An investigation into the fatty acid content of selected fish-based commercial infant foods in the UK and the impact of commonly practiced re-heating treatments used by parents for the preparation of infant formula milks.
The importance of dietary lipids during infancy is paramount for rapid growth and development. Linoleic acid (LA), α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) were quantified using RP-HPLC with charged aerosol detection in a range of complementary infant foods and formula milk. Total daily intake of fatty acids for infants aged 6-9 months was calculated based on the consumption of complementary infant foods and formula milk. Total daily intakes of ALA, AA and DHA were below, whereas LA was above the recommended intake. This provides scope for product optimisation, to improve the nutritive value of commercial infant food products. The impact of re-heating treatments by parents on fatty acid content of formula milk was investigated and statistically significant changes were observed. Furthermore, the transparency of the labelling information declared by the manufacturers was within recommendations despite a degree of significant variation.


Chronic dichlorvos exposure: microglial activation, proinflammatory cytokines and damage to nigrostriatal dopaminergic system.
Dopaminergic cells in the substantia nigra are highly vulnerable to the neurodegenerative process of Parkinson's disease. Therefore, mechanisms that enhance their susceptibility to injury bear important implications for disease pathogenesis. We have previously shown that chronic dichlorvos exposure caused nigrostriatal dopaminergic degeneration and significant behavioral impairments. In this study, we analyzed the relationship between microglial activation and dopaminergic neurodegeneration to examine the possibility that neuroinflammation may induce dopaminergic neuronal loss in the nigrostriatal system. Chronic dichlorvos exposure causes microglial activation including induction of NADPH oxidase and a selective loss of dopaminergic neurons in rat. Microglial marker expression was increased at transcription as well as translational levels in the substantia nigra (SN) and corpus striatum (CS) of rats exposed to dichlorvos. Activated microglia were seen in SN and CS of dichlorvos-treated animals but were rarely observed in controls. Immunostaining revealed lesser number of TH-positive neurons and higher number of microglia in SN and CS regions after dichlorvos treatment. The mRNA and protein levels of the NADPH oxidase main subunit gp91(phox) were significantly increased after dichlorvos administration. Dichlorvos exposure also leads to increased level of microglial noxious mediators such as IL-1β, TNF-α and IL-6 in ventral midbrain and CS at transcription as well as translational levels. Data indicate that microglial activation and consequent induction of NADPH oxidase and proinflammatory cytokines such as TNF-α, IL-1β and IL-6 may act as risk factors for Parkinson's disease by increasing the vulnerability of dopaminergic cells to dichlorvos toxic injury.


Puromycin-resistant lentiviral control shRNA vector, pLKO.1 induces unexpected cellular differentiation of P19 embryonic stem cells.
RNA silencing is used as a common method for investigating loss-of-function effects of genes of interest. In mammalian cells, RNA interference (RNAi) or RNA silencing can be achieved by transient siRNA (small or short interfering RNA) transfection or by stable shRNA (short hairpin RNA) systems. Various vectors are used for efficient delivery of shRNA. Lentiviral vectors offer an efficient delivery system for stable and long-term expression of the shRNA in mammalian cells. The widely used lentiviral pLKO.1 plasmid vector is very popular in RNAi studies. A large RNAi database, a TRC (the RNAi Consortium) library, was established based on the pLKO.1-TRC plasmid vector. This plasmid (also called pLKO.1-puro) has a puromycin-resistant gene for selection in mammalian cells along with designs for generating lentiviral particles as well for RNA silencing. While using the pLKO.1-puro TRC control shRNA plasmid for transfection in murine P19 embryonic stem (ES) cells, it was unexpectedly discovered that this plasmid vector induced robust endodermal differentiation. Since P19 ES cells are pluripotent and respond to external stimuli that have the potential to alter the phenotype and thus its stemness, other cell types used in RNA silencing studies do not display the obvious effect and therefore, may affect experiments in subtle ways that would go undetected. This study for the first time provides evidence that raises concern and warrants extreme caution while using the pLKO.1-puro control shRNA vector because of its unexpected non-specific effects on cellular integrity.


Bipolar versus unipolar issues in DDD pacing.
The relative merits of unipolar and bipolar systems are reviewed in the context of DDD pacing. In order to allow reliable atrial sensing in the presence of myopotentials and exogenous noise, bipolar atrial sensing is desirable. Bipolar ventricular sensing will reduce the incidence of myopotential sensing and may reduce susceptibility to cross-talk. Unipolar systems, however, generally offer better stimulation characteristics. Considerations have led to the development of a new DDD pacemaker with bipolar sensing and unipolar pacing characteristics. The bipolar-sense/unipolar-pace pulse generator is simple to implement based upon a unipolar design and retains the simplicity, convenience, and reliability inherent in that mode.


[Genetic analysis of mutation sy2 which causes nonhomologous meiotic synapsis in chromosomes of diploid rye Secale cereale L].
Partially nonhomologous (heterologous) synapsis of meiotic chromosomes in a spontaneous desynaptic mutant form of rye is determined by two recessive genes, sy2a and sy2b, that have independent expression and inheritance. The third gene, dominant inhibitor suppressing the mutant phenotype, has been revealed in hybrid combinations between sy2 mutants and lines segregating other meiotic mutants: sy10 (heterologous synapsis), sy1, and sy9 (asynapsis). All three genes determining desynapsis (sy2a, sy2b, and I) were shown to be nonallelic to monogenic mutations sy10, sy1, and sy9, inherited independently of them and expressed at later stages of prophase I than the sy10 gene. The possibility of modifying monogenic segregation of mutation sy2 by gametophyte selection for a locus linked to the gene expressed as sy2 at particular frequencies of recombination between this gene and selected locus is discussed.


Rat immunoglobulin genes have comparable patterns of JH rearrangement in normal peripheral B cells and in pre-B and cultured TdT+ cells from bone marrow.
Pre-B cells from normal rat bone marrow were isolated by first rosette-depleting granulocytes, T cells and stem cells with W3/13 mAb and mature B cells with anti-Ig mAb, and then in some samples enriching by FACS-sorting HIS24+ cells. Presumptive precursors of these pre-B cells possessing terminal deoxy-nucleotidyl transferase were prepared by culture of normal marrow. The extent of rearrangement of kappa and heavy chain genes was estimated on both these types of cells and on mature peripheral B cells by measuring the disappearance of the germ-line restriction fragments encoding J segments (other than JH1) relative to a non-rearranging CK fragment. Pre-B cells and B cells showed similar degrees of rearrangement of their kappa genes, leaving roughly half in germ-line form; the TdT+-enriched cells showed approximately similar heavy chain rearrangement as the peripheral B cells. Some non-germ-line restriction fragments hybridising with JH in sufficient amount to register as discrete bands on Southern blots were found in common between these different cell populations taken from different individual donors. These may represent preferred D-JH or perhaps V-D-JH rearrangement arising repetitively in independent clones, or may be due to dominance by a few preferred clones.


2-(4-Chloro-3,3,7-trimethyl-2,3-dihydro-1H-indol-2-yl-idene)-2-cyano-acetamide.
Reaction of 2-(4-chloro-3,3,7-trimethyl-2,3-dihydro-1H-indol-2-yl-idene)propane-dial with hydroxyl-amine gives the title compound, C(14)H(14)ClN(3)O, in which the ring N atom is essentially planar [sum of angles around the ring N atom = 361°], indicating conjugation with the 2-cyano-acryl-amide unit. The orientation of the acetamide group arises from intra-molecular hydrogen bonding between the indole N-H and carbonyl groups. In the crystal, inversion-related acetamide groups form N-H⋯O hydrogen-bonded dimers in graph-set R(2) (2)(8) motifs, whilst dimers are also formed by pairs of amine-nitrile N-H⋯N hydrogen bonds in R(2) (2)(12) motifs. These inter-actions together generate ribbons that propagate along the b-axis direction.


Brain neuronal RNA metabolism during sustained low-level soman toxication.
Quantitative azure B-RNA cytophotometry was used to monitor metabolic responses of cholinergic elements of the rat brain during sustained low-level administration of soman (0.25-0.50 LD50, sc). RNA contents of caudate and cerebrocortical (Layers III and V) neurons were measured 60 min following 1-5 soman dosages given at 24 h intervals. Marked and progressive RNA depletion was evidenced after 1-4 soman injections, whereas partial or complete restitution of RNA levels was observed following the fifth injection. These data indicate that repetitive soman toxication is associated with metabolic correlates of impaired rather than accentuated activation of CNS cholinergic systems, and that tolerance is developed to CNS actions of the agent. It is postulated that impaired neuronal activation is related to soman or ACh-induced transmission block, and that the same adaptive processes responsible for recovery during acute poisoning may underlie the development of tolerance during repetitive administration of organophosphates.


Practice of pharmaceutical care by community pharmacists in response to self-medication request for a cough: a simulated client study.
Community pharmacy practice worldwide has been shifting from product-focused to patient-oriented. However, due to the absence of separation between prescribing and dispensing in Malaysia, community pharmacists may have limited roles in the provision of pharmaceutical care to patients with chronic diseases. Therefore, the main functions of community pharmacists in Malaysia are related to self-medication requests for minor ailments and the supply of non-prescription medications. The objective of this study was to determine the practice of pharmaceutical care by community pharmacists within the Klang Valley, Malaysia in response to self-medication requests for a cough. This study utilised a simulated client method. A research assistant, acting as a simulated client, visited community pharmacies in the Klang Valley, Malaysia to consult the pharmacists on the treatment of a cough experienced by his father. Upon leaving the pharmacy premise, the simulated client entered the pharmacist's responses in a data collection form which was structured based on pharmacy mnemonics for the response to symptoms, OBRA'90 on counselling elements, the five practice principles of pharmaceutical care by the American Pharmacists Association and literature review. Visits to the community pharmacies were conducted from September to October 2018. The simulated client visited a total of 100 community pharmacies. None of these community pharmacists practised adequate patients' data collection, with only a low proportion who practised all the components studied under medication information evaluation (13%), formulating a drug therapy plan (15%) and monitoring and modifying the plan (3%). Of the 100 community pharmacists, 98 recommended treatment but none of them provided all the counselling elements studied in implementing the drug therapy plan. The present study showed that community pharmacists within the Klang Valley, Malaysia were not providing adequate pharmaceutical care services to patients seeking self-medication for a cough. Such practice may compromise patient safety if inappropriate medicines or advice are given.


