Effects of replacing wheat bran by pistachio skins on feed intake, nutrient digestibility, milk yield, milk composition and blood metabolites of dairy Saanen goats.
The objective of this study was to investigate the effect of pistachio skins (PiS) as a replacement of wheat bran on feed intake, nutrient digestibility, milk yield, milk composition and blood metabolites of dairy Saanen goats. Eight multiparous lactating Saanen goats (55 ± 7.2 days post-partum, 45 ± 2 kg body weight) were randomly assigned to one of the four dietary treatments arranged in a replicated 4 × 4 Latin square design. The dietary treatments were 1) 0 g/kg PiS and 210 g/kg wheat bran in the TMR (0PiS), 2) 70 g/kg PiS and 140 g/kg wheat bran in the TMR (7PiS), 3) 140 g/kg PiS and 70 g/kg wheat bran in the TMR (14PiS) and 4) 210 g/kg PiS and 0 g/kg wheat bran in the TMR (21PiS). The trial consisted of four 21-day periods, each composed of 14 days adaptation and 7 days data collection. Dry matter intake (p < 0.05) and crude protein digestibility (p < 0.01) increased linearly with increasing PiS proportions in the diet. Increasing the proportion of PiS in the diet caused a quadratic increase in apparent digestibility of dry matter (p < 0.05), and tended (p = 0.05) to increase quadratically organic matter, and ether extract digestibility. Replacing wheat bran with PiS in the diet had no effects on milk yield, whereas milk fat concentration increased linearly (p < 0.01) with increasing inclusion of PiS in the diet. As the dietary proportion of PiS increased, ruminal pH tended (p = 0.07) to increase linearly, whereas ammonia-N concentration declined in the rumen. Plasma concentrations of glucose and BUN remained unaffected, whereas triglycerides (p < 0.05) and cholesterol (p < 0.01) concentrations increased linearly with increasing inclusion of PiS in the diet. It was concluded that PiS based on local ingredients can successfully replace wheat bran in diets of dairy goats without detrimental effects on feed intake, nutrient digestibility and milk production.


The Influence of Natural Head Position on the Cervical Sagittal Alignment.
This study investigated the relationship between the parameters related to the natural head position and cervical segmental angles and alignment of patients with neck pain. The lateral radiographs of the cervical spine were collected from 103 patients and were used to retrospectively analyze the correlation between the natural head position, cervical local sagittal angles, and alignment. Sagittal measurements were as follows: cervical curvature classification, slope of McGregor's line (McGS), local sagittal angles (C0-C2 angle, C2-C5 angle, C5-C7 angle, and C2-C7 angle), T1 slope, center of gravity of the head to sagittal vertical axis (CG-C7 SVA), and local sagittal alignment (C0-C2 SVA and C2-C7 SVA). McGS was significantly correlated to C0-C2 angle (r = 0.57), C0-C2 SVA (r = -0.53), C2-C7 SVA (r = -0.28), and CG-C7 SVA (r = -0.47). CG-C7 SVA was also significantly correlated to curvature type (r = 0.27), C5-C7 angle (r = -0.37), and C2-C7 angle (r = -0.39). A backward shift with an extended head position may accompany a relatively normal curvature of the cervical spine. The effect of posture control in relieving abnormal mechanical state of the cervical spine needs to be further confirmed by biomechanical analysis.


Enhancement of phagocytic and chemokinetic activities of rainbow trout head kidney cells by C-reactive protein.
To investigate immunostimulating activity of purified rainbow trout (Oncorhynchus mykiss) C-reactive protein (CRP) on trout phagocytic cells. 20 rainbow trout and 2 rabbits. The effect of CRP on phagocytic activity of head kidney (HK) cells was examined by use of a phagocytosis assay with plastic particles. The enhancing effect of CRP on migration activity of HK cells was examined by use of the blind well assay. Glass-adherent cells from clinically normal trout had increased dose-dependent phagocytic activity against plastic particles when cells were incubated in the presence of CRP. Pretreatment of particles with CRP also enhanced phagocytic activity of the cells, indicating an opsonic effect of CRP. Rabbit anti-trout CRP serum suppressed the enhancing activity of CRP. The HK cells had significant dose-dependent chemokinetic activity against CRP that was not inhibited by anti-CRP serum, indicating that a CRP-antibody complex also could be chemokinetic. Rainbow trout CRP has immunostimulating activity for HK cells, resulting in enhanced phagocytic and chemokinetic activities.


Association between predominantly plant-based diets and iron status in Chinese adults: a cross-sectional analysis.
Current evidence of the relationship between diets and Fe status is mostly derived from studies in developed countries with Western diets, which may not be translatable to Chinese with a predominantly plant-based diet. We extracted data that were nationally sampled from the 2009 wave of China Health and Nutrition Survey; dietary information was collected using 24-h recalls combined with a food inventory for 3 consecutive days. Blood samples were collected to quantify Fe status, and log-ferritin, transferrin receptor and Hb were used as Fe status indicators. In total, 2905 (1360 males and 1545 females) adults aged 18-50 years were included for multiple linear regression and stratified analyses. The rates of Fe deficiency and Fe-deficiency anaemia were 1·6 and 0·7 % for males and 28·4 and 10·7 % for females, respectively. As red meat and haem Fe consumption differed about fifteen to twenty times throughout the five groups, divided by quintiles of animal protein intake per 4·2 MJ/d, only Fe status as indicated by log-ferritin (P=0·019) and transferrin receptor (P=0·024) concentrations in males was shown to be higher as intakes of animal foods increased. Log-ferritin was positively associated with intakes of red meat (B=0·3 %, P=0·01) and haem Fe (B=12·3 %, P=0·010) in males and with intake of non-haem Fe in females (B=2·2 %, P=0·024). We conclude that diet has a very limited association with Fe status in Chinese adults consuming a traditional Chinese diet, and a predominantly plant-based diet may not be necessarily responsible for poor Fe status.


Osteopetrosis in a Patient of Systemic Sclerosis Sine Scleroderma: A Rare Association.
Systemic sclerosis is a connective tissue disorder of unknown etiology. Although it is a multisystemic disorder, skin thickening is considered as a hallmark of the disease. It usually involves the lungs, gastrointestinal, and musculoskeletal systems. However, a rare subset of systemic sclerosis, systemic sclerosis sine scleroderma, is characterized by internal organ involvement and positive serologic markers with the total or partial absence of cutaneous manifestations. We present a rare association of osteopetrosis in a case of systemic sclerosis sine scleroderma, in a 22-year-old male patient, who presented with pulmonary symptoms as his chief complaints, unreported so far in literature.


Invited review: intracellular signaling in contracting skeletal muscle.
Physical exercise is a significant stimulus for the regulation of multiple metabolic and transcriptional processes in skeletal muscle. For example, exercise increases skeletal muscle glucose uptake, and, after exercise, there are increases in the rates of both glucose uptake and glycogen synthesis. A single bout of exercise can also induce transient changes in skeletal muscle gene transcription and can alter rates of protein metabolism, both of which may be mechanisms for chronic adaptations to repeated bouts of exercise. A central issue in exercise biology is to elucidate the underlying molecular signaling mechanisms that regulate these important metabolic and transcriptional events in skeletal muscle. In this review, we summarize research from the past several years that has demonstrated that physical exercise can regulate multiple intracellular signaling cascades in skeletal muscle. It is now well established that physical exercise or muscle contractile activity can activate three of the mitogen-activated protein kinase signaling pathways, including the extracellular signal-regulated kinase 1 and 2, the c-Jun NH(2)-terminal kinase, and the p38. Exercise can also robustly increase activity of the AMP-activated protein kinase, as well as several additional molecules, including glycogen synthase kinase 3, Akt, and the p70 S6 kinase. A fundamental goal of signaling research is to determine the biological consequences of exercise-induced signaling through these molecules, and this review also provides an update of progress in this area.


Ventricular tachycardia storm management in a COVID-19 patient: a case report.
Coronavirus disease 2019 (COVID-19) has been associated with myocardial involvement. Among cardiovascular manifestations, cardiac arrhythmias seem to be fairly common, although no specifics are reported in the literature. An increased risk of malignant ventricular arrhythmias and electrical storm (ES) has to be considered. We describe a 68-year-old patient with a previous history of coronary artery disease and severe left ventricular systolic disfunction, who presented to our emergency department describing cough, dizziness, fever, and shortness of breath. She was diagnosed with COVID-19 pneumonia, confirmed after three nasopharyngeal swabs. Ventricular tachycardia (VT) storm with multiple implantable cardioverter defibrillator (ICD) shocks was the presenting manifestation of cardiac involvement during the COVID-19 clinical course. A substrate-based VT catheter ablation procedure was successfully accomplished using a remote navigation system. The patient recovered from COVID-19 and did not experience further ICD interventions. To date, COVID-19 pneumonia associated with a VT storm as the main manifestation of cardiac involvement has never been reported. This case highlights the role of COVID-19 in precipitating ventricular arrhythmias in patients with ischaemic cardiomyopathy who were previously stable.


Site-specific dephosphorylation of tau protein at Ser202/Thr205 in response to microtubule depolymerization in cultured human neurons involves protein phosphatase 2A.
Tau proteins isolated from paired helical filaments, the major building blocks of Alzheimer's disease neurofibrillary tangle, are abnormally phosphorylated and unable to bind microtubules. To examine the dynamics of tau phosphorylation and to identify specific tau phosphorylation sites involved in the stabilization of microtubules, we treated cultured postmitotic neuron-like cells (NT2N) derived from a human teratocarcinoma cell line (NTera2/D1) with drugs that depolymerize microtubules (i.e. colchicine or nocodazole). This led to the recovery of dephosphorylated tau from the NT2N cells as monitored by a relative increase in the electrophoretic mobility of tau and an increase in the turnover of [32P]PO4-labeled tau. However, not all phosphorylation sites on tau are affected by colchicine or nocodazole. Ser202/Thr205 appears to be completely and specifically dephosphorylated by protein phosphatase 2A since this dephosphorylation was blocked by inhibitors of protein phosphatase 2A but not by inhibitors of protein phosphatase 2B. These findings, together with the recent observation that protein phosphatase 2A is normally bound to microtubules in intact cells, suggest that the polymerization state of microtubules could modulate the phosphorylation state of tau at specific sites in the normal and Alzheimer's disease brain.


