Lycopene Attenuates Tulathromycin and Diclofenac Sodium-Induced Cardiotoxicity in Mice.
Recent experiments showed a potential cardiotoxic effect of the macrolide antibiotic (tulathromycin). This study was performed to investigate whether diclofenac sodium (DFS) potentiates the cardiotoxicity of tulathromycin and increases the cardioprotective effects of lycopene against DFS and tulathromycin. Seven groups (eight per group) of adult Swiss albino mice received saline (control), tulathromycin (a single subcutaneous dose of 28 mg/kg/bw on day 14), DFS (a single oral dose of 100 mg/kg/bw on day 14), tulathromycin plus DFS, or lycopene (oral, 10 mg/kg/bw daily for 15 d) combined with tulathromycin, DFS, or both. Compared to the control group, the administration of tulathromycin or DFS (individually or in combination) caused significantly elevated (p < 0.05) serum levels of Creatine kinase-myocardial B fraction (CK-MB), lactate dehydrogenase, and cardiac-specific troponin-T and tissue levels of nitric oxide and malondialdehyde that were accompanied by significantly decreased tissue reduced glutathione content and glutathione peroxidase, superoxide dismutase, and catalase antioxidant enzyme activity. Upon histopathological and immunohistochemical examination, the mean pathology scores and the percentages of caspase-3-, Bax-, and CK-positive regions were significantly higher in the tulathromycin- and/or DFS-treated groups than in control mice. For all these parameters, the pathological changes were more significant in the tulathromycin-DFS combination group than in mice treated with either drug individually. Interestingly, co-administration of lycopene with tulathromycin and/or DFS significantly ameliorated the changes described above. In conclusion, DFS could potentiate the cardiotoxic effects of tulathromycin, whereas lycopene can serve as a cardioprotective agent against DFS and tulathromycin.


Electronic Structure Studies on the Whole Keplerate Family: Predicting New Members.
A comprehensive study of the electronic structure of nanoscale molecular oxide capsules of the type [{MVI (MVI )5 O21 }12 {M'V2 O2 (μ-X)(μ-Y)(Ln- )}30 ](12+n)- is presented, where M,M'=Mo,W, and the bridging ligands X,Y=O,S, carried out by means of density functional theory. Discussion of the electronic structure of these derivatives is focused on the thermodynamic stability of each of the structures, the one having the highest HOMO-LUMO gap being M=W, M'=Mo, X=Y=S. For the most well-known structure M=M'=Mo, X=Y=O, [Mo132 O372 ]12- , the chemical bonding of several ligands to the {MoV2 O2 (μ-O)2 } linker moiety produces negligible effects on its stability, which is evidence of a strong ionic component in these bonds. The existence of a hitherto unknown species, namely W132 with both bridging alternatives, is discussed and put into context.


Towards accurate all-electron quantum Monte Carlo calculations of transition-metal systems: spectroscopy of the copper atom.
In this work we present all-electron fixed-node diffusion Monte Carlo (FN-DMC) calculations of the low-lying electronic states of the copper atom and its cation. The states considered are those which are the most relevant for the organometallic chemistry of copper-containing systems, namely, the (2)S, (2)D, and (2)P electronic states of Cu and the (1)S ground state of Cu(+). We systematically compare our FN-DMC results to CCSD(T) calculations using very large atomic-natural-orbital-type all-electron basis sets. The FN-DMC results presented in this work provide, to the best of our knowledge, the most accurate nonrelativistic all-electron correlation energies for the lowest-lying states of copper and its cation. To compare our results to experimental data we include the relativistic contributions for all states through numerical Dirac-Fock calculations, which for copper (Z=29) provide almost the entire relativistic effects. It is found that the fixed-node errors using Hartree-Fock nodes for the lowest transition energies of copper and the first ionization potential of the atom cancel out within statistical fluctuations. The overall accuracy achieved with quantum Monte Carlo for the nonrelativistic correlation energy (statistical fluctuations of about 1600 cm(-1) and near cancelation of fixed-node errors) is good enough to reproduce the experimental spectrum when relativistic effects are included. These results illustrate that, despite the presence of the large statistical fluctuations associated with core electrons, accurate all-electron FN-DMC calculations for transition metals are nowadays feasible using extensive but accessible computer resources.


Antinociceptive and toxicological effects of Dioclea grandiflora seed pod in mice.
The acute treatment of mice with an ethanolic extract from the seed pod of Dioclea grandiflora (EDgP) at doses of 75, 150 and 300 mg/kg by intraperitoneal administration produced a significant antinociceptive effect as displayed by the acetic acid-induced writhing test and the formalin test. The antinociception was observed through the first (neurogenic pain) and second (inflammatory pain) phases in the formalin test. The hot plate test did not show an increase in the antinociceptive latency whereas the motor performance was affected by the administration at 300 mg/kg at the beginning (30 minutes) of the observation period but not at later periods (60 and 120 minutes). These results suggest that EDgP has a central antinociceptive action and a possible anti-inflammatory activity in mice.


Simultaneous determination of phytoestrogens in different medicinal parts of Sophora japonica L. by capillary electrophoresis with electrochemical detection.
A high-performance capillary electrophoresis with electrochemical detection (CE-ED) method has been developed for the determination of phytoestrogens from the pericarps and seeds of Sophora japonica L. in this work. Genistin, genistein, rutin, kaempferol and quercetin are important bioactive constituents in these plants. The effects of several factors such as the acidity and concentration of running buffer, the separation voltage, the applied potential and the injection time on the CE-ED procedure were investigated. Under the optimum conditions, the five analytes could be well separated within 18 min in a 75 cm length capillary (i.d. 25 microm) at the separation voltage of 16 kV in a 50 mmol L(-1) borax running buffer (pH 9.0). A 300 microm diameter carbon disk electrode was used as the working electrode positioned carefully opposite the outlet of the capillary in a wall-jet configuration at the potential of +950 mV (vs SCE). Detection limits (S/N = 3) ranged from 1.1 x 10(-7) to 2.8 x 10(-7) g mL(-1) for all fi ve analytes. This method was successfully used to analyse dried Flos sophorae immaturus, pericarps and seeds of dried Fructus sophorae after a relatively simple extraction procedure, and the assay results were satisfactory.


Triggering gel-sol transition by weak magnetic field.
The self-assembly of small and always chiral molecules into fiber-like structures is a mysterious process, as the physics underlying such self-assembly is unclear. The energy necessary for this process exceeds the one provided by common dispersion interactions and hydrogen bonding. The recent results obtained by the scientific group of Prof. Naaman from the Weizmann Institute of Science fed light on the nature of forces providing for the self-assembly of chiral molecules and attributed these forces to spin-exchange interactions. Therefore, the self-assembly of chiral molecules should be magneto-sensitive. We found such sensitivity in solutions of trifluoroacetylated α -amino alcohols, and the process was inhibited by the magnetic field when fibers grew on the surface of the substrate. On the contrary, in bulk, the self-assembly was enhanced by the magnetic field and led to the formation of a dense gel, while no gelation was observed in the absence of the external magnetic field. The latter observations are the theme of this short report, aimed to declare the effect itself but not pretend to describe it in full.


Phytochemical Quantification and the In Vitro Acetylcholinesterase Inhibitory Activity of Phellodendron chinense and Its Components.
The dried bark of Phellodendron chinense has been used as a traditional herbal medicine to remove damp heat, relieve consumptive fever, and cure dysentery and diarrhea. In the present study, we performed quantitative analyses of the two components of P. chinense, phellodendrine and berberine, using high-performance liquid chromatography. A 70% ethanol extract of P. chinense was prepared and the two components were separated on a C-18 analytical column using a gradient solvent system of acetonitrile and 0.1% (v/v) aqueous trifluoroacetic acid. The ultraviolet wavelength used for detection was 200 nm for phellodendrine and 226 nm for berberine. The analytical method established here showed high linearity (correlation coefficient, ≥0.9991). The amount of phellodendrine and berberine used was 22.255 ± 0.123 mg/g and 269.651 ± 1.257 mg/g, respectively. Moreover, we performed an in vitro acetylcholinesterase (AChE) activity assay and an amyloid-β aggregation test to examine the biological properties of phellodendrine and berberine as therapeutic drugs for Alzheimer's disease. Phellodendrine and berberine inhibited AChE activity in a dose-dependent manner (IC50 = 36.51 and 0.44 μM, respectively). In contrast, neither phellodendrine nor berberine had an effect on amyloid-β aggregation. The P. chinense extract and phellodendrine, but not berberine, exhibited antioxidant activity by increasing radical scavenging activity. Moreover, P. chinense demonstrated a neuroprotective effect in hydrogen peroxide-treated HT22 hippocampal cells. Overall, our findings suggest that P. chinense has potential as an anti-Alzheimer's agent via the suppression of the enzymatic activity of acetylcholinesterase and the stimulation of antioxidant activity.


Virome analysis of an ectomycorrhizal fungus Suillus luteus revealing potential evolutionary implications.
Suillus luteus is a widespread edible ectomycorrhizal fungus that holds significant importance in both ecological and economic value. Mycoviruses are ubiquitous infectious agents hosted in different fungi, with some known to exert beneficial or detrimental effects on their hosts. However, mycoviruses hosted in ectomycorrhizal fungi remain poorly studied. To address this gap in knowledge, we employed next-generation sequencing (NGS) to investigate the virome of S. luteus. Using BLASTp analysis and phylogenetic tree construction, we identified 33 mycovirus species, with over half of them belonging to the phylum Lenarviricota, and 29 of these viruses were novel. These mycoviruses were further grouped into 11 lineages, with the discovery of a new negative-sense single-stranded RNA viral family in the order Bunyavirales. In addition, our findings suggest the occurrence of cross-species transmission (CST) between the fungus and ticks, shedding light on potential evolutionary events that have shaped the viral community in different hosts. This study is not only the first study to characterize mycoviruses in S. luteus but highlights the enormous diversity of mycoviruses and their implications for virus evolution.


Entomopathogenic nematode-gastropod interactions.
Entomopathogenic nematodes (EPNs) infect and kill insects and have been successfully used in the biological control of some insect pests. Slugs and snails are known to be significant pests of agriculture and serve as vectors for disease-causing microbes that can affect crops and humans. The potential of EPNs to be used in the biological control of gastropods has not been well-studied. The few studies that have been performed on the efficacy of EPNs in controlling gastropod pests and vectors were reviewed. Suggested criteria for further assessments of EPN-gastropod interactions are: Dose of EPNs used, length of infection assays, host biology, nematode biology and development, and Koch's postulates. There are provocative data suggesting that EPNs may be useful biological control agents against gastropod pests of agriculture and vectors of disease, though additional studies using the suggested criteria are needed, including the publication of negative data or studies where EPNs were not efficacious or successful in controlling gastropods.


