O2. The calculated activation barrier for a concerted four-centered elimination (ΔE(‡) = 32.86 kcal/mol) strongly suggests that in the absence of interactions with the local environment a spontaneous elimination is not feasible. A proton shuttle from the N5 hydrogen to the proximal oxygen of the OOH moiety involving three water molecules has an activation barrier that is reduced to 17.11 kcal/mol. Calculations that utilize CH3OH to model the role of a local Thr or Ser residue shows that an alcohol functionality hydrogen bonded to the N5 H-atom can catalyze the elimination of H2O2 with a free energy of activation of 21.5 kcal/mol. Interaction of amines and amide residues (CH3NH2 and CH3(C═O)NH2) with the N5 locus of C(4a)-hydroperoxyflavin markedly reduce the activation barrier for H2O2 elimination relative to the concerted pathway. Proton transfer from a COOH group (ΔG(‡) = 8.36 kcal/mol) or the NH2 group of a positively charged Arg model (ΔG(‡) = 9.99 kcal/mol) to the proximal oxygen of the OOH moiety of C(4a)-FLHOOH in the TS for H2O2 elimination strongly enhances elimination of H2O2.


Treatment of infected pilon nonunions with small pin fixators.
Six consecutive patients with infected intra-articular fractures of the distal tibia were studied. They were treated with resection of all infected or necrotic bone, systemic antibiotics, and instrumentation with a small pin fixator (Ilizarov external fixator). The fixator was used to perform an ankle arthrodesis and to fill the defect created by bone resection with distraction osteogenesis. In all cases, the infections were eradicated, and a solid arthrodesis was attained. The patients required from zero to two revision procedures (average 1.3), and their time in the fixator varied from 3 to 13 months (average 8 months). All of the patients experienced at least minor complications during treatment (superficial pin tract infections). At final follow-up, no patient demonstrated shortening of more than 1.5 cm. One patient has an internal rotation deformity of 15 degrees; a second has a varus deformity of 10 degrees and occasionally uses lateral support (a cane) secondary to unsteadiness on uneven ground; and one patient uses aspirin occasionally for subtalar pain. All are pleased with their results and would undergo the same procedure again without reservation.


Educational advantage.
THE JUNE ISSUE OF JERHRE features three themes: (1) Managing risks or unanticipated events that arise in research and pose serious ethical and practical questions. (2) Collaborating across cultures when relevant values are not shared, in particular values of individualism found largely in Western cultures versus community values which are more frequently found in traditional cultures. (3) Challenges to researchers and their mentors of learning and teaching how to responsibly resolve or ameliorate difficult ethical challenges.


Cortical activity changes as related to oral irritation-an fNIRS study.
We present the first investigation of how the cortical regions of the brain respond to the sensations related to oral irritation, using functional near-infrared spectroscopy (fNIRS). fNIRS is used to record irritant-induced activities in the prefrontal and somatosensory regions of nine healthy individuals. Two types of solutions, irritant-free and soft tissue-irritant-contained, are adopted as the stimuli for the control and task experiments, respectively. Our findings reveal that both somatosensory and prefrontal regions show activity as a result of oral irritation. Furthermore, using moving window analysis, we identify the time interval during which the largest number of channels (indicative of high involvement of cortical regions) show irritant-induced activity. Our results indicate that fNIRS can be used to study brain activities related to oral irritation.


Synthesis and Biological Application of Polylactic Acid.
Over the past few decades, with the development of science and technology, the field of biomedicine has rapidly developed, especially with respect to biomedical materials. Low toxicity and good biocompatibility have always been key targets in the development and application of biomedical materials. As a degradable and environmentally friendly polymer, polylactic acid, also known as polylactide, is favored by researchers and has been used as a commercial material in various studies. Lactic acid, as a synthetic raw material of polylactic acid, can only be obtained by sugar fermentation. Good biocompatibility and biodegradability have led it to be approved by the U.S. Food and Drug Administration (FDA) as a biomedical material. Polylactic acid has good physical properties, and its modification can optimize its properties to a certain extent. Polylactic acid blocks and blends play significant roles in drug delivery, implants, and tissue engineering to great effect. This article describes the synthesis of polylactic acid (PLA) and its raw materials, physical properties, degradation, modification, and applications in the field of biomedicine. It aims to contribute to the important knowledge and development of PLA in biomedical applications.


[Analyses of the population structures of Mallophaga infesting urban pigeons].
A total of 70 pigeons from Cracow area was examined and the representation of bird lice (Mallophaga) infesting them estimated. Mostly the populations of two dominant species: Columbicola columbae columbae (L.) and Campanulotes bidentatus compar (Burm.) were assessed. 47% of birds inspected had less than 100 specimens of Mallophaga, although the highest infested one had 900 specimens. Sex and age of pigeons did not influence the number of bird lice present, and only weak health condition of individuals allowed higher infestation. The sex structure of ectoparasites was balanced, with a slightly higher number of females during the year of study. The highest number of bird lice was detected in autunm and the larvae definitely predominated then, as well. Similar tendency was observed in C. c. columbae populations. The course of age dynamic of C. b. compar was somewhat different, having the peak in July, and the imago stage dominated in this species. The populations of in C. c. columbae showed developmental signs, whereas the population structures of C. b. compar gave evidence of their regression.


Effects of addition of rituximab to chemotherapy on central nervous system events in patients with diffuse large B-cell lymphoma.
The aim of this study was to evaluate whether the addition of rituximab to chemotherapy reduces central nervous system (CNS) events and to identify the risk factors associated with CNS involvement. Patients who were diagnosed with diffuse large B-cell lymphoma (DLBCL) between January, 1995 and December, 2012, without prior CNS disease, were recruited in this study. The patients received chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) or CHOP with rituximab (R-CHOP), with curative intent. The incidence rate of subsequent CNS events was compared between the two groups. A total of 110 patients were recruited, 45 (41%) of whom received CHOP and 65 (59%) R-CHOP. A total of 12 patients (10.9%) subsequently exhibited CNS involvement. The median time from the initial DLBCL diagnosis to CNS disease was 6.7 months (range, 1.3-23.8 months). The CNS disease rate was 15.5% (7/45) in the CHOP group vs. 7.6% (5/65) in the R-CHOP group. The projected 3-year CNS disease rate was 18% in the CHOP group vs. 9% in the R-CHOP group (P=0.15). The survival of patients with CNS disease was poor, with a median survival of 5.8 months. On multivariate analysis using the Cox proportional model, stage IV disease remained an independent predictor of CNS disease (hazard ratio = 7.75, 95% confidence interval: 1.67-35.92, P=0.009). In conclusion, the addition of rituximab to chemotherapy did not appear to reduce the risk of CNS events in our study. Other effective prophylactic measures are required to reduce the incidence of CNS events. High-dose intravenous methotrexate crosses the blood-brain barrier and may be used as CNS prophylaxis in high-risk patients.


