Circulating Anti-Matrix Metalloproteinase-7 Antibodies May Be a Potential Biomarker for Oral Squamous Cell Carcinoma.
The present study was conducted to evaluate the diagnostic and prognostic values of serum autoantibody against matrix metalloproteinase-7 (MMP-7) in patients with oral squamous cell carcinoma (OSCC). Anti-MMP-7 antibodies were measured in sera from 204 patients with OSCC and 212 normal controls using enzyme-linked immunosorbent assay, and clinicopathologic characteristics were correlated. Prognostic consequence was assessed with Kaplan-Meier curve and log-rank tests using Cox proportional hazard models. To check whether anti-MMP-7 antibody was related to tumor associated antigen, real-time polymerase chain reaction and western blot were used to measure MMP-7 mRNA and protein expression in tumor tissues from all 204 patients with OSCC. Serum anti-MMP-7 antibody was higher in patients with OSCC (P < .05), and those with poorly differentiated tumors had more anti-MMP-7 antibody than those with well to moderate tumor differentiation (P < .01, P < .01, respectively). Patients with OSCC at late TNM stages (III, IV) and lymph node metastases had relatively higher serum anti-MMP-7 antibody levels than those with earlier stages (I, II) and those who lacked lymph node metastases (P < .05 for the 2 comparisons). OSCC prediction sensitivity as measured by receiver operating characteristics analysis was 0.485 and specificity was 0.896 (area under the curve, 0.761; 95% confidence interval, 0.716 to 0.806). Cox analysis showed that serum anti-MMP-7 antibody positivity independently predicted poor overall survival in patients with OSCC (hazard ratio, 1.82; 95% confidence interval, 1.07 to 4.61). MMP-7 mRNA and protein expression was increased in tumor tissues from patients with OSCC and high serum anti-MMP-7 antibody. Serum anti-MMP-7 antibody might be a novel diagnostic and prognostic biomarker for OSCC.


Matrix effects, nonuniform reduction and dispersion in risk assessment for Escherichia coli O157.
To assess the importance of the variation (or spatial heterogeneity) in the doses of Escherichia coli O157 ingested by individuals when estimating the group risk. Exposure scenarios, which differed in how the same total number of E. coli O157 cells were distributed across a group of persons were simulated and the risks of illness in the population estimated using available dose-response data. Differences in the degree of spatial heterogeneity within routes such as direct contact with sheep faeces, consumption of hamburgers and drinking water could affect the magnitude of the predicted risk by over 1000-fold and contribute to an apparent matrix effect. The effect of barriers, such as cooking, on the spatial heterogeneity of E. coli O157 cells remaining in undercooked hamburgers affects the magnitude of the risk by eightfold. Furthermore, a 100-fold reduction in E. coli O157 concentrations by cooking may reduce the risk of illness from consumption of the burgers by only 12-fold (and not the 100-fold perhaps expected). The development of microbiological risk assessment (MRA) models for E. coli O157 requires information on the degree of dispersion of faeces within routes such as the environment, food and water, so that the proportion of persons actually exposed to faeces, and hence pathogen, can be quantified. The effect of dispersion is greater for pathogens for which there is greater variation in susceptibility within the population. In terms of public health protection, minimizing the dispersion of cattle/sheep faeces reduces the risks to humans by confining exposure to fewer individuals. For MRA, estimating the reduction in risk by a treatment process, e.g. cooking, is complicated by spatial heterogeneity. Regional differences in dispersion (e.g. because of rainfall) may contribute to regional differences in the observed attack rate.


Cost-utility analysis of cochlear implants in Korea using different measures of utility.
All cost-utility ratios obtained using the various measures of utility except quality well-being (QWB) were below 25,000 dollars per quality-adjusted life year (QALY). Therefore, treatment of post-lingual deaf adults with cochlear implants improves the quality of life at a reasonable direct cost and appears to produce net savings for Korean society. To determine the quality of life and the cost consequences of cochlear implants for deaf adults. We performed a cost-utility analysis using data from 11 post-lingual deaf adults who had received cochlear implants between 1990 and 2002 in Seoul, Korea. The average age of the participants was 49.6 years. The main outcome was the direct cost per QALY calculated using the visual analog scale (VAS), health utility index (HUI), EuroQol (EQ-5D) measure and QWB measure. Costs and utility were discounted 3% annually. Recipients used implants for an average of 5.6 years. The mean VAS, HUI, EQ-5D, and QWB score increased by 0.33 (from 0.27 before implantation to 0.60 at survey), 0.36 (0.29 to 0.65), 0.26 (0.52 to 0.78), and 0.16 (0.45 to 0.61), respectively. The discounted direct cost was 22,320 dollars, which yielded a cost-utility ratio of 19,223 dollars per QALY using VAS, 17,387 dollars per QALY using HUI, 24,604 dollars per QALY using EQ-5D, and 40,474 dollars per QALY using QWB.


Introduction of the SARS-CoV-2 Beta variant from Comoros into the Marseille geographical area.
We describe the epidemiology of the first cases diagnosed in our institute of infections with the SARS-CoV-2 Beta variant and how this variant was imported to Marseille. The Beta variant was identified based on analyses of sequences of viral genomes or of a spike gene fragment obtained by next-generation sequencing using Illumina technology, or by a real-time reverse-transcription-PCR (qPCR) specific of the Beta variant. The first patient diagnosed as infected with the SARS-CoV-2 Beta variant was sampled on January 15, 2021. Twenty-nine patients were diagnosed in January 2021 (two weeks). Fifteen (52%) patients were of Comorian nationality. Eight (28%) had travelled abroad, including six who had returned from Comoros. Phylogeny based on SARS-CoV-2 genomes from 11 of these patients and their best BLAST hits from the GISAID database showed that seven patients, including the four returning from Comoros, were clustered with 27 other genomes from GISAID that included the six first Beta variant genomes described in Comoros in January 2021. Our analyses highlight that, as for the case of other SARS-CoV-2 variants that have been diagnosed in Marseille, the Beta variant was imported to Marseille through travel from abroad. It had limited spread in our geographical area.


Predictors of drinking and functional outcomes for men and women following inpatient alcohol treatment.
This prospective study uses path analytic models to examine baseline characteristics associated with both functioning and drinking outcomes 12 months after inpatient alcohol treatment. Alcohol-dependent participants (N = 101) were recruited during inpatient alcohol treatment and assessed monthly 1 year after discharge. Alcohol severity was negatively associated with education and self-efficacy; marital status was positively associated with self-efficacy; and education and self-efficacy were negatively associated with drinking outcomes. Low alcohol severity, not having a depression diagnosis, and being married were associated with less social support impairment, which was in turn associated with better drinking outcomes. Having a history of sexual abuse did not influence drinking outcomes. However, having a history of sexual abuse was negatively associated with global functioning. Drinking outcomes were associated with education, self-efficacy, social support, and diagnosis of depression at baseline; however, global functioning 1 year following treatment was primarily and negatively associated with sexual abuse history. Future treatment research should include measures of both functioning and drinking behavior outcomes.


The Efficacy of Superior Laryngeal Nerve Block for Neurogenic Cough: A Placebo-Controlled Trial.
Chronic cough is a common and debilitating problem. The objective of this study is to assess the efficacy and safety of superior laryngeal nerve (SLN) block for neurogenic cough through a placebo-controlled, prospective trial. Patients were recruited in an outpatient tertiary care center. Inclusion criteria included a history consistent with neurogenic cough and age ≥ 18. Exclusion criteria included patients with untreated other etiologies of chronic cough (i.e., uncontrolled reflux) and current neuromodulating medication use. Patients were randomized into the treatment (1-2 mL of a 1:1 triamcinolone 40 mg: 1% lidocaine with 1:200,000 epinephrines) or placebo (saline) group and received two unilateral injections at approximately 2-week intervals. Outcomes were measured primarily by the Leicester Cough Questionnaire (LCQ) and a patient symptom log including a visual analog scale of cough severity. 17 patients completed the study, including 10 in the treatment group and seven in the placebo group. Eight (80%) patients in the treatment group reported improvement with at least one of the injections, whereas only 1 (14.3%) patient reported improvement in the placebo group (p < 0.0001). Average total LCQ scores increased in the treatment group from 10.09 to 13.15 (p = 0.03), with the most change occurring in the social domain. There was no statistically significant change in LCQ scores for the placebo group. There were no serious adverse events. An SLN block is a safe and efficacious procedure for the treatment of neurogenic cough. Further studies are needed to optimize treatment protocol and assess long-term follow-up of patient outcomes. 2 Laryngoscope, 133:3068-3074, 2023.


Regularization techniques for 3D surface reconstruction from four quadrant backscattered electron detector images.
In scanning electron microscopy (SEM), a four quadrants backscattered electron detector (FQBSD) provides signals that can be combined to obtain a tridimensional reconstruction of the surface. The main challenge of the reconstruction operation consists of integrating the gradient field obtained as the normalized signal difference from each pair of opposite quadrants. Owing to the presence of electronic noise that eventually turns into image noise, a least square integration approach has been widely adopted for surface reconstruction. In the present work, we demonstrate the possibility of adopting regularization techniques (Tichonov's and Dirichlet's) to the surface reconstruction from FQBSD images to reduce the distortions due to sensitivity variations amongst the detector quadrants or an imprecise alignment of the FQBSD with the gun axis. This allows for a substantial improvement in the 3D surface reconstruction quality in terms of resolution and reduction of artifacts. These procedures have been experimentally validated on AISI 316L stainless steel polished surfaces with hardness indentation and on laser-patterned aluminum and silicon samples showing promising results.


Research progress of active ingredients of Scutellaria baicalensis in the treatment of type 2 diabetes and its complications.
Diabetes mellitus is a common disorder of endocrine and metabolic disorders. Long term hyperglycemia can lead to a variety of serious chronic complications, such as diabetic nephropathy, diabetic retinopathy, diabetes cardiovascular disease, and so on, threatening human life, health and safety. Scutellaria baicalensis Georgi is one of the most commonly used traditional Chinese medicine. Flavonoids are the main effective components of Scutellaria baicalensis Georgi. The flavonoids are mainly baicalin, baicalein, wogonoside and wogonin. The four have the effects of improving the renal function, insulin resistance and retinopathy of type 2 diabetic patients. The aim of this review is to summarize the pathogenesis and clinical research progress of baicalin, baicalein, wogonoside and wogonin in Scutellaria baicalensis Georgi in the treatment of type 2 diabetes mellitus and its complications.


