Control of ice crystal nucleation and growth during the food freezing process.
Freezing can maintain a low-temperature environment inside food, reducing water activity and preventing microorganism growth. However, when ice crystals are large, present in high amounts, and/or irregularly distributed, irreversible damage to food can occur. Therefore, ice growth is a vital parameter that needs to be controlled during frozen food processing and storage. In this review, ice growth theory and control are described. Macroscopic heat and mass transfer processes, the relationship between the growth of ice crystals and macroscopic heat transfer factors, and nucleation theory are reviewed based on the reported theoretical and experimental approaches. The issues addressed include how heat transfer occurs inside samples, variations in thermal properties with temperature, boundary conditions, and the functional relationship between ice crystal growth and freezing parameters. Quick freezing (e.g., cryogenic freezing) and unavoidable temperature fluctuations (e.g., multiple freeze-thaw cycles) are both taken into consideration. The approaches for controlling ice crystal growth based on the ice morphology and content are discussed. The characteristics and initial mechanisms of ice growth inhibitors (e.g., antifreeze proteins (AFPs), polysaccharides, and phenols) and ice nucleation agents (INAs) are complex, especially when considering their molecular structures, the ice-binding interface, and the dose. Although the market share for nonthermal processing technology is low, there will be more work on freezing technologies and their theoretical basis. Superchilling technology (partial freezing) is also mentioned here.


[Acute viral infections in association with idiopathic peripheral facial paralysis].
The possible association of some viral infections with the onset of Bell's palsy was examined in a study of 29 patients. The results were compared with a sex- and age-matched control group. The number of probable recent viral infections, as judged by a fourfold increase in antibody titers or the presence of specific IgM antibodies, differed statistically from that found in the control group. In seven patients with Bell's palsy the enzyme-linked-immunosorbent assay (ELISA) indicated an acute viral infection (herpes simplex 4; varicella zoster 2; cytomegalovirus 1). All these infections were due to viruses belonging to the herpesvirus group. Clinical evidence of herpesvirus infection was found in three cases (Herpetic eruption). The aetiological relationship between the virological findings and Bell's palsy is discussed. Reactivated herpes simplex virus and transient demyelination of the facial nerve could be one cause of an idiopathic facial palsy.


Desflurane and sevoflurane elimination kinetics and recovery quality in horses.
To evaluate pharmacokinetics, recovery times, and recovery quality in horses anesthetized with 1.2 times the minimum alveolar concentration of sevoflurane or desflurane. 6 healthy adult horses. Anesthesia was maintained with sevoflurane or desflurane for 2 hours at 1.2 times the minimum alveolar concentration. Horses recovered without assistance. During recovery, end-tidal gas samples were collected until horses spontaneously moved. Anesthetic concentrations were measured by use of gas chromatography. After a 1-week washout period, horses were anesthetized with the other inhalation agent. Video recordings of anesthetic recovery were evaluated for recovery quality on the basis of a visual analogue scale by investigators who were unaware of the anesthetic administered. Anesthetic washout curves were fit to a 2-compartment kinetic model with multivariate nonlinear regression. Normally distributed interval data were analyzed by means of paired Student t tests; ordinal or nonnormally distributed data were analyzed by means of Wilcoxon signed rank tests. Horses recovered from both anesthetics without major injuries. Results for subjective recovery evaluations did not differ between anesthetics. Area under the elimination curve was significantly smaller and time to standing recovery was significantly less for desflurane than for sevoflurane, although distribution and elimination constants did not differ significantly between anesthetics. Differences in area under elimination the curve between anesthetics indicated more rapid clearance for desflurane than for sevoflurane in horses, as predicted by anesthetic blood solubility differences in this species. More rapid elimination kinetics was associated with faster recovery times, but no association with improved subjective recovery quality was detected.


Hapten-specific blockade of CBA/N x C3H/HeN F1 B cell responses in a cell transfer system.
CBA/N mice harbor an X-linked B cell defect which is transmitted by CBA/N female mice to their hybrid male progeny. Hapten-specific plaque-forming cell (PFC) responses to haptenated proteins by B cell-defective CBA/N mice and CBA/N X C3H/HeN F1 male mice can be blockaded by concomitant exposure to polysaccharide agents bearing the same hapten. Various experimental approaches were explored in an attempt to study this phenomenon in a syngeneic cell transfer system. Unprimed donor spleen cells were unable to mount adequate PFC responses to dinitrophenylated-hemocyanin (DNP-KLH) in irradiated, syngeneic recipients. DNP-KLH-primed donor spleen cells produced strong PFC responses after challenge in irradiated recipients, and these secondary responses were subject to hapten-specific blockade by DNP-derivatized polysaccharide agents. Both direct and indirect PFC responses could be blocked. DNP conjugated to bovine serum albumin also produced hapten-specific blockade in this cell transfer system. Under some cell transfer conditions normal CBA/N X C3H/HeN F1 female spleen cells were just as susceptible to hapten-specific blockade as defective F1 male spleen cells.


Photoacoustic Tomography Detects Response and Resistance to Bevacizumab in Breast Cancer Mouse Models.
Angiogenesis is an established prognostic factor in advanced breast cancer, yet response to antiangiogenic therapies in this disease remains highly variable. Noninvasive imaging biomarkers could help identify patients that will benefit from antiangiogenic therapy and provide an ideal tool for longitudinal monitoring, enabling dosing regimens to be altered with real-time feedback. Photoacoustic tomography (PAT) is an emerging imaging modality that provides a direct readout of tumor hemoglobin concentration and oxygenation. We hypothesized that PAT could be used in the longitudinal setting to provide an early indication of response or resistance to antiangiogenic therapy. To test this hypothesis, PAT was performed over time in estrogen receptor-positive and estrogen receptor-negative breast cancer xenograft mouse models undergoing treatment with the antiangiogenic bevacizumab as a single agent. The cohort of treated tumors, which were mostly resistant to the treatment, contained a subset that demonstrated a clear survival benefit. At endpoint, the PAT data from the responding subset showed significantly lower oxygenation and higher hemoglobin content compared with both resistant and control tumors. Longitudinal analysis revealed that tumor oxygenation diverged significantly in the responding subset, identifying early treatment response and the evolution of different vascular phenotypes between the subsets. Responding tumors were characterized by a more angiogenic phenotype when analyzed with IHC, displaying higher vessel density, yet poorer vascular maturity and elevated hypoxia. Taken together, our findings indicate that PAT shows promise in providing an early indication of response or resistance to antiangiogenic therapy. Photoacoustic assessment of tumor oxygenation is a noninvasive early indicator of response to bevacizumab therapy, clearly distinguishing between control, responding, and resistant tumors within just a few weeks of treatment.


Transplantation of GABAergic neurons but not astrocytes induces recovery of sensorimotor function in the traumatically injured brain.
Embryonic stem (ES) cells have been investigated in many animal models of injury and disease. However, few studies have examined the ability of pre-differentiated ES cells to improve functional outcome following traumatic brain injury (TBI). The purpose of the present study was to compare the effect of murine ES cells that were pre-differentiated into GABAergic neurons or astrocytes on functional recovery following TBI. Neural and astrocyte induction was achieved by co-culturing ES cells on a bone marrow stromal fibroblast (M2-10B4) feeder layer and incubating them with various mitogenic factors. Rats were initially prepared with a unilateral controlled cortical contusion injury of the sensorimotor cortex or sham procedure. Rats were transplanted 7 days following injury with approximately 100K GABAergic neurons, astrocytes, fibroblasts, or media. Animals were assessed on a battery of sensorimotor tasks following transplantation. The stromal fibroblast cells (M2-10B4), as a control cell line, did not differ significantly from media infusions. Transplantation of GABAergic neurons facilitated complete and total recovery on the vibrissae-forelimb placing test as opposed to all other groups, which failed to show any recovery. It was also found that GABAergic neurons reduced the magnitude of the initial impairment on the limb use test. Histological analysis revealed infiltration of host brain with transplanted neurons and astrocytes. The results of the present study suggest that transplantation of pre-differentiated GABAergic neurons significantly induces recovery of sensorimotor function; whereas, astrocytes do not.


Prospective Validation of the Emergency Heart Failure Mortality Risk Grade for Acute Heart Failure.
Improved risk stratification of acute heart failure in the emergency department may inform physicians' decisions regarding patient admission or early discharge disposition. We aimed to validate the previously-derived Emergency Heart failure Mortality Risk Grade for 7-day (EHMRG7) and 30-day (EHMRG30-ST) mortality. We conducted a multicenter, prospective validation study of patients with acute heart failure at 9 hospitals. We surveyed physicians for their estimates of 7-day mortality risk, obtained for each patient before knowledge of the model predictions, and compared these with EHMRG7 for discrimination and net reclassification improvement. We also prospectively examined discrimination of the EHMRG30-ST model, which incorporates all components of EHMRG7 as well as the presence of ST-depression on the 12-lead ECG. We recruited 1983 patients seeking emergency department care for acute heart failure. Mortality rates at 7 days in the 5 risk groups (very low, low, intermediate, high, and very high risk) were 0%, 0%, 0.6%, 1.9%, and 3.9%, respectively. At 30 days, the corresponding mortality rates were 0%, 1.9%, 3.9%, 5.9%, and 14.3%. Compared with physician-estimated risk of 7-day mortality (PER7; c-statistic, 0.71; 95% CI, 0.64-0.78) there was improved discrimination with EHMRG7 (c-statistic, 0.81; 95% CI, 0.75-0.87; P=0.022 versus PER7) and with EHMRG7 combined with physicians' estimates (c-statistic, 0.82; 95% CI, 0.76-0.88; P=0.003 versus PER7). Model discrimination increased nonsignificantly by 0.014 (95% CI, -0.009-0.037) when physicians' estimates combined with EHMRG7 were compared with EHMRG7 alone ( P=0.242). The c-statistic for EHMRG30-ST alone was 0.77 (95% CI, 0.73-0.81) and 30-day model discrimination increased nonsignificantly by addition of physician-estimated risk to 0.78 (95% CI, 0.73-0.82; P=0.187). Net reclassification improvement with EHMRG7 was 0.763 (95% CI, 0.465-1.062) when assessed continuously and 0.820 (0.560-1.080) using risk categories compared with PER7. A clinical model allowing simultaneous prediction of mortality at both 7 and 30 days identified acute heart failure patients with a low risk of events. Compared with physicians' estimates, our multivariable model was better able to predict 7-day mortality and may guide clinical decisions. URL: https://www.clinicaltrials.gov . Unique identifier: NCT02634762.


