Active species for Ce(IV)-induced hydrolysis of phosphodiester linkage in cAMP and DNA.
The hydrolysis of cyclic adenosine 3',5'-monophosphate and 2'-deoxythymidylyl(3'-5')2'-deoxythymidine by Ce(NH4)2(NO3)6 was kinetically studied. The rate of hydrolysis was fairly proportional to the concentration of [Ce2(IV) (OH)4]4+ , showing that this is the catalytically active species. According to quantum-chemical calculation, the two Ce(IV) ions in this [Ce2(IV) (OH)4]4+ cluster are bridged by two OH residues. Upon the complex formation with H2 PO4- (a model compound for the phosphodiesters), these two Ce(IV) ions bind the two oxygen atoms of the substrate and enhance the electrophilicity of the phosphorus atom. The catalytic mechanism of Ce(IV)-induced hydrolysis of phosphodiesters has been proposed on the basis these results.


Systematic review and meta-analysis of performance of wearable artificial intelligence in detecting and predicting depression.
Given the limitations of traditional approaches, wearable artificial intelligence (AI) is one of the technologies that have been exploited to detect or predict depression. The current review aimed at examining the performance of wearable AI in detecting and predicting depression. The search sources in this systematic review were 8 electronic databases. Study selection, data extraction, and risk of bias assessment were carried out by two reviewers independently. The extracted results were synthesized narratively and statistically. Of the 1314 citations retrieved from the databases, 54 studies were included in this review. The pooled mean of the highest accuracy, sensitivity, specificity, and root mean square error (RMSE) was 0.89, 0.87, 0.93, and 4.55, respectively. The pooled mean of lowest accuracy, sensitivity, specificity, and RMSE was 0.70, 0.61, 0.73, and 3.76, respectively. Subgroup analyses revealed that there is a statistically significant difference in the highest accuracy, lowest accuracy, highest sensitivity, highest specificity, and lowest specificity between algorithms, and there is a statistically significant difference in the lowest sensitivity and lowest specificity between wearable devices. Wearable AI is a promising tool for depression detection and prediction although it is in its infancy and not ready for use in clinical practice. Until further research improve its performance, wearable AI should be used in conjunction with other methods for diagnosing and predicting depression. Further studies are needed to examine the performance of wearable AI based on a combination of wearable device data and neuroimaging data and to distinguish patients with depression from those with other diseases.


The inevitable Hajj cough: Surveillance data in French pilgrims, 2012-2014.
Respiratory tract infections are the most common infection affecting Hajj pilgrims, and the ''Hajj cough'' is considered by pilgrims almost de rigueur. French pilgrims were recruited between January 2012-December 2014 and information on demographics, medical history, compliance with preventive measures and health problems during travel were collected. A total of 382 pilgrims were included with 39.3% aged ≥65 years and 55.1% suffering from a chronic disease, most frequently hypertension and diabetes. The prevalence of cough was 80.9% and a high proportion presented with associated sore throat (91.0%), rhinitis (78.7%) and hoarseness (63.0%). Myalgia was reported in 48.3% of cases and subjective fever in 47.3%. The incubation time of respiratory symptoms was 7.7 days (range 0-25 days) and 51.9% of pilgrims presenting with a cough during their stay were still symptomatic on return. Among pilgrims with a cough, 69.4% took antibiotics. The prevalence of cough was significantly higher among females than men, but age, chronic conditions and preventive measures had no significant effect. The Hajj cough is highly common, likely a result of crowded conditions at religious places. Pilgrims should be advised to carry symptomatic relief for the Hajj cough such as cough suppressant, soothing throat lozenges and paracetamol. Use of antibiotics should be discouraged.


Soluble Compounds of Filamentous Fungi Harm the Symbiotic Fungus of Leafcutter Ants.
Chemical compounds are key to understand symbiotic interactions. In the leafcutter ant-microbe symbiosis a plethora of filamentous fungi continuously gain access the ant colonies through plant substrate collected by workers. Many filamentous fungi are considered transient in attine ant colonies, however, their real ecological role in this environment still remains unclear. A possible role of these microorganisms is the antagonism towards Leucoagaricus gongylophorus, the mutualistic fungus that serve as food for several leafcutter ant species. Here, we showed the antagonism of filamentous fungi isolated from different sources, and the negative impacts of their metabolites on the growth of the ant-fungal cultivar. Our results demonstrate that the chemical compounds produced by filamentous fungi can harm the mutualistic fungus of leafcutter ants.


Differential effects of M1- and M2-muscarinic drugs on striatal dopamine release and metabolism in freely moving rats.
A dialysis loop cannula was implanted into rat striatum under anesthetized condition, and the area was perfused with Ringer's solution under freely moving condition after 3 days for surgical recovery. Dopamine (DA) and 3,4-dihydroxyphenylacetic acid recovered in the dialysate were measured by high-performance liquid chromatography with electrochemical detection. The effects of M1- and M2-muscarinic receptor agents, which were perfused continuously into the striatum through the dialysis membrane, were investigated. Continuous perfusion of AF102B, an M1-selective agonist, and oxotremorine, a non-selective agonist, resulted in a dose-dependent increase in the striatal DA release. Pirenzepine (10(-5) and 10(-7) M), an M1-selective antagonist, decreased the release of DA, and the stimulatory effect of AF102B (10(-5) M) was completely inhibited by 10(-5) and 10(-7) M pirenzepine, while the stimulatory effect of oxotremorine (10(-4) M) was only partly inhibited by 10(-5) M pirenzepine. AF-DX116 (10(-5) M), an M2-selective antagonist, increased the DA release, and showed an additive effect on the DA release evoked by AF102B (10(-5) M), whereas it produced no significant effect on oxotremorine (10(-5) M)-evoked DA release. These results suggest that in vivo DA release in the rat striatum is modulated by different subtypes of muscarinic receptors; i.e., the stimulatory effect is mainly mediated by M1-sites and inhibitory effect is mainly mediated by M2-sites. The changes in the DA release induced by the various drugs were prevented by pretreatment with tetrodotoxin (TTX). Since action potential-dependent DA release (exocytosis) is blocked by the pretreatment with TTX, those drugs affect DA release by means of action potential-dependent processes.


Population inversion X-ray laser oscillator.
Oscillators are at the heart of optical lasers, providing stable, transform-limited pulses. Until now, laser oscillators have been available only in the infrared to visible and near-ultraviolet (UV) spectral region. In this paper, we present a study of an oscillator operating in the 5- to 12-keV photon-energy range. We show that, using the [Formula: see text] line of transition metal compounds as the gain medium, an X-ray free-electron laser as a periodic pump, and a Bragg crystal optical cavity, it is possible to build X-ray oscillators producing intense, fully coherent, transform-limited pulses. As an example, we consider the case of a copper nitrate gain medium generating ∼ 5 × [Formula: see text] photons per pulse with 37-fs pulse length and 48-meV spectral resolution at 8-keV photon energy. Our theoretical study and simulation of this system show that, because of the very large gain per pass, the oscillator saturates and reaches full coherence in four to six optical-cavity transits. We discuss the feasibility and design of the X-ray optical cavity and other parts of the oscillator needed for its realization, opening the way to extend X-ray-based research beyond current capabilities.


Transport of choline by Madin-Darby canine kidney cells.
Choline is an essential precursor for the synthesis of phosphatidylcholine, the most abundant phospholipid classes in renal cells, as well as for the synthesis of the osmolyte glycerophosphorylcholine. The characteristics of choline uptake in the renal epithelial cell line MDCK were investigated. In the range of physiological concentrations, choline entered MDCK cells, grown as a monolayer on solid support, via a specific sodium-independent transport system (apparent Km = 43 microM, apparent Vmax = 284 pmol/mg protein per 5 min). Cell ATP depletion, addition of KCl to the medium to reduce the cell membrane potential, and hemicholinium-3 (HC-3) inhibited choline uptake. Specific binding of [3H]HC-3 was detected on the apical membrane of cells grown on plastic dishes, whereas it occurred only on the basolateral domain of cells grown on permeant support. When growing cells on filter, choline uptake from the basolateral side was 10-times the apical uptake. This suggests that the choline carrier present at the apical domain of cells grown on solid support is either inactivated or no longer targeted to the apical but to the basolateral membrane of MDCK cells grown on filter.


Topical glucocorticoid reduces the topical decongestant-induced histologic changes in an animal model nasal mucosa.
To investigate the histologic consequences of simultaneous nasal glucocorticosteroid and xylometazoline HCl administration in the rabbit nasal mucosa. Prospective randomized study. Twenty New Zealand male rabbits were randomly placed into three groups: group I, control (n = 6); group II, xylometazoline HCl (n = 8); or group III, xylometazoline HCl-fluticasone furoate (n = 6). Group I received no treatment. Groups II and III received two intranasal puffs of xylometazoline HCl 0.5 mg/mL twice daily or two puffs of xylometazoline HCl 0.5 mg/mL twice daily plus one puff of 27.5 μg fluticasone furoate twice daily to each nostril (110 μg), respectively. At the end of 3 weeks, the rabbits were sacrificed. The mucosa of the nasal cavities was excised. Specimen sections (5 μm) were stained with hematoxylin and eosin, mucicarmine, and Gomori one-step trichrome and were examined under a light microscope. The presence of edema, congestion, inflammatory cell infiltration, nasociliary loss, epithelial and nerve-ending degeneration, and goblet cell increase were evaluated semiquantitatively (grades 0-3). Statistically significant differences were detected between groups II and III in terms of edema, congestion, inflammatory cell infiltration, nasociliary loss, and epithelial degeneration (P = .006, P = .049, P = .015, P = .014, and P = .049, respectively). Nerve-ending degeneration, goblet cell increase, and quantitative goblet and neutrophil cell counts did not yield statistically significant differences between groups II and III (P = .137, P = .580, P = .770, and P = .616, respectively). The combined simultaneous intranasal administration of xylometazoline HCl and fluticasone furoate appears to be beneficial in minimizing the long-term usage-associated congestion, edema, inflammatory cell infiltration, epithelial degeneration, and nasociliary loss in the rabbit model nasal mucosa.


