Protective effects of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside in the MPTP-induced mouse model of Parkinson's disease: Involvement of reactive oxygen species-mediated JNK, P38 and mitochondrial pathways.
Parkinson's disease (PD) is characterized by the selective death of dopaminergic neurons in the substantia nigra pars compacta. Oxidative stress-induced neuron loss is thought to play a crucial role in the pathogenesis of PD. Previous work from our group suggests that 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG), an active component extracted from a traditional Chinese herb, Polygonum multiflorum thunb, can attenuate 1-methyl-4-phenyl pyridium-induced apoptosis in the neuronal cell line PC12, by inhibiting reactive oxygen species generation and modulating c-Jun N-terminal kinases (JNK) activation. Here, we investigated the protective effects of TSG against 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine (MPTP)-induced loss of tyrosine hydroxylase positive cells in mice and the underlying mechanisms. The results showed that MPTP-induced loss of tyrosine hydroxylase positive cells and reactive oxygen species generation were prevented by TSG in a dose-dependent manner. The reactive oxygen species scavenger N-acetylcysteine could also mitigate reactive oxygen species generation. Moreover, JNK and P38 were activated by MPTP, but extracellular signal-regulated protein kinases phosphorylation did not change after MPTP treatment. TSG at different doses blocked the activation of JNK and P38. The protective effect of TSG was also associated with downregulation of the bax/bcl-2 ratio, reversed the release of cytochrome c and smac, and inhibited the activation of caspase-3, -6, and -9 induced by MPTP. In conclusion, our studies demonstrated that the protective effects of TSG in the MPTP-induced mouse model of PD are involved, at least in part, in controlling reactive oxygen species-mediated JNK, P38, and mitochondrial pathways.


Opsoclonus associated with salmonellosis in a 6-week-old infant.
A 6-week-old male infant presented with 2 days of fever, emesis, and diarrhea, associated with episodic and chaotic rapid eye movements, determined to be opsoclonus. An electroencephalogram (EEG) obtained during the events was normal. He was treated empirically for meningitis, and an initial workup for neuroblastoma including urine homovanillic acid and vanillylmandelic acid levels, abdominal ultrasonography, and computed tomography (CT) of the chest, abdomen, and pelvis was negative. Stool and blood cultures were positive for Salmonella, and antibiotic regimen was adjusted appropriately. Over the next few days, his fever, emesis, and diarrhea subsided, and the opsoclonus resolved by hospital day 6. He was back to baseline by hospital day 9. Although there have been cases of parainfectious opsoclonus associated with Lyme disease, enterovirus, Streptococcus, and West Nile virus, this represents the first reported pediatric case of opsoclonus associated with salmonellosis. Only 2 such cases in adults have been reported in the literature.


Intracranial auditory pathways: anatomy correlated with evoked response data.
The intracranial auditory pathways are complex, and they have been incompletely mapped. The purpose of the communication is to summarize what is known about these fibers onto clinically relevant imaging sections. Anatomic information is correlated with the clinical auditory evoked responses currently used to localize lesions in these pathways. This linkage will improve communication between imagers and clinicians. In addition, it can be used for teaching.


Offering assistance at road traffic incidents while off duty.
Every year in the UK road traffic incidents cause 320,000 injuries--40,000 of which are serious--and over 3,200 deaths. The public, patients and relatives expect nurses to be able to assist and provide first aid at the scene of any emergency. As a healthcare professional you should therefore ensure you are up to date with first aid skills.


Can people with Alzheimer's disease improve their day-to-day functioning with a tablet computer?
New technologies, such as tablet computers, present great potential to support the day-to-day living of persons with Alzheimer's disease (AD). However, whether people with AD can learn how to use a tablet properly in daily life remains to be demonstrated. A single case study was conducted with a 65-year-old woman with AD. A specific and structured intervention tailored to her needs was conceptualised for the use of a calendar application on a tablet computer according to the following learning stages: Acquisition, Application and Adaptation. In spite of her severe episodic memory deficit, she showed progressive learning of the tablet application during the intervention phase. Furthermore, data compiled over 12 months post-use show that she used the tablet successfully in her day-to-day life. She was even able to transfer her newly acquired ability to other available applications designed to monitor regular purchases, consult various recipes and play games. Tablet computers thereby offer a promising avenue for cognitive rehabilitation for persons with AD. This success was mainly achieved through a one-on-one individual programme tailored to this person. The limits and constraints of utilising tablet computers for persons with AD are discussed.


The Ross procedure in children: a systematic review.
The Ross procedure involves autograft transplantation of the native pulmonary valve into the aortic position and reconstruction of the right ventricular outflow tract (RVOT) with a homograft. The operation offers the advantages of a native valve with excellent hemodynamic performance, the avoidance of anticoagulation, and growth potential. Conversely, the operation is technically demanding and imposes the risk of turning single-valve disease into double-valve disease. This systematic review reports outcomes of pediatric patients undergoing the Ross procedure. An electronic search identified studies reporting outcomes on pediatric patients (mean age <18 years, max age <21 years) undergoing the Ross procedure. Long-term outcomes, including early mortality, late mortality, sudden unexpected unexplained death, reoperation due to failure of the pulmonary autograft or RVOT reconstruction, thromboembolic events, bleeding events, and endocarditis-related complications, were evaluated. Upon review of 2,035 publications, 30 studies and 3,156 pediatric patients were included. Patients had a median age of 9.5 years and median follow-up period of 5.7 years. Early mortality rates varied from 0.0 to 17.0% and were increased in the neonatal population. Late mortality rates were much lower (0.04-1.83%/year). Reoperation due to pulmonary autograft failure occurred at rates of 0.37-2.81%/year and reoperation due to RVOT reconstruction failure was required at rates of 0.34-4.76%/year. Thromboembolic, bleeding, and endocarditis events were reported to occur at rates of 0.00-0.58, 0.00-0.39, and 0.00-1.68%/year, respectively. The Ross operation offers a durable aortic valve replacement (AVR) option in the pediatric population that offers favorable survival, excellent hemodynamics, growth potential, decreased risk of complications, and avoidance of anticoagulation. Larger multi-institutional registries focusing on pediatric patients are necessary to provide more robust evidence to further support use of the Ross procedure in this population.


Hexafluoroisopropanol-Promoted Disulfidation and Diselenation of Alkyne, Alkene, and Allene.
Hexafluoroisopropanol (HFIP)-promoted disulfidation and diselenation of C-C unsaturated bonds is reported. Reactions of unactivated alkyne, alkene, and allene, respectively, with disulfides or diselenides in HFIP led to desired products in good to excellent yields (up to 96%). In contrast, other solvents, such as isopropanol and dichloroethane, could not promote the same reaction. This method revealed an example of HFIP-promoted transformations under the mild conditions, which greatly highlighted the unique reactivity of this special solvent.


Aquatic animals promote antibiotic resistance gene dissemination in water via conjugation: Role of different regions within the zebra fish intestinal tract, and impact on fish intestinal microbiota.
The aqueous environment is one of many reservoirs of antibiotic resistance genes (ARGs). Fish, as important aquatic animals which possess ideal intestinal niches for bacteria to grow and multiply, may ingest antibiotic resistance bacteria from aqueous environment. The fish gut would be a suitable environment for conjugal gene transfer including those encoding antibiotic resistance. However, little is known in relation to the impact of ingested ARGs or antibiotic resistance bacteria (ARB) on gut microbiota. Here, we applied the cultivation method, qPCR, nuclear molecular genetic marker and 16S rDNA amplicon sequencing technologies to develop a plasmid-mediated ARG transfer model of zebrafish. Furthermore, we aimed to investigate the dissemination of ARGs in microbial communities of zebrafish guts after donors carrying self-transferring plasmids that encode ARGs were introduced in aquaria. On average, 15% of faecal bacteria obtained ARGs through RP4-mediated conjugal transfer. The hindgut was the most important intestinal region supporting ARG dissemination, with concentrations of donor and transconjugant cells almost 25 times higher than those of other intestinal segments. Furthermore, in the hindgut where conjugal transfer occurred most actively, there was remarkable upregulation of the mRNA expression of the RP4 plasmid regulatory genes, trbBp and trfAp. Exogenous bacteria seem to alter bacterial communities by increasing Escherichia and Bacteroides species, while decreasing Aeromonas compared with control groups. We identified the composition of transconjugants and abundance of both cultivable and uncultivable bacteria (the latter accounted for 90.4%-97.2% of total transconjugants). Our study suggests that aquatic animal guts contribute to the spread of ARGs in water environments.


Trauma-Related Guilt Mediates the Relationship between Posttraumatic Stress Disorder and Suicidal Ideation in OEF/OIF/OND Veterans.
Posttraumatic stress disorder (PTSD) and trauma-related guilt are risk factors for suicidal ideation (SI) in veterans. Components of trauma-related guilt were examined as serial mediators of the relationship between PTSD and SI. In a sample of 53 OEF/OIF/OND combat veterans, PTSD had an indirect effect on SI through a serial mediation chain of guilt cognitions, distress, and global guilt, suggesting that trauma-related guilt via cognitions, distress, and global guilt is a pathway from PTSD to SI. Attention should be given to assessing and addressing trauma-related guilt in veterans experiencing PTSD to prevent SI.


Successful Treatment of Infection- Associated Hemophagocytic Syndrome with Intravenous Immunoglobulin.
Hemophagocytic syndrome is a rare disorder characterized by a group of clinical, laboratory and histopathological findings such as fever, hepatosplenomegaly, cytopenia, hypertriglyceridemia, and hemophagocytosis in the bone marrow, spleen, and lymph nodes. Hemophagocytic syndrome may occur as a primary or secondary disease. Primary type of hemophagocytic syndrome is also known as familial erythrophagocytic lymphohistiocytosis and secondary type is mostly associated with an viral infection and known as infection-associated hemophagocytic syndrome (IAHS). Rapid diagnosis is very important in these patients since suggested treatment strategies for the two types have been different and mortality rate is very high. In this report we present the clinical and laboratory findings and the outcome of two children with IAHS to emphasize the importance of early diagnosis and the effectiveness of intravenous immunoglobulin therapy in these patients.


Better governance will lead to better taxonomy: response to Raposo et al. (2017).
We welcome the recent paper by Raposo et al. (2017) debating our Nature Comment on inadequacies in taxonomic governance and the impact this has on conservation and society (Garnett Christidis 2017), as well as the opportunity to clarify our views. We admit to surprise at meanings read into our paper by Raposo et al. (2017) that we never intended and that we had not thought were there. As we have also made clear in a separate discussion of our paper (Garnett Christidis 2018 in response to Thomson et al. 2018), we wish to make clear at the start: (i) that we have no wish to stifle taxonomic research, only to strengthen the legitimacy of its findings; and (ii) we believe that taxonomic research should not consider the consequences for conservation, or society, in its conclusions once transparent taxonomic criteria have been established (Garnett Christidis 2007), but that taxonomists have an obligation to improve their governance to ensure taxonomic conclusions are of the highest standard.