[Research of myopia development in children with self-regression of retinopathy of prematurity and in children with regression after cryotherapy].
The aim of the paper is to estimate the influence of self-regression of retinopathy of prematurity (ROP) and regression after cryotherapy for development of axial myopia in premature babies. The researches concerned 4 groups of premature babies in the 6th, 12th and 24th month of life. Group 1--without ROP, group 2--with self-regression of ROP, group 3--with regression of ROP after cryotherapy and group 4--with one eye with self-regression of ROP and second eye with regression after cryotherapy. In the 6th and 24th month of life mean axial length of eyeball in children from group 3 was statistically significantly higher than mean axial length of eyeball in children from group 1 and 2. In the 12th month of life mean axial length of eyeball in children from group 3 was statistically significantly higher than mean axial length of eyeball in children from group 1. In group 4 mean axial length of eyeball with regression of ROP after cryotherapy was statistically significantly higher than mean axial length of eyeball with self-regression of ROP. Self-regression of ROP and regression of ROP after cryotherapy may cause development of axial myopia in premature babies.


Endocytosis, proteolysis, and exocytosis of exogenous proteins by cultured myotubes.
The endocytic activity of chick myotubes in cultures was investigated. Differentiated myotubes internalized the fluid-phase marker horseradish peroxidase in membrane-bound particles which typically displayed reaction product at the inner surface of the vesicle. Pulse-chase experiments demonstrated a rapid decrease in the number of horseradish peroxidase-containing vesicles and a redistribution from a uniform to a perinuclear pattern. Horseradish peroxidase uptake was extensively inhibited by incubation at 0-4 degrees C consistent with an endocytic mechanism. To further characterize the process, the fate of labeled protein was investigated. Following uptake [3H] hemoglobin A was extensively degraded (40-50%) to acid-soluble products within 10 h. Degradation displayed a biphasic pattern with a rapid early phase followed by a much slower second phase. The decreasing rate of proteolysis can be accounted for, in part, by a simultaneous exocytosis of a substantial fraction (25-30%) of acid-insoluble label from myotubes. The lysosomotropic agents methylamine, monensin, and chloroquine significantly inhibited (23-75%) proteolysis, indicating a lysosomal site of degradation. Part of the inhibitory effect results from an increase in exocytosis in the presence of these agents. Degradation of endocytosed [3H]hemoglobin A was not inhibited by insulin. In contrast degradation of endogenous myotube proteins was inhibited (40%) by insulin and blocked by methylamine. These results suggest that cultured myotubes possess a coupled endocytic/exocytic pathway for macromolecules and that a fraction of the internalized substrate is degraded by an insulin-insensitive lysosomal pathway.


Cytofluorographic and molecular identification of a CD8-positive, TCR-alpha/beta-negative intraocular T cell lymphoma: a case report and review of the literature.
Cytofluorographic and molecular techniques are effective adjuncts in diagnosing intraocular lymphoma. Primary intraocular lymphoma is an uncommon entity predominantly of B cell origin and rarely with a T cell phenotype. The aim of the present paper is to report a case of a CD8-positive, TCR-alpha/beta-negative intraocular T cell lymphoma and review the literature. T cell neoplasia was detected based on flow cytometric demonstration of an abnormal T cell population and polymerase chain reactions for immunoglobulin and T-cell receptor rearrangements demonstrating evidence of monoclonality. Flow cytometry revealed a T cell population aberrantly expressing T-cell lineage markers. This T cell population expressed CD2, bright CD3, CD8, bright CD7, CD38, CD69, and variable CD25. T-cell receptor gamma gene rearrangement studies demonstrated evidence of T-cell gene rearrangement confirming that the T cells were monoclonal. We herein report the rare case of a TCR alpha/beta-negative CD8+ intraocular T-cell lymphoma suggestive of gamma/delta origin diagnosed by flow cytometry and polymerase chain reaction.


Effect of quinolone treatment on selection and persistence of quinolone-resistant Escherichia coli in swine faecal flora.
To study the effect of oral administration of a quinolone on emergence of resistance in an indicator bacterial species from faecal flora. Quinolone resistance was studied in Escherichia coli obtained from the faecal contents of pigs housed in nine commercial farrow-to-finish herds in France after administration of flumequine to sows. The percentage of quinolone-resistant E. coli increased in the faeces of sows after administration of flumequine (mean 21.78% at day 7 vs 6.42% before treatment for nalidixic acid) and then decreased (mean 12.6 and 10.4 at days 30 and 60, respectively for nalidixic acid), being not significantly different from initial values 1 month post-treatment. In young pigs, the proportion of resistant strains was lower and decreased over rearing period. Moreover, changes over time of both total E. coli and the proportion of resistant bacteria exhibited great inter-individual variability. Restoration of susceptible faecal flora occurred within 2 months after flumequine treatment. Effect of flumequine treatment of sows on the quinolone resistance of faecal E. coli of both sows and their progeny is noticeable but transitory.


On the mechanism of one-electron reduction of quinones by microsomal flavin enzymes: the kinetic analysis between cytochrome B5 and menadione.
Univalent oxidation-reduction reactions coupled with the menadione (MK)/menadione semiquinone (MK.-) system were investigated by using microsomal flavin enzymes. NADPH-cytochrome P-450 reductase gave a dynamic equilibrium of oxidation-reduction of cytochrome b5 in the presence of menadione (MK), the level of which depended on the concentration of O2 and superoxide dismutase. The data suggest that the superoxide and menadione radicals are involved as an active intermediate in this system. The overall reaction at steady state appears to be composed of four main reactions, eqs. 2-5, and eqs. 2 and 4 are in equilibrium.


Influences on intentions for obstetric practice among family physicians and residents in Canada: an explorative qualitative inquiry.
Many family medicine residency graduates indicate a desire to provide obstetric care, but a low proportion of family physicians (FPs) provide obstetric care within their practice. This suggests personal preference alone may not account for the low proportion of FPs who ultimately provide full obstetric care. If decisionmakers plan to augment the number of FPs providing obstetric care, barriers to the provision of such care must first be identified. Within this paper, we explore the perspectives of both family practice residents and early-career FPs on the factors that shaped their decision to provide obstetric care. In this qualitative study, we analyzed a subset of interview data from three Canadian provinces: British Columbia, Ontario, and Nova Scotia (n = 18 family practice residents; n = 39 early-career FPs). We used thematic analysis to analyze data relevant to obstetric care practice, applying the socio-ecological model and comparing themes across participant types, gender, and province. Participants described influences affecting their decision about providing obstetric care. Key influencing factors aligned with the levels of the socio-ecological model of public policy (i.e., liability), community (i.e., community needs), organizational (e.g., obstetric care trade-offs, working in teams, sufficient exposure in training), interpersonal practice preferences (i.e., impact on family life, negative interactions with other healthcare professionals), and individual factors (i.e., defining comprehensive care as "everything but obstetrics"). Many participants were interested in providing obstetric care within their practice but did not provide such care. Participants' decision-making around providing or not providing obstetric care included considerations of personal preferences and outside influences. Individual-level factors alone do not account for the decrease in the type and amount of obstetric care offered by FPs. Instead, FPs' choice to provide or not provide obstetric care is influenced by factors at higher levels of the socio-ecological model. Policymakers who want to encourage obstetric practice by FPs should implement interventions at the public policy, community, organizational, interpersonal, and individual levels.


Midday depression in net photosynthesis and stomatal conductance in Yucca glauca : Relative contributions of leaf temperature and leaf-to-air water vapor concentration difference.
Yucca glauca in the Colorado shortgrass prairie undergoes a pronounced midday depression in net photosynthesis and stomatal conductance under summer field conditions. This phenomenon can be duplicated in the laboratory using potted plants by simulating a typical summer daily pattern of leaf temperature and leaf-to-air water vapor concentration difference (Δw). The decrease in photosynthetic rate appears to be due primarily to high leaf temperatures, while the decrease in stomatal conductance can be attributed mainly to high Δw values. Stomatal conductance also decreases when leaf temperatures exceed a critical threshold value, even when Δw is artificially maintained at a constant level. The threshold temperature is commonly attained for leaves in situ, but only after substantial stomatal closure has already occurred as a result of high Δw values.The photosynthetic temperature optimum and threshold temperature which promotes stomatal closure increases substantially as the growing season progresses. As a result, the midday depression in photosynthesis occurs at higher temperatures in mid-summer than in late spring. Preliminary evidence suggests that the photosynthetic temperature optimum closely follows the naturally-occurring morning leaf temperatures, while the threshold temperature for stomatal closure matches afternoon leaf temperatures.


Discontinuation and reduction of asthma medications after metabolic and bariatric surgery: A systematic review and meta-analysis.
Obesity is a risk factor for asthma. Metabolic and bariatric surgery (MBS) is a safe and effective treatment option for obesity. Weight reduction via MBS, in turn, may improve asthma outcomes and decrease the need for asthma medications. The aim of the systematic review and meta-analysis is to explore the available evidence focused on the impact of MBS on the improvement of asthma outcomes via the discontinuation and reduction of asthma medications. After a comprehensive search in the PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases, 15 studies, including pre-post MBS data on asthma medication use among adults, were eligible for the systematic review. Thirteen studies reported the proportion of patient who discontinued asthma medication post-MBS and was meta-analyzed using random effects. Results showed 54% patients completely discontinued asthma medications (95% confidence interval 42%-67%, I2 = 86.2%, p < 0.001). The average number of asthma medications was also decreased by approximately 22%-46%. MBS provides strong therapeutic benefits for patients with asthma, as evidenced by the complete discontinuation of asthma medications in over 50% of MBS completers. The inference was limited by the small number, variations in follow-up time and rates, and heterogeneity of studies. Studies that include more ethnically diverse participant samples are needed to improve generalizability.


Upregulation of mitogen-inducible gene 6 triggers antitumor effect and attenuates progesterone resistance in endometrial carcinoma cells.
Researches regarding mitogen-inducible gene 6 (Mig-6) have confirmed its role as a tumor suppressor and progesterone resistance factor in endometrium. In this study, after confirming the downregulation of Mig-6 protein in endometrial carcinoma (EC) tissues, the expression of Mig-6 was upregulated in Ishikawa cells by pCMV6-Mig-6 plasmid. We observed the increased apoptosis, decreased proliferation and invasion potential of Ishikawa cells after upregulation of Mig-6. The proapoptosis ability of P4 significantly enhanced by 39.36%, the antiproliferation ability increased by 37.90% and the anti-invasion ability increased by 48.89%, suggesting the antiprogesterone resistance potential of Mig-6 in endometrium. In addition, the results suggested that Mig-6 may induce Ishikawa cell apoptosis through the mitochondrial pathway, inhibit cell proliferation via the extracellular signal-regulated kinase pathway and the anti-invasion potential may associate with matrix metalloproteinase (MMP)-2 and MMP-9 downexpression. Therefore, upregulation of Mig-6 may add a new strategy to suppress endometrial tumorigenesis and attenuate the progesterone resistance during P4 treatment.