Current state of clinical and morphological features in human NCL.
The neuronal ceroid lipofuscinoses (NCL) are a large group of autosomal recessive lysosomal storage disorders with both enzymatic deficiency and structural protein dysfunction. Previously, diagnosis of NCL was based on age at onset and clinicopathological (C-P) findings described 4 forms, classified as infantile (INCL) (2), late-infantile (LINCL) (5), juvenile (JNCL) (6), and adult (ANCL) (12). Most patients with NCL have progressive ocular and cerebral dysfunction, including cognitive/motor dysfunction and uncontrolled seizures. After reviewing 520 patients with NCL, we found that about 104 (20%) did not fit this classification of NCL. With further research, 4 additional forms have been recognized: Finnish (13), Gypsy/Indian (14), Turkish (15)--variants of LINCL, and Northern epilepsy (16), also known as progressive epilepsy with mental retardation. These eight NCL forms resulted from 151 different mutations in genes CLN1 to CLN8 causing different phenotypes (http://www.ucl.ac.uk/ncl). The genes CLN1 and CLN2 encode lysosomal palmitoyl protein thioesterase and tripeptidyl peptidase 1. The diagnosis of NCL is based on clinicopathological (C-P) findings, enzymatic assay, and molecular genetic testing. Ultrastructural studies must be performed to confirm the presence and nature of lysosomal storage material (fingerprint or curvilinear profiles, or granular osmiophilic deposits) before doing biochemical testing. Pheno/genotypic correlation studies are discussed.


[Apparatus and electrodes for nerve stimulation].
To successfully accomplish stimulation of a nerve a portable stimulator with bipolar electrodes has been designed. The level of the nerve trunk resistance was found to comprise 6 kOm. The threshold pulsed current amplitude at which the effect becomes apparent lies within the range of 1-2 mA, with the threshold of the potential pulses amplitude amounting to 4-12 V. The construction of the electrodes is described and the block diagram along with technical characteristics of the stimulator are presented.


Variance maps as a novel tool for localizing regions of interest in imaging studies of individual differences.
Cognitive neuroimaging studies of individual differences seek to reveal brain mechanisms of cognition by associating intersubject variability in brain activation with other variables of interest, such as sex, personality trait, or mood state. The choice of a priori regions of interest (ROIs) raises problems, because the selection criterion is typically consistent activation across prior studies, suggesting little intersubject variability. Here, we introduce a novel approach for selecting regions that are defined on the basis of their variance characteristics, rather than on the basis of their location or because of theoretical expectations. These regions of variance (ROVs) constitute the search space with which to assess how much of the observed variance can be ascribed to specific variables of interest. We compare the ROI and ROV approaches by applying each to the same data set and suggest that the conjunction of both methods may yield the greatest likelihood of capturing the rich relation between brain and behavior, while limiting the search space for statistical analyses and minimizing false positive errors.


Anion permeability and conduction of adenine nucleotides through a chloride channel in cardiac sarcoplasmic reticulum.
Cardiac sarcoplasmic reticulum (SR) membrane contains several chloride (Cl-) channels. We have characterized a 116-pS Cl- channel (500 mM cis, 50 mM trans Cl-) in cardiac SR that is activated by protein kinase A-dependent phosphorylation. To understand its function further, we examined the permeation of various anions and adenine nucleotides using the planar lipid bilayer-vesicle fusion technique. This Cl- channel showed a high selectivity to anions and its permeability sequence was Br- > Cl- > I- > NO3- > F-. When all anions were replaced with ATP in the cis solution, channel activity persisted. The conductance was 78 pS with 200 mM ATP and 68 pS with 100 mM ATP. The reversal potentials were +63 mV and +41 mV in 200 mM ATP and in 100 mM ATP, respectively. With 100 mM ADP or AMP in the cis solution, channel activities were also observed. The conductances were 87 pS with 100 mM ADP and 115 pS with 100 mM AMP. The apparent adenine selectivity of this channel was ATP > ADP > AMP, assuming that they exist as divalent anions. These results suggest that the SR Cl- channel in cardiac cells may serve as a transporter for the movement of adenine nucleotides between cytosol and SR lumen.


Halogen Bonds Formed between Substituted Imidazoliums and N Bases of Varying N-Hybridization.
Heterodimers are constructed containing imidazolium and its halogen-substituted derivatives as Lewis acid. N in its sp³, sp² and sp hybridizations is taken as the electron-donating base. The halogen bond is strengthened in the Cl < Br < I order, with the H-bond generally similar in magnitude to the Br-bond. Methyl substitution on the N electron donor enhances the binding energy. Very little perturbation arises if the imidazolium is attached to a phenyl ring. The energetics are not sensitive to the hybridization of the N atom. More regular patterns appear in the individual phenomena. Charge transfer diminishes uniformly on going from amine to imine to nitrile, a pattern that is echoed by the elongation of the C-Z (Z=H, Cl, Br, I) bond in the Lewis acid. These trends are also evident in the Atoms in Molecules topography of the electron density. Molecular electrostatic potentials are not entirely consistent with energetics. Although I of the Lewis acid engages in a stronger bond than does H, it is the potential of the latter which is much more positive. The minimum on the potential of the base is most negative for the nitrile even though acetonitrile does not form the strongest bonds. Placing the systems in dichloromethane solvent reduces the binding energies but leaves intact most of the trends observed in vacuo; the same can be said of ∆G in solution.


Parental experiences on the role of wheelchairs in the lives of their children with mobility impairments: a qualitative exploration in Dubai.
To explore parental experiences on the role of wheelchairs in the lives of their children with mobility impairments in Dubai. Seven participants were recruited through purposive sampling and their experiences were explored by conducting semi-structured interviews. The audio recordings were transcribed and thematically analysed. The findings showed that wheelchairs were an essential part of the children`s lives, which enabled their participation in the home, the school and the community. Procurement processes were difficult owing to a lack of assessment and prescription processes as well as insurance companies providing little assistance with payment. The participants described Dubai as a wheelchair friendly city and two overarching themes emerged; firstly, The wheelchair: "It is her life", and, secondly, Participation: Isolation versus inclusion. The study is the first of its kind in Dubai and indicated that the wheelchair played an important role in the children's lives and allowed participation in life roles that brought joy and fulfilment. Without wheelchairs, children would be isolated and frustrated. However, some of the participants were not satisfied with their child's current wheelchair and felt the chair was not appropriate. Recommendations to specific stakeholders included: the development of policies to guide wheelchair service provision by government. In addition, insurance providers could collaborate with the government to adhere to the policy to ensure healthy lives and promote well-being for all.IMPLICATIONS FOR REHABILITATIONThe wheelchair provided children the mobility to participate in life roles instead of being isolated.Not all children had appropriate wheelchairs.Service providers and medical insurance did not give sufficient support during wheelchair selection and procurement.


Incidence and clinical significance of left ventricular thrombus in tako-tsubo cardiomyopathy assessed with echocardiography.
Left ventricular (LV) thrombus is a known complication of tako-tsubo cardiomyopathy (TC). However, current literature almost exclusively consists of isolated case reports. The aim of this study was to determine the incidence and clinical significance of LV thrombus formation in TC. Over a 33-month period 52 patients with TC were assembled into a database at our institution. A retrospective database search was performed to identify patients with LV thrombus among these patients. LV thrombus, by echocardiography, was discovered in four patients[(8%); 95% confidence interval 3-19%]. Thrombus was present at the time of diagnosis in three patients. In one patient thrombus was absent initially and developed later. The LV apex was the site of thrombus formation in two patients, but the true apex was spared in the other two. All four patients had elevated serum levels of C-reactive protein (CRP). Two patients also had thrombocytosis. Treatment with low molecular weight heparin (LMWH) led to resolution of thrombus in all cases. Our findings suggest that LV thrombus is a noteworthy complication in TC. It can occur both at initial presentation or at anytime later during the disease course. Elevated CRP levels and thrombocytosis may indicate a higher risk of thrombus formation.


Mecillinam in urinary tract infections and in septicaemia.
The clinical and bacteriological efficacy as well as the tolerance of mecillinam, a new beta-lactam antibiotic, administered parenterally in a dose of 40 mg/kg body weight, was investigated in 21 hospitalized patients with urinary tract infections or septicaemia. Success, defined as eradication of infecting organisms two to five days after treatment, was found in eight of 16 patients with urinary tract infections. Persistence of the original pathogen after treatment was seen in four patients, all with complicated urinary tract infection. Reinfection was seen in two patients, while the results were unevaluable in two cases. The five patients with septicaemia were all cured of their infection, this result being attributed solely to mecillinam in two cases, while a combined action of mecillinam and another antibiotic produced a cure in the other three cases. Escherichia coli resistant to mecillinam were isolated from two patients with persistence of bacteriuria following mecillinam treatment. Impairment of renal function may have been a contributory factor to the poor treatment response in patients with complicated urinary tract infection. Inasmuch as no important side-effects were recorded and mecillinam appears safe in patients with impaired renal and liver function, a higher dose may be indicated in these more complicated cases.


Facile synthesis of dispirooxindole-fused heterocycles via domino 1,4-dipolar addition and Diels-Alder reaction of in situ generated Huisgen 1,4-dipoles.
A facile synthetic protocol was developed for the efficient synthesis of complex dispirooxindole-fused heterocycles via a three-component reaction. The key strategies involve a domino 1,4-dipolar addition and Diels-Alder reaction of the in situ generated Huisgen 1,4-dipoles from the addition reaction of 4-dimethylaminopyridine with acetylenedicarboxylate to 3-phenacylideneoxindole.


Functional expression and characterization of a sodium-dependent nucleoside transporter hCNT2 cloned from human duodenum.
We have cloned and functionally expressed a sodium-dependent human nucleoside transporter, hCNT2, from a CNS cancer cell line U251. Our cDNA clone of hCNT2 had the same predicted amino acid sequence as the previously cloned hCNT2 transporter. Of the several cell lines studied, the best hCNT2 transport function was obtained when transiently expressed in U251 cells. Na(+)-dependent uptake of [3H]inosine in U251 cells transiently expressing hCNT2 was 50-fold greater than that in non-transfected cells, and uptake in Na(+)-containing medium was approximately 30-fold higher than that at Na(+)-free condition. The hCNT2 displayed saturable uptake of [3H]inosine with K(m) of 12.8 microM and V(max) of 6.66 pmol/mg protein/5 min. Uptake of [3H]inosine was significantly inhibited by the purine nucleoside drugs dideoxyinosine and cladribine, but not by acyclic nucleosides including acyclovir, ganciclovir, and their prodrugs valacyclovir and valganciclovir. This indicates that the closed ribose ring is important for binding of nucleoside drugs to hCNT2. Among several pyrimidine nucleosides, hCNT2 favorably interacted with the uridine analogue floxuridine. Interestingly, we found that benzimidazole analogues, including maribavir, 5,6-dichloro-2-bromo-1-beta-D-ribofuranosylbenzimidazole (BDCRB), and 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), were strong inhibitors of inosine transport, even though they have a significantly different heterocycle structure compared to a typical purine ring. As measured by GeneChip arrays, mRNA expression of hCNT2 in human duodenum was 15-fold greater than that of hCNT1 or hENT2. Further, the rCNT2 expression in rat duodenum was 20-fold higher than rCNT1, rENT1 or rENT2. This suggests that hCNT2 (and rCNT2) may have a significant role in uptake of nucleoside drugs from the intestine and is a potential transporter target for the development of nucleoside and nucleoside-mimetic drugs.


