A near-infrared fluorogenic probe with fast response for detecting sodium dithionite in living cells.
Developing a reliable fluorescence probe is crucial for accurately monitoring sodium dithionite (Na2S2O4, SDT) in biosystems, but the current reported azo-based ones suffers from short excitation/emission wavelengths and relative slow response speed. To address this issue, we herein present a novel near-infrared emissive fluorescence probe for SDT, namely DCM-MQ, consisting of a dicyanomethylene-benzopyran fluorogenic reporter and a 1-methylquinolinium as recognition moiety. On the basis of the specific reduction mechanism, DCM-MQ exhibited a rapid colorimetric and fluorescent recognition for SDT (less than 3 s) with large Stokes shift (112 nm) and high sensitivity (detection limit was 19 nM). The fluorescence imaging results demonstrate that DCM-MQ is competent for monitoring SDT in living systems.


The relationship between body weight and risk of death and serious injury in motor vehicle crashes.
We sought to investigate the effect of increased body weight on the risk of death and serious injury to occupants in motor vehicle crashes. We employed a retrospective cohort study design utilizing data from the National Automotive Sampling System, Crashworthiness Data System (CDS), 1993-1996. Subjects in the study included occupants involved in tow-away crashes of passenger cars, light trucks, vans and sport utility vehicles. Two outcomes were analyzed: death within 30 days of the crash and injury severity score (ISS). Two exposures were considered: occupant body weight and body mass index (BMI; kg/m2). Occupant weight was available on 27263 subjects (76%) in the CDS database. Mortality was 0.67%. Increased body weight was associated with increased risk of mortality and increased risk of severe injury. The odds ratio for death was 1.013 (95% CI: 1.007, 1.018) for each kilogram increase in body weight. The odds ratio for sustaining an injury with ISS > or = 9 was 1.008 (95% CI: 1.004, 1.011) for each kilogram increase in body weight. After adjustment for potentially confounding variables (age, gender, seatbelt use, seat position and vehicle curbweight), the significant relationship between occupant weight and mortality persisted. After adjustment, the relationship between occupant weight and ISS was present, although less marked. Similar trends were found when BMI was analyzed as the exposure. In conclusion, increased occupant body weight is associated with increased mortality in automobile crashes. This is probably due in part to increased co-morbid factors in the more overweight occupants. However, it is possibly also due to an increased severity of injury in these occupants. These findings may have implications for vehicle safety design, as well as for transport safety policy.


Maternal pre-pregnancy overweight status and obesity as risk factors for cesarean delivery.
To determine the extent to which, if at all, maternal pre-pregnancy adiposity and other anthropometric factors are related to risk of cesarean delivery. This hospital-based prospective cohort study included 738 nulliparous women who initiated prenatal care prior to 16 weeks gestation. Participants provided information about their pre-pregnancy weight and height and other sociodemographic and reproductive covariates. Labor and delivery characteristics were obtained from maternal and infant medical records. Risk ratios (RR) and 95% CI were estimated by fitting generalized linear models. The proportion of cesarean deliveries in this population was 26%. Women who were overweight (BMI 25.00-29.99 kg/m2) were twice as likely to deliver their infants by cesarean section as lean women (BMI<20.00 kg/m2) (RR=2.09; 95% CI 1.27-3.42). Obese women (BMI>or=30.00 kg/m2) experienced a three-fold increase in risk of cesarean delivery when compared with this referent group (RR=3.05; 95% CI 1.80-5.18). The joint association between maternal pre-pregnancy overweight status and short stature was additive. When compared with tall (height>or=1.63 m), lean women, short (<1.63 m), overweight (BMI>or=25.00 kg/m2) women were nearly three times as likely to have a cesarean delivery (RR=2.79; 95% CI 1.72-4.52). Our findings suggest that nulliparous women who are overweight or obese prior to pregnancy, and particularly those who are also short, have an increased risk of delivering their infants by cesarean section.


A rapid fluorescence polarization immunoassay for the determination of T-2 and HT-2 toxins in wheat.
A rapid fluorescence polarization (FP) immunoassay has been developed for the simultaneous determination of T-2 and HT-2 toxins in naturally contaminated wheat samples. Syntheses of four fluorescein-labelled T-2 or HT-2 toxin tracers were carried out and their binding response with seven monoclonal antibodies was evaluated. The most sensitive antibody-tracer combination was obtained by using an HT-2-specific antibody and a fluorescein-HT-2 tracer. The developed competitive FP immunoassay in solution showed high cross-reactivity for T-2 toxin (CR% = 100%) while a very low CR% for neosolaniol (0.12%) and no cross-reactivity with other mycotoxins frequently occurring in wheat. A rapid extraction procedure using 90% methanol was applied to wheat samples prior to FP immunoassay. The average recovery from spiked wheat samples (50 to 200 μg kg(-1)) was 96% with relative standard deviation generally lower than 8%. A limit of detection of 8 μg kg(-1) for the combined toxins was determined. Comparative analyses of 45 naturally contaminated and spiked wheat samples by both the FP immunoassay and high-performance liquid chromatography/immunoaffinity clean-up showed a good correlation (r = 0.964). These results, combined with the rapidity (10 min) and simplicity of the assay, show that this method is suitable for high throughput screening as well as for quantitative determination of T-2 and HT-2 toxins in wheat.


Cingulate role in Tourette syndrome.
This chapter comprehensively reviews the published record for neurosurgical, neurostimulatory, and neuroimaging evidence of the involvement of the cingulate gyrus in Gilles de la Tourette syndrome (TS). The most noteworthy evidence comes from neuroimaging. Neuroimaging findings were rarely exclusive to the cingulate cortex and tended to implicate multiple other cortices as well. Some results are reflective of obsessive-compulsive (OC) symptoms of TS. Copious findings, however, drawn from structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS), resting-state functional magnetic resonance imaging (rsfMRI), task fMRI, and positron emission tomography (PET) implicate six of the eight cingulate subregions in TS. Gauged by MRI, cortical thinning and/or below-normal volume are seen in subgenual anterior cingulate cortex (sACC), pregenual anterior cingulate cortex (pACC), anterior middle cingulate cortex (aMCC), and posterior middle cingulate cortex (pMCC), correlating with tic severity in sACC, pACC, and aMCC. Moreover, in pMCC, dorsal posterior cingulate cortex (dPCC), and ventral posterior cingulate cortex (vPCC), cortical thickness is a candidate biomarker shared across siblings with TS. Loss of cortex may reflect excitotoxicity secondary to insufficient local GABAergic inhibition, a notion supported by the few relevant MRS and PET studies conducted to date, recommending continued development of GABAergic and glutamatergic pharmacologic agents to treat TS. Measurements of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) obtained with DTI indicate that the white matter proximal to sACC, pACC, pMCC, and dPCC may also represent a seat of pathology in TS. rsfMRI reveals abnormal functional connectivity of pACC and dPCC with the globus pallidus internus, a favored target of therapeutic deep brain stimulation (DBS) for TS. In whole-brain network (graph theory) analysis, dPCC functional connectivity is related to the severity and complexity of tics. In task fMRI, in contrast, the pMCC seems to play a preeminent role in premonitory urges and preparation for tics as well as normal urges to urinate, swallow, and yawn. Strong monkey PET and EEG evidence ties vocal tics to spike discharges, α-activity, and regional blood flow in the pACC unleashed by failure of GABAergic inhibition in the ventral striatum. Tic suppression in fMRI scans is associated with increased blood oxygenation level-dependent activity in sACC, pACC, and aMCC, but decreased activity in pMCC and dPCC. Activity in the former three subregions may represent volitional effort, physical discomfort, and emotional distress that accompanies mounting tic urges; pMCC and dPCC may be more instrumental in amplifying than suppressing urges. Needs for future neuroimaging work in TS include longitudinal studies-particularly those striving to predict which individual pediatric patients will continue to suffer from TS as adults and studies of treatment response-particularly of behavioral therapies, which are as efficacious as pharmacology. Transcranial magnetic stimulation and related therapies such as cranial electrotherapy stimulation, which showed good efficacy in a recent trial, merit continued exploration. TS research using DTI, MRS, and PET will no doubt continue to benefit in coming years from technological advances such as ultrahigh-field scanners, multichannel head coils, and novel (including GABAergic and glutamatergic) ligands.


A prospective, blinded trial of touch prep analysis versus frozen section for intraoperative evaluation of sentinel lymph nodes in breast cancer.
Sentinel lymph node biopsy (SLNB) has largely replaced axillary dissection (ALND) for axillary staging in early breast cancer. However, intense pathologic evaluation is not routinely available intraoperatively; therefore, patients with SLN metastasis may require a second surgery for completion ALND. We hypothesized that a single-section approach (by either frozen section [FS] or touch preparation analysis [TPA]) could be accurate for intraoperative SLN evaluation. We performed a prospective, blinded study of patients undergoing SLNB for breast cancer from September 2004 to July 2006. SLNs were bivalved along the long axis, underwent FS and TPA of the facing halves, followed by routine sentinel node processing (serial sectioning with hematoxylin/eosin staining). A single pathologist reviewed all study slides and was blinded to the permanent section interpretation. We analyzed 233 nodes from 118 patients. Overall, 21% of patients (N = 25) had SLN metastasis by serial-section histopathology. Single-section FS and TPA had similar sensitivities (0.67 and 0.66, P = .82) and specificities (0.995 and 0.995, P = 1.0) for detection of SLN metastasis, yielding equivalent accuracies (95%). All micrometastases (<2 mm; N = 4) were missed by both techniques. False positives were rare-only one in each group (2% overall). Single-section TPA and FS have similar accuracies and can be safely used to identify the majority of patients with SLN metastasis, sparing these patients a delayed ALND. False-negative results from TPA or FS occur in patients with micrometastatic disease, for which the role of completion ALND remains controversial.


Carbachol depresses synaptic responses in the medial but not the lateral perforant path.
The effects of applications of carbachol on evoked synaptic responses recorded in the dentate gyrus of guinea pig hippocampal slices were examined. Carbachol depressed potentials recorded extracellularly in the medial perforant path terminal zone, but did not significantly alter field potentials recorded in the lateral perforant path terminal zone. Carbachol-induced depression was reversed by applications of the muscarinic antagonists, atropine or pirenzepine. It was suggested that the difference observed in carbachol-induced depression of medial versus lateral perforant path field potentials may be due to regional differences in acetylcholine receptor distribution in the molecular layer of the dentate gyrus.