Three-dimensionally designed protein-responsive RNA devices for cell signaling regulation.
The three-dimensional (3D) structures of many biomacromolecules have been solved to reveal the functions of these molecules. However, these 3D structures have rarely been applied to constructing efficient molecular devices that function in living cells. Here, we demonstrate a 3D structure-based molecular design principle for constructing short hairpin RNA (shRNA)-mediated genetic information converters; these converters respond to specific proteins and trigger the desired gene expression by modulating the function of the RNA-processing enzyme Dicer. The inhibitory effect on Dicer cleavage against the shRNA designed to specifically bind to U1A spliceosomal protein was correlated with the degree of steric hindrance between Dicer and the shRNA-protein complex in vitro: The level of the hindrance was predicted based on the models. Moreover, the regulation of gene expression was achieved by using the shRNA converters designed to bind to the target U1A or nuclear factor-κB (NF-κB) p50 proteins expressed in human cells. The 3D molecular design approach is widely applicable for developing new devices in synthetic biology.


Islet function in offspring of mothers on low-protein diet during gestation.
A low-protein diet (8 vs. 20%) administered during pregnancy affects the structure and function of the endocrine pancreas of the offspring. At 21.5 days of gestation, we reported a reduction of cell proliferation, islet size, islet vascularization, and pancreatic insulin content. In this study, we demonstrated an impairment of insulin secretion of these fetal islets when stimulated in vitro with amino acids such as arginine and leucine. If the offspring is kept on the same low-protein diet during suckling, weaning, and adulthood, fasting insulin levels remain low in the presence of normal blood glucose levels. Glucose tolerance at 70 days is impaired, with lower insulin response. In addition, permanent functional damage seems to be induced in utero by a low-protein diet, because a normal diet given from birth to adulthood does not restore normal insulin response after a glucose challenge. Our experimental results stress the impact of a balanced diet with qualitative and quantitative amino acid composition for the fetal endocrine pancreas to develop normally, without lasting functional and structural consequences in adulthood.


A Metagenomic Approach to Cyanobacterial Genomics.
Cyanobacteria, or oxyphotobacteria, are primary producers that establish ecological interactions with a wide variety of organisms. Although their associations with eukaryotes have received most attention, interactions with bacterial and archaeal symbionts have also been occurring for billions of years. Due to these associations, obtaining axenic cultures of cyanobacteria is usually difficult, and most isolation efforts result in unicyanobacterial cultures containing a number of associated microbes, hence composing a microbial consortium. With rising numbers of cyanobacterial blooms due to climate change, demand for genomic evaluations of these microorganisms is increasing. However, standard genomic techniques call for the sequencing of axenic cultures, an approach that not only adds months or even years for culture purification, but also appears to be impossible for some cyanobacteria, which is reflected in the relatively low number of publicly available genomic sequences of this phylum. Under the framework of metagenomics, on the other hand, cumbersome techniques for achieving axenic growth can be circumvented and individual genomes can be successfully obtained from microbial consortia. This review focuses on approaches for the genomic and metagenomic assessment of non-axenic cyanobacterial cultures that bypass requirements for axenity. These methods enable researchers to achieve faster and less costly genomic characterizations of cyanobacterial strains and raise additional information about their associated microorganisms. While non-axenic cultures may have been previously frowned upon in cyanobacteriology, latest advancements in metagenomics have provided new possibilities for in vitro studies of oxyphotobacteria, renewing the value of microbial consortia as a reliable and functional resource for the rapid assessment of bloom-forming cyanobacteria.


Antimicrobial Drug Administration and Antimicrobial Resistance of Salmonella Isolates Originating from the Broiler Production Value Chain in Nigeria.
Salmonella is among the pathogens on the high global priority lists for monitoring for studies on the discovery of new antimicrobials and understanding of how antimicrobial resistance (AMR) develops. AMR in connection with antibiotic usage patterns has been considered as a strong factor and contributor to the AMR pool. The purposes of use, pattern of antimicrobial drug administration, as well as the prevalence of AMR in Salmonella originating from the Nigeria broiler production value chain (NBPVC) was explored. A well-structured questionnaire on antimicrobial usage (n = 181) was used for sampling that focused on 21 antimicrobials from 151 locations. Simultaneously, AMR testing for 18 commonly used antimicrobials on Salmonella in humans was also carried out. Antimicrobial resistance Salmonella spp. were isolated in 23% of the samples (261 of 1135 samples from the broiler input, products, and the environment) using modified ISO 6579 and invA PCR protocols. Over 80% of the antimicrobials used in the NBPVC were administered without a veterinarian prescription. Prevalence of antimicrobial administration without prescription were as follows: live-bird-market (100%), hatchery (86.7%), grow-out-farm (75%), and breeder (66.7%). Widespread prophylactic and metaphylactic use of antimicrobials were recorded with the highest use seen for enrofloxacin (63% and 24%), tetracycline (58% and 33%), and erythromycin (50% and 17%). Antimicrobial resistance was highest for flumequine (100%), penicillin (95%), and perfloxacin (89%). High levels of use without laboratory support of a newer generation of a class of antibiotics suspected to confer high resistance on older generations of the same class (quinolones) was observed.


Spin labeling analysis of structure and dynamics of the Na(+)/proline transporter of Escherichia coli.
With respect to the functional importance attributed to the N-terminal part of the Na(+)/proline transporter of Escherichia coli (PutP), we report here on the structural arrangement and functional dynamics of transmembrane domains (TMs) II and III and the adjoining loop regions. Information on membrane topography was obtained by analyzing the residual mobility of site-specifically-attached nitroxide spin label and by determination of collision frequencies of the nitroxide with oxygen and a polar metal ion complex using electron paramagnetic resonance (EPR) spectroscopy. The studies suggest that amino acids Phe45, Ser50, Ser54, Trp59, and Met62 are part of TM II while Gly39 and Arg40 are located at a membrane-water interface probably forming the cytoplasmic cap of the TM. Also Ala67 and Glu75 are at a membrane-water interface, suggesting a location close to the periplasmic ends of TMs II and III, respectively. Ser71 between these residues is clearly in a water-exposed loop (periplasmic loop 3). Spin labels attached to positions 80, 86, and 91 show EPR properties typical for a TM location (TM III). Leu97 may be part of a structured loop region while Ala107 is clearly located in a water-exposed loop (cytoplasmic loop 4). Finally, spin labels attached to the positions of Asp33 and Leu37 are clearly on the surface of the transporter and are directed into an apolar environment. These findings strongly support the recently proposed 13-helix model of PutP [Jung, H., Rübenhagen, R., Tebbe, S., Leifker, K., Tholema, N., Quick, M., and Schmid, R. (1998) J. Biol. Chem. 273, 26400-26407] and suggest that TMs II and III of the transporter are formed by amino acids Ser41 to Gly66 and Ser76 to Gly95, respectively. In addition to the topology analysis, it is shown that binding of Na(+) and/or proline to the transporter alters the mobility of the nitroxide group at the positions of Leu37 and Phe45. From these findings, it is concluded that binding of the ligands induces conformational alterations of PutP that involve at least parts of TM II and the preceding cytoplasmic loop.


Comparative structural neck responses of the THOR-NT, Hybrid III, and human in combined tension-bending and pure bending.
This study evaluated the biofidelity of both the Hybrid III and the THOR-NT anthropomorphic test device (ATD) necks in quasistatic tension-bending and pure-bending by comparing the responses of both the ATDs with results from validated computational models of the living human neck. This model was developed using post-mortem human surrogate (PMHS) osteoligamentous response corridors with effective musculature added (Chancey, 2005). Each ATD was tested using a variety of end-conditions to create the tension-bending loads. The results were compared using absolute difference, RMS difference, and normalized difference metrics. The THOR-NT was tested both with and without muscle cables. The THOR-NT was also tested with and without the central safety cable to test the effect of the cable on the behavior of the ATD. The Hybrid III was stiffer than the model for all tension-bending end conditions. Quantitative measurement of the differences in response showed more close agreement between the THOR-NT and the model than the Hybrid III and the model. By contrast, no systematic differences were observed in the head kinematics. The muscle cables significantly stiffened the THOR-NT by effectively reducing the laxity from the occipital condyle (OC) joint. The cables also shielded the OC upper neck load cell from a significant portion of the applied loads. The center safety significantly stiffened the response and decreased the fidelity, particularly in modes of loading in which tensile forces were large and bending moments small. This study compares ATD responses to computational models in which the models include PMHS response corridors while correcting for problems associated with cadaveric muscle. While controversial and requiring considerable diligence, these kinds of approaches show promise in assessing ATD biofidelity.


Endoscopy-assisted wide-vertex craniectomy, "barrel-stave" osteotomies, and postoperative helmet molding therapy in the early management of sagittal suture craniosynostosis.
The purpose of this study was to assess the efficacy, safety, associated complications, and outcome in patients with sagittal suture craniosynostosis in whom endoscopy-assisted wide-vertex craniotomy and "barrel-stave" osteotomy were performed. During a 4-year period, 59 patients with sagittal suture synostosis underwent endoscopy-assisted wide-vertex craniectomies, barrel stave-like osteotomies, and postoperatively were fitted with custom-made molding helmets. Data on operative time, blood loss, transfusion rates, hospital length of stay, complications, and hospital charges were collected prospectively. The mean patient age at the time of surgery was 3.7 months. The average blood loss was 31.8 ml; and only one patient required an intraoperative blood transfusion. Nine patients received transfusions of donor blood postoperatively. The mean operative time was 50 minutes, and all but three patients were discharged from the hospital the morning following surgery. There were no intraoperative complications. Normocephaly as well as normal cephalic indices were observed at latest follow up. The authors conclude that early treatment of infants with sagittal suture craniosynostosis by using minimally invasive, endoscopy-assisted wide-vertex craniectomies provides excellent results and a significantly lower morbidity rate than traditional calvarial vault reconstructive procedures.