Bees' subtle colour preferences: how bees respond to small changes in pigment concentration.
Variability in flower colour of animal-pollinated plants is common and caused, inter alia, by inter-individual differences in pigment concentrations. If and how pollinators, especially bees, respond to these small differences in pigment concentration is not known, but it is likely that flower colour variability impacts the choice behaviour of all flower visitors that exhibit innate and learned colour preferences. In behavioural experiments, we simulated varying pigment concentrations and studied its impact on the colour choices of bumblebees and honeybees. Individual bees were trained to artificial flowers having a specific concentration of a pigment, i.e. Acridine Orange or Aniline Blue, and then given the simultaneous choice between three test colours including the training colour, one colour of lower and one colour of higher pigment concentration. For each pigment, two set-ups were provided, covering the range of low to middle and the range of middle to high pigment concentrations. Despite the small bee-subjective perceptual contrasts between the tested stimuli and regardless of training towards medium concentrations, bees preferred neither the training stimuli nor the stimuli offering the highest pigment concentration but more often chose those stimuli offering the highest spectral purity and the highest chromatic contrast against the background. Overall, this study suggests that bees choose an intermediate pigment concentration due to its optimal conspicuousness. It is concluded that the spontaneous preferences of bees for flower colours of high spectral purity might exert selective pressure on the evolution of floral colours and of flower pigmentation.


Persistence of visna virus in cultured ferret brain cortex and fibroblasts.
Cerebral cortex tissue fragments from newborn ferrets have been cultured in vitro and, when exposed to visna virus, failed to exhibit a cytopathic effect but retained the genome of the virus in a quiescent state for 46 d before synthesizing plaque-forming virus for the subsequent 26 d. In contrast, infection of an established line of cells derived from a ferret's brain with visna virus resulted in the formation of the polykaryocytes typically produced by this virus and a limited synthesis of plaque-forming virus. Ferret cerebral cortex cultures may be suitable in vitro hosts for studies to define the virus-host interactions that result in virus-induced demyelination.


Effects of whole-body vibration training on physical function, bone and muscle mass in adolescents and young adults with cerebral palsy.
We performed a clinical trial on the effects of whole-body vibration training (WBVT) on muscle function and bone health of adolescents and young adults with cerebral palsy. Forty participants (11.3-20.8 years) with mild to moderate cerebral palsy (GMFCS II-III) underwent 20-week WBVT on a vibration plate for 9 minutes/day 4 times/week at 20 Hz (without controls). Assessments included 6-minute walk test, whole-body DXA, lower leg pQCT scans, and muscle function (force plate). Twenty weeks of WBVT were associated with increased lean mass in the total body (+770 g; p = 0.0003), trunk (+410 g; p = 0.004), and lower limbs (+240 g; p = 0.012). Bone mineral content increased in total body (+48 g; p = 0.0001), lumbar spine (+2.7 g; p = 0.0003), and lower limbs (+13 g; p < 0.0001). Similarly, bone mineral density increased in total body (+0.008 g/cm(2); p = 0.013), lumbar spine (+0.014 g/cm(2); p = 0.003), and lower limbs (+0.023 g/cm(2); p < 0.0001). Participants reduced the time taken to perform the chair test, and improved the distance walked in the 6-minute walk test by 11% and 35% for those with GMFCS II and III, respectively. WBVT was associated with increases in muscle mass and bone mass and density, and improved mobility of adolescents and young adults with cerebral palsy.


Evaluation of ELISA for the detection of Toxoplasma antibodies in swine sera.
Enzyme-linked immunosorbent assay (ELISA) is compared with the indirect fluorescent antibody test (IFAT), the indirect haemagglutination test (IHAT) and the latex agglutination (LA) test for the detection of toxoplasma antibodies in swine sera. The 100 swine sera examined represent ELISA values from greater than 0 to 154 EIU. The agreement was highest (0.67) between ELISA and IFAT with an ELISA cut-off value of 30 EIU, and between ELISA and the LA test with an ELISA cut-off value of 50 EIU (0.74). All sera giving less than 10 EIU were negative in the other tests, and all those with greater than 70 EIU were positive in 1, 2 or all of the reference tests. In order to avoid false positive results with ELISA, all sera giving 10-70 EIU should be confirmed with a test which has a good specificity, e.g. IFAT. ELISA is a sensitive test and is highly suitable for the screening of large amounts of samples, but it may be too complicated for screening toxoplasma antibodies in the laboratories of abattoirs.


Estimation by an electrophysiological method of the expression of oxytocin receptor mRNA in human myometrium during pregnancy.
In order to evaluate the changes in uterine oxytocin receptor-specific mRNA during pregnancy, receptor expression in Xenopus oocytes are examined electrophysiologically following microinjection of mRNA from human uterus. In voltage-clamped oocytes injected with term myometrial mRNA, oxytocin elicited an inward current response. The amplitude of the oxytocin-induced current increased with increasing dose of oxytocin, but no current was elicited following stimulation with vasopressin. The oxytocin-induced current was completely eliminated as a result of pretreatment with a specific oxytocin antagonist. 21 of 27 oocytes injected with term myometrial mRNA showed a large amplitude (77.0 +/- 16.1 nA) reaction to oxytocin. In comparison, only 3 of 13 oocytes injected with early gestational myometrial mRNA exhibited a small amplitude (4.6 +/- 1.4 nA) reaction to oxytocin. No oxytocin response was observed in oocytes injected with non-pregnant myometrial mRNA. These results indicate that the striking increment in oxytocin sensitivity in term uterus depends on the increase in mRNA encoding oxytocin receptors.


Sarcopenia: Inflammatory and Humoral Markers in Older Heart Failure Patients.
Sarcopenia is highly prevalent in heart failure (HF) patients, and the involvement of biomarkers in its pathophysiology is suggested, but little has been studied concerning HF sarcopenic patients. To evaluate the association between inflammatory and humoral markers with sarcopenia, as well as the impact of sarcopenia on quality of life and functional capacity in older HF patients. In this cross-sectional study, 90 outpatient HF patients, aged ≥ 60 years, were evaluated for sarcopenia (EWGSOP2 diagnostic criteria), inflammation (high-sensitive C-reactive protein [hs-CRP], Interleukin-6 [IL-6], tumor necrosis factor alpha [TNF-α]) and humoral markers (total testosterone and insulin-like growth factor-1 [IGF-1]), physical activity (International Physical Activity Questionnaire), quality of life (Minnesota Living with Heart Failure Questionnaire), and functional capacity (6-minute walk test). The adopted level of significance was p<0.05. Patients had a mean age of 69.4 ± 7.2 years, 67.8% were male, with left ventricular ejection fraction (LVEF) of 35.9 ± 11.9% and 22 (24.4%) were sarcopenic. Age (73.1 ± 8.1 and 68.3 ± 6.5 years; p= 0.006), body mass index (BMI) (23.1 ± 2.8 and 28.2 ± 4.2 kg/m2; p <0.001), and LVEF (29.9 ± 8.8 and 37.9 ± 12.1%; p= 0.005) were different between groups with and without sarcopenia, respectively. After adjusting for age, ethnicity, BMI, LVEF, and the use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers, sarcopenia was associated with higher serum levels of IL-6 and worse functional capacity. In HF patients, sarcopenia was associated with IL-6 levels and functional capacity.


N-butanol extract of Hedyotis diffusa protects transgenic Caenorhabditis elegans from Aβ-induced toxicity.
Hedyotis diffusa Willd (Rubiaceae) is a widely used and resourceful traditional Chinese medicine that exerts protection against aging and age-related diseases. However, the underlying mechanisms of the protective effects remain largely unclear. Alzheimer's disease (AD) is an age-related neurodegenerative disease, of which β-amyloid (Aβ)-induced toxicity has been suggested as a main cause. Herein, we use the transgenic Caenorhabditis elegans CL4176, CL2006, and CL2355 strains, which express human Aβ1-42 peptide, to investigate the effects and the possible mechanisms of n-butanol extract of H.diffusa (HDB)-mediated protection against Aβ toxicity in vivo. During the experiments, a method of quality control for HDB was established by HPLC. Additionally, we examined the effects of HBD on gene expression changes with qRT-PCR, aggregation of Aβ plagues with thioflavin-S staining, and protein detection with GFP labeling. HDB improved lifespan, locomotion, and stress resistance. Further study showed that HDB decreased paralysis, the accumulation of ROS, and AChE activity. Moreover, HDB suppressed neuronal Aβ-expression-induced defects in chemotaxis behavior and increased SOD activity. HDB also downregulated the Aβ mRNA level and decreased the number of Aβ deposits. Furthermore, HDB increased the expression levels of sod-3, daf-16, hsf-1, and hsp-16.2 gene and upregulated hsp-16.2::GFP and gst-4::GFP expression. Taken together, these results suggest that HDB may protect against Aβ-induced toxicity in C. elegans via the insulin/insulin-like growth factor-1 (IGF-1) signaling pathway.


Modeling catalytic mechanism of nitrile hydratase by semi-empirical quantum mechanical calculation.
Nitrile hydratase (NHase) is an important industrial enzyme capable of converting nitriles to corresponding amides. Utilizing the method of semi-empirical quantum mechanical (QM) calculation by TRITON, the bioconversion process of acrylonitrile to acrylamide catalyzed by NHase was successfully performed on a computer. Crystal structure of a Co-type NHase from Pseudonocardia thermophila JCM 3095 (PDB code 1IRE) was selected as the target for acrylonitrile autodock. In silico calculations were performed on the NHase-acrylonitrile complex to simulate the enzyme catalysis mechanism by quantitatively comparing energy changes of each reaction pathway. Simulation results showed that active site activation is the first step of NHase catalysis, in which the Co2+ coordinated to a water molecule forms a Co-OH complex mediated by the oxidized alpha-CEA113. Then the oxygen atom in the Co-OH attacks the C atom in the -CN triple bond of acrylonitrile, forming a precursor of acrylamide. Consequently, proton rearrangement happens transforming the precursor into the final product of acrylamide, under the assistance of the hydrogen atom in the -OH group of alpha-SER112. Gibbs energy changes of three steps corresponding to the active center activation, nucleophilic attack and proton rearrangement are around -31, 23 and -12 kcal/mol, respectively.