Effect of ammonium chloride on the multiplication of infectious pancreatic necrosis virus.
The multiplication of IPNV in CHSE cells is inhibited by ammonium chloride. This inhibition is complete if NH4Cl is added early in the infective cycle. Immunofluorescence analysis shows that NH4Cl reduces the number of virus producing cells and thus suggests it may act by inhibiting virus internalization. In addition, NH4Cl can produce partial inhibition of IPNV multiplication if added later in the replicative cycle. Analysis of 3H-uridine incorporation into viral RNA shows that this later effect could be an inhibition of viral RNA synthesis.


General practitioners' detection of patients' smoking status.
We examined the detection of smoking by 50 randomly-selected general practitioners. The practitioners said that they should detect smokers among their patients with a high degree of accuracy: a median of 100% of smokers under ideal conditions, and a median of 80% of smokers given the realities of practice. Practitioners actually identified 56.2% of their patients who were smokers--360 of 641 smokers among 2044 patients in the study. Some 65% of patients with a smoking-caused or smoking-exacerbated disease were detected, and this degree of detection was not related to age. For smokers of greater than 50 years of age and without any obvious smoking-related condition, the detection rates were similar to those of patients with smoking-related disease; however, in those patients who were less than 30 years of age, only 41% of smokers were detected--although the prevalence of smoking was higher in the younger than it was in the older patients. For all age-groups, the prevalence of smoking in men was about 15% higher than it was in women, but there was no significant difference between the detection rates in the sexes. In spite of their higher risks from smoking, the detection rates for pregnant women, or women who were taking oral contraceptive agents, were no higher than those for other women of less than 35 years of age. The doctors said that they had treated for smoking 78% of the detected smokers who had smoking-caused disease, compared with 35% of detected smokers with no smoking-related condition. They rated the value of such treatment higher in the former group than in those patients who had not yet developed smoking-related problems. Doctors appear to respond to the evidence of disease that is caused by smoking more than to the habit itself, which is a handicap in the prevention of smoking-related disease.


Na⁺ transport in the normal and failing heart - remember the balance.
In the heart, intracellular Na(+) concentration ([Na(+)]i) is a key modulator of Ca(2+) cycling, contractility and cardiac myocyte metabolism. Several Na(+) transporters are electrogenic, thus they both contribute to shaping the cardiac action potential and at the same time are affected by it. [Na(+)]i is controlled by the balance between Na(+) influx through various pathways, including the Na(+)/Ca(2+) exchanger and Na(+) channels, and Na(+) extrusion via the Na(+)/K(+)-ATPase. [Na(+)]i is elevated in HF due to a combination of increased entry through Na(+) channels and/or Na(+)/H(+) exchanger and reduced activity of the Na(+)/K(+)-ATPase. Here we review the major Na(+) transport pathways in cardiac myocytes and how they participate in regulating [Na(+)]i in normal and failing hearts. This article is part of a Special Issue entitled "Na(+) Regulation in Cardiac Myocytes."


Pulmonary vasculitis complicating childhood ulcerative colitis.
A case of pulmonary vasculitis complicating ulcerative colitis is presented, and the literature is reviewed. Unexplained pulmonary problems complicating severe ulcerative colitis should prompt a review of rare etiologies to include pulmonary vasculitis, apical pulmonary fibrosis, and salicylazosulfapyridine-induced lung disease. Lung biopsy will establish a diagnosis of pulmonary vasculitis.


Characterization and removal of dissolved organic matter (DOM) from landfill leachate rejected by nanofiltration.
Dissolved organic matter (DOM) from wastewater rejected by nanofiltration from a landfill leachate treatment plant was fractionated into humic acid (HA), fulvic acid (FA) and hydrophilic (HyI) fractions. It was found that humic substances (HA and FA) composed 75% of the total dissolved organic carbon (DOC) concentration of the DOM, with an average molecular weight of about 1000 Da. Elemental analysis, infrared spectroscopy, UV-visible spectroscopy and acid-base titration observations showed that the HA and FA of the DOM exhibited lower fractions of condensed aromatic functional groups but larger fractions of acidic groups compared with other aquatic DOMs. The properties of HA and FA were similar, but HA exhibited more complete humification, while the HyI fraction had more acidic groups. An aminated polymeric adsorbent NDA-8 was used to adsorb the DOM in the wastewater along with primary coagulation. Results of bench-scale experiments indicated that the treatment process could effectively remove the DOM and heavy metals while desorption liquid was 10 times more condensed than raw wastewater. Results of desorption and reproducibility tests consolidated the strong application potential of this treatment process as an advanced landfill leachate treatment technology.


Diffraction-free beams generated with programmable spatial light modulators.
Diffraction-free beams are generated by the use of diffractive optical elements written on a spatial light modulator (SLM). By alteration of the pattern placed on the SLM, the axis of propagation can be both shifted laterally and rotated. We present experimental results obtained by use of a magneto-optic SLM.


Effect of the Post-Spinning Solvent Exchange on the Performance of Asymmetric, Polyimide Hollow Fibers Prepared by Using a Triple-Orifice Spinneret.
Hollow fibers (HFs) are widely applied in different membrane operations, particularly in gas separation. The present work investigates the effect of post-spinning treatment on the gas transport properties of polyimide-based HFs. The membranes were spun by using both a conventional spinneret and a triple-orifice spinneret. A systematic analysis was carried out by considering different alcohols as the first fluid for the solvent exchange, with or without n-hexane as a second fluid. The HFs were characterized by exploring the change of the morphology and the permselective properties as a consequence of the operation conditions for spinning and post-treatments. According to the morphology, for a specific hollow fiber type, an optimal post-treatment was identified. The HFs prepared with the triple-orifice spinneret, using a solvent-rich shell fluid, can take advantage of the post-treatment using larger alcohols, while smaller alcohols should be preferred for the conventional spun HFs that present inside-outside double skin layers.


The tendency to altered perception of airflow resistance in aged subjects might be due mainly to a reduction in diaphragmatic proprioception.
Elderly patients with asthma, particularly those above the age of 80 years, appear less able to detect early worsening of their airflow resistance and hence might not take 'rescue' bronchodilator medication promptly. No consistent explanation for the observation has been posited. We hypothesize that deterioration in the sensitivity and accuracy of inspiratory (mainly diaphragmatic) proprioception is a plausible mechanism. This contention is supported by observations that indicate the central role of afferent phrenic nerve fibres arising from mechanoreceptors in diaphragmatic muscle and entheses in the ability to sense changes in intrathoracic pressure and volume. Other sensory afferent sources appear less important in this context because the ability to detect intrathoracic pressure and volume changes is preserved in patients with heart-lung transplants (parenchymal and airway denervation), topically anaesthetized upper airways and spinal cord transection below C4 (intact phrenic function) but not cord transection above C2 (phrenic function absent) if the airways are simultaneously anaesthetized. Further support for the hypothesis comes from demonstration of reduced integrated proprioceptive function in older subjects, such as increased postural sway, reduced ability to judge changes in joint position and slower recovery from eye and hand perturbation. In the context of asthma, the detection of a change in airflow resistance depends mainly on the subconscious detection of a mismatch between the inspiratory effort and the volume change achieved; the resulting discrepancy between length (volume) and tension (muscular effort) is felt as a sensation of obstructed breathing, resulting in greater effort to breath and conscious actions such as self-medication. Our hypothesis proposes that a reduced ability to detect accurately the volume change during tidal breathing delays the sensing of the obstruction in older subjects.


Comments on "Reporting quality of randomized controlled trial abstracts in the seven highest-ranking anesthesiology journals".
Randomized controlled trials are considered the gold standard in assessing treatment regimens, and since abstracts may be the only part of a paper that a physician reads, accurate reporting of data in abstracts is essential. The CONSORT checklist for abstracts was designed to standardize data reporting; however, for papers submitted to anesthesiology journals, the level of adherence to the CONSORT checklist for abstracts is unknown. Therefore, we commend Janackovic and Puljak for their efforts in determining the adherence of reports of trials in the highest-impact anesthesiology journals between 2014 and 2016. The results of their study are extremely important; however, we believe that that study had some methodological limitations, which we discuss in this manuscript.


Elevation of hemoglobin A1c increases the risk of decline in left ventricular systolic function among patients with coronary artery disease.
The aim of this study was to investigate the association of HbA1c and left ventricular (LV) systolic function among patients with coronary artery disease (CAD). CAD patients from the Cardiorenal ImprovemeNt II (CIN-II, NCT05050877) registry were included in the study. They were separated into four groups based on HbA1c levels (Q1: HbA1c<5.7%; Q2: 5.7% ≤ HbA1c < 6.1%; Q3: 6.1% ≤ HbA1c < 6.9%; Q4: HbA1c ≥ 6.9%). The endpoint was decline in LV systolic function, defined as an absolute decrease in LV ejection fraction (LVEF) ≥10% from baseline to follow-up with 3-12 months. The association of HbA1c and LVEF was assessed by logistics regression models. CAD patients (n = 3,994) (age 62.9 ± 10.6 years; 22.2% female) were included in the final analysis. A decline in LV systolic function was recorded in 429 (11%) patients during follow-up. After fully adjusting for confounders, HbA1c was significantly associated with the high risk of decline in LV systolic function (OR 1.12 [95%CI 1.05-1.20] P = 0.001). By stratifying HbA1c as four groups, there is a significantly increased risk of decline in LV systolic function when HbA1c ≥6.1% (Q2, Q3 and Q4 vs Q1, with OR 1.22 [0.88-1.68] P = 0.235; OR 1.48 [1.07-2.05] P = 0.019; OR 1.60 [1.160-2.22] P = 0.004, respectively). Meanwhile, patients with decline in LV systolic function had a higher risk of cardiovascular death. Elevated HbA1c is a predictor of decline in LV systolic function in CAD patients. Clinicians should be aware of the risk of decline in LV systolic function in CAD patients with elevated HbA1c, and take measures as soon as possible.


Proton transport and Na+/H+ exchange in vesicles isolated from sockeye salmon (Oncorhynchus nerka) kidneys during migration from salt to fresh water.
Renal epithelial function, proton flux and sodium stimulated proton flux, was observed in vesicles isolated from the brush border of the proximal tubule of Sockeye Salmon (Oncorhynchus nerka) during migration. Brush border membrane vesicles (BBMV) were isolated from the body kidney of Sockeye Salmon using aggregation/differential centrifugation techniques. Vesicle purity was tested using a series of epithelial and basal lateral markers including alkaline phosphatase, maltase, gamma-glutamyl transferase (GGTP), Mg(2+)-activated ATP-ase, Na(+)+K(+)-activated ATPase, and 5'-nucleotidase and the lysosomal marker acid phosphatase. An enrichment/depletion factor for each marker was determined by comparison of purified BBMV with kidney homogenate. Vesicles exhibit an enrichment factor for alkaline phosphatase, GGTP, maltase, Mg(2+)-activated ATP-ase, Na(+)+K(+)-activated ATPase, and 5'-nucleotidase. A depletion factor was observed for acid phosphatase. Vesicle integrity was tested by measuring the time course of proton flux in the presence of a pH gradient. Amiloride sensitive sodium stimulated proton flux was observed in these vesicles. The presence of sodium caused a saturable increase in the rate of proton flux, indicating the activity of a sodium/proton antiport protein in BBMV.