Efferent arterioles in glomerular haemodynamics.
In haemorrhagic rats norepinephrine normalises BP but maintains renal cortical pressures at low levels. Dopamine, however, can normalise both BP and renal cortical pressures. Dopamine is therefore useful in treating haemorrhagic hypotension in addition to or while awaiting blood transfusion. The efferent arteriole in superficial nephrons is a passive resistance in glomerular haemodynamics.


Aspects of the pharmacology of beta-adrenoceptor agonists and antagonists.
A short review is given of the distribution of and effects mediated through beta-receptors. The pharmacodynamic profiles of some beta-receptor agonists and antagonists are briefly outlined and the clinical advantages and disadvantages of different pharmacodynamic properties are discussed.


Pearl Jane Manson Sproule, MD (1879-1961) Canada's first woman otolaryngologist: a belated tribute.
Pearl Jane Manson enrolled in the Ontario Medical College for Women in 1904 and graduated with an M.D. degree from the University of Toronto in 1907. She was admitted to the Royal College of Surgeons of England in 1911 and worked at a hospital in England during World War I. On returning to Toronto she held positions both at Toronto General Hospital and Women's College Hospital, where she became Chief of the ENT Department in 1926. She was keenly interested in epidemiology and the prevention of infections in women and children. In 1931 she became a Fellow of the Royal College of Physicians and Surgeons of Canada and also the American College of Surgeons. She was the first woman physician in Canada to become a specialist and gain recognition as a clinical scientist.


Unveiling the roles of interspecific competition and local adaptation in phenotypic differentiation of parapatric frogs.
Understanding how ecological processes affect phenotypic evolution has been and continues to be an important goal of ecology and evolutionary biology. Interspecific competition for resources can be a selective force driving phenotypic differentiation that reduces competition among sympatric species (character divergence), enabling closely-related species to coexist. However, although patterns of character divergence are well documented in both empirical and theoretical researches, how local adaptation to abiotic environment affects trait evolution in the face of interspecific competition is less known. Here, we investigate how patterns in morphological traits of 2 parapatric frog species, Feirana quadranus and F. taihangnica, vary among allopatric and sympatric regions using range-wide data derived from extensive field surveys. Feirana quadranus was overall larger than F. taihangnica in body size (i.e., snout-vent length [SVL]), and the difference between SVL of both species in sympatry was larger than that in allopatry. From allopatry to sympatry, the 2 species diverged in foot and hand traits, but converged in eye size and interorbital span, even when we controlled for the effects of geographic gradients. Sympatric divergence in SVL, hand and foot traits is likely acting as a case of evolutionary shift caused by interspecific competition. In contrast, sympatric convergence of eye-related traits may derive at least partly from adaptation to local environments. These results imply the relative roles of interspecific competition and local adaptation in shaping phenotypic diversification. Our findings illustrate how traits evolve in parapatric species pair due to sympatric divergent and convergent evolution. It thus provides insights into understanding underlying evolutionary processes of parapatric species, that is, competition and local adaptation.


De novo synthesis of PCR templates for the development of SARS diagnostic assay.
A novel coronavirus was identified as the cause for severe acute respiratory syndrome (SARS). The complete sequence of SARS genome has provided an opportunity for the development of molecular diagnostic assays. To restrain further outbreak of SARS, the World Health Organization has posted several pairs of polymerase chain reaction (PCR) primers for early diagnosis and urged more research to be done on PCR protocols. Here we report a strategy for the de novo synthesis of PCR templates complimentary to the SARS virus genome, which has the advantage of working on PCR templates without concern about viral infection and also has the advantage that it can be used by those who do not have access to the SARS virus. This highly efficient and safe strategy for obtaining SARS gene fragments is useful for the development of PCR assays, as well as for the preparation of reliable positive controls for PCR testing kits.


Racemization-free synthesis of (S)-(+)-tylophorine from L-proline by radical cyclization.
The phenanthroindolizidine alkaloid (S)-(+)-tylophorine was synthesized from L-proline in nine linear steps including a double bromination and a free-radical cyclization of an N-aziridinylimine as the key steps. The phenanthrene moiety was prepared from homoveratric acid and veratraldehyde and permits the variation of each oxygen-substituted ring.


Atherosclerosis in abdominal aortic aneurysms: a causal event or a process running in parallel? The Tromsø study.
The pathogenesis of abdominal aortic aneurysm (AAA) formation is poorly understood. We investigated the relationship between carotid, femoral, and coronary atherosclerosis and abdominal aortic diameter, and whether atherosclerosis was a risk marker for AAA. Ultrasound of the right carotid artery, the common femoral artery, and the abdominal aorta was performed in 6446 men and women from a general population. The burden of atherosclerosis was assessed as carotid total plaque area, common femoral lumen diameter, and self-reported coronary heart disease. An AAA was defined as maximal infrarenal aortic diameter > or =30 mm. No dose-response relationship was found between carotid atherosclerosis and abdominal aortic diameter <27 mm. However, significantly more atherosclerosis and coronary heart disease was found in aortic diameter > or =27 mm and in AAAs. The age- and sex-adjusted odds ratio (OR) (95% CI) for AAA in the top total plaque area quintile was 2.3 (1.5 to 3.4), as compared with subjects without plaques. The adjusted OR (95% CI) was 1.7 (1.1 to 2.6). No independent association was found between femoral lumen diameter and AAA. The lack of a consistent dose-response relationship between atherosclerosis and abdominal aortic diameter suggests that atherosclerosis may not be a causal event in AAA but develops in parallel with or secondary to aneurismal dilatation.


Epidural haematoma in a paediatric population.
Over a period of 3 years, 23 cases of epidural haematoma were observed in our department. The Data of these 23 cases were analyzed; in a few of them the statistics of the world literature was confirmed, but 17 of the 23 had a few interesting and characteristic features, which are studied and discussed.


Continuous Interscalene Block for Postoperative Analgesia and Shoulder Immobilization After Pectoralis Major Tendon Reinsertion: A Case Report.
We present the case of a 38-year-old man undergoing surgical repair of his pectoralis major tendon. An interscalene catheter was placed between the middle and lower trunks of the brachial plexus. Postoperatively, ropivacaine 0.2% was infused through postoperative day 3. The patient had excellent pain control requiring minimal opioid analgesics. A catheter between the middle and lower trunks of the brachial plexus provided excellent postoperative analgesia after pectoralis major tendon reinsertion. Additionally, the block likely protected the surgical repair during emergence from anesthesia and in the early postoperative period by providing a motor block of the pectoralis major muscle.


Predicting CRISPR-Cas12a guide efficiency for targeting using machine learning.
Genome editing through the development of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeat)-Cas technology has revolutionized many fields in biology. Beyond Cas9 nucleases, Cas12a (formerly Cpf1) has emerged as a promising alternative to Cas9 for editing AT-rich genomes. Despite the promises, guide RNA efficiency prediction through computational tools search still lacks accuracy. Through a computational meta-analysis, here we report that Cas12a target and off-target cleavage behavior are a factor of nucleotide bias combined with nucleotide mismatches relative to the protospacer adjacent motif (PAM) site. These features helped to train a Random Forest machine learning model to improve the accuracy by at least 15% over existing algorithms to predict guide RNA efficiency for the Cas12a enzyme. Despite the progresses, our report underscores the need for more representative datasets and further benchmarking to reliably and accurately predict guide RNA efficiency and off-target effects for Cas12a enzymes.


Elapsed time since BNT162b2 vaccine and risk of SARS-CoV-2 infection in a large cohort.
Israel was among the first countries to launch a large-scale COVID-19 vaccination campaign, and quickly vaccinated its population, achieving early control over the spread of the virus. However, the number of COVID-19 cases is now rapidly increasing, which may indicate that vaccine protection decreases over time. To determine whether time elapsed since the second BNT162b2 messenger RNA (mRNA) vaccine (Pfizer-BioNTech) injection is significantly associated with the risk of post-vaccination COVID-19 infection. This is a retrospective cohort study performed in a large state-mandated health care organization in Israel. All fully vaccinated adults who have received a RT-PCR test between May 15, 2021 and July 26, 2021, at least two weeks after their second vaccine injection were included. Patients with a history of past COVID-19 infection were excluded. Positive result for the RT-PCR test. The cohort included 33,993 fully vaccinated adults, 49% women, with a mean age of 47 years (SD, 17 years), who received an RT-PCR test for SARS-CoV-2 during the study period. The median time between the second dose of the vaccine and the RT-PCR test was 146 days, interquartile range [121-167] days. 608 (1.8%) patients had positive test results. There was a significantly higher rate of positive results among patients who received their second vaccine dose at least 146 days before the RT-PCR test compared to patients who have received their vaccine less than 146 days before: odds ratio for infection was 3.00 for patients aged over 60 (95% CI 1.86-5.11); 2.29 for patients aged between 40 and 59 (95% CI 1.67-3.17); and 1.74 for patients aged between 18 and 39 (95% CI 1.27-2.37); P<0.001 in each age group. In this large population study of patients tested for SARS-CoV-2 by RT-PCR following two doses of mRNA BNT162b2 vaccine, we observe a significant increase of the risk of infection in individuals who received their last vaccine dose since at least 146 days ago, particularly among patients older than 60.


The first national clinical audit for rheumatoid arthritis.
The first national audit for rheumatoid and early inflammatory arthritis has benchmarked care for the first 3 months of follow-up activity from first presentation to a rheumatology service. Access to care, management of early rheumatoid arthritis and support for self care were measured against National Institute for Health and Care Excellence quality standards; impact of early arthritis and experience of care were measured using patient-reported outcome and experience measures. The results demonstrate delays in referral and accessing specialist care and the need for service improvement in treating to target, suppression of high levels of disease activity and support for self-care. Improvements in patient-reported outcomes within 3 months and high levels of overall satisfaction were reported but these results were affected by low response rates. This article presents a summary of the national data from the audit and discusses the implications for nursing practice.


