Strain Sensors Made of MXene, CNTs, and TPU/PSF Asymmetric Structure Films with Large Tensile Recovery and Applied in Human Health Monitoring.
Designing flexible wearable sensors with a wide sensing range, high sensitivity, and high stability is a vulnerable research direction with a futuristic field to study. In this paper, Ti3C2Tx MXene/carbon nanotube (CNT)/thermoplastic polyurethane (TPU)/polysulfone (PSF) composite films with excellent sensor performance were obtained by self-assembly of conductive fillers in TPU/PSF porous films with an asymmetric structure through vacuum filtration, and the porous films were prepared by the phase inversion method. The composite films consist of the upper part with finger-like "cavities" filled by MXene/CNTs, which reduces the microcracks in the conductive network during the tensile process, and the lower part has smaller apertures of a relatively dense resin cortex assisting the recovery process. The exclusive layer structure of the MXene/CNTs/TPU/PSF film sensor, with a thickness of 46.95 μm, contains 0.0339 mg/cm2 single-walled carbon nanotubes (SWNTs) and 0.348 mg/cm2 MXene only, providing functional range (0-80.7%), high sensitivity (up to 1265.18), and excellent stability and durability (stable sensing under 2300 fatigue tests, viable to the initial resistance), endurably cycled under large strains with serious damage to the conductive network. Finally, the MXene/CNTs/TPU/PSF film sensor is usable for monitoring pulse, swallow, tiptoe, and various joint bends in real time and distributing effective electrical signals. This paper implies that the MXene/CNTs/TPU/PSF film sensor has broad prospects in pragmatic applications.


Effect of catabolite repression on the mer operon.
The plasmid-determined mer operon, which provides resistance to inorganic mercury compounds, was subject to a 2.5-fold decrease in expression when glucose was administered at the same time as the inducer HgCl2. This glucose-mediated transient repression of the operon was overcome by the addition of cyclic AMP. Permanent catabolite repression of the operon was observed in the 1.6- to 1.9-fold decrease in expression in mutants lacking either adenyl cyclase (cya) or the catabolite activator protein (crp). The effect of the cya mutation on mer expression could be overcome by the addition of cyclic AMP at the time of induction, In addition to these effects on the whole cells of a wild-type strains, we examined the effect of catabolite repression on the expression of the mercuric ion [Hg(II)] reductase enzyme, assayable in cell extracts, and on the Hg(II) uptake system, assayable in a mutant strain which lacked reductase activity. There was a two- to threefold effect of repression on the Hg(II) reductase enzyme assayable in vitro after induction under catabolite repressing conditions (either with glucose or in the crp and cya mutants). We did not find a similar repressing effect on the induction of the Hg(II) uptake system, which is also determined by the mer operon.


Efficacy and safety of a retrieval hook for removal of retrievable expandable tracheobronchial stents.
To evaluate the efficacy and safety of use of a retrieval hook for removal of retrievable expandable tracheobronchial stents. With fluoroscopic guidance, a retrieval hook was used to remove 45 retrievable expandable tracheobronchial stents in 31 patients. Indications for stent removal included tissue hyperplasia (n = 16), stent migration (n = 10), stent misplacement (n = 2), tumor overgrowth (n = 2), persistent gastrobronchial fistula (n = 1), and incompletely expanded stent (n = 1). Thirteen stents were electively removed after temporary use. The success rate, causes of failure, and complications related to stent removal with a retrieval hook were analyzed. Forty-one of 45 stents (91.1%) were successfully removed with a retrieval hook. The following difficulties were encountered: disruption of the polyurethane membrane (n = 3) and an untied drawstring (n = 1). The removal procedure failed in four cases (8.9%) because of excessive tissue hyperplasia (n = 4) in the proximal portion of the stent. The hook wire fractured in two of the four failed cases. The overall complication rate was 4.4% (minor bleeding, n = 2). For complications with or temporary use of retrievable expandable tracheobronchial stents, removal with a retrievable hook shows promising initial results.


Desensitisation of beta-adrenergic responsiveness in vivo. Decreased coupling between receptors and adenylate cyclase in isolated brown-fat cells.
Chronic catecholamine stimulation in vivo of brown adipose tissue during acclimation of hamsters to cold does not result in any alteration of beta-adrenergic receptor number or affinity when determined in isolated adipocytes by (-)-[3H]dihydroalprenolol binding. Norepinephrine displacement of (-)-[3H]dihydroalprenolol showed the same Ki for both groups. However, the slope of the displacement curve was shallower for cells from cold-acclimated animals than for controls. Cyclic AMP accumulation was stimulated by norepinephrine in cells from both groups of animals, although the dose-response curve for cells from cold-acclimated animals was shifted to the right and the maximum value obtained was less than half that found in cells from control animals. The slope of the curve was again lower. Other catecholamines stimulated cAMP accumulation with an order of potency in agreement with a response mediated through beta 1-adrenergic receptors. The dose-response curve for norepinephrine-stimulated oxygen consumption was also shifted to the right for cells from cold-acclimated animals, although the maximal respiration was only slightly reduced. The slope factor was again decreased. The results are interpreted in terms of a reduced coupling between the beta-receptor and the metabolic response in isolated brown adipocytes from cold-acclimated animals as a result of chronic catecholamine stimulation in vivo.


Neurovascular and neuroimmune aspects in the pathophysiology of rosacea.
Rosacea is a common skin disease with a high impact on quality of life. Characterized by erythema, edema, burning pain, immune infiltration, and facial skin fibrosis, rosacea has all the characteristics of neurogenic inflammation, a condition induced by sensory nerves via antidromically released neuromediators. To investigate the hypothesis of a central role of neural interactions in the pathophysiology, we analyzed molecular and morphological characteristics in the different subtypes of rosacea by immunohistochemistry, double immunofluorescence, morphometry, real-time PCR, and gene array analysis, and compared the findings with those for lupus erythematosus or healthy skin. Our results showed significantly dilated blood and lymphatic vessels. Signs of angiogenesis were only evident in phymatous rosacea. The number of mast cells and fibroblasts was increased in rosacea, already in subtypes in which fibrosis is not clinically apparent, indicating early activation. Sensory nerves were closely associated with blood vessels and mast cells, and were increased in erythematous rosacea. Gene array studies and qRT-PCR confirmed upregulation of genes involved in vasoregulation and neurogenic inflammation. Thus, dysregulation of mediators and receptors implicated in neurovascular and neuroimmune communication may be crucial at early stages of rosacea. Drugs that function on neurovascular and/or neuroimmune communication may be beneficial for the treatment of rosacea.


The whale shark genome reveals patterns of vertebrate gene family evolution.
Chondrichthyes (cartilaginous fishes) are fundamental for understanding vertebrate evolution, yet their genomes are understudied. We report long-read sequencing of the whale shark genome to generate the best gapless chondrichthyan genome assembly yet with higher contig contiguity than all other cartilaginous fish genomes, and studied vertebrate genomic evolution of ancestral gene families, immunity, and gigantism. We found a major increase in gene families at the origin of gnathostomes (jawed vertebrates) independent of their genome duplication. We studied vertebrate pathogen recognition receptors (PRRs), which are key in initiating innate immune defense, and found diverse patterns of gene family evolution, demonstrating that adaptive immunity in gnathostomes did not fully displace germline-encoded PRR innovation. We also discovered a new toll-like receptor (TLR29) and three NOD1 copies in the whale shark. We found chondrichthyan and giant vertebrate genomes had decreased substitution rates compared to other vertebrates, but gene family expansion rates varied among vertebrate giants, suggesting substitution and expansion rates of gene families are decoupled in vertebrate genomes. Finally, we found gene families that shifted in expansion rate in vertebrate giants were enriched for human cancer-related genes, consistent with gigantism requiring adaptations to suppress cancer.


Adding to the evidence of gene-disease association of RAP1B and syndromic thrombocytopenia.
Syndromic constitutive thrombocytopenia encompasses a heterogeneous group of disorders characterised by quantitative and qualitative defects of platelets while featuring other malformations. Recently, heterozygous, de novo variants in RAP1B were reported in three cases of syndromic thrombocytopenia. Here, we report two additional, unrelated individuals identified retrospectively in our data repository with heterozygous variants in RAP1B: NM_001010942.2(RAP1B):c.35G>A, p.(Gly12Glu) (de novo) and NM_001010942.2(RAP1B):c.178G>A, p.(Gly60Arg). Both individuals had thrombocytopenia, as well as congenital malformations, and neurological, behavioural, and dysmorphic features, in line with previous reports. Our data supports the causal role of monoallelic RAP1B variants that disrupt RAP1B GTPase activity in syndromic congenital thrombocytopenia.


[Study of a factor released during myocardial ischemia reperfusion and its effects on myocardial, coronary and peripheral vessels].
The effect of reoxygenated coronary effluent of an isolated guinea-pig heart on a sequentially perfused second heart, right auricle trabecula and arterial vessel rings was studied after 20 min ischaemia of the first heart. It has been shown that a factor released after myocardial ischemia/reperfusion stimulates arrhythmia, decreases myocardial contractility of the second heart and depresses tonical tension of the right auricle trabecula and arterial vessel rings. Storage of the coronary effluent up to 24 h did not modify its effects. These results suggest stable factor released from an isolated heart after ischaemia at reperfusion to exert humoral effect not only on a myocardial contractility and coronary circulation but on the peripheral vessels tonus.


Challenges for the European governance of synthetic biology for human health.
Synthetic biology is a series of scientific and technological practices involved in the application of engineering principles to the design and production of predictable and robust biological systems. While policy discussions abound in this area, emerging technologies like synthetic biology present considerable challenges in the articulation of concrete policy options given that their introduction into society may still be in the distant future. This paper reports on a series of governance workshops that focused on synthetic biology's ethical, legal, and social implications (ELSI) as they pertain to human health, and discusses particular limitations of the ELSI approach that we encountered in our work. In an attempt to avoid policymaking for potential implications of uncertain future applications we instead conclude by proposing tangible forms of anticipatory governance that may be more adequate in addressing the more immediate concerns raised by synthetic biology.