Effect of phenobarbital on the carcinogenesis of N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide in rats.
Male Fischer rats were fed a N-[4-(5-nitro-2-furyl]-2-thiazolyl]formamide (FANFT) diet for 6 weeks followed by a phenobarbital (PB) diet for an additional 86 weeks. PB significantly increased the incidence of bladder tumors, but not the incidence of hepatic foci and areas of cellular alterations caused by FANFT. The results suggest that PB may be a weak promoter for bladder carcinogenesis, and that FANFT may not be an initiator for hepatocarcinogenesis.


Platelet glycoprotein VI cluster size is related to thrombus formation and phosphatidylserine exposure in collagen-adherent platelets under arterial shear.
Collagen-induced platelet activation is predominantly mediated by glycoprotein (GP) VI through formation of receptor clusters that coincide with the accumulation of signaling molecules and are hypothesized to drive strong and sustained platelet activation. To determine the importance of GPVI clusters for thrombus formation in whole blood under shear. We utilized whole blood microfluidics and an anti-GPVI nanobody (Nb), Nb28, labeled with AlexaFluor 488, to assess the distribution of GPVI on the surface of platelets adhering to a range of collagen-like substrates with different platelet activation potentials. Automated analysis of GPVI surface distribution on platelets supported the hypothesis that there is a relationship between GPVI cluster formation, thrombus size, and phosphatidylserine (PS) exposure. Substrates that supported the formation of macroclusters also induced significantly bigger aggregates, with increased amounts of PS-exposing platelets in comparison to substrates where no GPVI clusters were detected. Furthermore, we demonstrate that only direct inhibition of GPVI binding, but not of downstream signaling, is able to disrupt cluster formation. Labeled anti-GPVI Nb28 permits visualization of GPVI clustering under flow conditions. Furthermore, whilst inhibition of downstream signaling does not affect clustering, it does prevent thrombus formation. Therefore, GPVI macroclustering is a prerequisite for thrombus formation and platelet activation, namely, PS exposure, on highly GPVI-dependent collagen surfaces.


DNA strand breaks, neurodegeneration and aging in the brain.
Defective responses to DNA single- or double-strand breaks can result in neurological disease, underscoring the critical importance of DNA repair for neural homeostasis. Human DNA repair-deficient syndromes are generally congenital, in which brain pathology reflects the consequences of developmentally incurred DNA damage. Although, it is unclear to what degree DNA strand-break repair defects in mature neural cells contributes to disease pathology. However, DNA single-strand breaks are a relatively common lesion which if not repaired can impact cells via interference with transcription. Thus, this lesion, and probably to a lesser extent DNA double-strand breaks, may be particularly relevant to aging in the neural cell population. In this review we will examine the consequences of defective DNA strand-break repair towards homeostasis in the brain. Further, we also consider the utility of mouse models as reagents to understand the connection between DNA strand breaks and aging in the brain.


Yeast diversity investigation of Vitis davidii Föex during spontaneous fermentations using culture-dependent and high-throughput sequencing approaches.
Vitis davidii Föex is widely planted in South China as a potential wine making grape. In this study, yeast communities during the spontaneous fermentations of two varieties of Vitis davidii Föex in Guizhou, China were investigated. Hanseniaspora uvarum, Pichia terricola, Saccharomyces cerevisiae/S. mikatae, and Schizosaccharomyces japonicus were the four main yeast species detected by culture-dependent and high-throughput sequencing approaches. However, the composition of minor yeast species was quite different as revealed by the two approaches. Ten yeast species including Debaryomyces hansenii, Rhodotorula mucilaginosa, Sporidiobolus paraoseus, Starmerella bacillaris, Zygoascus meyerae, etc. were detected by culture-dependent approaches, whereas the other five species were found by high-throughput sequencing analysis. S. japonicus was widely found during spontaneous fermentations and its concentrations were mostly higher than that of S. cerevisiae. The difference in grape varieties and fermentation conditions contributed to yeast diversity. The results of this study provide basic information on indigenous yeast diversity from Vitis davidii Föex in Guizhou, which would help to exploit the potential of non-Saccharomyces yeast species with good oenological attributes.


[Expressions of CXCL16/CXCR6 and CXCL12/CXCR4 in first-trimester human trophoblast cells].
To investigate the transcription and protein expressions of chemokines CXCL16, CXCL12 and their receptors CXCR6, CXCR4 in first-trimester human cytotrophoblast cells and human choriocarcinoma cell line JAR. Transcriptions of CXCR6, CXCL16, CXCR4, CXCL12 in purified first-trimester human trophoblast cells and JAR line were assessed by semi-quantitative RT-PCR, and protein expressions of CXCR6, CXCL16, CXCR4, CXCL12 were analyzed in primary cultured villous cytotrophoblasts (VCT), extravillous cytotrophoblasts (EVCT), JAR line and placentas by immunostaining. CXCR6 and CXCR4 were highly transcribed in primary cultured trophoblast cells with mRNA relative level of 1.12 +/- 0.25 and 1.08 +/- 0.11 respectively, and their ligands CXCL16 and CXCL12 were transcribed moderately with mRNA relative level of 0.89 +/- 0.11 and 0.78 +/- 0.10 respectively. It was demonstrated that CXCL16, CXCL12, CXCR6 and CXCR4 were expressed in primary cultured VCT, EVCT, JAR line and placentas by immunostaining. The co-expression of CXCL16/CXCR6 and CXCL12/CXCR4 in trophoblast cells may play a role in the proliferation and differentiation of first-trimester trophoblast cells in a manner of autocrine.


Experimental verification and investigation of disks scattering slab modes in metal-dielectric heterostructures.
A thin dielectric plate can support conventional slab modes such as leaky Fabry-Perot, guided waves and radiation modes. When the plate is coated on a metallic subwavelength disk array, it can result in new confined modes, hereby named 'disks scattering slab modes' (DSSMs). By use of a terahertz time-domain spectroscopy system, we experimentally verify the existence of two types of DSSMs in terahertz range: one we refer to as highly confined disks scattering Fabry-Perot-like modes (DSFPMs) and the other as, weakly confined disks scattering radiation-like modes (DSRMs). Spectral characteristics of these confined modes are measured and numerically simulated. Particularly, based on the experimental results and a dipole-scattering model developed here, we show that the features of the DSFPMs can be tuned by changing the filling fraction of the disk array. We believe these results can make important contributions to the designs of new terahertz devices, including tunable absorbers and filters.


The digestive tract of the whiteback griffon vulture and its role in disease transmission among wild ungulates.
The digestive tract of the whiteback vulture (Gyps africanus) is described. Some disease organisms were fed to a captive bird to discover if they could survive passage through the tract, and the role of these scavenging birds in the spread of diseases among wild ungulates is discussed.


Locally delivered chemotherapy and repeated surgery can improve survival in glioblastoma patients.
We treated 54 patients, newly diagnosed for glioblastoma, with systemic chemotherapy (carmustine (BCNU) 100 mg/m2 and cisplatin 90 mg/m2 every 6 weeks) and radiotherapy soon after surgery. In 10 cases the treatment was combined with locoregional chemotherapy (1 mg bleomycin on days 1-2, and 3 mg mitoxantrone on day 3, repeated every 20 days) administered from an Ommaya reservoir. At tumor recurrence, all patients were treated with procarbazine, lomustine and vincristine (PCV); 15 of 54 were reoperated and treated with locoregional chemotherapy. The median time to disease progression (TTP) and overall survival time (ST) for the whole group were 10.8 and 23.1 months, respectively. The ST of the 15 reoperated patients who also received locoregional treatment at disease recurrence was 27.6 months; this was significantly longer than that of patients not reoperated and not treated locally (log-rank p=0.04). The results in our reoperated subgroup support the opinion that a second operation could be suitable if it is part of the whole program of treatment.


Nivolumab-induced diffuse type 2 rhinosinusitis: A case report.
Nivolumab, an immune checkpoint inhibitor is used to treat advanced metastatic malignancies. Data showed that nivolumab can cause exacerbated response of T-Helper 2 cells and lead to airway inflammation. To present the upper airway findings of a 69-year-old woman after treatment with nivolumab. Case report. A 69-year old woman with no history of chronic rhinosinusitis developed complaints of nasal congestion, rhinorrhea, sneezing, and anosmia. These symptoms started after one year of treatment with nivolumab. Pale polyps were observed on fiberoptic endoscopy examination. A gradual increase in eosinophil blood counts was noted. On histopathology, heavy infiltrates of eosinophils were seen in the tissue. Nivolumab is used to treat various advanced metastatic malignancies, with a good safety profile. Nevertheless, physicians must be alert to the possibility of evolving type II inflammation in patients, as appropriate therapy can be provided to improve their quality of life.


Deferoxamine preconditioning enhances the protective effects of stem cells in streptozotocin-induced Alzheimer's disease.
Stem cell-based therapy is one of the promising strategies in the treatment of Alzheimer's disease (AD), but the short lifespan and low homing of transplanted cells continue to be a major obstacle in this method. Preconditioning of stem cells before transplantation could increase cell therapy efficiency. Herein, we examined whether the treatment of stem cells with deferoxamine (DEF) prior to graft could enhance the neuroprotective effects of stem cells in the streptozotocin (STZ)-treated male rats. After induction of the AD model, the rats were transplanted with DEF-preconditioned Adipose-derived mesenchymal stem cells (AMSCs) or untreated cells. Memory function, antioxidant capacity, cell density, and homing of transplanted cells were assessed using Morris water maze and shuttle box tasks as well as biochemical and histochemical methods. Transplantation of AMSCs caused a memory improvement when compared to the AD model. The injection of DEF-preconditioned AMSCs was more effective in improving learning and memory than the untreated cells through an increase in the antioxidant capacity. Moreover, the homing of transplanted cells was higher in the rats that received the preconditioned cells than that of the naïve cell-injected group. It seems that the transplantation of DEF-treated cells may increase the efficiency of stem cells via an increase in the antioxidant capacity.