Evolutionary trade-offs among decomposers determine responses to nitrogen enrichment.
Evolutionary trade-offs among ecological traits are one mechanism that could determine the responses of functional groups of decomposers to global changes such as nitrogen (N) enrichment. We hypothesised that bacteria targeting recalcitrant carbon compounds require relatively high levels of N availability to support the construction costs of requisite extracellular and transport enzymes. Indeed, we found that taxa that used more recalcitrant (i.e. larger and cyclic) carbon compounds were more prevalent in ocean waters with higher nitrate concentrations. Compared to recalcitrant carbon users, labile carbon users targeted more organic N compounds, were found in relatively nitrate-poor waters, and were more common in higher latitude soils, which is consistent with the paradigm that N-limitation is stronger at higher latitudes. Altogether, evolutionary trade-offs may limit recalcitrant carbon users to habitats with higher N availability.


The war on obesity: a social determinant of health.
The weight-centred health paradigm is an important contributor to the broader cultural paradigm in which corpulence is eschewed in favour of leanness. The desirability to reduce body fat or weight or to prevent gaining 'excess' fat is driven by both aesthetic and health ideals. The 'war on obesity' is a broad health-based set of policies and programs designed to problematise 'excess' body fat and create solutions to the 'problem'. There is a substantial body of literature that claims to demonstrate the harmful effects of 'excess' body fat. Recent critiques of 'obesity prevention' programs have highlighted the importance of focusing on environmental changes rather than individuals due in part to the risk of harmful consequences associated with individualistic, victim-blaming approaches. Beyond this, there are suggestions that framing body weight as the source of health problems - known as the weight-centred health paradigm - is in itself a harmful approach. The range of harms includes body dissatisfaction, dieting, disordered eating, discrimination and death. Health promotion policies and programs that operate within the weight-centred paradigm have the potential to have a negative impact on the health and well-being of individuals and communities.


Secretion pattern of immunoreactive inhibin in men.
Chronological changes in serum concentrations of inhibin, a gonadal glycoprotein hormone, were studied in healthy male volunteers (age 24-27 years). Secretion profiles of immunoreactive inhibin (ir-inhibin) were compared with those of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone. Blood samples were collected every 15 min for 24 h. Serum inhibin concentrations were measured by a two-site immunoenzymatic assay with antibodies raised against distinct epitopes of the recombinant 1-32 amino acids of the alpha-subunit of human inhibin. The normal range for men was 0.79-3.1 U/l x 10(-3), the sensitivity of the assay was 0.1 U/l x 10(-3) (cv: within-assay, 6.8%; between-assay, 8.2%). Luteinizing hormone and FSH were measured by immunoradiometric assay and testosterone by radioimmunoassay. Secretion profiles of inhibin and testosterone were tested for diurnal variations by cosinor rhythmometry. Highest ir-inhibin concentrations were observed in the morning at 08.00 h, with peak values of 2.45-3.20 U/l x 10(-3). During the evening and the night, ir-inhibin levels were relatively low; lowest concentrations were observed between 01.00 h and 02.00 h at night: 1.20-1.86 U/l x 10(-3). Highest testosterone levels were observed in the morning (20.5-36.6 pmol/l), lowest concentrations were detected at night (7.35-12.6 pmol/l). Cosinor rhythmometry supported the suggestion that there is a clear circadian secretion of ir-inhibin and testosterone, respectively. The secretion pattern of ir-inhibin was analyzed by the Cluster pulse analysis computed algorithm, which identified four to seven inhibin pulses per day, depending on the person under observation.2+ volunteers follow a clear diurnal rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)


Reducing and restoring stimulus-response compatibility effects by decreasing the discriminability of location words.
In two experiments, we compared level of activation and temporal overlap accounts of compatibility effects in the Simon task by reducing the discriminability of spatial and non-spatial features of a target location word. Participants made keypress responses to the non-spatial or spatial feature of centrally presented location words. The discriminability of the spatial feature of the word (Experiment 1), or of both the spatial and non-spatial feature (Experiment 2), was manipulated. When the spatial feature of the word was task-irrelevant, lowering the discriminability of this feature reduced the compatibility effect. The compatibility effect was restored when the discriminability of both the task-relevant and task-irrelevant features were reduced together. Results provide further evidence for the temporal overlap account of compatibility effects. Furthermore, compatibility effects when the spatial information was task-relevant and those when the spatial information was task-irrelevant were moderately correlated with each other, suggesting a common underlying mechanism in both versions.


Different arms of the adaptive immune system induced by a combination vaccine work in concert to provide enhanced clearance of influenza.
Current split influenza virus vaccines that induce strain-specific neutralising antibodies provide some degree of protection against influenza infection but there is a clear need to improve their effectiveness. The constant antigenic drift of influenza viruses means that vaccines are often not an exact match to the circulating strain and so levels of relevant antibodies may not be sufficiently high to afford protection. In the situation where the emergent influenza virus is completely novel, as is the case with pandemic strains, existing vaccines may provide no benefit. In this study we tested the concept of a combination vaccine consisting of sub-optimal doses of split influenza virus vaccine mixed with a cross-protective T-cell inducing lipopeptide containing the TLR2 ligand Pam2Cys. Mice immunised with combination vaccines showed superior levels of lung viral clearance after challenge compared to either split virus or lipopeptide alone, mediated through activation of enhanced humoral and/or additional cellular responses. The mechanism of action of these vaccines was dependent on the route of administration, with intranasal administration being superior to subcutaneous and intramuscular routes, potentially through the induction of memory CD8+ T cells in the lungs. This immunisation strategy not only provides a mechanism for minimising the dose of split virus antigen but also, through the induction of cross-protective CD8+ T cells, proves a breadth of immunity to provide potential benefit upon encounter with serologically diverse influenza isolates.


Detecting the Non-physiological, Surgically Tailored Ileocolic Anastomosis Using the Wireless Motility Capsule. A Pre- and Post-operative, Prospective, Within Subject Trial.
Wireless motility capsule (WMC) detects the ileocolic junction (ICJ) in most non-operated patients. We find no data concerning this examination in patients where the ileocolic valve is replaced by a per definition incompetent, surgically created ICJ. We wanted to see if WMC could detect the ICJ after a right colectomy and assess the competency. Prospective cohort study using a within-subject design to eliminate subject-subject variability. Selected patients operated with right colectomy underwent 3 WMC examinations (pre-operatively, 3 weeks, and 6 months after surgery). Twenty patients (8 men) included, 7 (4 men) excluded due to poor recordings (4) and unforeseen events (3). Thirteen patients (4 men), median age 63 years completed 3 tests. Median bowel lengths removed were 11 cm for ileum and 21 cm for colon. Thirty-nine examinations analyzed by 2 physicians who found all 13 ICJs at 3 examinations with high inter-rater reliability (intra-class correlation coefficient: 0.99, 0.91, and 0.99 respectively), whereas the computer found 9, 8, and 10 out of the 13 ICJs, respectively. Computed values significantly more often deviated from the 2 raters. Mean magnitude and duration of pH-drop at the ICJ (3 examinations) was 1.16-1.02-1.13 pH units and 3.15-4.78-3.75 minutes, respectively. pH-drop was smaller and duration longer at 3 weeks. We found no differences between the pre-operative (competent ICJ) and post-operative 6-month examinations (incompetent ICJ). Highest pressure immediately prior to ICJ was equal before and after surgery. WMC can identify the non-physiological ICJ after right colectomy. Ileocolic competence cannot be assessed.


[Diagnostics of ischemic ocular lesions in carotid arterial pathology].
The aim of the study was to evaluate blood flow in ocular vessels and the carotid arteries of patients with various clinical forms of ischemic ocular lesion (IOL). The subjects were 165 patients with IOL aged 35 to 70 years. Of these, in 115 patients the lesion was acute, and in 50 patients it was chronic. Ultrasound examination using Doppler color mapping (DCM) and energetic mapping (EM) was performed to evaluate ocular and carotid blood flow. The use of DCM and EM made it possible to detect hemodynamically significant changes in acute and chronic IOL in carotid arterial pathology. Duplex scanning of the carotid arteries allowed for timely diagnostics of occlusive-stenotic carotid arterial lesion and determination of atherosclerotic plaque type. DCM and EM are highly informative methods of diagnostics of pathological vascular changes in IOL.


[THE INFLUENCE OF DEFICIT OF ENDOGENOUS NEUROPEPTIDES ON THE CLINICAL COURSE OF CORONARY HEART DISEASE].
The study is aimed at elucidating the relationship between the blood b-endorphin level in patients with coronary heart disease (CHD) with metabolic syndrome (MS) and cardiovascular risk factors and evaluating the possibility to correct them by dalargin therapy. The study included 123 patients (61 men and 62 women) at the mean age 57.6±5,2 years randomized into 2 groups. The patients of group 1 (n=63) were given the standard treatment, those of group 2 (n=60) additionally received 2 mg/day of dalargin for 10 days (3 courses during 3 months). The group of comparison (n=84) contained 84 CHD patients without MS. Biochemical and immunological characteristics were measured by immuno enzyme and immunochemiluminescent assays before and 3 months after treatment. The study revealed inverse correlation between b-endorphin levels and those of leptin, insulin, cortisol, TNF-a, IL-6, oxidized LDLP, triglycerides (TG), and HDLP cholesterol. Standard therapy resulted in a 6.5% reduction of insulin level, 9,4% , 6,1%, and 17,4% reduction of TNF-a , IL-6, TG levels respectively; it increased the HDLP cholesterol level by 10,3% (p<0,05 for all values) but did not change other parameters of interest. Dalargin therapy caused a 32,6% and 17,4%, rise in the b-endorphin and HDLP cholesterol levels but decreased leptin, insulin, cortisol, TNF-a, IL-6, LDLP, and tG levels by 36,1%, 22,4%, 23,9%, 55%, 56,3%, 14% and 27,2% respectively (p<0,001). It is concluded that the decrease of the blood b-endorphin level in the patients with coronary heart disease and metabolic syndrome is associated with enhanced blood atherogenicity, hyperinsulinemia, hypercortisolemia, activation of pro-inflammatory cytokines and lipid peroxidation. Supplementation of conventional therapy with dalargin results in the increased b-endorphin level, enhanced anti-atherogenic effect, reduced activity of pro-inflammatory cytokines and lipid peroxidation, reduction of leptin, insulin and cortisol levels.