PHAB toxins: a unique family of predatory sea anemone toxins evolving via intra-gene concerted evolution defines a new peptide fold.
Sea anemone venoms have long been recognized as a rich source of peptides with interesting pharmacological and structural properties, but they still contain many uncharacterized bioactive compounds. Here we report the discovery, three-dimensional structure, activity, tissue localization, and putative function of a novel sea anemone peptide toxin that constitutes a new, sixth type of voltage-gated potassium channel (KV) toxin from sea anemones. Comprised of just 17 residues, κ-actitoxin-Ate1a (Ate1a) is the shortest sea anemone toxin reported to date, and it adopts a novel three-dimensional structure that we have named the Proline-Hinged Asymmetric β-hairpin (PHAB) fold. Mass spectrometry imaging and bioassays suggest that Ate1a serves a primarily predatory function by immobilising prey, and we show this is achieved through inhibition of Shaker-type KV channels. Ate1a is encoded as a multi-domain precursor protein that yields multiple identical mature peptides, which likely evolved by multiple domain duplication events in an actinioidean ancestor. Despite this ancient evolutionary history, the PHAB-encoding gene family exhibits remarkable sequence conservation in the mature peptide domains. We demonstrate that this conservation is likely due to intra-gene concerted evolution, which has to our knowledge not previously been reported for toxin genes. We propose that the concerted evolution of toxin domains provides a hitherto unrecognised way to circumvent the effects of the costly evolutionary arms race considered to drive toxin gene evolution by ensuring efficient secretion of ecologically important predatory toxins.


Disparities in occupational injury hospitalization rates in five states (2003-2009).
Achievement of health equity and elimination of disparities are overarching goals of Healthy People 2020, yet there is a paucity of population-based data regarding race/ethnicity-based disparities in occupational injuries. Hospital discharge data for five states (Arizona, California, Florida, New Jersey, and New York) were obtained from the Healthcare Cost & Utilization Project (HCUP) for 2003-2009. Age-adjusted rates and trends for work-related injury hospitalizations were calculated using negative binomial regression (reference category: non-Latino white). Latinos were significantly more likely to have a work-related traumatic injury hospitalization. The disparity for Latinos was greatest for machinery-related hospitalizations. Latinos were also more likely to have a fall-related hospitalization. African-Americans were more likely to have an occupational assault-related hospitalization, but less likely to have a fall-related hospitalization. We found evidence of substantial multistate disparities in occupational injury-related hospitalizations. Enhanced surveillance and further research are needed to identify and address underlying causes.


IL-17+ regulatory T cells in the microenvironments of chronic inflammation and cancer.
Foxp3(+)CD4(+) regulatory T (Treg) cells inhibit immune responses and temper inflammation. IL-17(+)CD4(+) T (Th17) cells mediate inflammation of autoimmune diseases. A small population of IL-17(+)Foxp3(+)CD4(+) T cells has been observed in peripheral blood in healthy human beings. However, the biology of IL-17(+)Foxp3(+)CD4(+) T cells remains poorly understood in humans. We investigated their phenotype, cytokine profile, generation, and pathological relevance in patients with ulcerative colitis. We observed that high levels of IL-17(+)Foxp3(+)CD4(+) T cells were selectively accumulated in the colitic microenvironment and associated colon carcinoma. The phenotype and cytokine profile of IL-17(+)Foxp3(+)CD4(+) T cells was overlapping with Th17 and Treg cells. Myeloid APCs, IL-2, and TGF-β are essential for their induction from memory CCR6(+) T cells or Treg cells. IL-17(+)Foxp3(+)CD4(+) T cells functionally suppressed T cell activation and stimulated inflammatory cytokine production in the colitic tissues. Our data indicate that IL-17(+)Foxp3(+) cells may be "inflammatory" Treg cells in the pathological microenvironments. These cells may contribute to the pathogenesis of ulcerative colitis through inducing inflammatory cytokines and inhibiting local T cell immunity, and in turn may mechanistically link human chronic inflammation to tumor development. Our data therefore challenge commonly held beliefs of the anti-inflammatory role of Treg cells and suggest a more complex Treg cell biology, at least in the context of human chronic inflammation and associated carcinoma.


Do Patients Detect Changes in Breathing After Orthognathic Surgery?
Orthognathic surgery addresses facial aesthetics and function in patients with dentofacial deformities. It is associated with changes in upper airway volume (UAV). If changes in UAV are perceived by asymptomatic patients is unclear. The purpose was to measure associations between changes in UAV and patient-reported benefits using patient-reported outcome measures. A sample presenting dentofacial deformities without reported breathing problems undergoing orthognathic surgery was retrospectively studied. Patients aged 18-30 years with 12-month follow-up were included. Patients with systemic disease, drug abuse, mental health disorder, or temporomandibular joint dysfunction were excluded. The predictor variable was changes in UAV measured in 3-dimensional computed tomography. Subjects were grouped into increased or decreased UAV. The primary outcome variable was changes in health-related quality of life measured with Oral Health Impact Profile 49 (OHIP-49). Weight, height, age, sex, and sub-scaled OHIP-49 were registered. Cephalometric measurements of hard tissue movements were recorded. Mean, standard deviation, and a level of statistical significance at P < .05 were used. Differences in OHIP-49 were compared using unpaired t-test. The correlation between covariates and outcomes was analyzed using the Spearman's rank test. Analysis of covariance between the predictor and outcome, adjusted for covariates (body mass index), was performed. Fifty-four subjects with a mean age of 20.89 years and 52% males were enrolled. The mean change in UAV was 0.12 cm3 (standard deviation [SD] 9.21, P = .93) with a mean absolute deviation of 7.28 cm3 (SD 5.54). The mean change in OHIP-49 score was 20.93 (SD 28.90). Twenty-seven (50%) subjects had increased UAV (7.4 cm3, SD 6.13) and the other had decreased (-7.17 cm3, SD 5.01) (P = .01). At follow-up, equal levels of mean OHIP-49 score were found, but because of a baseline difference (15.74, P = .048), the subjects with and without increased UAV improved in OHIP-49 score 13.04 (SD 30.53) and 28.81 (SD 25.33), respectively (P = .04). Because equal levels of OHIP-49 score at follow-up, changes in UAV could not be associated with patient-reported health-related quality of life. Patient-reported outcome measure evaluations of orthognathic surgical treatment for airway obstruction should be performed in patients with a perceived impairment.


Liquid ethylene glycol: prediction of physical properties, conformer population and interfacial enrichment with a refined non-polarizable force field.
Periodic density functional theory based molecular dynamics simulations confirm the fraction of molecules in neat liquid ethylene glycol with their central OCCO dihedral in the trans conformation to be 21% at ambient conditions, while the rest are gauche conformers. Using this result as a benchmark, two non-polarizable force fields are developed herein to reproduce the conformer populations in the liquid, an important aspect inadequately addressed in several generic force fields. The mean dipole moment of a molecule in the liquid is estimated to be about 40% enhanced over its value in the gas phase, a feature discerned via AIMD simulations and fairly reproduced by our force fields. They are also shown to quantitatively predict all the physical properties of the liquid. Molecules present at the liquid-vapor interface of ethylene glycol are oriented with their methylene groups pointing towards the vapor phase, a requirement that enriches the interface with gauche conformers, in line with polarized sum frequency generation spectroscopy results.


Chromosomal instability in in vitro cultured mouse hematopoietic cells associated with oxidative stress.
Hematopoietic stem cells (HSCs) that give rise to all blood cell types are important vehicles for cell-based and gene therapies. After isolation from the bone marrow, HSCs are often cultured in laboratory settings for purposes of ex vivo expansion, gene transduction, and bone marrow transplantation for the treatment of various disorders of the blood and immune systems. Here we demonstrate that during in vitro culturing outside of hypoxic bone marrow niches, HSCs may genetically alter even after short durations of time. Lineage(-) Scal-1(+) c-Kit(+) (LSK) cells that are enriched with HSCs revealed significant levels of genomic instability following culture, as evidenced by the emergence of aneuploid cells. To further determine the effects of in vitro culturing conditions, whole bone marrow cells were cultured in a hypoxic environment of 3% oxygen, mimicking conditions within the body's bone marrow, following which, cells proved to undergo less genetic alterations. Proper dosages of the antioxidant N-Acetyl-Cysteine (NAC) similarly decreased occurrences of chromosomal change. Furthermore, analysis of aged hematopoietic cells revealed enhanced in vitro normoxic culture-induced chromosomal instability compared to that of young hematopoietic cells due to noted increased oxidative stress in aged cells. These results reveal that in vitro cell culturing does indeed cause genomic instability in hematopoietic cells. Reduced oxygen to physiological levels and additions of antioxidants can be employed as possible strategies to lower oxidative stress and decrease chances of chromosomal transformation. Because hematopoietic cells are commonly processed in laboratory settings before transplantation for patient treatment, our findings also raise a concern on the therapeutic use of cultured hematopoietic cells.


A model order selection criterion with applications to cardio-respiratory-renal systems.
We introduce a model order selection criterion called signal prediction error (SPE) for the identification of a linear regression model, which can be an adequate representation of a resting physiologic system. SPE is an estimate of the prediction error variance due only to model estimation error and not unobserved noise, which distinguishes it from the widely used final prediction error (FPE). We then present a theoretical analysis of SPE, which predicts that its ability to select correctly the model order is more dependent on the signal-to-noise ratio (SNR) and less dependent on the number of data samples available for analysis. We next propose a heuristic procedure based on SPE (called SPE(D)) to improve its robustness to SNR levels. We then demonstrate, through simulated physiologic data at high SNR levels, that SPE will be equivalent to consistent model order selection criteria for long data records but will become superior to FPE and other model order selection criteria as the size of the data record decreases. The simulated data results also show that SPE(D) is indeed a significant improvement over SPE in terms of robustness to SNR. Finally, we demonstrate the applicability of SPE and SPE(D) to actual cardio-respiratory-renal data.


The survival of Escherichia coli in an aerosol at air temperatures of 15 and 30 degrees C and a range of humidities.
The survival of Escherichia coli in an aerosol was studied at several temperatures and over a range of relative humidities using a Henderson apparatus. Death occurred in two phases, the first lasting approximately 1 min; in the second the number of viable microorganisms declined exponentially. E. coli was robust and remained viable for many hours. Death was most rapid at low humidities (less than 50% r.h.) at 15 and 30 degrees C, with half-lives of 14 and 3 min respectively. In humid conditions the half-lives were much longer, approximately 83 and 14 min respectively. Based on this work, preliminary recommendations for the climate of livestock buildings can now be given to control the airborne spread of E. coli.