Development of gastric cancer in nonatrophic stomach with highly active inflammation identified by serum levels of pepsinogen and Helicobacter pylori antibody together with endoscopic rugal hyperplastic gastritis.
This study aimed to elucidate groups at high risk of developing cancer among patients with serologically identified Helicobacter pylori infection and nonatrophic stomach. Annual endoscopy was performed for a mean of 5.4 years in 496 asymptomatic middle-aged men who were H. pylori antibody-positive and pepsinogen (PG) test-negative. Subjects were stratified according to the activity of H. pylori-associated gastritis measured by serum levels of PG and H. pylori antibody, and/or by endoscopic findings of rugal hyperplastic gastritis (RHG), and cancer development was investigated. During the study period, seven cases of cancer developed in the cohort (incidence rate, 261/100,000 person-years), with 85.7% developing in the group showing a PGI/II ratio ≤ 3.0, reflecting active inflammation-based high PGII levels. Cancer incidence was significantly higher in this group (750/100,000 person-years) than in groups with less active gastritis. Furthermore, cancer incidence for this group was significantly higher in the subgroup with high H. pylori antibody titers than in the low-titer subgroup. Meanwhile, endoscopic findings revealed that 11.7% of subjects showed RHG reflecting localized highly active inflammation, and cancer risk was significantly higher in patients with RHG than in patients without. Combining the two serum tests and endoscopic examination for RHG allowed identification of subjects with more active gastritis and higher cancer risk. No cancer development was observed in these high-risk subjects after H. pylori eradication. Subjects with highly active gastritis identified by the two serological tests and endoscopic RHG constitute a group at high risk of cancer development with H. pylori-infected nonatrophic stomach.


HFE gene mutations analysis in Basque hereditary haemochromatosis patients and controls.
C282Y/C282Y genotype is the prevalent genotype in Hereditary Haemochromatosis (HH), however, other genotypes have been associated with the disease. The objective of our study was to analyse the frequency of the three main mutations of HFE gene in HH patients and controls from the Basque population with differential genetic characteristics. Thirty five HH patients and 116 controls were screened for C282Y, H63D and S65C mutations using a PCR-RFLP technique. The association of HLA-A and-B alleles and HFE mutations was also studied in Basque controls. The frequency of C282Y homozygotes in the group of patients was only 57%. The rest of the patients presented heterogeneous genotypes, including compound heterozygotes: 11% of them were C282Y/H63D; and 2.85% were H63D/S65C. H63D or S65C heterozygotes had a frequency of 11% and 2.85 respectively and 5.71% patients lacked any mutation The high frequency of H63D in the healthy Basque population is confirmed in this study. A considerable incidence of S65C is observed either in controls and in HH (3%) or in iron overloaded patients. The peculiar genetic characteristics of Basques could explain the heterogeneity of genotypes in HH patients of this group. Further studies should be carried out to confirm these findings although the implication of other genetic or external factors in the development of HH is suggested.


Plasma polyol levels in patients with cataract.
Galactitol and sorbitol concentrations in plasma were determined in patients (with or without cataract) in whom homo- or heterozygosity for galactokinase, galactose-1-phosphate uridyltransferase, systemic or peripheral UDP-galactose epimerase and sorbitol dehydrogenase deficiency was confirmed. For the above disorders it can be concluded that elevation of plasma polyols is not always related to the presence or absence of cataract. In all cases with cataract, however, the plasma galactitol or sorbitol levels were elevated. In another group of patients with unexplained congenital or infantile cataracts, but without apparent enzyme defects, mild to moderately elevated concentrations of plasma galactitol or sorbitol were found in about 45%. In 8% of this group the cataract and the elevated plasma galactitol concentration could possibly have been related to partial maternal enzyme deficiency. In all the other cases the elevated plasma polyol concentration remains unexplained but could indicate a further cause of cataract formation due to a hitherto unknown galactose or glucose metabolic aberration.


Effectiveness of maternal immunisation with a three-component acellular pertussis vaccine at preventing pertussis in infants in the United States: Post-hoc analysis of a case-control study using Bayesian dynamic borrowing.
Immunisation during pregnancy with a tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine can protect infants against pertussis between birth and paediatric vaccination. We aimed to estimate the vaccine effectiveness (VE) of third-trimester pregnancy immunisation with the three-component acellular pertussis (Td3ap) vaccine at preventing pertussis in infants <2 months in the United States (US), to support a label update. We performed a post-hoc sub-analysis of a case-control study conducted in six US Emerging Infections Program Network states between 2011 and 2014. Our analysis included only cases and controls whose mothers were either vaccinated with Td3ap or did not receive any Tdap vaccine. The association between Td3ap maternal immunisation and pertussis in infants was assessed for US data using a frequentist method with conditional logistic regression. A robustified analysis was conducted using Bayesian dynamic borrowing of non-US data, considering a mixing-weighted prior of 90% for historical non-US VE data, and of 10% for a vague prior. VE was estimated as (1-odds ratio) × 100%. Sensitivity analyses accounting for the impact of each non-US study, different mixing weights and missing/ambiguous data were performed. We included 108 cases and 183 controls. Based on US data, the estimated VE of third-trimester maternal immunisation with Td3ap at preventing pertussis in infants <2 months was 78.0% (95% confidence interval: -38.0; 96.5). VE estimated by Bayesian dynamic borrowing of non-US data (with a 90% weight for historical data) was 83.4% (95% credible interval: 55.7; 92.5); sensitivity analyses produced similar VE estimates. Effectiveness of third-trimester pregnancy immunisation with Td3ap at preventing infant pertussis in the US is very likely to be ≥ 50% and is most likely ∼ 80%. Bayesian dynamic borrowing of non-US VE data allowed overcoming the limited power (due to small sample size) of a brand-specific sub-analysis by considering additional evidence.


Cystic fibrosis: the prognosis for five-year survival.
Statistical discriminant analysis is applied to 41 concomitant variables obtained during the first year of study of 226 patients with cystic fibrosis. A discriminant function based on six variables is developed which can be used as a predictive index. This index estimates the probability of 5-year survival for an individual patient and can also be used to classify patients into one of two groups: (1) will live for 5 years or (2) will die within 5 years. Speculation A classification rule for cystic fibrosis is presented which correctly assigns 90% of the 5-year survivors and 84% of those who expire. Such a classification scheme is useful for clinical and research purposes.


Nutritional Quality and Physicochemical Characteristics of Defatted Bovine Liver Treated by Supercritical Carbon Dioxide and Organic Solvent.
Defatted bovine liver (DBL) is a potential source of protein and minerals. Supercritical carbon dioxide (SC-CO2) and a traditional organic solvent method were used to remove lipid from bovine liver, and the quality characteristics of a control bovine liver (CBL), bovine liver defatted by SC-CO2 (DBLSC-CO2) at different pressures, and bovine liver defatted by organic solvent (DBL-OS) were compared. The DBLSC-CO2 samples had significantly higher (p<0.05) protein, amino acid, carbohydrate, and fiber contents than CBL and DBL-OS. There was a higher yield of lipid from CBL when using SC-CO2 than the organic solvent method. SDS-PAGE analysis demonstrated that the CBL and DBLSC-CO2 had protein bands of a similar intensity and area, whereas DBL-OS appeared extremely poor bands or no bands due to the degradation of proteins, particularly in the 50 to 75 kDa and 20 to 25 kDa molecular weight ranges. In addition, DBLSC-CO2 was shown to have superior functional properties in terms of total soluble content, water and oil absorption, and foaming and emulsification properties. Therefore, SC-CO2 treatment offers a nutritionally and environmentally friendly approach for the removal of lipid from high protein food sources. In addition, SC-CO2 may be a better substitute of traditional organic solvent extraction for producing more stable and high quality foods with high-protein, fat-free, and low calorie contents.


Thromboembolism and bleeding risk in atrial fibrillation ablation with uninterrupted anticoagulation between new oral anticoagulants and vitamin K antagonists: insights from an updated meta-analysis.
Cumulative reports comparing the efficacy and safety outcomes between uninterrupted NOACs and vitamin K antagonists (VKA) in AF ablation had been freshly published. This meta-analysis aimed at offering a more comprehensive evaluation between these two anticoagulants in uninterrupted strategy. We searched in PUBMED, EMBASE, and Cochrane Library (inception to June 10, 2019) for eligible studies. Fixed-effects model was preferred in pooled analysis if I2 < 50%. Publication bias was also evaluated. A total of 23 studies involving 12,725 individuals were analyzed in this literature. There were no difference between uninterrupted NOACs and VKA groups in incidence of Stroke/TIA (RR 0.98, 95% CI 0.54-1.77, P = 0.93, I2 = 0%), silent cerebral embolism (RR 1.09, 95% CI 0.82-1.43, P = 0.56, I2 = 0%), minor bleeding complication (RR 0.97, 95% CI 0.83-1.14, P = 0.73, I2 = 0%), cardiac tamponade (RR 0.95, 95% CI 0.63-1.42, P = 0.80, I2 = 0%). Uninterrupted NOACs was associated with significantly lower major bleeding incidence (RR 0.67, 95% CI 0.49-0.92, P = 0.01, I2 = 0%), pericardial effusion (RR 0.75, 95% CI 0.56-1.00, P = 0.048, I2 = 9%). In sub-analysis, no difference was found in all sub-analyses for Stroke/TIA while significant major bleeding risk reduction in uninterrupted NOACs was identified in the subgroup of CHA2DS2-VASc score ≥ 2 and target activated clotting time (ACT) > 300 s. In conclusions, uninterrupted NOACs was more effective than uninterrupted VKA in reducing major bleeding and pericardial effusion risk without increasing thromboembolism risk, and the benefits of uninterrupted NOACs on major bleeding complication could be more pronounced if CHA2DS2-VASc score ≥ 2 or target ACT > 300 s.


Induction chemotherapy with vinblastine, bleomycin, and cis-diamminedichloroplatinum in squamous cell carcinoma of the head and neck.
The results of induction chemotherapy with vinblastine, bleomycin, and cis-platinum II are reported. No survival advantage was seen when the entire treatment group was compared with an historical control group. Special attention is directed to the meaning of complete response and the potential treatment options and survival advantages of the complete responders subgroup.


Ambient temperature and emergency room admissions for acute coronary syndrome in Taiwan.
Acute coronary syndrome (ACS) is an important public health problem around the world. Since there is a considerable seasonal fluctuation in the incidence of ACS, climatic temperature may have an impact on the onset of this disease. The objective of this study was to assess the relationship between the average daily temperature, diurnal temperature range and emergency room (ER) admissions for ACS in an ER in Taichung City, Taiwan. A longitudinal study was conducted which assessed the correlation of the average daily temperature and the diurnal temperature range to ACS admissions to the ER of the city's largest hospital. Daily ER admissions for ACS and ambient temperature were collected from 1 January 2000 to 31 March 2003. The Poisson regression model was used in the analysis after adjusting for the effects of holiday, season, and air pollutant concentrations. The results showed that there was a negative significant association between the average daily temperature and ER admissions for ACS. ACS admissions to the ER increased 30% to 70% when the average daily temperature was lower than 26.2 degrees C. A positive association between the diurnal temperature range and ACS admissions was also noted. ACS admissions increased 15% when the diurnal temperature range was over 8.3 degrees C. The data indicate that patients suffering from cardiovascular disease must be made aware of the increased risk posed by lower temperatures and larger changes in temperature. Hospitals and ERs should take into account the increased demand of specific facilities during colder weather and wider temperature variations.