Recombinant human bone morphogenetic protein-2 versus iliac crest bone graft in anterior cervical discectomy and fusion: Dysphagia and dysphonia rates in the early postoperative period with review of the literature.
Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a growth factor utilized to stimulate bone development in several clinical scenarios. Although the U.S. Food and Drug Administration approved this therapeutic modality for only two applications, it is frequently used off-label in anterior cervical discectomy and fusion (ACDF) procedures as an alternative to iliac crest bone graft (ICBG), the prior standard of care. This usage has been a source of controversy in the medical community due to evidence of increased rates of postoperative edema and dysphagia. This retrospective cohort study investigates two groups of 200 patients having undergone ACDF, one using rhBMP-2 and the other using ICBG, to evaluate the incidence of complications in the early postoperative period. A significant reduction in average length of stay was found in the rhBMP-2 cohort (1.40days) compared to the ICBG cohort (1.85days) as well as a significantly increased rate of dysphagia (25.5% in rhBMP-2 vs. 15% in ICBG; p=0.01). An increased rate of dysphonia was observed among patients undergoing revision surgery (25.0%) compared to primary surgery (1.6%), but stratification by number of levels, gender, and smoking status yielded no differences in complication rates. Our evaluation of two large cohorts along with review of the literature on the topic sheds light on potential benefits and risks of rhBMP-2 in ACDF procedures. Further investigation is warranted to determine if clinical gains outweigh the potential harms of rhBMP-2 use in this setting.


[Effects of nerve growth factor on intracellular free Ca2+ in oxygen/glucose-deprived cultures from cerebral cortex of fetal rats].
Oxygen/glucose deprived cortical cell cultures were used to explore the involvement of calcium in the mechanism of hypoxic/hypoglycemic insults and protection of nerve growth factor (NGF). Neuron viability and lactate dehydrogenase(LDH) efflux in the bathing medium of cerebral cortex cultures of fetal rats were measured as indication of the NGF effect. Calcium fluorescence indicator Fura-2/AM was used to measure free intracellular calcium([Ca2+]i). When cultures were deprived of oxygen/glucose, massive neuronal death occurred 16-24 h following the onset of hypoxia/hypoglycemia. NGF(3-100 micrograms.L-1) dose-dependenly attenuated the 24 h hypoxia/hypoglycemia-induced efflux of LDH and elevated the number of surviving neurons. Hypoxia/hypoglycemia induced a reduction in [Ca2+]i in early stage and then a large elevation of [Ca2+]i in 12-24 h. NGF 50 micrograms.L-1 brought [Ca2+]i to normal limits during the early stage of hypoxia/hypoglycemia and prevented the later elevation in [Ca2+]i. The [Ca2+]i elevation may be involved in the cell damage in hypoxia/hypoglycemia deprived cultures. It is believed that NGF protect cerebral cortical neurons against hypoxic/hypoglycemic insults via 'stabilizing' [Ca2+]i level or preventing the late rise in [Ca2+]i.


Immunoregulatory molecules and IL 2 receptors identified in multiple sclerosis brain.
Frozen brain specimens from eight multiple sclerosis (MS) patients were examined for the presence of leukocytes and their cell products by using a panel of monoclonal antibodies. The results presented here demonstrated that in the MS lesion, there was a marked accumulation of HLA-Dr-positive (Ia-positive) cells. These Ia-positive cells were identified as being glial fibrillary acidic protein positive by using double staining methods. Furthermore, the cells in the MS lesion expressed the interleukin 2 (IL 2) receptor, as identified by the anti-TAC monoclonal antibody. The cells in the region of the plaque also exhibited positive staining with antibodies to IL 1, IL 2, and prostaglandin E. Neither normal brain nor brain specimens from progressive multifocal leukoencephalopathy or Alzheimer's disease showed such patterns of staining. These results suggest that stimulated cells are present in the MS brain, thus implicating an active immune mechanism in the pathogenesis of MS.


Lung function and respiratory symptoms in association with mortality: The HUNT Study.
Whether respiratory symptoms are associated with mortality independent of lung function is unclear. The authors explored the association of the exposures i) lung function, ii) respiratory symptoms, and iii) lung function and respiratory symptoms combined, with the outcomes all-cause and cardiovascular mortality. The study included 10,491 adults who participated in the Nord-Trøndelag Health Study (HUNT) Lung Study in 1995-1997 and were followed through 2009. Cox regression was used to calculate adjusted hazard ratios (HRs) with 95% confidence intervals for all-cause and cardiovascular mortality associated with pre-bronchodilator% predicted forced expiratory volume in 1 second (ppFEV1), chronic obstructive pulmonary disease (COPD) grades, and respiratory symptoms (chronic bronchitis, wheeze, and levels of dyspnoea). Lung function was inversely associated with all-cause mortality. Compared to ppFEV1 ≥100, ppFEV1 <50 increased the HR to 6.85 (4.46-10.52) in women and 3.88 (2.60-5.79) in men. Correspondingly, compared to normal airflow, COPD grade 3 or 4 increased the HR to 6.50 (4.33-9.75) in women and 3.57 (2.60-4.91) in men. Of the respiratory symptoms, only dyspnoea when walking remained associated with all-cause mortality after controlling for lung function (HR 1.73 [1.04-2.89] in women and 1.57 [1.04-2.36] in men). Analyses of lung function and dyspnoea when walking as a combined exposure further supported this finding. Overall, associations between lung function and cardiovascular mortality were weaker, and respiratory symptoms were not associated with cardiovascular mortality. In conclusion, lung function was inversely associated with all-cause and cardiovascular mortality, and dyspnoea when walking was associated with all-cause mortality independent of lung function.


Spin susceptibility of two-dimensional electrons in narrow AlAs quantum wells.
We report measurements of the spin susceptibility in dilute two-dimensional electrons confined to a 45 A wide AlAs quantum well. The electrons in this well occupy an out-of-plane conduction-band valley, rendering a system similar to two-dimensional electrons in Si-MOSFETs but with only one valley occupied. We observe an enhancement of the spin susceptibility over the band value that increases as the density is decreased, following closely the prediction of quantum Monte Carlo calculations and continuing at finite values through the metal-insulator transition.


Toxic epidermal necrolysis related to AP (pemetrexed plus cisplatin) and gefitinib combination therapy in a patient with metastatic non-small cell lung cancer.
Toxic epidermal necrolysis (TEN) is a rare acute life-threatening mucocutaneous disorder that is mostly drug-related (80%-95%). It is clinically characterized as a widespread sloughing of the skin and mucosa. AP regimen (pemetrexed plus cisplatin) has been the preferred first-line chemotherapy for metastatic non-squamous non-small cell lung cancer (NSCLC). Gefitinib, a small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has already been recommended as a first-line treatment in EGFR-mutant metastatic NSCLC. We report rare presentation of TEN involving adverse effects of AP and gefitinib combination treatment in a 42-year-old woman diagnosed with metastatic NSCLC harboring an EGFR mutation. On the 21st day after administration of the first cycle of AP regimen and the 8th day after the initiation of gefitinib treatment, she developed an acne-like rash, oral ulcer, and conjunctivitis, which later became blisters and ultimately denuded. The characteristic clinical courses were decisive for the diagnosis of TEN. Treatment with systemic steroids and immunoglobulin as well as supportive treatment led to an improvement of her general condition and a remarkable recovery.


DNA fingerprints of Streptococcus pyogenes are M type specific.
DNA from group A streptococci of various M and T types was cleaved with endonucleases to produce a DNA fingerprint. Comparison of DNA fingerprints proved to be a very useful tool for studying the epidemiology of isolates from various outbreaks of streptococcal disease. Patterns of DNA fragments from HindIII digests of samples of total DNA were conserved among strains of the same M serotype yet were easily distinguished from those of different M serotypes. Different M types were associated with specific restriction enzyme profiles. DNA fingerprints of strains of the same M type were stable enough to establish a clonal relationship between strains obtained from an isolated outbreak of disease or strains endogenous to people geographically isolated by continent. Strains of the same serotype from different continents had very similar, but distinguishable, restriction profiles. Those strains unable to be typed with standard typing sera were also amenable to comparison because they yielded unique fingerprints.


Contextual learning requires synaptic AMPA receptor delivery in the hippocampus.
The hippocampus plays a central role in learning and memory. Although synaptic delivery of AMPA-type glutamate receptors (AMPARs) contributes to experience-dependent synaptic strengthening, its role in hippocampus-dependent learning remains elusive. By combining viral-mediated in vivo gene delivery with in vitro patch-clamp recordings, we found that the inhibitory avoidance task, a hippocampus-dependent contextual fear-learning paradigm, delivered GluR1-containing AMPARs into CA3-CA1 synapses of the dorsal hippocampus. To block the synaptic delivery of endogenous AMPARs, we expressed a fragment of the GluR1-cytoplasmic tail (the 14-aa GluR1 membrane-proximal region with two serines mutated to phospho-mimicking aspartates: MPR-DD). MPR-DD prevented learning-driven synaptic AMPAR delivery in CA1 neurons. Bilateral expression of MPR-DD in the CA1 region of the rat impaired inhibitory avoidance learning, indicating that synaptic GluR1 trafficking in the CA1 region of the hippocampus is required for encoding contextual fear memories. The fraction of CA1 neurons that underwent synaptic strengthening positively correlated with the performance in the inhibitory avoidance fear memory task. These data suggest that the robustness of a contextual memory depends on the number of hippocampal neurons that participate in the encoding of a memory trace.


Recurrence Quantification Analysis of Crowd Sound Dynamics.
When multiple individuals interact in a conversation or as part of a large crowd, emergent structures and dynamics arise that are behavioral properties of the interacting group rather than of any individual member of that group. Recent work using traditional signal processing techniques and machine learning has demonstrated that global acoustic data recorded from a crowd at a basketball game can be used to classify emergent crowd behavior in terms of the crowd's purported emotional state. We propose that the description of crowd behavior from such global acoustic data could benefit from nonlinear analysis methods derived from dynamical systems theory. Such methods have been used in recent research applying nonlinear methods to audio data extracted from music and group musical interactions. In this work, we used nonlinear analyses to extract features that are relevant to the behavioral interactions that underlie acoustic signals produced by a crowd attending a sporting event. We propose that recurrence dynamics measured from these audio signals via recurrence quantification analysis (RQA) reflect information about the behavioral dynamics of the crowd itself. We analyze these dynamics from acoustic signals recorded from crowds attending basketball games, and that were manually labeled according to the crowds' emotional state across six categories: angry noise, applause, cheer, distraction noise, positive chant, and negative chant. We show that RQA measures are useful to differentiate the emergent acoustic behavioral dynamics between these categories, and can provide insight into the recurrence patterns that underlie crowd interactions.