The first route to highly stable crystalline microporous zirconium phosphonate metal-organic frameworks.
The first crystalline microporous zirconium phosphonate metal-organic framework (UPG-1) was synthesized using the novel tritopic ligand 2,4,6-tris(4-(phosphonomethyl)phenyl)-1,3,5-triazine. Its crystal structure was solved ab initio from laboratory powder X-ray diffraction data. UPG-1 displays remarkable thermal stability and hydrolysis resistance and has a good absorption affinity towards n-butane and CO2.


An Interactive Web-Based Intervention to Achieve Healthy Weight in Young Children.
This prospective, randomized, controlled trial for parents of overweight and obese 3- to 7-year-olds was performed to assess the feasibility of a program promoting healthy eating and lifestyle by targeting parents as agents of change. The intervention was composed of 6-in-person group sessions and a customized website over 12 months. The control group received customary care. The primary outcome was feasibility of the intervention to promote healthy behavior change measured by attendance. The secondary outcome was effectiveness assessed by attaining reduced body mass index (BMI) z scores, healthy behavior changes and increased parent self-efficacy. Seventy-three child-parent dyads were enrolled; 14 parents never attended any sessions. Participation in follow-up assessments did not meet the hypothesized level. Ultimate BMI z scores did not differ between control and intervention groups. Parenting skills did not improve in the intervention group. This intervention to achieve healthy lifestyle changes in children via their parents as "change agents" was unsuccessful.


Carbon monoxide and Ca2+-activated K+ channels in cerebral arteriolar responses to glutamate and hypoxia in newborn pigs.
Large-conductance calcium-activated potassium (K(Ca)) channels regulate the physiological functions of many tissues, including cerebrovascular smooth muscle. l-Glutamic acid (glutamate) is the principal excitatory neurotransmitter in the central nervous system, and oxygen tension is a dominant local regulator of vascular tone. In vivo, glutamate and hypoxia dilate newborn pig cerebral arterioles, and both dilations are blocked by inhibition of carbon monoxide (CO) production. CO dilates cerebral arterioles by activating K(Ca) channels. Therefore, the present study was designed to investigate the effects of glutamate and hypoxia on cerebral CO production and the role of K(Ca) channels in the cerebral arteriolar dilations to glutamate and hypoxia. In the presence of iberiotoxin or paxilline that block dilation to the K(Ca) channel opener, NS-1619, neither CO nor glutamate dilated pial arterioles. Conversely, neither paxilline nor iberiotoxin inhibited dilation to acute severe or moderate prolonged hypoxia. Both glutamate and hypoxia increased cerebrospinal fluid (CSF) CO concentration. Iberiotoxin that blocked dilation to glutamate did not attenuate the increase in CSF CO. The guanylyl cyclase inhibitor, 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (ODQ), which blocked dilation to sodium nitroprusside, did not inhibit dilation to hypoxia. These data suggest that dilation of newborn pig pial arterioles to glutamate is mediated by activation of K(Ca) channels, consistent with the intermediary signal being CO. Surprisingly, although 1) heme oxygenase (HO) inhibition attenuates dilation to hypoxia, 2) hypoxia increases CSF CO concentration, and 3) K(Ca) channel antagonists block dilation to CO, neither K(Ca) channel blockers nor ODQ altered dilation to hypoxia, suggesting the contribution of the HO/CO system to hypoxia-induced dilation is not by stimulating vascular smooth muscle K(Ca) channels or guanylyl cyclase.


Antioxidant status of erythrocytes after acupuncture treatment.
A course of acupuncture therapy in patients with locomotor, peripheral nervous system, gynecological, and bronchopulmonary diseases led to complete or partial normalization of nonspecifically changed MDA content, catalase and glutathione peroxidase activities in erythrocytes. SOD activity increased after therapy and did not differ from the control. Acupuncture stabilized disordered LPO processes and improved the antioxidant status of erythrocytes.


Treg-inducing capacity of genomic DNA of Bifidobacterium longum subsp. infantis.
Background: Allergic and autoimmune diseases comprise a group of inflammatory disorders caused by aberrant immune responses in which CD25+ forkhead box P3-positive regulatory T cells (Treg) cells that normally suppress inflammatory events are often poorly functioning. This has stimulated an intensive investigative effort to find ways of increasing Tregs as a method of therapy for these conditions. Commensal microbiota known to have health benefits in humans include the lactic acid-producing, probiotic bacteria B. longum subsp. infantis and Lactobacillus rhamnosus. Mechanistically, several mechanisms have been proposed to explain how probiotics may favorably affect host immunity, including the induction of Tregs. Analysis of emerging data from several laboratories, including our own, suggest that DNA methylation may be an important determinant of immune reactivity responsible for Treg induction. Although methylated CpG moieties in normal mammalian DNA are both noninflammatory and lack immunogenicity, unmethylated CpGs, found largely in microbial DNA, are immunostimulatory and display proinflammatory properties. Objective: We hypothesize that microbiota with more DNA methylation may potentiate Treg induction to a greater degree than microbiota with a lower content of methylation. The purpose of the present study was to test this hypothesis by studying the methylation status of whole genomic DNA (gDNA) and the Treg-inducing capacity of purified gDNA in each of the probiotic bacteria B. longum subsp. infantis and L. rhamnosus, and a pathogenic Escherichia coli strain B. Results: We showed that gDNA from B. longum subsp. infantis is a potent Treg inducer that displays a dose-dependent response pattern at a dose threshold of 20 µg of gDNA. No similar Treg-inducing responses were observed with the gDNA from L. rhamnosus or E. coli. We identified a unique CpG methylated motif in the gDNA sequencing of B. longum subsp. infantis which was not found in L. rhamnosus or E. coli strain B. Conclusion: Although the literature indicates that both B. longum subsp. infantis and L. rhamnosus strains contribute to health, our data suggest that they do so by different mechanisms. Further, because of its small molecular size, low cost, ease of synthesis, and unique Treg-inducing feature, this methylated CpG oligodeoxynucleotide (ODN) from B. longum would offer many attractive features for an ideal novel therapeutic vaccine candidate for the treatment of immunologic diseases, such as the allergic and autoimmune disorders, in which Treg populations are diminished.