[Changes in metabolism of the nervous system in exposure to ionizing radiation at supralethal doses].
Some biochemical disorders in the animals' central nervous system mainly in brain have been analysed after the exposure to superlethal doses of ionizing radiation as well in a state of the so-called early transient incapacity. The metabolism of gamma-aminobutyric acid, ammonia, histamine, cyclic nucleotides, prostaglandins and other biologically active substances is compared. Their investigation as metabolic regulators and modulators for nerve tissue seems to be of particular importance for deciphering the molecular mechanisms of changes in the central nervous system functional state and for discovering the possibility of its maintaining at a given level of activity.


Modulation of extracellular gamma-aminobutyric acid in the ventral pallidum using in vivo microdialysis.
Intracranial microdialysis was used to investigate the origin of extracellular gamma-aminobutyric acid (GABA) in the ventral pallidum. Changes in basal GABA levels in response to membrane depolarizers, ion-channel blockers, and receptor agonists were determined. Antagonism of Ca2+ fluxes with high Mg2+ in a Ca(2+)-free perfusion buffer decreased GABA levels by up to 30%. Inhibition of voltage-dependent Na+ channels by the addition of tetrodotoxin also significantly decreased basal extracellular GABA concentrations by up to 45%, and blockade of Ca2+ and Na+ channels with verapamil reduced extracellular GABA by as much as 30%. The addition of either the GABAA agonist, muscimol, or the GABAB agonist, baclofen, produced a 40% reduction in extracellular GABA. GABA release was stimulated by high K+ and the addition of veratridine to increase Na+ influx. High K(+)-induced release was predominantly Ca(2+)-dependent, whereas the effect of veratridine was potentiated in the absence of extracellular Ca2+. Both high K(+)- and veratridine-induced elevations in extracellular GABA were inhibited by baclofen, whereas only veratridine-induced release was antagonized by muscimol. These results demonstrate that at least 50% of basal extracellular GABA in the ventral pallidum is derived from Ca(2+)- or Na(+)-dependent mechanisms. They also suggest that Na(+)-dependent release of GABA via reversal of the uptake carrier can be shown in vivo.


Zoledronic Acid Modulates Cytokine Expression and Mitigates Bone Loss during the Development of Induced Apical Periodontitis in a Mice Model.
Bisphosphonates are antiresorptive drugs used worldwide to treat systemic bone pathologies. This study aimed to assess the impact of zoledronic acid on the progression of induced apical periodontitis and the expression of cytokines interleukin (IL)-1β, IL-10, IL-6, and tumor necrosis factor alpha (TNF-α) in a mouse model. Sixteen female isogenic BALB/c mice 6 weeks of age were distributed into 2 groups: mice with induced apical periodontitis (the AP group, n = 8) and mice with induced apical periodontitis treated with zoledronic acid (the AP-ZA group, n = 8). The AP-ZA group received a dose of 125 μg/kg zoledronic acid diluted in sterile saline solution administered intraperitoneally once a week for 4 weeks before pulp exposure, whereas the AP group received only saline solution. Pulp exposures were performed on the maxillary first molars for the induction of apical periodontitis, and mice were euthanized after 7 and 21 days. The jaws were collected; scanned using micro-computed tomographic imaging; and processed for polymerase chain reaction analysis of IL-1β, IL-10, IL-6, and TNF-α. The Student t test was performed for parametric data, and Mann-Whitney U tests were used for nonparametric data. The level of significance was set at 5%. Micro-computed tomographic imaging revealed higher bone resorption in the AP group compared with the AP-ZA group at both time points (P < .05). Real-time polymerase chain reaction demonstrated higher TNF-α expression in the AP group at both time points and higher IL-6 and IL-1β expression in the AP group at the 7- and 21-day time points, respectively, compared with the AP-ZA group (P < .05). No differences were observed regarding IL-10 expression between the groups. Zoledronic acid had significant anti-inflammatory and antiresorptive effects on apical periodontitis in mice.


Phase I immunotherapy with a modified vaccinia virus (MVA) expressing human MUC1 as antigen-specific immunotherapy in patients with MUC1-positive advanced cancer.
The MUC1 protein is a highly glycosylated mucin normally found at the apical surface of mucin-secreting epithelial cells in many types of tissues. MUC1 is expressed, but heavily underglycosylated, in different human tumors. TG4010 is a viral suspension of a recombinant vaccinia vector (MVA) containing DNA sequences coding for the human MUC1 antigen and interleukin-2 (IL-2). This product was developed for use as a vaccine in cancer patients whose tumors express the MUC1 antigen. The objective of the present study was to determine the safety of the product and to define the dose of TG4010 to be used in further clinical trials. Thirteen patients with different solid tumors were treated by repeated intramuscular injection with increasing doses of TG4010 in two separate phase I studies, one in Europe (Basel-CR) and one in the United States (UCLA-RF): a total of 6 patients were treated at a dose of 5 x 10(6) pfu, 3 patients at 5 x 10(7) pfu, and 4 patients at 10(8) pfu. Safety, efficacy, and different immunological tests were the endpoints of the study. Tolerance of TG4010 was excellent, and side effects mainly consisted of injection site pain and influenza-like symptoms. There was no apparent detrimental effect of repeated injections of the vaccinia virus. Four of thirteen evaluable patients showed stabilization of their disease for 6 to 9 months. One lung cancer patient who was initially progressing after the first injections later showed a marked decrease in the size of his metastases that lasted for 14 months. Some T cell proliferative immune responses were seen in five patients. The administration of TG4010 was generally well tolerated in patients with metastatic tumors, and transient disease stabilization was observed in several patients, warranting further clinical studies with the product.


Development of β-TCP-Ti6Al4V structures: Driving cellular response by modulating physical and chemical properties.
Load-bearing implants success is strongly dependent on several physical and chemical properties that are known to drive cellular response. In this work, multi-material β-TCP-Ti6Al4V cellular structures were designed to combine Ti6Al4V mechanical properties and β-Tricalcium Phosphate bioactivity, in order to promote bone ingrowth as the bioactive material is being absorbed and replaced by newly formed bone. In this sense, the produced structures were characterized regarding roughness, wettability, β-TCP quantity and quality inside the structures after fabrication and the pH measured during cell culture (as consequence of β-TCP dissolution) and those aspects were correlated with cellular viability, distribution, morphology and proliferation. These structures displayed a hydrophilic behavior and results showed that the addition of β-TCP to these cellular structures led to an alkalization of the medium, aspect that significantly influences the cellular response. Higher impregnation ratios were found more adequate for lowering the media pH and toxicity, and thus enhance cell adhesion and proliferation.


Interprofessional bedside rounding improves quality of feedback to resident physicians.
Obtaining high quality feedback in residency education is challenging, in part due to limited opportunities for faculty observation of authentic clinical work. This study reviewed the impact of interprofessional bedside rounds ('iPACE™') on the length and quality of faculty narrative evaluations of residents as compared to usual inpatient teaching rounds. Narrative comments from faculty evaluations of Internal Medicine (IM) residents both on usual teaching service as well as the iPACE™ service (spanning 2017-2020) were reviewed and coded using a deductive content analysis approach. Six hundred ninety-two narrative evaluations by 63 attendings of 103 residents were included. Evaluations of iPACE™ residents were significantly longer than those of residents on usual teams (109 vs. 69 words, p < 0.001). iPACE™ evaluations contained a higher average occurrence of direct observations of patient/family interactions (0.72 vs. 0.32, p < 0.001), references to interprofessionalism (0.17 vs. 0.05, p < 0.001), as well as specific (3.21 vs. 2.26, p < 0.001), actionable (1.01 vs. 0.69, p < 0.001), and corrective feedback (1.2 vs. 0.88, p = 0.001) per evaluation. This study suggests that the iPACE™ model, which prioritizes interprofessional bedside rounds, had a positive impact on the quantity and quality of feedback, as measured via narrative comments on weekly evaluations.


Characteristics of incidence hip fracture cases in older adults participating in the longitudinal AGES-Reykjavik study.
Poor physical function and body composition my partly predict the risk of falls leading to fracture regardless of bone mineral density. To examine the relationship between body composition, physical function, and other markers of health with hip fractures in older community-dwelling Icelandic adults. A prospective cohort of 4782 older adults from the AGES-Reykjavik study. Baseline recruitment took place between 2002 and 2006, and information on hip fractures occurring through 2012 was extracted from clinical records. Using multivariate regression analyses, baseline measures of bone health, physical function, and body composition were compared between those who later experienced hip fractures and to those who did not. Associations with the risk of fractures were quantified using Cox regression. Mean age was 76.3 years at baseline. After adjustment for age, regression showed that male hip fracture cases compared with non-cases had (mean (95% confidence interval)) significantly lower thigh muscle cross-sectional area - 5.6 cm2 (- 10.2, - 1.1), poorer leg strength - 28 N (- 49, - 7), and decreased physical function as measured by longer timed up and go test 1.1 s (0.5, 1.7). After adjustment for age, female cases had, compared with non-cases, lower body mass index - 1.5 kg/m2 (- 2.1, - 0.9), less lean mass - 1.6 kg (- 2.5, - 0.8), thigh muscle cross-sectional area - 4.4 cm2 (- 6.5, - 2.3), and worse leg strength - 16 N (- 25, - 6). These differences largely persisted after further adjustment for bone mineral density (BMD), suggesting that body composition may contribute to the risk of fracture independent of bone health. When examining the association between these same factors and hip fractures using Cox regression, the same conclusions were reached. After accounting for age and BMD, older adults who later experienced a hip fracture had poorer baseline measures of physical function and/or body composition, which may at least partly contribute to the risk of falls leading to fracture.