The scaffolding protein Cnk binds to the receptor tyrosine kinase Alk to promote visceral founder cell specification in Drosophila.
In Drosophila melanogaster, the receptor tyrosine kinase (RTK) anaplastic lymphoma kinase (Alk) and its ligand jelly belly (Jeb) are required to specify muscle founder cells in the visceral mesoderm. We identified a critical role for the scaffolding protein Cnk (connector enhancer of kinase suppressor of Ras) in this signaling pathway. Embryos that ectopically expressed the minimal Alk interaction region in the carboxyl terminus of Cnk or lacked maternal and zygotic cnk did not generate visceral founder cells or a functional gut musculature, phenotypes that resemble those of jeb and Alk mutants. Deletion of the entire Alk-interacting region in the cnk locus affected the Alk signaling pathway in the visceral mesoderm and not other RTK signaling pathways in other tissues. In addition, the Cnk-interacting protein Aveugle (Ave) was critical for Alk signaling in the developing visceral mesoderm. Alk signaling stimulates the MAPK/ERK pathway, but the scaffolding protein Ksr, which facilitates activation of this pathway, was not required to promote visceral founder cell specification. Thus, Cnk and Ave represent critical molecules downstream of Alk, and their loss genocopies the lack of visceral founder cell specification of Alk and jeb mutants, indicating their essential roles in Alk signaling.


cDNA sequence and tissue expression of Fugu rubripes prion protein-like: a candidate for the teleost orthologue of tetrapod PrPs.
We report the isolation and characterization of a cDNA coding for Fugu rubripes prion protein (PrP)-like of 180 amino acids which includes the PrP-conserved hydrophobic region homologous to that of Xenopus PrP. In addition to the hydrophobic region, Fugu PrP-like has several features common to PrPs, such as a signal sequence, a basic nature (pI 9.7) and a single intron in the 5' untranslated region. A possible glycosyl phosphatidylinositol (GPI) anchor site also exists in PrP-like. In expression analysis, PrP-like mRNA was detected in retina, skin, and brain, all of which express PrP mRNA in mammals. In a genome fragment clone (T002589, 31945 bp) sequenced by the Fugu Genomics Project, PrP-like located between KIAA0168 and SLC231A homologues. In human chromosome 20p13, PrP, Doppel, KIAA0168, and SLC231A align in this order. The close gene arrangement between the Fugu and human genomes suggests that Fugu PrP-like is a real orthologue of human PrP. However, Fugu PrP-like does not possess tandem repeats or a region with two glycosylation sites and a disulphide bridge. We do not declare that the cloned Fugu PrP-like represents fish PrP due to structural inconsistency, but believe that it will offer new insights into the evolution of PrPs from fish to tetrapods.


Common genetic signatures of Alzheimer's disease in Down Syndrome.
Background: People with Down Syndrome (DS) are born with an extra copy of Chromosome (Chr) 21 and many of these individuals develop Alzheimer's Disease (AD) when they age. This is due at least in part to the extra copy of the APP gene located on Chr 21. By 40 years, most people with DS have amyloid plaques which disrupt brain cell function and increase their risk for AD. About half of the people with DS develop AD and the associated dementia around 50 to 60 years of age, which is about the age at which the hereditary form of AD, early onset AD, manifests. In the absence of Chr 21 trisomy, duplication of APP alone is a cause of early onset Alzheimer's disease, making it likely that having three copies of APP is important in the development of AD and in DS. In individuals with both DS and AD, early behavior and cognition-related symptoms may include a reduction in social behavior, decreased enthusiasm, diminished ability to pay attention, sadness, fearfulness or anxiety, irritability, uncooperativeness or aggression, seizures that begin in adulthood, and changes in coordination and walking. Methods: We investigate the relationship between AD and DS through integrative analysis of genesets derived from a MeSH query of AD and DS associated beta amyloid peptides, Chr 21, GWAS identified AD risk factor genes, and differentially expressed genes in DS individuals. Results: Unique and shared aspects of each geneset were evaluated based on functional enrichment analysis, transcription factor profile and network analyses. Genes that may be important to both disorders: ACSM1, APBA2, APLP1, BACE2, BCL2L, COL18A1, DYRK1A, IK, KLK6, METTL2B, MTOR, NFE2L2, NFKB1, PRSS1, QTRT1, RCAN1, RUNX1, SAP18 SOD1, SYNJ1, S100B. Conclusions: Our findings indicate that oxidative stress, apoptosis, and inflammation/immune system processes likely underlie the pathogenesis of AD and DS.


Proximal interphalangeal joint silicone arthroplasty for posttraumatic arthritis.
The long-term results of 16 silicone implant arthroplasties following severe destruction of the proximal interphalangeal joint and surrounding soft tissue in 14 patients were evaluated. Two implants were revised (1 arthrodesis and 1 amputation) and are not included in the results. On a visual analog scale of 0 to 100, the subjective evaluation relating to the quality of function and the ability to perform activities of daily living scored 73 on average (range, 0-100; median, 75). The range of active motion compared with the opposite side ranged from 0% to 100% (average, 47%; median, 56%). The lateral deviation, either radial or ulnar, averaged 4 degrees (range, 0 degrees to 9 degrees; median, 4 degrees). Rotational deformity, either radial or ulnar, averaged 8 (range, 0 degrees to 32 degrees; median, 4 degrees). Pinch strength of the operated finger on average was 75% of the opposite nonoperated finger (range, 14% to 164%; median, 70%). Possible statistical correlation between objective and subjective results was evaluated. Subjectively, most patients were satisfied because they were pain free. Objectively, notable rotational deformity, alignment deviation, and loss of pinch strength and range of motion were observed, but these did not correlate well with the subjective assessment. Silicone implant arthroplasty for posttraumatic arthrosis should be used for those cases in which associated adhesions may be corrected by simple tenolysis, allowing for active range of motion shortly following arthroplasty. Even in these cases, the objective results of silicone arthroplasty may not be as good as its subjective outcome.


[Effect of electroacupuncture on cholecystokinin gene expression in rat hippocampus during penicillin-induced epileptic seizure].
Northern Blot and hybrization in situ techniques were used to investigate the effect of electroacupuncture (EA) on the changes of cholecystokinin (CCK) mRAN levels of the hippocampus in rat penicillin-induced epilepsy model. Epilepsy can significantly increase CCK mRNA levels in dentate gyrus and CA3 areas of hippocampus in diencephalic sections after penicillin-induced seizure, whereas EA not only can attenuate the seizure behaviors and EEG changes, but also can decrease the increase of CCK mRNA contents induced by the seizure. However, in the subiculum, dentate gyrus and CA3 areas of mesencephalic sections of rat hippocampus, EA can further increase the enhancement of CCK mRNA concentration induced by penicillin-induced seizure. The results suggest that EA inhibitory effects on the seizure's behaviors and epileptiform activities may be related to the alteration of CCK gene expression in the different area of hippocampus.


Non-invasive Assessment of Vaccine-Induced HPV Antibodies via First-Void Urine.
The potential of first-void (FV) urine as a non-invasive method to monitor human papillomavirus (HPV) vaccination has been reported, mainly focusing on urine as a sample to assess HPV DNA. Besides HPV DNA, vaccine-induced HPV antibodies originating from cervicovaginal secretions were recently shown to be detectable in FV urine as well. This presents a novel opportunity for non-invasive sampling to monitor HPV antibody status in women participating in large epidemiological studies and HPV vaccine trials. The simultaneous assessment of both HPV infection and immunogenicity on a non-invasive, readily obtained sample is particularly attractive.


[Inhibitive effect of exogenous carbon monoxide-releasing molecules 2 on the activation of Janus kinase/signal transducer and activator of transcription pathway in sepsis].
To study the inhibitive effect of exogenous carbon monoxide-releasing molecules 2 (CORM-2) on the activation of Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway in sepsis. RAW264.7 cells were divided into normal control group, LPS group (10 mg/mL LPS, the same concentration below), LPS + inactive CORM-2 (iCORM-2) group, LPS + 50 mmol/L CORM-2 group, and LPS + 100 mmol/L CORM-2 group. TNF-alpha level in the supernatant was determined with ELISA, and the phosphorylation levels of JAK1 and JAK3 were determined with Western blot. Thirty-five male BALB/c mice were divided into normal control group, cecal ligation and puncture (CLP) group, CLP + iCORM-2 (8.0 mg/kg) group and CLP + CORM-2 group (8.0 mg/kg) according to the random number table. Mice in CLP + CORM-2 group were treated the same as mice in CLP group except for administration of CORM-2 after CLP. The plasma levels of TNF-alpha, IL-1beta, and the phosphorylation levels of JAK1, JAK3 in liver tissue were determined with ELISA 24 hours post CLP. Data were processed with t test. Compared with that of normal control group [(1.9 +/- 0.3) pg/mL], the TNF-alpha level [(8.2 +/- 2.7) pg/mL, t = 2.844, P < 0.01] and phosphorylation levels of JAK1, JAK3 in LPS group increased significantly; while TNF-alpha levels in LPS + 50 mmol/L CORM-2 and LPS + 100 mmol/L CORM-2 groups decreased obviously as compared with that of LPS group [(5.7 +/- 1.4), (3.2 +/- 0.9) pg/mL, with t value respectively 2.104 and 2.363, P values all below 0.05], and it was the same with phosphorylation levels of JAK1, JAK3 in a dose-dependent manner. Compared with those of normal control group, plasma levels of TNF-alpha and IL-1beta and phosphorylation levels of JAK1, JAK3 in liver tissue significantly increased in CLP group (with t value respectively 2.916 and 2.796, and P values all below 0.05); while plasma levels of TNF-alpha and IL-1beta and the phosphorylation levels of JAK1, JAK3 in liver tissue decreased significantly in CLP + CORM-2 group (with t value respectively 2.115 and 2.398, and P values all below 0.05). Exogenous CORM-2 can obviously inhibit the phosphorylation of JAKs molecules and then inhibit the activation of JAK/STAT signal pathway in sepsis, and decrease the expression of downstream cytokines to effectively prevent cascade reaction in the inflammatory response after severe infection.


Genome-Wide Prediction of DNA Methylation Using DNA Composition and Sequence Complexity in Human.
DNA methylation plays a significant role in transcriptional regulation by repressing activity. Change of the DNA methylation level is an important factor affecting the expression of target genes and downstream phenotypes. Because current experimental technologies can only assay a small proportion of CpG sites in the human genome, it is urgent to develop reliable computational models for predicting genome-wide DNA methylation. Here, we proposed a novel algorithm that accurately extracted sequence complexity features (seven features) and developed a support-vector-machine-based prediction model with integration of the reported DNA composition features (trinucleotide frequency and GC content, 65 features) by utilizing the methylation profiles of embryonic stem cells in human. The prediction results from 22 human chromosomes with size-varied windows showed that the 600-bp window achieved the best average accuracy of 94.7%. Moreover, comparisons with two existing methods further showed the superiority of our model, and cross-species predictions on mouse data also demonstrated that our model has certain generalization ability. Finally, a statistical test of the experimental data and the predicted data on functional regions annotated by ChromHMM found that six out of 10 regions were consistent, which implies reliable prediction of unassayed CpG sites. Accordingly, we believe that our novel model will be useful and reliable in predicting DNA methylation.