Photoreceptor-like outer segments in the pineal organ of the lovebird, Uroloncha domestica (Aves: passeriformes). A scanning electron microscopic study.
In the pineal organ of the lovebird, Uroloncha domestica, bulbous, cup-shaped and elongated outer segments of photoreceptor-like pinealocytes are demonstrated by scanning electron microscopy. These scarce outer segments, 4-11 micron in length, extend into the pineal lumen. The present structural observations speak in favor of photosensitive pinealocytes in the pineal organ of Uroloncha domestica. The relation of the photoreceptor-like pinealocytes to acetylcholinesterase-positive nerve cells and a nervous connection between the pineal and the brain indicate that the pineal organ of this passeriform species may be the site of neuroendocrine and photoreceptive functions.


Worm control practices on sheep farms in the Slovak Republic.
A questionnaire to obtain information on worm control practices and sheep management was performed on 49 sheep farms in 2003 and 2004. The majority of Slovak farms kept native breeds Tsigai (22 farms) and Improved Valachian (14 farms). Farms were divided according to their altitude to lowland, upland and lower highland farms. Sizes of pastures and stocking rates for lowland, upland and lower highland farms were 81.5, 269.2, and 316.7 ha and 6.3, 2.6, and 2.9 sheep/ha, respectively. One third of farmers (33.3%) used permanent pastures and two thirds of breeders (66.7%) rotated sheep between pastures. Mean drenching rate for lambs and yearlings/adults was 1.76 and 1.70, respectively. The most frequently used drugs during period from 1999 to 2004 were albendazole and ivermectin. On 13 farms benzimidazole drugs were applied in spring before turn out and macrocyclic lactones in autumn before turn in. Benzimidazoles and macrocyclic lactones were used almost exclusively on 7 and 9 farms, respectively. Visual appraisal was the most common practice to determine weight of animals (87.8% of farmers). Weights of the heaviest animals were used for determination of anthelmintic doses only on 16.7% of farms. Coprological examinations were performed on 47.9% of farms, usually in frequency once per year (75%).


Twenty-four-hour ambulatory blood pressure variability and association with ischemic stroke subtypes in the subacute stage.
Blood pressure (BP) variability (BPV) increases the risk of cerebral disease in both hemorrhagic and ischemic strokes. However, whether BPV is associated with different types of ischemic stroke remains unclear. In this study, we explored the relationship between BPV and ischemic stroke subtypes. We enrolled consecutive patients aged 47-95 years with ischemic stroke in the subacute stage. We categorized them into four groups based on their artery atherosclerosis severity, brain magnetic resonance imaging markers, and disease history: large-artery atherosclerosis, branch atheromatous disease, small-vessel disease, and cardioembolic stroke. Twenty-four-hour ambulatory blood pressure monitoring was performed, and the mean systolic blood pressure/diastolic blood pressure, standard deviation, and coefficient of variation were calculated. A multiple logistic regression model and random forest were used to test the relationship between BP and BPV in the different types of ischemic stroke. A total of 286 patients, including 150 men (73.0 ± 12.3 years) and 136 women (77.8 ± 9.6 years) were included in the study. Of these, 86 (30.1%) patients had large-artery atherosclerosis, 76 (26.6%) had branch atheromatous disease, 82 (28.7%) had small-vessel disease, and 42 (14.7%) had cardioembolic stroke. There were statistically significant differences in BPV between subtypes of ischemic stroke in 24-h ambulatory blood pressure monitoring. The random forest model showed that BP and BPV were important features associated with ischemic stroke. Multinomial logistic regression analysis demonstrated that systolic blood pressure levels; systolic blood pressure variability at 24 h, daytime and nighttime; and nighttime diastolic blood pressure were independent risk factors for large-artery atherosclerosis after adjustment for confounders. When compared to branch atheromatous disease and small-vessel disease, nighttime diastolic blood pressure and standard deviation of diastolic blood pressure were significantly associated with patients in the cardioembolic stroke group. However, a similar statistical difference was not seen in patients with large-artery atherosclerosis. The results of this study indicate a discrepancy in blood pressure variability among different ischemic stroke subtypes during the subacute stage. Higher systolic blood pressure and systolic blood pressure variability during the 24 h, daytime, and nighttime, and nighttime diastolic blood pressure were independent predictors for large-artery atherosclerosis stroke. Increased nighttime diastolic BPV was an independent risk factor for cardioembolic stroke.


Dominance wave propagation during binocular rivalry in mild glaucoma.
Glaucoma is both a progressive optic neuropathy and a neurodegenerative disease affecting structures in the primary visual pathway. Other vision-associated areas may also be affected, including the corpus callosum which is involved in inter-hemispheric transfer. This study evaluated dominance wave propagation during binocular rivalry to probe the efficacy of the inter-hemispheric transfer in 20 patients with mild open angle glaucoma and 25 age-matched controls. The two groups were matched for functional measures such as stereo-acuity, binocular visual acuity, and visual field mean deviation. Monocular functional and structural measures were equivalent for the left and right eye of each participant. Using Wilson et al.'s travelling wave paradigm [Nature, 412 (2001) 907-910], intra- and inter-hemispheric failure rates of traveling wave transmission and the travelling wave propagation times were recorded for the two groups. For the control group, the wave propagation failure rate was significantly greater for the inter- than for the intra-hemispheric condition, but for the glaucoma group, the failure rates were equally high for the two conditions. The wave propagation time was significantly longer for the inter- than for the intra-hemispheric condition for the control group, while the opposite was true for the glaucoma group. These results reveal changes in the wave dynamics of rivalry dominance in patients with mild glaucoma who otherwise have normal performance on standard functional measures.


Inhalation of 50% Oxygen Does Not Impair Respiratory Depression During Midazolam Sedation.
To investigate how inhalation of 50% oxygen during intravenous midazolam sedation affects respiratory variables and thus the availability of oxygen. Study subjects were 21 healthy adult volunteers (American Society of Anesthesiologists physical status I). They were allocated to undergo midazolam sedation during high-concentration oxygen inhalation (group H) or during normal air inhalation (group N) in a single-blinded randomized crossover design, with an interval of at least 3 days between the 2 sedation sessions. In each experiment, midazolam 0.05 mg/kg was administered, after which the following variables were measured for 40 minutes: oxygen saturation by pulse oximetry (SpO2), end-tidal carbon dioxide partial pressure (ETCO2), respiration rate (RR), tidal volume (VT), and minute volume (MV). Subsequently, flumazenil 0.5 mg was administered, and the same variables were measured for 10 minutes. SpO2 decreased after midazolam administration in the 2 groups. SpO2 in group H was higher than that in group N at all time points. RR increased and VT decreased after midazolam administration in the 2 groups; however, in contrast to SpO2, the levels of these parameters did not meaningfully differ between groups at any time point. MV remained unchanged in the 2 groups. ETCO2 decreased similarly after midazolam administration in the 2 groups. Inhalation of 50% oxygen during midazolam sedation did not enhance respiratory depression by midazolam. This suggests that high-concentration oxygen inhalation during midazolam sedation could prevent hypoxia.


Effect of surface treatments on the bond strength of etched-metal resin-bonded retainers.
The effects of surface treatments on the shear bond strength of etched metal to bovine enamel were evaluated. Abraded etched metal without contamination had the highest shear bond, while debonding occurred within the resin interface rather than in the resin to etched metal or resin to enamel.


β-Escin reduces cancer progression in aggressive MDA-MB-231 cells by inhibiting glutamine metabolism through downregulation of c-myc oncogene.
The c-myc oncogene, which causes glutamine dependence in triple negative breast cancers (TNBC), is also the target of one of the signaling pathways affected by β-Escin. We sought to determine how c-myc protein affects glutamine metabolism and the proteins, glutamine transporter alanine-serine-cysteine 2 (ASCT2) and glutaminase (GLS1), in β-Escin-treated MDA-MB-231 cells using glutamine uptake and western blot analysis. Cell viability, colony formation, migration and apoptosis were also evaluated in MDA-MB-231 cells in response to β-Escin treatment using MTS, colony forming, wound healing, and Annexin-V assay. We determined that β-Escin decreased glutamine uptake and reduced c-myc and GLS1 protein expressions and increased the expression of ASCT2. In addition, this inhibition of glutamine metabolism decreased cell proliferation, colony formation and migration, and induced apoptosis. In this study, it was suggested that β-Escin inhibits glutamine metabolism via c-myc in MDA-MB-231 cells, and it is thought that as a result of interrupting the energy supply in these cells via c-myc, it results in a decrease in the carcinogenic properties of the cells. Consequently, β-Escin may be promising as a therapeutic agent for glutamine-dependent cancers.


Age and gender distribution of hepatitis C virus genotypes in the metropolitan area of Naples.
To assess any time-related variations in the distribution of hepatitis C virus (HCV) genotypes in the metropolitan area of Naples, Italy. HCV genotypes were analysed in 255 HCV RNA-positive patients with chronic HCV infection, observed from 2009 to 2011, and compared with data pertaining to a sample of 176 HCV RNA-positive patients observed from 2006 to 2008. In both periods of analysis, genotype 1b was predominant (51.8 and 48.3%, respectively), followed by genotype 2 (27.9 and 31.7%, respectively). These HCV genotypes were particularly prevalent in older patients, whereas genotypes 3a and 1a were observed more frequently in the younger population. Genotype 1b was particularly common in females compared to males in both study periods (39.3% of 89 males vs. 64.3% of 87 females in the 3-year period 2006-2008, p < 0.001; 41.5% of 118 males vs. 54.0% of 137 females in the period 2009-2011, p < 0.05). The prevalence of patients with genotype 1b in the age range 51-60 years was higher in the 2006-2008 period than in 2009-2011 (76.9 vs. 37.7%; p < 0.0005) and lower in the over 60 year olds (55.1 vs. 59.6%; p = 0.5). Genotype 1b, historically the most prevalent in Italy, is still predominant; however, when comparing the two time periods, a cohort effect evidencing the increasing prevalence of genotype 1b among elderly patients was revealed.


