Change of the peripheral blood immune pattern and its correlation with prognosis in patients with liver cancer treated by sorafenib.
To study the change of the peripheral blood immune pattern and its correlation with prognosis in patients with liver cancer after treated by sorafenib. Patients with advanced liver cancer admitted in our hospital were enrolled and treated with sorafenib. After two months of the treatment, their peripheral blood was collected. The immune cell subset and cytokines level were determined by flow cytometry and luminex technology. According to the reaction expressed by patients towards sorafenib, patients were divided into the response group and the no response group. The changes of the peripheral blood immune pattern and its correlation with prognosis of patients in the two groups were compared. Before and after treatment of sorafenib, there was no significant difference in the ratios of T cells, NK cells and their subtypes in peripheral blood of patients between the two groups; while after treatment the ratio of B cells and regulatory B cells (Breg) of patients in the response group was significant higher than that of the no response group (P < 0.05), and the prognosis conditions of patients with decreased ratio of Breg cells were better than other patients after undergoing chemotherapy. The levels of plasma cytokines IL-6, IL-10, IL-12, IL17, FIL-3L, IFN-γ, TNF-α, MCP-1 and VEGF showed no significant differences. After treatment of sorafenib, the prognosis conditions of patients of advanced liver cancer with a reduced Breg ratio are better than patients with an unaltered or increased Breg ratio. The ratio of Breg in peripheral blood may be considered as early biological indicator for the prediction of the curative effects of sorafenib.


Feedback inhibition of Jak/STAT signaling by apontic is required to limit an invasive cell population.
In both normal development and in a variety of pathological conditions, epithelial cells can acquire migratory and invasive properties. Border cells in the Drosophila ovary provide a genetically tractable model for elucidating the mechanisms controlling such behaviors. Here we report the identification of a mutant, apontic (apt), in which the migratory population expanded and separation from the epithelium was impeded. This phenotype resembled gain-of-function of JAK/STAT activity. Gain-of-function of APT also mimicked loss of function of STAT and its key downstream target, SLBO. APT expression was induced by STAT, which bound directly to sites in the apt gene. The data suggest that a regulatory circuit between STAT, APT, and SLBO functions to convert an initially graded signal into an all-or-nothing activation of JAK/STAT and thus to proper cell specification and migration. These findings are supported by a mathematical model, which accurately simulates wild-type and mutant phenotypes.


Neuropeptide Y-immunoreactive neuronal system and colocalization with FMRFamide in the optic lobe and peduncle complex of the octopus (Octopus vulgaris).
The distribution of neuropeptide Y (NPY)-like immunoreactivity and its colocalization with FMRFamide were investigated in the optic lobe and peduncle complex of the octopus ( Octopus vulgaris) by using immunohistochemical techniques. In the optic lobe cortex, NPY-immunoreactive (NPY-IR) fibers were observed in the plexiform layer, although no NPY-IR somata were observed in the outer or inner granular cell layers. In the optic lobe medulla, NPY-IR somata were seen in the cell islands, and abundant NPY-IR varicose fibers were observed in the neuropil. Most of the NPY-IR structures in the medulla showed FMRFamide-like immunoreactivity. In the peduncle lobe, abundant NPY-IR and FMRFamide-IR (NPY/FMRF-IR) varicose fibers were seen in the basal zone neuropil of the peduncle lobe. In the olfactory lobe, NPY/FMRF-IR varicose fibers were also abundant in the neuropil of the three lobules. NPY/FMRF-IR somata, with processes running to various neuropils, were scattered in the median and posterior lobules. In the optic gland, many NPY/FMRF-IR varicose fibers formed a honeycomb pattern. These observations suggest that NPY/FMRF-IR neurons in the optic lobes participate in the modulation of visual information and that those in the optic gland are involved in the regulation of endocrine function.


Glycerol kinase deficiency in adults: Description of 4 novel cases, systematic review and development of a clinical diagnostic score.
Glycerol kinase deficiency (GKD) is a rare genetic disorder characterized by hyperglycerolemia and glyceroluria, which could be misdiagnosed as a moderate to severe hypertriglyceridemia (HTG). We aimed to describe four novel cases of GKD, to complete a systematic review of all cases of isolated GKD published so far, and to develop a suspicion clinical diagnostic score for GKD. We reported four cases with suspicion of GKD and compared their phenotype with 584 males with triglycerides (TG) > 300 mg/dL, selected as control group (HTG non-GKD). The GK gene was sequenced in all cases. Lipoprotein particle concentrations were measured in all cases with GKD. The systematic review involved a PubMed, Cochrane and Scopus databases search to identify anthropometric and biochemical characteristics of all described cases with GKD. The systematic review retrieved a total of 15 articles involving 39 subjects with GKD. GKD cases reported a history of high TG levels resistant to lipid-lowering therapy. Compared to GKD subjects (n = 43), HTG non-GKD subjects (n = 584) showed significantly higher BMI, total cholesterol, non-HDL cholesterol and gamma-glutamyltransferase, significantly lower HDL cholesterol and TG, and higher prevalence of diabetes. The proposed diagnostic score was significantly higher in GKD than in HTG non-GKD subjects. This is the first systematic review that compiles all GKD cases reported to date including 4 novel cases, and examine the differential GKD phenotype compared to other types of HTG. The proposed score would have a broad utility in clinical practice to avoid unwarranted lipid lowering treatment in GKD patients.


The Landmark Series: Chemotherapy for Non-Metastatic Colon Cancer.
Micrometastatic disease that is present at the time of surgery is responsible for the overwhelming majority of deaths in patients with what is otherwise perceived to be local and regional colon cancer. The goal of perioperative therapy is to eliminate microscopic residual disease that would otherwise be left behind following surgery. A secondary goal specific to neoadjuvant (preoperative) therapy is to downstage tumors deemed potentially not amenable to an R0 resection on the basis of a suspected T4b primary (locally invading into a surrounding structure). In this landmark series paper, we review the current standard for perioperative therapy in patients with colon cancer.


Protective effects of hesperidin on oxidative stress, dyslipidaemia and histological changes in iron-induced hepatic and renal toxicity in rats.
The present study was to evaluate the protective role of hesperidin (HDN) against iron-induced hepatic and renal toxicity in rats. Administration of iron (30 mg/kg body weight) intraperitoneally for 10 days, the levels of serum hepatic markers, renal functional markers, lipid profile, lipid peroxidation markers and iron concentration in blood were significantly (p < 0.05) increased. The toxic effect of iron was also indicated by significant (p < 0.05) decrease in the levels of plasma, liver and kidney of enzymatic and non-enzymatic antioxidants. Administration of hesperidin at different doses (20, 40 and 80 mg/kg body weight) significantly (p < 0.05) reversed the levels of serum hepatic markers, renal functional markers, lipid profile, lipid peroxidation markers, restored the levels of hepatic, renal enzymatic antioxidants and non-enzymatic antioxidants with decrease in iron concentration in blood. Hesperidin at a dose of 80 mg/kg body weight exhibits significant protection on hepatic and renal when compared with other two doses (20 and 40 mg/kg body weight). All these changes were corroborating by histological observations of liver and kidney. This study demonstrated the protective role of hesperidin in reducing toxic effects of iron in experimental rats.


New real-time analytical applications of electrochemical quartz crystal microbalance Stoichiometry and phase composition monitoring of electrodeposited thin chalcogenide films.
The electrochemical quartz crystal microbalance (EQCM) has recently gained increasing popularity as a powerful tool for electrochemical interface examinations. This paper reports on its great potential for developing new real-time analytical protocols. Potentiostatic coulometry is used in conjunction with quartz crystal microgravimetry (QCMg) with controlled hydrodynamics to develop two new analytical procedures: real-time stoichiometry monitoring of electrodeposited binary chalcogenide films and phase composition quantification of electrodeposited ternary chalcogenide compounds. The newly developed EQCM methods are illustrated on the examples of Ag2+deltaSe-electrodeposited films and the electroformation of ternary CuAgSe-films. Both compounds have been successfully used as ion-selective membranes for flow-injection detectors. The experimental set-up including hydrodynamic control, the main strategy of the approach used and its scope and limitations are broadly discussed. The obtained data allow for real time profile monitoring of either stoichiometry (Ag2+deltaSe-case) or phase composition (CuAgSe-case).


Sources and targets of nitric oxide in rat cerebellum.
Nitric oxide (NO) mediates cell-cell signalling in the brain and stimulates cyclic GMP (cGMP) production in target cells. We have used NADPH-diaphorase (reduced nicotinamide adenine dinucleotide phosphate-diaphorase) histochemistry to identify NO-producing neurones and cGMP immunohistochemistry to locate the targets of NO in rat cerebellum. NADPH-diaphorase staining was prominent in granule cells and in the molecular layer. cGMP immunostaining in cerebellar slices stimulated with the NO donors, nitroprusside and SIN-1, was found in granule cells, glomeruli, fibres, Bergmann glia and in other astrocytes. The results provide visible evidence that NO mediates neuron-neuron and neuron-glia communication.


Contribution of proteasome-catalyzed peptide cis-splicing to viral targeting by CD8+ T cells in HIV-1 infection.
Peptides generated by proteasome-catalyzed splicing of noncontiguous amino acid sequences have been shown to constitute a source of nontemplated human leukocyte antigen class I (HLA-I) epitopes, but their role in pathogen-specific immunity remains unknown. CD8+ T cells are key mediators of HIV type 1 (HIV-1) control, and identification of novel epitopes to enhance targeting of infected cells is a priority for prophylactic and therapeutic strategies. To explore the contribution of proteasome-catalyzed peptide splicing (PCPS) to HIV-1 epitope generation, we developed a broadly applicable mass spectrometry-based discovery workflow that we employed to identify spliced HLA-I-bound peptides on HIV-infected cells. We demonstrate that HIV-1-derived spliced peptides comprise a relatively minor component of the HLA-I-bound viral immunopeptidome. Although spliced HIV-1 peptides may elicit CD8+ T cell responses relatively infrequently during infection, CD8+ T cells primed by partially overlapping contiguous epitopes in HIV-infected individuals were able to cross-recognize spliced viral peptides, suggesting a potential role for PCPS in restricting HIV-1 escape pathways. Vaccine-mediated priming of responses to spliced HIV-1 epitopes could thus provide a novel means of exploiting epitope targets typically underutilized during natural infection.