Moment theory for the analytical determination of rate constants for solute permeation at the interface of spherical molecular aggregates.
Moment equations were developed on the basis of the Einstein equation for diffusion and the random walk model to analytically determine the rate constant for the interfacial solute permeation from a bulk solvent into molecular aggregates (kin ) and the inverse rate constant from the molecular aggregates to the bulk solvent (kout ). The moment equations were in good agreement with those derived in a different manner. To demonstrate their effectiveness in one concrete example, the moment equations were used to analytically determine the values of kin and kout of three electrically neutral solutes, i.e. resorcinol, phenol, and nitrobenzene, from the first absolute (μ1A ) and second central (μ2C ) moments of their elution peaks, as measured by electrokinetic chromatography (EKC), in which the sodium dodecyl sulfate (SDS) micelles were used as a pseudostationary phase. The values of kin and kout should be determined with no chemical modifications and no physical action with the molecular aggregates because they are dynamic systems formed through weak interactions between the components. The moment analysis of the elution peak profiles measured by EKC is effective to unambiguously determine kin , kout , and the partition equilibrium constant (kin /kout ) under appropriate experimental conditions.


Transhepatic tract hemostasis using thermal-ablation after percutaneous portal vein access.
Bleeding risk after percutaneous portal vein access procedures is not negligible. Various agents, coils and plug, have been used to minimize this risk, each with their own advantages and disadvantages. This study reports the results of coagulation using thermal-ablation (radiofrequency or microwave ablation) as an alternative to trans-hepatic puncture tract closure. Ten patients who benefited from portal vein recanalization or portal hypertension-relative bleeding complication embolization using percutaneous portal vein access and who underwent thermal-ablation of the puncture tract between December 30, 2019 and July 16, 2020 were included. Early efficiency and safety were evaluated using imaging (ultrasound and/or CT scan) and laboratory data (hemoglobin, hepatic function) at 24 h. Follow-up was performed until August 2020. No bleeding from the puncture tract and no embolization-related complications were observed in all 10 patients at 24 h or during follow-up with median of 3 months (range 1-8 months), even in case of ascites or therapeutic coagulation. Thermal-ablation seems to be a safe, effective and rapid technique to avoid bleeding after percutaneous transhepatic direct portal vein access. Thermal-ablation could be an alternative for transhepatic puncture tract closure especially for patients with high bleeding risk.


Targeted therapies in bone sarcomas.
The treatment of sarcoma urgently requires new, innovative therapeutic strategies. The most recent improvements in the cure of patients with localized disease have been achieved by dose-intensification, in turn paying the price of acute severe toxicity and secondary malignancies. Keeping side-effects to a minimum is an important goal for pediatric patients and this may be achieved by combining standard cytotoxic chemotherapy with targeted approaches. In addition, after first-line therapy, very limited treatment options remain for patients with disease progression, who, like patients with metastasis at diagnosis, are in urgent need of more effective drugs. The present review highlights key examples of target identification in bone sarcomas, including chimeric oncoproteins, insulin-like growth factor receptor (IGF-IR), and tumor/microenvironment interactions. The review identifies questions and concerns that still need to be addressed before proceeding to safe clinical trials with agents against these promising new targets.


Role of Nasopharyngeal Bacteria and Respiratory Viruses in Acute Symptoms of Young Children.
The spectrum of acute symptoms in young outpatient children with respiratory tract infection (RTI) is variable, and it cannot be explained by the diagnosis of acute otitis media (AOM) versus uncomplicated RTI. We studied that the variation of symptoms is explained by the nasopharyngeal bacteria and/or respiratory viruses. Children aged 6-35 months with acute symptoms with AOM (n = 201) or without AOM (n = 225) were eligible in this cross-sectional study. We analyzed their nasopharyngeal samples for pathogenic bacteria by culture and for respiratory viruses by polymerase chain reaction. We surveyed 17 symptoms (fever, respiratory, ear related, nonspecific, gastrointestinal) with a structured questionnaire. Fever had a positive association with influenza viruses [odds ratio (OR): 6.61; 95% confidence interval (CI): 1.66-26.27], human metapneumovirus (OR: 3.84; 95% CI: 1.25-11.77), coronaviruses (OR: 3.45; 95% CI: 1.53-7.75) and parainfluenza viruses (OR: 2.18; 95% CI: 1.07-4.47). Rhinitis (OR: 5.07; 95% CI: 1.93-13.36), nasal congestion (OR: 2.03; 95% CI: 1.25-3.31) and cough (OR: 1.91; 95% CI: 1.15-3.17) had positive associations with Moraxella catarrhalis. Furthermore, cough had a positive association with respiratory syncytial virus (OR: 7.20; 95% CI: 1.59-32.71) and parainfluenza viruses (OR: 2.79; 95% CI: 1.02-7.69). The variation of acute symptoms in young children may be influenced by both nasopharyngeal bacteria and respiratory viruses. Our results showed a strong association between fever and respiratory viruses; rhinitis, nasal congestion and cough were associated with M. catarrhalis in the presence of viruses. Further studies are required to determine the possible synergistic role of M. catarrhalis in symptoms of RTI.


Sensitivity of bovine corpora lutea to prostaglandin F2alpha is dependent on progesterone, oxytocin, and prostaglandins.
Prostaglandin (PG) F2alpha that is released from the uterus is essential for spontaneous luteolysis in cattle. Although PGF2alpha and its analogues are extensively used to synchronize the estrous cycle by inducing luteolysis, corpora lutea (CL) at the early stage of the estrous cycle are resistant to the luteolytic effect of PGF2alpha. We examined the sensitivity of bovine CL to PGF2alpha treatment in vitro and determined whether the changes in the response of CL to PGF2alpha are dependent on progesterone (P4), oxytocin (OT), and PGs produced locally. Bovine luteal cells from early (Days 4-5 of the estrous cycle) and mid-cycle CL (Days 8-12 of the estrous cycle) were preexposed for 12 h to a P4 antagonist (onapristone: OP; 10(-4) M), an OT antagonist (atosiban: AT; 10(-6) M), or indomethacin (INDO; 10(-4) M) before stimulation with PGF2alpha. Although OP reduced P4 secretion (p < 0.001) only in early CL, it reduced OT secretion in the cells of both phases examined (p < 0.001). OP also reduced PGF2alpha and PGE2 secretion (p < 0.01) from early CL. However, it stimulated PGF2alpha secretion in mid-cycle luteal cells (p < 0.001). AT reduced P4 secretion in early and mid-cycle CL (p < 0.05). Moreover, PGF2alpha secretion was inhibited (p < 0.05) by AT in early CL. The OT secretion and the intracellular level of free Ca2+ ([Ca2+]i) were measured as indicators of CL sensitivity to PGF2alpha. PGF2alpha had no influence on OT secretion, although [Ca2+]i increased (p < 0.05) in the early CL. However, the effect of PGF2alpha was augmented (p < 0.01) in cells after pretreatment with OP, AT, and INDO in comparison with the controls. In mid-cycle luteal cells, PGF2alpha induced 2-fold increases in OT secretion and [Ca2+]i. However, in contrast to results in early CL, these increases were magnified only by preexposure of the cells to AT (p < 0.05). These results indicate that luteal P4, OT, and PGs are components of an autocrine/paracrine positive feedback cascade in bovine early to mid-cycle CL and may be responsible for the resistance of the early bovine CL to the exogenous PGF2alpha action.


Land-level changes produced by the Mw 8.8 2010 Chilean earthquake.
We observed vertically displaced coastal and river markers after the 27 February 2010 Chilean earthquake [moment magnitude (Mw) 8.8]. Land-level changes range between 2.5 and -1 meters, evident along an approximately 500-kilometers-long segment identified here as the maximum length of coseismic rupture. A hinge line located 120 kilometers from the trench separates uplifted areas, to the west, from subsided regions. A simple elastic dislocation model fits these observations well; model parameters give a similar seismic moment to seismological estimates and suggest that most of the plate convergence since the 1835 great earthquake was elastically stored and then released during this event.


National estimates of central line-associated bloodstream infections in critical care patients.
OBJECTIVE. Recent studies have demonstrated that central line-associated bloodstream infections (CLABSIs) are preventable through implementation of evidence-based prevention practices. Hospitals have reported CLABSI data to the Centers for Disease Control and Prevention (CDC) since the 1970s, providing an opportunity to characterize the national impact of CLABSIs over time. Our objective was to describe changes in the annual number of CLABSIs in critical care patients in the United States. Monte Carlo simulation. Setting. U.S. acute care hospitals. Nonneonatal critical care patients. We obtained administrative data on patient-days for nearly all US hospitals and applied CLABSI rates from the National Nosocomial Infections Surveillance and the National Healthcare Safety Network systems to estimate the annual number of CLABSIs in critical care patients nationally during the period 1990-2010 and the number of CLABSIs prevented since 1990. We estimated that there were between 462,000 and 636,000 CLABSIs in nonneonatal critical care patients in the United States during 1990-2010. CLABSI rate reductions led to between 104,000 and 198,000 fewer CLABSIs than would have occurred if rates had remained unchanged since 1990. There were 15,000 hospital-onset CLABSIs in nonneonatal critical care patients in 2010; 70% occurred in medium and large teaching hospitals. Substantial progress has been made in reducing the occurrence of CLABSIs in U.S. critical care patients over the past 2 decades. The concentration of critical care CLABSIs in medium and large teaching hospitals suggests that a targeted approach may be warranted to continue achieving reductions in critical care CLABSIs nationally.


Five leading U.S. commercial brands of moist snuff in 1994: assessment of carcinogenic N-nitrosamines.
Moist snuff is the only tobacco product in the United States with increasing sales (an increase of 38.4% between 1981 and 1993) and with increased consumption, primarily by male adolescents aged 12-18 years old and young adults aged 19 years old or older. It is known from previous studies that levels of nicotine and the proportion of unprotonated (free) nicotine, as well as the pH, which affects nicotine delivery, vary considerably among the leading snuff brands. Whether concentrations of major carcinogens, such as the nicotine-derived tobacco-specific N-nitrosamines (TSNAs), like N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), also vary among these brands has not been determined previously. Our purpose was threefold: 1) to determine the concentrations of major carcinogenic nicotine-derived N-nitrosamines in each of the five most popular moist snuff brands; 2) to analyze the quantitative differences in the various snuff components (e.g., NNN) between two major brand categories: a category comprising the brands known to have high levels of unprotonated nicotine (Copenhagen, Skoal fine cut, and Kodiak) versus a category comprising the brands known to have low levels (Hawken and Skoal Bandits); and 3) to compare the differences in the concentrations of nicotine (previously determined), NNN, NNK, and total TSNAs between these two major brand categories. Three boxes of each of the five leading U.S. moist snuff brands were bought in July 1994 from retailers in six areas and transferred immediately to the analytical laboratory. After extraction, N-nitrosamino acids and TSNAs were determined on a gas chromatograph interfaced with a thermal energy analyzer (GC-TEA) and integrator. Each 5-g sample of ground, freeze-dried tobacco was extracted twice, and each extract was analyzed twice by GC-TEA. All P values reported are two sided. Copenhagen, Skoal fine cut, and Kodiak as a group had statistically significant higher levels of nicotine (P = .0017), NNN (P < .0001), NNK (P = .0119), and total TSNAs (P < .0001) than the Hawken and Skoal Bandits group. Concentrations (means +/- SD) of nicotine, NNN, NNK, and total TSNAs comparing the two major brand categories are as follows: nicotine--11.6 +/- 1.01 mg/g versus 6.96 +/- 3.62 mg/g (P = .0017), NNN--7.74 +/- 1.70 micrograms/g versus 4.17 +/- 1.35 micrograms/g (P < .0001), NNK--1.23 +/- 0.68 micrograms/g versus 0.61 +/- 0.41 micrograms/g (P = .0119), and total TSNAs--14.3 +/- 3.82 micrograms/g versus 6.3 +/- 2.56 micrograms/g (P < .0001). The three leading U.S. snuff brands (Copenhagen, Skoal fine cut, and Kodiak; making up 92% of the U.S. market) showed not only high levels of pH, nicotine, and unprotonated (free) nicotine, but also high concentrations of the strongly carcinogenic TSNAs in comparison with the fourth and fifth best selling moist snuff brands, Hawken and Skoal Bandits (3% of the U.S. market).