Attenuation of polyglutamine-induced toxicity by enhancement of mitochondrial OXPHOS in yeast and fly models of aging.
Defects in mitochondrial biogenesis and function are common in many neurodegenerative disorders, including Huntington's disease (HD). We have previously shown that in yeast models of HD, enhancement of mitochondrial biogenesis through overexpression of Hap4, the catalytic subunit of the transcriptional complex that regulates mitochondrial gene expression, alleviates the growth arrest induced by expanded polyglutamine (polyQ) tract peptides in rapidly dividing cells. However, the mechanism through which HAP4 overexpression exerts this protection remains unclear. Furthermore, it remains unexplored whether HAP4 overexpression and increased respiratory function during growth can also protect against polyQ-induced toxicity during yeast chronological lifespan. Here, we show that in yeast, mitochondrial respiration and oxidative phosphorylation (OXPHOS) are essential for protection against the polyQ-induced growth defect by HAP4 overexpression. In addition, we show that not only increased HAP4 levels, but also alternative interventions, including calorie restriction, that result in enhanced mitochondrial biogenesis confer protection against polyQ toxicity during stationary phase. The data obtained in yeast models guided experiments in a fly model of HD, where we show that enhancement of mitochondrial biogenesis can also protect against neurodegeneration and behavioral deficits. Our results suggest that therapeutic interventions aiming at the enhancement of mitochondrial respiration and OXPHOS could reduce polyQ toxicity and delay disease onset.


Optimized Informed Consent for Psychotherapy: Protocol for a Randomized Controlled Trial.
Informed consent is a legal and ethical prerequisite for psychotherapy. However, in clinical practice, consistent strategies to obtain informed consent are scarce. Inconsistencies exist regarding the overall validity of informed consent for psychotherapy as well as the disclosure of potential mechanisms and negative effects, the latter posing a moral dilemma between patient autonomy and nonmaleficence. This protocol describes a randomized controlled web-based trial aiming to investigate the efficacy of a one-session optimized informed consent consultation. The optimized informed consent consultation was developed to provide information on the setting, efficacy, mechanisms, and negative effects via expectation management and shared decision-making techniques. A total of 122 participants with an indication for psychotherapy will be recruited. Participants will take part in a baseline assessment, including a structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders-fifth edition (DSM-5) disorders. Eligible participants will be randomly assigned either to a control group receiving an information brochure about psychotherapy as treatment as usual (n=61) or to an intervention group receiving treatment as usual and the optimized informed consent consultation (n=61). Potential treatment effects will be measured after the treatment via interview and patient self-report and at 2 weeks and 3 months follow-up via web-based questionnaires. Treatment expectation is the primary outcome. Secondary outcomes include the capacity to consent, decisional conflict, autonomous treatment motivation, adherence intention, and side-effect expectations. This trial received a positive ethics vote by the local ethics committee of the Center for Psychosocial Medicine, University-Medical Center Hamburg-Eppendorf, Hamburg, Germany on April 1, 2021, and was prospectively registered on June 17, 2021. The first participant was enrolled in the study on August 5, 2021. We expect to complete data collection in December 2022. After data analysis within the first quarter of 2023, the results will be submitted for publication in peer-reviewed journals in summer 2023. If effective, the optimized informed consent consultation might not only constitute an innovative clinical tool to meet the ethical and legal obligations of informed consent but also strengthen the contributing factors of psychotherapy outcome, while minimizing nocebo effects and fostering shared decision-making. PsychArchives; http://dx.doi.org/10.23668/psycharchives.4929. DERR1-10.2196/39843.


Radioactive colloidal solutions and suspensions for medical use.
Radioactive colloidal solutions and suspensions are being widely used in the diagnosis and treatment of various diseases. The author considers the behaviour or radioactive disperse preparations in the body and devotes particular attention to the reasons for isotope transition from the colloidal to the ionic state. Questions concerned with producing and investigating radioactive colloidal solutions are discussed. In the light of the physical and chemical properties of the radioisotopes and of the disperse systems themselves, the author considers methods of producing the more important radioactive disperse preparations: colloidal solutions of noble metals; colloidal solutions containing phosphorus-32, yttrium-90 and isotopes of the rare-earth elements; colloidal solutions with with indium-113m, gallium-68, technetium-99m and rhenium-186; suspensions (macroaggregates and microspheres) for the diagnosis of lung diseases; and radioactive colloidal solutions based on quaternary ammonium base compounds.


Pulsed electromagnetic field improves cardiac function in response to myocardial infarction.
Extracorporeal pulsed electromagnetic field (PEMF) has been shown the ability to improve regeneration in various ischemic episodes. Here, we examined whether PEMF therapy facilitate cardiac recovery in rat myocardial infarction (MI), and the cellular/molecular mechanisms underlying PEMF-related therapy was further investigated. The MI rats were exposed to active PEMF for 4 cycles per day (8 minutes/cycle, 30 ± 3 Hz, 5 mT) after MI induction. The data demonstrated that PEMF treatment significantly inhibited cardiac apoptosis and improved cardiac systolic function. Moreover, PEMF treatment increased capillary density, the levels of vascular endothelial growth factor (VEGF) and hypoxic inducible factor-1α in infarct border zone. Furthermore, the number and function of circulating endothelial progenitor cells were advanced in PEMF treating rats. In vitro, PEMF induced the degree of human umbilical venous endothelial cells tubulization and increased soluble pro-angiogenic factor secretion (VEGF and nitric oxide). In conclusion, PEMF therapy preserves cardiac systolic function, inhibits apoptosis and trigger postnatal neovascularization in ischemic myocardium.


[Significance of Helicobacter pylori infection for stomach lymphoma and stomach carcinoma].
The discovery of Helicobacter pylori in 1983 revolutionised pathogenetic hypotheses of almost all gastric diseases and markedly enhanced research especially in the field of malignant tumours of this organ. Based on epidemiological studies indicating an association of H. pylori infection and malignant gastric tumours the WHO classified this bacterium as "class I carcinogen" already in 1994. Although the high prevalence of this germ worldwide is sharply contrasting the low incidence of gastric carcinomas and lymphomas its role as independent risk factor in the carcinogenesis of these tumours today is reasonably evidence-based. Thus, epidemiologists are calculating a reduction of 80% of all MALT-type lymphomas and of about 60% of gastric "non cardia" carcinomas in the scenario of an "H. pylori-free" world. However, complete remission of 80% of early lymphomas of MALT-type confined to mucosa and submucosa, only, after antibiotic eradication of the bacterium is well established in literature and follow-up data are confirming sustained response after years. The strength of impact of an H. pylori infection on gastric carcinogenesis will be figured out by prospective studies on a non infected population in the future.


Competition, seed dispersal and hunting: what drives germination and seedling survival in an Afrotropical forest?
Disentangling the contributions of different processes that influence plant recruitment, such as competition and seed dispersal, is important given the increased human-mediated changes in tropical forest ecosystems. Previous studies have shown that seedling communities in an Afrotropical rainforest in southeastern Nigeria are strongly affected by the loss of important seed-dispersing primates, including Cross River gorillas (Gorilla gorilla diehli), chimpanzee (Pan troglodytes elioti) and drill (Mandrillus leucophaeus). Here we study how germination and survival of tree seedlings are affected by competition and reduced seed dispersal in three contiguous forest reserves, in southeastern Nigeria, with similar mature tree species composition and structure. We use an experimental design aimed at manipulating the effect of competition among seedlings in three protected and three hunted sites within the reserves. We use a total of sixty 5 × 5 m plots of three types: plots cleared of all seedlings, plots selectively cleared of all primate-dispersed seedlings and control plots. All seedlings were identified, measured, assigned to dispersal mode and tagged, and after 1 year we evaluated survival, mortality and new recruits. We found that in hunted sites germination of abiotically dispersed species was over four times higher in cleared plots compared to control plots, whereas germination of primate-dispersed species was the same, which indicated that dispersal limitation was the dominant force in seedling recruitment in hunted sites. This was supported by the fact that the germination of all dispersal modes in the selectively cleared plots in protected sites was similar to the control plots in the same sites, but germination of abiotically dispersed species was significantly lower than in cleared plots in hunted sites. Competition among seedlings was mostly evident from the fact that 75 % more seedlings of primate-dispersed species germinated in cleared compared to control plots in protected sites. We conclude that inter-seedling competition may be irrelevant to seedling recruitment in hunted sites, where dispersal limitation appears to be a much stronger force shaping the seedling plant community, and thus hunting indirectly reverses the importance of competition and dispersal limitation in structuring seedling communities.


An integrated approach to fragment-based lead generation: philosophy, strategy and case studies from AstraZeneca's drug discovery programmes.
Fragment-based lead generation (FBLG) has recently emerged as an alternative to traditional high throughput screening (HTS) to identify initial chemistry starting points for drug discovery programs. In comparison to HTS screening libraries, the screening sets for FBLG tend to contain orders of magnitude fewer compounds, and the compounds themselves are less structurally complex and have lower molecular weight. This report summarises the advent of FBLG within the industry and then describes the FBLG experience at AstraZeneca. We discuss (1) optimising the design of screening libraries, (2) hit detection methodologies, (3) evaluation of hit quality and use of ligand efficiency calculations, and (4) approaches to evolve fragment-based, low complexity hits towards drug-like leads. Furthermore, we exemplify our use of FBLG with case studies in the following drug discovery areas: antibacterial enzyme targets, GPCRs (melanocortin 4 receptor modulators), prostaglandin D2 synthase inhibitors, phosphatase inhibitors (protein tyrosine phosphotase 1B), and protease inhibitors (b-secretase).