Gendered Racial Microaggressions, Self-silencing, Substance Use, and HIV Outcomes Among Black Women Living with HIV: A Structural Equation Modeling Approach.
To better understand factors that may contribute to HIV outcomes experienced by Black women living with HIV (BWLWH), the present study examined the relationships among gendered racial microaggressions (GRM; subtle daily insults due to racism and sexism), self-silencing, substance use, antiretroviral therapy (ART) medication adherence, and viral suppression using structural equation modeling and path analysis. Self-silencing and substance use were examined as potential mediators. Participants were 119 BWLWH residing in South Florida. Results of this study showed that GRM was directly and positively associated with self-silencing and indirectly and negatively associated with medication adherence via self-silencing. GRM was directly related to higher alcohol use disorder severity. Self-silencing was directly and negatively associated with medication adherence. Medication adherence was directly and negatively related to viral suppression. The model fit the data well. Identifying the negative consequences of GRM in conjunction with self-silencing and substance use may help inform prevention and intervention strategies to improve mental health and HIV-related outcomes among BWLWH.


Validity of self-reported migraine in adolescents and children.
To assess agreement for migraine day between self-report and diagnostic guidelines for children and adolescents using a headache diary. Trial guidelines recommend prospective collection of headache features and adoption of migraine day as an outcome measure, but there is no clear consensus on the definition of migraine day. This is a secondary analysis of data from two projects-a prospective cohort study validating a pediatric scale of treatment expectancy and a clinical trial of occipital nerve blocks to treat status migrainosus. Participants completed a text message-based diary for 4 or 12 weeks (depending on treatment), and a detailed headache assessment on a random 20% of headache days. Using this assessment, we determined whether a headache day qualified for migraine or probable migraine, based on the International Classification of Headache Disorders, 3rd edition (ICHD-3). Of 122 enrolled children and adolescents, 106 (86.9%) completed ≥1 detailed headache assessment (438 entries). We found moderate agreement between self-reported and ICHD-derived migraine day, with a Cohen's Kappa of 0.50 (positive predictive value [PPV]: 0.66; negative predictive value [NPV]: 0.85; correlation: 0.51). Allowing for ICHD-derived probable migraine significantly increased PPV (0.66 vs. 0.94; 95% CI: 0.57-0.74 vs. 0.90-0.97), but decreased NPV (0.85 vs. 0.293; CI: 0.77-0.90 vs. 0.199-0.40), Cohen's Kappa (0.50 vs. 0.237; CI: 0. 389-0.60 vs. 0.139-0.352), and correlation (r = 0.51 vs. 0.302; CI: 0.41-0.61 vs. 0.192-0.41). Pain severity (OR: 5.7; CI: 2.39-13.8), photophobia (OR: 4.1; CI: 1.02-16.6), and phonophobia (OR: 7.5; CI: 1.95-29.3) were significantly associated with participants' perception of migraine. We found only moderate agreement between self-reported and ICHD-derived migraine day, suggesting both measures are not equal but may represent overlapping aspects of migraine as a disease. This highlights the difficulty of applying ICHD criteria to individual attacks. We recommend greater methodological transparency in future research to avoid readers conflating both measures.


Mindfulness meditation program for the elderly in Korea: A preliminary review for planning the program.
The significance of mindfulness meditation (MM) has increased in recent years in both clinical settings and public health. However, ways to implement MM as a disease prevention or treatment method in the elderly is still a major challenge. A comprehensive analysis of previous studies on MM programs for the elderly in Korea will help build future integrated care programs that incorporate MM. Seven international and Korean domestic electronic databases were searched to collect relevant clinical studies until May 30, 2020. Sixteen articles with twelve clinical studies were included in this review. The MM program was generally offered once a week over eight weeks with a duration of between 60 and 90 min per session. The main reason for participants' drop out was poor program compliance attributed to conflicting schedules, physical illness, or a change of mind. The program results were either positive or mixed, but the mindfulness level of the participants was improved. This review summarizes information obtained from previously published studies in Korea, on the design considerations, characteristics, and preliminary effectiveness of the MM program for the elderly. The findings can be used as preliminary data by future practitioners and/or researchers to design MM programs targeted toward the elderly; it could also help policymakers integrate MM-based strategies into integrated care programs to promote their mental health and well-being.


Moringa oleifera: a valuable insight into recent advances in medicinal uses and pharmacological activities.
Moringa oleifera is an important medicinal plant in several countries; for example, Nigeria, the USA, Turkey, Germany, Greece, and Ukraine. The abundant bioactive and nutritional properties of this plant make it useful in many and diverse areas of life, including the health, cosmetic, agricultural, and food industries to mention but a few. Research has found that the presence of proteins, carbohydrates, lipids, vitamins, minerals, flavonoids, phenols, alkaloids, fatty acids, saponins, essential oils, folate, aromatic hydrocarbons, sterols, glucosinolates, and glycosides, among others, characterize the moringa nutrient profile and, as a result, give rise to its remedial effects on ailments such as wounds, stomach and duodenal ulcers, allergies, obesity, diabetes, inflammation, asthma, and so on. It is the aim of this review to provide an insight into such medicinal and pharmacological remedies attributed to moringa, stating both the past and recent discoveries. This review article also takes a look into the botanical features, bioactive compounds, antinutrients, food applications, bacterial fermentation products, biosafety, industrial applications, and other uses of moringa. Finally, with the belief that knowledge is progressive, we acknowledge that there are things yet undiscovered about this wonder plant that will be of value both to medicine and general life; we therefore recommend that research work continues on the moringa plant. © 2023 Society of Chemical Industry.


Down-regulation of phorbol diester binding to NG115-401L neuronal cells is dependent on structure, concentration and time.
The down-regulation of [3H]PDBu binding to a neural cell line, NG115-401L, has been examined in response to two biologically active phorbol diesters, PDBu and PMA. Chronic treatment with PDBu or PMA causes a concentration- and time-dependent loss of specific [3H]PDBu binding. The action of PMA is biphasic with respect to both concentration and time dependence.


Flibanserin, a potential antidepressant drug, lowers 5-HT and raises dopamine and noradrenaline in the rat prefrontal cortex dialysate: role of 5-HT(1A) receptors.
(1) Using in vivo intracerebral microdialysis in conscious, freely moving rats, we examined the effect of flibanserin, a potential antidepressant drug with high affinity for human 5-HT(1A) receptors and four-50-fold lower affinity for 5-HT(2A) and D(4) receptors, on basal extracellular concentrations of serotonin (5-hydroxytryptamine, 5-HT), dopamine (DA) and noradrenaline (NA) in selected regions of the rat brain. (2) Flibanserin at 3 and 10 mg kg(-1) significantly reduced extracellular 5-HT in the prefrontal cortex (by 30 and 45%) and dorsal raphe (35 and 44%), but had no effect on extracellular 5-HT in the ventral hippocampus. The 3 and 10 mg kg(-1) doses raised extracellular NA to a similar extent in the prefrontal cortex (47 and 50%). In all, 10 mg kg(-1) raised extracellular DA in the prefrontal cortex (63%) whereas 3 mg kg(-1) had no significant effect. (3) Pretreatment with the selective 5-HT(1A) receptor antagonist WAY100,635 (0.3 mg kg(-1)) 30 min before 10 mg kg(-1) flibanserin completely antagonized the latter's effects on extracellular 5-HT, DA and NA in the prefrontal cortex. WAY100,635 by itself had no effect on cortical extracellular monoamines. (4) The results show that the stimulation of 5-HT(1A) receptors plays a major role in the effect of flibanserin on brain extracellular 5-HT, DA and NA.


Ambiguities within the ASTRO consensus definition of biochemical failure: never assume all is equal.
To quantitate the impact of a number of variables within the American Society of Therapeutic Radiology and Oncology consensus definition (ACD) of biochemical failure (bF) for prostate cancer. The prostate-specific antigen (PSA) data of 1050 men with prostatic adenocarcinoma treated between 1990 and 1997 with external beam radiotherapy monotherapy was examined. A total of 10,872 PSA results were examined for the effect of backdating, stable values, possible nadir date variations, assay resolution, and assay lower limit. Test timing was analyzed according to attendance frequency (mean time between tests [MTBT]) and regularity (using a derived "Irregularity Index" [II]). Median biochemical follow-up was 76 months. Nadir date alterations varied the rate of bF beyond 5 years between 0.8% and 5.3%. The bF rate of all MTBT and II quartiles subgroups differed significantly except between the two most regular and the two most infrequent quartiles. Multivariate analysis showed PSA, MTBT, and II to be statistically significant independent predictors of bF (p < 0.0001 for all). Many variables exist within the ACD that can produce inconsistencies in bF determination or alter the calculated date of bF. Detection bias issues, especially related to test timing, play a significant role in the derived outcomes.


Cataract and type 1 diabetes mellitus.
To evaluate the prevalence of cataract and the possible factors associated with cataract in young type 1 diabetes mellitus (DM). 293 patients were evaluated. The association of cataract with diabetic retinopathy (DR), retinal laser treatment, hypertension, body mass index, peripheral neuropathy, lipid profile, glycemic control, serum creatinine and albuminuria was evaluated. Cataract was present in 19.8% (n=58) of the sample. Patients with cataracts were older, had a higher frequency of history of retina photocoagulation treatment, higher serum creatinine values and higher prevalence of arterial hypertension. There was a progressive increase in cataract frequency according to the number of risk factors, starting to rise with two or more. In logistic regression model cataract was associated with mild/moderate DR (odd ratio (OR) 4.28 95% CI 1.63-11.29), severe DR (OR 4.07 95% CI 1.63-10.23) and macroalbuminuria (OR 2.34 95% CI 1.06-5.16). These data indicate a high prevalence of cataract in subjects with type 1 DM attending a general hospital in Southern Brazil and suggest that the more severe the disease process the greater is the risk of having this diabetic complication. Cataract should be suspected in young patients with two or more risk factors.


The polyhedric reality of the interaction between COVID-19, asthma and inhaled corticosteroids.
The impact of ICS on the prognosis for #COVID19 in #asthma patients requires a thorough evaluation of a range of factors that interact in this process, in order to draw solid conclusions, since at the present time the debate continues https://bit.ly/3xLNBrc.


Judicious Heteroatom Doping Produces High-Performance Deep-Blue/Near-UV Multiresonant Thermally Activated Delayed Fluorescence OLEDs.
Two multiresonant thermally activated delayed fluorescence (MR-TADF) emitters are presented and it is shown how further borylation of a deep-blue MR-TADF emitter, DIDOBNA-N, both blueshifts and narrows the emission producing a new near-UV MR-TADF emitter, MesB-DIDOBNA-N, are shown. DIDOBNA-N emits bright blue light (ΦPL = 444 nm, FWHM = 64 nm, ΦPL = 81%, τd = 23 ms, 1.5 wt% in TSPO1). The deep-blue organic light-emitting diode (OLED) based on this twisted MR-TADF compound shows a very high maximum external quantum efficiency (EQEmax ) of 15.3% for a device with CIEy of 0.073. The fused planar MR-TADF emitter, MesB-DIDOBNA-N shows efficient and narrowband near-UV emission (λPL = 402 nm, FWHM = 19 nm, ΦPL = 74.7%, τd = 133 ms, 1.5 wt% in TSPO1). The best OLED with MesB-DIDOBNA-N, doped in a co-host, shows the highest efficiency reported for a near-UV OLED at 16.2%. With a CIEy coordinate of 0.049, this device also shows the bluest EL reported for a MR-TADF OLED to date.