Comparative Evaluation of the Remineralizing Potential of Silver Diamine Fluoride, Casein Phosphopeptide-amorphous Calcium Phosphate, and Fluoride Varnish on the Enamel Surface of Primary and Permanent Teeth: An In Vitro Study.
With the paradigm shift in the management of dental caries, the focus is now laid on remineralization therapies that can arrest the progression of the disease and remineralize the subsurface lesions. The purpose of this study was to determine and compare the remineralizing potential of silver diamine fluoride (SDF), casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), and fluoride varnish (FV) on enamel surfaces in primary and permanent teeth. A total of 120 primary anterior teeth and 120 premolars were used to prepare enamel blocks in acrylic resin. The mean baseline surface microhardness (SMH) for each sample was determined using a microvickers hardness testing machine. Thereafter, the samples were randomly and equally distributed into groups and subgroups based on the materials used, that is, SDF, CPP-ACP, FV, and distilled water (control). After subjecting the samples to a pH cycling regime, SMH was determined again and the percentage change in SMH was calculated. The data were tabulated and subjected to statistical analysis using an independent t-test and one-way analysis of variance (ANOVA). In primary teeth, the least mean percentage reduction in SMH was observed after the application of FV followed by SDF, CPP-ACP, and control. In permanent teeth, both SDF and FV showed the least percentage reduction of enamel SMH followed by CPP-ACP and control. Silver diamine fluoride (SDF), FV, and CPP-ACP showed remineralizing potential in both primary and permanent teeth. Kaur S, Bhola M, Bajaj N, et al. Comparative Evaluation of the Remineralizing Potential of Silver Diamine Fluoride, Casein Phosphopeptide-amorphous Calcium Phosphate, and Fluoride Varnish on the Enamel Surface of Primary and Permanent Teeth: An In Vitro Study. Int J Clin Pediatr Dent 2023;16(S-1):S91-S96.


The influence of different contrast medium concentrations and injection protocols on quantitative and clinical assessment of FDG-PET/CT in lung cancer.
To compare the effects of two different contrast medium concentrations for use in computed X-ray tomography (CT) employing two different injection protocols on positron emission tomography (PET) reconstruction in combined 2-(18)F-desoxyglucose (FDG) PET/CT in patients with a suspicion of lung cancer. 120 patients with a suspicion of lung cancer were enrolled prospectively. PET images were reconstructed with the non-enhanced and venous phase contrast CT obtained after injection of iopromide 300 mg/ml or 370 mg/ml using either a fixed-dose or a body surface area adapted injection protocol. Maximum and mean standardized uptake values (SUV(max) and SUV(mean)) and contrast enhancement (HU) were determined in the subclavian vein, ascending aorta, abdominal aorta, inferior vena cava, portal vein, liver and kidney and in the suspicious lung lesion. PET data were evaluated visually for the presence of malignancy and image quality. At none of the sites a significant difference in the extent of the contrast enhancement between the four different protocols was found. However, the variability of the contrast enhancement at several anatomical sites was significantly greater in the fixed dose groups than in the BSA groups for both contrast medium concentrations. At none of the sites a significant difference was found in the extent of the SUV(max) and SUV(mean) increase as a result of the use of the venous phase contrast enhanced CT for attenuation. Visual clinical evaluation of lesions showed no differences between contrast and non-contrast PET/CT (P=0.32). Contrast enhanced CT for attenuation correction in combined PET/CT in lung cancer affects neither the clinical assessment nor image quality of the PET-images. A body surface adapted contrast medium protocol reduces the interpatient variability in contrast enhancement.


Prediction of Myocardial Infarction From Patient Features With Machine Learning.
This study proposes machine learning-based models to automatically evaluate the severity of myocardial infarction (MI) from physiological, clinical, and paraclinical features. Two types of machine learning models are investigated for the MI assessment: the classification models classify the presence of the infarct and the persistent microvascular obstruction (PMO), and the regression models quantify the Percentage of Infarcted Myocardium (PIM) of patients suspected of having an acute MI during their reception in the emergency department. The ground truth labels for these supervised models are derived from the corresponding Delayed Enhancement MRI (DE-MRI) exams and manual annotations of the myocardium and scar tissues. Experiments were conducted on 150 cases and evaluated with cross-validation. Results showed that for the MI (PMO inclusive) and the PMO (infarct exclusive), the best models obtained respectively a mean error of 0.056 and 0.012 for the quantification, and 88.67 and 77.33% for the classification accuracy of the state of the myocardium. The study of the features' importance also revealed that the troponin value had the strongest correlation to the severity of the MI among the 12 selected features. For the proposal's translational perspective, in cardiac emergencies, qualitative and quantitative analysis can be obtained prior to the achievement of MRI by relying only on conventional tests and patient features, thus, providing an objective reference for further treatment by physicians.


Oral ondansetron for paediatric gastroenteritis in primary care: a randomised controlled trial.
Acute gastroenteritis (AGE) affects almost all children aged ≤5 years. In secondary care, ondansetron was found to be effective at reducing vomiting. To determine the effectiveness of adding oral ondansetron to care as usual (CAU) to treat vomiting in children with AGE attending out-ofhours primary care (OOH-PC). A pragmatic randomised controlled trial at three OOH-PC centres in the north of the Netherlands (Groningen, Zwolle, and Assen), with a follow-up of 7 days. Children were included if they were: aged 6 months-6 years; AGE diagnosed by a GP; ≥4 reported episodes of vomiting in the 24 hours before presentation; ≥1 reported episode of vomiting in the 4 hours before presentation; and written informed consent from both parents. Children were randomly allocated to either the control group or the intervention group. The control group received CAU, namely oral rehydration therapy. The intervention group received CAU plus one dose of oral ondansetron (0.1 mg/kg). In total, 194 children were included for randomisation. One dose of oral ondansetron decreased the proportion of children who continued vomiting within 4 hours from 42.9% to 19.5%, with an odds ratio of 0.37 (95% confidence interval [CI] = 0.20 to 0.72, number needed to treat: four). Ondansetron also decreased the number of vomiting episodes within 4 hours (incidence rate ratio 0.51 [95% CI = 0.29 to 0.88]) and improved overall parental satisfaction with treatment (P = 0.027). Children with AGE and increased risk of dehydration due to vomiting could be treated with ondansetron in primary care to stop vomiting more quickly and increase parental satisfaction with treatment. These results could be used to improve the quality and efficacy of general practice medicine.


Evidence-based (informed) macro practice: process and philosophy.
Evidence-informed practice and policy at the macro level offers great potential for honoring ethical guidelines to integrate practice and research, to involve clients as informed participants, to respond ethically to problems of scarce resources, to enhance social and economic justice, and to empower clients. The process and philosophy of evidence-informed practice and care as described in original sources suggest a decision-making process designed to help social workers to integrate ethical, evidentiary, and application concerns. As with all innovations, objections will and should be raised. There are many challenges and obstacles to integrating evidentiary, ethical, and application concerns in practice.


A bioinspired metal-organic approach to cross-linked functional 3D nanofibrous hydro- and aero-gels with effective mixture separation of nucleobases by molecular recognition.
The direct reaction between Cu(CH3COO)2 and uracil-1-acetic acid in water gives rise to the formation of a hydrogel consisting of entangled nanometric ribbons of a crystalline antiferromagnetic 1D Cu(ii) coordination polymer (CP) decorated with biocompatible uracil nucleobases. This hydrogel is the precursor for the preparation of a meso/macroporous ultralight aerogel that shows a remarkable Young's modulus. As a proof-of-concept of the molecular recognition capability of the terminal uracil moieties anchored at Cu(ii) CP chains, this material has been tested as the selective stationary phase for the separation of nucleobase derivatives in HPLC columns.


GSE1 predicts poor survival outcome in gastric cancer patients by SLC7A5 enhancement of tumor growth and metastasis.
Gastric cancer remains a malignancy with poor survival outcome. We herein report that GSE1, a proline-rich protein, possesses a role in the progression of human gastric cancer. The expression of GSE1 was observed to be much higher in human gastric cancer tissues compared with normal gastric tissues, and GSE1 expression correlated positively with lymph node metastasis, histological grade, depth of invasion, and clinical stage in gastric cancer patients. Moreover, GSE1 expression was also associated with decreased post-operative relapse-free survival and overall survival in the cohort. The forced expression of GSE1 in gastric cancer cell lines resulted in increased cell proliferation, increased colony formation, enhanced cell migration, and invasion. Furthermore, forced expression of GSE1 also increased tumor size and enhanced lung metastasis in xenograft models. The depletion of endogenous GSE1 with shRNAs decreased the oncogenicity and invasiveness of gastric cancer cells both in vitro and in vivo In addition, GSE1 was determined to be a direct target of miR-200b and miR-200c. Furthermore, GSE1 positively regulated the downstream gene SLC7A5 (also known as LAT-1), which was scanned and verified from mRNA sequencing. GSE1 therefore possesses an oncogenic role in human gastric cancer, and targeted therapeutic approaches to inhibit GSE1 function in gastric cancer warrant further consideration.


New loci and neuronal pathways for resilience to heat stress in cattle.
While understanding the genetic basis of heat tolerance is crucial in the context of global warming's effect on humans, livestock, and wildlife, the specific genetic variants and biological features that confer thermotolerance in animals are still not well characterized. We used dairy cows as a model to study heat tolerance because they are lactating, and therefore often prone to thermal stress. The data comprised almost 0.5 million milk records (milk, fat, and proteins) of 29,107 Australian Holsteins, each having around 15 million imputed sequence variants. Dairy animals often reduce their milk production when temperature and humidity rise; thus, the phenotypes used to measure an individual's heat tolerance were defined as the rate of milk production decline (slope traits) with a rising temperature-humidity index. With these slope traits, we performed a genome-wide association study (GWAS) using different approaches, including conditional analyses, to correct for the relationship between heat tolerance and level of milk production. The results revealed multiple novel loci for heat tolerance, including 61 potential functional variants at sites highly conserved across 100 vertebrate species. Moreover, it was interesting that specific candidate variants and genes are related to the neuronal system (ITPR1, ITPR2, and GRIA4) and neuroactive ligand-receptor interaction functions for heat tolerance (NPFFR2, CALCR, and GHR), providing a novel insight that can help to develop genetic and management approaches to combat heat stress.