Anesthetic modulation of water diffusion: Insights from a diffusion tensor imaging study.
Diffusion tensor imaging (DTI) in animal models are essential for translational neuroscience studies. A critical step in animal studies is the use of anesthetics. Understanding the influence of specific anesthesia regimes on DTI-derived parameters, such as fractional anisotropy (FA) and mean diffusivity (MD), is imperative when comparing results between animal studies using different anesthetics. Here, the quantification of FA and MD under different anesthetic regimes, alpha-chloralose and isoflurane, is discussed. We also used a range of b-values to determine whether the anesthetic effect was b-value dependent. The first group of rats (n = 6) was anesthetized with alpha-chloralose (80 mg/kg), whereas the second group of rats (n = 7) was anesthetized with isoflurane (1.5%). DTI was performed with b-values of 500, 1500, and 1500s/mm2, and the MD and FA were assessed individually. Anesthesia-specific differences in MD were apparent, as manifested by the higher estimated MD under isoflurane anesthesia than that under alpha-chloralose anesthesia (P < 0.001). MD values increased with decreasing b-value in all regions studied, and the degree of increase when rats were anesthetized with isoflurane was more pronounced than that associated with alpha-chloralose (P < 0.05). FA quantitation was also influenced by anesthesia regimens to varying extents, depending on the brain regions and b-values. In conclusion, both scanning parameters and the anesthesia regimens significantly impacted the quantification of DTI indices.


Fundamental and practical aspects of machine learning for the peak picking of biomolecular NMR spectra.
Rapid progress in machine learning offers new opportunities for the automated analysis of multidimensional NMR spectra ranging from protein NMR to metabolomics applications. Most recently, it has been demonstrated how deep neural networks (DNN) designed for spectral peak picking are capable of deconvoluting highly crowded NMR spectra rivaling the facilities of human experts. Superior DNN-based peak picking is one of a series of critical steps during NMR spectral processing, analysis, and interpretation where machine learning is expected to have a major impact. In this perspective, we lay out some of the unique strengths as well as challenges of machine learning approaches in this new era of automated NMR spectral analysis. Such a discussion seems timely and should help define common goals for the NMR community, the sharing of software tools, standardization of protocols, and calibrate expectations. It will also help prepare for an NMR future where machine learning and artificial intelligence tools will be common place.


Oculo-facio-cardio-dental syndrome in a mother and daughter.
Oculo-facio-cardio-dental (OFCD) syndrome is a rare X-linked dominant syndrome characterized by canine teeth with extremely large roots (radiculomegaly), congenital cataract, dysmorphic facial features and congenital heart disease. A case of mother-daughter vertical transmission of OFCD is reported. Dental findings were important in confirming the diagnosis in the mother.


Angiotensin converting enzyme inhibitor attenuates oxidative stress-induced endothelial cell apoptosis via p38 MAP kinase inhibition.
The effects of angiotensin converting enzyme (ACE) inhibitors on oxidative stress-induced apoptosis of endothelial cells and the intracellular signaling were investigated. Cultured endothelial cells derived from a bovine carotid artery were treated with H2O2 or TNF-alpha to induce apoptosis. Apoptosis was evaluated by DNA fragmentation and cell viability, p38 MAP kinase activity by Western blotting, and oxidative stress by formation of 8-isoprostane. The effects of ACE inhibitors were examined by adding them into the medium throughout the experiments. Apoptosis was attenuated by ACE inhibitors, temocapril and captopril, in a dose-dependent manner (1-100 micromol/l). H2O2 (0.2 mmol/l for 1.5 h) or TNF-alpha (10 ng/ml for 72 h) treatment stimulated the activities of p38 MAP kinase. Temocapril and captopril decreased the activity of p38 MAP kinase as well as 8-isoprostane formation induced by H2O2. A p38 MAP kinase inhibitor, SB203580, partially inhibited the effect of temocapril on apoptosis. These results suggest that ACE inhibitors protect endothelial cells from oxidative stress-induced apoptosis, and that p38 MAP kinase plays a critical role in the process.


Use of the supportive care framework to explore haematological cancer survivors' unmet needs: a qualitative study.
Some sub-types of haematological cancers are acute and require intensive treatment soon after diagnosis. Other sub-types are chronic, relapse over many years and require life-long cycles of monitoring interspersed with bouts of treatment. This often results in significant uncertainty about the future, high levels of depression and anxiety, and reduced quality of life. Little is known about how to improve care for haematological cancer survivors. This study explored qualitatively, in a sample of haematological cancer survivors, (i) their unmet needs experienced as a result of their disease and treatment; and (ii) strategies that may help address these needs. Semi-structured interviews were conducted with 17 adult haematological cancer survivors. Data was analysed using qualitative content analysis. The Supportive Care Framework guided data collection and analysis. Participants had a mean age of 57 years (SD 13). Most were male (n = 10, 59%). Five themes emerged from the data: (i) changes in unmet needs across the care trajectory (with greatest unmet needs experienced soon after diagnosis, at discharge from hospital and with cancer recurrence); (ii) informational unmet needs requiring improved patient-centred communication; (iii) uncertainty about treatment and the future; (iv) coordinated, tailored and documented post-treatment care planning as a strategy for optimal care delivery; and (v) ongoing support services to meet psychosocial and practical unmet needs by involving peer support, less bureaucratic transport services and flexible work arrangements. To our knowledge, this is the first qualitative investigation using the Supportive Care Framework to explore unmet needs of haematological cancer survivors. Our findings offer fresh insights into this important area of study. Written, take-home care plans which provide simple but tailored guidance on where to seek additional support may help decrease uncertainty and feelings of vulnerability post-treatment for adult haematological cancer survivors. Future research should further develop and test strategies aimed at addressing unmet needs of haematological cancer survivors identified in this study.


Electromagnetically induced transparency metamaterial based on spoof localized surface plasmons at terahertz frequencies.
We numerically and experimentally demonstrate a plasmonic metamaterial whose unit cell is composed of an ultrathin metallic disk and four ultrathin metallic spiral arms at terahertz frequencies, which supports both spoof electric and magnetic localized surface plasmon (LSP) resonances. We show that the resonant wavelength is much larger than the size of the unit particle, and further find that the resonant wavelength is very sensitive to the particle's geometrical dimensions and arrangements. It is clearly illustrated that the magnetic LSP resonance exhibits strong dependence to the incidence angle of terahertz wave, which enables the design of metamaterials to achieve an electromagnetically induced transparency effect in the terahertz frequencies. This work opens up the possibility to apply for the surface plasmons in functional devices in the terahertz band.


Patterns, contexts, and motivations for polysubstance use among people who inject drugs in non-urban settings in the U.S. Northeast.
Polysubstance use (i.e., using ≥2 psychoactive substances concomitantly) is associated with increased morbidity and mortality and complicates drug treatment needs among people who inject drugs (PWID). We explored patterns, contexts, motivations, and perceived consequences of polysubstance use among PWID in small cities and towns in the U.S. Northeast. Between October 2018 and March 2019, we conducted semi-structured interviews with 45 PWID living outside of the capital cities of Rhode Island and Massachusetts recruited online and through community-based organizations. Written transcripts were coded inductively and deductively using a team-based approach and analyzed thematically. All participants reported recent polysubstance use, with most using five or more classes of substances in the past three months. Polysubstance use often followed long personal drug use histories (i.e., years or decades of occasional drug use). Reasons for polysubstance use included obtaining synergistic psychoactive effects as a result of mixing drugs (i.e., using drugs to potentiate effects of other drugs) and managing undesirable effects of particular drugs (e.g., offsetting the depressant effects of opioids with stimulants or vice-versa). Polysubstance use to self-medicate poorly managed physical and mental health conditions (e.g., chronic pain, anxiety, and depression) was also reported. Inadequately managed cravings and withdrawal symptoms prompted concomitant use of heroin and medications for opioid use disorder, including among individuals reporting cocaine or crack as their primary "issue" drugs. Polysubstance use was perceived to increase overdose risks and to be a barrier to accessing healthcare and drug treatment services. Healthcare services and clinicians should acknowledge, assess, and account for polysubstance use among patients and promote harm reduction approaches for individuals who may be using multiple drugs. Comprehensive healthcare that meets the social, physical, mental health, and drug treatment needs of PWID may decrease the perceived need for polysubstance use to self-medicate poorly managed health conditions and symptoms.


Type 2 innate lymphoid cells-new members of the "type 2 franchise" that mediate allergic airway inflammation.
Type 2 innate lymphoid cells (ILC2s) are members of an ILC family, which contains NK cells and Rorγt(+) ILCs, the latter including lymphoid tissue inducer (LTi) cells and ILCs producing IL-17 and IL-22. ILC2s are dedicated to the production of IL-5 and IL-13 and, as such, ILC2s provide an early and important source of type 2 cytokines critical for helminth expulsion in the gut. Several studies have also demonstrated a role for ILC2s in airway inflammation. In this issue of the European Journal of Immunology, Klein Wolterink et al. [Eur. J. Immunol. 2012. 42: 1106-1116] show that ILC2s are instrumental in several models of experimental asthma where they significantly contribute to production of IL-5 and IL-13, key cytokines in airway inflammation. This study sheds light over the relative contribution of ILC2s versus T helper type 2 cells (Th2) in type 2 mediated allergen-specific inflammation in the airways as discussed in this commentary.


BIBP 3226 inhibition of nicotinic receptor mediated chromaffin cell secretion.
(R)-N 2-(diphenacetyl)-N-[(4-hydroxyphenyl)methyl]-argininamide (BIBP 3226) is a selective neuropeptide Y Y1 receptor antagonist with structural similarity to the C-terminal tripeptide of neuropeptide Y. Based on this similarity we questioned whether BIBP 3226 could act as an agonist. Incubation of BIBP 3226 with bovine chromaffin cells in culture results in the inhibition of nicotinic receptor-stimulated catecholamine secretion (IC50 = 2.4 microM). The effect of BIBP 3226 is independent of neuropeptide Y action since the presence of neuropeptide Y in the culture medium does not alter the effect of BIBP 3226. BIBP 3226 decreased the efficacy of the nicotinic receptor agonist, 1,1-dimethyl-4-phenylpiperizinium (DMPP), but did not change its potency suggesting non-competitive inhibition. BIBP 3226 has a similar effect on nicotinic receptor-stimulated 45Ca2+ influx. BIBP 3226 does not inhibit [3H]norepinephrine release induced by high K+ and its effect is not pertussis toxin-sensitive. We conclude that not only can BIBP 3226 act as a neuropeptide Y receptor antagonist in bovine chromaffin cells but also act as an agonist and inhibit catecholamine secretion.