[Explaining radiation dose exposure : The role of the banana equivalent dose compared to the effective dose in patient communication].
Communicating the amount and effects of ionizing radiation to patients prior to an examination using x‑rays is associated with challenges: first, calculating the expected dose prior to the examination and, second, quantifying and illustrating cancer risks. Analogies, such as comparing radiation exposure to accident risks, have limitations and may evoke unease. This study explores and compares two new approaches to discuss radiation exposure from common clinical examinations with patients: effective dose and exposure based on radioactive potassium-40 intake from the ingestion of bananas, the banana equivalent dose (BED). The effective doses of the diagnostic reference levels (DRL) for computed tomography (CT) and X-ray examinations in adults were calculated using mean conversion factors for specific anatomic body regions. For the BED calculation of the diagnostic reference levels, the radiation dose from a conventional banana ingested over 50 years per becquerel was calculated. The outcomes were juxtaposed against an equivalent number of bananas and its respective radiation doses. The calculated doses, namely effective dose and BED, of the German DRL can serve as a reliable metric to discuss radiation exposure from medical imaging with patients prior to an examination. This is the first study to calculate the effective doses of the current DRL and to compare these with the pseudoscientific unit BED. While the BED serves as an interesting illustration to metaphorize radiation exposure, it is recommended to use the calculated effective dose of the DRL as the basis for educational consultations with patients.


Multiple choroidal metastasis from bronchial carcinoid treated with photocoagulation and proton beam irradiation.
A 23-year-old man had bilateral multiple choroidal lesions eight years after removal of a bronchial carcinoid tumor. Choroidal biopsy confirmed that the clinical diagnosis and conventional radiotherapy to one eye resulted in rubeosis iridis, neovascular glaucoma, cataract, and vitreous hemorrhage. We were able to destroy the tumors in the other eye by photocoagulation and proton beam irradiation without any adverse effects. The patient is in good health 1 1/2 years after therapy and he has 6/6 (20/20) vision in the eye that was treated.


Targeting EGFR pathway in metastatic colorectal cancer- tumour heterogeniety and convergent evolution.
Despite significant progress in management of metastatic colorectal cancer (mCRC) pertaining to better screening procedures and amelioration of the therapeutic armamentarium with targeted therapies, prognosis remains poor. Targeting epidermal growth factor receptor (EGFR) has been of particular interest owing to favourable efficacy benefits demonstrated by monoclonal antibodies (cetuximab and panitumumab) in various clinical settings and development of predictive biomarkers informing treatment decisions respectively. In spite of optimal patient selection based on RAS mutation status, primary and secondary resistance to monoclonal antibodies is higher than desired. Further research into predictive biomarkers is therefore essential, but has, to date, been conducted with considerable limitations. Whilst molecular heterogeneity has been demonstrated by several studies in mCRC, for incomprehensible reasons, multiple resistant genetic alterations that emerge under the selective pressure of EGFR-targeted therapies are somehow able to influence the biological and clinical behaviour of cancer cells, despite being detectable at extremely low frequencies. Intriguingly, these subclonal events largely seem to converge on RAS/RAF/MAPK pathway in patients treated with EGFR-targeted monoclonal antibodies. This review describes the clinical and biological evolution and development of EGFR targeted therapies in mCRC, the challenges in the presence of molecular complexities, the role of cell free (cf)-DNA and future strategies that could lead to further optimal discovery of clinically meaningful biomarkers and application of precision medicine.


Mechanisms of extracellular vesicle uptake in stressed retinal pigment epithelial cell monolayers.
Extracellular vesicles (EVs) can mediate long-distance communication in polarized RPE monolayers. Specifically, EVs from oxidatively stressed donor cells (stress EVs) rapidly reduced barrier function (transepithelial resistance, TER) in naïve recipient monolayers, when compared to control EVs. This effect on TER was dependent on dynamin-mediated EV uptake, which occurred rapidly with EVs from oxidatively stressed donor cells. Here, we further determined molecular mechanisms involved in uptake of EVs by naïve RPE cells. RPE cells were grown as monolayers in media supplemented with 1% FBS followed by transfer to FBS-free media. Cultures were used to collect control or stress EVs upon treatment with H2O2, others served as naïve recipient cells. In recipient monolayers, TER was used to monitor EV-uptake-based activity, live-cell imaging confirmed uptake. EV surface proteins were quantified by protein chemistry. Clathrin-independent, lipid raft-mediated internalization was excluded as an uptake mechanism. Known ligand-receptor interactions involved in clathrin-dependent endocytosis include integrins and proteoglycans. Desialylated glycans and integrin-receptors on recipient cells were necessary for EV uptake and subsequent reduction of TER in recipient cells. Protein quantifications confirmed elevated levels of ligands and neuraminidase on stress EVs. However, control EVs could confer activity in the TER assay if exogenous neuraminidase or additional ligand was provided. In summary, while EVs from both stressed cells and control contain cargo to communicate stress messages to naive RPE cells, stress EVs contain surface ligands that confer rapid uptake by recipient cells. We propose that EVs potentially contribute to RPE dysfunction in aging and disease.


Nutritional status and depression, sleep disorder, and quality of life in hemodialysis patients.
The malnutrition-inflammation score (MIS) is a scoring system that measures malnutrition and inflammation. We sought to explore its associations with depression, sleep disturbance, and quality of life. This was a cross-sectional study. This study took place at the Baskent University Outpatient Hemodialysis Unit (Ankara, Turkey). We enrolled 67 hemodialysis patients (male/female, 34/33; age, 47.7 +/- 11.4 years [mean +/- SD]; hemodialysis duration, 103.7 +/- 59.1 months [mean +/- SD]). We retrospectively recorded patients' monthly clinical and laboratory findings from the previous 6 months. The same physician calculated MIS scores. We interviewed all patients, and each completed a Beck Depression Inventory (BDI) assessment. We used the Pittsburgh Sleep Quality Index (PSQI) to assess quality of sleep, and the Medical Outcomes Study 36-item short form (SF-36) questionnaire to evaluate health-related quality of life. The main outcome measures involved the univariate and multivariate relationships of the MIS with BDI, PSQI, and SF-36. Patients with PSQI scores of < or = 5 ("good sleepers") had lower MIS scores than did poor sleepers (6.8 +/- 2.5 vs. 8.8 +/- 3.2, P < .05). Patients with moderate-to-severe depression (BDI score > or = 19) had higher MIS scores (9.0 +/- 3.2 vs. 6.5 +/- 2.5, P = .005) and higher PSQI scores (7.6 +/- 2.1 vs. 4.7 +/- 1.8, P = .001), compared with patients with BDI scores < 19. Increased MIS scores were correlated with increased comorbidity (P = .01) and poor SF-36 scores (P = .009). Increased MIS is significantly associated with the presence of depression, sleep disorders, and poor quality of life. This close relationship may help establish the MIS as an important determinant of the increased morbidity and mortality of hemodialysis patients.


Hydrofluoric acid burns of the hand: mechanism of injury and treatment.
Hydrofluoric acid is one of the strongest inorganic acids and is used extensively in industry and research. It differs from other acids in that the fluoride ion readily penetrates the skin, causing destruction of deep tissue layers and even bone. Authors have previously described numerous topical treatments. This report describes one method of treatment emphasizing immediate skin cleansing and the application of calcium gluconate gel, which is followed by calcium gluconate subcutaneous injections when necessary. An accurate occupational history and physical examination are important aspects of patient assessment. Prompt treatment resulted in relief of pain and a satisfactory clinical result in all cases. A significant delay in treatment was responsible for permanent impairment in 2 of 14 patients.


Primary mycetoma of the calcaneum: Case report on an unusual hazard of barefoot walking.
Mycetoma is a rare tropical fungal infection characterized by a clinical triad of subcutaneous swelling, multiple discharging sinuses, and a purulent discharge containing granules. If left untreated, the disease can progress from cutaneous to intraosseous and can cause osteomyelitis. In very rare instances labeled "primary mycetoma", the fungus is insidiously inoculated directly into the bone and causes osteomyelitis without any preceding cutaneous involvement. This can make the diagnosis very difficult. A twelve-year-old girl with a history of walking barefoot, presented with pain and inability to bear weight on her left foot. There was no overlying cutaneous involvement. X-ray showed an osteolytic lesion in the calcaneum. After the failure of antibiotic treatment, the diseased bone was excised. Black granules were discovered inside the lesion and their histopathology confirmed a diagnosis of primary eumycetoma. After some time, the disease relapsed, necessitating another debridement. This occurred many times with worsened severity in each successive episode. Because of worsening disease and failure of both antifungal and surgical treatment, foot amputation was done. Primary mycetoma is an insidious fungal infection that causes osteomyelitis without any cutaneous findings. Timely diagnosis and treatment provide the best chance of preventing an amputation. A high index of suspicion must be maintained for patients presenting with symptoms of osteomyelitis without any skin involvement so that timely diagnosis and treatment can prevent the progression of the disease and the need for amputation.


Synthesis and antitumor evaluation of 2,3-diarylbenzofuran derivatives on HeLa cells.
2,2-Dihydroxyarylethanones, readily prepared from the commercially available aromatic ethyl ketones, were reacted with resorcinol, 3-methoxyphenol or 2-methoxyphenol in multi steps one-pot manner promoted by trifluoroacetic acid to furnish the 2,3-diarylbenzofuran derivatives in 22-95% yield. Sixteen targeted compounds were synthesized and characterized by 1H NMR, 13C NMR and HRMS. MTT assay indicated that most compounds possessed effectively inhibitory activities against the proliferation of HeLa cell. Among them, 4f had the highest inhibitory activities, with the IC50 being 13.40±2.04µmol/L. Cell cycle analysis, Annexin V-FITC/propidium iodide dual staining assay and western blotting analysis revealed that 4f inhibited the proliferation of Hela cell through apoptosis induction in a dose-dependent manner via obviously up-regulated the levels of Bak and Bim, while striking down-regulated the level of Bcl-2 and Bcl-xL protein.


Hypoglycemic, lipid-lowering and metabolic regulation activities of metforminium decavanadate (H2Metf)3 [V10O28]·8H2O using hypercaloric-induced carbohydrate and lipid deregulation in Wistar rats as biological model.
Because of the increasing global spread of type 2 diabetes mellitus, there is a need to develop new antidiabetic agents. Recently we have synthesized new decavanadates using metformin as counterion. In particular, the compound containing three metforminium dications has been obtained in high yield and has been completely characterized. Biological studies using Wistar rats that have been fed with a high caloric diet inducing insulin resistance and metabolic syndrome were carried out. Results of the impact on key biochemical parameters mediated by metformin alone and the new compound are here presented. The metforminium decavanadate (H2Metf)3[V10O28]·8H2O, abbreviated as Metf-V10O28, was shown to have pharmacological potential as a hypoglycemic, lipid-lowering and metabolic regulator, since the resulting compound made of the two components with antidiabetic activities, reduces both dosage and time of administration (twice a week). Hence, due to the beneficial effects induced by the metforminium decavanadate we recommend to continue the exploration into the mechanism and toxicology of this new compound.