[The analysis of cases of delayed diagnosis of tuberculosis among the population of the Cheliabisk district].
There was a steady-state rise in tuberculosis morbidity in the Chelyabinsk Region in the 1990s. At the same time, the number of patients whose disease is untimely detected was on the increase and in some cases the disease is found just at autopsy. These facts result from the lower efficiency of tuberculosis controlling measures, from low training of general physicians in detecting and diagnosing tuberculosis, and from failure to meet the standards for examining all those who have fallen ill.


The Stability of Intact Parathyroid Hormone (PTH) in Different Types of Blood Collection Tubes.
Over past decades, the instability of parathyroid hormone (PTH) causes great interference for the clinical laboratory. Contradictory results were reported in many reports about storage conditions and suitable blood collection tubes to ensure PTH stability in the pretreatment phase. This study recruited 30 participants including 10 healthy persons, 10 hemodialysis, and 10 hyperparathyroidism patients. Five types of blood collection tubes (EDTA-K3 tube, coagulant tube, heparin anticoagulant tube, gel separating tube, and plain tube) were included to determine whether they were suitable as blood-collecting vessels. The time points and conditions for testing samples included less than 2 hours, 4 hours, and 8 hours at room temperature, and, in parallel, 24 hours, 48 hours, and 72 hours in refrigeration. Two different judgement criteria were used to compare the stability of PTH in different blood vessels. Purely statistical analysis showed that 4 types of blood collection tubes could not perform the same storage ability as EDTA-K3 tube at "T0" time point. Plain tube had the largest drop among all types of blood collection tubes. Compared by pairwise t-test, EDTA-K3 tube could maintain intact PTH for 8 hours (p = 0.998) at room temperature and 24 hours (p = 0.053) in refrigeration. When comparing the total change limit (TCL = 18.8%), at room temperature, EDTA-K3 tube (7.0%), heparin tube (12.7%), coagulant tube (16.2%), and plain tube (17.6%) could maintain intact PTH for 8 hours, and GST can preserve PTH for 4 hours (18.2%). In refrigeration, EDTA-K3 tube could maintain PTH for 72 hours (7.5%) and heparin tube could maintain 24 hours (18.4%). The other three blood collection tubes could not preserve PTH in refrigeration (GST = 22.1%, coagulant tube = 20.3%, plain tube = 20.8%). PTH seems more stable in the EDTA-K3 tube than any other blood collection tubes and is followed next by the heparin anticoagulant tube. Plain tube and GST have faster degradation than other tubes and are not suggested to preserve intact PTH.


Segmentation and interpretation of MR brain images: an improved active shape model.
This paper reports a novel method for fully automated segmentation that is based on description of shape and its variation using point distribution models (PDM's). An improvement of the active shape procedure introduced by Cootes and Taylor to find new examples of previously learned shapes using PDM's is presented. The new method for segmentation and interpretation of deep neuroanatomic structures such as thalamus, putamen, ventricular system, etc. incorporates a priori knowledge about shapes of the neuroanatomic structures to provide their robust segmentation and labeling in magnetic resonance (MR) brain images. The method was trained in eight MR brain images and tested in 19 brain images by comparison to observer-defined independent standards. Neuroanatomic structures in all testing images were successfully identified. Computer-identified and observer-defined neuroanatomic structures agreed well. The average labeling error was 7%+/-3%. Border positioning errors were quite small, with the average border positioning error of 0.8+/-0.1 pixels in 256 x 256 MR images. The presented method was specifically developed for segmentation of neuroanatomic structures in MR brain images. However, it is generally applicable to virtually any task involving deformable shape analysis.


Intracranial complications of rhinosinusitis. A review, typical imaging data and algorithm of management.
Intracranial complications of acute bacterial sinusitis remain life-threatening. We aimed to study the current features of the condition--illustration, clinical presentations, risk factors, and define a management strategy. A retrospective study. Review of inpatients treated for meningoencephalitic infections related to sinusitis in a tertiary emergency care center between 1992 and 2005. Data retrieved on age, sex, signs at admission, bacterial findings, sinus involvement, intracranial complications and outcome. We analyzed the relation of bacterial infection to sinus involvement, initial signs of intracranial complications, and risk factors, and reviewed the literature to define a management strategy. We retrieved 25 files. Intracranial complications related to sinusitis involved largely men between second and third decade. No risk factor was clearly identified. Frontal and sphenoid sinuses were the most common site involved. Diffuse headache or two-step evolution headache and altered mental status were strongly correlated with meningitis and brain abscess. Empyema was the most common complication. A management algorithm has been defined: computed tomography was early performed to diagnose intracranial collection, and was repeated after 48 h if the clinical course was not favorable. The sinus was always drained by the safest way. Sequelae occurred in 16% of patients. No death occurred with this treatment strategy. Intracranial complications of acute sinusitis are exceptional but remain potentially severe and may lead to death. Early imaging data and aggressive management, associating sinus and brain drainage, as well as combined antibiotic therapy, can limit mortality and the incidence of sequelae.