Gastrointestinal perforation caused by obstruction in Trinidadian neonates.
A review was conducted of neonates treated over a 7-year period for gastrointestinal tract perforation secondary to obstruction, for comparison with previous reports. Demographic and clinical characteristics, results of laboratory studies, underlying diagnoses, surgical treatment, and outcomes were studied. Only 1 of the 6 babies was premature. The underlying cause of obstruction was Hirschsprung's disease (HD) twice, duodenal, sigmoid, and rectal atresia, and malrotation with midgut volvulus, once each. The perforation was located in the stomach in two cases, the jejunum in one case, and the large bowel in 3 children. There were no fatalities. Unusual features were that both gastric perforations were secondary to duodenal obstruction, and only 1 infant was premature. The jejunum was affected once, secondary to HD of the descending colon. In contrast to previous reports, there were no perforations of the ileum caused by intestinal obstruction in this neonatal population during the period reviewed.


Comparison of mannitol and citric acid cough provocation tests.
Citric acid has been used as a cough provocation test for decades. However, the methods of administration have not been standardized. Inhaled mannitol is a novel cough provocation test, which has regulatory approval and can be performed utilizing a simple disposable inhaler in a standardized manner. To compare the mannitol and citric acid cough provocation tests with respect to their ability to identify subjects with chronic cough and their tolerability. Subjects with chronic cough (n = 36) and controls (n = 25) performed provocation tests with mannitol and citric acid. Both tests were video recorded. Cough sensitivity was expressed as coughs-to-dose ratios (CDR) and the cumulative doses to mannitol or concentration to citric acid evoking 5 coughs (C5). Forced expiratory volume in 1 s (FEV1), visual analogue scales (VAS), test completion rates and the total cough frequencies were analysed. Mannitol and citric acid CDR both effectively separated those with cough and the control subjects (AUC 0.847 and 0.803, respectively) as did C5 (AUC 0.823 and 0.763, respectively). There was a good correlation between the cough sensitivity provoked by the two stimuli, either expressed as CDR (r = 0.65, p < 0.001) or C5 (r = 0.53, p = 0.001). Both tests were similarly tolerated in terms of VAS, although more patients discontinued the mannitol test early, primarily due to cough. Mannitol and citric acid tests correlated well, equally identified subjects with chronic cough and their tolerability was similar. The feasibility issues, strict standardisation and regulatory approval may favour mannitol to be used in clinical cough research.


[Treatment of Guillain-Barré syndrome with high-dose intravenous immunoglobulins--a comparison with plasma exchange].
We used high-dose intravenous immunoglobulin (IVIG) in the treatment of Guillain-Barré syndrome (GBS) and compared its therapeutic effects with those who were treated by plasma exchange (PE). For this study, we selected patients who had been within seven days from the onset and unable to walk without support at that time. Four patients (3 male, 1 female, mean age 41.8) were treated by plasma exchange with 3,000-4,000 ml exchange of plasma/day for 4-6 days. Other four patients (2 male, 2 female, mean age 45.7) were treated with intravenous high-dose immunoglobulin: 400 mg/kg/day for 3-5 days. The functional scale was measured at study entry and after the treatment daily. The mean times to the recovery of independent walk (a functional grade 2) were 23.8 and 10.0 days for PE and IVIG respectively. Although there was a difference of disease severity between these two groups, IVIG was at least as effective as PE in the treatment of GBS.


Leaf Senescence in a Nonyellowing Mutant of Festuca pratensis: Metabolism of Cytochrome f.
In a mutant genotype of Festuca pratensis Huds., net degradation of a number of thylakoid membrane proteins during senescence is impaired. Previous studies have suggested that the highly hydrophobic intrinsic chlorophyll-binding proteins were the definitive subjects of the metabolic lesion. In the present study we find that cytochrome f, as determined by haem-staining, Western blotting, enzyme-linked immunosorbent assay, and immunogold electron microscopy, is also abnormally stable in the mutant. The structural feature common to all the proteins in the mutant so far recognized to be abnormally stable is possession of a tetrapyrrole prosthetic group. It is suggested that degradation of chlorophyll and haem may regulate degradation of the associated apoproteins, and hence has an important role to play in membrane protein turnover and in mobilisation of amino acids during chloroplast disassembly.


Harmonized pretreatment quantitative volume-based FDG-PET/CT parameters for prognosis of stage I-III breast cancer: Multicenter study.
This study investigated harmonized pretreatment volume-based quantitative FDG-PET/CT parameters in breast cancer patients for prognostic value. During a median overall follow-up period of 5.3 years, 91 patients had recurrence and 40 died. Multivariate analysis of ER-positive/HER2-negative patients showed high maximum standardized uptake value (SUVmax) (p = 0.018), high total lesion glycolysis (TLG) (p = 0.010), and clinical N-classification (p = 0.0027) as independent negative predictors of RFS, while high maximum SUVmax (p = 0.037), advanced clinical T-classification (p = 0.030), and advanced TNM stage (p = 0.0067) were independent negative predictors of OS. For recurrence and death in HER2-positive patients, high total TLG (p = 0.037, p = 0.0048, respectively) and advanced TNM stage (p = 0.048, p = 0.046, respectively) were independent prediction factors. In the triple-negative group, independent factors related to recurrence and death were high maximum SUVmax (p = 0.0014, p = 0.0003, respectively) and advanced TNM stage (p < 0.0001, p < 0.0001, respectively). Records of 546 stage I-III invasive breast cancer patients, including 344 estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative, 110 HER2-positive, and 92 triple-negative cases, treated at four institutions were reviewed retrospectively. Harmonized primary tumor and nodal maximum SUVmax, metabolic tumor volume (MTV), and TLG indicated in pretreatment FDG-PET/CT results were analyzed. Evaluations of relationships of clinicopathological factors, volume-based quantitative parameters, recurrence-free survival (RFS), and overall survival (OS) for each subtype were performed with a Cox proportional hazards model and log-rank test. The results indicated that potential surrogate markers for prognosis in patients with the three main subtypes of operable breast cancer include harmonized pretreatment quantitative volume-based FDG-PET/CT parameters, particularly whole-lesion SUVmax and TLG.


Presence of a glycosylphosphatidylinositol lipid anchor on rose arabinogalactan proteins.
Arabinogalactan proteins constitute a class of plant cell surface proteoglycans with widespread occurrence and suggested functions in various aspects of plant growth and development, including cell proliferation, expansion, marking, and death. Previous investigations of subcellular fractions from suspension-cultured cells of "Paul's Scarlet" rose (Rosa sp.) have revealed extensive structural similarity between some soluble arabinogalactan proteins from the cell wall space and some plasma membrane-associated arabinogalactan proteins, thus inspiring the present investigation of the mechanism through which these inherently water-soluble molecules are held on the plasma membrane. Several lines of evidence gained through a combination of methods including reversed-phase chromatography, treatment with phosphatidylinositol-specific phospholipase C, and chemical structural analysis now show that some rose arabinogalactan proteins carry a ceramide class glycosylphosphatidylinositol lipid anchor. The predominant form of the ceramide is composed of tetracosanoic acid and 4-hydroxysphinganine. Plasma membrane vesicles readily shed arabinogalactan proteins by an inherent mechanism that appears to involve a phospholipase. This finding has significance toward understanding the biosynthesis, localization, and function of arabinogalactan proteins and toward stimulating other studies that may expand the currently very short list of higher plant proteins found to carry such membrane lipid anchors.


Diabetes and Its Cardiovascular Complications: Comprehensive Network and Systematic Analyses.
Diabetes mellitus is a worldwide health problem that usually comes with severe complications. There is no cure for diabetes yet and the threat of these complications is what keeps researchers investigating mechanisms and treatments for diabetes mellitus. Due to advancements in genomics, epigenomics, proteomics, and single-cell multiomics research, considerable progress has been made toward understanding the mechanisms of diabetes mellitus. In addition, investigation of the association between diabetes and other physiological systems revealed potentially novel pathways and targets involved in the initiation and progress of diabetes. This review focuses on current advancements in studying the mechanisms of diabetes by using genomic, epigenomic, proteomic, and single-cell multiomic analysis methods. It will also focus on recent findings pertaining to the relationship between diabetes and other biological processes, and new findings on the contribution of diabetes to several pathological conditions.


Genome-wide association study identifies candidate genes related to oleic acid content in soybean seeds.
Soybean oil is a complex mixture of five fatty acids (palmitic, stearic, oleic, linoleic, and linolenic). Soybean oil with a high oleic acid content is desirable because this monounsaturated fatty acid improves the oxidative stability of the oil. To investigate the genetic architecture of oleic acid in soybean seeds, 260 soybean germplasms from Northeast China were collected as natural populations. A genome-wide association study (GWAS) was conducted on a panel of 260 germplasm resources. Phenotypic identification results showed that the oleic acid content varied from 8.2 to 35.0%. A total of 2,311,337 single-nucleotide polymorphism (SNP) markers were obtained. GWAS analysis showed that there were many genes related to oleic acid content with a contribution rate of 7%. The candidate genes Glyma.11G229600.1 on chromosome 11 and Glyma.04G102900.1 on chromosome 4 were detected in a 2-year-long GWAS. The candidate gene Glyma.11G229600.1 showed a positive correlation with the oleic acid content, and the correlation coefficient was 0.980, while Glyma.04G102900.1 showed a negative correlation, with a coefficient of - 0.964. Glyma.04G102900.1 on chromosome 4 and Glyma.11G229600.1 on chromosome 11 were detected in both analyses (2018 and 2019). Glyma.04G102900.1 and Glyma.11G229600.1 are new key candidate genes related to oleic acid in soybean seeds. These results will be useful for high-oleic soybean breeding.