A spontaneous mesenteric hematoma with a fistula between the transverse colon resected by laparoscopic surgery: A case report.
A spontaneous mesenteric hematoma is rare, and its etiology is unclear. We present a very rare case of spontaneous mesenteric hematoma with a fistula to the transverse colon. A 90-year-old male visited our hospital because of lower abdominal pain. The physical examination revealed tenderness in the lower abdomen. The laboratory data revealed anemia and low estimated glomerular filtration rate (eGFR). The abdominal contrast-enhanced computerized tomography (CT) indicated a mass with coexisting low- and high-density areas adjacent to the transverse colon. The mass was diagnosed as a mesenteric hematoma. We selected conservative therapy, because the patient's condition was stable. After 15 days from discharge, he was admitted to the hospital again for the complaint of bloody stool. A fistula with blood flowing out at the splenic flexure was reported on colonoscopy. In the laparoscopic operative findings, the hematoma adhered to the stomach, pancreas and omentum. A hand-assisted laparoscopic transverse colectomy including hematoma in the mesentery was successful. The pathological reports revealed that a spontaneous mesenteric hematoma formed the fistula to the colon. The patient was discharged without any postoperative complication on day 10. Generally, laparotomy is often chosen for the treatment of mesenteric hematoma. The laparoscopic approach for mesenteric hematoma is useful under the specific condition that the preoperative patient's condition is stable. This is the first case of a spontaneous mesenteric hematoma with a fistula to the colon resected safely by laparoscopic surgery.


Dendritic cells: clinical aspects.
Clinical aspects of dendritic cells have yet to be studied intensively. One obstacle, that of isolating and identifying dendritic cells from human blood and other tissues like skin and tonsil, is being overcome, although the field would be facilitated by dendritic-cell-specific monoclonals or other probes. Many of the specializations that dendritic cells exhibit as antigen-presenting cells in other mammals are being verified in man. New properties, particularly their capacity to induce clonal expansion of T cells and to be infected with retroviruses, have become evident. Four areas where it may be productive to give more attention to dendritic cells are transplantation, protective T-cell immunity, autoimmunity and HIV-1 infection.


Interactive responses to stimulation of the amygdaloid central nucleus and baroreceptor afferent activation in the rabbit.
Recent evidence suggests that the amygdaloid central nucleus (ACE) may contribute to the regulation of arterial baroreceptor-vagal reflex sensitivity. To obtain additional data relevant to this suggestion, interactions between stimulation of the ACE and arterial baroreceptor afferent activation were examined. New Zealand rabbits were anesthetized with alpha-chloralose and a stimulating electrode was implanted stereotaxically in the ACE. In the first series of experiments, cardiovascular responses to stimulation of the ACE were assessed during periods in which blood pressure was decreased using sodium nitroprusside or increased in the rostral arterial compartment by inflating the tip of a Swan-Ganz catheter positioned in the descending aorta. It was found that the magnitude of bradycardia to stimulation of the ACE was correlated with the level of arterial blood pressure at the onset of stimulation, such that higher blood pressures were associated with larger bradycardic responses. These data suggest that arterial baroreceptor afferent activity may be an important factor in the elicitation of bradycardia from the ACE. In the second series of experiments, the aortic nerve was isolated, and cardiovascular responses to stimulation of the aortic nerve and to low frequency (5 Hz) stimulation of the ACE were assessed both alone and in combination. Stimulation of the aortic nerve during low frequency stimulation of the ACE was found to produce bradycardia of a significantly larger magnitude than the sum of the responses produced by each stimulus presented alone. These data demonstrate that bradycardia to stimulation of baroreceptor afferent fibers is augmented significantly during low frequency stimulation of the ACE. Taken together, these results are consistent with the notion that the ACE may contribute to the sensitivity of the arterial baroreceptor-vagal reflex.


PATTERN OF DERMATOLOGICAL ADMISSIONS IN A REFERRAL SERVICE HOSPITAL.
The pattern of dermatological admissions based on retrospective study of 1578 Armed Forces personnel who were hospitalised during period of Jan 1984 to Dec 1994 at Command Hospital Southern Command, Pune were analysed. Average yearly admission was 144. Eczema was the most common skin disease requiring admission and accounted for 29.5 per cent cases followed by infections and infestations 25.5, papulo-squamous disorders 21.4, urticaria 4.2, connective tissue disorders 4.2, bullous disorders 2.8, and others 12.4 per cent.


Simulation of CA3 region of hippocampus by kinetic models.
The global activities of the hippocampal CA3 field which are induced by stimuli coming from entorhinal cortex have been investigated through computional experiments. The simulations are based on a mathematical model formulated within the frame of a kinetic theory of neural systems. To obtain a description closer to the real biological system, the kinetic model has been supplemented with elements describing the dynamics of neurotransmitters in synaptic clefts. Because high frequency activities occur in the CA3 field, elements for the description of receptor saturation and vesicle depletion phenomena have also been taken into account. The computational experiments show that CA3 model reacts to simulated stimuli from entorhinal sources activating the pyramidal neurons. This activity self-organizes within some limited areas, and spreads to the whole CA3 as a patterned reverberation of short period which requires both excitatory and inhibitory neural populations. The reverberating activity is then stopped by massive inhibition produced by slow-inhibitory neural population. The relationships between the parameters linked to the synaptic dynamic and the elements characterizing these patterns have been investigated.


Long-lasting complete remission in a patient with systemic metastases of recurrent breast cancer treated with cyclin-dependent kinases 4/6 inhibitors: a case report.
The prognosis for recurrence cases of hormone receptor-positive HER2-negative breast cancer remains poor, and treatment strategies that emphasize quality of life have often been chosen, with few physicians aiming for a cure. Our objective is to assess the validity of such current treatment strategies. A 74-year-old Asian woman with multiple lung and liver metastases after local recurrence of breast cancer was treated with two different cyclin-dependent kinases 4/6 inhibitors sequentially in combination with endocrine therapy. Flow cytometric analysis of the patient's peripheral blood mononuclear cells was also performed to evaluate the host's immune status. Complete remission was achieved without cytotoxic agents and the patient remains disease free to this day, 6 years after the initial relapse. Additionally, no increase in the population of the immunosenescent T cells with a phenotype of CD8+CD28- was observed in the patient's peripheral blood mononuclear cells, suggesting that the immune system was well maintained. We present this case study to develop new treatment strategies for recurrent breast cancer that is not only bound to misinterpretations of the Hortobagyi algorithm, but also aim for a cure with noncytotoxic agents to maintain the host's immune system and early detection of recurrence.


Animal models of human leukocyte antigen B27-linked arthritides.
The major histocompatibility complex class I allele human leukocyte antigen (HLA) B27 is strongly associated with human spondyloarthropathies. To date, 12 subtypes of HLA-B27 are known and most of them are linked with human spondyloarthropathies in different ethnic populations. Although these subtypes differ from each other by a few amino acids, the have an identical B pocket in the base of the antigen-binding groove. Considering the structure of HLA-B27 subtypes and their peptide binding specificity, it is important to consider their role as antigen-presenting molecules. Many B27-linked diseases begin after an infection with an enterobacteria, suggesting a role for environmental antigens in addition to an HLA-B27 molecule. To delineate the role of infection, studies have been carried out in animal models of reactive arthritidis. More recently, transgenic animal models have been used to understand the handling of environmental antigens by HLA-B27 molecule. This article discusses some of these transgenic and nontransgenic animal models of human diseases.


MiR-17-5p enhances pancreatic cancer proliferation by altering cell cycle profiles via disruption of RBL2/E2F4-repressing complexes.
The members of the miR-17-92 cluster are upregulated in various cancers and function as a cluster of oncogenic miRNA. Our study characterized a new function of miR-17-5p, a member of the miR-17-92 cluster, in regulating cell proliferation in pancreatic cancer. Our results indicate that miR-17-5p was up-regulated in pancreatic adenocarcinoma and directly targeted the retinoblastoma-like protein 2 (RBL2), a tumor suppressor belonging to the Rb family. High levels of miR-17-5p and low levels of RBL2 were associated with poor prognosis. RBL2 interacted with the transcription factor E2F4 and bound to the promoter regions of the E2F target genes. Disruption of the RBL2/E2F4 complex by miR-17-5p overexpression shifted the activity of E2F from gene repressing to gene activating, which induced cell cycle entry and proliferation. These results suggest that miR-17-5p promoted proliferation in pancreatic ductal adenocarcinoma cells (PDAC), and altered cell cycle profiles in vivo and in vitro, by disrupting the RBL2/E2F4-associated gene repressing complexes via direct targeting of RBL2. The new regulatory network, involving miR-17-5p and RBL2, emerges as a new target of PDAC treatment.


Pharmacogenetics of N-methylation: heritability of human erythrocyte histamine N-methyltransferase activity.
Histamine N-methyltransferase (HNMT) catalyzes the N tau-methylation of histamine. HNMT is present in many human tissues, including the red blood cell (RBC). Our study evaluated the possible role of inheritance in the regulation of individual variations in human RBC HNMT activity. HNMT activity was measured in RBC lysates from 241 members of 51 nuclear families. After correction for the gender-specific effects of age, the frequency distribution of RBC HNMT activities was unimodal, and activities varied threefold within 2 SDs of the mean. The correlation of HNMT activities in RBCs from 45 pairs of spouses was only 0.070, indicating that shared environment did not result in similar activities among genetically unrelated individuals. Correlation coefficients were also calculated for pairs of genetically related individuals. All of these correlations were significant except the mother-oldest son correlation. The majority of the correlations did not differ significantly from those predicted for a trait with a heritability of 1.0 (100%). Our results demonstrate a significant familial aggregation of human RBC HNMT activity and suggest that inheritance may play an important role in the regulation of variation in the activity of this N-methyltransferase enzyme in the human RBC.


Specificity of binding of a strain of uropathogenic Escherichia coli to Gal alpha 1----4Gal-containing glycosphingolipids.
A strain of Escherichia coli originally isolated from urine of a patient with acute pyelonephritis was studied in detail for binding to glycosphingolipids. Bacteria labeled metabolically with [14C]glucose were layered over a glycolipid chromatogram and bound bacteria were detected by autoradiography. The detection was down to a few ng of glycolipid (pmol level) under these assay conditions. At a test level of 500 ng all glycolipids (more than a dozen molecular species analyzed) with Gal alpha 1----4Gal as an internal or terminal part bound the bacteria strongly while glycolipids known to lack this sequence were negative. Conformational analysis using hard sphere calculations including the exo-anomeric effect showed a bend in the saccharide chain at this disaccharide with a largely hydrophobic surface of the convex side, probably being part of the binding epitope. Mixtures of glycolipids isolated from a human ureter scraping and from urinary sediments bound bacteria in the 2- to 7-sugar interval. Thus, this infectious strain of E. coli recognizes glycolipids being present in epithelial cells lining the urinary tract.