IL-8/CXCL8 Upregulates 12-Lipoxygenase Expression in Vascular Smooth Muscle Cells from Spontaneously Hypertensive Rats.
We previously demonstrated remarkable differences in the expression of IL-8/CXCL8 in aortic tissues and vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) compared to VSMC from normotensive Wistar-Kyoto rats (WKY). In the present study, we investigated the direct effect of IL-8/CXCL8 on expression of 12-lipoxygenase (LO), a hypertensive modulator, in SHR VSMC. Cultured aortic VSMC from SHR and WKY were used. Expression of 12-LO mRNA was determined by real-time polymerase chain reaction. Phosphorlyation of ERK1/2 and production of 12-LO and angiotensin II subtype 1 (AT(1)) receptor were assessed by Western blots. IL-8/CXCL8-stimulated DNA synthesis was determined by measuring incorporation of [(3)H]-thymidine. And effect of IL-8/CXCL8 on vascular tone was determined by phenylephrine-induced contraction of thoracic aortic rings. Treatment with IL-8/CXCL8 greatly increased 12-LO mRNA expression and protein production compared to treatment with angiotensin II. IL-8/CXCL8 also increased the expression of the AT(1) receptor. The increase in 12-LO induced by IL-8/CXCL8 was inhibited by treatment with an AT(1) receptor antagonist. The induction of 12-LO mRNA production and the proliferation of SHR VSMC by IL-8/CXCL8 was mediated by the ERK pathway. The proliferation of SHR VSMC and the vascular contraction in the thoracic aortic ring, both of which were induced by IL-8/CXCL8, were inhibited by baicalein, a 12-LO inhibitor. These results suggest that the potential role of IL-8/CXCL8 in hypertensive processes is likely mediated through the 12-LO pathway.


Community-based service requests and utilization among pregnant women incarcerated in jail.
Pregnant incarcerated women represent a unique population in the criminal justice system that has been largely overlooked in terms of their service-related needs. The present study examines 241 pregnant incarcerated women's service requests and preincarceration service utilization related to material help (e.g., food, housing), mental health (e.g., counseling), family services (e.g., home-visiting nurses), and health care (e.g., insurance). A subsample (n = 74) also provided information about service utilization following their release from jail. Analyses examined request and utilization patterns in relation to other sociodemographic risk experiences. Results show that specific risk factors such as age, as well as the accumulation of multiple risk factors, served as barriers to requesting and accessing community-based services. The present study illuminates unique challenges pregnant incarcerated women experience requesting and utilizing services. The results support the use of a gender-responsive, trauma-informed approach to better address the needs of these women. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


The role of twin pore domain and other K+ channels in hypoxic pulmonary vasoconstriction.
Hypoxic pulmonary vasoconstriction (HPV) describes the vasoconstrictor response of pulmonary arteries to hypoxia, which directs blood flow towards better ventilated areas of the lung. Exactly how pulmonary arteries sense oxygen and mediate this response is widely debated and several hypotheses have emerged. One has smooth muscle K+ channels as the primary O2 sensor, hypoxia causing K+ channel inhibition, membrane depolarization and voltage-dependent Ca2+ influx. Even if this mechanism is not the primary response of pulmonary arteries to hypoxia, inhibition of K+ channel activity probably plays a role in HPV, due to enhanced membrane excitability and Ca2+ influx. Hypoxia inhibits several different K+ channels expressed in pulmonary artery smooth muscle, most from the K(v) class of voltage-gated K+ channels, but the properties of many K(v) channels are incompatible with a role in initiating HPV. Twin-pore domain K+ channels have emerged as prime candidates for controlling the resting membrane potential of cells. The identification of the twin-pore channel, TASK, in pulmonary artery smooth muscle, along with reports that it is inhibited by hypoxia, raises the possibility that a member of this family of channels acts as an O2 sensor in pulmonary artery. An unidentified low-threshold, voltage-dependent K+ channel might also contribute.


Generation and simple characterization of flat, liquid jets.
We present an approach to determine the absolute thickness profile of flat liquid jets, which takes advantage of the information of thin film interference combined with light absorption, both captured in a single microscopic image. The feasibility of the proposed method is demonstrated on our compact experimental setup used to generate micrometer thin, free-flowing liquid jet sheets upon collision of two identical laminar cylindrical jets. Stable operation was achieved over several hours of the flat jet in vacuum (10-4 mbar), making the system ideally suitable for soft x-ray photon spectroscopy of liquid solutions. We characterize the flat jet size and thickness generated with two solvents, water and ethanol, employing different flow rates and nozzles of variable sizes. Our results show that a gradient of thickness ranging from a minimal thickness of 2 µm to over 10 µm can be found within the jet surface area. This enables the tunability of the sample thickness in situ, allowing the optimization of the transmitted photon flux for the chosen photon energy and sample. We demonstrate the feasibility of x-ray absorption spectroscopy experiments in transmission mode by measuring at the oxygen K-edge of ethanol. Our characterization method and the description of the experimental setup and its reported performance are expected to expand the range of applications and facilitate the use of flat liquid jets for spectroscopy experiments.


Content Among Locally Approved HIPAA Authorization forms for Research.
THIS STUDY WAS DESIGNED TO ASSESS differences in the content of HIPAA authorization forms now required for clinical research. Authorization forms were collected from 111 institutions, including academic medical centers and commercial Institutional Review Boards. The requirement for an element covering the use of information acquired was fulfilled in 95% of the forms, and 100% had a statement fulfilling the core requirement of a description of the data to be collected. However, only 19% distinguished between entities that could see personal identifiers versus aggregate data. Significant differences existed in how long the disclosure agreement would remain in effect, and complex legalistic language was common. Thus, while research authorization forms technically met the requirements, the complex language and confusion over personal identifiers may raise concerns in prospective research participants.


Smoking-related violence in a mental health setting following the implementation of a comprehensive smoke-free policy: A content analysis of incident reports.
Smoke-free policies in mental health settings are important to protect health but are often impeded by staff concerns that physical violence may increase. We aimed to address the literature gap about the frequency, nature, and management of physical violence in relation to smoking. We compared the antecedents and containment of smoking-related incidents of physical violence over a two-year period, (12 months when an indoor-only smoke-free policy was in place, followed by 12 months after a new comprehensive smoke-free policy was introduced) using incident reports completed by staff in a large mental health organization in London, UK. Sixty-one smoking-related incidents occurred during the indoor-only smoke-free policy period; 32 smoking-related incidents occurred during the comprehensive smoke-free policy. We identified four antecedent categories for physical violence: i) patient request to smoke denied by staff; ii) during a supervised smoking break; iii) staff response to a patient breach of the smoke-free policy iv) asking for, trading or stealing smoking materials. The antecedent pattern changed across the two policy periods, with fewer incidents of denying a patient's request to smoke and a greater number of incidents involving staff responding to breaches occurring after the introduction of the comprehensive smoke-free policy. The prohibition of smoking breaks removed this source of violence. Timeout and PRN medication were the most common containment interventions. Understanding the context of smoking-related violence may inform clinical guidelines about its prevention and management.