Epoxide hydrase and glutathione S-transferase activities with selected alkene and adrene oxides in several marine species.
Epoxide hydrase and glutathione (GSH) S-transferase activities were measured in subcellular fractions prepared from liver or hepatopancreas and some extrahepatic organs of a number of marine species common to Maine or Florida. These activities were easily detected in the species studied. In fish, hepatic GSH S-transferase activities were normally higher than hepatic epoxide hydrase activities for the alkene oxide (styrene oxide and octene oxide) and arene oxide (benzo[a]pyrene 4,5-oxide) substrates studied, whereas in crustacea, hepatopancreas epoxide hydrase activities were higher than hepatopancreas GSH S-transferase activities with the same substrates. Extrahepatic organs from fish and crustacea usually had higher GSH S-transferase activities than epoxide hydrase activities with the alkene and arene oxide substrates. GSH S-transferase activity was also found in liver or hepatopancreas of every aquatic species studied and in a number of extrahepatic organs, when 1,2-dichloro-4-nitrobenzene or 1-chloro-2,4-dinitrobenzene served as substrate.


Burkholderia gladioli infection isolated from the blood cultures of newborns in the neonatal intensive care unit.
Burkholderia gladioli was described as a plant pathogen, and it is a rare cause of infection in humans that is primarily associated with human pulmonary infections, such as chronic granulomatous disease and cystic fibrosis. The neonatal respiratory system is not fully developed and cannot expel bacterial aerosol properly. A total of 2,676 newborns in the neonatal intensive care unit were retrospectively analysed in Putian City, Fujian Province, China, from 2011 to 2014. All of the blood samples were tested for C-reactive protein (CRP), procalcitonin (PCT) and white blood cell (WBC). B. gladioli infections were determined and analysed using a blood culture system. Antibiotic susceptibility testing was performed using the K-B method. Of the 2,676 participants, 87 (3.25 %) had a positive B. gladioli blood culture that occurred >72 h after birth, including a premature group (54.0 %, asphyxia [vs. 9.20 %], fever [vs. 13.80 %], pneumonia [vs. 6.90 %] and hyperbilirubinaemia [vs. 8.05 %]) and newborns with necrotising enterocolitis (NEC) (vs. 5.75 %). The mean ± standard deviation (SD) of the CRP level was 12.31 ± 0.26 mg/L and that of the PCT level was 1.53 ± 0.21 ng/ml in the 87 B. gladioli-infected newborns. Most of the B. gladioli isolates were sensitive to many antimicrobial agents and did not lead to serious consequences. All of the B. gladioli-infected newborns were unhealthy, especially the premature infants. B. gladioli might be a causative bacteraemia agent in neonates, it appears to have pathogenic potential in newborns and its sensitivity to antibiotics may be a beneficial factor.


Intermittent left cervical vagal nerve stimulation damages the stellate ganglia and reduces the ventricular rate during sustained atrial fibrillation in ambulatory dogs.
The effects of intermittent open-loop vagal nerve stimulation (VNS) on the ventricular rate (VR) during atrial fibrillation (AF) remain unclear. The purpose of this study was to test the hypothesis that VNS damages the stellate ganglion (SG) and improves VR control during persistent AF. We performed left cervical VNS in ambulatory dogs while recording the left SG nerve activity (SGNA) and vagal nerve activity. Tyrosine hydroxylase (TH) staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to assess neuronal cell death in the SG. We induced persistent AF by atrial pacing in 6 dogs, followed by intermittent VNS with short ON-time (14 seconds) and long OFF-time (66 seconds). The integrated SGNA and VR during AF were 4.84 mV·s (95% confidence interval [CI] 3.08-6.60 mV·s) and 142 beats/min (95% CI 116-168 beats/min), respectively. During AF, VNS reduced the integrated SGNA and VR, respectively, to 3.74 mV·s (95% CI 2.27-5.20 mV·s; P = .021) and 115 beats/min (95% CI 96-134 beats/min; P = .016) during 66-second OFF-time and to 4.07 mV·s (95% CI 2.42-5.72 mV·s; P = .037) and 114 beats/min (95% CI 83-146 beats/min; P = .039) during 3-minute OFF-time. VNS increased the frequencies of prolonged (>3 seconds) pauses during AF. TH staining showed large confluent areas of damage in the left SG, characterized by pyknotic nuclei, reduced TH staining, increased percentage of TH-negative ganglion cells, and positive TUNEL staining. Occasional TUNEL-positive ganglion cells were also observed in the right SG. VNS damaged the SG, leading to reduced SGNA and better rate control during persistent AF.


Mapping protein electron transfer pathways with QM/MM methods.
Mixed quantum mechanics/molecular mechanics (QM/MM) methods offer a valuable computational tool for understanding the electron transfer pathway in protein-substrate interactions and protein-protein complexes. These hybrid methods are capable of solving the Schrödinger equation on a small subset of the protein, the quantum region, describing its electronic structure under the polarization effects of the remainder of the protein. By selectively turning on and off different residues in the quantum region, we are able to obtain the electron pathway for short- and large-range interactions. Here, we summarize recent studies involving the protein-substrate interaction in cytochrome P450 camphor, ascorbate peroxidase and cytochrome c peroxidase, and propose a novel approach for the long-range protein-protein electron transfer. The results on ascorbate peroxidase and cytochrome c peroxidase reveal the importance of the propionate groups in the electron transfer pathway. The long-range protein-protein electron transfer has been studied on the cytochrome c peroxidase-cytochrome c complex. The results indicate the importance of Phe82 and Cys81 on cytochrome c, and of Asn196, Ala194, Ala176 and His175 on cytochrome c peroxidase.


Neoendothelialization of small-diameter polytetrafluoroethylene arterial grafts is not delayed by aspirin and dipyridamole.
The effect of aspirin and dipyridamole on neoendothelialization of polytetrafluoroethylene (PTFE) was studied in the rabbit aortic graft model. Forty-three New Zealand white rabbits were allocated to receive a combination of aspirin 10 mg/kg/day and dipyridamole 10 mg/kg/day (n = 23) or placebo (n = 20). Both regimens began 3 days before insertion of PTFE aortic grafts (10 mm long and 3 mm internal diameter). Serum thromboxane B2 concentration in the control group averaged 254 +/- 22 ng/ml (+/- standard error of the mean) and 40 +/- 23 ng/ml in the treatment group (p less than 0.001). Grafts and adjacent aorta were harvested at 2 weeks (n = 4), 4 weeks (n = 9), 8 weeks (n = 13), and 12 weeks (n = 17) after implantation. Morphologic techniques, including conventional light microscopy, immunoperoxidase staining for endothelial factor VIII-related antigen, and scanning electron microscopy (SEM) demonstrated that neointima was composed of endothelial cells arising by ingrowth at anastomotic site and as islands in the center of the graft. The percentage of graft neoendothelialization was measured by SEM. At 2 weeks 18% +/- 2% of the PTFE surface was covered with endothelium in the aspirin/dipyridamole group. The percentages of graft neoendothelialization for the treatment and control groups at 4 weeks were 44% +/- 13% (n = 5) and 46% +/- 10% (n = 4) (p = NS), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Metabolism of linear and angular furanocoumarins by Papilio polyxenes CYP6B1 co-expressed with NADPH cytochrome P450 reductase.
One challenge in the heterologous expression of microsomal cytochrome P450 monooxygenases (P450s) is fulfilling their obligatory requirement for electrons transferred from NADPH P450 reductase. We have established co-expression parameters for Papilio polyxenes CYP6B1 and house fly P450 reductase in baculovirus-infected Sf9 cells that allow for efficient expression of both components and significantly enhance metabolic turnover of this insect P450's substrates. These expression conditions have allowed us to reexamine the turnover capacities of CYP6B1 toward linear and angular furanocoumarins present in the host plants for the specialist caterpillar P. polyxenes. Coexpression of CYP6B1 and P450 reductase at equivalent viral concentrations [MOI (multiplicity of infection) ratio of 1] results in turnover rates for the linear furanocoumarins xanthotoxin and psoralen, which are increased 32-33 fold over the turnover rates obtained with CYP6B1 expressed alone. The turnover rate for the angular furanocoumarin angelicin is also significantly increased to 4.76 nmol/min/nmol P450 compared to its barely detectable level obtained with CYP6B1 expressed alone. Substrate binding analyses indicate that all three of these compounds elicit typical type I binding spectra but with varying magnitudes and affinities that are indicative of each substrate's effectiveness at coordinating with the heme iron. The relative proportions of high spin state generated with these substrates are consistent with CYP6B1 metabolizing these furanocoumarins in the rank order xanthotoxin>psoralen>angelicin. These differential activities for CYP6B1 suggest that it may have been an ancient participant in the coevolutionary arms race between papilionid butterflies and their apiaceous host plants. Due to its ability to handle a range of furanocoumarin structures, CYP6B1 may have contributed to P. polyxenes' early colonization of linear furanocoumarin-containing plants and to its subsequent colonization of angular furanocoumarin-containing plants.


The thoughts of breast cancer survivors regarding the need for starting hormone replacement therapy.
There is not only a need for scientific data regarding the risk of recurrence of breast cancer by starting hormone replacement therapy (HRT) but also regarding the patients' needs for HRT. To examine the severity of climacteric complaints in breast cancer patients and to examine if they are willing to take HRT. In November 2003, a questionnaire was sent to 469 breast cancer survivors. The survey examined on a scale base the severity of climacteric complaints and the patient's opinion on starting HRT. More than 76% of the patients complained that they experience or had experienced hot flushes or night sweating. More than half (53%) of this group found the inconvenience severe to extreme, affecting the patient's quality of life. A majority (80.5%) patients who had already taken HRT, found that it improved their quality of life substantially. When the results of observational studies were explained regarding HRT in breast cancer survivors, a majority said they would take or would consider taking HRT (57.9%). While physicians are more reserved in prescribing HRT in breast cancer survivors, a combination of severe symptomatic climacteric complaints and the willingness of the patient to be treated should at least result in a "consideration" of prescribing HRT.