Muscarinic receptor-dependent activation of phospholipase C in the developing human fetal central nervous system.
The coupling of muscarinic-cholinergic receptors (mAChR) to adenylate cyclase and phospholipase C (PLC) second messenger systems has been demonstrated in many animal species. However, little is known about this association in the developing human central nervous system. Because of the proposed role of acetylcholine in the regulation of development and differentiation of neural cells, an understanding of these relationships during human fetal development gains importance. We report, in this communication, the coupling of mAChR with PLC in the human fetal brain. This coupling was determined using two independent approaches that relied upon estimating the accumulation of inositol phosphates (IPs) and cytidine diphosphate diacylglycerol (CDP-DAG). Carbachol treatment of brain slices, in the presence of lithium, resulted in the accumulation of IPs. Analysis of the kinetics of this accumulation showed that IP3 and IP2 increased rapidly, reaching a peak or plateau before IP. The results also showed that agonist-stimulated PLC produced two second messengers, IP3 and DAG. The production of DAG was strongly supported by the carbachol-dependent increase of CDP-DAG. The accumulation of IP and CDP-DAG was dependent on agonist concentration. The obtained EC50 values were approximately: carbachol 47 microM; acetylcholine 6 microM; and oxotremorine 25 microM. Unexpectedly, all three agonists demonstrated a similar efficacy. The cholinergic stimulation of inositide hydrolysis appears to be the result of activation of the m1 muscarinic receptor.


EDTA-dependent pseudo thrombocytopenia mimicking dengue fever-associated persistent thrombocytopenia: A case report.
No hemorrhagic manifestations, presence of platelet clumps on the peripheral blood smear, normal manual count, and normal autoanalyzer count after collecting blood in citrate vial help confirm the diagnosis of EDTA-dependent thrombocytopenia.


Wetting film stability and flotation kinetics.
Single bubble experiments performed with different size fractions of quartz particles and different, but known, contact angles revealed two modes of flotation dynamics in superclean water. (1.) A monotonic increase of collection efficiency Ecoll with increasing particle size was observed at high particle hydrophobicity and, correspondingly, a low wetting film stability (WFS). (2.) At low particle hydrophobicity and, correspondingly, high WFS, an extreme dependence of Ecoll on particle size was observed. The use of superclean water in our experiments prevented the retardation of bubble surface movement caused by surfactants or other impurities that is usual for other investigations and where particle-bubble inertial hydrodynamic interactions are suppressed. In the present study the free movement of the bubble surface enhances particle-bubble inertial interaction, creating conditions for different flotation modes, dependent on WFS. At the instant of inertial impact, a particle deforms the bubble surface, which may cause its rebound. Where the stability of the thin water film, formed between opposing surfaces of a bubble and a particle, is low, its rupture is accompanied with three phase contact line extension and contact angle formation before rebound. This prevents rebound, i.e. the first collision is accompanied by attachment. A high WFS prevents rupture during an impact. As a result, a contact angle does not arise and rebound is not prevented. However, rebound is accompanied by a second collision, the kinetic energy of which is smaller and can cause attachment at repetitive collision. These qualitative considerations are confirmed by the model quantification and comparison with measured Ecoll. For the first time the Sutherland equation (SE) for Ecoll is confirmed by experiment for smaller particle sizes and, correspondingly, very small Stokes numbers. The larger the particle size, the larger is the measured deviation from the SE. The SE is generalized, accounting for the centrifugal force, pressing hydrodynamic force and drainage in the low WFS case and, correspondingly, attachment occurs at first collision or during sliding. The derived generalized Sutherland equation (GSE) describes experimental data at low WFS. However, its application without account for possible rebound does not explain the measured extreme dependence in the case of high WFS. The theory for drainage during particle impact and the beginning of rebound enables conditions for either attachment or rebound in terms of the normal component of the impact velocity and the critical film thickness to be derived. Combining this condition with the GSE allowed the equation for Ecoll to be derived, accounting for attachment area shrinkage and attachment during a repetitive collision. This equation predicts the extreme dependence. Thus the WFS determines the modes of flotation dynamics and, in turn, probably affects the mechanisms, which control the flotation domain. At low WFS its upper boundary is controlled by the stability of the particle-bubble aggregate. At high WFS the upper boundary can be controlled by rebound because the latter reduces the attachment efficiency by a factor of 30 or more even with repetitive collision.


Factors that influence the provision of sexual health care by Dutch cancer nurses.
A descriptive-correlational design was used with a sample of Dutch cancer nurses (n = 104) to describe provision of sexual health care (SHC) and to explore influential factors. This report is limited to the second goal. The Theory of Reasoned Action provided the conceptual framework for investigation of five previously identified factors and one unexplored factor. Knowledge, comfort, attitude (towards sexuality) and subjective norm were significantly related with provision of SHC. Multiple regression analysis demonstrated that knowledge and comfort were significant explanatory variables, accounting for 37% of the variance.


p53 and p73 in suppression of Myc-driven lymphomagenesis.
Induction of apoptosis by the tumor suppressor p53 is known to protect from Myc-driven lymphomagenesis. The p53 family member p73 is also a proapoptotic protein, which is activated in response to oncogenes like Myc. Here, we have investigated whether p73 provides a similar protection from Myc-driven lymphomas as p53. Confirming previous studies, the inactivation of a single p53 allele (p53+/-) strongly reduced the median survival of Emu-Myc transgenic mice from 103 to 39 days and was invariably associated with a loss of the wild-type p53 allele. In contrast, mutational inactivation of a p73 allele (p73+/-) reduced the median survival by only 12 days. Lymphomas that developed in the p73+/- background showed no loss of heterozygosity (LOH). Furthermore, gene expression profiling of p73+/+, p73+/- and p73-/- lymphomas indicated that p73+/- lymphomas retained p73 transcriptional activity. Subtle gene expression differences between p73+/+ and p73+/- lymphomas, however, suggest a haploinsufficient phenotype on some p73 target genes. This might help to explain why p73+/- animals succumbed to disease slightly earlier than their p73+/+ littermates (log-rank test p<0.0395) and why p73 often shows monoallelic inactivation in human lymphomas. Together these data demonstrate that in Myc-driven lymphomagenesis p73 has weak tumor suppressor activity compared with p53.


Comparison between the efficacy of 10% zinc sulfate solution with 4% hydroquinone cream on improvement of melasma.
Melasma, a common disorder of hyperpigmentation, is often difficult to treat. Although 10% zinc sulfate solution has been reported to be useful for patients with melasma, controlled trials are lacking. 72 women with moderate to severe melasma were divided randomly into 2 groups. Group A were treated with 10% zinc sulfate solution and group B with 4% hydroquinone cream twice-daily. The results were evaluated by photoevaluation by patients based on subjective satisfaction and a blinded dermatologist using MASI score. Assessments were obtained at baseline and at 2 and 6 months after starting treatment. According to MASI score changes during treatment, there was a reduction in both groups at 2 months, however, the reduction in group B was more significant (the reduction in mean ± SD MASI was 0.7 ± 0.7 in group A vs. 2.7 ± 1.6 in group B). In addition, the patients in group B continued to decrease MASI score for the remainder of the study period at 6 months follow-up (0.3 ± 0.5) in comparison with patients in group A who did not show more reduction in MASI score. The study indicates that topical zinc sulfate is not as effective in treating disease as was observed in the previous open study. A comparative study with sunscreen and placebo is necessary to determine if topical zinc sulfate is truly superior to sunscreen and placebo in this respect.


Time-resolved Fluorescence and Generalized Polarization: Innovative tools to assess bull sperm membrane dynamics during slow freezing.
During slow freezing, spermatozoa undergo membrane alterations that compromise their ability of fertilizing. These alterations are cause either by cold shock or by the use of cryoprotectants known to be cytotoxic. However, little is known about the membrane changes that occurred during freezing. Here, we combined Generalized Polarization (GP), Time-resolved Fluorescence and laurdan fluorescence properties to investigate the changes in membrane fluidity and dynamics during slow freezing of bull sperm. We successfully demonstrated that laurdan may be distributed in three different local environments that correspond to different membrane lipid composition. These environments wont behave the same way when the cells will be subjected to either a chemical treatment (adding the cryoprotectants) or a physical treatment (freezing).


[The liver and drugs. Blood chemical and ultrastructural findings after experimental administration of 7-cromanol-3-methyl-taxifoline].
An experimental model which, unlike classical animal pharmacology models, stresses behaviour not of the organ or organism as a whole but of the cell ultrastructures of linked metabolic areas, is proposed. The new model would appear capable, within limits, of surmounting some of the main objections made when extrapolating animal data and referring it to humans. The application of the model to the analysis of the effects induced by administration of 7C3MT at the level of the liver cell metabolic areas described. Electron microscope observations show the substance has a positive influence on the functioning of structures engaged in synthesis and those occupied in breaking down drugs, thus supporting the hypothesis that the substance improves the liver's functional kinetics.


Effect of human Apo AIV against lipid peroxidation of very low density lipoproteins.
Recent studies have demonstrated that Apo AIV exerts a protective effect against atherosclerosis. Moreover, Qin et al. (Am. J. Physiol. 274 (1998) H1836) have demonstrated that Apo AIV, isolated from rat plasma, exerts an inhibitory effect against Cu(2+)-induced lipid peroxidation of intestinal lymph and LDL. The aim of the study was to investigate whether human Apo AIV exerts a protective effect against Cu(2+)-induced lipid peroxidation. Our results demonstrated that human Apo AIV exerted an inhibitory effect against Cu(2+) and AAPH induced lipid peroxidation of VLDL, as shown by the lower increase in the levels of TBARS and conjugated dienes in lipoproteins preincubated with Apo AIV. In addition, the tryptophan (Trp) and probe 2-(dimethylamino)-6-lauroylnaphthalene (Laurdan) fluorescence studies demonstrated that the modifications of spectral properties in both lipoproteins preincubated with Apo AIV were lower with respect to ox-lipoproteins, suggesting that Apo AIV prevents the modification of physico-chemical properties due to peroxidation.