Impact of Health-Promoting Educational Intervention on Lifestyle (Nutrition Behaviors, Physical Activity and Mental Health) Related to Vaginal Health Among Reproductive-Aged Women With Vaginitis.
Vaginitis is one of the most common diseases in reproductive-aged women (15 - 49 years of age). Side effects of vaginitis can affect other aspects of health, which could be prevented by promoting a healthy lifestyle related to vaginal health. This study aimed at determining the impact of health-promoting educational intervention on lifestyle (nutrition behaviors, physical activities, and mental health) related to vaginal health among reproductive-aged women with vaginitis. The data set was collected as part of an experimental study conducted on 350 reproductive-aged women with vaginitis. Participants were selected through a stratified two-stage clustered sampling and simple randomization from 10 attending health centers affiliated with Kermanshah University of Medical Sciences in five regions (North, South, East, West, and Center) of Kermanshah (a city in western Iran) in 2015. Two clinics in each region were selected; patients from the first center were chosen as the intervention group and patients from the second center made up the control group. To collect data, a questionnaire including socio-demographic and lifestyle questions was used. The questionnaire was designed and validated via the psychometric process. Educational intervention was performed over twenty sessions of 25 to 35 minutes. The intervention group was followed up with face-to-face education, a pamphlet, phone contact, and by social media. The control group continued the routine treatment without contacting the intervention group. Data were collected from both groups before the intervention and six months after the intervention. Data were analyzed using the SPSS-20 package, using the independent t-test, paired t-test, chi-square test, and analysis of covariance (ANCOVA) test. The confidence interval was 95% and P < 0.05 was considered statistically significant. ANCOVA showed that after adjusting for effects of pretest scores, the difference between mean scores on the scale of lifestyle related to vaginal health in the intervention group (28.48 ± 0.38) and control group (23.65 ± 1.23) was significant (P < 0.001). Intervention has a positive significant effect on increasing the mean scores of lifestyle in the intervention group (P < 0.001). Comparing mean differences between the two groups indicated significant difference between them (P < 0.001). Results of the paired t-test in the control group did not show significant changes in lifestyle scores after 6 months (P > 0.05). The independent t-test did not show significant statistical differences between the two groups in terms of demographic characteristics (P > 0.05). According to the findings, educational intervention is beneficial in promoting three aspects of women's lifestyle related to vaginal health. Therefore, a health-promoting lifestyle seems essential for having a healthy vagina and for preventing vaginitis.


Oxidative Stress Disrupted Prepubertal Rat Testicular Development after Xenotransplantation.
In the past two decades, testicular tissue grafting and xenografting have been well established, with the production of fertilization-competent sperm in some studies. However, few studies have been carried out to observe the development of grafted prepubertal testicular tissue of rats and compare the biological differences between in situ testis and grafted testis. In this study, we established the prepubertal testicular tissue xenografting model using a 22-day-old rat and evaluated certain parameters, including testicular histology, testosterone production, and ultrastructure of the grafted testes. We also assessed gene expression of cell proliferation markers, testicular cell markers, and antioxidative defense system. Our results showed that 47 days after transplantation, intratesticular testosterone concentration was not significantly altered; however, cell proliferation, spermatogenesis, and Sertoli cell markers in the transplanted testes were significantly disrupted compared with the control group, accompanied by aggravated apoptosis and oxidative damage. Moreover, the transplanted testes showed smaller tubular diameter and disrupted spermatogenic epithelium with apparent vacuoles, distorted and degenerated germ cells with obscure nuclear margin, and no spermatids in the center of the tubules. Although testis xenografting has been extensively tested and attained great achievement in other species, the prepubertal rat testicular tissue xenografting to immunodeficient mice exhibited obvious spermatogenesis arrest and oxidative damage. The protocol still needs further optimization, and there are still some unknown factors in prepubertal rat testes transplantation.


Home surveillance of leaking wounds after hip and knee arthroplasty: a prospective audit.
Leaking postoperative wound is a frequent finding after hip and knee arthroplasty. A prospective audit was undertaken to evaluate the feasibility and effectiveness of surveillance of leaking wounds at patients' homes by trained orthopaedic nurses.


Collagen Hydrogels Loaded with Silver Nanoparticles and Cannabis Sativa Oil.
Wounds represent a major healthcare problem especially in hospital-associated infections where multi-drug resistant strains are often involved. Nowadays, biomaterials with therapeutic molecules play an active role in wound healing and infection prevention. In this work, the development of collagen hydrogels loaded with silver nanoparticles and Cannabis sativa oil extract is described. The presence of the silver nanoparticles gives interesting feature to the biomaterial such as improved mechanical properties or resistance to collagenase degradation but most important is the long-lasting antimicrobial effect. Cannabis sativa oil, which is known for its anti-inflammatory and analgesic effects, possesses antioxidant activity and successfully improved the biocompatibility and also enhances the antimicrobial activity of the nanocomposite. Altogether, these results suggest that this novel nanocomposite biomaterial is a promising alternative to common treatments of wound infections and wound healing.