[Exploring new therapeutic approaches to the treatment of inflammatory disorders--lipoxins].
The prevalence of inflammatory disorders continues to increase and its optimal treatment still remains a challenge. Lipoxins, endogenous eicosanoids biosynthesised in vivo at inflammatory sites, are potent anti-inflammatory mediators. Therefore, it is of interest to investigate the potential effects of lipoxins that could attenuate chronic inflammation. Currently, only limited data on the effects of lipoxins in clinical investigations are available. Nevertheless, lipoxins caused inhibition of hyper-responsiveness and allergic airway inflammation in asthma. They could also impact the progression of inflammatory arthritides through the reduction of the inflammatory infiltrates and limiting tissue destruction. Lipoxins may play important anti-inflammatory roles in intestinal inflammation as well as in a number of cutaneous inflammatory disorders like psoriasis or atopic dermatitis. Taken together, the available data suggests that lipoxins may have broad therapeutic potential in inflammatory disorders and could provide an alternative to corticosteroids in certain clinical settings.


Histological and clinical evaluation of discarded kidneys in a European cohort of deceased brain death donor kidneys of marginal quality.
Despite organ shortages, the discard rate of deceased donor kidneys is high. Risk factors for this trend warrant further study. We investigated reasons for discard in a cohort of brain death donors with marginal kidneys and procurement biopsies. Paraffin embedded procurement biopsies were systematically reevaluated and graded for the purpose of the study. Assessment included percentage of global glomerulosclerosis, Banff Lesion scores and tubular epithelial damage. Donor-, transplant process-, perfusion quality-, histopathology-, and recipient-related parameters were compared between discarded and transplanted organs. Although most clinical characteristics were similar between donors whose kidneys were transplanted and those whose kidneys were procured but discarded, discarded kidneys were more likely to be from donors with hepatitis C, to have undergone wedge biopsies, to show changes of acute and chronic injury and to be deemed poor quality. Except for obvious anatomic abnormalities, kidneys were often discarded due to the findings of procurement biopsies. Donors of kidneys discarded for histologic reasons more often had hypertension, coronary artery disease, stroke, and increased serum creatinine. The reason for discard was unknown in 20% of cases. Discarded kidneys came from donors who appeared to be clinically similar to donors whose kidneys were utilized for transplant. A considerable proportion of discarded kidneys were of acceptable quality. The analysis of the outcome of every recovered organ could help to overcome this problem. Procurement biopsies more often lead to discard than to transplantation of recovered organs. Proper handling during allocation has to be determined.


Decreased Na+K+ATPase activity in the aortic endothelium and smooth muscle of the spontaneously hypertensive rats.
The activity of Na+K+ ATPase in the endothelium and smooth muscle of the aortae of normotensive and hypertensive rats was investigated. The enzyme activity in the endothelium and smooth muscle of the spontaneously hypertensive rats (SHR) was 2.15 +/- 0.48 and 12.98 +/- 0.99 respectively. These values were significantly lower (P less than 0.05) than the enzyme activity in the corresponding tissues (10.10 +/- 1.78 for endothelium, 20.77 +/- 2.54 for smooth muscle) of the normotensive Wistar Kyoto (WKY) rats. However, with the low blood pressure spontaneously hypertensive rats (LBP-SHR) i.e. in those animals whose blood pressures were below 150 mm Hg, the enzyme activity in both tissues was not significantly different from those of the WKY. Since Na+ K+ ATPase is coupled to the sodium-potassium pump whose activity affects the functions of other pumps, the results indicate that the development of high blood pressure in the SHR may be related to an alteration in the transport of cations across the cell membrane.


Biosynthesis of Sulfur-Containing tRNA Modifications: A Comparison of Bacterial, Archaeal, and Eukaryotic Pathways.
Post-translational tRNA modifications have very broad diversity and are present in all domains of life. They are important for proper tRNA functions. In this review, we emphasize the recent advances on the biosynthesis of sulfur-containing tRNA nucleosides including the 2-thiouridine (s²U) derivatives, 4-thiouridine (s⁴U), 2-thiocytidine (s²C), and 2-methylthioadenosine (ms²A). Their biosynthetic pathways have two major types depending on the requirement of iron-sulfur (Fe-S) clusters. In all cases, the first step in bacteria and eukaryotes is to activate the sulfur atom of free l-cysteine by cysteine desulfurases, generating a persulfide (R-S-SH) group. In some archaea, a cysteine desulfurase is missing. The following steps of the bacterial s²U and s⁴U formation are Fe-S cluster independent, and the activated sulfur is transferred by persulfide-carrier proteins. By contrast, the biosynthesis of bacterial s²C and ms²A require Fe-S cluster dependent enzymes. A recent study shows that the archaeal s⁴U synthetase (ThiI) and the eukaryotic cytosolic 2-thiouridine synthetase (Ncs6) are Fe-S enzymes; this expands the role of Fe-S enzymes in tRNA thiolation to the Archaea and Eukarya domains. The detailed reaction mechanisms of Fe-S cluster depend s²U and s⁴U formation await further investigations.


A Critical Review of Data Science Applications in Resource Recovery and Carbon Capture from Organic Waste.
Municipal and agricultural organic waste can be treated to recover energy, nutrients, and carbon through resource recovery and carbon capture (RRCC) technologies such as anaerobic digestion, struvite precipitation, and pyrolysis. Data science could benefit such technologies by improving their efficiency through data-driven process modeling along with reducing environmental and economic burdens via life cycle assessment (LCA) and techno-economic analysis (TEA), respectively. We critically reviewed 616 peer-reviewed articles on the use of data science in RRCC published during 2002-2022. Although applications of machine learning (ML) methods have drastically increased over time for modeling RRCC technologies, the reviewed studies exhibited significant knowledge gaps at various model development stages. In terms of sustainability, an increasing number of studies included LCA with TEA to quantify both environmental and economic impacts of RRCC. Integration of ML methods with LCA and TEA has the potential to cost-effectively investigate the trade-off between efficiency and sustainability of RRCC, although the literature lacked such integration of techniques. Therefore, we propose an integrated data science framework to inform efficient and sustainable RRCC from organic waste based on the review. Overall, the findings from this review can inform practitioners about the effective utilization of various data science methods for real-world implementation of RRCC technologies.


[Microbiological characteristics and spectrum of infections of 108 Streptococcus anginosus isolated].
The aim of the present study was to assess the key microbiologic characteristics aid in the identification of Streptococcus anginosus in the laboratory and know the spectrum of clinical infections it produces. From March 1991 to April 1992 all the isolated strains of clinical significant samples were collected. For identification the API 20 STREP (BioMérieux) system was used. The histories of the patients with infection by S. anginosus were retrospectively reviewed to collect clinical and microbiologic data of interest. The 108 strains of St. anginosus isolated were diminute colonies on sheep blood agar with CO2 enrichment. They had a characteristic smell, were beta-hemolitic or non hemolitic and of the Lancefield group A, C, F, G or not groupable. All had invariable biochemical features in the API 20 STREP: produced acetone and alkaline phosphatase, hydrolized arginine, did not hydrolize hypurate nor did they ferment ribose. Streptococcus anginosus produced purulent infections of different localization: abdominal, head-neck, pleuro-pulmonary, muscle-skeletal, skin and soft tissues and miscellaneous. Most of these infections were polymicrobial (81.5%). St. anginosus was easily identified in the laboratory by its morphologic characteristics and biochemical reaction in the API 20 STREP. It produced a wide variety of supurative infections, some being severe: cerebral, pulmonary, hepatic, empyema abscess. The identification of this microorganism at a species level should contribute to better recognition as a pathogen of occassionally severe supurative infections.


Infections in the first year after heart transplantation in a Latin American country.
Heart transplantation is the therapy of choice in patients with advanced heart failure refractory to other medical or surgical management. However, heart transplants are associated with complications that increase posttransplant morbidity and mortality. Infections are one of the most important complications after this procedure. Therefore, infections in the first year after heart transplantation were evaluated. A retrospective cohort study of infections after heart transplants was conducted in a teaching hospital in Colombia between 2011 and 2019. Patients registered in the institutional heart transplant database (RETRAC) were included in the study. Microbiological isolates and infectious serological data were matched with the identities of heart transplant recipients and data from clinical records of individuals registered in the RETRAC were analyzed. The cumulative incidences of events according to the type of microorganism isolated were estimated using Kaplan-Meier survival analyses. Seventy-nine patients were included in the study. Median age was 49 years (37.4-56.3), and 26.58% of patients were women. Eighty-seven infections were documented, of which 55.17% (48) were bacterial, 22.99% (20) were viral, and 12.64% (11) were fungal. Bacterial infections predominated in the first month. In the first year, infections caused 38.96% of hospital admissions and were the second cause of death after heart transplants (25.0%). Posttransplant infections in the first year of follow-up were frequent. Bacterial infections predominated in the early posttransplant period. Infections, mainly bacterial, were the second most common cause of death and the most common cause of hospitalization in the first year after heart transplantation.


The Combination of Trichoderma harzianum and Chemical Fertilization Leads to the Deregulation of Phytohormone Networking, Preventing the Adaptive Responses of Tomato Plants to Salt Stress.
Plants have evolved effective mechanisms to avoid or reduce the potential damage caused by abiotic stresses. In addition to biocontrol abilities, Trichoderma genus fungi promote growth and alleviate the adverse effects caused by saline stress in plants. Morphological, physiological, and molecular changes were analyzed in salt-stressed tomato plants grown under greenhouse conditions in order to investigate the effects of chemical and biological fertilizations. The application of Trichoderma harzianum T34 to tomato seeds had very positive effects on plant growth, independently of chemical fertilization. The application of salt stress significantly changed the parameters related to growth and gas-exchange rates in tomato plants subject to chemical fertilization. However, the gas-exchange parameters were not affected in unfertilized plants under the same moderate saline stress. The combined application of T34 and salt significantly reduced the fresh and dry weights of NPK-fertilized plants, while the opposite effects were detected when no chemical fertilization was applied. Decaying symptoms were observed in salt-stressed and chemically fertilized plants previously treated with T34. This damaged phenotype was linked to significantly higher intercellular CO2 and slight increases in stomatal conductance and transpiration, and to the deregulation of phytohormone networking in terms of significantly lower expression levels of the salt overlay sensitivity 1 (SOS1) gene, and the genes involved in signaling abscisic acid-, ethylene-, and salicylic acid-dependent pathways and ROS production, in comparison with those observed in salt-challenged NPK-fertilized plants.