Preceding human metapneumovirus infection increases adherence of Streptococcus pneumoniae and severity of murine pneumococcal pneumonia.
Coinfection with respiratory virus and Streptococcus pneumoniae has been frequently reported in several epidemiologic studies. The aim of this study was to explore the effect of preceding human metapneumovirus (hMPV) inoculation on subsequent pneumococcal infection. Hep-2 and A549 cells were infected with hMPV then inoculated with S. pneumoniae. Bacterial adhesion was measured using colony forming unit and cytometric-fluorescence assays. In vivo bacterial adhesion was examined in hMPV-infected mice after inoculation of fluorescence-conjugated S. pneumoniae. Pulmonary inflammation (bacterial titers, cytokine levels, and histopathology) of hMPV-infected mice was investigated after inoculation with S. pneumoniae. In vitro results of bacterial infection with S. pneumoniae on A549 and Hep-2 monolayer cells showed that even though cellular adherence was variable among different serotypes, there was significantly enhanced bacterial adherence in A549 cells with preceding hMPV infection. In addition, in vivo study of hMPV-infected mice showed increased adhesion of S. pneumoniae on the bronchial epithelium with delayed bacterial clearance and exacerbated histopathology. Furthermore, mice with preceding hMPV infection showed repressed recruitment of airway neutrophils with decreased expression of neutrophil chemoattractants during pneumococcal infection. These results suggest that hMPV-infected airway cells, especially the lower airway epithelium, express increased adherence with S. pneumoniae. Furthermore, hMPV-infected mice showed impaired recruitment of airway neutrophils, possibly leading to delayed bacterial clearance and exacerbated pulmonary inflammation, after secondary infection with pneumococcal isolates.


A National Canadian Survey of Antithrombotic Therapy After Urgent and Emergent Limb Revascularization.
Patients with peripheral artery disease who undergo urgent or emergent lower extremity revascularization have the highest risk of major adverse cardiac and limb events. Although available evidence suggests that antithrombotic therapy reduces this risk, optimal antithrombotic therapy is unclear. In this report, we aim to describe current practice patterns for use of antithrombotic therapies after urgent/emergent peripheral artery revascularization. A self-administered online survey was distributed to all active vascular surgeons registered through the Canadian Society of Vascular Surgery (n = 149) between March 19 and April 29, 2019. The overall response rate was 53% (79/149). More than half of the respondents use a medical specialist service in aiding decision-making (52% (95% confidence interval [CI], 40.9%-63.0%). When concerned for high rethrombosis risk, respondents most commonly favoured initiation of either aspirin plus full dose anticoagulation (60% [95% CI, 49.2%-70.8%]) or dual antiplatelet therapy (58% (95% CI, 47.1%-68.9%]). Intraoperative findings and patient characteristics prompting concern for high rethrombosis risk include residual proximal/distal occlusive disease (75% [95% CI, 65.5%-84.5%]), poor-quality venous conduit (76% [95% CI, 66.6%-85.4%]), distal/infrapopliteal synthetic conduit (77% [95% CI, 67.7%-86.3%]), and history of multiple previous failed vascular interventions (98% [95% CI, 94.9%-100%]). More than 90% of respondents believe significant uncertainty exists in antithrombotic decision-making after urgent/emergent peripheral revascularization. Substantial uncertainty exists regarding antithrombotic therapy after urgent/emergent revascularization. In patients at high perceived rethrombosis risk, vascular surgeons preferentially choose aspirin with full-dose anticoagulation or dual antiplatelet therapy. Because of the clinical uncertainty in this domain, trials to determine optimal antithrombotic therapy in this high-risk population are required.


Using text-mined trait data to test for cooperate-and-radiate co-evolution between ants and plants.
Mutualisms may be "key innovations" that spur lineage diversification by augmenting niche breadth, geographic range, or population size, thereby increasing speciation rates or decreasing extinction rates. Whether mutualism accelerates diversification in both interacting lineages is an open question. Research suggests that plants that attract ant mutualists have higher diversification rates than non-ant associated lineages. We ask whether the reciprocal is true: does the interaction between ants and plants also accelerate diversification in ants, i.e. do ants and plants cooperate-and-radiate? We used a novel text-mining approach to determine which ant species associate with plants in defensive or seed dispersal mutualisms. We investigated patterns of lineage diversification across a recent ant phylogeny using BiSSE, BAMM, and HiSSE models. Ants that associate mutualistically with plants had elevated diversification rates compared to non-mutualistic ants in the BiSSE model, with a similar trend in BAMM, suggesting ants and plants cooperate-and-radiate. However, the best-fitting model was a HiSSE model with a hidden state, meaning that diversification models that do not account for unmeasured traits are inappropriate to assess the relationship between mutualism and ant diversification. Against a backdrop of diversification rate heterogeneity, the best-fitting HiSSE model found that mutualism actually decreases diversification: mutualism evolved much more frequently in rapidly diversifying ant lineages, but then subsequently slowed diversification. Thus, it appears that ant lineages first radiated, then cooperated with plants.


Arsenic toxicity in a sediment-dwelling polychaete: detoxification and arsenic metabolism.
The accumulation, subcellular distribution and speciation of arsenic in the polychaete Arenicola marina were investigated under different laboratory exposure conditions representing a range of metal bioavailabilities, to gain an insight into the physiological mechanisms of how A. marina handles bioaccumulated arsenic and to improve our understanding of the potential ecotoxicological significance of bioaccumulated arsenic in this deposit-feeder. The exposure conditions included exposure to sublethal concentrations of dissolved arsenate, exposure to sublethal concentrations of sediment-bound metal mining mixtures, and exposure to lethal concentrations of sediment-bound metal mining mixtures and arsenic- and multiple metal-spiked sediments. The sub-lethal exposures indicate that arsenic bioaccumulated by the deposit-feeding polychaete A. marina is stored in the cytosol as heat stable proteins (~50%) including metallothioneins, possibly as As (III)-thiol complexes. The remaining arsenic is mainly accumulated in the fraction containing cellular debris (~20%), with decreasing proportions accumulated in the metal-rich granules, organelles and heat-sensitive proteins fractions. A biological detoxified metal compartment including heat stable proteins and the fraction containing metal-rich granules is capable of binding arsenic coming into the cells at a constant rate under sublethal arsenic bioavailabilities. The remaining arsenic entering the cell is bound loosely into the cellular debris fraction, which can be subsequently released and diverted to an expanding detoxified pool. Our results suggest that a metal sensitive compartment comprising the cellular debris, enzymes and organelles fractions may be more representative of the toxic effects observed.


Phosphorylation in the activation loop as the finishing touch in c-Kit activation.
Receptor tyrosine kinases are a group of transmembrane proteins that transmit signals in response to stimulation by ligands including growth factors and cytokines. They share a common mechanism of activation through receptor dimerization or oligomerization, but subsequent routes to their full activation appear to be various. A recent paper published by DiNitto et al. (Function of activation loop tyrosine phosphorylation in the mechanism of c-Kit autoactivation and its implication in sunitinib resistance. J. Biochem. 2010;147:601-609) analysed a process of c-Kit autoactivation in detail. They revealed that phosphorylation in the activation loop, which is crucial for activation of many types of tyrosine kinases, is dispensable for c-Kit activation. However, the phosphorylation affects the sensitivity of c-Kit to kinase inhibitors, thus representing the finishing touch in c-Kit activation.


Association between pre-transplant dialysis modality and patient and graft survival after kidney transplantation.
Previous studies have found inconsistent associations between pre-transplant dialysis modality and subsequent post-transplant survival. We aimed to examine this relationship using the instrumental variable method and to compare the results with standard Cox regression. We included 29 088 patients (age >20 years) from 16 European national or regional renal registries who received a first kidney transplant between 1 January 1999 and 31 December 2008 and were on dialysis before transplantation for a period between 90 days and 10 years. Standard multivariable Cox regression examined the association of individually assigned pre-transplant dialysis modality with post-transplant patient and graft survival. To decrease confounding-by-indication through unmeasured factors, we applied the instrumental variable method that used the case-mix adjusted centre percentage of peritoneal dialysis (PD) as predictor variable. Standard analyses adjusted for age, sex, primary renal disease, donor type, duration of dialysis, year of transplantation and country suggested that PD before transplantation was associated with better patient [hazard ratio, HR (95% CI) = 0.83 (0.76-0.91)] and graft survival (HR (95% CI) 0.90 (0.84-0.96)) when compared with haemodialysis (HD). In contrast, the instrumental variable analysis showed that a 10% increase in the case-mix adjusted centre percentage of patients on PD was neither associated with post-transplant patient survival [HR (95% CI = 1.00 (0.97-1.04)] nor with graft survival [HR (95% CI) = 1.01 (0.98-1.04)]. The instrumental variable method failed to confirm the associations found in standard Cox regression between pre-transplant dialysis modality and patient and graft survival after transplantation. The lack of association in instrumental variable analysis may be due to better control of residual confounding.


Remission status after long-term sertraline treatment of pediatric obsessive-compulsive disorder.
Despite its high chronicity, few studies have evaluated the effectiveness of long-term treatment for pediatric obsessive-compulsive disorder (OCD). The goal of the current analysis is to evaluate remission among children and adolescents with OCD treated with sertraline for 12 months. Children (6-12 years old, n = 72) and adolescents (13-18 years old, n = 65) with Diagnostic and Statistical Manual of Mental Disorders (third edition, revised) OCD, who had completed a 12-week, double-blind, placebo-controlled sertraline study, were administered open-label sertraline 50-200 mg for 52 weeks. Full remission was defined by a Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) score of 8 or less, and partial remission was defined as a CY-BOCS score of 15 or less. Using an last observation carried forward analysis, 47% of patients achieved a full remission, and an additional 25% achieved a partial remission. Among study completers, full remission was achieved by 55% of patients and partial remission by 31%. Two thirds of patients with severe OCD at baseline (CY-BOCS of 26 or greater) achieved full or partial remission. Children were more likely to achieve a full remission than adolescents. Sertraline is effective in the treatment of childhood and adolescent OCD, with initial acute response converting to remission and improved functional status in a substantial proportion of patients. More research is needed to develop pharmacologic and psychotherapeutic strategies that facilitate the achievement of full remission in the remaining patients suffering from this chronic and disabling illness.