Using field-based epidemiological methods to investigate FMD outbreaks: an example from the 2002 outbreak in Korea.
Relevant to foot and mouth disease (FMD), most published epidemiological studies have been conducted using quantitative methods and substantial regional or national datasets. Veterinary epidemiology also plays a critical role during outbreak investigations, both to assist with herd-level decision-making and to contribute relevant information to assist with ongoing national or regional control strategies. Despite the importance of this role, however, little information has been published on the use of applied (field-based) epidemiological methods during disease outbreaks. In this study, we outline an investigative template for FMD, and a case study of its use during the 2002 FMD outbreak in Korea. Suitable for use during field-based epidemiological investigations of individual farms within a broader regional/national response, the template considers three steps including confirming infection, estimating date of introduction and determining method of introduction. A case study was conducted on IP13 (the 13th infected premises), the only IP during the 2002 FMD outbreak in Korea that was geographically isolated from all other known cases. The authorities first became aware of FMD on IP13 on 2 June, however, infection may have been present from 12 May. Infection was confirmed on 3 June 2002. FMD was probably spread to IP13 by a contract worker who had participated during 2-4 May in the culling operations on IP1. Other routes of spread were ruled out during the investigation. The contract worker lived in the locality of IP13 and worked on a part-time basis at a pork-processing plant that was adjacent to this farm. The contractor became heavily contaminated during the cull, but did not comply fully with cleaning and disinfection requirements once the cull had been completed. The investigative template contributed structure and focus to the field-based investigation. Results from this case study demonstrate the need for strict management of personnel in disease control and adherence to the sanitary rules by all those involved.


The temperament of pre-term, low birth weight infants and its potential biological substrates.
Temperament profiles of pre-term, low birth weight (LBW) infants were assessed at 6 months of age using standardized norms from the Revised Infant Temperament Questionnaire (RITQ). The contributions of perinatal risk, ethnicity, and gender to various temperament dimensions were examined. The sample included 152 infants with a mean birth weight of 1687 g and a mean gestational age of 31 weeks. Eighty percent of the infants were classified as having temperaments that were difficult to manage. Irregularity of the infants' biorhythms, slowness in their ability to adapt to changes, and distractibility were the most problematic. Birth weight, gestational age, and gender were not associated with temperament. Perinatal morbidity was related to the temperament dimension of infant persistence, with implications for the infant's attention span and task performance. Euro American infants were rated as more persistent and less intense in emotional expression than were infants of other ethnic groups. Results suggest the need for a more direct assessment of the effects of neurobiological processes on development of temperament phenotypes and for measurement of temperament that is socioculturally appropriate.


Increased 3-nitrotyrosine in both sporadic and familial amyotrophic lateral sclerosis.
The pathogenesis of neuronal degeneration in both sporadic and familial amyotrophic lateral sclerosis (ALS) associated with mutations in superoxide dismutase may involve oxidative stress. A leading candidate as a mediator of oxidative stress is peroxynitrite, which is formed by the reaction of superoxide with nitric oxide. 3-Nitrotyrosine is a relatively specific marker for oxidative damage mediated by peroxynitrite. In the present study, biochemical measurements showed increased concentrations of 3-nitrotyrosine and 3-nitro-4-hydroxyphenylacetic acid in the lumbar and thoracic spinal cord of ALS patients. Increased 3-nitrotyrosine immunoreactivity was observed in motor neurons of both sporadic and familial ALS patients. Neurologic control patients with cerebral ischemia also showed increased 3-nitrotyrosine immunoreactivity. These findings suggest that peroxynitrite-mediated oxidative damage may play a role in the pathogenesis of both sporadic and familial ALS.


Autologous Fat Transfer for Breast Augmentation: A Review.
The use of autologous fat transfer for breast augmentation is still controversial due to ongoing concerns regarding its efficacy and safety, most notably, concerns about breast cancer risk and detection. To summarize the current knowledge on the safety and efficacy of autologous fat transfer for breast augmentation with focus on clinical techniques, outcome, and complications. A thorough search of the literature was conducted using the terms autologous fat transfer, autologous fat grafting, and breast augmentation in the Medline and Embase databases, and relevant English and German language articles were included. Findings were categorized in a step-by-step approach to the fat grafting procedure divided into technique (harvesting, processing, and injection), postoperative care, graft viability enhancement, outcome, complications, and breast cancer risk. Autologous fat transfer for breast augmentation is not yet standardized. Therefore, outcomes vary widely depending on the surgeon's expertise. The majority of reported complications are of low morbidity, and based on available data, the procedure has a good long-term safety profile. Although there is no evidence that fat grafting increases breast malignancy risk, long-term follow-up is required.


[Principles of organization of a center for pain evaluation and treatment].
Since the development during the sixties of the pioneer pain clinics in the United-States, the need of a pluridisciplinary approach of the chronic pain patient has progressively compelled recognition. The principles of organization of this new care units--the pin center--are now clearly determined. It has become classic to compare acute pain as a warning symptom with chronic pain as an illness in itself with its constellation of psychosocial factors. Chronic pain refers to a daily pain persisting for 3 to 6 months. Neurophysiological, neuropsychological and behavioral differences legitimate the acute/chronic distinction. We will consider the following items: the types of patient, the multidisciplinary model, the team functioning, the initial consultation, the multidisciplinary synthesis discussion, the somatician role, the psychiatrist role and the possible disadvantages. Beside the care mission, multidisciplinary pain centers also have a key role in clinical research and teaching.


Chemical composition, UV/vis absorptivity, and antioxidant activity of essential oils from bark and leaf of phoebe zhennan S. K. Lee & F. N. Wei.
The chemical composition of essential oils (EO) from bark and leaf of P. zhennan was identified by GC-MS. The compounds of α-calacorene, τ-cadinol, β-eudesmol and d-cadinene were found in the essential oils from both bark and leaf. The UV-Vis spectra results indicated the EO could completely absorbed the UV light at the wavelength range of 200-370 nm, revealing that EO had great potential as additives for manufacturing UV light blocking products. The radical DPPH scavenging activity assay showed that both the bark and leaf EO possessed strong DPPH radical scavenging activity of 90.25% and 82.10% respectively, which provides an important theoretical guiding in exploiting the value of P. zhennan bark and leaf.[Formula: see text].


Transition from nursing student to staff nurse: a personal reflection.
Mentors, buddies, qualified nurses and other healthcare professionals shape the practice experiences of nursing students and change their perceptions on how care is delivered in the healthcare environment. Based on these experiences and perceptions, the student will decide whether to continue with a career in nursing. Once qualified, nurses cannot be expected to know everything. Clinical teams must be supportive of staff learning needs, acknowledging that relationships with mentors, supervisors and other staff will affect an individual's ability to fit in, to ask questions and to feel safe.