A methodological study on the combination of qualitative and quantitative methods in cognitive interviewing for cross-cultural adaptation.
The aim of this study is to explore the use of the Questionnaire Appraisal System with a combination of qualitative and quantitative methods in cognitive interviewing for cross-cultural adaptation. This is a descriptive methodological study. Using the Mandarin version of the Post-Stroke Checklist as an example, cognitive interviews were conducted with 27 stroke survivors in Guangzhou between November 2020 and February 2021. The Questionnaire Appraisal System was applied as a codebook in focus group discussions to perform quantitative data collections and quantitative content analysis. Thirty-eight problems were proposed in focus group discussions and identified all but four of the 30 questions that emerged in the cognitive interviews. A new item was added to the Questionnaire Appraisal System for better categorization. Four categories and six subcategories of problems in the checklist were revealed.


Mitophagy in Yeast: A Screen of Mitophagy-Deficient Mutants.
Mitochondrial autophagy (mitophagy) is a process that selectively degrades mitochondria via autophagy. Recent studies have shown that mitophagy plays an important role in mitochondrial homeostasis by degrading damaged or excess mitochondria. The budding yeast Saccharomyces cerevisiae is a powerful model organism that has been employed to study several biological phenomena. Recently, there has been significant progress in the understanding of mitophagy in yeast following the identification of Atg32, a mitochondrial outer membrane receptor protein for mitophagy. In this chapter, we describe protocols to study mitophagy in yeast via a genome-wide screen for mitophagy-deficient mutants using fluorescence microscopy and immunoblotting.


Design of the injection beamline for the Californium Rare Isotope Breeder Upgrade electron beam ion source charge breeder.
The design of the ion injection line connecting the electron beam ion source (EBIS) charge breeder and the Californium Rare Isotope Breeder Upgrade radio frequency quadrupole cooler-buncher at the Argonne Tandem Linear Accelerator System was investigated with particle tracking simulations. The injection line was configured to accommodate several differential pumping sections, individual optical components were optimized to minimize emittance growth, and the ion beam parameters were matched with the EBIS electron beam acceptance to minimize losses upon injection.


Water reclamation during drinking water treatments using polyamide nanofiltration membranes on a pilot scale.
The aim of this study was to investigate the performances of polyamide nanofiltration membranes during water reclamation. The study was conducted using nanofiltration concentrates obtained from two different nanofiltration drinking water treatment plants placed in the northern part of Serbia (Kikinda and Zrenjanin). Used nanofiltration concentrates contained high concentrations of arsenic (45 and 451 μg/L) and natural organic matter (43.1 and 224.40 mgKMnO4/L). Performances of polyamide nanofiltration membranes during water reclamation were investigated under various fluxes and transmembrane pressures in order to obtain drinking water from nanofiltration concentrates and, therefore, reduce the amount of produced concentrates and minimize the waste that has to be discharged in the environment. Applied polyamide nanofiltration membranes showed better removal efficiency during water reclamation when the concentrate with higher content of arsenic and natural organic matter was used while the obtained permeates were in accordance with European regulations. This study showed that total concentrate yield can be reduced to ~5 % of the optimum flux value, in both experiments. The obtained result for concentrate yield under the optimum flux presents considerable amount of reclaimed drinking water and valuable reduced quantity of produced wastewater.


Femtosecond lasers in ophthalmology.
To provide an update and review of femtosecond (FS) lasers in clinical ophthalmology. Perspective, literature review, and commentary. Selected articles from the literature and the authors' clinical and laboratory studies. The FS laser employs near-infrared pulses to cut tissue with minimal collateral tissue damage. Although its major use at present is in the cutting of laser in situ keratomileusis flaps, the laser has proven its versatility in laser-assisted anterior and posterior lamellar keratoplasty, cutting of donor buttons in endothelial keratoplasty, customized trephination in penetrating keratoplasty, tunnel creation for intracorneal ring segments, astigmatic keratotomy, and corneal biopsy. Current laboratory studies include all-FS laser refractive keratomileusis sans flap, cutting corneal pockets for insertion of biopolymer keratoprostheses, noninvasive transscleral glaucoma surgery, retinal imaging and photodisruption, presbyopia surgery, and anterior lens capsulorrhexis. Advances in ultra-fast laser technology continue to improve the surgical safety, efficiency, speed, and versatility of FS lasers in ophthalmology.


Nurse students' competences in interprofessional pharmaceutical care in Europe: Cross-sectional evaluation.
Safe pharmaceutical care requires competent nurses with specific knowledge, skills and attitudes. It is unclear whether nursing students are adequately prepared to perform pharmaceutical care in practice. Mapping their pharmaceutical care competences can lead to a better understanding of the extent to which curricula fit expectations of the labour market. To assess pharmaceutical care competences of final-year nursing students of different educational levels. A cross-sectional survey design. In 14 European countries, nursing schools who offer curricula for level 4 to 7 students were approached. Through convenience sampling 1741 final-year student nurses of level 4 to 7 were included. Sampling strategies were country-specific. A web-platform was developed with an assessment of the level in which students mastered pharmaceutical care competences. Knowledge questions, case studies (basic/advanced level), self-reported practical skills and attitudes were evaluated. Mean scores for knowledge questions differed significantly (p < 0.001) between level 5 (56/100), level 6 (68/100) and level 7 students (72/100). For basic cases level 5 students reached lower scores (64/100) compared with level 6 (71/100) and level 7 (72/100) students (p = 0.002 and p = 0.005). For more advanced cases no difference between levels was observed (overall mean 61/100). Most students (63-90 %) considered themselves skilled to perform pharmaceutical care and had positive attitudes towards their participation in pharmaceutical care (65-97 %). Relatively low knowledge scores were calculated for final-year student nurses. In some domains, lower levels of students might be insufficiently prepared to take up responsibilities in pharmaceutical care. Our assessment can be used as a tool for educators to evaluate how prepared nursing students are for pharmaceutical care. Its further implementation for students of different educational levels will allow benchmarking between the levels, both within and between countries.


Weighted gene coexpression network analysis reveals ESR1, FLNA and Furin as hub genes for DEHP-induced prepubertal testicular injury.
Di-(2-ethylhexyl) phthalate (DEHP) is an environmental endocrine disruptor that accumulates in organisms in various ways and induces male reproductive system disorders. In this study, we established a testicular injury model by gavage with different concentrations of DEHP. The testes were then collected for RNA sequencing (RNA-seq), and the results were analyzed by bioinformatics and verified by experiments. Our research results show that different concentrations of DEHP interfere with testicular development differently. Weighted gene coexpression network analysis (WGCNA) generated sixteen modules and identified the turquoise module as key. Then, estrogen receptor 1 (ESR1), filamin A (Flna) and Furin were identified as hub genes. qPCR and immunohistochemistry results revealed that all three hub genes were upregulated. We detected the locations of these genes by immunohistochemistry. ESR1 was mainly located in Leydig cells; Flna immunostaining is observed in the Leydig and some germ cells and Furin staining was seen in almost all types of testicular cells. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed enrichment mainly in MAPK signaling pathways, p53 signaling pathways, HIF-1 signaling pathways, protein processing in the endoplasmic reticulum, apoptosis, the cell cycle, RNA degradation, etc. This is the first study using WGCNA to investigate the mechanism of DEHP-induced injury in the prepubertal testis, providing new research angles to further understand the mechanism of DEHP-induced injury in the prepubertal testis.


[Toxicologic evaluation of individual chemical compounds and complex mixtures using a motile cell test object].
The possibility of quantitative prognosis of chemical compounds and complex mixtures toxicity by means of a biotechnical system with suspension of bull spermatozoa sensor was investigated. The concentration of some chemical compounds, inhibiting by half spermatozoa motility has been experimentally determined. A correlation between the values determined and acute toxicity of the compounds tested has been established. The possible use of the biotechnical system for the screening of medical polymer materials has been demonstrated.


An automated method for defining anatomic coordinate systems in the hindfoot.
The absence of a standardized method for defining hindfoot bone coordinate systems makes it difficult to compare kinematics results from different research studies. The purpose of this study was to develop a reliable and robust procedure for defining anatomical coordinate systems for the talus and calcaneus. Four methods were evaluated based upon their anatomic consistency across subjects, repeatability, and their correspondence to functional axes of rotation. The four systems consisted of: 1) interactively identified bony landmarks, 2) a principal component analysis, 3) automatically identified bony landmarks, and 4) translating the tibial coordinate system to the hindfoot bones. The four systems were evaluated on 40 tali and 40 calcanei. The functional axes of rotation were determined using dynamic biplane radiography to image the hindfoot during gait. Systems 2 and 3 were the most repeatable and consistent due to the lack of operator intervention when defining coordinate systems. None of the coordinate systems corresponded well to functional axes of rotation during gait. System 3 is recommended over System 2 because it more closely mimics established bone angles measured clinically, especially for the calcaneus. This study presents an automated method for defining anatomic coordinate systems in the talus and calcaneus that does not rely on manual placement of markers or fitting of spheres to the bone surfaces which are less reliable due to operator-dependent measurements. Using this automated method will make it easier to compare hindfoot kinematics results across research studies.


Estimates of life expectancy by adolescents and young adults with congenital heart disease.
This study sought to determine what adolescents and young adults with moderate to complex congenital heart disease (CHD) believe their life span to be and to examine correlates of their beliefs. Patients with moderate to complex CHD have a shortened life expectancy. Patients' perceptions of their life expectancy have not been examined. Young adults and older adolescents with moderate or complex CHD (n = 296) estimated their own life expectancy and that of healthy peers, and rated their health status and risk of CHD complications. Adults with CHD discussed reasons for life expectancy ratings in an interview. Patients with CHD expected to live to age 75 +/- 11 years, only 4 years less than their healthy peers. Over 85% of patients expected to live longer than our estimates of their life expectancy. Poorer health status and higher perceived risk of CHD complications related to shorter perceived life expectancy. Young adults lacked awareness and understanding of CHD-specific risks, and their life expectancy perceptions often related to risk factors for coronary artery disease. Patients with moderate to complex CHD expect to live almost as long as their healthy peers. For most patients, this is unlikely. The implications of these beliefs on health behaviors and life choices are unknown, but should be examined. Nevertheless, patients need accurate information delivered in a sensitive manner to make informed life choices regarding education, careers, and family.


Fungal strain and incubation period affect chemical composition and nutrient availability of wheat straw for rumen fermentation.
Eleven white-rot fungi were examined for their potency to degrade lignin and to improve the rumen fermentability of wheat straw. The straw was inoculated with the fungi and incubated under solid state conditions at 24°C for 0-49 days to determine changes in in vitro gas production and chemical composition. Results show that some fungi could degrade lignin by as much as 63%, yet the delignification was highly correlated with the degradation of hemicellulose (r=0.96). Reduction in lignin was poorly (r=0.47), but the ratio between lignin and cellulose loss was strongly (r=0.87) correlated with the increase in gas production. Treatment with Ceriporiopsis subvermispora for 49 days increased total gas production of the straw from 200 to 309 ml/g organic matter (OM). It was concluded that some fungi highly selective for lignin and not for cellulose are able to improve the nutritive value of wheat straw as a ruminant feed.