Salivary Gland Dysfunction, Protein Glycooxidation and Nitrosative Stress in Children with Chronic Kidney Disease.
This study is the first to evaluate protein glycooxidation products, lipid oxidative damage and nitrosative stress in non-stimulated (NWS) and stimulated whole saliva (SWS) of children with chronic kidney disease (CKD) divided into two subgroups: normal salivary secretion (n = 18) and hyposalivation (NWS flow < 0.2 mL min-1; n = 12). Hyposalivation was observed in all patients with severe renal failure (4-5 stage CKD), while saliva secretion > 0.2 mL/min in children with mild-moderate CKD (1-3 stage) and controls. Salivary amylase activity and total protein content were significantly lower in CKD children with hyposalivation compared to CKD patients with normal saliva secretion and control group. The fluorescence of protein glycooxidation products (kynurenine, N-formylkynurenine, advanced glycation end products), the content of oxidative damage to lipids (4-hydroxynonneal, 8-isoprostanes) and nitrosative stress (peroxynitrite, nitrotyrosine) were significantly higher in NWS, SWS, and plasma of CKD children with hyposalivation compared to patients with normal salivary secretion and healthy controls. In CKD group, salivary oxidation products correlated negatively with salivary flow rate, -amylase activity and total protein content; however, salivary oxidation products do not reflect their plasma level. In conclusion, children with CKD suffer from salivary gland dysfunction. Oxidation of salivary proteins and lipids increases with CKD progression and deterioration of salivary gland function.


The effects of coordinative locomotor training on coordination and gait in chronic stroke patients: a randomized controlled pilot trial.
The purpose of this study was to investigate the effects of coordinative locomotor training (CLT) on coordination and gait in chronic stroke patients. Thirteen stroke patients were randomly assigned to one of two groups: The experimental group (EG, n=7) and control group (CG, n=6). After balanced random assignment, interventions were provided to all patients in twelve 30-min sessions during a 4-week period (3 sessions a week). The EG group underwent CLT after performing the sprinter and skater patterns in four postures. The CG group was provided with conventional neurodevelopment treatment. The primary outcomes were measured using the gait assessment and intervention tool (GAIT) as well as G-WALK. The secondary outcomes were measured using a 10-m walk test (10 MWT) and Timed Up and Go Test. There was no statistically significant difference in the mean values between the two groups. Within both groups there were significant differences in GAIT and 10MWT. There were significant differences in gait speed and stride length in the experimental group, but not in the control group. CLT showed a more positive improvement in gait and coordination after stroke than conventional rehabilitation exercise.


[The informational support of statistical observation related to children disability].
Within the framework of the Convention on rights of the disabled the revision is specified concerning criteria of identification of disability of children and reformation of system of medical social expertise according international standards of indices of health and indices related to health. In connection with it, it is important to consider the relationship between alterations in forms of the Federal statistical monitoring in the part of registration of disabled children in the Russian Federation and classification of health indices and indices related to health applied at identification of disability. The article presents analysis of relationship between alterations in forms of the Federal statistical monitoring in the part of registration of disabled children in the Russian Federation and applied classifications used at identification of disability (International classification of impairments, disabilities and handicap (ICDH), international classification of functioning, disability and health (ICF), international classification of functioning, disability and health, version for children and youth (ICF-CY). The intersectorial interaction is considered within the framework of statistics of children disability.


Measuring child maltreatment: a comparison of prospective parent reports and retrospective adolescent reports.
Using Lehigh Longitudinal Study data (N = 457), the authors compare prospective parent self-reports and retrospective adolescent reports of early childhood physical abuse, exploring their correspondence, predictive equivalence, and outcomes associated with conflicting reports. Correspondence between prospective and retrospective reports of child maltreatment was moderate (Phi = 0.27). Concurrence rates were similar for males and females. Analyses of the relative predictive capacity of prospective and retrospective measures revealed both to be significant predictors of key outcomes in adolescence. Findings support the predictive validity of both measures of childhood maltreatment and underscore the methodological challenges of measuring this important construct. Given the abundance and salience of research on the consequences of childhood maltreatment, greater attention to such measurement issues is due.


Anamorelin for patients with cancer cachexia: an integrated analysis of two phase 2, randomised, placebo-controlled, double-blind trials.
Cancer anorexia-cachexia syndrome is associated with increased morbidity and mortality. Anamorelin is an oral ghrelin-receptor agonist with appetite-enhancing and anabolic activity. We assessed the effects of anamorelin on body composition, strength, quality of life, biochemical markers, and safety in patients with cancer anorexia-cachexia. Data were pooled, a priori, from two completed phase 2, multicentre, placebo-controlled, double-blind trials in patients with advanced or incurable cancer and weight loss of 5% or more. Patients were stratified by weight loss severity (5-15%, >15%) and randomly allocated (1:1) with a computer-generated randomisation schedule to anamorelin hydrochloride 50 mg or placebo once-daily for 12 weeks. Primary outcome was lean body mass by dual-energy x-ray absorptiometry over the 12 week treatment period in eligible patients who had at least one dose of study drug and post-treatment efficacy assessment. We assessed safety in all patients who received at least one dose of study drug. The trials are registered with ClinicalTrials.gov, numbers NCT00219817 and NCT00267358. Between June 29, 2005, and Oct 26, 2006, we enrolled 44 patients in the anamorelin group and 38 patients in the placebo group. 74 patients were eligible for the efficacy analyses. Over 12 weeks, lean body mass increased in 38 patients in the anamorelin group by a least-squares mean of 1.89 kg (95% CI 0.84 to 2.95) compared with a decrease of a least-squares mean of -0.20 kg (-1.23 to 0.83) for 36 patients in the placebo group (difference 2.09 kg [0.94-3.25]; p=0.0006). 42 (95%) of 44 patients treated with anamorelin and 33 (87%) of 38 patients treated with placebo had adverse events. The most common grade 3-4 adverse events (treatment-related or not) in the anamorelin group were fatigue, asthenia, atrial fibrillation, and dyspnoea (two [5%] each); in the placebo group, such events were pneumonia (three [8%]) and anaemia, thrombocytopenia, abdominal pain, anxiety, and dyspnoea (two [5%] each). Anamorelin treatment for 12 weeks had a favourable clinical response profile in patients with cancer anorexia-cachexia syndrome. These findings support further investigation in this setting. Helsinn Therapeutics (US), Helsinn Healthcare SA.


An exploratory, cross-cultural study on perception of putative cyclical changes in facial fertility cues.
Although many researchers have argued that facial traits evolved as honest cues to women's current fertility (possibly via changes in facial femininity), evidence that women's facial attractiveness is significantly, positively related to probability of conception throughout menstrual cycle is mixed. These mixed results could reflect differences among studies in the methods used to assess facial attractiveness (i.e., forced choice versus rating-scale methods), differences in how fertility was assessed, differences in perceiver characteristics (e.g., their own attractiveness), and facial preferences possibly being moderated by the characteristics of the living environment. Consequently, the current study investigated the putative effect of cyclical changes in fertility on women's facial attractiveness and femininity (1) using forced choice and rating-scale method, (2) conducting both ovulation tests and repeated daily measures of estradiol assessing the conception probability, (3) based on a culturally diverse sample of perceivers, while (4) controlling for inter-individual variation. Although we found some limited evidence that women's faces became more attractive when conception probability increased, these effects differed depending on the methods used to assess both attractiveness and fertility. Moreover, where statistically significant effects were observed, the effect sizes were extremely small. Similarly, there was little robust evidence that perceivers' characteristics reliably predicted preferences for fertility cues. Collectively, these results suggest that mixed results in previous studies examining cyclical fluctuation in women's facial attractiveness are unlikely to reflect inter-cultural differences and are more likely to reflect differences in the methods used to assess facial attractiveness and fertility.


Histological Effects of the Combined Administration of Eldecalcitol and a Parathyroid Hormone in the Metaphyseal Trabeculae of Ovariectomized Rats.
Intermittent administration of human parathyroid hormone (1-34) (hPTH(1-34)) promotes anabolic action in bone by stimulating bone remodeling, while eldecalcitol, an analog of active vitamin D3, suppresses osteoclastic bone resorption, and forms new bone by minimodeling. We have examined the biological effects of combined administration of eldecalcitol and hPTH(1-34) on 9-week-old Wistar rats that underwent an ovariectomy (OVX) or Sham operation. They were divided into a Sham group, OVX with vehicle (OVX group), OVX with 10 µg/kg/day of hPTH(1-34) (PTH group), OVX with 20 ng/kg/day of eldecalcitol (eldecalcitol group) or OVX with 10 μg/kg/day of hPTH(1-34), and 20 ng/kg/day of eldecalcitol (combined group) for 4 or 8 weeks. As a consequence, the combined group showed a marked increase in bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N) than OVX and had the highest bone mineral density (BMD) compared with other groups. OVX and PTH groups exhibited a high osteoblastic surface/bone surface (Ob.S/BS), mineral apposition rate (MAR), and bone formation rate/bone surface (BFR/BS) indices and many TRAP-reactive osteoclasts. Contrastingly, eldecalcitol and combined groups tended to attenuate the indices of osteoclastic surface/bone surface (Oc.S/BS) and Ob.S/BS than that the other groups. The combined group revealed histological profiles of minimodeling- and remodeling-based bone formation. Thus, the combined administration of eldecalcitol and hPTH(1-34) augments their anabolic effects by means of minimodeling and remodeling.


[22q11 deletion syndrome].
22q11 deletion syndrome (formerly named CATCH22, DiGeorge, Velo-Cardio-Facial, Caylor, Kinouchi and Shprintzen syndrome) occurs in approximately 1/2000 to 4000 children. The genetic lesion is remarkably uniform, occurring mainly as 3 or 1.5 MB deletions in the 22q11.2 region. However, the clinical manifestations are variable and manifestation in several organ systems often occur. In this review we describe the various manifestations of the syndrome. Finally, we suggest strategies for diagnosing, evaluating and organizing the treatment for Danish patients with this syndrome.


Polystyrene Nanofiber Materials for Visible-Light-Driven Dual Antibacterial Action via Simultaneous Photogeneration of NO and O2((1)Δg).
This contribution reports on the preparation, characterization, and biological evaluation of electrospun polystyrene nanofiber materials engineered with a covalently grafted NO photodonor and ionically entangled tetracationic porphyrin and phthalocyanine photosensitizers. These photofunctional materials exhibit an effective and simultaneous photogeneration of two antibacterial species such as nitric oxide (NO) and singlet oxygen, O2((1)Δg) under illumination with visible light, as demonstrated by their direct detection using amperometric and time-resolved spectroscopic techniques. Dual-mode photoantibacterial action is demonstrated by antibacterial tests carried out on Escherichia coli.


[How threatening is a diverticulitis: what do we know about the long-term course?].
In the context of the controversy regarding the appropriate management of colon diverticulitis without generalised peritonitis - conservative or operative - a review of the literature was per-formed. The progress in diagnostic and therapeutic measures has led to a change in the therapeutic approach during the last 10 years. Because of the lack of randomised controlled trials in patients with diverticulitis (without generalised -peritonitis) comparing medical and surgical treatments, there are still several unanswered questions, such as whether and when to operate and what the recurrence rate is, especially after medical treatment. The therapeutic management should be oriented to the individual symptoms, the comorbidity and the age of the patients.