Nanoscale biomaterials for terahertz imaging: A non-invasive approach for early cancer detection.
Terahertz (THz) technology is developing a non-invasive imaging system for biosensing and clinical diagnosis. THz medical imaging mainly benefits from great sensitivity in detecting changes in water content and structural variations in diseased cells versus normal tissues. Compared to healthy tissues, cancerous tumors contain a higher level of water molecules and show structural changes, resulting in different THz absorption. Here we described the principle of THz imaging and advancement in the field of translational biomedicine and early detection of pathologic tissue, with a particular focus on oncology. In addition, although the main forte of THz imaging relies on detecting differences in water content to distinguish the exact margin of tumor, THz displays limited contrast in living tissue for in-vivo clinical imaging. In the last few years, nanotechnology has attracted attention to aid THz medical imaging and various nanoparticles have been investigated as contrast enhancements to improve the accuracy, sensitivity, and specificity of THz images. Most of these multimodal contrast agents take advantage of the temperature-dependent of THz spectrum to the conformational variation of the water molecule. We discuss advances in developing THz contrast agents to accelerate the advancement of non-invasive THz imaging with improved sensitivity and specificity for translational clinical oncology.


Suggested involvement of ketone bodies in the pathogenesis of the metabolic syndrome.
Untreated brain mitochondria are strong producers of H2O2. High peroxide production (in the presence of glutamate and pyruvate) is strictly succinate-dependent. Importantly, it is inhibited by the ketone body acetoacetate (AcAc) starting at 10 μM (maximal effect at 0.5mM). Butyrate derives from the fermentation of prebiotics, is present physiologically in the colon and is a strong producer of AcAc: indeed butyrate induces in the colon the transcription of mitochondrial 3-hydroxy-3-methyl glutarylCoA (HMGCoA) synthase, a key enzyme in ketone body synthesis. Obesity and insulin resistance were shown to be dependent on increased permeability of the colon epithelium to bacterial lipopolysaccharide (LPS); the process is evident particularly upon ingestion of lipids (a peroxidative event, inhibited by vitamin E) and is likely sensitive to AcAc. The oxidation of butyrate and the production of AcAc in the colon appear to be inhibited by high luminal sulphides and high NH3, a situation that presumably facilitates LPS permeation (on the contrary beta-hydroxy-butyrate oxidation is not inhibited). It is proposed that these damaging events may be opposed by the delivery of ketone bodies directly to the colon.


Two-chain structure of T-suppressor factor: antigen-specific T-suppressor factor occurs as a single molecule and as separate antigen-binding and I-J+ parts, both of which are required for biological activity.
Antigen-specific T-suppressor factor (TsF), which acts at the expression stage of the contract sensitivity reaction, was produced by culturing the lymphoid cells of mice injected with picryl-sulphonic (trinitrobenzenesulphonic) acid and then painted with picryl chloride. Supernatant activity was found around 50-60 and 90 kDa on Sephadex gel filtration. The activity at 50-60 kDa was due to two separate (or readily separable) molecules, one antigen binding and the other bearing I-J determinants as shown by affinity chromatography on insolubilized antigen and anti-I-J. These two separate molecules were inactive alone but complemented each other and may be designated as the variable chain of TsF (TsFv) and the I-J+ chain. The use of gel filtration and sequential absorption of individual pools on anti-I-J antibody followed by antigen, together with a complementation assay, also showed a TSFv chain at 30-40 kDa and an I-J+ chain at 20-30 kDa. The higher-molecular-weight activity around 90 kDa was due to a single molecule which was both antigen binding and I-J+. This molecule dissociated on treatment with the reducing agent dithioerythritol followed by alkylation into two separate chains, one antigen binding and the other I-J+, both of which were required for activity. There was a requirement for genetic matching between the antigen-binding chain (TsFv) and the I-J+ chain for biological activity. These data support a two-chain model of TsF in which TsFv and the I-J+ chain occur as a single disulphide-bonded molecule around 90 kDa, or as two separate (or readily separable) chains of lower molecular weight which were inactive alone but complemented each other.


The Role of Sex in Sleep Deprivation Related Changes of Nociception and Conditioned Pain Modulation.
Sex matters both in the clinical field of pain and sleep medicine. Sleep disturbances are highly prevalent in chronic pain patients and have been shown to deteriorate the pain condition. The pathomechanisms by which insomnia aggravates pain are currently unknown. Descending pain control may be compromised by disturbed sleep, but respective studies are few, inconsistent and largely imbalanced with respect to sex. We studied the role of sex on the effect of sleep deprivation on endogenous pain modulation and on nociceptive thresholds in a highly homogenous study population of 18 female (23.8 ± 3.4 years) and 18 male (23.3 ± 2.7) healthy students. One night of total sleep deprivation (TSD) was contrasted with one night of habitual sleep in a balanced cross-over design. A cold pressor test was used to explore the effect of TSD on supraspinal pain control. The effect of TSD on nociception was examined by Quantitative Sensory Testing (QST). RM-ANOVA was used for statistical analysis. We found a sex-dependent effect of TSD on descending pain pathways, since the endogenous capacity to inhibit pain was only reduced in sleep deprived females (interaction between 'sleep condition' and 'sex': p = 0.023). While TSD-induced cold and mechanical hyperalgesia were independent of sex, heat pain thresholds did only significantly decrease in sleep deprived females (p = 0.041). Our results point to a sex specific impact of TSD on descending pain inhibition. In the future, therapeutic strategies for pain patients with co-morbid insomnia may need to more explicitly respect the specific role of sex.


Synthesis of andrographolide derivatives and their TNF-alpha and IL-6 expression inhibitory activities.
The synthesis of a series of andrographolide derivatives was described and their inhibitory effects on TNF-alpha and IL-6 secretion in mouse macrophages were also evaluated. Most of the tested compounds showed inhibitory effects, and the compounds with the structure of 12-hydroxy-14-dehydroandrographolide showed better inhibitory activity than the compounds with the structure of isoandrographolide.


Subcortical substrates of TMS induced modulation of the cortico-cortical connectivity.
Transcranial magnetic stimulation (TMS) can modulate transiently the physiological brain oscillations, e.g. the alpha rhythm. It has been hypothesized that this effect is not limited to the stimulated region but involves subcortical and distant cortical areas. We applied single pulse TMS to the primary motor cortex (M1) of healthy subjects to interfere the cortical oscillatory activity recorded by simultaneous EEG and calculated the cortico-cortical coherence and power in the alpha and beta band. To study the structural substrate of the functional connectivity we performed diffusion tensor imaging and fractional anisotropy analysis (FA). To capture the pathways involved we applied probabilistic tractography to reconstruct the entire network. Suprathreshold TMS of M1 induced a consistent enhancement of interhemispheric cortico-cortical alpha band coherence that lasted ca. 175 ms. after the pulse has been applied. The changes were confined to the interhemispheric central EEG electrodes (i.e. C3-C4). There were no consistent changes in the beta band. Power analysis revealed a longer lasting increase in the beta band after TMS pulses. A cluster in the contralateral thalamus showed a linear relationship between regional FA and TMS induced change in alpha band coherence. Probabilistic tractography presents the transcallosal and the contralateral thalamocortical pathways as essential for the observed oscillatory synchronisation. TMS induces an enhancement of oscillatory interaction between corresponding central regions of both hemispheres in the alpha band. The contralateral thalamus, transcallosal fibres and the contralateral thalamocortical pathways may constitute critical brain structures mediating the TMS induced change in oscillatory coupling.


The role of myogenic mechanisms in human cerebrovascular regulation.
Although myogenic mechanisms have been hypothesized to play a role in cerebrovascular regulation, previous data from both animals and humans have not provided an unequivocal answer. However, cerebral autoregulation is explicitly non-linear and most prior work relied on simple linear approaches for assessment, potentially missing important changes in autoregulatory characteristics. Therefore, we examined cerebral blood flow responses to augmented arterial pressure oscillations with and without calcium channel blockade (nicardipine) during blood pressure fluctuations (oscillatory lower body negative pressure, OLBNP) across a range of frequencies in 16 healthy subjects. Autoregulation was characterized via a robust non-linear method (projection pursuit regression, PPR). Blockade resulted in significant tachycardia, a modest but significant elevation in mean arterial pressure, and reductions in mean cerebral blood flow and end-tidal CO2 during OLBNP. The reductions in flow were directly related to the reductions in CO2 (r = 0.57). While linear cross-spectral analysis showed that the relationship between pressure-flow fluctuations was preserved after blockade, PPR showed that blockade significantly altered the non-linearity between pressure and flow, particularly at the slowest fluctuations. At 0.03 Hz, blockade reduced the range of pressure fluctuations that can be buffered (7.5 ± 1.0 vs. 3.7 ± 0.8 mmHg) while increasing the autoregulatory slope (0.10 ± 0.05 vs. 0.24 ± 0.08 cm s(-1) mmHg(-1)). Furthermore, the same rate of change in pressure elicited a change in flow more than twice as large as at baseline. Thus, our results show that myogenic mechanisms play a significant role in cerebrovascular regulation but this may not be appreciated without adequately characterizing the non-linearities inherent in cerebrovascular regulation.


Resurrection grasses in India.
A search for desiccation tolerant grasses in India revealed nine grass species (in the genera Eragrostiella, Oropetium and Tripogon) whose ability to recover from airdryness had not previously been reported. Dry leaves of these species recover uninjured within 24 h of plants receiving water. Desiccation tolerance limits were 0%-11% RH (at 28°C). Some species were relatively tall and vigorous and may be useful for grazing purposes in arid areas.


Cassava root meal in diets for growing rabbits.
The effects of substituting imported cassava root meal for barley meal in rations for growing rabbits were examined. Four diets were used. Diet 1 contained 500 g/kg barley meal, the remainder of the diet consisted of soya bean meal, barley straw, vitamins and minerals. Diets 2, 3 and 4 contained increasing amounts of cassava root meal in place of barley meal at 165, 335 and 500 g/kg respectively with L-lysine and DL methionine supplements. A growth trial was carried out using 48 individually caged rabbits from 0.8 kg to 2.0 kg and the digestibilities of the diets were determined in balance trials. Growth rates were similar on all treatments (41.6, 43.1, 40.6 and 41.0 g/d respectively, s.e.d. 2.39), as were dry matter food conversion ratios (2.27:1 overall). The cassava meal appeared to have a digestible energy approximately 1.6 MJ/kg DM higher than that of the barley meal. There appeared to be no adverse effects of feeding diets containing 500 g/kg cassava root meal on animal health. The intrinsic variability in chemical composition of cassava root products is discussed.