Effect of professional mechanical plaque removal on secondary prevention of periodontitis and the complications of gingival and periodontal preventive measures: consensus report of group 4 of the 11th European Workshop on Periodontology on effective prevention of periodontal and peri-implant diseases.
The scope of this working group was to review: (1) the effect of professional mechanical plaque removal (PMPR) on secondary prevention of periodontitis; (2) the occurrence of gingival recessions and non-carious cervical lesions (NCCL) secondary to traumatic tooth brushing; (3) the management of hypersensitivity, through professionally and self administered agents and (4) the management of oral malodour, through mechanical and/or chemical agents. Patients undergoing supportive periodontal therapy including PMPR showed mean tooth loss rates of 0.15 ± 0.14 teeth/year for 5-year follow-up and 0.09 ± 0.08 teeth/year (corresponding to a mean number of teeth lost ranging between 1.1 and 1.3) for 12-14 year follow-up. There is no direct evidence to confirm tooth brushing as the sole factor causing gingival recession or NCCLs. Similarly, there is no conclusive evidence from intervention studies regarding the impact of manual versus powered toothbrushes on development of gingival recession or NCCLs, or on the treatment of gingival recessions. Local and patient-related factors can be highly relevant in the development and progression of these lesions. Two modes of action are used in the treatment of dentine hypersensitivity: dentine tubule occlusion and/or modification or blocking of pulpal nerve response. Dentifrices containing arginine, calcium sodium phosphosilicate, stannous fluoride and strontium have shown an effect on pain reduction. Similarly, professionally applied prophylaxis pastes containing arginine and calcium sodium phosphosilicate have shown efficacy. There is currently evidence from short-term studies that tongue cleaning has an effect in reducing intra-oral halitosis caused by tongue coating. Similarly, mouthrinses and dentifrices with active ingredients based on Chlorhexidine, Cetylpyridinium chloride and Zinc combinations have a significant beneficial effect.


A self-regulation perspective on how and when regulatory focus differentially relates to citizenship behaviors.
Although previous research suggests that regulatory focus matters for organizational citizenship behaviors, it is unclear how promotion and prevention focus relate to such behaviors. Integrating regulatory focus theory with theories of self-regulation, we propose a conceptual model that links trait promotion and prevention foci with specific citizenship behaviors through an emotion-related self-regulation mechanism. Using a sample of 227 nurses working in a hospital context, we observed that trait promotion focus and trait prevention focus predict helping and voice via differential effects on emotional exhaustion. Specifically, trait promotion focus had unconditional indirect effects on helping (positive) and voice (negative) through lower levels of emotional exhaustion. In contrast, trait prevention focus was positively related to voice but negatively related to helping through higher levels of emotional exhaustion. Moreover, these indirect effects of trait prevention focus were moderated by employees' reappraisal of their emotional experiences at work, such that trait prevention focus had weaker relations with helping and voice when reappraisal was higher (vs. lower). We discuss theoretical and practical implications of these findings and highlight avenues for future research. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Use of Community Based Participatory Research to Design Interventions for Healthy Lifestyle in an Alternative Learning Environment.
Childhood obesity develops as the result of the interplay between individual and environmental factors. Community based participatory research (CBPR) is an effective tool for improving health of communities. There is limited research on CBPR for facilitating healthy lifestyle in community schools with an alternative learning environment. The objective of the study was to explore student and staff perspectives via focus groups on barriers and facilitators for healthy eating and physical activity in a community school with alternative learning environment and to prioritize, design, and implement suggested interventions to improve healthy lifestyle. We conducted qualitative research through 8 focus groups of middle and high school students (n = 40) and 2 focus groups of school staff (n = 8). The school community and research team subsequently identified and implemented interventions for facilitating healthy lifestyle in students within the school environment. Barriers identified for healthy lifestyle included lack of motivation, lack of healthy food options at school, inadequate knowledge about healthy lifestyle and insufficient opportunities for physical activity. Facilitators for healthy lifestyle were support and motivation from mentors and knowledge about healthy nutrition. Key strategies implemented were addition of healthier food options, educational materials for healthy eating, creation of a walk path, standing desks in classrooms and additional equipment in the school gymnasium. Formative feedback from students and staff was helpful in the implementation of strategies for facilitating healthy lifestyle among students within a community school with an alternative learning environment.


Malaria parasites require TLR9 signaling for immune evasion by activating regulatory T cells.
Malaria is still a life-threatening infectious disease that continues to produce 2 million deaths annually. Malaria parasites have acquired immune escape mechanisms and prevent the development of sterile immunity. Regulatory T cells (Tregs) have been reported to contribute to immune evasion during malaria in mice and humans, suggesting that activating Tregs is one of the mechanisms by which malaria parasites subvert host immune systems. However, little is known about how these parasites activate Tregs. We herein show that TLR9 signaling to dendritic cells (DCs) is crucial for activation of Tregs. Infection of mice with the rodent malaria parasite Plasmodium yoelii activates Tregs, leading to enhancement of their suppressive function. In vitro activation of Tregs requires the interaction of DCs with parasites in a TLR9-dependent manner. Furthermore, TLR9(-/-) mice are partially resistant to lethal infection, and this is associated with impaired activation of Tregs and subsequent development of effector T cells. Thus, malaria parasites require TLR9 to activate Tregs for immune escape.


The long-term results of chymopapain. Ten-year follow-up of 268 patients after chemonucleolysis.
The effect of chymopapain injection was investigated in myelographically confirmed intervertebral disc herniation in 268 patients after ten years. Mean age is 39.4 years, 178 males and 90 females. Sixty-two patients had compensation or litigation and 12 had prior lumbar spine surgery. Discography was performed in 223 patients, resulting in 134 one-level injections, 124 two-level injections, and ten three-level injections. Forty percent of the patients experienced postoperative muscle spasm for several days. No complications were seen in 241 patients (92%) who were available for follow-up examination at ten years; 86% had less leg pain, 82% were employed at a capacity equal to or greater than before injection, 9% were at a less strenuous job, 1% were disabled, and 8% had retired. In 22 patients treated surgically within one year of chemonucleolysis, disc-related pathology was present in 14 cases and spondylosis or spinal stenosis was present in seven cases. One had a negative exploration and continued to be disabled. Eight patients came to surgical intervention after one year because of persisting symptoms: four patients had disc protrusion, three had laminectomy and spinal fusion, and one had a decompressive laminectomy secondary to spondylotic change. Chemonucleolysis did not prejudice the outcome of subsequent surgical treatment with good results following this intervention. One tumor, a neurofibroma, was found in this study. Chemonucleolysis with chymopapain was a safe and effective treatment of radicular complaints caused by well-documented intervertebral disc herniation.


Creating a literature database of low-calorie sweeteners and health studies: evidence mapping.
Evidence mapping is an emerging tool used to systematically identify, organize and summarize the quantity and focus of scientific evidence on a broad topic, but there are currently no methodological standards. Using the topic of low-calorie sweeteners (LCS) and selected health outcomes, we describe the process of creating an evidence-map database and demonstrate several example descriptive analyses using this database. The process of creating an evidence-map database is described in detail. The steps include: developing a comprehensive literature search strategy, establishing study eligibility criteria and a systematic study selection process, extracting data, developing outcome groups with input from expert stakeholders and tabulating data using descriptive analyses. The database was uploaded onto SRDR™ (Systematic Review Data Repository), an open public data repository. Our final LCS evidence-map database included 225 studies, of which 208 were interventional studies and 17 were cohort studies. An example bubble plot was produced to display the evidence-map data and visualize research gaps according to four parameters: comparison types, population baseline health status, outcome groups, and study sample size. This plot indicated a lack of studies assessing appetite and dietary intake related outcomes using LCS with a sugar intake comparison in people with diabetes. Evidence mapping is an important tool for the contextualization of in-depth systematic reviews within broader literature and identifies gaps in the evidence base, which can be used to inform future research. An open evidence-map database has the potential to promote knowledge translation from nutrition science to policy.


Prevalence and risk factors of human polyomavirus infections in non-malignant tonsils and gargles: the SPLIT study.
The prevalence of 13 polyomaviruses (PyVs) in the tonsil brushings and gargles of immunocompetent children and adults was assessed. Patients undergoing tonsillectomy for benign indications were recruited in 19 centres in France. After resection, the entire outer surface of the right and left halves of the tonsils was brushed extensively. Gargles were also collected prior to surgery in selected adults. A species-specific multiplex assay was used to detect the DNA of 13 PyVs. In tonsil brushings (n=689), human PyV 6 (HPyV6) and Merkel cell PyV (MCPyV) were the most prevalent (≈15 %), followed by trichodysplasia spinulosa-associated PyV (TSPyV), BKPyV, Washington University PyV (WUPyV) and human PyV 9 (HPyV9) (1 to 5 %), and human PyV 7 (HPyV7), John Cunningham PyV (JCPyV) and Simian virus 40 (SV40) (<1 %), while no Karolinska Institute PyV (KIPyV), Malawi PyV (MWPyV), human PyV 12 (HPyV12) or Lyon IARC PyV (LIPyV) were detected. The prevalence of TSPyV and BKPyV was significantly higher in children versus adults, whereas for HPyV6 the opposite was found. HPyV6 and WUPyV were significantly more prevalent in men versus women. In gargles (n=139), MCPyV was the most prevalent (≈40 %), followed by HPyV6, HPyV9 and LIPyV (2 to 4 %), and then BKPyV (≈1 %), while other PyVs were not detected. MCPyV and LIPyV were significantly more prevalent in gargles compared to tonsil brushings, in contrast to HPyV6. We described differing patterns of individual PyV infections in tonsils and gargles in a large age-stratified population. Comparison of the spectrum of PyVs in paired tonsil samples and gargles adds to the current knowledge on PyV epidemiology, contributing towards a better understanding of PyV acquisition and transmission and its potential role in head and neck diseases.


Protective effects of vitamin E and curcumin on L-thyroxine-induced rat testicular oxidative stress.
Present study examines effects of curcumin and vitamin E on oxidative stress parameters, antioxidant defence enzymes and oxidized (GSSG) and reduced glutathione (GSH) levels in testis of L-thyroxine (T4)-induced hyperthyroid rats. The oxidative stress in T4-treated rat testis was evident from elevation in oxidative stress parameters such as lipid peroxide and protein carbonyl contents, decrease in superoxide dismutase (SOD) and catalase (CAT) activities and increase in glutathione peroxidase (GPx) activity. This is accompanied with decrease in number and mortality of epididymal sperms. When the T4-treated rats were fed with vitamin E and/or curcumin, the lipid peroxide and protein carbonyl contents in crude homogenates of testes decreased to normal level. Treatment of curcumin and/or vitamin E to T4-treated rats resulted in elevation of SOD level in postmitochondrial fraction (PMF) and mitochondrial fraction (MF) and CAT in PMF, with decreased GPx activity in MF. However, curcumin or vitamin E was unable to change GPx activity alone but in together they elevated the GPx in PMF of T4-treated rat testis. Both the antioxidants are incapable of producing significant changes in GSH:GSSG ratio of PMF of T4-treated rats. In MF, GSH:GSSG ratio elevated and decreased respectively by curcumin and vitamin E treatments to T4-treated rats, however, in together these antioxidants caused an elevated GSH:GSSG ratio with a value less than when vitamin E given alone to T4-treated rats. Vitamin E not the curcumin elevates total sperm count and percentage of live sperm impaired by hyperthyroid state. In summary, both vitamin E and curcumin are efficient in protecting testis from oxidative stress generated by T4 mainly in restoring antioxidant enzymes to the level of euthyroid animals up to some extent but vitamin E is more efficient than curcumin.