GM1 ganglioside induces phosphorylation and activation of Trk and Erk in brain.
We investigated the ability of GM1 to induce phosphorylation of the tyrosine kinase receptor for neurotrophins, Trk, in rat brain, and activation of possible down-stream signaling cascades. GM1 increased phosphorylated Trk (pTrk) in slices of striatum, hippocampus and frontal cortex in a concentration- and time-dependent manner, and enhanced the activity of Trk kinase resulting in receptor autophosphorylation. The ability of GM1 to induce pTrk was shared by other gangliosides, and was blocked by the selective Trk kinase inhibitors K252a and AG879. GM1 induced phosphorylation of TrkA > TrkC > TrkB in a region-specific distribution. Adding GM1 to brain slices activated extracellular-regulated protein kinases (Erks) in all three brain regions studied. In striatum, GM1 elicited activation of Erk2 > Erk1 in a time-and concentration-dependent manner. The GM1 effect on Erk2 was mimicked by other gangliosides, and was blocked by the Trk kinase inhibitors K252a and AG879. Pertussis toxin, as well as Src protein tyrosine kinase and protein kinase C inhibitors, did not prevent the GM1-induced activation of Erk2, apparently excluding the participation of Gi and Gq/11 protein-coupled receptors. Intracerebroventricular administration of GM1 induced a transient phosphorylation of TrkA and Erk1/2 in the striatum and hippocampus complementing the in situ studies. These observations support a role for GM1 in modulating Trk and Erk phosphorylation and activity in brain.


Bleomycin A2 and B2 purification by flash chromatography for chemical and biochemical studies.
The clinically used formulation of the anticancer antibiotic, Blenoxane, is a mixture of bleomycin congeners. A new approach to separating the major A2 and B2 congeners has been developed utilizing the flash chromatography technique. A 5-6-inch column of fine mesh silica gel with a solvent system of 1% ammonium formate:methanol (2:3) was used. Low air pressure was applied to the column to increase the flow rate such that separation was complete in approximately 20 min. Reverse phase size exclusion gravity chromatography with Sephadex G-15 column bedding was an effective, rapid procedure for removal of the 1% ammonium formate, the lowest percentage practical for separating the bleomycins. This separation approach does not damage the antibiotics, as demonstrated by NMR spectroscopy, thin layer chromatography, and DNA cleaving activity. Although not as useful for detection of trace amounts of the drug in biological systems as some of the known HPLC methods, this method is excellent for separating large quantities of the drug (8-32 mg) in order to obtain congeners pure enough for synthetic, biochemical, and biophysical studies.


Occurrence of a high temperature sensitivity of chloroplast ribosome formation in several higher plants.
A specific high temperature-induced deficiency of chloroplast ribosome formation, as indicated by the absence of chloroplast rRNA, has been observed in the leaves of light- or dark-grown seedlings of Avena sativa L., Hordeum vulgare L., and Triticum aestivum L. at certain temperatures between 28 and 34 C. While the growth of the leaves (size, morphology, total amino nitrogen content) was little affected by the elevated temperature, chlorophyll accumulation was strongly inhibited, amounting to only 2 to 20% of its content in 22 C-grown leaves which were used as a reference for normal development. The carotenoid contents were also lower but still reached at least 15 to 20% of the corresponding measurements at 22 C. Ribulose-1,5-bisphosphate carboxylase was absent at the higher temperature while NADP-glyceralde-hydephosphate dehydrogenase reached high activities. For the peroxisomal marker enzyme hydroxypyruvate reductase, 30 to 70% of the activity present in 22 C-grown leaves was found in extracts from high temperature-grown leaves. Fumarase reached 1.5- to 4-fold higher activities at the elevated growth temperature than at 22 C. Leaves of Pisum sativum L. were completely chlorotic and deficient of 70S ribosomes at 33 C but simultaneously suffered from a severe general inhibition of their growth. In Zea mays L., a formation of chlorotic leaves was not observed at elevated temperatures.


Use of large animals to assess human safety of heart valves and other medical devices.
The use of large animals are critical for the evaluation of safety of human valves and other medical devices. Preclinical assessment includes many factors oriented at maximizing safety and performance. The final step of the device approval for patient's use goes through an exhaustive regulatory process to prevent clinical complications or any other close or distant injuries. The development of reproducible animal models, the better understanding of the implantation of medical devices and the follow through with specific clinical trials will complete the significant steps required for the evaluation of safety of human heart valves and other medical devices.


ICF Core Sets for low back pain.
To report on the results of the consensus process integrating evidence from preliminary studies to develop the first version of a Comprehensive ICF Core Set and a Brief ICF Core Set for low back pain. A formal decision-making and consensus process integrating evidence gathered from preliminary studies was followed. Preliminary studies included a Delphi exercise, a systematic review and an empirical data collection. After training in the ICF and based on these preliminary studies, relevant ICF categories were identified in a formal consensus process by international experts from different backgrounds. The preliminary studies identified a set of 503 ICF categories at the second, third and fourth ICF levels with 211 categories on body functions, 47 on body structures, 190 on activities and participation and 55 on environmental factors. Eighteen experts from 15 different countries attended the consensus conference on low back pain. Altogether 78 second-level categories were included in the Comprehensive ICF Core Set with 19 categories from the component body functions, 5 from body structures, 29 from activities and participation and 25 from environmental factors. The Brief ICF Core Set included a total of 35 second-level categories with 10 on body functions, 3 on body structures, 12 on activities and participation and 10 on environmental factors. A formal consensus process integrating evidence and expert opinion based on the ICF framework and classification led to the definition of ICF Core Sets for low back pain. Both the Comprehensive ICF Core Set and the Brief ICF Core Set were defined.


Pigmented mesenteric lymphadenopathy in familial adenomatous polyposis - an unusual cause of intraoperative abandonment of ileo-anal pouch.
Familial adenomatous polyposis (FAP) is an autosomal dominant condition with near complete penetrance, characterised by the presence of numerous adenomatous polyps of the colon and rectum. Melanosis coli describes the brownish-black discolouration of the colon resulting from the accumulation of a granular pigment in the phagosomes of macrophages in the colonic lamina propria. The presence of melanosis pigment in pericolonic lymph nodes has been reported in patients with coincidental melanosis coli, following segmental colonic resection. We report a unique case of FAP with melanosis pigment in lymph nodes in the small bowel mesentery that initially prevented a restorative proctocolectomy but that resolved following a colectomy, subsequently facilitating formation of an ileo-anal pouch.


Structural elucidation of the mechanistic basis of degeneracy in the primary humoral response.
The mechanistic basis for efficient combating of the infinite range of foreign Ags by the limited repertoire of naive Abs expressed on primary B cell surfaces during their first encounter was addressed through elegantly designed crystallographic analyses. Resolution of the discrepancy arising from the limited number of possible germline Ab receptors on primary B cells for recognizing the unlimited pool of possible Ags has been attempted by invoking the degenerate recognition potential of the germline Abs. Structural analyses of germline mAb BBE6.12H3 in an Ag-free state, as well as bound to four different peptide Ags, established the correlation of its degenerate specificity with conformational versatility of the paratope. Six distinct paratope topologies observed for a single germline mAb provided a quantitative description of the primary Ag recognition repertoire at the tertiary structural level. Each of the four different peptide Ags was bound specifically to a distinct conformation of the paratope, which was also different from that of the Ag-free states of the same germline mAb. A minimal conserved motif in the pristine Ag-combining site essential for multispecificity and Ag binding-mediated change in the elbow angle of Fab was also discernible. It is proposed that the generation of a primary Ab repertoire involves large, yet finite, germline Ab clones, each capable of adopting discrete conformations, which in turn exhibit diverse binding modes.


Reduced vital capacity after methacholine challenge in early childhood--is it due to trapped air or loss of motivation.
In a previous study we assessed the feasibility of measuring bronchial-reactivity (BHR) in young asthmatic children by the determination of PC(20)-FEV(1) along with clinical end-of-test criteria during a methacholine challenge test (MCT). The end-point was associated with a significant reduction in both flow and vital capacity values. The findings could be due to the children's loss of motivation, which may preclude use of this test. Alternatively, if it reflects air trapping during airway obstruction, it might reinforce its applicability in preschool age children. To elucidate the mechanism of low vital capacity at PC(20)-FEV(1) in preschool age children. Twenty-eight children (3.3-6.9 years) with recurrent respiratory symptoms. An MCT was carried out using tripling doses (0.06-13.9 mg/ml) delivered by a dosimeter. Spirometry was measured at baseline and after each inhalation in duplicate sets. Whole body plethysmography was measured at baseline and at end-of-test (defined by clinical criteria) according to the recommendations for older populations. Plethysmography was reliably performed by 20 children before and after MCT. At baseline, lung function was within the healthy range. At end-of-test (PC(20)-FEV(1)=4.02+/-3.47 mg/ml), the spirometry parameters and specific conductance values were markedly reduced in correlation with a significant increase in residual volume and resistance. The study shows that diminished vital capacity is due to the increase in FRC at end-of-test. Our findings support the use of PC(20)-FEV(1) during BHR in young children and suggest that lung volume measurement by a plethysmograph may be feasible in early childhood. Larger studies should be performed to establish the clinical applicability of PC20-FEV1 determination in the preschool age.


Delivery of floxuridine derivatives to cancer cells by water-soluble organometallic cages.
The self-assembly of 2,4,6-tris(pyridin-4-yl)-1,3,5-triazine (tpt) triangular panels with p-cymene (pPr(i)C(6)H(4)Me) ruthenium building blocks and 2,5-dioxydo-1,4-benzoquinonato (dobq) or 5,8-dioxydo-1,4-naphthoquinonato (donq) bridges, in the presence of a pyrenyl-nucleoside derivatives (pyreneR), affords the triangular prismatic host-guest compounds [(pyrene-R)⊂Ru(6)(pPr(i)C(6)H(4)Me)(6)(tpt)(2)(dobq)(3)](6+) ([(pyrene-R)⊂1](6+)) and [(pyrene-R)⊂Ru(6)(pPr(i)C(6)H(4)Me)(6)(tpt)(2)(donq)(3)](6+) ([(pyrene-R)⊂2](6+)), respectively. The inclusion of six monosubstitutedpyrenyl-nucleosides (pyrene-R1 = 5'-(1-pyrenyl butanoate)-2'-deoxyuridine, pyrene-R2 = 5-fluoro-5'-(1-pyrenyl butanoate)-2'-deoxyuridine, pyrene-R3 = 5'-{N-[1-oxo-4-(1-pyrenyl)butyl]-glycyl}-2'-deoxyuridine, pyrene-R4 = 5-fluoro-5'-{N-[1-oxo-4-(1-pyrenyl)butyl]-glycyl}-2'-deoxyuridine, pyrene-R5 = 5-fluoro-5'-{N-[1-oxo-4-(1-pyrenyl)butyl]-phenylalanyl}-2'-deoxyvuridine, pyrene-R6 = 5-fluoro-5'-{N-[1-oxo-4-(1-pyrenyl)butyl]-phenylalanyl}-2'-deoxyuridine) has been accomplished. The carceplex nature of [(pyrene-R)⊂1](6+) with the pyrenyl moiety firmly encapsulated in the hydrophobic cavity of the cage with the nucleoside groups pointing outward was confirmed by NMR spectroscopy and electrospray ionization mass spectrometry (ESI-MS), while the host-guest nature of [(pyrene-R)⊂2](6+) was studied in solution by NMR techniques. In contrast to the floxuridine compounds used in the clinic, the host-guest complexes are highly water-soluble. Consequently, the cytotoxicities of these water-soluble compounds have been established using human ovarian A2780 and A2780cisR cancer cells. All the host-guest systems are more cytotoxic than the empty cages alone [1][CF(3)SO(3)](6) (IC(50) = 23 μM) and [2][CF(3)SO(3)](6) (IC(50) = 10 μM), the most active compound [pyrene-R4⊂1][CF(3)SO(3)](6)being 2 orders of magnitude more cytotoxic (IC(50) = 0.3 μM) on these human ovarian cancer cell lines (A2780 and A2780cisR).