Impairments in the acquisition, retention and selection of spatial navigation strategies after medial caudate-putamen lesions in rats.
Using the Morris swimming pool test of spatial navigation, medial caudate-putamen lesions in rats produce impairments in the acquisition and retention of both place and cue tasks, and impair the selection of normal navigation strategies. Also described are some novel features of spatial navigation behaviour displayed by control animals in cue and place tasks that provide insights into the performance of the caudate-putamen rats. Analyses of the swim patterns on postacquisition probe trials, in which the target platform was removed or relocated, showed that the strategy used by the caudate-putamen lesioned rats was dependent upon the task that they were required to solve. Control rats used a place strategy and distal visual cues to identify the location of the start points, the routes from the start points to the platform, and the location of the platform on both the cue and place tasks. The caudate-putamen lesioned rats used distal visual cues and a place strategy only to acquire the place task. They solved the cue task using a taxon strategy consisting of a combination of proximal and position response cues. The results suggest that when necessary, medial caudate-putamen lesioned rats, like normal rats, can use place strategies for spatial navigation, but if an alternate, perhaps simpler, taxon solution is available they seemingly ignore place information and navigate using the simpler strategy. The deficit, which has features of a neglect rather than a loss of ability per se, suggests that medial caudate-putamen neural systems are involved in the selection of alternative strategies in spatial navigation tasks.


Insulinoma: clinical manifestations, diagnosis and treatment. The significance of the prolonged fasting test and of the fasting blood glucose-insulin relationship.
This paper describes the clinical manifestations and the significance of the fasting blood glucose-insulin relationship and the prolonged fasting test in the diagnosis of insulinoma. Pre-and postoperative results are reported. In addition, a description is given of the angiographic demonstration and the results of the surgical removal of the insulinomas.


Estimating the gap between demand and supply of medical appointments by physicians for hypertension care: a pooled analysis in 191 countries.
With a growing number of people with hypertension, the limited number of physicians could not provide treatment to all patients. We quantified the gap between medical appointments available and needed for hypertension care, overall and in relation to hypertension treatment cascade metrics. Ecological descriptive analysis. We combined country-year-specific data on hypertension prevalence, awareness, treatment and control (from Non-Communicable Disease Risk Factor Collaboration) and number of physicians (from WHO). We estimated from 1 to 12 medical appointments per year for patients with hypertension. We assumed that physicians could see 25 patients per day, work 200 days/year and dedicate 10% of their time to hypertension care. We studied 191 countries. Forty-one countries would not have enough physicians to provide at least one medical appointment per year to all the population with hypertension; these countries were low/lower middle income and in sub-Saharan Africa or East Asia and Pacific. Regardless of the world region, ≥50% of countries would not have enough physicians to provide ≥8 medical appointments to their population with hypertension. Countries where the demand exceeded the offer of medical appointments for hypertension care had worse hypertension diagnosis, treatment and control rates than countries where the demand did not exceed the offer. There were positive correlations between the physician density and hypertension diagnosis (r=0.70, p<0.001), treatment (r=0.70, p<0.001) and control (r=0.59, p<0.001). Where physicians are the only healthcare professionals allowed to prescribe antihypertensive medications, particularly in low and middle-income countries, the healthcare system may struggle to deliver antihypertensive treatment to patients with hypertension.


Retinectomy vs vitrectomy combined with scleral buckling in repair of posterior segment open-globe injuries with retinal incarceration.
PurposeTo evaluate the anatomic and functional outcome of pars plana vitrectomy (PPV) combined with scleral buckling (SB) vs retinectomy in treating posterior segment open-globe injuries with retinal incarceration.MethodsPatients (38 eyes) with posterior segment open-globe injuries and retinal incarceration were identified, and they underwent either PPV combined with SB (PPV+SB, n=19) or retinectomy (n=19). The two groups were matched in the following categories: the severity of injury (including wound length), the location of the incarceration site and the presence of retinal detachment. Anatomic reattachment of the retina and best-corrected visual acuity (BCVA) were measured at the time of 12 months after operation.ResultsAt 12 months after operation, the PPV+SB group demonstrated a better anatomic retinal attachment rate (84.2% vs 68.4%, P=0.252) and BCVA (73.7% vs 47.4%, P=0.247) compared with the retinectomy group, however, the differences failed to reach statistical significance. Compared with the PPV+SB group, the rectinectomy group had significantly higher rates of hemorrhage (47.4% vs 15.8%, P=0.036), inflammation (42.1% vs 10.5%, P=0.027), and a lower intraocular pressure (IOP, 9.8±3.1 vs 13.6±4.1 mmHg, P=0.002) after silicone oil (SO) removal.ConclusionsFor patients with posterior segment open-globe injuries and retinal incarceration, PPV and SB treatments resulted in a better anatomic and functional outcome and less post-operation complications compared with the retinectomy.


Effect of opioid-substitution therapy and mental health counseling on HIV risk among hepatitis C-infected individuals.
Understanding differences in HIV incidence among people living with hepatitis C virus (HCV) can help inform strategies to prevent HIV infection. We estimated the time to HIV diagnosis among HCV-positive individuals and evaluated factors that could affect HIV-infection risk in this population. The British Columbia Hepatitis Testers Cohort includes all BC residents (~1.5 million: about a third of all residents) tested for HCV and HIV from 1990 to 2013 and is linked to administrative health care and mortality data. All HCV-positive and HIV-negative individuals were followed to measure time to HIV acquisition (positive test) and identify factors associated with HIV acquisition. Adjusted HRs (aHRs) were estimated using Cox proportional-hazard regression. Of 36,077 HCV-positive individuals, 2,169 (6%) acquired HIV over 266,883 years of follow-up (overall incidence of 8.1 per 1,000 person years). Overall median (IQR) time to HIV infection was 3.87 (6.06) years. In Cox regression, injection-drug use (aHR 1.47, 95% CI 1.33-1.63), HBV infection (aHR 1.34, 95% CI 1.16-1.55), and being a man who has sex with men (aHR 2.78, 95% CI 2.14-3.61) were associated with higher risk of HIV infection. Opioid-substitution therapy (OST) (aHR 0.59, 95% CI 0.52-0.67) and mental health counseling (aHR 0.48, 95% CI 0.43-0.53) were associated with lower risk of HIV infection. Injection-drug use, HBV coinfection, and being a man who has sex with men were associated with increased HIV risk and engagement in OST and mental health counseling were associated with reduced HIV risk among HCV-positive individuals. Improving access to OST and mental health services could prevent transmission of HIV and other blood-borne infections, especially in settings where access is limited.


Contrast Extravasation is Predictive of Poor Clinical Outcomes in Patients Undergoing Endovascular Therapy for Acute Ischemic Stroke in the Anterior Circulation.
To investigate whether contrast extravasation on dual-energy computed tomography (DECT) in patients with acute ischemic stroke (AIS) after endovascular therapy (EVT) are related to hemorrhagic transformation (HT) and poor short-term clinical outcomes. A retrospective analysis was conducted on AIS patients who underwent EVT at Xuanwu hospital between November 2016 and January 2019. DECT was performed on all patients within 24 hours after EVT. Baseline demographic and clinical data were analyzed between patients with and without contrast extravasation and between patients with HT and non-HT, good and poor outcomes at 3 months post-EVT. A total of 166 patients were included in the study with 51 (30.7%) patients experiencing contrast extravasation. Compared to patients without contrast extravasation, patients with contrast extravasation had longer onset to reperfusion time (444.8 minutes versus 374.0 minutes, P = .044) and higher percentages of greater than 3 retriever passes (16.7% versus 31.4%, P = .030). Contrast extravasation was associated with higher risk of HT (P = .038), poor outcome after discharge (P = .030), and longer hospital stay (P = .034). Multivariate analysis showed that contrast extravasation occurrence was an independent factor for HT (OR = 2.150, 95% CI 1.060-4.360, P = .034) and poor short-term outcome (OR = 2.936; 95% CI 1.147-7.518, P = .025). The presence of contrast extravasation within 24 hours of EVT may be associated with higher risks of HT and may be predictive of unfavorable functional outcomes in AIS patients.


CFTR mediated chloride secretion in the avian renal proximal tubule.
In primary cell cultures of the avian (Gallus gallus) renal proximal tubule parathyroid hormone and cAMP activation generate a Cl(-)-dependent short circuit current (I(SC)) response, consistent with net transepithelial Cl(-) secretion. In this study we investigated the expression and physiological function of the Na-K-2Cl (NKCC) transporter and CFTR chloride channel, both associated with Cl(-) secretion in a variety of tissues, in these proximal tubule cells. Using both RT-PCR and immunoblotting approaches, we showed that NKCC and CFTR are expressed, both in proximal tubule primary cultures and in a proximal tubule fraction of non-cultured (native tissue) fragments. We also used electrophysiological methods to assess the functional contribution of NKCC and CFTR to forskolin-activated I(SC) responses in filter grown cultured monolayers. Bumetanide (10 μM), a specific blocker of NKCC, inhibited forskolin activated I(SC) by about 40%, suggesting that basolateral uptake of Cl(-) is partially mediated by NKCC transport. In monolayers permeabilized on the basolateral side with nystatin, forskolin activated an apical Cl(-) conductance, manifested as bidirectional diffusion currents in the presence of oppositely directed Cl(-) gradients. Under these conditions the apical conductance appeared to show some bias towards apical-to-basolateral Cl(-) current. Two selective CFTR blockers, CFTR Inhibitor 172 and GlyH-101 (both at 20 μM) inhibited the forskolin activated diffusion currents by 38-68%, with GlyH-101 having a greater effect. These data support the conclusion that avian renal proximal tubules utilize an apical CFTR Cl(-) channel to mediate cAMP-activated Cl(-) secretion.


A novel approach to sustained pseudoephedrine release: differentially coated mini-tablets in HPMC capsules.
We developed and optimized a novel pseudoephedrine hydrochloride (PSE) sustained-release dosage form. The system comprises immediate-release mini-tablets (IRMT) and sustained-release mini-tablets (SRMT) contained in a hydroxypropyl methylcellulose (HPMC) capsule. The IRMT contained PSE, excipients and low-substituted hydroxypropyl cellulose (a disintegrant), and the tablets were coated with HPMC, a water-soluble polymer. IRMT prepared with varying amounts of low-substituted hydroxypropyl cellulose all dissolved completely within the first 60min, so low-substituted hydroxypropyl cellulose content does not greatly influence PSE release. The SRMT contained only PSE and excipients, and were coated with a mixture of HPMC and the water-insoluble polymer ethylcellulose. The PSE release profile for the SRMT could be controlled by varying the thickness of the coat, and the lag time could be controlled by varying the amount of ethylcellulose present in the polymer coat. PSE was released immediately from our encapsulated mini-tablet system and release was sustained over an extended period of time: the PSE in the IRMT dissolved within 60min, whereas the PSE in the SRMT was released over 8-10h. This system can be modified to yield various extended drug-release profiles, thereby harnessing the benefits of both SRMT and IRMT.