Association of varicella zoster virus load in the aqueous humor with clinical manifestations of anterior uveitis in herpes zoster ophthalmicus and zoster sine herpete.
To investigative whether clinical manifestations of anterior uveitis are associated with the viral load of varicella zoster virus (VZV) in the aqueous humor in patients with herpes zoster ophthalmicus (HZO) and zoster sine herpete (ZSH). After informed consent was given, an aliquot of aqueous humor was collected from patients with VZV anterior uveitis (n = 8). Genomic DNA of the human herpes viruses was measured in the aqueous humor by two PCR assays: a qualitative multiplex PCR and a quantitative real-time PCR. All patients had unilateral acute anterior uveitis with high intraocular pressure, mutton fat keratic precipitates with some pigmentation, and trabecular meshwork pigmentation. Multiplex PCR demonstrated VZV genomic DNA in all of the samples, but not in other human herpes virus samples (human simplex virus types 1 and 2, Epstein-Barr virus, cytomegalovirus and human herpes virus types 6, 7 and 8). Real-time PCR revealed a high copy number of VZV DNA in the aqueous humor. After the initial onset of anterior uveitis, iris atrophy and distorted pupil with paralytic mydriasis developed. The intensity of iris atrophy and pupil distortion, but not ocular hypertension, correlated with the viral load of VZV in the aqueous humor. VZV viral load in the aqueous humor correlated significantly with damage to the iris (iris atrophy and pupil distortion) in patients with HZO and ZSH.


Malignant peritoneal mesothelioma.
Malignant mesothelioma is a highly aggressive neoplasm. The incidence of malignant mesothelioma is increasing worldwide. Diffuse malignant peritoneal mesothelioma (DMPM) represents one-fourth of all mesotheliomas. Association of asbestos exposure with DMPM has been observed, especially in males. The great majority of patients present with abdominal pain and distension, caused by accumulation of tumors and ascitic fluid. In the past, DMPM was considered a pre-terminal condition; therefore attracted little attention. Patients invariably died from their disease within a year. Recently, several prospective trials have demonstrated a median survival of 40 to 90 mo and 5-year survival of 30% to 60% after combined treatment using cytoreductive surgery and perioperative intraperitoneal chemotherapy. This remarkable improvement in survival has prompted new search into the medical science related to DMPM, a disease previously ignored as uninteresting. This review article focuses on the key advances in the epidemiology, diagnosis, staging, treatments and prognosis of DMPM that have occurred in the past decade.


Sodium Toxicity in the Nutritional Epidemiology and Nutritional Immunology of COVID-19.
Dietary factors in the etiology of COVID-19 are understudied. High dietary sodium intake leading to sodium toxicity is associated with comorbid conditions of COVID-19 such as hypertension, kidney disease, stroke, pneumonia, obesity, diabetes, hepatic disease, cardiac arrhythmias, thrombosis, migraine, tinnitus, Bell's palsy, multiple sclerosis, systemic sclerosis, and polycystic ovary syndrome. This article synthesizes evidence from epidemiology, pathophysiology, immunology, and virology literature linking sodium toxicological mechanisms to COVID-19 and SARS-CoV-2 infection. Sodium toxicity is a modifiable disease determinant that impairs the mucociliary clearance of virion aggregates in nasal sinuses of the mucosal immune system, which may lead to SARS-CoV-2 infection and viral sepsis. In addition, sodium toxicity causes pulmonary edema associated with severe acute respiratory syndrome, as well as inflammatory immune responses and other symptoms of COVID-19 such as fever and nasal sinus congestion. Consequently, sodium toxicity potentially mediates the association of COVID-19 pathophysiology with SARS-CoV-2 infection. Sodium dietary intake also increases in the winter, when sodium losses through sweating are reduced, correlating with influenza-like illness outbreaks. Increased SARS-CoV-2 infections in lower socioeconomic classes and among people in government institutions are linked to the consumption of foods highly processed with sodium. Interventions to reduce COVID-19 morbidity and mortality through reduced-sodium diets should be explored further.


A decision-based velocity ramp for minimizing the effect of misclassifications during real-time pattern recognition control.
Real-time pattern recognition control is frequently affected by misclassifications. This study investigated the use of a decision-based velocity ramp that attenuated movement speed after a change in classifier decision. The goal was to improve prosthesis positioning by minimizing the effect of unintended movements. Non-amputee and amputee subjects controlled a prosthesis in real-time using pattern recognition. While performing a target achievement test in a virtual environment, subjects had a significantly higher completion rate (p < 0.05) and a more direct path (p < 0.05) to the target with the velocity ramp than without it. Using a physical prosthesis, subjects stacked a greater average number of 1 cubes (p < 0.05) in three minutes with the velocity ramp than without it (76% more blocks for non-amputees; 89% more blocks for amputees). Real-time control using the velocity ramp also showed significant performance improvements above using majority vote. Eighty-three percent of subjects preferred to control the prosthesis using the velocity ramp. These results suggest that using a decision-based velocity ramp with pattern recognition may improve user performance. Since the velocity ramp is a post-processing step, it has the potential to be used with a variety of classifiers for many applications.


[The functional evaluation of dysphagia in the neonatal intensive care unit].
The objectives of this study were: 1) to detect clinical criteria on the evaluation of dysphagy in preterm newborns; 2) to analyze the association between the functional and the videoendoscopy findings and 3) to show the relevance of the joint work of the Speech Therapist and the Otolaryngologist criteria on the evaluation of dysphagy in preterm syndromic and pathologic newborns. The sample comprised fifteen infants born in Maternity Campinas Hospital, Campinas-SP, to whom was requested a Speech Therapist evaluation by the Neonatologist. All the infants were evaluated once by the same Speech Therapist and the Otolaryngologist. The functional evaluation of swallowing considered: a) the extra oral tactile sensibility, b) the intra oral tactile sensibility, c) the nauseous reflex and d) the buccinator movement. The evaluation of the videoendoscopy swallowing analyzed a) the sensibility in the arytenoid cartilage, b) the crying, c) the aspiration, d) desaturation and e) the penetration. The exact test of Fisher was applied for small samples and each hypothesis was tested with significance level of 0.05. At the end of the study, a statistically dependence relation between the variants was noticed: 1) aspiration after pharyngeal phase and penetration (high and low) and 2) extra oral sensibility on the cheeks and the sensibility on the arytenoid cartilage. This last result shows the association between a functional finding obtained by the Speech Therapist and a videoendoscopy finding achieved by the Otolaryngologist, that shows clearly the relevance of the team work among these two health professionals.


Only half the problem is being addressed: underinsurance is as big a problem as uninsurance.
This article examines the sociodemographic and health characteristics of the underinsured-people who have some health insurance but are having trouble paying for health care or medications. It uses data from the Boston Area Community Health (BACH) Survey, a large (N=5503) community-based random sample of Boston residents aged 30 to 79 years (1767 black, 1,877 Hispanic, and 1859 white; 2301 men and 3202 women). The authors found that minorities were less likely than whites to have health insurance (for men and women, respectively, 30% and 19% of Hispanics, 16% and 9% of blacks, and 9% and 7% of whites lacked health insurance). Blacks were the most likely to be underinsured (for men and women, respectively, 18% and 20% of blacks vs. 9% and 14% of Hispanics and 8% and 12% of whites were underinsured). Those of lower and middle socioeconomic status were also more likely to be uninsured or underinsured. The health status of the uninsured was similar to that of the adequately insured, whereas those who were underinsured reported more co-morbidities and depression. The underinsured are generally older and sicker, and make greater use of the health care system, and may present a larger public health and health policy challenge than the uninsured.


Assessment of disease activity and progression in Takayasu's arteritis.
Takayasu's arteritis (TA) is a rare, chronic panarteritis of the aorta and its major branches presenting commonly in young ages. Physical examination findings, presence of constitutional features, elevated acute-phase reactants, and new vessel involvement in imaging are major features of an active disease. However, assessment of disease activity and damage in TA is problematic given the chronic, indolent disease course and lack of specific laboratory and imaging findings. Although CT, MRI, and FDG-PET are commonly used imaging modalities, their lack of specificity to discriminate active disease from damage, limit their usefulness in routine practice. Two recently introduced multi-systemic clinical assessment tools, the DEI.Tak and the ITAS (both derived from BVAS), seem to be helpful in assessing disease activity and damage in TA. However, physician's global assessments of disease activity and decisions regarding treatments are still strongly influenced by changes in the acute-phase response and imaging. A comprehensive approach to both systemic and vascular features of TA to define a validated set of outcome measures for use in clinical trials and clinical practice is clearly needed. The OMERACT Vasculitis Working Group has taken on this task and has embarked on a research agenda to advance outcome measure development in TA.


Occupational exposure to diesel and gasoline emissions and lung cancer in Canadian men.
The International Agency for Research on Cancer classifies diesel exhaust as a probable human carcinogen; this decision is based largely from lung cancer evidence. Gasoline exhaust is classified as a possible carcinogen. Epidemiological studies are needed that improve upon some of the limitations of previous research with respect to the characterization of exposure, and the control for the potential confounding influence of smoking and other occupational exposures. Our objective was to investigate associations between occupational exposure to diesel and gasoline engine emissions and lung cancer. We used a case-control study design that involved men 40 years of age and older at the time of interview. Analyses are based on 1681 incident cases of lung cancer and 2,053 population controls. A self-reported questionnaire elicited a lifetime occupational history, including general tasks, and information on other potential risk factors. Occupational exposures to diesel and gasoline emissions, crystalline silica, and asbestos were assigned to each job held by study subjects by industrial hygienists who were blind to case-control status. Exposure metrics for diesel and gasoline emissions that were modeled included: ever exposure, cumulative exposure, and concentration of exposure. We found a dose-response relationship between cumulative occupational exposure to diesel engine emissions and lung cancer. This association was more pronounced for the squamous and large cell subtypes with adjusted odds ratios across the three increasing tertiles of cumulative lifetime exposure relative to those with no exposure of 0.99, 1.25, and 1.32 (p=0.04) for squamous cell carcinoma, and 1.06, 1.19, 1.68 (p=0.02) for large cell carcinoma. While the association with cumulative exposure to gasoline was weakly positive, it was not statistically significant. Our findings suggest that exposure to diesel engine emissions increases the risk of lung cancer particularly for squamous and large cell carcinoma subtypes.