Treatment of localized prostate cancer using high-intensity focused ultrasound.
To evaluate the biochemical disease-free survival (DFS), predictors of clinical outcome and morbidity of patients with localized prostate cancer treated with high-intensity focused ultrasound (HIFU), a noninvasive treatment that induces complete coagulative necrosis of a tumour at depth through the intact skin. In all, 63 patients with stage T1c-2bN0M0 localized prostate cancer underwent HIFU using the Sonablate system (Focus Surgery, Inc., Indianapolis, IN, USA). None of the patients received neoadjuvant and/or adjuvant therapy. Biochemical recurrence was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology consensus definition, i.e. three consecutive increases in prostate-specific antigen (PSA) level after the nadir. The median (range) age, PSA level and follow-up were 71 (45-87) years, 8.5 (3.39-57.0) ng/mL and 22.0 (3-63) months, respectively. The overall biochemical disease-free rate was 75% (47 patients). The 3-year biochemical DFS rates for patients with a PSA level before HIFU of <10, 10.01-20 and >20 ng/mL were 82%, 62% and 20% (P < 0.001), respectively. The 3-year biochemical DFS rates for patients with a PSA nadir of <0.2, 0.21-1 and >1 ng/mL were 100%, 74% and 21% (P < 0.001), respectively. Final follow-up sextant biopsies showed that 55 (87%) of the patients were cancer-free. Multivariate analysis showed that the PSA nadir (P < 0.001) was a significant independent predictor of relapse. HIFU therapy appears to be a safe, effective and minimally invasive therapy for patients with localized prostate cancer, and the PSA nadir is a useful predictor of clinical outcome.


Activation of thromboxane A2 receptors alters lipopolysaccharide-induced adherence of THP-1 cells.
U46619, a thromboxane A2 (TXA2) mimetic, inhibits human monocyte chemotactic responses, suggesting that TXA2, an arachidonic acid metabolite, may alter monocyte adhesion. We tested the hypothesis that TXA2 alters Lipopolysaccharide (LPS)-induced adhesion of THP-1 cells, a human monocytic leukemia cell line. Salmonella enteritidis endotoxin (1 microgram/mL) induced a significant (p < .05; n = 6) increase in the adherence of THP-1 cells (basal, 5.7 +/- 1.8 micrograms/well; LPS, 78.8 +/- 4.9 micrograms/well). Treatment of THP-1 cells with indomethacin or TXA2 receptor antagonists before LPS stimulation significantly (p < .05) enhanced adhesion, suggesting that endogenously produced TXA2 or prostaglandins alter LPS-induced THP-1 cell adhesion. TXA2 mimetics significantly decreased (p < .05; n = 5 and n = 3, respectively) LPS-induced THP-1 cell adhesion. This effect was blocked by three structurally dissimilar TXA2 receptor antagonists. These results support the hypothesis that TXA2 alters LPS-induced adhesion of THP-1 cells.


Vasorelaxant Effect of Prunus mume (Siebold) Siebold & Zucc. Branch through the Endothelium-Dependent Pathway.
Korean plum (Prunus mume (Siebold) Siebold & Zucc.) has long been used as a health food or herbal medicine in Asia. Previous studies have shown that several plants of the genus Prunus have vasodilatory and antihypertensive effects; we hypothesized that P. mume branches may have a vasorelaxant effect. In this study, we evaluated the effects and action mechanism of 70% ethanol extract of P. mume branch (PMB) on isolated rat aortic rings. Inhibitors such as NG-nitro-l-arginine methyl ester, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, methylene blue, indomethacin, atropine, tetraethylammonium chloride, glibenclamide, 4-aminopyridine and BaCl2 were used to investigate the mechanism of vasodilation responsible for the vascular relaxation. PMB (2-30 μg/mL) induced vasorelaxation in the presence of vascular endothelium, and all inhibitors used in this study affected the degree of relaxation. These results suggest that the vasorelaxant effect of PMB is endothelium-dependent and affects the nitric oxide-cyclic guanosine monophosphate pathway, prostacyclin pathway, muscarinic receptor pathway, and potassium channels. Our study explains that PMB may be another approach to hypertension treatment to reduce the burden of cardiovascular disease.


Tumor cell specific expression of MMP-2 correlates with tumor vascularisation in breast cancer.
The metastatic potential of tumors is dependent on the ability of tumor cells to degrade extracellular matrix components by the expression of matrix metalloproteinases (MMPs) and to induce vascularisation of the tumor tissue. Thus, expression of MMPs and the number of blood vessel in tumor tissue may serve as prognostic markers of aggressive and metastasizing tumor growth. We have determined the vascularisation and the expression of MMP-2 by immuno-histochemical staining of 19 benign and 75 malignant breast tissue specimens with CD31- and MMP-2 specific antisera. The degree of vascularisation was expressed by intratumoral microvascular density (IMD), which takes into account all vessels present in a hot spot irrespective of their size. In addition, we have introduced a novel parameter, vascular grading (VG), which describes the percentage of small microvessels of <20 microm in diameter in the total number of blood vessels. IMD tended to indicate an elevated risk for metastasis formation and disease recurrence, while VG did not correlate with metastasis formation. Similarly, MMP-2 expression neither correlated with the clinical outcome of the disease nor with the classical histo-pathological parameters such as stage, grade, lymph node involvement and estrogen receptor status. Tumor cell-specific MMP-2 expression, however, showed a highly significant correlation with VG but not with IMD. These results indicate that MMP-2 expression is rather involved in the formation of small capillaries than in vessel maturation and tumor cell invasion. Thus, MMP-2 expression by tumor cells may serve as indicator of strong angiogenic induction potential of breast tumor cells.


Economic evaluation of therapeutic interventions to prevent Type 2 diabetes in Canada.
To compare the health and economic outcomes of using acarbose, an intensive lifestyle modification programme, metformin or no intervention to prevent progression to diabetes in Canadian individuals with impaired glucose tolerance (IGT). A model was developed to simulate the course of individuals with IGT under each treatment strategy. Patients remain in the IGT state or transition from IGT to diabetes, to normal glucose tolerance (NGT) or to death. Effectiveness and resource use data were derived from published intervention trials. A comprehensive health-care payer perspective incorporating all major direct costs, reported in 2000 Canadian dollars, was adopted. Over a decade, 70 of the 1000 untreated patients are expected to die and 542 develop diabetes. Intensive lifestyle modification is estimated to prevent 117 cases of diabetes, while metformin would prevent 52 and acarbose 74 cases. The proportion of those who return to NGT also increases with any treatment. While lifestyle modification is more effective, it can increase overall costs depending on how it is implemented, whereas acarbose and metformin reduce costs by nearly $1000 per patient. Lifestyle modification was cost effective, varying from CAD $10 000/LYG vs. acarbose. Acarbose costs somewhat more than metformin, but is more effective: CAD $1798/LYG. The results of this model suggest that the treatment of IGT in Canada is a cost-effective way to prevent diabetes and may generate savings. While pharmacological treatments tended to be less costly, intensive lifestyle modification, if maintained, led to the greatest health benefits at reasonable incremental costs.


TPPU Pre-Treatment Rescues Dendritic Spine Loss and Alleviates Depressive Behaviours during the Latent Period in the Lithium Chloride-Pilocarpine-Induced Status Epilepticus Rat Model.
Epileptogenesis may be responsible for both of recurrent seizures and comorbid depression in epilepsy. Disease-modifying treatments targeting the latent period before spontaneous recurrent seizures may contribute to the remission of seizures and comorbid depression. We hypothesized that pre-treatment with 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), a soluble epoxide hydrolase (sEH) inhibitor, which has anti-inflammatory and neuroprotective effects might rescue status epilepticus (SE)-induced dendritic spine loss and alleviate depressive behaviours. Rats were either pre-treated with TPPU (0.1 mg/kg/d) intragastrically or with vehicle (40% polyethylene glycol 400) from 7 days before to 7 days after SE that was induced with lithium chloride and pilocarpine intraperitoneally. Rats in the Control group were given saline instead. The forced swim test (FST) was performed on the 8th day after SE to evaluate the depression-like behaviours in rats. The results showed that seizures severity during SE was significantly decreased, and the immobility time during FST was significantly increased through TPPU pre-treatment. Moreover, pre-treatment with TPPU attenuated inflammations including microglial gliosis and the level of proinflammatory cytokine IL-1β in the hippocampus; in addition, neuronal and dendritic spine loss in the subfields of hippocampus was selectively rescued, and the expression of NR1 subunit of N-methyl-D-aspartate (NMDA) receptor, ERK1/2, CREB, and their phosphorylated forms involved in the dendritic spine development were all significantly increased. We concluded that pre-treatment with TPPU attenuated seizures severity during SE and depressive behaviours during the period of epileptogenesis probably by rescuing dendritic spine loss in the hippocampus.


The prevalence of temporomandibular disorders among two different denture-wearing populations.
The aim of this clinicostatistical study was to profile the complete denture wearers of two different populations, to determine any possible relationship between the prevalence of temporomandibular disorders (TMDs) and factors involved in complete denture wearing and to compare this prevalence between the groups. Denture wearers who attended the clinics of the Dental School and Hospital, University of Bristol, U.K. (group A) and the Dental School, University of Athens, Greece (group B), were examined. An approximately equal number of patients; 115 for group A and 136 for group B, were selected. The examination included: (a) a history record with reference to sex, age, years of complete denture experience, sets of dentures used, age of the current dentures, time period of every day denture wearing, any difficulties on opening the mouth, and/or pain at the temporomandibular joint (TMJ) region and (b) a craniomandibular clinical examination in relation to midline deviation, pain and sounds from the joints, pain in the related muscles and inspection of the vertical dimension of occlusion. Data collected were analyzed using the chi-square test. Denture wearers of group A were older, presented with greater experience in complete denture wearing, used more sets of dentures, most wore dentures exhibiting decreased vertical dimension of occlusion and wore their dentures only in the day time. The TMDs prevalence was not statistically significantly different between A and B groups (34.8% and 41.2% respectively). In group B the TMDs prevalence was greater in females. There was a decreasing TMDs prevalence with increasing age. Neither of the groups showed significant TMDs prevalence in relation to the denture experience, the number of dentures used, the age of the present denture nor the vertical dimension of occlusion. Group B showed a decreasing TMDs prevalence in relation to continuous denture wearing. This clinicostatistical study showed that two different population groups of complete denture wearers who presented with different profiles have similar prevalence of TMDs.