Protocol to evaluate hyperlipidemia in zebrafish larvae.
In this report, we describe an approach to generate a zebrafish larval model of lipid accumulation that can be used as an in vivo system to study hyperlipidemic conditions such as atherosclerosis. Furthermore, we detail steps on staining techniques, lipid estimation assays, RNA isolation, and utilization of ImageJ to evaluate larval dimensions and to explore the model in the context of hyperlipidemia. Researchers should be aware of context specificity of the proposed protocols and interpret results accordingly. For complete details on the use and execution of this protocol, please refer to Balamurugan et al., (2022).


Wrist range of motion and motion frequency during toy and game play with a joint-specific controller specially designed to provide neuromuscular therapy: A proof of concept study in typically developing children.
Upper extremities affected by hemiplegic cerebral palsy (CP) and other neuromuscular disorders have been demonstrated to benefit from therapy, and the greater the duration of the therapy, the greater the benefit. A great motivator for participating in and extending the duration of therapy with children is play. Our focus is on active motion therapy of the wrist and forearm. In this study we examine the wrist motions associated with playing with two toys and three computer games controlled by a specially-designed play controller. Twenty children (ages 5-11) with no diagnosis of a muscular disorder were recruited. The play controller was fitted to the wrist and forearm of each child and used to measure and log wrist flexion and extension. Play activity and enjoyment were quantified by average wrist range of motion (ROM), motion frequency measures, and a discrete visual scale. We found significant differences in the average wrist ROM and motion frequency among the toys and games, yet there were no differences in the level of enjoyment across all toys and games, which was high. These findings indicate which toys and games may elicit the greater number of goal-directed movements, and lay the foundation for our long-term goal to develop and evaluate innovative motion-specific play controllers that are engaging rehabilitative devices for enhancing therapy and promoting neural plasticity and functional recovery in children with CP.


Leptospirosis. A re-emerging zoonotic disease.
Leptospirosis is a re-emerging infectious disease that occurs in dogs in urban and rural environments. It is caused by a filamentous spiral bacterium that has a predilection for renal tubules. Acute renal failure, hepatic dysfunction, and hemorrhagic diathesis are the most common clinical signs. Treatment with antibiotics and supportive care can manage a high percentage of cases successfully. Newer vaccines developed in response to the change in frequency of certain serovars may decrease the incidence of clinical disease. Leptospirosis affects a wide variety of species and is zoonotic.


A Regional Experience with Carotid Endarterectomy in Patients with a History of Neck Radiation.
Historically, a history of neck radiation has been considered as an anatomic risk factor for poor outcomes after carotid endarterectomy (CEA). However, this is based on small and primarily single institution reports with few comparative series. This study uses a regional quality database to compare perioperative outcomes of CEA in patients with and without a history of neck radiation (RAD and NORAD, respectively). The Vascular Study Group of New England database was queried for all CEA from 2003 to 2017. The RAD group included a history of neck radiation. Primary end points included perioperative stroke (30-day), myocardial infarction (MI) (in-hospital), death (30-day), a composite end point including major adverse events (MAEs: stroke, MI, and death), and long-term survival. Overall, 18,832 patients underwent CEA (18,551 NORAD, 281 RAD). Baseline demographics differed in the following: the RAD group more frequently had a history of contralateral carotid artery stenting (1.4% vs. 0.3%, P = 0.009), anatomic high risk features (12.8% vs. 1.3%, P < 0.001), and contralateral carotid occlusion (5.3% vs. 2.4%, P = 0.005). The NORAD cohort comprised mostly women (38.9% vs. 29.5%, P < 0.001), had American Society of Anesthesiologists class 4 or 5 (8.0% vs. 4.6%, P = 0.035), had higher body mass index (28.3 ± 5.6 vs. 27.1 ± 5.4, P < 0.001), on a beta blocker preoperatively (68.0% vs. 62.3%, P = 0.042), and had major cardiovascular comorbidities including coronary artery disease (29.6% vs. 22.1%, P = 0.006). There were no differences in the percent stenosis, proportion symptomatic (37.4% vs. 34.2%, P = 0.259), use of preoperative antiplatelet agents or statins. Electroencephalography monitoring was more frequently used in RAD (54.5% vs. 46.0%, P = 0.005). There was no difference in perioperative complications, including stroke (RAD 0.4% vs. NORAD 0.7%, P > 0.999), MI (0.4% vs. 0.9%, P = 0.736), death (0.7% vs. 0.6%, P = 0.683), MAE (2.1% vs. 2.2%, P > 0.999), or long-term survival (79.9% vs. 85.0%, P = 0.357). When only symptomatic or asymptomatic stenosis was considered, there remained no difference in primary end points. However, perioperative neurologic events (transient ischemic attack or stroke) was higher in symptomatic RAD versus symptomatic NORAD (6.7% vs. 2.6%, P = 0.020). This regional experience with CEA in RAD patients shows similar perioperative morbidity, mortality, and long-term survival when compared with CEA for standard surgical patients (NORAD). Symptomatic presentation was associated with higher perioperative neurologic events, but this was not reflected in stroke rates. RAD is not always a contraindication to CEA and select patients can expect outcomes comparable to standard surgical patients.


GlobalUsefulNativeTrees, a database documenting 14,014 tree species, supports synergies between biodiversity recovery and local livelihoods in landscape restoration.
Tree planting has the potential to improve the livelihoods of millions of people as well as to support environmental services such as biodiversity conservation. Planting however needs to be executed wisely if benefits are to be achieved. We have developed the GlobalUsefulNativeTrees (GlobUNT) database to directly support the principles advocated by the 'golden rules for reforestation', including planting tree mixtures that maximize the benefits to local livelihoods and the diversity of native trees. Developed primarily by combining data from GlobalTreeSearch with the World Checklist of Useful Plant Species (WCUPS), GlobUNT includes 14,014 tree species that can be filtered for ten major use categories, across 242 countries and territories. The 14,014 species represent roughly a quarter of the tree species from GlobalTreeSearch and a third of the plant species from WCUPS. GlobUNT includes over 8000 species used as materials (9261 species; 68.4% of the total in WCUPS for that use category) or medicines (8283; 31.1%), over 2000 species with environmental uses (3317; 36.9%), used as human food (3310; 47.0%) or fuel (2162; 85.5%), over 1000 species used as gene sources (1552; 29.8%), animal food (1494; 33.7%), social uses (1396; 53.8%) or poisons (1109; 36.8%), and 712 species (68.4%) as insect food.


Effects of whole body UV-irradiation on oxygen delivery from the erythrocyte.
In 16 healthy caucasian volunteers (mean age: 22.2 years) the influence of whole body UV-irradiation on the oxygen transport properties of erythrocytes was investigated. Four hours after irradiation with UV (using the minimal erythema dose, MED) no variation of haemoglobin concentration, hematocrit, mean corpuscular haemoglobin concentration, pH or standard bicarbonate could be found, whereas inorganic plasma phosphate (Pi), calcium, the intraerythrocytic 2,3-diphosphoglycerate (2,3-DPG), the activity of erythrocytic phosphofructokinase (PFK) and pyruvatekinase (PK) increased significantly. The half saturation tension of oxygen (P50-value) tended to increase. The increase of Pi causes--via a stimulation of the glycolytic pathway--an increase in 2,3-DPG concentration and thus results in a shift of the oxygen dissociation curve. It is therefore possible to enhance tissue oxygenation by whole body UV-irradiation.


P2Y1 receptors mediate inhibitory neuromuscular transmission and enteric neuronal activation in small intestine.
There is increasing evidence that adenosine 5'-triphosphate or a related purine plays a crucial role in smooth muscle relaxation and enteric synaptic neurotransmission. Accordingly, the aim of the present work is to investigate the role P2Y(1) receptors in purinergic inhibitory neurotransmission (pig ileum) and enteric neuronal activation in the small intestine (guinea-pig ileum). Using contractility measurements, micro-electrode recordings and Ca(2+) imaging we found that (i) adenosine 5'-Omicron-2-thiodiphosphate (ADPbetaS) (10 micromol L(-1)) caused smooth muscle relaxation and hyperpolarization that was antagonized by MRS2179 (10 micromol L(-1)) a P2Y(1) receptor antagonist and apamin (1 micromol L(-1)); (ii) electrical field stimulation (EFS) caused a non-nitrergic inhibitory junction potential (IJP) and relaxation that was antagonized by MRS2179 (10 micromol L(-1)); (iii) P2Y(1) receptors were immunolocalized in smooth muscle cells and enteric neurons; (i.v.) superfusion of ADPbetaS (1 micromol L(-1)) induced Ca(2+) transients in myenteric neurons that were inhibited by MRS2179 (1 micromol L(-1)), but not by tetrodotoxin (1 micromol L(-1)); and (v) EFS induced calcium transients were partially inhibited by MRS2179 (1 micromol L(-1)). We conclude that in the small intestine purinergic neuromuscular transmission responsible for the IJP and non-nitrergic relaxation is mediated by P2Y(1) receptors located in smooth muscle cells. Functional P2Y(1) receptors are also present in guinea-pig myenteric neurons. Therefore, P2Y(1) receptors might be an important pharmacological target to modulate gastrointestinal functions.


Mode of action of endo-beta-1,4-xylanases of families 10 and 11 on acidic xylooligosaccharides.
Mode of action of endo-beta-1,4-xylanases (EXs) of glycoside hydrolase families 10 (GH-10) and 11 (GH-11) was examined on various acidic xylooligosaccharides. As expected, none of the enzymes of GH-10 cleaved aldotetraouronic acid (MeGlcA3Xyl3), which is the shortest acidic product of the action of these EXs on glucuronoxylan. Surprisingly, aldopentaouronic acid (MeGlcA3Xyl4) was also not attacked. Only aldohexaouronic acid (MeGlcA3Xyl5) served as a substrate and was cleaved to xylobiose and aldotetraouronic acid. These results suggested that binding of xylopyranosyl residue in the -2 subsite is prerequisite for cleavage of the linkage adjacent to the xylopyranosyl unit carrying MeGlcA. EXs of family GH-11 cleaved neither aldotetraouronic acid, nor aldopentaouronic acid, which is in agreement with their action on glucuronoxylan. Aldohexaouronic acid was cleaved to aldopentaouronic acid and xylobiose without any production of xylose, suggesting that a xylosyl transfer reaction is involved in the degradation of the substrate by EXs of GH-11.