Beyond conventional DMARDs: extending TNF-regulant therapies to the vast majority/less privileged who do need them.
This article is a plea to find (better) ways to extend the benefits of anti-cytokine therapies to ensure they will become available as widely as possible. Pessimistically, this will probably involve substituting more affordable, although somewhat less specific, non-biological agents for present target-specific bio-DMARDs (disease-modifying antirheumatic drugs) to ensure far wider distribution of benefits. Optimistically, new developments in technology and bio-engineering might dramatically reduce costs of present 'biological' therapies. (The antibiotics we now take for granted were once also horrendously expensive.). Pragmatically, one goal for this mission should include seriously pursuing more research and pilot clinical trials of non-protein combination therapies able to control: (i) TNF or other pro-inflammatory cytokines; and also (ii) other mediators sustaining chronic inflammation (-->pain, effusion, fibrosis, porosis, etc.). This can be immediately facilitated by drawing upon the immense resources of non-prescription Asia-Pacific traditional therapies--particularly when these have already been shown to either reduce TNF synthesis or control TNF-induced responses in preclinical studies. Could this be a major goal for the next decade, helping rectify some of the omissions of the current Bone & Joint Decade 2000-2010?


Hypertension and childhood stroke.
Cerebrovascular disease (stroke) is one of the ten leading causes of death in children and adolescents. Multiple etiologies, from arteriopathies to prothrombic states, can cause stroke in youth. In adult stroke, hypertension has been shown to be the single most important modifiable risk factor. Although hypertension has not been strongly identified as a risk factor in childhood stroke to date, there is preliminary evidence that suggests that hypertension may also be associated with stroke in children. In this review, we summarize the literature that may link hypertension to stroke in the young. We have identified a series of barriers and limitations in the fields of pediatric hypertension and pediatric neurology that might explain why hypertension has been overlooked in childhood stroke. We suggest that hypertension may be a relevant risk factor that, alone or in combination with other multiple factors, contributes to the development of stroke in children. Currently, there are no consensus guidelines for the management of post-stroke hypertension in children. Thus, we recommend that blood pressure be assessed carefully in every child presenting with acute stroke in order to better understand the effects of hypertension in the development and the outcome of childhood stroke. We suggest a treatment algorithm to help practitioners manage hypertension after a stroke.


Translation and validation of the Greek version of the Somatic Symptom Scale-8 (SSS-8) in patients with chronic low back pain.
To translate and validate the Greek version of the Somatic Symptom Scale-8 (SSS-8) in patients with chronic low back pain (CLBP). The Greek SSS-8, created through forth and back translation and cultural adaption processes, was handed over to 145 patients recruited using simple random sampling. Test-retest, composite, and internal consistency reliability were assessed. Construct validity was examined by assessing correlations with Patient Health Questionnaire-15 (PHQ-15), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and EuroQoL 5-dimension 5-level (EQ-5D-5L) instruments. Structural validity was assessed using confirmatory factor analysis (CFA). Convergent, discriminant, and known group validity were also evaluated. The response rate was 95.1% (138 subjects, mean age 43.2 ± 11.7) and the overall Cronbach's alpha was 0.831. Test-retest reliability assessment revealed excellent results (Pearson's r > 0.996; Lin's concordance coefficient > 0.995; intraclass correlation coefficient >0.995, all p < 0.001). Composite reliability scores for the pain, cardiopulmonary, and fatigue domains were 0.712, 0.787, and 0.567, respectively. The correlation analyses indicated good construct validity. CFA revealed excellent fit results and known group validity output indicated a linear increasing trend in the severity of somatic symptom disorders (SSDs), depression, and anxiety with higher PHQ-15, PHQ-9, and GAD-7 scores (Jonckheere-Terpstra test, p value < 0.001). The Greek SSS-8 was shown to be a reliable and valid tool for measuring SSDs in patients with CLBP.Implications for RehabilitationAccording to the Global Burden of Diseases Study 2017, LBP was one of the leading causes of disability for both sexes combined since 1990.Strategies to identify SSDs in patients with LBP at an earlier stage are essential both for the provision of an optimal targeted treatment and for minimizing its direct and indirect economic burden.The Greek SSS-8 is a standardized and validated instrument, which its utilization will enhance the physical therapy assessment process in the Greek population.Not only is the SSS-8 an easy-to-use and highly accurate diagnostic tool for detecting SSDs, but also a short alternative to PHQ-15 in settings with limited assessment time.


Thinking outside the medicine cabinet: a comparative content analysis of direct-to-consumer advertisements for prescription drug treatments.
This study content analyzed online direct-to-consumer advertisements (DTCA) for prescription drug treatments to explore whether ads for prescription treatments for psychiatric conditions, which are commonly untreated, differ from other drug advertisements. Coded variables included the presence of interactive technological components, use of promotional incentives, and the social contexts portrayed in images shown on each site. Statistical analysis revealed ads for psychiatric medications contained fewer interactive website features, financial incentives, and calls to action than other types of prescription drug advertisements. Implications for health communication researchers are discussed.


Agonist stimulation at human μ opioid receptors in a [(35)S]GTPγS incorporation assay: observation of "bell-shaped" concentration-response relationships under conditions of strong receptor G protein coupling.
The appearance of "bell"- (or "inverted U"-) shaped agonist concentration-response curves (CRCs) in in vitro pharmacological experiments is a frequently observed but poorly communicated phenomenon. In the context of G protein coupled receptor research, it is commonly attributed to the recruitment of secondary targets or to desensitization or feedback processes, but the concrete background of these observations often remains intriguing. Here, we addressed the subject of bell-shaped agonist CRCs at the µ opioid receptor (µOR) by testing the impact of experimental conditions favoring G protein coupling. G protein activation by recombinant human µORs heterologously expressed in CHO cells was assessed in [(35)S]GTPγS binding assays using the opioid ligands DAMGO, morphine, fentanyl and naloxone. Experimental conditions were varied by changing the NaCl (10-300 mM) and the GDP concentration (0.3-30 µM). Both the sodium and the GDP concentration were inversely related to G protein coupling, as evident by an increase in basal [(35)S]GTPγS incorporation at low sodium and low GDP levels and by the concomitant appearance of the partial agonist activity of the µOR antagonist, naloxone. Bell-shaped CRCs were observed for the efficacious agonists DAMGO, fentanyl and morphine, and this phenomenon was promoted by low sodium as well as by low GDP concentrations. µOR agonist CRCs show a non-monotonic behavior with a decline of maximal stimulation under conditions of strong receptor-G protein coupling, and this behavior is visible at the level of G protein activation itself.


Primers specific for the fimbrial major subunit gene stdA can be used to detect Salmonella enterica serovars.
The feasibility of using two primers internal to the stdA gene (which encodes the fimbrial major subunit of the std fimbrial gene cluster in Salmonella enterica serovar Typhi) to detect Salmonella by PCR was explored. The 518-bp stdA specific sequence was conserved among 268 strains from 45 serovars of S. enterica. One Salmonella bongori CCUG 30042 strain and 34 non-Salmonella strains did not possess this sequence. A sensitivity test revealed that the stdA-specific primer set detected 3.4 x 10(-1) pg of genomic DNA and 3.0 x 10(5) CFU/ml with serial dilutions of Salmonella Typhimurium cells. In vitro testing for specificity using pig carcass sponge samples contaminated with Salmonella Typhimurium also was performed. An initial Salmonella Typhimurium inoculum of 4.4 x 10(1) CFU/ml in pig carcass exudates reached the stdA primer detection level after preenrichment in buffered peptone water at 37 degrees C for 18 h in the presence of indigenous non-Salmonella flora at 4.0 X 10(7) CFU/ml, but the detection level decreased to 4.4 x 10(0) CFU/ml after selective enrichment in Rappaport-Vassiliadis R10 broth for 18 h at 42 degrees C. The PCR method with primers specific for stdA is a quick and sensitive tool for detecting S. enterica, which is an important cause of foodborne disease.


Inhibitory effect of alpha-fetoprotein on the binding of myasthenia gravis antibody to acetylcholine receptor.
The binding of myasthenia gravis antibody acetylcholine receptor (AcChoR) as measured in vitro by Radioimmunoassay with 125I-labeled alpha-bungarotoxin (alpha-BuTx), can be blocked by amniotic fluid, maternal serum, and umbilical cord serum. This inhibitory effect is due to alpha-fetoprotein present in high concentrations in amniotic fluid and serum, as shown by: (i) selective removal of several components from amniotic fluid and serum; (ii) selective addition of different components present in amniotic fluid and serum, including alpha-fetoprotein, to be radioimmunoassay; (iii) correlation between the inhibitory effect of both amniotic fluid and serum and between the amounts of alpha-fetoprotein they contain; (iv) blocking of the alpha-fetoprotein in vitro suggests a similar effect in vivo in pregnant women with myasthenia gravis. This effect may explain in part the variability in the development of neonatal myasthenia gravis in the babies, due to transplacental transfer of maternal anti-AcChoR antibody, only after delivery and only in the minority of the cases. It also may explain the appearnace of remissions in females with myasthenia gravis during the second and third trimesters of pregnancy. Similar phenomena observed during pregnancy in other autoimmune and immunopathogenic diseases also might be attributed to activity of alpha-fetoprotein.


A stress-associated protein, LmSAP, from the halophyte Lobularia maritima provides tolerance to heavy metals in tobacco through increased ROS scavenging and metal detoxification processes.
Agricultural soil pollution by heavy metals is a severe global ecological problem. We recently showed that overexpression of LmSAP, a member of the stress-associated protein (SAP) gene family isolated from Lobularia maritima, in transgenic tobacco led to enhanced tolerance to abiotic stress. In this study, we characterised the response of LmSAP transgenic tobacco plants to metal stresses (cadmium (Cd), copper (Cu), manganese (Mn), and zinc (Zn)). In L. maritima, LmSAP expression increased after 12 h of treatment with these metals, suggesting its involvement in the plant response to heavy metal stress. LmSAP transgenic tobacco plants subjected to these stress conditions were healthy, experienced higher seedling survival rates, and had longer roots than non-transgenic plants (NT). However, they exhibited higher tolerance towards cadmium and manganese than towards copper and zinc. LmSAP-overexpressing tobacco seedlings accumulated more cadmium, copper, and manganese compared with NT plants, but displayed markedly decreased hydrogen peroxide (H2O2) and lipid peroxidation levels after metal treatment. Activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) were significantly higher in transgenic plants than in NT plants after exposure to metal stress. LmSAP overexpression also enhanced the transcription of several genes encoding metallothioneins (Met1, Met2, Met3, Met4, and Met5), a copper transport protein CCH, a Cys and His-rich domain-containing protein RAR1 (Rar1), and a ubiquitin-like protein 5 (PUB1), which are involved in metal tolerance in tobacco. Our findings indicate that LmSAP overexpression in tobacco enhanced tolerance to heavy metal stress by protecting the plant cells against oxidative stress, scavenging reactive oxygen species (ROS), and decreasing the intracellular concentration of free heavy metals through its effect on metal-binding proteins in the cytosol.