Study of polymorphisms in the TP53 and RB1 genes in children with retinoblastoma in northern Mexico.
To determine the frequency and association of polymorphisms in the TP53 and RB1 genes with clinical characteristics in a group of children with retinoblastoma (RB) in northern Mexico. A prospective, longitudinal, and analytical study of 11 patients diagnosed with RB was conducted. Endpoint PCR and high-resolution real-time PCR were performed. Chi-square and Student t tests were used to evaluate associations between variables. Allelic frequencies, as well as genotypic and Hardy-Weinberg equilibriums, were evaluated using Guo and Thompson's method. We found a statistically significant difference between the polymorphism RB1-GG/rs9568036 and tumor chemoresistance (p<0.05). The allelic variants RB1-AA and AG/rs9568036 were determined to be associated with tumor chemosensitivity (p<0.05). A statistically significant relation between the polymorphism RB1-GG/rs9568036 and males (p = 0.0386), rate ratio (RR) = 2.0 (95% confidence interval [CI] = 0.76-5.32), as well as between the allelic variants RB1-AA and AG/rs9568036 and females (p = 0.0027), RR = 8.0 (95% CI = 1.28-50.04), was observed. We also observed a statistically significant association between the rs1042522 polymorphism in the TP53 gene and unilateral presentation of the disease. The rs9568036 polymorphism in the RB1 gene and the allelic variants can be associated with type of response to medical therapy and associated with male sex, while the allelic variant rs1042522 polymorphism in the TP53 gene is associated with the unilateral presentation of the disease in a group of Mexican children with RB.


Nature of the guest-host interactions for dibromine in the T, P, and H clathrate cages.
The guest-host intermolecular potentials for the ground states of Br2 in the tetrakaidecahedral (T), pentakaidecahedral (P), and hexakaidecahedral clathrate (H) cages have been calculated using ab initio local correlation methods. Applying the local correlation energy partitioning analysis together with first-order symmetry adapted perturbation theory, we obtain a detailed understanding of the nature of the interactions. In particular, the debated question concerning the possible presence of halogen bonding (XB) is carefully analyzed. In the case of the T cage, given its smaller size, the Br-O distance is too short leading to a larger exchange-repulsion for XB orientations which therefore do not represent minima. For the other two cages, the Br-O distance is too large leading to little orbital overlap effects and thus weaker donor-acceptor interactions; however, these orientations coincide with the global minima.


Influence of Epicuticular Physicochemical Properties on Porcine Rotavirus Adsorption to 24 Leafy Green Vegetables and Tomatoes.
Foodborne diseases are a persistent problem in the United States and worldwide. Fresh produce, especially those used as raw foods like salad vegetables, can be contaminated, causing illness. In this study, we determined the number of rotaviruses adsorbed on produce surfaces using group A porcine rotaviruses and 24 cultivars of leafy vegetables and tomato fruits. We also characterized the physicochemical properties of each produce's outermost surface layer, known as the epicuticle. The number of rotaviruses found on produce surfaces varied among cultivars. Three-dimensional crystalline wax structures on the epicuticular surfaces were found to significantly contribute to the inhibition of viral adsorption to the produce surfaces (p = 0.01). We found significant negative correlations between the number of rotaviruses adsorbed on the epicuticular surfaces and the concentrations of alkanes, fatty acids, and total waxes on the epicuticular surfaces. Partial least square model fitting results suggest that alkanes, ketones, fatty acids, alcohols, contact angle and surface roughness together can explain 60% of the variation in viral adsorption. The results suggest that various fresh produce surface properties need to be collectively considered for efficient sanitation treatments. Up to 10.8% of the originally applied rotaviruses were found on the produce surfaces after three washing treatments, suggesting a potential public health concern regarding rotavirus contamination.


Acquired and isolated asymmetrical palatal palsy.
Benign acquired and isolated asymmetrical palatal palsy is a rare condition in childhood. We report on three cases. Typical features include: sudden onset, abnormality of the palatal components of speech (rhinolalia), nasal escape of fluids from the ipsilateral nostril. It is supposed to be caused by viral infection, but attempts at viral isolation were unsuccessful. Complete spontaneous recovery is usual, taking a few weeks. Our paper seems to be the first report of magnetic resonance imaging of the brain in this condition. It did not disclose any abnormalities in the 2 cases in which it was performed.


The 2013 US Government Shutdown (#Shutdown) and health: an emerging role for social media.
In October 2013, multiple United States (US) federal health departments and agencies posted on Twitter, "We're sorry, but we will not be tweeting or responding to @replies during the shutdown. We'll be back as soon as possible!" These "last tweets" and the millions of responses they generated revealed social media's role as a forum for sharing and discussing information rapidly. Social media are now among the few dominant communication channels used today. We used social media to characterize the public discourse and sentiment about the shutdown. The 2013 shutdown represented an opportunity to explore the role social media might play in events that could affect health.


Effect of calcium supplementation on bone loss in postmenopausal women.
The use of calcium supplements slows bone loss in the forearm and has a beneficial effect on the axial bone density of women in late menopause whose calcium intake is less than 400 mg per day. However, the effect of a calcium supplement of 1000 mg per day on the axial bone density of postmenopausal women with higher calcium intakes is not known. We studied 122 normal women at least three years after they had reached menopause who had a mean dietary calcium intake of 750 mg per day. The women were randomly assigned to treatment with either calcium (1000 mg per day) or placebo for two years. The bone mineral density of the total body, lumbar spine, and proximal femur was measured every six months by dual-energy x-ray absorptiometry. Serum and urine indexes of calcium metabolism were measured at base line and after 3, 12, and 24 months. The mean (+/- SE) rate of loss of total-body bone mineral density was reduced by 43 percent in the calcium group (-0.0055 +/- 0.0010 g per square centimeter per year) as compared with the placebo group (-0.0097 +/- 0.0010 g per square centimeter per year, P = 0.005). The rate of loss of bone mineral density was reduced by 35 percent in the legs (P = 0.02), and loss was eliminated in the trunk (P = 0.04). Calcium use was of significant benefit in the lumbar spine (P = 0.04), and in Ward's triangle the rate of loss was reduced by 67 percent (P = 0.04). Calcium supplementation had a similar effect whether dietary calcium intake was above or below the mean value for the group. Serum parathyroid hormone concentrations tended to be lower in the calcium group, as were urinary hydroxyproline excretion and serum alkaline phosphatase concentrations. Calcium supplementation significantly slowed axial and appendicular bone loss in normal post-menopausal women.


An Ab Initio Computational Study of Electronic and Structural Factors in the Isomerization of Donor-Acceptor Stenhouse Adducts.
In this work, the photochemically and thermally induced isomerization of multiple donor-acceptor Stenhouse adducts (DASAs) of the first, second, and third generation is studied by means of state-of-the-art ab initio electronic structure methods leading to new insight into multiple facets of the reaction mechanism. Importantly, prior to any studies of the reaction mechanism, a set of test calculations demonstrate the suitability of the applied ADC(2) and CC2 methods in the present context. An important aspect in this regard is the availability of electronic energies and gradients under implicit consideration of solvent effects. On the basis of calculated reaction energies and barriers as well as a thorough analysis of the wave function compositions, interesting features of the reaction mechanism are deduced. For example, the closed form of second- and third-generation DASAs can be significantly stabilized by π - π interactions between the donor and acceptor termini when certain structural requirements are fulfilled. The central point of this work concerns the delicate balance between neutral and zwitterionic resonance structures that governs the relative barrier height for the crucial C2-C3 and C3-C4 bond rotations. Finally, a set of calculations on yet unreported derivatives highlights how this balance and hence the barrier heights can be tuned through variation of the donor-acceptor strength as well as the solvent polarity.


Forecasting hospital census at a tertiary care children's hospital.
Developing a forecasting tool for patient census allows for improved staffing, better resource utilization and mobilization, and improved timing of educational campaigns around the disease control process. Using a neural network approach we evaluated several different models and variables for predicting patient census prospectively. These initial studies enabled selection of a subset of predictor variables and show that different network models, and variables must be used based on the season.


Insights from a Review of Medical Cannabis Clinical Trials.
The Minnesota Legislature passed a law establishing a medical cannabis program in 2014. One of the first tasks of staff in the new Office of Medical Cannabis at the Minnesota Department of Health was to review scientific literature on medical cannabis. The review was limited to studies involving products similar to those allowed in Minnesota. This article explains how the review was conducted and presents three themes that emerged from it.


Transition metal complexes with functionalized indenyl phosphine ligands: structures and catalytic properties.
Transition-metal indenyl complexes usually exhibit different reactivities compared with their cyclopentadienyl analogues. Up to now, at least 10 metal-indenyl bonding modes have been reported. Because of the "indenyl effect", transition-metal indenyl complexes usually show enhanced reactivity in substitution and related reactions. This review provides an overview on the use and impact of indenyl phosphines in organometallic chemistry and transition-metal-catalysed reactions in the recent two decades. Some cationic and zwitterionic metal complexes supported by P,N-substituted indene or indenide ligands are described. They have been reported to induce the cleavage of E-H (E = H, Si and B) bonds and can be used as catalysts for addition of E-H bonds to unsaturated substrates. 2-Aryl indenyl phosphine ligands L3-L11 have been proven to be a class of versatile ligands for palladium-catalysed C-C and C-N cross-coupling reactions. Moreover, optically active tethered indenyl phosphine ligands can have better stereoselective control over the chirality arising at the metal center in the oxidative addition of their rhodium complexes with alkyl halides.


[Accelerated diagnosis and treatment initiation for head and neck cancer patients].
Acceleration of diagnosis and initiation of treatment for head and neck cancer requires optimal organisation and multidisciplinary collaboration. A project at the Head and Neck Oncology Centre, Aarhus University Hospital aimed at accelerating patient flow. The initiatives were implemented throughout 2007. Focus was on optimizing logistics for all patients referred to the centre with suspected head and neck cancer. Initiatives included a full-time coordinator, pre-booked slots for clinical work-up and weekly tumour boards. Key dates were registered and relevant intervals were quantitatively evaluated and compared to a reference group from 2006. We registered 446 patients. Waiting times for first clinical examination at the ENT department were reduced from medially eight to two days through 2007 (p < 0.0001). Time from first clinical examination to referral for treatment was reduced from medially 21 to nine days (p < 0.0001). Time from referral to treatment to initiation of treatment was reduced from medially 26 to 15 days (p < 0,001). The net result of these reductions was a reduced overall median time (from primary referral to initiation of treatment) from medially 57 days by end of 2006 to medially 29 days by end of 2007 (p < 0,0001). Logistic changes and especially introduction of a full-time coordinator, a multidisciplinary tumour board and a generally higher priority for head and neck cancer patients resulted in a significant acceleration regarding diagnosis and start of treatment from 2006 to 2007.