AVP2, a sequence-divergent, K(+)-insensitive H(+)-translocating inorganic pyrophosphatase from Arabidopsis.
Plant vacuolar H(+)-translocating inorganic pyrophosphatases (V-PPases; EC 188.8.131.52) have been considered to constitute a family of functionally and structurally monotonous intrinsic membrane proteins. Typified by AVP1 (V. Sarafian, Y. Kim, R.J. Poole, P.A. Rea [1992] Proc Natl Acad Sci USA 89: 1775-1779) from Arabidopsis, all characterized plant V-PPases share greater than 84% sequence identity and catalyze K(+)-stimulated H(+) translocation. Here we describe the molecular and biochemical characterization of AVP2 (accession no. AF182813), a sequence-divergent (36% identical) K(+)-insensitive, Ca(2+)-hypersensitive V-PPase active in both inorganic pyrophosphate hydrolysis and H(+) translocation. The differences between AVP2 and AVP1 provide the first indication that plant V-PPases from the same organism fall into two distinct categories. Phylogenetic analyses of these and other V-PPase sequences extend this principle by showing that AVP2, rather than being an isoform of AVP1, is but one representative of a novel category of AVP2-like (type II) V-PPases that coexist with AVP1-like (type I) V-PPases not only in plants, but also in apicomplexan protists such as the malarial parasite Plasmodium falciparum.


Recent Developments and Advancements in Graphene-Based Technologies for Oil Spill Cleanup and Oil-Water Separation Processes.
The vast demand for petroleum industry products led to the increased production of oily wastewaters and has led to many possible separation technologies. In addition to production-related oily wastewater, direct oil spills are associated with detrimental effects on the local ecosystems. Accordingly, this review paper aims to tackle the oil spill cleanup issue as well as water separation by providing a wide range of graphene-based technologies. These include graphene-based membranes; graphene sponges; graphene-decorated meshes; graphene hydrogels; graphene aerogels; graphene foam; and graphene-coated cotton. Sponges and aerogels modified by graphene and reduced graphene oxide demonstrated effective oil water separation owing to their superhydrophobic/superoleophilic properties. In addition, oil particles are intercepted while allowing water molecules to penetrate the graphene-oxide-coated metal meshes and membranes thanks to their superhydrophilic/underwater superoleophobic properties. Finally, we offer future perspectives on oil water separation that are hindering the advancements of such technologies and their large-scale applications.


Quinolines: A Promising Heterocyclic Scaffold for Cancer Therapeutics.
The quinoline scaffold is a widely recognized heterocycle with applications across various disease categories, ranging from malaria and viral infections to bacterial infections, high cholesterol, and even tumors. Consequently, quinoline plays a crucial role in the development of new drugs, and the field greatly benefits from advancements in computer-aided drug design. This review aims to provide insights into the evolution of quinoline and its derivatives, offering a comprehensive exploration of both marketed and developing drugs. Furthermore, the function and mechanism of quinoline compounds are introduced. Many studies rely on cell experiments to demonstrate drug cytotoxicity. In the concluding section of this review, the interaction between quinoline compounds and targets is simulated using computer-aided drug design methods. A thorough analysis is conducted on the potential influencing factors affecting the binding state between quinoline compounds and targets. Notably, the Pi-Alkyl interaction emerges as a significant contributor, while hydrogen bonding is identified as a pivotal bond in these interactions. This review serves as a valuable overview of the potential contributions of quinoline compounds to cancer treatment. It seamlessly combines the essential functions of marketed quinoline drugs with the promise held by emerging quinoline-based compounds. Additionally, the simulation of interactions between quinoline compounds and proteins through computer-aided design enhances our understanding of these compounds' efficacy.


Reactive oxygen species stimulate mitochondrial allele segregation toward homoplasmy in human cells.
Mitochondria that contain a mixture of mutant and wild-type mitochondrial (mt) DNA copies are heteroplasmic. In humans, homoplasmy is restored during early oogenesis and reprogramming of somatic cells, but the mechanism of mt-allele segregation remains unknown. In budding yeast, homoplasmy is restored by head-to-tail concatemer formation in mother cells by reactive oxygen species (ROS)-induced rolling-circle replication and selective transmission of concatemers to daughter cells, but this mechanism is not obvious in higher eukaryotes. Here, using heteroplasmic m.3243A > G primary fibroblast cells derived from MELAS patients treated with hydrogen peroxide (H2O2), we show that an optimal ROS level promotes mt-allele segregation toward wild-type and mutant mtDNA homoplasmy. Enhanced ROS level reduced the amount of intact mtDNA replication templates but increased linear tandem multimers linked by head-to-tail unit-sized mtDNA (mtDNA concatemers). ROS-triggered mt-allele segregation correlated with mtDNA-concatemer production and enabled transmission of multiple identical mt-genome copies as a single unit. Our results support a mechanism by which mt-allele segregation toward mt-homoplasmy is mediated by concatemers.


Sexual Offending: The Intrepid Professional-Adventurer and The Dejected Revenger-Victim.
The Criminal Narrative Experience (CNE) is a framework developed within Invest-igative Psychology, which combines the emotions and narrative roles experienced by the offender during the commission of their offense, to understand their personal experience of crime . Previous research proposes four distinct themes within CNE; The Elated Hero, The Calm Professional, The Distressed Revenger, and The Depressed Victim , however little attention has yet been paid to the potential differences in themes across various offense types. The current study explored the CNE model within a sample of sexual offenders. Results found evidence of two CNE themes; The Intrepid Professional-Adventurer and The Dejected Revenger-Victim, this has implications stretching further than theorical, and are particularly poignant for therapists and treatment managers, who may be providing intervention to groups of sexual offenders at any one time.


Genetic and phylogenetic consequences of island biogeography.
Island biogeography theory predicts that the number of species on an island should increase with island size and decrease with island distance to the mainland. These predictions are generally well supported in comparative and experimental studies. These ecological, equilibrium predictions arise as a result of colonization and extinction processes. Because colonization and extinction are also important processes in evolution, we develop methods to test evolutionary predictions of island biogeography. We derive a population genetic model of island biogeography that incorporates island colonization, migration of individuals from the mainland, and extinction of island populations. The model provides a means of estimating the rates of migration and extinction from population genetic data. This model predicts that within an island population the distribution of genetic divergences with respect to the mainland source population should be bimodal, with much of the divergence dating to the colonization event. Across islands, this model predicts that populations on large islands should be on average more genetically divergent from mainland source populations than those on small islands. Likewise, populations on distant islands should be more divergent than those on close islands. Published observations of a larger proportion of endemic species on large and distant islands support these predictions.


How clinicians make (or avoid) moral judgments of patients: implications of the evidence for relationships and research.
Physicians, nurses, and other clinicians readily acknowledge being troubled by encounters with patients who trigger moral judgments. For decades social scientists have noted that moral judgment of patients is pervasive, occurring not only in egregious and criminal cases but also in everyday situations in which appraisals of patients' social worth and culpability are routine. There is scant literature, however, on the actual prevalence and dynamics of moral judgment in healthcare. The indirect evidence available suggests that moral appraisals function via a complex calculus that reflects variation in patient characteristics, clinician characteristics, task, and organizational factors. The full impact of moral judgment on healthcare relationships, patient outcomes, and clinicians' own well-being is yet unknown. The paucity of attention to moral judgment, despite its significance for patient-centered care, communication, empathy, professionalism, healthcare education, stereotyping, and outcome disparities, represents a blind spot that merits explanation and repair. New methodologies in social psychology and neuroscience have yielded models for how moral judgment operates in healthcare and how research in this area should proceed. Clinicians, educators, and researchers would do well to recognize both the legitimate and illegitimate moral appraisals that are apt to occur in healthcare settings.


Outcome evaluation of gabapentin as add-on therapy for partial seizures. "NEON" Study Investigators Group. Neurontin Evaluation of Outcomes in Neurological Practice.
The safety, tolerability, efficacy, and impact on quality of life of gabapentin (Neurontin) as adjunctive therapy to carbamazepine (CBZ) and/or phenytoin (PHT) was assessed in epileptic patients with partial seizures. NEON (Neurontin Evaluation of Outcomes in Neurological Practice) was an open-label, prospective, multicentre study conducted in patients on a stable dose of CBZ and/or PHT and experiencing an average of up to 4 complex partial seizures with or without secondary generalization per month, with no seizure-free months. The treatment lasted 20 weeks. Gabapentin was started at 400 mg/day and was individually titrated to effective tolerable dose up to 2400 mg/day. Quality of life was evaluated using the QOLIE-10 questionnaire. A total of 141 patients were enrolled at 36 sites; 114 patients were evaluable for efficacy analyses. The mean maintenance dose of gabapentin was 1600 mg/day (range = 300-3200). A decrease of 50% or more in frequency of complex partial + secondary generalized seizures was observed in 81 (71%) patients (p = 0.0001). Fifty two (46%) patients were seizure-free during the last 8 weeks of treatment. A significant improvement (p < 0.05) was observed in 5 of the 10 questions of the QOLIE-10, as well as in the composite QOL score (p = 0.0002). The most frequent adverse events included somnolence (16%), dizziness (9%), and asthenia (6%). Twenty-five (18%) patients prematurely discontinued the study, 16 (11%) of them due to adverse events. This study indicates that treatment with gabapentin as adjunctive therapy to standard antiepileptic drugs in this group of patients not only provides significant improvement in seizure control, but also has a positive impact on quality of life. The clinical benefits in efficacy, safety and tolerability demonstrated at 20 weeks are sustained, and no tolerance develops with gabapentin in longer term use.