Anxiety and Depression in Facial Injuries: A Comparative Study.
This study was performed to identify the presence of anxiety and depression in patients who had sustained facial injuries; additionally we aimed to identify other variables that may modify the psychological response to trauma that include gender and age. The participants were 153 patients from multimodal trauma centers in Bangalore city who sustained disfiguring facial injuries were taken up. Of the 153 patients, 81 patients were male (51 less than 50 years of age and 30 more than 50 years of age) and 72 patients were female (40 less than 50 years of age and 32 more than 50 years of age) and 111 patients with non-disfiguring facial injuries out of which 54 were male patients and 57 were female patients. The assessments were carried out at 3 time intervals (the date of discharge [DOD], 1-month post-operatively and 6 months post-operatively) of the follow-up. The hospital anxiety and depression scale (HADS) was used to assess the anxiety and depression of the facial trauma patients. Statistically significant higher means of HADS both for anxiety and depression were present in patients with disfiguring facial injuries compared to non-disfiguring facial injuries, female patients compared to male patients after the 1-month and 6 months post-operatively, the mean anxiety and depression scores of males and female patients were significantly higher for those who aged less than 50 years compared to those who aged more than 50 years. The results of this study led to the conclusion that in comparison with patients who had facial disfiguring injuries and non-disfiguring facial injuries, the mean HADS scores were significantly higher in the disfiguring facial injury patient. This indicates increased Anxiety and Depression levels and this was observed at all three study intervals (DOD, 1-month and 6 months post-operatively). The HADS was higher in female patients who were lesser than 50 years age compared to male patients of the same age group, which implies higher anxiety and depression levels.


[Expression of IRX1 in cervical cancer and its correlation with clinical stage of cervical cancer].
Objective: To study the expression of IRX1 (Iroquois homeobox gene) in cervical cancer and its correlation with clinical stage of cervical cancer. Methods: A total of 61 patients with cervical cancer from January 2015 to January 2017 were enrolled in this study, of which 15 were classified as phase Ⅰ of cervical cancer, 22 patients were classified as phase Ⅱ, 19 cases were classified as phase Ⅲ, 5 cases were classified as phase Ⅳ followed FIGO staging criteria.The expression of IRX1 protein in Hela, C4-1 and Siha cell lines were detected by Western blot compared with the normal human cervical epithelial cells HCerEpiC.Collected cancerous tissue of cervical cancer as experimental samples, the expression of IRX1 mRNA in cancer tissues and paracancerous tissue were detected by qPCR.Immunohistochemistry was used to detect the expression of IRX1 in different stages of cervical cancer, the correlation between IRX1 expression and clinical stage was analyzed. Results: The results of Western blot showed that IRX1 expression in cervical cancer cells were higher than that in normal cervical epithelial cells, and the results of qPCR also showed that the expression of IRX1 increased with the stage of cancer at the gene level.The difference was statistically significant.The expression of IRX1 in the nucleus and cytoplasm were detected by immunohistochemistry.Immunohistochemical results showed that the higher the stage of cancer was, the higher the expression rate of IRX1 was. Conclusion: IRX1 expression is associated with the clinical stage of cervical cancer, suggesting that IRX1 may be involved in the development and progression of cervical cancer.IRX1 is expected to be a new molecular target for the diagnosis and treatment of cervical cancer. This study will provide a new theoretical basis for the treatment of cervical cancer.


[Medullary carcinoma experience in breast oncology unit of Hospital Juarez Mexico].
Medullary breast cancer is a rare type, considered of good prognosis. To know the epidemiological and clinical characteristics of the population attended in the Hospital Juarez de Mexico, to know if they are alike to described worldwide and if the treatments proposed internationally are applicable for this hospitable center. We performed a retrospective analysis. Reviewing the records with histopathologic diagnosis of medullary breast cancer from February 1993 to February 2011. Finding 41 patients in the oncology unit of the institution. We report an incidence of 3.04%, originating in 11 Mexican States, with a low to middle socioeconomic level in 39.02%. The average age at the time of diagnosis was 50 years. No family history was reported but some patients had medical history for type 2 diabetes, hypertension and previous breast cancer. 63.41% were menopausal. The average clinical size of the tumor was 58 mm. The 63% of the cases were located in the left breast. The 53.1% were clinical stages I and II, 46.3% were clinical stages III and in 9.6% of the cases primary tumor could not be assessed. Only 47% of the patients had positive axillary lynph nodes at diagnosis. The inmunohistochemestry was only reported in 14 of the 41 patients, according to the molecular classification of breast cancer: 8 were triple negative, 2 luminal A, 1 luminal B and 3 Her2neu. The Mexican population presents epidemiological and clinical characteristics similar to those patients described in other studies worldwide.


The differences in the nitrogen isotope composition between a maize hybrid and its parents.
Understanding of nitrogen stable isotope variation in maize hybrids might help obtaining information on nitrogen absorption and distribution in different maize hybrids. In this study, we examined the nitrogen isotopic composition of different parts of maize hybrids under a laboratory culture experiment. The results showed that the δ15N values of different parts of the maize hybrid and its parents were ordered as follows: δ15Nstem>δ15Nleaf>δ15Nroot. The variation pattern of δ15N between the roots and leaves(Δδ15Nroot-leaf) of the maize hybrid was the same as that of δ15N between the roots and stems (Δδ15Nroot-stem). Therefore, the order of Δδ15Nroot-leaf as well as Δδ15Nroot-stem was as follows: Δδ15Nroot-leaf of the maize hybrid>Δδ15Nroot-leaf of the female parent (T4)>Δδ15Nroot-leaf of the male parent (803) and Δδ15Nroot-stem of the maize hybrid>Δδ15Nroot-stem of the female parent (T4)>Δδ15Nroot-stem of the male parent (803). This order is consistent with heterosis, indicating that differences in δ15N reflect the phenomenon of heterosis. The present study provides data in support of using the isotope technique to determine nitrogen distributions inside a plant and guide crossbreeding.


The mature osteoblast phenotype is characterized by extensive plasticity.
While both morphological and biochemical-molecular attributes demarcate differentiation stages in specific cell and tissue types, what constitutes necessary and sufficient expression to define particular cell types is not always known. For example, mature osteoblasts (OBs) are defined morphologically as the cuboidal, biosynthetically active, basophilic cells residing on bone surfaces and responsible for the deposition of osteoid matrix. However, several recent observations suggest that not all mature OBs are identical. To explore further the validity of the hypothesis that heterogeneity of phenotype exists among mature OBs, we grew fetal rat calvaria cells in vitro at low density under conditions in which bone nodules form and mineralize in isolation of other contaminating cell and colony types. Cells resident in mature OB colonies, i.e., those comprising mainly cuboidal cells associated with an osteoid matrix that had begun to mineralize, were analyzed in situ for protein expression by immunocytochemistry with antibodies against collagen type I, alkaline phosphatase, osteopontin, bone sialoprotein, and osteocalcin. Consistent with the expected phenotype of mature OBs, many OBs expressed high levels of all of these markers, but strikingly even adjacent morphologically indistinguishable cuboidal OBs had differences in protein expression, especially in relation to osteopontin, bone sialoprotein, and osteocalcin expression. Double-labeling with Hoechst 33258 and osteocalcin indicated that the variation in antibody labeling intensity/protein expression appeared independent of a variation in cell cycle. To further ascertain the extent of this heterogeneity, 20 single cells were micromanipulated from colonies and subjected to poly(A)-PCR to analyze the simultaneous coexpression profiles of the same five markers analyzed by immunocytochemistry and two other markers, the OB-osteocyte transition marker E11 and the parathyroid hormone/parathyroid hormone-related protein receptor. Notably, the repertoire of genes expressed and their levels of expression varied markedly in individual OBs. The observed heterogeneity suggests that the mature OB phenotype is not a single unique phenotype but rather encompasses a flexible pattern of expression from the repertoire of OB-associated markers.


The Intestinal Microbiota and Metabolites in the Gut-Kidney-Heart Axis of Chronic Kidney Disease.
Emerging evidences demonstrate the involvement of gut microbiota in the progression of chronic kidney disease (CKD) and CKD-associated complications including cardiovascular disease (CVD) and intestinal dysfunction. In this review, we discuss the interactions between the gut, kidney and heart in CKD state, and elucidate the significant role of intestinal microbiota in the gut-kidney-heart axis hypothesis for the pathophysiological mechanisms of these diseases, during which process mitochondria may serve as a potential therapeutic target. Dysregulation of this axis will lead to a vicious circle, contributing to CKD progression. Recent studies suggest novel therapies targeting gut microbiota in the gut-kidney-heart axis, including dietary intervention, probiotics, prebiotics, genetically engineered bacteria, fecal microbiota transplantation, bacterial metabolites modulation, antibiotics, conventional drugs and traditional Chinese medicine. Further, the identification of specific microbial communities and their corresponding pathophysiological metabolites and the illumination of the gut-kidney-heart axis may contribute to innovative basic research, clinical trials and therapeutic strategies against CKD progression and uremic complications in CKD patients.


Severe burns in children, 1964-1974.
580 children were admitted to the paediatric burns unit of Guy's Hospital between 1964 and 1974, of which 97 had burns exceeding 20% of the surface area, and 33 died (34% mortality). 80% of those with burns exceeding 50% of the surface area died. Young children died after less extensive burns. Respiratory failure, sepsis, and malnutrition were the most lethal complications. The prompt use and careful control of intravenous fluids had reduced the immediate complications associated with shock, and acute renal failure is now uncommon. Respiratory failure resulted in many deaths during the first week after injury. The need for intensive respiratory care involving paediatric, anaesthetic, and surgical staff is stressed. Sepsis and malnutrition remain major threats to survival. Improved methods of bacteriological control by laminar air flow units and topical antibacterial agents may help to reduce infection in the future. Reduction of energy expenditure by temporary skin coverings and a high environmental temperature, combined with a high calorie intake by oral and intravenous routes, may improve the outlook for severly burned children in the next decade.