Simulation Method Linking Dense Microalgal Culture Spectral Properties in the 400-750 nm Range to the Physiology of the Cells.
This work describes a method to model the optical properties over the (400-750 nm) spectral range of a dense microalgal culture using the chemical and physical properties of the algal cells. The method was based on a specific program called AlgaSim coupled with the adding-doubling method: at the individual cell scale, AlgaSim simulates the spectral properties of one model, three-layer spherical algal cell from its size and chemical composition. As a second step, the adding-doubling method makes it possible to retrieve the total transmittance of the algal medium from the optical properties of the individual algal cells. The method was tested by comparing the simulated total transmittance spectra for dense marine microalgal cultures of Isochrysis galbana (small flagellates) and Phaeodactylum tricornutum (diatoms) to spectra measured using an experimental spectrophotometric setup. Our study revealed that the total transmittance spectra simulated for the quasi-spherical cells of Isochrysis galbana were in good agreement with the measured spectra over the whole spectral range. For Phaeodactylum tricornutum, large differences between simulated and measured spectra were observed over the blue part of the transmittance spectra, probably due to non-spherical shape of the algal cells. Prediction of the algal cell density, mean size and pigment composition from the total transmittance spectra measured on algal samples was also investigated using the reversal of the method. Mean cell size was successfully predicted for both species. The cell density was also successfully predicted for spherical Isochrysis galbana, with a relative error below 7%, but not for elongated Phaeodactylum tricornutum with a relative error up to 26%. The pigments total quantity and composition, the carotenoids:chlorophyll ratio in particular, were also successfully predicted for Isochrysis galbana with a relative error below 8%. However, the pigment predictions and measurements for Phaeodactylum tricornutum showed large discrepancies, with a relative error up to 88%. These results give strong support for the development of a promising tool providing rapid and accurate estimations of biomass and physiological status of a dense microalgal culture based on only light transmittance properties.


PIK3CA and AKT1 mutations have distinct effects on sensitivity to targeted pathway inhibitors in an isogenic luminal breast cancer model system.
Activating mutations in the phosphoinositide-3-kinase (PI3K)/AKT/mTOR pathway are present in the majority of breast cancers and therefore are a major focus of drug development and clinical trials. Pathway mutations have been proposed as predictive biomarkers for efficacy of PI3K-targeted therapies. However, the precise contribution of distinct PI3K pathway mutations to drug sensitivity is unknown. We describe the creation of a physiologic human luminal breast cancer cell line model to study the phenotype of these mutations using the MCF-7 cell line. We used somatic cell gene targeting to "correct" PIK3CA E545K-mutant alleles in MCF-7 cells to wild-type sequence. The AKT1 E17K hotspot mutation was knocked in on this wild-type background. Loss of mutant PIK3CA dramatically reduced phosphorylation of AKT proteins and several known AKT targets, but other AKT target proteins and downstream effectors of mTOR were not affected. PIK3CA wild-type cells exhibited reduced proliferation in vitro and in vivo. Knockin of the AKT1 E17K hotspot mutation on this PIK3CA wild-type background restored pathway signaling, proliferation, and tumor growth in vivo. PIK3CA, but not AKT1 mutation, increased sensitivity to the PI3K inhibitor GDC-0941 and the allosteric AKT inhibitor MK-2206. AKT1 E17K is a bona fide oncogene in a human luminal breast cancer context. Distinct PI3K pathway mutations confer differential sensitivity to drugs targeting the pathway at different points and by distinct mechanisms. These findings have implications for the use of tumor genome sequencing to assign patients to targeted therapies.


Inhibitory action of daunorubicin on lipopolysaccharide-stimulated inducible-type nitric oxide synthase induction in alveolar macrophages.
The purpose of this study was to investigate the effects of daunorubicin on lipopolysaccharide (LPS)-stimulated inducible-type nitric oxide synthase (iNOS) expression in macrophages. LPS-stimulated iNOS expression and NO production were significantly inhibited in alveolar macrophages from rats administrated daunorubicin (4 mg/kg body weight per day) for 5 consecutive days. Incubation of macrophages with daunorubicin at 1 muM but not at 0.1 and 0.5 muM significantly inhibited LPS-stimulated NO production and iNOS induction. Activation of extracellular regulated kinase (ERK) by LPS was markedly attenuated in both macrophages isolated from in vivo daunorubicin-treated rats and those incubated in vitro with daunorubicin at 1 microM. ERK activation, iNOS induction, and NO production following LPS stimulation were all markedly inhibited in the presence of U0126, an ERK inhibitor. The viability of macrophages was decreased by incubation with daunorubicin at 0.5 and 1 microM, while treatment of rats with daunorubicin did not affect viability of macrophages isolated from the rats. These results suggest that in vivo treatment of rats with daunorubicin attenuates LPS-induced iNOS expression of macrophages through inhibition of ERK activation, while inhibition of iNOS induction by in vitro incubation with daunorubicin may be mainly due to its cytotoxicity.


Ruptured anastomotic pseudoaneurysms after prosthetic vascular graft bypass procedures.
Pseudoaneurysms of prosthetic vascular grafts are a well-recognized phenomenon. In the past year we treated four patients with ruptured pseudoaneurysms, each of whom originally underwent surgery after March 1981. The main etiological factors were infection and mismatching between the physical characteristics of the prosthetic graft and the host artery. Once this diagnosis is suspected, pseudoaneurysms should be treated as an emergency. They should be resected, a new extraanatomical bypass constructed, and the wound left open.


Poly[[tetra-aqua-μ(4)-fumarato-di-μ(3)-fumarato-dineodymium(III)] trihydrate].
The title coordination polymer, {[Nd(2)(C(4)H(2)O(4))(3)(H(2)O)(4)]·3H(2)O}, was synthesized by the reaction of neodymium(III) nitrate hexa-hydrate with fumaric acid in a water-methanol (7:3) solution. The asymmetric unit comprises two Nd(3+) cations, three fumarate dianions (L(2-)), four aqua ligands and three uncoordinated water mol-ecules. The carboxyl-ate groups of the fumarate dianions exhibit different coordination modes. In one fumarate dianion, two carboxyl-ate groups chelate two Nd(3+) cations, while one of the O atoms is coordinated to another Nd(3+) cation. Another fumarate dianion bridges three Nd(3+) cations: one of the carboxyl-ate groups chelates one Nd(3+) cation, while the other carboxyl-ate group bridges two Nd(3+) cations in a monodentate mode. The third fumarate dianion bridges four Nd(3+) cations, where one of the carboxyl-ate groups chelates one Nd(3+) cation and coordinates in a monodentate mode to a second Nd(3+), while the second carboxyl-ate groups bridges two Nd(3+) cations in a monodentate mode and one O atom is coordinated to one Nd(3+) cation. The Nd(3+) cations are in a distorted tricapped-trigonal prismatic environment and coordinated by seven O atoms from the fumarate ligands and two O atoms from water mol-ecules. The Nd(3+) cations are linked by two carboxyl-ate O atoms and two carboxyl-ate groups, generating infinite Nd-O chains to form a three-dimensional framework. There are O-H⋯O and C-H⋯O hydrogen-bonding interactions between the coordin-ated and uncoordinated water mol-ecules and carboxyl-ate O atoms.


Role of osteopontin in the development of neointimal hyperplasia in vein grafts.
Neointimal hyperplasia and superimposed atherosclerosis are central to late vein graft failure following coronary artery bypass grafting. Recent studies on post-injury arterial vessels have suggested a role of osteopontin (OPN) in the process of vascular remodelling. This study was designed to assess the in vivo performance of OPN following vein grafting. Bilateral saphenous vein-carotid artery interposition grafting was performed in 16 Large White pigs (35-45 kg). All patent vein grafts were removed and fixed at 1, 2, 4 (n = 8 grafts in each group) and 12 weeks (n = 6 grafts) following surgery. Multiple histological sections from each graft were prepared. The expression of OPN in the vein grafts was determined by immunostaining and western blot assay. Proliferating cell nuclear antigen (PCNA) was detected by immunocytochemistry. Vein graft morphology was assessed using computer-aided planimetry. The expression of OPN remarkably increased in the intima of the vein grafts at the first week postoperatively and then gradually declined from the second postoperative week, although OPN expression remained significantly higher than the baseline level at the end of the 3-month study period. More importantly, the number of PCNA-positive cells and matrix metalloproteinases (MMPs) expression correlated well with the OPN expression. Early induction of OPN in vein grafts may contribute to the subsequent increase in MMPs activities as well as vascular smooth muscle cell proliferation. Therefore, OPN could play an important role in the development of neointimal hyperplasia in venous conduits after coronary artery bypass grafting.


Mobile App Use in Adults with Comorbid Type 2 Diabetes and Depression.
The purpose of this preliminary study was to determine smartphone usage, expressed level of interest, and intent to use mHealth apps among adults with comorbid type 2 diabetes (T2D) and depression. A convenience sample of adults (N=35) completed a Demographic and Mobile App Survey and the CESD-R-10. A majority reported using mobile apps (n=23, 65.7%) and felt comfortable or very comfortable using mobile apps (n=14, 46.7%). However, few respondents used a health app (n=6, 17.1%) or a diabetes-specific app for diabetes management (n=3, 8.6%). Adjusted, age and education were the two variables that independently impacted app use; those aged less than 55 years as well as those with a graduate degree were more likely to use apps. Being younger and having an advanced degree increased the odds of using a diabetes-specific app. The findings suggest that adults with T2D are amenable to using mHealth apps to manage diabetes.


Bedside implantation of a new temporary vena cava inferior filter - Safety and efficacy results of the European ANGEL-Registry.
Pulmonary embolism (PE) is a frequently occurring complication in critically ill patients. Simultaneous occurrence of PE and life-threatening bleeding, may render medical anticoagulation impossible. For these patients, inferior vena cava filters (IVCF) present a valuable therapeutic alternative. The Angel® catheter is a novel IVCF that provides temporary protection from PE and is implanted at bedside. The primary objective of the European Angel® catheter registry is to evaluate the safety and efficacy of this IVCF. The European Angel® catheter registry is an observational, multi-centre registry. Patients from four countries and eight sites that have undergone Angel® catheter implantation between March 2013 and February 2017 were enrolled. A total of 114 critically ill patients were included. The main indication for implantation was a high-risk for PE in combination with contraindications for anticoagulation (69.3%). One clinically non-significant PE (0.9%) occurred in a patient with an indwelling Angel® catheter. No cases of catheter associated serious complications were observed. Data shows that the Angel® catheter is a safe and effective approach to overcome the acute phase of critically ill patients with a high risk for the development of PE or an established PE, when an anticoagulation therapy is contraindicated.