Bladder paragangliomas: a pictorial review.
Bladder paragangliomas (bPGL) are rare neuroendocrine tumors arising from the sympathetic paraganglia present in the bladder wall. Bladder PGLs are typically submucosal or intramural but when subserosal may not be readily visible at cystoscopy. The average size at presentation is 3.9 cm (range 1.0-9.1 cm). When small, bPGL are usually spherical, well-marginated and homogeneous. Larger bPGL are typically more complex with peri- and intra-tumoral neovascularity and central necrosis. On ultrasound, increased color Doppler signal is typical. The increased soft tissue resolution of MRI enables localization of bPGL within the bladder wall more accurately than CT. Restricted diffusion and avid contrast enhancement help differentiate small bPGLs from leiomyomas, which have similar appearances on ultrasound and CT. Nuclear medicine techniques identify bPGLs and their metastases with high specificity, 68Ga-DOTATATE PET/CT having largely replaced 123I-mIBG SPECT/CT as the first line functional investigation. Imaging is essential to aid surgical planning, as endoscopic resection is often not possible or incomplete due to tumor location. For patients with advanced disease, 68Ga-DOTATATE PET/CT and 123I-mIBG SPECT/CT assess suitability for peptide receptor radionuclide therapy. Up to 63% of bPGL patients have a germline mutation, most commonly in the SDHB subunit gene, increasing their risk of developing pheochromocytomas and further paragangliomas; lifelong annual biochemical and periodic imaging screening from skull base to pelvis is therefore recommended.


The protective effect of indomethacin on photocarcinogenesis in hairless mice.
Orally administered indomethacin at 10-600 micrograms per mouse per day has been shown to inhibit UV radiation-induced erythema dose responsively. At the higher doses tested (200-600 micrograms) there was evidence of drug toxicity. Indomethacin administered orally at 20 micrograms per mouse daily during photocarcinogenesis induction both increased the probability of remaining tumour free and reduced the average tumour multiplicity. When indomethacin was administered only during the UV irradiation period (initiation), a reduction in tumour multiplicity and in the progression of tumours to malignant squamous cell carcinomas was observed; when administered only during the post-irradiation promotion period, there was a significant increase in the probability of remaining tumour free. Thus both tumour initiation and promotion by UV radiation appear to be indomethacin-sensitive, possibly affected by different mechanisms.


Thoraco dorsal artery perforator flap for trismus release in a young girl.
Trismus is a frequent complication occurring after treatment of tumors of the pterygomaxillary fossa. Local flaps and full-thickness skin grafts fail to release it because they usually lead to scar contracture in previously irradiated tissues. We propose to release it with a thoracodorsal artery perforator flap, which is feasible in children like other perforator flaps. It is interesting because it is thinner than the anterolateral thigh flap and its scar may be less disgraceful and easier to hide.


Comparative effects of schisandrin A, B, and C on Propionibacterium acnes-induced, NLRP3 inflammasome activation-mediated IL-1β secretion and pyroptosis.
Propionibacterium acnes, a common pathogen associated with acne, is also responsible for various surgical infections. Schisandrin A, schisandrin B and schisandrin C, the representative lignans of Schisandra chinensis (Turcz.) Baill. extract, inhibit P. acnes-induced inflammation. However, their effects on P. acnes-induced IL-1β secretion and pyroptosis mediated by NLRP3 inflammasome activation remain unknown. In this study, we compared the effects of schisandrin A, B, and C (Sch A, B, and C) on IL-1β secretion and pyroptosis in P. acnes-infected THP-1 cells. As NLRP3 plays important roles in P. acnes-mediated inflammation and pyroptosis, we also investigated the effects of Schs on P. acnes-induced NLRP3 inflammasome activation by measuring the levels of NLRP3, active caspase-1, and mature IL-1β, and activity of caspase-1. Our results showed that Sch A, B, and C suppressed P. acnes-induced pyroptosis. Further, the three lignans significantly suppressed NLRP3 inflammasome activation, with the following potency: Sch C > Sch B > Sch A. Three lignans also inhibited the production of mitochondrial ROS and ATP release. Additionally, Sch B and C almost completely prevented the efflux of K+., whereas Sch A had a relatively weak effect. Collectively, our novel findings showed that Sch A, B, and C effectively suppressed IL-1β secretion and pyroptosis by inhibiting NLRP3 inflammasome activation in P. acnes-infected THP-1 cells. Thus, Schs may be promising agents for the treatment of P. acnes-related infections.


The effects of intranigral injections of picrotoxin and carbachol in cats with a lesioned nigrostriatal pathway.
Picrotoxin, carbachol and atropine were injected intranigrally through chronically implanted crannulae in cats. The drug-induced behavioural syndromes, mainly asymmetric behaviour, were analyzed. The changes in these syndromes after 6-hydroxydopamine (6-OHDA) lesion of the substantia nigra (SN) indicate that, in addition to the dopaminergic (DA), a non-catecholaminergic (non-CA) nigral output exists, both being responsible for asymmetric behaviour. It is further suggested that gamma-aminobutyric acid (GABA) receptors are present on both dopaminergic and non-CA nigral output neurons, while acetylcholine (ACh) receptors, responsible for asymmetric behaviour, are almost exclusively located on non-CA nigral output neurons.


Early Sweet Tooth: Juice Introduction During Early Infancy is Related to Toddler Juice Intake.
To assess if 100% fruit juice intake prior to 6 months is associated with juice and sugar-sweetened beverage (SSB) intake at 24 months and whether this differs by sociodemographic factors. We used longitudinal data from infants enrolled in the control (no obesity intervention) arm of Greenlight, a cluster randomized trial to prevent childhood obesity which included parent-reported child 100% fruit juice intake at all well child checks between 2 and 24 months. We studied the relationship between the age of juice introduction (before vs after 6 months) and juice and SSB intake at 24 months using negative binomial regression while controlling for baseline sociodemographic factors. We report results for 187 participants (43% Hispanic, 39% non-Hispanic Black), more than half (54%) of whom had reported 100% fruit juice intake before 6 months. Average 100% fruit juice intake at 24 months was greater than the recommended amount (of 4 oz) and was 8.2 oz and 5.3 oz for those who had and had not, respectively, been introduced to juice before 6 months. In adjusted models, early introduction of juice was associated with a 43% (95% confidence interval: 5%-96%) increase in juice intake at 24 months. 100% fruit juice intake exceeding recommended levels at 6 and 24 months in this diverse cohort was prevalent. Introducing 100% fruit juice prior to 6 months may put children at greater risk for more juice intake as they age. Further research is necessary to determine if early guidance can reduce juice intake.


Analysis of the Antigenic Properties of Membrane Proteins of Mycobacterium tuberculosis.
Tuberculosis (TB) is a continuing major threat to global health and a leading cause of death, particularly in developing countries. In this study, we aimed to identify a specific and sensitive diagnostic biomarker and develop a vaccine to prevent this disease. We investigated membrane proteins to reveal biomarkers in serum and peripheral blood mononuclear cells (PBMCs) obtained from TB patients. We employed Western blotting to evaluate serological immunoglobulin G levels, and Enzyme Linked Immunospot (ELISpot) to assess the antigen-specific cellular interferon-γ secretion from PBMCs after membrane protein stimulation. A total of 219 membrane proteins were identified, 52 exhibited at a higher levels than the 38-kDa prositive control. Of these 18 exhibited reacted ratios above 1, especially Rv1111c (427-981), with a ratios at 3.38. Accuracy and sensitivity were markedly higher for the top two antigen candidates, Rv0232 and Rv1115, after two rounds of ELISpot tests than ESAT-6 in the commercial kit (42.15 and 43.62%, respectively). These two proteins were administered to mice to detect whether they acted as effective antigens in vivo. These data provide a comprehensive view of the membranes involved in humoural and cellular immune responses that may be used as biomarkers for TB and candidates for a vaccine.


Educating patients with limited literacy skills: the effectiveness of printed and videotaped materials about colon cancer.
We investigated whether printed or videotaped information is more effective in enhancing colon cancer knowledge. Subjects (n = 1100) were randomized into three groups: to receive a booklet, view a videotape, or receive no intervention. Subjects receiving the intervention showed increased knowledge compared with control subjects (booklet = 23% and videotape = 26% vs no intervention = 3%). Findings suggest that personalized educational materials are effective in enhancing colon cancer knowledge.


Jianpi Jiedu Recipe inhibits colorectal cancer liver metastasis via regulating ITGBL1-rich extracellular vesicles mediated activation of cancer-associated fibroblasts.
Extracellular vesicles (EVs) contribute greatly to the formation of pre-metastatic niche and tumor metastasis. Our previous study has revealed that tumor-derived ITGBL1 (integrin beta- like 1)-rich EVs activate fibroblasts through the NF-κB signaling to promote colorectal cancer (CRC) metastasis. Targeting ITGBL1-loaded EVs may be a new and effective therapy for treating CRC metastasis. Simultaneously, our preliminary clinical trial has demonstrated that Jianpi Jiedu Recipe (JPJDR) was an ideal alternative traditional Chinese medicine for the prevention and treatment of CRC metastasis. However, the underlying mechanism of JPJDR in the prevention of CRC metastasis is not clear. In this study, we will investigate the regulatory effect of JPJDR on ITGBL1 levels in CRC-derived EVs, and to detect how JPJDR regulate ITGBL1-rich EVs mediated activation of fibroblasts to inhibit CRC metastasis. EVs derived from CRC cells with/without JPJDR treatment were obtained by ultracentrifugation, following by characterization with electron microscopy, LM10 nanoparticle characterization system and western blot. The migration and growth of CRC cells were tested by transwell assay, wound healing assay and colony formation assay. The effect of JPJDR on the fibroblasts-activation associated inflammatory factors including IL-6, IL-8 and α-SMA was detected by real-time PCR. The levels of IL-6, IL-8 and α-SMA in the cell culture supernatant were detected by ELISA. The protein expressions of TNFAIP3, ITGBL1, p-NF-κB, IκBα and β-actin were detected by western blot. Liver metastasis model in mice was established by injecting MC38 single cell suspension into the spleen of mice to observe the effect of JPJDR on CRC liver metastasis. Immunohistochemistry were applied to detect the expression of ITGBL1 and TNFAIP3 in the liver metastatic tissues. Tissue immunofluorescence detection was performed to observe the regulatory effect of JPJDR on the ITGBL1-NF-κB signaling pathway. Cancer-associated fibroblasts (CAFs) in the liver metastatic tissues were sorted and characterized by platelet-derived growth factor receptor β (PDGFRβ) with flow cytometry, following by the detection of inflammatory factors including IL-6, IL-8 and α-SMA using real-time PCR. JPJDR reduced the ITGBL1 levels in CRC cells-derived EVs. JPJDR inhibited the migration and growth of CRC cells via regulating ITGBL1-rich EVs mediated fibroblasts activity. Mechanically, JPJDR decreased fibroblasts activation by regulating ITGBL1-rich EVs mediated TNFAIP3-NF-κB signaling. Further in vivo experiments demonstrated that JPJDR reduced CRC liver metastasis by regulating ITGBL1-rich EVs secretion from CRC and blocked the fibroblasts activation by regulating ITGBL1-TNFAIP3- NF-κB signaling. Our research demonstrated that JPJDR preventd CRC liver metastasis via down-regulating CRC-derived ITGBL1-loaded EVs mediated activation of CAFs, providing the experimental evidence for the clinical application of JPJDR in the prevention and treatment of CRC metastasis. More importantly, our study confirmed the great benefits of therapeutic targeting the EVs-mediated metastasis and warranted future clinical validation.