Spectral tilt change in stop consonant perception by listeners with hearing impairment.
To evaluate how perceptual importance of spectral tilt is altered when formant information is degraded by sensorineural hearing loss. Eighteen listeners with mild to moderate hearing impairment (HI listeners) and 20-23 listeners with normal hearing (NH listeners) identified synthesized stimuli that varied in second formant (F(2)) frequency and spectral tilt. Experiments 1 and 2 examined utterance-initial stops (/ba/ and /da/), and Experiments 3 and 4 examined medial stops (/aba/ and /ada/). Spectral tilt was manipulated at either consonant onset (Experiments 1 and 3), vowels (Experiments 2 and 4), or both (Experiment 5). Regression analyses revealed that HI listeners weighted F(2) substantially less than NH listeners. There was no difference in absolute tilt weights between groups. However, HI listeners emphasized tilt as much as F(2) for medial stops. NH listeners weighted tilt primarily when F(2) was ambiguous, whereas HI listeners weighted tilt significantly more than NH listeners on unambiguous F(2) endpoints. Attenuating changes in spectral tilt can be as deleterious as taking away F(2) information for HI listeners. Recordings through a wide dynamic range compression hearing aid show compromised changes in spectral tilt, compressed in range by up to 50%.


Granulocyte-activating mediators (GRAM). II. Generation by human epidermal cells--relation to GM-CSF.
In the present study we investigated the capability of human epidermal cells to generate granulocyte-activating mediators (GRAM). It could be shown that human epidermal cells as well as an epidermoid carcinoma cell line (A431) produce an epidermal cell-derived granulocyte-activating mediator (EC-GRAM) which stimulates human granulocytes to release significant levels of toxic oxygen radicals as measured by a lucigenin-dependent chemiluminescence (CL). For further characterization of EC-GRAM the A431 cell line was used. Supernatants of A431 cells usually contained maximal EC-GRAM levels within 24 h of incubation. Factor production was enhanced by bacterial lipopolysaccharide (LPS), but not by silica particles and PHA. Moreover, freeze-thaw lysates of A431 cells and extracts of heat-separated human epidermis contained significant levels of EC-GRAM. Preincubation of granulocytes with EC-GRAM resulted in an enhanced response to subsequent stimulation with the chemotactic peptide f-met-phe. In contrast EC-GRAM did not affect the response to PMA or zymosan particles. However, EC-GRAM treated granulocytes were unresponsive to restimulation with EC-GRAM. Upon high performance liquid chromatography (HPLC) gel filtration EC-GRAM eluted within two major peaks exhibiting a molecular weight of 17 kD and 44 kD.(ABSTRACT TRUNCATED AT 250 WORDS)


Antioxidants restore protoporphyrinogen oxidase in variegate porphyria patients.
Variegate porphyria (VP) is the result of decreased protoporphyrinogen oxidase (PPOX) activity and results in the accumulation of porphyrins and porphyrin precursors. Our aims were to analyse the basal antioxidant defences and oxidative damage markers and the effects of a diet supplementation with vitamins E and C on the oxidant/antioxidant status and PPOX gene expression in lymphocytes of variegate porphyria (VP) patients. Twelve women affected by VP and 12 control women participated in a randomized and double-blind crossover study. Each participant took either 50 mg/day vitamin E and 150 mg/day vitamin C or a placebo for 6 months. Lymphocyte PPOX gene expression, together with catalase and glutathione peroxidase activities, was reduced in VP women. No differences were observed in the levels of malondialdehyde and protein carbonyl derivatives. Stimulated lymphocyte H2 O2 production was higher in porphyric women. Supplementation with antioxidant vitamins increased PPOX expression in VP patients. Glutathione reductase (GRd) and superoxide dismutase (SOD) activities were higher in the treatment groups. Lymphocytes from VP patients show reduced PPOX expression and present a greater susceptibility to producing H2 O2 and impaired H2 O2 detoxifying mechanisms. Supplementation with vitamins E and C restores PPOX expression in VP patients and enhances GRd and SOD activity, suggesting the potential benefits of a diet rich in vitamins E and C in these patients.


Clinical Features of Tourette Syndrome and Tic Disorders.
Tourette syndrome (TS) is a neurodevelopmental disorder characterized by motor and vocal tics--rapid, repetitive, stereotyped movements or vocalizations lasting at least one year in duration. The goal of this article was to review the long-term clinical course of tics and frequently co-occurring conditions in children with TS. We conducted a traditional literature search to locate relevant articles regarding long-term outcome and prognosis in TS and tic disorders. Tics typically have an onset between the ages of 4 and 6 years and reach their worst-ever severity between the ages of 10 and 12 years. By age 10 years, most children are aware of nearly irresistible somatosensory urges that precede the tics. A momentary sense of relief typically follows the completion of a tic. Over the course of hours, tics occur in bouts, with a regular inter-tic interval. Tics increase during periods of psychosocial stress, emotional excitement and fatigue. Tics can become "complex" in nature and appear to be purposeful. Tics can be willfully suppressed for brief intervals and can be evoked by the mere mention of them. Tics typically diminish during periods of goal-directed behavior. Over the course of months, tics wax and wane. By early adulthood, roughly three-quarters of children with TS will have greatly diminished tic symptoms and more than one-third will be virtually tic free. Although tics are the defining aspect of TS, they are often not the most enduring or impairing symptoms in children with TS. Indeed in TS tics rarely occur in isolation, and other coexisting conditions--such as behavioral disinhibition, hypersensitivity to a broad range of sensory stimuli, problems with visual motor integration, procedural learning difficulties, attention-deficit hyperactivity disorder, obsessive-compulsive disorder, depression, anxiety, and emotional instability--are often a greater source of impairment than the tics themselves. Measures used to enhance self-esteem, such as encouraging independence, strong friendships and the exploration of interests, are crucial to ensuring positive adulthood outcome.


How food and fluid affect drug absorption: results of initial studies.
The rate and extent of absorption of many drugs may be influenced by the presence of food in the gastrointestinal tract and by the volume of fluid ingested with the dose. In most cases, food appears to inhibit or delay drug absorption. Relatively large fluid volume, on the other hand, appears to enhance absorption.


HLA expression on human ejaculated sperm.
The expression of human leukocyte antigen (HLA) on human ejaculated sperm has been investigated by using cellular binding radioimmunoassay (CB-RIA) with sperm samples purified by Percoll discontinuous gradient and monoclonal antibodies specific to the frame work of HLA molecules. The results in packed sperm obtained from ten healthy males indicated that HLA class II and its subclasses, DP, DQ, and DR, were expressed at a low level on human ejaculated sperm, while HLA class I was not detected. Furthermore, we could not detect the individual variation of HLA expression on ejaculated sperm in the cases of twenty healthy males. K562, which is B lymphoid cell line and lacks HLA class I molecules, showed detectable amounts of HLA class I molecules after exposure to interferon gamma (IFN-gamma) and/or tumor necrosis factor alpha (TNF-alpha). However, the treatment of sperm with IFN-gamma and/or TNF-alpha had no effect on the expression of HLA class I and class II molecules.


A modified surgical technique for treatment of radiation-induced vesicovaginal fistulas.
To present a modified surgical technique in the management of radiation-induced vesicovaginal fistulas. Radiation-induced vesicovaginal fistulas pose a great challenge to the treating surgeon owing to the fibrotic, poorly vascularized tissue in the area. Various techniques have been used to promote healing and prevent fistula recurrence, but most centers still recommend urinary diversion or more individualized management. We used the left rectus abdominis muscle based on the deep inferior epigastric vessels as an interposition flap in 3 patients presenting with vesicovaginal fistulas 19, 28, and 34 years after radiotherapy for cervical cancer. The fistulas were isolated using an abdominal approach, and the distal half of the left rectus abdominis muscle was mobilized. Without closure of the 2 defects, the muscle was then interposed between the bladder and vagina, where it was fixed using single sutures around the edges of the 2 defects. The operations were performed by a team that included both a urologist and a plastic surgeon. All 3 patients underwent successful treatment. With a follow-up of 5-8 years, there has been no recurrence of symptoms. This modified surgical technique offers well-vascularized, nonirradiated tissue to be used as an interposition flap based on the inferior epigastric vessels in the management of radiation-induced vesicovaginal fistulas. The technique allows obstruction of the fistula without the need for closure of the mucosal defects in the bladder and vagina.


Encephalitic presentation of Neonatal Chikungunya: A Case Series.
To describe clinical features and early neurological outcomes in neonatal Chikungunya. Clinical, pathological and radiological details of neonates with acute encephalitic features and typical rash, later diagnosed as Chikungunya, are presented. Neurodevelopmental evaluation and imaging was done at discharge/three months. Abnormal neurological examination with fever was typical presentation in all 13 babies with/without seizures/peri-oral rashes; 12 had persistent neurological abnormalities at discharge. A follow-up at three months revealed continued neurodevelopmental deficits. Neuroimaging abnormalities were seen in eight out of ten cases. Perinatal Chikungunya should be considered in neonates presenting within first week with fever, encephalopathy and perioral rashes with/without seizures with history of maternal Chikungunya within last week before delivery.


Anterior dislocation of the shoulders with bilateral brachial plexus injury.
A case of bilateral anterior shoulder dislocation accompanied by bilateral brachial plexus injuries is presented. A 53-year-old man fell and landed on his chest and arms flexed at the elbows. The dislocations were satisfactorily reduced using the forward elevation, flexion maneuver. Electromyography and nerve conduction studies confirmed bilateral brachial plexus lesions. Arthrogram of the right shoulder demonstrated a rotator cuff tear. The patient is undergoing physical therapy and making a slow recovery.


Vascular aging in the young: New carotid stiffness centiles and association with general and abdominal obesity - The KIGGS cohort.
The evidence for an association between obesity and increased carotid intima-media thickness (CIMT) and carotid stiffness (CS) in the young has been limited by methodological challenges related to study populations, measurements, methods of percentile derivation and comprehensiveness of obesity markers investigated. This nationwide general population study developed new CS and CIMT centiles in the young and used them to study associations with body mass index, waist circumference, waist-to-height-ratio, bioimpedance-derived absolute and relative fat mass, fat-free mass, subscapular skinfold thickness and blood pressure. In its 11-year follow-up, the KiGGS cohort, which is based on a nationally representative sample, included semi-automated state-of-the-art sonographic CIMT and CS measurements in 4,709 participants aged 14 to 28. Distensibility coefficient (DC), stiffness index β, Young's elastic modulus (YEM) and Peterson's elastic modulus (Ep) centiles were modelled by sex, age and height simultaneously. CS increased with age in both sexes, and young men had stiffer arteries than young women at all ages. All obesity measures at baseline and at follow-up, except for subscapular skinfold thickness, were positively associated with several CS parameters with moderate relative risks (RR), e.g. cross-sectional RR 2.23 (95% CI 1.26-3.93) for DC ≥ 90th percentile when waist circumference ≥90th percentile; RR 5.98 (3.38-10.56) for elevated DC associated with simultaneously elevated waist circumference and BP. These new state-of-the-art CS percentiles show consistent associations of obesity with CS in the young and support primary prevention efforts starting at a young age.