RIght VErsus Left Apical transvenous pacing for bradycardia: Results of the RIVELA randomized study.
To compare cardiac function when pacing from the right or left ventricular apex in patients with preserved left ventricular systolic function, at 1-year follow-up. Prospective, multicentre centre randomizing conventional right ventricular apical (RVA) versus left ventricular apical (LVA) pacing using a coronary sinus lead in patients requiring ventricular pacing for bradycardia. Follow-up was performed using 3D-echocardiography at 6 and 12 months. A total of 36 patients (age 75.4 ± 8.7 years, 21 males) were enrolled (17 patients in the RVA group and 19 patients in the LVA group). A right ventricular lead was implanted in 8 patients in the LVA group, mainly because of high capture thresholds. There were no differences in the primary endpoint of LVEF at 1 year (60.4 ± 7.1% vs 62.1 ± 7.2% for the RVA and LVA groups respectively, P = 0.26) nor in any of the secondary endpoints (left ventricular dimensions, left ventricular diastolic function, right ventricular systolic function and tricuspid/mitral insufficiency). LVEF did not change significantly over follow-up in either group. Capture thresholds were significantly higher in the LVA group, and two patients had unexpected loss of capture of the coronary sinus lead during follow-up. Left univentricular pacing seems to be comparable to conventional RVA pacing in terms of ventricular function at up to 1 year follow-up, and is an option to consider in selected patients (e.g. those with a tricuspid valve prosthesis).


Midwives' knowledge and attitudes when encountering Gender-Based Violence in their practice at a maternity-hospital in Kingston, Jamaica.
Gender-based violence (GBV) can have devastating consequences for pregnancy because both mother and child are at risk. Midwives are in a strategic position to identify and empower pregnant women experiencing GBV; however, currently midwives in Jamaica are not required to screen for GBV, neither are they prepared to do so. This study forms the baseline of a larger study designed to improve the capacity of midwives to identify and treat pregnant women experiencing GBV in Jamaica. This specific component assessed midwives' knowledge and attitudes when encountering GBV in their practice in Kingston, Jamaica. A qualitative study design was used. Six practicing midwives were purposely selected to participate in a focus group discussion at the antenatal clinic of a hospital in Kingston, Jamaica. All six respondents said it was very important to screen for GBV among pregnant women in their care. The findings from their report revolved around six themes, namely midwives have suboptimal knowledge, are exposed to women experiencing GBV in pregnancy, lack professional preparedness, report gaps in the institutional framework to guide their practice, are concerned for their safety and security, and are willing to intervene. This study confirmed that midwives are aware of the problem and are willing to intervene but are faced with lack of formal procedures to detect and treat pregnant women who are experiencing GBV. Findings could be used to inform a protocol which is being developed to guide midwives' practice. Findings could also be incorporated in the national strategy to eliminate GBV.


An assessment of nutritional status in children of rural, northern KwaZulu-Natal province.
Childhood malnutrition in South Africa is largely perceived as one of undernutrition, with the opposite end of the spectrum (overnutrition) being evidenced in the increasing prevalence of childhood obesity, demonstrated to be associated with chronic metabolic diseases in adulthood. Targeting childhood malnutrition is a potential interventional strategy to prevent non-communicable diseases amongst adults. As the prevalence of malnutrition (undernutrition and overnutrition) in rural, northern KwaZulu-Natal province, South Africa, is largely unknown, this study aimed to determine the baseline nutritional status of children attending primary healthcare facilities within the Bethesda Hospital catchment area. This quantitative, cross-sectional study included children aged 6 weeks to 19 years, attending any primary healthcare clinics for over a 3 months period. Anthropometric measurements were obtained to categorise the children according to the World Health Organisation's (WHO) nutritional classifications. Stunting in children aged less than 5 years was found to be lower (14%) than nationally representative studies (27%); however, 14.4% of the infants aged 6 weeks to 5 months were overweight, increasing to 32.3% in those aged 14-19 years. Males in the 6-weeks to 5-month age group were more likely to be overweight/obese and stunted than females in the same age group. Undernutrition is showing a downward trend, which is a testament to initiatives to reduce food insecurity amongst the poor. However, the emerging upward trend of overweight/obesity in children of all ages, indicates the need to have a national discussion on over- and undernutrition, its causes and implications.


Nucleic-acid amplification testing of urine vs. patient complaint-driven evaluation.
The present pilot study compared the ability of a conventional patient complaint-driven approach to that of nucleic-acid amplification testing (NAAT) of urine to identify those individuals among an adult, urban, Emergency Department (ED) population infected with Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Trichomonas vaginalis (TV). Urine for NAAT was collected for testing after individuals had completed a questionnaire and before being seen by a physician. A total of 614 subjects were enrolled, and complete physical examinations were performed on 348 (56.6%) individuals, with women being significantly more likely to receive such an evaluation (odds ratio [OR] 3.09; 95% confidence interval [CI] 1.96-4.86); p < 0.001). A total of 153 (24.9%) of the study cohort tested positive for a least one sexually transmitted disease (STD), and only a reported history of STD (OR 1.74; 95% CI (1.18-2.57); p = 0.005) and a history of a new sexual partner in the last 3 months (OR 1.79; 95% CI 1.13-2.82); p = 0.012) were predictive of a positive STD test. NAAT of urine samples on patients who did not receive a complete physical examination resulted in a 33% (51/153) increase in diagnostic yield in this cohort of ED attendees.


Intimate Relationships in Times of COVID-19: A Descriptive Study of Belgian Partners and their Perceived Well-Being.
How did couples in Belgium cope during the early phases of the COVID-19 pandemic? In this study, grounded in relationship science, we investigated in a descriptive manner several factors that could affect how couples perceived individual and relational wellbeing during this time. Specifically, we examined the associations between gender, sexual orientation, parental status, and relationship duration on participants' self-reported individual and relational well-being after the first lockdown (more generally and more specific in response to COVID-19). Additionally, we investigated if relational well-being predicted perceived change in individual well-being from pre- to post-COVID-19 regulations. To test these hypotheses, self-report data was collected during the Summer of 2020 in both the Dutch and French speaking part of Belgium. Data from 679 participants suggested that individual and relational well-being only differed based on parental status (and not by gender nor sexual orientation). Importantly, parents reported lower relational well-being than participants without children, while participants without children reported higher perceived increases in depression. People that had been in a relationship for longer also reported lower relational well-being, but this relationship was explained by other confounding factors. Relational well-being buffered increases in individual distress that people perceived to have occurred pre-COVID-19 regulations to after COVID-19 regulations went into effect. These findings might inform practice and policy for individuals in a romantic relationship during the COVID-19 pandemic.


Regulation of fatty acid transport protein and fatty acid translocase mRNA levels by endotoxin and cytokines.
The cloning of two novel fatty acid (FA) transport proteins, FA transport protein (FATP) and FA translocase (FAT), has recently been reported; however, little is known about their in vivo regulation. Endotoxin [lipopolysaccharide (LPS)], tumor necrosis factor (TNF), and interleukin-1 (IL-1) stimulate adipose tissue lipolysis and enhance hepatic lipogenesis and reesterification while suppressing FA oxidation in multiple tissues. Hence, in this study we examined their effects on FATP and FAT mRNA levels in Syrian hamsters. Our results demonstrate that LPS decreased FATP and FAT mRNA expression in adipose tissue, heart, skeletal muscle, brain, spleen, and kidney, tissues in which FA uptake and/or oxidation is decreased during sepsis. In the liver, where FA oxidation is decreased during sepsis but the uptake of peripherally derived FA is increased to support reesterification, LPS decreased FATP mRNA expression by 70-80% but increased FAT mRNA levels by four- to fivefold. The effects of LPS on FATP and FAT mRNA levels in liver were observed as early as 4 h after administration and were maximal by 16 h. TNF and IL-1 mimicked the effect of LPS on FATP and FAT mRNA levels in both liver and adipose tissue. These results indicate that the mRNAs for both transport proteins are downregulated by LPS in tissues in which FA uptake and/or oxidation are decreased during sepsis. On the other hand, differential regulation of FATP and FAT mRNA in liver raises the possibility that these proteins may be involved in transporting FA to different locations inside the cell. FATP may transport FA toward mitochondria for oxidation, which is decreased in sepsis, whereas FAT may transport FA to cytosol for reesterification, which is enhanced in sepsis.


EBV-specific CD8 T lymphocytes and B cells during glatiramer acetate therapy in patients with MS.
Infection with Epstein-Barr virus (EBV) has been associated with clinical activity and risk of developing MS. The purpose of this study is to investigate the impact of glatiramer acetate (GA) therapy on EBV-specific immune responses and disease course. We characterized EBV-specific CD8 T lymphocytes and B cells during disease-modifying treatments in 2 groups of patients with MS. We designed a 2-pronged approach consisting of a cross-sectional study (39 untreated patients, 38 patients who had undergone 12 months of GA treatment, and 48 healthy donors compatible for age and sex with the patients with MS) and a 12-month longitudinal study (35 patients treated with GA). CD8 EBV-specific T cells and B lymphocytes were studied using pentamers and multiparametric flow cytometry. We find that treatment with GA enhances viral recognition by inducing an increased number of circulating virus-specific CD8 T cells (p = 0.0043) and by relieving their features of exhaustion (p = 0.0053) and senescence (p < 0.0001, p = 0.0001). B cells, phenotypically and numerically tracked along the 1-year follow-up study, show a steady decrease in memory B-cell frequencies (p = 0.025), paralleled by an increase of the naive B subset. GA therapy acts as a disease-modifying therapy restoring homeostasis in the immune system, including anti-EBV responses.


Imaging and Treatment of Posttraumatic Ankle and Hindfoot Osteoarthritis.
Posttraumatic osteoarthritis of the ankle and hindfoot is a common and frequently debilitating disorder. 70% to 90% of ankle osteoarthritis is related to prior trauma that encompasses a spectrum of disorders including fractures and ligamentous injuries that either disrupt the articular surface or result in instability of the joint. In addition to clinical evaluation, imaging plays a substantial role in the treatment planning of posttraumatic ankle and hindfoot osteoarthritis. Imaging evaluation must be tailored to specific clinical scenarios and includes weight bearing radiography that utilizes standard and specialty views, computed tomography which can be performed with a standard or a weight bearing technique, magnetic resonance imaging, and ultrasound evaluation. This review article aims to familiarize the reader with treatment rationale, to provide a brief review of surgical techniques and to illustrate expected imaging appearances of common operative procedures performed in the setting of posttraumatic ankle and hindfoot osteoarthritis, such as joint-preserving procedures, ankle fusion, subtalar fusion, tibiotalarcalcaneal fusion and ankle arthroplasty. Preoperative findings will be discussed along with the expected postoperative appearance of various procedures in order to improve detection of their complications on imaging and to provide optimal patient care.