Reductive Alkylation of 2-Bromoazoles via Photoinduced Electron Transfer: A Versatile Strategy to Csp(2)-Csp(3) Coupled Products.
Access to Csp(2)-Csp(3)-coupled products is a challenging goal at the forefront of catalysis. The photocatalytic reductive coupling of aryl bromides with unactivated alkenes is introduced as a convenient method that circumvents any need for synthesis of sp(3)-hybridized coupling partners. The reaction takes place via photoinduced electron transfer from a tertiary amine to an aryl bromide that fragments to provide an aryl radical and subsequently reacts with an alkene to form a C-C bond. Conveniently, the amine also serves as the final reductant. The method is operationally simple, functional group tolerant, and takes place with selectivities that will allow it to be used in the context of complex molecule synthesis.


Increased susceptibility to intensive care unit-acquired pneumonia in severe COVID-19 patients: a multicentre retrospective cohort study.
The aim of this study is to determine whether severe COVID-19 patients harbour a higher risk of ICU-acquired pneumonia. This retrospective multicentre cohort study comprised all consecutive patients admitted to seven ICUs for severe COVID-19 pneumonia during the first COVID-19 surge in France. Inclusion criteria were laboratory-confirmed SARS-CoV-2 infection and requirement for invasive mechanical ventilation for 48 h or more. Control groups were two historical cohorts of mechanically ventilated patients admitted to the ICU for bacterial or non-SARS-CoV-2 viral pneumonia. The outcome of interest was the development of ICU-acquired pneumonia. The determinants of ICU-acquired pneumonia were investigated in a multivariate competing risk analysis. One hundred and seventy-six patients with severe SARS-CoV-2 pneumonia admitted to the ICU between March 1st and 30th June of 2020 were included into the study. Historical control groups comprised 435 patients with bacterial pneumonia and 48 ones with viral pneumonia. ICU-acquired pneumonia occurred in 52% of COVID-19 patients, whereas in 26% and 23% of patients with bacterial or viral pneumonia, respectively (p < 0.001). Times from initiation of mechanical ventilation to ICU-acquired pneumonia were similar across the three groups. In multivariate analysis, the risk of ICU-acquired pneumonia remained independently associated with underlying COVID-19 (SHR = 2.18; 95 CI 1.2-3.98, p = 0.011). COVID-19 appears an independent risk factor of ICU-acquired pneumonia in mechanically ventilated patients with pneumonia. Whether this is driven by immunomodulatory properties by the SARS-CoV-2 or this is related to particular processes of care remains to be investigated.


Crystal Structure of the Solid Electrolyte(C5H5NH) Ag5I6 at -30{degrees}C.
The crystal structure of pyridinium hexaiodopentaargentate, (C(5)H(5)NH) Ag(5)l(6), is unique among those of the halide and chalcogenide solid electrolytes in that face-sharing iodide octahedra as well as face-sharing tetrahedra and face-sharing between octahedra and tetrahedra provide the paths for silver ion transport. There are two formula units in a hexagonal cell, space group P6/mcc (D6h(2)). At -30 degrees C, the lattice constants are a = 11.97 +/- 0.02, c = 7.41 +/- 0.01 A. The structure has three sets of sites for the silver ions. At -30 degrees C two of these sets are apparently filled with the ten silver ions per unit cell, while the third set of tetrahedrally coordinated general positions is empty. Therefore, the conductivity at this temperature is limited by the thermal excitation of the silver ions into the empty tetrahedra.


Vascular function assessed with cardiovascular magnetic resonance predicts survival in patients with advanced chronic kidney disease.
Increased arterial stiffness is associated with mortality in patients with chronic kidney disease. Cardiovascular magnetic resonance (CMR) permits assessment of the central arteries to measure aortic function. We studied the relationship between central haemodynamics and outcome using CMR in 144 chronic kidney disease patients with estimated glomerular filtration rate <15 ml/min (110 on dialysis). Aortic distensibilty and volumetric arterial strain were calculated from cross sectional aortic volume and pulse pressure measured during the scan. Median follow up after the scan was 24 months. There were no significant differences in aortic distensibilty or aortic volumetric arterial strain between pre-dialysis and dialysis patients. Aortic distensibilty and volumetric arterial strain negatively correlated with age. Aortic distensibilty and volumetric arterial strain were lower in diabetics, patients with ischaemic heart disease and peripheral vascular disease. During follow up there were 20 deaths. Patients who died had lower aortic distensibilty than survivors. In a survival analysis, diabetes, systolic blood pressure and aortic distensibilty were independent predictors of mortality. There were 12 non-fatal cardiovascular events during follow up. Analysing the combined end point of death or a vascular event, diabetes, aortic distensibilty and volumetric arterial strain were predictors of events. Deranged vascular function measured with CMR correlates with cardiovascular risk factors and predicts outcome. CMR measures of vascular function are potential targets for interventions to reduce cardiovascular risk.


Isozyme-specific enzyme inhibitors. 11. L-homocysteine-ATP S-C5' covalent adducts as inhibitors of rat methionine adenosyltransferases.
The title compounds (14a,b) were 5' epimers of a derivative of a phosphonate isostere of ATP in which the CH2OP alpha system of ATP was replaced by CH(R)CH2P alpha [R = L-S(CH2)2CH(NH2)CO2H]. They resisted synthesis via attempted S-alkylation of the corresponding epimeric 5'-mercapto derivatives. A practicable route to 14a,b commenced with Michael condensation of L-homocysteine with the diphenyl ester of the 5',6'-vinyl phosphonate analogue of 2',3'-O-isopropylideneadenosine 5'-phosphate. The resulting epimeric 5' thioethers were separated by reverse-phase HPLC. The two phenyl groups were replaced by benzyl groups, after which the alpha-amino acid residue was protected as an N-Boc methyl ester. Both benzyl groups were removed by hydrogenolysis, and the resulting phosphonic acid was converted into its pyrophosphoryl derivative. Blocking groups were then removed under conditions that furnished 14a and 14b without racemization of their L-amino acid residues. Also synthesized were the P beta-NH-P gamma imido analogue (15a) of 14a and the sulfoxide derivative (16a) of 14a. The structures of 14a and 16a were verified by FAB mass spectra, which revealed the protonated molecular ions of their sodium salts. All adducts appeared to function as dual substrate site inhibitors (competitive to ATP and to methionine) of the rat normal tissue (MAT-2) form of methionine adenosyltransferase (MAT); 14a and 15a [KM(ATP)/Ki = 4 and 9, respectively] were the most effective. Adduct 15a was the most effective inhibitor [KM(ATP)/Ki = 13] of the MAT-T form from rat hepatoma tissue; the kinetic data indicated dual-site inhibition by 15a with apparently complete coverage of the ATP site and incomplete coverage of the methionine site. The inhibition properties of the adducts indicated little preference in the order in which the two MAT forms bound ATP and methionine.