Formulation of two lipid-based membrane-core nanoparticles for FOLFOX combination therapy.
FOLFOX is a combination of folinic acid (FnA), 5-fluorouracil (5-Fu) and oxaliplatin (OxP). It has been used as the standard treatment for colorectal cancer (CRC) and hepatocellular carcinoma (HCC). This treatment is effective, but its high toxicity is dose limiting, and the drugs need to be taken for a long time. To lower the toxicity so that higher doses can be administered with minimal side effects, two lipid-based membrane-core (MC) nanoformulations, Nano-Folox and Nano-FdUMP, have recently been developed by using the nanoprecipitation technique. The combination of Nano-Folox (containing platinum drug and FnA) and Nano-FdUMP (containing fluorine drug) significantly improves the antitumor effect against CRC and HCC relative to FOLFOX (the combination of free drugs), resulting in long-term survival of animals without significant toxic signs. Here, we describe two formulation protocols. First, for Nano-Folox, a Pt(DACH)•FnA nanoprecipitate is formed by [Pt(DACH)(H2O)2]2+ (the active form of OxP) and FnA2-, and the resultant nanoprecipitate is encapsulated inside the lipid nanoparticles (NPs) modified with the PEGylated aminoethyl anisamide (AEAA, a targeting ligand for sigma-1 receptor overexpressing on CRC and HCC). Second, for Nano-FdUMP, FdUMP (the active metabolite of 5-Fu) is entrapped inside the amorphous Ca3(PO4)2 nanoprecipitate, and the resultant Ca3(PO4)2•FdUMP nanoprecipitate is encapsulated into the AEAA-targeted PEGylated lipid NPs. The procedures for Nano-Folox and Nano-FdUMP take ~17 h and ~4 h, respectively (~17 h if they are prepared simultaneously). Procedures for the physicochemical (~30 h) and cytotoxic (~54 h) characterization are also described.


Protective factors against child neglect among families in poverty.
Despite neglect being the most common form of maltreatment, it is still understudied relative to other maltreatment types. Further, there is limited evidence on mechanisms through which to prevent child neglect and on mechanisms that might buffer the risk of poverty. The current study estimated how different protective factors decreased subtypes of neglect, both physical and supervisory, across early childhood and in relation to poverty. The final sample included 2980 mothers from the Fragile Families and Child Wellbeing Study. The current study used linear regressions in a structural equation modeling framework to estimate how protective factors at years 1 and 3 were related to neglectful parenting at years 3 and 5, as well as whether protective factors buffered the association between poverty and neglect. Mothers' perceived instrumental social support, part-time employment, and full-time employment were associated with less physical neglect at both time points (β range from -0.15 to -0.05; all p < 0.05). Perceived instrumental social support was also related to less supervisory neglect at both times (β = -0.05, p < 0.05 for both times). Perceived instrumental social support significantly moderated the association between poverty at year 1 and physical neglect at year 3 (β = 0.06, p < 0.01). These findings provide important information to practitioners and policymakers on potential mechanisms to reduce neglect, as well as reducing neglect among economically disadvantaged families.


MicroRNAs as regulators of epithelial-mesenchymal transition.
Epithelial-mesenchymal transition (EMT) describes the molecular reprogramming and phenotypic changes involved in the conversion of polarised immotile epithelial cells to motile mesenchymal cells. This process allows the remodelling of tissues during embryonic development and is implicated in the promotion of tumor invasion and metastasis. Several recent studies have identified the miR-200 family and miR-205 as key regulators of EMT and enforcers of the epithelial phenotype. The miR-200 family participates in a signalling network with the E-cadherin transcriptional repressors ZEB1/deltaEF1 and ZEB2/SIP1, and TGFbeta2 that is postulated to facilitate maintenance of stable epithelial or mesenchymal states but also allow reversible switching between these states in response to EMT effectors (such as TGFbeta). This review summarises these recent findings and their implications in both developmental EMT and tumor progression.


[Characterization of poisoning by the coconut crab, Birgus latro, in New Caledonia: aspects of clinical and toxicological features and treatment in 23 cases].
We report 23 cases of poisoning, 4 fatal, due to ingestion of coconut crab, Birgus latro, in New Caledonia. Clinical and biological features of this poisoning are characterized, and the toxin complex is described. We suggest a treatment strategy based on digoxin-specific antibody fragments for patients in a life-threatening condition.


On the interactions of sensitive and resistant Mycobacterium tuberculosis to antibiotics.
In this work we propose a system of non linear ordinary differential equations for the dynamics of Mycobacterium tuberculosis (Mtb) within the host, in order to study the role of macrophages, T cells and antibiotics in the control of sensitive and resistant Mtb. Conditions for the persistence of sensitive and resistant bacteria are given in terms of the secondary infections produced by bacteria and macrophages, the immune response, and the antibiotic treatment. Model analysis predicts backward bifurcations for certain values of the parameters. In this case, the dynamics is characterized by the coexistence of two infection states with low and high bacteria load, respectively.


Pharmacologic management of myxomatous mitral valve disease in dogs.
Myxomatous mitral valve disease (MMVD) causing mitral regurgitation is the most important disease of the heart in small animal cardiovascular medicine. Because MMVD is an example of a chronic disease that progresses from mild to severe over years, treatment strategies change with the stage of the disease. In this review the treatment options are compared and contrasted as they are discussed relative to the recently published ACVIM consensus statement regarding the treatment of MMVD. Results from clinical trials and evidence-based medicine are likely to provide significant improvements in the management of MMVD in the coming decades.


Stage IV ovarian cancer: prognostic factors and survival beyond 5 years.
Ovarian cancer continues to be the leading cause of death due to gynecologic malignancies and most patients still present with advanced disease. In the present study we evaluated long-term survival and prognostic factors in patients with stage IV ovarian cancer. The charts of 62 consecutive women with FIGO stage IV epithelial ovarian cancer were reviewed. Chemotherapy was the only factor associated with longer survival. Three patients (5%) survived for longer than 5 years. One died of disease at 6.3 years and two are alive without evidence of disease at 12.4 and 14.9 years, respectively. Survival seemed to correlate with the possibility of administering chemotherapy. Patients with verified stage IV ovarian cancer, in whom due to the initial tumor load, operative extent and concomitant illness, the possibility of postoperative chemotherapy administration seems questionable, might be considered for primary chemotherapy followed by surgery.


Photoelectrochemical water splitting enhanced by self-assembled metal nanopillars embedded in an oxide semiconductor photoelectrode.
Production of chemical fuels by direct solar energy conversion in a photoelectrochemical cell is of great practical interest for developing a sustainable energy system. Various nanoscale designs such as nanowires, nanotubes, heterostructures and nanocomposites have been explored to increase the energy conversion efficiency of photoelectrochemical water splitting. Here we demonstrate a self-organized nanocomposite material concept for enhancing the efficiency of photocarrier separation and electrochemical energy conversion. Mechanically robust photoelectrodes are formed by embedding self-assembled metal nanopillars in a semiconductor thin film, forming tubular Schottky junctions around each pillar. The photocarrier transport efficiency is strongly enhanced in the Schottky space charge regions while the pillars provide an efficient charge extraction path. Ir-doped SrTiO3 with embedded iridium metal nanopillars shows good operational stability in a water oxidation reaction and achieves over 80% utilization of photogenerated carriers under visible light in the 400- to 600-nm wavelength range.


Impact of transcatheter closure of atrial septal defects on cardiac function.
The purpose of this study was to investigate the effects of transcatheter closure of atrial septal defects (ASD) on left ventricular function. Conventional and three-dimensional echocardiographic methods (3D) were performed in 20 patients who underwent ASD closure. Diastolic and systolic volumes (LVVd and LVVs) and ejection fractions (EF) were determined by 3D methods. Doppler and tissue Doppler indices were also measured before and 1 day after the procedure. We determined the predictors of patients with a mitral early Doppler/tissue Doppler velocity ratio (E/E') ≥8 after closure. Ejection fraction decreased (from 70 ± 8 to 63 ± 8%, p = 0.005) after the procedure because of an equivalent increase in LVVs and LVVd maintaining the same cardiac output. Among the echocardiographic variables before ASD closure that correlated with E/E' after closure, the receiver operating characteristic curve of E' gave the largest area under the curve with E' of 12.2 cm/s as the best predictor of patients with E/E' ≥8 after ASD closure. Atrial septal defect closure decreased EF on the surface, thereby maintaining the same stroke volume and cardiac output. Patients with diastolic dysfunction before closure might have a higher risk of developing congestive heart failure after ASD closure.


[Acute inpatient multimodal pain therapy and rehabilitation: Framework conditions, tasks and differentiated patient allocation].
Multimodal pain treatment programs are widely accepted as the medical treatment standard in the management of patients with chronic pain syndromes. The concepts and treatment strategies are based on the biopsychosocial model of pain and programs for early restoration of function. Although this concept is primarily implemented in the curative field, i.e. in hospitals for the treatment of patients with chronic pain diseases, modified programs based on the International Classification of Functioning (ICF) can now also be found in rehabilitation clinics. Despite the assumed similarities, significant differences in, for example the aims of the therapy and relevant structural and process variables have to be kept in mind when allocating patients to a program as provided by a hospital or a rehabilitation clinic. The aim of this article is to present the framework structures of both treatment levels with respect to the implementation of multimodal pain therapy programs and to elucidate the differential diagnostic approach to the indications.


Patterns of retinal hemorrhage associated with cardiac arrest and cardiopulmonary resuscitation.
Hypoxia and cardiopulmonary resuscitation (CPR) have been proposed as causes of retinal hemorrhage (RH) in children evaluated for abusive head trauma (AHT). We sought to determine the prevalence and characteristics of RH in children who underwent CPR after cardiac arrest. This was a prospective, single-center, consecutive observational study of 38 children (<18 years of age). Indirect ophthalmoscopic examination was completed by an ophthalmologist within 48 hours of CPR. Extensive medical records data were collected to assess for potential confounding factors. Outcomes included the presence and pattern of RH. Of the 38 children, 20 had in-hospital arrest; 18 had out-of-hospital arrest. The median duration of CPR was 10 minutes. Seven children had RH, of whom 6 had an RH pattern consistent with coexistent medical conditions: 4 AHT diagnosable with nonocular findings, including subdural and subarachnoid hemorrhage, rib fractures, abdominal injury (RH pattern: diffuse, numerous, intraretinal and/or multilayered RH); 1 septic shock (RH pattern: 1-2 posterior pole RH); 1 ruptured arteriovenous malformation (RH pattern: 4-8 peripapillary RH). The seventh child had unwitnessed cardiac arrest due to nonfatal drowning and a single superficial intraretinal peripapillary hemorrhage. CPR for cardiac arrest is rarely associated with RH, which, absent coexisting conditions causing retinal hemorrhage, are intraretinal, few in number, and located in the posterior pole. In children who have undergone CPR, when RH are multilayered, or are more than a few in number, or extend outside the posterior pole, another etiology for the RH should be sought.