Detection of DNA mutations by fluorescence resonance energy transfer-based preferential homoduplex formation assay.
Molecularly targeted agents for cancer therapy are recognized as being effective and are gaining in popularity. However, the efficacy of the agents depends on the status of the targeted molecule such as the number of molecules expressed, activity, and mutation. Therefore, the use of companion diagnostics for investigating the status of the targeted molecule prior to therapy is highly important. We developed a simple and cost-effective somatic mutation detection method called the fluorescence resonance energy transfer-based preferential homoduplex formation assay (FRET-PHFA). By using double-stranded labeled DNA and fluorescence measurement with thermal control, this method provides higher reproducibility, easier handling, less risk for contamination, shorter assay time (only ∼15min), and less cost compared with conventional PHFA. Here we report the evaluation of FRET-PHFA on the detection of multiallelic KRAS mutations in codons 12 and 13 compared with the TheraScreen clinical diagnostics kit. We found that FRET-PHFA detected KRAS mutations (1.25-50%) from all cell line DNA titration samples.


Natural speech markers of Alzheimer's disease co-pathology in Lewy body dementias.
An estimated 50% of patients with Lewy body dementias (LBD), including Parkinson's disease dementia (PDD) and Dementia with Lewy bodies (DLB), have co-occurring Alzheimer's disease (AD) that is associated with worse prognosis. This study tests an automated analysis of natural speech as an inexpensive, non-invasive screening tool for AD co-pathology in biologically-confirmed cohorts of LBD patients with AD co-pathology (SYN + AD) and without (SYN-AD). We analyzed lexical-semantic and acoustic features of picture descriptions using automated methods in 22 SYN + AD and 38 SYN-AD patients stratified using AD CSF biomarkers or autopsy diagnosis. Speech markers of AD co-pathology were identified using best subset regression, and their diagnostic discrimination was tested using receiver operating characteristic. ANCOVAs compared measures between groups covarying for demographic differences and cognitive disease severity. We tested relations with CSF tau levels, and compared speech measures between PDD and DLB clinical disorders in the same cohort. Age of acquisition of nouns (p = 0.034, |d| = 0.77) and lexical density (p = 0.0064, |d| = 0.72) were reduced in SYN + AD, and together showed excellent discrimination for SYN + AD vs. SYN-AD (95% sensitivity, 66% specificity; AUC = 0.82). Lower lexical density was related to higher CSF t-Tau levels (R = -0.41, p = 0.0021). Clinically-diagnosed PDD vs. DLB did not differ on any speech features. AD co-pathology may result in a deviant natural speech profile in LBD characterized by specific lexical-semantic impairments, not detectable by clinical disorder diagnosis. Our study demonstrates the potential of automated digital speech analytics as a screening tool for underlying AD co-pathology in LBD.


Equilibrium sampling: partitioning of organochlorine compounds from lipids into polydimethylsiloxane.
Polydimethylsiloxane (PDMS) can be used for equilibrium sampling of environmental pollutants in a large variety of matrices including biota. For comparison with lipid-normalized concentrations e.g. from biota monitoring programmes, reliable lipid to PDMS partition ratios (K(Lipid,PDMS)) are required. Additionally, K(Lipid,PDMS) facilitate comparison of equilibrium sampling data obtained in various environmental media and can be helpful to convert equilibrium sampling data into a more informative form. This work investigated the equilibrium partitioning of polychlorinated biphenyls (PCBs) and selected organochlorine pesticides (OCPs) between lipids from biota of different trophic levels and PDMS. One vegetable oil, a fish oil and seal oil were investigated. The lipid to PDMS partition ratios were compound-specific and ranged from 14.5 to 62.9 g/g with correction for lipid uptake into the PDMS and from 13.0 to 54.8 g/g without correction. Additionally, PDMS served as a reference partitioning phase for the accurate determination of lipid to lipid partition ratios, which for all analytes were close to unity. Evaluating the results in a bioaccumulation context, they indicate that the equilibrium partitioning of neutral lipophilic environmental contaminants into the lipids of the three investigated species will be very similar, although they represent three distinct trophic levels.


A comparison of the effectiveness of intravenous immunoglobulin and plasma exchange as preoperative therapy of myasthenia gravis.
Immunomodulation with plasma exchange is effective in preparing patients for thymectomy. Newer forms of immunomodulation, such as intravenous immunomodulation, require evaluation in this clinical setting. We conducted a retrospective chart review to determine if plasma exchange and intravenous immunoglobulin had comparable effectiveness in the preoperative preparation of patients with myasthenia gravis. The results show that intravenous immunoglobulin may have comparable efficacy in the preoperative preparation of patients with myasthenia gravis and that this therapy is a reasonable alternative to plasma exchange in this clinical setting.


Traumatic brain injury rehabilitation, the programs applied in French UEROS units, and the specificity of the Limoges experience.
First created in 1996, the French evaluation, retraining, social and vocational orientation units (UEROS) now play a fundamental role in the social and vocational rehabilitation of patients with brain injury. As of today, there exist 30 UEROS centers in France. While their care and treatment objectives are shared, their means of assessment and retraining differ according to the experience of each one. The objective of this article is to describe the specific programs and the different tools put to work in the UEROS of Limoges. The UEROS of Limoges would appear to offer a form of holistic rehabilitation management characterized by the importance of psycho-education and its type of approach towards vocational reintegration.


Adjuvant therapy for periampullary carcinoma and the significance of histopathological typing: A systematic review.
This review investigates the role of adjuvant therapy (AT) and the importance of histopathological typing in periampullary carcinoma (PAC) treatment. PAC is a relatively rare gastrointestinal malignancy. The regimen and effect of AT in PAC are still controversial. However, there is a treatment based on histopathological types (pancreaticobiliary-type, PB-type or intestinal-type, IN-type), but there are no clear guidelines indicating that typing can be used to guide the selection of AT drugs. A literature search of PubMed and Web of Science databases was conducted for studies published from January 2001 to August 2021 on the use of AT in PAC. A total of 75 studies were included in this review. According to existing studies, AT for PAC is mostly based on 5-FU or gemcitabine, but the effect is unknown. However, when PAC is classified into different histopathological types, AT with gemcitabine is beneficial for patients with the PB-type of PAC, while 5-FU-based AT is beneficial for patients with the IN-type of PAC. In addition, the benefits of AT are more pronounced in patients with a high-risk disease, such as patients with stage II/III, T3/T4 tumors, or positive lymph node involvement. There are few studies on targeted therapy and immunotherapy for PAC. This review suggests that AT has potential survival benefits, especially when based on the histopathologic type that helps the choice of drugs during AT in PAC patients.


What are the development priorities for management of type 2 diabetes by general practitioners in Ningbo, China: a qualitative study of patients' and practitioners' perspectives.
To explore patients' and general practitioners' (GPs') perspectives on primary care management of patients with type 2 diabetes mellitus (T2DM) in Ningbo, China. We aimed to understand the current benefits and challenges and to identify development priorities. Exploratory qualitative descriptive study using face-to-face interviews and analysed by thematic, inductive analysis. 11 primary care facilities spread across the city of Ningbo, China. 23 patients with T2DM and 20 GPs involved in caring for patients with T2DM. GPs were considered the first point of contact and providers of information. However, the care varied, and many GPs lacked confidence and felt overworked. The medication was a particularly weak area. The diagnostic screening commenced late, leading to crisis presentations. Patients were variably informed about their condition, contributing to poor adherence. Future developments of primary care for T2DM in Ningbo should centre around improving GP confidence and workload and patient education and adherence.


Asymmetric epiphyseal closure of the femoral head as a potential cause of the primary cam lesion: a case report.
Cam-type femoroacetabular impingement is a pathologic condition caused by repetitive impact of the abnormal femur on a normal acetabular rim, resulting in damage to the articular cartilage. Excluding cases with known underlying diseases, the development of primary cam deformity is not well understood. Here, we describe a patient with cam-type femoroacetabular impingement exhibiting delayed epiphyseal closure at the site of the cam lesion. The authors believe that this may represent a cause of primary cam deformity, and hereby report the case with review of the literature.


Functional alpha-1B adrenergic receptors on human epicardial coronary artery endothelial cells.
Alpha-1-adrenergic receptors (α1-ARs) regulate coronary arterial blood flow by binding catecholamines, norepinephrine (NE), and epinephrine (EPI), causing vasoconstriction when the endothelium is disrupted. Among the three α1-AR subtypes (α1A, α1B, and α1D), the α1D subtype predominates in human epicardial coronary arteries and is functional in human coronary smooth muscle cells (SMCs). However, the presence or function of α1-ARs on human coronary endothelial cells (ECs) is unknown. Here we tested the hypothesis that human epicardial coronary ECs express functional α1-ARs. Cultured human epicardial coronary artery ECs were studied using quantitative real-time reverse transcription polymerase chain reaction, radioligand binding, immunoblot, and (3)H-thymidine incorporation. The α1B-subtype messenger ribonucleic acid (mRNA) was predominant in cultured human epicardial coronary ECs (90-95% of total α1-AR mRNA), and total α1-AR binding density in ECs was twice that in coronary SMCs. Functionally, NE and EPI through the α1B subtype activated extracellular signal-regulated kinase (ERK) in ECs, stimulated phosphorylation of EC endothelial nitric oxide synthase (eNOS), and increased deoxyribonucleic acid (DNA) synthesis. These results are the first to demonstrate α1-ARs on human coronary ECs and indicate that the α1B subtype is predominant. Our findings provide another potential mechanism for adverse cardiac effects of drug antagonists that nonselectively inhibit all three α1-AR subtypes.