Barrett's esophagus: the American perspective.
The American Gastroenterological Association (AGA) defines Barrett's esophagus as the condition in which any extent of metaplastic columnar epithelium that predisposes to cancer development replaces the squamous epithelium that normally lines the distal esophagus. Although cardiac mucosa may be metaplastic, its malignant predisposition is not clear, and the AGA still requires the demonstration of intestinal metaplasia (with goblet cells) for a diagnosis of Barrett's esophagus. The AGA generally recommends endoscopic eradication therapy for patients with high-grade dysplasia, who otherwise develop esophageal adenocarcinoma at the rate of 6% per year. Endoscopic therapy is often curative for mucosal neoplasms in Barrett's esophagus because the risk of lymph node metastases is only 1-2%. American gastroenterologists generally do not recommend endoscopic therapy for patients whose neoplasms involve any portion of the submucosa because of the high rate of lymph node metastases that has been described in these cases. The management of low-grade dysplasia is disputed because of poor agreement among pathologists on the diagnosis and because of contradictory data on the natural history, but the AGA recommends that radiofrequency ablation (RFA) should be a therapeutic option for patients with confirmed low-grade dysplasia in Barrett's esophagus. Arguments for using RFA to treat nondysplastic Barrett's metaplasia are based on the premise that RFA decreases cancer risk, but no study has established that premise. In the absence of definitive data, concerns about the frequency and importance of buried metaplastic glands and recurrent metaplasia should temper enthusiasm for treating nondysplastic Barrett's esophagus with RFA.


Identification of fecal Escherichia coli from humans and animals by ribotyping.
Fecal pollution of water resources is an environmental problem of increasing importance. Identification of individual host sources of fecal Escherichia coli, such as humans, pets, production animals, and wild animals, is prerequisite to formulation of remediation plans. Ribotyping has been used to distinguish fecal E. coli of human origin from pooled fecal E. coli isolates of nonhuman origin. We have extended application of this technique to distinguishing fecal E. coli ribotype patterns from human and seven individual nonhuman hosts. Classification accuracy was best when the analysis was limited to three host sources. Application of this technique to identification of host sources of fecal coliforms in water could assist in formulation of pollution reduction plans.


Endocrinopathies after allogeneic and autologous transplantation of hematopoietic stem cells.
Early and late endocrine disorders are among the most common complications in survivors after hematopoietic allogeneic- (allo-) and autologous- (auto-) stem cell transplant (HSCT). This review summarizes main endocrine disorders reported in literature and observed in our center as consequence of auto- and allo-HSCT and outlines current options for their management. Gonadal impairment has been found early in approximately two-thirds of auto- and allo-HSCT patients: 90-99% of women and 60-90% of men. Dysfunctions of the hypothalamus-pituitary-growth hormone/insulin growth factor-I axis, hypothalamus-pituitary-thyroid axis, and hypothalamus-pituitary-adrenal axis were documented as later complicances, occurring in about 10, 30, and 40-50% of transplanted patients, respectively. Moreover, overt or subclinical thyroid complications (including persistent low-T3 syndrome, chronic thyroiditis, subclinical hypo- or hyperthyroidism, and thyroid carcinoma), gonadal failure, and adrenal insufficiency may persist many years after HSCT. Our analysis further provides evidence that main recognized risk factors for endocrine complications after HSCT are the underlying disease, previous pretransplant therapies, the age at HSCT, gender, total body irradiation, posttransplant derangement of immune system, and in the allogeneic setting, the presence of graft-versus-host disease requiring prolonged steroid treatment. Early identification of endocrine complications can greatly improve the quality of life of long-term survivors after HSCT.


The Relationship of Core Strength and Activation and Performance on Three Functional Movement Screens.
Johnson, CD, Whitehead, PN, Pletcher, ER, Faherty, MS, Lovalekar, MT, Eagle, SR, and Keenan, KA. The relationship of core strength and activation and performance on three functional movement screens. J Strength Cond Res 32(4): 1166-1173, 2018-Current measures of core stability used by clinicians and researchers suffer from several shortcomings. Three functional movement screens appear, at face-value, to be dependent on the ability to activate and control core musculature. These 3 screens may present a viable alternative to current measures of core stability. Thirty-nine subjects completed a deep squat, trunk stability push-up, and rotary stability screen. Scores on the 3 screens were summed to calculate a composite score (COMP). During the screens, muscle activity was collected to determine the length of time that the bilateral erector spinae, rectus abdominis, external oblique, and gluteus medius muscles were active. Strength was assessed for core muscles (trunk flexion and extension, trunk rotation, and hip abduction and adduction) and accessory muscles (knee flexion and extension and pectoralis major). Two ordinal logistic regression equations were calculated with COMP as the outcome variable, and: (a) core strength and accessory strength, (b) only core strength. The first model was significant in predicting COMP (p = 0.004) (Pearson's Chi-Square = 149.132, p = 0.435; Nagelkerke's R-Squared = 0.369). The second model was significant in predicting COMP (p = 0.001) (Pearson's Chi-Square = 148.837, p = 0.488; Nagelkerke's R-Squared = 0.362). The core muscles were found to be active for most screens, with percentages of "time active" for each muscle ranging from 54-86%. In conclusion, performance on the 3 screens is predicted by core strength, even when accounting for "accessory" strength variables. Furthermore, it seems the screens elicit wide-ranging activation of core muscles. Although more investigation is needed, these screens, collectively, seem to be a good assessment of core strength.


A review of methods for the analysis of orphan and difficult pesticides: glyphosate, glufosinate, quaternary ammonium and phenoxy acid herbicides, and dithiocarbamate and phthalimide fungicides.
This article reviews the chromatography/MS methodologies for analysis of pesticide residues of orphan and difficult chemical classes in a variety of sample matrixes including water, urine, blood, and food. The review focuses on pesticide classes that are not commonly included in multiresidue analysis methods such as highly polar or ionic herbicides including glyphosate, glufosinate, quaternary ammonium, and phenoxy acid herbicides, and some of their major degradation or metabolite products. In addition, dithiocarbamate and phthalimide fungicides, which are thermally unstable and have stability issues in some solvents or sample matrixes, are also examined due to their special needs in residue analysis.


Quantum theory cannot consistently describe the use of itself.
Quantum theory provides an extremely accurate description of fundamental processes in physics. It thus seems likely that the theory is applicable beyond the, mostly microscopic, domain in which it has been tested experimentally. Here, we propose a Gedankenexperiment to investigate the question whether quantum theory can, in principle, have universal validity. The idea is that, if the answer was yes, it must be possible to employ quantum theory to model complex systems that include agents who are themselves using quantum theory. Analysing the experiment under this presumption, we find that one agent, upon observing a particular measurement outcome, must conclude that another agent has predicted the opposite outcome with certainty. The agents' conclusions, although all derived within quantum theory, are thus inconsistent. This indicates that quantum theory cannot be extrapolated to complex systems, at least not in a straightforward manner.


Probing gorge dimensions of cholinesterases by freeze-frame click chemistry.
Freeze-frame click chemistry is a proven approach for design in situ of high affinity ligands from bioorthogonal, reactive building blocks and macromolecular template targets. We recently described in situ design of femtomolar reversible inhibitors of fish and mammalian acetylcholinesterases (EC 18.104.22.168; AChEs) using several different libraries of acetylene and azide building blocks. Active center gorge geometries of those AChEs are rather similar and identical triazole inhibitors were detected in situ when incubating the same building block libraries in different AChEs. Drosophila melanogaster AChE crystal structure and other insect AChE homology models differ more in their overall 3D structure than other members of the cholinesterase family. The portion of the gorge proximal to the catalytic triad and choline binding site has a approximately 50% reduction in volume, and the gorge entrance at the peripheral anionic site (PAS) is more constricted than in the fish and mammalian AChEs. In this communication we describe rationale for using purified recombinant Drosophila AChE as a template for in situ reaction of tacrine and propidium based libraries of acetylene and azide building blocks. The structures of resulting triazole inhibitors synthesized in situ are expected to differ appreciably from the fish and mammalian AChEs. While the latter AChEs exclusively promote synthesis of syn-substituted triazoles, the best Drosophila AChE triazole inhibitors were always anti-substituted. The anti-regioisomer triazoles were by about one order of magnitude better inhibitors of Drosophila than mammalian and fish AChEs. Moreover, the preferred site of acetylene+azide reaction in insect AChE and the resulting triazole ring formation shifts from near the base of the gorge to closer to its rim due to substantial differences of the gorge geometry in Drosophila AChE. Thus, in addition to synthesizing high affinity, lead inhibitors in situ, freeze-frame, click chemistry has capacity to generate species-specific AChE ligands that conform to the determinants in the gorge.


Diminished lipoxin biosynthesis in severe asthma.
Severe asthma is characterized by increased airway inflammation that persists despite therapy with corticosteroids. It is not, however, merely an exaggeration of the eosinophilic inflammation that characterizes mild to moderate asthma; rather, severe asthma presents unique features. Although arachidonic acid metabolism is well appreciated to regulate airway inflammation and reactivity, alterations in the biosynthetic capacity for both pro- and antiinflammatory eicosanoids in severe asthma have not been determined. Patients with severe asthma were identified according to National Heart, Lung, and Blood Institute Severe Asthma Research Program criteria. Samples of whole blood from individuals with severe or moderate asthma were assayed for biosynthesis of lipoxygenase-derived eicosanoids. The counterregulatory mediator lipoxin A4 was detectable in low picogram amounts, using a novel fluorescence-based detection system. In activated whole blood, mean lipoxin A4 levels were decreased in severe compared with moderate asthma (0.4 [SD 0.4] ng/ml vs. 1.8 [SD 0.8] ng/ml, p=0.001). In sharp contrast, mean levels of prophlogistic cysteinyl leukotrienes were increased in samples from severe compared with moderate asthma (112.5 [SD 53.7] pg/ml vs. 64.4 [SD 24.8] pg/ml, p=0.03). Basal circulating levels of lipoxin A4 were also decreased in severe relative to moderate asthma. The marked imbalance in lipoxygenase-derived eicosanoid biosynthesis correlated with the degree of airflow obstruction. Mechanisms underlying airway responses in severe asthma include underproduction of lipoxins. This is the first report of a defect in lipoxin biosynthesis in severe asthma, and suggests an alternative therapeutic strategy that emphasizes natural counterregulatory pathways in the airways.