The genetic basis of novel water utilisation and drinking behaviour traits and their relationship with biological performance in turkeys.
There is increasing interest in the definition, measurement and use of traits associated with water use and drinking behaviour, mainly because water is a finite resource and its intake is an important part of animal health and well-being. Analysis of such traits has received little attention, due in part to the lack of appropriate technology to measure drinking behaviour. We exploited novel equipment to collect water intake data in two lines of turkey (A: 27,415 and B: 12,956 birds). The equipment allowed continuous recording of individual visits to the water station in a group environment. Our aim was to identify drinking behaviour traits of biological relevance, to estimate their genetic parameters and their genetic relationships with performance traits, and to identify drinking behaviour strategies among individuals. Visits to the drinkers were clustered into bouts, i.e. time intervals spent in drinking-related activity. Based on this, biologically relevant traits were defined: (1) number of visits per bout, (2) water intake per bout, (3) drinking time per bout, (4) drinking rate, (5) daily bout frequency, (6) daily bout duration, (7) daily drinking time and (8) daily water intake. Heritability estimates for most drinking behaviour traits were moderate to high and the most highly heritable traits were drinking rate (0.49 and 0.50) and daily drinking time (0.35 and 0.46 in lines A and B, respectively). Genetic correlations between drinking behaviour and performance traits were low except for moderate correlations between daily water intake and weight gain (0.46 and 0.47 in lines A and B, respectively). High estimates of breeding values for weight gain were found across the whole range of estimated breeding values for daily water intake, daily drinking time and water intake per bout. We show for the first time that drinking behaviour traits are moderately to highly heritable. Low genetic and phenotypic correlations with performance traits suggest that current breeding goals have not and will not affect normal water drinking behaviour. Birds express a wide range of different drinking behaviour strategies, which can be suitable to a wide range of environments and production systems.


Voluntary intake and milk production in F1 Holstein × zebu cows in confinement.
The objective of this study was to evaluate the nutrient intake and milk production in Holstein × zebu (F1) cows in feedlot. Eighteen F1 cows were used, divided into three treatments; six were Holstein × Gir (HGI), six were Holstein × Guzerat (HGU), and another six were Holstein × Nelore (HNE), which had recently calved, distributed into simple, random samples, under the same feeding conditions of corn silage and concentrate with 20% crude protein. The three-marker method was used (LIPE, titanium dioxide, and iADF) to estimate the individual intake and digestibility of the nutrients for the cows in group. The mathematical model used to establish the lactation curves was: Y = at(b)e(-ct) by Wood (Nature 216:164-165, 1967). The statistical analyses for the nutrient intake and digestibility, as well as parameters of metabolic efficiency, were performed using multiple linear regression (α = 5%). No effect (P > 0.05) of genetic group was observed for any of the variables studied. The intake and digestibility of the nutrients and the microbial nitrogen presented quadratic curves as a function of the lactation period (P < 0.05). The HGU cows exhibited an accumulated milk production of 4,946.81 kg at 305 days, whereas the HGI cows produced 4,821.78 kg. The HNE cows displayed inferior performance, with a production of 3,674.98 kg. It was concluded that, in confinement, F1 cows from different genetic groups do not exhibit different intake, digestibility, or metabolic efficiency. The HGU and HGI cows have greater cumulative production at 305 days.


Lateral plate mesoderm cell-based organoid system for NK cell regeneration from human pluripotent stem cells.
Human pluripotent stem cell (hPSC)-induced NK (iNK) cells are a source of off-the-shelf cell products for universal immune therapy. Conventional methods for iNK cell regeneration from hPSCs include embryoid body (EB) formation and feeder-based expansion steps, which are time-consuming and cause instability and high costs of manufacturing. Here, we develop an EB-free, organoid aggregate method for NK cell regeneration from hPSCs. In a short time-window of 27-day induction, millions of hPSC input can output over billions of iNK cells without the necessity of NK cell expansion feeders. The iNK cells highly express classical toxic granule proteins, apoptosis-inducing ligands, as well as abundant activating and inhibitory receptors. Functionally, the iNK cells eradicate human tumor cells via mechanisms of direct cytotoxicity, apoptosis, and antibody-dependent cellular cytotoxicity. This study provides a reliable scale-up method for regenerating human NK cells from hPSCs, which promotes the universal availability of NK cell products for immune therapy.


Steady shear flow properties of Cordia myxa leaf gum as a function of concentration and temperature.
The steady shear flow properties of dispersions of Cordia myxa leaf gum (CMLG) were determined as a function of concentration (0.5-2.5%, w/w), and temperature (10-50 °C). The CMLG dispersions exhibited strong shear-thinning behavior at all concentrations and temperatures. The Power-law (Ostwald-Waele's) and Herschel-Bulkley models were employed to characterize flow behavior of CMLG solutions at 0.1-100 s(-1) shear rate. Non-Newtonian shear-thinning behavior was observed at all temperatures and concentrations. While increase in temperature decreased the viscosity and increased the flow behavior indices, adverse effect was obtained by increasing the concentration. The Power-law model was found the best model to describe steady shear flow behavior of CMLG. The pseudoplasticity of CMLG increased markedly with concentration. An Arrhenius-type model was also used to describe the effect of temperature. The activation energy (Ea) appeared in the range of 5.972-18.104 kJ/mol, as concentration increased from 0.5% to 2.5%, at a shear rate of 10 s(-1).


[Surface changes of enamel, root cementum and fillings after treatment with tooth cleaning instruments].
The effect of new, automatic tooth cleaning instruments on tooth surface and surfaces and margins of amalgam and composite fillings were studied by profilometric measurements and SEM and compared with each other. On the surfaces of teeth and fillings, in particular at the margins, ultrasound treatment resulted in the significantly highest maximum roughness values. These values were lower when turbin-operated scalers were used. Results demonstrate that during tooth cleaning direct contact between ultrasound and turbine-operated scalers and tooth and filling surfaces should be prevented.


Browsers or Grazers? New Insights into Feral Burro Diet Using a Non-Invasive Sampling and Plant DNA Metabarcoding Approach.
Ungulates play a large role in shaping ecosystems and communities by influencing plant composition, structure, and productivity. We investigated the summer diets of feral burros in two ecosystems in which they are found in the United States: a subtropical desert in Arizona and a temperate juniper shrubland in Utah. Between 24 June and 16 July of 2019, we gathered 50 burro fecal samples from each location and used plant DNA metabarcoding to determine the burros' diets. We found that during our sampling period the burros in the Sonoran Desert consumed a higher proportion of woody browse and had a narrower dietary niche breadth and lower degree of diet diversity compared to the burros in the juniper shrubland ecosystem, where the burros consumed higher proportions of graminoids and forbs and had a higher diet diversity index and broader dietary niche breadth. The burros in the Sonoran Desert relied primarily on Prosopis spp. (mesquite) and Poaceae grasses, whereas the burros in the juniper shrubland relied on a wider variety of forb and grass species, likely due to the greater variability in the forage species temporally and spatially available in that temperate ecosystem. We found that feral burros are highly adaptable with respect to diet and appear to be employing a mixed feeding strategy, similar to their ancestor, the African wild ass, to meet their nutritional needs in whichever ecosystem they are found.


Drug-drug interaction between rifabutin and dolutegravir: A population pharmacokinetic model.
Rifampicin, a potent enzyme inducer, causes marked reduction of dolutegravir exposure. Rifabutin, a less potent enzyme inducer, may offer an alternative to rifampicin. We aimed to characterize the population pharmacokinetics of dolutegravir when co-administered with rifabutin. We extended an existing dolutegravir model to include data from volunteers co-administered with dolutegravir 50 mg and rifabutin 300 mg once daily. We ran simulations of dolutegravir with and without rifabutin co-administration and compare dolutegravir trough concentrations with the IC90 and EC90 of 0.064 and 0.3 mg/L, respectively. Rifabutin decreased dolutegravir's volume of distribution by 33.1% (95% confidence interval 25.1%-42.3%) but did not affect the area under the concentration-time curve. Simulations showed that when 50 mg dolutegravir is co-administered with rifabutin once daily, the probability to attain trough concentrations above the IC90 of 0.064 mg/L is more than 99%. Therefore, there is no need for dolutegravir dose adjustment. Rifabutin may offer an alternative to rifampicin for the treatment of HIV/tuberculosis co-infected individuals.


Structure-affinity relationships of adenosine A2B receptor ligands.
Many selective and high affinity agonists and antagonists have been developed for the adenosine A(1), A(2A), and A(3) receptors. Very recently such compounds have been identified for the adenosine A(2B) receptors. This review presents an overview of the structure-affinity relationships of antagonists and agonists for this receptor subtype as published in the scientific and patent literature. To date the most selective >370-fold, high affinity adenosine A(2B) receptor antagonist is the xanthine analog, compound 16 (8-(1-(3-phenyl-1,2,4-oxadiazol-5-yl)methyl)-1H-pyrazol-4-yl)-1,3-dipropyl-1H-purine-2,6(3H,7H)-dione). The pyrrolopyrimidine analog OSIP339391 (73) is slightly less selective, 70-fold, but has a higher affinity 0.41 nM compared to 1 nM for compound 16. Other promising classes of compounds with selectivities ranging from 10- to 160-fold and affinities ranging from 3 to 112 nM include triazolo, aminothiazole, quinazoline, and pyrimidin-2-amine analogs. Progress has also been achieved concerning the development of selective high affinity agonists for the adenosine A(2B) receptor. For years the most potent, albeit non-selective adenosine A(2B) receptor agonist was (S)PHPNECA (88). Last year, a new class of non-ribose ligands was reported. Several compounds displayed selectivity with respect to adenosine A(2A) and A(3) receptors. In addition, full and partial agonists for the adenosine A(2B) receptor were identified with EC(50) values of 10 nM (LUF5835, 103) and 9 nM (LUF5845, 105), respectively.


The sequence of an antibiotic resistance gene from an antibiotic-producing bacterium. Homologies with transposon genes.
The APH gene of a butirosin-producing Bacillus circulans has been cloned and sequenced; a comparison of the translated protein sequence with those from TN5 and TN903 indicates that they may have a common origin.