Repeating patterns of sleep restriction and recovery: Do we get used to it?
Despite its prevalence in modern society, little is known about the long-term impact of restricting sleep during the week and 'catching up' on weekends. This common sleep pattern was experimentally modeled with three weeks of 5 nights of sleep restricted to 4h followed by two nights of 8-h recovery sleep. In an intra-individual design, 14 healthy adults completed both the sleep restriction and an 8-h control condition, and the subjective impact and the effects on physiological markers of stress (cortisol, the inflammatory marker IL-6, glucocorticoid receptor sensitivity) were assessed. Sleep restriction was not perceived to be subjectively stressful and some degree of resilience or resistance to the effects of sleep restriction was observed in subjective domains. In contrast, physiological stress response systems remain activated with repeated exposures to sleep restriction and limited recovery opportunity. Morning IL-6 expression in monocytes was significantly increased during week 2 and 3 of sleep restriction, and remained increased after recovery sleep in week 2 (p<0.05) and week 3 (p<0.09). Serum cortisol showed a significantly dysregulated 24h-rhythm during weeks 1, 2, and 3 of sleep restriction, with elevated morning cortisol, and decreased cortisol in the second half of the night. Glucocorticoid sensitivity of monocytes was increased, rather than decreased, during the sleep restriction and sleep recovery portion of each week. These results suggest a disrupted interplay between the hypothalamic-pituitary-adrenal and inflammatory systems in the context of repeated exposure to sleep restriction and recovery. The observed dissociation between subjective and physiological responses may help explain why many individuals continue with the behavior pattern of restricting and recovering sleep over long time periods, despite a cumulative deleterious physiological effect.


Analysis of DNA repair helicase UvrD from Arabidopsis thaliana and Oryza sativa.
Mismatch repair (MMR) proteins play important roles in maintaining genome stability in all the organisms. Studies of MMR genes in plants have identified several homologs of the Escherichia coli genes. Crop yield is directly related to genome stability, which is crucially required for optimal plant growth and development. Numerous genotoxic stresses such as UV light, radiations, pollutants and heavy metals cause DNA damage leading to genome instability, which can interfere with the plant growth and crop productivity. But the efficient repair mechanisms can help to overcome the deleterious effects of the damage. Therefore it is important to study the genes involved in various repair pathways in the plants in greater detail. UvrD helicase is a component of MMR complex and plays an essential role in the DNA repair by providing the unwinding function. In the present manuscript we present an in silico analysis of UvrD helicase from two plant species (Arabidopsis and rice). The Arabidopsis thaliana and Oryza sativa UvrD are 1149 (~129 kDa) and 1165 amino-acids (~130 kDa) proteins, respectively. These proteins contain all the conserved domains and are larger than the E. coli UvrD because they contain a longer N-terminal extension. In order to decipher the role of plant UvrD in various stresses it will be important to study the biochemical and functional properties of this enzyme.


Severe conditioned taste aversion elicited by venom of Russell's viper.
Conditioned taste aversion (CTA) established in rats by associating saccharin drinking with subsequent poisoning by Russell's viper venom. Retention test revealed 76 and 56% reduction of saccharin intake in venom and antivenom-venom groups. No CTA was observed in antivenom and control groups.


Love thy neighbor: Facilitation and inhibition in the competition between parallel predictions.
Ample evidence suggests that during word recognition and production, simultaneously activated lexical and sublexical representations interact, demonstrating varied patterns of facilitation and inhibition in various tasks and measures. A separate line of research has led to a growing consensus that prediction during sentence processing involves activating multiple possible predictions. However, very little is known about the nature of the interactions between parallel predictions. The current study employed a speeded cloze task to probe competition between simultaneously activated predictions. We focused on the modal response (the most probable completion for a sentence) and its strongest competitor (the second most probable completion). Examining production latencies of the modal response, the results showed an interaction between competitor strength and the semantic relatedness between the competitor and the modal: when the two were related, the stronger the competitor was, the more it facilitated production; however, when the two were unrelated, the stronger the competitor was, the more inhibition it caused. These results contrast with the pattern observed for the influences of near and distant semantic neighbors on word recognition and production. However, we show that when the different nature of the tasks is taken into consideration, these patterns of interaction between parallel predictions can be accounted for by the interactive activation and competition (IAC) model used to account for previous neighborhood effects (Chen & Mirman, 2012).


Partial volume tolerance of the liver to radiation.
The use of conformal radiotherapy (RT) and the follow-up of patients for radiation liver toxicities has led to a quantitative understanding of partial liver RT tolerance. The most common toxicity is radiation-induced liver disease (RILD), a syndrome of anicteric ascites and hepatomegaly. Elevation of transaminases and reactivation of viral hepatitis have also been reported after liver RT. The Lyman normal tissue complication probability (NTCP) model and a local damage-organ injury NTCP model have been used to describe the partial tolerance of the liver to RT. The liver exhibits a large volume effect and a low threshold volume for RILD. The RT tolerance of the liver is reduced in patients with primary liver cancer versus metastases. Elevated transaminases are more common in the presence of poor liver function and hepatitis B infection. If the effective liver volume irradiated is less than 25%, very high RT doses may be delivered with little risk of liver toxicity. The mean liver doses associated with a 5% risk of classic RILD for primary and metastatic liver cancer are 28 Gy and 32 Gy, respectively, in 2 Gy per fraction.


Double-blind, placebo-controlled immunotherapy with mixed grass-pollen allergoids. I. Rush immunotherapy with allergoids and standardized orchard grass-pollen extract.
Forty-five grass pollen-allergic patients were randomly assigned to three groups according to their skin test and RAST sensitivities and the severity of seasonal rhinitis. Eleven patients were treated with placebo (group 1), 19 patients (group 2) were treated with a six-mixed grass-pollen allergoid prepared by mild formalinization with a two-step procedure, and 15 other patients were treated with a standardized orchard grass-pollen extract (group 3). Because of a different immunotherapy schedule, only patients placed in groups 1 and 2 received the extracts in a double-blind fashion. Rush immunotherapy was performed in 3 to 6 days, and the maintenance dose was subsequently administered weekly for 4 weeks and every 2 weeks until the end of the grass-pollen season. During the season, a coseasonal treatment was administered. Systemic reactions occurred during the rush protocol in 36.8% of patients treated with allergoid and 20% of patients who received the standardized extract. Only patients treated with allergoid had systemic reactions during maintenance dose. The reactions observed with the standardized extract were more severe. Total doses of allergoid ranged from 2350 to 13,500 protein nitrogen units. Symptoms and medication scores during the peak of the season were analyzed. Patients treated with the standardized allergen had a significant reduction of the number of days of symptoms during the month of June (9.5 +/- 6.7 days; p less than 0.005) and of medication scores (1.3 +/- 1.4; p less than 0.01) compared to patients receiving placebo (19.4 +/- 8.1 days; medication score, 2.8 +/- 2.1).(ABSTRACT TRUNCATED AT 250 WORDS)


Skilled nursing facilities--a clinical opportunity for pharmacists.
It is suggested that nursing homes, as opposed to hospitals, provide the pharmacist with one of the best opportunities to practice clinical pharmacy. Restraining forces to clinical pharmacy include the reluctance of other health professionals to accept the pharmacist in clinical roles, and inadequate reimbursement for monitoring services. These restraining forces are less prevalent in nursing homes. Further, the great reliance on drug therapy in nursing homes, coupled with regulations requiring the pharmacist to assume a drug monitoring role, create a favorable atmosphere for clinical pharmacy practice. The importance of documenting the benefits of clinical pharmacy service is discussed.


Hot and Cold Spine Tumor Ablations.
The vertebral column is the most common site of osseous metastasis, and percutaneous minimally invasive thermal ablation is becoming an important contributor to multidisciplinary treatment algorithms. Continuously evolving minimally invasive image-guided percutaneous spine thermal ablation procedures have proven safe and effective in management of selected patients with spinal metastases to achieve pain palliation and/or local tumor control. This article details the armamentarium available and the most recent advances in minimally invasive, percutaneous image-guided thermal ablation for management of spinal metastases.


AhR-STAT3-HO-1/COX-2 signalling pathway may restrict ferroptosis and improve hMSC accumulation and efficacy in mouse liver.
The low efficacy of mesenchymal stem cells (MSCs) has restricted their application in the treatment of liver disease. Emerging evidence suggested that ferroptosis may provoke hepatocyte dysfunction and exacerbate damage to the liver microenvironment. Here, we have investigated the contribution of liver ferroptosis to the elimination and effectiveness of human MSC (hMSC). Furthermore, potential links between liver ferroptosis and aryl hydrocarbon receptors (AhR) were explored. Two mouse models, iron supplement-induced hepatic ferroptosis and hepatic ischaemia/reperfusion (I/R) injury, were used to identify effects of ferroptosis on hMSC pharmacokinetics (PK)/pharmacodynamics (PD). AhR inhibition attenuated hepatic ferroptosis and improved survival of hMSCs. hMSC viability was decreased by iron supplementation or serum from I/R mice. The AhR antagonist CH223191 reversed iron overload and oxidative stress induced by ferroptosis and increased hMSC concentration and efficacy in mouse models. Effects of CH223191 were greater than those of deferoxamine, a conventional ferroptosis inhibitor. Transcriptomic results suggested that the AhR-signal transducer and activator of transcription 3 (STAT3)-haem oxygenase 1/COX-2 signalling pathway is critical to this process. These results were confirmed in a mouse model of hepatic I/R injury. In mice pre-treated with CH223191, hMSC exhibited more potent protective effects, linked to decreased hepatic ferroptosis. Our findings showed that ferroptosis was a critical factor in determining the fate of hMSCs. Inhibition of AhR decreased hepatic ferroptosis, thereby increasing survival and therapeutic effects of hMSCs in mouse models of liver disease.


Septal destruction in infant rats and the ontogeny of drinking behaviors.
Male and female albino rat pups sustained septal destruction at 10 days of age and body weight and water intakes were measured daily throughout development until 200 days of age. During development the septal and control rats received a battery of drinking tests (e.g., cellular dehydration, hypovolemia, renin). Septal rats (males and females) were hyperdipsic for daily water intakes as early as 31 days of age and the daily hyperdipsia persisted through 200 days of age. On the battery of drinking tests, septal rats consumed water at control volumes on all tests except water deprivation (following which females were hyperdipsic) and food deprivation (during which both males and females were hyperdipsic). Urine output-water intake relationships were determined, and a series of food deprivation tests were conducted during development to determine the etiology of the developmental septal hyperdipsia. All results suggest that hyperdipsia associated with septal destruction during the preweaning period is a primary condition and not secondary to altered output mechanisms, abnormal feeding-drinking patterns, or displacement behavior.