The effects of caffeine on heart rate variability in newborns with apnea of prematurity.
Apnea of prematurity is a common complication in premature newborns and caffeine is a widespread medication used to treat this complication. Caffeine may have adverse effects on the cardiovascular and central nervous system, yet its effects on the autonomic nervous system modulation of heart rate have not been studied in premature newborns, which was the objective of our study. We prospectively studied 21 premature newborns who were treated with caffeine. We analyzed heart rate variability by power spectral density and by dynamic nonlinear analyses methods. There were no changes in heart rate, blood pressure or the autonomic nervous system tone following administration of caffeine, nor were the nonlinear dynamical properties of the system altered by caffeine. Caffeine does not have detrimental effects on heart rate variability, heart rate or blood pressure in conventional doses given to premature newborns.


Prognosis of acute invasive fungal rhinosinusitis related to underlying disease.
Acute invasive fungal rhinosinusitis (AIFRS) is a rare disease with high morbidity and mortality rates. The objective of this study was to correlate the initial clinical features of AIFRS to the prognosis after surgery. Thirty-two patients with AIFRS were evaluated retrospectively. The correlation of underlying disease, fungus isolated, and extent of the disease to the clinical outcome of AIFRS was also evaluated. The most common underlying disease was hematological malignancy and aplasia (n=20). Aspergillus (n=13) and Mucoraceae (n=11) were the main fungi found in AIFRS. Mucosal biopsy confirmed fungal invasion to the nasal mucosa in all cases. Computed tomography and endoscopic findings showed a predominance of unilateral disease, with various stages of nasal involvement. All patients underwent surgical debridement and systemic antifungal therapy immediately after diagnosis. Sixteen patients died (50%) due to AIFRS. A poor prognosis was related to the extensiveness of AIFRS and to the underlying disease (patients with aplastic anemia and diabetes had the worst outcomes), but not to the fungus isolated. Early medical and surgical treatment is essential to improve the prognosis of AIFRS patients. A poorer prognosis was associated with underlying disease and extensiveness of AIFRS, but not to the fungus isolated.


[Reduced radioiodine uptake at increased iodine intake and 131I-induced release of "cold" iodine stored in the thyroid].
The extent of urinary iodine excretion (UIE) provides information about iodine supply and release. In the present study we investigated correlations between UIE and radioiodine uptake (RIU) as well as effects of radioiodine therapy on UIE in patients with autonomous goitre. In 197 consecutive patients with thyroid autonomy, UIE was measured twice during radioiodine test (RITe) and correlated with RIU. In 98 of these patients, thyroglobulin and thyroid volume (V) were determined prior to therapy. Individual changes in urinary iodine excretion (DeltaUIE) and TG (DeltaTG) could be investigated four weeks (4W) and six months (6M) after radioiodine therapy. Additionally, DeltaV was determined 6M after therapy. DeltaUIE, DeltaTG and DeltaV were correlated with target dose and target volume. Patients with higher iodine excretion exhibited significantly lower thyroidal radioiodine uptake values. Twofold increased UIE prior to therapy decreased radioiodine uptake by 25%. Compared with pretherapeutic values, UIE and TG were significantly increased four weeks after radioiodine therapy (p < 0.001). Median values of both parameters were found to be doubled. The product of target dose and target volume was not only correlated with a decrease of thyroid volume 6M after therapy, but also with an increase of UIE and TG in the early phase after therapy. It was confirmed that UIE during RITe is a measure for iodine intake and can be used to investigate the competition between stable iodine and radioiodine. The increase of UIE and TG four weeks after therapeutic administration of radioiodine can be explained by disintegrated thyroid follicles. The therapy-induced iodine release may be one important cause for the development of hyperthyroidism in some patients during the first weeks after radioiodine therapy. It may contribute to the known decrease of radioiodine uptake after preapplications of 131I in various thyroid diseases.


Reliability and validity of the Edinburgh Visual Gait Score for cerebral palsy when used by inexperienced observers.
The Edinburgh Visual Gait Score (EVGS) for cerebral palsy has been validated for observer reliability and validity for observers experienced in gait analysis. This study investigated the reliability and validity of the EVGS for observers inexperienced in gait analysis. Six medical students used the score to analyse videotapes from the original study by Read et al. [Read HS, Hazlewood ME, Hillman SJ, Prescott RJ, Robb JE. Edinburgh visual gait score for use in cerebral palsy. J Pediatr Orthop 2003;23:296-301]. These were viewed on two separate occasions to provide inter- and intra-observer reliability, and the results of the numerical items were compared to those from three-dimensional (3D) gait analyses for validity. Observer agreement was tested using Coefficient of Repeatability (CoR), percentage of complete agreement and the kappa statistic. The CoR for inter-observer agreement for inexperienced observers was 5.99/5.07 (Session 1/Session 2) compared to 4.60/3.95 (Session 1/Session 2) for experienced observers. The CoR for intra-observer agreement for inexperienced observers was 5.15 compared to 4.21 for experienced observers. There was complete agreement for 52% of the 10 numerical items with 3D-gait analysis data for inexperienced observers compared to 64% for experienced observers. Ranking of reliability of individual items was similar between the two groups and was generally best for events occurring at the foot and ankle. Observations of gait events by the inexperienced observers using the EVGS were reasonably reliable but not very accurate when compared to experienced observers and 3D-gait analysis.


Activity-based air pollution exposure assessment: Differences between homemakers and cycling commuters.
Long-term air pollution exposure may lead to an increase in incidences and mortality rates of chronic diseases and adversely affect human health. The effects of long-term air pollution exposure have not been comprehensively studied due to the lack of human mobility data collected over a long period. In this study, we develop and apply a personal mobility model to long-term hourly air pollution concentration predictions to quantify personal long-term air pollution exposure for all individuals. We implement our model assuming mobility patterns for commuters and homemakers, and separate between weekdays and weekend. Our results show that NO2 exposure of commuters are on average slightly higher and vary less spatially as they are exposed to NO2 at multiple locations.


Hepatic Mast Cells in Mice with Experimental Amyloidosis.
We studied the response of mast cells in mouse liver to experimental amyloidosis modeled by administration of aqueous solution of soy cream substitute and its correction by spontaneous dry red wine intake per os. Mast cells in mice with amyloidosis and intact mice were presented by α-ortho- and β1-metachromatic non-degranulating forms. In mice with amyloidosis, the relative content of β1-metachromatic mast cells in the capsule and parenchyma of the liver was by 1.8 and 1.5 times higher than in intact animals, respectively. In mice with amyloidosis receiving dry red wine, the proportions of mast cells with different degrees of metachromasy and degranulation were similar to those in intact mice, but the relative content of β1-metachromatic mast cells in the liver parenchyma in these animals was by 1.6 times higher than in intact mice. Therefore, mast cells respond to amyloidosis development by changes in both the metachromasy and degranulation degree; dry red wine can be considered as a factor of amyloidosis prevention.


The complexity of treatments for persons with epilepsy.
The purpose of this study was to describe the types of antiepileptic medication regimens and the types of actions required to take medications for a group of patients with epilepsy. The Epilepsy Medication and Treatment Complexity Index (EMTCI) was used to gather information about medications and treatments. The sample of 314 reported on 585 epilepsy medications. The majority (56%) were on more than one treatment. On average, an individual took 1.86 medications per day (range, 1-6) and 7.98 pills per day (range, 1-36 pills). Most medications (54%) were taken twice a day. The most common special instruction was taking different doses on the same day. Taking more than one tablet per dose was the most common administrative action. Data presented here raise interesting areas for further research as well as important clinical implications.


Accumulation of estrogen in a vocal control brain region of a duetting song bird.
Tritiated estradiol (E) was injected into bay wrens (Thryothorus nigricapillus), a tropical species in which females sing complex vocal duets with males. Autoradiographic analysis revealed that males and females have equal proportions of cells labeled by estradiol or its metabolites (E target cells) in a telencephalic region involved in song: the caudal nucleus of the ventral hyperstriatum (HVc). Other forebrain song regions failed to show labeling by E. E or its metabolites were accumulated, however, by cells in the midbrain song region ICo (the intercollicular nucleus) and in hypothalamic regions. This pattern of accumulation in the song system differs from that observed in a previous study in which bay wrens were injected with tritiated testosterone (T); T or its metabolites were accumulated by cells in HVc, RA (robust nucleus of the archistriatum), MAN (magnocellular nucleus of the neostriatum), ICo, and nXII (hypoglossal (nucleus). Such comparison suggests that cells in HVc have different steroid accumulation properties from those in other song regions. Bay wrens differ from zebra finches (Poephilia guttata), in which HVc contains very few E target cells. The wrens are more similar to canaries (Serinus canarius), because both species have E target cells in HVc, and females of both species are able to sing. The interspecies comparison raises the question of whether the ability of HVc cells to accumulate E or its metabolites in both species constitutes a precondition for the bisexual potential for song production.


The BrainMap strategy for standardization, sharing, and meta-analysis of neuroimaging data.
Neuroimaging researchers have developed rigorous community data and metadata standards that encourage meta-analysis as a method for establishing robust and meaningful convergence of knowledge of human brain structure and function. Capitalizing on these standards, the BrainMap project offers databases, software applications, and other associated tools for supporting and promoting quantitative coordinate-based meta-analysis of the structural and functional neuroimaging literature. In this report, we describe recent technical updates to the project and provide an educational description for performing meta-analyses in the BrainMap environment. The BrainMap project will continue to evolve in response to the meta-analytic needs of biomedical researchers in the structural and functional neuroimaging communities. Future work on the BrainMap project regarding software and hardware advances are also discussed.


Dexamethasone enhances colonization of soft agar by tumorigenic mouse lung-derived cell lines.
When cultured on plastic, tumorigenic mouse lung-derived cell lines exhibit different proliferative responses to glucocorticoids; some lines are inhibited while others are stimulated or unaffected. In contrast to the variable dexamethasone responses when cells are cultured on plastic, soft agar colonization by each of these cell lines is enhanced by dexamethasone. Enhanced soft agar growth is unlikely to result from expression of a mutant glucocorticoid receptor, since dexamethasone also enhanced colony formation in two cell lines that stably express a transfected normal glucocorticoid receptor gene. Thus, cell attachment influences the effect of glucocorticoids on cell cycle progression.