Loss of exosomal micro-RNA-200b-3p from hypoxia cancer-associated fibroblasts reduces sensitivity to 5-flourouracil in colorectal cancer through targeting high-mobility group box 3.
Hypoxia-mediated tumor progression is a major problem in colorectal cancer (CRC). MicroRNA (miR)-200b-3p can attenuate tumorigenesis in CRC, while exosomal miRNAs derived from cancer-associated fibroblasts (CAFs) can promote cancer progression. Nevertheless, the function of exosomal miR-200b-3p derived from CAFs in CRC remains unclear. In this study, CAFs and normal fibroblasts (NFs) were isolated from CRC and adjacent normal tissues. Next, exosomes were isolated from the supernatants of CAFs cultured under normoxia and hypoxia. Cell viability was tested using the cell counting kit-8 assay, and flow cytometry was used to assess cell apoptosis. Cell invasion and migration were evaluated using the transwell assay. Dual-luciferase was used to investigate the relationship between miR-200b-3p and high-mobility group box 3 (HMBG3). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to determine the miR-200b-3p and HMBG3 level. Our results found that the miR-200b-3p level was sharply reduced in CRC tissues compared to adjacent normal tissues. Additionally, the miR-200b-3p level was reduced in exosomes derived from hypoxic CAFs compared to exosomes derived from CAFs under normoxia. Exosomes derived from hypoxic CAFs weakened the sensitivity of CRC cells to 5-fluorouracil (5-FU) compared to hypoxic CAFs-derived exosomes. However, hypoxic CAFs-derived exosomes with upregulated miR-200b-3p increased the sensitivity of CRC cells to 5-fluorouracil (5-FU) compared to hypoxic CAFs-derived exosomes. In addition, HMBG3 was identified as the downstream target of miR-200b-3p in CRC cells, and its overexpression partially reversed the anti-tumor effect of the miR-200b-3p agomir on CRC via the mediation of the β-catenin/c-Myc axis. Furthermore, compared to exosomes derived from normoxia CAFs, exosomes derived from hypoxic CAFs weakened the therapeutic effects of 5-FU on CRC in vivo via the upregulation of HMGB3 levels. Collectively, the loss of exosomal miR-200b-3p in hypoxia CAFs reduced the sensitivity to 5-FU in CRC by targeting HMGB3. Thus, our research outlines a novel method for the treatment of CRC.


The effect of cue type on directive-following in children with moderate to severe autism spectrum disorder.
For this study, 11 children with moderate to severe autism spectrum disorder (ASD) were given directives containing prepositions in three cue conditions: (a) spoken alone, (b) a short video clip along with spoken cues, and (c) a sequence of three graphic symbols accompanied by spoken cues. Participants followed directives significantly more accurately with the video clip than with spoken cues only, and significantly more accurately with spoken cues only relative to the sequence of graphic symbols. Results suggest that the short video clip along with spoken cues may be an optimal mode for enhancing learners' ability to follow directives containing prepositions. In addition, results reveal three statistically significant correlations between participants' preexisting skills and directive-following accuracy: a positive correlation between spoken preposition preassessment total score and accuracy in the spoken-alone condition; a positive correlation between spoken noun preassessment total score and accuracy in the video-clip condition; and a positive correlation between ASD severity and the need for repetition in the video-clip condition. Results also suggested that, for children with more severe ASD symptoms, the video clips require repetitions so that the relationships illustrated within it can gain more semantic salience. Implications for clinical practice and future research are discussed.


mTOR Inhibition and T-DM1 in HER2-Positive Breast Cancer.
In patients with trastuzumab-resistant HER2-positive breast cancer, the combination of everolimus (mTORC1 inhibitor) with trastuzumab failed to show a clinically significant benefit. However, the combination of mTOR inhibition and the antibody-drug conjugate (ADC) trastuzumab-emtansine (T-DM1) remains unexplored. We tested T-DM1 plus everolimus in a broad panel of HER2-positive breast cancer cell lines. The combination was superior to T-DM1 alone in four cell lines (HCC1954, SKBR3, EFM192A, and MDA-MB-36) and in two cultures from primary tumor cells derived from HER2-positive patient-derived xenografts (PDX), but not in BT474 cells. In the trastuzumab-resistant HCC1954 cell line, we characterized the effects of the combination using TAK-228 (mTORC1 and -2 inhibitor) and knockdown of the different mTOR complex components. T-DM1 did not affect mTOR downstream signaling nor induct autophagy. Importantly, mTOR inhibition increased intracellular T-DM1 levels, leading to increased lysosomal accumulation of the compound. The increased efficacy of mTOR inhibition plus T-DM1 was abrogated by lysosome inhibitors (chloroquine and bafilomycin A1). Our experiments suggest that BT474 are less sensitive to T-DM1 due to lack of optimal lysosomal processing and intrinsic resistance to the DM1 moiety. Finally, we performed several in vivo experiments that corroborated the superior activity of T-DM1 and everolimus in HCC1954 and PDX-derived mouse models. In summary, everolimus in combination with T-DM1 showed strong antitumor effects in HER2-positive breast cancer, both in vitro and in vivo. This effect might be related, at least partially, to mTOR-dependent lysosomal processing of T-DM1, a finding that might apply to other ADCs that require lysosomal processing. Inhibition of mTOR increases the antitumor activity of T-DM1, supporting that the combination of mTOR inhibitors and antibody-drug conjugates warrants clinical evaluation in patients with HER2-positive breast cancer.


Near-Peer Tutor: A Solution For Quality Medical Education in Faculty Constraint Setting.
Near-peer mentoring is a formal relationship in which more qualified students guide immediate junior students. It is an innovative approach to increase students' engagement from varied backgrounds and cultures in the health profession. This systematic review and meta-analysis aimed to investigate and compare the effectiveness of near-peer tutoring and faculty/expert teaching in health science undergraduates on knowledge and skill outcome. The review question considered was "how effective is near-peer tutor compare to faculty/expert teaching for undergraduate health science students?" A comprehensive systematic search was undertaken in PubMed, Embase, Scopus, and Cochrane and screened initially in Rayyan software (Qatar Computing Research Institute, Qatar). Identified articles were screened independently for eligibility by two reviewers and extracted the data. Data were analyzed using standardized mean difference with Review manager version 5.5 (Cochrane Campbell Collaboration). Sixteen studies were analyzed. Heterogeneity (I2) among studies was high in knowledge and skill scores. Heterogeneity was reduced by 30-40% after sensitivity analysis. No difference in knowledge and skill score was found among the near-peer and expert teaching groups. Students had a satisfactory learning experience with near-peer tutors except for some issues related to teaching proficiency in near-peers. Near-peer teaching was found to be as effective as faculty/expert teaching. Students were more comfortable with near-peers. As mentioned by students, some challenges were differences in teaching skills and level of knowledge among near-peers.


Peptidase PepP is a novel virulence factor of Campylobacter jejuni contributing to murine campylobacteriosis.
Mechanisms of host-pathogen interactions resulting in immunopathological responses upon human Campylobacter jejuni infection are not completely understood, but the recent availability of murine infection models mimicking key features of campylobacteriosis helps solving this dilemma. During a screen for proteases expressed by C. jejuni, we identified a peptidase of the M24 family as a potential novel virulence factor, which was named PepP. The gene is strongly conserved in various Campylobacter species. A constructed deletion mutant ΔpepP of C. jejuni strain 81-176 grew as efficiently compared to isogenic wild-type (WT) or pepP complemented bacteria. To shed light on the potential role of this protease in mediating immunopathological responses in the mammalian host, we perorally challenged microbiota-depleted IL-10-/- mice with these strains. All strains stably colonized the murine gastrointestinal tract with comparably high loads. Remarkably, pepP deficiency was associated with less severe induced malaise, with less distinct apoptotic and innate immune cell responses, but also with more pronounced proliferative/regenerative epithelial cell responses in the large intestine at d6post-infection. Furthermore, pro-inflammatory mediators were lower in the colon, ileum, and mesenteric lymph nodes of mice that had been challenged with the ΔpepP mutant compared to the WT or pepP complemented strains. This also held true for extra-intestinal organs including liver, kidneys, and lungs, and, strikingly, to systemic compartments. Taken together, protease PepP is a novel virulence determinant involved in mediating campylobacteriosis. The finding that apoptosis in the colon is significantly diminished in mice infected with the pepP mutant highlights the epithelial layer as the first and main target of PepP in the intestine.


Double-muscling character influences the trans-18:1 and conjugated linoleic acid profiles in concentrate-fed yearling bulls.
Seventy-five yearling bulls of the "Asturiana de los Valles" northern-Spanish beef breed (double-muscled, mh/mh, n=24; heterozygous, mh/+, n=26; normal, +/+, n=25) were produced under intensive conditions and the effects of double-muscling genotype on trans-18:1 and CLA isomer profiles were examined. Total trans-18:1 contents, measured as percentages of total fatty acid methyl esters, were 10.98-15.07% in backfat and 8.64-9.46% in muscle, and the major isomer was 10t-18:1 in all animals. In mh/+ animals, 11t-18:1 was the second most abundant trans isomer in muscle whereas in mh/mh and +/+ animals 11t-18:1 and 13t/14t-18:1 were relatively similar. Total CLA percentages were 0.71-0.85% in backfat and 0.32-0.40% in muscle. The highest total CLA percentage found was in mh/+, intermediate in +/+ and lowest in mh/mh animals (P<0.05). Heterozygous animals had significantly higher percentages of 9c,11t- (P<0.01), 11t,13c- (P<0.01) and 9c,11c-18:2 (P<0.05) and also significantly higher percentages of the sum of 9c,11t-/11t,13c-/11t,13t-18:2. Overall, mh/+ animals produced meat with a slightly better trans and CLA profile (i.e., less 10t-18:1 and more 11t-18:1 and 9c,11t-18:2) than other genotypes, however, further improvements would still be necessary to achieve a profile with a positive health image.


Optimizing Quantum Control Pulses with Gaussian Process Priors: The Spectral Way.
This study presents the Gaussian Process Prior Optimization for Pulse Shaping (GPPOPS) methodology, a novel approach to pulse shaping engineering. Its main objective is to efficiently identify laser pulse shapes that can achieve a desired task encoded in a cost function while being experimentally implementable. The AlH+ molecule was utilized as a test case to find pulse shapes that maximized vibronic transitions. The results demonstrate that optimal pulses can be readily implemented using current laser technology and that their control capabilities can withstand noise. The study emphasizes the benefits of constructing a surrogate approach to the control landscape during the optimization process. This approach is expected to be versatile, efficient and readily implementable in the laboratory. Its demonstrated robustness to noise sets it apart from other numerical pulse shaping engineering methods. By reducing the required experimental labor, this method has the potential to facilitate breakthroughs in quantum engineering.