Association of rs1059004 polymorphism in the OLIG2 locus with functional brain network in first-episode negative schizophrenia.
Schizophrenia has often been viewed as a disorder of connectivity. The single nucleotide polymorphism rs1059004 in the oligodendrocyte lineage transcription factor 2 gene locus has been reported to be associated with schizophrenia. We measured the functional connectivity and functional brain network topology properties in 49 schizophrenic patients and 47 healthy controls. We compared the strength and diversity of the functional connectivity and topological properties of functional networks between different genotypes. The correlations among functional connectivity, topological properties and behavioral performances were also investigated in this study. We found that the connectivity strength of schizophrenic patients carrying the risk A allele was generally decreased whereas connectivity diversity was increased. Regarding topological properties, all groups showed small-world properties, the nodal efficiency showed significant differences in the right precuneus and left middle temporal pole between different genotypes in schizophrenic patients. Moreover, the nodal efficiency in the left middle temporal pole was positively correlated with the neuropsychological assessment battery results of the schizophrenic patients who were homozygous for the C allele. Our results elucidate the contribution of rs1059004 to the functional brain network, and may help enhance the present understanding of the role of risk gene in the functional dysconnectivity of schizophrenia.


Baseline Risk Factors for Prolonged Opioid Use Following Spine Surgery: Systematic Review and Meta-Analysis.
To conduct a comprehensive systematic review and meta-analysis of current retrospective cohort studies to identify significant preoperative risk factors for prolonged postoperative opioid use following spine surgery. Studies were identified according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses through a search of PubMed, Google Scholar, Scopus, and Cochrane databases. Unique articles were screened by 2 independent reviewers. Primary research articles reporting odds ratios of risk factors for prolonged opioid use following spine surgery were included. Prolonged opioid use was defined as continued use ≥3 months following surgery, and study quality was evaluated using the Newcastle-Ottawa Scale. Random-effects meta-analysis was performed to calculate pooled odds ratios and confidence intervals. The initial search yielded 648 studies. Following duplicate removal, 492 titles and abstracts were screened. After full-text review of 68 studies, 19 final studies including 168,961 patients were eligible for meta-analysis. Newcastle-Ottawa Scale scores ranged from 6 to 9. Meta-analysis assessed 17 risk factors for long-term opioid use. Preoperative opioid use, depression, depression and/or anxiety, drug abuse or dependency, female gender, fibromyalgia, lower back pain, tobacco use, and chronic pulmonary disease were found to be statistically significant risk factors for prolonged opioid use. Several patient-level factors may play a role in the tendency to persistently use opioids after spine surgery. By preoperatively identifying these characteristics, clinicians may be better able to identify patients who are at risk and employ methods to mitigate potential long-term opioid use.


Glioma immunotherapy enhancement and CD8-specific sialic acid cleavage by isocitrate dehydrogenase (IDH)-1.
The promise of adaptive cancer immunotherapy in treating highly malignant tumors such as glioblastoma multiforme (GBM) can only be realized through expanding its benefits to more patients. Alleviating various modes of immune suppression has so far failed to achieve such expansion, but exploiting endogenous immune enhancers among mutated cancer genes could represent a more direct approach to immunotherapy improvement. We found that Isocitrate Dehydrogenase-1 (IDH1), which is commonly mutated in gliomas, enhances glioma vaccine efficacy in mice and discerns long from short survivors after vaccine therapy in GBM patients. Extracellular IDH1 directly enhanced T cell responses to multiple tumor antigens, and prolonged experimental glioma cell lysis. Moreover, IDH1 specifically bound to and exhibited sialidase activity against CD8. By contrast, mutant IDH1R132H lacked sialidase activity, delayed killing in glioma cells, and decreased host survival after immunotherapy. Overall, our findings identify IDH1 as an immunotherapeutic enhancer that mediates the known T cell-enhancing reaction of CD8 desialylation. This uncovers a new axis for immunotherapeutic improvement in GBM and other cancers, reveals novel physiological and molecular functions of IDH1, and hints at an unexpectedly direct link between lytic T cell function and metabolic activity in target cells.


Immunomodulatory effects of intravenous BIS-1 F(ab')2 administration in renal cell cancer patients.
We report the immunomodulatory effects of an intravenous treatment with F(ab')2 fragments of the bispecific monoclonal antibody BIS-1 during subcutaneous recombinant interleukin 2 (rIL-2) therapy of renal cell cancer (RCC) patients. BIS-1 is directed against both the CD3 antigen on T cells and the EGP-2 molecule on carcinoma cells and some normal epithelia. The amount of BIS-1 F(ab')2 bound to peripheral blood lymphocytes (PBLs) increased dose-dependently. This occupation degree was highest at the end of the 2 h infusion and rapidly decreased subsequently. During the first hour of BIS-1 F(ab')2 infusion the number of PBLs decreased slowly. This was followed by an increase in serum tumour necrosis factor alpha (TNF-alpha) concentrations and a rapid decrease in the numbers of peripheral blood lymphocytes, monocytes and eosinophils. In our view, the most likely explanation for the observed decrease in occupation degree of BIS-1 F(ab')2 and the rise in TNF-alpha levels is based on the assumption that BIS-1-carrying T cells leave the circulation. The CD3 antigens on these extravasated T cells become cross-linked by EGP-2 antigens, inducing TNF-alpha secretion. This results in an enhanced decrease in the numbers of PBLs, monocytes and eosinophils. These preliminary results suggest that BIS-1 F(ab')2 treatment during IL-2 therapy may induce local T-cell activation.


[Occurrence of deoxynivalenol (DON) and zearalenone (ZEA) in wheat, rye and triticale: results from the 2001 and 2002 harvests in Germany].
Deoxynivalenol and Zearalenone contents were determined in wheat, rye and triticale samples which were representative of the 2001 and 2002 harvests in Germany. The frequency of DON and ZEA detection and the mean levels of these toxins were higher in wheat, rye and triticale in 2002 in comparison to 2001. The influence of varieties and preceding crop on DON contents in wheat and triticale is presented.


Experimental production of manifest and concealed ventricular rhythms in man.
Analysis of clinical ventricular ectopy has provided deductive evidence for the existence of concealed ventricular rhythms. Studies in the experimental animal have demonstrated that when ventricular extrastimuli are applied near the ventricular effective refractory period of consecutive sinus beats, extrastimuli may not be conducted after sinus beats immediately following the post-estrasystolic pause. This sequence may be due to a prolongation of the effective refractory period of ventricular muscle produced by the increased cycle length resulting from the post-extrasystolic pause. The purpose of this study was to extend these observations to the human ventricle in an attempt to produce concealed ventricular rhythms by programmed ventricular extrastimuli. Twelve patients with normal PR intervals and QRS complexes with a mean age of 49 years were studied with ventricular extra-stimuli at programmed intervals following normally conducted sinus impulses. Premature ventricular impulses were introduced after every sinus beat at intervals 10 to 120 msec outside the effective refractory period. In eleven patients without ventricular interpolation, stimuli applied within 40 msec of the effective refractory period produced from one to three concealed (non-conducted) ventricular stimuli following the post-extrasystolic pause; stimuli applied greater than 40 msec outside the effective refractory period at identical current levels produced manifested bigeminy in all cases. In one patient with interpolated premature ventricular beats without a compensatory pause, programmed ventricular extrastimuli produced manifest bigeminy at all coupling intervals. This study demonstrates the experimental production of concealed and manifest ventricular rhythms in man and confirms the importance of the relationship between the ventricular effective refractory period, the timing of the premature ventricular impulse, and the occurence of a compensatory pause.


Potassium ferrate combined with ultrafiltration for treating secondary effluent: Efficient removal of antibiotic resistance genes and membrane fouling alleviation.
Antibiotic resistance genes (ARGs) are considered as emerging environmental contaminants, which should be controlled by wastewater treatment plants to prevent their discharge into the environment. However, conventional treatment techniques generally fail to successfully reduce ARGs, and the release of cell-free ARGs was underestimated. In this study, potassium ferrate (Fe(VI)) pretreatment combined with ultrafiltration (UF) process was developed to remove both cell-associated and cell-free ARGs in real secondary effluent, compared to ferric chloride (Fe(III)) and poly-aluminum chloride (PACl) pretreatment processes. It was found that total ARGs especially cell-free ARGs were effectively removed by Fe(VI) oxidation. However, due to the poor settleability of the negatively charged particles formed by Fe(VI) in the secondary effluent, the removal of cell-associated ARGs was less compared to Fe(III) and PACl pretreatments. The combination of Fe(VI) and UF removed the most ARGs (3.26 - 5.01 logs) due to the efficient removal of cell-free ARGs by Fe(VI) (> 2.15 logs) and co-interception of both cell-associated ARGs and Fe(VI) formed particles of the UF. High-throughput sequencing revealed that Fe(VI) decreased the viability and relative abundances of the potential ARGs hosts. Fe(VI)-UF exhibited the best performance on humic-like fluorescent organic matters removal, as well as the least phytotoxicity in the effluent. Moreover, membrane fouling was remarkably alleviated by Fe(VI) pretreatment because (1) Fe(VI) removed macromolecules such as protein-like and polysaccharide-like substances which would block the membrane pores, (2) Fe(VI) improved the hydrophilicity of foulants and reduced the hydrophobic adsorption between foulants and membrane. In short, Fe(VI)-UF is a promising technology to efficiently remove ARGs (especially cell-free ARGs) and alleviate UF membrane fouling in wastewater reclamation.


Hydric constraints upon foraging in a terrestrial salamander, Desmognathus ochrophaeus (Amphibia: Plethodontidae).
The time until salamanders voluntarily abandoned foraging (the "water time limit") and the amount of water lost when salamanders abandoned foraging ("dehydration deficit") were determined for terrestrial plethodontid salamanders, Desmognathus ochrophaeus, foraging at various vapor pressure gradients in the laboratory. Salamander activity was correlated with the rate of water loss and was inversely related to the water time limit. Animals at 0.35-0.86 kPa vapor pressure gradients abandoned foraging and returned to moist retreats significantly sooner than animals in water-saturated air. The early retreat of animals in dry air was related in part to high rates of water loss and in part to the modest dehydration deficit (3.8%) at which animals abandoned foraging. Locomotor performance and foraging ability were unaffected by dehydration until dehydration deficits exceeded 12%. This suggests that salamanders in unsaturated air abandoned foraging at a low dehydration deficit to conserve and replenish water reserves rather than to avoid outright incapacitation or death.