The Power of the Pill for the Next Generation: Oral Contraception's Effects on Fertility, Abortion, and Maternal & Child Characteristics.
This paper considers how oral contraception's diffusion to young unmarried women affected the number and parental characteristics of children born to these women. In the short-term, pill access caused declines in fertility and increases in both the share of children born with low birthweight and the share born to poor households. In the long-term, access led to negligible changes in fertility while increasing the share of children with college-educated mothers and decreasing the share with divorced mothers. The short-term effects appear to be driven by upwardly-mobile women opting out of early childbearing while the long-term effects appear to be driven by a retiming of births to later ages. These effects differ from those of abortion legalization, although we find suggestive evidence that pill diffusion lowered abortions. Our results suggest that abortion and the pill are on average used for different purposes by different women, but on the margin some women substitute from abortion towards the pill when both are available. JELNo. I0, J13, N12.


Cell-to-cell communication via plasmodesmata during Arabidopsis embryogenesis.
In Arabidopsis embryogenesis, positional information establishes the overall body plan and lineage-dependent cell fate specifies local patterning. Position-dependent gene expression and responses to the plant hormone auxin are also crucial. Recently, another mechanism that delivers positional information has been uncovered. This pathway utilizes cell-to-cell communication via plasmodesmata. Plasmodesmata span the walls between neighboring plant cells. Groups of cells that allow intercellular transport of biotic and abiotic tracers form symplastic domains of shared communication. Initially, cells of the embryo form one symplast. As development proceeds, symplastic sub-domains that correspond to the major morphological regions of the plant (i.e. shoot apex, cotyledons, hypocotyl, and root) are formed. These sub-domains further resolve into tissue-specific domains of communication (such as protodermal and vascular regions). Cell-to-cell communication via plasmodesmata between embryonic and maternal tissues ceases as development proceeds.


Characterization of the primary antibody response to Plasmodium falciparum antigens in infants living in a malaria-endemic area.
The primary antibody (Ab) response to Plasmodium falciparum is a critical step in developing immunity to malaria. Information on the initial Ab responses of babies in malaria-endemic areas is incomplete, in part, because babies receive maternal IgG via transplacental-transfer and usually become infected before maternal IgG wanes. The study aimed to identify the primary IgM and IgG Ab responses to malarial antigens in Cameroonian babies. Infants (n = 70) living in a high malaria transmission area were followed from birth throughout the first year of life (mean 341 ± 42 days, an average of 8.5 time points per infant). Malaria infection was assessed by microscopy and PCR, and IgM and IgG antibodies (Abs) were measured using a multiplex immunoassay to AMA1, EBA-175, MSP1-42, MSP2, MSP3, RESA, LSA1, and CSP. The half-life of maternal IgG varied among the antigens, ranging from 0.7 to 2.5 months. The first infection of 41% of the babies was sub-microscopic and only 11 to 44% of the babies produced IgM to the above antigens; however, when the first infection was detected by microscopy, 59-82% of the infants made IgM Abs to the antigens. Infants were able to produce IgM even when maternal IgG was present, suggesting maternal Abs did not suppress the baby's initial Ab response. Using longitudinal regression models that incorporated time-varying covariates, infants were found to produce IgG Ab to only AMA-1 when the first infection was sub-microscopic, but they produced IgG Abs to MSP1-42 (3D7, FVO), AMA1 (3D7, FVO) MSP2-FC27, MSP3, RESA, and LSA1, but not MSP 2-3D7, EBA-175, and CSP during their first slide-positive infection. Notably, the primary and secondary IgG responses were short-lived with little evidence of boosting. The primary Ab response of babies who had maternal IgG was similar to that reported for primary infections in malaria-naïve adults.


[A single-center study on the distribution and antibiotic resistance of pathogens causing bloodstream infection in patients with hematological malignancies].
Objective: To study the incidence of bloodstream infections, pathogen distribution, and antibiotic resistance profile in patients with hematological malignancies. Methods: From January 2018 to December 2021, we retrospectively analyzed the clinical characteristics, pathogen distribution, and antibiotic resistance profiles of patients with malignant hematological diseases and bloodstream infections in the Department of Hematology, Nanfang Hospital, Southern Medical University. Results: A total of 582 incidences of bloodstream infections occurred in 22,717 inpatients. From 2018 to 2021, the incidence rates of bloodstream infections were 2.79%, 2.99%, 2.79%, and 2.02%, respectively. Five hundred ninety-nine types of bacteria were recovered from blood cultures, with 487 (81.3%) gram-negative bacteria, such as Klebsiella pneumonia, Escherichia coli, and Pseudomonas aeruginosa. Eighty-one (13.5%) were gram-positive bacteria, primarily Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecium, whereas the remaining 31 (5.2%) were fungi. Enterobacteriaceae resistance to carbapenems, piperacillin/tazobactam, cefoperazone sodium/sulbactam, and tigecycline were 11.0%, 15.3%, 15.4%, and 3.3%, with a descending trend year on year. Non-fermenters tolerated piperacillin/tazobactam, cefoperazone sodium/sulbactam, and quinolones at 29.6%, 13.3%, and 21.7%, respectively. However, only two gram-positive bacteria isolates were shown to be resistant to glycopeptide antibiotics. Conclusions: Bloodstream pathogens in hematological malignancies were broadly dispersed, most of which were gram-negative bacteria. Antibiotic resistance rates vary greatly between species. Our research serves as a valuable resource for the selection of empirical antibiotics.


A study of bacterial response to polypeptide antibiotics.
When Escherichia coli cells are treated with either polymixin or gramicidin at concentrations that block protein and RNA synthesis, they accumulate a significant amount of guanosine tetraphosphate ppGpp. Such accumulation occurs in stringent (relA+) as well as in relaxed (relA) strains and no guanosine pentaphosphate pppGpp is then detected within the cells. These observations suggest that polypeptide antibiotics elicit ppGpp formation through a mechanism different from the stringent control system triggered by amino acid starvation of bacteria. Experiments based on tetracycline action indicate, moreover, that the accumulation of ppGpp under polymixin or gramicidin treatment is connected with a strong restriction of the degradation rate of this nucleotide.


The use of laboratory-identified event surveillance to classify adverse outcomes due to Clostridioides difficile infection in Canadian long-term care facilities.
Adverse outcomes following Clostridioides difficile infection (CDI) are not often reported for long-term care facility (LTCF) residents. We focused on the adverse outcomes due to CDI identified in Alberta LTCFs. All positive Clostridioides difficile stool specimens identified by laboratory-identified (LabID) event surveillance in Alberta from 2011 to 2018, along with Alberta Continuing Care Information System, were used to define CDI in Alberta LTCFs. CDI cases were classified as long-term care onset, hospital onset, and community onset. Laboratory records were linked to provincial databases to analyze acute-care admissions and mortality within 30-day post CDI. Age, sex, case classification, episode, and operator type, were investigated using logistic regression. Overall, 902 CDI cases were identified in 762 LTCF residents. Of all CDI events, 860 (95.3%) were long-term care onset, 38 (4.2%) were hospital onset, and 4 (0.4%) were community onset. The CDI rate was 2.0 of 100,000 resident days. In total, 157 residents (20.6%) had 30-day all-cause mortality, 126 CDI cases (14.0%) had 30-day all-cause acute-care admissions. The 30-day all-cause mortality rate was significantly higher in residents aged >80 versus ≤80 years (24.9 vs 12.3 per 100 residents; P < .05). Residents aged >80 years, with hospital-onset CDI, and those staying in private or voluntary LTCFs were more likely to have 30-day all-cause acute-care admissions. The prevalence of CDI adverse outcomes is in LTCFs was found to be high using LabID event surveillance. Annual review of CDI adverse outcomes using LabID event can minimize the burden of surveillance and standardize the process across all Alberta LTCFs.


Qualitative and quantitative changes in traffic and waste incineration PCDD/Fs in urban air and soils under different seasonal conditions (Metropolitan Area of Barcelona).
A sampling and analysis scheme was implemented to discriminate between inputs of polychlorodibenzo-p-dioxins and polychlorodibenzofurans (PCDD/Fs) at low concentrations in urban areas. Ambient air and soils were sampled and analyzed in five stations in the Metropolitan area of Barcelona (2018-2019); one located in a reference urban traffic site and four in the area of influence of an integrated waste management facility (IWMF) that included a solid waste incinerator. Seasonality was the main factor determining the PCDD/F composition, and involved lower values in the warmer months. This seasonal effect was related to enhanced photooxidation of PCDDs compared to PCDFs and faster depletion of the less chlorinated congeners due to volatility at higher ambient temperature; consistent with the compounds' octanol-air partition coefficients. The ratio 2,3,7,8-tetrachlorobenzofuran/1,2,3,4,6,7,8-heptachlorobenzofuran allowed, for the first time, identifying cases of preferential contributions of IWMF and traffic inputs, i.e. values of 0.06 and 0.32, respectively. Combination of this ratio with the airborne PCDD/F levels illustrated that the quantitative PCDD/F levels were not a useful criterion for elucidation between IWMF and traffic inputs. PCDD/Fs levels in soils ranged between 9.0 and 22 pg WHO-TEQ/g in the two sites closest to the IWMF, while the other sites, including the traffic site, showed values between 0.8 and 1.9 pg WHO-TEQ/g. The levels in the former group were higher than those observed in other urban areas and above 5 pg WHO-TEQ/g, which is a limit reference value in several European countries. The C7 and C8 observed congener distributions in all soils examined were different from those in the air samples and similar to those reported in sewage sludge from waste water treatment plants, not showing influences from IWMF or traffic PCDD/F inputs.


Patient and caregiver perspectives on seizure prediction.
One of the goals of the Fourth International Workshop on Seizure Prediction was to provide an opportunity for patients with epilepsy and their caregivers to voice their perspectives on seizure prediction and related matters toward the goal of influencing the design of solutions. In an attempt to fulfill this goal, a survey of patients and caregivers, who often make or influence patient choices, was conducted on issues pertaining to living with epilepsy, epilepsy treatments, seizure prediction, and the use of implantable devices for the control of seizures. The results of this survey are reported here.