Uptake of and response to norepinephrine by certain tissues of hypertensive rats.
A decrease in the capacity of the sympathetic nervous system of hypertensive rats to take up norepinephrine (NE) has been previously described. In the present study, rats were made hypertensive by one of the following technics: "adrenal regeneration," figure-of-eight knot around one kidney, ingestion of a 10% NaCl solution. After 2 mo, the adrenal regeneration rats were hypertensive, and there was a significant decrease in the capacity of their hearts to take up NE as well as a significant increase in the inotropic response to the amine. Similar results were obtained with hearts and aortic strips of renal hypertensive rats, as well as of rats made hypertensive by drinking a 10% NaCl solution. In renal hypertensive rats, there was no appreciable difference in the time of appearance of hypertension, the decrease in NE uptake by the heart or aorta, or the increase of the inotropic response. Previous work showing a decrease of NE uptake in rats made hypertensive by administration of deoxycorticosterone has been confirmed utilizing three other models of the disease.


Storyboarding as an aid to learning about death in children's nursing.
The sudden or anticipated death of a child is one of the most challenging and unique experiences that children's nursing students will encounter in practice. There is evidence to suggest that the effect this can have on a practitioner can affect quality of care. Although education for nurses about dealing with death has been studied, there is limited research into the education of those working with dying children and how effective it is in preparing them to deal with the situation. This deficit presents those involved in children's nurse education with a significant challenge and an opportunity to be innovative. This article examines the use of storyboarding as a creative teaching tool to enable children's nursing students to reflect on their experiences of working with children and families in death situations. The wider implications for the use of this technique in practice and education are considered.


Metabolic syndrome: a closer look at the growing epidemic and its associated pathologies.
Obesity is reaching epidemic proportions with recent worldwide figures estimated at 1.4 billion and rising year-on-year. Obesity affects all socioeconomic backgrounds and ethnicities and is a pre-requisite for metabolic syndrome. Metabolic syndrome is a clustering of risk factors, such as central obesity, insulin resistance, dyslipidaemia and hypertension that together culminate in the increased risk of type 2 diabetes mellitus and cardiovascular disease. As these conditions are among the leading causes of deaths worldwide and metabolic syndrome increases the risk of type 2 diabetes mellitus fivefold and cardiovascular disease threefold, it is of critical importance that a precise definition is agreed upon by all interested parties. Also of particular interest is the relationship between metabolic syndrome and cancer. Metabolic syndrome has been associated with a plethora of cancers including breast, pancreatic, colon and liver cancer. Furthermore, each individual risk factor for metabolic syndrome has also an association with cancer. Our review collates internationally generated information on metabolic syndrome, its many definitions and its associations with life-threatening conditions including type 2 diabetes mellitus, cardiovascular disease and cancer, providing a foundation for future advancements on this topic.


Fibroblasts from ataxia telangiectasia (AT) and AT heterozygotes show an enhanced level of residual DNA double-strand breaks after low dose-rate gamma-irradiation as assayed by pulsed field gel electrophoresis.
Skin fibroblasts from ataxia telangiectasia (AT) patients, obligate AT heterozygotes (ATH) and normal individuals were studied for colony-forming ability and repair of DNA double-strand breaks (dsb) after gamma-irradiation. AT cells were three to four times more radiosensitive than normal cells at high and low dose-rate exposures; ATH cells, however, showed a marginally increased radiosensitivity after high dose-rate gamma-irradiation and an intermediate response after low dose-rate exposure. The repair of DNA dsb was studied by pulsed field gel electrophoresis. After high dose-rate gamma-irradiation the repair time constant (t1/2) was around 1 h for normal, ATH and AT cells. After low dose-rate gamma-irradiation the fraction of residual dsb was 1.4% for normal, 2.1% for ATH and 5.2% for AT cells, demonstrating a deficiency in the repair of a small fraction of dsb in AT. Thus the fraction of residual dsb after low dose-rate exposure was not only four times higher in AT than in normal cells, but was also significantly increased in ATH compared to normal cells.


Cytotoxicity and gene expression changes induced by inorganic and organic trivalent arsenicals in human cells.
Inorganic arsenic (iAs) is a human urinary bladder, skin and lung carcinogen. iAs is metabolized to methylated arsenicals, with trivalent arsenicals more cytotoxic than pentavalent forms in vitro. In this study, cytotoxicity and gene expression changes for arsenite (iAs(III)), monomethylarsonous acid (MMA(III)) and dimethylarsinous acid (DMA(III)) were evaluated in three human cell types, urothelial (1T1), keratinocyte (HEK001) and bronchial epithelial (HBE) cells, corresponding to target organs for iAs-induced cancer. Cells were exposed to arsenicals to determine cytotoxicity and to study gene expression changes. Affymetrix chips were used to determine differentially expressed genes (DEGs) by statistical analysis. Lethal concentrations (LC50) for trivalent arsenicals in all cells ranged from 1.6 to 10μM. MMA(III) and DMA(III) had 4-12-fold greater potency compared to iAs. Increasing concentrations of iAs(III) induced more genes and additional signaling pathways in HBE cells. At equivalent cytotoxic concentrations, greater numbers of DEGs were induced in 1T1 cells compared to the other cells. Each arsenical altered slightly different signaling pathways within and between cell types, but when altered pathways from all three arsenicals were combined, they were similar between cell types. The major signaling pathways altered included NRF2-mediated stress response, interferon, p53, cell cycle regulation and lipid peroxidation. These results show a similar process qualitatively and quantitatively for all three cell types, and support a mode of action involving cytotoxicity and regenerative proliferation.


Opportunities for Chemistry at the SwissFEL X-ray Free Electron Laser.
X-ray techniques have long been applied to chemical research, ranging from powder diffraction tools to analyse material structure to X-ray fluorescence measurements for sample composition. The development of high-brightness, accelerator-based X-ray sources has allowed chemists to use similar techniques but on more demanding samples and using more photon-hungry methods. X-ray Free Electron Lasers (XFELs) are the latest in the development of these large-scale user facilities, opening up new avenues of research and the possibility of more advanced applications for a range of research. The SwissFEL XFEL project at the Paul Scherrer Institute will begin user operation in the hard X-ray (2.1-12.4 keV) photon energy range in 2018 with soft X-ray (240-1930 eV) user operation to follow and here we will present the details of this project, it's operating capabilities, and some aspects of the experimental stations that will be particularly attractive for chemistry research. SwissFEL is a revolutionary new machine that will complement and extend the time-resolved chemistry efforts in the Swiss research community.


Phase noise suppression technique based on an improved reference interferometer scheme.
The reference interferometer scheme is an effective noise reduction method, but the optical path length difference (OPD) of the two interferometers must be strictly equal, which limits its application in practical environments. In this paper, an improved reference interferometer demodulation technique without strictly equal OPDs is proposed to suppress phase noise. By introducing a reference interferometer, the phase noise can be removed from the demodulation results. The combination of the differential self-multiplication algorithm and the fitted phase modulation depth calculation formula can evaluate the phase modulation depth of both interferometers in real time and simultaneously eliminate the nonlinear distortion caused by phase modulation depth drift and the effect of different OPDs on the reference interferometer scheme. The experimental results show that the technique can obtain highly stable and accurate demodulation results even if the OPDs of the two reference interferometers are different. The phase modulation depth calculation error is less than 0.57%, the maximum phase noise reduction is 15 dB, the average reduction is 9 dB, the minimum total harmonic distortion is 0.17%, and the SINAD reaches 35.90 dB.


Contrasting coordination behavior of Group 12 perchlorate salts with an acyclic N3O2 donor ligand by X-ray crystallography and (1)H NMR.
An unbranched N3O2 ligand 2,6-bis[((2-pyridinylmethyl)oxy)methyl]pyridine (L1) was used to prepare new mononuclear heteroleptic Group 12 perchlorate complexes characterized by IR, (1)H NMR and X-ray crystallography. Racemic complexes with pentadentate L1 and one to four oxygens from either water or perchlorate bound to a metal ion were structurally characterized. Octahedral [Zn(L1)(OH2)](ClO4)2 (1) and pentagonal bipyramidal [Cd(L1)(OH2)(OClO3)]ClO4 (2) structures were found with lighter congeners. The polymorphic forms of [Hg(L1)(ClO4)2] characterized (3 in P1[combining macron] and 4 in P21/c) had a mix of monodentate, anisobidentate and bidentate perchlorates, providing the first examples of a tricapped trigonal prismatic Hg(ii) coordination geometry, as well as additional examples of a rare square antiprismatic Hg(ii) coordination geometry. Solution state (1)H NMR characterization of the Group 12 complexes in CD3CN indicated intramolecular reorganization remained rapid under conditions where intermolecular M-L1 exchange was slow on the chemical shift time scale for Zn(ii) and on the J(M(1)H) time scale for Cd(ii) and Hg(ii). Solution studies with more than one equivalent of ligand also suggested that a complex with a 1 : 2 ratio of M : L1 contributed significantly to solution equilibria with Hg(ii) but not the other metal ions. The behavior of related linear pentadentate ligands with Group 12 perchlorate salts is discussed.


Magnitude and Determinants of Uncontrolled Blood Pressure Among Adult Hypertensive Patients on Follow-Up at Nekemte Referral Hospital, Western Ethiopia.
Hypertension is the leading cause of morbidity and mortality among non-communicable diseases. The rate of blood pressure (BP) control among hypertensive patients is poor and the reasons for poor control of BP remain poorly understood globally. Therefore, this study aimed to assess the magnitude and determinants of uncontrolled blood pressure among adult hypertensive patients on follow-up at Nekemte referral hospital (NRH). A hospital-based cross-sectional study was conducted from February to April 2018 at NRH. BP control status was determined by the average consecutive BP recordings across the 3 months. The data was entered and analyzed using SPSS version 20.0 and p-value <0.05 was considered statistically significant. Out of 297 study participants included, the majority were females, 181 (60.9%), and the mean age of the patients was 59.4 ±10.4 years. About half, 137 (46.12%), of the patients had at least one comorbidity and the most common class of anti-hypertensive medication was angiotensin-converting enzyme inhibitors (88.2%). The mean of systolic blood pressure was 132.41± 15.61mmHg, while the mean of diastolic blood pressure was 84.37± 9.32 mmHg. The proportion of participants with optimally controlled BP was 63.6% and 36% were adherent to their medications. Male sex (Adjusted Odd Ratio [AOR]: 1.89, 95% CI: 1.09-4.84), illiteracy (AOR= 1.56, 95% CI: 1.22-6.78), duration of hypertension diagnosis > 10 years (AOR= 2.01, 95% CI: 1.04-16.11), non-adherence (AOR= 3.14, 95% CI: 1.35-10.76) and lack of physical exercise (AOR= 2.8, 95% CI: 1.16-6.74) were positively associated with uncontrolled BP status. Whereas age older than 55 years (AOR= 0.38, 95% CI: 0.11-0.92) was negatively associated with uncontrolled BP. BP control was relatively achieved in about two-third of pharmacologically treated patients. We recommend better health education and care of patients to improve the rate of BP control status.