National trends and outcomes of heart-kidney transplantation using hepatitis C positive donors.
This study evaluated the outcomes of combined heart-kidney transplantation in the United States using hepatitis C positive (HCV+) donors. Adults undergoing combined heart-kidney transplantation from 2015 to 2020 were identified in the United Network for Organ Sharing registry. Patients were stratified by donor HCV status. Kaplan-Meier curves with multivariable Cox regression models were used for risk-adjustment in a propensity-matched cohort. A total of 950 patients underwent heart-kidney transplantation of which 7.8% (n = 75) used HCV+ donors; 68% (n = 51) were viremic and 32% (n = 24) were non-viremic donors. Unadjusted 1-year recipient survival was similar between HCV+ versus HCV- donors (84% vs 88%, respectively; P = .33). Risk-adjusted analysis in the propensity-matched cohort showed HCV+ donor use did not confer increased risk of 1-year mortality (hazard ratio .63, 95% CI .17-2.32; P = .49). Sub-group analysis showed viremic and non-viremic HCV+ donors had similar 1-year survival as well (84% vs 84%; P = .95). Compared with recipients of HCV- donor dual heart-kidney transplants, recipients of HCV+ organs had comparable 1-year survival and clinical outcomes after combined transplantation. Although future studies should evaluate other outcomes related to HCV+ donor use, this practice appears safe and should be expanded further in the heart-kidney transplant population.


Enteric immunization reveals a T cell network for IgA responses and suggests that humans possess a common mucosal immune system.
The local IgA response is a result of two related events, the induction of sensitized T and B cells in gut- or bronchial-associated lymphoreticular tissues (GALT or BALT) and the final differentiation of IgA plasma cells in mucosal tissues where IgA is produced and transported to become secretory IgA (S-IgA) antibodies into external secretions. Oral administration of various types of antigens/vaccines may result in two types of response, i.e., S-IgA antibodies at mucosa and systemic unresponsiveness to antigen, a state termed oral tolerance. Regulatory T cells in GALT help account for both S-IgA responses and oral tolerance and thus serve to fine tune responses to orally encountered antigens. Studies in animal models and humans have shown that oral administration of antigens sensitize lymphoid cells in GALT which subsequently home to mucosa and result in S-IgA responses in several external secretions. The significant promise of oral vaccines for prevention of microbial diseases including neisserial diseases is discussed.


Efavirenz as a cause of ataxia in children.
Acute ataxia in childhood is often caused by toxin ingestion. With the increasing number of paediatric patients on antiretroviral medication, we are seeing more side-effects of these drugs. We report two cases of efavirenz toxicity causing ataxia.


An outcome study of anorexia nervosa in an adolescent unit.
This paper describes a follow-up study of 21 adolescent girls treated for anorexia nervosa in an adolescent unit operating a strict refeeding programme with hospital stay averaging six months. Outcome at three-year follow-up (using Morgan's General Outcome categories) was good for ten girls (48 per cent), intermediate for four (19 per cent) and poor for five (24 per cent). Two girls were unclassified; one was diagnosed as manic depressive psychosis and the other as bulimia nervosa. An interesting finding is the lack of separation from parents at long-term follow-up. The relevance of the findings to the particular treatment approach and provision of future services is discussed.


The accuracy of maxillary positioning using digital model planning and 3D printed wafers in bimaxillary orthognathic surgery.
Orthognathic wafers may be made using digital model movements and CAD-CAM technology. This paper analysed the accuracy of maxillary movements using this new process. Retrospective study of pre and post-operative cephalograms. Thirty consecutive orthognathic patients undergoing bimaxillary osteotomies in a UK hospital. Jaw movements were planned using cephalometric and Orthoanalyzer™ software. The resultant intermediate and final wafer occlusal relationships were used for wafer fabrication by 3D printing of the inter-occlusal space. Pre- and post-operative lateral cephalograms were compared in terms of maxillary antero-posterior and vertical movements. Statistical analyses including the paired t-test, two-sample t-test and Fisher's exact test. Wide individual variation was observed between the planned and actual movements. Thirteen cases (43%) had a 2 mm discrepancy in at least one variable. Statistically significant differences between the planned and actual maxillary vertical movements were observed for the molar (U6y: p < 0.0001) and anterior maxillary (Ay: p < 0.01) differences. Analysis of a subgroup with primarily impaction movements demonstrated a statistically significant bias towards excessive maxillary advancement (U1x: p < 0.01) and incisor impaction (U1y: p < 0.01) in this group. This new digital surgical wafer technique achieves a similar level of accuracy to the conventional facebow and model surgery process.


Gastrointestinal transit and gastric acid secretion in patients with achalasia.
Previous studies suggest that patients with achalasia exhibit degenerative changes of extraesophageal nerve fibers. We investigated whether these morphological alterations are associated with functional abnormalities of the gastrointestinal tract. Patients with achalasia had a normal acid secretory response (5.5 +/- 1.5 mmol/hr) to vagal stimulation when compared to controls (6.0 +/- 5.3 mmol/hr). However, the half time of gastric emptying of liquids was significantly shorter in patients with achalasia (10.4 +/- 1.8 min) than in control subjects (19.3 +/- 11.3 min) (P less than 0.01). Although there was a tendency towards a more rapid gastrointestinal transit in patients with achalasia, these changes failed to reach statistical significance. It is concluded that patients with achalasia have a gastric emptying disorder that could either be explained by a selective defect of extraesophageal vagal inhibitory nerve fibers or as an epiphenomenon occurring as a consequence of impaired esophageal emptying.


Bioprinting: A focus on improving bioink printability and cell performance based on different process parameters.
Three-dimensional (3D) bioprinting is an emerging biofabrication technique that shows great potential in the field of tissue engineering, regenerative medicine and advanced drug delivery. Despite the current advancement of bioprinting technology, it faces several obstacles such as the challenge of optimizing the printing resolution of 3D constructs while retaining cell viability before, during, and after bioprinting. Therefore, it is of great significance to fully understand factors that influence the shape fidelity of printed structures and the performance of cells encapsulated in bioinks. This review presents a comprehensive analysis of bioprinting process parameters that influence bioink printability and cell performance, including bioink properties (composition, concentration, and component ratio), printing speed and pressure, nozzle characteristics (size, length, and geometry), and crosslinking parameters (crosslinker types, concentration, and crosslinking time). Key examples are provided to analyze how these parameters could be tailored to achieve the optimal printing resolution as well as cell performance. Finally, future prospects of bioprinting technology, including correlation between process parameters and particular cell types with predefined applications, applying statistical analysis and artificial intelligence (AI)/machine learning (ML) technique in parameter screening, and optimizing four-dimensional (4D) bioprinting process parameters, are highlighted.


Post-transplant lymphoproliferative disorder of the pediatric airway: Presentation and management.
Post-transplant lymphoproliferative disorder (PTLD) is a rare complication of immunosuppression with little consensus on its evaluation and management. The purpose of this contemporary review is to describe a pediatric patient with PTLD of the airway and review the literature to provide multidisciplinary recommendations regarding management. Retrospective chart and literature review. A pediatric patient with PTLD of the airway is described. An extensive literature search to review the existing data on pediatric PTLD of the upper airway was also performed. A pediatric patient with mixed fetal/embryonal hepatoblastoma developed laryngo-tracheal PTLD following liver transplantation. Diagnostic positron emission tomography (PET) scan demonstrated multiple sites of abnormal fluorodeoxyglucose (FDG) uptake within the larynx, distal esophagus, cervical lymph nodes, and abdomen concerning for PTLD. Laryngeal biopsy demonstrated Epstein-Barr virus (EBV) positive cells confirming the diagnosis. Rituximab therapy and reduction of immunosuppression resulted in resolution of his laryngeal disease in 3 months. An extensive literature search to review the existing data on pediatric PTLD of the larynx and trachea revealed 14 reported cases. PTLD of the pediatric airway is an EBV-associated disease that requires a high index of suspicion as patients can often present with non-specific signs and symptoms but progress to have significant airway compromise. Evaluation consists of peripheral blood polymerase chain reaction (PCR) assays, biopsy, and PET/CT imaging. Management options include reduction of immunosuppression and/or systemic therapies.


Corrigendum: Patients Unmet Needs in Chronic Rhinosinusitis With Nasal Polyps Care: A Patient Advisory Board Statement of EUFOREA.
[This corrects the article DOI: 10.3389/falgy.2021.761388.].


Association between SLC2A9 (GLUT9) gene polymorphisms and gout susceptibility: an updated meta-analysis.
The relationship between the SLC2A9 (solute carrier family 2, member 9) gene polymorphisms and gout was still inconsistent among the individual genetic association studies. Therefore, this present research was aimed to systematically evaluate the association between SLC2A9 gene polymorphisms and gout susceptibility. Relevant studies were enrolled by searching databases systematically. The pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the associations. The heterogeneity between each of the studies was calculated by using the Q statistic methods, and Begg's funnel plot and Egger's tests were performed to evaluate publication bias. A total of 13 studies investigated four single nucleotide polymorphisms (SNPs) in SLC2A9 were included. In this study, we found that the allele C of rs3733591 was higher in patients than in controls in both all-pooled population [C vs. T: OR (95 % CI) = 1.432 (1.213-1.691)] and Asians-pooled population [C vs. T: OR (95 % CI) = 1.583 (1.365-1.835)]. The allele frequency C of s6449213 was lower in the gout patients than in controls in both all-pooled population and Caucasians-pooled population. Additionally, the allele frequency T of rs16890979 and the allele frequency C of rs1014290 were lower in gout patients than in controls. This study demonstrated that the genetic susceptibility for gout is associated with the SLC2A9 gene polymorphisms. Four of them except for the rs3733591 are protective SNPs in Caucasians, and rs16890979 and rs1014290 are protective SNPs in both Caucasians and Asians, while rs3733591 may be susceptibility SNP in Asians.


Recovery from 2,5-hexanediol intoxication of the retinotectal tract of the rat. An ultrastructural study.
Rats were given 2,5-hexanediol, a metabolite of n-hexane, in the drinking water until they developed a marked degree of paresis over about 7 weeks and were then allowed to recover naturally. The time course and the manner of removal of the neurofilamentous masses accumulated within axons caused by the intoxication were followed by electron microscopy over the subsequent 8 weeks. The neurofilamentous masses slowly disappeared completely from the axons of this tract, without there being any degeneration, over 6-7 weeks. They disappeared first from the fibres in the brachium of the superior colliculus, perhaps by transport towards the terminals, and later from the axons within the superior colliculus itself. Particularly in preterminal fibres in the superior colliculus the filamentous accumulations became permeated by a network of smooth endoplasmic reticulum which may have played a part in the removal of the filaments. Accumulations of mitochondria and dense bodies in preterminal regions, presumed to be caused by obstruction to retrograde transport, disappeared pari passu with loss of the filaments. The significance of these events in relation to neurofilament metabolism is discussed.