Acute Distress Respiratory Syndrome and Cardiac Shock after AngioJet Thrombectomy for Acute Occlusion of an Aortic Endograft.
Partial thrombosis or total occlusion of aortic or limb graft are possible complications after endovascular aneurysm repair. Different strategies for therapeutic management are available; these include open surgical techniques or endovascular treatments. The choice of the treatment depends on the patient's clinical conditions and on the timing of the thrombosis. Bypass still remains the first choice in case of chronic occlusion but in the last 10 years, the use of percutaneous mechanical/rheolytic thrombectomy systems is increasing. These devices can be used in case of acute or subacute onset of native arterial and venous thrombosis or embolism and in case of graft occlusion. AngioJet is a percutaneous rheolytic mechanical thrombectomy system. Through a pressurized saline solution jet, a low-pressure zone is made up and the thrombus is fragmented and aspirated by the device. Different transient adverse effects caused by lysis of the thrombus are described such as hemoglobinuria but in some cases the release of high doses of the thrombus degradation products such as heme and adenosine diphosphate can lead to fatal consequences for the patient. We reported a case of an acute onset of acute distress respiratory syndrome, pulmonary edema, cardiac shock, and renal failure following AngioJet thrombectomy in an 81-year-old man with an acute occlusion of an aortic endograft.


Concordance regarding disease type and phenotypic characteristics among patients with familial inflammatory bowel disease.
The phenotypic concordance among familial cases of inflammatory bowel disease (IBD) has been rarely reported. Thus, the present study aimed to evaluate the concordance regarding disease type and phenotypic features in a large cohort of Korean patients with IBD. A total of 6647 patients with IBD who visited the Asan Medical Center between June 1989 and September 2016 were enrolled in the study. When at least two familial cases existed in our cohort, they were included in the concordance analysis (κ index). The concordance between younger and older members for IBD type [Crohn's disease (CD) and ulcerative colitis (UC)] and phenotypic characteristics such as disease extent and location, disease behavior, the use of medication, and need for surgery were evaluated. A positive family history of IBD was noted in 216 patients with CD (7.0%) and in 238 patients with UC (6.7%). Of all patients, 167 consanguineous pairs in 146 families were identified. The crude concordance rate for IBD type was 82.6% with a κ index of 0.656 [95% confidence interval (CI): 0.545-0.768, good concordance]. There was mild concordance for disease location in CD (κ = 0.256; 95% CI: 0.007-0.505) and for the use of antitumor necrosis factor agents in UC (κ = 0.354; 95% CI: -0.049-0.757). The concordance for IBD type and several phenotypes in first-degree relative pairs was better than that in the entire pairs. Disease type and phenotypic characteristics of patients with familial IBD may be anticipated.


Radiotherapy departmental automation.
Cost-effective radiotherapy departmental information systems have been developed to answer a growing need for facility management and clinical research. These systems provide scheduling and management support to improve patient flow, facility utilization, charge capture, quality assurance and clinical studies. Typical data base definition, system utilization and costs are presented.


Cognitive Functioning in Schizophrenia, Methamphetamine-induced Psychotic Disorder, and Healthy People: A Comparative Study.
Methamphetamine-induced psychotic disorder (MIP) cannot be easily differentiated from other psychotic disorders. Some studies have reported that patients with MIP and schizophrenia have differences in their cognitive functioning. We hypothesized that their performance would be different on neuropsychological tests which assess executive functions and visual memory. In a cross-sectional study, 30 patients with MIP, 31 patients with schizophrenia, and 31 healthy controls were assessed by Rey-Osterrieth complex figure (ROCF) test and visual search and attention test (VSAT). One-way analysis of variance was performed to compare the mean scores of tests. Tukey's HSD test was used for post hoc analysis. Three groups had significant differences according to ROCF test (F = 15.76, P < 0.0001), VSAT (F = 39.78, P < 0.0001), left VSAT (F = 37.96, P < 0.0001), right VSAT (F = 40.40, P < 0.0001), and the time of the test administration (F = 3.26, P = 0.04). The post hoc analysis showed that the mean score of ROCF test and VSAT (total, right, and left) was significantly higher in the control group than in the other two groups. The time of administering the test in the control group was significantly shorter than in the MIP group (P < 0.03) and nonsignificantly shorter than in the schizophrenia group (P = 0.54). The mean score of right side VSAT was significantly higher in the MIP group than in the schizophrenia group. ROCF could not differentiate MIP from schizophrenia. The better performance of patients with MIP on right side VSAT that is reported in this and in the previous study needs to be reevaluated in more controlled studies.


In situ-derived carbon nanotube-decorated nitrogen-doped carbon-coated nickel hybrids from MOF/melamine for efficient electromagnetic wave absorption.
Carbon nanotube-decorated nitrogen-doped carbon-coated nickel (CNT/Ni@N-C) microspheres have been fabricated by pyrolyzing the mixture of nickel-based metal organic framework (Ni-MOF) and melamine. The resultant composite is assembled from CNTs and spherical Ni@N-C composite. Besides, the CNT/Ni@N-C composite contains abundant nitrogen (N) dopants that contribute to defect dipole polarization. The melamine content is important for controlling the amount of N element and N dopant state in the composite. The optimized CNT/Ni@N-C composite with high content of pyridinic N exhibits strong absorption of -55.1 dB at 10.56 GHz with the thickness of 2.5 mm, and the effective absorbing bandwidth (reflection loss < -10 dB) is 11.2 GHz (6.0-17.2 GHz) with the thickness range of 1.5-4.0 mm. These results indicate that the N content and N dopant state have a great influence on electromagnetic wave absorption properties. This strategy will contribute to fabricate the carbon hybrid network consisting of metal organic frameworks derived metal/carbon hybrid and CNTs for electromagnetic wave absorption.


Atomistic understanding of the C·T mismatched DNA base pair tautomerization via the DPT: QM and QTAIM computational approaches.
It was established that the cytosine·thymine (C·T) mismatched DNA base pair with cis-oriented N1H glycosidic bonds has propeller-like structure (|N3C4C4N3| = 38.4°), which is stabilized by three specific intermolecular interactions-two antiparallel N4H…O4 (5.19 kcal mol(-1)) and N3H…N3 (6.33 kcal mol(-1)) H-bonds and a van der Waals (vdW) contact O2…O2 (0.32 kcal mol(-1)). The C·T base mispair is thermodynamically stable structure (ΔG(int) = -1.54 kcal mol(-1) ) and even slightly more stable than the A·T Watson-Crick DNA base pair (ΔG(int) = -1.43 kcal mol(-1)) at the room temperature. It was shown that the C·T ↔ C*·T* tautomerization via the double proton transfer (DPT) is assisted by the O2…O2 vdW contact along the entire range of the intrinsic reaction coordinate (IRC). The positive value of the Grunenberg's compliance constants (31.186, 30.265, and 22.166 Å/mdyn for the C·T, C*·T*, and TS(C·T ↔ C*·T*), respectively) proves that the O2…O2 vdW contact is a stabilizing interaction. Based on the sweeps of the H-bond energies, it was found that the N4H…O4/O4H…N4, and N3H…N3 H-bonds in the C·T and C*·T* base pairs are anticooperative and weaken each other, whereas the middle N3H…N3 H-bond and the O2…O2 vdW contact are cooperative and mutually reinforce each other. It was found that the tautomerization of the C·T base mispair through the DPT is concerted and asynchronous reaction that proceeds via the TS(C·T ↔ C*·T*) stabilized by the loosened N4-H-O4 covalent bridge, N3H…N3 H-bond (9.67 kcal mol(-1) ) and O2…O2 vdW contact (0.41 kcal mol(-1) ). The nine key points, describing the evolution of the C·T ↔ C*·T* tautomerization via the DPT, were detected and completely investigated along the IRC. The C*·T* mispair was revealed to be the dynamically unstable structure with a lifetime 2.13·× 10(-13) s. In this case, as for the A·T Watson-Crick DNA base pair, activates the mechanism of the quantum protection of the C·T DNA base mispair from its spontaneous mutagenic tautomerization through the DPT.


Bacteroides fragilis type VI secretion systems use novel effector and immunity proteins to antagonize human gut Bacteroidales species.
Type VI secretion systems (T6SSs) are multiprotein complexes best studied in Gram-negative pathogens where they have been shown to inhibit or kill prokaryotic or eukaryotic cells and are often important for virulence. We recently showed that T6SS loci are also widespread in symbiotic human gut bacteria of the order Bacteroidales, and that these T6SS loci segregate into three distinct genetic architectures (GA). GA1 and GA2 loci are present on conserved integrative conjugative elements (ICE) and are transferred and shared among diverse human gut Bacteroidales species. GA3 loci are not contained on conserved ICE and are confined to Bacteroides fragilis Unlike GA1 and GA2 T6SS loci, most GA3 loci do not encode identifiable effector and immunity proteins. Here, we studied GA3 T6SSs and show that they antagonize most human gut Bacteroidales strains analyzed, except for B. fragilis strains with the same T6SS locus. A combination of mutation analyses,trans-protection analyses, and in vitro competition assays, allowed us to identify novel effector and immunity proteins of GA3 loci. These proteins are not orthologous to known proteins, do not contain identified motifs, and most have numerous predicted transmembrane domains. Because the genes encoding effector and immunity proteins are contained in two variable regions of GA3 loci, GA3 T6SSs of the species B. fragilis are likely the source of numerous novel effector and immunity proteins. Importantly, we show that the GA3 T6SS of strain 638R is functional in the mammalian gut and provides a competitive advantage to this organism.