Autophagy in Crohn's Disease: Converging on Dysfunctional Innate Immunity.
Crohn's disease (CD) is a chronic inflammatory bowel disease marked by relapsing, transmural intestinal inflammation driven by innate and adaptive immune responses. Autophagy is a multi-step process that plays a critical role in maintaining cellular homeostasis by degrading intracellular components, such as damaged organelles and invading bacteria. Dysregulation of autophagy in CD is revealed by the identification of several susceptibility genes, including ATG16L1, IRGM, NOD2, LRRK2, ULK1, ATG4, and TCF4, that are involved in autophagy. In this review, the role of altered autophagy in the mucosal innate immune response in the context of CD is discussed, with a specific focus on dendritic cells, macrophages, Paneth cells, and goblet cells. Selective autophagy, such as xenophagy, ERphagy, and mitophagy, that play crucial roles in maintaining intestinal homeostasis in these innate immune cells, are discussed. As our understanding of autophagy in CD pathogenesis evolves, the development of autophagy-targeted therapeutics may benefit subsets of patients harboring impaired autophagy.


Social Fear in US Infants: The Roles of Hair and Salivary Cortisol.
Elevated social fear in infancy poses risk for later social maladjustment and psychopathology. Hair cortisol concentration (HCC), an index of cumulative cortisol exposure, and diurnal salivary cortisol slope, a biomarker of acute stress regulation, have been associated with social fear behaviors in childhood; however, no research has addressed their relations in infancy. Elucidating potential biomarkers of infant social fear behaviors, as well as environmental factors associated with these biomarkers, may grant insights into the ontogeny of fear behaviors that increase risk for internalizing and externalizing psychopathologies later in life. The current study used multiple linear regression to examine if infant HCC, infant diurnal cortisol slope, and income-to-needs ratios (ITN) were differentially associated with observed social fear responses to a Stranger Approach task at 12 months. Using a sample of 90 infants (Mage = 12.26m, SD = 0.81m, 50% female), results indicated that increased infant HCC was associated with increased distress vocalizations during the Stranger Approach task, while steeper diurnal cortisol slope was associated with fewer distress vocalizations. Ordinary least squares path analyses did not reveal group differences between economically strained and non-strained infants in how cortisol measures and social fear responses related. Findings underscore very early psychobiological correlates of fearfulness that may increase risk for fear-related disorders and adverse mental health symptomology across childhood.


Calcium restriction allows cAMP activation of the B-Raf/ERK pathway, switching cells to a cAMP-dependent growth-stimulated phenotype.
cAMP can be either mitogenic or anti-mitogenic, depending on the cell type. We demonstrated previously that cAMP inhibited the proliferation of normal renal epithelial cells and stimulated the proliferation of cells derived from the cysts of polycystic kidney disease (PKD) patients. The protein products of the genes causing PKD, polycystin-1 and polycystin-2, are thought to regulate intracellular calcium levels, suggesting that abnormal polycystin function may affect calcium signaling and thus cause a switch to the cAMP growth-stimulated phenotype. To test this hypothesis, we disrupted intracellular calcium mobilization by treating immortalized mouse M-1 collecting duct cells and primary cultures of human kidney epithelial cells with calcium channel blockers and by lowering extracellular calcium with EGTA. Calcium restriction for 3-5 h converted both cell types from a normal cAMP growth-inhibited phenotype to an abnormal cAMP growth-stimulated phenotype, characteristic of PKD. In M-1 cells, we showed that calcium restriction was associated with an elevation in B-Raf protein levels and cAMP-stimulated, Ras-dependent activation of B-Raf and ERK. Moreover, the activity of Akt, a negative regulator of B-Raf, was decreased by calcium restriction. Inhibition of Akt or phosphatidylinositol 3-kinase also allowed cAMP-dependent activation of B-Raf and ERK in normal calcium. These results suggest that calcium restriction causes an inhibition of the phosphatidylinositol 3-kinase/Akt pathway, which relieves the inhibition of B-Raf to allow the cAMP growth-stimulated phenotypic switch. Finally, M-1 cells stably overexpressing an inducible polycystin-1 C-terminal cytosolic tail construct were shown to exhibit a cAMP growth-stimulated phenotype involving B-Raf and ERK activation, which was reversed by the calcium ionophore A23187. We conclude that disruption of calcium mobilization in cells that are normally growth-inhibited by cAMP can derepress the B-Raf/ERK pathway, thus converting these cells to a phenotype that is growth-stimulated by cAMP.


[A genetic viewpoint of focal glomerular sclerosis: fom genes to glomerular pathophysiology [corrected]].
Recent studies of Mendelian disease have begun to clarify the clinical spectrum of the group of disorders that make up familial, focal segmental glomerulosclerosis (FSGS) and nephrotic syndromes. In familial forms of focal segmental glomerulosclerosis (FSGS), both autosomal recessive and dominant inheritance patterns have been reported. At least three genes have been identified which, when defective, cause familial FSGS or nephrosis: the NPHS1 gene, encoding nephrin; the NPHS2 gene, encoding podocin; and the ACTN4 gene, encoding a-actinin-4. Because the majority of FSGS cases occur as sporadic disease, the recently described mutations in the NPHS2 gene "in approximately 25 percent of cases of apparently sporadic, steroid-resistant FSGS in children" have claimed great interest. The applicability of these observations to adults, including the possible importance of the nephrin and alpha-actinin-4 genes in the sporadic disease, remain to be determined. Finally, the mechanisms of podocyte damage and the molecular basis of glomerulosclerosis are reviewed.


Lateralization of responses to vibrissal stimulation: connectivity and information integration in the rat sensory-motor cortex assessed with fMRI.
Rats move their whiskers or vibrissae to gain sensory information about the world surrounding them. A single whisker can work as an independent detector but normal whisking involves the use of several vibrissae in a bilateral fashion. Here we used blood oxygen level dependent (BOLD) contrast to acquire functional magnetic resonance images (fMRI) of the rat brain activity during uni- and bilateral whisker stimulations with different timing schemes under Isoflurane anesthesia. Experiments were performed to assess the integration of bilateral information produced by normal whisking behavior. First, we showed that it was possible to obtain BOLD whisker activations using Isoflurane harmless for the animals and thus allowing for future repetitive/longitudinal studies. Second, we obtained different BOLD activation patterns depending on the number of stimulated whiskers and timing of the stimulation scheme. Third, we found lateralization of BOLD activations in the somatosensory-motor cortex. It manifested itself in considerably larger activations in the right hemisphere during equal bilateral whisker stimulation. Fourth, we found Granger Causality Analysis (GCA) to be a useful tool in information integration analysis, as it reproduced the stimulus specific Cross-correlation Analysis results. Both analyses showed that the amount of whiskers stimulated and the timing of stimulation lead to specific dynamic connectivity patterns. Finally, by adding directionality information GCA revealed meaningful lateralization of information processing in the rat whisker system consistent with the observed BOLD activation patterns.


The influence of ionic strength on potassium contractures and calcium movements in frog muscle.
Frog toe muscles were bathed in isotonic, sodium-free Tris chloride, methanesulfonate, or sulfate solutions containing sucrose or mannitol and varying in ionic strength from 0.006 to 0.291. By decreasing the ionic strength the curve relating the peak tension of the K contractures to the log [K] was reversibly shifted to lower [K]. Increasing the [Ca] from 1 to 4 mM almost abolished this effect. The resting uptake of (45)Ca was increased more than two times by decreasing the ionic strength from 0.125 to 0.039. It was not increased significantly by raising [Ca] from 1 to 4 mM at low or normal ionic strength. The additional uptake of (45)Ca during contractures provoked by 120 mM K was not significantly different at the two levels of ionic strength. The rate of emergence of (45)Ca from muscles loaded with (45)Ca at reduced ionic strength, was decreased. The effects of low ionic strength are discussed in terms of changes in the potential difference across a membrane with fixed negative charges on the outer surface.


miR-204 regulates the biological behavior of breast cancer MCF-7 cells by directly targeting FOXA1.
MicroRNAs (miRNAs) are short, non-protein-coding RNAs and transcripts that are 18-24 nt in length. miR-204 was first identified as an anti-oncogene and is reported to be downregulated in non-small cell lung cancer, glioma, gastric and thyroid cancer. Recent studies have proposed that a low level of miR-204 expression is associated with tumor progression and disease outcome in breast cancer. Forkhead box A1 (FOXA1), a transcription factor, plays a crucial role in breast cancer and has been predicted as a target of miR-204. In the present study, we integrated the results of microarray analyses of breast cancer tissues obtained from an online database with our own determination of the expression of miR-204 in breast cancer MCF-7 cells using real-time qPCR (RT-qPCR). The proliferative capacity of the cells was assessed using MTT assays, and cell mobility and invasiveness were evaluated using cell migration and invasion assays, respectively. Flow cytometry was used to analyze apoptosis. FOXA1 levels were detected using RT-qPCR and western blot analysis. Luciferase assays were performed to confirm that FOXA1 is directly targeted by miR-204. The results showed that miR-204 was downregulated in breast cancer cells, and we found that miR-204 was expressed at a lower level in MCF-7 cells than that observed in normal breast epithelial HBL-100 cells. Overexpression of miR-204 inhibited cell proliferation, migration and invasion and promoted apoptosis. Western blot analysis revealed that the expression of FOXA1 at the protein level was significantly reduced after cells were transfected with miR-204-expressing viruses. Luciferase assays demonstrated that FOXA1 is a direct target of miR-204, which binds to FOXA1 in a complementary region. In conclusion, miR-204 regulates the biological behavior of breast cancer cells, including cell proliferation, invasion, metastasis and apoptosis, by directly targeting FOXA1. Thus, miR-204 may act as a tumor-suppressor, and the results of the present study provide a reference for future research into the potential mechanisms underlying breast cancer progression.


Child abuse and neglect: a diagnostic guide for the optometrist.
Since approximately 40% of all physically abused children have ocular complications, it is increasingly important for optometrists to be prepared for an encounter with a child patient who has been abused. This review of the literature was undertaken to develop a diagnostic guide for the optometrist in face of a growing incidence of child abuse. It describes different types of abuse and their physical, emotional and behavioral manifestations. A special emphasis has been placed on head trauma and associated ocular signs. A list of state child protective services agencies, and how to contact them, is included.