Congenital lung disease in the adult: guide to the evaluation and management.
A high index of suspicion is required to consider the diagnosis of adult congenital lung disease because of the rarity of presentation in adulthood. The purpose of this article is to provide a framework for evaluation of these lesions and a guide to management. Adults may be asymptomatic, and the abnormality identified as an incidental imaging finding or the individual may present with symptoms of cough, hemoptysis, or recurrent pneumonia. The diagnosis may be readily apparent on computed tomography imaging because of a characteristic appearance, or the abnormality may require further evaluation for diagnosis with supplemental magnetic resonance imaging. Surgical resection provides a definitive diagnosis. The congenital lung malformation may be a solitary lesion or part of a complex group of abnormalities. A detailed review of all the components of the thorax is required to identify additional lesions. Management is typically surgical resection because of the propensity of these lesions to enlarge and to become infected as well as the potential risk for malignant transformation. Computed tomography surveillance may be appropriate for small asymptomatic lesions or lesions with either no or very low risk for developing malignancy.


Brevinin-1GHd: a novel Hylarana guentheri skin secretion-derived Brevinin-1 type peptide with antimicrobial and anticancer therapeutic potential.
Host-defense antimicrobial peptides (AMPs) from amphibians are usually considered as one of the most promising next-generation antibiotics because of their excellent antimicrobial properties and low cytotoxicity. In the present study, one novel Brevinin-1 type peptide, Brevinin-1GHd, was isolated and characterized from the skin secretion of the frog, Hylarana guentheri. Brevinin-1GHd was found to possess a wide range of antimicrobial activity through penetrating the bacterial membrane within a short time while showing low hemolysis at bactericidal concentrations, even against the resistant strains. It also inhibited and eradicated biofilms that are thought to be closely related to the rise in resistance. Meanwhile, Brevinin-1GHd exhibited wide-spectrum anti-proliferation activity toward human cancer lines. Taken together, these results indicate that Brevinin-1GHd with its excellent antimicrobial and anticancer activities is a promising candidate for a novel antibiotic agent, and study of its structure-activity relationships also provided a rational template for further research and peptide analog design.


Increased serum levels of soluble interleukin-2 receptor in patients with systemic lupus erythematosus and rheumatoid arthritis.
In this study we investigated the serum levels of a released soluble form of the interleukin-2 receptor (sIL-2R) in 42 patients with rheumatoid arthritis and in 12 cases of systemic lupus erythematosus. Data were evaluated in relationship to the clinical phase and compared with those observed in normal controls (N = 56) and in osteoarthritis (N = 7). Increased levels were observed in both rheumatoid arthritis (mean +/- SE, 604 +/- 49 U/ml) and systemic lupus erythematosus (1438 +/- 481 U/ml). These values were significantly higher than in control (256 +/- 15 U/ml; P less than 0.001) and in osteoarthritis (298 +/- 33 U/ml; P less than 0.001) groups. In addition, the highest values were associated with the active phases of both rheumatoid arthritis (active vs inactive, 771 +/- 78 vs 451 +/- 39 U/ml; P less than 0.001) and systemic lupus erythematosus (active vs inactive, 2108 +/- 489 vs 499 +/- 75 U/ml; P less than 0.001). Our findings suggest that the detection of sIL-2R in rheumatoid arthritis and in systemic lupus erythematosus may represent a good marker of disease activity, which indirectly indicates the ongoing activation and/or proliferation of immunoreactive cells which are involved in the pathogenetic events of these autoimmune conditions.


Clinical and molecular characterization of an almost complete ring chromosome 4 in two sisters, with recurrence due to gonadal mosaicism.
Autosomal ring chromosomes are rare cytogenetic findings that arise from breakage and fusion of the chromosome ends. Rings are mitotically unstable, usually sporadic and associated with a 'ring syndrome', characterized by a variable phenotype: growth retardation, no significant dysmorphisms and normal to moderately disabled intelligence. We describe the clinical features and molecular characterization of two sisters with ring chromosome 4. Karyotype analysis was performed on both sisters and parents. Chromosome microarray was performed on both sisters to delineate the breakpoint imbalance. Both sisters had a large ring 4 chromosome in the majority of cells analyzed on karyotype. Microarray results were identical in the sisters, showing a 55.8 kb duplication on the terminal 4p arm and a 1.5 Mb deletion on the terminal 4q arm. No genes of interest were identified in these regions. Parental karyotypes on lymphocytes and fibroblasts were normal, with no finding of mosaicism for the ring 4 chromosome. Polymorphic marker analysis revealed the maternal origin of the ring. To our knowledge, this is the first reported instance of a ring 4 chromosome recurring in siblings after extensive parental testing, which suggests this was due to maternal gonadal mosaicism.


Versatile cold atom source for multi-species experiments.
We present a dual-species oven and Zeeman slower setup capable of producing slow, high-flux atomic beams for loading magneto-optical traps. Our compact and versatile system is based on electronic switching between different magnetic field profiles and is applicable to a wide range of multi-species experiments. We give details of the vacuum setup, coils, and simple electronic circuitry. In addition, we demonstrate the performance of our system by optimized, sequential loading of magneto-optical traps of lithium-6 and cesium-133.


Insulating tethered bilayer lipid membranes to study membrane proteins.
Tethered bilayer lipid membranes are stable and promising model systems that mimic several properties of biological membranes. They provide an electrically insulating platform for the incorporation and study of functional membrane proteins, especially ion channels. Covalently linked to a solid support, they also offer enhanced stability compared with other model architectures. If the support can be used as an electrode, electrical characterisation of the system is possible and biosensing applications can be envisioned.Here, we will review some tethered bilayer structures developed in the past and show some examples of functional protein incorporation, both on oxide and gold substrates.


Interaction of nucleoside diphosphate kinase B with heterotrimeric G protein betagamma dimers: consequences on G protein activation and stability.
It is generally accepted that G protein coupled receptors (GPCR) activate heterotrimeric G proteins by inducing a GDP/GTP exchange at the G protein alpha subunit. In addition, the transfer of high energetic phosphate by nucleoside diphosphate kinase (NDPK) and/or the beta subunit of G proteins (Gbeta) can induce G protein activation. Recent evidence suggests that the NDPK isoform B (NDPK B) forms a complex with Gbetagamma dimers. In this complex, NDPK B acts as a protein histidine kinase phosphorylating Gbeta at histidine residue 266 (His266). The high energetic phosphoamidate bond on His266 allows for a phosphate transfer specifically onto GDP and thus local formation of GTP, which binds to and thereby activates the respective G protein alpha subunit. Apparently, this process occurs independent of the classical GPCR-induced GDP/GTP exchange at least for members of the G(s) and G(i) subfamilies of heterotrimeric G proteins. By using a mutant of Gbeta(1) in which His266 was replaced by Leu, it was recently demonstrated that NDPK B/Gbetagamma-mediated G(s) activation contributes by about 50% to basal cAMP formation and contractility in rat cardiac myocytes. Besides its apparent role in G protein activation, the complex formation of NDPK B with Gbetagamma dimers might be essential for G protein stability. Depletion of either the NDPK B orthologue or Gbeta(1) isoforms in zebrafish embryos led to a similar phenotype displaying contractile dysfunction in the heart accompanied by a complete loss of heterotrimeric G protein expression. In conclusion, the interaction of NDKP B with Gbetagamma dimers might play an important role in signal transduction, and alterations in this novel pathway might be of pathophysiological importance.


CERAD (Consortium to Establish a Registry for Alzheimer's Disease) Neuropsychology Assessment Battery: 35 Years and Counting.
In 1986, the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) was mandated to develop a brief neuropsychological assessment battery (CERAD-NAB) for AD, for uniform neuropsychological assessment, and information aggregation. Initially used across the National Institutes of Aging-funded Alzheimer's Disease Research Centers, it has become widely adopted wherever information is desired on cognitive status and change therein, particularly in older populations. Our purpose is to provide information on the multiple uses of the CERAD-NAB since its inception, and possible further developments. Since searching on "CERAD neuropsychological assessment battery" or similar terms missed important information, "CERAD" alone was entered into PubMed and SCOPUS, and CERAD-NAB use identified from the resulting studies. Use was sorted into major categories, e.g., psychometric information, norms, dementia/differential dementia diagnosis, epidemiology, intervention evaluation, genetics, etc., also translations, country of use, and alternative data gathering approaches. CERAD-NAB is available in ∼20 languages. In addition to its initial purpose assessing AD severity, CERAD-NAB can identify mild cognitive impairment, facilitate differential dementia diagnosis, determine cognitive effects of naturally occurring and experimental interventions (e.g., air pollution, selenium in soil, exercise), has helped to clarify cognition/brain physiology-neuroanatomy, and assess cognitive status in dementia-risk conditions. Surveys of primary and tertiary care patients, and of population-based samples in multiple countries have provided information on prevalent and incident dementia, and cross-sectional and longitudinal norms for ages 35-100 years. CERAD-NAB has fulfilled its original mandate, while its uses have expanded, keeping up with advances in the area of dementia.


A better way to do this? Views of mental health nursing directors about preparation for mental health nursing practice.
Nursing directors in mental health services hold important leadership positions that include responsibility for the nursing workforce. The comprehensive or generalist approach to undergraduate nursing education consistently poses significant recruitment problems. Specialisation in mental health within Bachelor of Nursing programs has been suggested as a potential solution. This paper presents the views and opinions of mental health nursing directors regarding undergraduate specialisation. A qualitative exploratory study was undertaken. Thirteen nursing directors from Queensland Mental Health Services participated in an in-depth telephone interview. The data were analysed thematically. Nursing directors were very supportive of specialisation in mental health at the undergraduate level. Thematic analysis revealed four main themes: perceived advantages of the specialist stream; knowledge and experience; increased recruitment; and commitment. Nursing directors are important stakeholders in educational preparation for practice in mental health settings. The research participants described many potential benefits to undergraduate specialisation. Their voice provides an important contribution to this issue.


Comparative survival of first-stage larvae of small lungworms Muellerius capillaris and Neostrongylus linearis of goats in alfalfa and ryegrass plots.
Faeces from a goat infected with M capillaris and from another infected with N linearis were used to assess survival of first-stage larvae under natural conditions in northwest France in mid-autumn, at the high-risk period. The faeces were deposited on 3 plots covered respectively with ryegrass, short cut alfalfa and high alfalfa. The desiccation of faeces and survival of larvae were tested at 1, 7, 14 and 21-d intervals. Survival of M capillaris was much higher than that of N linearis in all plots. The lower desiccations were observed in the high alfalfa plot whereas the best survivals were found in the 2 other plots. Vegetation where faeces are deposited may thus play a part in the accumulation of parasitic risk on a pasture.