Two-step particle swarm optimization algorithm for effective deconvolution and resolution enhancement of various overlapping peaks.
The existing particle swarm optimization (PSO) algorithms are only effective in deconvoluting the overlapping peaks in ion mobility spectra with fewer than four component peaks, which limits the applicability of these algorithms. A high-performance two-step particle swarm optimization (TSPSO) algorithm was developed. Compared to the existing PSO algorithms, TSPSO can narrow the search ranges of all coefficients for the overlapping peaks through Gaussian model calculation, and thus can deconvolute various overlapping peaks with high accuracy, even for 30-component overlapping peaks. In addition, the TSPSO could be further applied to enhance the resolution of the spectra by narrowing the peak widths after the peak deconvolution. Simulated overlapping peaks were first used to evaluate the performance of TSPSO as compared to the dynamic inertia weight particle swarm optimization (DIWPSO) algorithm. The results showed that the profiles of the peaks deconvoluted by using TSPSO were more consistent with the original ones. The fitness values and the standard deviations of the fitness values from TSPSO were also at least an order of magnitude less than those from DIWPSO. By applying TSPSO, the overlapping peaks from both mass spectrometry (MS) and field asymmetric waveform ion mobility spectrometry (FAIMS) spectra can also be well deconvoluted. In addition, the resolutions of the MS and FAIMS spectra can be effectively enhanced after peak deconvolution. The enhanced spectra matched excellently with the experimental ones acquired at high-resolution modes. The experiment results convincingly demonstrate that the TSPSO algorithm is capable of both deconvoluting complex overlapping peaks and enhancing the spectrum resolution with high accuracy.


Low-density lipoprotein binding affinity of arterial chondroitin sulfate proteoglycan variants modulates cholesteryl ester accumulation in macrophages.
Proteoglycans are considered to facilitate lipid accumulation in the arterial wall, as part of the injury and repair process in atherogenesis. The present study determined (1) characteristics of arterial tissue chondroitin sulfate proteoglycan (CS-PG) monomers of versican type that vary in binding affinity to low-density lipoproteins (LDL), and (2) the ability of these variants to modulate LDL metabolism by macrophages. A large CS-PG devoid of dermatan sulfate (DS) was isolated and purified from bovine aorta intima-media under dissociative conditions. The proteoglycan was further subfractionated by LDL affinity chromatography into CS-PGI and CS-PGII variants, the former eluting at 0.1 M NaCl and the latter at 1.0 M NaCl. The core protein of both variants had a similar molecular mass (1.7 x 10(5). However, CS-PGII contained more glycosaminoglycan (GAG) chains (30 vs. 25) with higher average molecular mass (4.2 x 10(4) vs. 3.8 x 10(4)) than CS-PGI. Furthermore, CS-PGII contained a relatively higher proportion of CS6-sulfate to CS4-sulfate (65: 35 vs. 52: 48). Sulfate-to-hexosamine molar ratio of GAG measured approximately 1 in both variants. In terms of metabolism by macrophages, when compared to complex of LDL and CS-PGI, complex of LDL and CS-PGII produced consistent increase in degradation (10.3-fold vs. 8.4-fold over native LDL) and cell association (16.3-fold vs. 10.2-fold over native LDL) of the ligand, and stimulation of cholesteryl ester synthesis (8.4-fold vs. 6.4-fold over native LDL). CS-PGII was as potent as native CS/DS-PG aggregate, which is a complex made of proteoglycan monomers, hyaluronate, and link protein(s), in stimulating the above activities in macrophages. Thus, variations in LDL-binding affinity of CS-PG can potentially modulate the lipid accumulation in atherogenesis.


Pancreatitis with coexistent pancreatic duct stone and carcinoma. Early diagnosis by endoscopic retrograde pancreatography.
We had a patient with cancer of the pancreas that was diagnosed by endoscopic retrograde pancreatography where conventional diagnostic methods (including arteriography) were negative. Pancreatic resection was possible and examination of the surgical specimen showed microscopic adenocarcinoma coexistent with an intraductal stone and pancreatitis.


A novel colon pouch and its comparison with a straight coloanal and colon J-pouch--anal anastomosis: preliminary results in pigs.
Early functional results after complete rectal resection and straight coloanal anastomosis are often characterized by frequent bowel movements, urgency, and varying degrees of stool incontinence. The formation of a colon reservoir improves early and long-term function. We evaluated the feasibility of a novel, modified design of a colon pouch--anal anastomosis in pigs and compared the results with those of pigs with straight coloanal anastomosis and colon J-pouch. Complete rectal resection followed by either a straight coloanal anastomosis, a colon J-pouch, or a novel design of a colon pouch was performed in equal numbers in 15 pigs. By transversely closing a longitudinal colotomy, the new, technically simpler pouch is formed. Functional results were assessed during a period of 6 weeks. All 15 procedures were successful. The novel colon pouch required less surgical time than the colon J-pouch, and the formation of the pouches did not reduce tissue perfusion as assessed by laser Doppler flowmetry. The mean volume of the novel colon pouch was significantly smaller than the volume of the colon J-pouch. All the pigs with the novel colon pouch had normal stool frequency and consistency during a period of 6 weeks. In the group with straight coloanal anastomosis, two pigs had increased frequency of defecation, one pig showed signs of urgency and perianal dermatitis, and three had substantially reduced stool consistency. Of the four pigs with colon J-pouch, three had signs of impaired pouch evacuation and two had reduced stool frequency. The novel colon pouch is feasible in pigs and technically simpler than the colon J-pouch. These preliminary results indicate that the smaller capacity of this pouch seems sufficient for normal defecation. Its short-term functional results were better than those after reconstruction with a colon J-pouch or a straight coloanal anastomosis.


Brain-gut microbiota multimodal predictive model in patients with bipolar depression.
The "microbiota-gut-brain axis" which bridges the brain and gut microbiota is involved in the pathological mechanisms of bipolar disorder (BD), but rare is known about the exact association patterns and the potential for clinical diagnosis and treatment outcome prediction. At baseline, fecal samples and resting-state MRI data were collected from 103 BD depression patients and 39 healthy controls (HCs) for metagenomic sequencing and network-based functional connectivity (FC), grey matter volume (GMV) analyses. All patients then received 4-weeks quetiapine treatment and were further classified as responders and non-responders. Based on pre-treatment datasets, the correlation networks were established between gut microbiota and neuroimaging measures and the multimodal kernal combination support vector machine (SVM) classifiers were constructed to distinguish BD patients from HCs, and quetiapine responders from non-responders. The multi-modal pre-treatment characteristics of quetiapine responders, were closer to the HCs compared to non-responders. And the correlation network analyses found the substantial correlations existed in HC between the Anaerotruncus_ unclassified,Porphyromonas_asaccharolytica,Actinomyces_graevenitzii et al. and the functional connectomes involved default mode network (DMN),somatomotor (SM), visual, limbic and basal ganglia networks were disrupted in BD. Moreover, in terms of the multimodal classifier, it reached optimized area under curve (AUC-ROC) at 0.9517 when classified BD from HC, and also acquired 0.8292 discriminating quetiapine responders from non-responders, which consistently better than even using the best unique modality. Lack post-treatment and external validation datasets; size of HCs is modest. Multi-modalities of combining pre-treatment gut microbiota with neuroimaging endophenotypes might be a superior approach for accurate diagnosis and quetiapine efficacy prediction in BD.


Impact of immobilization technology in industrial and pharmaceutical applications.
The current demands of the world's biotechnological industries are enhancement in enzyme productivity and development of novel techniques for increasing their shelf life. Compared to free enzymes in solution, immobilized enzymes are more robust and more resistant to environmental changes. More importantly, the heterogeneity of the immobilized enzyme systems allows an easy recovery of both enzymes and products, multiple reuse of enzymes, continuous operation of enzymatic processes, rapid termination of reactions, and greater variety of bioreactor designs. This review summarizes immobilization definition, different immobilization methods, advantages and disadvantages of each method. In addition, it covers some food industries, protein purification, human nutrition, biodiesel production, and textile industry. In these industries, the use of enzymes has become an inevitable processing strategy when a perfect end product is desired. It also can be used in many other important industries including health care and pharmaceuticals applications. One of the best uses of enzymes in the modern life is their application in diagnose and treatment of many disease especially when used in drug delivery system or when used in nanoform.


Minced Meniscus: Biologic Augmented Meniscal Implant Treatment.
Applications of meniscus scaffolds are crucial for preserving articular cartilage tissue, restoring normal joint mechanics, and stabilizing joints with partial meniscus deficits. Studies are still being conducted to determine how meniscus scaffold applications can create viable and durable tissue. The surgical procedure described in this study uses the meniscus scaffold and minced meniscus tissue.


Synthesis and microwave assisted polymerization of fluorinated 2-phenyl-2-oxazolines: the fastest 2-oxazoline monomer to date.
The living cationic ring-opening polymerization of 2-oxazolines with fluorinated aromatic substituents was found to be strongly accelerated by o-fluoro substituents.


Labeling PIEZO2 activity in the peripheral nervous system.
Sensory neurons detect mechanical forces from both the environment and internal organs to regulate physiology. PIEZO2 is a mechanosensory ion channel critical for touch, proprioception, and bladder stretch sensation, yet its broad expression in sensory neurons suggests it has undiscovered physiological roles. To fully understand mechanosensory physiology, we must know where and when PIEZO2-expressing neurons detect force. The fluorescent styryl dye FM 1-43 was previously shown to label sensory neurons. Surprisingly, we find that the vast majority of FM 1-43 somatosensory neuron labeling in mice in vivo is dependent on PIEZO2 activity within the peripheral nerve endings. We illustrate the potential of FM 1-43 by using it to identify novel PIEZO2-expressing urethral neurons that are engaged by urination. These data reveal that FM 1-43 is a functional probe for mechanosensitivity via PIEZO2 activation in vivo and will facilitate the characterization of known and novel mechanosensory processes in multiple organ systems.


The Mediating Role of Cognitive Emotion Regulation in BIS/BAS Sensitivities, Depression, and Anxiety Among Community-Dwelling Older Adults in China.
The behavioral inhibition system (BIS) and behavioral activation system (BAS), which primarily underlie emotions and behaviors, are associated with depression and anxiety. However, the reasons behind these associations require further exploration. This study aims to examine the mediating effects of cognitive emotion regulation between BIS/BAS and depression/anxiety among community-dwelling elderly Chinese. A cross-sectional survey was conducted with a sample of 836 elderly individuals. Structural equation modeling was used to determine relationships among BIS/BAS, cognitive emotion regulation, and depression/anxiety. Participants reporting higher BIS sensitivity were more likely to use maladaptive cognitive emotion regulation strategies, which were in turn associated with higher rates of depression and anxiety. BAS sensitivity was more likely to lead to adaptive cognitive emotion regulation strategies, which resulted in lower levels of depression and anxiety. Our findings suggest that incorporating emotional regulation in interventions targeting BIS/BAS sensitivities may enhance the accuracy and efficiency of these treatments for depression and anxiety.