Detection and quantification of a toxic salt substitute (LiCl) by using laser induced breakdown spectroscopy (LIBS).
The use of Li salts in foods has been prohibited due to their negative effects on central nervous system; however, they might still be used especially in meat products as Na substitutes. Lithium can be toxic and even lethal at higher concentrations and it is not approved in foods. The present study focuses on Li analysis in meatballs by using laser induced breakdown spectroscopy (LIBS). Meatball samples were analyzed using LIBS and flame atomic absorption spectroscopy. Calibration curves were obtained by utilizing Li emission lines at 610nm and 670nm for univariate calibration. The results showed that Li calibration curve at 670nm provided successful determination of Li with 0.965 of R2 and 4.64ppm of limit of detection (LOD) value. While Li Calibration curve obtained using emission line at 610nm generated R2 of 0.991 and LOD of 22.6ppm, calibration curve obtained at 670nm below 1300ppm generated R2 of 0.965 and LOD of 4.64ppm.


Consequences of domain insertion on sequence-structure divergence in a superfold.
Although the universe of protein structures is vast, these innumerable structures can be categorized into a finite number of folds. New functions commonly evolve by elaboration of existing scaffolds, for example, via domain insertions. Thus, understanding structural diversity of a protein fold evolving via domain insertions is a fundamental challenge. The haloalkanoic dehalogenase superfamily serves as an excellent model system wherein a variable cap domain accessorizes the ubiquitous Rossmann-fold core domain. Here, we determine the impact of the cap-domain insertion on the sequence and structure divergence of the core domain. Through quantitative analysis on a unique dataset of 154 core-domain-only and cap-domain-only structures, basic principles of their evolution have been uncovered. The relationship between sequence and structure divergence of the core domain is shown to be monotonic and independent of the corresponding type of domain insert, reflecting the robustness of the Rossmann fold to mutation. However, core domains with the same cap type share greater similarity at the sequence and structure levels, suggesting interplay between the cap and core domains. Notably, results reveal that the variance in structure maps to α-helices flanking the central β-sheet and not to the domain-domain interface. Collectively, these results hint at intramolecular coevolution where the fold diverges differentially in the context of an accessory domain, a feature that might also apply to other multidomain superfamilies.


Quantitative risk assessment of FMDV introduction in a FMD free country through bone-in beef and offal importation from a FMD free with vaccination country/zone.
Quantitative risk assessment was used to estimate the risk of introducing foot-and-mouth disease (FMD) through bone-in beef from Argentina (FMD-free with vaccination status) into other FMD-free countries. A stochastic model was built to characterize all the steps from primary production to bone-in beef export and introduction into an FMD-free country. The probability that bone-in beef from at least one animal infected with the FMD virus (FMDV) was exported during a year was 5.27 × 10-3 (95% CI <10-10 - 5.19 x 10-2) or in other words one case in 190 years. The risk of FMDV introduction was sensitive to the probability of an outbreak occurring in Argentina (r [Spearman´s rank correlation] = 0.99) and the number of herds affected during an outbreak (r = 0.10). Additionally, the probability that susceptible animals in the importing country came into contact with infective material (bones) and generated an outbreak was 6.16 × 10-4 (95% CI <10-10 - 6.20 ×10-3) or one FMD outbreak every 1623 years on average. Based on the quantitative risk assessment results, the probability of FMDV introduction into a FMD-free country where vaccination is not practiced from a FMD-free country where vaccination is practiced associated with bone-in beef trade from Argentina was negligible. The risk of an FMD outbreak caused by the potential introduction of the FMDV was associated with the existing conditions in the country. Thus, maintaining the FMD-free status with or without vaccination would not be relevant.


Effect of biostimulation and social organization on the interval from calving to resumption of ovarian cyclicity in postpartum Angus cows.
The objective was to assess the effect of biostimulation by the male presence and social organization on the interval from calving to resumption of ovarian cyclicity (ICR). Thirty Angus cows were allocated according parity into three groups (10 per group); two groups were exposed to bulls, and a third group not exposed to bulls served as a control. Dominance values (with subsequent arc-sin transformation) were calculated from daily recorded agonistic interactions and later organized into dominance order comprising three social categories as follows: dominant (D), intermediate (I), and subordinates (S). The ICR was established by determining presence of luteal tissue and a rise of blood progesterone concentration above 1 ng/mL using ultrasonography and a solid-phase, nonextraction radioimmunoassay (Coat-a-Count; Diagnostics Products Corporation, Los Angeles, CA, USA), respectively. The effect of biostimulation, dominance order, and treatment by dominance order on ICR was statistically analyzed applying ANOVA using PROC GLM of SAS (2010). The ICR was influenced by biostimulation (P < 0.002) and dominance order (P < 0.004). The ICR increased as dominance order decreased (D = 34.5 ± 6 days; I = 45.0 ± 6; S = 53.1 ± 4 days; P < 0.01). However, when comparing cows within social categories, ICR was reduced in the group exposed to bulls (D = 26.3 ± 8.2 days; I = 42.0 ± 6.4 days; S = 46.1 ± 4.1 days) compared with those not exposed to bulls (D = 43.0 ± 8.2 days; I = 48.0 ± 10.1 days; S = 60.2 ± 6.4 days) cows. In conclusion, biostimulation and social dominance influenced the ICR.


[Direct skeletal traction by a wire with san olive-shaped plug].
A new method of treatment of dislocated fractures and apophyseal fractures, using direct traction by pins on the bone fragments, and cast is presented. The authors describe the technique employed and report the results of the 22 cases treated.


Mucosal-associated invariant T-cell tumor infiltration predicts long-term survival in cholangiocarcinoma.
Cholangiocarcinoma (CCA) is a malignancy arising from biliary epithelial cells of intra- and extrahepatic bile ducts with dismal prognosis and few nonsurgical treatments available. Despite recent success in the immunotherapy-based treatment of many tumor types, this has not been successfully translated to CCA. Mucosal-associated invariant T (MAIT) cells are cytotoxic innate-like T cells highly enriched in the human liver, where they are located in close proximity to the biliary epithelium. Here, we aimed to comprehensively characterize MAIT cells in intrahepatic (iCCA) and perihilar CCA (pCCA). Liver tissue from patients with CCA was used to study immune cells, including MAIT cells, in tumor-affected and surrounding tissue by immunohistochemistry, RNA-sequencing, and multicolor flow cytometry. The iCCA and pCCA tumor microenvironment was characterized by the presence of both cytotoxic T cells and high numbers of regulatory T cells. In contrast, MAIT cells were heterogenously lost from tumors compared to the surrounding liver tissue. This loss possibly occurred in response to increased bacterial burden within tumors. The residual intratumoral MAIT cell population exhibited phenotypic and transcriptomic alterations, but a preserved receptor repertoire for interaction with tumor cells. Finally, the high presence of MAIT cells in livers of iCCA patients predicted long-term survival in two independent cohorts and was associated with a favorable antitumor immune signature. MAIT cell tumor infiltration associates with favorable immunological fitness and predicts survival in CCA.


Placing a lumen-apposing metal stent despite ascites: feasibility and safety.
Placing a lumen-apposing metal stent (LAMS) through ascites carries serious risks, including death from leakage around the LAMS and failure to create a mature fistula between the 2 lumens. However, sometimes no options exist or are equally dangerous. We present 5 patients who underwent LAMS placement despite ascites in 2 different locations. This is a retrospective review of 5 patients who underwent LAMS placement despite ascites in 2 different locations from 2016 to 2018. Three patients with cholecystitis and 2 patients with afferent limb syndrome and severe ascites were treated with a combination of preprocedural and intraprocedural paracentesis. Serum ascites albumin gradient was measured. Weight was recorded daily. Patients were encouraged to sleep at an incline, and periodic paracentesis (every 3-7 days) was performed when ascites reaccumulated over 4 weeks. Median volume of ascites aspirated was 2 L preprocedurally and 300 mL intraprocedurally. Only 1 patient had ascites with a high serum ascites albumin gradient and was treated with diuretics. Technical and clinical success was achieved in all 5 patients without any adverse events over a median follow-up of 28 weeks. In situations in which no better options remain, LAMS placement appears to be safe after adequate and aggressive treatment of the underlying ascites pre-, intra-, and postprocedurally. Larger studies are needed to establish the safety of this approach.


Evaluation of a novel cellulose powder as a filler-binder for direct compression of tablets.
A novel form of cellulose powder was evaluated as a filler-binder in tablets. The particle, powder, flow and binding properties of this experimental cellulose material were compared with those of two commercial microcrystalline celluloses, Avicel PH 101 and Emcocel. The effect of various storage conditions on the physical stability of tablets compressed from celluloses was also evaluated. The particle size and shape of experimental cellulose powder differed markedly from those of microcrystalline celluloses. Experimental cellulose contained mainly large and roughly spherical agglomerates of particles, among which were few smaller regularly shaped particles. Because of spherical particle shape, the experimental cellulose powder flowed better than microcrystalline celluloses, which consisted of much more irregularly shaped particles. Experimental cellulose formed stronger tablets than microcrystalline celluloses. It also acted more effectively than microcrystalline celluloses as a binding material in tablets containing poorly compressible ascorbic acid and acetaminophenone. This may be due to the extensive surface area of the particles of experimental cellulose powder. The specific surface area of this material was over 50 times as great as that of microcrystalline celluloses. This indicates an extremely porous structure of cellulose agglomerates. Tablets containing experimental cellulose powder were able to resist a permanent loss in tablet strength at different storage conditions better than tablets containing microcrystalline celluloses. According to the results of this study an experimental agglomerated form of cellulose powder is a very advantageous material as a filler-binder for direct compression of tablets.


Regulation of natural killer cell cytotoxicity by prostaglandin E in the peripheral blood and cerebrospinal fluid of patients with multiple sclerosis and other neurological diseases. Part 1. Association between amount of prostaglandin produced, natural killer, and endogenous interferon.
MS patients' peripheral blood mononuclear cells (MNC) spontaneously produced more prostaglandin E1&2 (PGE) in vitro than did OND or normal control MNC correlating with lower levels of NK activity and endogenous interferon (IFN) production while there were no differences between OND and normal controls. MS neat CSF contained significantly higher levels of measurable PGE with concomitantly lower NK activity and % IFN-positive cells than was seen in OND CSF. The PGE producing cells were depleted in the nylon wool-passed (NWP) and enriched in the nylon wool-adherent (NWAd) populations in direct correlation with depletion and enrichment of esterase-positive monocyte/macrophages, respectively, suggesting that at least some of the PGE-producing cells were adherent monocyte/macrophages. At 24 and 48 h after stimulation with PHA, MS unfractionated MNC produced significantly more PGE than OND and normal MNC; at 24 and 72 h, MS NWAd cells produced significantly more PGE than normals and ONDs. MS and ONDs produced the same amount of PGE at 48 h in the stimulated NWAd fraction.