The epidemiology of severe malaria at Manhiça District Hospital, Mozambique: a retrospective analysis of 20 years of malaria admissions surveillance data.
Most malaria burden estimates rely on modelling infection prevalence to case incidence data, with insufficient attention having been paid to the changing clinical presentation of severe disease and its relationship with changing transmission intensity. We present 20 years of longitudinal surveillance data to contribute to the understanding of the relationship between malaria transmission and the burden and clinical presentation of severe malaria and to inform policy. This retrospective analysis of clinical surveillance hospital data included all children younger than 15 years admitted with malaria to Manhiça District Hospital (MDH), Mozambique, from July 1, 1997, to June 30, 2017. Case fatality ratios (CFRs) were calculated as the number of patients who died having a specific diagnosis or syndrome divided by the total number of patients with known outcome admitted with that diagnosis or syndrome. Over the study period, 32 138 children were admitted to MDH with a malaria diagnosis. Malaria accounted for a large proportion of admissions, ranging from 4083 (76·9%) of 5307 admissions in 2000-01 to 706 (27·5%) of 2568 admissions in 2010-11. Since 2000-02, the absolute and relative number of malaria admissions and deaths presented a decreasing trend. The age pattern of patients with malaria shifted to older ages with a median age of 1·7 years (IQR 0·9-3·0) in 1997-2006 and 2·6 years (IQR 1·3-4·4) in 2006-17, although most malaria deaths (60-88% in 2009-17) still occurred in children younger than 5 years. The clinical presentation of severe malaria changed, with an increase in cerebral malaria and a decrease in severe anaemia and respiratory distress, leading to similar yearly cases for the three syndromes. CFRs for severe malaria fluctuated between 1·1% (2 of 186 in 2014-15) and 7·2% (11 of 152 in 2010-11), varying by severe malaria syndrome (3·3% [70 of 2105] for severe anaemia, 5·1% [191 of 3777] for respiratory distress, and 14·8% [72 of 487] for cerebral malaria). Overall malaria CFRs (1·8% [543 of 30 163]) did not vary by age group. Despite the unprecedented scale up of malaria control tools, malaria still represented around 30-40% of paediatric hospital admissions in 2006-17. The age shift towards older children was not accompanied by an increase in severe malaria or deaths; however, control programmes should consider adapting their high-risk target groups to include older children. Malaria remains a leading cause of disease and health-care system use and the massive unfinished malaria control agenda warrants intensified efforts. Spanish Agency for International Cooperation and Development.


'Simultaneous' urethral pressure profilometry in the bitch: methodology and reproducibility of the technique.
The technique of 'simultaneous' urethral pressure profilometry in the bitch is described. Four consecutive recordings were made from each of 100 bitches. From each recording, the maximum urethral closure pressure and functional profile length were measured and assessed for reproducibility. Analyses of variance revealed no significant differences (P greater than 0.2) between the measurements of functional profile length (means: 3.84, 3.84, 3.83, 3.80 cm; standard error of the differences: 0.037) but there were significant variations (P less than 0.001) in maximum urethral closure pressure (means of square roots: 2.26, 2.18, 2.12, 2.08 cm water; standard error of the differences: 0.042). Overall, there was a significant dependence of maximum urethral closure pressure on the measurement order (P less than 0.001). Thus, while functional profile length is a highly reproducible parameter, maximum urethral closure pressure is subject to significant variation.


A continuum of care model for postpartum hemorrhage.
The leading cause of maternal mortality is hemorrhage, generally occurring in the postpartum period. Current levels of PPH-related morbidity and mortality in low-resource settings result from institutional, environmental, cultural and social barriers to providing skilled care and preventing, diagnosing and treating PPH. Conventional uterotonics to prevent PPH are typically not available or practical for use in low-resource settings. In such deliveries, most often taking place at home or in rural health centers, underestimation of blood loss leads to a delay in diagnosis. Deficiencies in communication and transportation infrastructure impede transfer to a higher level of care. Inability to stabilize a patient who is in hemorrhagic shock rapidly results in death. To address these individual factors, we propose a continuum of care model for PPH, including routine use of prophylactic misoprostol or other appropriate uterotonic, a standardized means of blood loss assessment, availability of a non-pneumatic anti-shock garment, and systemization of communication, transportation, and referral. Such a multifaceted, systematic, contextualized PPH continuum of care approach may have the greatest impact for saving women's lives. This model should be developed and tested to be region-specific.


Infection with Schistosoma mansoni in mice induces changes in nociception and exploratory behavior.
In this study, CD-1 mice were infected percutaneously with 1600 cercariae of Schistosoma mansoni and their pain sensitivity and exploratory behavior were analyzed in well-standardized tests (hot-plate, hole-board, open-field, novel object investigation and black/white box). Schistosome infection produced body weight reduction, increased analgesia, induced changes in the number of fecal pellets emitted during the hole-board and the black/white tests, induced decreased locomotion in the open-field, decreased sniffing, rearing, wall-rearing and time spent in exploratory activity. The infection also lengthened the latency time to the first transition from the white into the black compartment in the black/white box, index of enhanced anxiety. The present findings indicate that the analgesia is one of the main effects of the disease suggesting that schistosome infection induces maladaptive response in exploratory behavior and in locomotor activity of the host associated with altered motivational and attentional levels. Furthermore, though mouse behavioral changes appear to be similar to those observed in parasite/host systems where the changes are supposed to be adaptive for the parasite, in the case of Schistosoma/mouse system, the changes in host behavior resulted to be not adaptive for the parasite.


Peritonitis due to Pseudomonas putida in a patient receiving automated peritoneal dialysis.
A patient, who had recently undergone a laparoscopic ovarian cyst operation, receiving nightly automated peritoneal dialysis treatment, was discovered to have peritonitis due to Pseudomonas putida. She was successfully treated with a 21-day course of intraperitoneal ceftazidime and gentamicin, without needing to remove the dialysis catheter. No recurrence was observed over 3 months of follow-up.


Cocaine use in pregnancy: perinatal morbidity and mortality.
With the increasing use of cocaine in the United States, there has been growing concern regarding its effects on the fetuses and neonates of pregnant cocaine abusers. Fifty-two cocaine-using women enrolled in a comprehensive perinatal addiction program were evaluated and compared with 73 women who had used narcotics in the past and were maintained on methadone during pregnancy. The groups were similar in maternal age, socioeconomic status, number of pregnancies and cigarette, marijuana and alcohol use. The cocaine-using women had a significantly higher rate of premature labor, precipitous labor, abruptio placentae, fetal monitor abnormality and fetal meconium staining than the women in the methadone group. Neonatal gestational age, birth weight, length and head circumference were not affected by cocaine use compared to methadone use. However, the Brazelton Neonatal Behavioral Assessment Scale revealed that infants exposed to cocaine had significant depression of organizational response to environmental stimuli (state organization) when compared to methadone-exposed infants. In another aspect of the study, an increased rate of SIDS (15%) was found for 66 cocaine-exposed infants as compared to a 4% rate of SIDS in 50 methadone-exposed infants.


Quantum jumps of conductance during formation of membrane channels at cell-cell junction.
The cell-to-cell conductance of a nascent cell junction increases by stable quantal steps. The steps evidently reflect the opening of stable cell-to-cell channels, all alike and growing progressively in number.


Biomarkers of Infection and Sepsis.
The role of biomarkers for detection of sepsis has come a long way. Molecular biomarkers are taking front stage at present, but machine learning and other computational measures using bigdata sets are promising. Clinical research in sepsis is hampered by lack of specificity of the diagnosis; sepsis is a syndrome with no uniformly agreed definition. This lack of diagnostic precision means there is no gold standard for this diagnosis. The final conclusion is expert opinion, which is not bad but not perfect. Perhaps machine learning will displace expert opinion as the final and most accurate definition for sepsis.


Newly Developed Sarcopenia as a Prognostic Factor for Survival in Patients who Underwent Liver Transplantation.
The relationship between a perioperative change in sarcopenic status and clinical outcome of liver transplantation (LT) is unknown. We investigated whether post-LT sarcopenia and changes in sarcopenic status were associated with the survival of patients. This retrospective study was based on a cohort of 145 patients from a single transplant center who during a mean of 1 year after LT underwent computed tomography imaging evaluation. The cross-sectional area of the psoas muscle of LT patients was compared with that of age- and sex-matched healthy individuals. The Cox proportional hazards regression model was used to determine whether post-LT sarcopenia and changes in sarcopenic status affect post-LT survival. The mean age at LT of the 116 male and 29 female patients was 50.2 ± 7.9 years; the mean follow-up duration was 51.6 ± 32.9 months. All pre-LT patients with sarcopenia still had sarcopenia 1 year after LT; 14 (15%) patients had newly developed sarcopenia. The mean survival duration was 91.8 ± 4.2 months for non-sarcopenic patients and 80.0 ± 5.2 months for sarcopenic patients (log-rank test, p = 0.069). In subgroup analysis, newly developed sarcopenia was an independent negative predictor for post-LT survival (hazard ratio: 10.53, 95% confidence interval: 1.37-80.93, p = 0.024). Sarcopenia in LT recipients did not improve in any of the previously sarcopenic patients and newly developed within 1 year in others. Newly developed sarcopenia was associated with increased mortality. Newly developed sarcopenia can be used to stratify patients with regard to the risk of post-LT mortality.


Visual evoked potentials in normal and sulfite oxidase deficient rats exposed to ingested sulfite.
Sulfite oxidase (SOX) is an essential enzyme in the pathway of the oxidative degradation of sulfur amino acids, and protects cells from sulfite (SO(3)(2-)) toxicity. Rats do not mimic responses seen in human, because of their relatively high SOX activity levels. Therefore, the present study used SOX deficient rats since they are a more appropriate model for studying sulfite toxicity. The aim of the study was to investigate the effect of sulfite exposure on visual evoked potentials (VEPs) and thiobarbituric acid reactive substances (TBARS) in normal and sulfite oxidase deficient rats. Rats were assigned to six groups (n=10 rats/group) as follows; control (C), sulfite (S), sulfite+vitamin E (SE), deficient (D), deficient+sulfite (DS) and deficient+sulfite+vitamin E (DSE). Sulfite oxidase deficiency was established by feeding rats a low molybdenum diet and adding to their drinking water 200 ppm tungsten (W). Sulfite (25img/kg) was administered to the animals via their drinking water. At the end of the experimental period, flash visual evoked potentials were recorded, and TBARS, hepatic sulfite oxidase levels and plasma S-sulphonate concentrations were determined. Sulfite treatment caused a significant delay in P1, N1P2, and P3 components of VEPs in the S and DS groups compared with the C group. These prolonged mean latencies of VEP components were reversed by vitamin E treatment in SE and DSE groups. In addition, the mean latencies of P1 and P3 components were increased in SOX deficient groups compared with the C group. Lipid peroxidation was increased in the brain in S, D, DS and DSE groups compared with the control group. There were also significant increases in the retina TBARS levels of S and DS groups. Vitamin E caused a significant decrease in brain and retina TBARS levels of SE and DSE groups with respect to their corresponding controls. However, there were no important changes in amplitudes of other groups. In conclusion, our results showed that sulfite treatment caused an increase in the lipid peroxidation process that was accompanied by changes in VEPs. Furthermore, sulfite exposure resulted in greater lipid peroxidation and more electrophysiological alterations in the SOX deficient rats than in the control rats. Additionally, the reduction of all VEP latencies in the DSE group with respect to the DS group clearly indicated that vitamin E has the potential to prevent sulfite induced-VEP changes arising from dysfunction of the SOX enzyme.