Effect of physiotherapy on spinal alignment in children with postural defects.
This paper assesses the effect of neurophysiological rehabilitation in children with postural defects on the depth of thoracic kyphosis, lateral spinal deviation and rotation of spinal motor segments. A total of 201 patients aged 8-15 years old with a postural defect diagnosed by medical examination were enrolled. The analyzed parameters were determined using the DIERS system before the first therapeutic session and after 4 weeks of therapy. The angle of thoracic kyphosis, lateral deviation of the spine and spinal rotation were assessed. The therapy employed techniques associated with the proprioceptive neuromuscular facilitation (PNF) and Vojta's approaches. The results were analyzed separately for both sexes and for patients rehabilitated solely with Vojta's techniques vs. patients rehabilitated according to combined Vojta's and PNF techniques. The χ2 test was used for statistical analyses, at p < 0.05. There was improvement in the angle of thoracic kyphosis, ranging from 0.14 (among boys with kyphosis < 42°) to 5.47 (among girls with kyphosis ≥ 42°), spinal rotation, from 0.37 (among boys with kyphosis ≥ 42°) to 4.33 (among patients with kyphosis ≥ 42° rehabilitated solely according to Vojta's method), and lateral deviations, ranging from 1.32 mm (among boys with kyphosis < 42°) to 2.99 mm (among patients with kyphosis ≥ 42° rehabilitated solely according to Vojta's method). Neurophysiological rehabilitation of patients with postural defects produced positive effects by improving the angle of thoracic kyphosis, spinal rotation and lateral deviation of the spine. Children with reduced thoracic kyphosis achieved less improvement in the kyphosis angle, lateral spinal deviation and spinal rotation than children with kyphosis ≥ 42°. The DIERS Formetric System enables precise monitoring of therapeutic outcomes. Int J Occup Med Environ Health. 2019;32(1):25-32.


Freshness-preserving non-interactive hierarchical key agreement protocol over WHMS.
The digitization of patient health information (PHI) for wireless health monitoring systems (WHMSs) has brought many benefits and challenges for both patients and physicians. However, security, privacy and robustness have remained important challenges for WHMSs. Since the patient's PHI is sensitive and the communication channel, i.e., the Internet, is insecure, it is important to protect them against unauthorized entities, i.e., attackers. Otherwise, failure to do so will not only lead to the compromise of a patient's privacy, but will also put his/her life at risk. This paper proposes a freshness-preserving non-interactive hierarchical key agreement protocol (FNKAP) for WHMSs. The FNKAP is based on the concept of the non-interactive identity-based key agreement for communication efficiency. It achieves patient anonymity between a patient and physician, session key secrecy and resistance against various security attacks, especially including replay attacks.


Effect of solvent quality on the conformations of a model comb polymer.
The effect of solvent quality on the equilibrium structure of a densely branched comb polymer is investigated based on the structure factor analyses by off-lattice Monte Carlo simulations. First, theta temperature (theta(infinity)) must be determined to identify the solvent condition. We locate the characteristic temperature theta(A)(N) at which the second virial coefficient vanishes and the transition temperature theta(R)(N) at which radius of gyration R(g) of the chain varies most rapidly with temperature, i.e., d(2)R(g)/dT(2)|(theta(R)) = 0. N represents the total number of monomers of a comb. As N --> infinity, theta(A) and theta(R) coincide to a point that is identified as the true theta temperature (theta(infinity)). The structure factors of the main chain, the side chain, and the whole polymer are calculated, respectively. It is found that at T = theta(infinity), the structural factors S(qR(g)) for the overall comb polymers match quite well with those of their Gaussian counterparts. When T< theta(infinity), the overall comb polymer assumes collapsed conformations, similar to a homogeneous sphere. However, the structure factor of the side chain indicates that it always remains in an expanded state regardless of the solvent condition. It is attributed to the strong interactions between side chains. The same effect leads to enhanced rigidity of the main chain in comparison to the linear chain, as clearly observed from the rescaled Kratky plot.


Pervasive lesion segregation shapes cancer genome evolution.
Cancers arise through the acquisition of oncogenic mutations and grow by clonal expansion1,2. Here we reveal that most mutagenic DNA lesions are not resolved into a mutated DNA base pair within a single cell cycle. Instead, DNA lesions segregate, unrepaired, into daughter cells for multiple cell generations, resulting in the chromosome-scale phasing of subsequent mutations. We characterize this process in mutagen-induced mouse liver tumours and show that DNA replication across persisting lesions can produce multiple alternative alleles in successive cell divisions, thereby generating both multiallelic and combinatorial genetic diversity. The phasing of lesions enables accurate measurement of strand-biased repair processes, quantification of oncogenic selection and fine mapping of sister-chromatid-exchange events. Finally, we demonstrate that lesion segregation is a unifying property of exogenous mutagens, including UV light and chemotherapy agents in human cells and tumours, which has profound implications for the evolution and adaptation of cancer genomes.


A series of bed exercises to improve lymphocyte count in allogeneic bone marrow transplantation patients.
The purpose of this study was to investigate the effect of a series of bed exercises on lymphocyte and T-cell subsets in allogeneic bone marrow transplantation patients during hospitalization. Thirty-five patients were randomly assigned, with 18 assigned to an exercise group and 17 to a control group. The bed exercise intervention was applied by a nurse to the exercise group for 30 min every day for 6 weeks. Patients in the exercise group had a mean increase of 40.9 lymphocyte cells/microL and patients in the control group had a mean decrease of 640.7 lymphocyte cells/microL. There were no significant differences in the percentage of cluster of differentiation (CD)3+, CD4+ and CD8+, and CD4+/CD8+ ratio between the two groups. These findings indicate that bed exercise could be an effective nursing intervention with patients undergoing bone marrow transplantation by increasing the lymphocyte count during hospitalization.


Screening of endophytic Streptomycetes isolated from Parthenium hysterophorus L. against nosocomial pathogens.
Parthenium hysterophorus L. is an obnoxious weed of the family asteraceae recognized for its detrimental effects and significant economic losses to agriculture. In this study 42 endophytic streptomycetes strains were isolated from its roots and leaves. The isolates were identified by morphological, microscopic, biochemical and physiological characterization as members of genus Streptomyces. In 16S rRNA gene sequencing the selected isolates exhibited maximum similarity with Streptomyces rochei (99%), Streptomyces litmocidini (99%), Streptomyces enissocaesili (99%), Streptomyces djakartensis (99%), Streptomyces olivaceus (99%), Streptomyces spp (99%), Streptomyces plicatus (99%), Streptomyces geysiriensis (99%) and Streptomyces vinaceusdrappus (99%). In biological screening the crude extracts of 12 strains exhibited significant antimicrobial activity against multi drug resistant nosocomial pathogens including Pseudomonas, Enterobacter, Bacillus, Escherichia coli, Staphlococcus aureus and Candida albicans. In chemical screening by thin layer chromatography (TLC) the extracts exhibited an impressive diversity of the bioactive secondary metabolites. Additionally high performance liquid chromatography (HPLC-UV) chromatographs revealed many impressive peaks of unidentified bioactive metabolites. As such this is a first study reporting the isolation, identification and screening of endophytic Streptomyces from the invasive weed. The results provide an insight into an untapped endophytic environment yet to be explored which might be a promising source of lead antimicrobial agents.


An unusual case of wheat dependent exercise induced anaphylaxis (WDEIA) triggered by Tri a 14 in a pediatric patient: a case report.
Anakinra, one of the novel biological agents, is a recombinant human IL-1 receptor antagonist. It is preferred as an alternative drug for familial Mediterranean fever cases where colchicine is not sufficient or cannot be used due to its side effects. Like all other biologics, hypersensitivity reactions to anakinra are quite rare. This is the first case which was successfully desensitized with anakinra after a severe immediate-type hypersensitivity reaction. We report a case of WDEIA in an asthmatic boy admitted to our Unit with suspected mushroom acute toxicity. The symptoms occurred during a gym session, approximately 2 hours after the ingestion of a meal based on pasta and cooked mushroom found in the family's garden. Acute toxicity due to mushroom ingestion was then excluded. Triptase serum levels resulted elevated in acute phase and normal after 24 hours. Food specific IgE showed a sensitization to lipid transfer protein Pru p 3 and to Tri a 14. This case highlights that WDEIA is underdiagnosed, especially when patients are firstly visited in Emergency Unit. Moreover, Tri a 14 is seldom described as responsible for WDEIA, compared to omega 5 gliadin.


Ureteric obstruction in stented renal transplants.
The use of renal stents in renal transplants is becoming increasingly popular and has been routine practice at this institution for the past 4 years. Despite this procedure, however, obstruction of the transplant ureter still occurs and we describe 7 patients who developed renal obstruction in the presence of a stented transplant ureter. The underlying causes of these findings are discussed together with suggested recommendations for optimum radiological assessment of transplant ureteric stents. The implication of these observations is that urine may flow down stented ureters between the ureter and the stent rather than down the stent lumen.


Unexpected Trends in the Stability and Dissociation Kinetics of Lanthanide(III) Complexes with Cyclen-Based Ligands across the Lanthanide Series.
We report a detailed study of the thermodynamic stability and dissociation kinetics of lanthanide complexes with two ligands containing a cyclen unit, a methyl group, a picolinate arm, and two acetate pendant arms linked to two nitrogen atoms of the macrocycle in either cis (1,4-H3DO2APA) or trans (1,7-H3DO2APA) positions. The stability constants of the Gd3+ complexes with these two ligands are very similar, with log KGdL values of 16.98 and 16.33 for the complexes of 1,4-H3DO2APA and 1,7-H3DO2APA, respectively. The stability constants of complexes with 1,4-H3DO2APA follow the usual trend, increasing from log KLaL = 15.96 to log KLuL = 19.21. However, the stability of [Ln(1,7-DO2APA)] complexes decreases from log K = 16.33 for Gd3+ to 14.24 for Lu3+. The acid-catalyzed dissociation rates of the Gd3+ complexes differ by a factor of ∼15, with rate constants (k1) of 1.42 and 23.5 M-1 s-1 for [Gd(1,4-DO2APA)] and [Gd(1,7-DO2APA)], respectively. This difference is magnified across the lanthanide series to reach a 5 orders of magnitude higher k1 for [Yb(1,7-DO2APA)] (1475 M-1 s-1) than for [Yb(1,4-DO2APA)] (5.79 × 10-3 M-1 s-1). The acid-catalyzed mechanism involves the protonation of a carboxylate group, followed by a cascade of proton-transfer events that result in the protonation of a nitrogen atom of the cyclen unit. Density functional theory calculations suggest a correlation between the strength of the Ln-Ocarboxylate bonds and the kinetic inertness of the complex, with stronger bonds providing more inert complexes. The 1H NMR resonance of the coordinated water molecule in the [Yb(1,7-DO2APA)] complex at 176 ppm provides a sizable chemical exchange saturation transfer effect thanks to a slow water exchange rate of (15.9 ± 1.6) × 103 s-1.