Penetration of sodium hypochlorite into root canal dentine: effect of surfactants, gel form and passive ultrasonic irrigation.
To assess the penetration of sodium hypochlorite (NaOCl) gel or NaOCl solutions with surfactants, and the effect of passive ultrasonic irrigation (PUI) on penetration into dentinal tubules. Bovine incisor root canals were instrumented, the roots sectioned and the dentine blocks obtained were stained with crystal violet. Dentine blocks (n = 10 per group) were exposed to 3% NaOCl gel or 3% NaOCl solution for 10 and 20 min. Other dentine blocks (n = 10 per group) were exposed to Chlor-Extra (6% NaOCl + surfactant), 6% NaOCl, 2.5% NaOCl with 0.2% cetrimide and 2.5% NaOCl for 10 and 20 min. The penetration depth of irrigants into dentinal tubules was measured in micrometres by viewing the bleached crystal violet under a stereomicroscope. Additionally, bovine incisor root canals, instrumented and stained with crystal violet, were distributed into two groups (n = 10) and irrigated with 2.5% NaOCl with PUI or conventional syringe irrigation (CSI). The penetration depth of irrigants into dentinal tubules was assessed 3 and 7 mm from the apex. Statistical analysis was performed by ANOVA and Tukey tests (α = 0.05). There was significantly greater penetration of 3% NaOCl solution into dentinal tubules compared with the gel form (P < 0.05). There was no difference (P > 0.05) between 6% NaOCl and Chlor-Extra, and between 2.5% NaOCl and 2.5% NaOCl + cetrimide. PUI significantly increased the penetration depth of NaOCl into dentinal tubules when compared with CSI (P < 0.05). In extracted bovine incisors, NaOCl gel penetrated less into dentinal tubules than NaOCl solution. The addition of surfactants did not increase the penetration depth. The use of PUI significantly increased NaOCl penetration into dentinal tubules.


Intragastric cannulation procedures and rats' food intake and body weight maintenance.
Effects upon food and water intakes and body weight maintenance of two procedures for preparing rats with chronic intragastric cannulae were examined. A transient aphagia and rapid weight loss followed installation of the classic nasopharyngeal cannula. Growth was resumed after about a week, but subsequent food and water intakes were chronically depressed in comparison to sham operated animals of the same age. Body weight was also chronically subnormal. The response of these animals to caloric dilution of the diet was, however, normal. In contrast to the nasopharyngeal procedure, a method involving direct cannulation of the stomach wall did not lead to either behavioral or weight regulatory deficits and is therefore recommended.


A size-structured, non-conservative ODE model of the chemostat.
We study a class of size-structured, ODE models of growth in the chemostat, that take into account cell maintenance and substrate dependent cell mortality. Unlike most classical chemostat models, they are supposed to be non-conservative, in the sense that they do not verify the mass conservation principle. However, using a change of time scale, we are able to obtain qualitative results. Then, using a Lyapunov functional, we prove the global stability of the non-trivial equilibrium. Some examples of the possible structure of the models are given to finish with.


Machine learning in neurosurgery: a global survey.
Recent technological advances have led to the development and implementation of machine learning (ML) in various disciplines, including neurosurgery. Our goal was to conduct a comprehensive survey of neurosurgeons to assess the acceptance of and attitudes toward ML in neurosurgical practice and to identify factors associated with its use. The online survey consisted of nine or ten mandatory questions and was distributed in February and March 2019 through the European Association of Neurosurgical Societies (EANS) and the Congress of Neurosurgeons (CNS). Out of 7280 neurosurgeons who received the survey, we received 362 responses, with a response rate of 5%, mainly in Europe and North America. In total, 103 neurosurgeons (28.5%) reported using ML in their clinical practice, and 31.1% in research. Adoption rates of ML were relatively evenly distributed, with 25.6% for North America, 30.9% for Europe, 33.3% for Latin America and the Middle East, 44.4% for Asia and Pacific and 100% for Africa with only two responses. No predictors of clinical ML use were identified, although academic settings and subspecialties neuro-oncology, functional, trauma and epilepsy predicted use of ML in research. The most common applications were for predicting outcomes and complications, as well as interpretation of imaging. This report provides a global overview of the neurosurgical applications of ML. A relevant proportion of the surveyed neurosurgeons reported clinical experience with ML algorithms. Future studies should aim to clarify the role and potential benefits of ML in neurosurgery and to reconcile these potential advantages with bioethical considerations.


Effect of saliva composition and flow on inter-individual differences in the temporal perception of retronasal aroma during wine tasting.
In order to determine if inter-individual differences in saliva composition and flow influence the perception of specific aromatic stimuli elicited by esters after wine consumption, ten individuals were selected and instructed in the recognition of four aromatic stimuli elicited by four ester compounds, which were added to a rosé wine. The whole panel was firstly characterised by their salivary flow, composition (pH, total protein content, macro- and micro- minerals) and rheological properties (viscosity), and secondly, the panellists were trained in a dynamic sensory method for the evaluation of retronasal aroma intensity at discrete time intervals (5, 60, 120, and 180 s) after wine expectoration. Significant inter-individual differences (p < 0.05) in saliva composition were found in most salivary parameters. Differences in the intensity ratings among individuals were also found for the four aroma attributes. Spearman correlation analysis between saliva parameters and aroma intensity over time showed a strong positive correlation between salivary flow and aroma perception for some aroma and time points. This correlation was higher in the immediate than in the long lasting perception and greater for aroma attributes elicited by short chain length esters (isoamyl acetate, ethyl butanoate and ethyl hexanoate) (than for attributes elicited by larger esters (ethyl decanoate).


Investigations of the symptomatology and the significance of immediate skin test reactivity in canine atopic dermatitis.
Immediate skin test reactivity was determined with skin threshold concentrations of different allergen solutions in 208 dogs suspected of atopic dermatitis. Thirty-eight of the dogs (18.3 per cent) exhibited no reaction. Multisensitivity occurred in 59.1 per cent. House dust (39.4 per cent), human dandruff (39.9 per cent), dog dandruff (25.0 per cent), cat dandruff (29.8 per cent) and grasses (21.2 per cent) caused most of the positive reactions. The number of immediate skin reactions per dog was increased in those dogs that had had clinical signs for two to three years, as compared to dogs having had clinical signs for five or more years. Involvement of the extensor aspect of the carpal joint (41.2 per cent) and the flexor surface of the tarsal joint (30.6 per cent) was noticed only in dogs with positive immediate skin test reactivity. Together with the frequent occurrence of lichenification (84.1 per cent) this distribution pattern in dogs seems to mimic the signs of atopic dermatitis in man more closely than has been described previously.


Rhabdomyoma of the pharyngeal wall.
Rhabdomyoma is a rare benign tumor of skeletal muscle, and the head and neck region is the most common extracardiac area for these tumors to occur. Twenty-one cases have previously been reported, and this report, "A Rhabdomyoma of the Pharyngeal Wall," brings the total to 22. Pathologically, these tumors show abundant polygonal skeletal muscle cells with demonstrable cross striations. Differential diagnosis of these tumors has included granular cell myoblastoma and rhabdomyoscarcoma. Treatment is usually complete excision.


Concentration dependence of the binding constant of antibodies.
By simultaneous dilution of the antigen (AG) and the antibody (AB) used in an immune precipitation reaction, at the equivalence AG/AB ratio, it was found that the association constant, Ka, increased from 1.7 X 10(7) 1/M at the highest concn of AG and AB, to 6.5 X 10(11) 1/M at 100-fold dilution of both. An important (but not the only) reason for this increase is taken to be the fact that the AB solution was polyclonal.


Orphan receptor COUP-TF I antagonizes retinoic acid-induced neuronal differentiation.
Chicken ovalbumin upstream promoter-transcription factors (COUP-TF) are expressed in the developing nervous system and interact with nuclear hormone receptors to regulate expression of different genes. The role of COUP-TF orphan receptors in neurogenesis is virtually unknown. To study the possible function of COUP-TF I during neuronal differentiation, we generated COUP-TF I overexpressing teratocarcinoma PCC7 cell lines and analyzed retinoic acid (RA)-induced neuronal differentiation of these cells. COUP-TF I overexpression results in the blockade of morphological differentiation after induction to differentiate. COUP-TF I represses expression of microtubule-associated protein 2 (MAP2) gene and delays induction of growth-associated protein 43 (GAP43) gene expression. In contrast, expression of the neurofilament light subunit (NF-L) gene is not affected by COUP-TF I overexpression during neuronal differentiation. Also, cells overexpressing COUP-TF I do not stop proliferating after RA and dBcAMP treatment and possess suppressed transcriptional activation from different RA response elements. These results suggest that COUP-TF I plays an important role in regulating RA-induced neuronal differentiation.


Pneumococcal vaccine improves pulmonary clearance of live pneumococci after splenectomy.
The efficacy of pneumococcal capsular polysaccharide vaccines after splenectomy to decrease the incidence of postsplenectomy pneumococcal sepsis is controversial. We examined the effect of pneumococcal vaccine on clearance of live pneumococci from lungs of splenectomized and sham-operated mice following an aerosol challenge of pneumococci. Splenectomy impaired clearance of pneumococci from mouse lungs and allowed for increased translocation of pneumococci to tracheobronchial lymph nodes compared to shams (P less than 0.01). Pneumococcal vaccine improved lung clearance in both splenectomized and sham-operated mice compared to saline controls (P less than 0.01), but the number of live pneumococci recovered from lung pairs was greater in splenectomized mice compared to shams (P less than 0.01). Pneumococcal vaccination facilitated earlier translocation of pneumococci to tracheobronchial lymph nodes, and probably promoted bactericidal activity in these nodes, in both splenectomized and sham-operated mice. Survival in splenectomized mice was improved by vaccination, but remained significantly less than that in saline-treated sham-operated mice (P less than 0.0009). The data show that pneumococcal vaccine can improve lung antipneumococcal defenses in splenectomized mice, but not to the same degree as in mice retaining their spleens. Pneumococcal vaccine should be given after splenectomy, but surgeons should caution patients that it may be less effective than when given to individuals with intact spleens or before elective surgery.


Inactivation mechanism of chlorination in Escherichia coli internalized in Limnoithona sinensis and Daphnia magna.
Zooplankton may harbor microorganisms in the aquatic environment, thus protecting them from disinfection during drinking water treatment. However, few studies have evaluated the protective effect of internalization by zooplankton against bacterial disinfection. In this study, we investigated the role of zooplankton (Limnoithona sinensis and Daphnia magna) as a refuge for ingested bacteria against inactivation by chlorination. Only 30% of chlorine reached the internalized bacteria inside the digestive tract of zooplankton. However, this was sufficient to achieve 1.4 log inactivation of internalized Escherichia coli in L. sinensis and 1.2 log inactivation in D. magna at Ct values of 80 mg min/L. Inactivation of internalized bacteria was achieved through the active transfer of free chlorine in the bulk water into the zooplankton digestive tract during grazing activity. D. magna was more sensitive to hypochlorous acid than L. sinensis, and its grazing behavior was inhibited during the inactivation experiment.