Epitaxial Growth of Step-Like Cr2 S3 Lateral Homojunctions Towards Versatile Conduction Polarities and Enhanced Transistor Performances.
For expanding the applications of 2D transition metal dichalcogenides (TMDCs), integrating functional devices with diverse conduction polarities in the same parent material is a very promising direction. Improving the contact issue at the metal-semiconductor interface also holds fundamental significance. To achieve these concurrently, step-like Cr2 S3 vertical stacks with varied thicknesses are achieved via a one-step chemical vapor deposition (CVD) method route. Various types of 2D Cr2 S3 lateral homojunctions are thus naturally evolved, that is, pm -ambipolar/n, p/ambipolar, ambipolar/n, and nm -ambipolar/n junctions, allowing the integration of diverse conduction polarities in single Cr2 S3 homojunctions. Significantly, on-state current density and field-effect mobility of the thinner 2D Cr2 S3 flakes stacked below are detected to be ≈5 and ≈6 times increased in the lateral homojunctions, respectively. This work should hereby provide insights for designing 2D functional devices with simpler structures, for example, multipolar field-effect transistors, photodetectors, and inverters, and provide fundamental references for optimizing the electrical performances of 2D materials related devices.


[The activity of the glutathione-dependent enzymes of erythrocytes in chronic liver diseases in children].
Activities of red cell glutathione-dependent enzymes, glutathione peroxidase (GP), glutathione reductase, and glutathione transferase (GT), were measured in 70 children suffering from chronic hepatitis and liver cirrhosis with various forms and activities of the conditions. Manifest changes in GP and GT activities were revealed. Measurements of GT activities are recommended for assessment of the liver process severity and for early detection of the liver detoxifying function stress.


Cerebral syphilitic gumma mimicking a brain tumor in the relapse of secondary syphilis in a human immunodeficiency virus-negative patient.
Diagnosis of cerebral syphilitic gumma is frequently determined at the time of surgery, because imaging and laboratory findings demonstrate the elusive results. A 59-year-old woman presenting dysarthria showed a mass on her brain computed tomography. She was first suspected of brain tumor, but histological results from surgical resection revealed cerebral gumma due to neurosyphilis. After operation, she presented fever and rash with an infiltration on a chest X-ray. Histological assessment of skin was consistent with syphilis. Fluorescent treponemal antibody absorbed test IgG in cerebrospinal fluid was positive. She was successfully treated with ceftriaxone for 14 days.


S. choloroleuca, S. mirzayanii and S. santolinifolia protect PC12 cells from H(2)O (2)-induced apoptosis by blocking the intrinsic pathway.
Several studies have shown that neuronal cell death due to apoptosis is the major reason for cognitive decline in Alzheimer's disease. In this study, we report the anti-apoptotic effects of three Salvia species from Iran-S. choloroleuca, S. mirzayanii and S. santolinifolia-against H(2)O(2)-induced cytotoxicity in neuron-like PC12 cells. We showed that these antioxidant species could interfere with the intrinsic pathway of apoptosis by attenuating Bax/Bcl-2 ratio, decreasing outer mitochondrial membrane break and decreasing cytochrome c release to cytoplasm. Interestingly, we found that these species were able to replenish reduced glutathione level which affects cellular redox status and cytochrome c activity. Moreover, the decreased level of caspase-3, the executioner caspase, resulted in decrease of PARP-1 cleavage. Anti-apoptotic effects of these species along with their antioxidant effects, may represent a promising approach for treatment of neurodegenerative diseases.


A randomized controlled trial with ≥5 years of follow-up comparing minimally invasive and open transforaminal lumbar interbody fusion in disc herniation at single level.
Minimally invasive transforaminal lumbar interbody fusion (m-TLIF) using transpedicular screws has various advantages over classical open (c-) TLIF. Up to date, comparative analyses of the TLIF procedures were following patients for <5 years. The objective of the present study was to compare the clinical effectiveness and complications of m- and c-TLIF in patients with single-level disc herniation with ≥5 years follow-up. Between June 2008 to July 2010, 91 patients with single-level lumbar degeneration were recruited and were randomly divided into two groups: m-TLIF and c-TLIF. The analyzed outcome measurements included: Surgery duration, intraoperative blood loss, X-ray exposure time, T2 relaxation time in magnetic resonance imaging (MRI), visual analogue scale (VAS) scores, Japanese orthopedic association (JOA) scores, fusion rate and complications during follow-up. No significant differences between m- and c-TLIF were observed with respect to surgery duration (P=0.077), volume of blood loss (P=0.115), complications and the need for an additional surgery (P=0.632). Significant differences between the groups were observed for X-ray exposure time (P<0.001) and MRI T2 relaxation times at 3 months post-surgery (P<0.001). At day 7 post surgery, recorded VAS and JOA scores were significantly improved in the m-TLIF compared with the c-TLIF group and non-significant differences between the groups were observed at >1 month follow-up. m-TLIF was a safe and effective tool in treating single-level lumbar disc herniation. However, careful attention to the surgical technique and precise anatomical knowledge were required. Further studies and refinement of the surgical techniques are necessary prior to treating multiple or more extensive lesions using the m-TLIF method.


Quality improvement in low resource settings: an Ethiopian experience.
Improving surgical and anaesthetic mortality in the developing world is a global health priority. Quality improvement processes have a role to play in addressing this need and are applicable to low-resource settings despite difficulties in their implementation. International initiatives to reduce perioperative mortality can be focussed to support interventions at the level of individual departments, but this requires integration with existing local systems and an understanding of the specific needs of the institutions concerned. There is a small but growing evidence base for quality improvement in low resource settings, but this needs to be locally accessible to allow self-sustaining evidence-based quality improvement.