Molecular dynamics and mutational analysis of the catalytic and translocation cycle of RNA polymerase.
During elongation, multi-subunit RNA polymerases (RNAPs) cycle between phosphodiester bond formation and nucleic acid translocation. In the conformation associated with catalysis, the mobile "trigger loop" of the catalytic subunit closes on the nucleoside triphosphate (NTP) substrate. Closing of the trigger loop is expected to exclude water from the active site, and dehydration may contribute to catalysis and fidelity. In the absence of a NTP substrate in the active site, the trigger loop opens, which may enable translocation. Another notable structural element of the RNAP catalytic center is the "bridge helix" that separates the active site from downstream DNA. The bridge helix may participate in translocation by bending against the RNA/DNA hybrid to induce RNAP forward movement and to vacate the active site for the next NTP loading. The transition between catalytic and translocation conformations of RNAP is not evident from static crystallographic snapshots in which macromolecular motions may be restrained by crystal packing. All atom molecular dynamics simulations of Thermus thermophilus (Tt) RNAP reveal flexible hinges, located within the two helices at the base of the trigger loop, and two glycine hinges clustered near the N-terminal end of the bridge helix. As simulation progresses, these hinges adopt distinct conformations in the closed and open trigger loop structures. A number of residues (described as "switch" residues) trade atomic contacts (ion pairs or hydrogen bonds) in response to changes in hinge orientation. In vivo phenotypes and in vitro activities rendered by mutations in the hinge and switch residues in Saccharomyces cerevisiae (Sc) RNAP II support the importance of conformational changes predicted from simulations in catalysis and translocation. During simulation, the elongation complex with an open trigger loop spontaneously translocates forward relative to the elongation complex with a closed trigger loop. Switching between catalytic and translocating RNAP forms involves closing and opening of the trigger loop and long-range conformational changes in the atomic contacts of amino acid side chains, some located at a considerable distance from the trigger loop and active site. Trigger loop closing appears to support chemistry and the fidelity of RNA synthesis. Trigger loop opening and limited bridge helix bending appears to promote forward nucleic acid translocation.


Infectious complications of hepatic cryosurgery.
Hepatic cryosurgery is a novel procedure for patients with metastatic liver disease. To date, no reviews of the infectious complications of this procedure have been published. One hundred and fifty patients underwent 158 hepatic cryosurgical procedures at Allegheny General Hospital (Pittsburgh) from November 1987 through July 1995. Gastrointestinal malignancies accounted for 93% of the underlying diagnoses. The following 12 infections were directly related to the cryosurgical procedure: hepatic abscess (six), intraperitoneal abscess (three), ascending cholangitis (two), and an intrahepatic device (Infusaid; Strato/Infusoid, Norwood, MA) infection (one). Enterococcus was the most commonly isolated organism. Seven of the 12 infections were polymicrobial. The patients who developed infections had longer hospital stays (26 days vs. 13 days) and had more days of fever (6.5 days vs. 2.3 days). than those who did not develop infections. If perioperative manipulation of the biliary tree is avoided, the infection rate in patients who undergo hepatic cryosurgery may be decreased even further. Overall, cryoablation of the liver is not related to an increased risk of infection.


TRIM21 Promotes Rabies Virus Production by Degrading IRF7 through Ubiquitination.
Rabies, a highly fatal zoonotic disease, is a significant global public health threat. Currently, the pathogenic mechanism of rabies has not been fully elucidated, and no effective treatment for rabies is available. Increasing evidence shows that the tripartite-motif protein (TRIM) family of proteins participates in the host's regulation of viral replication. Studies have demonstrated the upregulated expression of tripartite-motif protein 21 (TRIM21) in the brain tissue of mice infected with the rabies virus. Related studies have shown that TRIM21 knockdown inhibits RABV replication, while overexpression of TRIM21 exerted the opposite effect. Knockdown of interferon-alpha and interferon-beta modulates the inhibition of RABV replication caused by TRIM21 knockdown and promotes the replication of the virus. Furthermore, our previous study revealed that TRIM21 regulates the secretion of type I interferon during RABV infection by targeting interferon regulatory factor 7 (IRF7). IRF7 knockdown reduced the inhibition of RABV replication caused by the knockdown of TRIM21 and promoted viral replication. TRIM21 regulates RABV replication via the IRF7-IFN axis. Our study identified TRIM21 as a novel host factor required by RABV for replication. Thus, TRIM21 is a potential target for rabies treatment or management.


Saliva sampling strategies affecting the salivary glucose measurement.
Characterized by sustained elevated blood glucose levels, diabetes mellitus has become one of the largest global public health concerns by imposing a heavy global burden on socio-economic development. To date, regular blood glucose level check by performing a finger-prick test has been a routine strategy to monitor diabetes. However, the intrusive nature of finger blood prick tests makes it challenging for individuals to maintain consistent testing routines. Recently, salivary glucose measurement (SGM) has increasingly become a non-invasive alternative to traditional blood glucose testing for diabetes. Despite that, further research is needed to standardize the collection methods and address the issues of variability to ensure accurate and reliable SGM. To resolve possible remaining issues in SGM, we here thoroughly explored saliva sampling strategies that could impact the measurement results. Additionally, the effects of supplements taken, mouth washing, gum chewing, and smoking were collectively analyzed, followed by a continuous SGM over a long period, forming the stepping stone for the practical transitional development of SGM in non-invasive diabetes monitoring.


[Comparison of in vivo pharmacokinetics of five constituents in Zhishi Zhizi Chi Decoction in normal rats and CUMS-induced depressive rats].
A LC-MS/MS method was developed for the rapid and simultaneous determination of genipin-1-β-D-gentiobioside,geniposide,naringin,hesperidin and neohesperidin in SD rat plasma.The linear relationships of these five constituents in rats were validated,and the specificity,accuracy,precision and stability met the requirements.Their pharmacokinetic parameters were calculated by DAS 3.2.2,and the results showed that the metabolic process in vivo of the five constituents accorded with the characteristics of noncompartmental model.Their main pharmacokinetic parameters were listed as follows:(1) genipin-1-β-D-gentiobioside:t_(1/2)(3.20±0.51)h,C_(max)(403.15±96.93)μg·L~(-1)and AUC_(0-t)(612.56±148.50)μg·L~(-1)·h for the model group,while t_(1/2)(3.07±0.75) h,C_(max)(229.50±60.63)μg·L~(-1)and AUC_(0-t)(413.14±76.37)μg·L~(-1)·h for the normal group;(2) geniposide:t_(1/2)(3.24±0.68) h,C_(max)(2 961.40±688.02)μg·L~(-1),and AUC_(0-t)(10 972.87±1 992.96)μg·L~(-1)·h for the model group,while t_(1/2)(4.56±0.96) h,C_(max)(1 833.27±558.13)μg·L~(-1),and AUC_(0-t)(8 996.27±3 053.48)μg·L~(-1)·h for the normal group;(3) naringin:t_(1/2)(1.64±0.59) h,C_(max)(415.13±259.54)μg·L~(-1),and AUC_(0-t)(608.62±289.05)μg·L~(-1)·h for the model group,while t_(1/2)(1.02±0.25) h,C_(max)(355.08±180.00)μg·L~(-1),and AUC_(0-t)(501.07±242.68)μg·L~(-1)·h for the normal group;(4) hesperidin:t_(1/2)(0.86±0.29) h,C_(max)(95.17±22.80)μg·L~(-1)and AUC_(0-t)(141.19±54.63)μg·L~(-1)·h for the model group,while t_(1/2)(0.95±0.31) h,C_(max)(46.48±18.33)μg·L~(-1)and AUC_(0-t)(69.51±14.73)μg·L~(-1)·h for the normal group;(5) neohesperidin:t_(1/2)(0.89±0.29) h,C_(max)(828.78±361.56)μg·L~(-1)and AUC_(0-t)(1 292.29±553.73)μg·L~(-1)·h for the model group,while t_(1/2)(0.90±0.31) h,C_(max)(314.68±172.45)μg·L~(-1)and AUC_(0-t)(385.99±138.55)μg·L~(-1)·h for the normal group.


Potatoes - A crop resistant against input of heavy metals from the metallicaly contaminated soil.
The objective of our study was to assess the extent of accumulation of cadmium, lead and zinc in potato tubers depending on the concentration of these heavy metals in soil and to evaluate the resistance of 11 cultivars of potato cultivated in 5 localities of the Slovakia against input of these heavy metals into the consumption part of potato. Contents of Cd (Pb, Zn) in soil were 0.94-2.54 (18.03-24.90, 35.71-72.40) mg/kg in soil extract by aqua regia and 0.030-0.188 (0.149-0.356, 0.052-0.238) mg/kg in soil extract by NH4NO3. The contents of Cd, Pb, and Zn were determined in potatoes in extracts of freeze-dried samples and expressed in mg/kg of fresh matter (FM). Determined contents of heavy metals were in the range of ND-0.058 mg Cd/kg FM, 0.020-0.630 mg Pb/kg FM, 1.836-3.457 mg Zn/kg FM, resp. The statistically significant correlation between heavy metal content in soil and its content in potato tubers were confirmed only: cv. Laura - Spissky Stvrtok (Cd), cv. Red Anna - Odorin (Pb) and Marabel, Red Anna - Odorin, cv. Marabel - Belusa, cv. Volumia - Imel (Zn).


Active Particle Based Selective Transport and Release of Cell Organelles and Mechanical Probing of a Single Nucleus.
Self-propelling micromotors are emerging as a promising microscale tool for single-cell analysis. The authors have recently shown that the field gradients necessary to manipulate matter via dielectrophoresis can be induced at the surface of a polarizable active ("self-propelling") metallo-dielectric Janus particle (JP) under an externally applied electric field, acting essentially as a mobile floating microelectrode. Here, the application of the mobile floating microelectrode to trap and transport cell organelles in a selective and releasable manner is successfully extended. This selectivity is driven by the different dielectrophoretic (DEP) potential wells on the JP surface that is controlled by the frequency of the electric field, along with the hydrodynamic shearing and size of the trapped organelles. Such selective and directed loading enables purification of targeted organelles of interest from a mixed biological sample while their dynamic release enables their harvesting for further analysis such as gene/RNA sequencing or proteomics. Moreover, the electro-deformation of the trapped nucleus is shown to be in correlation with the DEP force and hence, can act as a promising label-free biomechanical marker. Hence, the active carrier constitutes an important and novel ex vivo platform for manipulation and mechanical probing of subcellular components of potential for single cell analysis.