Giant migrating contractions and their myoelectric correlates in the small intestine.
We investigated the characteristics of spontaneously and pharmacologically induced giant migrating contractions (GMC) in the small intestine of conscious dogs. Myoelectric and contractile activities were recorded from eight sites, 40-70 cm apart, by surgically implanted bipolar electrodes and strain-gauge transducers, respectively. In addition to the usual phasic contractions in the fasted state, we observed spontaneous GMCs that generally originated in the mid or distal small intestine and migrated caudad. These contractions occurred infrequently and irregularly. The amplitude and duration of these giant contractions were severalfold larger than those of usual phasic contractions during phase III activity. The giant contractions migrated caudad at a velocity of approximately 1 cm/s. These contractions were preceded and followed by a period of inhibition of spontaneous motor activity. Some dogs whined and showed restlessness when giant contractions originated in the mid to upper small intestine. Intravenous morphine at 20, 50, 100, and 200 micrograms.kg-1 .h-1 or gastric instillation of 100 ml of 60% vinegar solution also initiated GMCs whose characteristics were similar to those of spontaneous GMCs. The GMC in response to these stimuli originated at more proximal sites than the spontaneous giant contractions. The GMC in response to morphine infusions occurred repeatedly, but in response to vinegar they occurred only once as a burst of contractions. These agents did not induce GMCs in the fed state. In most cases, the upstroke of a giant contraction was associated with a brief burst of electrical response activity. In some cases the burst of response activity lasted for the entire duration of giant contractions.


Histone deacetylase inhibitors in cancer therapy.
Histone deacetylase inhibitors (HDAC inhibitors) represent a novel class of antineoplastic agents that act by promoting acetylation of histones, leading in turn to uncoiling of chromatin and activation of a variety of genes implicated in the regulation of cell surivival, proliferation, differentiation, and apoptosis. The major classes of HDIs include shortchain fatty acids, hydroxamic acid derivatives, synthetic benzamide derivatives, and cyclic tetrapeptides. Members of each of these classes have now entered clinical trials in humans. Despite their shared capacity to trigger histone deacetylation, individual HDIs exert diverse actions on cell cycle regulatory, signal transduction, and survival-related proteins which in all probability accounts for their disparate actions. Major areas of investigation surrounding HDIs include elucidating the mechanisms by which they induce apoptosis in neoplastic cells, and characterizing the factors responsible for the decision of such cells to undergo maturation versus cell death in the response to these agents. In this context, attention has recently focused on the ability of HDIs to induce perturbations in cell cycle regulatory proteins (e.g., p21(CIP1)), downregulation of survival signaling pathways (e.g., Raf/MEK/ERK), and disruption of cellular redox state (e.g., induction of reactive oxygen species; ROS). Aside from efforts to combine HDIs with established cytotoxic drugs, attempts are underway to establish a rational basis for combining HDIs with differentiation- inducing agents (e.g., ATRA, hypomethylating agents such as 5'-deoxyazacytine) with the goal of triggering re-expression of turn or suppressor and/or differentiation-associated genes. Finally, the results of recent preclinical studies provide a strong rationale for combining HDIs with other novel, molecularly targeted agents, including inhibitors of survival signaling pathways or cell cycle progression. Collectively, these findings should provide a fertile environment for the development of novel HDI-containing regimens in the treatment of cancer for many years to come.


Endoscopic vs. tactile evaluation of subgingival calculus.
Endoscopic technology has been developed to facilitate imagery for use during diagnostic and therapeutic phases of periodontal care. The purpose of this study was to compare the level of subgingival calculus detection using a periodontal endoscope with that of conventional tactile explorer in periodontitis subjects. A convenience sample of 26 subjects with moderate periodontitis in at least 2 quadrants was recruited from the University of Minnesota School of Dentistry to undergo quadrant scaling and root planing. One quadrant from each subject was randomized for tactile calculus detection alone and the other quadrant for tactile detection plus the Perioscope ™ (Perioscopy Inc., Oakland, Cali). A calculus index on a 0 to 3 score was performed at baseline and at 2 post-scaling and root planing visits. Sites where calculus was detected at visit 1 were retreated. T-tests were used to determine within-subject differences between Perioscope™ and tactile measures, and changes in measures between visits. Significantly more calculus was detected using the Perioscope™ vs. tactile explorer for all 3 subject visits (p<0.005). Mean changes (reduction) in calculus detection from baseline to visit 1 were statistically significant for both the Perioscope™ and tactile quadrants (p<0.0001). However, further reductions in calculus detection from visit 1 to visit 2 was only significant for the Perioscope™ quadrant (p<0.025), indicating that this methodology was able to more precisely detect calculus at this visit. It was concluded that the addition of a visual component to calculus detection via the Perioscope™ was most helpful in the re-evaluation phase of periodontal therapy.


Potential for nitrogen fixation in maize genotypes in Brazil.
N(2) fixation in field-grown maize (Zea mays L.) plants was estimated by a nondestructive acetylene reduction method which permitted the plants to continue growing and produce seeds. Samples from six areas revealed mean nitrogenase activities of 74-2167 nmol of C(2)H(4)/(g of dry roots x hr) for 10 plants. Among 276 S(1) lines planted in two field experiments, 17 lines were selected for further nitrogenase activity assays after prescreening. Variability within lines was high but significant differences among lines were obtained in one experiment. The best lines showed mean nitrogenase activities of 2026, 2315, and 7124 nmol of C(2)H(4)/(g of dry roots x hr), whereas the original cultivar reduced only 313 nmol. The highest value approaches the nitrogenase activity of soybean. If the theoretical 3:1 (C(2)H(4)/N(2) reduced) conversion factor is used, a potential daily N(2) fixation of 2 kg of N(2)/hectare can be calculated. Periodic sampling within a brachytic maize cultivar revealed that maximum nitrogenase activity occurred at about the 75% silking stage. Soil effects also were pronounced. N(2)-fixing Spirillum sp. could be isolated from all active root pieces when they were surface sterilized. These organisms appear to be primarily responsible for root nitrogenase activity in maize.


Voltage spread in an identified interneuron of the barnacle's visual system.
1. The interneuron that is postsynaptic to barnacle photoreceptors (the inverting, or I-cell) receives similar synaptic input from the receptors onto its two distinct and separate arbors. We compared the spread of light-evoked synaptic potentials from the proximal and distal arbors with the cell's soma in order to ascertain how well voltages spread in this cell. 2. The proximal and distal arbors are connected by a commissural process approximately 200 microns in length and 2 microns in diameter. Voltages spreading from the distal arbor along this process were 20-60% of their original value, and delayed 15-20 ms, when recorded at the cell's soma. 3. The reversal potential of the receptor's input to the distal arbor, determined by injecting current into the soma, appeared substantially negative (-150 mV) to that of the identical input to the proximal arbor (-80 mV). Assuming identical reversal potentials in the two arbors, this difference indicates that more current must be injected into the I-cell's soma to change the voltage of the distal arbor to a given potential than to change that of the proximal arbor to the same potential. 4. Comparison of input from a lateral eye to the ipsilateral arbor with that from the median eye to the same arbor indicates that these two inputs are at an electrically equivalent distance from the soma. 5. Uneven illumination of the eyes may, through local conductance changes, cause the arbors to function independently, even to the point where one arbor may depolarize when the other is hyperpolarized.


Source, transport, and toxicity of emerging contaminants in aquatic environments: A review on recent studies.
Emerging contaminants (ECs) are gaining global attention owing to their widespread presence and adverse effects on human health. ECs comprise numerous composite types and pose a potential threat to the growth and functional traits of species and ecosystems. Although the occurrence and fate of ECs has been extensively studied, little is known about their long-term biological effects. This review attempts to gain insights into the unhindered connections and overlaps in aquatic ecosystems. Microplastics (MPs), one of the most representative ECs, are carriers of other pollutants because of their strong adsorption capacity. They form a complex of pollutants that can be transmitted to aquatic organisms and humans through the extended food chain, increasing the concentration of pollutants by tens of thousands of times. Adsorption, interaction and transport effects of emerging contaminants in the aquatic environment are also discussed. Furthermore, the current state of knowledge on the ecotoxicity of single- and two-pollutant models is presented. Herein, we discuss how aquatic organisms within complex food networks may be particularly vulnerable to harm from ECs in the presence of perturbations. This review provides an advanced understanding of the interactions and potential toxic effects of ECs on aquatic organisms.


Factors Associated with Failure of Non-invasive Positive Pressure Ventilation in a Critical Care Helicopter Emergency Medical Service.
Non-invasive positive pressure ventilation (NIPPV) is used to treat severe acute respiratory distress. Prehospital NIPPV has been associated with a reduction in both in-hospital mortality and the need for invasive ventilation. The authors of this study examined factors associated with NIPPV failure and evaluated the impact of NIPPV on scene times in a critical care helicopter Emergency Medical Service (HEMS). Non-invasive positive pressure ventilation failure was defined as the need for airway intervention or alternative means of ventilatory support. A retrospective chart review of consecutive patients where NIPPV was completed in a critical care HEMS was conducted. Factors associated with NIPPV failure in univariate analyses and from published literature were included in a multivariable, logistic regression model. From a total of 44 patients, NIPPV failed in 14 (32%); a Glasgow Coma Scale (GCS)<15 at HEMS arrival was associated independently with NIPPV failure (adjusted odds ratio 13.9; 95% CI, 2.4-80.3; P=.003). Mean scene times were significantly longer in patients who failed NIPPV when compared with patients in whom NIPPV was successful (95 minutes vs 51 minutes; 39.4 minutes longer; 95% CI, 16.2-62.5; P=.001). Patients with a decreased level of consciousness were more likely to fail NIPPV. Furthermore, patients who failed NIPPV had significantly longer scene times. The benefits of NIPPV should be balanced against risks of long scene times by HEMS providers. Knowing risk factors of NIPPV failure could assist HEMS providers to make the safest decision for patients on whether to initiate NIPPV or proceed directly to endotracheal intubation prior to transport.