The molecular regulation of exercised-induced muscle fibre hypertrophy in the common carp: expression of MyoD, PCNA and components of the calcineurin-signalling pathway.
Growth was investigated over 16 d in juvenile common carp (Cyprinus carpio L.) held in either static water (tank rested, TR16) or exercised in a flume at 2.5-3.2 body lengths s-1 for 18 h a day (exercised, E16). Relative to the start of the experiment (TR0), the TR16 group showed a 31% increase in body mass (specific growth rate, 1.57% d-1), whereas there was no net change in the E16 group. There was, however, a significant exercise-induced hypertrophy of slow muscle fibres with average fibre cross-sectional area (FCSA) increasing by 35% in the E16 group, compared with 11% in the TR16 group. In contrast, FCSA of fast muscle fibres increased by 34% in the TR16 group compared to just 18% in the E16 group. The relative concentrations and subcellular localisation of proteins hypothesised to play a role in the regulation of muscle growth were measured. MyoD concentration was similar in the TR0, TR16 and E16 groups in both slow and fast muscle. However, there was a small (5%-10%) but statistically significant increase in nuclear localisation of MyoD in those groups showing a significant increase in FCSA over the time course of the experiment. PCNA concentration was 31% and 12% higher in the TR16 than in either the TR0 or E16 groups for slow and fast muscle, respectively. Exercise resulted in a approximately 10% increase in nuclear factor of T-cells (NFAT2) concentration in slow muscle but no change in NFAT2 localisation. Calcineurin B concentration was similar in tank rested and exercised groups. The results do not support a major role for the calcineurin-signalling pathway in the regulation of muscle hypertrophy in the common carp.


Anti-fibrillin-1 autoantibodies in normal pregnancy and recurrent pregnancy loss.
The aim of this study was to investigate anti-fibrillin-1 autoantibody in patients with a history of recurrent pregnancy loss (RPL) and during normal pregnancy. Anti-fibrillin-1 IgG and IgM antibodies were measured by a home made ELISA in serum samples of 48 medically and obstetrically normal pregnant women, classified to three trimester groups, 15 female patients with RPL and 26 healthy non-pregnant women classified to two control subgroups: (a) women who had already had at least one previous successful pregnancy and (b) women who had never been pregnant. Differences in anti-fibrillin-1 autoantibodies between the groups were analyzed for statistical significance (P<0.05) with one-way analysis of variance (ANOVA) and multiple comparison test - Post Hoc test, Least Significant Difference method. Anti-fibrillin-1 IgM autoantibodies were significantly decreased in the second and third trimester pregnant women compared to the nulligravida controls. RPL patients had significantly increased anti-fibrillin-1 IgM antibody compared to control group (a). Fibrillin-1 degradation seems to be decreased during the second and third trimester of normal pregnancy. Increased anti-fibrillin-1 IgM antibodies in RPL patients may be a secondary phenomenon of increased fibrillin-1 degradation and contribute to the pathogenesis of pregnancy losses.


Cortical recordings reveal hidden early signs of recovery following traumatic brain injury: A case report.
Prognosticating recovery of consciousness after severe traumatic brain injury (TBI) is a difficult task. Understanding the mechanism of recovery of consciousness in these patients will undoubtedly help clarify this issue. Recent research has underscored the importance of electrophysiological data in characterizing the state of the brain during this period of unconsciousness. Here, we investigated cortical electrophysiological recordings from a single TBI patient and discovered that high-frequency activity associated with the return of consciousness reappeared in a spatiotemporal fashion. We observed a shift toward higher frequencies first in the anterior cingulate cortex, and then later in the dorsolateral prefrontal cortex. This finding suggests that recovery may originate in more internal cortices and progress to superficial ones. Although this observation occurred in a single patient, it points to a potential mechanism for recovery of normal cortical activity in the return of consciousness following TBI.


Release of colloidal particles in natural porous media by monovalent and divalent cations.
We study mobilization of colloidal particles from natural porous media, such as soils and groundwater aquifers. Extensive laboratory scale column experiments of particle release from four different subsurface materials are presented. The important characteristics of the release process are (i) its non-exponential kinetics, (ii) the finite supply of colloidal particles and (iii) the strong dependence of the release kinetic on the nature of the adsorbed cations. Particle release depends most sensitively on the relative saturation of the medium with divalent cations. We propose a mathematic model, which captures all these aspects quantitatively, and can be used to describe the coupling between transport of major cations and the release of colloidal particles. The present experimental investigations as well as the developed modeling framework represent an important step towards the understanding of colloid-facilitated transport phenomena in natural porous media.


Phosphorylation-dephosphorylation states at different sites affect phosphoprotein phosphatase 1 activity.
We have previously reported that the binding of type I collagen to its receptor initiates platelet aggregation involving phosphoprotein phosphatase 1 (PP 1), which coprecipitates with the 65-kDa platelet type I collagen receptor. Phosphorylation of the anti-PP1 precipitation PP1 decreases its enzyme activity. In the present investigation, the mechanism of the decreased enzyme activity was studied by examining the phosphorylation of PP 1 on serine/threonine or tyrosine residues. Phosphoamino acid analysis of the PP 1 indicates that serine, threonine, and tyrosine can all be phosphorylated. We find that the activity of PP 1 decreases with serine/threonine phosphorylation but that phosphorylation of tyrosine residue activates enzyme activity. These results indicate that the activity of platelet phosphoprotein phosphatase 1 is controlled by phosphorylation and dephosphorylation states at multiple, different site(s).


[Relevance of the hemovigilance regional database for the shared medical file identity server].
The French Health Products Safety Agency coordinates the national initiative of computerization of blood products traceability within regional blood banks and public and private hospitals. The Auvergne-Loire Regional French Blood Service, based in Saint-Etienne, together with a number of public hospitals set up a transfusion data network named EDITAL. After four years of progressive implementation and experimentation, a software enabling standardized data exchange has built up a regional nominative database, endorsed by the Traceability Computerization National Committee in 2004. This database now provides secured web access to a regional transfusion history enabling biologists and all hospital and family practitioners to take in charge the patient follow-up. By running independently from the softwares of its partners, EDITAL database provides reference for the regional identity server.


Effect of La Doping on Kinetic and Thermodynamic Performances of Ti1.2CrMn Alloy upon De/Hydrogenation.
Development of efficient hydrogen storage materials is one of the great challenges in the area of hydrogen energy and fuel cells. Herein, a La-doped Ti1.2CrMn alloy with high hydriding capacity (2.1 wt % H) and dehydriding capacity (1.8 wt % H) was successfully developed. The crystallographic characteristics, microstructural evolution, and hydrogen storage mechanisms of the alloy were investigated systematically. It was found that the introduction of La increased the cell volume of alloy and thus improved the hydrogenation kinetic, practical hydrogenation capacity, and cyclic property. The hydrogenation kinetic results of the La-doped alloy indicate that it exhibited a higher hydrogenation rate than that of the La-free alloy. It is ascribed to the formation of LaH3, which provides a fast diffusion channel for hydrogen atoms to enter the alloy matrix. The dehydrogenation enthalpy (ΔH) of the La-doped alloy was calculated by the van't Hoff equation and PCT curves to be ∼18.2 kJ/mol. The cycle test proves that the La-doped Ti1.2CrMn alloy, due to La addition, reduces the lattice expansion and lattice stress and exhibits excellent durability.


Characterization and photocatalytic performance of cement mortars with incorporation of TiO2 and mineral admixtures.
As the main components of the building envelope, construction materials have a straight relation with air contaminants from anthropogenic origins. Titanium dioxide has been recently applied in construction industry products since its photocatalytic properties can be used for pollutant degradation purposes. This study evaluated the performance of cement-based mortars with the incorporation of TiO2 nanoparticles and mineral admixtures. Six mortar compositions were defined by considering two reference mixes (with and without TiO2 incorporation), two mineral admixtures (bentonite and metakaolin) as partial cement replacement and one waste from ornamental stone processing in two levels of partial substitution of natural sand. Consistency index, density, and entrained air content of mixtures were investigated at fresh state. Compressive strength, water absorption, sorptivity, and micrographs from scanning electron microscopy were used to characterize mortars at hardened state. It was observed that incorporation of TiO2 does not considerably change mortar's properties at fresh and hardened state, despite a denser microstructure and improved interfacial transition zone. In general, the relation between the water-to-cement ratio and porosity on the performances of TiO2-added mortars was shown, which is strongly related to their photocatalytic efficiency. Metakaolin mixtures were more efficient to NO conversion, and high selectivity was observed for the bentonite mortars.


[Tuberculous otitis media].
Tuberculous otitis media is a rare disease. Its diagnosis is often made late. We report the case of a 13-year-old girl presenting with a right chronic otitis media and a massive and painful cervical adenitis. High resolution CT-scan revealed cervical and mediastinal adenitis associated with extensive lesions involving the middle ear, mastoid air cells, and sphenoidal bone. The diagnosis of tuberculous otitis media was made on a positive tuberculin skin test and on the identification of Mycobacterium tuberculosis in gastric juices. The young girl progressed well after 9 months of antituberculous chemotherapy.


The radiographic recognition of two clinically elusive mass lesions of the cavernous sinus: meningiomas and aneurysms.
Cavernous sinus syndromes secondary to chronic mass lesions, although a relatively rare cause of ophthalmoplegia, represent a distinct challenge in neuroradiologic diagnosis. Puzzling neuro-ophthalmologic signs and often subtle radiologic changes consistently lead to erroneous and delayed diagnoses as exemplified by a review of 20 patients; a correct clinical or radiographic diagnosis was initially not made in any individual.


Test of a model of decision processes in an intense conflict situation.
A particularly intense form of conflict. It is a situation in which at most one of some set of participants may obtain an objective and in which it is possible that none will obtain their objective. A mathematical model is derived from basic assumptions about the decision making process in a three-person uelative conflict situation, a truel. It is proposed that the model is generalizable to n-person situations. A preliminary test of the model that varied only one of the parameters revealed support for the model. More extensive tests of the model are warranted. In addition, the applicability of the model to internation or intergroup conflict is explored.


Measurement for gap balancing technique in patients undergoing total knee arthroplasty: a large retrospective observational study.
Many traditional methods are available to prevent unbalance of extension and flexion gap during total knee arthroplasty (TKA), but there are no reports on the use of measurement and positioning method before tibial osteotomy with self-made tools. We designed a self-made tool measuring the location before tibial osteotomy and determined the clinical effect. The retrospective study included patients who received TKA at our hospital, between January 1, 2012 and December 31, 2015. A new method, named as the measurement and localization before osteotomy with self-made tools, was developed to measure the osteotomy position of the posterior femoral condyle during TKA. They were divided into two groups, one that received the new method (Group I), and the other that received the traditional method as a control (Group I I). HSS score, Oxford score, VAS score and knee joint activity were evaluated in two groups. One hundred and eighty-seven of 210 eligible patients were included. The function of knee joint in all patients was improved and the pain was obviously relieved. Significant differences were found in the HSS score, Oxford score, VAS score, knee joint activity between two groups at 5-year follow-up (p < 0.05). The biomet knee prosthesis was selected for all intraoperative implants. All operations were completed by the same senior surgeon. The use of self-made tools may contribute to improve the balance between flexion and extension gaps as well as the balance between internal and external gaps during TKA, and overcome knee flexion instability.