Clinical, epidemiological, and virological features of Mpox in Beijing, China - May 31-June 21, 2023.
The first locally acquired case in the Chinese mainland was reported on May 31, 2023, lagging behind other countries. In this study, we aimed to examine the early clinical and epidemiological characteristics of the earliest cases of Mpox in Beijing, China. Additionally, we investigated the sequence and transmission patterns of the Mpox virus (MPXV). We analyzed 37 reported cases of Mpox in Beijing from May 31, 2023 to June 21, 2023. The age range of the subjects was 24-51 years. Thirty-six cases (97.3%) were identified in men who have sex with men (MSM), and 19 cases (51.4%) tested positive for the human immunodeficiency virus. Thirty-three cases were symptomatic, while four were asymptomatic. Skin lesions were observed in 32 cases (97.0%), fever in 26 (78.8%), and swollen lymph nodes in 17 (51.5%). Rash typically appeared in the genital or perianal area 1-3 days before fever onset, with a minimum incubation period of 2 days. For individuals with skin rashes, the skin lesion samples showed 100% positivity and low Ct values. There were high oropharyngeal swab (75.8%) and blood (84.6%) positivity rates. All MPXV strains belonged to the B.1.3 branch of the West African lineage. These strains carried 76-86 nucleotide substitutions compared with the reference human MPXV genome, and genetic diversity was observed. Our findings provide the first insights into the landscape of early transmission of Mpox in Beijing and help inform policy formulation in the Chinese mainland.


Genetic Consequences of Pleistocene Sea-Level Change on Hawaiian Megalagrion Damselflies.
The Hawaiian Islands have long been an important laboratory for evolutionary research because their geological histories offer many natural experiments. For example, the Maui Nui complex, 4 islands that have been repeatedly connected and separated by fluctuating sea levels, lie near Hawaii Island, which has never been connected to another island. Here, we examine the genetic consequences of fluctuating island areas and connectivity using microsatellite analysis of 2 widespread, endemic Hawaiian damselflies. We screened 152 Megalagrion xanthomelas individuals from 5 islands at 14 loci and 34 Megalagrion pacificum from 3 islands at 11 loci to explore dispersal patterns and genetic diversity. Our data suggest that Pleistocene fluctuations in sea level alternated between creating land bridges that facilitated gene flow between once and future islands, and ocean channels that inhibited dispersal. Furthermore, interglacial periods of high sea stands likely reduced suitable habitat availability, causing the loss of genetic diversity on Maui Nui due to bottlenecks and founder events. Finally, we propose that gene flow from Molokai to Lanai may be enhanced by assisted dispersal from the trade winds that are channeled between volcanoes on western Maui and eastern Molokai. Our results emphasize the importance of variable microevolutionary processes in Hawaiian biogeography.


Quantitative genetic variation of leaf size and shape in a mixed diploid and triploid population of Populus.
In the interspecific cross of Populus trichocarpa x P. deltoides, unexpected simultaneous occurrence of diploid hybrids and triploid hybrids (with two alleles from the female parent and one from the male parent at each locus) led us to examine the evolutionary genetic significance of this phenomenon. As expected, leaf size and shape of the triploid progeny are closer to the female P. trichocarpa than male P. deltoides parent. Although the pure triploid progeny population did not have higher genetic variance in leaf traits than the pure diploid population, the former appears to hide much non-additive genetic variance and display strong genetic control over the phenotypic plasticity of leaf traits. It is suggested that the cryptic non-additive variance, especially epistasis, can be released when a population is disturbed by changes in the environment. A mixed diploid and triploid progeny population combines phenotypic and genetic characteristics of both pure hybrids and is considered to be of adaptive significance for populars to survive and evolve in a fluctuating environment. The significant effect due to general and specific combining ability differences at the population level suggests that the population divergence of these two species is under additive and non-additive genetic control.


Use of surface-wave spectroscopy to characterize tilt modes of a vortex in a Bose-Einstein condensate.
A vortex in a condensate in a nonspherical trapping potential will in general experience a torque. The torque will induce tilting of the direction of the vortex axis. We observe this behavior experimentally and show that by applying small distortions to the trapping potential, we can control the tilting behavior. By suppressing vortex tilt, we have been able to hold the vortex axis along the line of sight for up to 15 sec. Alternatively, we can induce a 180 degrees tilt, effectively reversing the charge on the vortex as observed in the lab frame. We characterize the vortex nondestructively with a surface-wave spectroscopic technique.


Aryl-homoserine lactone quorum sensing in stem-nodulating photosynthetic bradyrhizobia.
Many Proteobacteria possess LuxI-LuxR-type quorum-sensing systems that produce and detect fatty acyl-homoserine lactone (HSL) signals. The photoheterotroph Rhodopseudomonas palustris is unusual in that it produces and detects an aryl-HSL, p-coumaroyl-HSL, and signal production requires an exogenous source of p-coumarate. A photosynthetic stem-nodulating member of the genus Bradyrhizobium produces a small molecule signal that elicits an R. palustris quorum-sensing response. Here, we show that this signal is cinnamoyl-HSL and that cinnamoyl-HSL is produced by the LuxI homolog BraI and detected by BraR. Cinnamoyl-HSL reaches concentrations on the order of 50 nM in cultures of stem-nodulating bradyrhizobia grown in the presence or absence of cinnamate. Acyl-HSLs often reach concentrations of 0.1-30 μM in bacterial cultures, and generally, LuxR-type receptors respond to signals in a concentration range from 5 to a few hundred nanomolar. Our stem-nodulating Bradyrhizobium strain responds to picomolar concentrations of cinnamoyl-HSL and thus, produces cinnamoyl-HSL in excess of the levels required for a signal response without an exogenous source of cinnamate. The ability of Bradyrhizobium to produce and respond to cinnamoyl-HSL shows that aryl-HSL production is not unique to R. palustris, that the aromatic acid substrate for aryl-HSL synthesis does not have to be supplied exogenously, and that some acyl-HSL quorum-sensing systems may function at very low signal production and response levels.


Population-level investigation of the knowledge of ocular chemical injuries and proper immediate action.
Although the eyes occupy 0.1% of the total body surface, eye injuries are serious because vision is arguably the most important sense. We aimed to assess knowledge of Saudi Arabian residents regarding steps to be taken in cases of chemical eye injury, in order to promote awareness of such procedures. A cross-sectional design was done. A random sampling method was utilized to select 888 individuals in the Saudi community. Participants completed an electronic closed ended, validated, anonymous, self-administered questionnaire. Two experts assessed content and face validity. Respondents were 18-29 years of age. 74 (8.3%) had a history of chemical eye injury. Regarding the first step taken in case of chemical eye injury, 697 (78.5%) respondents indicated washing with water, 164 (18.5%) indicated visiting the emergency department, 11 (1.2%) indicated using eye drops, and 5 (0.6%) indicated covering the eye immediately. Seventy-five (8.4%) respondents agreed that an eye injured with an acidic material should be washed with an alkaline solution. These results should be confirmed by health authorities and appropriate interventions should be developed for improving knowledge among masses, thereby promoting a healthier society.


Pregnancy, contraception and emergency contraception: the language of urban adolescent young women.
We sought to characterize how a group of urban adolescent females understands the domains of pregnancy, contraception, and emergency contraception (EC). We used the research strategy of freelisting as part of an in-depth interview study. Urban adolescent females presenting to a Pediatric Emergency Department. Participants were enrolled using a purposive sampling strategy if they were black, English-speaking females, 15-19 years old, who resided in 1 of 11 zip codes surrounding the hospital. Smith's saliency score. Freelists were analyzed for the entire sample, as well as for subgroups. Thirty adolescents completed the interview. We found that this group of adolescents uses different words to characterize the domains of pregnancy, contraception, and EC. The only overlapping salient term was "abortion," which appeared in the overall lists for pregnancy and EC and in the younger group's list for contraception. In addition, lack of knowledge was cited as an important factor related to contraception. Adolescent patients may not fully understand the concepts of contraception and EC. Providers should consider the potential need to provide an explanation for terms used, and they should consider explicitly differentiating between routine forms of contraception and EC, as well as between EC and abortion.


Development of organophosphate hydrolase activity in a bacterial homolog of human cholinesterase.
We applied a combination of rational design and directed evolution (DE) to Bacillus subtilis p-nitrobenzyl esterase (pNBE) with the goal of enhancing organophosphorus acid anhydride hydrolase (OPAAH) activity. DE started with a designed variant, pNBE A107H, carrying a histidine homologous with human butyrylcholinesterase G117H to find complementary mutations that further enhance its OPAAH activity. Five sites were selected (G105, G106, A107, A190, and A400) within a 6.7 Å radius of the nucleophilic serine Oγ. All 95 variants were screened for esterase activity with a set of five substrates: pNP-acetate, pNP-butyrate, acetylthiocholine, butyrylthiocholine, or benzoylthiocholine. A microscale assay for OPAAH activity was developed for screening DE libraries. Reductions in esterase activity were generally concomitant with enhancements in OPAAH activity. One variant, A107K, showed an unexpected 7-fold increase in its k cat/K m for benzoylthiocholine, demonstrating that it is also possible to enhance the cholinesterase activity of pNBE. Moreover, DE resulted in at least three variants with modestly enhanced OPAAH activity compared to wild type pNBE. A107H/A190C showed a 50-fold increase in paraoxonase activity and underwent a slow time- and temperature-dependent change affecting the hydrolysis of OPAA and ester substrates. Structural analysis suggests that pNBE may represent a precursor leading to human cholinesterase and carboxylesterase 1 through extension of two vestigial specificity loops; a preliminary attempt to transfer the Ω-loop of BChE into pNBE is described. Unlike butyrylcholinesterase and pNBE, introducing a G143H mutation (equivalent to G117H) did not confer detectable OP hydrolase activity on human carboxylesterase 1 (hCE1). We discuss the use of pNBE as a surrogate scaffold for the mammalian esterases, and the importance of the oxyanion-hole residues for enhancing the OPAAH activity of selected serine hydrolases.


Association between gastroesophageal reflux and endobronchial carcinoid: a case report.
Children with neurological disorders may suffer from gastroesophageal reflux disease (GERD). Typical symptoms are vomiting, regurgitation and hematemesis. Patients present with respiratory symptoms only in cases with swallowing disorders causing chronic airway aspiration. We report the case of a patient affected by chromosome 8 p deletion syndrome with mental retardation, referred to our unit for suspected GERD. Chest X-ray, performed at admission for coexisting respiratory complaints, showed left lower lobe pneumonia; esophageal pH monitoring and upper endoscopy were normal for GERD. To rule out chronic airway aspiration, gastroesophageal 99 mTc scintigraphy with lung scan 18 to 24 h after a test meal and video fluoroscopy swallowing study were performed, both negative. Two months later, a second episode of left lower lobe pneumonia occurred. A chest CT scan was performed and showed an endobronchial mass; the biopsy taken during the broncoscopy was not conclusive. Surgical excision resulted in a diagnosis of pulmonary carcinoid. Bronchial carcinoids, although rare, should be taken into consideration as a potential cause of recurrent pneumonia even in the presence of demonstrated GERD where severe respiratory infections only occur with coexisting chronic pulmonary aspiration, even in neurologically impaired people.


On the horizon: possible neuroprotective role for glatiramer acetate.
Inflammation and neurodegeneration characterize the pathogenesis of multiple sclerosis (MS). Slow axonal degeneration, rather than acute inflammation, is considered the cause of chronic disability in MS. The signs of acute axonal damage and loss have been shown to occur early in the lesion development of patients with chronic MS and often correlate with demyelination and inflammation. While immune activity in the central nervous system has traditionally been considered to be a detrimental event in MS, recent studies have found that autoimmune T cells may play an important role in protecting neurons from the ongoing spreading damage. Neuroprotection in MS is a new and evolving concept, and many questions remain with regard to potential targets for therapeutic intervention. Preliminary studies, both in animals and in humans, have suggested that glatiramer acetate (GA) may confer neuroprotective activity in addition to bystander suppression. Additional research is needed to determine if these promising neuroprotective effects correlated with the long-term effect of GA in MS.


Enantioselective synthesis of dihydrocoumarin derivatives by chiral scandium(III)-complex catalyzed inverse-electron-demand hetero-Diels-Alder reaction.
An asymmetric inverse-electron-demand hetero-Diels-Alder reaction between o-quinone methides and azlactones to generate potentially pharmacological active dihydrocoumarins has been achieved efficiently by using a chiral N,N'-dioxide-Sc(III) complex as the catalyst. The desired products were obtained in high yields with excellent enantioselectivities and diastereoselectivities (up to 94% yield, 96% ee and >19 : 1 dr) under mild reaction conditions. A concerted reaction pathway was confirmed by Operando IR and control experiments.


Cranial vault trauma and selective mortality in medieval to early modern Denmark.
To date, no estimates of the long-term effect of cranial vault fractures on the risk of dying have been generated from historical or prehistoric skeletons. Excess mortality provides a perspective on the efficacy of modern treatment, as well as the human cost of cranial injuries largely related to interpersonal violence in past populations. Three medieval to early modern Danish skeletal samples are used to estimate the effect of selective mortality on males with cranial vault injuries who survived long enough for bones to heal. The risk of dying for these men was 6.2 times higher than it was for their uninjured counterparts, estimated through a simulation study based on skeletal observations. That is about twice the increased risk of dying experienced by modern people with traumatic brain injuries. The mortality data indicate the initial trauma was probably often accompanied by brain injury. Although the latter cannot be directly observed in skeletal remains, it can be inferred through the relative risks of dying. The ability to identify the effects of selective mortality in this skeletal sample indicates it must be taken into account in paleopathological research. The problem is analogous to extrapolating from death register data to modern communities, so epidemiological studies based on mortality data have the same inherent possibility of biases as analyses of ancient skeletons.


Fall Risk Score at the Time of Discharge Predicts Readmission Following Total Joint Arthroplasty.
Readmission among Medicare recipients is a leading driver of healthcare expenditure. To date, most predictive tools are too coarse for direct clinical application. Our objective in this study is to determine if a pre-existing tool to identify patients at increased risk for inpatient falls, the Hendrich Fall Risk Score, could be used to accurately identify Medicare patients at increased risk for readmission following arthroplasty, regardless of whether the readmission was due to a fall. This study is a retrospective cohort study. We identified 2437 Medicare patients who underwent a primary elective total joint arthroplasty (TJA) of the hip or knee for osteoarthritis between 2011 and 2014. The Hendrich Fall Risk score was recorded for each patient preoperatively and postoperatively. Our main outcome measure was hospital readmission within 30 days of discharge. Of 2437 eligible TJA recipients, there were 226 (9.3%) patients who had a score ≥6. These patients were more likely to have an unplanned readmission (unadjusted odds ratio 2.84, 95% confidence interval 1.70-4.76, P < .0001), were more likely to have a length of stay >3 days (49.6% vs 36.6%, P = .0001), and were less likely to be sent home after discharge (20.8% vs 35.8%, P < .0001). The effect of a score ≥6 on readmission remained significant (adjusted odds ratio 2.44, 95% confidence interval 1.44-4.13, P = .0009) after controlling for age, paralysis, and the presence of a major psychiatric disorder. Increased Hendrich fall risk score after TJA is strongly associated with unplanned readmission. Application of this tool will allow hospitals to identify these patients and plan their discharge.


Hidden figures: Revisiting doping prevalence estimates previously reported for two major international sport events in the context of further empirical evidence and the extant literature.
High levels of admitted doping use (43.6% and 57.1%) were reported for two international sport events in 2011. Because these are frequently referenced in evaluating aspects of anti-doping, having high level of confidence in these estimates is paramount. In this study, we present new prevalence estimates from a concurrently administered method, the Single Sample Count (SSC), and critically review the two sets of estimates in the context of other doping prevalence estimates. The survey featuring the SSC model was completed by 1,203 athletes at the 2011 World Championships in Athletics (WCA) (65.3% of all participating athletes) and 954 athletes at the 2011 Pan-Arab Games (PAG) (28.2% of all participating athletes). At WCA, athletes completed both UQM and SSC surveys in randomised order. At PAG, athletes were randomly allocated to one of the two surveys. Doping was defined as "having knowingly violated anti-doping regulations by using a prohibited substance or method." Estimates with the SSC model for 12-month doping prevalence were 21.2% (95% CI: 9.69-32.7) at WCA and 10.6% (95% CI: 1.76-19.4) at PAG. Estimated herbal, mineral, and/or vitamin supplements use was 8.57% (95% CI: 1.3-16.11) at PAG. Reliability of the estimates were confirmed with re-sampling method (n = 1,000, 80% of the sample). Survey non-compliance (31.90%, 95%CI: 26.28-37.52; p < 0.0001) was detected in the WCA data but occurred to a lesser degree at PAG (9.85%, 95% CI: 4.01-15.69, p = 0.0144 and 11.43%, 95% CI: 5.31-11.55, p = 0.0196, for doping and nutritional supplement use, respectively). A large discrepancy between those previously reported from the UQM and the prevalence rate estimated by the SSC model for the same population is evident. Caution in interpreting these estimates as bona fide prevalence rates is warranted. Critical appraisal of the obtained prevalence rates and triangulation with other sources are recommended over "the higher rate must be closer to the truth" heuristics. Non-compliance appears to be the Achilles heel of the indirect estimation models thus it should be routinely tested for and minimised. Further research into cognitive and behaviour aspects, including motivation for honesty, is needed to improve the ecological validity of the estimated prevalence rates.


Principles for collaborative risk communication: Reducing landslide losses in Puerto Rico.
Landslides are frequent and damaging natural hazards that threaten the people and the natural and built environments of Puerto Rico. In 2017, more than 70,000 landslides were triggered across the island by heavy rainfall from Hurricane María, prompting requests by local professionals for landslide education and outreach materials. This article describes a novel collaborative risk communication framework that was developed to meet those requests and shaped the creation of a Spanish- and English-language Landslide Guide for Residents of Puerto Rico. Collaborative risk communication is defined here as an iterative process guided by a set of principles for the interdisciplinary coproduction of hazards information and communication products by local and external stakeholders. The process that supports this form of risk communication involves mapping out the risk communication stakeholders in the at-risk or -disaster-affected location-in this case Puerto Rico-and collaborating over time to address a shared challenge, such as landslide hazards. The approach described in this article involved the formation of a core team of government and university partners that expanded in membership to conduct collaborative work with an informal network of hazards professionals from diverse sectors in Puerto Rico. The following principles guided this process: cultural competence, ethical engagement, listening, inclusive decision -making, empathy, convergence research, nested mentoring, adaptability, and reciprocity. This article contributes to the field of risk communication and emergency management by detailing these principles and the associated process in order to motivate collaborative risk communication efforts in different geographic and cultural contexts. While the work described here focuses on addressing landslides, the principles and process are transferable to other natural, technological, and willful human-caused hazards. They may also serve as a roadmap for future partnerships among government agencies and university researchers to inform the cocreation of science education and outreach tools.


Radiation therapy in the prevention of heterotopic ossification after total hip arthroplasty.
The administration of radiation to prevent heterotopic bone formation after total hip arthroplasty has been highly successful in this prospective study. It was extremely effective in high-risk patients, including those with preexisting heterotopic ossification. No early deleterious effects were noted. Long-term follow-up is planned to observe for late tumor induction. No wound complications were encountered. Trochanteric nonunions did occur and may be in part related to the radiation. This study demonstrated the importance of the early initiation of treatment. Ninety-eight percent of high-risk patients who began treatment on the second to fourth day postoperatively were free of heterotopic bone after surgery. Meticulous technique is always employed to eliminate debris in the surgical wound, and soft tissues are handled carefully. The search continues for a more complete explanation of the pathogenesis of heterotopic bone formation. A current study has been constructed to demonstrate the minimum dose of radiation that will continue to be effective. Further evaluation of methods to more accurately identify the high-risk patient continues. The effectiveness of radiation therapy in the prevention of heterotopic bone following total hip replacement has been shown.