Production of extracellular alkaline alpha-amylase by solid state fermentation with a newly isolated Bacillus sp.
Production of alkaline alpha-amylase employing our laboratory isolate, Bacillus sp., under solid state fermentation, was optimized. The effect of wheat bran and lentil husk was examined. Lentil husk exhibited the highest enzyme production. The appropriate incubation time, inoculum size, moisture level, and buffer solution level were determined. Maximum yields of 216,000 and 172,800 U/g were achieved by employing lentil husk and wheat bran as substrates in 0.1 M carbonate/bicarbonate buffer at pH 10.0 with 30% initial moisture level at 24 h. Inoculum size and buffer solution level were found to be 20% and 1:0.5 for two solid substrates.


A Glasgow-Blatchford Bleeding Score of >2 Is a Poor Predictor of Endoscopic Intervention in Nonvariceal Upper GI Bleeding.
Recent data show that a Glasgow-Blatchford Bleeding Score (GBS) >2 does not identify patients with upper gastrointestinal (GI) bleeding who benefit from inpatient esophagogastroduodenoscopy (EGD). This study aimed to determine the rate of endoscopic hemostatic interventions (HI) in patients with nonvariceal acute GI bleeding (NVAUGIB) admitted with a GBS >2. Secondary aims included comparison of clinical outcomes in patients with and without HI and cost of nontherapeutic EGDs. We conducted a retrospective review of medical records of patients admitted to a referral hospital for NVAUGIB from January 2015 to December 2017. Mortality, blood transfusion rates, length of stay, length of intensive care unit stay, and cost of a nontherapeutic EGD were outcomes of interest. Patients 18 years of age and older of both sexes were included. The accuracy of the GBS >2 cutoff was determined using receiver operating characteristic curve analysis. A total of 357 patients were included and only 58 (16.2%) required HI. The area under the curve for GBS >2 as a predictor of HI was 0.57. The performance of HI did not influence mortality (P = 0.33), blood transfusion rates (P = 0.51), length of stay (P = 0.2), or length of intensive care unit stay (P = 0.36). The estimated cost of performing nontherapeutic EGD was approximately $855,000 for the 299 patients who did not need HI. A GBS cutoff of >2 is not an accurate criterion to triage patients with NVAUGIB for inpatient emergent EGD. More clinically meaningful and cost-effective methods to triage these patients are necessary.


The differential distribution and relationship of serotoninergic and peptidergic fibers to sympathoadrenal neurons in the intermediolateral cell column of the rat: a combined retrograde axonal transport and immunofluorescence study.
The preganglionic sympathetic neurons in the intermediolateral cell column of the thoracic and upper lumbar segments of the spinal cord which innervate the chromaffin cells in the adrenal medulla, sympathoadrenal preganglionic neurons, were identified by the method of retrograde axonal transport of the fluorescent dyes Fast Blue and True Blue. In rats, Fast Blue or True Blue was injected into the medulla of the left adrenal gland. After a survival period of 5 days, the animals were perfusion fixed, the thoracic and lumbar spinal cord sectioned and processed for the immunofluorescent localization of met-enkephalin, neurophysin, oxytocin, serotonin, somatostatin and substance P immunoreactivity. Neuronal perikarya which were retrogradedly-labeled with Fast Blue or True Blue were observed in the intermediolateral cell column from the T1 to the L2 spinal cord segments. The distribution of the sympathoadrenal neurons was determined by counting the number of retrogradedly-labeled neurons per spinal cord segment. In the five animals used for quantifying the sympathoadrenal preganglionic neurons, the majority (72.3%) of the retrogradely-labeled neurons counted per spinal cord were located within the T7-T12 segments. The T9 segment contained the largest average number (20.1%) of retrogradely-labeled cells in a single segment. Met-enkephalin, serotonin and substance P immunoreactive fibers were prominent in the intermediolateral cell column, whereas oxytocin, neurophysin and somatostatin immunoreactive fibers were sparse. The met-enkephalin, serotonin and substance P fibers were seen surrounding both unlabeled and retrogradely-labeled neurons; somatostatin fibers appeared to preferentially contact retrogradely-labeled neurons; whereas, the neurophysin and oxytocin fibers were not found in proximity to retrogradely-labeled neurons. Met-enkephalin, neurophysin, oxytocin, somatostatin and substance P immunoreactivity were depleted in the intermediolateral cell column below the level of a spinal cord transection. Serotonin immunoreactivity was depleted in the intermediolateral cell column below the level of the transection for five to six segments, but sparse networks of immunoreactive fibers were observed in both the intermediolateral cell column and the ventral horn in more caudal segments. Met-enkephalin, serotonin, somatostatin and substance P immunoreactivity were decreased in both the contralateral and ipsilateral intermediolateral cell column below the level of a spinal cord hemisection, suggesting that both crossed and uncrossed descending pathways exist. Neurophysin and oxytocin immunoreactivity were depleted below the level of the hemisection in the ipsilateral intermediolateral cell column without noticeable decrease in the level of immunoreactivity in the contralateral intermediolateral cell column, suggesting that a decussation does not occur at the level of the spinal cord, but may exist above the level of the hemisection...


No influence of high- and low-carbohydrate diet on the oral glucose tolerance test in pregnancy.
Our objective was to determine the influence of the carbohydrate content of the diet preceding the oral glucose tolerance test (OGTT) in pregnancy on the test results and to evaluate the necessity of the recommended preparatory high-carbohydrate diet. Thirty-four women from our outpatient clinic were enrolled in this prospective study. After giving informed consent, each women underwent a 90-min lesson (supervised by a dietary assistant) covering the carbohydrate, protein and fat content of different foods. Women were then randomized and in a crossover design started a diet with either a low or a high carbohydrate content. We were aiming at a carbohydrate intake of 40% in the low-carbohydrate week (LCH) and 50% in the high-carbohydrate week (HCH). Compliance was monitored by a detailed food diary which the women kept and which included the weight of the foods they consumed. The actual dietary intakes as calculated from the food diaries showed that the mean caloric intake was 1801 +/- 314 kcal in the LCH and 2118 +/- 312 kcal in the HCH week (<0.001). During the LCH diet, CH intake was 39 +/- 6.1% and 49 +/- 6.6% in the HCH week (P < 0.001). The carbohydrate intake per kilogram bodyweight was 30 +/- 5.3 kcal vs. 35 +/- 5.2 kcal (P < 0.001). The number of patients diagnosed with gestational diabetes was two in the LCH and three in the HCH week (not significant). The sum of the OGTT values (fasting, 1 h and 2 h) after the LCH was 18.9 +/- 2.1 mmol/l vs. 18.8 +/- 2.1 mmol/l after the HCH (P = 0.51). No differences could be found in both groups regarding the fasting, 1-h, or 2-h glucose values. Including patients with a CH difference of at least 5%, 10%, and 15% carbohydrate between the weeks, we still did not observe any differences in the OGTT sum. We also looked at a possible influence of the CH content of the diet on the day before the test and of the last meal before the OGTT results and observed there was none. This is the first study which has observed the influence of the previous day's meal on the test results. We conclude from our results that the carbohydrate percentage of the preparatory diet did not influence the results of an OGTT, even when we increased the difference in carbohydrate intake stepwise up to 15%. This might indicate that a preparatory diet before the OGTT is not necessary for women with normal nutritional behavior.


Why luteinizing-hormone-releasing-hormone nasal spray will not replace orchiopexy in the treatment of boys with undescended testes.
Two courses of LHRH nasal spray (400 micrograms three times a day for 28 days), partly administered in a double-blind placebo-controlled study, resulted in the descent of 48 of 281 testes (18%) in 237 prepuberal boys. Logistic regression analysis confirmed the clinical observation that pretreatment testicular position was the major factor influencing treatment results: the lower the pretreatment testicular position, the better the result. Of the unsuccessfully treated boys, 170 with 196 undescended testes subsequently underwent orchiopexy revealing anatomic anomalies that accounted for failure of hormonal treatment in 80% of the cases. Most frequent finding amounted to an underdeveloped processus vaginalis, extending no further than the level of the pubic bone, often associated with major epididymal deformities and a lack of obliteration of the processus vaginalis (107 of 196 operations). Obstruction of the scrotal entrance due to abnormal Scarpa's fascia or abnormal gubernacular remnant was found in 35 and testicular absence in 15 cases. LHRH nasal spray might be effective when the testis can be manipulated to at least the scrotal entrance before treatment, but in view of our surgical findings, LHRH nasal spray will not replace orchiopexy.


Evaluation of manufacturing feasibility and safety of an MDCK cell-based live attenuated influenza vaccine (LAIV) platform.
Cell culture based live attenuated influenza vaccines (LAIV) as an alternative to egg-based LAIV have been explored because of lack of easy access to SPF eggs for large scale production. In this study, feasibility of MDCK platform was assessed by including multiple LAIV strains covering both type A (H1 and H3) and type B seasonal strains as well as the candidate pandemic potential strains like A/H5 and A/H7 for the growth in MDCK cells. A risk assessment study was conducted on the cell banks to evaluate safety concerns related to tumorigenicity with a regulatory perspective. Tumorigenic potential of the MDCK cells was evaluated in nude mice (107cells/mouse) model system. The 50% tumor producing dose (TPD50) of MDCK cells was studied in SCID mice to determine the amount of cells required for induction of tumors. Further, we conducted an oncogenicity study in three sensitive rodent species as per the requirements specified in the WHO guidelines. We determined TPD50 value of 1.9 X 104 cells/mice through subcutaneous route. Our results suggest that, the intranasal route of administration of the cell culture based LAIV pose minimal to no risk of tumorigenicity associated with the host cells. Also, non-oncogenic nature of MDCK cells was demonstrated. Host cell DNA in the vaccine formulations was < 10 ng/dose which ensures vaccine safety. Production efficiency and consistency were characterized and the observed titer values of the viral harvest and the processed bulk were comparable to the expansion in embryonated eggs. The present study clearly establishes the suitability of MDCK cells as a substrate for the manufacture of a safe and viable LAIV.