Ethnicity, catastrophizing, and qualities of the pain experience.
It is generally well established that catastrophizing exerts a potent influence on individuals' experience of pain and accompanying emotional distress. Further, preliminary evidence has shown that meaningful differences among various pain relevant outcomes (e.g., pain ratings, endogenous pain inhibitory processes) can be attributed to individuals' ethnic background. The mechanisms that might explain ethnic differences in pain outcomes are unclear, and it remains to be fully established whether the relation between ethnicity and pain response may be indirectly affected by pain catastrophizing. In the current study, we examined differences in pain responses by ethnicity among healthy, young adults (N=62), and attempted to determine whether such an ethnicity-pain relation was mediated by catastrophizing using the standard Pain Catastrophizing Scale (PCS) and a modified version of the PCS reflecting situational catastrophizing during a cold pressor task. Results showed that pain responses varied by ethnicity, as did reported catastrophizing. Catastrophizing mediated the relation between ethnicity and affective and sensory pain responses. To better explicate our findings, we described the context in which these findings occurred following a "who, what, where, when, and why" approach. This approach provides an efficient description of how our findings align with previous research, while identifying future research that should clarify the theoretical underpinnings of catastrophizing and pain and also inform clinical intervention.


Laser emission from flash ignition of Zr/Al nanoparticles.
We report the first laser emission from flash ignition of Zr/Al nanoparticles with the addition of strong oxidizer KClO4 using Nd: YAG as a laser medium. The mixture Zr/Al/Kp-45 (mass ratio = 33%Zr: 33%Al: 34%KClO4) has the highest brightness temperature Tb = 4615 K and the adiabatic flame temperature Tf = 4194 K with the duration of 20 ms. At 1064 nm we measured a maximum output energy of 702.5 mJ with the duration of nearly 10 ms by using only 100 mg mixture with an output coupler (transmission T = 10%). Further optimizing the concentration cavity and increasing the mixture content will yield much higher efficiency and output energy.


Novel ex vivo screening assay to preselect farm specific pre- and probiotics in pigs.
A novel rapid ex vivo assay was developed as part of a concept to determine potential tailor-made combinations of pre- and probiotics for individual farms. Sow faecal slurries from 20 German pig farms were anaerobically incubated with pre- and probiotics or their combinations together with pathogenic strains that are of interest in pig production. Aliquots of these slurries were then incubated with media containing antibiotic mixtures allowing only growth of the specific pathogen. Growth was monitored and lag time was used to determine the residual fitness of the pathogenic strains. The background growth could be inhibited for an Escherichia coli- and a Clostridium difficile- but not for a Clostridium perfringens strain. The prebiotic fructo-oligosaccharides (FOS) and its combination with probiotics reduced the residual fitness of the E. coli strain in some farms. However, notable exceptions occurred in other farms where FOS increased the fitness of the E. coli strain. Generally, combinations of pre- and probiotics did not show additive effects on fitness for E. coli but displayed farm dependent differences. The effects of pre- and probiotics on the residual fitness of the C. difficile strain were less pronounced, but distinct differences between single application of prebiotics and their combination with probiotics were observed. It was concluded that the initial composition of the microbiota in the samples was more determinative for incubations with the C. difficile strain than for incubations with the E. coli strain, as the presumed fermentation of prebiotic products showed less influence on the fitness of the C. difficile strain. Farm dependent differences were pronounced for both pathogenic strains and therefore, this novel screening method offers a promising approach for pre-selecting pre- and probiotics for individual farms. However, evaluation of farm metadata (husbandry, feed, management) will be crucial in future studies to determine a tailor-made solution for combinations of pre- and probiotics for individual farms. Also, refinement of the ex vivo assay in terms of on-farm processing of samples and validation of unambiguous growth for pathogenic strains from individual farms should be addressed.


A trade-off model of intentional thinking for pleasure.
We investigated intentional thinking for pleasure, defined as the deliberate attempt to have pleasant thoughts while disengaged from the external world. We propose a Trade-Off model that explains when and why thinking for pleasure is enjoyable: People focus on personally meaningful thoughts when thinking for pleasure (especially when prompted to do so), which increases their enjoyment, but they find it difficult to concentrate on their thoughts, which decreases their enjoyment. Thus, the net enjoyment of thinking for pleasure is a trade-off between its benefits (personal meaningfulness) and costs (difficulty concentrating). To test the model, we compared intentional thinking for pleasure to four alternate activities in three studies. Thinking for pleasure was more enjoyable than undirected thinking (Study 1) and planning (Study 3), because it was more meaningful than these activities while requiring a similar level of concentration. Thinking for pleasure was just as enjoyable as playing a video game (Study 2) or unprompted idle time activities (Study 3), but for different reasons: It was more meaningful than these activities, but required more concentration. We discuss the implications of these findings for what people might choose to do during idle times. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Complications and mortality among patients hospitalised with COVID-19.
The course of disease, complications and hospital mortality among patients with COVID-19 admitted to Norwegian hospitals has not been widely described. The purpose of this study was to survey patients with COVID-19 admitted to a local hospital. The data were retrieved from a prospective observational study of all patients admitted with COVID-19 to Bærum Hospital since the start of the coronavirus outbreak. A total of 73 patients with COVID-19 admitted in the period 9 March 2020-7 May 2020 were included. The mean age was 67.9 years, and 43 patients (59 %) were men. The average number of days hospitalised was 10.1. Altogether 19 patients (26 %) had a very severe course of disease, and 14 (19 %) died during their stay in hospital. The mean age among the patients who died was 79.5 years. A total of 49 patients (67 %) had hypoxaemia and required oxygen therapy for an average of 10.1 days. Of these, 9 patients were given invasive respiratory support for a median 18 days. Symptoms of delirium occurred in 26 patients (36 %) and was the most frequent non-respiratory complication. The majority of the patients hospitalised with COVID-19 needed prolonged oxygen therapy, and there was a high incidence of severe complications.


New leaders drive managed care. Sensitivity with a bulletproof attitude required.
It's been a time of rapid-fire change in the managed-care industry--change that has included high-profile turnover in the executive suites at many of the large publicly held HMOs. Stepping into the top jobs has been a new generation of leaders with skills and qualities unheard of in boardrooms just a decade ago. But those skills will be tested as the industry continues to evolve.


Germline excision of the transposable element Tc1 in C. elegans.
We have examined eight germline revertants generated by the excision of Tc1 from a site within the unc-22 gene of Caenorhabditis elegans. A rich variety of rearrangements accompanied Tc1 excision at this site, including transposon 'footprints', deletions of sequences flanking the insertion site and direct nontandem duplications of flanking DNA. With only modest modification the double-strand gap repair model for transposition, recently proposed by Engles and coworkers (Cell 62: 515-525 1990), can explain even the most complex of these rearrangements. In light of this model rearrangements of the target site accompanying transposition/excision may not be the end result of imprecise excision of the element. Instead, these rearrangements may be the result of imprecise repair of the double-strand gap by the host replication and repair machinery. Sequences surrounding an insertion site influence the fidelity of gap repair by this machinery. This may lead to a number of possible resolutions of a double-strand gap as documented here for a Tc1 site in unc-22.


Surgical management of pressure ulcers.
Surgical management of pressure ulcers ranges from office or bedside debridement to formal debridement in the operating room for the more extensive necrosis. Closure of these wounds may be by advancement flap closure for the simple ulcers and by local muscle or myocutaneous flap closure for the more complex ulcers and defects. Some pressure ulcers recur following previous surgery or following conservative treatment. The simple recurrences can be managed by the use of simple techniques while the surgical options for the management of the more difficult recurrent ulcers are limited involving more complex surgery like sensate flaps, expanded flaps, free tissue transfers and fillet flaps.


A randomized controlled trial of vitamin D supplementation on perinatal depression: in Iranian pregnant mothers.
Mood disorders in pregnancy and post-partum period are common and considered as a public health issue. Researchers have studied the relationship between low serum vitamin D concentration and perinatal depression, although no clinical trial has been conducted on vitamin D's effects on depression related to childbirth. This study evaluated the effect of vitamin D3 supplementation on perinatal depression scores. This randomized clinical trial was done in pregnant women who were under prenatal care in a teaching hospital in Shiraz, Iran. The inclusion criteria were: being 18 years or older, no history of mental illness and internal diseases, a singleton live fetus, without any pregnancy complications, gestational age of 26-28 weeks upon enrollment, and depression score of 0 to 13. The Edinburgh Postnatal Depression scale was used to evaluate depression scores. A total of 169 participants were assigned to the two groups of placebo and vitamin D through block randomization design. Vitamin D group received 2000 IU vitamin D3 daily from 26 to 28 weeks of gestation until childbirth. Maternal serum 25-hydroxyvitamin D concentrations were measured at baseline and childbirth. Besides, depression scores were evaluated four times: at 26-28 and 38-40 weeks of gestation, and finally at 4 and 8 weeks after birth. The two groups were similar in relation to baseline 25-hydroxyvitamin D concentrations. However, at childbirth, the vitamin D group had significantly higher 25-hydroxyvitamin D concentration in comparison to the control group (p < 0.001). At baseline, no correlation was observed between 25-hydroxyvitamin D concentration and depression score (r = 0.13, p = 0.09). There was no significant difference between the two study groups in relation to the baseline depression score. While, the vitamin D group had greater reduction in depression scores than the control group at 38-40 weeks of gestation (p = 0.01) also, at 4 and 8 weeks after birth (p < 0.001). The present trial showed that consuming 2000 IU vitamin D3 daily during late pregnancy was effective in decreasing perinatal depression levels. We suggest further clinical trial in pregnant mothers who are at risk for postnatal depression. Iranian Registry of Clinical Trials IRCT2015020310327N11 . Date of registration: March 9th 2015.


Molecular cloning and characterization of a P-glycoprotein from the diamondback moth, Plutella xylostella (Lepidoptera: Plutellidae).
Macrocyclic lactones such as abamectin and ivermectin constitute an important class of broad-spectrum insecticides. Widespread resistance to synthetic insecticides, including abamectin and ivermectin, poses a serious threat to the management of diamondback moth, Plutella xylostella (L.) (Lepidoptera: Plutellidae), a major pest of cruciferous plants worldwide. P-glycoprotein (Pgp), a member of the ABC transporter superfamily, plays a crucial role in the removal of amphiphilic xenobiotics, suggesting a mechanism for drug resistance in target organisms. In this study, PxPgp1, a putative Pgp gene from P. xylostella, was cloned and characterized. The open reading frame (ORF) of PxPgp1 consists of 3774 nucleotides, which encodes a 1257-amino acid peptide. The deduced PxPgp1 protein possesses structural characteristics of a typical Pgp, and clusters within the insect ABCB1. PxPgp1 was expressed throughout all developmental stages, and showed the highest expression level in adult males. PxPgp1 was highly expressed in midgut, malpighian tubules and testes. Elevated expression of PxPgp1 was observed in P. xylostella strains after they were exposed to the abamectin treatment. In addition, the constitutive expressions of PxPgp1 were significantly higher in laboratory-selected and field-collected resistant strains in comparison to their susceptible counterpart.


Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease.
Recently, several genome-wide association studies (GWASs) have led to the discovery of nine new loci of genetic susceptibility in Alzheimer's disease (AD). However, the landscape of the AD genetic susceptibility is far away to be complete and in addition to single-SNP (single-nucleotide polymorphism) analyses as performed in conventional GWAS, complementary strategies need to be applied to overcome limitations inherent to this type of approaches. We performed a genome-wide haplotype association (GWHA) study in the EADI1 study (n=2025 AD cases and 5328 controls) by applying a sliding-windows approach. After exclusion of loci already known to be involved in AD (APOE, BIN1 and CR1), 91 regions with suggestive haplotype effects were identified. In a second step, we attempted to replicate the best suggestive haplotype associations in the GERAD1 consortium (2820 AD cases and 6356 controls) and observed that 9 of them showed nominal association. In a third step, we tested relevant haplotype associations in a combined analysis of five additional case-control studies (5093 AD cases and 4061 controls). We consistently replicated the association of a haplotype within FRMD4A on Chr.10p13 in all the data set analyzed (OR: 1.68; 95% CI: (1.43-1.96); P=1.1 × 10(-10)). We finally searched for association between SNPs within the FRMD4A locus and Aβ plasma concentrations in three independent non-demented populations (n=2579). We reported that polymorphisms were associated with plasma Aβ42/Aβ40 ratio (best signal, P=5.4 × 10(-7)). In conclusion, combining both GWHA study and a conservative three-stage replication approach, we characterised FRMD4A as a new genetic risk factor of AD.


Using Brain Activation to Evaluate Arrangements Aiding Hand-Eye Coordination in Surgical Robot Systems.
To realize intuitive, minimally invasive surgery, surgical robots are often controlled using master-slave systems. However, the surgical robot's structure often differs from that of the human body, so the arrangement between the monitor and master must reflect this physical difference. In this study, we validate the feasibility of an embodiment evaluation method that determines the arrangement between the monitor and master. In our constructed cognitive model, the brain's intraparietal sulcus activates significantly when somatic and visual feedback match. Using this model, we validate a cognitively appropriate arrangement between the monitor and master. In experiments, we measure participants' brain activation using an imaging device as they control the virtual surgical simulator. Two experiments are carried out that vary the monitor and hand positions. There are two common arrangements of the monitor and master at the brain activation's peak: One is placing the monitor behind the master, so the user feels that the system is an extension of his arms into the monitor; the other arranges the monitor in front of the master, so the user feels the correspondence between his own arm and the virtual arm in the monitor. From these results, we conclude that the arrangement between the monitor and master impacts embodiment, enabling the participant to feel apparent posture matches in master-slave surgical robot systems.


Using text messaging to assess adolescents' health information needs: an ecological momentary assessment.
Use of mobile technology has made a huge impact on communication, access, and information/resource delivery to adolescents. Mobile technology is frequently used by adolescents. The purpose of this study was to understand the health information needs of adolescents in the context of their everyday lives and to assess how they meet their information needs. We gave 60 adolescents smartphones with unlimited text messaging and data for 30 days. Each smartphone had applications related to asthma, obesity, human immunodeficiency virus, and diet preinstalled on the phone. We sent text messages 3 times per week and asked the following questions: (1) What questions did you have about your health today? (2) Where did you look for an answer (mobile device, mobile application, online, friend, book, or parent)? (3) Was your question answered and how? (4) Anything else? Our participants ranged from 13-18 years of age, 37 (62%) participants were male and 22 (37%) were female. Of the 60 participants, 71% (42/60) participants identified themselves as Hispanic and 77% (46/60) were frequent users of mobile devices. We had a 90% (1935/2150) response rate to our text messages. Participants sent a total of 1935 text messages in response to the ecological momentary assessment questions. Adolescents sent a total of 421 text messages related to a health information needs, and 516 text messages related to the source of information to the answers of their questions, which were related to parents, friends, online, mobile apps, teachers, or coaches. Text messaging technology is a useful tool for assessing adolescents' health behavior in real-time. Adolescents are willing to use text messaging to report their health information. Findings from this study contribute to the evidence base on addressing the health information needs of adolescents. In particular, attention should be paid to issues related to diet and exercise. These findings may be the harbinger for future obesity prevention programs for adolescents.


[Percutaneous management of severe hemoptysis in a patient after fontan surgery].
We present the case of a patient with a history of single ventricle, tricuspid atresia, double outlet of the left ventricle and hypoplasia of the pulmonary artery ring. The patient was treated with Glenn's surgery at the age of 7 and at age 16, the patient received fenestrated extracardiac Fontan surgery. After 1 month of Fontan surgery she presented severe hemoptysis without adequate response to medical management. Percutaneous closure of aortopulmonary fistulas with coils was performed, with favorable evolution, without presenting recurrences of hemoptysis.


Vagus Nerve Stimulation in Ischemic Stroke.
Vagus nerve stimulation (VNS) has emerged as a potential therapeutic approach for neurological and psychiatric disorders. In recent years, there has been increasing interest in VNS for treating ischemic stroke. This review discusses the evidence supporting VNS as a treatment option for ischemic stroke and elucidates its underlying mechanisms. Preclinical studies investigating VNS in stroke models have shown reduced infarct volumes and improved neurological deficits. Additionally, VNS has been found to reduce reperfusion injury. VNS may promote neuroprotection by reducing inflammation, enhancing cerebral blood flow, and modulating the release of neurotransmitters. Additionally, VNS may stimulate neuroplasticity, thereby facilitating post-stroke recovery. The Food and Drug Administration has approved invasive VNS (iVNS) combined with rehabilitation for ischemic stroke patients with moderate to severe upper limb deficits. However, iVNS is not feasible in acute stroke due to its time-sensitive nature. Non-invasive VNS (nVNS) may be an alternative approach for treating ischemic stroke. While the evidence from preclinical studies and clinical trials of nVNS is promising, the mechanisms through which VNS exerts its beneficial effects on ischemic stroke are still being elucidated. Therefore, further research is needed to better understand the efficacy and underlying mechanisms of nVNS in ischemic stroke. Moreover, large-scale randomized clinical trials are necessary to determine the optimal nVNS protocols, assess its long-term effects on stroke recovery and outcomes, and identify the potential benefits of combining nVNS with other rehabilitation strategies.


From Loci to Biology: Functional Genomics of Genome-Wide Association for Coronary Disease.
Genome-wide association studies have provided a rich collection of ≈ 58 coronary artery disease (CAD) loci that suggest the existence of previously unsuspected new biology relevant to atherosclerosis. However, these studies only identify genomic loci associated with CAD, and many questions remain even after a genomic locus is definitively implicated, including the nature of the causal variant(s) and the causal gene(s), as well as the directionality of effect. There are several tools that can be used for investigation of the functional genomics of these loci, and progress has been made on a limited number of novel CAD loci. New biology regarding atherosclerosis and CAD will be learned through the functional genomics of these loci, and the hope is that at least some of these new pathways relevant to CAD pathogenesis will yield new therapeutic targets for the prevention and treatment of CAD.


The significant influence of having children on the postoperative prognosis of patients with nonsmall cell lung cancer: A propensity score-matched analysis.
The aim of this study was to elucidate the relationship between family-associated factors and the postoperative prognosis in patients with nonsmall cell lung cancer (NSCLC). Additionally, we investigated whether having children was associated with the postoperative maintenance of the nutritional status. We selected 438 NSCLC patients who had undergone curative lung resection between 2004 and 2011 at Kyushu University (Fukuoka, Japan), whose family-associated factors were available. Nutritional indices, including the prognostic nutritional index (PNI), were used to estimate the change in the nutritional status for 1 year after surgery. A propensity score analysis was conducted after adjusting the following variables: sex, age, smoking history, performance status, pathological stage, and histological type. Three hundred patients (68.5%) had both children and partners. Forty-nine patients (11.2%) only had children, and 56 (12.8%) patients only had a partner. Thirty-three patients (7.5%) did not have a partner or children. The overall survival (OS) and disease-free survival (DFS) of the partner-present and partner-absent patients did not differ to a statistically significant extent (P = .862 and P = .712, respectively). However, childless patients showed significantly shorter OS and DFS in comparison with patients with children (P = .005 and P = .002, respectively). The postoperative exacerbation of PNI was significantly greater in childless patients than in patients with children (P = .003). These results remained after propensity score matching. Childless patients had a significantly poorer postoperative prognosis than those with children. Surgeons caring for childless NSCLC patients should be aware of the poorer postoperative outcomes in this population.


A review of potential methods of determining critical effect size for designing environmental monitoring programs.
The effective design of field studies requires that sample size requirements be estimated for important endpoints before conducting assessments. This a priori calculation of sample size requires initial estimates for the variability of the endpoints of interest, decisions regarding significance levels and the power desired, and identification of an effect size to be detected. Although many programs have called for use of critical effect sizes (CES) in the design of monitoring programs, few attempts have been made to define them. This paper reviews approaches that have been or could be used to set specific CES. The ideal method for setting CES would be to define the level of protection that prevents ecologically relevant impacts and to set a warning level of change that would be more sensitive than that CES level to provide a margin of safety; however, few examples of this approach being applied exist. Program-specific CES could be developed through the use of numbers based on regulatory or detection limits, a number defined through stakeholder negotiation, estimates of the ranges of reference data, or calculation from the distribution of data using frequency plots or multivariate techniques. The CES that have been defined often are consistent with a CES of approximately 25%, or two standard deviations, for many biological or ecological monitoring endpoints, and this value appears to be reasonable for use in a wide variety of monitoring programs and with a wide variety of endpoints.